Podcasts about pge2

Play Episode Listen Later Jun 26, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.23.546291v1?rss=1 Authors: Mellentine, S. Q., Ramsey, A. S., Li, J., Brown, H. N., Tootle, T. Abstract: A key regulator of collective cell migration is prostaglandin (PG) signaling. However, it remains largely unclear whether PGs act within the migratory cells or their microenvironment to promote migration. Here we use Drosophila border cell migration as a model to uncover the cell-specific roles of two PGs in collective migration. Prior work shows PG signaling is required for on-time migration and cluster cohesion. We find that the PGE2 synthase cPGES is required in the substrate, while the PGF2 synthase Akr1B is required in the border cells for on-time migration. Akr1B acts in both the border cells and their substrate to regulate cluster cohesion. One means by which Akr1B regulates border cell migration is by promoting integrin-based adhesions. Additionally, Akr1B limits myosin activity, and thereby cellular stiffness, in the border cells, whereas cPGES limits myosin activity in both the border cells and their substrate. Together these data reveal that two PGs, PGE2 and PGF2, produced in different locations, play key roles in promoting border cell migration. These PGs likely have similar migratory versus microenvironment roles in other collective cell migrations. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Disulfiram Exerts anti-pulmonary Fibrosis Effect by Activating PGE2 Synthesis

Play Episode Listen Later Apr 17, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.16.537099v1?rss=1 Authors: Pei, X., Zheng, F., Li, Y., Lin, Z., Zhang, Y., Han, X., Feng, Y., Li, F., Yang, J., Li, T., Tian, Z., Cao, K., Ren, D., Li, C. Abstract: Idiopathic pulmonary fibrosis (IPF) is marked with the replacement of normal alveolar tissue by thicker and harder fibrous material, damaged exchange ability. Currently, nintedanib and pirfenidone, are the only FDA-approved drugs with limited efficacy for IPF, which indicated an urgent need to explore new therapies. Disulfiram (DSF), an acetaldehyde dehydrogenase inhibitor, used as anti-alcohol treatment. Despite reported with anti-hepatic fibrosis effect of DSF, the underlying mechanism remains unclear. In our study, DSF exhibited regulative impact on abnormal proliferation, EMT and ECM production in cell models of IPF including primary DHLF-IPF cells and TGF-{beta}1-stimulated A549 cells. The absence of COX-2 was restored by DSF treatment, together with elevated prostaglandin biosynthesis both in vitro and in vivo models of IPF. Furthermore, the anti-fibrotic effect of DSF was impeded with COX-2 knockdown or pharmacological inhibition in TGF-{beta}1-stimulated A549 cells, however, exogenous PGE2 reclaimed with anti-EMT function. In established animal model of IPF, DSF ameliorated declined lung function and histopathological changes, and restrained the lung hydroxyproline content. Together, these findings suggest that the anti-fibrotic effect of DSF was achieved through re-activation of COX-2 mediated PGE2 biosynthesis. The above results suggest that DSF can be applied therapeutically in fibrotic conditions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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NG2 glia protect against prion neurotoxicity by inhibiting prostaglandin E2 signaling

Play Episode Listen Later Apr 4, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.04.535590v1?rss=1 Authors: Liu, Y., Guo, J., Matoga, M., Korotkova, M., Jakobsson, P.-J., Aguzzi, A. Abstract: Oligodendrocyte-lineage cells of patients and animal models undergo prominent changes in various neurodegenerative disorders. This raises the question of how myelinating cells interact with neurodegenerative processes. Here, we investigated the role of oligodendrocyte precursor cells (NG2 glia) in prion infections. We found that NG2 glia were activated in prion-infected cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology, suggesting a protective effect for NG2 glia. Loss of NG2 glia unleashed a microglial reaction promoting the biosynthesis of prostaglandin E2 (PGE2), which augmented prion toxicity in HovS cells and COCS through binding to the EP1 and EP4 receptors. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, antagonized the enhanced neurodegeneration in NG2 glia-depleted COCS and brains after prion infection, and dampened the acceleration of prion disease in NG2 glia-depleted mice. These data unveil a non-cell-autonomous interaction involving NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Neurovascular Coupling is Required for Amygdala Neuronal Activation and Associated Emotional Behaviors in Mice, Depending on NMDA Receptor Subunit 2D-expressing Cerebral Arteriolar Smooth Muscle Cells

Play Episode Listen Later Feb 14, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.13.527949v1?rss=1 Authors: Ruan, J., Xie, H., Quan, X., Zhang, Y., Zhang, D., Wang, W., Hu, X., Tao, Y., Zhao, B., Lu, D., Jia, J.-M. Abstract: Proper brain function depends on intact neurovascular coupling (NVC). Through NVC, local cerebral blood flow (CBF) is rapidly increased in activated cerebral regions to meet the corresponding demands of neural activities. NVC has been believed to support advanced cerebral functions such as complex emotional homeostasis. However, few studies provide causal link evidence with specific molecular and cellular identities. Here, using RNAscope, cell-type specific conditional knockout (cKO) perturbation in BL6/C57 mice, laser speckle contrast imaging, and mouse behavior assays, we demonstrated that the N-methyl-D-aspartic acid (NMDA) receptor noncore subunit NR2D is only expressed in cerebral arteriole smooth muscle cells (aSMCs) but not in peripheral aSMCs. Both aSMC-NR2D cKO and aSMC-NR2D+NMDA receptor subunit 1 (NR1) double cKO mice displayed a severe decline in functional hyperemia induced by whisker stimulation. In addition, the NR2D pathway was independent of previously demonstrated COX-2-PGE2-dependent mechanism and high-fat diet (HFD)-induced impairments in NVC. Caldesmon is a potential downstream protein in the NR2D pathway for NVC regulation. Notably, we demonstrated that NVC deficits caused abnormalities in complex emotional behaviors, such as anxiety-like behaviors (exhibiting increased defecation and urine), reduced curiosity and decreased fear instinct (displaying less fear of aggressive CD1 mice). Furthermore, fear-response gene c-FOS expression in the amygdala neurons was attenuated in aSMC-NR2D knockout mice after response to acute stresses. In contrast, its expression level remained unchanged in the non-fear-related cerebral regions such as the piriform cortex and hippocampus. These findings demonstrated that inadequate functional hyperemia impaired cerebral complex emotional functions and suggested a co-existence of anxiety and fearlessness in single individuals. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

96.5 The curious case of Zithromax and viral respiratory infections

ERCAST

Play Episode Listen Later Feb 6, 2023 13:48

When you have a patient who requests a Z-pack for what is almost certainly an acute viral respiratory infection, you probably respond internally or externally (possibly both) that antibiotics do not treat viruses. But could there be some effect on their symptoms, or the viral infection itself, that is not part of the common discussion when it comes to such things? We know that azithromycin is an antibiotic, but it turns out that azithromycin actually has some activity in the viral arena. This absolutely shocked me. The question is, does it matter? Interested in one-on-one coaching? Learn more at roborman.com To support the show - visit our Patreon site and help keep the wind in the sails. For our full catalog of shows with complete show notes, visit our podcast page To wit… In vitro studies show azithromycin reduces rhinovirus replication and release. Another in vitro study on respiratory cells from lung transplant patients found azithromycin reduces rhinovirus-associated cellular inflammation. Kids with coronavirus (the pre-COVID, old-school coronavirus) had reduced viral load with azithromycin. In enterovirus-infected mice, azithromycin improved survival. Patients infected with influenza a who were given azithromycin had reduced interleukins 6, 8, 17, tumor necrosis factor, and CRP, indicating anti-inflammatory properties in flu patients. This study, however, did not show improved clinical outcomes with azithromycin. Another study using a similar methodology did not see any change in inflammatory markers but had a slight improvement in sore throat and fever resolution in the azithromycin group. A 2009 paper found that azithromycin did not improve disease course in hospitalized infants with a respiratory synovial virus. There has been signal of clarithromycin decreasing hospitalization in patients with severe RSV, but the preponderance of data are fairly consistent that there is no benefit in hospital stay, length of illness, or oxygen utilization. Selective poison Every medication is a selective poison and azithromycin poisons a lot of stuff: interleukin beta production, PGE2 synthesis, tumor necrosis factor, cytokine expression, it slows membrane trafficking towards lysosomes, and inhibits the fluid phase of endocytosis of macromolecules. Suffice it to say, there's a lot going on here. When we see these changes in inflammatory markers or in vitro decreased viral loads, it isn't far-fetched. By extension, it frankly wouldn't be far-fetched if this drug improved resolution and severity of illness in viral upper respiratory infections. When it comes to the flu, an illness with cytokine dysregulation, a medication such as azithromycin, with its immunomodulatory and anti-inflammatory effects, looks very tasty. Bottom line: It's pretty clear that something happens when a patients take this drug. It's even possible that they may even have a sense of feeling better. I can't refute that. My assumption is that their cold or acute sinusitis improves despite their taking an antibiotic, but maybe there is something subtle afoot that is as yet unmeasured. Unfortunately, the data to date do not show observable clinical outcome benefits with azithromycin and viral infections.

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96.5 The curious case of Zithromax and viral respiratory infections

Stimulus.

Play Episode Listen Later Feb 6, 2023 13:48

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Calcium transients trigger switch-like discharge of prostaglandin E2 (PGE2) in an ERK-dependent manner

Play Episode Listen Later Feb 3, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.01.526734v1?rss=1 Authors: Watabe, T., Yamahira, S., Takakura, K., Thumkeo, D., Narumiya, S., Matsuda, M., Terai, K. Abstract: Prostaglandin E2 (PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2 secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin-Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors we demonstrate that calcium transients in a single cell cause PGE2-mediated radial spread of PKA activation (RSPA) in neighboring cells. By in vivo imaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2 discharge in response to the increasing cytoplasmic Ca2+ concentrations. The cell density of MDCK cells correlated with the frequencies of calcium transients and the following RSPA. The ERK MAP kinase activation also enhanced the frequency of RSPA in MDCK and in vivo. Thus, the PGE2 discharge is regulated temporally by calcium transients and ERK activity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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ImmunoEpigeneticsXIX. Diet-induced and db/db mouse model Type 2 diabetes is dissimilar to the human pathophysiology but shares epigenetic mechanisms controlling pro-inflammatory PLA2/COX2/PGE2.

Authentic Biochemistry

Play Episode Listen Later Jan 20, 2023 29:58

References Dr. Guerra's lipid lectures JCI Insight. 2020 Sep 3;5(17):e138443 Proc Natl Acad Sci U S A. 1998 Mar 31; 95(7): 4061–4065. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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January 2023 Discover CircRes

Discover CircRes

Play Episode Listen Later Jan 19, 2023 30:49

This month on Episode 44 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the January 6th and January 20th issue of Circulation Research. This episode also features an interview with Dr Timothy McKinsey and Dr Marcello Rubino about their study, Inhibition of Eicosanoid Degradation Mitigates Fibrosis of the Heart. Article highlights: Prasad, et al. ACE2 in Gut Integrity and Diabetic Retinopathy Cui, et al. Epsins Regulate Lipid Metabolism and Transport Li, et al. Endothelial H2S modulates EndoMT in HF Luo, et al. F. plautii Attenuates Arterial Stiffness Cindy St. Hilaire: Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's Journal Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to be highlighting articles from our January 6th and January 20th issues of Circulation Research. I'm also going to have a chat with Dr Timothy McKinsey and Dr Marcello Rubino about their study, Inhibition of Eicosanoid Degradation Mitigates Fibrosis of the Heart. But before the interview, I want to get to a few articles to highlight. Cindy St. Hilaire: The first article is titled, Maintenance of Enteral ACE2 Prevents Diabetic Retinopathy in Type 1 Diabetes. The first authors are Ram Prasad and Jason Floyd, and the corresponding author is Maria Grant, and they are from the University of Alabama. Type 1 Diabetes has a complex etiology and pathology that are not entirely understood. In addition to the destruction of insulin-producing cells, a recently discovered feature of the disease in both humans and in rodent models is that the levels of angiotensin converting enzyme 2 or ACE2 can be unusually low in certain tissues. ACE2 is a component of the renin angiotensin system controlling hemodynamics and interestingly, genetic deficiency of ACE2 in rodents exacerbates aspects of diabetes such as gut permeability, systemic inflammation and diabetic retinopathy, while boosting ACE2 has been shown to ameliorate diabetic retinopathy in mice. This study shows that ACE2 treatment also improves gut integrity and systemic inflammation as well as retinopathy. Six months after the onset of diabetes in a mouse model, oral doses of a bacteria engineered to express humanized ACE2 led to a reversal of the animal's gut barrier dysfunction and its retinopathy. Humans with diabetic retinopathy also displayed evidence of increased gut permeability in low levels of ACE2. This study suggests they may benefit from a similar probiotic treatment. Cindy St. Hilaire: The next article I want to highlight is titled, Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression. The first authors are Kui Cui, Xinlei Gao and Beibei Wang, and the corresponding authors are Hong Chen and Kaifu Chen and they're from Boston Children's Hospital. Epsins are a family of plasma membrane proteins that drive endocytosis. They're expressed at varying levels throughout the tissues of the body, and recent research shows that they are unusually abundant on macrophages within atherosclerotic lesions. In mice, macrophage specific Epsin loss results in a reduction in foam cell formation and atherosclerotic plaque development. This study now shows that this effect on foam cells is because Epsins normally promote the internalization of lipids into macrophages through their endosytic activity. But that's not all. The proteins also impede cholesterol efflux from macrophages to further exacerbate lipid retention. It turns out out Epsins regulate the endocytosis and the degradation of a cholesterol efflux factor called ABCG1. Importantly, these pro atrogenic activities of Epsins can be stopped. Using macrophage targeted nanoparticles carrying Epson specific silencing RNA, the team could suppress reduction of the protein in cultured macrophages and could reduce the size and number of plaques in atherosclerosis prone mice. Together these results suggest blocking Epsins via nanotherapy or other means could be a therapeutic approach to stopping or slowing atherosclerotic plaque progression. Cindy St. Hilaire: The third article I want to highlight is coming from our January 20th issue of Circ Res and is titled, Hydrogen Sulfide Modulates Endothelial-Mesenchymal Transition in Heart Failure. The first author is Zhen Li, and the corresponding author is David Lefer and they're from Cedars-Sinai. Hydrogen sulfide is a critical endogenous signaling molecule that exerts protective effects in the setting of heart failure. Cystathionine γ-lyase, or CSE, is one of the three hydrogen sulfide producing enzymes, and it's predominantly localized in the vascular endothelium. Genetic deletion of CSE, specifically in the endothelium, leads to reduced nitric oxide bioavailability, impaired vascular relaxation and impaired exercise capacity, while genetic over-expression of PSE in endothelial cells improves endothelial cell dysfunction, and attenuates myocardial infarction following myocardial ischemia-reperfusion injury. In this study, endothelial cell specific CSE knockout mice and endothelial cell specific CSE overexpressing transgenic mice were subjected to transverse aortic constriction to induce heart failure with reduced ejection fraction. And the goal was to investigate the contribution of the CSE hydrogen sulfide access in heart failure. Endothelial specific CSE knockout mice exhibited increased endothelial to mesenchymal transition and reduced nitric oxide bioavailability in the myocardium. And this was associated with increased cardiac fibrosis, impaired cardiac and vascular function, and it worsened the vascular performance of these animals. In contrast, genetic overexpression of CSE in endothelial cells led to increased myocardial nitric oxide, decreased EndoMT and decreased cardiac fibrosis. It also improved exercise capacity. These data demonstrate that endothelial CSE modulates endothelial mesenchymal transition and ameliorated the severity of pressure overload induced heart failure , in part through nitric oxide related mechanisms. This data further suggests that endothelium derived hydrogen sulfide is a potential therapeutic for the treatment of heart failure with reduced ejection fraction. Cindy St. Hilaire The last article I want to highlight is titled, Flavonifractor plautii Protects Against Elevated Arterial Stiffness. The first authors are Shiyun Luo and Yawen Zhao, and the corresponding author is Min Xia, and they are at Sun Yat-sen University. Dysbiosis of gut microbiota contributes to vascular dysfunction and gut microbial diversity has been reported to be inversely correlated with arterial stiffness. However, the causal role of gut microbiota in the progression of arterial stiffness and the specific species along with the molecular mechanisms underlying this change remain largely unknown. In this study, the microbial composition in metabolic capacities were compared in participants with elevated arterial stiffness and in normal controls free of medication. And these groups were age and sex match. Human fecal metagenomic sequencing identified a significant presence of Flavonifractor plautii or F. plautii in normal controls, which was absent in the subjects with elevated arterial stiffness. The microbiome of normal controls exhibited an enhanced capacity for glycolysis and polysaccharide degradation, whereas individuals with increased arterial stiffness exhibited increased biosynthesis of fatty acids and aromatic amino acids. Additionally, experiments in the angiotensin II induced and humanized mouse model show that replenishment with F. plautii or its main effector cis-aconitic acid or CCA improved elastic fiber network and reversed increased pulse wave velocity through the suppression of matrix metalloproteinase-2 and through the inhibition of monocyte chemoattractant protein-1. And this was seen in both the angiotensin II induced and humanized models of arterial stiffness. This study now identifies a novel link between F. plautii and arterial function and raises the possibility of sustaining vascular health by targeting the gut microbiota. Cindy St. Hilaire: Today with me I have Dr Tim McKinsey and Dr Marcello Rubino from the University of Colorado Anschutz Medical Campus, and we're here to talk about their paper Inhibition of Eicosanoid Degradati`on Mitigates Fibrosis of the Heart. And this article is in our January 6th issue of Circulation Research, so thank you both so much for joining me today. Timothy McKinsey: Thank you for inviting us. Marcello Rubino: Yeah, thank you for the opportunity. Cindy St. Hilaire: And so Dr McKinsey, you're a professor at the University of Colorado. How long have you been investigating cardiac fibrosis? Timothy McKinsey: Oh, a long time. Before I started the lab here in 2010, I was in industry working in biotech with Myogenic Gilead, and we were very interested in cardiac fibrosis all the way back then. Cindy St. Hilaire: Oh wow, so you actually made an industry to academia transfer. Timothy McKinsey: Yes. Cindy St. Hilaire: Good topic for another podcast. That is really great. Timothy McKinsey: Yeah, it's of interest to a lot of people, including trainees. Cindy St. Hilaire: Yeah, I bet. Dr Rubino, you were or are a postdoc in the McKinsey lab? Marcello Rubino: Yeah, I was a postdoc in Timothy McKinsey lab. I spent four years in Tim's lab. It was my first time studying cardio fibrosis, so it was a little bit difficult at the end, but I think I was right choosing Tim, so I'm really happy now. Cindy St. Hilaire: Nice and are you sticking with fibrosis or are you moving on? Marcello Rubino: Yeah, so now I'm back in Milan where I did my PhD student and postdoc. I am like an independent researcher, but it's still not a principal investigator, so I want to become one of the that, studying cardiac fibrosis. Yeah. And inflammation and epigenetics, so yeah, I'm going try to go to my way, thanks to Tim, I think that I find my own way. Cindy St. Hilaire: I'm sure you will. I mean, based on the great work in this study, right. Building upon that, I'm sure you'll be a success. Timothy McKinsey: No doubt about it. Cindy St. Hilaire: So your manuscript, this study, it's investigating whether eicosanoid availability can attenuate fibrosis in the heart. But before we kind of jump into this study, why is fibrosis in the heart a bad thing? Is it always detrimental? Is there some level of fibrosis that's necessary or even helpful? Timothy McKinsey: I mean, a certain level of extracellular matrix is deposited in your heart and that maintains the structure of the heart. Fibrosis can also be good after you have a myocardial infarction and a big piece of the muscle of your heart has died, it needs to be replaced with a fibrotic scar, essentially to prevent rupture of the ventricle. So fibrosis isn't always bad, but chronic fibrosis can be really deleterious to the heart and contribute to stiffening of the heart and cause diastolic dysfunction. It can create substrates for arrhythmias and sudden cardiac death. So we're really trying to block the maladaptive fibrosis that occurs in response to chronic stress. Cindy St. Hilaire: Yeah, yeah. And what about eicosanoids? What are they and what role do they play in cardiac fibrosis or what was known about their role in this process before your study? Timothy McKinsey: Eicosanoids are lipids, they're basically fatty acids, 20 carbon in length and a lot is known about them. It's a very complex system. There are many different eicosanoids, but they're produced from arachidonic acid through the action of cyclooxygenase enzymes like COX-2. And so you're probably familiar with the literature showing that non-steroidal anti-inflammatory drugs that target the COX enzymes can actually increase the risk of cardiac disease, so there was a lot known about what produces eicosanoids in the heart, but our study is really the first to address how they're degraded and how that controls cardiac fibrosis. Cindy St. Hilaire: What I thought you did really well in the introduction and what I guess I didn't really fully appreciate until I had read your study, was that your goal was to identify compounds that could attenuate fibrosis. And you spent some time emphasizing the differences between a targeted small molecule screen and a phenotype based screen. And I was wondering if you could just expand on this difference for the audience and maybe just explain why in your case you went with the latter. Timothy McKinsey: Well, we wanted to use an unbiased approach and some people call this a chemical biology approach where we took a targeted library, meaning we took compounds with known activities, meaning compounds that with known targets and we screened that library using a phenotypic assays that we developed in the lab. And the phenotypic assay is an unbiased assay, right? We're just screening for compounds that have the ability to block the activation of fibroblasts. And we monitor activation by looking at markers of fibroblast activation such as alpha smooth muscle Actin. And we can do this in a very quantitative and high throughput manner using this imaging system, high content imaging system that we have in the lab. It was an unbiased screen looking for inhibitors of fibroblasts activation across organ systems. We not only studied cardiac fibroblasts, but we also studied lung and renal fibroblasts looking for compounds with a common ability to block the activation state of each of those cell types. One of the things that I get asked frequently is how do we maintain the cardiac fibroblasts in a quiescent state? Because you may know this, but when fibroblasts are plated on cell culture plastic, which has a very high 10 cell strength, they tend to spontaneously activate, so we actually spent a couple of years working out the conditions to maintain the cells in quiescent state, and I think that will also be of great interest to the field. Cindy St. Hilaire: Probably even the smooth muscle cell biology field where I hang out and even valve interstitial cells that we study. All of those, I guess basic things related to cell culture, we have taken for granted that plastic is not physiological. Timothy McKinsey: Right. Cindy St. Hilaire: And so I think with this really nice phenotypic or chemical screen that you conducted, you first identified nine compounds, but what made you zero in on this one, SW033291? Timothy McKinsey: When we got the hits, we were intrigued by the SW compound SW033291 because there was only one paper describing its action and there was a paper published in Science showing that SW or inhibition of this enzyme 15-PGDH could enhance organ regeneration. Cindy St. Hilaire: Oh, okay. Timothy McKinsey: And there's a very interesting interplay between fibrosis and organ regeneration where fibrosis inhibits regeneration and if you can stimulate regenerative pathways, they can actually block fibrosis, so there's this back and forth. And so that's really the main reason we were interested in pursuing SW just because of the novelty and the potential. And also it was a compound that behaved beautifully in our cell culture models with beautiful dose-dependent inhibition of each of the fibroblast types. Cindy St. Hilaire: It's kind of like the cleanest thing to start with. Also, if there's nothing known, it's ripe for investigation, so that's great. You just said this SW compound acts on 15-PGDH, so what is the role of that protein in fibroblasts and what if any known effects are there on this protein's inhibition in other cell types or disease states? Marcello Rubino: In fibroblasts team, I would like to say that this was really the first article that was published. Maybe there was just one published in Pulmonary Fibrosis, but like last year, but I didn't really talk about 15-PGDH, so you need to consider that 15-PGDH is an inhibitor, an enzyme that degrades prostaglandin, so if you inhibit the inhibitor, the release increase production, a lot of prostaglandin. And so a lot of paper were talking about this effect, so they will see we are just using SW in order to increase Prostaglandin E2 level and that was why we had this like anti-inflammatory or whatever effect. I would like to say that until now, maybe this can be the first really paper talking about no more than not just prostaglandin but 15-PGDH. Its action total level, a global level at particularly on fibroblasts. To answer your question, I would like to say that this was also our question first and we checked by level other browser to try to find the answer to your question. We figured out that it was known that 15-PGDH was increasing a pathology condition in different organ, not just related by fibroblasts, not just related to cardiac disease, about the function with discover a function in macrophage that interested us because it can regulate maybe the polarization macrophage, so still involving the prostaglandin production inflammation, so that's why also we decide to take a look because it was still novel in fibrolbasts and we still know that it was doing something important and we were trying not to put the piece together and find something new in that we were lucky for this. Timothy McKinsey: 15-PGDH is actually expressed at very low levels in fibroblasts. It's much more highly expressed in macrophage, just as Marcello pointed out, so in the future we're very interested in knocking out or inhibiting 15-PGDH in different cell types to see how that contributes to inhibition of cardiac fibrosis. Cindy St. Hilaire: Really interesting. Related to that, you used a couple different animal models for fibrosis. They're all different or special in their own way. How well did these recapitulate what we observe in humans. Are there any limitations of benefits? Timothy McKinsey: They're always limitations to animal models. We started out with a very robust commonly used model of cardiac fibrosis, which relies on Angiotensin II infusion in mice. We like that model because it's robust and quick so we can get answers quickly. And then we transitioned into a model of diastolic dysfunction that we've been working with in a lab where we remove a kidney from a mouse and we implant something called DOCA, which is an aldosterone memetic. And so the animals develop hypertension that leads to a mild but significant diastolic dysfunction with preserved ejection fraction. And that's a model that we like a lot. It has something that we call hidden fibrosis, so if you just do standard histochemical staining of the hearts from the DOCA unit, nephrectomy model, that diastolic dysfunction model, you really can't see robust fibrosis. It's only when you dive more deeply with more sensitive assays like mass spectrometry or atomic force microscopy that you can detect this fibrosis and stiffening of the heart, so we usually lead with a robust model of fibrosis, cardiac fibrosis, and then transition into a slightly more complex model but more physiologically relevant model or disease relevant model. Cindy St. Hilaire: Obviously you showed some really nice robust results with this SW compound. So in the continuum of heart failure in human, what do you think or what would you speculate would be the ideal timeframe for administration of this compound? Timothy McKinsey: Wouldn't want to give it immediately after someone's had a heart attack. As we discussed earlier, you need that reparative scar to form so you don't want to block that fibrotic remodeling. We believe that there's kind of smoldering fibroblast activation in the heart, even in someone who's had heart disease for many, many years. And if we can dampen that, we can either prevent further progression of heart failure or perhaps reverse it. We don't really know if we can reverse really established fibrosis in the heart yet. But I would want to try to catch fibrosis fairly early on in the disease process in someone who has chronic hypertension or obesity or a variety of different comorbidities and then start delivering an antifibrotic therapy at that point. Marcello Rubino: I would like to add that, so it is really tricky when we talk about clinical trials because a lot of molecules that maybe they can work hopefully in a preclinical model don't work at the end in the clinical model. That's because can be some off target also like you just asked what is really important is when you do the administration of the molecule and talk about this in SW, like things say we don't want to prevent the fibrosis because there is something like called a kneeling at the beginning, so it is the good fibrosis we like to say, but the good thing of SW compound is that is affecting in a good way the proliferation of fibroblast that is different for all the other. I would like to say all the other inhibitor that we saw so far, because I remember the first time that I presented this work, there was an expert told me that he didn't believe that all my data because the compound was inhibiting fibrosis, it was inhibiting proliferation. And I show him, no, this is contrary, so oh okay, I like it. We need to consider this that the action seems to be not like the retire for the cell, so because the cells continue to proliferate, they can proliferate more. But the good thing and we need to investigate more is that SW action seems to increase when the cell are more fibrotic, because we show just few human fibroblasts isolating from a human patient and we saw a higher positive effect of SW compound when the cell were more fibrotic. That can be interesting. I think that it's worth to try to test in the future like in different preclinical models and maybe in patients at the end because if we really can find something like maybe SW that can be specific for the state of pathology, that will be wonderful. I don't really know if we can really do it, but we need some therapy like this, so that's why we were really excited about what we discovered for this compound. Timothy McKinsey: We have a lot more to learn about this pathway and about fibrosis in general. Cindy St. Hilaire: Yeah. Timothy McKinsey: It's a very exciting time to be doing science because of the amazing technologies that we have at our disposal to address detailed mechanisms of disease. Cindy St. Hilaire: What was the most challenging aspect of the study? Timothy McKinsey: This was an incredibly difficult study. I can't even stress to you how much work went into this. Spearheaded by Marcello's awesome leadership. There was huge input from a big team. Keith Cook and I worked together in industry and we were able to recruit him over here for a few years as part of our fibrosis center called the CFReT. It's an advertisement. And Keith was able to implement some of the drug discovery approaches that we used in biotech and create this imaging system that we initially employed for the screens. That was challenging. Maintaining the cells in a quiescent state was very challenging as I mentioned. That took a couple of years and then just following up on SW and trying to figure out its mechanism of action was really challenging as well because as Marcello mentioned, most people have attributed SW's effects to an increase in PGE2 levels, so PGE2 is an eicosanoid that is degraded by 15-PGDH. And definitely when you inhibit 15-PGDH with SW, you see increased PGE2. But surprisingly we couldn't find that PGE2 was doing anything in our cell culture systems, meaning when we added it exogenously it was not blocking fibroblast activation, so then Marcello set out to identify which eicosanoid that is regulated by 15-PGDH is actually the antifibrotic eicosanoid. And that led him to something called 12(S)-HETE. That was challenging. And then just determining at the molecular level what was going on was also challenging. And that led Marcello to this kind of paradoxical discovery that it activating ERK signaling was actually blocking fibroblast activation. Cindy St. Hilaire: And of course ERK does everything right? Marcello Rubino: It does. Everything. Timothy McKinsey: And sort of the dogma is that ERK is promoting fibrosis in the heart, but Marcello's data suggests otherwise. Timothy McKinsey: And then other shout outs, Josh Travers, who's the second author of the paper provided huge input, especially after Marcello left. Josh helped get this across the finish line. We have an amazing in vivo team conducting the animal model studies. Maria Cavasin and Elizabeth Hardy. I could go on and on. There are a lot of authors and if I didn't mention one of them, it doesn't mean that they weren't key contributors. I just wanted to throw that out there. We also had great collaborators. I think another component of this paper that is of great interest to us, and initially I was against doing any of this, is that Marcello and Josh created this biobank of human cardiac fibroblasts that we obtained from explanted hearts from individuals undergoing heart transplantation. And initially I thought it was going to be a waste of time and money for Marcello and Josh to do that, but they were persistent and they started isolating these cells. And the cells are really fascinating because even after you take them out of that failed human heart and culture them, they maintain this constituently active state, which is different than the cells we were using for screening where we kept them quiescent and then we stimulated them with TGF-β to activate them. These human cardiac fibroblasts from the failed human hearts are just on all the time. Cindy St. Hilaire: Wow. Timothy McKinsey: And SW does a really amazing job of reversing that activated state. Cindy St. Hilaire: Very cool and excellent resource I'm sure for future studies. So my last question is what's next? You know, you discovered a lot in this paper. What's the next thing you want to tackle? Timothy McKinsey: Cell type specific roles for 15-PGDH in the heart, in the control of cardiac homeostasis and disease. Basically we want to knock it out in fibroblasts. We want to knock it out in our macrophages and see what the consequences are. That's one thing. We want to really pursue the whole GPR31 12(S)-HETE pathway in the heart. That's something that has never been studied. And so GPR31 is a G protein coupled receptor that is bound by this eicosanoid called 12(S)-HETE. And that seems to be blocking fibroblast activation, so we're going to further pursue that pathway. And then we think that this paradoxical finding related to ERK signaling in the heart is also worthy of pursuit. Why is it that stimulating ERK in a cardiac fibroblast is actually blocking the activation state of that cell? Marcello Rubino: I'm interested in this like Tim says, but also interested in the role of the interaction of the cell because it's important to study like a specific gene inhibitor, whatever role in a specific cell, but what happened to the other cell, the interaction the other cell when you do knocking in some specific cell, so that's what I'm trying to do in general. Now I move back in Italy, like I told you, I'm like a kind of independent research and I'm studying a lot single cell sequencing right now. Try to do also try to see what happened to interaction, understand during pathology. The idea is to study like inhibitor treatment and to see what really happened because gene expression is important, but we need to consider also of course the protein shape, the protein interaction, the cell interaction, so I try to grow in this field and see what really happened because the problem of the cell, they're just cell in vitro. They can mimic what happened, but it's not what really happened in vivo, so can we use this novel technology to improve our knowledge, that's what I want to try to do. Cindy St. Hilaire: Well that's great. Dr McKinsey, Dr Rubino, thank you so much for taking the time to speak with me today. Title of their article was Inhibition of Eicosanoid Degradation Mitigates Fibrosis of the Heart. It's in our January 6th issue of Circ Res. And thank you both so much for joining me today and thank you to you and all of your colleagues who worked so hard on this for this amazing study. Timothy McKinsey: Thank you. We really enjoyed this visit and we're grateful to have our work published in Circulation Research. Cindy St. Hilaire: That's it for highlights from the January 6th and 20th issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle @CircRes or #DiscoverCircRes. Thank you to our guests, Dr Tim McKinsey and Dr Marcello Rubino. This podcast is produced by Ishara Rantayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on-the-go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022. The opinions expressed by the speakers of this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahajournals.org.

Prostaglandin E2 prevents radiotherapy-induced alopecia by attenuating transit amplifying cell apoptosis through promoting G1 arrest

Play Episode Listen Later Nov 24, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.24.517788v1?rss=1 Authors: Lai, S.-f., Huang, W.-Y., Wang, W.-H., Hong, J.-B., Kuo, S.-H., Lin, S.-J. Abstract: Growing hair follicles (HFs) harbor actively dividing transit amplifying cells (TACs), rendering them highly sensitive to radiotherapy (RT). Clinically, there is still a lack of effective treatment for radiotherapy-induced alopecia (RIA). We aimed to dissect the effect and mechanism of local prostaglandin E2 (PGE2) pretreatment in RIA prevention. We found that PGE2 pretreatment reduced RIA by preventing premature termination of anagen through enhancing HF self-repair. Mechanistically, PGE2 did not activate HF stem cells, but preserved more TACs for regenerative attempts. Pretreatment of PGE2 lessened radiosensitivity of TACs by transiently arresting them in the G1 phase, thereby reducing TAC apoptosis and mitigating HF dystrophy. The preservation of more TACs accelerated HF self-repair and bypassed RT-induced premature catagen entry. Promoting G1 arrest by systemic administration of palbociclib isethionate (PD0332991), a CDK4/6 inhibitor, offered a similar protective effect against RT. Therefore, PGE2 protects HF TACs from RT by transiently inducing G1 arrest, and the regeneration of HF structures lost from RT is accelerated to resume anagen growth, thus bypassing the long downtime of hair loss. PGE2 has the potential to be repurposed as a preventive treatment for RIA. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

llc promoting copy arrest wang rt transit hong huang induced amplifying ria g1 prevents alopecia tac clinically hf kuo radiotherapy apoptosis hfs biorxiv cdk4 tacs pretreatment prostaglandin pge2

NSAID'ler ve Nefrotoksik Etkileri- Literatür derlemesi

Acilci.Net Podcast

Play Episode Listen Later May 27, 2022 14:14

Nonsteroid antienflamatuar ilaçlar (NSAID), antipiretik, antiinflamatuar ve analjezik ajanlar olarak kullanılan FDA onaylı bir ilaç sınıfıdır1. Bu etki mekanizmaları nsaidleri; dismenore, artritik durumlar, ateş, gut, migren tedavisinde faydalı kılar2 3,4 ve nsaidlerin dünyada en cok reçete edilen ilaçlar arasında yer almasını sağlar5. Narkotik ajanlara göre analjezik etkinlikleri daha düşük olsa da bağımlılık yapıcı yan etkileri olmamaları sayesinde acil servislerde de nsaidlerin parenteral ve oral formlarının sık kullanılması söz konusudur. NSAID etki mekanizması NSAID'lerin ana etki mekanizması, siklooksijenaz (COX) enziminin inhibisyonudur. Araşidonik asidi tromboksanlara, prostaglandinlere ve prostasiklinlere dönüştürmek için COX gereklidir. NSAID'lerin terapötik etkileri ve advers reaksiyonları, COX inhibisyonuyla bu eikosanoidlerin eksikliğine atfedilir6. COX-1 ve COX-2 olmak üzere iki siklooksijenaz izoenzimi vardır. COX-1 vücutta yapısal olarak eksprese edilir ve gastrointestinal mukoza zarının, böbrek fonksiyonunun ve trombosit agregasyonunun korunmasında rol oynar. COX-2 vücutta yapısal olarak yoktur; ve bunun yerine, inflamatuar yanıt ile indüklenerek eksprese olur. NSAID'lerin mide mukozası başta olmak üzere gastrointestinal sistemi, nefroloji sistemini, kardiyovasküler sistemi ve hematolojik sistemi etkileyen yan etkileri vardır. Acil hekimleri de dahil olmak üzere; nsaidleri hasta ile buluşturmada, hekimlerin en büyük endişelerinden biri nsaidlerin bu yan etki profilidir. Biz de bu yazımızda NSAIDlerin böbrek fonksiyonlarına etkisi ve akut böbrek hasarı riski ile ilgili literatürden derlediğimiz çalışmalardan bahsedeceğiz: NSAID ler ve Böbrek NSAID'ler, araşidonik asit kaskadını inhibe ederek, prostaglandinlerin oluşumunu inhibe eder. Prostaglandinler (esas olarak prostasiklinler, PGE2, PGD2 ) böbrekte renin anjiyotensin aldesteron sisteminin (RAAS) inhibisyonu ve afferent arteriyolde vazodilatörler etki ile böbrek perfüzyonunu artırır. NSAID'lerin özellikle COX-1 inhibisyonu ile bu mekanizmayı inhibe etmesi ile yan etki olarak akut böbrek hasarı riskini arttırdığı düşünülmektedir. COX-2 inflamatuar yanıt ile indüklenebilir bir reseptör olsa da son çalışmalarda normal fizyolojide de önemli bir rol oynadığı gösterilmiştir. Özellikle nefronlarda makula densada ve henle kulpunun çıkan kolunda su ve elektrolit dengesinin korunmasında rol oynar. Bu yüzden hem selektif hem nonselektif nsaidlerin akut böbrek hasarı gelişiminde rolü olduğu düşünülmektedir.89 Akut Böbrek Hasarı ve NSAID'ler Akut böbrek hasarı(AKI), akut böbrek yetmezliğini ifade etmek için kabul görmüş yeni bir terimdir. Kreatinin ve üre gibi nitrojen metabolizması ürünlerinin ve klinik olarak ölçülemeyen diğer atık ürünlerin birikmesiyle böbrek boşaltım fonksiyonunda saatler ile günler içinde hızlı azalma ile karakterize klinik bir sendromu ifade eder10.KDIGO rehberine göre; Akut böbrek hasarı (AKI): 48 saat içinde serum kreatininde ≥0,3 mg/dl artış , son 7 gün içinde serum kreatininde bazal değerinin ≥1.5 katına artış ya da 6 saat boyunca idrar hacmi ≤0.5 ml/kg/saat olarak tanımlanmaktadır. İnsidansı, popülasyonlar arasında değişiklik gösterse de diyaliz gerektirmeyen akut böbrek hasarı için yılda milyonda 5000 vakadan, diyaliz gerektiren AKI için ise yılda milyonda 295 vakaya kadar olduğu tahmin edilmektedir. Hastanede yatan hastalarda görülme sıklığı %1,9'dur ve özellikle sepsis varlığında yoğun bakım hastalarında prevalansının %40'tan fazla olduğu tahmin edilmektedir11. NSAID'ler ile tedavi edilen hastalarda nefrotoksisite prevalansı nispeten düşük olmasına rağmen, bu ajanların yaygın kullanım profili birçok kişinin risk altında olduğunu göstermektedir.12 Griffin ve arkadaşları 1987-1991 yılları arasında 65 ve üstündeki yaş grubunda toplum kökenli AKI tanısı ile hastaneye yatırılan hastaları dahil eden bir vaka kontrol çalışması gerçekleştirdiler. Akut böbrek yetmezliği olan 1.

fda bu cox biz aki akut nsaid raas literat acil pge2 narkotik kreatinin

The Gary Null Show - 04.12.22

The Gary Null Show

Play Episode Listen Later Apr 12, 2022 59:06

Polyphenol pills counter inflammation in women on hormonal contraceptives: RCT Universidade Federal do Rio Grande do Sul (Brazil), April 7, 2022 Supplements containing a mixture of polyphenols may counter increases in pro-inflammatory markers in women of childbearing age using combined hormonal contraceptives, says a new study. The supplements, formulated with resveratrol, catechin, quercetin, chlorogenic acid and cyanidin, were also found to prevent the increases in markers of systemic oxidative stress like F2-isoprostane. “The increase in biomarkers of inflammation and oxidative stress observed in the present study were possibly caused by the use of hormonal contraceptives, as verified in the [control group], and this change was not observed in the group that used polyphenols,” wrote researchers from the Institute of Cardiology and the Universidade Federal do Rio Grande do Sul in Brazil. “Therefore, the results of this polyphenol supplementation showed that the antioxidant and anti-inflammatory effects observed in the studied population is due to the reduction in plasma levels of PGE2, supporting the conceptual hypothesis, by its action on the inflammatory cascade, probably by COX inhibition.” (NEXT) The power of kindness in improving brain health Center for BrainHealth at The University of Texas, April 11, 2022 Kindness is powerful and does not just affect the recipient's feelings—kindness can also impact an entire family's brain health. A cross-disciplinary team of researchers and clinicians from Center for BrainHealth at The University of Texas at Dallas sought to understand whether an online kindness training program improves preschooler's prosocial behaviors and their parents' resilience during the COVID-19 pandemic. (NEXT) Omega-3 supplementation could offer MCI benefits: Pilot study University of California-Los Angeles, April 10, 2022 Supplementation with a drink containing 2000 mg of omega-3 and mixed botanicals could have ‘significant' immune and biochemical effects in people that have minor cognitive impairment (MCI), new research suggests. The pilot study, published in The FASEB Journal, investigated the immune and pro- and anti-inflammatory effects of nutritional supplementation with a drink (Smartfish) that combines high levels of the omega-3 fatty acids DHA and EPA with a mixture of vitamins and botanicals including resveratrol vitamin D3, “thus targeting several facets of AD [Alzheimer's disease] pathogenesis.” (NEXT) Magic mushroom compound increases brain connectivity in people with depression after use by Imperial College London, April 11, 2022 Psilocybin, the psychedelic compound found in magic mushrooms, helps to "open up" depressed people's brains, even after use, enabling brain regions to talk more freely to one another. These are the findings of a new analysis of brain scans from close to 60 people receiving treatment for depression, led by Imperial College London's Centre for Psychedelic Research. The team behind the study believes it may have untangled how psilocybin exerts its therapeutic effects on the brain. (NEXT) Regular cycling helps patients with 'accelerated aging' disease McMaster University, April 11, 2022 A study led by McMaster University researchers has found that regular cycling can greatly improve mobility in patients with myotonic dystrophy (MD), a genetic disease that causes muscle degeneration. Senior author Mark Tarnopolsky said that cycling for 35 minutes three times a week for 12 weeks led to a 32 percent increase in overall fitness in people with MD. Patients who took part in the study also saw a 1.6-kilogram increase in their muscle massand a two percent reduction of body fat. They were also able to walk an extra 47 meters in six minutes, when tested by researchers at the end of the 12-week trial.

How to fight inflammation and sarcopenia while building muscle naturally!

Ask The Doctor Podcast

Play Episode Listen Later Mar 26, 2022 50:00

Dr Michael Lange host of "ask the dr" has been hosting live call-in talk show called "Ask The Dr" since April of 93 all over the world . Tune in each week while he discusses the latest in anti aging, eye care and nutrition. todays show both Dr Michael Lange and Dr Richard Hall discuss inflammation and how it can effect the eyes and entire body. They also discuss the muscle wasting age related disease called Sarcopenia and How Fortifeye Fit especially when combined with Fortifeye Super Protein or Fortifeye Grass fed whey isolate can bring nutritional support to sarcopenia. Dr Lange discusses how whey protein is not only great for building muscles but also amazing for building a powerful immune system. He says if you have negative reactions to milk you may still be able to take whey protein since the casein and lactose have been removed. Dr Michael Lange says when buying a whey protein make sure you look for 3 things on the label. 1. grass fed, 2. non denatured 3. where the cows come from ex: new Zealand , America etc... A grass fed non denatured whey protein is one of the best ways to stimulate glutathione production form the covalent bonded cystine in non denatured whey protein. Drinking a good grass fed whey protein that is non denatured can promote less inflammation and less body fat less enhance muscle production and improve immune system. They discuss the importance of reading labels of omega 3 fish oil and how important tg form omega 3 fish oil is. This is actually called rTG form omega3 fish oil or re esterified triglyceride form omega 3 fish oil. Most omega 3 fish oil is an ethyl ester or ee form that has ethanol attached to the backbone. This is an inferior cheaper way to make omega 3 fish oil that is very unstable and in efficient since it must go thru your liver to cleav off the ethanol and replace with a triglyceride (TG) backbone. Fortifeye Super Omega and Fortifeye Super Omega 3 Max are already in the TG form and are two of the purest and most potent tg omega 3 fish oils in the industry at 2 per day dosing. many competitors in the omega 3 fish oil market you have to take 3-6 capsules to be equivalent to 1-2 Fortifeye Super omega or Super Omega Max capsules. Fortifeye Super Omega is one of the nutrients in the dry eye vitamin Pak called Fortifeye Advanced Dry Eye Therapy. When combining this omega 3 with GLA form Black currant seed oil and Fortifeye Focus it helps to quell the inflammatory cascade in the eye and body. GLA form black current seed oil stimulates PGE1 and helps to reduce inflammation in the eyes and body. EPA form omega 3 fish oil helps to block D5D ( delta 5 desaturase enzyme) and lessen the inflammatory effects of arachidonic acid by decreasing the cox and lox inflammatory pathways and helping to stop this inflammatory cascade from leading to the endpoint pro inflammatory PGE2 and Leukotrienes. Omega 3 fish oil also helps to promote the ant inflammatory pathway of PGE3. Reduce inflammation in the eyes and body and also help to reduce associated pain with Fortifeye Advanced Dry Eye Therapy. For the best deals on all Fortifeye Supplements go to the Bundle section at www.fortifeye.com They both discussed natural treatments for rosacea especially when involving the eye and meibomian glands. Support the show: https://www.drmichaellange.com/category/ask-the-doctor/ See omnystudio.com/listener for privacy information.

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09 Could this be causing your cramps, headaches, or nausea?

Menstrual Memoirs

Play Episode Listen Later Jul 2, 2021 8:53

Hi ladies, welcome back! Prostaglandins may be the culprit to your period issues such as cramps, nausea, vomiting, diarrhea, and headaches! This episode dives into the three types of prostaglandins : PgE1, PgE2, and PgE3 and their direct connection with our Omega-3:Omegas-6 ratios. Great news is we can do some simple dietary changes to help support this bodily process and see changes in our menstrual cycle. Tuen in to find out all the deets! Click to get on the email list for special offers and discounts! Click to download your free period journal! Click to get $10 off period panties! Click to connect on Instagram!

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The Gary Null Show - 04.20.21

The Gary Null Show

Play Episode Listen Later Apr 20, 2021 63:32

Study strengthens links between red meat and heart disease Queen Mary University (UK), 15 April 2021 An observational study in nearly 20,000 individuals has found that greater intake of red and processed meat is associated with worse heart function. The research is presented at ESC Preventive Cardiology 2021, an online scientific congress of the European Society of Cardiology (ESC).1 "Previous studies have shown links between greater red meat consumption and increased risk of heart attacks or dying from heart disease," said study author Dr. Zahra Raisi-Estabragh of Queen Mary University of London, UK.2,3 "For the first time, we examined the relationships between meat consumption and imaging measures of heart health. This may help us to understand the mechanisms underlying the previously observed connections with cardiovascular disease." The study included 19,408 participants of the UK Biobank.4 The researchers examined associations of self-reported intake of red and processed meat with heart anatomy and function. Three types of heart measures were analysed. First, cardiovascular magnetic resonance (CMR) assessments of heart function used in clinical practice such as volume of the ventricles and measures of the pumping function of the ventricles. Second, novel CMR radiomics used in research to extract detailed information from heart images such as shape and texture (which indicates health of the heart muscle). Third, elasticity of the blood vessels (stretchy arteries are healthier). The analysis was adjusted for other factors that might influence the relationship including age, sex, deprivation, education, smoking, alcohol, exercise, high blood pressure, high cholesterol, diabetes, and body mass index (BMI) as a measure of obesity. The researchers found that greater intake of red and processed meat was associated with worse imaging measures of heart health, across all measures studied. Specifically, individuals with higher meat intake had smaller ventricles, poorer heart function, and stiffer arteries - all markers of worse cardiovascular health. As a comparison, the researchers also tested the relationships between heart imaging measures and intake of oily fish, which has previously been linked with better heart health. They found that as the amount of oily fish consumption rose, heart function improved, and arteries were stretchier. Dr. Raisi-Estabragh said: "The findings support prior observations linking red and processed meat consumption with heart disease and provide unique insights into links with heart and vascular structure and function." The associations between imaging measures of heart health and meat intake were only partially explained by high blood pressure, high cholesterol, diabetes, and obesity. "It has been suggested that these factors could be the reason for the observed relationship between meat and heart disease," said Dr. Raisi-Estabragh. "For example, it is possible that greater red meat intake leads to raised blood cholesterol and this in turn causes heart disease. Our study suggests that these four factors do play a role in the links between meat intake and heart health, but they are not the full story." She noted that the study did not look into alternative mechanisms. But she said: "There is some evidence that red meat alters the gut microbiome, leading to higher levels of certain metabolites in the blood, which have in turn been linked to greater risk of heart disease." Dr. Raisi-Estabragh said: "This was an observational study and causation cannot be assumed. But in general, it seems sensible to limit intake of red and processed meat for heart health reasons." More Fruits and Veggies Improves Sleep for Young Adults University of Michigan, April 15, 2021 Eating more fruits and vegetables can help young adults, especially young women, sleep better, a new study shows Young adults who reported eating less than five servings of fruits and vegetables per day reported a high prevalence of chronic insomnia symptoms, with over one-third reporting difficulties with falling asleep or maintaining sleep at least three times per week for three months or longer. Women who increased their fruit and vegetable intake by three or more servings over a three-month period were more than twice as likely to experience an improvement in these insomnia symptoms, according to the study in the Sleep Health Journal. “We were very excited to see that a fairly simple dietary intervention, such as encouraging an increase in fruit and vegetable consumption, could make such an impact on sleep,” says lead author Erica Jansen, research assistant professor of nutritional sciences at the University of Michigan’s School of Public Health. “We know from other literature that improving sleep improves overall quality of life and many other health outcomes, so the benefits likely extend beyond the sleep changes.” Jansen and senior author Gwen Alexander, a researcher in the public health sciences department at Henry Ford Health System, and colleagues analyzed data of more than 1,400 participants compiled by Detroit-based Henry Ford and the more rural Geisinger Health System headquartered in Danville, Pennsylvania. “From my health educator perspective, our study shows a link between dietary choices and improved sleep for young people who wish to improve their overall health and well-being,” Alexander says. “Our study was unique in that it investigated an understudied population of generally healthy young adults. Future research designed for this population has great potential to lead to better health habits.” Eligible young adults included those ages 21-30, who received any medical care at the centers and who reported eating less than five servings of fruits and vegetables per day. Researchers randomized the participants into one of three groups: one had an untailored web-based program to encourage higher fruits and vegetables consumption; the second had an age-targeted tailored web-based program; and the third group also included personalized e-coaching support. Young adults who increased their fruit and vegetable consumption by at least three servings experienced modest improvements in sleep latency (time to fall asleep) and insomnia over a three-month period, compared to participants with no change or smaller increases in fruits and vegetable intake, although there were no differences in sleep duration. Women who increased their fruit and vegetable intake by three or more servings reported a four-minute shorter time, on average, to fall asleep at follow-up, and twofold higher odds of improvement in insomnia symptoms. “What is unique about our study is that we were able to see that as fruit and vegetable intake changed, insomnia-related sleep characteristics also changed,” Jansen says. “We still cannot rule out that sleep characteristics changed first, which in turn caused a change in fruit and vegetable intake, but since the participants were part of a trial to increase fruit and vegetable intake, it is more likely the other way around. The participants were not told to change anything about their sleep habits.” The researchers hope the findings will be incorporated into other sleep hygiene principles, which include things like maintaining a consistent bedtime and rise time, eliminating screens prior to going to bed, sleeping in a dark, cool environment, and not drinking caffeine or alcohol before bed. Additional coauthors are from the University of South Carolina School of Medicine and the Henry Ford Health System. Multivits, omega-3, probiotics, vitamin D may lessen risk of positive COVID-19 test British Medical Journal, April 20, 2021 Taking multivitamins, omega-3, probiotics or vitamin D supplements may lessen the risk of testing positive for SARS-CoV-2, the virus responsible for COVID-19 infection—at least among women—indicates a large population study, published online in the journal BMJ Nutrition Prevention & Health. But taking any of vitamin C, zinc, or garlic supplements wasn't associated with a lower risk of testing positive for the virus, the findings show. There has been plenty of celebrity endorsement of the use of dietary supplements to both ward off and treat COVID-19 infection since the start of the pandemic, note the researchers. In the UK alone, market share rose by 19.5% in the period leading up to the first national 'lockdown' on March 23 last year, with sales of vitamin C rising by 110% and those of multivits by 93%. Similarly, zinc supplement sales rose by 415% in the first week of March, at the height of COVID-19 fears in the U.S.. Dietary supplements can help to support a healthy immune system, but whether specific supplements might be associated with a lower risk of catching SARS-CoV-2 isn't known. In a bid to plug this knowledge gap, the researchers drew on adult users of the COVID-19 Symptom Study app to see if regular supplement users were less likely to test positive for SARS-CoV-2. The app was launched in the UK, the US, and Sweden in March 2020 to capture self-reported information on the evolution of the pandemic. Initially, it recorded the location, age and core health risk factors of its users. But as time went on, subscribers were asked to provide daily updates on a range of issues, including symptoms, coronavirus test results, and healthcare. People without obvious symptoms were also encouraged to use it. For the purposes of this study, the researchers analysed information supplied by 372,720 UK subscribers to the app about their regular use of dietary supplements throughout May, June, and July 2020 during the first wave of the pandemic as well as any coronavirus swab test results. Between May and July,175,652 UK subscribers regularly took dietary supplements;197,068 didn't. Around two thirds (67%) were women and over half were overweight (BMI of 27). In all, 23,521 people tested positive for SARS-CoV-2 and 349,199 tested negative between May and July. Taking probiotics, omega-3 fatty acids, multivits or vitamin D was associated with a lower risk of SARS-CoV-2 infection: by 14%, 12%, 13% and 9%, respectively, after accounting for potentially influential factors, including underlying conditions and usual diet. No such effects were observed among those taking vitamin C, zinc, or garlic supplements. And when the researchers looked specifically at sex, age and weight (BMI), the protective associations for probiotics, omega-3 fatty acids, multivits and vitamin D were observed only in women of all ages and weights. No such clear associations were seen in men. Despite some differences, the same overall patterns were mirrored in both the US (45,757) and Swedish (27,373) subscribers. The equivalent figures for the US and Sweden were a reduced risk of:18% and 37%, respectively for probiotics; 21% and 16%, respectively, for omega-3 fatty acids; 12% and 22%, respectively for multivits; and 24% and 19%, respectively, for vitamin D supplements. This is an observational study, and as such, can't establish cause. The researchers also acknowledge several limitations, including that the study relied on self reported data and a self selected group. No information was collected on supplement doses or ingredients either. But although the observed effects were modest, they were significant, note the researchers, who call for large clinical trials to inform evidence-based therapeutic recommendations. "We know that a range of micronutrients, including vitamin D, are essential for a healthy functioning immune system. This, in turn, is key to prevention of, and recovery from, infections. "But to date, there is little convincing evidence that taking nutritional supplements has any therapeutic value beyond maintaining the body's normal immune response," comments Professor Sumantra Ray, Executive Director, NNEdPro Global Centre for Nutrition and Health, which co-owns the journal. "What's more, this study wasn't primarily designed to answer questions about the role of nutritional supplements in COVID-19. This is still an emerging area of research that warrants further rigorous study before firm conclusions can be drawn about whether specific nutritional supplements might lessen the risk of COVID-19 infection," he cautions. Vitamin D deficiency may impair muscle function Garvan Institute of Medical Research (Australia), April 16, 2021 Vitamin D deficiency may impair muscle function due to a reduction in energy production in the muscles, according to a mouse study published in the Journal of Endocrinology. Vitamin D deficient mice were found to have impaired muscle mitochondrial function, which may have implications for muscle function, performance and recovery. This may suggest that preventing vitamin D deficiency in older adults could help maintain better muscle strength and function and reduce age related muscle deterioration, but further studies are needed to confirm this. Vitamin D is a hormone well known to be important for maintaining bone health and preventing rickets and osteoporosis. In recent years, vitamin D deficiency has been reported to be as prevalent as 40% in European populations and linked to increased risk for several conditions, including COVID-19, cancer and diabetes. Although these studies report association rather than causation, the benefits of vitamin D supplementation are now a major subject of health debate. Multiple studies have also linked low vitamin D levels to poor muscle strength, particularly in older people. Skeletal muscle enables us to move voluntarily and perform everyday activities. It is essential that they have enough energy to power these movements. Specialised organs in cells, called mitochondria, convert nutrients in to energy to meet this demand. Previous studies indicate that impaired muscle strength in people with vitamin D deficiency may be linked to impaired muscle mitochondrial function. Determining the role of vitamin D in muscle performance of older people is also difficult, as they may suffer from a number of pre-existing health conditions that can also affect their vitamin D status. Therefore, previous studies have been unable to determine how vitamin D may directly affect muscle performance. Dr Andrew Philp and his team at the Garvan Institute of Medical Research in Australia, and collaborating universities, used a mouse model to determine the effects of diet-induced vitamin D deficiency on skeletal muscle mitochondrial function in young, male mice. Mice were either fed a diet with normal quantities of vitamin D, or with no vitamin D to induce deficiency, for a period of 3 months. A typical vitamin D level for humans is 40-50 nmol.L-1, and acute vitamin D deficiency is diagnosed when levels drop below 12 nmol.L-1. On average, the mice in this study had vitamin D levels of 30 nmol.L1, with diet-induced vitamin D deficiency leading to levels of just 3 nmol.L-1. Although this level was more extreme than typically observed in people, it is still within the clinically-recognised range. Tissue and blood samples were collected monthly to quantify vitamin D and calcium concentrations and to assess markers of muscle mitochondrial function and number. After 3 months of diet-induced vitamin D deficiency skeletal muscle mitochondrial function was found to be impaired by up to 37%. This was not due to a reduced number of mitochondria or a reduction in muscle mass. "Our results show there is a clear link between vitamin D deficiency and oxidative capacity in skeletal muscle. They suggest that vitamin D deficiency decreases mitochondrial function, as opposed to reducing the number of mitochondria in skeletal muscle." Dr Philp comments. "We are particularly interested to examine whether this reduction in mitochondrial function may be a cause of age related loss in skeletal muscle mass and function." These findings suggest that vitamin D deficiency may impair mitochondrial function and reduce the amount of energy produced in the muscles, which may lead to poor muscle function. Therefore, preventing vitamin D deficiency in older people may help maintain muscle performance and reduce the risk of muscle related diseases, such as sarcopenia. However, further studies that investigate the direct effect of vitamin D deficiency on muscle function and strength are necessary to confirm this. Whilst this study indicates that vitamin D deficiency can alter mitochondrial function in skeletal muscle, Dr Philp and his team were unable to determine precisely how this process occurred. Therefore, their future work aims to establish how vitamin D deficiency alters mitochondrial control and function in skeletal muscle. Psychedelic experience may not be required for psilocybin's antidepressant-like benefits So-called 'magic mushroom' drug seems to work through multiple brain mechanisms for its different effects University of Maryland School of Medicine, April 16, 2021 University of Maryland School of Medicine (UMSOM) researchers have shown that psilocybin--the active chemical in "magic mushrooms"-- still works its antidepressant-like actions, at least in mice, even when the psychedelic experience is blocked. The new findings suggest that psychedelic drugs work in multiple ways in the brain and it may be possible to deliver the fast-acting antidepressant therapeutic benefit without requiring daylong guided therapy sessions. A version of the drug without, or with less of, the psychedelic effects could loosen restrictions on who could receive the therapy, and lower costs, making the benefits of psilocybin more available to more people in need. In all clinical trials performed to date, the person treated with psilocybin remains under the care of a guide, who keeps the person calm and reassures them during their daylong experience. This can include hallucinations, altered perception of time and space, and intense emotional and spiritual encounters. Researchers in the field have long attributed psilocybin's effectiveness to the intense psychedelic experience. "We do not understand the mechanisms that underlie the antidepressant actions of psilocybin and the role that the profound psychedelic experience during these sessions plays in the therapeutic benefits," says Scott Thompson, Ph.D., Professor and Chair, Department of Physiology at UMSOM and senior author of the study. "The psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate." Several barriers prevent the wide-spread use of psychedelic compounds. For example, there is fear that the psychedelic experience may promote psychosis in people who are predisposed to severe mental disorders, like bipolar disorder and schizophrenia, so the clinical therapy sessions performed to-date have been limited to a highly selected screened group without a family history of these disorders. Dr. Thompson adds that there may also be an equity issue because not everyone can take several days off work to prepare and engage in the experience. The costs of staffing a facility with at least one trained guide per treated person per day and a private space may also be prohibitive to all but a few. He says it is conceivable that a depression treatment derived from psilocybin could be developed without the psychedelic effects so people can take it safely at home without requiring a full day in a care facility. For their study, led by UMSOM MD/PhD student Natalie Hesselgrave, the team used a mouse model of depression in which mice were stressed for several hours a day over 2-3 weeks. Because researchers cannot measure mouse moods, they measure their ability to work for rewards, such as choosing to drink sugar water over plain water. People suffering from depression lose the feeling of pleasure for rewarding events. Similarly, stressed mice no longer preferred sugar water over plain water. However, 24 hours after a dose of psilocybin, the stressed mice regained their preference for the sugar water, demonstrating that the drug restored the mice's pleasure response. Psilocybin exerts its effects in people by binding to and turning on receptors for the chemical messenger serotonin. One of these receptors, the serotonin 2A receptor, is known to be responsible for the psychedelic response. To see if the psychedelic effects of psilocybin were needed for the anti-depressive benefits, the researchers treated the stressed mice with psilocybin together with a drug, ketanserin, which binds to the serotonin 2A receptor and keeps it from being turned on. The researchers found that the stressed mice regained their preference for the sugar water in response to psilocybin, even without the activation of the psychedelic receptor. "These findings show that activation of the receptor causing the psychedelic effect isn't absolutely required for the antidepressant benefits, at least in mice," says Dr. Thompson, "but the same experiment needs to be performed in depressed human subjects." He says his team plans to investigate which of the 13 other serotonin receptors are the ones responsible for the antidepressant actions. "This new study has interesting implications, and shows that more basic research is needed in animals to reveal the mechanisms for how these drugs work, so that treatments for these devastating disorders can be developed" says Albert E. Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. Tea compound promotes formation of osteoblasts under inflammatory environment and increases bone mass First Affiliated Hospital of Soochow University (China), April 7, 2021 According to news originating from Suzhou, People’s Republic of China, the research stated, “Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk.” Our news correspondents obtained a quote from the research from First Affiliated Hospital of Soochow University: “Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3’-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers in vivo. In vitro experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/b-Catenin and BMP/Smad signaling pathways inhibited by TNF-a, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually.” According to the news reporters, the research concluded: “In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.” Patients who are overweight or obese at risk of more severe COVID-19 Murdoch Children's Research Institute and University of Queensland, April 16, 2021 Patients who are overweight or obese have more severe COVID-19 and are highly likely to require invasive respiratory support, according to a new international study. The research, led by the Murdoch Children's Research Institute (MCRI) and The University of Queensland and published in Diabetes Care, found obese or overweight patients are at high risk for having worse COVID-19 outcomes. They are also more likely to require oxygen and invasive mechanical ventilation compared to those with a healthy weight. MCRI researcher Dr Danielle Longmore said the findings, which highlighted the relationship between obesity and increased COVID-19 disease burden, showed the need to urgently introduce strategies to address the complex socio-economic drivers of obesity, and public policy measures such as restrictions on junk food advertising. "Although taking steps to address obesity in the short-term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke," she said. The study looked at hospitalised SARS-CoV-2 patients from 18 hospitals in 11 countries including China, America, Italy, South Africa and The Netherlands. Among the 7244 patients aged 18 years and over, 34.8 per cent were overweight and 30.8 per cent were obese. COVID-19 patients with obesity were more likely to require oxygen and had a 73 per cent greater chance of needing invasive mechanical ventilation. Similar but more modest results were seen in overweight patients. No link was found between being overweight or obese and dying in hospital from COVID-19. Cardiovascular and pre-existing respiratory diseases were associated with increased odds of in-hospital deaths but not a greater risk for needing oxygen and mechanical ventilation. For patients with pre-existing diabetes, there was increased odds of needing invasive respiratory support, but no additionally increase in risk in those with obesity and diabetes. Men were at an increased risk of severe COVID-19 outcomes and needing invasive mechanical ventilation. In those aged over 65 years, there was an increased chance of requiring oxygen and higher rates of in-hospital deaths. The University of Queensland's Dr Kirsty Short, who co-led the research, said almost 40 per cent of the global population was overweight or obese. "Obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue and SARS-CoV-1," she said. Dr Short said while previous reports indicated that obesity was an important risk factor in the severity of COVID-19, almost all this data had been collected from single sites and many regions were not represented. Moreover, there was a limited amount of evidence available about the effects of being overweight or obese on COVID-19 severity. "Given the large scale of this study we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalised with COVID-19," she said. MCRI Professor David Burgner, who co-led the research, said the data would help inform immunisation prioritisation for higher-risk groups. "At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease. Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority," he said. Neuroprotective Herbs for the Management of Alzheimer’s Disease University of Central Florida and University of California, Los Angeles Background—Alzheimer’s disease (AD) is a multifactorial, progressive, neurodegenerative disease that is characterized by memory loss, personality changes, and a decline in cognitive function. While the exact cause of AD is still unclear, recent studies point to lifestyle, diet, environmental, and genetic factors as contributors to disease progression. The pharmaceutical approaches developed to date do not alter disease progression. More than two hundred promising drug candidates have failed clinical trials in the past decade, suggesting that the disease and its causes may be highly complex. Medicinal plants and herbal remedies are now gaining more interest as complementary and alternative interventions and are a valuable source for developing drug candidates for AD. Indeed, several scientific studies have described the use of various medicinal plants and their principal phytochemicals for the treatment of AD. This article reviews a subset of herbs for their anti-inflammatory, antioxidant, and cognitive-enhancing effects. Methods—This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer’s disease and pre-Alzheimer’s disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions—Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD. 1.1. Ashwagandha (Withania somnifera) Ashwagandha, commonly called Indian ginseng or winter cherry, is one of the most prominent herbs prescribed as a brain rejuvenator for AD. It is prescribed to increase energy, improve overall health and longevity, and as a nerve tonic [86]. Ashwagandha has been shown to possess antioxidant activity, free radical scavenging activity, as well as an ability to support a healthy immune system [87]. Ashwagandha contains several bioactive compounds of great interest, such as ergostane-type steroidal lactones, including withanolides A-Y, dehydrowithanolide-R, withasomniferin-A, withasomidienone, withasomniferols A-C, withaferin A, withanone, and others. Other constituents include the phytosterols sitoindosides VII-X and beta-sitosterol and alkaloids [86,88]. A subset of these components has been shown to scavenge free radicals generated during the initiation and progression of AD. Molecular modeling studies showed that withanamides A and C uniquely bind to the active motif of Aβ25-35 and prevent fibril formation. Furthermore, these compounds protected PC-12 cells and rat neuronal cells from β-amyloid-induced cell death [89,90,91]. Treatment with the methanol extract of ashwagandha triggered neurite outgrowth in a dose- and time-dependent manner in human neuroblastoma cells [29], and, in another study involving cultured rat cortical neurons, treatment with Aβ peptide induced axonal and dendritic atrophy and loss of pre-and postsynaptic stimuli [92]. Subsequent treatment with withanolide A induced significant regeneration of both axons and dendrites and restored the pre- and post-synapses in the cultured cortical neurons. In vivo, withanolide A inhibited Aβ(25–35)-induced degeneration of axons, dendrites, and synapses in the cerebral cortex and hippocampus and also restored Aβ-peptide-induced memory deficits in mice [93]. The in vivo ameliorative effects were maintained even after the discontinuation of the drug administration. Aqueous extracts of ashwagandha increased acetylcholine (ACh) content and choline acetyl transferase activity in rats, which might partly explain the cognition-enhancing and memory-improving effects [29,94,95]. Treatment with the root extract caused the upregulation of the low-density lipoprotein receptor-related protein, which enhanced the Aβ clearance and reversed the AD pathology in middle-aged and old APP/PS1 mice [96]. Oral administration of a semi-purified extract of ashwagandha reversed behavioral deficits and blocked the accumulation of Aβ peptides in an APP/PS1 mouse model of AD. This therapeutic effect of ashwagandha was mediated by the liver low-density lipoprotein receptor-related protein [96]. Using an AD model of Drosophila melanogaster, researchers noted that treatment with ashwagandha mitigated Aβ toxicity and also promoted longevity [97]. Despite the extensive literature on the therapeutic effects of ashwagandha, there are limited data on its clinical use for cognitive impairment [98]. In a prospective, randomized, double-blind, placebo-controlled pilot study involving 50 subjects with mild cognitive impairment, subjects were treated with either ashwagandha root extract (300 mg twice daily) or placebo for eight weeks. After eight weeks of study, the ashwagandha treatment group demonstrated significant improvements in both immediate and general memory tests compared to the placebo group. Furthermore, the treatment group showed significant improvement in executive function, sustained attention, and information-processing speed [99]. These studies lend credence to ashwagandha’s role in enhancing memory and improving executive function in people with SCI or MCI. 1.2. Brahmi (Bacopa monnieri) Brahmi, or Bacopa monnieri (Bm), is a perennial creeper medicinal plant found in the damp and marshy wetlands of Southern and Eastern India, Australia, Europe, Africa, Asia, and North and South America. In the Ayurvedic system of medicine, Bm is recommended for mental stress, memory loss, epilepsy, insomnia, and asthma [34,36]. The bioactive phytochemicals present in this plant include saponins, bacopasides III, IV, V, bacosides A and B, bacosaponins A, B, C, D, E, and F, alkaloids, sterols, betulic acid, polyphenols, and sulfhydryl compounds, which may be responsible for the neuroprotective roles of the plant. Both in vitro and in vivo studies show that these phytochemicals have an antioxidant and free radical scavenging action by blocking lipid peroxidation in several areas of the brain [36,100,101,102]. Bm acts by reducing divalent metals, scavenging reactive oxygen species, decreasing the formation of lipid peroxides, and inhibiting lipoxygenase activity [103]. Numerous studies have also shown Bm’s role in memory and intellect [33,56,100,104,105,106]. To determine the neuroprotective effect of Bm in a rat model of AD, researchers tested an alcoholic extract of Bm at doses of 20, 40, and 80 mg/kg for a period of 2 weeks before and 1 week after the intracerebroventricular (icv) administration of ethylcholine aziridinium ion (AF64A). Spatial memory was tested using the Morris water maze (MWM), and the cholinergic neuron density was determined using histological techniques. The researchers showed that Bm extract improved the escape latency time in the MWM test and blocked the reduction of cholinergic neuron densities [35]. Another group reported the reversal of colchicine-induced cognitive deficits by a standardized extract of Bm. In addition to reversing colchicine-triggered cognitive impairment, the Bm extract also attenuated colchicine-induced oxidative damage by decreasing the protein carbonyl levels and restoring the activities of the antioxidant enzymes [107]. Most of the studies exploring the cognitive-enhancing effects of Bm in humans focused on normal, aged individuals. In a double-blind, randomized, placebo-controlled trial on 35 individuals aged above 55 years, subjects received either 125 mg of Bm extract or a placebo twice a day for a period of 12 weeks, followed by a placebo period of another four weeks. Subjects underwent a battery of memory tests, including general information, orientation, mental control, logical memory, digit forward, digit backward, visual reproduction, and paired association learning. Subjects were scored on each sub-test, and total memory score was calculated by adding the score of all subtests. A significant improvement was observed in mental control, logical memory, and paired association learning in Bm-treated patients compared to the placebo group at 8 and 12 weeks after initiation of the trial [37]. The results suggested the use of Bm in the treatment of age-associated memory impairment. Ten subjects were given 500 mg of Sideritis extract, 320 mg Bm extract, or a combination using a crossover design. Sideritis extract is rich in a variety of flavonoids and has been shown to improve cognition in animal models of AD [108]. The Attention d2 Test is a neuropsychological measure of selective and sustained attention and visual scanning speed. Assessment tests revealed that Sideritis extract combined with a low-dose Bm extract resulted in improvement in the d2 concentration test score [109]. A similar effect of Bm alone was observed only after repetitive dosing, suggesting that the long-term memory effects seen with repetitive dosing of Bm may be a promising therapeutic option for subjects suffering from MCI [109]. In another prospective, non-comparative, multicenter trial involving 104 subjects who suffered from MCI, Bm extract in combination with astaxanthin, phosphatidylserine, and vitamin E was given for 60 days. The tested combination formula was well tolerated. Cognitive and mnemonic performance was assessed with validated instruments including Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and Clock-Drawing Test (CDT) that can assess the risk of MCI progression to AD. Researchers noted significant improvements in ADAS-cog and CDT scores [110]. The observed sixty-day improvements in ADAS-cog and CDT were statistically significant as compared with baseline values. Memory is affected by several factors, including focus and attention, neurotransmitters, hormones, trophic factors, cyclic AMP, ion channels, protein transcription, synapse formation, and nutrients. Some of these processes can be modulated by Bm extract alone or in combination with other compounds. The abovementioned study design is similar to our therapeutic program for people with SCI and MCI, where Bm is administered in combination with other nutraceuticals and cogniceuticals [15,111]. 1.3. Cat’s Claw (Uncaria tomentosa) Cat’s claw (CC) is a tropical vine with hooked thorns that resemble the claws of a cat and is mainly recommended for its potential role in the treatment of AD and pre-AD. It is found mainly in the Amazon rainforest and other areas of South and Central America. This medicinal plant contains oxindole alkaloids, polyphenols (flavonoids, proanthocyanidins, and tannins), glycosides, pentacyclic alkaloids, and sterols [38,39]. CC is known for its immune-modulating and anti-inflammatory effects and for its role as a free radical scavenger. Based on in vitro studies, the anti-inflammatory effect of CC is attributed to its ability to inhibit iNOS gene expression, nitrate formation, cell death, PGE2 production, and the activation of NF-κB and TNF-α [45]. Using a transgenic mouse model of Alzheimer’s disease, a significant reduction in the Aβ load (by 59%) and plaque number (by 78%) in the hippocampus and cortex was observed after treating 8-month-old mice with the CC extract for 14 days [44]. CC extract also caused a significant reduction in astrocytosis and microgliosis, and it improved hippocampus-dependent memory. Some of the components in the CC extract crossed the blood–brain barrier (BBB) and entered the brain parenchyma following intravenous injection [44]. Pre-clinical studies suggest that CC extract inhibits the formation of plaques and tangles, reduces astrocytosis and microgliosis and improves memory in mouse models of AD [43,44]. CC extract not only prevented the formation and aggregation of Aβ fibrils and tau protein paired helical filaments, but it also facilitated the disaggregation of preformed fibrils and tau protein tangles [43,44]. While proanthocyanidin B2 was identified as the primary phytochemical with plaque-and tangle-dissolving activity, other polyphenols present in the CC extract also possess plaque-reducing activity [44]. Based on pre-clinical studies, Cat’s claw may be effective for memory loss and cognitive decline associated with AD, although no studies have been carried out in humans. 1.4. Ginkgo Biloba Ginkgo biloba (Gb) has been in the spotlight primarily for its potential role in treating AD. Gb also appears promising as a therapeutic agent for several other chronic and acute forms of diseases. The main pharmacologically active groups of compounds are flavonoids and terpenoids. Almost all clinical studies use Gb extract that contains a combination of flavonoid glycosides, terpene lactones, and ginkgolic acids [50]. Gb extract has shown beneficial effects in treating Alzheimer’s, cardiovascular diseases, cancer, tinnitus, and other age-associated conditions [49,50]. The suggested mechanisms of the Gb extract are its antioxidant effect, anti-platelet activating factor activity for vascular diseases, inhibition of β-amyloid peptide aggregation in AD, and decreased expression of peripheral benzodiazepine receptor for stress alleviation [48,49,50]. Gb is popular as a treatment for early-stage AD and vascular dementia. Gb extract reverses β-amyloid and NO-induced toxicity in vitro and reduces apoptosis both in vitro and in vivo [112,113,114]. Treatment with Gb extract enhanced memory retention in young and old rats and improved short-term memory in mice [49,115]. Several studies indicate that ginkgo delays the progression of AD and is as effective as the cholinesterase inhibitors for treating AD. A modest improvement in cognitive function was observed in AD subjects in various randomized, double-blind, placebo-controlled trials [116,117,118]. Gb extract also improves ADLs among AD individuals and is preferred over other AD medications because of its negligible adverse effects [119,120]. 1.5. Gotu Kola (Centella asiatica) Considered both a nutraceutical and cogniceutical, Gotu kola (Gk) is a staple in Chinese, Indonesian, and Ayurvedic medicine [57]. This medicinal plant is used to strengthen the brain, heal skin issues, and promote liver and kidney health. Gk is considered a rejuvenating herb for nerve and brain cells as it is believed to promote intelligence and improve memory [54,55,56,57]. In vitro studies using various Gk plant derivatives (asiaticosides, asiatic acid, madecassoside, and madasiatic acid) showed that these compounds were capable of blocking H2O

covid-19 america women university amazon california health australia europe uk china school future young phd professor africa michigan chinese european executive director italy management medicine study pennsylvania south detroit south africa north nutrition indian mba md attention sweden memory pc treatments netherlands alzheimer's disease cat southern thompson south america swedish public health iv researchers morris previous similar world health organization queensland obesity cognitive thursday night football oral central america vitamin d ach gb cc sars cov central florida indonesians bmi mice physiology numerous subjects ayurvedic bbb henry ford molecular eligible jansen dietary adas subsequent tissue spatial medicinal 2a bm h2o medical research research institute endocrinology b2 danville gk l1 cdt google scholar maryland school ashwagandha queen mary university of london medical affairs mci european society skeletal scott thompson nfb drosophila philp cmr inos specialised wnt south carolina school uk biobank henry ford health system mwm adls aqueous scopus murdoch children postmenopausal between may geisinger health system maryland baltimore garvan institute mapk gotu gary null john z pge2 cardiology esc catenin

The Gary Null Show - 04.12.21

The Gary Null Show

Play Episode Listen Later Apr 12, 2021

Sufficient vitamin D during gestation and early life can lower susceptibility to allergy in infants Wageningen University (Netherlands), April 5, 2021 According to news originating from Wageningen, Netherlands, the research stated, “Worldwide, the prevalence of allergies in young children, but also vitamin D deficiency during pregnancy and in newborns is rising. Vitamin D modulates the development and activity of the immune system and a low vitamin D status during pregnancy and in early life might be associated with an increased risk to develop an allergy during early childhood.” Our news editors obtained a quote from the research from Wageningen University and Research: “This review studies the effects of vitamin D during gestation and early life, on allergy susceptibility in infants. The bioactive form of vitamin D, 1,25(OH)2D, inhibits maturation and results in immature dendritic cells that cause a decreased differentiation of naive T cells into effector T cells. Nevertheless, the development of regulatory T cells and the production of interleukin-10 was increased. Consequently, a more tolerogenic immune response developed against antigens. Secondly, binding of 1,25(OH)2D to epithelial cells induces the expression of tight junction proteins resulting in enhanced epithelial barrier function. Thirdly, 1,25(OH)2D increased the expression of anti-microbial peptides by epithelial cells that also promoted the defense mechanism against pathogens, by preventing an invasive penetration of pathogens.” According to the news editors, the research concluded: “Immune intervention by vitamin D supplementation can mitigate the disease burden from asthma and allergy. In conclusion, our review indicates that a sufficient vitamin D status during gestation and early life can lower the susceptibility to develop an allergy in infants although there remains a need for more causal evidence.” Training in compassion improves the well-being of relatives to people with mental illness Aarhus University (Denmark), April 7, 2021 If relatives of people with mental illness become better at accepting the difficult emotions and life events they experience - which is what training in compassion is about - their anxiety, depression and stress is reduced. These are the results of a new study from the Danish Center for Mindfulness at Aarhus University. Being a relative of a person with a mental illness can be very burdensome. It can feel like a great responsibility, and many people struggle with feelings of fear, guilt, shame and anger. A new study from the Danish Center for Mindfulness shows that eight weeks of training in compassion can significantly improve the well-being of relatives. Compassion is a human quality that is anchored in the recognition of and desire to relieve suffering. In other words, compassion occurs when we come into contact with our own or others' suffering and feel motivated to relieve our own or others pain. "After completing the course, the relatives had increased their well-being on several parameters. They could deal with the illness in a new and more skillful way, and we saw that the training reduced their symptoms of depression, anxiety and stress," says psychologist and PhD student Nanja Holland Hansen, who is behind the study. And the positive results were maintained after a six month follow-up. Trying to fix what is difficult "The relatives learned that the more they turn towards what is difficult, the more skillful they may act. For example, relatives often try to 'fix' the problem or the challenge - so as to relieve their loved ones of what is difficult. That's a huge pressure to constantly deal with, and very few people can bear it," says Nanja Holland Hansen. Living with chronic fear She goes on to explain that training in compassion helps people to find the strength and courage to bear pain and suffering when life is difficult. It may seem both sensible and intuitive to guard yourself from the confrontation or avoid what is difficult and unpleasant. But this is the paradox of the training, explains the researcher. Because it is precisely actions and thoughts like these that shut down our compassion and thereby maintain the suffering. "Fear and grief are emotions that take up a lot space for relatives of people with mental illness. For example chronic fear, which is a real fear that parents of a child with schizophrenia have about whether their child is going to commit suicide, or whether a child with autism will ever enjoy a 'normal life'," explains Nanja Holland Hansen and continues: "Our suffering is maintained inside of us when we don't work with it. To avoid feeling pain, we may resort to behaviour such as working too much or buying things that we don't need. It's therefore in all these everyday actions that our compassion training becomes important and can be used to help alleviate what is difficult," she says. No one escapes The purpose of training in compassion is thus more than just feeling empathy or worrying about another person. "Not a single person can completely avoid experiencing painful things in their life. In this way we're all the same. But what isn't the same for everyone is our ability to deal with the pain and suffering we experience. Training programmes in compassion have been developed because the research shows that we can train and strengthen our mental health. With systematic training of compassion, we generate more attention - and understanding of - our own thoughts, feelings and behaviour. And this helps us to develop the tools and skills to engage in healthier relations with ourselves and others," she explains. A total of 161 relatives of people with mental illness participated in the study. This makes the study one of the largest of its kind in the world, and also the first scientific randomised clinical trial carried out with relatives in Denmark. The relatives were between 18 and 75 of age and were family members to people with various psychiatric disorders such as e.g. ADHD, schizophrenia and depression. Meditation as homework The relatives met once a week in groups of twenty participants over an eight-week period. Each session lasted two hours and was structured with small group exercises, large group discussions, instruction in the theme of the week and meditation. The homework consisted of twenty minutes of daily meditation. "There is definitely a shortage of offers for these relatives. They're often told that they should remember to take care of themselves, but they haven't learned how to. We found that those who were involved in the study received the tools for precisely this," says Nanja Holland Hansen. The results have just been published in the scientific journal JAMA. "My hope is that local authorities and regions can offer this type of intervention for relatives. It should be an option and could easily be incorporated into our healthcare system. Economically and socially, a healthy person going on sick leave solely because he or she is a relative is a huge loss," says the researcher. [Billedtekst:]: "Up to fifty percent of relatives of people with mental illness risk becoming ill themselves. That's why it's important that we also keep them and their well-being in mind," says Nanja Holland Hansen. Sesaminol prevents Parkinson's disease by activating the Nrf2-ARE signaling pathway Osaka City University (Japan), March 331, 2021 Parkinson's disease (PD) is a neurodegenerative disease caused by the degeneration of substantia nigra neurons due to oxidative stress. Sesaminol has strong antioxidant and anti-cancer effects. We investigated the preventive effect on PD as a new physiological action of sesaminol produced from sesaminol glycoside using in vitro and in vivo PD models. To prepare an in vitro PD model, 6-hydroxydopamine (6-OHDA) was added to human neuroblastoma (SH-SY5Y cells). The viability of SH-SY5Y cells decreased dose-dependently following 6-OHDA treatment, but the addition of sesaminol restored viability to the control level. 6-OHDA increased intracellular reactive oxygen species production, and the addition of sesaminol significantly suppressed this increase. No Nrf2 expression in the nucleus was observed in the control group, but a slight increase was observed in the 6-OHDA group. The sesaminol group showed strong expression of Nrf2 in the cytoplasm and nucleus. NAD(P)H: quinone oxidoreductase (NQO1) activity was enhanced in the 6-OHDA group and further enhanced in the sesaminol group. Furthermore, the neurotoxine rotenone was orally administrated to mice to prepare an in vivo PD model. The motor function of rotenone-treated mice was shorter than that of the control group, but a small amount of sesaminol restored it to the control level. The intestinal motility in the rotenone group was significantly lower than that in the control group, but it remained at the control level in the sesaminol group. The expression of α-synuclein in the substantia nigra increased in the rotenone group but decreased in the sesaminol group. The rotenone group exhibited shortening and damage to the colonic mucosa, but these abnormalities of the colonic mucosa were scarcely observed in the sesaminol group. These results suggest that sesaminol has a preventative effect on PD. Study finds connection between lifestyle choices, Alzheimer disease Brigham Young University, April 8, 2021 A recent study out of BYU has linked lifestyle choice to Alzheimer's disease, at least to some degree, through findings that show a possible energy gap between the amount of glucose and ketones being used to power the brain. BYU professor Ben Bikman, who studies diabetes and insulin resistance, thought of a fundamental question surrounding Alzheimer's disease and insulin resistance in the brain. Bikman said there has been growing evidence that the brains in humans with Alzheimer's disease are deficient in the use of glucose. "The brain has a certain energy demand, let's say that is 100%," Bikman said. "In most instances, glucose is providing virtually all of that energy, nearly 100% all of the time. There is a secondary fuel known as ketones, so the average brain is consuming almost all of its energy from glucose with a little bit of energy coming from ketones at any moment. In some individuals, the brain starts to become deficient in its ability to use glucose. So now glucose can only provide about 60% of that energy, and then ketones would be expected to fill up the rest of that energy. The tragedy is that the average individual has almost undetectable levels of ketones and that's entirely a matter of lifestyle." This lack of ketones as well as the brain's resistance to insulin is linked to lifestyle. Insulin is expected to stimulate tissues or cells to take in the glucose and use it for energy. As the brain becomes more insulin resistant, it can't take in glucose anymore and this is something Bikman said has been shown in other research. The BYU research expanded on some of those findings. "We found that indeed the expression of genes involved in glucose metabolism was significantly down, very broad across every cell type we looked at in the brain," Bikman said. "All of the cell types we looked at had significant reductions in glucose-related genes, but the ketone-related genes were almost totally normal." This is key because it shows that if the brain can receive more ketones, there is a possibility that one could overcome that energy gap. While it may not be able to be filled in with glucose, it can be with ketones but ketones need to be produced by one's body. With many people having diets that are high in refined sugars and starches, insulin is elevated all of the time, and ketones are only produced when insulin levels are low. These conditions include fasting or low-carb diets, also known as keto diets. Ph.D. student Erin Saito is another one of the lead authors of the study and is doing this project as her dissertation. Another collaborator included Washington University of Saint Louis, which gave the BYU research team access to various brain banks. "BYU is a wonderfully collaborative environment, not only encouraging collaborations within the university but also outside of the university," Bikman said. "Thus communicating with our internal and external collaborators was very easy and very natural. There was very much a common interest to work on this project together, a common enthusiasm for answering a question that had not been asked yet. It would not have been possible without that mutual collaboration and enthusiasm." He added that managing the project with enthusiastic students was a delight, making it easy because of the enthusiasm surrounding the project. Bikman said it is gratifying for him to be able to contribute to what little is known about Alzheimer's disease, because traditional strategies and approaches have continued to fail. "Looking at Alzheimer's disease as a metabolic problem, I would say, is the greatest breakthrough in our understanding of the disease in decades," Bikman said. Looking at it through the metabolic side of things allows people to possibly detect the problem years in advance, looking at changes in brain glucose metabolism long before Alzheimer's sets in. Bikman believes that someday the metabolic approach to Alzheimer's will be the standard of care. Moving forward, Bikman said he hopes that people feel empowered when it comes to Alzheimer's disease. He wants people to not look at it as a passive process where they are the victim, but rather acknowledging that their lifestyle choices can either act as the culprit or the cure. "For too long we have viewed Alzheimer's disease as a disease that is no respecter of person, no respecter of choices and that is simply not true," Bikman said. "We have long known that people with metabolic disorders, like type 2 diabetes and insulin resistance, are at significantly greater risk of developing Alzheimer's disease and we have more evidence suggesting that dietary choices and changes do make significant improvements in someone's cognition." Even someone in the midst of Alzheimer's disease can see improvements in memory and learning with a lifestyle change, according to Bikman, and he added that he hopes this evidence will help to strengthen that view and empower individuals to take matters into their own hands. New Study Shows Broad Benefits Of High-CBD Cannabis Health Canada Research Institute, April 6, 2021 With CBD exploding in popularity, new studies continue to reveal its potential benefits. A new study published in the journal Aging-US reported that high-CBD cannabis has anti-inflammatory and anti-cancer properties and may even help reduce COVID symptoms. Cannabidiol, or CBD, is a non-psychoactive compound in cannabis and is legal in all 50 states. “Cannabis sativa, especially those high in the anti-inflammatory cannabinoid cannabidiol, has been found to alter gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties,” the researchers at Health Canada concluded. As such, they say specific CBD extracts “may become a useful and safe addition to the prevention/treatment of COVID-19 as an adjunct therapy.” Researchers hypothesized that high-CBD C. sativa extracts may be used to down-regulate ACE2 expression in target COVID-19 tissues. Using artificial 3D human models of oral, airway and intestinal tissues, they identified 13 high-CBD C. sativa extracts that decrease ACE2 protein levels. Some C. sativa extracts down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV-2 entry into host cells. This is not the first study to suggest that CBD could combat respiratory illnesses like COVID. In April 2020, researchers at the University of Nebraska and the Texas Biomedical Research Institute published a peer-reviewed article suggesting that CBD could be included in the treatment regimen for the COVID-19 coronavirus as THC and CBD both appeared to reduce the severe lung inflammation associated with the virus. In July 2020, researchers at the Dental College of Georgia and Medical College of Georgia found early evidence that Cannabidiol, or CBD, may help reduce the cytokine storm and excessive lung inflammation that killed many patients with COVID-19. “Our laboratory studies indicate pure CBD can help the lungs recover from the overwhelming inflammation, or cytokine storm, caused by the COVID-19 virus, and restore healthier oxygen levels in the body,” says co-author Dr. Jack Yu, physician-scientist and chief of pediatric plastic surgery at MCG. In October 2020, the same research group published a follow-up peer-reviewed study identifying the mechanism they believe was responsible for the encouraging results of using CBD to reduce lung inflammation. “One way CBD appears to reduce the “cytokine storm” that damages the lungs and kills many patients with COVID-19 is by enabling an increase in levels of a natural peptide called apelin, which is known to reduce inflammation and whose levels are dramatically reduced in the face of this storm,” they concluded. While this is incredibly encouraging news for relief from COVID, businesses that sell CBD edibles and oils are not allowed to mention these benefits in advertising because the FDA has not officially approved it for any specific treatment. Apparently, experimental vaccines are okay to advertise but natural plant extracts aren’t. The new study above is just another to suggest cannabis and CBD can help fight cancer. There have been many studies as well as countless confirmed anecdotal accounts. In 2018, a 44-year-old UK mom refused chemo for her aggressive triple-negative breast cancer. She opted for CBD oil instead and was declared cancer-free five months later. In 2019, an 81-year-old diagnosed with lung cancer shrunk his tumors in half by taking CBD oil. The case study was published in the peer-reviewed journal Sage. More recently, a Colorado State University study showed that CBD extract can slow growth and kill cancer cells in aggressive brain cancer. “Our experiments showed that CBD slows cancer cell growth and is toxic to both canine and human glioblastoma cell lines,” said Chase Gross, a doctoral student participating in the study. “Importantly, the differences in anti-cancer affects between CBD isolate and extract appear to be negligible.” That’s not all, CBD has shown potential for treating a variety of other ailments such as arthritis, seizures, chronic pain, high blood pressure, Alzheimer’s and more – with little to no severe side effects that are common with leading pharmaceuticals. Big Pharma hopes more people don’t discover natural treatments to common health issues, like CBD, because it could severely impact their profits and influence. Polyphenol pills counter inflammation in women on hormonal contraceptives: RCT Universidade Federal do Rio Grande do Sul (Brazil), April 7, 2021 Supplements containing a mixture of polyphenols may counter increases in pro-inflammatory markers in women of childbearing age using combined hormonal contraceptives, says a new study. The supplements, formulated with resveratrol, catechin, quercetin, chlorogenic acid and cyanidin, were also found to prevent the increases in markers of systemic oxidative stress like F2-isoprostane, according to findings published in Prostaglandins, Leukotrienes and Essential Fatty Acids . “The increase in biomarkers of inflammation and oxidative stress observed in the present study were possibly caused by the use of hormonal contraceptives, as verified in the [control group], and this change was not observed in the group that used polyphenols,” wrote researchers from the Institute of Cardiology and the Universidade Federal do Rio Grande do Sul in Brazil. “Therefore, the results of this polyphenol supplementation showed that the antioxidant and anti-inflammatory effects observed in the studied population is due to the reduction in plasma levels of PGE2, supporting the conceptual hypothesis, by its action on the inflammatory cascade, probably by COX inhibition.” Study details The Brazil-based researchers recruited 40 women aged between 25 and 35 using contraceptives, and randomly assigned them to receive either placebo or polyphenols (3,000 mg per day) for 15 days. “A higher dosage was chosen in order to reduce the risk of food ingestion of control group to overcome the dosage of polyphenol supplementation in the [polyphenol group],” they explained. Data from the 28 women who completed the study indicated that, as expected, markers of inflammation (PGE2 and C-reactive protein) and oxidative stress (F2-isoprostane) increased significantly in women in the placebo group. However, no such increases were observed in the polyphenol group. “Among participants of the polyphenols group, an inverse correlation was observed between the consumption of polyphenols estimated by the [food frequency questionnaire] with PGE2 levels at the end of the study. This finding had not yet been previously described in the literature and reinforces the hypothesis of the present study regarding the action of polyphenols in reducing PGE2 levels,” wrote the researchers. “The liver is the main organ involved in the metabolism of polyphenols, and metabolites are secreted in bile and urine. Excretion of polyphenols in participants of the [polyphenol group] was significantly higher than in the [control group], confirming the effective ingestion of capsules and absorption of compounds, which can vary depending on the amount ingested, the chemical structure of the substance and the intestinal flora of the subjects.” Childhood diet and exercise creates healthier, less anxious adults University of California Riverside, April 9, 2021 Exercise and a healthy diet in childhood leads to adults with bigger brains and lower levels of anxiety, according to new UC Riverside research in mice. Though diet and exercise are consistently recommended as ways to promote health, this study is the first to examine the long-lasting, combined effects of both factors when they are experienced early in life. "Any time you go to the doctor with concerns about your weight, almost without fail, they recommend you exercise and eat less," said study lead and UCR physiology doctoral student Marcell Cadney. "That's why it's surprising most studies only look at diet or exercise separately. In this study, we wanted to include both." The researchers determined that early-life exercise generally reduced anxious behaviors in adults. It also led to an increase in adult muscle and brain mass. When fed "Western" style diets high in fat and sugar, the mice not only became fatter, but also grew into adults that preferred unhealthy foods. These findings have recently been published in the journal Physiology and Behavior. To obtain them, the researchers divided the young mice into four groups -- those with access to exercise, those without access, those fed a standard, healthy diet and those who ate a Western diet. Mice started on their diets immediately after weaning, and continued on them for three weeks, until they reached sexual maturity. After an additional eight weeks of "washout," during which all mice were housed without wheels and on the healthy diet, the researchers did behavioral analysis, measured aerobic capacity, and levels of several different hormones. One of those they measured, leptin, is produced by fat cells. It helps control body weight by increasing energy expenditure and signaling that less food is required. Early-life exercise increased adult leptin levels as well as fat mass in adult mice, regardless of the diet they ate. Previously, the research team found that eating too much fat and sugar as a child can alter the microbiome for life, even if they later eat healthier. Going forward, the team plans to investigate whether fat or sugar is more responsible for the negative effects they measured in Western-diet-fed mice. Together, both studies offer critical opportunities for health interventions in childhood habits. "Our findings may be relevant for understanding the potential effects of activity reductions and dietary changes associated with obesity," said UCR evolutionary physiologist Theodore Garland. In other words, getting a jump start on health in the early years of life is extremely important, and interventions may be even more critical in the wake of the pandemic. "During the COVID-19 lockdowns, particularly in the early months, kids got very little exercise. For many without access to a park or a backyard, school was their only source of physical activity," Cadney said. "It is important we find solutions for these kids, possibly including extra attention as they grow into adults." Given that exercise was also shown to reduce adult anxiety, Cadney believes children who face these challenges may face unique physical and mental health issues as they become adults in the coming decade.

Translational profiling of mouse dopaminoceptive neurons reveals a role of PGE2 in dorsal striatum

Play Episode Listen Later Sep 3, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.02.279240v1?rss=1 Authors: Montalban, E., Giralt, A., Taing, L., Nakamura, Y., Martin, C., de Pins, B., Pelosi, A., Goutebroze, L., Castell, L., Wang, W., Daila Neiburga, K., Vestito, L., Nairn, A. C., Valjent, E., Herve, D., Heintz, N., Gambardella Le Novere, N., Greengard, P., Roussarie, J.-P., Girault, J.-A. Abstract: Forebrain dopaminoceptive neurons play a key role in movement, action selection, motivation, and working memory. Their activity is dysregulated in addiction, Parkinson's disease and other conditions. To characterize the diverse dopamine target neuronal populations, we compare translating mRNAs in neurons of dorsal striatum and nucleus accumbens expressing D1 or D2 dopamine receptor and prefrontal cortex expressing D1 receptor. We identify D1/D2 and striatal dorso-ventral differences in the translational and splicing landscapes, which establish the characteristics of dopaminoceptive neurons. Expression differences and network analyses identify novel transcription factors with presumptive roles in these differences. Prostaglandin E2 appears as a candidate upstream regulator in the dorsal striatum, a hypothesis supported by converging functional evidence indicating its role in enhancing D2 dopamine receptor action. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns, and reveals the unforeseen role of prostaglandin E2 in the dorsal striatum. Copy rights belong to original authors. Visit the link for more info

#398 Chronic Spinal Pain and Food

Life By Design Podcast

Play Episode Listen Later Sep 2, 2020 6:22

You are what you eat. Maybe not literally, but to pretend that what you put into your body doesn't affect your health and performance is nonsense. Today we review a study from the University of Michigan seeking to establish an association between chronic spinal pain and diet. In some ways, we already know (there was a Nobel prize given in 1982 for the PGE2 and Omega-6 link) that a poor diet can lead to increased pain byways of inflammation. But this study wants to link chronic spinal pain to more certain types of diets and people who eat those diets. The purpose of this podcast is to review the data, give our opinions and let you know how we believe this applies to your life and what you can do to make your health better. What We Cover Spinal pain (pain in the back, neck, and hip) affects 54% to 80% of adults and is a leading cause of physical disability and associated problems, including decreased quality of life, unemployment, and mood disorders. How the costs add up! The impact of chronic spinal pain is approximately $253 billion annually. What are the mechanisms linking diet to chronic pain? How does sugar intake affect chronic pain?

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Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Play Episode Listen Later Aug 3, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.31.231753v1?rss=1 Authors: Tavares-Ferreira, D., Ray, P., Sankaranarayanan, I., Mejia, G. L., Wangzhou, A., Shiers, S., Uttarkar, R. S., Megat, S., Barragan-Iglesias, P., Dussor, G., Akopian, A. N., Price, T. J. Abstract: Background: There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences. Methods: We used Translating Ribosome Affinity Purification (TRAP) sequencing and behavioral pharmacology to test the hypothesis that nociceptor (Nav1.8 expressing neurons) translatomes would differ by sex. Results: We found 66 genes whose mRNA were sex-differentially bound to nociceptor ribosomes. Many of these genes have known neuronal functions but have not been explored in sex differences in pain. We focused on Ptgds, which was increased in female mice. The mRNA encodes the prostaglandin D2 (PGD2) synthesizing enzyme. We observed increased Ptgds protein and PGD2 in female mouse DRG. The Ptgds inhibitor AT-56 caused intense pain behaviors in male mice but was only effective at high doses in females. Conversely, female mice responded more robustly to another major prostaglandin, PGE2, than did male mice. Ptgds protein expression was also higher in female cortical neurons, suggesting DRG findings may be generalizable to other nervous system structures. Conclusions: Nociceptor TRAP sequencing (TRAP-seq) reveals unexpected sex differences in one of the oldest known nociceptive signaling molecule families, the prostaglandins. Our results demonstrate that translatome analysis reveals physiologically relevant sex differences important for fundamental protective behaviors driven by nociceptors. Copy rights belong to original authors. Visit the link for more info

price trap copy mice mrna conversely divergent male and female mejia signaling sex differences drg biorxiv transcriptome prostaglandin pge2 nav1 megat nociceptor

July 29, 2020

The COVID-19 LST Report

Play Episode Listen Later Aug 3, 2020 5:52

On today's episode we discuss: — Climate: The Immunization Action Coalition and the Vanderbilt School of Medicine discuss the progress of developing a COVID-19 vaccine, detailing the 11 vaccines in phase 1/2 clinical trials and the inclusion of multiple countries in the development of a Target Product Profile, a tool for quantifying critical vaccine characteristics. The authors emphasize the need for well-established infrastructure and logistical planning in order to distribute a potential COVID-19 vaccine safely and effectively to the world in a timely manner. — Epidemiology: Researchers in the United States and United Kingdom used Twitter data to predict human mobility in and out of China and estimate global spread of COVID-19 and found a high correlation between country-level Twitter user visits and reported COVID-19 cases. These findings highlight the utility of geolocated platforms for public health authorities to develop response protocols and assess impending risks of COVID-19. — Transmission and Prevention: Based on literature of prostaglandins in SARS-CoV-1 and MERS-CoV, a group from the University of Edinburgh cite the potential roles of multiple prostaglandins (including PGD2, PGE2, PGI2) in the pathogenesis of COVID-19 and consider the possible benefits of NSAID usage in COVID-19 patients. — Management: A study found that among 59 patients with symptoms consistent with COVID-19, fibrinogen levels were markedly higher in patients who ultimately tested positive on RT-PCR compared to those who tested negative. Additionally, the neutrophil-to-lymphocyte ratio was increased in critically ill COVID-19 patients. These results suggest that fibrinogen may have value as a diagnostic marker in patients with suspected COVID-19 and that neutrophil to lymphocyte ratio may be useful as a prognostic marker indicative of COVID-19 disease severity. — Adjusting Practice: A cross sectional study of 26 heart failure patients found a 16.2% decrease in daily step count on wearable accelerometers during the first 3 weeks of quarantine compared to regular activity suggesting that widespread COVID-19 quarantine mandates were detrimental to physical activity habits in these patients. These findings highlight the importance of physical activity during the pandemic in reducing deterioration in cardiovascular health. — R&D Diagnosis and Treatment: Investigators in China measured SARS-CoV-2-specific antibodies among moderate and severe COVID-19 patients as well as non-COVID-19 patients and found that IgA and IgG were higher among severe patients compared to moderate patients whereas no difference was observed between the groups in IgM. Based on their findings, the authors suggest that IgA-IgG serological diagnosis of COVID-19 may be more effective than the traditional detection of IgM-IgG combined antibodies. --- Support this podcast: https://anchor.fm/covid19lst/support

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Oncotarget: miR-708-5p targets oncogenic prostaglandin E2 production in lung cancer cell

Oncotarget

Play Episode Listen Later Jul 7, 2020 3:36

Volume 11, Issue 26 of Oncotarget reported that Lung cancer is of particular importance, as it is the deadliest cancer worldwide. In this study, the authors show that high mi R-708 expression is associated with survival rates in lung squamous cell carcinoma patients. mi R-708 also represses PGE2 production by suppressing both COX-2 and mPGES-1 expression in lung cancer cells. Moreover, mi R-708 decreases proliferation, survival, and migration of lung cancer cells, which can be partially attributed to mi R-708's inhibition of PGE2 signaling. Lastly, they identify novel mi R-708 predicted targets and possible regulators of mi R-708 expression in lung cancer. Collectively, these data demonstrate that dysregulated mi R-708 expression contributes to exacerbated PGE2 production, leading to an enhanced pro-tumorigenic phenotype in lung cancer cells. Dr. Carol S. Lutz from The Department of Microbiology, Biochemistry, and Molecular Genetics at Rutgers Biomedical & Health Sciences, New Jersey Medical School, School of Graduate Studies in Newark New Jersey USA said, "Lung cancer is the most common cancer, with more than 2.09 million lung cancer cases worldwide in 2018." More importantly, lung cancer is the deadliest cancer in the world, with more than 1.79 million lung cancer-related deaths in 2018. Lung cancer is a collection of several distinct subtypes, with non-small cell lung cancer accounting for 85% of all lung tumors. mi R-708 also indirectly regulates the expression of genes involved in PI3K signaling, cell cycle progression, epithelial-mesenchymal transition, and cancer cell stemness. In this study, the authors aim to decipher novel mi R-708 targets and suggest a solution to the controversy on whether mi R-708 is an oncogenic or tumor-suppressive mi RNA in lung cancer. The Lutz Research Team concluded in their Oncotarget Research Paper that collectively, their findings suggest further study of mi R-708 in lung cancer. The data paired with previous studies highlight a potential value for mi R-708 as a diagnostic in differentiating lung tumors, as well as a potential therapeutic intervention, particularly in lung squamous cell carcinomas. Their work has identified novel tumor-suppressive mi R-708 functions by suppressing oncogenic PGE2 production through targeting of COX-2 and mPGES-1. These findings could be the foundation for identifying novel mi R-708 targets, as well as regulators of mi R-708 expression in cancer. Moreover, the study highlights the need to better understand lung cancer biology to improve the diagnosis and treatment of lung cancer, ultimately aiming to increase positive patient outcomes. Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/oncotarget.27614 Full text - https://www.oncotarget.com/article/27614/text/ Correspondence to - Carol S. Lutz - lutzcs@njms.rutgers.edu Keywords - miR-708-5p, miR-708, lung cancer, COX-2, mPGES-1 About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105

Neuroendocrine mechanisms governing sex-differences in chronic pain involve prolactin receptor sensory neuron signaling

Play Episode Listen Later Apr 27, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.25.061663v1?rss=1 Authors: Paige, C., Barba-Escobedo, P. A., Mecklenburg, J., Patil, M., Goffin, V., Grattan, D., Dussor, G., Akopian, A. N., Price, T. J. Abstract: Many clinical and preclinical studies report higher prevalence and severity of chronic pain in females. We used hyperalgesic priming with interleukin 6 (IL6) priming and PGE2 as a second stimulus as a model for pain chronicity. Intraplantar IL6 induced hypersensitivity was similar in magnitude and duration in both males and females, while both paw and intrathecal PGE2 hypersensitivity was more persistent in females. This difference in PGE2 response was dependent on both circulating estrogen and translation regulation signaling in the spinal cord. In males, the duration of hypersensitivity was regulated by testosterone. Since the prolactin receptor (Prlr) is regulated by reproductive hormones and is female-selectively activated in sensory neurons, we evaluated whether Prlr signaling contributes to hyperalgesic priming. Using a competitive Prlr antagonist, and a mouse line with ablated Prlr in the Nav1.8 sensory neuronal population, we show that Prlr in sensory neurons is necessary for the development of hyperalgesic priming in female but not male mice. Overall, sex-specific mechanisms in the initiation and maintenance of chronic pain are regulated by the neuroendocrine system and, specifically, sensory neuronal Prlr signaling. SIGNIFICANCE STATEMENT: Females are more likely to experience chronic pain than males, but the mechanisms that underlie this sexual dimorphism are not completely understood. Here, we demonstrate that the duration of mechanical hypersensitivity is dependent on circulating sex hormones in mice, where estrogen caused an extension of sensitivity and testosterone was responsible for a decrease in the duration of the hyperalgesic priming model of chronic pain. Additionally, we demonstrated that Prolactin receptor expression in Nav1.8+ neurons was necessary for hyperalgesic priming in female, but not male mice. Our work demonstrates a female-specific mechanism for the promotion of chronic pain involving the neuroendrocrine system and mediated by sensory neuronal prolactin receptor. Copy rights belong to original authors. Visit the link for more info

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Microneedling + Topical PGE2 – The Most Effective Hair Growth Agonist?

Play Episode Listen Later Apr 14, 2020 10:04

topical hair growth microneedling agonist pge2

Episode 148: Gastric Brooding and Other Frogs

Strange Animals Podcast

Play Episode Listen Later Dec 2, 2019 12:59

Thanks for Merike for suggesting the gastric brooding frog and to Hally for suggesting newly-discovered frogs!! The Gastric brooding frog: Darwin's frog, round boi: The Surinam toad carries her eggs and tadpoles in the skin of her back: Kermit the frog and a newly discovered glass frog: Show transcript: Welcome to Strange Animals Podcast. I’m your host, Kate Shaw. This week we have another fantastic listener suggestion, about frogs! Merike is a herpetologist from Estonia, who suggested the gastric brooding frog, and another listener, Hally, also wanted to learn about some of the new frog species discovered recently. The gastric brooding frog is native to eastern Australia, specifically Queensland. There are two species, and both of them live in creeks in separate rainforests. The habitat is specific and small, and unfortunately both species went extinct less than forty years ago. Researchers aren’t sure why they went extinct, but it was probably due to pollution and habitat loss. The gastric brooding frog was a slender frog, with the northern gastric brooding frog being about three inches long, or about 8 cm, while the southern gastric brooding frog was about half that size. Females were larger than males. It was grey or brown-gray in color with some darker and lighter patches on the back with a lighter belly. During the day it spent most of its time at the water’s edge, hidden in leaf litter or among rocks, although it generally only fully came out of the water when it was raining. It ate insects and may have hibernated in winter. As you may have guessed from its name, the gastric brooding frog had a unique way of taking care of its eggs. After the eggs were fertilized, the female would actually swallow the eggs and keep them in her stomach while they developed. Even after the eggs hatched into tadpoles, they stayed in the mother’s stomach. As they grew larger, the stomach also grew larger, until it pretty much filled up the mother’s insides, to the point where she couldn’t even use her lungs to breathe. Fortunately many frogs, including the gastric brooding frog, can absorb a certain amount of oxygen through the skin. Finally the tadpoles metamorphosed into little frogs, at which point the mother regurgitated one or a few of them at a time, or sometimes all of them at once if she felt threatened. So how did the mother keep from digesting her own eggs or tadpoles? How did she eat when her stomach was full of babies? How did the babies eat? The jelly around the gastric brooding frog’s eggs contained prostaglandin E2, also called PGE2, which causes the stomach to stop producing hydrochloric acid. That’s a digestive acid, so once the eggs were inside the stomach, the stomach basically stopped stomaching. There is some speculation that the first eggs the mother frog swallowed actually got digested, but then the acid production stopped and the rest of the eggs remained. Once the eggs hatched, the tadpoles also produced PGE2 in the mucus in their gills. The tadpoles continued to live off the yolk sac from their eggs as they developed, and in fact their mouths weren’t even connected to their gut yet. As for the mother, she just didn’t eat until the babies were developed and released into the water on their own, which took about six weeks. The gastric brooding frog is the only frog known to raise its babies this way, but other frog species have interesting variations of the usual way frogs reproduce. Most female frogs lay their eggs, and then the male fertilizes them. But about a dozen species of frog have developed internal fertilization, where the female retains the eggs in her body until the male fertilizes them. The tailed frog from California in the United States, in North America, gets its name from a structure that looks like a tail, but is actually an extension of the cloaca. That’s the opening used for both excretion and reproduction. Only males have the tail,

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Oral Castor Oil For Hair Loss Review – My Experience And Others

Practicing Gospel Podcast

Play Episode Listen Later Nov 7, 2019 15:39

After I made my first oral castor oil for hair loss post a couple of months ago, I received hundreds of DM's, private messages, YouTube comments, emails and tweets asking me to post an update. Well, here it is. After trying oral castor oil for hair loss for 2 months, I have concluded that it is an effective growth promoter, and is far more potent than topical castor oil.…

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Michael Hawn Racial Reconciliation 2 – PGE2

Play Episode Listen Later Oct 23, 2019 58:47

This episode is a continuation of the discussion on racial reconciliation. In this episode Dr. Michael Hawn discusses cross-cultural worship and especially the use of music a valence or combining and binding medium for facilitating racial reconciliation through cross-cultural worship. He establishes the practice of cross-cultural worship in the event of the first Christian disciples at Pentecost, which was a boundary-crossing experience. Michael discusses many of the concepts and practices developed in his book, One Bread, One Body: Exploring Cultural Diversity in Worship.

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Oral Castor Oil for Hair Loss Prevention?

Play Episode Listen Later Sep 19, 2019 15:10

Oral castor oil is something not thoroughly explored in the hair loss community, despite a significant amount of promising data backing its potential efficacy. Typically, castor oil is topically applied. In practical application, its effect on hair loss prevention topically seems to be minimal when it comes to dealing with androgenic alopecia as opposed to a skin condition.…

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Old Man Reverses Hair Loss Via A Scalp Burn In A Coal Fire!?