Podcasts about preclinical

Today we're joined by Patrick Andre, Chief Scientific Officer at Diagonal Therapeutics.A trained vascular biologist, Patrick's career spans groundbreaking work at Pfizer, Acceleron, Pliant Therapeutics, and earlier companies, where he focused on TGF-β superfamily signaling and receptor pathways that keep blood vessels healthy. Now at Diagonal, he's leading a bold mission: developing clustering antibodies that correct the root cause of serious genetic vasculopathies, rather than just managing symptoms.In this episode, Patrick walks us through his personal journey into science, the company's DIAGONAL platform, and their lead program DIAG723, which recently received Orphan Drug Designation for the rare disease HHT, and is advancing toward the clinic. We also discuss Diagonal's oversubscribed $125 million Series B financing that closed in January 2026, and what clustering antibodies could mean for patients with HHT, pulmonary arterial hypertension, and beyond.01:33 Meet Patrick Andre08:01 Diagonal's mission11:39 What are clustering antibodies16:05 Receptor clustering benefits for HHT and PAH20:24 Preclinical data on preventing and reversing HHT pathology22:39 The impact of the $125 Million Series B financing roundInterested in being a sponsor of an episode of our podcast? Discover how you can get involved here! Stay updated by subscribing to our newsletterTo dive deeper into the topic: Vaderis emerges from stealth to start HHT trialPulmonary hypertension after Winrevair: where GSK's $950M bet fitsNew treatment for pulmonary hypertension: what biotech holds in store?

What should a neurologist do when a routine MRI for migraine reveals incidental white matter lesions that look remarkably like Multiple Sclerosis (MS), despite the patient having no neurological symptoms? The Editors' Choice paper for the April 2026 issue of Practical Neurology is a practical guide to the clinical diagnosis and management of radiologically isolated syndrome (RIS). Author Dr. Audrey Reynolds¹ joins PN podcast editor Dr. Amy Ross Russell to discuss her work on how updated diagnostic criteria and advanced imaging markers now enable a more proactive, biological approach to the disease. Their discussion highlights the importance of risk stratification - using tools like CSF analysis and spinal imaging - to identify those most likely to benefit from early intervention with disease-modifying therapies. They also examine the delicate balance between preventing future disability and avoiding misdiagnosis in this rapidly evolving area of neurology. Read the paper: Radiologically isolated syndrome: a practical guide. (1) St Vincent's University Hospital, Dublin; University College Dublin, Ireland Please subscribe to the Practical Neurology podcast on your favourite platform to get the latest episodes. If you enjoy our podcast, you can leave us a review or a comment on Apple Podcasts (https://apple.co/3vVPClm) or Spotify (https://spoti.fi/4baxjsQ). We'd love to hear your feedback on social media - @PracticalNeurol. This episode was hosted by PN's podcast editor Dr. Amy Ross Russell. Production by Amy Ross Russell and  Brian O'Toole. Editing by Brian O'Toole. Thank you for listening.

Dr Andrew M. Kiselica, narrating a new blog he wrote for the Dementia Researcher website.Why are preclinical Alzheimer's trials struggling to show results? Andrew and colleagues argue the issue may not just be biology or timing, but how we define “normal.” By grouping cognitively unimpaired individuals together, trials overlook meaningful differences in subtle symptoms. This blog explores how recognising objective subtle cognitive decline, supported by digital tools and refined measures, could improve participant selection and increase the chances of detecting real treatment effects.Find the original text, and narration here on our website.https://www.dementiaresearcher.nihr.ac.uk/blog-why-normal-cognition-is-hindering-preclinical-alzheimers-trials/--Dr Andrew M. Kiselica is an Associate Professor at the University of Georgia whose work focuses on early detection of cognitive decline in Alzheimer's disease. He contributes to the Working Group on Objective Subtle Cognitive Decline in Alzheimer's Disease.Follow us on social media:https://www.instagram.com/dementia_researcher/ https://www.facebook.com/Dementia.Researcher/https://www.twitter.com/demrescommunityhttps://www.linkedin.com/company/dementia-researcher https://bsky.app/profile/dementiaresearcher.bsky.socialDownload and Register with our Community App:https://www.onelink.to/dementiaresearcher

In this episode, Molecular Therapy Editor-in-Chief Dr. Joseph Glorioso and Dr. Rita Perlingeiro (University of Minnesota) will discuss an article recently published in Molecular Therapy titled, “Preclinical quality, safety, and efficacy of a CGMP iPSC-derived myogenic progenitor product for the treatment of muscular dystrophies.” Music: 'Electric Dreams' by Scott Buckley - released under CC-BY 4.0. www.scottbuckley.com.auShow your support for ASGCT!: https://asgct.org/membership/donateSee omnystudio.com/listener for privacy information.

Interview with Dr. Mark Williams, President & CSO, and  J. Roderick Matheson, Director & CEO of Marvel Bioscience Corp.Recording date: 16th March 2026Marvel Biosciences is advancing MB-204, a first-in-class treatment for social withdrawal conditions across autism spectrum disorder, depression, and Alzheimer's disease. The clinical-stage biotechnology company targets an underserved therapeutic area affecting millions globally, with autism prevalence reaching one in 36 children in the United States and depression impacting one in eight adults currently on antidepressants. The addressable market spans hundreds of billions of dollars in healthcare costs and lost productivity.The compound is based on a modified version of an approved Parkinson's medication, providing an established safety foundation for clinical development. Preclinical data demonstrates rapid symptom reversal within one hour of oral dosing in animal models. In head-to-head comparisons, MB-204 outperformed trofinetide, the only FDA-approved Rett syndrome treatment, across all measured behavioral endpoints. Critically, animals treated with MB-204 maintained improvements for two to three weeks after treatment cessation, suggesting semi-permanent neurological changes, while trofinetide benefits disappeared immediately upon stopping.Marvel's clinical strategy prioritizes orphan disease indications, specifically Rett syndrome and Fragile X syndrome, where Phase 3 success rates exceed 50% due to genetically homogeneous patient populations and validated regulatory pathways. The company has completed manufacturing of clinical-grade material and toxicology studies, positioning MB-204 for immediate Phase 1 entry in Australia within six to twelve months. The Australian regulatory environment offers efficient processes and a 43% research tax credit that significantly reduces development costs.Marvel holds composition of matter patents in China and Japan, with additional jurisdictions pending. The company has engaged in preliminary partnership discussions, aligning with neuroscience sector dynamics where approximately 70% of companies complete licensing or acquisition deals before Phase 2. Historical precedents show neuroscience acquisitions typically occur at valuations exceeding $80 million at this stage. Trading at $9 million CAD market capitalization, Marvel represents a significant discount to comparable Phase 1 neuroscience firms, with several peers valued between $100-400 million.Sign up for Crux Investor: https://cruxinvestor.com

Dr Deb Muth 00:03Well, welcome back to Let’s Talk Wellness Now. I am your host, Dr. Deb. And what is the most talked-about peptides in functional medicine? aren’t actually FDA approved. Not because they don’t work, but because no one’s funded the research to prove it yet. The truth is, some of the compounds that dominate wellness forums, BPC-157, TB-500, thymosin beta-4, epitalin, occupy a fascinating space between breakthrough science and unregulated experimentation. In today’s episode, we’re stepping into that grey zone, the world of investigational peptides, to separate mechanism from marketing. I’m going to walk you through the science that actually shows and where it stops, how to evaluate claims when human data don’t yet exist, and the quality, purity, and safety red flags that you need to recognise. Dr Deb Muth 01:06I created it in a previous episode, so go check that one out. And why honesty is the most important prescription in peptide medicine. If you’ve ever wondered whether these research-only peptides are the frontier of healing or the next functional medicine fad, this episode is for you. So grab your cup of tea or coffee, get comfortable, and let’s talk about what it really means to use peptides that are promising but still under investigation. So we’re going to break just for a second here and have a word from our sponsor. It is because of them that we stay on the air. So thank you for this. And we will be right back. Did you know sweating can literally heal your cells? Infrared saunas don’t just relax you. They detox your body, balance hormones, and boost mitochondrial energy. I’m obsessed with my Health Tech sauna. And right now, you can save $500 with my code at healthtechhealth.com slash dr-muth-req-25. Dr. Deb Muth 02:15All right, guys, welcome back. Let’s dive into investigational peptides, the evidence gap. So the following peptides we’re about ready to discuss are extensively in integrative, functional, and regenerative medicine circles. They may have intriguing mechanisms and promising preclinical data. However, they lack FDA approval, and the evidence quality varies dramatically. from interesting preliminary research to essentially no human data at all. And this distinction is really critical for maintaining scientific integrity. So let’s talk about immune-modulating peptides. There’s thymus and alpha-1, and this is an international story on the thymic peptides. Thymusin alpha-1, known as TA1, is marketed internationally as zidaxin. Dr. Deb Muth 03:16It’s a 28-amino acid polypeptide originally isolated from thymusin fraction 5, which was extracted from bovine thymus tissue. Modern production uses synthetic peptide synthesis. The thymus gland is located behind the sternum and is the primary site for T cell maturation, and thymic peptides like TA1 play roles in human system development and regulation. Now, I love thymus peptides. I love thymus glandular products. I’ve used thymus glandular products for decades. Ground-up animal thymus gland is basically what it is. There are a couple of different supplement companies that I’ve used over the years that are amazing with this. And they do a fantastic job, and they really do help to support the immune system. So when thymus peptides came out, it was really exciting because it took the whole idea of thymus support to a new level. Dr. Deb Muth 04:17The mechanism actually behind the thymus in alpha-1 is complex and involves multiple aspects of immune function. At the cellular level, TA1 enhances T cell maturation and differentiation, particularly the development of helper T cells and cytotoxic T cells. It modulates T cell receptor expression and can influence the balance between Th1 cell-mediated immunity and Th2 humoral immunity responses. And it also enhances the natural killer cell activity and modulates dendritic cell function, which are critical for antigen presentation. and initiation of adaptive immune responses. And on the cytokine level, TA1 influences production of interleukin-2, IL-2, interferon gamma, IFN-γ, and interleukin-10, IL-10. Dr. Deb Muth 05:19These create immune modulatory rather than simple immune stimulatory effects. This is a very important distinction because TA1 appears to help balance the immune system rather than simply ramping this up, which theoretically makes it safer in conditions where immune overstimulation would be a problem, such as an autoimmune disease. Hashimoto’s, autoimmune, lupus, Sjogren’s, any of those autoimmune diseases, we don’t want to overstimulate their immune system. So you want to use a product like this that’s non-stimulating. Now, the regulatory status on TA1 is geographically variable and represents one of the challenges in discussing this peptide with patients. It is not FDA-approved in the United States. However, it is approved in several other countries for specific conditions. Dr. Deb Muth 06:19In Italy, it’s approved for the treatment of chronic hepatitis B and hepatitis C. In China, it’s approved for chronic hepatitis B and adjunct immune compromised patients receiving vaccinations or suffering from certain infections. It has an orphan drug designation in the United States for certain cancer indications, but its designation does not constitute approval. It simply provides regulatory incentives for further development. So the evidence base for thymosin alpha-1 is substantial in some areas but comes primarily from non-US populations and research groups, which creates challenges in evaluating quality and generalizable information. So in hepatitis B and C, multiple clinical trials, many conducted in China and Italy, have examined TA1 as an adjunct to antiviral therapy. Dr. Deb Muth 07:21A meta-analysis by Wu and colleagues published in the Journal of Viral Hepatitis in 2013 examined 23 randomized controlled trials, including over 2,000 patients with chronic hepatitis B. The analysis found that combining TA1 with nucleoside analogs like LAMVDUDE or an and TCAVAR improved the hepatitis antigen seroconversion rates by HBV DNA clearance compared to its nucleoside analogs alone. And the effect sizes were modest but statistically significant, with the HBE-AG seroconversion rates improving from about 24% with antivirals alone to 38% in combined therapy. Now in hepatitis C, early trials before the development of direct-acting antivirals showed that TA1 combined with interferon alpha improved sustained virological responses, and compared to interferon alpha, Dr. Deb Muth 08:30Furon alone, particularly in difficult-to-treat populations like those with a genotype one or a high viral load. However, the advent of highly effective direct acting antivirals that achieve SRV rates, sorry, SVR rates exceeding 95%, the role of TA1 in hepatitis C has become less clear. Now in sepsis and critical illness, more recent interest has focused on TA1 in severe cases of sepsis and septic shock. Ren and colleagues published a systematic review and meta-analysis in the Frontiers of Immunology in 2022, analyzing 18 randomized controlled trials, including 1787 patients with severe sepsis or septic shock the pooled analysis showed that ta1 administration was associated with reduced 28-day mortality relative risk at 0.70 meaning a 30 reduction in mortality compared to the standard care alone and the effect appeared Dr. Deb Muth 09:39most pronounced in patients with sepsis-induced immunosuppression measured by HLA-DR expression in monocytes. Now, this is amazing because going forward, we’re going to talk about something that’s commonly known as cytokine storm. Now, cytokine storm really became apparent since 2020 with the viral infection that we’re dealing with in the world today. But they were already looking at this kind of cytokine storm produced by sepsis or sepsis-induced immunosuppression. And it triggered this hyperinflammatory response called the cytokine storm. And many patients who survived the initial phase of the immune suppressed stata, characterized by a T cell exhaustion, reduced antigen presentation, and increased susceptibility to secondary infections. Thymusin alpha-1, TA1, may help restore this immune competence in this phase. However, it’s important to note that patient selection and timing are critical. Dr. Deb Muth 10:43Giving this immune stimulant during a hyperinflammatory phase could theoretically worsen outcomes. So you don’t want to give it to them while they’re in the flare up or the sepsis or the infection, but given to them during the immunosuppression phase afterwards might be beneficial. Now there is also some cancer immunotherapy that we see with TA1 and has been studied as an adjunct in cancer treatment with the hypothesis that it could enhance immune surveillance and response to tumors. And a comprehensive review of Garci and colleagues published in Expert Opinion on Biological Therapy in 2007 examined multiple trials in melanoma, lung cancer, hepatocellular carcinoma, and other malignancies. And the results were mixed. Some trials showed improvement in the immune parameters, increased CD4 in T-cells. improved lymphocyte proliferation responses and some actually showed trends toward improved progression free survival but overall survival benefits were inconsistent and the heterogeneity of the cancer types treatment protocols and outcome measures makes a definitive conclusion difficult as a vaccine adjunct several studies particularly from china have examined ta1 as an adjunct to enhance vaccine responses Dr. Deb Muth 12:11in immune-compromised populations, including the elderly, dialysis patients, and transplant recipients. The rationale is sound. These populations often mount suboptimal antibody responses to vaccines, and TA1’s immune-enhancing effects might improve protection. There are small trials. They have shown improvement in seroconversion rates of hepatitis B vaccines and influenza vaccine in these populations. And though large-scale confirmatory studies are limited, there is a possibility here. Now, on their safety profile, one of the appealing aspects of thymusin alpha-A TA1 is that it’s apparently favorable safety profile in clinical trials. There are some injection site reactions with a little redness, a mild discomfort, and most commonly reported adverse effects. is that their severe adverse events attributable to TA1 have been rare in published trials. However, comprehensive long-term safety data are limited Dr. Deb Muth 13:13And theoretically, concern exists that immune modulation could potentially trigger or exasperate autoimmune conditions in susceptible individuals. Though this hasn’t been clearly demonstrated in clinical trials, integrative medicine considerations for integrative practitioners concerning the thymus and alpha-1, several factors require careful thought. First, sourcing and quality control are critical concerns. Since it’s not FDA approved, TA1 available in the United States typically will come from a compounding pharmacy or an international supplier with variable quality assurance. And pharmaceutical grade product with certificates of analysis showing purity, sterility, and endotoxin testing is essential, but it is readily available from many of these companies. Second, patient selection matters immensely. TA1 should be considered in complex cases where conventional approaches have been insufficient, such as chronic viral infections not responding adequately Dr. Deb Muth 14:21to standard antivirals, post-viral syndromes with evidence of immune dysfunction, cancer patients with immune suppression in consultation with oncology, and it should generally be avoided in active autoimmune disease unless there’s a compelling rationale and close monitoring. Now, TA1 is not a standalone therapy. In cases of chronic viral infection, Comprehensive immune support includes addressing nutritional deficiencies, optimizing vitamin D levels to be between 50 and 80, adequate zinc, selenium, and vitamin A, optimizing gut health since 80% of our immune function is in the gut, you need to optimize gut function. Managing stress from the HPA access dysfunction, chronic cortisol elevation, suppression, and immunity, ensuring adequate sleep, immune memory consolidations during sleep, addressing any metabolic dysfunction, insulin resistance, repairs in the immune function, and the bottom line on thymus and alpha-1 is Dr. Deb Muth 15:26is that it represents legitimate medicine in other countries with a substantial evidence base in specific contexts, but it remains experimental in the U.S., and practitioners using it should provide comprehensive, informed consent about its regulatory status, evidence quality, and source verification. while ensuring it’s part of comprehensive protocols. It is not a magic bullet. And again, what you’re gonna hear me say quite often here is that many of these peptides should be used in conjunction with something else. They should not be used alone. And can peptides be stacked? The answer is yes, they can. So if somebody has an insulin resistance, or a metabolic dysfunction, they can tier TA1 with a GLP-1 like terzepatide or semiglutide. That is not a problem to do that. You need to just work with a practitioner that understands how to do that effectively. So let’s look at BPC-157. Dr. Deb Muth 16:26This is a phenomenon I love BPC-157. Let’s separate it from marketing to actual mechanism of actions here. So BPC-157 stands for Body Protection Compound 157. It is a chain of 15 amino acids that are described as a partial sequence of body protection compound, a protein found in human gastric juice. It has become one of the most hyped peptides in regenerative medicine inside the athletic performance and biohacking communities with claims ranging from healing tendons and ligaments to repairing gut lining or reversing organ damage. The challenge is separating the legitimate mechanisms of science from the marketing hype. The proposed mechanism of BPC-157 are biologically plausible and intriguing. The research suggests that it may influence several growth factor pathways, including vascular endothelial growth factor, VEGF, which promotes new blood vessel formation and has improved better supply of blood flow to injured tissues, theoretically accelerating healing. Dr. Deb Muth 17:40It may also affect fibrous blast growth factor, FGF, and transforming growth factor beta, TGF beta pathways. both involved in tissue repair and remodeling. And some studies actually suggest that BPC-157 modulates inflammatory cascades, potentially reducing excessive inflammation while promoting the resolution phase that allows tissue rebuilding. Now I want to talk just a few moments here about these different tests that we’re talking about tgf beta veg f for those of you who are in our mold world you are very familiar with these uh lab tests we do this to see if you have a mold exposure what’s happening to your body and it’s been very challenging to try to heal this part of the mold illness and manipulate these VEGFs and TGF betas. And so with the fact that BPC helps us modulate this inflammatory cascade, BPC can be very helpful in the world of mold or mycotoxin illness in repairing those parts of the body that have been damaged by the mycotoxins. Dr. Deb Muth 18:48Now there is animal research on BPC-157. It is extensive and primarily from a research group led by pre-drag, oh, I can never say these names, Cyrek at the University of Zagreb in Croatia. Published studies in animal models have shown accelerated healing in a remarkable variety of injury types. A 2011 paper by Chang and colleagues in the Journal of Applied Physiology demonstrated that BPC-157 improved therapy tendon healing in rats with Achilles tendon injuries, and the treated rats showed increased tendon outgrowth, better cell survival in the injured area, enhanced cell migration to the injury site, and improved biochemical strength of the healed tendon compared to controls. Multiple other animal studies have shown similar promising effects. Ligament tears, healing faster in rabbits, muscle damage recovering more quickly in rodent models, gastric ulcers healing in rats given experimental induced ulcerations, inflammatory bowel lesions improving in mouse models of colitis, and even bone to tendon healing showing enhancement in animal studies. Dr. Deb Muth 20:02The breadth of injury types showing benefit in preclinical models explains the enthusiasm of this peptide. However, this is critical. These animal studies, primarily in rodents and rabbits, animal models of injury healing don’t reliably translate to human clinical outcomes. And the doses used in these animal studies when converted to human equivalent doses vary widely. And optimal human dosing is completely unknown at this point. it is all considered experimental and perhaps most importantly there are essentially no peer-reviewed controlled clinical trials in human published in humans published in major medical journals in a 2001 review of arthroscopy and the journal of arthroscopic and related surgery specifically examined in the evidence of bpc 157 and other peptides in musculoskeletal medicine The authors concluded bluntly that BPC-157 lacks evidence from randomized controlled trials and has an unknown safety profile in humans. Dr. Deb Muth 21:09 They emphasized that the jump from animal data to recommending peptides for humans use bypasses the fundamental requirement for Phase I safety studies, Phase II dose-finding studies, and Phase III efficacy trials that would establish whether BPC-157 actually works in humans and whether or not it’s safe. The absence of human safety data is particularly concerning given BPC-157’s proposed mechanisms. Peptides that influence growth factor signaling and angiogenesis could theoretically have off-target effects. Uncontrolled angiogenesis, for instance, is a hallmark of cancer progression. Tumors require blood vessel formation to grow beyond a certain size. And while there’s no evidence that BPC 157 promotes cancer, The complete absence of long term human safety studies means we simply don’t know. This isn’t fear mongering. It’s acknowledging uncertainty and uncertainty exists and understanding that if you’re choosing to use peptides like BPC 157, you are doing it in an experimental model. Dr. Deb Muth 22:17We’re experimenting with the doses that are being used. And there is potential for it to cause cancer cells in your body to grow. And you need to be aware of this and understand the risks that you’re taking when you’re using an investigational or off label use peptide. Now, quality control issues with BPC also exist. It’s not FDA approved for any indication in the US. It’s not approved in any major regulatory jurisdiction worldwide. It’s marketed as a research chemical explicitly to bypass FDA oversight. And commercial sources selling BPC-157 range from compounding pharmacies, which have some quality standards but are not FDA inspected. You can take that for what you want to believe on that one. to overseas suppliers operating with absolutely no quality assurance whatsoever. If you are choosing to use BPC-157, you have to understand who’s manufacturing it for you, where you are getting it from, how pure it is. Dr. Deb Muth 23:26You want to make sure that you have the certificate of analysis and that it does not contain bacterial endotoxins that can contaminate the peptide or degrade the peptide and cause other issues for you. So when you talk about peptides with patients regarding BPC-157 or if you’re listening to this and you’re already using BPC-157 or other peptides, that are quote-unquote not for human consumption, an evidence-based response acknowledges both the appeal and the limitations. And you want to talk about the animal data that’s definitely showing some progress and some potential, but we don’t know what we don’t know in humans. If people are willing to take that risk, that is up to them to do that. But using BPC right now is experimental and people need to be aware of that. Are there evidence-based alternatives for patients with tendon or ligament injuries? Dr. Deb Muth 24:26And there are. There’s PRP, which has been studied in multiple randomized controlled trials. for conditions like lateral epicondylitis, tennis elbow, Achilles issues, patellar issues, knee issues. However, I want to caution you on this too. So the study that was done by Cox and colleagues in muscles, ligaments, and tendons in the Journal of 2014 showed modest benefits in pain and function compared to controls. And though the effects vary by injury type, PRP preparations can be helpful. You have to understand that a lot of times when people are doing PRP injections in their office, they are not doing it exactly the same way it was done in the study. And not to mention, if you’re using your own PRP to heal a ligament or a tendon or help your arthritis and you’re 60 or 70 years old, That is not good quality protein rich plasma. It is old protein rich plasma. And you’re not going to see necessarily the same benefits that you would see if you were using placental tissue or umbilical tissue. Dr. Deb Muth 25:33You also want to address the nutritional deficiencies or support that’s needed for connective tissue healing. And these are collagen peptides dosed at 15 grams a day. And this has been shown in a study by Shaw and colleagues in the American Journal of Clinical Nutrition in 2017 to augment collagen synthesis when combined with intermittent loading. Vitamin C is also an essential cofactor for collagen production and stabilization of collagen structure at a dose of around 500 to 1000 milligrams a day to support this process. You also need to have good adequate intake of copper and zinc. These are cofactors in collagen. Silica is also important. This comes from horsetail extract. This provides additional support as well. So more importantly, I think remembering that rehabilitation matters as well. Doing these protocols without doing some rehab is not going to get you where you want to go. Dr. Deb Muth 26:33There’s a research study by Alfredson and others for Achilles tendinopathy using the control lengthening of muscle tendon units under load to promote tendon remodeling and healing. These protocols have solid evidence and cost nothing beyond professional guidance from a physical therapist. They are important for patients seeking cutting edge regenerative approaches. Stem cell therapies, growth factors, concentrates derived from patients’ own tissues like PRP. These have a lot of good endogenous materials and they have good safety profiles. BPC-157 represents the perfect example of how promising Preclinical science gets marketed far beyond the evidence and it may eventually prove to be valuable. I think it will. But right now that determination does require some human studies and hopefully with the administration that we have right now and Bobby Kennedy, we will actually start to see some of that occur. Now the next peptide I want to talk about is TB4, thymus and beta-4. Dr. Deb Muth 27:36This is a wound healing peptide. It is a 43 amino acid peptide that’s naturally present in virtually all human cells except red blood cells. It’s actually one of the most abundant peptides in the human body, particularly concentrated in blood platelets, wound fluid, and many tissues. It’s naturally ubiquity makes it mechanistically interesting. The body wouldn’t produce it in such abundance if it didn’t serve a function. So the primary role of TB4 involves building G-actin. It’s a form of monomeric actin. And it’s structural protein that forms the microfilaments within the cells, providing cellular structure and enabling cell movement. TB4 prevents from F-actin filaments. I’m not going to talk too much about this. It’s really critical for wound healing as cells need to migrate into the injury sites. Dr. Deb Muth 28:37so the cell shape changes and the cellular response to the injury. So think of this as though you tore your meniscus and the body created all this TB4 to come to that injury to try to heal that site. That’s exactly what the TB4 is doing inside the body when there’s an injury. It’s been shown in research to help produce new blood vessel formation, promote endothelial cells, It helps modulate inflammatory cytokines, potentially reducing TNF-alpha, IL-1, and possibly protecting in programmed cell death, which we call apoptosis. And some studies suggest that it is cardioprotective in its effects in animal models of myocardial infarction, so heart attack, and neuroprotective in other models for brain injury. Now, these remain to be preliminary, but they are being seen. So the regulatory status on TB4 can create some confusion. Dr. Deb Muth 29:40The natural TB4 molecule itself is not FDA approved as a drug. However, TB4 based drug candidates called RGN259, formerly TB4, has been in the development by regen tree for corneal injuries of the dry eye disease. And as of recent updates, this drug is completed phase three trials for its neurotrophic keratopathy, severe corneal condition. But the FDA approval is still pending. So that means that the most advanced TB4-based pharmaceuticals hasn’t yet crossed the finish line for approval. The commercial peptide market further muddies the picture with TB500, which is often described as the synthetic fragment of TB4. However, this extract’s relationship between TB500 and TB4 varies depending on the source. Dr. Deb Muth 30:41So some claim that TB500 is identical to TB4, but positions 1 through 4 suggest it’s a different fragment. and the quality control across suppliers is not existent. So this confusion is part of why recommending TB500 becomes problematic for practitioners and patients, often because they aren’t certain what molecule they’re actually getting. The evidence base for TB4 in humans is limited, primarily to eye research, and the studies from Sohn’s and colleagues published in journals like Vitamins and Hormones in 2016 have examined topical TB4 for corneal injuries and neurotrophic keratopathy, dry eye, and other surface diseases. Now, these studies showed some promise in promoting this, and there is, however, a topical application to the cornea that is vastly different from a systemic injection. So for systemic use in wound healing, musculoskeletal issues, Dr. Deb Muth 31:42cardiac protection, neuroprotection, human clinical trials. There is scarce to non-existent evidence in humans. Most of the evidence remains in animal models or cell culture studies. And a review by Flip and colleagues in the Journal of Investigational Dermatology in 2006 detailed TB4’s effects on the matrix remodeling during wound repair in animal models, showing effects on collagen disposition, granulation, tissue reformation, and wound contraction. Another review by Ho and colleagues in expert opinion on biological therapy in 2007 discussed TB4’s potential in tissue regeneration and regenerative medicine, but noted the field remained largely blank. preclinical. So this is really important again to understand that there is just not enough human data. So there is a concern with cell division and migration. This theoretically exists Dr. Deb Muth 32:45for the potential effects on cancer cells, which would also rely on migration and division and other intended consequences of disrupting normal cellular architecture. These aren’t proven risks, but they are unexplored questions that we need to be aware of when we’re using peptides. This can cause cancerous tissue to grow. Very similar to what we talked about with BPC-157. These are also sold as research chemicals. There is no FDA oversight. So purity, potency, contaminations all still exist for these peptides. Now from an integrative perspective, the natural presence of TB4 in wound fluid and its biological roles in healing are legitimate science. in presence does not equal therapeutic utility. The body tightly regulates where and when and how much TB4 is present through natural production and bypassing that regulation with external dosing may or may not cause us to have beneficial or introduce risk. Dr. Deb Muth 33:49So we need to know that this is experimental use. Those people who are seeking wound healing and tissue repair the evidence-based approach of the body’s own capacity to heal is huge definitely want to be increasing your protein intake optimizing your zinc copper vitamin c and vitamin a and then managing glucose is really important during this time as well so let’s talk about a fun topic now and that’s growth hormone secretagogues this is the anti-aging hype machine these peptides in this category are things like semoralin ipameralin cjc 1220 1295 and others and among the most aggressively marketed in anti-aging and longevity medicine they all share a common goal stimulating the pituitary gland to release more growth hormone and the appeal is understandable. GH levels decline with age, and this decline is associated with increased fat mass, decreased lean muscle, reduced bone density, and other aspects of aging. Dr. Deb Muth 34:55The other times we’ll see growth hormone levels decline significantly is with chronic illness, and the logic is to restore youthful GH levels and youthful physiology. Now, semirelin from an FDA approved diagnostic to compound anti-aging product. Semirelin is a 29 amino acid peptide representing the first 29 amino acids of the full 44 amino acid human growth releasing hormone, GHRH. We talked about this on another episode of the podcast. And you can go back and listen to that one a little bit if you want. This fragment contains the complete biological activity of the full GHRH molecule and it binds to GHRH receptors in the anterior pituitary and stimulates growth releasing peptides, growth hormone releasing peptides. Semirelin was previously FDA approved as diagnostic testing of growth hormone secretion, essentially, to determine if the pituitary could still respond to GHRH stimulation in patients being evaluated for growth hormone deficiency. Dr. Deb Muth 36:06However, the manufacturer was discontinued and there was no longer an FDA approved semirelin product on the market in the United States. What exists now is semirelin available from compounding pharmacies used off label for anti-aging, body composition, and general growth hormone optimization purposes. This represents a significant gray area. Again, compounding medications serve a very important role, but they need to meet certain recommendations and regulations, as we’ve talked about in the past. You want to make sure that your compounding pharmacy that you’re obtaining semirelin from is qualified to do that, that they are doing best practices, and that you’re getting a good product. The theoretical advantage to semirelin over direct growth hormone administration is that it preserves more of the physiological growth hormone secretion patterns. Natural GH is released in pulses, primarily during sleep, not as a continuous elevation. Dr. Deb Muth 37:07So semirelin stimulates the pulses rather than providing a constant super physiological growth hormone level. And that pulsatile pattern is thought to reduce some of the side effects and metabolic concerns that we have with continuous growth hormone exposure. However, the evidence supporting semirelin for anti-aging and body composition in healthy adults is minimal. Most of the data comes from studies conducted in the 1990s when the FDA approved product existed. Not that that means it’s bad. We have drugs that have been in the market for over a hundred years that are still there, that still have the research and are still being used successfully and safely today. So we don’t want to let that really make us think that this product isn’t safe. So a 2006 review from Walker in Clinical Interventions of Aging suggested that semirelin might be a better approach than direct GH for adult onset growth hormone insufficiency, but they do acknowledge that the evidence was limited. Dr. Deb Muth 38:12And although we don’t have any large scale trials that we can examine for semirelin’s efficacy, it is now commonly prescribed. And the optimal dosing for anti-aging purposes is still unknown. It is considered experimental and it does vary from person to person, but it is still unstudied. The effects on cancer risk, cardiovascular disease, metabolic dysfunction over long time periods are also still unknown. I would argue that the side effects or the risk factors of not having growth hormone are equally as bad as the unknowns that we have here. We’re not looking to try to get super physiological doses. We’re trying to restore youthful GH levels. Typically, we’re not trying to restore back to a 20-year-old. We’re trying to restore back maybe 10 years. That is a better way of doing this. And I think that’s important for people to understand. Now, ipamirelin is the ghrelin mimicker. Dr. Deb Muth 39:12Ipamirelin is a pent-up peptide, five amino acid, that acts as a growth hormone secretagogue receptor, a GHS-R agonist. It mimics the action of ghrelin, the hunger hormone, that also stimulates growth hormone release. The proposed advantage over earlier secretagogues is that ipamirelin stimulates growth hormone release without significantly affecting cortisol, prolactin, or other glucose things, which can be increased by growth hormone secretagogues. The regulatory status is clear. Ipamirelin is not FDA approved for any indication. It’s sold as a research chemical. Human evidence is thin. It’s limited to single dose studies examining how quickly it’s absorbed and metabolized with minimal data on dosing and clinical outcomes. Now there are marketing claims for ipamirelin and they are extensive. Dr. Deb Muth 40:13It increases lean muscle mass, it decreases body fat, it improves sleep quality, faster recovery from workouts, enhanced injury healing, better skin quality. The evidence supporting these claims in humans is not available we don’t have it these are claims that are made by the effects that we know from growth hormone so it’s not necessarily a bad thing we know what growth hormone does we know growth hormone does all of these things if ipamorelin is a precursor to that it will obviously help improve those things making that correlation of what growth hormone does So there are safety concerns that mirror the same as any other growth hormone elevating therapy. It can cause fluid retention, joint pain, carpal tunnel syndrome, insulin resistance, glucose intolerance, and theoretically, can it increase calcium? cancer risks? It can because IGF-1 promotes cell proliferation and can inhibit apoptosis in cancer cells. Now remember, your body makes IGF-1. Dr. Deb Muth 41:15If it’s not making enough of it, that’s a problem. If it’s making too much of it, That’s a problem. So just understand that if you are adding these things, and especially in elevated doses, you are taking a potential risk. So there is also now CJC 1295 is a modified GHRH analog of 30 amino acid peptide based on GHRH structure, but with modifications. So it includes the addition of drug affinity complex, DACC, DAC, which involves conjugation with a small albumin binding molecule, dramatically extends the peptide’s half-life from minutes to as much as potentially a week or more. And this creates sustained growth hormone elevation rather than that pulsatile release. There are actually two versions of this. There’s CJC 1295 with DAC, longer acting version, and CJC 1295 without DAC, which is essentially a shorter duration of semirelin. Dr. Deb Muth 42:19And so when we’re comparing products, it is… only the difference between long acting and short acting. The human evidence for CJC 1295 is limited to a single published phase one study by Techman and colleagues in the Journal of Clinical Nutrition and Metabolism in 2006. And the study involves 18 healthy young adults showed that CJC 1295 with DAC produced a sustained elevation of GH and IGF-1 lasting several days after the injection. That’s essentially the entire published human evidence of this peptide. There are no phase two studies examining optimal dose. So that is all considered experimental. And there is no phase three studies examining clinical efficacy. So the sustained GH levels created by CJC 1295 with DAC raises specific concerns because the natural GH secretion It goes up and down, up and down, up and down. Dr. Deb Muth 43:19And that constant elevation may have a different metabolic and cellular effect. And we just really don’t know what that’s going to be yet. So we can understand that elevated IGF-1 levels can theoretically increase cancer concerns and metabolic risks. So rather than always injecting peptides, which are very expensive… You can do other things. And there was a study by Hartman and colleagues in the Journal of Clinical Endocrinology and Metabolism in 1992 that demonstrated the 48-hour fast increased integrated growth hormone secretion five-fold through increased GH levels. Now, the problem with this is fasting for 48 hours is a challenge. And how long is it going to increase the growth hormone secretion without causing issues? Or in general, how long is it going to go up? Dr. Deb Muth 44:19So we have to be cautious about that as well. Sleep optimization is non-negotiable. The majority of growth hormone secretion occurs during sleep, slow wave sleep, typically the first sleep cycle, and poor sleep quality or insufficient sleep typically. can dramatically affect your growth hormone levels. And then high intensity interval training, HIIT resistance training can stimulate growth hormone as well. This was seen in a study by Godfrey and colleagues in sports medicine in 2003 and was examined in exercise-induced growth hormone responses to athletes. So we definitely see these kinds of things. So let’s talk about some longevity peptides now. These expand the telomere. So there’s epitalin and epithalamin and when these are used in anti-aging they can produce some amazing results. Dr. Deb Muth 45:22So epitalin is a synthetic terapeptide, just four amino acids. It was originally synthesized as a simplified version of epithalamine. a pineal gland extract containing multiple peptides. The synthetic four amino acid version was created to isolate what researchers believed might be the active anti-aging component. The mechanism produced for epitalin centers on telomere and telomerase, Telomeres are protective caps at the end of the chromosomes consisting of repetitive DNA sequencing. And every time a cell divides, telomeres shorten slightly because DNA polymers cannot fully replicate the ends of the linear chromosomes. So this progressive shortening acts as a molecular clock. After 50 or 70 divisions, the telomeres become critically short, triggering a cellular senescence. Dr. Deb Muth 46:22This telomere shortening is one mechanism of cellular aging and telomeres in the enzyme that can rebuild telomeres by adding these caps back onto the end of the chromosome. It’s active in stem cells, germ cells, and unfortunately in about 85 to 90% of the cancer cells. In most adult somatic cells, telomerase is inactive or present at very low levels, allowing the telomeres to shorten with division. The research on epitalin suggests it might activate this telomeres act telomeres process primarily from a research group led by Vladimir in Russia. Vladimir Kavasan in Russia. He is a huge peptide researcher or was he passed away with publications dating back to the early 2000s and a study published in bio gerontology in 2000 by Kavasan Dr. Deb Muth 47:25and colleagues examined the effect of epitalin on the lifespan of fruit flies, and they treated fruit flies that showed a modest increase in mean and maximum lifespan compared to its controls by approximately 10 to 15% lifespan extension in some experimental groups. And there were other studies in 2003 that examined epitalamine in a female Swiss-derived mouse. This was done by Ann Simove and colleagues. And the researchers reported that epitalin treatment was associated with increased lifespan as well. And the most cited mechanistic work comes from cell culture studies. And that is also Cavason’s group that published this research in 2003, showing increased telomeres activity in cultured somatic cells again. More recently, between 20 and 25, the series of publications have continued to explore epithelial effects on telomere dynamics in cell cultures. Dr. Deb Muth 48:32So there is a lot of research that’s been done. The mass majority has been done on epithelin. And most of it has been done by a single research group in Russia. There is some restrictions on some of the cell culture data that we’re seeing. And it does show that epithelin sometimes can be described as a regulating hormone. Carcadian rhythm for melatonin production, which is derived by the penile extracts. And however the evidence for this affects minimally and mechanistically unclear, the pineal gland primarily functions as melatonin secretion in that light-dark cycles. So Epithalin or epitalin is not FDA approved. It is not approved for any major regulatory jurisdiction. It is sold as a research chemical only. Dr. Deb Muth 49:33So you need to follow the same safety profiles that we’ve talked about in other episodes and in today’s episodes. And when we’re talking about epithalin, and we’re excited about it being an anti-aging science, we should balance this with the honesty and the evidence of the quality of that evidence. We don’t know its safety effect. We don’t know if it’s going to increase the risk of cancer. We can’t verify that. And we need to be using it in an experimental use of unknown risks only. Of course, diet, physical activity, stress management, sleep quality, all of those things are important for us to be looking at when we’re looking at these peptides. Now, I want to get into some of the brain peptides. This is the nootrophic frontier. C-Max and C-Lank, there is Russian pharmacology that’s done. C-Max and C-Lank represent an interesting case study in how different regulatory environments and research traditions Dr. Deb Muth 50:36create challenges in evaluating this evidence. Both peptides were developed in Russia, are approved for their specific indications and have substantial Russian language and literature supporting their use. However, the FDA approval in the United States is still not there. C-Max is a seven amino acid. It’s a synthetic analog. It is a fragment, particularly ACTH 4 through 10. It’s sometimes called the melanocortin effects because it involves the melanocortin receptors of the central nervous system. CMAX was developed by the Institute of Molecular Genetics of Russia Academy of Sciences and is approved in Russia for several indications, including acute stroke, transient ischemic attacks, cognitive disorders. It has Russian approval and is based on clinical trials primarily in Russia. Dr. Deb Muth 51:39It does help to increase brain-derived neurotrophic factor, BDNF, a protein critical for neuroplasticity, the brain’s ability to form new connections and adapt to the challenges. BDNF supports neuronal survival and promotes growth of these new neurons. C-Max also influences neurotransmitter systems, particularly dopamine and serotonin, and there is some research that suggests it affects on metabolism as well, and endogenous opioid peptides that involve pain reception and mood regulation. So it has some good potentials there. There is also C-Link, which is a hepatopeptide structurally similar to Tufts’ and an immune modulatory peptide. It was also developed in Russia and was approved for anxiety disorders as a neurotropic. Its effects involve anxiolytic effects, possibly through the GABAnergic system or the GABA system of the brain, and immune modulation. Dr. Deb Muth 52:44The Russian research is examined by C-Link for anxiety disorders. and finding reductions in anxiety without sedation. There is a dependency potential or cognitive impairment does not exist like it does with benzodiazepines with C-Link. So that is really good. And they do report attention and memory improvement using C-Link. There is a study that was done in neuroscience and behavioral psychology in 2018 that examined C-Linx effects and proposed that it exerts cytoprotective effects through BDNF pathways similar to C-Max. So both of these are Russian research-based They’re not wrong or fraudulent. It’s just that they are from Russia and we all have our concerns with Russia. However, that does not necessarily mean their research doesn’t hold quality. Dr. Deb Muth 53:49Neither peptide is approved by the FDA, and so you are using this off-label. The same rules apply for all of the other peptides that we’ve talked about that are produced off label. You want to do the same things that you would do with anything else. Good protein, omegas, B vitamins, acetylcarnitine, exercise, sleep, all of that still applies when we’re using these peptides. So I want to talk briefly about clinical decision and framework when we’re looking at this. First and foremost, we always want to go to FDA-approved peptides. Secondly, we would look at international approval with peptides that are established in other countries but lack FDA approval. And then preclinical evidence only or experimental peptides. These can be used, but they are not ethically recommended in the traditional medicine world. Dr. Deb Muth 54:50 If patients use them, we need to have appropriate counseling about the evidence surrounding them, the safety, and where to find them. how to find them and how to ask for these certificates of analysis. So I think it’s really good that we were exploring all these peptides and understanding what they are. There’s a lot of controversy out there. There’s a lot of concern out there. And what we can say with confidence is that peptides are powerful biological signaling molecules. Some peptide based medications, semi-glutide, triseptide, PT 141, Lupron that are all FDA approved. can dramatically improve outcomes in patients that are obviously selected for the correct ones. There are many other peptides that we address that are integrative and longevity space in the regenerative medicine. These peptides are all experimental. That does not automatically make them wrong. Dr. Deb Muth 55:50It just means that we need to be honest about what we’re doing with them and we need to be cautious with the patients so that they can make a decision to be part of an experimental study. in looking at how to use these peptides. So peptides are tools like any other tools. They work best in the hands of skilled people, and they are applied to appropriate situations, integrating into comprehensive approaches that address root causes. The most powerful peptide administered to a patient with untreated inflammation, hormonal chaos, nutritional deficiencies, and disorders of sleep will disappoint. The simplest evidence-based interventions apply. to a patient whose foundational physiology has been optimized. And this is the art of the science of peptide, right? If done right, respecting both the power of these molecules and the complexity of human beings that we are privileged to serve can make a difference in their lives. So thank you for listening to this episode. Dr. Deb Muth 56:52I hope this was helpful. If you can know of somebody that might benefit from this, please like, share, and subscribe. It means a lot to us. And I hope you join us for our next episode of Let’s Talk Wellness Now. Welcome to Let’s Talk Wellness Now, where we bring expert insights directly to you. Please note that the views and information shared by our guests are their own and do not necessarily reflect those of Let’s Talk Wellness Now, its management, or our partners. Each affiliate, sponsor, and partner is an independent entity with its own perspectives. Today’s content is provided for informational and educational purposes only and should not be considered specific advice, whether financial, medical, or legal. While we strive to present accurate and useful information, we cannot guarantee its completeness or relevance to your unique circumstances. We encourage you to consult with a qualified professional to address your individual needs. Dr. Deb Muth 57:54Your use of information from this broadcast is entirely at your own risk. By continuing to listen, you agree to indemnify and hold Let’s Talk Wellness Now and its associates harmless from any claims or damages arising from the use of this content. We may update this disclaimer at any time and changes will take effect immediately upon posting or broadcast. Thank you for tuning in. We hope you find this episode both insightful and thought-provoking. Listener discretion is advised.The post Episode 258 – Investigational Peptides: What's Promising, What's Hype & What You Must Know first appeared on Let's Talk Wellness Now.

Hard-to-treat cancers like pancreatic ductal adenocarcinoma (PDAC) have long defied conventional therapies. Radiopharmaceuticals, combining targeted therapy with diagnostic power, are creating new opportunities in precision oncology.Host David Brühlmann speaks with Bryan Miller of Crown Bioscience, who explains how Crown's strategic partnerships, rigorous quality standards, and adaptive study design are shaping radiopharmaceutical development—delivering speed, safety, and real clinical impact.In this episode, you'll learn:The promise and practical implications of theranostics—agents used for both diagnosis and treatment (02:44)Definitions and distinctions between CDX (cell line-derived xenograft) and PDX (patient-derived xenograft) models, and why PDX models better recapitulate tumor heterogeneity (05:11)Strategies for building more predictive, clinically relevant research models (06:09)Balancing rapid innovation with rigorous quality standards—why robust QC systems enable speed without compromising safety (08:01)Key advice for scientists entering radiopharmaceutical development, including how to choose the right research partners (09:53)Why effective collaboration between biotech companies and CROs is akin to a well-chosen partnership (10:50)The future outlook for radiopharmaceuticals and their impact on hard-to-treat cancers (12:21)Strategic insight:Focusing on theranostic radiopharmaceuticals—agents that combine diagnostics and therapy—offers a high-impact strategy for hard-to-treat cancers like PDAC. By enabling simultaneous patient stratification and targeted treatment, theranostics can accelerate development, improve clinical outcomes, and create a competitive advantage in areas where traditional therapies are limited.Where do you see radiopharmaceuticals and advanced preclinical models making the biggest impact in oncology or beyond?Explore the full conversation to learn how Bryan Miller and Crown Bioscience are scaling innovation for the next generation of cancer therapies.Connect with Bryan Miller:LinkedIn: www.linkedin.com/in/bryan-miller-148344aaCrown Bioscience: www.crownbio.comNext step:Need fast CMC guidance? → Get rapid CMC decision support hereSupport the show

Imagine treating cancer with the precision of a guided missile—delivering radioactive payloads directly to tumor cells. Radiopharmaceuticals are reshaping cancer diagnostics and therapy by pairing tumor-targeting molecules with radioisotopes for diagnosis or therapy. But what does it really take to develop these therapies, and why is interest from scientists, biotech companies, and pharma accelerating?In this episode, we're joined by Bryan Miller, Director of Scientific and Technical Operations at Crown Bioscience UK. From a PhD in cardiac disease to leading preclinical oncology and radiopharmaceutical programs, Bryan brings hands-on insight into building advanced cancer models and translating innovative therapies from bench to clinic.Topics discussed include:Bryan Miller's path from cardiac disease research to leading preclinical cancer model development (03:03)Crown Bioscience's comprehensive cancer model platforms, from organoids to PDX and humanized in vivo models (04:05)How radiopharmaceuticals differ from traditional chemotherapies in terms of safety and speed, including the concept of theranostics (07:32)The reasons behind the surge of interest in radiopharmaceuticals within science and industry (09:04)The importance of selecting the right preclinical model for success—and how AI and data-driven approaches will shape future workflows (10:11)Critical pitfalls and unique technical challenges in radiopharmaceutical drug development (12:46)Crown Bioscience's collaborative approach with Medicines Discovery Catapult to navigate the complexities of radiopharmaceutical research (13:35)The diverse client needs, from small startups to global pharma companies, and how mature their development programs can be (14:20)Strategies for scaling preclinical and translational capabilities to meet growing demand in radiopharmaceutical studies (16:04)Strategic insight:Radiopharmaceutical success requires integrated design from the start—combining precise model selection, targeting strategy, isotope choice, linker chemistry, and rigorous QC. Programs that establish this comprehensive foundation early move faster and with higher translational confidence than those addressing these elements sequentially or treating any aspect as a downstream refinement.If you're curious about the real challenges of drug development, the rise of theranostics, and how data-driven approaches (including AI) are shaping preclinical workflows, this episode delivers actionable strategies and insider perspectives for scientists and biotech innovators alike.Connect with Bryan Miller:LinkedIn: www.linkedin.com/in/bryan-miller-148344aaCrown Bioscience: www.crownbio.comNext step:Need fast CMC guidance? → Get rapid CMC decision support hereSupport the show

Peptides in Pain Management: BPC-157, Risks, Reality, and the Business of Regenerative Medicine Episode Length: ~12–15 minutes Target Audience: Pain physicians, anesthesiologists, PM&R, sports medicine, and regenerative medicine clinicians Hosted by: Dr. David Rosenblum, MD Produced by: PainExam | NRAP Academy

Peptides in Pain Management: BPC-157, Risks, Reality, and the Business of Regenerative Medicine Episode Length: ~12–15 minutes Target Audience: Pain physicians, anesthesiologists, PM&R, sports medicine, and regenerative medicine clinicians Hosted by: Dr. David Rosenblum, MD Produced by: PainExam | NRAP Academy

What happens when we move beyond oversimplified cell cultures and truly embrace the complexity of human biology? In this episode of the Smart Biotech Scientist Podcast, we explore how advanced 3D cell models are reshaping preclinical research—recreating human tissue microenvironments to better understand tumors, immunotherapies, and gene and cell therapies.David's guest is Catarina Brito, Principal Investigator at ITQB NOVA and Head of the Advanced Cell Models Laboratory at iBET and ITQB NOVA (Portugal). Her work bridges academia and industry through iBET, a unique partnering organization that integrates cell engineering, bioprocessing, and translational modeling.Catarina's pioneering models help both pharma leaders and startups predict drug resistance and immunogenicity earlier and more reliably, accelerating the path to safer, more effective therapies—well before clinical trials begin.Topics discussed:Understanding the contribution of stromal and immune cells to therapy outcomes in tumor microenvironments (03:42)Studying immune responses to gene therapy vectors with advanced neural models (04:31)Combining multi-omics and spatial data with AI for predictive biology and patient-specific digital twins (05:16)Catarina's advice: Start simple, let the biological question dictate model design, and avoid premature overengineering (06:53)Importance of reproducibility, process controls, and standardization in advanced models (08:10)How academic-industry collaborations drive model development, scalability, and real-world relevance (08:42)Common pitfalls: Overengineering, poor cell source selection, insufficient system validation (11:03)Next steps for precision medicine and translational research using advanced cell models (13:08)Want to know how leading scientists make advanced cell models actionable and collaborative for pharma breakthroughs? Tune in for practical strategies, real-world collaborations, and pitfalls to avoid as you scale your own translational research.Connect with Catarina Brito:LinkedIn: www.linkedin.com/in/catarina-brito-ibetAdvanced Cell Models Lab – iBET: www.ibet.pt/laboratories/advanced-cell-models-labNext step:Need fast CMC guidance? → Get rapid CMC decision support hereSupport the show

What if the failure rate in clinical trials isn't about picking the wrong drug candidates—but about testing them in the wrong models?When you move cells from a 2D culture plate into a bioreactor, you're not simply scaling volume. You're fundamentally changing the biological context. Cell density shifts. Mass transfer dynamics evolve. Mechanical cues emerge. The cells sense these changes and respond—often in ways that derail strategies built on oversimplified assumptions.Most preclinical research still relies on flat plastic surfaces and animal models that miss critical aspects of human biology. The result? Therapeutics fail late in development because the models couldn't predict how human tissues would actually respond.In this episode, David Brühlmann speaks with Catarina Brito, Principal Investigator at ITQB NOVA and Head of the Advanced Cell Models Laboratory at iBET and ITQB NOVA in Portugal. Catarina's career-defining insight came early: studying glycan-protein interactions in murine versus human cells revealed that species differences weren't just nuances—they were fundamental gaps that could mislead entire research programs.Catarina and her team have developed neural, liver, and tumor models that capture the multicellular complexity and microenvironmental cues that 2D cultures cannot replicate. Her work creates preclinical models sophisticated enough to predict human responses while remaining scalable for drug development workflows.Highlights of the episode:Limitations of traditional 2D cell cultures and animal models in capturing realistic tissue behavior and therapeutic responses (06:27)Catarina Brito's personal scientific journey: from discovering model limitations to pioneering 3D culture systems in neural and liver tissues (04:19)How advanced 3D models recreate cell-to-cell interactions, tissue-specific microenvironments, diffusion gradients, and multicellular complexity (10:35)Regulatory movements toward reducing animal models, and the challenge of validating advanced alternatives for systemic biology studies (09:10)Key differences in designing bioreactors for various cell types, with practical examples from liver and neural models (15:16)The impact of scalable, robust 3D models on accelerating drug development and improving selection of candidate therapies (17:22)Key Takeaway:Bioprocess development starts when you choose the model that validates your therapeutic approach. If that model can't capture the biology that matters, every downstream optimization is built on a flawed foundation.In Part 2, Catarina reveals how 3D tumor microenvironments expose drug resistance mechanisms invisible in 2D cultures, and her vision for AI-powered digital twins enabling personalized medicine.Subscribe & Review:If this conversation changed how you think about preclinical model selection, leave a review on Apple Podcasts. Your reviews help other biotech scientists discover these insights.For more CMC development insights, visit smartbiotechscientist.com.Connect with Catarina Brito:LinkedIn: www.linkedin.com/in/catarina-brito-ibetAdvanced Cell Models Lab – iBET: www.ibet.pt/laboratories/advanced-cell-models-labNext step:Need fast CMC guidance? → Get rapid CMC decision support hereSupport the show

Scaling a product from preclinical development to commercial manufacturing is one of the most complex transitions life science teams face—and one of the easiest places to lose time and momentum.In this episode of The Life Science Rundown, host Nick Capman speaks with Jackie Klecker, Executive Vice President of Quality and Development Services at Lifecore Biomedical, about how sponsors and CDMOs can build robust, phase-appropriate quality systems without over-engineering early or under-preparing later.Drawing on decades of experience across pharmaceutical drug products, medical devices, APIs, and biologics, Jackie shares practical guidance on knowledge transfer, risk management, QMS maturity, and regulatory expectations across the U.S. and EU. The conversation focuses on what actually prevents costly delays—and how disciplined communication and documentation make scaling achievable.A few key takeaways:Early quality work should be right-sized, not commercialized prematurelyDesign space, material variability, and sensitivities must be understood and documented earlyFMEA works best when it evolves with the product—not when it's treated as a one-time exerciseFDA and EU requirements can diverge in ways that materially affect submission timingClear documentation and regular, direct communication prevent avoidable delaysJackie Klecker is Executive Vice President of Quality and Development Services at Lifecore Biomedical, a fully integrated CDMO with decades of experience supporting pharmaceutical drug products, medical devices, biologics, and APIs. She has led quality systems and development programs across multiple global manufacturing sites and brings deep expertise in FDA 21 CFR 210, 211, and 820, ISO 13485, EU GMP, and ICH Q7 environments. Her background spans chemical engineering, process development, validation, risk management, and cross-functional leadership.About The FDA GroupThe FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle—from clinical development to commercialization—with a focus on staff augmentation, auditing, remediation, QMS, and other specialized project work in Quality Assurance, Regulatory Affairs, and Clinical Operations. Learn more: ⁠⁠https://www.thefdagroup.com/

Host: Ryan Quigley Triple-negative breast cancer (TNBC) remains one of the hardest subtypes to treat, with limited options and high relapse rates—so identifying new therapeutic targets is critical. In this AudioAbstract, Ryan Quigley spotlights research presented at the San Antonio Breast Cancer Symposium that implicates ribosome biogenesis as a key vulnerability. Tune in to learn how this approach could inform the next generation of TNBC therapies.

Host: Ryan Quigley Triple-negative breast cancer (TNBC) remains one of the hardest subtypes to treat, with limited options and high relapse rates—so identifying new therapeutic targets is critical. In this AudioAbstract, Ryan Quigley spotlights research presented at the San Antonio Breast Cancer Symposium that implicates ribosome biogenesis as a key vulnerability. Tune in to learn how this approach could inform the next generation of TNBC therapies.

In this episode of The Pet Food Science Podcast Show, Dr. Katie Tolbert and Dr. Kylie Grady from Texas A&M University explore emerging insights in canine gastrointestinal health and preclinical enteropathy. They explain how early biomarkers, breed predispositions, and advanced diagnostics reveal hidden GI dysfunction in dogs long before symptoms appear. The conversation highlights how nutrition-focused interventions may support intestinal health and guide future research. Listen now on all major platforms!“Subclinical intestinal changes identified in predisposed dogs resemble early inflammatory and functional alterations observed in human gastrointestinal disease long before clinical signs appear.” - Kylie GradyMeet the guests: Dr. Katie Tolbert is a Clinical Associate Professor in Small Animal and Comparative Gastroenterology at Texas A&M University, with extensive research in small animal nutrition and gastrointestinal diseases. Dr. Kylie Grady is a Graduate Assistant Researcher at Texas A&M University, focusing on canine gastroenterology and nutritional impacts on intestinal health. Liked this one? Don't stop now — Here's what we think you'll love!Don't miss the chance to be part of the Pet Food Inner Circle!Join now and connect with leading experts in pet nutrition: https://petfoodinnercircle.com/What will you learn:(00:00) Highlight(00:50) Introduction(02:20) Preclinical markers(05:33) Breed risk(07:56) Diet study(12:54) Oxidative stress(23:49) Fatty acids(30:25) Final QuestionsThe Pet Food Science Podcast Show is trusted and supported by innovative companies like:* Kemin* Trouw Nutrition- Biorigin

Lantern Pharma CEO Panna Sharma joined Steve Darling from Proactive to discuss the company's latest clinical milestone and its broader mission to transform oncology drug development through the use of artificial intelligence, machine learning, and genomic data. Lantern's proprietary RADR® AI platform integrates billions of biological and clinical data points to identify predictive biomarkers, forecast drug response, and design more targeted and efficient clinical trials aimed at delivering precision cancer therapies to patients. The company announced additional details from its recently completed Phase 1a dose-escalation study of LP-184, its lead drug candidate. The trial produced encouraging results, demonstrating durable disease control in 63 heavily pre-treated patients with advanced solid tumors, many of which exhibited deficiencies in DNA damage repair pathways—an area where LP-184 is designed to be particularly effective. Sharma told Proactive that the Phase 1a study successfully met all primary endpoints for safety and tolerability, while also clearly establishing a recommended Phase 2 dose (RP2D). He emphasized that these outcomes validate both the scientific rationale behind LP-184 and the predictive capabilities of Lantern's AI-driven development approach. Building on these positive results, Lantern Pharma is now advancing an ambitious precision oncology strategy that includes multiple biomarker-guided Phase 1b/2 clinical trials. These studies will target major cancer indications such as triple-negative breast cancer (TNBC), glioblastoma multiforme (GBM), non-small cell lung cancer, and advanced bladder cancer. The commercial potential for LP-184 is significant. Lantern and independent industry analysts estimate that the aggregate annual market opportunity for the drug across these and additional targeted indications could exceed $10 billion. Preclinical models have shown nanomolar potency, while early clinical data indicate encouraging durability of response even in heavily pre-treated patient populations. LP-184 has also received important regulatory recognition from the U.S. Food and Drug Administration, including Fast Track Designation for TNBC and GBM, as well as Orphan Drug Designation for malignant gliomas, pancreatic cancer, and atypical teratoid/rhabdoid tumors (ATRT). Sharma noted that these designations support an accelerated development pathway as Lantern continues to move LP-184 toward later-stage clinical trials. #proactiveinvestors #laternpharma #nasdaq #ltrn #LanternPharma #PannaSharma #PrecisionOncology #CancerResearch #AIinHealthcare #MachineLearning #Genomics #ClinicalTrials #BiotechNews #OncologyInnovation #LP184 #Phase1a #Phase2Trials #BiomarkerDriven #TripleNegativeBreastCancer #Glioblastoma #LungCancer #BladderCancer #OrphanDrug #FastTrackDesignation #FDA #PrecisionMedicine

Send us a textMethods & challenges of establishing causal relationships in health research, emphasizing epidemiology, randomized trials, and genetic approaches.Topics:Epidemiology: Studies disease influences using observational designs like case-control and prospective cohorts, plus trials, to identify patterns and test hypotheses.Hierarchy of evidence critique: Rejects rigid pyramids favoring RCTs, as all studies can be biased; advocates triangulation integrating varied data types for robust conclusions.RCT strengths & weaknesses: Randomization balances confounders, but issues like poor blinding, attrition, or subversion can undermine results; large samples may yield spurious precision if biased.Confounding & reverse causation: Examples include yellow fingers and lung cancer (both from smoking) or early atherosclerosis inflating CRP-disease links; hard to fully control statistically.Nutrition epidemiology: Observational studies often overstate benefits (e.g., vitamin E for heart disease), leading to failed trials; incentives favor new findings over revisiting errors.Mendelian randomization: Uses genetic variants as proxies for exposures (e.g., ALDH2 for alcohol metabolism) to mimic randomization; reveals no heart benefits from alcohol, unlike observational data.Negative controls: Tests implausible outcomes (e.g., smoking and murder) or exposures (e.g., paternal smoking in pregnancy) to check for confounding artifacts.Evidence triangulation: Combines diverse studies with different biases (e.g., cross-cultural comparisons) for causality; applied to dismiss HDL-raising drugs despite initial promise.Practical Takeaways:Scrutinize health claims by checking for negative controls or variety in evidence sources to avoid mistaking correlation for causation.For personal decisions like alcohol intake, consider genetic studies showing risks at all levels, and aim for moderation or abstinence based on overall evidence.When evaluating supplements or diets, prioritize trials over observational data, and question media hype that ignores confounding factors.About the guest: Dr. George Davey Smith, MD, DSc is a professor of clinical epidemiology at the University of Bristol and director of the MRC Integrative Epidemiology Unit.*Not medical advice.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they're hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

Topics We Cover: 00:00 – New data from Harvard/Mass General may classify nearly 70% of adults as having obesity 03:00 – A new oral triple agonist shows record-setting absorption rates 07:00 – Fractal Health's Revita procedure: weight maintenance after stopping GLP-1s 12:00 – Zepbound vial prices drop (full breakdown by dose) 16:00 – Dave's personal experience switching off Mounjaro and intense hunger return 22:00 – Novo Nordisk's EVOKE/EVOKE+ Alzheimer's trial: what the data really means 29:00 – Why GLP-1 neurological research is just getting started 33:00 – Updates on access, partners, and major news coming soon for Medicare patients If you're on Wegovy, Mounjaro, Zepbound, Saxenda, Trulicity, or compounded versions, this episode gives you the insight and context you need to have more competent and confident conversations with your doctor. Bullet Point Summary of the Podcast Episode New Obesity Measurement Data (Harvard/Mass General Study) Harvard and Mass General propose adding waist circumference to BMI to better diagnose obesity. Traditional BMI misses key factors like muscle mass and body composition. Using the updated measure, Americans classified as obese jumps from ~43% to almost 69%. This means 7 out of 10 U.S. adults would now qualify as having the disease of obesity. Dave notes this validates many people who “feel” metabolically unwell despite a “normal” BMI. Reinforces his claim that “most people should be talking to their doctors about GLP-1s.” New Oral Triple Agonist (Ascletis – ASC41/ASC? Molecule) From Ascletis (A-S-C-L-E-T-I-S), developing an oral triple agonist targeting: GLP-1 GIP Glucagon Similar in mechanism to retatrutide, expected around 2027. Preclinical (animal) data show stunning results: Oral bioavailability of 4.2% 9× higher than tirzepatide 30× higher than oral semaglutide 6× higher than oral retatrutide 57× greater drug exposure than oral retatrutide Half-life ~56 hours Stronger receptor activation than retatrutide in vitro Suggests potential for the first powerful oral triple agonist—worth watching. ️ 3. Discussion of the Gray Market / TikTok Experience Dave briefly recounts losing his TikTok account and landing in an algorithm filled with teenagers promoting gray-market “retatrutide.” Expresses concern over unregulated peptide sales, especially to minors. Fractal Health's New Data – Weight Maintenance After Stopping GLP-1s New results from the Reveal One study (Fractal Health). Participants: lost 24% of body weight on GLP-1s → stopped injections → got one Revita procedure. At 6 months post-GLP-1 discontinuation: Weight changed only 1.5% (vs. ~10% regain in typical off-drug trials) HbA1c barely shifted Safety profile clean Suggests possible long-term weight maintenance without injections through gut mucosal re-lining. Dave describes his own recent attempt to switch drugs and significant hunger return. Food Noise & Biologic Hunger Dave discusses how stopping Mounjaro caused terrifying, primal hunger. Describes the distinction between: Food noise (brain-based thoughts) Hunger signals (biological/animalistic) Reinforces why many patients cannot maintain weight loss without support. Zepbound (Tirzepatide) Cash-Pay Price Reductions Eli Lilly drops cash-pay vial pricing: 2.5 mg: $349 → $299 5 mg: $499 → $399 7.5–15 mg: $499 → $449 Community feedback (informal poll): Most say still too high to leave compounded versions. Many would switch to branded if price hit $200–$300. Dave notes the Most Favored Nations agreement will push GLP-1 prices toward $250/month within 24 months. Alzheimer's Study (Novo Nordisk – EVOKE & EVOKE+) Oral semaglutide (Rybelsus, 14 mg) did not slow Alzheimer's clinical progression. Biomarkers improved but daily function and cognitive decline did not improve vs placebo. Important context: Oral Rybelsus is a weak form of semaglutide; stronger versions (like Wegovy 2.4 mg or upcoming high-dose oral Wegovy) not tested. Weight loss is not desirable in Alzheimer's patients, influencing drug selection. Dave emphasizes: This was a nearly $700M trial and an act of scientific courage. This is NOT the end of GLP-1 Alzheimer's research. Future molecules may target neurological pathways without suppressing appetite. Mentions Lilly's brenipatide, a GIP receptor agonist being developed for: Addiction Opioid dependency Possibly asthma ️ 8. Access, Cost, and Patient Empowerment Highlights Shed as a partner offering telehealth GLP-1 access. Notes many patients hide GLP-1 use from their primary care doctors. Reinforces OTP's mission: better, more honest conversations with clinicians. Shapa (Numberless Scale) & Dave's Personal Update Dave explains how the Shapa numberless scale helped him stay engaged during weight fluctuations. Finds stepping on “zones” (green/gray/blue) less emotionally damaging than numbers. Closing Notes Promises upcoming Eli Lilly savings card update. Encourages subscribing, liking, and enabling notifications for algorithm visibility. Thanks OTP community for amplifying patient-centric obesity medicine news. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

In this episode of ScaleUp Radio, we're diving into the groundbreaking world of personalised cancer treatments with Prasun Chakraborty, founder of Genevation – a biotech startup on a mission to revolutionise how we treat and potentially prevent cancer. Unlike the traditional one-size-fits-all approach to oncology, Genevation is using advanced AI and genetic sequencing to create custom mRNA cancer vaccines for individual patients – in just 14 days. Prasun shares the inspiring story behind the business, the massive challenges of scaling deep-tech biotech, and his clear vision of a future where cancer is not just treatable, but preventable. The conversation unfolds in three parts: Genevation's Business Model & Scaleup Journey From solo founder in 2022 to a lean but mighty team with key strategic partnerships, Prasun explains how Genevation is disrupting the cancer treatment space with a personalised, tech-first model that sidesteps the traditional limitations of clinical research. Scaling Challenges in Biotech & Beyond Prasun reflects on the key hurdles facing deep-tech startups – especially the funding gap created by investors' lack of scientific understanding and the fixation on short-term ROI. He shares candid insights into how Genevation is navigating these barriers and what it will take to unlock their next phase of growth. Quickfire Insights We round off with some powerful reflections from Prasun on leadership, mindset, and why it's essential to stay focused on the mission, even when the money and metrics don't align. Key Highlights: Genevation's AI algorithm cuts vaccine candidate selection time from 4 hours to 5 minutes. Preclinical data shows a single dose prevented tumour growth for 13 days in lung cancer models. The company is raising $5M to fund its IND application and unlock further investment. Strategic partners like Google, NVIDIA, AWS, and Illumina are backing Genevation with substantial resources. There's a lot in here – from AI innovation to biotech regulation, from strategic partnerships to the raw reality of raising millions in funding just to prove your concept. "Every cancer is unique – and it's time our treatments reflect that." Make sure you don't miss any future episodes by subscribing to ScaleUp Radio wherever you like to listen to your podcasts – and why not give us a follow. For now, continue listening for the full discussion with Prasun. Scaling up your business isn't easy, and can be a little daunting. Let ScaleUp Radio make it a little easier for you. With guests who have been where you are now, and can offer their thoughts and advice on several aspects of business. ScaleUp Radio is the business podcast you've been waiting for. If you would like to be a guest on ScaleUp Radio, please click here: https://bizsmarts.co.uk/scaleupradio/kevin You can get in touch with Kevin & Granger here: kevin@biz-smart.co.uk grangerf@biz-smart.co.uk   Kevin's Latest Book Is Available! Drawing on BizSmart's own research and experiences of working with hundreds of owner-managers, Kevin Brent explores the key reasons why most organisations do not scale and how the challenges change as they reach different milestones on the ScaleUp Journey. He then details a practical step by step guide to successfully navigate between the milestones in the form of ESUS - a proven system for entrepreneurs to scale up. More on the Book HERE - https://www.esusgroup.co.uk/   Prasun can be found here: https://www.linkedin.com/in/prasun-chakraborty-5090851b6/  

Welcome to The Peptide Podcast. If you want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going. https://pepties.com/partners/ Before we jump in, I want to quickly address a few comments I have received about the content here. Normally, I wouldn't spend time on something like this, but just for clarity — I have over nine years of formal education, including a Doctorate in Pharmacy, and sixteen years of clinical experience. That includes serving as an adjunct professor at a U.S. pharmacy school and working in oncology and inflammatory disease at a teaching hospital. And yes — for now, you just hear my voice, but that may change. I do plan to incorporate video in the future; I've simply held off because it takes significantly more time to produce, and my priority has been getting the education out to you consistently. Remember, the content is free and meant for education. If it's not for you, that's completely fine — you don't have to listen. It takes a lot of time and energy to put this together, and tuning in is entirely your choice. For my other listeners, thank you for your support and gratitude over the past few years. Now, today we're diving into a compound ATX‑304. It's often referred to as "exercise in a pill". And after we go through the science together you'll see why. We'll cover the back‑story, how it works, how it differs from typical mitochondrial supplements, animal and human data so far, who this may and may not be for — and importantly, what to watch out for.  The Backstory & Why It's Getting Attention ATX-304, was first developed in Sweden by Betagenon AB as a small-molecule AMPK activator designed to mimic the metabolic benefits of exercise and caloric restriction — with the goal of improving obesity, insulin resistance, and overall metabolic health. Early preclinical work in obese and diabetic mice showed impressive results, including better glucose uptake, enhanced fat-burning, improved insulin sensitivity, and even cardiovascular benefits. Human data followed in 2016–2017, where people with type 2 diabetes already on metformin took ATX-304 for about 28 days. Those studies showed reductions in fasting and plasma glucose, improved insulin resistance, and strong safety and tolerability. Today, Betagenon has evolved into Amplifier Therapeutics, and ATX-304 is now in Phase 2 development for metabolic, cardiovascular, and liver-related conditions, with ongoing work to refine oral delivery and broaden its potential uses. What exactly does AMPK do? Think of AMPK as a fuel gauge for your cells. When your cells are running low on energy (like when you haven't eaten, exercised, or your cells are stressed), AMPK turns on. When it's on, it tells the cell to stop storing energy (less fat and cholesterol production), start using energy (burn sugar and fat for fuel), and clean up damaged parts (autophagy, or cellular housekeeping). Basically, AMPK flips the switch from "energy saving" mode to "energy spending" mode, similar to how your body behaves during exercise or fasting. If AMPK is off or underactive, your cells tend to store energy instead of using it, which contributes to weight gain, insulin resistance, and low metabolic activity. So, activating AMPK — like with ATX‑304 — is like giving your body a nudge to burn energy, improve metabolism, and clean up the cells, even without intense exercise. And beyond just turning on AMPK, ATX‑304 also acts as a mild mitochondrial activator, meaning it helps the cell's "power plants" (mitochondria) run more optimally, increasing energy expenditure.  Because of this mechanism, ATX‑304 is sometimes called an "exercise mimetic." Even though it's not a substitute for movement, it triggers many of the same downstream pathways. How It Differs From Mitochondrial "Supplements" There are many supplements out there that claim "boost mitochondria" (e.g., PQQ, CoQ10, NAD precursors). These may support mitochondrial health or function, but typically they don't change the body's energy‑balance set‑point or shift you into a state of enhanced energy usage. ATX‑304, however, directly activates AMPK (the master switch) and supports mitochondrial output — so you get signaling plus hardware improvement. This dual action is what sets ATX‑304 apart.  Also: many mitochondrial supplements lack robust human metabolic‑dysfunction data; ATX‑304 has animal + early human trial data. What About Safety? In human trials (~28 days, T2D patients on metformin) ATX‑304 was safe, well tolerated, lowered fasting plasma glucose and insulin resistance. But because it's still early stage, long‑term safety and outcomes (fat‑loss, muscle preservation beyond short term, cardiovascular endpoints) are not fully proven yet. One of the most exciting things about ATX‑304 is that it encourages the body to burn fat while sparing lean muscle. Because AMPK activation improves muscle glucose uptake and mitochondrial efficiency, your body can preferentially use fat for energy instead of breaking down muscle. Preclinical and early human studies suggest it can reduce fat mass while preserving muscle, which makes it especially interesting for anyone transitioning off GLP‑1 therapies or looking to maintain muscle while losing fat. Practical Dosing in Wellness Context Some peptide clinics use ATX‑304 in doses ranging from 100 to 400 mg a day. It usually comes in 100 mg or 200 mg capsules, and people often take it in the morning to match the body's peak metabolic activity. Cost The last thing I want to discuss is cost. ATX‑304 is currently quite expensive, and there are a few reasons for that. Only a handful of companies manufacture it, so production volumes are small. The synthesis is complex, and the supply chain for key precursors is limited. Since it's still in early development (Phase 2), economies of scale haven't been established yet.  Thanks for listening to The Peptide Podcast.  If you want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going. Until next time, be well, and have a happy, healthy week.  

BUFFALO, NY – October 8, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 6, 2025, titled “ACTM-838, a novel systemically delivered bacterial immunotherapy that enriches in solid tumors and delivers IL-15/IL-15Rα and STING payloads to engage innate and adaptive immunity in the TME and enable a durable anti-tumor immune response.” In this study, led by first author Kyle R. Cron and corresponding author Akshata R. Udyavar, researchers from Actym Therapeutics developed a new form of bacterial immunotherapy called ACTM-838. This treatment safely delivers immune-activating proteins directly to solid tumors. The approach may offer a new option for cancer patients whose solid tumors are resistant to current immunotherapies. Solid tumors often suppress the immune system, making it difficult for treatments like immune checkpoint inhibitors to work effectively. ACTM-838 was designed to overcome this challenge by targeting phagocytic immune cells within the tumor microenvironment (TME). Once inside the tumor, the therapy delivers two immune-stimulating components: IL-15/IL-15Rα and a modified version of STING. Both are known to activate the body's innate and adaptive immune responses. This combination of immune-stimulating proteins helps shift the TME from immune-suppressive to immune-permissive, enabling the body's natural defenses to fight the cancer. “STACT is a modular, genetically engineered live attenuated S. Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration.” The study highlights how ACTM-838, built on a specially modified strain of Salmonella Typhimurium, safely targets tumors and avoids healthy tissue after intravenous injection. This targeted delivery reduces the risk of side effects while ensuring the immune-boosting agents reach their intended location. Importantly, ACTM-838 also showed significantly reduced inflammatory toxicity compared to its parent bacterial strain, which had previously presented challenges in clinical use. In preclinical tests, ACTM-838 shrank tumors and prevented their recurrence after treatment. Mice that were cured of tumors resisted re-injection with cancer cells, suggesting the development of long-lasting immune memory. The therapy also showed strong synergy with anti-PD1 drugs, a widely used class of cancer treatments, further improving outcomes in both treatment-resistant and responsive tumor models. Researchers also found that ACTM-838 changed the composition of immune cells within the tumor. It increased beneficial cells like cytotoxic T-cells and antigen-presenting macrophages, while reducing suppressive cell types such as regulatory T-cells and exhausted T-cells. These effects were confirmed through genetic analysis and cellular studies, pointing to a broad and coordinated immune response. This study offers proof-of-concept that live bacterial therapy can safely and effectively deliver gene-based immune modulators directly to tumors. With ACTM-838 now being tested in a Phase I clinical trial, the findings offer a new direction for cancer treatment strategies that activate the body's own immune system, particularly in difficult-to-treat cases where other therapies fail. DOI - https://doi.org/10.18632/oncotarget.28769 Correspondence to - Akshata R. Udyavar - akshata.udyavar@pfizer.com Abstract video - https://www.youtube.com/watch?v=fr5OR3tvC_I Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — October 3, 2025 — A new #research perspective was #published in Volume 17, Issue 9 of Aging-US on August 26, 2025, titled “Analysis of the current state of frailty indexes and their implementation for aging intervention studies.” In this work, led by first author Oliver G. Frost from Loughborough University alongside corresponding authors Abdelhadi Rebbaa and Amit Sharma, from the Lifespan Research Institute, the authors explore growing concerns about the lack of standardization in how frailty is measured in rodent aging studies, which may limit the development of effective interventions targeting age-related decline. Frailty, a key indicator of deteriorating health in older adults, is increasingly assessed in preclinical models using frailty indexes (FIs). These indexes quantify health deficits, such as reduced mobility, cognitive decline, or physical weakness. However, this perspective highlights that FI methodologies vary significantly across studies, from the selection of parameters to the cut-off thresholds used, resulting in inconsistent outcomes that affects reproducibility and translational value. The authors reviewed 18 rodent studies and found substantial variation in how frailty is defined and measured. Some FIs rely on clinical observations, such as appearance or beahaviour, while others focus on physical performance metrics like grip strength or locomotion. In several cases, applying different FIs to the same group of animals produced contradictory results, underscoring the importance of harmonized protocols. To illustrate these issues, the researchers applied an 8-item FI to mice of different ages and found that even young mice were sometimes scored as frail, depending on the scoring method and reference values. This finding emphasizes the need for consistent baselines and controlled environments, especially when comparing across studies. The authors recommend using each animal as its own baseline in longitudinal studies, a strategy that enhances reliability without adding significant cost. “Sex as a biological variable in FIs is an important consideration, as there is a known difference between male and female frailty onset and progression.” The authors also discuss emerging automated tools, such as video-based open-field testing, which can reduce observer bias and improve reproducibility. In the future, broader health indicators, such as cognition, circadian rhythms, social behavior, and body composition, may further enhance frailty assessments. Overall, this work underscores the urgent need for standardized, transparent, and reproducible methods for evaluating frailty in preclinical aging studies. Improved consistency in frailty scoring will better inform the development of healthspan-extending therapies and enhance the translational relevance of animal models. DOI - https://doi.org/10.18632/aging.206307 Corresponding authors - Abdelhadi Rebbaa - rebbaa@gmail.com, and Amit Sharma - amit.sharma@sens.org Abstract video - https://www.youtube.com/watch?v=eha3XA9LyWA Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206307 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, frailty, rodents, frailty index, phenotype To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Despite the many psychedelics clinical trials underway, there is still much we don't know about how these drugs work. Preclinical studies represent our best viable avenue to answer these lingering questions.

Today, I'm joined by Kiran Krishnan, a celebrated scientist best known as the innovative mind behind spore-based probiotics and someone who's made waves in both the practitioner and consumer health spaces. In this conversation, Kiran shares what inspired his leap from the world of microbiome science into the realm of ancestral and Ayurvedic medicine—specifically, his groundbreaking work with novel bioactives derived from the Ashwagandha root. To find out more, visit regenerive.co and use code NAT25 for 25% off.   Episode Timestamps: Kiran Krishnan's background and Regenerive overview ... 00:00:30 The promise and problems of herbal/Ayurvedic medicine ... 00:05:31 Ashwagandha: extraction, quality, and toxicity issues ... 00:11:02 Discovery of new Ashwagandha bioactives (ASHx4) ... 00:21:27 Preclinical and human clinical results (longevity, sirtuins, telomeres) ... 00:23:09 Physical and metabolic benefits in aging adults ... 00:48:33 Safety and dosing of Longfara supplement ... 00:57:38 Biohacks and healthy aging habits from Kiran ... 01:04:49 How to get Regenerive and wrap-up ... 01:07:32   Our Amazing Sponsors: Tro Zzz by Troscriptions -  This isn't just melatonin—it's a powerhouse! Oblipair gives you honokiol and agarin to enhance GABA binding, while adenosine and cordycepin boost sleep drive and deep sleep. CBD, CBN, and 5‑HTP round it out. Head to troscriptions.com, use NAT10, and get 10% off your first order.   NAD+ By Qualia - A groundbreaking formula that can increase NAD+ levels by up to 67%, using three of the most powerful precursors known to science: niacin, niacinamide, and NIAGEN. Go to qualialife.com/NATHALIE  and use promo code NATHALIE to get 15% off—and try it risk-free with their 100-day money-back guarantee.   Manukora honey - From remote forests in New Zealand, where bees collect nectar from the native Manuka tea tree. That nectar is naturally rich in antibacterial compounds like MGO, plus antioxidants and prebiotics that support immunity and gut health. Visit manukora.com/NAT to save up to 31% plus $25 worth of free gifts with the Starter Kit - you'll get an MGO 850+ Manuka Honey jar, 5 travel sticks, a wooden spoon, and a guidebook.   Nat's Links:  YouTube Channel Join My Membership Community Sign up for My Newsletter  Instagram  Facebook Group

Get My Book On Amazon: https://a.co/d/avbaV48Download The Peptide Cheat Sheet: https://peptidecheatsheet.carrd.co/Download The Bioregulator Cheat Sheet: https://bioregulatorcheatsheet.carrd.co/1 On 1 Coaching Application: https://hunterwilliamscoaching.carrd.co/Book A Call With Me: https://hunterwilliamscall.carrd.co/Supplement Sources: https://hunterwilliamssupplements.carrd.co/Amazon Storefront: https://www.amazon.com/shop/hunterwilliams/list/WE16G2223BXA?ref_=cm_sw_r_cp_ud_aipsflist_R7QWQC0P1RACB2ETY3DYSocials:Instagram: https://www.instagram.com/hunterwilliamscoaching/Podcast: https://hunterwilliamspodcast.buzzsprout.com/Video Topic Request: https://hunterwilliamsvideotopic.carrd.co/In this video, I break down ATX-304 (also known as OS-01 or OS-03) — a powerful small molecule AMPK activator being studied for fat loss, metabolic health, and longevity. If you've heard ATX-304 described as “exercise in a capsule,” you'll see why after going through the research, mechanisms, human trials, and potential applications.I also share how ATX-304 works differently than GLP-1s, why it preserves muscle while supporting fat loss, and what the future may hold for this compound in anti-aging medicine.

"Good morning, and in case I don't see ya, good afternoon, good evening, and good night!" We take our time to evaluate publicly available preclinical data for EPI-321 used to support the Epicrispr Biotechnology first-in-human gene therapy clinical trial for FSHD. We discuss the data in the context of what is known from other neuromuscular disease gene therapy trials and integrate their own data in respect to what metrics are likely needed to be met for have any chance at providing benefit to patients.

Vidcast:  https://www.instagram.com/p/DNd5NZfu7xU/Indian nano-bioengineers have developed 400 nanometer calcium-silicate plugs that can be magnetically guided into the microscopic channels within teeth. These tiny channels, named dentinal tubules, lead to sensitive nerve endings and are exposed due to enamel erosion and.or guys recession.  Once that happens, cool or warm liquids or food can reach these nerves and trigger intense dental pain.The nanobot plugs delicately seal these tubules stop these painful episodes.  Tests on extracted teeth show that the nanobots create tubule plugs in about 20 minutes.  Preclinical tests using mice reveal that this dentinal tubule plugging strategy effectively and completely insulates teeth from pain-inducing temperature changes.  The proprietary calcium-silicate bioceramic is well tolerated by living mammalian tissues.  The researchers are planning to begin clinical trials in the not-to-distant future.https://medicalxpress.com/news/2025-08-magnetically-nanobots-relief-tooth-sensitivity.html#google_vignettehttps://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202507664#nanobots #dental #pain #dentinaltubules #bioceramic 

BUFFALO, NY — July 8, 2025 — As populations worldwide continue to age, understanding the mechanisms and manifestations of cognitive aging is increasingly urgent for science, medicine, and society. Age-related cognitive decline ranges from mild memory lapses to the onset of dementia, and is shaped by a complex interplay of molecular, cellular, systemic, and social determinants. In this special collection, Aging (Aging-US) seeks to bring together cutting-edge research that spans the cellular and molecular underpinnings of cognitive aging with insights into the psychosocial, behavioral, and environmental factors that modulate its course. By integrating basic biology with translational and societal dimensions, this collection aims to foster a holistic understanding of how and why cognitive function changes with age—and what can be done to preserve it. We welcome original research articles, reviews, and perspectives across model systems and human studies, particularly those that promote interdisciplinary insights and translational potential. POTENTIAL TOPICS Molecular and Cellular Mechanisms -Senescence, inflammation, and neurodegeneration in cognitive decline -Mitochondrial dysfunction and oxidative stress in aging neurons -Neurovascular aging and blood-brain barrier integrity -Single-cell and spatial transcriptomics of the aging brain -mTOR, autophagy, and proteostasis in age-related cognitive impairment -The role of glial cells (microglia, astrocytes) in brain aging Genetics and Biomarkers -Genetic risk factors and epigenetic modifications associated with cognitive aging -Biomarkers of cognitive resilience and vulnerability -Neuroimaging and fluid-based biomarkers in aging populations Interventions and Lifestyle Factors -Cognitive benefits of caloric restriction, exercise, or senolytic therapies -Preclinical and clinical trials targeting aging pathways to prevent cognitive decline -Impact of sleep, nutrition, and metabolic health on cognition in older adults -Use of cognitive strategies and compensatory techniques to maintain or enhance function in aging Environmental and Social Contexts -Impact of social isolation, education, and socioeconomic status on cognitive trajectories -Lifelong cognitive reserve and its determinants -Cross-cultural and demographic studies on aging and cognition -Digital health tools for monitoring or enhancing cognitive function in the elderly SUBMISSION DETAILS: -Submission Deadline: March 31, 2026 -Manuscript Format: Please follow the journal's submission guidelines -Peer Review: All submissions will undergo a rigorous peer-review process -Submission Link: https://aging.msubmit.net/cgi-bin/main.plex To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Evaluating first-line treatment of metastatic ER-positive, HER2-positive breast cancer: heredERA Breast Cancer study (0:00) Kuemmel S et al. heredERA Breast Cancer: A phase III, randomized, open-label study evaluating the efficacy and safety of giredestrant plus the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with previously untreated HER2-positive, estrogen receptor-positive locally advanced or metastatic breast cancer. BMC Cancer 2024;24(1):641. Abstract  Treatment outcomes with CDK4/6 inhibitors and with elacestrant in real-world studies (4:13) Lloyd MR et al. CDK4/6 inhibitor efficacy in ESR1-mutant metastatic breast cancer. NEJM Evid 2024;3(5). Abstract  Lloyd M et al. Impact of prior treatment, ESR1 mutational (ESR1m) landscape, and co-occurring PI3K pathway status on real-world (RW) elacestrant outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC). San Antonio Breast Cancer Symposium 2024;Abstract PS7-05.  Evaluating the CNS activity of imlunestrant, an oral selective estrogen receptor degrader (SERD) (8:06) VandeKopple M et al. Preclinical characterization of imlunestrant, an oral brain-penetrant selective estrogen receptor degrader with activity in a brain metastasis (BM) model. ESMO Breast 2023;Abstract 41P.  Selective review of trials of oral SERDs in the adjuvant setting (11:27) A study of imlunestrant versus standard endocrine therapy in participants with early breast cancer (EMBER-4). NCT05514054 CME information and select publications

Dr. Dustin Sulak Home Healer Certification-BH Sales Kennel Kelp Holistic Healing Hour: Unlocking the Potential of Cannabinoids for Autism SupportOne area of exciting research involves the impact of cannabinoids – those fascinating compounds found in cannabis – on individuals with ASD. A study examining salivary biomarkers revealed that THC, CBD, and CBG each tend to influence distinct sets of these biological markers. This suggests that different cannabinoids might exert unique effects on the body's systems.Intriguingly, research has also indicated that some children with autism present with lower levels of certain circulating endocannabinoids – specifically AEA, OEA, and PEA. These are our body's own cannabis-like molecules, playing crucial roles in regulating various functions.A compelling 2019 Israeli study looked at children with autism who didn't initially respond to a THC:CBD ratio of 1:20. Interestingly, a significant number of these children showed better outcomes when their treatment was switched to a THC:CBD ratio of 1:6. This underscores the importance of finding the right balance and individualizing treatment.Grandpa Bill: So, as we digest these fascinating insights, two probing questions come to mind:Given the variability of ASD and the distinct impacts of different cannabinoids, how can we best personalize cannabinoid-based approaches to optimize individual outcomes?With limited FDA-approved medications for core autism symptoms, what further research is needed to rigorously evaluate the safety and efficacy of various cannabinoid ratios and combinations? #AutismSupport #Cannabinoids #HolisticHealing ,#Endo cannabinoid System,It's crucial to acknowledge that only two medications have received FDA approval to address the core symptoms of autism, underscoring the need for continued exploration of complementary approaches.Preclinical research also offers valuable insights. A rodent model of ASD showed that inhibiting the FAAH enzyme, which breaks down endocannabinoids, led to improvements in repetitive and compulsive behaviors. CBD is considered the most likely cannabinoid to replicate this mechanism.However, caution is warranted. High-dose CBD treatments have been associated with adverse effects, particularly in individuals with low appetite, low body weight, or increased sedation. Personalized dosing and careful monitoring are paramount.The "core symptoms" of autism often involve challenges in social communication and interaction, as well as restricted and repetitive behaviors. Interestingly, a specific study indicated that CBD-dominant treatment led to improvements in pica, the dangerous compulsion to consume non-food items.The research landscape surrounding cannabinoids and ASD is evolving rapidly. Key questions remain:How can we leverage the unique properties of different cannabinoids to create highly personalized interventions for individuals across the autism spectrum?What rigorous, large-scale clinical trials are necessary to definitively establish the safety and efficacy of various cannabinoid formulations for ASD?The journey of understanding and supporting individuals with ASD is complex and multifaceted. The potential of cannabinoids offers a promising avenue for exploration, but it must be approached with careful research, individualized strategies, and ongoing collaboration between researchers, clinicians, and the autism community, which over stating the OBVIOUS it is here!#AutismSpectrumDisorder #ASD #Cannabinoids #CBD ,#THC, #CBG, #EndocannabinoidSystem, #HolisticHealth, #Dr.DustinSulak ,#Research, #Neurodiversity, #BHSalesKennelKelpHolisticHealingHour ,#GrandpaBillsWisdom,

The potential of pluripotent stem cells and the ability to scale and differentiate them to generate large numbers of enriched cell populations has created new opportunities and approaches to treat human disease. Preclinical proof-of-principle data demonstrates that stem cell-derived neural grafts can be used to reverse symptoms of multiple neurological conditions, including Parkinson's Disease. Cell grafts enriched with dopaminergic neurons, can structurally and functionally integrate in the brain of Parkinson's Disease models to reverse motor deficits, a finding which has launched several clinical trials. While the results in animal models is essential proof-of-concept, the survival and integration of these cells is suboptimal compared to treatments from fetal-derived ventral midbrain grafts.  An area of preclinical and clinical research showing promise in influencing neuronal survival and plasticity is exercise. The benefits of exercise on neural function and disease progression have been widely reported and they have also been shown to enhance the survival and integration of transplanted cells in models of some neurological diseases. However, there is limited data on the benefit of exercise on the functional outcomes of neural grafts in Parkinson's Disease models. The guests on today's program will discuss their recent study looking at the effect of exercise on cellular engraftment and functional recovery in animal models of Parkinson's Disease and the implications for clinical outcomes. GuestsClare Parish, PhD, The Florey Institute of Neuroscience and Mental Health and University of Melbourne, Australia Niamh Moriarty, PhD, The Florey Institute of Neuroscience and Mental Health and University of Melbourne, AustraliaSupporting ContentPaper link: Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson's disease HostJanet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner FoundationAbout Stem Cell ReportsStem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.X: @StemCellReportsAbout ISSCRWith nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.ISSCR StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsMegan Koch, Senior Marketing ManagerJack Mosher, Scientific AdvisorHunter Reed, Senior Marketing Coordinator

Roadmap for Medical Device Startups Hello, this is Hall T. Martin with the Startup Funding Espresso -- your daily shot of startup funding and investing. The path for a medical device startup is clearly defined. In building a medical device startup or diligencing one, consider this roadmap. Market requirements -- establish the current state of the market, including size, needs, and current solutions. Product requirements -- define the requirements a medical device product must have to be successful with customers. Clinical unit -- a prototype that is used to run initial clinical tests. Preclinical validation -- initial test results with the clinical unit. First in human test -- clinical trials with human subjects. Clinical validation -- in human clinical test results. CE Mark -- regulatory approval to sell a product in Europe. First European orders -- initial sales of the product in Europe 510 K clearance -- regulatory approval to sell the clinical device in the US. First US orders -- initial sales of the product in the US. Break even -- sales equal operating costs. Growth then scale -- sales continue to grow. In reviewing a medical device startup, it's important to know the steps ahead and plan your fundraising for it.   Thank you for joining us for the Startup Funding Espresso where we help startups and investors connect for funding. Let's go startup something today. _______________________________________________________ For more episodes from Investor Connect, please visit the site at:   Check out our other podcasts here:   For Investors check out:   For Startups check out:   For eGuides check out:   For upcoming Events, check out    For Feedback please contact info@tencapital.group    Please , share, and leave a review. Music courtesy of .

Vidcast:  https://www.instagram.com/p/DJHoaqqROQk/An FDA-approved psoriasis drug turns help those addicted to alcohol turn the corner.  That drug is apremilast, a phosphodiesterase 4 inhibitor sold under the brand name Otezla.Preclinical testing of the drug at San Diego's Scripps Research Institute using mouse lines that are prone to over consume alcohol shows that apemilast not only reduces craving for the drink but also lessens a characteristic accompanying heightened pain sensitivity known as mechanical allodynia.  These beneficial effects occurred in both female and male mice.Seeking to explain the drug's effects, the investigators found that apemilast increases signaling by the amino acid neurotransmitter GABA, gamma-aminobutyric acid.  GABA is known to slow down and calm brain activity thereby reducing stress, anxiety and fear.  This drug is already FDA-approved for psoriasis and psoriatic arthritis nd that's a plus for getting it into the clinic for curbing alcoholism.The next step will be clinical trials of apemilast.  Once completed, this drug may well help those with alcohol use disorder kick the habit and suppress the heightened pain response that accompanies it.https://insight.jci.org/articles/view/189732https://www.sciencedaily.com/releases/2025/04/250422155830.htm#apremilast #otezla #alcohol #aud #pain

In this JCO PO Article Insights episode, host Harold Tan summarizes Low Kynurenine Levels Among Exceptional Responders on Phase Ib Trial of the HDAC Inhibitor Abexinostat with Pazopanib by Tsang et al, published November 07, 2024. Transcript Harold Nathan Tan: Welcome to JCO Precision Oncology Article Insights, where we explore cutting-edge discoveries in the world of cancer treatment and research. I'm Harold Nathan Tan, your host, and today we're taking a focused look at a compelling phase Ib trial led by Dr. Tsang, which investigates a combination of abexinostat, a histone deacetylase inhibitor, with pazopanib, a VEGF-targeting tyrosine kinase inhibitor, in patients with advanced solid tumors. VEGF inhibition has long been an established therapeutic strategy across a wide range of tumor types, including colorectal, ovarian, sarcoma, and renal cell carcinoma. These agents function by disrupting tumor angiogenesis, effectively limiting oxygen and nutrient delivery to malignant cells and contributing to improved survival outcomes. However, over time, acquired resistance remains a significant challenge. A key mechanism implicated in this resistance involves the upregulation of hypoxia-inducible factor 1-alpha, or HIF-1-alpha for short, a master regulator of angiogenesis that restores VEGF signaling under hypoxic conditions. Interestingly, HIF-1-alpha overexpression is mediated by histone deacetylases, especially HDAC2. Preclinical studies suggest that HDAC2 inhibition can suppress tumor cell migration and downregulate HIF-1-alpha activity, effectively disabling a critical escape pathway used by tumors under VEGF pressure. Moreover, combining HDAC inhibition with VEGF blockade has demonstrated synergy in pazopanib-resistant tumor models, forming a compelling rationale for this dual approach. The phase Ib trial by Tsang et al. was designed to evaluate the safety, tolerability, and preliminary efficacy of this dual-targeted approach in patients with heavily pretreated advanced solid tumors. A dose-expansion cohort focused on individuals with renal cell carcinoma, allowing for more detailed evaluation in this population. A central component of this study was the incorporation of biomarker analysis, particularly regarding HDAC2 expression levels. The results were noteworthy. Patients with high HDAC2 expression achieved a progression-free survival of 7.7 months compared to only 3.5 months in those with low expression. Even more compelling, overall survival reached 32.3 months for those with a high HDAC2 expression versus just 9.2 months for those with low expression. This suggests the potential role for HDAC2 as a predictive biomarker for response to combination HDAC and VEGF-targeted therapy. The authors also explored the metabolic landscape of these patients, conducting metabolomic analysis focused on kynurenine, a key tryptophan catabolite known to contribute to the immune suppression in the tumor microenvironment. Its reduction is driven by HIF-1-alpha and inflammatory cytokines, including interleukin-6 and tumor necrosis factor-alpha. What they found was striking. Exceptional responders, defined as patients with treatment responses lasting more than 3 years, had consistently lower levels of kynurenine both before and after treatment. This finding introduces kynurenine as a potential metabolic biomarker. It suggests that patients with lower kynurenine levels may have a less immunosuppressive microenvironment, making them more responsive to the combined effects of HDAC inhibition and VEGF blockade. Of note, VEGF levels themselves did not significantly differ between responders and nonresponders, highlighting that the treatment benefit is not purely VEGF-mediated but likely driven by epigenetic and metabolic modulation. On the safety front, the combination of abexinostat and pazopanib was generally well tolerated. However, this study did report a correlation between higher plasma concentrations of abexinostat and an increased incidence of thrombocytopenia, a class effect associated with HDAC inhibitors. This trial introduces several key considerations for future research. First, it calls for validation of HDAC2 as a predictive biomarker. If confirmed in larger cohorts, HDAC2 expression could be used to select patients most likely to benefit from HDAC inhibitor-based regimens, transforming how we approach trial enrollment and treatment planning. Second, the link between low kynurenine and exceptional response supports further investigation into how metabolic pathways can influence treatment response to combined HDAC and VEGF inhibition. Overall, HDAC inhibitors hold significant promise in precision oncology. Realizing their full therapeutic potential requires a deeper understanding of HDAC biology, refined combination strategies, and thorough preclinical and clinical evaluations tailored to individual patient profiles. This study exemplifies the potential of epigenetic-metabolic crosstalk as a therapeutic vulnerability and underscores the importance of precision stratification in clinical trial design. As research in this space progresses, the integration of molecular, epigenetic, and metabolic profiling will be essential in optimizing the use of HDAC inhibitors and expanding their role within precision oncology. Thank you for tuning into JCO Precision Oncology Article Insights. Don't forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. Until then, stay informed and stay inspired.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

BUFFALO, NY - April 4, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 27, 2025, titled “Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy reduces intracranial tumor burden, prolongs survival in orthotopic IDH-WT GBM mouse model, and suppresses MGMT." Researchers from Brown University, led by first author Lanlan Zhou and corresponding author Wafik S. El-Deiry, have shown that combining a new class of drugs called imipridones with standard glioblastoma treatments significantly improves outcomes in mice. The study tested ONC201 and its analog ONC206 in combination with radiation therapy and the chemotherapy drug temozolomide (TMZ), a regimen referred to as IRT. This triple therapy slowed tumor growth and extended survival in a mouse model of glioblastoma, offering a potential new strategy for one of the most aggressive and treatment-resistant brain cancers. Glioblastoma is a fast-growing brain tumor with a poor prognosis and limited treatment options. Standard care typically includes surgery, radiation, and TMZ, but most patients still face a short life expectancy. While ONC201 and ONC206 are currently being studied in clinical trials as single agents, there has been limited information on how they interact with standard therapies. This study is the first to show that both drugs work synergistically with radiation and TMZ, strengthening their overall effects. The results showed that in both laboratory-grown tumor cells and mice, the triple therapy significantly slowed cancer cell growth, reduced tumor size, and prolonged survival compared to using any single or double treatment. Mice treated with IRT lived an average of 123 days, with some surviving more than 200 days—far longer than the 44 to 103 days observed with other treatment combinations. In addition to directly killing tumor cells, ONC201 and ONC206 lowered the expression of MGMT, a protein that helps tumors resist chemotherapy, making the treatment more effective. The researchers also found that the triple therapy reshaped the tumor environment. It decreased levels of harmful molecules that promote tumor growth and immune evasion while increasing signals that activate the immune system. This dual action—directly attacking tumors and boosting immune responses—adds to the potential impact of this treatment approach. “Overall, our preclinical findings support further exploration of the ONC201 and ONC206 IRT regimen as a potential treatment for GBM and diffuse gliomas with H3K27M mutations.” While these findings are based on preclinical mouse models, they offer strong support for advancing this triple therapy to clinical trials. ONC201 and ONC206 are promising due to their ability to cross the blood-brain barrier and enhance the effects of standard treatment. This combination could lead to more effective therapies for glioblastoma and other hard-to-treat brain tumors. DOI - https://doi.org/10.18632/oncotarget.28707 Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Video short - https://www.youtube.com/watch?v=Q_mXy8mana0 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28707 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

This interview with JACC: Associate Editor Neha J. Pagidipati, MD, FACC, and author Kausik Ray, MD, FACC, reviews Dr. Ray's phase one study on solbinsiran, an siRNA therapy targeting ANGPTL3 to reduce triglycerides and cardiovascular risk. Dr. Ray explains the study's findings, including significant reductions in triglycerides, ApoB, and LDL, with a favorable safety profile. The conversation also touches on the broader landscape of ANGPTL3 inhibitors, the implications of HDL reduction, and the anticipation of phase two results to be presented at ACC 2025.

Introducing Part 4 – New Frontiers in AI & Drug Discovery from Science Will Win.Follow the show: Science Will WinSo far in this season, we've explored how innovations throughout history have brought us to where we are now. We talked about how drug discovery changed from a serendipity-based to data-based endeavor. Then, we explored the powerful hardware and smart software required to accommodate big data. Now, the door to the future of AI in drug discovery is open. In our final episode, we're looking toward the future, to understand where today's advancements could potentially take us. Featured Guests:–Charlotte Allerton, Head of Preclinical and Translational Sciences at Pfizer–Daniel Ziemek, Vice President of Integrative Biology and Systems Immunology at Pfizer–Enoch Huang, Head of Machine Learning and Computational Sciences at Pfizer–Dr. Raza Ali, group leader at the University of Cambridge Cancer Research UK Institute, pathologist Season 4 of Science Will Win is created by Pfizer and hosted by Jeremiah Owyang, entrepreneur, investor, and tech industry analyst. It's produced by Wonder Media Network. DISCLAIMER: Please note, this is an independent podcast episode not affiliated with, endorsed by, or produced in conjunction with the host podcast feed or any of its media entities. The views and opinions expressed in this episode are solely those of the creators and guests. For any concerns, please reach out to team@podroll.fm.

Introducing Part 4 – New Frontiers in AI & Drug Discovery from Science Will Win.Follow the show: Science Will WinSo far in this season, we've explored how innovations throughout history have brought us to where we are now. We talked about how drug discovery changed from a serendipity-based to data-based endeavor. Then, we explored the powerful hardware and smart software required to accommodate big data. Now, the door to the future of AI in drug discovery is open. In our final episode, we're looking toward the future, to understand where today's advancements could potentially take us. Featured Guests:–Charlotte Allerton, Head of Preclinical and Translational Sciences at Pfizer–Daniel Ziemek, Vice President of Integrative Biology and Systems Immunology at Pfizer–Enoch Huang, Head of Machine Learning and Computational Sciences at Pfizer–Dr. Raza Ali, group leader at the University of Cambridge Cancer Research UK Institute, pathologist Season 4 of Science Will Win is created by Pfizer and hosted by Jeremiah Owyang, entrepreneur, investor, and tech industry analyst. It's produced by Wonder Media Network. DISCLAIMER: Please note, this is an independent podcast episode not affiliated with, endorsed by, or produced in conjunction with the host podcast feed or any of its media entities. The views and opinions expressed in this episode are solely those of the creators and guests. For any concerns, please reach out to team@podroll.fm.

Introducing Part 4 – New Frontiers in AI & Drug Discovery from Science Will Win.Follow the show: Science Will WinSo far in this season, we've explored how innovations throughout history have brought us to where we are now. We talked about how drug discovery changed from a serendipity-based to data-based endeavor. Then, we explored the powerful hardware and smart software required to accommodate big data. Now, the door to the future of AI in drug discovery is open. In our final episode, we're looking toward the future, to understand where today's advancements could potentially take us. Featured Guests:–Charlotte Allerton, Head of Preclinical and Translational Sciences at Pfizer–Daniel Ziemek, Vice President of Integrative Biology and Systems Immunology at Pfizer–Enoch Huang, Head of Machine Learning and Computational Sciences at Pfizer–Dr. Raza Ali, group leader at the University of Cambridge Cancer Research UK Institute, pathologist Season 4 of Science Will Win is created by Pfizer and hosted by Jeremiah Owyang, entrepreneur, investor, and tech industry analyst. It's produced by Wonder Media Network. DISCLAIMER: Please note, this is an independent podcast episode not affiliated with, endorsed by, or produced in conjunction with the host podcast feed or any of its media entities. The views and opinions expressed in this episode are solely those of the creators and guests. For any concerns, please reach out to team@podroll.fm.

Degenerative or myxomatous mitral valve disease (MMVD) is a common canine cardiac disease. In this episode of the VetFolio Voice podcast, we discuss the importance of early diagnosis and treatment in order to slow the progression of this disease. Listen in as we chat about MMVD, from diagnosis through the preclinical stages of the disease. We review diagnostics that can be helpful in assessing this disease, such as thoracic radiographs and echocardiography, and what information can be obtained from each. We'll also explore how the treatment plan may change once the patient is symptomatic. Want to earn CE from this episode? Be sure to log into VetFolio and take the quiz to qualify for your CE credit! https://www.vetfolio.com/courses/treatment-of-preclinical-mitral-valve-disease-in-your-practice-podcast-quiz

In this episode of Let's Combinate, host Subhi Sadeh is joined by Marta New, CEO of Radyus Research, to discuss the importance of Target Product Profiles (TPPs) in drug development and combination products. Marta, with her unique background as a venture capitalist turned CRO founder, shares her insights on how TPPs serve as strategic documents that align clinical goals, regulatory requirements, and market strategies. The discussion delves into the key sections of a TPP, such as target indication, efficacy benchmarks, safety and toxicology, and regulatory strategy. Marta emphasizes the critical role of TPPs in preclinical stages and their impact on the overall success of drug development programs. The episode also explores the integration and collaboration required across various functions like R&D, quality, regulatory, and commercial teams to create and refine a robust TPP.00:00 Introduction and Welcome00:26 Meet Marta: CEO of Radius Research00:58 Understanding Target Product Profiles (TPPs)01:44 The Importance of TPPs in Drug Development01:59 Defining a TPP03:22 TPP as a Strategic Document05:28 TPP in Preclinical and Clinical Stages07:09 Challenges and Misconceptions in TPP Development14:27 Regulatory Considerations for TPPs14:53 Sections of a TPP39:07 Understanding Toxicology Evaluations39:34 FDA Requirements for Pre-IND Talks39:51 TPP and Toxicity Thresholds41:41 Go/No-Go Criteria in TPP42:50 PKPD and Drug Distribution45:40 Drug Formulation and Quality Attributes46:36 Regulatory Strategy and 505(b)(2) Pathway52:34 Differentiation and Risk Assessment01:03:42 Transition from Discovery to Development01:07:48 Combination Products and Delivery Systems01:09:35 Conclusion and Contact InformationMarta New PhD MBA is the CEO of Radyus Research. She is an experienced drug developer with a background in early-stage venture capital, considerable pharma R&D, and university technology transfer. She can be reached at mnew@radyusresearch.com

In today's VETgirl online veterinary CE podcast, we're going to talk about one of my favorite breeds, the super sweet Cavalier King Charles Spaniel (what we'll Cavaliers from now on, since it's a mouthful!). Unfortunately, we all know that this breed has horrible myxomatous mitral valve disease. So, if you see Cavaliers in your clinic, when should you decide to put these dogs on heart medications? After all, we know that the initiation of pimobendan can significantly delay the onset of congestive heart failure in dogs with stage B2 myxomatous mitral valve disease (or “mitral valve disease”), and that detection of the transition from stage B1 to B2 in this population of dogs is important so that therapy can be initiated expediently.Sponsored By: Antech

In today's VETgirl online veterinary CE podcast, we're going to talk about one of my favorite breeds, the super sweet Cavalier King Charles Spaniel (what we'll Cavaliers from now on, since it's a mouthful!). Unfortunately, we all know that this breed has horrible myxomatous mitral valve disease. So, if you see Cavaliers in your clinic, when should you decide to put these dogs on heart medications? After all, we know that the initiation of pimobendan can significantly delay the onset of congestive heart failure in dogs with stage B2 myxomatous mitral valve disease (or “mitral valve disease”), and that detection of the transition from stage B1 to B2 in this population of dogs is important so that therapy can be initiated expediently.Sponsored By: Antech

Dr. Reisa Sperling returns for another episode of Dementia Matters. After covering her research focused on preclinical Alzheimer's disease in part one, Dr. Sperling dives deeper into the different factors that can impact cognitive decline and early-stage Alzheimer's disease and how clinical trials are shaping the field's understanding of detecting, treating and preventing the disease. Guest: Reisa Sperling, MD, director, Center for Alzheimer Research and Treatment (CART), co-principal investigator, Harvard Aging Brain Study, principal investigator, Alzheimer's Clinical Trials Consortium (ACTC), co-leader, A4 Study, co-leader, AHEAD 3-45 Study, professor of neurology, Harvard Medical School   Show Notes Listen to our first episode with Dr. Sperling, “Defining and Addressing Preclinical Alzheimer's Disease,” on Spotify, Apple Podcasts and on our website. Read more about the Harvard Aging Brains Study on their website. Read more about the AHEAD Study on their website. Watch “Voices from the AHEAD Alzheimer's Disease Trial,” featuring Dr. Cynthia Carlsson and a research participant, on YouTube.  Learn more about the Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) study here. Learn more about Dr. Sperling in her profile on the Massachusetts General Hospital website.   Connect with us Find transcripts and more at our website. Email Dementia Matters: dementiamatters@medicine.wisc.edu Follow us on Facebook and Twitter. Subscribe to the Wisconsin Alzheimer's Disease Research Center's e-newsletter. Enjoy Dementia Matters? Consider making a gift to the Dementia Matters fund through the UW Initiative to End Alzheimer's. All donations go toward outreach and production.

What if there was a way to detect Alzheimer's disease before clinical signs and symptoms even appeared? Dr. Reisa Sperling joins Dementia Matters for a two-part series covering her research on detecting and treating Alzheimer's disease at the earliest possible stage, known as preclinical Alzheimer's. In this episode, Dr. Sperling goes in-depth on amyloid and tau proteins and the implications on early detection and treatment strategies forAlzheimer's disease. Guest: Reisa Sperling, MD, director, Center for Alzheimer Research and Treatment (CART), co-principal investigator, Harvard Aging Brain Study, principal investigator, Alzheimer's Clinical Trials Consortium (ACTC), co-leader, A4 Study, co-leader, AHEAD 3-45 Study, professor of neurology, Harvard Medical School   Show Notes Read more about the Harvard Aging Brains Study on their website. Read more about the AHEAD Study on their website. Watch “Voices from the AHEAD Alzheimer's Disease Trial,” featuring Dr. Cynthia Carlsson and a research participant, on YouTube.  Learn more about the Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) study here. Learn more about Dr. Sperling in her profile on the Massachusetts General Hospital website.   Connect with us Find transcripts and more at our website. Email Dementia Matters: dementiamatters@medicine.wisc.edu Follow us on Facebook and Twitter. Subscribe to the Wisconsin Alzheimer's Disease Research Center's e-newsletter. Enjoy Dementia Matters? Consider making a gift to the Dementia Matters fund through the UW Initiative to End Alzheimer's. All donations go toward outreach and production.

The pipeline of antibiotic discovery is a major necessity due to the continuous evolution of resistance to currently used antimicrobials. This pipeline faces important challenges due to the lack of investment on antimicrobial research in the private sector and an economic model that discourages investment. In the last few years, however, encouraging signs are occurring but major gaps still remain. The World Health Organization has regularly assessed the preclinical and clinical antibacterial development pipeline and the latest report is now available in the journal, lets discuss it! Watch this episode: https://youtu.be/IgqWmHDIx-0 Topics discussed: The process for review of the antibacterial pipeline. The progress and gaps in antibiotic discovery The opportunities to overcome the numerous hurdles in the early stages of the antibacterial research and development space Guest: Valeria Gigante Ph.D., Team Lead at the World Health Organization's (WHO) in the AMR Division, Geneva, Switzerland. Link: Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps. This episode is brought to you by the Antimicrobial Agents and Chemotherapy journal available at aac.asm.org. If you plan to publish in AAC, ASM Members get up to 50% off publishing fees. Visit asm.org/membership to sign up. Visit journals.asm.org/journal/aac to browse issues and/or submit a manuscript.

Duas torres de transmissão parecem usar seus cabos como se fossem cordas. Uma terceira torre parece "pular corda". Toda vez que ela pula, a imagem treme... E algumas pessoas conseguem "ouvir" um som! E você, "ouve" algo? A ciência explica esse fenômeno?Confira o papo entre o leigo curioso, Ken Fujioka, e o cientista PhD, Altay de Souza.> OUÇA (44min 59s)*Naruhodo! é o podcast pra quem tem fome de aprender. Ciência, senso comum, curiosidades, desafios e muito mais. Com o leigo curioso, Ken Fujioka, e o cientista PhD, Altay de Souza.Edição: Reginaldo Cursino.http://naruhodo.b9.com.br*PARCERIA: ALURASabe quem mais chegou com 2024? A primeira Imersão Front-End da Alura, perfeita para começar o ano se aprofundando em tecnologia.Em 5 aulas gratuitas, você vai mergulhar em HTML, mergulhar em CSS e criar uma página web responsiva e com layouts avançados. É 100% online, 100% gratuito e com certificado de participação, com a melhor didática e as melhores professoras e professores.Você ainda terá acesso gratuito à Luri, a IA da Alura, e vai interagir com a comunidade Dev e aproveitar o espaço para networking no Discord.Mais de um milhão de pessoas já mergulharam nas Imersões da Alura. Chegou a sua vez de explorar esse novo universo. Então faça sua inscrição grátis agora mesmo, porque as vagas são limitadas!alura.tv/naruhodo-imersaofrontend*REFERÊNCIASTuíte Original (12/2017)https://x.com/LisaDeBruine/status/937105553968566272A deafening flash! Visual interference of auditory signal detectionhttps://www.sciencedirect.com/science/article/pii/S1053810016303336?via%3DihubModality effects in the coding reproduction of rhythmshttps://link.springer.com/article/10.3758/BF03202611Sounds from seeing silent motion: Who hears them, and what looks loudest?https://www.sciencedirect.com/science/article/abs/pii/S0010945218300741Neurocognitive mechanisms of synesthesiahttps://pubmed.ncbi.nlm.nih.gov/16269367/Expectancies and the generation of perceptual experience: Predictive processing and phenomenological controlhttps://osf.io/preprints/psyarxiv/rjn3kHearing through Your Eyes: Neural Basis of Audiovisual Cross-activation, Revealed by Transcranial Alternating Current Stimulationhttps://direct.mit.edu/jocn/article-abstract/31/6/922/29031/Hearing-through-Your-Eyes-Neural-Basis-of?redirectedFrom=fulltextChapter 18 - Psychophysical and behavioral peripheral and central auditory testshttps://www.sciencedirect.com/science/article/abs/pii/B9780444626301000184From oppressiveness to stress: A development of Stress Reduction Theory in the context of contemporary high-density cityhttps://www.sciencedirect.com/science/article/pii/S0272494422001281?casa_token=tByMbwrf9pQAAAAA:E1ryVic2p1ma-p3u60KHQQvdaMhu_QVjp0378LVX8eSCFLEX9Z6JLOi1m5FaPMdcV72R9D-huUgSilence in the consumer experience: A conceptualization and research agendahttps://www.sciencedirect.com/science/article/pii/S0148296323003910?casa_token=3HI5ATTO9RoAAAAA:Ye-D9YXFjitUfVfK69VYtFAn0KaTdgEifLXLqE4XiG8KGrwQiM_bjoDWAku693jrXCVFjvoCo60The Diversity of Strategies Used in Working Memory for Colors, Orientations, and Positions: A Quantitative Approach to a First-Person Inquiryhttps://onlinelibrary.wiley.com/doi/full/10.1111/cogs.13333Hearing what you see: Distinct excitatory and disinhibitory mechanisms contribute to visually-evoked auditory sensationshttps://www.sciencedirect.com/science/article/pii/S0010945220302732?casa_token=fM-wF61tH7QAAAAA:U5V7vEtQ8gK9dR_Y0NIW_rmoQ4wbgWsuEufULaurgeaKWX2KOlWIN9yQaoUbtsTiBXe-hXCrkNkGreat expectations! How predictions about the magnitude of a forthcoming sound affect its perceptual and neural processinghttps://unsworks.unsw.edu.au/entities/publication/87b67f42-bb63-4935-8cf9-688c36809cac/fullBioelectronic medicine: Preclinical insights and clinical advanceshttps://www.cell.com/neuron/pdf/S0896-6273(22)00808-X.pdfExpected Experiences - The Predictive Mind in an Uncertain Worldhttps://www.taylorfrancis.com/books/edit/10.4324/9781003084082/expected-experiences-tony-cheng-jakob-hohwy-ryoji-satoExemplo Som Código Morsehttps://www.youtube.com/watch?v=Pz57ov1pV4MNaruhodo #270 - O que é e como se dá a sinestesia?https://youtu.be/fvfrWcEEDco?si=wmdegsj6KfcainaPNaruhodo #296 - Todas as pessoas imaginam as coisas do mesmo jeito?https://youtu.be/ZcNZ92bTZc4?si=_ImAQuNXIpp2jYI6Naruhodo #29 - O que é e como acontece o déjà vu?https://youtu.be/MsgpP0CWrZs?si=IvJ17lCAH8rTJLe0*APOIE O NARUHODO PELA PLATAFORMA ORELO!Um aviso importantíssimo: o podcast Naruhodo agora está no Orelo: https://bit.ly/naruhodo-no-oreloE é por meio dessa plataforma de apoio aos criadores de conteúdo que você ajuda o Naruhodo a se manter no ar.Você escolhe um valor de contribuição mensal e tem acesso a conteúdos exclusivos, conteúdos antecipados e vantagens especiais.Além disso, você pode ter acesso ao nosso grupo fechado no Telegram, e conversar comigo, com o Altay e com outros apoiadores.E não é só isso: toda vez que você ouvir ou fizer download de um episódio pelo Orelo, vai também estar pingando uns trocadinhos para o nosso projeto.Então, baixe agora mesmo o app Orelo no endereço Orelo.CC ou na sua loja de aplicativos e ajude a fortalecer o conhecimento científico.https://bit.ly/naruhodo-no-orelo