Podcasts about Cysteine

On today's episode of The Wholesome Fertility Podcast, I am joined by Dr. Nayan Patel @aurowellness, a pharmacist, researcher, and glutathione expert, to explore the critical role glutathione plays in fertility and overall health. Dr. Patel shares his journey from traditional pharmacy to developing a breakthrough delivery system for glutathione through the skin, and why this antioxidant is essential for protecting egg and sperm quality. In this episode, you'll learn how oxidative stress impacts fertility, why diet alone might not be enough, and how his innovative technology can support the body's natural detoxification process. Be sure to tune in for this fascinating conversation packed with practical advice and insights for anyone on the fertility journey! Key Takeaways:  Glutathione is the body's most abundant and powerful antioxidant. It plays a vital role in protecting reproductive health by reducing oxidative stress. Most oral supplements don't get absorbed effectively, making Dr. Patel's skin-delivery innovation a game-changer. A healthy lifestyle and cysteine-rich foods are essential for maintaining glutathione levels. Guest Bio: Dr. Nayan Patel @aurowellness is a highly sought-after pharmacist, wellness expert, and thought leader in his industry. Since 1999, he has collaborated with physicians to custom-develop medications and design patient-specific drug and nutrition regimens. As the pharmacist of choice for celebrities, CEOs, and physicians alike, Dr. Patel is recognized for his innovative approach to health and wellness. He is the author of The Glutathione Revolution: Fight Disease, Slow Aging & Increase Energy, which distills over a decade of clinical research on the master antioxidant, glutathione. His patented technology for delivering glutathione topically has revolutionized how the body absorbs this essential molecule. From this breakthrough, he also created the Auro GSH Antioxidant Delivery System, a skincare line designed to deliver antioxidants more efficiently and effectively than ever before. Websites/Social Media Links: Learn more about Dr. Patel's Products Follow Dr. Patel on Facebook For more information about Michelle, visit www.michelleoravitz.com  To learn more about ancient wisdom and fertility, you can get Michelle's book at: https://www.michelleoravitz.com/thewayoffertility  The Wholesome Fertility facebook group is where you can find free resources and support: https://www.facebook.com/groups/2149554308396504/  Instagram: @thewholesomelotusfertility Facebook: https://www.facebook.com/thewholesomelotus/ ------------------------------- Transcript: # TWF: Dr. Nayan Patel [00:00:00] [00:01:00]    **Michelle Oravitz:** So welcome to the podcast, Dr. Patel. **Dr. Nayan Patel:** Well, thank you for having me. I appreciate the time today. **Michelle Oravitz:** Yes, I'm very excited to talk about what we are going to discuss, which is glutathione. But before we get to that, I would love to get your backstory and how you got into the work that you're doing today. **Dr. Nayan Patel:** Oh my god, absolutely. So start off as a pharmacist, as a career as a pharmacist, and after graduation [00:02:00] from pharmacy school. In Southern California, we were, we were trained to take care of the patient's needs and medications. And very quickly I realized that the medications we have at that time were actually not solving any problem. They were just maintaining people's problems. And very, very early on, you know, you have an aha moment in your life. That oh my god, what what did I just do right? Oh, I'm just not solving any problems So I had to turn my career to a completely different angle no former educations in in making medications or doing compounding or customizing medications that dive into the that practice and 25 years later here we are today and looking back at that and said, what a journey, what a turning point I had, because it shaped me for who I am today. I had the privilege of making medications and design treatment plans and drug plans for so many individuals helping them in their health and wellness journey. And then all [00:03:00] roads led to me to a discovery of a novel technology that can deliver glutathione. And it all started because I was just curious to find out how we can help people solve their own problems instead of trying to figure out medications to solve the problems. Right? Even though glutathione is not a, it's, it's something that body produces internally we're using it as a supplement today, but. And overall my goal was not to do anything and just enhance the body's own ability to to defend itself. And so here we are today it's a very interesting career for me for sure. **Michelle Oravitz:** For  sure. And first of all, just for people listening that don't really know much about glutathione, I'd love for you to share really what it is and also why it could be so challenging to supplement with. **Dr. Nayan Patel:** Absolutely. so the glutathione in a nutshell Is three amino acids coming together in a single chain. It's a one of the smallest form of peptides we have You two amino acid chains, three amino [00:04:00] acid chains, four, five, 30, 40, 50, and thousands of the chains as well. The simplest form, of course, is glutathione, which is about three amino acids coming together. It's by far the most abundant molecule produced in the human body. And if that's produced so much, we ought to know what it's supposed to do for us. And so that's what my research came back for 140 years that we have known about glutathione. Nobody's ever figured out how to actually get inside your body. And so, 60 years ago, 70 years ago, we had a medication approved by FDA to enhance glutathione level. And as of today, that is the only medication that has been approved ever. In the whole, in the whole world, which is N acetylcysteine, which is one of the amino acids that's been used to produce chlorothione. And that's the only thing that has been available for the last 60, 70 years. **Michelle Oravitz:** So let's talk about what so we definitely, that's one of the things that um, I've been doing for egg health and also sperm [00:05:00] quality, cause it's such a high potent antioxidant. And one of the things that I have always suggested is N acetylcysteine because that's the precursor and we knew that that was like the one way that the body was able to produce it. Okay. Thank you. But then there were some supplements that still supplement with glutathione, liposomal, like different ways, which I know are not really shelf stable. So there's always been challenges with that, but before we continue on with that, I'd love for people to hear, like, what glutathione can benefit, how it can benefit the body. **Dr. Nayan Patel:** So, I understand your audience is interested more in the fertility side of the whole thing. So, you're dealing with rather younger individuals overall which is a good sign because younger patients have, everything at their disposal for the body to respond to even the smallest amount of nutrients that they receive. If the same amount of nutrients is given to an 85 year old person, they're not [00:06:00] going to feel anything, right? But if 20 year old person gets a small amount of good nutrition, they respond very, very well. And so I want to make sure that people understand that **Michelle Oravitz:** And also just to kind of mention um, sometimes we have 40 year olds too, that are trying to conceive or like trying to do IVF. So just kind of like, yeah, the whole, **Dr. Nayan Patel:** They're still spring chicken to **Michelle Oravitz:** okay. Okay. It's good for them to hear that. **Dr. Nayan Patel:** I mean, I've helped people in the very, I mean, in the late forties to get babies as well. So it's not something that's not doable. It's just gets incredibly hard after the age of 40. So it's, not that easy to do so, but the glutathione has multiple properties and understanding what glutathione does is, monument in over. in our therapies because with the two things that we do know is it's the ability for glutathione as an antioxidant to detoxify, neutralize all the free radicals in your body. But the second component is also help you detoxify by conjugating [00:07:00] inside your liver with metabolites and chemicals binding to them. So we can basically get rid of it from from your body. So the two functions that we do know That exists today. There's a lot more research still existing that we need to do. So we, we still are urging researchers to go back and use this new technology product and see if we can find out more things that glutathione can do for us. So one two the sperm or the egg quality is dependent on how your body is able to neutralize those free radicals. Those free radicals are actually toxic to all the embryonic membranes and embryos itself and the quality of the sperm and the egg itself. And neutralizing those free radical of body, there's three ways to do that part. One, you take outside products like vitamin C, and vitamin E, and CoQ10, and and C60s, and I mean, methylene blues, I mean, there's a slew of products that says, oh, we are so called antioxidants, right? So that's [00:08:00] category one. The category two of the products are produced endogenously inside your body are enzymes like catalase, supra oxide, puase, SOD, for short glutathione peroxidase, or GPX for short. So these are the enzymes that the body produces to deal with the oxidative stress or the free radicals. Okay, so those are the category one are the category two. The third category is only one product, which is glutathione. And if you look at it, the body produces so much of glutathione, and the effects of glutathione is so powerful, that if you combine the category one, which is all the antioxidants from outside sources, and the enzymes that your body produces, those two combine, Glutathione can surpass the antioxidant properties. And so I want listeners to understand very carefully is that the glutathione needs to be a basic cornerstone in everybody's arsenal. Every medicine chest in the world should have a [00:09:00] bottle says glutathione And in that bottle either you have a product or it have a note saying that eat healthy food to Let your body produce its own glutathione Either way that note has to be there on every medicine chest out there and you're right There's so much noise out there I want to cut to the noise today because if you just put your favorite search engine or your ai robot is going to tell you hey glirathion, there are a thousand different products out there. Choose one You Right. And as a consumer it's very hard to find out what to choose correctly and people hide behind a great technologies that that exists in the world and said, Oh, my, my product uses this technology. So it's the best one in the world. And you mentioned liposome technology, by the way, I just will let, you know, we were one of the very first few people that actually use liposome to produce the first liposomal glutathione. This was 25 plus years ago, right? And we made the liposome because at that time that was the [00:10:00] best technology that existed in the pharmaceutical world. And the doctor that owned the patents for those came to me and said, Hey, we've been very successful in making this for medications. Can you help me make nutraceuticals with it? Like vitamin C and CoQ10 and PQQ and S Xanthine and Glutathione and so on and so forth. And so we made the products for that doctor. And then a couple of years later. Some work, some did not work. Gluten was one of the products that did not work. So I go back and says, why is that working on everybody? The question I always ask is, hey, it helped my girlfriend. How come it's not helping me? Or it helped my sister. Why, how come it's not helping me? What, what, what am I, how am I different than the other human beings? and in reality, only your face is different. Internally, we are identical. A body has the same heart, the same organs, everything is the same, right? So we have not changed for the last 40, 000 plus years, [00:11:00] how to expect that I'm different than my sister, or I'm different than my girlfriend, or whatever, right? Maybe your genomic mixture is different, but your overall organs and organ systems are identical. And so to me, I said, okay, if it works in one person, it should work on everybody. If I get absorption in one person, I guess you should get absorption in everybody. What's the rate limiting factor? Why is it not happening? And so I didn't have answers at that time. I did not know what to do. So next story is that, okay, you know what? I'll make the intravenous form of glutathione. Hey, if I inject him into the bloodstream, my job's done. Again, took me a few months to figure that portion out how to make that part. And yes, This is long story short, we were Well, again, we were one of the first company pharmacy early on in 2001 to make the injectable form of glutathione. Now, very quickly, we realized that the effects of this glutathione was very short, right? And then I looked back in the research and said, there was a study done in 1991 [00:12:00] saying that if once you inject glutathione, it only stays in the body for between four It takes five to 15 minutes and everything gets destroyed or gets, get, get, it gets into the urine and you pee it out, but an hour and a half later, there was an increase of cysteine, which is one of the amino acids that went up in the blood. And so the researchers concluded that the body was breaking down this glutathione and cysteine was getting reabsorbed by the body and cysteine is being used for your body to produce its own glutathione. I said, okay, I don't care how the body makes it. As long as the body has a gluten, I don't care. But the results were very short lived. And I don't know if you know this thing, but back in early 2000s, one of the doctors came to me. I said, Hey, if it's short lived, that's okay. Let me take you to Vegas because when people drink, they deplete their glutathione levels. If it only stays for 15 minutes, I can revive somebody who's passed out drunk of their minds and I can get them. So. He literally took this product to Vegas and [00:13:00] start helping patients. I read scripts for those kinds of things. And again, I have nothing to do with it. I, unfortunately, I was just the supplier and I was just the maker of the product, but we saved so many lives. We helped so many people, but we were, we learned one thing that the action was not long term. And if I want the long term benefits, because if it's one of your patient, if it's one of your listener, who's, who's trying to get pregnant she, or he has to plan for A 30 day cycle, not a 15 minute. Give me some push right now and I'll be done. No, it's a 30 day cycle. You have to plan everything methodically, right? What am I supposed to do from day one to day seven and from day seven to day 14. And after ovulation, what do I do? And after post ovulation, if there's an embryo implantation, what do I do? And so on and so forth. It's a, it's a whole process and your body needs to be clean this whole time. And none of the products were actually getting the results I was looking for. Later on, I found out, this was 2011 [00:14:00] University of Texas in Austin did a study on the liposome technology product of glirathione. And what they found out was same thing that they saw in intravenous form. The body actually breaks down the glirathione, never absorbs a single molecule of it. Absorbs the cysteine and cysteine is later used to produce his own glutathione. And the end story is, it still works. It still works. But people need to understand, just because it works, it does not mean your body absorbed it. And there's a there's a difference between that one and maybe some people may not appreciate that part But I do appreciate that part because in my case i'm dealing with thousands of patients across the country across the globe now And I want to make sure that I want to give assurance to everybody that hey if I give you a glutathione product No matter what it is going to get inside your body [00:15:00] and absorb it And so the liposome technology product was great until now People got a lot of people got results for almost 80 got results from it but not because it absorbs it because the body was able to Conjugate or take the cysteine and make its own glirathione today Today the things have changed now. Why? because 15 20 years ago We started doing gene testing gene snips You Right at that time it was nobody can afford it. I was fifteen twenty thousand dollars for a blood test Oh gosh, no, nobody can afford that today Same test is 200 bucks 300 bucks, **Michelle Oravitz:** Right.  **Dr. Nayan Patel:** right? So now what's happened is that now everybody's doing these gene testings And finally got hey, do I have gene mutation where my body cannot produce gluothione if the answer is yes Then I don't care how much product you take from outside sources, the body is not [00:16:00] able to effectively produce glutathione correctly all the time. And so that to me is one more proof, one more proof that we need a product that your body can actually accept it, incorporate into their own DNA and use it when it needs to. Anyways, I just went off too many tangents no, Thanks very much, interesting. I want you to continue. So how did you find out and, and like how did you discover the product that you have now and what kind of technology does it use and how does it really impact the body? Absolutely. Those **Michelle Oravitz:** nerd in me wants to know **Dr. Nayan Patel:** Yeah. All great, great questions. And I want to, I really want to be an open book. I don't want to hide any information from anybody so that I'll be more than happy to open it up and let everybody know. So earlier when I first started the book. So we had a, we had a couple of barriers. One, what we knew was the body's not going to take any peptides, any amino acid chains to get it to and incorporate it into their own DNA. [00:17:00] What we, what I found out was the body has to make 100 percent of all peptides in the body, the body has to make it. Right. So we knew that I knew that part very early on. So I said, okay, there is no way on earth I'll be able to make a product that your body can use it up. Okay, so now I had to figure out Okay, how do I get this simple tripeptide three amino acid chain peptides into the body? So I first of all, I want to do, I want to create a stable molecule because if I have a stable molecule in my lab, I can work with it. If it's unstable, I don't have time to really experiment on it, right? So my first goal was to make a stable molecule. So that we achieved pretty fast. It took us a couple of years when we got the stable molecule. We took it by mouth. Again what we saw was Sistine went up, so it was not working really, it was getting broken down. We scored into the nose, I said, and if the nose was burning, I said, oh, nobody's going to use this on a daily basis. Of course not, right? It's not a, it's not a fun thing to do. I knew the [00:18:00] injectables was a little bit of an uphill battle because it requires FD approval and all those things. I said, you know what? The only route that was remaining was skin route. And of course, skin is a physical barrier, right? So it's a physical barrier that I have to overcome. And the physical barrier is, is a particle size barrier. So I had to reduce the particle size so small, It can get through the cracks or the pores of your skin and get inside your body. So that was the first challenge I had, which we were able to crack the code in about a couple of years. We had to take this peptides, twist it in such a form that doesn't get broken apart and gets a small, you know, like when you twist the towel, you know how it gets smaller and smaller and smaller, but you twist enough, it can get really small. And so that's what we did with this molecule. It forces microscopically, and we were able to reduce the particle size to much smaller. We got to the skin. The bigger challenge is this glutathione is inside your cells. So now the issue is that, [00:19:00] okay, we release a particle size, we get through your skin. Now, so the physical barrier, we, we all work in the physical barrier. The second was a chemical barrier. Because the cell wall is a lock and key. Hey, you say the magic word and the castle opens up and you can go inside. But if you don't say the magic word, the castle will never open for you. So the question then becomes is that what does the body needs? What does the cell needs to survive? All your mitochondria, the energy powerhouse in your body is in the cells, right? And that to produce the energy, what you need is carbohydrates and sugars. I cannot give you sugars because I give you diabetes and we already have an epidemic of diabetes in the United States across the world nowadays so I said, okay, how do I get a polysaccharide sugar type molecule? That doesn't doesn't do anything about the sugar is completely inert FDA has tested it out and it's completely safe to give to anybody pregnancy no pregnancy children's everybody And can I use that molecule? So we found [00:20:00] dextrin technology. This was a technology that has been out for about 20, 30 years now, but there are no good medications in the world. As even in today's state, there's not too many medications out there. People are still dabbling around. those technology products. And so we use the technology to literally, instead of working with medications, we start working with glutathione. We do the sugar molecule and stuff inside with glutathione. It's like, do you need M& Ms? Do you need **Michelle Oravitz:** No, not anymore,  **Dr. Nayan Patel:** Not anymore,  Okay, Good. Good. Do you, do you eat M& Ms for the peanuts or for the chocolate? **Michelle Oravitz:** I guess well, I used to like the chocolate ones when I was really, really little. And then later on peanuts, **Dr. Nayan Patel:** Exactly. But the thing is, you don't eat M& Ms for peanuts, you eat M& Ms for the chocolate. But the peanut inside, if you get a peanut, do you spit it out? Or you know what? It's not so bad. I can use it up. **Michelle Oravitz:** It's like I compare it to like, you know, the being able to take those pill things for your dogs where you put it inside a treat and get the dog to eat it. And[00:21:00]  **Dr. Nayan Patel:** That's exactly right, right? So I took the carbohydrate, the sugar molecule, stuffed the glutathione inside, you know, so the body, when the carbohydrate hits the cell wall, the cell goes, oh, I can use this up. Right? And sucks it in. Inside is glutathione. But he goes, well, I can use this up too. It's not something new to me, so I can use this up too. Right? And so now, it's like you somebody tells you that, hey, I have a billion dollar coming to you, but it's coming in the mail. Well, that's not helping me right now, but if it hits my wallet, gosh, I can spend it today. Right? So, you can check the mail, it's in a transit, but until it hits the wallet, you cannot do anything about it. Saving glutathione, if the glutathione is in your body, but it's not inside your cell, the, the cell says that, okay, I need the glutathione, but it's way out there. It's not in my cell. I cannot use it up. Here we got inside the cell directly. [00:22:00] When we did that part, like magic just happened. All of a sudden, the body has a product. The body needs it. The money's in the wallet right now. I can go spend it today. And the body can actually use the glutathione immediately To start doing what? Two things that we know of as of right now. One is start neutralizing all the free radicals. That's number one. Number two, start getting my liver cleaned up and start detoxifying all this, all this metabolism in my system. When you do those things up, all of a sudden your whole body or your temple, your, your the sanctuary in your body starts getting healed from inside, starts getting cleaner. And all of a sudden the, main thing, which is our sperm and the eggs. Are not been invaded or not been attacked by this toxic chemicals. **Michelle Oravitz:** Right? **Dr. Nayan Patel:** And so that's, there's, there's my technology. We discovered this in 2007, as you can imagine 2007 it was too far [00:23:00] ahead of the game. There was nothing in the world that exists something even close to this thing. And so there was no studies being done. There's no research articles published. There's nothing out there in the world that I can fall back and say, Hey, go ahead and use it safe. **Michelle Oravitz:** Yeah.  **Dr. Nayan Patel:** do that part. So it took me another 13, 14 more years to literally do everything that I can do on my own. I have no funding. I did everything on my own. I put every single thing I have back into this to basically research it out. Apply for the patents, all my work that I did. I, in fact, I published a book about three, four years ago. All the work I did for the first 13 years, I put in a book. I said, Hey. Guys, here's read it, right? This is this is all my work and it's just success stories that I've given to patients and clients and And found friends and family that uses product and and see how how much benefit they got in different areas of life right if you're an athlete versus if you have metabolic disorders versus you have [00:24:00] metabolism, defects if you're on the spectrum because spectrum patients have some sort of Metabolism issues of detoxification issues that they cannot clear the toxins out of the body And they are the autism or aspergers or whatever they got right? So i've all the stories and I have some stories about horses and and dogs and how how they it helped them as well in their in their wellness, thing as well as anyways So that's all the stories in the book the glutton revolution. That's my book. But after everything got done We had a pandemic **Michelle Oravitz:** Right. **Dr. Nayan Patel:** the product was not even released yet You And the pandemic comes around and I've been begged by all the doctors around the country. I said, oh my god Please give us the access to the glutathione because I was working with doctors So they knew about this product, but none of the consumers knew knew about it And so that's when we actually did a soft launch. We didn't have a bottling. We didn't have a boxing. We have nothing at that time No website, we had a website, but it was like a nothing nothing crazy So 2021 [00:25:00] was the first launch of the product now we are here today, but, so anyways, so thanks for asking me this question, but I just wanna make sure the story **Michelle Oravitz:** Yeah, no, I love the story because I think also I have very, very smart listeners, I'll be honest, like with a fertility journey, they are so educated. You know, it's such a motivator to really educate yourself. And a lot of times if I work with people in person online, I see the most educated people, they really know a lot. So I wanted to kind of have a background to really explain how the process works. Cause I feel like it's very empowering for them. And the two things that I know, like an N acetylcysteine. So that works as a precursor to get the cysteine. And then from that gets the body to produce glutathione. And then your product works through the skin and then is enveloped by the carbohydrates, right. Or the yeah,  **Dr. Nayan Patel:** is, it, it's, it's a polysaccharides is what we call 'em. And it's embedded inside that one. It's the, analogy I can [00:26:00] give you is that, hey if you need money, there's two ways to get money. One is I'll give you a job. You work at it. And you, you share your trades and then for the reward, I'll give you money. The second part is here's the money in your wallet. I'm not going to give you too much of it. I'm just going to give you enough to survive the rest. You still have to go make it yourself. Right. And so the second part, I give you enough to survive. Your body says to make the rest of the glutathione from the foods you eat and things like that. but a lot of people need, just need a little edge over everybody else. So I just give them extra glutathione to make sure that they are able to use up right now, because when you have a problem today, if you need the money today, and if you give you a job, I said, that's good, but I need the money now. I don't need money two weeks from now.  **Michelle Oravitz:** Yeah.  **Dr. Nayan Patel:** And so that makes it very, very useful. And in, in certain cases, I'm not saying that is good for everybody. What I am saying that is good for everybody, but the product may not be good for everybody,[00:27:00]  but having a healthier lifestyle, having the cysteine rich diet. Is absolutely a must I don't care what what age you are, right? That is absolutely a must So if you do that, if you have a healthy lifestyle, that means avoid the toxins that depletes the glutathione levels Having the diet that consumes that gives all the amino acids those two things combined Will will give you a fighting chance for long periods of time where you don't need any supplementations The supplementation is very good for people that need extra help or temporarily And then once your body gets under control then you can stop it, too **Michelle Oravitz:** Yeah. And then, so the couple of questions that come to my mind is you know, I'm, I'm a, also a big believer, obviously it sounds like it's doing something, but I'm also a big believer that like nature has a very a method for its madness. And I'm wondering, is there a reason why it's under such lock to allow um, glutathione in by itself, rather than having the body produce it? It was just [00:28:00] kind of like something that came to my mind.  **Dr. Nayan Patel:** know.  **Michelle Oravitz:** you were mentioning that. **Dr. Nayan Patel:** and you're right. I mean, the body is, is equipped to deal with, because any peptides that you, that the body can accept from outside sources can actually get embedded into your DNA. And so having the purity, what if you give somebody else's DNA inside your body? **Michelle Oravitz:** Right. **Dr. Nayan Patel:** Wow. Right. Think about it. Think about it. You're injecting somebody else's DNA. Some, some of the protein from something else that is not made by humans. The body is going to start going to cycle, react to it and say, Oh my God, what if well, we have vaccines right nowadays. What are the vaccines are proteins by outside of viruses, right? How about we use those embedded into our own DNA? So that's the, that's a scary part to me. And so that's the reason why a body does not allow anything from outside sources to get inside your body. It's very [00:29:00] very protective. Glutathione we do know is produced endogenously. It's inside your body, making sure that the glutathione the raw materials that we use Is of the highest highest quality. I would say 99. 99 percent pure is what we need. Otherwise, we just going to have a chance of making sure we have a chance that we can harm our body. And so just so for when I, when I first heard that in 2007, I quickly, I realized that I have to bring manufacturing in house. I can't trust anybody to do this for me. It literally took me eight years to build my own plant out small plant But just enough so that I can control every single thing making sure the water that I use is the highest quality Everything that goes inside is for the highest quality products. That's why I had to Ensure that so I brought everything in house. It was too costly to make it It's still too costly to make it and to [00:30:00] reduce the cost. I had to make sure that I I am, I'm going straight from the manufacturers to the consumers and there's no too many middlemen in between to reduce the cost down. And so we've been doing whatever it takes and you're right. The by doesn't take it. So having that technology to bypass this is somehow empowering that we can do that part. But it's scary is that we can use the same technology to, to hurt somebody too. **Michelle Oravitz:** Mm hmm. Yeah. Yeah. For sure. And thank you for answering that. And also, my question is, what have you seen in the research? Like, what have you seen short term, long term, because you, it sounds like you guys have been working with us for a long time, in the response of people's bodies and conditions. **Dr. Nayan Patel:** Absolutely. So just FYI of a human body gets everything gets, gets redone every 30, 60, 90 to 120 days. That means you get new cells in your bodies all the time.[00:31:00]  The body is constantly constantly making new cells, better cells so that you can rejuvenate yourself from inside out, right? So the body is, it's like you're having a house, constantly remodeling your house from inside all the time, right? So no matter what happens, if I make a hole in the wall, you know what, a few months from now it'll be a brand new wall again. I don't have to do anything, just have to wait and don't make it further damage the wall, right? And it'll be repaired by itself. So the body repairs itself. The issue is that. The glutathione can actually improve the repair process to the point where it repairs better. And you can feel the effects much, much faster. Now certain organs take them 12 to 18 months to repair. For example, liver, it takes a long time to repair. So, any, if you're looking for benefits for liver health that may take anywhere from 12 to 18 months. Even though if I have doctors I work with all the time and the doctor says, Oh, my, the liver function tests are coming normal. I said, just because the tests have [00:32:00] no, that doesn't mean the liver is normal, right? I guess you're right. Absolutely right. So they do ultrasounds. They do scans and things like that to figure that portion out. But again, it takes them 12 to 18 months to fix it. At a short term people when they have have issues with oxidative stress. The biggest issue I've seen is these are, these are people that have some gene mutations that cannot produce, they cannot conjugate and make enough glutathione. They have this brain fog that has been lingering on for decades, decades, right? For 10, 20 years sometimes. Of course, these are older people. These are not 20 year olds. And so they've been struggling and All of a sudden, they use a gluotide and about 15 minutes later, they can just see the, just brain just opens up. Now, it is not a, it's not a something to improve your memory. It's not this magic pill that you see in the movies. It's here, one pill, my brain just fires up and I'm, I can think and I can do anything I want to do. It's not that pill, it's a **Michelle Oravitz:** but I'm sure it can prevent things like Alzheimer's or things like that. Mm hmm, [00:33:00] mm **Dr. Nayan Patel:** well, Alzheimer's and Parkinson's and things like that as well. But in the short term, when people see the brain fog clears up, all it's doing is reducing oxidative stress. **Michelle Oravitz:** hmm. **Dr. Nayan Patel:** If you need to reduce oxidative stress, so I've seen results as much as 5 to 15 minutes. Up to two to four weeks in most individual And two three to six months in I would say 99 of the people they see some improvement in their health and wellness and they're most of them are working with the physicians So they're doing some blood tests before and after the doctors are saying what the heck you're doing I don't know what you're doing, but keep on doing it. It's very good for you. So  **Michelle Oravitz:** That's really interesting. And then also, if you were to get, you know, outside source of glutathione, the body feels the glutathione, will it make an impact on the body's own production of glutathione now that it feels that it has more. **Dr. Nayan Patel:** Absolutely. And the thing is [00:34:00] the the biggest concern that people have that hey What if if I take glutathione from outside sources with my body shut down his own production? And yes and no, I think the body probably may reduce the production, it probably will not shut it down because keep in mind when we're comparing, because most people have been burned by, hey, if you take steroids, your body will, it'll blow up like a balloon and because the body is not able to make its own regular, its own steroid production, which is true, which is 100 percent true. endocrine system is tightly regulated from your gonadal hormones, your pituitary and your ovaries and your testes and to the brain, which is the pituitary the hypothalamus, right? So they both work together, your brain tells your ovaries to produce the hormones, the ovaries produce the hormones, the ovaries cannot produce the hormones, The brain is going to keep on sending signals. Can you do more? Do more? Do more? Because I can't do anymore. I'm already tired. I'm burnt out. I'm just, I'm shriveled up. I can't do anymore. Right? Versus if you [00:35:00] take a hormone from outside sources, it affects straight to the pituitary. And the pituitaries will shut down and say, Hey, no more producing hormones. You got too much. I don't know where it's coming from,  but  **Michelle Oravitz:** like a thermostat,  **Dr. Nayan Patel:** Right? It's a negative feedback. But when it comes to glutathione, glutathione is not triggered by any brain or hypothalamus. Glutathione is taking three amino acids together, two enzymes, two molecules of ATP, which is energy, and one molecule of NAD for electron transfer. All this to come together to make glutathione. Right? Now this same energy, ATP energy, NAD energy is being used in thousands of chemical reactions that happens every single day. So keep in mind, if your body does not have to produce glutathione, your energy is never wasted. It's used to do other reactions all day long. But the good thing is that glutathione is by far the most abundant molecule produced in the human body. [00:36:00] And after a couple of weeks or so, the body is saying, hey, everything is not working great. Now for two weeks later you see some increasing energy because now the energy is is Getting excess and your body goes. Oh my god. I have excess energy now all of a sudden. It's not a car It's not a caffeine type energy It's not like jumping up and down type of energy, but you do feel good from inside out Right. You do feel good. And all of a sudden you pick up other habits, walking, jogging, cycling, you know, or just going out and just, you just have this, this energy inside your body that you want to do other things. You just feel alive from inside. And so, and then when you stop the glutathione, the body says, okay, oh, should we have, we need more glutathione. So the first energy goes towards producing glutathione, but if you have enough glutathione, that energy has been used to produce other peptides. Keep in mind, a muscle needs what? 6, 100 amino acids coming together. Takes a lot of energy to produce muscle fiber. So if you're not [00:37:00] using the energy to produce glutathione, hey, hopefully it goes to producing more muscle mass. I'm hoping for that. **Michelle Oravitz:** Yeah. . And is there like a limit on how long you should take it? you know, is there a limit that you have? **Dr. Nayan Patel:** So, I do know that your body needs glutathione until the last day you die. So, until that day, you have to take it. After you're dead, I'm not sure if your body needs glutathione or not. So, that's a joke. I'm sorry. But your body needs glutathione to survive. Every single day. So the needs are going to be the endless. the better question to me is that do I need to supplement every single day of my life? That's a way better question for me to answer is to that that question came to me in my mind long time ago as well. And so what I have found out is that the body needs glutathione. to survive. Your body has the ability to produce glutathione, plenty of it on a daily basis. And what I found in [00:38:00] my research that up until about the age of 30, there is no need for any supplementation. None. Improve your diet, reduce your exposure to toxicities. You should be fine. **Michelle Oravitz:** Right?  **Dr. Nayan Patel:** Between 32, 35, if you have a healthier lifestyle, don't drink alcohol. Don't expose yourself to heavy levels of toxicities. Don't do sunbathing a whole lot. And having a very clean diet, you might still be okay. 35 to 40, I would say 80, 90 percent of the people may need to supplement gluathione, over 40, I have yet to find somebody who has normal levels of gluathione and so the question that I ask is, Hey, what's Well, my mom in the fifties and sixties never had to use a gluathide, and she lived for long periods of time, so why is it today, right? But keep in mind, at that time, sixty years ago, maybe the world population was three billion, now we are eight billion population. And who are the biggest polluters in the world? Is it the [00:39:00] animals or the humans? **Michelle Oravitz:** Humans. **Dr. Nayan Patel:** Humans. Animals don't even wear clothing. They don't even do anything. They don't have to build any houses and, and destroy the world. They just live, enjoy the world and leave the world the way it was when they came in. Us humans wants to fly, wants to build a hundred story buildings and wants to drive cars and wants to do all kinds of things. So we are the biggest polluters and the pollution has literally what more than doubled in the last 60 years. So if we say that the, the modernist society is polluted, the answer is absolutely yes. And it's not, it's not like we are turning the tables and we're going on the other way around. So like it or not, nobody's willing to give the modern day conveniences at this point. They don't, they're not going to do that part. So the question is that yes, Maybe my mom did not need gluten until the age of 50 or 60 [00:40:00] maybe. That's dropped down to 30, 35 or 40 at this point. And I'm scared for my kids because they may need glutathione at the age of 25 That's that's not a good thing to do, but it's just just telling us that our memory is getting more and more polluted and we need to figure out every single thing that we can do to enhance our body to stay clean from inside. **Michelle Oravitz:** And is there a benefit to taking N acetylcysteine as well as the, the skin,  um, supplementation?  **Dr. Nayan Patel:** okay, so NAC or cysteine so there are about eight essential amino acids that you have to take every single day Cysteine is not one of them Cysteine, Glycerine, and Glycine. Those are the three amino acids that's used to produce glutathione. Those three are not even in the part of the eight essential amino acids. So if you take cysteine and the glutathione topical version that we have, the cysteine is not going to be used up to produce glutathione at all. It may be used up for some other components, but not for [00:41:00] glutathione. I would suggest that if you're doing that part, then save your money and just improve your diet, right? If you have the money, I would rather you invest in those eight essential amino acids. Those are much better to do that, like Lucid and Proline. And so those are much more better to for you to use it on a daily basis. I'd rather you spend the money on that than to spend the money on the SysTeam. **Michelle Oravitz:** Got it. And then what are some of the foods and, that you would recommend for the glutathione diet? **Dr. Nayan Patel:** Michelle, I've been told not to advise people on diet **Michelle Oravitz:** Okay. Thank you **Dr. Nayan Patel:** is worse than the religion and politics. So I'm going to tell you one thing. All right. So everybody has a, has an AI robot. Everybody has access to AI robot. Go type it up.  Sistine rich foods. **Michelle Oravitz:** Sistine Richards **Dr. Nayan Patel:** You're going to get your vegan choices, vegetarian choices, carnivore, [00:42:00] paleo, Atkins. I don't know what a longevity diet. I don't know. Don't die diet. I, I don't know. There's so many diets out there right there right now. All these diets are going to be satisfied if you just type in the word system food and see what food are you willing to eat and make and have a variety of foods from that list that you consume on a daily basis. Like what's in that list? I, you know, on an everyday basis, every single day.  **Michelle Oravitz:** Yeah **Dr. Nayan Patel:** in there, asparagus in there, there's oysters and chicken and turkey. And I mean, you can name it, right? There's so much stuff is in there that you can consume. It's not a small list, right? But you have to make it a part of the routine. But that's just one thing. That's just one thing. The second part, which is utmost important, is limit. Limit your exposure to toxicities, **Michelle Oravitz:** yes true [00:43:00] Oh, **Dr. Nayan Patel:** pure. Right is important and because of that guess what my technology I even dove into the skincare as well because because most of my customers were females. Well now they are like 50 50 today But at that time all my customers female and they look at the technology and say hey Can you give me all the antioxidants for my face as well? I said sure. It's that's easy, right? So I just went got all the antioxidants and I said, okay Put it squeeze the size right so I can shove a whole bunch of stuff into this couple of products And so I have like seven or eight different antioxidants in full concentration and some are even more in like two creams right And then two of the serums I give like 10x of what you what you get from any of the products in the marketplace today so I give you a vitamin c and glutathione in a very high concentration to your skin Gets your skin completely disperses really really fast and gets gets to the all the skin in your whole body And so anyways, so I did that [00:44:00]  **Michelle Oravitz:** if you do that, To your face, is that the same thing, the same technology that will get glutathione in your cells? So it's kind of like two in one? **Dr. Nayan Patel:** So it is, it is it's the same technology, but what we have to done is we have to identify the speed and how deep I want to go inside. So the skincare is more  for,  **Michelle Oravitz:** different. It's more  **Dr. Nayan Patel:** yeah, but I would always say that if you're using both that do not double up, do not double up, right? If you're using both that your skincare routine, as is the way it's been introduced to you, and then just add on the, the top of glue that just once a day. **Michelle Oravitz:** I  **Dr. Nayan Patel:** And you, and you still get the, I mean, you get full benefit. That's the ultimate Longevity hack is what I call them, right? Cause the beauty is inside out. The ultimate longevity hack is you do the full skincare routine and just do once a day of the glutathione. If you don't do the skincare routine, just the glutathione twice a day is, is, is, is what you need. That's an ultimate bio is, [00:45:00]  **Michelle Oravitz:** Oh, that's great.  **Dr. Nayan Patel:** I have. **Michelle Oravitz:** Well, listen, I mean, I'm curious. I'm sure people listening are very curious, how can we find out more? How can we buy this stuff and get ahold of it? **Dr. Nayan Patel:** Absolutely. So, my website is oral wellness. com. A U R O wellness. com. Go to the website. There is a two part on the top is skincare and wellness. Otherwise you can go to oral skincare. com as well. The same thing. My urge is that if you are any of this patients that is Not able to give up monitor conveniences or you may suspect that you may have low glutathione levels I would probably strongly suggest you try it for 30 days It is,  we do offer a hundred percent, a hundred percent money back guarantee. We don't charge shipping and handling. We'll refund you everything, right? We will, we will do full refund of everything. Cause I just want people to try it out. And once you try it for 30 days and if you see slight benefit of [00:46:00] it then it's the best thing that can happen to you for the rest of your life. It's one thing that I have, I have customers for now for 17 years, since the first we discovered this product. That will, that's like a, it's a go to product in the arsenal. It's like, it's always there. And I'll tell you, I'll give you another analogy right now, because I wanted people to really understand what this is, because as you age, your body is deteriorating, is diseased, and it is, is, is breaking down, right? It's like. You go to your, when you go to your home you leave your door open. And as soon as I leave the door open, the dust, the wind blows the leaves inside. And so what you do is you bring your vacuum out or your, or your broom out and start sweeping and guess what? There's more dust and more leaves coming out. Right? So what do you do? I'll say, Oh my God, I forgot to close the door. Once you close the door, you can literally clean the whole house from inside and make [00:47:00] it brand new again. Right? Oxidative stress, oxidative stress, production of free radicals is the opening of the door analogy in your body. Oxidative stress is not doing anything, but it's allowing every single thing to come inside your body. And destroy the body from inside and unless you block that and close it up You cannot buy your body does not heal from inside, right? So the glutathione is actually closing the door is actually closing the door and then allowing your body to what to start getting? Cleaned up from inside and start repairing itself inside So at the bare minimum at the bare minimum if you do for four months You're going to have every single day Products in your body, every single cells, organs, every single thing you're going to have allowed them the chance to [00:48:00] regenerate self. **Michelle Oravitz:** Yeah.  **Dr. Nayan Patel:** after four months, yeah, it's after four months, it's like game over. So I have people that even today's they, they said, I know what I have to do. It's just that I just keep on forgetting. I said, that's okay. You know, close the door first. You know, it's, it's no fun sweeping and wrecking your house every single day. **Michelle Oravitz:** No, no, it's not. I agree. Wow. This is amazing. Really, really fascinating information. I just love the fact that you have a background from, from ecology. I mean, that you understand it really from the inside out and that you were able to apply technology and really understand it from your perspective and that you had these ideas to create a product like that, that's really cool. **Dr. Nayan Patel:** and I, I wish I had this product when we were going through our early on in my life because my wife had a hard time conceiving and it took us nine years to have a first son. Yeah, and it's not that we were trying for nine years. It's just that [00:49:00] after marriage, it took us nine years to have the first son and we only tried for maybe about a couple of years before. And then. We did, I think we did one, one, I think two IVF cycles. And I said, this will be the last one. We'll never do it again because I know the damage it causes to the human body. And I wasn't the one suffering, but I know it was going to destroy her body for the rest of her life. So I was not willing to put up with make her go through the process, even though it was like something that is so blissful to you, right? When you have a kid. So, yeah, we did all the traditional because I was pharmacist. I knew I'll do all the hormone therapies. I did all the hormones correctly. Everything was just fine, but she just was not producing any follicles. The follicles were there, but they're not producing any eggs. I knew that it was oxygen stress, but at that time I had nolu thi product in me. And So uh, it is just so unfortunate, right? But today you have that if you are a young person that is trying to conceive you have this thing, [00:50:00] at the very least, just use it for a few months. It gives it by the chance. And and, and hopefully you have a healthy baby. That's, that's always my **Michelle Oravitz:** Yeah, that's the hope. Yes. And sending all of that good, good energy and good thoughts to everybody listening. So thank you so much, Dr. Patel for coming on. This is a great conversation. I will have all the links to the website and everything in the episode notes for people to view if they want to stop, stop the car and then go look, but thank you so much for coming on today. This is a great conversation. **Dr. Nayan Patel:** Appreciate your time today. It's my pleasure to be here today. Thank you. [00:51:00] [00:52:00]     

In today's video, I'm discussing how we can prevent or minimize the unwanted symptoms of norovirus. First, it's important to recognize that norovirus relies on oxidative stress-induced cell damage to spread and replicate in the body. So anything we can do to decrease oxidative stress by improving the antioxidant status of our cells decreases the opportunity for viral activity in our body. Norovirus also attacks and damages the intestinal lining, which is why vomiting and diarrhea are often a large part of the symptom picture. Making sure our gut health is on point is high value. Nutrient Support⬇️ Support gut health integrity and cellular antioxidant status by using probiotics like lactobacillus and bifidobacterium species as well as one of my favorites, N-acetyl Cysteine or NAC. NAC increases our master antioxidant glutathione to reduce cell damage and promote a hostile environment for norovirus. Vitamin C and selenium can also help in a similar fashion to NAC. Plus I share how to properly hydrate if you are vomiting, why I use a throat spray, and how acid blockers (proton pump inhibitor and H2 blockers) can increase susceptibility to a norovirus infection.   ➡️Healthy Meals Made Easy PDF https://go.drwholeness.com/healthy-meals-made-easy -------- Connect with Dr. Matt online:  

Dr. Nayan Patel is the author of the The Glutathione Revolution. His expertise lies in identifying and addressing the widespread deficiency of glutathione, a crucial antioxidant that plays a significant role in maintaining overall health. Dr. Patel believes that by understanding and increasing glutathione levels, we can prevent a range of chronic diseases and slow down the aging process. We had a wonderful conversation about what glutathione is, how artificial chemicals affect our bodies natural synthesis of glutathione, and what we can do to support the body's production of glutathione especially as we age.  WHAT WE DISCUSSED: [4:41]- How did realizing he was “only managing peoples problems” bring Dr. Patel to leave his conventional training and pursue 20+ years of research about glutathione?  [7:31]- What is glutathione and what role does it play in physiology?  [10:59]- How does glutathione protect against free radicals in the body?  [14:09]- Environmental toxins that are decreasing the body's ability to produce glutathione.  [19:01]- How do over the counter medications deplete glutathione? [22:00]- How can someone know if they are glutathione deficient?  [29:59]- What foods boost glutathione production?  [34:45]- Can you overdose on glutathione?  [47:47]- Is glutathione helpful for acne prevention and anti-aging effects?  [58:23]- What are the side effects of semaglutide peptides?  LINKS MENTIONED IN THIS EPISODE:  Special thanks to Dr. Patel's company, AURO Wellness, for sponsoring this week's episode. Shop the glutathione spray here!  FOR MORE INFORMATION FROM DR. NAYAN PATEL: Website: https://aurowellness.com/  Instagram: @aurowellness LET'S GET IN TOUCH:  Instagram: @shana.hussin.rdn Facebook: Fast To Heal With Shana Hussin Website: https://www.fasttoheal.info/ MY FREEBIES AND PROGRAMS: ENROLL in Low Insulin Academy ON-DEMAND HERE! My specialty course decoding everything about reversing metabolic illness!  If you want to work with me directly check out my coaching community! Find all my product recommendations and discount codes HERE. My FREE Starting Guides, a great place to learn more about the strategies I teach!  Register for my FREE webinar, You've Got Insulin Resistance and Blood Sugar Issues... NOW WHAT?!  Grab my metabolic testing guide!  Metabolic Makeover Starter Course teaches you how to transition from a sugar burner to a fat burner!  BE ON THE PODCAST by emailing support@fasttoheal.info and sharing your story of how Fast to Heal Services have changed your life!

BUFFALO, NY- August 27, 2024 – A new #research perspective was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 15 on July 25, 2024, entitled, “Trioxidized cysteine and aging: a molecular binomial that extends far beyond classical proteinopathic paradigms.” Oxidative stress (OS) - characterized by an imbalance between oxidants and antioxidants - leads to the formation of oxidative posttranslational modifications (PTMs), including those involving cysteine (Cys) residues in aging proteomes. Specifically, the formation of trioxidized Cys (t-Cys) results in permanent protein damage. Recent findings in rodents have revealed that irregular regulation of t-Cys residues in the aging proteome disrupts homeostatic phosphorylation signaling, leading to alterations in proteins similar to those caused by phosphorylated serine (p-Ser) residues. In this perspective, researchers José Antonio Sánchez Milán, María Mulet, Aida Serra and Xavier Gallart-Palau from University Hospital Arnau de Vilanova (HUAV) and University of Lleida (UdL), present novel data, validating the increase of specific t-Cys sites associated with aging in a blood-related circulating human proteome. "The scope and findings included here support the hypothesis that t-Cys residues may serve as important mechanistic and biological markers, warranting further exploration in the context of unhealthy aging and age-related major diseases.” DOI - https://doi.org/10.18632/aging.206036 Corresponding authors - Aida Serra - aida.serra@udl.cat, and Xavier Gallart-Palau - xgallart@irblleida.cat Video short - https://www.youtube.com/watch?v=roO_8WMGak8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206036 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, oxidative stress, unhealthy aging, t-Cys, aging diseases, aging proteome About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Bioconjugation of antibodies to drugs via chemical linkers is how antibody drug conjugates (ADCs) are made. We're joined by Matt Giese, Senior Scientist at Vector Laboratories, who talks us through the complex chemistry options and biodesign considerations that have to be considered and balanced when making a successful ADC.How does one build the skillset to work in biodesign of ADCs you might ask? Well, Matt's career path might not provide a clearcut roadmap like you might hope. That's because Matt started his career as an auto mechanic, moved into art, went back to auto mechanics, worked as baggage handler and as a construction worker, all before ever finding chemistry. If you think that's a convoluted path, just wait to hear about his academic and professional work journeys.  You'll revel in following this journey, and in the lessons and diverse skills learned along the way. Join us to hear it yourself, from who might just be the most interesting man in chemistry!Related episodes:Season 5, Ep.7: The life-altering impact of one chemist's sabbaticalSeason 2, Ep.1: Chemistry: a modern American dreamSeason 3, Ep.5: On the COVID pill and other process chemistry tales Bonus content!Access bonus content curated by this episode's guest by visiting www.thermofisher.com/chemistry-podcast for links to recent publications, podcasts, books, videos and more.View the video of this episode on www.thermofisher.com/chemistry-podcast. A free thank you gift for our listeners! Request your free Bringing Chemistry to Life t-shirt on our episode website.Use Podcast Code: LabRatsRul3 in July or OchemRcks in August. We read every email so please share your questions and feedback with us! Email helloBCTL@thermofisher.com

This podcast discusses the benefits of N-Acetyl-Cysteine (NAC), a liver antioxidant that reduces inflammation in the body.  NAC is a sulfur-based tripeptide that can detoxify the body and support liver health. It also serves as a precursor to glutathione, a master antioxidant.   Find NAC in Liver Prime at Mswnutrition.com

References J Pharm Bioallied Sci. 2019 May; 11(Suppl 2): S135–S139. J Oral Microbiol. 2017; 9(1): 1400858. J Dent Res. 2020 Jun;99(6):644-649. Mozart WA 1782. D major, K. 385. Symphony 35 (Haffner) --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Grandpa Bill today looks at What are the Health Benefits of NAC (N-Acetyl Cysteine)? benefits, including replenishing antioxidants and nourishing your brain. NAC is considered ‘conditionally essential' because your body can produce it from other amino acids. It becomes essential only when the dietary intake of methionine and serine is low. Cysteine is found in most high protein foods, such as chicken, turkey, yogurt, cheese, eggs, sunflower seeds, and legumes. Consuming adequate cysteine and NAC is important for various health reasons, including replenishing the most potent antioxidant in your body, glutathione. These amino acids also help with chronic respiratory conditions, fertility, and brain health. NAC helps replenish glutathione, arguably your body's most powerful antioxidant. Therefore, it may help improve a variety of health conditions. 1. Essential for making the powerful antioxidant glutathione 2. Helps with detoxification to prevent or diminish kidney and liver damage 3. May improve mental health conditions and substance use disorder 4. Helps relieve symptoms of respiratory conditions 5. Boosts brain health by regulating glutamate and replenishing glutathione 6. May improve fertility in both men and women 7. May stabilize blood sugar by decreasing inflammation in fat cells 8. May reduce heart disease risk by preventing oxidative damage 9. Ability to boost glutathione levels may improve immune function NAC plays several important roles in human health. Renowned for its ability to replenish levels of the antioxidant glutathione, it also regulates the important neurotransmitter glutamate. Additionally, NAC helps your body's detoxification system. These functions make NAC supplements a viable treatment option for multiple health conditions. Consult your doctor to determine whether NAC may benefit your health. Are You Using N-Acetyl Cysteine? Leave Your Replies at The BH Sales Kennel Kelp Holistic Healing Hour Message Board #nacetylcysteine #glutathione #nac #wellness #nutrition #covid #keyglutafever #keyglutathione #keyglutaph #antioxidants #theskinbureau #nopoliticsjustresults #repost #thefriendznetwork #integrativemedicine #naturopathicmedicine #uncensored #freespeech #censored #immunesystem #immunity #chronicillness #healthnews #naturalnews #mercola #naturalhealth #phlegm #liverdetox #capegate #simplynatural #glutathione #glutax #skincare #gluta #collagen #whitening #vitaminc #mg #antiaging #beauty #skinwhitening #luxxewhite #glutathioneph #gs #glutaph #cindella #tationil #glowingskin #acne #whiteningph #skin #nexentury #pemutihkulit #health #glutathioneinjection #pemutihbadan #vitamin #lglutathione #glutadrip #skincareroutineGrandpa Bill's Grunts & GroansNothing is so much to be feared as fear.Henry David Thoreau (1817-1862) --- Send in a voice message: https://podcasters.spotify.com/pod/show/bhsales/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.25.545688v1?rss=1 Authors: Tian, Y.-M., Holdship, P., To, T. Q., Ratcliffe, P. J., Keeley, T. P. Abstract: In animals, adaptation to changes in cellular oxygen levels is coordinated largely by the 2-oxoglutarate dependent prolyl-hydroxylase domain (PHD) dioxygenase family, which regulate the stability of their hypoxia-inducible factor (HIF) substrates to promote expression of genes that adapt cells to hypoxia. Recently, 2-aminoethanethiol dioxygenase (ADO) was identified as a novel O2-sensing enzyme in animals. Through N-terminal cysteine dioxygenation and the N-degron pathway, ADO regulates the stability of a set of non-transcription factor substrates; the regulators of G-protein signalling 4, 5 and 16, and interleukin-32. Here, we set out to compare and contrast the in cellulo characteristics of ADO and PHD enzymes in an attempt to better understand their co-evolution in animals. We find that ADO operates to regulate the stability of its substrates rapidly and with similar O2-sensitivity to the PHD/HIF pathway. ADO appeared less sensitive to iron chelating agents or transition metal exposure than the PHD enzymes, possibly due to tighter catalytic-site Fe2+ coordination. Unlike the PHD/HIF pathway, the ADO/N-degron pathway was not subject to feedback by hypoxic induction of ADO and induction of ADO substrates was well sustained in response to prolonged hypoxia. The data also reveal strong interactions between proteolytic regulation of targets by ADO and transcriptional induction of those targets, that shape integrated cellular responses to hypoxia. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.30.534617v1?rss=1 Authors: Gonzalez-Jimenez, P., Duarte, S., Martinez, A. E., Navarro-Carrasco, E., Lalioti, V., Pajares, M. A., Perez-Sala, D. Abstract: Cysteine residues can undergo multiple posttranslational modifications with diverse functional consequences, potentially behaving as tunable sensors. The intermediate filament protein vimentin has important implications in pathophysiology, including cancer progression, infection, and fibrosis, and maintains a close interplay with other cytoskeletal structures, such as actin filaments and microtubules. We previously showed that the single vimentin cysteine, C328, is a key target for oxidants and electrophiles. Here, we demonstrate that structurally diverse cysteine-reactive agents, including electrophilic mediators, oxidants and drug-related compounds, disrupt the vimentin network eliciting morphologically distinct reorganizations. As most of these agents display broad reactivity, we pinpointed the importance of C328 by confirming that local perturbations introduced through mutagenesis provoke structure-dependent vimentin rearrangements. Thus, GFP-vimentin wild type (wt) forms squiggles and short filaments in vimentin-deficient cells, the C328F, C328W, and C328H mutants generate diverse filamentous assemblies, and the C328A and C328D constructs fail to elongate yielding dots. Remarkably, vimentin C328H structures resemble the wt, but are strongly resistant to electrophile-elicited disruption. Therefore, the C328H mutant allows elucidating whether cysteine-dependent vimentin reorganization influences other cellular responses to reactive agents. Electrophiles such as 1,4-dinitro-1H-imidazole and 4-hydroxynonenal induce robust actin stress fibers in cells expressing vimentin wt. Strikingly, under these conditions, vimentin C328H expression blunts electrophile-elicited stress fiber formation, apparently acting upstream of RhoA. Analysis of additional vimentin C328 mutants shows that electrophile-sensitive and assembly-defective vimentin variants permit induction of stress fibers by reactive species, whereas electrophile-resistant filamentous vimentin structures prevent it. Together, our results suggest that vimentin acts as a break for actin stress fibers formation, which would be released by C328-aided disruption, thus allowing full actin remodeling in response to oxidants and electrophiles. These observations postulate C328 as a sensor transducing structurally diverse modifications into fine-tuned vimentin network rearrangements, and a gatekeeper for certain electrophiles in the interplay with actin. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Health consulting - adults: https://christianyordanov.com/health-consulting/Children's health consulting (autism, ADHD, gut dysfunction, etc.): https://christianyordanov.com/childrens-health-consulting/Some common health complaints we can help you address: Fatigue / low energy / running on coffee Low libido / hormone imbalances Gut problems Sleep issues Brain fog Anxiety / feeling too stressed Headaches Blood-sugar dysregulation Excess weightLinks to my book Autism Wellbeing Plan: How to Get Your Child Healthy:US Amazon: https://www.amazon.com/Autism-Wellbeing-Plan-Child-Healthy/dp/1916393004UK Amazon: https://www.amazon.co.uk/Autism-Wellbeing-Plan-Child-Healthy-ebook/dp/B084GBBDL9My podcast, Autism and Children's Health: https://podcasts.apple.com/us/podcast/autism-and-childrens-health-lab-testing-diet/id1512380225Get 3 FREE video courses instantly when you sign up to my members' community here: https://members.christianyordanov.com/The courses are: The Healthy Gluten-Free, Casein-Free Diet for Autism. ADHD, and Gut Dysfunction Nutrient Supplements for Autism, ADHD, and Children's Health Health Challenges Autistic Children ExperienceYou will learn a ton and there will be more educational content for parents on the free member plan. Members can also suggest topics for me to research and publish in the community platform. Join us today: https://members.christianyordanov.com/The above 3 courses cover topics such as gut dysfunction and infections, clostridia bacteria, Candida, oxalates, methylation, excitotoxicity, zinc / copper imbalance, going gluten-free and how to do it well, heavy metals and chemical toxicity, probiotic supplementation, mitochondrial dysfunction, immune system dysregulation, neuroinflammation, and much much more. I even show you how to select high-quality supplements and avoid the junk and hype - with real examples and analysis of ingredients on screen...Every parent of an autistic child must know this information that is why I want to share it with you for free. And parents with kids that have an any health complaint will also learn a ton. In fact, every parent will learn a lot of value information from each of these courses - so please help me share this information with more parents! Thank you so much.Website: https://christianyordanov.com/

Trichotillimania: https://www.mayoclinic.org/diseases-conditions/trichotillomania/symptoms-causes/syc-20355188 The Self Health podcast is for educational purposes only.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.22.529417v1?rss=1 Authors: Hino, C., Chan, G., Jordaan, G., Chang, S. S., Saunders, J., Bashir, M. T., Hansen, J. E., Gera, J., Weisbart, R. H., Nishimura, R. N. Abstract: Heat shock proteins (HSPs), especially Hsp70 (HSPA1), have been associated with cellular protection from various cellular stresses including heat, hypoxia-ischemia, neurodegeneration, toxins, and trauma. Endogenous HSPs are often synthesized in direct response to these stresses but in many situations are inadequate in protecting cells. The present study addresses the transduction of Hsp70 into cells providing protection from acute oxidative stress by H2O2. The recombinant Fv-Hsp70 protein and two mutant Fv-Hsp70 proteins minus the ATPase domain, and minus the ATPase and terminal lid domains were tested at 0.5 and 1.0 uM concentrations after two different concentrations of H2O2 treatment. All three recombinant proteins protected SH-SY5Y cells from acute H2O2 toxicity. This data indicated that the protein binding domain was responsible for cellular protection. In addition, experiments pretreating cells with inhibitors of antioxidant proteins catalase and gamma-glutamylcysteine synthase (GGCS) before H2O2 resulted in cell death despite treatment with Fv-Hsp70, implying that both enzymes were protected from acute oxidative stress after treatment with Fv-Hsp70. This study demonstrates that Fv-Hsp70 is protective in our experiments primarily by the protein-binding domain. The Hsp70 terminal lid domain was also not necessary for protection. Cellular protection was protective via the antioxidant proteins catalase and GGCS. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Peptides . 2020 Jan;123:170177 Molecular Cancer. 2020. volume 19, Article number: 39. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

VIDEO: No Bill Maher, Democracy Is NOT On The Ballot (5:00) Michael Moore's Nonstop Lies & Gaslighting For Democrats – Jimmy Dore Dem Party Turns On Anti-War Democratic Primary Winner (2:16 to 5:28) Society is going to COLLAPSE -Neil Oliver ( 5:24) Fear Psychosis and the Cult of Safety – Why are People so Afraid?  – Academy of Ideas (13:25) The Great Reset and Transhumanism | Beyond the Cover (17:50)   Study shows eating prunes daily can help prevent bone loss Penn State University, November 3, 2022 People often eat prunes to boost their digestive health, but a study published in the American Journal of Clinical Nutrition shows that consuming a handful of prunes a day may also help prevent bone loss when you are older. Researchers from Penn State University reported that women in their 60s who consumed prunes had significantly less bone loss in their hips in a year compared to those who didn't eat the dried fruits. This suggests that prunes can help reduce inflammation in the body, which is a key driver of bone loss. The researchers recruited 235 women for the study. The volunteers had an average age of 62 and had already gone through menopause. The participants were split into three equal groups: One group didn't consume prunes. Another group consumed at least 50 grams (g) of prunes a day, or four to six pieces daily. The last group consumed 100g of prunes, or 10 to 12 pieces daily. The volunteers ate the “Improved French” prune variety. All of their diet included calcium and vitamin D3 supplements, which can also help prevent bone loss. The research team used scans to measure bone density in the hip, neck and hip socket at the start of the study, after six months and after one year. They found that the hips of the non-eaters had an estimated 1.1 percent loss of bone density a year after the study began. Meanwhile, the bone density of those who consumed four to six prunes a day barely shifted. The result was similar for the group that ate more prunes, but the researchers noted that any protective effect could be masked because of its much higher dropout rate. Blood tests also showed that the women who consumed prunes had significantly lower inflammation levels than those who did not. There was no significant documented difference in bone mass in the spine or hip socket between the groups one year after the study began. Tracing tomatoes' health benefits to gut microbes Ohio State University, November 7, 2022 Two weeks of eating a diet heavy in tomatoes increased the diversity of gut microbes and altered gut bacteria toward a more favorable profile in young pigs, researchers found. After observing these results with a short-term intervention, the research team plans to progress to similar studies in people, looking for health-related links between tomatoes in the diet and changes to the human gut microbiome – the community of microorganisms living in the gastrointestinal tract. “It's possible that tomatoes impart benefits through their modulation of the gut microbiome,” said senior author Jessica Cooperstone, assistant professor at The Ohio State University. The tomatoes used in the study were developed by Ohio State plant breeder, tand co-author David Francis, and are the type typically found in canned tomato products. Ten recently weaned control pigs were fed a standard diet and 10 pigs were fed the standard diet fine-tuned so that 10% of the food consisted of a freeze-dried powder made from the tomatoes. Fiber, sugar, protein, fat and calories were identical for both diets. The control and study pig populations lived separately, and researchers running the study minimized their time spent with the pigs – a series of precautions designed to ensure that any microbiome changes seen with the study diet could be attributed to chemical compounds in the tomatoes. Results showed two main changes in the microbiomes of pigs fed the tomato-heavy diet – the diversity of microbe species in their guts increased, and the concentrations of two types of bacteria common in the mammal microbiome shifted to a more favorable profile. This higher ratio of the phyla Bacteroidota (formerly known as Bacteriodetes) compared to Bacillota (formerly known as Firmicutes) present in the microbiome has been found to be linked with positive health outcomes, while other studies have linked this ratio in reverse, of higher Bacillota compared to Bacteroidota, to obesity. Tomatoes account for about 22% of vegetable intake in Western diets, and previous research has associated consumption of tomatoes with reduced risk for the development of various conditions that include cardiovascular disease and some cancers. But tomatoes' impact on the gut microbiome is still a mystery, and Cooperstone said these findings in pigs – whose gastrointestinal tract is more similar than rodents' to the human GI system – suggest it's an avenue worth exploring. New study examines how breathing shapes our brains Aarhus University (Denmark), November 8, 2022 “Breathe in… Breathe out…” or “take a deep breath and count to ten.” The calming effect of breathing in stressful situations is a concept most of us have met before. Now Professor Micah Allen from the Department of Clinical Medicine at Aarhus University has come a step closer to understanding how the very act of breathing shapes our brain. The researchers synthesized results from more than a dozen studies with rodent, monkey, and human brain imaging, and used it to propose a new computational model that explains how our breathing influences the brain's expectations. “What we found is that, across many different types of tasks and animals, brain rhythms are closely tied to the rhythm of our breath. We are more sensitive to the outside world when we are breathing in, whereas the brain tunes out more when we breathe out. This also aligns with how some extreme sports use breathing, for example professional marksmen are trained to pull the trigger at the end of exhalation,” explains Professor Micah Allen. The study suggest that breathing is more than just something we do to stay alive, explains Micah Allen. “It suggests that the brain and breathing are closely intertwined in a way that goes far beyond survival, to actually impact our emotions, our attention, and how we process the outside world. Our model suggests there is a common mechanism in the brain which links the rhythm of breathing to these events.” Stabilizing our mind through breathing is a well-known and used tactic in many traditions such as yoga and meditation. The new study sheds light on how the brain makes it possible. It suggests that there are three pathways in the brain that control this interaction between breathing and brain activity. It also suggests that our pattern of breathing makes the brain more “excitable”, meaning neurons are more likely to fire during certain times of breathing Close friends linked to a sharper memory Northwestern University School of Medicine, November 1, 2022 Maintaining positive, warm and trusting friendships might be the key to a slower decline in memory and cognitive functioning, according to a new Northwestern Medicine study. SuperAgers—who are 80 years of age and older who have cognitive ability at least as good as people in their 50s or 60s—reported having more satisfying, high-quality relationships compared to their cognitively average, same-age peers, the study reports. Previous SuperAger research at the Cognitive Neurology and Alzheimer's Disease Center (CNADC) at Northwestern University Feinberg School of Medicine has focused on the biological differences in SuperAgers, such as discovering that the cortex in their brain is actually larger than their cognitively average, same-age peers. “You don't have to be the life of the party, but this study supports the theory that maintaining strong social networks seems to be linked to slower cognitive decline,” said senior author Emily Rogalski, associate professor at Northwestern's CNADC. Motivation is affected by oxidative stress, but nutrition can help Ecole Polytechnique Federale de Lausanne. Novembre 7. 2022 In life, motivation can be the difference between success and failure, goal-setting and aimlessness, well-being and unhappiness. And yet, becoming and staying motivated is often the hardest step, a problem which has prompted much research. How does stress affect our capacity for motivation?” asks Professor Carmen Sandi at EPFL's School of Life Sciences. “If that is the case, could nutritional interventions that can affect metabolite levels be an effective vehicle to improve motivated performance?” The researchers focused on an area deep into the brain called the “nucleus accumbens”, which is known to play a major role regulating functions like reward, reinforcement, aversion, and not least, motivation. The idea behind the study was that the brain itself—like all tissues in our body—is subjected to constant oxidative stress, as a result of its metabolism. The brain then is often subjected to excessive oxidative stress from its neurometabolic processes—and the question for the researchers was whether antioxidant levels in the nucleus accumbens can affect motivation. To answer the question, the scientists looked at the brain's most important antioxidant, a protein called glutathione (GSH), and its relationship to motivation. What they found was that higher levels of GSH in the nucleus accumbens correlated with better and steady performance in the motivation tasks. “N-acetylcysteine, the nutritional supplement that we gave in our study can also be synthesized in the body from its precursor cysteine,” says Sandi. “Cysteine is contained in ‘high-protein foods', such as meat, chicken, fish or seafood. Other sources with lower content are eggs, whole-grain foods such as breads and cereals, and some vegetables such as broccoli, onions, and legumes.” “Of course, there are other ways beyond N-acetylcysteine to increase GSH levels in the body, but how they relate to levels in the brain—and particularly in the nucleus accumbens—is largely unknown. Our study represents a proof of principle that dietary N-acetylcysteine can increase brain GSH levels and facilitate effortful behavior.” Purple corn found to improve libido in males University of Tlaxcala (Mexico), November 1, 2022 Purple corn (Zea mays) has been used as an aphrodisiac since the time of ancient Mexico. A study published in the journal Journal of Evidence-Based Integrative Medicine sought to understand the mechanisms behind this plant's effect. The researchers suspected that purple corn extract stimulated the ejaculatory response in males. They used an animal model composed of male rats able to copulate and male rats whose spinal cord had been transected. Three doses of purple corn extract (25, 50, and 75 mg/kg) were administered to the animals. The rats' copulating behavior was noted before and after the administration of the extracts. In the control group, the researchers noted no change in the animals' mount latency and the number of mounts performed. All doses, however, increased the number of intromissions performed by male animals. Ejaculation latency was decreased In the spinal group, the researchers successfully used the extract to stimulate an increase in the number of discharges of the ejaculatory motor patterns. According to the researchers, these are proof that purple corn extract has aphrodisiac effects.

Some supplements may be used periodically for special purposes. Some of these may be recommended for consistent use as well. Supplements such as Alpha Lipoic Acid, N-acetyl Cysteine, Co enzyme Q-10, Phospholipids, and other specialty supplements will be detailed. LINKS:DrA Online YouTube Channel: https://www.youtube.com/channel/UC1FLIaKDzkU5Z0knDYYKyPQ/videos DrA TikTok: https://www.tiktok.com/@dra_online DrA Links www.dranow.com “Get and Stay Healthy” podcast: https://youtu.be/5uFWq27ZjBo COVER-THREE SUPPLEMENT MENTIONED: https://coverthree.com/ Some integrative medicine referral links [for your reference only – no referral or implication of professional superiority is claimed or intended]:NAEM (Environmental Medicine) Providers: https://envmedicine.com/find-a-provider/US Naturopathic Physicians: https://naturopathic.org/search/custom.asp?id=5613 Canadian Naturopathic Physicians: https://www.cand.ca/findmynd/ Digestive Specialists: https://www.gastroanp.org/directoryMold and Environmental Illness Referrals: https://drcrista.com/doctor-finder/ New Hampshire Naturopathic Physicians NHAND.org A4M Integrative referral: https://www.a4m.com/find-a-doctor.htmlAssociation of Naturopathic Medical Colleges www.aanmc.org

NAC has gained a lot of publicity since the world changed in 2020. Why are people talking about it? Why is the FDA annoyed by its existence? Why do you need to know about it?  Should you consider using it? This essential nutrient plays a critical role in the health of your hair, liver, respiratory system, and more. Come join the brand new Vitality Radio Listeners Community page on Facebook here!!Visit the podcast website here: VitalityRadio.comJust a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure or prevent any disease. The advice given is not intended to replace the advice of your medical professional.You can follow us at @vitalityradio on Instagram, Facebook, and Twitter. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. If you'd like to shop our visit please visit us at vitalitynutrition.com. Thank you!

In this episode of the Lexman Artificial Podcast, we talk to Richard Dawkins about pollards and how to properly rig a commiter with them. Fromenty gives us an in-depth look at cysteine and spirea, and why they're so important.

I read from cysteine to cytochrome.     The word of the episode is "cystic fibrosis". https://en.wikipedia.org/wiki/Cystic_fibrosis https://www.cff.org/     Theme music from Tom Maslowski https://zestysol.com/     Merchandising! https://www.teepublic.com/user/spejampar     "The Dictionary - Letter A" on YouTube   "The Dictionary - Letter B" on YouTube   "The Dictionary - Letter C" on YouTube     Featured in a Top 10 Dictionary Podcasts list! https://blog.feedspot.com/dictionary_podcasts/     Backwards Talking on YouTube: https://www.youtube.com/playlist?list=PLmIujMwEDbgZUexyR90jaTEEVmAYcCzuq     dictionarypod@gmail.com https://www.facebook.com/thedictionarypod/ https://twitter.com/dictionarypod https://www.instagram.com/dictionarypod/ https://www.patreon.com/spejampar https://www.tiktok.com/@spejampar 917-727-5757

Are you someone who has never had allergies before and is feeling the effect? Allergy season is stronger than ever before. Learn more about NAC, a supplement that can help with your allergies today! Take advantage of an exclusive podcast offer today by visiting http://www.invitehealth.com/podcast. For more information on the products or studies mentioned in this episode, as well as a complete transcript of the audio, click here. 

Listen and learn. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Number one on the list of Vitamins, Minerals, and Supplements series is; N-Acetyl Cysteine Antioxidant. This vitamin is said to support the liver and detoxifies the body from free radicals. Note: this is not medical advice; this series is for educational purposes only.

Glutathione deficiency is a common feature that complicates infections. We review new research linking suboptimal glutathione levels with increased disease severity and discuss how glutathione is related to vitamin D status as well as ways to support glutathione levels from a nutrition and lifestyle standpoint. Related: Save on MYOXCIENCE Nutrition's new Electrolyte Stix: https://bit.ly/electrolyte-stix *Buy one get one 50% OFF ends January 24th, 2022 Link to research: https://bit.ly/3tHZoVa Time Stamps: 0:06 Vitamin D and Glutathione levels appear to be related 0:42 Diseases linked with low glutathione levels 1:43 Glutathione is found in high concentrations in the liver 3:04 Mitochondria health depends on glutathione status 3:31 Exercise and Glutathione: very important for mitochondrial health 4:50 Fatty liver, mitochondrial dysfunction and glutathione 5:34 Fascinating paper about glutathione and Vitamin D you should read 6:00 This image tells the story quite well 8:00 Please share this video if you're digging it 8:46 New Electrolyte pre-sale 11:03 Glutathione and The C*19 virus 12:14 Low Glutathione even in young people who get infected 14:47 Glutathione impacts vitamin D binding and metabolism 17:42 Glutathione Testing: GGT and liver enzymes 18:33 GGT is a marker of environmental chemical exposure 19:46 Cysteine rich foods that can increase glutathione levels

Cancer treatments in modern medicine often have long-lasting and harmful side effects. While modern treatments like chemotherapy can be useful in some cases, not all cancer patients need to — or should — resort to it.  When cancers aggressively develop, patients are often told how many weeks they have left to live. Why is this the case when there is still hope to be free from cancer?  Research and clinical studies have found natural therapies and dieting are possible cancer treatments. The truth is, you can starve cancer cells without harming your body! In this episode, Jane McLelland, author of How to Starve Cancer, discusses how cancer develops in the body and what causes dysfunctional mitochondria. She shares the importance of starving cancer cells and why cancer treatments should vary based on the type you have. Don't lose hope; you can beat cancer. Understand how it works metabolically and you'll soon be on the path to recovery.   If you want to learn more about beating cancer by starving it, then this episode is for you! Here are three reasons why you should listen to the full episode: Understand how cancer develops in our bodies and why mRNA can help us detect early cancer.  Learn why there is no one correct approach to cancer treatment. Instead, focus on understanding the principle of starving cancer by blocking specific pathways.  Discover Jane's recommendations on what to focus on for cancer treatment.  Get Customised Guidance for Your Genetic Make-Up For our epigenetics health programme, all about optimising your fitness, lifestyle, nutrition and mind performance to your particular genes, go to  https://www.lisatamati.com/page/epigenetics-and-health-coaching/. Customised Online Coaching for Runners CUSTOMISED RUN COACHING PLANS — How to Run Faster, Be Stronger, Run Longer  Without Burnout & Injuries Have you struggled to fit in training in your busy life? Maybe you don't know where to start, or perhaps you have done a few races but keep having motivation or injury troubles? Do you want to beat last year's time or finish at the front of the pack? Want to run your first 5-km or run a 100-miler? ​​Do you want a holistic programme that is personalised & customised to your ability, goals, and lifestyle?  Go to www.runninghotcoaching.com for our online run training coaching. Health Optimisation and Life Coaching Are you struggling with a health issue and need people who look outside the square and are connected to some of the greatest science and health minds in the world? Then reach out to us at support@lisatamati.com, we can jump on a call to see if we are a good fit for you. If you have a big challenge ahead, are dealing with adversity or want to take your performance to the next level and want to learn how to increase your mental toughness, emotional resilience, foundational health, and more, contact us at support@lisatamati.com. Order My Books My latest book Relentless chronicles the inspiring journey about how my mother and I defied the odds after an aneurysm left my mum Isobel with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again. Still, I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: https://shop.lisatamati.com/collections/books/products/relentless. For my other two best-selling books Running Hot and Running to Extremes, chronicling my ultrarunning adventures and expeditions all around the world, go to https://shop.lisatamati.com/collections/books. Lisa's Anti-Ageing and Longevity Supplements  NMN: Nicotinamide Mononucleotide, an NAD+ precursor Feel Healthier and Younger* Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time. What is NMN? NMN Bio offers a cutting edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and liver. Take charge of your energy levels, focus, metabolism and overall health so you can live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity and rigorously tested by an independent, third-party lab. Start your cellular rejuvenation journey today. Support Your Healthy Ageing We offer powerful third-party tested NAD+ boosting supplements so you can start your healthy ageing journey today. Shop now: https://nmnbio.nz/collections/all NMN (beta Nicotinamide Mononucleotide) 250mg | 30 capsules NMN (beta Nicotinamide Mononucleotide) 500mg | 30 capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 250mg | 30 Capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 500mg | 30 Capsules Quality You Can Trust — NMN Our premium range of anti-ageing nutraceuticals (supplements that combine Mother Nature with cutting edge science) combats the effects of aging while designed to boost NAD+ levels. Manufactured in an ISO9001 certified facility Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health  Metabolic Health My  ‘Fierce' Sports Jewellery Collection For my gorgeous and inspiring sports jewellery collection, 'Fierce', go to https://shop.lisatamati.com/collections/lisa-tamati-bespoke-jewellery-collection. Resources Gain exclusive access and bonuses to Pushing the Limits Podcast by becoming a patron!  How to Starve Cancer by Jane McLelland Learn Jane's four pillars to help you recover from cancer with the How to Starve Cancer Online Course  Episode 227: Fighting Cancer and Other Diseases Using the Ketogenic Diet with Dr Dominic D'Agostino  Boulder Longevity Institute  PubMed  Australian Integrative Medicine Association  Learn from Dr Elizabeth Yurth on the function of our mitochondria:  Episode 196: Rethinking the Function of Mitochondria for Our Health  Episode 187: Back to Basics: Slow Down Ageing and Promote Longevity    Connect with Jane: Website I Twitter I LinkedIn I Email (info@howtostarvecancer.com)  Episode Highlights [04:40] Why Jane Wrote ‘How to Starve Cancer' Jane shares that she was first diagnosed with cancer when she was 30. Her cancer developed to an advanced stage over a prolonged screening. Her mother had stage-IV breast cancer and passed away a few years later.  As her cancer developed further, Jane felt that the medical industry wasn't helping her enough.  There was already research on how glucose serves as a fuel for cancer. However, Jane found out that cancer can also metabolise glutamine and protein — even lipids.  Jane wrote her book to help people starve cancer without starving themselves. Starving cancer is about being blocking the different chemical pathways that cancer uses.  [13:10] How Cancer Develops In 1924, Warburg found that cancer cells use sugar up to 20 times more than normal cells; this an indication that cancer is a metabolic disease.  Jane argues that cancer is linked to the microenvironment and often develops when a patient has inflammation.    Inflammation can develop due to obesity, exposure to carcinogens, and more. Hormonal influences can also promote cancer growth. These influences include exposure to xenoestrogen, plastics, microwaves, and microplastics.  These influences can change mRNA to trigger changes in the mitochondrial DNA, leading to cancer development.  [19:25] How to Detect Early Cancer You can prevent cancer as long as you understand what's causing it.  Dysfunctional mitochondria are a symptom and not the cause.  It's critical to look at changes in the mRNA to detect early cancer.   [20:47] Learn to be Careful about what You Take There isn't a lot of data regarding mRNA-based COVID-19 vaccines and their long-term effects on the human immune system. We need to be careful about what we're putting in our bodies and their potential consequences.  For example, high doses of Vitamin E and NAC may be inappropriate for specific cancers.  Jane shares that small doses of NAC can be beneficial when you're trying to kill cancer and improve immunity post-chemotherapy. Stopping glutamine transport is also helpful to block fuel transport to cancer cells.     [25:45] There's no One Solution for Cancer Cancers work differently and can have different fuel sources. No single approach will beat all cancer types.  For example, B cell lymphoma is responsive to ferroptosis. However, you need to ensure that this method kills only the cancer cells and does not affect the brain.  HDAC inhibitors are also viable cancer treatments.   [30:31] How Homocysteine can Help or Worsen Your Condition Jane recommends having low to normal homocysteine levels by sometimes taking vitamin B. Cysteine can help provide backup replenishment for cells.  When you're trying to induce ferroptosis and have high homocysteine, the cancer cells may utilise the homocysteine instead.  This is why your homocysteine levels should be low before starting ferroptosis for cancer treatment.  [32:08] There are Better Cancer Treatments Most medical practitioners are often not updated with the latest clinical studies and tend to dismiss them.  For example, high doses of Vitamin C can be used as a pharmaceutical, and not an antioxidant. There are ways to treat terminal illnesses even when medical professionals tell you otherwise.   [43:50] Don't Focus on Only One Phase of Cancer Jane's book is a simplified discussion of cancer metabolism and how cancer develops.  Current cancer treatments often don't focus on earlier phases of cancer development. You need to tackle every phase of cancer and stop the tumour environment that helps cancer grow. Diet can make a huge difference.   Ketones and hydroxybutyrate are also HDAC inhibitors and can help with ferroptosis. Hyperbaric oxygen therapy can also help since cancer cells can't thrive with high oxygen levels.  [49:18] Cancer Treatment is Different Per Phase Lisa shares that her mother is currently following the Riordan Protocol. They use a blend of Vitamin C, hyperbaric oxygen therapy, and ketones. Fenugreek can help stimulate the production of free radicals, but you need to avoid antioxidants like luteolin and green tea.  You need to ensure you're getting the desired effect in the right phase. The kill phase tends to be more specific.  In the full episode, Jane discusses how berberine and metformin can help lower cancer markers.  [54:29] Jane's Recommendations Jane recommends being careful with taking DCA since some brands can cause inflammation.  Deoxy glucose is like fake glucose that the body recognises as glucose, but cancer cells don't.  Melatonin can block glycolysis pathways.  Jane recommends being selective when taking her course. You don't need to learn about every single pathway. She recommends focusing on glycolysis, glutamine, fats, and lipids.  Jane shares what she did to block her cancer pathways in the full episode.     [1:01:55] Remember, It's about the Metabolic Pathway Over the years, starving cancer has become the critical key to curing cancer.  Remember that cancer is about the metabolic pathway. You need to have the right combination of supplements and cancer treatments. 7 Powerful Quotes [01:51] "...if you're at all affected by cancer in your family, if you have high-risk factors, one in six of us is going to get cancer at some stage in our lives, and you need to know this stuff."   [09:11] "...the trick was trying to find ways that would actually starve the cancer without having to go on starving yourself."   [16:44] "I think a lot of people stop the estrogen, and I think it's a good idea, in many cases, to reduce or your estrogen exposure. That can be plastics, it can be cooking in the microwave, just all sorts of, you know. Now, it's just about everywhere. We've got tiny bits of microplastic in the air as well now. It's just pervasive."   [18:29] "There are these viruses that can cause cancer, and I think it's a combination of the influence of kind of like these things acting a bit like a parasite."   [23:38] "People should have the choice of doing that [going unvaccinated] if they want to run that risk. But the problem is it's putting other people at risk, and you get slated."   [27:03] "You have to tailor your approach a little bit. Is it feeding more on glutamine? Is it feeding more —? What are the mutations?"   [35:50] "...you have to fight for your rights. You really do. When it comes to this, they don't have the answer for cancer."   [53:10] "But it's all about getting the correct effect..you've got to be a little bit careful that what you're doing with one thing doesn't counteract something else. "   About Jane Jane McLelland trained as a Chartered Physiotherapist and was able to win the Sarah Leeson Memorial Award as a promising student. She then worked in the NHS and private practice for 12 years, specialising in orthopaedics and neurology. From 1994 to 2004, Jane battled two aggressive terminal cancers. For that reason, she put together a cancer-starving formula using natural therapies, exercise, and diet to save herself. After her recovery, Jane advocated for off label drugs for cancer therapy and wrote the book How to Starve Cancer. In 2019, she won the title of "Amazing Women Global" from the Lifetime Achievement Award.  Interested in Jane's work? Check out her website.  You can also connect with her on Twitter, LinkedIn, and email (info@howtostarvecancer.com). 

Check out these incredible benefits of NAC. Tylenol Poisoning: https://youtu.be/RtXSelhaI4Q FREE COURSE ➜ ➜ https://courses.drberg.com/product/how-to-bulletproof-your-immune-system/ FREE MINI-COURSE ➜ ➜ Take Dr. Berg's Free Keto Mini-Course! ADD YOUR SUCCESS STORY HERE: https://bit.ly/3z9TviS Talk to a Dr. Berg Keto Consultant today and get the help you need on your journey (free consultation). Call 1-540-299-1557 with your questions about Keto, Intermittent Fasting, or the use of Dr. Berg products. Consultants are available Monday through Friday from 8 AM to 10 PM EST. Saturday & Sunday from 9 AM to 6 PM EST. USA Only. Dr. Eric Berg DC Bio: Dr. Berg, 51 years of age is a chiropractor who specializes in weight loss through nutritional & natural methods. His private practice is located in Alexandria, Virginia. His clients include senior officials in the U.S. government & the Justice Department, ambassadors, medical doctors, high-level executives of prominent corporations, scientists, engineers, professors, and other clients from all walks of life. He is the author of The 7 Principles of Fat Burning. Dr. Berg's Website: http://bit.ly/37AV0fk Dr. Berg's Recipe Ideas: http://bit.ly/37FF6QR Dr. Berg's Reviews: http://bit.ly/3hkIvbb Dr. Berg's Shop: http://bit.ly/3mJcLxg Dr. Berg's Bio: http://bit.ly/3as2cfE Dr. Berg's Health Coach Training: http://bit.ly/3as2p2q Facebook: https://www.facebook.com/drericberg Messenger: https://www.messenger.com/t/drericberg Instagram: https://www.instagram.com/drericberg/ YouTube: http://bit.ly/37DXt8C

In this bonus episode, I'm talking about NAC. There's been so much discussion about it lately that I thought it was worth highlighting its many benefits. NAC supports production of our master antioxidant glutathione. In my own practice the most common use I see, given that I aim to keep patients far away from Tylenol, is in upper and lower respiratory infection and chronic respiratory illness like bronchiectasis and COPD. A little known fact is that NAC also supports sperm quality and motility in men.   Try NAC today! https://drwholeness.myshopify.com/collections/nutritional-supplements/products/nac   Ask your lifestyle health questions on social media, tag @drwholeness, and use #accumulatehealth. ----- Connect with Dr. Matt online:

Watch this at YouTube - https://youtu.be/gVR14DMm_D0Hyggee Natural Repair Serum at yesstyle: https://ys.style/tmRXARN7gkbUse Rewards Code NOBSBEAUTY for an additional discount!Hyggee Natural Repair Serum Full Ingredients List:Panax Ginseng Root Extract, Glycerin, Propanediol, 1,2-Hexanediol, Butylene Glycol, Niacinamide, Water, Simethicone, Panthenol, Gelidium Cartilagineum Extract, Laminaria Japonica Extract, Hizikia Fusiforme Extract, Ascophyllum Nodosum Extract, Ascorbic Acid Polypeptide, Lactobacillus Ferment, Glycyrrhiza Glabra (Licorice) Root Extract, Dextrin, Centella Asiatica Extract, Scutellaria Baicalensis Root Extract, Glycine, Polygonum Cuspidatum Root Extract, Serine, Glutamic Acid, Sesamum Indicum (Sesame) Seed Extract, Sophora Flavescens Root Extract, Camellia Sinensis Leaf Extract, Cimicifuga Racemosa Root Extract, Morus Alba Bark Extract, Paeonia Lactiflora Root Extract, Phellinus Linteus Extract, Angelica Gigas Root Extract, Polygonum Multiflorum Root Extract, Aspartic Acid, Leucine, Rosmarinus Officinalis (Rosemary) Leaf Extract, Chamomilla Recutita (Matricaria) Flower Extract, Paeonia Suffruticosa Root Extract, Alanine, Lysine, Arginine, Tyrosine, Phenylalanine, Valine, Pancratium Maritimum Extract, Threonine, Proline, Isoleucine, Histidine, Methionine, Cysteine, Cellulose Gum, Ammonium Acryloyldimethyltaurate/VP Copolymer, Sodium Polyacryloyldimethyl Taurate, Hydrogenated Polydecene, Ethylhexylglycerin, Adenosine, Trideceth-10, Theobroma Cacao (Cocoa) Extract, Disodium EDTA, t-Butyl Alcohol, Carbomer, Polyglutamic Acid, PVM/MA Copolymer, Betaine*******Podcast LinksApple - https://b.link/No_BS_Apple_PodcastGoogle - https://b.link/No_BS_Google_PodcastAmazon - https://b.link/No_BS_Amazon_PodcastSpotify - https://b.link/No_BS_Spotify_PodcastStitcher - https://b.link/No_BS_Stitcher_PodcastRSS - https://feeds.redcircle.com/671dd1b2-a989-41d5-94d5-30c014e06149********Sephora - https://fxo.co/1231867/sephoraUlta - https://fxo.co/1231867/ultaAmazon - https://www.amazon.com/shop/nobsbeautyYes Style - https://ys.style/kk2Vjrv798Style Korean - http://www.stylekorean.com/?af_id2=nobsbeautyThese are affiliate links if you purchase anything from one of these stores using this link No BS Beauty will make a small commission on what you buy.********I am proud to offer my very own beauty products at Amazon. We are starting small but hope to grow these offerings. Take a look and if you can pick one or two up, it helps keep this channel truly independent.My Products:No BS Beauty Travel Set - https://amzn.to/2PgPzFZNo BS Beauty Airless Jars - https://bit.ly/2Ev6X6N or https://amzn.to/2RCEq4sNo BS Beauty Color Switcher - https://amzn.to/2RCEAJ6See my own page on Amazon - https://www.amazon.com/shop/nobsbeautywww.noBSbeauty.net*******My Patreon - https://www.patreon.com/noBSbeauty*******PayPal Tip Jar - https://bit.ly/donate_NBSBIf you want to leave a tip ... Thanks! *****

I'm sure immunity is a topic that is on all of our minds. Our immune system is valuable, it protects us, but when it doesn't have the right tools or knowledge, or it may be faced with something that confuses it, it may not do the right things for our body. So joining us today at Maximal Being Fitness, Nutrition, and Gut Health, is Gian-Carlo Torres, a mission-driven entrepreneur. He has spent the past four years working closely alongside doctors, scientists, and world-renowned health publications to study the powerful effects of glutathione. Topics - The science behind the immune system- How does glutathione work and interact with your body and help your immune system?- Glutathione intake- What glutathione is and the role that it has in the human body- Other ways that we can help boost our immune systemDoc Mok an advanced GI doctor specializing in nutrition, gut health, and cancer. Joining him is the podcast's layman, Jacky P, smashing the broscience on this week's podcast. Their guest Gian-Carlo Torres is a mission-driven entrepreneur whose personal health, career, and life have all been shaped by the love he has for his family.If you enjoy the podcast, would you please consider leaving a short review on Apple Podcasts/iTunes? It takes less than 60 seconds, and it really makes a differenceReach Out to use team@maximalbeing.comOr Speak pipe https://www.maximalbeing.com/contact/Support the Show at https://www.patreon.com/maximalbeingOur sponsorsiHerb supplement – https://www.maximalbeing.com/iherbBDB5528 and receive 10% off your ordersInstacart – https://www.maximalbeing.com/instacartResourceshttps://www.maximalbeing.comSocialFacebook: https://www.facebook.com/maximalbeing/Twitter:  https://twitter.com/maximalbeingInstagram:  https://www.instagram.com/maximal_being/Pinterest: https://www.pinterest.com/maximalbeing/Linked'in: https://www.linkedin.com/in/maximal-being-13a5051a1/YouTube:  https://www.youtube.com/channel/UCi7KVUF8U-gfhOE1KSNAqIgJOIN OVER 3,418 MAXIMAL BEINGS AND GET OUR FREE 9 STEP GUIDE TO REMODELING YOUR GUT, FREE MACRO CALCULATOR, & 10% OFF COUPONhttps://maximalbeing.us4.list-manage.com/subscribe?u=ce1e2f527d19296e66d8a99be&id=2d68acf4e0Sign-up for our Kombucha Coursehttps://www.maximalbeing.com/product-category/courses/Need a FREE consult book it nowhttps://www.maximalbeing.com/contact/#start-booking-servicesNeed a Custom Nutrition, Fitness or Guthealth planhttps://www.maximalbeing.com/product-category/personalized-plans/Our Gearhttps://www.maximalbeing.com/product-category/clothing/Support the show (https://www.patreon.com/maximalbeing)

Dr. Jeni talks about N-Acetyl-Cysteine (NAC) and some of the benefits of taking this supplement. --- Send in a voice message: https://anchor.fm/drjeni/message

Please consider supporting my work by making a purchase using these links at one of my affiliates: https://chrismasterjohnphd.com/foursigmatic, https://chrismasterjohnphd.com/paleovalley, https://chrismasterjohnphd.com/seekinghealth, https://chrismasterjohnphd.com/ancestralsupplements, https://chrismasterjohnphd.com/magicspoon, https://chrismasterjohnphd.com/lmnt Plenty more at https://chrismasterjohnphd.com/support! Question: Should I supplement NAC if cysteine, taurine, and sulfate are low? You can supplement NAC, but you probably just need more animal protein. Although a vegan could supplement NAC instead of animal protein. If your homocysteine is on the high side, then you definitely want to increase methionine in order to increase SAMe to increase the breakdown of homocysteine. If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice.

If you're into health and wellness (of course you are, you're here!), then you probably have heard about NAC over the past month.  So now seems like the right time to shine some light on this topic.  We're going over what NAC actually is, and all the AWESOME benefits it has!  We're also cover some of the more recent controversies around NAC, and why it is getting taken off market stores and shelves.Don't forget!  Get 40% your first order of Life Boost Coffee by using promo code “AOE40” at lifeboostcoffee.com at checkout! Use this link to streamline the process: https://lifeboostcoffee.com/pages/healthy-coffee-ot2e-jhopkins?oid=1&affid=49Experience the lasting joy of cooking with Xtrema® 100% Pure Ceramic Cookware. Xtrema® redefines the cooking process by combining unparalleled versatility with the peace of mind, knowing that every piece of cookware will never leach chemicals, metal, cadmium, lead, or change the taste of your food.  Get 10% off Xtrema cookware using our code ARTOFEATING at checkout!With Culiraw, guilt-free desserts are possible!  They are made of natural organic ingredients that provide your body with fiber, minerals, vitamins and enzymes, sweetened with dates and agave only.  Use code is “aoepodcast” for 10% discount at checkout!Subscribe to Dr. Esposito's YouTube Channel: https://www.youtube.com/channel/UCHRpZFrFsbJIk5fbNIkj4pQ?sub_confirmation=1 Sign up for our newsletter at evokhealth.com and get our 14 Kick-start Recipes & Kitchen Secrets! Feel free to reach out to us at artofeatingpodcast@gmail.com.  You can also follow us on Instagram @artofeatingpodcast.   To reach your hosts, you can find Dr. Esposito at:Email: drvincentesposito@gmail.comIG: @drvincentespositoTikTok: @drvincentesposito Web: insideouthealthwellness.com You can find Dr. Kali at:Web: drkali.com   IG: @dr.kali   

Each serving of Health Ranger Select Organic Whey Protein Powder provides 24 grams of pure protein. It contains NO sweeteners, NO fillers and NO flavors. Just pure whey protein. This light, cream-colored powder delivers high levels of essential nutrients, such as calcium, iron, potassium, magnesium, phosphorus and vitamin A. It is also an excellent source of complete, high-quality protein that contains all of the essential amino acids, such as branched-chain amino acids (BCAAs), and even the non-essential amino acids, like cysteine. Our organic whey protein powder is also non-GMO, grass-fed, non-rBGH, certified Kosher, USDA certified organic, and lab-tested for glyphosate, heavy metals and microbiology. Health benefits of whey protein* Our whey protein concentrate contains bioactive proteins that offer a wide range of health benefits: Supports healthy muscle growth and recovery – Studies show that supplementing with whey protein before, after, or during a workout supports the growth and development of healthy muscles. Whey protein is also naturally rich in branched-chain amino acids (BCAAs), such as leucine, isoleucine, and valine, which can help improve muscle performance and recovery. Boosts the body’s antioxidant defenses – Whey protein is loaded with both essential and non-essential amino acids. Cysteine is one of the non-essential amino acids that play an important role in supporting your body's natural production of antioxidants like glutathione. By improving your levels of natural antioxidants, you can help protect your body from oxidative stress.Enhances athletic performance – Whey protein provides an abundance of amino acids, which are more efficiently used by your body than other proteins. Research indicates that supplementing with whey protein while engaged in strength or endurance training can help you maximize your workout. This can lead to increased muscle mass and strength, as well as improved overall athletic performance. Recipe for recovery Spicy Bean Dish READ MORE Roasted Potatoes with Garlic and Rosemary Potato Kugel After speaking with thousands of clients over the last 21/2 decades,Basically, superfoods provide the nutrition. Then consume the bulky whole foods primarily for entertainment (while providing a modicum of nutrients).Spicy Beans 1 lb. organic dry beans - pinto, black, navy, kidney or whatever you prefer 1/4 cup whey from organic, pasture-raised cows (or lemon juice) One 3" piece of kombu 2 tablespoons dried celery or parsley leaves 1 tablespoon garlic powder 1/2 - 1 tablespoon cumin powder, depending on taste 1 tablespoon onion powder 1-2 teaspoons smoked paprika, depending on taste 1-2 teaspoons smoked chipotle powder, depending on taste Himalayan salt to taste! bhsales.vpweb.com --- Send in a voice message: https://anchor.fm/bhsales/message

Let's talk about N-acetyl cysteine (NAC). By now you may have heard NAC has been banned from Amazon. Or maybe you've heard about the uncertainty circling around about the future availability of NAC. I know you probably have a ton of questions. Don't panic. If NAC is indeed pulled from the marketplace, there are plenty of alternatives for you. What are they? Join me for this week's episode, “What Happens If I Can't Get N-Acetyl Cysteine (NAC)?” You'll walk away with lots of tools after this one! #NAC #nacetylcysteine #dirtygenespodcast #dirtygenes

This podcast covers the sulfur-containing anti-oxidants N Acetyl Cysteine and Glutathione. Glutathione supplementation doesn't make it past the stomach acid. Acetyl Cysteine is better for supplementation. But cruciate sulfur-containing vegetables are best - asparagus, brussels sprouts, broccoli, etc. We also geek out on a little metabolic pathway discussion,  showing relationships between the anti-oxidant vitamins  A, C, E, Glutathione, and the Methylation pathways involving the B complex vitamins and homocysteine.For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources:  ·PrevMed's website·PrevMed's YouTube channel·PrevMed's Facebook page

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.10.363747v1?rss=1 Authors: Johe, P., Jaenicke, E., Neuweiler, H., Schirmeister, T., Kersten, C., Hellmich, U. A. Abstract: Rhodesain is the lysosomal cathepsin L-like cysteine protease of T. brucei rhodesiense, the causative agent of Human African Trypanosomiasis. The enzyme is essential for the proliferation and pathogenicity of the parasite as well as its ability to overcome the blood-brain barrier of the host. Lysosomal cathepsins are expressed as zymogens with an inactivating pro-domain that is cleaved under acidic conditions. A structure of the uncleaved maturation intermediate from a trypanosomal cathepsin L-like protease is currently not available. We thus established the heterologous expression of T. brucei rhodesiense pro-rhodesain in E. coli and determined its crystal structure. The trypanosomal pro-domain differs from non-parasitic pro-cathepsins by a unique, extended -helix that blocks the active site and whose interactions resemble that of the antiprotozoal inhibitor K11777. Interdomain dynamics between pro- and core protease domain as observed by photoinduced electron transfer fluorescence correlation spectroscopy increase at low pH, where pro-rhodesain also undergoes autocleavage. Using the crystal structure, molecular dynamics simulations and mutagenesis, we identify a conserved interdomain salt bridge that prevents premature intramolecular cleavage at higher pH values and may thus present a control switch for the observed pH-sensitivity of pro-enzyme cleavage in (trypanosomal) CathL-like proteases. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.30.362137v1?rss=1 Authors: Suda, N., Cendejas-Hernandez, J., Poulton, J., Jones, J. P., Konsoula, Z., Smith, C., Parker, W. Abstract: Based on several lines of evidence, numerous investigators have suggested that paracetamol exposure during early development can induce neurological disorders. We had previously postulated that paracetamol exposure early in life, if combined with antioxidants that prevent accumulation of NAPQI, the toxic metabolite of paracetamol, might be innocuous. In this study, we administered paracetamol at or below the currently recommended therapeutic dose to male laboratory rat pups aged 4-10 days. The antioxidants cysteine and mannitol were included to prevent accumulation of NAPQI. In addition, animals were exposed to a cassette of common stress factors: an inflammatory diet, psychological stress, antibiotics, and mock infections using killed bacteria. At age 37-49 days, observation during introduction to a novel conspecific revealed increased rearing behavior, an asocial behavior, in animals treated with paracetamol plus antioxidants, regardless of their exposure to oxidative stress factors (2-way ANOVA; P < 0.0001). This observation would suggest that the initial hypothesis is incorrect, and that oxidative stress mediators do not entirely eliminate the effects of paracetamol on neurodevelopment. This study provides additional cause for caution when considering the use of paracetamol in the pediatric population, and provides evidence that the effects of paracetamol on neurodevelopment need to be considered both in the presence and in the absence of oxidative stress. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.347534v1?rss=1 Authors: Mellott, D., Tseng, C.-T., Drelich, A., Fajtova, P., Chenna, B. C., Kostomiris, D., Hsu, J. C., Zhu, J., Taylor, Z., Tat, V., Katzfuss, A., Li, L., Giardini, M. A., Skinner, D., Hirata, K., Beck, S., Carlin, A. F., Clark, A. E., Berreta, L., Maneval, D., Frueh, F., Hurst, B. L., Wang, H., Kocurek, K. I., Raushel, F. M., O'Donoghue, A., Siqueira-Neto, J. L., Meek, T. D., McKerrow, J. H. Abstract: K777 is a di-peptide analog that contains an electrophilic vinyl-sulfone moiety and is a potent, covalent inactivator of cathepsins. Vero E6, HeLa/ACE2, Caco-2, A549/ACE2, and Calu-3, cells were exposed to SARS-CoV-2, and then treated with K777. K777 reduced viral infectivity with EC50 values of inhibition of viral infection of: 74 nM for Vero E6,

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.06.326603v1?rss=1 Authors: Patra, S., Lin, C.-W., Ghosh, M. K., Havens, S. M., Cory, S. A., Russell, D. H., Barondeau, D. P. Abstract: Iron-sulfur (Fe-S) clusters have a key role in many biochemical processes and are essential for most life forms. Despite recent mechanistic advances in understanding the Fe-S cluster biosynthetic pathway, critical questions remain unresolved. Although human NFS1 and E. coli IscS share ~60% sequence identity, NFS1 exhibits low activity and requires activation by the Friedreich's ataxia protein frataxin (FXN) for in vivo function. Surprisingly, structures of the human complex reveal three distinct quaternary structures with one form exhibiting the same subunit interactions as IscS. An architectural switch model has been proposed in which evolutionarily lost interactions between NFS1 subunits results in the formation of low-activity architectures; FXN binding compensates for these lost interactions and facilitates a subunit rearrangement to activate the complex. Here, we used a structure and evolution-guided approach to identify three conserved residues proposed to weaken interactions between NFS1 subunits and transplanted these amino acids into IscS. Compared to native IscS, the engineered variant had a 4000-fold weaker dimer interface and diminished activity that correlated with the absence of the second catalytic subunit. Remarkably, the addition of the FXN homolog to the engineered variant stimulated the decay of the Cys-quinonoid pyridoxal 5'-phosphate intermediate, shifted IscS from the monomeric to dimeric form, and increased the cysteine desulfurase activity, reproducing results from the human system and supporting the architectural switch model. Overall, these studies indicate a weakening of the homodimeric interface was a key development during the evolution of the eukaryotic system and provide new insights into the role of FXN. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.25.308866v1?rss=1 Authors: Mahootchi, E., Raasakka, A., Luan, W., Muruganandam, G., Loris, R., Haavik, J., Kursula, P. Abstract: Pyridoxal 5'-phosphate (PLP) is an important cofactor for amino acid decarboxylases with many biological functions, including the synthesis of signalling molecules, such as serotonin, dopamine, histamine, -aminobutyric acid, and taurine. Taurine is an abundant amino acid with multiple physiological functions, including osmoregulation, pH regulation, antioxidative protection, and neuromodulation. In mammalian tissues, taurine is mainly produced by decarboxylation of cysteine sulphinic acid to hypotaurine, catalysed by the PLP-dependent cysteine sulphinic acid decarboxylase (CSAD), followed by non-enzymatic oxidation of the product to taurine. We determined the crystal structure of mouse CSAD and compared it to other PLP-dependent decarboxylases in order to identify determinants of substrate specificity and catalytic activity. Recognition of the substrate involves distinct side chains forming the substrate-binding cavity. In addition, the backbone conformation of a buried active-site loop appears to be a critical determinant for substrate side chain binding in PLP-dependent decarboxylases. Phe94 was predicted to affect substrate specificity, and its mutation to serine altered both the catalytic properties of CSAD and its stability. Using small-angle X-ray scattering, we further showed that similarly to its closest homologue, GADL1, CSAD presents open/close motions in solution. The structure of apo-CSAD indicates that the active site gets more ordered upon internal aldimine formation. Taken together, the results highlight details of substrate recognition in PLP-dependent decarboxylases and provide starting points for structure-based inhibitor design with the aim of affecting the biosynthesis of taurine and other abundant amino acid metabolites. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.260521v1?rss=1 Authors: Qiu, Y., Liu, J., Li, Y., Xue, Y., WANG, H., Liu, W. Abstract: 2-Aminovinyl-cysteine (AviCys) is an unusual thioether amino acid shared by a variety of ribosomally synthesized and posttranslationally modified peptides (RiPPs), as part of a macrocyclic ring system that contains the C-terminal 4 or 6 residues of a precursor peptide. This amino acid is nonproteinogenic and arises from processing the C-terminal Cys residue and an internal Ser/Thr residue to form an unsaturated thioether linkage. Enzyme activities for forming lanthionine (Lan), a distinct saturated thioether residue characteristic of lanthipeptide-related RiPPs, has long been speculated to be necessary for AviCys formation. Based on investigations into the biosynthesis of thioviridamide non-lanthipeptdes in Streptomyces sp. NRRL S-87, we here report an alternative path for AviCys formation that is independent of known Lan synthetase activity. This path relies on four dedicated enzymes for posttranslational modifications of the precursor peptide, in which TvaES-87, a phosphotransferase homolog, plays a critical role. It works with LanD-like flavoprotein TvaFS-87 to form a minimum AviCys synthetase complex that follows the combined activity of TvaCDS-87 for Thr dehydration and catalyzes Cys oxidative decarboxylation and subsequent Michael addition of the resulting enethiol nucleophile onto the newly formed dehydrobutyrine residue for cyclization. With TvaES-87, TvaFS-87 activity for Cys processing can be coordinated with TvaCDS-87 activity for minimizing competitive or unexpected spontaneous reactions and forming AviCys effectively. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.260323v1?rss=1 Authors: WANG, H., Lu, J., Wu, Y., Li, J., Li, Y., Li, Y., Bai, Z., Zheng, J., Zhu, J. Abstract: Thioamitides are a group of ribosomally synthesized and post-translational modified peptides with potent antiproliferative and proapoptotic activities. Their biosynthesis remains largely unknown, especially for the characteristic C-terminal 2-aminovinyl-Cysteine (AviCys) motifs. Herein, we report the discovery that homologs of class III lanthipeptide synthetases (LanKCts)encoded outside putative thioamitide biosynthetic gene clusters (BGCs) fully dehydrate the precursor peptides. Remarkably, LanKCt enzymes bind tightly to cysteine decarboxylases encoded inside thioamitide BGCs, and the resulting complex complete the macrocyclization of AviCys rings. Furthermore, LanKCt enzymes are present in the genomes of many thioamitide-producing strains and are functional when in complex with cysteine decarboxylases to produce AviCys macrocycles. Thus, our study reveals the participation of lanthipeptide synthetases as a general strategy for dehydration and AviCys formation during thioamitides biosynthesis and thus paves the way for the bioengineering of this class of bioactive natural products. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.248914v1?rss=1 Authors: LYu, X., Zou, Y., Li, L. Abstract: Cysteine S-sulphenylation (CSO), as a novel post-translational modification (PTM), has emerged as a potential mechanism to regulate protein functions and affect signal networks. Because of its functional significance, several prediction approaches have been developed. Nevertheless, they are based on a limited dataset from Homo sapiens and there is a lack of prediction tools for the CSO sites of other species. Recently, this modification has been investigated at the proteomics scale for a few species and the number of identified CSO sites has significantly increased. Thus, it is essential to explore the characteristics of this modification across different species and construct prediction models with better performances based on the enlarged dataset. In this study, we constructed a few classifiers and fond that the long short-term memory model with the word-embedding encoding approach, dubbed LSTMWE, performs favorably to the traditional machine-learning models and other deep-learning models across different species, in terms of cross-validation and independent test. The area under the ROC curve values for LSTMWE ranged from 0.82 to 0.85 for different organisms, which is superior to the reposted CSO predictors. Moreover, we developed the general model based on the integrated data from different species and it showed great universality and effectiveness. We provided the on-line prediction service called DeepCSO that included both species-specific and general models, which is accessible through http://www.bioinfogo.org/DeepCSO. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.31.231134v1?rss=1 Authors: Tran, T. H., Chan, A. H., Young, L. C., Bindu, L., Neale, C., Messing, S., Dharmaiah, S., Taylor, T., Denson, J.-P., Esposito, D., Nissley, D. V., Stephen, A. G., McCormick, F., Simanshu, D. K. Abstract: A vital first step of RAF activation involves binding to active RAS, resulting in the recruitment of RAF to the plasma membrane. To understand the molecular details of RAS-RAF interaction, we solved crystal structures of wild-type and oncogenic mutants of KRAS complexed with the RAS-binding domain (RBD) and the membrane-interacting cysteine-rich domain (CRD) from the N-terminal regulatory region of RAF1. Our structures revealed that RBD and CRD interact with each other to form one structural entity in which both RBD and CRD interact extensively with KRAS. Mutation at the KRAS-CRD interface resulted in a significant reduction in RAF1 activation despite only a modest decrease in binding affinity. Combining our structures and published data, we provide a model of RAS-RAF complexation at the membrane, and molecular insights into RAS-RAF interaction during the process of RAS-mediated RAF activation. Copy rights belong to original authors. Visit the link for more info

Welcome to the Sober is Dope Podcast with your host, POP Buchanan. This episode is inspired by a lecture from Dr. Eric Berg about The Best Foods for a Recovering Alcoholic. This episode is extremely informative. For more information from Dr. Eric Berg, see links below. Enjoy The Best Foods for a Recovering Alcoholic https://youtu.be/T4qLZzjIq-k Are you a recovering alcoholic? This may really help.  Find Out More at drberg.com:  http://bit.ly/2RFX7p3 Intermittent Fasting: https://www.youtube.com/watch?v=3dHcT... Prolonged Fasting: https://www.youtube.com/watch?v=EX_kg... Timestamps  0:06 What health issues are a recovering alcoholic dealing with? 0:18 The best foods for a recovering alcoholic 3:13 Intermittent fasting and periodic fasting  4:04 Kombucha tea 4:35 Taking it to the next level In this lecture, we’re going to talk about the best foods for a recovering alcoholic.  What health issues are a recovering alcoholic most likely dealing with? • Liver damage  • Inflammation • Cirrhosis  • Nutritional deficiencies  The best foods for a recovering alcoholic: 1. Cruciferous vegetables  2. Shellfish  3. Sunflower seeds/nutritional yeast  4. Fish—omega 3 fatty acids 5. Large salads  A recovering alcoholic should also try doing intermittent fasting (1-2 meals a day) as well as periodic fasting. You want to do intermittent fasting to create autophagy, which will clean up old damaged proteins and turn them into healthy new amino acids. This happens roughly around 18 hours a day of fasting. Periodic fasting will also help speed up your results.  Kombucha tea is a really good substitute for beer or wine. Just be sure it’s the one with the lowest amount of sugar. It’s similar to alcohol in that it can help you feel more relaxed and calm. It does have a very small amount of alcohol, but it’s an insignificant amount that should not cause problems.  If you're a recovering alcoholic and you want to take this to the next level, you may want to try these nutrients: • Cysteine  • Glycine  • Glutamine  • NAC • Vitamin C • Zinc  • B-vitamins • Milk thistle  Dr. Eric Berg DC Bio: Dr. Berg, 53 years of age is a chiropractor who specializes in Healthy Ketosis & Intermittent Fasting. He is the author of The New Body Type Guide and other books published by KB Publishing. He has taught students nutrition as an adjunct professor at Howard University. He no longer practices, but focuses on health education through social media. DR. BERG'S SHOP: http://bit.ly/2S2HSs4 Follow us on FACEBOOK: https://fb.me/DrEricBerg Send a Message to his team: m.me/DrEricBerg ABOUT DR. BERG: http://bit.ly/2M6bIYS --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/soberisdope/message

Health benefits of whey protein*in GENERAL below here's our CelluVie Glutathione can add many potential benefits to those of us who workout or train regularly. It has been known to not only assist faster recovery times but also to increase overall performance and maximization of the workouts. Exercise increases the bodies need for glutathione. Our whey protein concentrate contains bioactive proteins that offer a wide range of health benefits: Supports healthy muscle growth and recovery – Studies show that supplementing with whey protein before, after, or during a workout supports the growth and development of healthy muscles. Whey protein is also naturally rich in branched-chain amino acids (BCAAs), such as leucine, isoleucine, and valine, which can help improve muscle performance and recovery. Boosts the body’s antioxidant defenses – Whey protein is loaded with both essential and non-essential amino acids. Cysteine is one of the non-essential amino acids that play an important role in supporting your body's natural production of antioxidants like glutathione. By improving your levels of natural antioxidants, you can help protect your body from oxidative stress. Supports sensible weight management plans – Whey protein may help you feel satiated for a longer period of time and help curb your appetite. This can help you reduce your overall calorie intake. Combined with proper exercise and a well-balanced diet, whey protein can serve as an excellent aid in your sensible weight management goals. Supports healthy cardiovascular function – Regular supplementation with whey protein can support a healthy cardiovascular system. Studies indicate that the consumption of whey protein can support healthy blood pressure levels already within the normal range. Whey protein is also a heart-healthy alternative to casein protein. Enhances athletic performance – Whey protein provides an abundance of amino acids, which are more efficiently used by your body than other proteins. Research indicates that supplementing with whey protein while engaged in strength or endurance training can help you maximize your workout. This can lead to increased muscle mass and strength, as well as improved overall athletic performance. Supports healthy digestion – Compared with other types of protein, whey protein has a fast absorption rate that allows your body to utilize it quickly and efficiently. It is one of the best protein supplements for supporting a healthy gut flora. Promotes a healthy immune system – Whey protein contains high levels of the non-essential amino acid, cysteine. This amino acid can support your body’s natural production of the major antioxidant glutathione, which can protect your body from harmful elements and bolster your immune function. Whey protein also contains bioactive peptides, such as lactoferrin, that can support immune health. Supports healthy liver function – The cysteine in whey protein promotes your body’s production of glutathione, a potent antioxidant that can combat oxidative stress and promote your overall liver health. Whey protein also contains a powerful combination of nutrients that can nourish your liver. Promotes cognitive health – Alpha-lactalbumin is a potent bioactive peptide that accounts for 36% of the protein in whey. This peptide is linked to supporting healthy memory and cognitive function. Protein has a positive effect on the brain, so supplementing with whey protein can help support normal brain health. --- Send in a voice message: https://anchor.fm/bhsales/message Support this podcast: https://anchor.fm/bhsales/support

Protein is vital after a workout, CelluVie- offers bioactive proteins that offer a wide range of health benefits: Whey protein is loaded with both essential and non-essential amino acids. Cysteine is one of the non-essential amino acids that play an important role in supporting your body's natural production of antioxidants like glutathione. By improving your levels of natural antioxidants, you can help protect your body from oxidative stress. Supports sensible weight management plans – Whey protein may help you feel satiated for a longer period of time and help curb your appetite. This can help you reduce your overall calorie intake. Combined with proper exercise and a well-balanced diet, whey protein can serve as an excellent aid in your sensible weight management goals. Supports healthy muscle growth and recovery – Studies show that supplementing with whey protein before, after, or during a workout supports the growth and development of healthy muscles. Whey protein is also naturally rich in branched-chain amino acids (BCAAs), such as leucine, isoleucine, and valine, which can help improve muscle performance and recovery. Supports healthy cardiovascular function – Regular supplementation with whey protein can support a healthy cardiovascular system. Studies indicate that the consumption of whey protein can support healthy blood pressure levels already within the normal range. Whey protein is also a heart-healthy alternative to casein protein. Enhances athletic performance – Whey protein provides an abundance of amino acids, which are more efficiently used by your body than other proteins. Research indicates that supplementing with whey protein while engaged in strength or endurance training can help you maximize your workout. This can lead to increased muscle mass and strength, as well as improved overall athletic performance. Supports healthy digestion – Compared with other types of protein, whey protein has a fast absorption rate that allows your body to utilize it quickly and efficiently. It is one of the best protein supplements for supporting a healthy gut flora. Your body's production of glutathione depends on certain amino acids. An amino acid called cysteine is a particularly important amino acid that is involved in glutathione synthesis. ... Summary Whey protein is a good source of cysteine, which helps maintain adequate glutathione production. Whey proteins are rich in cysteine as well as in GSH precursor peptides. poor sleep, bad diet, stress, and DRINKING ALCOHOL drastically deplete your glutathione levels and restrict natural replenishment Cell death in the liver may be exacerbated by a deficiency in antioxidants, including glutathione. This can lead to fatty liver disease in both those who misuse alcohol and those who don't. ... A study reported that glutathione was most effective when given to people with fatty liver disease intravenously, in high doses https://bhsales.vpweb.com/ https://tourmalinespring.com/?rfsn=3081786.b5dc92 https://www.primallifeorganics.com/?idev_id=12 --- Send in a voice message: https://anchor.fm/bhsales/message Support this podcast: https://anchor.fm/bhsales/support

Dr. Pastore discusses the vital role sleep plays in immunity, how lack of sleep and poor quality sleep can lower your immune system, sleep duration guidelines for optimal health and steps you can take to improve your sleep.    What is “poor” sleep [1:00] Quality sleep for adults 7-9 continuous, uninterrupted hours of sleep per night  Likely not possible for parents, like Dr. Pastore  Teenagers require 8-10 continuous, uninterrupted hours of sleep per night  6.5 - 7 hours for teenagers can have same effect as being inebriated  Sleep science still needs much more research  Those staying home & safe during COVID-19 can cause COVID-19 dreams Intense/horror dreams due to inability to normalize stress/anxiety during the day   Lack of quality sleep mentioned above is directly associated with higher likelihood of being sick after being exposed to a virus [3:55] Studies on common cold  Lack of sleep or disrupted sleep increases risk of getting a virus    Lack of sleep impacted how fast you recover if you do get sick [4:40] Dr. Pastore treating patients & working with other doctors treating patients with COVID-19, those recovering slower & have the virus longer have worse sleep  21 & 23 days of having the active COVID-19 infection  Seen faster COVID-19 recovery of 9 days with better, quality sleep    Quality sleep needs to be uninterrupted [7:05] Difficult for parents waking up for children 7-9 for adults, 8-10 hours for teenager straight    Long-term poor quality sleep increase risk of obesity & diseases that further the risk for infections [9:05]   Medical fact: poor sleep causes cardiovascular disease, diabetes & obesity  Cardiovascular disease, diabetes & obesity increase risk for infections such as COVID-19 or regular flu  Inflammasome is byproduct of being overweight & obesity  Proinflammatory response that can lower immune system  Quality sleep drastically improves fat loss progress  Lack of sleep (as little as 2-3 nights in a row) - cells become temporarily insulin resistant which causes elevation in glucose, can lead to weight gain & fat storage  Chronic lack of sleep can make cells permanently insulin resistant  Quality sleep improves cell-signalling communication between insulin receptor cells & GLUT receptors to let glucose into the cells    Poor sleep lowers your immune system, makes it longer to recover from a virus, increases risk of diseases that can further lower the immune system, and can worsen health if pre-existing disease exists [13:00]  We're all biochemically & genetically unique  Knowing genetics, medical history, biological markers, calcium score    Why does decreased sleep lower the immune system? [14:55] Sleep supports & enhances the initiation of an adaptive immune system response  Adaptive immune system response process: Trouble maker / invading antigen / virus invading body Human immune system takes up antigen & appropriates it Breaks apart the antigen & presents fragments of antigen to T Helper Cells T Helper Cells signal cytokines Interleukin 12 Interleukin 12 calls in T-Helper Cell One Response, supports antigen specific T-Cells T-Helper Cell 1 Response starts B-Cell production of antibodies to always be able to recognize the invading antigen / virus  If the invading antigen is presented in the body again, the body will attack it  Produced in the lymph nodes  Vaccines are a great example of adaptive immunity, producing herd immunity  Sleep turns this response on, lack of sleep turns it off Immune cannot identify the invading antigen  Sleep deprived hepatitis A vaccine patients vs quality sleep hepatitis A vaccine patients Poor sleep patients did not have amplified adaptive immune system response to vaccine Parents typically lose hundreds of hours of sleep    Prescription medications to improve sleep quality [21:05] Dr. James Maas, “Father of Sleep” & other sleep doctors confirm prescription sleep medications will not lead to a perfect night's sleep or “sleep saviours” Have seductive-type affects Can affect memory & perception of sleep quality  Our Neurochemistry of Sleep Podcast  LINK Be aware of side effects Rebound insomnia Dizziness Headaches Difficult swallowing or breathing Worsening depression & suciride ideation Study showed those with highest sleep medication prescriptions had highest risk of all-cause mortality  Study showed increased risk of various cancers, increased risk of dementia  Not getting into a deep sleep, interferes with glucose & cell receptor response    Could be underlying issue or health concern causing lack of sleep [24:20] Chronic pain & arthritis  Breathing disorders  Dietary supplements & stimulants (caffeine) close to bed  Gastoresophorefluz disorder Hypothyroidism, Graves Disease Chronic back pain  Sinus disorder or allergies  Medications can disrupt sleep Birth control Cold medicine  Asthma medication High blood pressure medication  Depression  Thyroid medication Talk to your doctor to find the underlying cause  Pharmacogenetics - PGX  Test genetics to determine drug response based on individual genetics  Medications aren't a one-size fits all Could be nutritional deficiency  Magnesium, Vitamin D Request bloodwork from physician  40% population at risk for low magnesium  Undiagnosed sleep apnea  Temporarily stop breathing, adrenaline wakes you up    Lifestyle changes to implement to improve sleep [29:30] Address stress  Get regular physical activity & exercise  Exercise helps lower stress Caffeine consumption Genetic variations to process caffeine faster/slower Avoid caffeine after 3-4PM  Green tea, diet cola, soft drinks with caffeine  Exposure to artificial light Disrupts normal neurological signalling for sleep, turns off melatonin production Can upregulate alert/excitatory neurotransmitters to keep you awake Blue light blocking glasses Night mode on electronics reducing blue light Limit alcohol  Sedative effect - can help you fall asleep initially  Later in night, causes dopamine rush & interferes with adaptive immune response More consistent alcohol consumption will continue to lower immune system nightly Limit or eliminate nicotine  Vaping, chewing tobacco  Nicotine neurotoxin, extremely addictive Makes it difficult to fall asleep  Sleep in a cool bedroom  Lower temperature helps with sleep   Melatonin for sleep [35:30] Melatonin is both a hormone and neurotransmitter Excreted from penial gland  Exposure to natural light during day, as sun sets, darkness cues melatonin production Helps stimulate our sleep - high affinity melatonin receptors in SCN  MTA & MT1A, MT2 & MT2B receptors - absorbs melatonin & slows excitatory function to prepare for sleep  Promotes sleep by stimulating acute inhibition of neurological firing of awake neurotransmitters in SCN Helps initiate sleep process, but won't benefit rest of sleep cycle  Helps regulate circadian rhythm (sleep/wake cycles) Taking a “low” dose of 1mg of melatonin is still incredibly high compared to what the brain produces naturally   Can produce “hangover” in the morning Fatigued, tired, brain fog, delayed responses Suppressing dopamine responses  Receptors of SCN turned off way past sleep period  Up to 18 hours of hangover Walking wounded: feel better at 8-10PM and take another dose High-dose (1mg+) melatonin should not be a nightly supplement for sleep    Effective natural products for sleep do exist [40:50] Dr. Pastore's poor sleep practicing as a doctor, then being a father Developed sleep supplement Power OFF for his own sleep issues as nothing else worked https://poweronpoweroff.com/products/power-off We can provide you with the scientific paper Dr. Pastore wrote  Help turn off excitatory neurotransmitters before bed to fall asleep Help stay asleep without waking up   Studies on theanine + 5 hydroxytryptophan shown to keep you asleep GABA to help you fall asleep  Most GABA can't cross blood-brain barrier Blood-brain barrier: only allows certain nutrients/neurotransmitters into the brain from the bloodstream to protect the brain  Dr. Pastore used his PhD in nanomedicine to make GABA pass the blood brain barrier  Magnolia plant - honokiol   Studies show honokiol primes receptor for GABA uptake Combination of ingredients address mechanism of turning off cellular stress response constantly being fired by ephedrine (excitatory / awake neurotransmitter) at night  Requires sulphur enzyme system - enzyme phenalethol…..help :)  Cysteine & dimer to create cystine Helps fall back asleep after interrupted sleep Won't prevent you from waking up if needed Formula evolves as new studies & research comes out    Antihistamines / Benadryl before bed [52:55] Dangerous for long-term health Harvard in 2005 urged doctors to advise patients to stop using antihistamines for sleep Antihistamines reduce acetylcholine, which over time increases risk of age-related mental decline Disrupts memory, cognitive sharpness, more forgetful    Wrap-Up [55:15] Aim for 7-9 hours per night Work with physician to find underlying cause for lack of sleep  Stay away from prescription sleep aids & over the counter sleep aids as much as possible Be mindful of melatonin  help@poweronpoweroff.com & https://poweronpoweroff.com/products/power-off www.drrobetpastore.com & @drrobetpastore

How does this healing molecule fly so under the radar?    Glutathione is the “mother” of all antioxidants and is one of the key molecules that is usually deficient when looking at chronic diseases.    Glutathione is a tripeptide composed of three amino acids (Glycine, Cysteine, Glutamine) and is naturally produced in the liver, as well as in meats and produce.   Glutathione acts as a magnet for things like free radicals and heavy metals!    Listen to learn more about this powerful molecule.

Question: Are bilirubin and uric acid useful markers of antioxidant defense and oxidative stress? What are better markers? I think intracellularly where most of antioxidant support is highly relevant, then they're not that big a deal. In the plasma, they can be a big deal. It's quite possible that uric acid is one of the most important antioxidants in plasma. But I would say it's highly debatable whether we put uric acid into the blood specifically to achieve that versus that happens to be an accidental sort of just incidental to making uric acid during the excretion of purines, which make up the building blocks of DNA and ATP and things like that. I think the best marker of oxidative stress in plasma is the cysteine to cystine ratio. Cysteine is the reduced form of the amino acid cysteine. Cystine is the oxidized form. There are good studies at a general population level showing that that is the major specific indicator of oxidative stress that takes place in the plasma. The glutathione couple, glutathione reduced versus oxidized, is probably the best marker in the blood of what's happening with oxidative stress intracellularly. Unfortunately, the only test that looks at this is HDRI. I feel very, very torn about whether we should be working with HDRI because I know a lot about measuring glutathione. I've had some clients who got their glutathione test. What you need to do to accurately measure glutathione to preserve the sample, according to my client who did the test, is not at all part of the instructions or process that they use, so I am very skeptical of using them. No one else offers the reduced to oxidized version of glutathione. So, what I would recommend to assess oxidative stress would be Genova's Oxidative Stress 2.0 panel. It does give you the cysteine to cystine ratio. I'll put a note to put a link to that in the show notes. I think that's the best marker. They do have glutathione on there, and they do have a bunch of other things that can be useful in assessing oxidative stress. I would use that.  This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a

Garlic is perhaps the easiest vegetable to grow. In the Spring you plant it, wait for it to grow, and then pick it when the stems, like onions, start to die. Collect your garlic, clip the ends, and then place it in a hanging onion bag. Store in a cool, dry area. I hang ours in the basement and then pull one out when I need it for cooking or for when I want to mince garlic like I will show you in this article. Minced garlic is one more thing you can add to your DIY food projects. Why go to the store and spend money on something that takes very little time at home to make? When you purchase food from the store, you never know what's in it, not really. Garlic bought from the store is stored in preservatives, but here we are going to use olive oil. Knowing precisely what you're eating is priceless. Garlic has many benefits which you can read about here https://heatherearles.com/garlic/. Besides how it can help you health-wise, there are different ailments that garlic can alleviate, like curing an earache https://heatherearles.com/earache/. No matter how you look at it, the only thing not going for garlic is the smell on your breath and sometimes body odor, but they can be eliminated by: Mouth washLemon waterBrushing and flossingEating fresh veggies and fruitDrink a cup of green teaChew gum (non-aspartame)Drink milkChew fresh herbs such as mintWashing and using good hygein Why do garlic and onions cause bad breath? Allicin. When the insides of a garlic bulb are exposed to air, a substance called alliin turns into allicin, which then changes into several sulfur-containing compounds that give garlic its smell.Allyl methyl sulfide. This compound is released from both garlic and onions when they are cut. Once eaten, the substance is absorbed into the bloodstream, and emitted through the lungs and skin pores.Cysteine sulfoxide. This sulfuric compound in garlic and onions causes an unpleasant odor on the breath almost immediately after the vegetables are eaten.Medical News Today Well, now that we got that straight let's move right into why you came to read this article in the first place. How do you make minced garlic? Step #1 You'll need several heads of garlic and pure olive oil. Step #2 press the head of garlic down on the chopping board to loosen the cloves. Separate your cloves by pressing the head of the garlic with the palm of your hand. Step #3 Place the wide part of a knife or other flat object on each clove and lightly crush, making it easier to peel and remove the paper type skin. Cut the ends. Do this to all of the cloves. Step #4 Now add all of your peeled cloves into your blender. Turn on and blend until they are coarsely or finely minced. Step #5 Using a spatula, place your cloves in a clean glass jar and pour your pure olive oil over the minced garlic until it is covered. Step #6 Cover the jar and store it in your refrigerator up to two months. Step #7 Use your now, minced garlic in Italian dishes, salad dressings, as a rub over meat, and other recipes. Note: Always keep the garlic covered with the oil. Keep refrigerated and use pure olive oil. If you don't use pure olive oil, it will solidify when you place it in the fridge. Well that's it folks. Go out and find some garlic and help your heart and blood pressure. Also get those antioxidant, anti viral, anti fungal, and cancer preventer properties that garlic has to offer. -Heather Earles

Today's podcast comes from this blog post, Spotlight on: N-Acetyl Cysteine (NAC)

Jane Ferguson:                 Hello, welcome to Getting Personal: Omics of the Heart. It is June 2018, and this is podcast episode 17. I'm Jane Ferguson, an assistant professor of medicine at Vanderbilt University Medical Center, and a proponent of precision medicine, genomics, and finding ways to prevent and treat heart disease. Jane Ferguson:                 This podcast is brought to you by Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. Jane Ferguson:                 For our interview this month, early career member, Jennie Lin talked to Beth McNally about science and careers in genomic medicine. We'll have more on that later but first I want to tell you about the cool papers we published in the journal this month. Jane Ferguson:                 First up, Orlando Gutierrez, Marguerite Irvin, Jeffrey Kopp, Cheryl Winkler, and colleagues from the University of Alabama at Birmingham, and the NIH, published an article entitled APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults. This study was conducted in over 10 thousand participants of the Reasons for Geographic and Racial Differences in Stroke, or, REGARDS Study. They examined associations between APOL1 variants and incident coronary heart disease, ischemic stroke, or composite CVD outcome. Because there are coding variants in the APOL1 Gene that are only found in individuals of African ancestry, these are hypothesized to contribute to the disparities in cardiovascular and renal disease in African Americans. Jane Ferguson:                 The authors found that carrying the risk variants was associated with increased risk of ischemic stroke, but only in individuals who did not have diabetes, or chronic kidney disease. They hypothesize that because diabetes and kidney disease already increase CVD risk, the variant does not have an additional effect on risk in individuals with existing comorbidities. But, it contributes to small vessel occlusion and stroke in individuals without diabetes. Jane Ferguson:                 They also found that the magnitude and strength of the association became stronger in a model adjusted for African ancestry, suggesting an independent effect of the APOL1 risk variants. Jane Ferguson:                 While future work is needed to study this more, this is an important step in understanding the complex relationship between APOL1 and disease. Jane Ferguson:                 Next up, Daniela Zanetti, Erik Ingelsson, and colleagues from Stanford, published a paper on Birthweight, Type 2 Diabetes, and Cardiovascular Disease: Addressing the Barker Hypothesis with Mendelian Randomization. The Barker Hypothesis considers that low birthweight as a result of intrauterine growth restriction, causes a higher future risk of hypertension, type 2 diabetes, and cardiovascular disease. However, observational studies have been unable to establish causality or mechanisms. Jane Ferguson:                 In this paper, the authors used Mendelian Randomization as a tool to address causality. They used data from the UK Biobank, and included over 237,000 participants who knew their weight at birth. They constructed genetic predictors of birthweight from published genome wide association studies, and then looked for genetic associations with multiple outcomes, including CAD, stroke, hypertension, obesity, dyslipidemia, dysregulated glucose and insulin metabolism, and diabetes. Jane Ferguson:                 The Mendelian randomization analysis indicated that higher birthweight is protective against CAD type 2 diabetes, LDL cholesterol, and high 2 hour glucose from oral tolerance test. But, higher birthweight was associated with higher adult BMI. This suggests that the association between low birthweight and higher disease risk is independent of effects on BMI later in life. While the study was limited to a well nourished population of European ancestry, and would need to be confirmed in other samples, and through non-genetic studies, it suggests that improving prenatal nutrition may be protective against future cardiometabolic disease risk. Jane Ferguson:                 Laura Muino-Mosquera, Julie De Backer, and co-authors from Ghent University Hospital, delved into the complexities of interpreting genetic variants, as published in their manuscript, Tailoring the ACMG and AMP Guidelines for the Interpretation of Sequenced Variants in the FBN1 Gene for Marfan Syndrome: Proposal for a Disease- and Gene-Specific Guideline. Jane Ferguson:                 With a large number of variants being uncovered through widespread sequencing efforts, a crucial challenge arises in their interpretation. The American College of Medical Genetics and Genomics, and the Association for Molecular Pathology put forward variant interpretation guidelines in 2015, but these were not tailored to individual genes. Because some genes have unique characteristics, the guidelines may not always allow for uniform interpretation. Jane Ferguson:                 In their manuscript, the authors focused on variants in fibrillin-1 that cause Marfan Syndrome, and reclassified 713 variants using the guidelines, comparing those classifications to previous in-depth methods which had indicated these variants' causal or uncertain significance. They find 86.4% agreement between the two methods. Jane Ferguson:                 Applying the ACMG, AMP guidelines without considering additional evidence may thus miss causal mutations. And it suggests that adopting gene specific guidelines may be helpful to improve clinical decision making and accurate variant interpretation. Jane Ferguson:                 Delving deeper into FBN1 and Marfan Syndrome, Norifumi Takeda, Ryo Inuzuka, Sonoko Maemura, Issei Komuro, and colleagues from the University of Tokyo examined the Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome. They evaluated 248 patients with pathogenic, or likely pathogenic, FBN1 variants, and examined the effect of variant subtype on severe aortopathy, including aortic root replacement, type A dissections, and related death. They found that the cumulative aortic event risk was higher in individuals with haploinsufficient type variants, compared with dominant negative variants. Jane Ferguson:                 Within individuals with dominant negative variants, those that affected Cysteine residues, or caused in-frame deletions, were associated with higher risk compared with other dominant negative mutations, and were comparable to the risk of the haploinsufficient variants. These results highlight the heterogeneity and risk of the FBN1 variants, and suggest that individuals with haploinsufficient variants, and those carrying dominant negative variants affecting Cysteine residues or in-frame Deletions, may need more careful monitoring for development of aortic root aneurysms. Jane Ferguson:                 Lydia Hellwig, William Klein, and colleagues from the NIH, investigated the Ability of Patients to Distinguish Among Cardiac Genomic Variant Subclassifications. In this study, they analyzed whether different subclassifications of variants of uncertain significance were associated with different degrees of concern amongst recipients of genetic test results. 289 subjects were recruited from the NIH ClinSeq Study, and were presented with three categories of variants, including variants of uncertain significance, possibly pathogenic, and likely pathogenic variants. Participants were better able to distinguish between the categories when presented with all three. Whereas, a result of possibly pathogenic given on its own, produced as much worry as a result of likely pathogenic. The authors conclude that multiple categories are helpful for subjects to distinguish pathogenicity subclassification, and that subjects receiving only a single uncertain result, may benefit from interventions to address their worry and to calibrate their risk perceptions.  Jane Ferguson:                 Erik Ingelsson and Mark McCarthy from Stanford, published a really nice review article entitled Human Genetics of Obesity and Type 2 Diabetes: Past, Present, and Future. Over the past decade, we've had a lot of excitement, optimism, and also disappointment in what genome-wide association studies can deliver. Doctors Ingelsson and McCarthy do a great job laying out the history and the successes in the field of genetic interrogation of obesity and diabetes, as well as acknowledging where reality may not live up to the hype, what challenges remain, and what the future may hold. They also have a figure that uses an analogy of a ski resort to emphasize the importance of taking a longitudinal perspective. And I would argue that any paper that manages to connect apres-ski with genomics is worth reading, for that alone. Jane Ferguson:                 Robert Roberts wrote a perspective on the 1986 A.J. Buer program, pivotal to current management and research of heart disease. Highlighting how the decision by the AHA in 1986 to establish centers to train cardiologists and scientists in molecular biology, has led to huge advances in knowledge and treatment of heart disease. Jane Ferguson:                 Finally, rounding out this issue, Kiran Musunuru and colleagues, representing the AHA Council on Genomic and Precision Medicine, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Radiology and Intervention, Council on Peripheral Vascular Disease, Council on Quality of Care and Outcomes Research, and the Stroke Council, published a scientific statement on Interdisciplinary Models for Research and Clinical Endeavors in Genomic Medicine. Jane Ferguson:                 This paper lays out the field of cardiovascular research in the post genomic era, highlights current practices in research and treatment, and outlines vision for interdisciplinary, translational research and clinical practice, that could improve how we understand disease, and how we use those understandings to help patients. Jane Ferguson:                 Our guest interviewer today is Dr. Jennie Lin, an Assistant Professor at Northwestern Universities Feinberg School of Medicine, and the incoming Vice Chair of the Early Career Committee of the AHA Council on Genomic and Precision Medicine. As an aside, Jennie is a great person to follow on Twitter for insights into genomics and kidney disease, and as a bonus, she also posts the occasional dog photo. So she's well worth following just for that. You can find her on Twitter @jenniejlin. As you'll hear, Jennie talked to Dr. Beth McNally about her view on genomic medicine, and Beth also shared some really great practical tips for early career investigators building their independent labs. So make sure you listen all the way to the end. Take it away Jennie. Dr. Lin:                                  Thank you for tuning in to this edition of Getting Personal: Omics of the Heart, a podcast by the Genomic and Precision Medicine Council of the American Heart Association, and by Circulation: Genomic and Precision Medicine. Today I am joined by Dr. Elizabeth McNally, the Elizabeth J Ward Professor of Genetic Medicine, and director of the Center for Genetic Medicine at Northwestern University. Beth, thank you for taking time to chat with all of us. Dr. McNally:                       Happy to be here. Dr. Lin:                                  As a successful physician scientist, you have been interviewed in the past about your life, your scientific interests, and advice for budding investigators. I don't want to rehash everything you have already stated beautifully in an interview with Circ Res, for example. But instead wanted to focus more on your views of genetic medicine and genome science today. Dr. Lin:                                  So you mentioned in that prior Circ Res interview that you started your laboratory science training and career during college, when you participated in a project focused on genetic variation among children with muscular diseases. What have you found to be most interesting about the process of identifying functional genetic variants back then, and also that on-going work now. Dr. McNally:                       Well, I think over the years I've been doing this is the tools have gotten so much better, to be able to actually define the variants much more comprehensibly than we ever could in the past. And then also to be able to study them, and very much to be able to study them in context. And so I look at the revolutions in science that will cause people to look back on this era as the era of genetics. It began obviously with PCR, we couldn't have gotten anywhere without that. Dr. Lin:                                  Right. Dr. McNally:                       And then you leap forward to things like next generation sequencing, and IPS cells, and now CRISPR/Cas gene editing. And to realize that the last three happened within a decade of each other, is going to be so meaningful when you think about the next few decades, and what will happen. So being able to take an IPS cell and actually study a mutation or a variant in context of that patient, the rest of their genome, is really important to be able to do. Dr. Lin:                                  Okay, Great. And so, where do you envision ... with taking say for example, this next gen. technology, CRISPR/Cas9, studying variants in an IPS cell, for example. How do you envision this really revolutionizing the study of human genetics for patients? And how far do you think we've come in fulfilling that vision, and what do you think should be our focus going forward? Dr. McNally:                       I think broadly thinking about human genetics we're really very much still at the beginning, which I know is hard to say and hard to hear. But, we've spent a lot of the last 15 years very focused on that fraction of the genome that has high frequency, or common variation, through a lot of the GWA studies. With those common variants, we had a lot of associations, but relatively small effects of a lot of those, causing a lot of people to focus on the missing heritability and where we might find that hiding. And of course, now that we have deep sequencing, and we have deep sequencing where we've really sampled so much more of the genome, and from so many more people, I think we're just at the beginning of really appreciating that rare variation. And beginning again to really appreciate that 80-85% of the variation that's in each of our genomes is really characterized as rare. Dr. McNally:                       And so we really each are quite unique, and that when we understand a variant we do have to understand it in the context of all that other variation. So computationally that's very challenging to do. Obviously requires larger and larger data sets. But even in doing that, you are not going to find exact replicates of the combinations that you see in any one individual. While I know everybody would love that we're going to have the computational answer to all of this, it's still going to come down to a physician and a patient and making what you think is that best decision for the patient, based hopefully on some genetic data that helps inform those decisions. Dr. Lin:                                  Right, right. So it kind of gets into this whole concept of precision medicine, which has gained a lot of popularity and buzz in recent years, and Obama has really brought it to the forefront in the public arena. You mention rare variants in ... finding rare variants in each patient, for example. And moving a little bit away from some of the common variants that we find in GWAs. What does it mean for a patient to have a rare variant and come see you in your cardiomyopathy clinic, is it going to be precision for that patient, or suing rare variants among many different individual patients to try to find function for a gene? Dr. McNally:                       It's a great question. So I think the first way we approach it is, it depends who's asking the question. So if it's somebody who comes to me who has cardiomyopathy, or has a family history of cardiomyopathy and sudden death, that's a very different question to ask what's going on with their rare variants, for example in cardiomyopathy genes. Now if you translate that over to, I have a big population of people, I don't particularly know what their phenotype is, and I see rare variants for cardiomyopathy, those are two fundamentally different questions. So we very much know a lot about how to interpret rare variants for cardiomyopathy in the context of a patient or a family who has disease, and I do emphasize the latter part of that, the family, working with families and seeing how variants segregate within families. We interpret that very differently, and I think it's appropriate to interpret that very differently in that context. And that's completely different than again, going against what is the regular population, notice I'm not calling it normal population- Dr. Lin:                                  Right. Dr. McNally:                       ... but the general population that's out there. The first step in doing that is the list of the ACMG, American College of Medical Genetics, actionable genes. So this is an interesting question in and of itself. It's 59 genes, of course that list is too small, and it should be bigger than that, and ultimately that will happen. But to take a population based approach to those actionable genes, and looking across the population, finding someone who's got variants in, lets say our favorite genes MYH7, MYBPC3. Knowing what that risk means on a population level is very different than knowing what that means in the context of a patient who comes to you, who has that variant, runs in their family, and has clear disease. Those again, really two different questions, and we have to come up with what's the best practices on that, how to answer either of those questions. Dr. McNally:                       I think the first step working with patients and families who have known disease and have clear variants that segregate with disease, I think its very powerful. I think we've probably got close to a good decade of doing that already. It's incredibly useful for those patients and families. It helps us reduce their risk. It helps us treat them early, it helps us manage their arrhythmias. There's no question that that information is incredibly valuable, but we're still learning how to process that across the population, and how to answer that question for people who are coming who don't already have disease. Dr. Lin:                                  Right, right. That makes sense. And I guess that kind of plays into a follow up question about whether or not we need to test, or think about every variant of unknown significance in lab, and ... the- Dr. McNally:                       It's a great ... You know again, you always have to very carefully consider the context in which the question's being asked. So again, if you're talking about a relatively normal population, well, walking, healthy person, and you're seeing variants of uncertain significance, that's a very different question than somebody who's coming in to you with cardiomyopathy and has a highly suspicious variant of uncertain significance that falls right within the head domain of MYH7. We know a lot about that, and we can do a lot of interpretation in that case. Dr. McNally:                       However, I would say that to put too much value on what we do in the research lab ... Just putting a regulatory hat on for a second and thinking about it, there's nothing from a regulatory standpoint that really validates what we do in the research lab, to say that we can really fairly adjudicate a VUS or not. We can't do that, that's over-valuing what we do in research lab. Dr. McNally:                       So I think, how do we consider variants among certain significance? I think it's really important to recognize that it's exactly that, it's a variant of uncertain significance. And so when you're a clinician taking that to a patient, you have to approach it from the standpoint of saying, this is a variant of uncertain significance. Which means we don't know whether it's pathogenic, but we also don't know that its benign. Because I think right now what we've seen, a lot of clinicians, and even researchers, fall into the path of this believing that variant of uncertain significance is the equivalent of benign. That's not true. It is simply ... That is a rare variant, and we don't know whether it's pathogenic or non-pathogenic. And hopefully overtime we will learn more to better assess that, and better provide the interpretation of what that means in the context of that patient. Dr. McNally:                       It's a good conversation to have. It's important to recognize they're not necessarily pathogenic, but they're also not necessarily benign. Dr. Lin:                                  Mm-hmm (affirmative). So do you see a role, for example, when you see this variant of uncertain significance, is there a role to go back into lab, for example, and try to knock that mutation to IPSC's and test to see if its pathogenic? Or is that going a step too far? Dr. McNally:                       In some cases, that is the right thing to do. Because genetics is so powerful, genetics doesn't only give you the association of a gene with an outcome, and GWAs was fabulous at doing that ... giving us a lot of variants, and often nearby genes, sometimes far away genes, but linking genes to phenotypes, and that's very powerful. But specific variants can actually tell you a lot about mechanism, about how a gene and protein actually function, and how it functions when it's broken. And so, particularly where you can gain a lot from the research front in understanding mechanism, then I think it's really powerful to take those things to the laboratory and to use that to learn about mechanism. Dr. McNally:                       Sometimes you can do it to help adjudicate whether something's pathogenic or not, but again, I think we want to be cautious in doing that. Because what we do in the res ... I always like to say, "What we do in the research lab isn't exactly CLIA certified." Dr. Lin:                                  Right. Dr. McNally:                       There isn't anything magical about what we do, but we definitely ... It is so powerful what's available out there in terms of the genetic variants, and teaching us about how genes and proteins interact. And so I think it is such a rich resource of information right now. The things I bring back to the laboratory, and get my students and trainees excited about working on, is usually where I think we can gain something new about mechanism. Dr. Lin:                                  Right, right, right. Since you are a role model physician scientist, and you think about questions in lab that will ultimately benefit your patients, and you are a genetic cardiologist. What are your thoughts on doing genome editing as a possible therapy for your patients? It's a little bit of a loaded question [crosstalk 00:21:51], it's a little bit controversial. Dr. McNally:                       So I think, no doubt CRISPR/Cas9 gene editing is transforming what we do in the research setting. It's a fantastic tool. Is it a perfect tool? No. Anybody who has been using it a lot in the lab knows that it is much better than anything we've had before, but still quite limited in fidelity and efficiency. And so imagining that we are going to do that in patients is still pretty daunting to me. We do enough gene editing in cells to know that you have to select through an awful lot of cells before you get the one that has the exact variant you are trying to make. So that's not something we can tolerate in the human setting. But we're not there yet, we know that. Dr. McNally:                       Many of the disorders I see clinically are things that are autosomal dominant due to very precise single base-pair changes. And so envisioning how we're going to correct only one copy of an allele and do in a very precise manner, we don't have those tools available yet. Now on the other hand, if you look at a disease like one of the diseases I spend a lot of time on, Duchenne muscular dystrophy, where the majority of mutations are deletions. It's X-linked, it's male, so there's only one copy of the gene, and we know a whole lot about the structure and function of the gene. We know that if we take out this other part we can skip around that mutation and make an internally truncated protein. That's actually a very good use of gene editing, because it only requires making deletions. They don't need to be very precise, and there's only one copy of it that you have to do the gene editing on. Dr. McNally:                       So I see that being something in the near term that will happen, simply because the genetics positions it well to be something where that could be successful. The hard part is still how are we going to get the guides, and how are we going to get the Cas9 in safely into all the cells that need to be treated? And ultimately that lands us back at looking at what our delivery vehicles are. Which at this point in time is still viral delivery, and still has a lot of issues around can we make enough of it? Are people immune to it? So all those questions that come with viral delivery. So still lots of hurdles, but you can see some paths where it makes sense to go forward. Dr. Lin:                                  Very interesting. Okay great. Well thank you for providing your thought on human genetics and genome science. We're going to switch gears for the last portion of this podcast, and talk about your thoughts on career development issues for young investigators. At a recent AHA Scientific Sessions meeting, you participated on a panel that was assembled to provide advice to early career scientists. When you were starting out, what were some of the biggest challenges you faced when you were transitioning to independence and building your own lab, and what's your advice to those facing the same challenges today? Dr. McNally:                       Well, even though I did it quite a few years ago, many of the things are still the same. Transitioning to independence, I think is easier if you pick up and move and start in a new place. I think it's much easier to establish your independence when you're not in the same place as your mentor. That said, we have many more people who now stay in the same place as where their mentors were and we have many more approaches towards doing that. So I think people are much more open to both possibilities as being ways of doing that. But at some level it still comes down to starting your own lab, and you hopefully have been given some start-up resources and you have to think about how to wisely spend them, and how to really get things going. I don't think this is changed either. Dr. McNally:                       I usually tell people, don't just start in one area, if you can, start in two areas because things don't work, and sometimes things do work. In reality when you look at people who are successful, they're often working in more than one area. And so the sooner you start getting comfortable working in more than one area, that's a good thing. Now ideally, they should be areas that have some relationship to each other, and then feed each other in terms of information so that they grow off each other. But what does that practically mean? I always say, "Well if you can hire two people and start them on two different paths, that's a really good way to get going." And practical things like look at all different kinds of private foundations and things like that for getting some good pilot start up money to help develop new projects in the lab. And always be looking at how can these projects help me develop a bigger data package, that's going to put me in a good competitive position for example bigger grants and federal funding, and things along those lines. Dr. McNally:                       Very much a stepwise process. People want to shoot for the moon and get the biggest things first, but sometimes just focusing on the smaller steps which are definitely achievable and building your path towards those bigger steps is the smarter way of doing it. Dr. Lin:                                  That's great advice. You also mentioned recently that young investigators should try to have as many mentors as possible. What advice would you have for, in particular, early career genomics investigators, for finding these mentors passed the postdoc phase? Some of us get introduced at the postdoc phase to maybe some other collaborating labs, but those are really collaborations of our mentors per se. Dr. McNally:                       Well I think especially in the field of genetics and genomics, collaboration is key, and I will say one of the things that has changed over since I started doing this is there is a lot more understanding of the need to collaborate. Not so many years ago, it wasn't really an independent investigator went and started a lab, and it would be your trainees and the papers would have only those people on it. Dr. McNally:                       I think these days, the best science is where you've tackled a problem from multiple different directions, one or two of those being genetics, genomics directions. And then sometimes there's other ways that you've approached that scientific problem. And by necessity, that usually involves collaborating with other people. And your role is sometimes to be the coordinator of all those collaborators, and that's where again you might be in a senior author position then doing that. But your role sometimes is to be the good collaborator. And so when I look at people being successful right now, seven, eight years in to running their own lab, I like to see that they've been the organizer of some of those, that they've collaborated with people who are even senior to them, and that they've established those good collaborations, but that they've taken the leading role in doing that. But also that they've had middle author contributions, that they've been a good collaborator as well. Dr. McNally:                       And so, part of that is not being afraid to collaborate, and to recognize the value of doing that. And what's so great about doing that is you can collaborate with people at your same institution where you are, but you can also collaborate with people all over the world, and I think that's what we do. You go to where you need somebody who is using a technique or an approach that really helps answer the question you want to have answered. And so that's reaching out to people and really establishing again that network and good collaborators which you can do by a whole bunch of ways. You can do it by meeting somebody at a meeting, scientific meeting. You can do it through emails, phone calls, Skype, all sorts of different ways that you can reach out and collaborate with people. Dr. McNally:                       It is easier than ever to share data and share ideas, but that negotiation of how to establish the terms of the collaboration and how to make it be successful is a critically important part of being a scientist. And what we now know when we look at the promotion process, is people who do that effectively, that's a really important mark of being a successful scientist, and marks them as somebody who should be promoted through the process. So great. Dr. Lin:                                  Yeah. No I agree. Certainly with the direction science is moving, it's definitely very difficult to work in a siloed manner. Dr. McNally:                       Yeah. Well you won't get very far. You'll be able to have some really good first ideas, and show some proof of principle approaches. But to really, really address an important scientific problem, we know that you have to see those signals using multiple different methods. And once you have five different ways showing you that that's the right answer, then you're much More confident that you've gotten to the right answer. Dr. Lin:                                  Right. Alright, so I think we're going to wrap up. Do you have any other final thoughts for any other young investigators or genomics researchers listening to this podcast? Dr. McNally:                       It's a great time to be doing genetics and genomics, and particularly human genetics, where we now finally have all this information on humans, and we'll have even more of it in the future. So I think humans are coming close to becoming a real experimental system. Dr. Lin:                                  Excellent. Alright well thank you so much for your time. It was a pleasure having you on this podcast. Dr. McNally:                       Great. Thank you for doing this. Jane Ferguson:                 As a reminder, all of our original research articles come with an accompanying editorial, and these are really nice to help give some more background and perspective to each paper. To read all of these papers, and the accompanying commentaries, log on to circgenetics.ahajournals.org. Or, you can access video summaries of all our original articles from the circgen website, or directly from our YouTube channel, Circulation Journal. And lastly, follow us on Twitter @circ_gen, or on Facebook, to get new content directly in your feed. Jane Ferguson:                 Okay, that is it from us for June. Thank you for listening, and come back for more next month.  

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Ep. 269: What Is a Real Detox and What Is Bunk? In this episode, we discuss the difference between trendy detoxes and helpful ones and explain how your body really detoxes. Click here to listen in iTunes If you enjoy the show, please review it in iTunes! The Paleo View (TPV), Episode 269: What Is a Real Detox and What Is Bunk? News and Views (0:41) Sarah and Stacy are recording during the day, and Sarah isn't in her PJ's (for once!) Sarah's still tired because she's been recording videos for the Autoimmune Protocol Lecture Series videos all week. Stacy is excited about the next few shows because she got to pick the topics! After finishing Paleo Principles (which is 672 pages) Sarah went right into filming videos. Her feet have been swelling at night with no real explanation, and this got worse during filming. Sarah's FIFTH formulation of her thyroid medication has been working really well, and she is happy that she's lost some weight as a side effect. Stacy says that Sarah is a good example of weight loss coming on the heels of improved health. But it might also be triggering her swollen feet... The Truth About Detoxes This week's episode is Stacy's suggestion, but it comes at a great time because of Sarah's swollen feet! Sarah's Functional Medicine specialist suggested that estrogen stored in her fat, which was released during her rapid fat loss, might be causing the swelling in her feet. So, her doctor recommended a medical detox from Douglas Labs, which helped reduce the swelling right away! Stacy thinks there's a lack of education around other types of detoxes, as well as marketers who prey on "detox" searches on the web. Sarah says lots of detoxes have no grounding in science; a lot of them are fiber-rich and make you poop a lot. Another example is the coffee enema, which can actually be dangerous. Read Sarah's post "Coffee Enemas: What the Science Says versus What You've Heard" for more. Interestingly, lots of detoxes, like juice cleanses, can have immediate beneficial effects because you're eating more veggies and pulling out inflammatory foods (such as FODMAP's and alcohol). However, they're not a good solution because they starve your beneficial gut bacteria. Detoxification happens in the liver, but these cleanses don't support the liver. Most "Toxins" are fat-soluble, including heavy metals, metabolic by-products, and excess hormones. Liver detox: Phase 1: Liver transforms them into water-soluble forms. Nutrients for this include B Vitamins, Vitamin A, Magnesium, Zinc, Selenium. Phase 2: Conjugation - the water-soluble molecule is combined with something to neutralize it, and by-products are secreted into small intestine and eliminated or sent to kidneys and eliminated Nutrients for this include Amino Acids, Glutamine, Methionine, Taurine, Cysteine, Vitamin B and C, Selenium. Liver stores the nutrients needed for detoxification, so eating liver (or taking Vital Proteins Liver Pills) is a great "detox" strategy. Fiber from veggies (especially non-starchy), water, organ meats, bone broth, seafood, and fruit are all great detox foods - i.e. the Paleo diet! It's also important to stay hydrated. If your liver can't keep up, supporting Phase 1 or Phase 2 with botanicals like Milk Thistle can be helpful. This is what a medical detox looks like; it should only be done under a doctor's supervision. In contrast, most detoxes just clear out your good bacteria and don't support your liver at all. Stacy really doesn't like that companies use misleading "marketing techniques" to convince people to buy their detox products that don't work. Find a good functional medicine doctor to work with! Stacy and Sarah both love Vital Proteins beef liver pills. Rate and review us. Goodbye! Outro (53:09) Support us by shopping through links on our sidebars, please!

In today’s podcast Andrew is joined by dietician Belinda Reynolds. Belinda has over 15 years experience in Integrative Medicine. She is a senior educator and lecturer for BioCeuticals, and has a true gift for pulling clinically relevant information from research. Today she takes us through extemporaneous dispensing of N-acetyl-cysteine (NAC). Her expert clinical knowledge reveals just how broad the use of this compound is outside the conventional medical uses for paracetamol (acetaminophen) toxicity and respiratory disease.

GPx4 besitzt vielfältige Funktionen im Redox-Metabolismus von Zellen. Ursprünglich wurde sie als ein Enzym beschrieben, das hoch effizient Phospholipidhydroperoxide zu den entsprechenden Alkoholen unter GSH-Verbrauch reduzieren kann. Weiterhin hatte sich in den letzten 10 bis 15 Jahren gezeigt, dass sie eine essenzielle Rolle als Thiolperoxidase in der Spermienreifung ausübt. Eine weitere Funktion stellt möglicherweise die eines Redox-Sensors dar, der auf die Änderung des zellulären Redox-Milieus mit der Aktivierung von antioxidativen Zellsignalwegen reagiert. Diese Funktion konnte bislang nur für das GPx4-Homolog in der Hefe nachgewiesen werden und kann aufgrund der Rolle, die die GPx4 bei der Spermienreifung in Mäusen spielt, auch für Säugetiere postuliert werden. Es handelt sich dabei um die Fähigkeit der GPx4 in ihrer Funktion als Thiolperoxidase Disulfid- oder auch Selenylsulfidbindungen zwischen anderen Proteinen zu bilden. Dabei ist die GPx4 vermutlich auch in der Lage, ihre eigenen Cysteine als Substrat zu akzeptieren, was allerdings im Falle der Spermienreifung zu einer Inaktivierung der peroxidativen Funktion führt. Diese Thiolperoxidasefunktion ist abhängig von der Menge an freiem GSH. Der Schwerpunkt dieser Arbeit war es, mögliche Interaktionspartner in somatischen Zellen zu identifizieren, wobei die Thiolperoxidasefunktion der GPx4 bei Änderung des zellulären Redox-Milieus in Form von oxidativem Stress ausgenutzt werden sollte. Als Methode wählten wir ein modifiziertes Tandem-Affinity-Purification-enhanced-Verfahren (TAPe). Mit Hilfe dessen wurde eine mit einem Strep/Flag-Tag versehene GPx4 oder verschiedene Mutanten stabil in induzierbaren GPx4 Knockout murinen embryonalen Fibroblasten exprimiert, sodass die getaggte GPx4 mittels des TAPe Verfahren aus den Zellen aufgereinigt werden konnte. Um intrazelluläre GSH-Konzentrationen zu reduzieren und die GPx4 zu oxidieren, wurden die Zellen vor der Lyse mit BSO und tBOOH vorbehandelt. Die Eluate aus diesen Aufreinigungen wurden anschließend anhand der Massenspektrometrie, Silberfärbung und Western Blots analysiert. Es ließen sich eine ganze Reihe von Proteinen identifizieren, die ebenfalls eine wichtige Rolle in der Aufrechterhaltung des intrazellulären Redox-Milieus spielen und an der Regulierung von Zellsignalwegen beteiligt sind. Nach den bisherigen Analysen bedarf es aber noch einer Bestätigung mittels co-Immunpräzipitation und Immunoblot-Analysen. Besonders aktuelle Erkenntnisse, die neue Zelltodsignalwege, wie zum Beispiel die Ferroptose, analysieren, stellen eine interessante und äußerst relevante Richtung für zukünftige Projekte in der Erforschung der GPx4 und ihrer Rolle als Redox-Sensor und Regulator von Zelltodsignalwegen dar.

Oct 29, 2014 Podcast: The Best Remedies For Hot Flashes, Does N-Acetyl Cysteine Increase Glutathione, How To Increase Shoulder Mobility, and Getting Rid of Scar Tissue. Have a podcast question for Ben? Click the tab on the right, use the Contact button on the app, call 1-877-209-9439, Skype “pacificfit” or use the “” form... but be prepared to wait - we prioritize audio questions over text questions. ----------------------------------------------------- News Flashes: You can receive these News Flashes (and more) every single day, if you follow Ben on , and . Would YOU do any of these Which one? Do ? The answer may surprise you. Wow. Good article. ----------------------------------------------------- Special Announcements: Need to fix your gut, build new muscle, or enhance the effectiveness of your probiotic? The brand new has arrived. Go to and use code GREEN1 for a 20% discount on your third lung. November 17-21, 2014: Ben interviews 23 of the world's leading experts in performance, recovery, nutrition, fat loss, brain, sleep and hormone optimization, and you get a free all-access pass. . Go ask your burning Obstacle Racing questions at for the brand new Obstacle Dominator podcast. Other places you can meet Ben: Nov 2-9 London (meet-up and drinks at , November 8 at 6pm), Nov 9-16 Israel, Dec 4-7 January 30th - 31st, 2015, Ben will be speaking in Dubai - Talise Fitness and Jumeirah Emirates Towers, proudly invite you to take part in an exclusive two day seminar held by the renowned nutrition and fitness expert, best selling author, coach, speaker, ex-bodybuilder and Ironman triathlete, Ben Greenfield. Grab this package that comes with a tech shirt, a beanie and a water bottle. And of course, this week's top iTunes review - gets some BG Fitness swag straight from Ben - ! ----------------------------------------------------- Listener Q&A: As compiled, deciphered, edited and sometimes read by , the Podcast Sidekick and Audio Ninja. The Best Remedies For Hot Flashes Graeme asks: His wife has been experiencing pre-menopause hot flushes. Most of the supplements focus on eostrogen i.e. Are phytoeostrogens which they are NOT a fan of due to increased risk of breast cancer etc. She has been using Magnesium which is helping a LOT, plus some Vitamin E and they have also heard Kelp powder (iodine) helps. Do you happen to have any other suggestions? In my response I recommend: -This article on -This article on -Black Cohosh/dong quai (e.g. ) - - - Does N-Acetyl Cysteine Increase Glutathione? Brian asks: He is interested in learning more about N-Acetyl Cysteine. He has read some articles that say it can help with a wide variety of health issues - helping to make things better for the body. One of the major questions he had was how does it work to reduce pre and post exercise oxidative stress? Also, could you recommend a pure quality product? Are there any side effects from taking NAC? In my response I recommend: - - How To Increase Shoulder Mobility Mark asks: In June this year he did a Tough Mudder and had fun and felt really good. The next day he played two, back to back, soft ball games. He felt a tweak in his shoulder every time he threw the ball but didn't think much of it. From that day on he has had tightness in his shoulder and his range of motion was very limited (reaching for high things is difficult, playing golf is hard and even playing his dreadnought guitar is painful). It is getting better, very slowly, but it is still very tight in the morning and interrupts his sleep at night. Do you know why this is taking so long to heal, why it is tight in the morning and what he can do to speed up the healing? In my response I recommend: - book - (esp. shoulder flossing and lacrosse ball shoulder) Getting Rid of Scar Tissue Yvonne asks: About a year ago she ripped her thigh muscle doing an aerobic workout. She now has some scar tissue at the top of her leg. Now she gets a burning sensation in her thigh muscle and wonders what it could be. Can you tell her? In my response I recommend: - ----------------------------------------------------- -- And don't forget to go to -- Prior to asking your question, do a search in upper right hand corner of this website for the keywords associated with your question. Many of the questions we receive have already been answered here at Ben Greenfield Fitness! Podcast music from 80s Fitness (Reso Remix) by KOAN Sound. !

Vincent, Michele, and Michael discuss how a gene from bacteria protects a tick from plant cyanide poisoning, and enhanced transmission of Streptococcus pneumoniae by influenza virus co-infection in mice.

Hosts: Vincent Racaniello and Dickson Despommier Vincent and Dickson discuss reversible inhibitors of cruzipain as new drugs for treating Chagas disease. Links for this episode: Reversible cysteine protease inhibitors for Chagas (AAC) New drug candidates for Chagas (ScienceDaily) Pancake ice (YouTube) Letters read on TWiP 66 Contact Send your questions and comments (email or mp3 file) to twip@twiv.tv Subscribe Subscribe to TWiP (free) in iTunes, by the RSS feed or by email  

Thu, 19 Dec 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17337/ https://edoc.ub.uni-muenchen.de/17337/1/Darisipudi_Venkata.pdf Darisipudi, Venkata Surya Narayana Murty ddc:610, ddc:600, Medizinische Fakultät

Background: G. diazotrophicus and A. vinelandii are aerobic nitrogen-fixing bacteria. Although oxygen is essential for the survival of these organisms, it irreversibly inhibits nitrogenase, the complex responsible for nitrogen fixation. Both microorganisms deal with this paradox through compensatory mechanisms. In A. vinelandii a conformational protection mechanism occurs through the interaction between the nitrogenase complex and the FeSII protein. Previous studies suggested the existence of a similar system in G. diazotrophicus, but the putative protein involved was not yet described. This study intends to identify the protein coding gene in the recently sequenced genome of G. diazotrophicus and also provide detailed structural information of nitrogenase conformational protection in both organisms. Results: Genomic analysis of G. diazotrophicus sequences revealed a protein coding ORF (Gdia0615) enclosing a conserved "fer2" domain, typical of the ferredoxin family and found in A. vinelandii FeSII. Comparative models of both FeSII and Gdia0615 disclosed a conserved beta-grasp fold. Cysteine residues that coordinate the 2[Fe-S] cluster are in conserved positions towards the metallocluster. Analysis of solvent accessible residues and electrostatic surfaces unveiled an hydrophobic dimerization interface. Dimers assembled by molecular docking presented a stable behaviour and a proper accommodation of regions possibly involved in binding of FeSII to nitrogenase throughout molecular dynamics simulations in aqueous solution. Molecular modeling of the nitrogenase complex of G. diazotrophicus was performed and models were compared to the crystal structure of A. vinelandii nitrogenase. Docking experiments of FeSII and Gdia0615 with its corresponding nitrogenase complex pointed out in both systems a putative binding site presenting shape and charge complementarities at the Fe-protein/MoFe-protein complex interface. Conclusions: The identification of the putative FeSII coding gene in G. diazotrophicus genome represents a large step towards the understanding of the conformational protection mechanism of nitrogenase against oxygen. In addition, this is the first study regarding the structural complementarities of FeSII-nitrogenase interactions in diazotrophic bacteria. The combination of bioinformatic tools for genome analysis, comparative protein modeling, docking calculations and molecular dynamics provided a powerful strategy for the elucidation of molecular mechanisms and structural features of FeSII-nitrogenase interaction.

Editorial interview - Systems Biology, A spectral library searching method for peptide identification, Cysteine synthase as a key player in the aluminium response in rice, Reconstructing biochemical pathways from time course data, Discovery of novel nucleolar proteins based on automatic analysis of MEDLINE.

Editorial interview - Systems Biology, A spectral library searching method for peptide identification, Cysteine synthase as a key player in the aluminium response in rice, Reconstructing biochemical pathways from time course data, Discovery of novel nucleolar proteins based on automatic analysis of MEDLINE.

The Gin inversion system of bacteriophage Mu requires the formation of a synaptic complex of unique topology, where the two Gin dimers bound at the recombination gix sites are interacting to form an enzymatically active tetramer, which then catalyses the site-specific recombination reaction. After the assembly of the synaptic complex the DNA strand cleavage is activated by the DNA-bending protein FIS bound at the recombinational enhancer sequence. During reaction the complex undergoes conformational changes resulting in a site-specific inversion of a DNA segment in the phage Mu genome. In this thesis the protein interactions in the synaptic complex were analysed. First, the question on the interactions between FIS and Gin during formation of the synaptic complex was addressed. In a genetic test system a mutant fisS14P has been selected that can rescue the recombination-deficient phenotype of the mutant Gin H106T. FIS S14P was shown to activate the Gin H106T mutant in vivo but not in vitro. The possible reasons are the differences in the in vivo and in vitro conditions, and the observed altered DNA bending ability of the FIS S14P mutant. The position of the mutation S14P in the “β-hairpin arm” of the FIS N-terminus suggests it could directly interact with the hydrophobic dimerisation interface of Gin around the position H106. Next, the predictions of the preliminary model of the Gin invertasome organisation have been verified and the catalytic domains of Gin were demonstrated indeed to be involved in tetramer formation. To do this, specific mutations at the proposed synaptic interfaces were introduced and biochemical studies of different mutants of Gin invertase affected in their ability to promote synapsis were performed. It was possible to show that in addition to the already identified surfaces of the Gin dimer-dimer interactions, comprising of the αE helix and the flexible loop between the β2 sheet and the αB helix of Gin, also the αD helix and the loop between αA helix and β2 sheet are involved in the stabilisation of the Gin tetramer. Cysteine substitutions placed on these surfaces could be efficiently cross-linked in the tetramer in the presence of DNA and FIS, indicating their close proximity in the synapse. Furthermore, Gin mutants with either increased or decreased tetramerisation abilities were isolated and characterised, and the effects of these mutations on recombination were studied. These data led to the notion that the tetramer structure should be flexible, since all mutations that stabilise the complex cause inversion deficiency. In turn, the complexes formed by the hyperactive mutants seem to have high conformational flexibility, although at the expense of the loss of specificity. Notably, introduction of substitutions that stabilise the Gin tetramer also lead to suppression of hyperactive features. A chimeric recombinase protein, containing the N-terminal catalytic domain from Gin and the DNA-binding domain of ISXc5 resolvase, was found to form a more stable tetramer complex, than Gin. The chimera ISXc5G10 is inversion deficient, but can still catalyse resolution. Again, these observations support the notion that the stabilisation of the tetramer can strongly impair the ability to catalyse inversion, but may have less effect on the resolution activity. The DNA-binding domain of ISXc5G10 chimera was mutagenised to obtain a protein with an inversion proficient phenotype, but no mutants of this type could be found, perhaps because in the chimera not only the DNA binding domain, but the gross organisation of the protein is different. Thus, according to the obtained data the Gin dimers bound to the recombination sites are interacting with each other via catalytic domains and recombination involves gross reorganisations of contact surfaces. The obtained results allowed to clearly distinguish between the two previously proposed mechanistically different models of recombination (the “subunit exchange” and “static subunits” models), and favour the “subunit exchange” model. Such a model serves as a useful working hypothesis for future experiments dedicated to the detailed understanding of the mechanism of recombination reaction catalysis by members of the serine recombinase family.

Die TIM22-Translokase in der mitochondrialen Innenmembran vermittelt die Insertion von polytopen Innenmembranproteinen mit internen Signalsequenzen wie der mitochondrialen Metabolit-Carrier. Dabei unterstützt eine Gruppe von strukturell verwandten Proteinen mit charakteristischem Metallbindungsmotiv (Cys4-Motiv) die Passage der hydrophoben Vorstufenproteine über den Intermembranraum. Dies sind in der Hefe Tim9, Tim10 und Tim12 sowie Tim8 und Tim13. Die Familie dieser kleinen Tim-Proteine ist evolutionär konserviert. Im Menschen wurden sechs Mitglieder dieser Proteinfamilie identifiziert: Tim9, Tim10a und Tim10b sowie DDP1, DDP2 und Tim13. Im Rahmen dieser Arbeit wurden die Komponenten der TIM22-Translokase der Säugetiere strukturell und funktionell charakterisiert. Bei ihnen handelt es sich ebenfalls um mitochondriale Intermembranraumproteine. Sie sind in der Lage, mittels der vier konservierten Cysteinreste ein Zn2+-Ion zu binden und damit vermutlich eine Zinkfinger-Struktur auszubilden. Mutationen, die zu einem Verlust des DDP1 Proteins führen, sind die Ursache für das Mohr-Tranebjaerg Syndrom, einer neurodegenerativen Erkrankung, die sich im Wesentlichen durch Taubheit und Dystonie auszeichnet. Eine Punktmutation im DDP1-Gen, die zu einem Austausch eines der konservierten Cysteine führt (DDP1C66W), verursacht den Verlust der Zinkbindungskapazität und resultiert in einem fehlgefalteten, instabilen Protein. Es wurde gezeigt, dass das mutierte DDP1 nicht mehr in der Lage ist, mit seinem Partnerprotein Tim13 zu interagieren und keinen funktionellen DDP1-Tim13 Komplex ausbilden kann. Die menschlichen Proteine der Tim9 und Tim10-Gruppen, Tim9, Tim10a und Tim10b sind wie ihre homologen Hefeproteine in zwei hetero-oligomeren Komplexen organisiert, einem 70 kDa-Komplex bestehend aus Tim9 und Tim10a sowie einem 450 kDa Tim9-10a-10b-Komplex. Beide Komplexe sind fest mit der Innenmembran assoziiert. Tim10b zeigt eine geringere Sequenzhomologie zu Hefe-Tim10 als Tim10a. Es liegt genauso wie Tim12 nur in dem hochmolekularen Komplex vor und weist die stärkste Membranassoziation auf. Es zeigt damit strukturelle Ähnlichkeit zu Tim12. Aufgrund der Membranassoziation der kleinen TIM-Komplexe entfällt aber wahrscheinlich die Funktion des Tim12 als Vermittler zwischen dem löslichen Komplex und der Membran. Tim9, Tim10a und Tim10b sind wie die Hefe-Proteine am Import von mitochondrialen Carriern beteiligt. Die Bindung an Translokationsintermediate von Carrier-Vorstufenproteinen erfolgt in Abhängigkeit von zweiwertigen Kationen wie Zn2+. Die Struktur des TIM22-Komplexes weist signifikante Unterschiede zu der aus der Hefe bekannten Organisation auf. Humanes Tim22 ist im Vergleich zu Hefe-Tim22 wenig konserviert. Es liegt kein stabiler Komplex vor, der Tim22 und die kleinen Tim-Proteine enthält. Sie befinden sich vermutlich in dynamischer Interaktion mit Tim22, die wahrscheinlich nur während der Translokation eines Vorstufenproteins auftritt. Bisher ist kein Komplexpartner des humanen Tim22 bekannt. Homologe zu Tim54 und Tim18, den membranintegralen Komplexpartnern des Tim22, wurden in menschlichen Datenbanken nicht identifiziert. Aufgrund der veränderten strukturellen Organisation ist das menschliche Tim22 nicht in der Lage, mit den Proteinen aus der Hefe funktionell zu kooperieren. Es hat vermutlich eine Anpassung an veränderte Substratspezifizitäten stattgefunden, die auch die Beteiligung weiterer bisher unidentifizierter Komponenten der TIM22-Translokase einschließen könnte. Ein neues Intermembranraumprotein menschlicher Mitochondrien, Cmi1, ist an der Biogenese der kleinen Tim-Proteine beteiligt. Eine Überexpression im Hefesystem führt zur signifikanten Erhöhung der Proteinmengen von kleinen Tim-Proteinen im mitochondrialen Intermembranraum. Cmi1 unterstützt vermutlich die rasche stabile Faltung der neu importierten kleinen Tim-Proteine. Da Cmi1 in der Lage ist, Metall-Ionen zu binden vermittelt es möglicherweise den Transfer von Zink-Ionen.

Two projects are described within the scope of this thesis. The first project characterizes the ubiquitin-specific protease UBP41 as a protein which upon overexpression causes apoptosis induction in several mammalian cancer cell lines. The second project investigates a possible involvement of the lysosomal cysteine proteases cathepsin-L and cathepsin-B in apoptosis pathways induced by distinct death stimuli, in particular by the tumor necrosis factor a (TNF-a). Therefore, both projects examine a possible regulation of apoptosis induction by proteases that are part of one of the two major systems of protein degradation. UBP41 as a protease with deubiquitylating activity is expected to play a role in the ubiquitin/proteasome system which is the major proteolytic apparatus for the degradation of cytosolic proteins. Cathepsins, on the other hand, are lysosomal proteases that participate in the breakdown of membrane-associated proteins and of extracellular proteins that are taken up by endocytosis. Both, the ubiquitin/proteasome system as well as lysosomal proteases have been previously implicated in the regulation and mediation of apoptosis, and it therefore appeared particularly attractive to further study the effect of UBP41 and cathepsins on cell death signalling in more detail.

Fri, 1 Jan 1993 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9433/1/9433.pdf Nast-Kolb, Dieter; Joka, T.; Jochum, Marianne; Fröhlich, D.; Billing, A.; Assfalg-Machleidt, I.; Machleidt, W.

Wed, 1 Jan 1992 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9837/1/9837.pdf Schmitt, M.; Jänicke, F.; Jochum, Marianne; Assfalg-Machleidt, I.; Machleidt, W. ddc:610,