Podcasts about nf kb

The Energy Balance Podcast

Play Episode Listen Later Jul 12, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.12.548684v1?rss=1 Authors: Pranty, A. I., Wruck, W., Adjaye, J. Abstract: Bilirubin induced neurological damage (BIND), which is also known as Kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus resulting in unconjugated bilirubin (UCB) to cross the blood brain barrier (BBB) and accumulation. Severe hyperbilirubinemia can be caused by a mutation within the UGT1A1 encoding gene. This mutation has a direct contribution towards bilirubin conjugation leading to Kernicterus as a symptom of Crigler Najjar Syndromes (CNS1, CNS2) and Gilbert syndrome, which results in permanent neurological sequelae. In this comparative study, we used human induced pluripotent stem cells (hiPSCs) derived 3D-brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of UCB in the developing human brain. hiPSC derived from healthy and CNS patients were differentiated into day 20 brain organoids, these were then stimulated with 200nM UCB. Analyses at 24 and 72 hrs post-treatment point at UCB induced neuro-inflammation in both cell lines. Transcriptome and associated KEGG and Gene Ontology analyses unveiled activation of distinct inflammatory pathways such as cytokine cytokine receptor interaction, MAPK signaling, calcium signaling, NFkB activation. Furthermore, both mRNA expression and secretome analysis confirmed an upregulation of proinflammatory cytokines such as IL6 and IL8 upon UCB stimulation. In summary, this novel study has provided insights into how a human iPSC derived 3D-brain organoid model can serve as a prospective platform for studying the etiology of BIND Kernicterus. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Ep. 94: How Stress Crashes Your Metabolism & Why Hormesis Is NOT The Answer (Stress & Mitochondria Part 2)

Play Episode Listen Later Jul 6, 2023 90:35

In this episode we discuss: Why uncoupling is harmful in certain contexts and how PUFA cause constant, low-level uncoupling The involvement of uncoupling, mitochondrial biogenesis, autophagy, heat shock proteins, and hypoxia-inducible factors in the stress response How stress prevents our mitochondria from effectively producing energy How chronic stress causes insulin resistance, high blood pressure, weight gain, depression, and cardiovascular disease How sugar and fat cravings result from stress and why listening to them is beneficial How adaptations to stress get passed on through generations Sign up for the Free Energy Balance Mini-Course here: https://jayfeldmanwellness.com/energy Click here to check out the show notes: https://www.jayfeldmanwellness.com/ep-94-how-stress-crashes-your-metabolism-why-hormesis-is-not-the-answer-stress-mitochondria-part-2/ Timestamps: 0:00 – intro 2:59 – the details of how mitochondrial respiration can become disrupted, especially from glucocorticoids 6:05 – the short-term effects of catecholamines 8:34 – why uncoupling is harmful in certain contexts and how PUFA cause constant, low-level uncoupling 14:40 – the protective effects of uncoupling as a part of the stress response 20:08 – the role of cytokines (TNF-alpha, IL-1, IL-6, heat-shock proteins, NF-kB, HIF) in the stress response 37:33 – the effect of acute stress on energy production in mitochondria 45:18– the effect of chronic stress on energy production in mitochondria 48:15 – how stress drives degeneration and the evidence for increased activity of hormetic pathways (including effects like mitochondrial biogenesis and autophagy) in degenerative states 1:05:24 – the relationship between mental health, mood, and metabolic function 1:10:21 – how adaptations to stress get passed on through mitochondrial DNA 1:18:32 – how to best improve mitochondrial function and our health

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SALL3 mediates the loss of neuroectodermal differentiation potential in human embryonic stem cells with chromosome 18q loss

Play Episode Listen Later Jun 26, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.26.546513v1?rss=1 Authors: Spits, C., Lei, Y., Al Delbany, D., Krivec, N., Regin, M., Couvreu de Deckersberg, E., Janssens, C., Ghosh, M., Sermon, K. D. Abstract: Human pluripotent stem cell (hPSC) cultures are prone to genetic drift, as cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but currently their functional consequences in differentiating cells are scarcely described. An accurate assessment of the risk associated with these genetic variants in both research and clinical settings is therefore lacking. In this work, we established that one of these recurrent abnormalities, the loss of chromosome 18q, impairs neuroectoderm commitment and affects the cardiac progenitor differentiation of hESCs. We show that downregulation of SALL3, a gene located in the common 18q loss region, is responsible for failed neuroectodermal differentiation. Knockdown of SALL3 in control lines impaired differentiation in a manner similar to the loss of 18q, while transgenic overexpression of SALL3 in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show by gene expression analysis that loss of 18q and downregulation of SALL3 leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, including the WNT, NOTCH, JAK-STAT, TGF-beta and NF-kB pathways, suggesting that these cells are in an altered state of pluripotency. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Histone chaperone HIRA, Promyelocytic Leukemia (PML) protein and p62/SQSTM1 coordinate to regulate inflammation during cell senescence and aging.

Play Episode Listen Later Jun 26, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.24.546372v1?rss=1 Authors: Dasgupta, N., Lei, X., Arnold, R., Teneche, M. G., Miller, K. N., Rajesh, A., Davis, A., Anschau, V., Campos, A. R., Gilson, R., Havas, A., Yin, S., Chua, Z. M., Proulx, J., Alcaraz, M., Rather, M. I., Baeza, J., Schultz, D. C., Berger, S. L., Adams, P. D. Abstract: Cellular senescence, a stable proliferation arrest caused by a range of cellular stresses, is a bona fide cause of cell and tissue aging. As well as proliferation arrest, cell senescence is associated with a potent pro-inflammatory phenotype, the senescence-associated secretory phenotype (SASP). Recent studies have shown the importance of cytoplasmic DNA and chromatin, either reverse transcribed expressed retrotransposons or cytoplasmic chromatin fragments (CCF) expelled from the nucleus, in activation of nuclear SASP gene expression via the cGAS/STING cytoplasmic DNA-sensing pathway. As a source of chronic inflammation, over the long term SASP promotes tissue aging and disease. Thus, it is important to better define the mechanism of SASP activation in senescence. We show here that both the Promyelocytic Leukemia (PML) protein and HIRA histone chaperone are required for SASP expression in senescent cells. PML protein is the key organizer of PML nuclear bodies, nuclear features up to 1 micron in diameter, containing many proteins and previously implicated in diverse cellular processes, including control of cell senescence and cellular intrinsic anti-viral immunity. HIRA is a histone chaperone best known for its ability to incorporate histone variant H3.3 into nuclear chromatin in a DNA replication-independent manner, including in non-proliferating senescent cells. HIRA localizes to PML nuclear bodies in senescent cells. We show that both HIRA and PML are required for activation of NF-kB and SASP. We found that HIRA regulates cytoplasmic NF-kB signaling in senescent cells through the CCF-cGAS-STING-TBK1 pathway. HIRA physically interacts with the autophagy cargo receptor p62 Sequestosome-1 (p62), and HIRA and p62 antagonistically regulate SASP. PML is required to maintain integrity of colocalized HIRA and p62 foci in the cell nucleus. Overall, our findings point to functions for HIRA and PML in coordination of cytoplasmic signalling and nuclear gene expression to regulate inflammation during cell senescence and aging. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

TNF-NFkB-p53 axis restricts in vivo survival of hPSC-derived dopamine neuron

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Play Episode Listen Later Mar 31, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.29.534819v1?rss=1 Authors: Kim, T. W., Koo, S. Y., Riessland, M., Cho, H., Chaudhry, F., Kolisnyk, B., Russo, M. V., Saurat, N., Mehta, S., Garippa, R., Betel, D., Studer, L. Abstract: Ongoing, first-in-human clinical trials illustrate the feasibility and translational potential of human pluripotent stem cell (hPSC)-based cell therapies in Parkinson's disease (PD). However, a major unresolved challenge in the field is the extensive cell death following transplantation with less than 10% of grafted dopamine neurons surviving. Here, we performed a pooled CRISPR/Cas9 screen to enhance the survival of postmitotic dopamine neurons in vivo. We identified p53-mediated apoptotic cell death as a major contributor to dopamine neuron loss and uncovered a causal link of TNFa-NFkB signaling in limiting cell survival. As a translationally applicable strategy to purify postmitotic dopamine neurons, we performed a cell surface marker screen that enabled purification without the need for genetic reporters. Combining cell sorting with adalimumab pretreatment, a clinically approved and widely used TNFa inhibitor, enabled efficient engraftment of postmitotic dopamine neurons leading to extensive re-innervation and functional recovery in a preclinical PD mouse model. Thus, transient TNFa inhibition presents a clinically relevant strategy to enhance survival and enable the engraftment of postmitotic human PSC-derived dopamine neurons in PD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Jodi Duval: Key Skincare Ingredients, Skin Trauma, and The Self-Care Link

Biohacking Beauty

Play Episode Listen Later Feb 8, 2023 85:29

Welcome to another episode of the Biohacking Beauty podcast brought to you by Young Goose Skincare! In this episode, host Amitay Eshel, the CEO of Young Goose, is joined and interviewed by Jodi Duval–which originally aired on the the Revital Health Podcast. The two discuss how you can optimize how your skin behaves by providing it with the right building blocks for your skin to function well and not only appear younger but behave younger.Jodi Duval is the Head Naturopath and owner of Revital Health. She is also the CEO of HomeHope Australia, host of the Revital Health Podcast, and lecturer at Endeavour College.What we discuss:01:10: How did Young Goose start?09:40: What's the science and difference behind quality skincare products?21:26: Which key ingredients do Young Goose products contain?30:50: What are indications of the skincare working?33:17: What is Amitay's perspective of peptides?45:10: What is skin trauma?58:03: What are the possible harms of skincare?1:08:14: What can you do to optimize your skin?1:23:34: How can you support your skin's health from an internal perspective?Key Takeaways:Resveratrol is a naturally-occurring compound present in grapes, some berries, and other fruits and nuts. This plant compound acts as an antioxidant. But what people don't know is that when applied to the skin, we don't benefit from the resveratrol itself, but from the defense mechanism of the plant compound. It acts as an antioxidant and thus can protect cells against oxidative damage of free radicals and UV radiation on the skin by reducing the expression of AP-1 and NF-kB factors. It also slows down the process of photoaging the skin. Glycation is a process that is caused by the presence of excess glucose in skin fibers. This excess triggers an internal reaction in which sugar molecules adhere to the collagen and elastin proteins, which normally help keep skin firm and supple. As a direct result of glycation, our skin becomes more rigid which may increase the appearance of concerns such as puffiness, loss of elasticity, wrinkles, and fine lines.Both mineral and chemical sunscreen technically do the job, they aren't made equally! Mineral sunscreens allow your skin to detoxify itself in a way that chemical sunscreen does NOT. With this process being crucial for your body's detoxification process, you can't afford to go the chemical sunscreen route.Skin trauma is the process in which the skin shows the appearance of past emotional traumas. Whether they are from repressed emotions or the expression of many negative emotions over time, these tend to manifest in the skin through different types of fine lines and wrinkles on one's skin. To learn more about Jodi:Instagram: @ketoconWebsite: https://www.revitalhealth.com.au/ Podcast: To learn more about Young Goose:Website: https://www.younggoose.com/Instagram: @young_goose_skincareGet 20% off your first purchase by using code PODCAST20 at www.younggoose.com

Myddosome clustering in IL-1 receptor signaling regulates the formation of an NF-kB activating signalosome

Play Episode Listen Later Jan 6, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.06.522894v1?rss=1 Authors: Cao, F., Deliz-Aguirre, R., Gerpott, F. H. U., Ziska, E., Taylor, M. J. Abstract: Signaling pathways can produce digital outputs that are invariant and analogue outputs that scale with the amount of stimulation. In IL-1 receptor (IL-1R) signaling both types of outputs require the Myddosome, a multi-protein complex. The Myddosome is required for polyubiquitin chain formation and NF-kB signaling. However, the ways in which these signals are spatially and temporally regulated to drive switch-like and proportional outcomes is not understood. We find that during IL-1R signaling, Myddosomes dynamically re-organize into large, multi-Myddosome clusters at the cell membrane. Blockade of Myddosome clustering using nanoscale extracellular barriers reduces NF-kB activation. We find that Myddosomes function as a scaffold that assembles an NF-kB signalosome consisting of E3-ubiquitin ligases TRAF6 and LUBAC, K63/M1-linked polyubiquitin chains, phospho-IKK, and phospho-p65. This signalosome preferentially assembles at regions of high Myddosome density, which enhances the recruitment of TRAF6 and LUBAC. Extracellular barriers that restrict Myddosome clustering perturbed the recruitment of both ligases. We found that LUBAC was especially sensitive to clustering, with a sevenfold lower recruitment to single Myddosomes than clustered Myddosomes. This data reveals that the clustering behavior of Myddosome provides the basis for digital and analogue IL-1R signaling. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Mesenchymal Progenitors set the homeostatic inflammatory milieu via the TAK1-NFkB axis.

Play Episode Listen Later Dec 11, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.11.519940v1?rss=1 Authors: Theret, M., Messing, M., White, Z., Henry, L. W., Rempel, L., Hamer, M., Hashimoto, J., Li, F. F., Brassard, J., Li, Y., Sauge, E., Shin, S., Day, K., Uppal, M., Low, M., Eisner, C., Sato, S., Akira, S., Bernatchez, P., McNagny, K., Rossi, F. M. V. Abstract: The ability of mesenchymal stromal cells to modulate inflammation is at the basis of the ongoing interest in their therapeutic potential. Yet, reliable success in clinical trials is limited, possibly due to a limited understanding of their impact on the inflammatory milieu in physiological conditions. Here we show that, at steady state, mesenchymal progenitors regulate the balance between type 1 and type 2 inflammatory milieus by acting on innate immune cells through the TAK1-NFkB pathway. Suppressing the constitutive activity of this pathway in MPs leads to skewing of the immune system toward systemic Type 2 inflammation (Th2). These changes have significant effects on diseases with an important inflammatory component, leading to a worsening of disease in a preclinical model of Th2-dependent Asthma, and a reduction of symptoms associated with Th1/Th17-dependent experimental autoimmune encephalitis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The Gary Null Show - 11.18.22

Play Episode Listen Later Nov 18, 2022 63:31

Videos : Niall Ferguson – Woke Totalitarianism (0:19 to 18:14) Heather Mac Donald On How The Delusion of Diversity Destroys Our Common Humanity (11:14) Elon Musk: “Klaus Schwab Is LYING!!!” (9:45) Lycopene, lutein supplements show skin protection from within against UV radiation Leibniz Research Institute for Environmental Medicine (Germany), November 10, 2022 The study's findings, published in the British Journal of Dermatology , indicated that oral supplementation with the carotenoids changed the expression of genes that are indicators of oxidative stress, photo-dermatoses and photo-aging. “To the best of our knowledge we show here for the 1st time that (i) tomato nutrient complex as well as lutein do not only protect healthy human skin against UVB/A, but also against long wave UVA1 radiation, and (ii) that oral photo-protection of healthy human skin can be demonstrated at the level of HO-1, ICAM-1 and MMP-1 gene expression,” wrote researchers from IUF – Leibniz Research Institute for Environmental Medicine in Dusseldorf. Heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-1 (MMP-1) are reported to be UVA1/UVB radiation-inducible genes. “On top of that, as part of the photo-aging process we have evidence of the effect of our ingredients on the levels of expression of genes involved in collagen degradation, suggesting a link not only to skin health but also to skin appearance. This study suggests an effect of natural antioxidants on overall skin wellness, which is relevant for men and women in all age groups.” The new study included 65 healthy volunteers aged between 18 and 60. The participants were randomly assigned to randomly consume 20 mg per day of the tomato nutrient complex or placebo for 12 weeks, or 20 mg per day of lutein or placebo for 12 weeks. A two-week washout period separated the placebo and active intervention periods. At the beginning and at the end of each phase the skin was irradiated.Results of the placebo-controlled, double blinded, randomized cross-over study indicated that the tomato nutrient complex (TNC) totally inhibited the upregulation of HO-1, ICAM-1 and MMP1 mRNA by both UVA1 and UVA/B. On the other hand, lutein only completely inhibited gene expression if taken during the first 12 weeks (ie. prior to placebo), while a significantly smaller effect was observed if it was taken during the second 12 week phase (ie. after placebo), compared to TNC. (NEXT) Diallyl trisulfide in garlic induces apoptosis in primary effusion lymphoma Kyoto Pharmaceutical University (Japan), November 7, 2022 Reports from Kyoto Pharmaceutical University stated, “The allyl sulfides, including diallyl sulfide (DAS), diallyl disulfide (DAD), and diallyl trisulfide (DAT), contained in garlic and members of the Allium family, have a variety of pharmacological activities. Therefore, allyl sulfides have been evaluated as potential novel chemotherapeutic agents.” Our news editors obtained a quote from the research, “Here, we found that DAT inhibited nuclear factor-kB (NF-kB) signaling and induced apoptosis in primary effusion lymphoma (PEL), a subtype of non-Hodgkin's B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). We examined the cytotoxic effects of DAS, DAD and DAT on PEL cells. DAT significantly reduced the viability of PEL cells compared with uninfected B-lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9. DAT induced stabilization of IkBa, and suppressed NF-kB transcriptional activity in PEL cells. We examined the mechanism underlying DAT-mediated IkBa stabilization. The results indicated that DAT stabilized IkBa by inhibiting the phosphorylation of IkBa by the IkB kinase (IKK) complex. Furthermore, DAT induced proteasomal degradation of TRAF6, and DAT suppressed IKKb-phosphorylation through downregulation of TRAF6. It is known that activation of NF-kB is essential for survival of PEL cells. In fact, the NF-kB inhibitor BAY11-7082 induced apoptosis in PEL cells. In addition, DAT suppressed the production of progeny virus from PEL cells. The administration of DAT suppressed the development of PEL cells and ascites in SCID mice xenografted with PEL cells.” According to the news editors, the research concluded: “These findings provide evidence that DAT has antitumor activity against PEL cells in-vitro and in-vivo, suggesting it to be a novel therapeutic agent for the treatment of PEL.” (NEXT) PTSD May Speed Up Cellular Aging Boston University, November 13, 2022 From birth to death, a lot may change, but our DNA—the long, double-helix molecule that contains all of a person's genetic code—stays the same. The instructions for reading that code can shift, however, as the chemical tags on and around a DNA sequence change throughout our lives, depending on our age, environment, and behavior. This outside influence on how our genes are read and expressed by cells is called epigenetics—and researchers studying it have discovered clues that may show why some veterans live longer than others. In a new study of military veterans published in Translational Psychiatry, researchers report findings that suggest former service personnel with PTSD are at greater risk of early death. “Our study found that PTSD and comorbid conditions, like substance misuse, are associated with a cellular marker of early death found in DNA methylation patterns,” says Erika Wolf, a professor of psychiatry at the Boston University School of Medicine and senior author of the study. The study included two samples of veterans that had representative levels of trauma and other psychiatric conditions, like substance use and personality disorders. One group included 434 veterans in their early 30s, who had served in post-9/11 conflicts; the other group included 647 middle-age veterans and their trauma-exposed spouses. Both groups were assessed for a range of psychological conditions, and had blood drawn to obtain genetic information and to test for levels of a variety of inflammatory molecules. The results indicate PTSD symptoms were a factor in faster cellular aging—.36 of a year faster. So, for every year that the cells of someone without PTSD age, the cells of someone with more severe PTSD symptoms age a year and a third. (NEXT) Higher sense of purpose in life may be linked to lower mortality risk Boston University, November 14, 2022 Growing research indicates that one's purpose—i.e., the extent to which someone perceives a sense of direction and goals in their life—may be linked to health-protective benefits such as better physical functioning and lower risks of cardiovascular disease or cognitive decline. Now, a new study led by a Boston University School of Public Health (BUSPH) researcher found that people with higher levels of purpose may have a lower risk of death from any cause, and that this association is applicable across race/ethnicity and gender. Published in the journal Preventive Medicine, the study results did suggest that this association is slightly stronger among women than it is among men, but there was no significant difference by race/ethnicity. “In another study I led, we found that the effect of purpose on lowering all-cause mortality may differ by socioeconomic status. In this study, we extended the prior evidence and found that the beneficial effect of purpose persisted regardless of gender and race/ethnicity.” For the study, the team assessed self-reported sense of purpose among more than 13,000 people, based on the “purpose in life” of the Ryff Psychological Well-being Scales, a widely used tool that measures different aspects of well-being and happiness. The researchers also examined mortality risk over an eight-year period beginning between 2006-2008. The results showed that people with the highest sense of purpose indicated the lowest risk of death (15.2 percent mortality risk), compared to people with the lowest sense of purpose (36.5 percent mortality risk). The team also gathered data on additional factors that can influence health, such socioeconomic status, other demographic characteristics, baseline physical health, and depression, and found that an increase in these factors was also associated with increases in a higher sense of purpose. (NEXT) Hibiscus compound shows anti-Alzheimer disease activity Pohang University of Science and Technology, November 16 2022. A report published in Alzheimer's Research & Therapy revealed that gossypetin, a flavonoid occurring in the calyx of the hibiscus flower, activates a process that reduces brain accumulation of amyloid beta, a protein that clumps to form toxic brain plaques in people with Alzheimer disease. Gossypetin has been reported to have antioxidant, antiatherosclerotic and anticancer effects. Earlier research had suggested a benefit for gossypetin, which is structurally similar to quercetin, against the aggregation of amyloid beta and tau proteins that occurs in Alzheimer disease. However, gossypetin's action in animal models of the disease had not been evaluated. Researchers at Pohang University of Science and Technology administered gossypetin or a control substance to mice that were bred to develop a condition similar to that of Alzheimer disease in humans. After 13 weeks of daily treatment, mice that received the flavonoid had less amyloid beta in the brain's hippocampus (an area involved in memory and learning) and cortex in comparison with the control mice. Gossypetin-treated animals also demonstrated better spatial learning and memory than untreated mice. Rather than affecting the production of amyloid beta, the research team found that gossypetin helped clear it by enhancing the scavenging ability of the brain's immune cells, which are known as microglia. Microglia normally consume amyloid beta but can become exhausted by continual exposure, which leads to a chronic damaging inflammatory reaction. (NEXT) Over a billion young people are potentially at risk of hearing loss from headphones, earbuds, loud music venues Mayo Clinic, November 15, 2022 More than 1 billion teens and young people are potentially at risk of hearing loss because of their use of headphones and earbuds and attendance at loud music venues, concludes a pooled data analysis of the available evidence, published in the open access journal BMJ Global Health. The World Health Organization (WHO) estimates that over 430 million people worldwide currently have disabling hearing loss. Young people are particularly vulnerable because of their use of personal listening devices (PLDs), such as smartphones, headphones and earbuds, and attendance at loud music venues, amid poor regulatory enforcement. Previously published research suggests that PLD users often choose volumes as high as 105 dB while average sound levels at entertainment venues range from 104 to 112 dB, exceeding permissible levels (80 dB for adults; 75 dB for children) even if for very short periods of time. A group of 33 studies, corresponding to data from 35 records and 19,046 participants, was included; 17 records focused on PLD use and 18 focused on loud entertainment venues. The pooled data analysis indicates that the prevalence of unsafe listening practices from PLD use and attendance at loud entertainment venues is common worldwide—24% and 48%, respectively, among teens and young people. Based on these figures, the researchers estimate that the global number of teens and young adults who could potentially be at risk of hearing loss as a result ranges from 0.67 to 1.35 billion.

IκBα controls dormancy induction in Hematopoietic stem cell development via retinoic acid

Play Episode Listen Later Nov 17, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.17.516971v1?rss=1 Authors: Thambyrajah, R., Fadlullah, Z., Proffitt, M., Neo, W. H., Guillen, Y., Casado-Pelaez, M., Herrero-Molinero, P., Brujas, C., Castelluccio, N., Gonzalez, J., Iglesias, A., Marruecos, L., Ruiz-Herguido, C., Esteller, M., Mereu, E., Lacaud, G., Espinosa, L., Bigas, A. Abstract: Recent findings are challenging the classical hematopoietic model in which long-term hematopoietic stem cells (LT-HSC) are the base of the hematopoietic system. Clonal dynamics analysis of the hematopoietic system indicate that LT-HSC are not the main contributors of normal hemapoiesis in physiological conditions and the hematopoietic system is mainly maintained by multipotent progenitors (MPPs, hereafter HPC) and LT-HSCs are mostly in a non-active state. The first HSCs emerge from the aorta-gonad and mesonephros (AGM) region along with hematopoietic progenitors (HPC) within hematopoietic clusters. Molecular pathways that determine the HSC fate instead of HPC are still unknown, although inflammatory signaling, including NF-KB has been implicated in the development of HSCs. Here, we identify a chromatin binding function for IKB (also known as the inhibitor of NF-KB) that is Polycomb repression complex 2 (PRC2)- dependent and specifically determines dormant vs proliferating HSCs from the onset of their emergence in the AGM. We find a specific reduction of LT-HSCs in the IKB knockout new-born pups. This defect is manifested at the FL stage already, and traceable to the first emerging HSCs in the E11.5 AGM, without affecting the general HPC population. IKB-deficient LT-HSCs express dormancy signature genes, are less proliferative and can robustly respond to activation stimuli such as in vitro culture and serial transplantation. At the molecular level, we find decreased PRC2-dependent H3K27me3 at the promoters of several retinoic acid signaling elements in the IKB- deficient aortic endothelium and E14.5 FL LT-HSCs. Additionally, IKB binding itself is found in the promoters of retinoic acid receptors rar in the AGM, and rar{gamma} in the LT-HSC of FL. Overall, we demonstrate that the retinoic acid pathway is over-activated in the hematopoietic clusters of IKB-deficient AGMs leading to premature dormancy of LT- HSCs that persists in the FL LT-HSCs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Gaq-PKD/PKCμ regulates the IkB transcription to limit the NF-kB mediated inflammatory response essential for early pregnancy

Play Episode Listen Later Oct 17, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.17.512513v1?rss=1 Authors: Jiang, Y., He, Y., Liu, S., Li, G., Chen, D., Deng, W., Li, P., Zhang, Y., Wu, J., Li, J., Wang, L., Lin, J., Wang, H., Kong, S., Shi, G. Abstract: Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here we demonstrated that knockout of Gaq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gaq resulted in over-activation of nuclear factor (NF)-{kappa}B signaling, due to the decreased expression of NF{kappa}BIA, which encode the I{kappa}B protein and is the negative regulator for NF{kappa}B. Mechanistically, Gaq deficiency decreased the PKD/PKC phosphorylation levels, so leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HADC5 retarded histone acetylation to inhibit NF{kappa}BIA transcription during decidualization. Consistently, pharmacological activation of the PKD/PKC or inhibition of the HDAC5 signaling restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gaq deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gq as a key regulator of the inflammatory cytokine's expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Circulation September 20, 2022 Issue

Circulation on the Run

Play Episode Listen Later Sep 19, 2022 29:03

This week, please join author Jonathan Sterne and Associate Editor Shinya Goto as they discuss the article "Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Oh, Greg, we've got a special treat for everyone today. We have a third co-host and he is none other than Peder Myhre from Norway! Really adding to the diversity of our podcast: me from Asia, you from the US, and Peder from Europe. Welcome, Peder. Dr. Peder Myhre: Thank you so much, Carolyn. It's truly an honor to be here and I'm looking forward to being part of this podcast today. Dr. Carolyn Lam: Awesome. Well, here we go. Looks like we have a feature paper, Greg? Dr. Greg Hundley: Absolutely, Carolyn. Peder, welcome. So, listeners, our feature today will involve COVID-19 and its association with arterial and venous thrombotic diseases. But before we get to that, we're going to all grab a cup of coffee from all over the world and get into some of the other articles in the issue. Peder, Carolyn, how about I go first? My first study involves a prospective cohort of 94,000 individuals from the UK Biobank, who had device-measured physical activity from 2013 to 2015 and were free from myocardial infarction and heart failure. Now, Peder and Carolyn, the study was performed because although objectively measured physical activity has been found associated with acute cardiovascular outcomes, it has not been found associated with heart failure and, of course, a syndrome that's been expanding worldwide. As such this study led by Carlos Celis-Morales from the University of Glasgow aimed to investigate the dose response relationship between device-measured physical activity and heart failure by intensity of the physical activity. Now physical activity was measured with a wrist-worn accelerometer and time spent on light, moderate, and vigorous intensity physical activity was extracted. Incidental heart failure was ascertained from linked hospital and death records. Dr. Peder Myhre: Wow, Greg. That sounds amazing. Tell us, what did they find? Dr. Greg Hundley: You bet, Peder! These investigators found that, compared with participants who undertook no moderate to vigorous intensity physical activity, those who performed 150 to 300 minutes per week of moderate intensity physical activity or 75 to 150 minutes per week of vigorous intensity physical activity were at lower risk of heart failure. Now, interestingly, the association between vigorous intensity physical activity and heart failure was a reverse J-shaped curve with a potentially lower risk reduction above 150 minutes per week. And so, the take-home message for this first paper is that device-measured physical activity, especially moderate intensity physical activity, was associated with a lower risk of heart failure. Probably current vigorous intensity physical activity recommendations should be encouraged, but not necessarily increased. In contrast, increasing moderate intensity physical activity may be beneficial, even among those meeting current recommendations. Dr. Peder Myhre: Wow, Greg. That was a great summary. And the second original research article today is about high density lipoproteins. As you know, raising HDL cholesterol levels to prevent cardiovascular disease remains a hot topic. HDL plays a key role in reverse cholesterol transport and may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin cholesterol acyl transferase, LCAT, is the rate limiting enzyme in the reverse cholesterol transport and a recombinant human LCAT called MEDI6012 has previously been shown to increase HDL cholesterol. So in this study from the corresponding author, Marc Bonaca from University of Colorado School of Medicine, the investigators in the real team is 63B multicenter placebo control trial investigated whether randomized patients to, MEDI6012 or placebo would reduce the infarct size as measured by cardiac MRI, 10 to 12 weeks after the STEMI. Dr. Greg Hundley: Very interesting, Peder. So, MRI assessments of LV mass after PCI. So, what did they find? Dr. Peder Myhre: So, Greg, the authors successfully enrolled 593 patients with a median age of 62 years and 78% males. And the median time from symptom onset to randomization was 146 minutes and only 13 minutes from hospitalization to randomization. And the index MI was anterior in 70% and 65% had TIMI Flow grade 0-1. And then to the main results at 12 weeks, the infarct size did not defer between the treatment group. So that was a 9.7% infarct size for MEDI6012 versus 10.5% for placebo with a P value of 0.79. And there was also no difference in noncalcified black volume. So the authors conclude that enhanced reverse cholesterol transport with recombinant human LCAT did not reduce infarct size or late regression of noncalcified coronary REPL at 12 weeks. Okay, Greg. So tell me about the 3rd paper you have today? Dr. Greg Hundley: Peder, what a great description on that previous paper, beautiful job there. So Peder, this next article pertains to cardio toxicity related to the administration of anthracycline-based chemotherapy. And an example would be Doxorubicin. And this occurs in patients often with certain types of cancer. As you know, Doxorubicin is still utilized for the treatment of leukemia, lymphoma, soft tissue sarcoma and in the setting of adjuvant breast cancer treatment. And so to this end, the authors, led by Lorrie Kirshenbaum from St. Boniface Hospital abstract research, wanted to assess cytokine mediated inflammation in myocellular injury, as a result of some of the inflammation that's induced by the administration of Doxorubicin. So as a little bit of background, cytokines, such as TNF alpha, have been implicated in cardiac dysfunction and toxicity associated with Doxorubicin. Now, while TNF alpha can elicit different cellular responses, including survival or death, the mechanisms underlying these divergent outcomes in the heart really somewhat remain cryptic. The E3 ubiquitin ligase, TRAF2, provides a critical signaling platform for K63 length poly ubiquitin nation of rip K1, crucial for NF-kB activation by TNF alpha and survival. Whether alterations in TNF alpha, TRAF2, NF-kB activation signaling underlie the cardiotoxic effects of Doxorubicin, remains poorly understood. So herein, these authors investigated TRAF2 signaling in the pathogenesis of Doxorubicin cardio toxicity. Dr. Peder Myhre: Oh wow, Greg. So we're talking mitochondrial dysfunction in Doxorubicin cardiomyopathy. So please tell me, what did they find and what were the clinical implications? Dr. Greg Hundley: Very nice. Peder, you remind me of Carolyn, asking me the clinical implications. Okay, so first, in mouse models and in vitro measures in rats, mouse and human pluripotent stem cell derived cardiomyocytes, these investigators monitored TNF alpha levels, LDH, cardiac ultra structure and function, mitochondrial biogenics, as you just suggested, and cardiac cell viability. They found that a novel signaling axis exists that functionally connects the cardiotoxic effects of Doxorubicin to proteasomal degradation of TRAF2. Disruption of the critical TRAF2 survival pathway by Doxorubicin, sensitizes cardiomyocytes to TNF alpha and BNIP3 mediated necrotic cell death. Perhaps, interventions that stabilize TRAF2, so here's the clinical implication, may prove beneficial in mitigating the cardiotoxic effects in cancer patients undergoing anthracycline-based chemotherapy. Dr. Carolyn Lam: So Greg, he may sound like me, but this is me going what an amazing summary and especially in something that is your specialty cardio-oncology, that's amazing. Thank you. Peder, I assume you've got one more paper? Dr. Peder Myhre: So Greg, now I'm going to sound like you and say that we are going to stay within the world of preclinical science. So genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease. However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. And there is evidence to suggest that the genetic influence of coronary artery disease sociability may partly act through vascular smooth muscle cells. So corresponding author, Shu Ye from University of Leicester, performed genotyping, RNA sequencing and cell behavior assays on the large bank of vascular smooth muscle cells with an N of almost 1500. And through these extensive analysis, they saw to identify genes whose expression was influenced by coronary artery disease associated variants. Dr. Greg Hundley: Very nice, Peder. So, more about cardiac gene expression. So, what did they find? Dr. Peder Myhre: Approximately 60% of the known coronary artery disease associated variants show statistically significant effects in vascular smooth muscle cells and the study identified 84 candidate causal genes whose expression quantitative trait, loci signals in vascular smooth muscle cells, significantly co-localized with reported coronary artery disease association signals, of which 38 of them are potentially druggable, so, that was the clinical implications. The authors conclude that a large percentage of coronary artery disease loci can modulate genes, gene expression in vascular smooth muscle cells and influence these cell behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets. And Greg, accompanying this paper is a beautiful editorial by doctors O'Donnell and Bradner entitled "Bridging the Gap to Translating Genome-Wide Discoveries into Therapies to Prevent and Treat Atherosclerotic Cardiovascular Disease." Dr. Greg Hundley: Very nicely done Peder, very nicely done. Well, as usual, we have some other items, we call it in the mail bag because we receive these wonderful research letters and also research correspondence. So I'll go first. First, Dr. Al-Khatib has a research letter entitled, "Duration of Anticoagulation Interruption before Invasive Procedures and Outcomes in Patients with Atrial Fibrillation Insights from the Aristotle Trial." And also there's a nice ECG analysis by Dr. Tsai entitled, "A Peculiar Wide-Complex Tachycardia During Flecainide Treatment." Dr. Peder Myhre: Nice, Greg, and there's also an exchange on letters to the editors and the response from Professors Zhao and Ding, and again, a response from Professor Zhang regarding the prior letter by Jin et al. pertaining to the previously published article "Micro RNA, 210 Controls, Mitochondrial Metabolism and Protects Heart Function in Myocardial Infarction." Dr. Greg Hundley: Beautifully done, Peder. Oh, wow. Welcome to this team. We're so excited to have you. And now Carolyn, I think we're going to jump over to that feature discussion and learn a little bit more about COVID-19 and arterial and venous thrombotic disease. Dr. Carolyn Lam: You bet! Let's go, Greg and Peder. Now we all know that infection with COVID 19 induces a pro-thrombotic state, but the long term effects of COVID-19 on the incidence of vascular disease, both arterial and venous, remain unclear. That is until today's feature paper. We're so grateful to have corresponding author Dr. Jonathan Stern, from the University of Bristol, as well as our associate editor, Dr. Shinya Goto from Tokai University School of Medicine to join us and discuss this very important paper today. Jonathan, could you start us off on telling us why it's so important to look at this? Haven't we always known that infections, COVID or not, are associated with pro-thrombotic state? So what's so different about what you did and what you found this time? Dr. Jonathan Stern: So, yes, I think we already knew that serious infections, in particular infections leading to hospitalization, can result in thrombotic events, either arterial or venous. And it was also clear from January, February, March 2020, that COVID led to very serious infection and therefore was likely to lead to vascular events. The questions that we set out to address, beyond simply establishing that COVID does indeed do this, was to quantify by how much COVID multiplies the rate at which these thrombotic events occurred, to do that separately for different events, such as myocardial infarction, stroke, venous thromboembolism, pulmonary embolism. And then to importantly, because we analyzed a very large dataset, which we might want to talk about, to try to separate out the amount by which the rating events was multiplied over time and in important subgroups, for example, in hospital people who were hospitalized for their COVID, compared with people who weren't hospitalized for their COVID, by age and sex, and by other demographic characteristics. Dr. Carolyn Lam: I love that, you see, that really set out the novel information this added with, may I add, very important clinical implications, which we'll get to them. You've already teed me up to talk about this 48 million adults that you managed to look at. Oh my goodness! Tell us, how in the world did you do that? Dr. Jonathan Stern: Well, I think the first thing to say is that it's my absolute privilege to talk about this paper on behalf of a really incredible team that put the work together. And a lot of that work, or that work started with really unlocking the power of NHS data because of the COVID pandemic. So in the UK, we have a national health service, free at the point of delivery to everybody. The NHS assembled electronic health records, and there's been a long and proud history of research based on electronic health records in the UK. But for the first time, because of the pandemic, a combined data resource for the whole of England, so that's a population of about 58 million people, was established and that linked primary care data - data from family doctors, data on secondary care hospital admissions, data on COVID testing and subsequently, although it's not the subject of this paper, data on vaccination. So those data were all linked and put into one place within what's called a trusted research environment with very strict controls on what can be output from the environment in order to protect patient privacy. And that was really done during 2020. And then the analyses for this paper took place during 2021, and it was an enormous amount of work by a large and absolutely fantastic team of people across multiple UK universities and national health service institutions. Dr. Carolyn Lam: Wow. Bravo! We talk about big data, we talk about using it. I trained in the NHS system. Who knew that this could come out to reveal such important results? So thank you for that as a background, but now, tell us what you found please? Dr. Jonathan Stern: So we found that rates of these conditions, they were primarily acute lymph infarction and ischemic stroke, which we grouped together with other conditions as arterial thrombotic events, and then deep vein thrombosis and pulmonary embolism, which we grouped together with other conditions as venous events. And we found that rates were substantially multiplied immediately after a diagnosis of COVID by up to 748 times, that the amount by which rates were multiplied diminished with time since COVID, but importantly that even six months to a year after that first diagnosis of COVID, rates of venous events were still about double in people who'd had COVID, compared to people who had COVID. And we found, it seemed quite clear that the persistence of the elevated risk was longer for venous events than for arterial events. Dr. Carolyn Lam: Just really fascinating results and Shinya, could I ask, what are your thoughts on this? And as you were managing this paper, the implications? Dr. Shinya Goto: First of all, thank you very much, Jonathan, for choosing saturation for your great paper. I'm handling quite a lot of papers, but your paper was very attractive. As Carolyn mentioned, it's huge data! 48 million, it's surprising, and also you also pick up booster rate of arterial embolism event for years, and you have also shown adjusted rate is initially increased quite a lot and then decreased gradually. And even after two months, three months still, there is a persisted higher risk. And as you mentioned, for the venous thrombo embolism, it's persisted for more than year to year. It's surprising. COVID-19's a different disease. Perhaps COVID-19 infection cuts to the vascular endarterial cell, perhaps, your research raised a lot of research questions, like endarterial damage induced by COVID-19 in the past 6 months; I would say more than half a year to one year. So that mechanistical insight is very important. And you raise a lot of any clinical questions. Dr. Jonathan Stern: Well, thank you very much for your kind words and you are right, I think we are left with questions about maybe in three areas. Firstly, for how long is there an elevation in risk? I should probably say, for those who haven't read the paper, that these results relate to events that occurred in England and Wales during 2020. And so that is in an era before vaccination and when we were dealing with the original variant, and to some extent, the alpha variant. So we are still waiting to see what the implications were over longer periods, and we will be doing that, we will be extending follow up. In fact, we are at the moment extending those results. I think, secondly, we are left with questions about the mechanisms, which you articulated, and thirdly, there's the question about, well, what are the implications for clinical management of patients with COVID-19? And in particular, for patients who've had severe COVID-19, for example, severe enough to be hospitalized for it? Dr. Shinya Goto: Yeah, you have also showed a very important point that even known hospitalization for COVID-19, the risk of thrombosis becomes high. So it's very surprising. And even non-hospitalized patients have a higher risk of thrombosis. That is probably the huge difference between other virus infections and COVID-19. Dr. Jonathan Stern: Yes. The good news, if you weren't hospitalized for your COVID, is that the elevation in risk declines more rapidly for people with less severe COVID who weren't hospitalized than for people with more severe COVID who were hospitalized. But nonetheless, as you say, particularly in the first week, two weeks, three weeks after COVID, there is a clear elevation in the risk of both arterial and venous events, even if you were not hospitalized for your COVID. We should probably also bear in mind that these results for 2020, when there were severe constraints for some of the time on health service resources. So you probably had to be pretty sick to get hospitalized at that time. Dr. Carolyn Lam: That was a very important caveat that you just highlighted. So thank you for contextualizing those findings for us, Jonathan, but then I kind of wish all podcast guests were like you, and you already asked a question, I was going to ask you. Which is, okay, so what's the clinical implication? Should we all be taking some low dose NOAC or aspirin? Whether you're hospitalized or not? Or if you were in 2020? Because, jokes aside, I know that you found some very important risk factors? Or these events which had clinical implications? Could you expand on it? Dr. Jonathan Stern: So maybe I'd start by saying that we didn't find that these patterns varied dramatically either by sex or by age. And in fact, when we were planning the analyses, I was convinced that we would see dramatic differences in these hazard ratios by age. And, broadly speaking, the facts on a multiplicative scale, the amount by which your rate is multiplied, looked similar across age groups and by sex. On the other hand, we did see the amount by rates of arterial and venous events were multiplied, appeared greater in people of Asian ethnicity or Black ethnicity than in people of White ethnicity. A counterintuitive finding was that the amount by which your rate was multiplied is lower, if you've had a prior event than if you hadn't. Those are the sorts of extents to which we can say something about how your own characteristics predict the consequences once you've had COVID. In terms of management, obviously the pandemic has been tumultuous for medicine and for medical research and things have moved on greatly since the pre-vaccination era, 2020 and early 2021, to which these analyses relate. So the first thing to say is, don't get hospitalized with COVID, and the best way to not be hospitalized with COVID, is to be fully vaccinated for COVID. And that's a message that I think the whole of the medical profession has communicated loudly and clearly for a long time now. So the second thing is, well, okay, what about if, nonetheless, you got COVID, particularly severe COVID, and we discussed this in the team extensively, and I particularly want to mention the senior clinical author, Dr. Will Whiteley from the University of Edinburgh in this regard, and I think the main message here is that risk factor management, cardiovascular risk factor management is always important, but it's probably particularly important in people who've had severe COVID to review risk factor management and make sure that existing guidelines in terms of cholesterol lowering, blood pressure lowering and so on, are being adhered to. We don't... So the most important thing is adherence to existing cardiovascular risk management guidelines. I think we don't have evidence that specific additional interventions are indicated in people who've had COVID, and COVID now in the era of Omicron and widespread vaccination is not the same as COVID during 2020. Dr. Shinya Goto: Jonathan, you have raised a very important issue. I strongly recommend all audiences to read this paper. We have to know persistent or higher risk of myocardial infarction, ischemic stroke, may be controlled more regularly controlled. Don't fear the COVID-19 infection to visiting the healthcare professional. In my country, some of the population stopped coming to the healthcare professional because they fear so much about infection from the hospital or clinic. But it's very important to keep that regular control like static and blood pressure control. Maybe we don't have that data about aspiring or not, but strong message your paper gave is that risk factor control after COVID-19 is very important. Dr. Jonathan Stern: I completely agree. Dr. Carolyn Lam: And I would add to that, remember the days when people were stopping their ACE inhibitors and so on for those fear? So what a great message and thank you for giving us a little bit of a peek into the future of what you're planning next with more follow up, in a population that is vaccinated from a different strain perhaps. And I think this still encourages hopefully more trials and research into this whole area of how we should be managing these patients. Well, thank you so much both of you for discussing this very, very current relevant, important paper. Thank you for publishing it in circulation with us. And to the audience, thank you for joining us today. From Greg and I, you've been listening to Circulation on the Run, and don't forget to tune in again next week. Speaker 6: This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

NUDT6, the Antisense Protein of FGF2 Gene, Plays a Depressogenic Role by Promoting Inflammation and Suppressing Neurogenesis without Altering FGF2 Signaling

Danica Patrick Pretty Intense Podcast

Play Episode Listen Later Sep 6, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.05.506638v1?rss=1 Authors: Uzay, B., Hokelekli, F. O., Yilmaz, M., Esen, E. C., Basar, K., Bahadir-Varol, A., Ayhan, Y., Dalkara, T., Eren-Kocak, E. Abstract: Fibroblast growth factor-2 (FGF2) is involved in the regulation of affective behavior and shows antidepressant effects through Akt and ERK1/2 pathways. NUDT6 is a protein encoded from the antisense strand of the FGF2 gene and its role in the regulation of affective behavior is unclear. Here, we show that increasing NUDT6 expression in the hippocampus results in depression-like behavior in rats without changing FGF2 levels or activating its downstream effectors, Akt and ERK1/2. Instead, NUDT6 acts by inducing inflammatory signaling, specifically by increasing S100A9 levels, activating NF-kB, and rising microglia number along with a reduction in neurogenesis. Conversely, inhibition of hippocampal NUDT6 expression by shRNA results in antidepressant effects and increases neurogenesis without altering FGF2 levels. Together these findings suggest that NUDT6 may play a role in major depression by inducing a proinflammatory state and serve as a novel therapeutic target for antidepressant development. The opposite effects of NUDT6 and FGF2 on depression-like behavior may serve as a mechanism to fine-tune affective behavior. Our findings open up new venues for studying the differential regulation and functional interactions of sense and antisense proteins in neural function and behavior as well as in neuropsychiatric disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

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Dr. Garry Nolan

Play Episode Listen Later Jul 14, 2022 75:59

I am the Rachford and Carlota A. Harris Professor in the Department of Pathology at Stanford University School of Medicine. I trained with Leonard Herzenberg (for my Ph.D.) and Nobelist Dr. David Baltimore (for postdoctoral work for the first cloning/characterization of NF-kB p65/RelA and the development of 293T rapid retroviral production systems). I have published 307 peer-reviewed research papers, hold 40 US patents, and have been honored as one of the top 25 inventors at Stanford University.I am well known for my ability to bring novel technologies to commercial fruition. My contributions to the implementation of mass cytometry (CyTOF) and its use for immuno-oncology research are a case in point, winning Nature's “Outstanding Research Achievement” for 2011. My current research is focused on the development of multiparameter, single-cell tissue imaging technologies and computational approaches for systems immuno-oncology. Two recent innovations from my lab include multiplexed ion beam imaging (MIBI) and CO-Detection by indEXing (CODEX), which allow for simultaneous spatial quantification of 50+ parameters in a single tissue section. Another focus of my lab is the development and utilization of machine learning algorithms to interpret the large, high-dimensional datasets produced by CyTOF, multiplexed ion beam imaging (MIBI), and CODEX. Collectively, our efforts are to provide a deeper understanding of normal and impaired immune function - including detailed substructures of the immune system as it relates to various cancerous states - to enable wholly new understandings that lead to improved clinical outcomes. Additionally, I am dedicated to teaching and mentoring. I am currently mentoring 9 postdoctoral fellows and 5 graduate students, and I have taught multiple courses at Stanford and through NIH-sponsored programs. I have assisted students and colleagues in commercializing technologies via eight companies with a sum estimated present market capitalization of $800 million.

nature medicine stanford stanford university rela nih garry collectively pathologies codex stanford university school garry nolan nf kb

64 - Hormones and Health: Pillar 5 - Inflammation

Inflammation Nation with Dr. Steven Noseworthy

Play Episode Listen Later Jun 30, 2022 26:58

The 5th and final pillar of hormone balance and control is your inflammatory load. But is taking antiinflammatory supplements like Turmeric the right thing to do? Turns out it's better to find and fix the mechanisms causing inflammation, which is messing up your hormones. Hit the subscribe or follow button to be notified when new episodes drop. Rate and review your favorite episodes to let me know the things you like so I can keep delivering great content that brings value to your life and health. Check out my online DIY programs for thyroid, gut health and detox. https://www.drnoseworthy.com/store

health diy hormones inflammation pillar turmeric nf kb

The Gary Null Show - 06.15.22

This Week in Addiction Medicine from ASAM

Play Episode Listen Later Jun 15, 2022 60:46

Videos: 1.Covid has torn apart our social fabric (Feat. Dr. Matt Strauss) 2. A Christian Response to Wokeness (FULL VIDEO) | Noelle Mering | Leadership Institute (21:51) 3. NBC News just SMEARED real journalists in shameful hit piece | Redacted with Clayton Morris (22:00) 4. COME HELL OR HIGH WATER! Four minutes of WOW! (talking about the shootings and blame) Vitamin D deficiency directly linked to dementia University of South Australia, June 14, 2022 Dementia is one of the major causes of disability and dependency among older people worldwide, affecting thinking and behaviors as you age. But what if you could stop this degenerative disease in its tracks? A world-first study from the University of South Australia could make this a reality as new genetic research shows a direct link between dementia and a lack of vitamin D. Investigating the association between vitamin D, neuroimaging features, and the risk of dementia and stroke, the study found: low levels of vitamin D were associated with lower brain volumes and an increased risk of dementia and stroke genetic analyses supported a causal effect of vitamin D deficiency and dementia. in some populations as much as 17% of dementia cases might be prevented by increasing everyone to normal levels of vitamin D (50 nmol/L). Flaxseed supplements linked to improved blood pressure: Meta-analysis University of Medicine and Pharmacy (Romania), June 9, 2022 Supplements of flaxseed may effectively management blood pressure, says a new meta-analysis of 15 clinical trials. Data from 1,302 participants indicated that flaxseed supplements are associated with significant reductions in both systolic and diastolic blood pressure of about 2.85 mmHg and 2.39 mmHg, respectively. “The results obtained in the present meta-analysis – a decrease of 2.85/2.39 mmHg after flaxseed supplementation – might be valuable for the hypertension management using nutraceuticals, since Heart Outcome Evaluation study demonstrated that a 3.3/1.4 mmHg reduction was associated with a 22% decline of relative risk of cardiovascular mortality,” wrote scientists from Romania, Iran, Australia and Poland in Clinical Nutrition . The scientists also report that supplementation for longer than 12 weeks resulted in even greater reductions in systolic and diastolic blood pressure of 3.10 mmHg and 2.62 mmHg, respectively, compared to trials of shorter duration. The potential biological mechanism are not completely understood, said the researchers, but could be linked to the lignan content of flaxseed. Specifically, a lignan named SDG is known to be an angiotensin-converting enzyme (ACE) inhibitor. ACE inhibitors work by inhibiting the conversion of angiotensin I to the potent vasoconstrictor, angiotensin II, thereby improving blood flow and blood pressure. Finally, an arginine-rich protein fraction (KCl-F1) from flaxseed may also impact blood pressure. Flaxseed powder supplements were found to affect systolic blood pressure (SBP) and diastolic blood pressure (DBP), whereas flaxseed oil preparations only affected DBP. On the other hand, lignan extracts was not associated with any changes in SBP and DBP, they said. Keep calm and carry on — for the sake of your long-term health Penn State University, June 9, 2022 Reacting positively to stressful situations may play a key role in long-term health, according to researchers. In a study measuring adults' reactions to stress and how it affects their bodies, researchers found that adults who fail to maintain positive moods such as cheerfulness or calm when faced with the minor stressors of everyday life appear to have elevated levels of inflammation. Furthermore, women can be at heightened risk. Nancy Sin, in the Center for Healthy Aging, Penn State and her colleagues showed that the frequency of daily stressors, in and of itself, was less consequential for inflammation than how an individual reacted to those stressors. “A person's frequency of stress may be less related to inflammation than responses to stress,” said Sin. “It is how a person reacts to stress that is important.” In the short-term, with illness or exercise, the body experiences a high immune response to help repair itself. However, in the long term, heightened inflammatory immune responses may not be healthy. Individuals who have trouble regulating their responses may be at risk for certain age-related conditions, such as cardiovascular disease, frailty and cognitive decline, Sin said. “To our knowledge, this paper is the first to link biomarkers of inflammation with positive mood responses to stressors in everyday life,” said Jennifer E. Graham-Engeland, associate professor of biobehavioral health, Penn State. For breast cancer prevention, diet quality matters Healthy, plant-based diet linked with lower cancer risk for postmenopausal women Paris-Saclay University (France), June 14, 2022 Research shows that what we eat can influence our cancer risk, but it's not always clear which foods or dietary patterns are best for cancer prevention. Results from a new study suggest that the quality or overall healthiness of a person's diet may be key. The study, based on data from over 65,000 postmenopausal women who were tracked for more than two decades, found that a healthy plant-based diet was linked with a 14% lower risk of breast cancer while an unhealthy plant-based diet was linked with a 20% higher risk of breast cancer. The findings were consistent across all breast cancer subtypes. “These findings highlight that increasing the consumption of healthy plant foods and decreasing the consumption of less healthy plant foods and animal foods might help prevent all types of breast cancer,” said Sanam Shah, at Paris-Saclay University, Gustave Roussy, France, the study's lead author. Previous studies have examined cancer risks associated with various dietary patterns such as the Western diet, the Mediterranean diet and vegetarian diets. Although some studies suggest diets with less or no meat consumption offer health benefits, results have been somewhat mixed. For the new study, researchers focused on differentiating between healthy plant-based foods — such as whole grains, fruit, vegetables, nuts, legumes, vegetable oils and tea or coffee — and plant-based foods the study categorized as less healthy including fruit juices, refined grains, potatoes, sugar-sweetened beverages and desserts. Regular exercise beneficial in suppressing inflammation in rheumatic disease Exercise results in physiological changes that decrease inflammation on a local and systemic level Ohio State University, June 12, 202 Research findings suggest that exercise transiently suppresses local and systemic inflammation, reinforcing the beneficial effects of exercise and the need for this to be regular in order to achieve clinical efficacy in rheumatic disease. These new research findings focused on the physiological changes created by exercise and their impact on inflammation. The researchers have found that exercise generates a true biological response and induces changes on a molecular level that stimulate anti-inflammatory effects. This in-vivo study measured the regulation and activation of NF-kB* in mice. NF-kB, a protein complex that controls many genes involved in inflammation, is found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease and arthritis. The effect of exercise on the inhibition of NF-kB activation was identified as a transient effect, lasting only 24 hours after exercise.The role of exercise in inhibiting NF-kB activation was linked to the suppression of multiple pro-inflammatory cytokines. Keeping the faith – or your willingness to push yourself – as you grow older Norwegian University of Science and Technology, June 14, 2022 So you could have become a pro footballer when you were younger, you say? Or really good at chess? Perhaps a world-renowned chef? Well, maybe not anymore, we think as we get older. And maybe that's actually okay. A research group has investigated how important the motivational factors for becoming really proficient at a skill change over the years. “We wanted to see how the passion, grit and belief that you'll succeed at getting better – your growth mindset – change with age and in relation to gender,” says Hermundur Sigmundsson, a professor at the Norwegian University of Science and Technology's (NTNU) Department of Psychology. “The passion for what you used to burn for declines. And so does the belief that you can succeed at becoming really good at it,” says Professor Sigmundsson. But this is where it is important to take hold of yourself and not give up. You might not become a world champion in anything, but you could still get really proficient if you go for it. Or at least better. “That's when it's important to maintain a growth mindset. You can't stop believing in growth even though you're getting older,” says Sigmundsson. “Passion and a growth mindset decrease with age, but the willingness to persevere increases if we look at the elderly population as a whole,” says Sigmundsson.

covid-19 university australia science technology france passion data psychology western medicine sin iran videos poland regular results previous individuals romania mediterranean penn state vitamin d investigating nbc news feat south australia redacted christian response healthy aging sdg clinical nutrition norwegian university sbp smeared flaxseed mmhg clayton morris dbp gustave roussy nf kb gary null matt strauss sigmundsson hermundur sigmundsson come hell or high water

Prof. Benedict C. Albensi of Nova SouthEastern University on Nuclear Factor Kappa B and Mitochondria

Scientific Sense ®

Play Episode Listen Later Jun 14, 2022 47:41

What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion? Evidence for the Involvement of TNF and NF-kB in Hippocampal Synaptic Plasticity, NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus, Early Growth Response 2 (Egr-2) Expression is Triggered by NF-κB Activation, and Chronic dietary creatine enhances hippocampaldependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB Scientific Sense ® by Gill Eapen: Prof. Benedict C. Albensi is a Professor and Chair of the Department of Pharmaceutical Sciences and the co-director of the BRAIN Center at Nova SouthEastern University. His research interests include factors involved in ageing, cognition, and Alzheimer's disease (AD), such as nuclear factor kappa B (NF-kB), a mediator of inflammation but also a required molecule for memory. Please subscribe to this channel: https://www.youtube.com/c/ScientificSense?sub_confirmation=1 --- Send in a voice message: https://anchor.fm/scientificsense/message Support this podcast: https://anchor.fm/scientificsense/support

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Lead Story: Getting to the Heart of Cannabis Health Risks

Play Episode Listen Later May 31, 2022 5:33

Getting to the Heart of Cannabis Health Risks Cell Press Cannabis has deleterious effects on cardiovascular physiology. Wei et al. (Cell 185, May 12, 2022) confirm that important inflammatory markers increase transiently after a single marijuana joint and prove a mechanistic link between THC induced vascular inflammation, endothelial dysfunction, cellular oxidative stress, and atherosclerosis using cell-based and mouse models of atherosclerosis. They provide a pharmacological model in which THC-mediated activation of CB1 receptor signaling pathways converge on MAP kinase, TNFa, and NF-kB outputs to create a proinflammatory and atherogenic environment in endothelial cells. That genistein can antagonize the negative effects of THC with minimal central effects is exciting because genistein is a common component of soy and is already a widely consumed dietary product. Electronic Cigarettes Versus Nicotine Patches for Smoking Cessation in Pregnancy: A Randomized Controlled Trial Nature Medicine Pregnant smokers were randomized to use either nicotine replacement therapy with patches (NRT, n=571) or e-cigarettes (n=569) for smoking cessation. For the primary outcome, validated prolonged quit rates at the end of pregnancy, the results were 4.4% for NRT and 6.8% for e-cigarettes (P=0.08). However, 25 participants in the NRT arm who reported abstinence also used e-cigarettes. When these participants were excluded from data analysis the quit rates were 3.6% for NRT and 6.8% for e-cigarettes (P=0.02). Low birthweight was less common in the e-cigarette arm, 9.6% versus 14.8% for NRT (P=0.01). The authors conclude that “e-cigarettes were markedly more effective than patches” and do not pose more risk. Daily Cannabis Use, Cannabis Use Disorder, and Any Medical Cannabis Use Among US Adults: Associations Within Racial, Ethnic, and Sexual Minoritized Identities in a Changing Policy Context Preventive Medicine Reports Cannabis use has steadily increased in the United States, with daily and medical use associated with cannabis use disorder (CUD) and the negative consequences more frequent among marginalized groups. In this study, the authors use the National Survey on Drug Use and Health (NSDUH) to examine medical and daily use and CUD across the intersections of racial, ethnic, and sexual minorities. They found that sexual minorities were more likely to have medical and daily use and CUD than their heterosexual counterparts within each racial and ethnic group. However, when examining the intersection of race, ethnicity and sexual identity, there was more heterogeneity across these groups. In addition, they found that in states with medical cannabis laws (MCL) daily cannabis use was higher across all intersectional groups. Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial AJP Psychiatry Altered glutamatergic neurotransmission is implicated in the pathogenesis of major depressive disorder. AXS-05 (dextromethorphan-bupropion) is an oral NMDA receptor antagonist and sigma-1 receptor agonist, which utilizes inhibition of CYP2D6 to increase its bioavailability. This phase 2 trial assessed the efficacy and safety of dextromethorphan-bupropion in the treatment of major depressive disorder. In patients with major depression, dextromethorphan-bupropion (AXS-05) significantly improved depressive symptoms compared with bupropion and was generally well tolerated. The most common adverse events were dizziness, nausea, dry mouth, decreased appetite, and anxiety. Dextromethorphan-bupropion was not associated with psychotomimetic effects, weight gain, or sexual dysfunction. Mental Health and Substance Use Among Homeless Adolescents in the US JAMA Network This study evaluated mental health and substance use outcomes among homeless and non-homeless adolescents in 2019. Alcohol, cigarette, marijuana, and binge drinking during the prior 30 days was assessed, along with lifetime use of cocaine, methamphetamine, heroin, ecstasy, and injection drugs or prescription opioid misuse. Results found current substance use ranging from cigarettes to alcohol were higher among homeless adolescents. Lifetime cocaine use was significantly higher among homeless adolescents, as were methamphetamine, heroin, ecstasy, and injection drug use. Homeless adolescents experience worse mental health outcomes, including depression and suicidality, and struggle with more SUDs than their counterparts. The Importance of Federal Action Supporting Overdose-Prevention Centers NEJM In this prospective piece, the authors discuss the need for new approaches to harm reduction and substance use disorder treatment in the face of substantially increasing overdose deaths, particularly since the start of the COVID-19 pandemic. One such strategy they discuss is overdose-prevention centers, which operate in other countries and are associated with significant reductions in opioid-overdose morbidity and mortality. However, under Section 856 of the Controlled Substances Act, such facilities may be subject to federal legal sanctions. The authors recommend that the Biden administration declare they will not interfere with such public health interventions or declare that section 856 does not apply to legally sanctioned centers. Further, Congress should modify the Controlled Substance Act to exempt overdose-prevention centers. Complex Persistent Benzodiazepine Dependence—When Benzodiazepine Deprescribing Goes Awry JAMA Psychiatry Benzodiazepines remain popular medications among patients due to rapid symptom relief and reinforcing effects. As clinicians and patients become more aware of potential risks, and clinical guidelines increasingly urge caution in prescribing, guidance for benzodiazepine deprescribing is needed. The authors propose a new clinical concept for patients experiencing significant psychological or functional decline during or after a benzodiazepine taper—complex persistent benzodiazepine dependence (CPBD). CPBD can be described as symptomatic or functional decompensation with or without the development of aberrant medication behaviors in the setting of benzodiazepine deprescribing–in the absence of a benzodiazepine use disorder. Further research is needed to validate this concept. What is Success in Treatment for Opioid Use Disorder? Perspectives of Physicians and Patients in Primary Care Settings JSAT Opioid abstinence and treatment retention are typically used as measures of success of MOUD treatment. This study sought to identify other important treatment outcomes and patient-centered measures of success. Qualitative, structured interviews were conducted with physicians (n=14) and patients (n=18) in 2 family medicine residency programs. The physicians (7 faculty and 7 residents) were experienced buprenorphine prescribers. Both patients and physicians identified 5 themes: staying sober, and improvement in physical health, mental health, relationships, and role functioning. Patients, but not physicians, identified 2 additional themes: tapering off buprenorphine, and decreased stigma and shame. The authors conclude that “clinicians and researchers need to consider a broader scope of success indicators.”

Bep32 - 6 shades of NF-kB #2

Antibuddies

Play Episode Listen Later Feb 27, 2022 52:19

We continue our discussion with Dr. Adewunmi Adelaja (M.D., Ph.D.), from the University of California Los Angeles, about NFkB signaling and how signals to different stimuli are relayed inside macrophages.

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Vitamin D Deficiency & Critical illness: New Study Offers Strongest Proof Yet

High Intensity Health with Mike Mutzel, MS

Play Episode Listen Later Feb 21, 2022 19:06

Scientists from Israel make a compelling case that Vitamin D should be a major part of the conversation when it comes to preventing severe COVID-19 and respiratory infections. Save on Electrolyte Stix by MYOXCIENCE; featuring Real Salt, Chelated Magnesium, Potassium, Taurine and Creatine: https://bit.ly/electrolyte-stix Use code podcast at checkout to save Link to show notes and video: https://bit.ly/33J3Mc8 Time Stamps: 0:00 Intro 0:25 Most convincing study to date 4:25 Strange trend in science 5:11 Vitamin D and your immune system 5:38 Various studies show it's protective 5:45 Vitamin D lowers background inflammation 7:00 Vitamin D receptor and NFKB, TNF-alpha and IL-6 8:31 Sunscreen is being recommended often, worsening deficiency 9:35 People over 60 need to consider vitamin D supplementation 9:50 WATCH: This table tells the story!! 11:30 Majority of patients with mild disease had sufficient Vitamin D3 levels 12:41 Super-majority of critically ill patients were deficient in vitamin D 13:07 Pre-infection levels of Vitamin D were assessed in this stuy

Bep31 - 6 shades of NF-kB #1

Antibuddies

Play Episode Listen Later Feb 18, 2022 49:54

We sit down with Dr. Adewunmi Adelaja (M.D., Ph.D.) from the University of California Los Angeles to discuss NFkB signaling and how signals to different stimuli are relayed inside macrophages.

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019 Weight Loss and Inflammation Part 7 - Herbs that control NfKB to not be inflamed

Inflammation Nation with Dr. Steven Noseworthy

Play Episode Listen Later Jan 23, 2022 11:10

All inflammatory triggers have one thing in common...they are trying to activate something called NFkB. Luckily, nature gives us several natural compounds that have been extensively researched for their ability to shut down NFkB and reduce inflammation. Hit the subscribe or follow button to be notified when new episodes drop. Rate and review your favorite episodes to let me know the things you like so I can keep delivering great content that brings value to your life and health.

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027 - Mold, Mycotoxins and Autoimmunity

The Autoimmune Doc Podcast w/ Dr. Taylor Krick

Play Episode Listen Later Nov 16, 2021 34:11

Youtube Video: Mold Toxicity and Mycotoxin IllnessYoutube Video: Research Review - Neural Antibodies in Patients with Symptoms and Histories of Mold/Chemical ExposuresYoutube Video: Research Review - Mycotoxins Induce NeurotoxicityI say this all the time, but mold toxicity is crazy. Indoor molds such as Aspergillus, Penicillium, and Stachybotrys produce mycotoxins, which are also crazy. Mold and mycotoxins can both disrupt the immune system in a myriad of different ways, which is why they are associated with autoimmunity in many ways.In this podcast, I didn't want to just read stats or research, I wanted to talk about the mechanisms by which molds and mycotoxins can affect the immune system, which are varied and complex. The research is out there on mold, but it can be hard to find because mold toxicity goes by several names - Sick Building Syndrome, Dampness and Mold Hypersensitivity Syndrome, Chronic Inflammatory Response Syndrome, Mixed Mold Mycotoxicosis, Hypersensitivity Pneumonitis to name a few - and there are many different molds, and many mycotoxins. When you work with patients and you are aware of these mechanisms, mold is an incredibly common problem. It never ceases to amaze me how many people I see whose symptoms or disease timeline correlate with a prolonged exposure to water damage, a damp or moldy environment, or a history of repeated mold exposures!Mold is ubiquitous, so your body tries really hard immunologically to tolerate it, and sometimes it tolerates it for a looong time - until one day it stops tolerating it. Mycotoxins from mold can remain indefinitely in tissues, and many have an affinity for the brain, where they disrupt mitochondrial ATP production. Some molds and mycotoxins suppress the immune system, some activate the immune system, some suppress innate immune function and increase adaptive, some do the opposite. Some people have several mycotoxins present at once, doing several different things, along with other pathogens and toxins accumulating faster due to the effects of mold. You can see how mold exposure and toxicity can quickly become quite complex immunologically! Molds and mycotoxins can cause leaky gut, leaky sinus, leaky lung, leaky brain, they can deplete glutathione, impact the microbiome, increase pathogen burdens like EBV and CMV, disrupt Th1/Th2 balance, and turn on vicious cycles of inflammation (NFkB, iNOS, NO-ONOO, Th17) - - all of which are underlying mechanisms of autoimmunity. When you hear all these various mechanisms, you begin to understand why molds and mycotoxins can contribute to autoimmunity, cancer, chronic infection, and even death, not to mention the most common symptoms of fatigue, anxiety, depression, brain fog, ENT symptoms, pituitary/thryoid/adrenal/reproductive imbalances, headaches, insomnia. There are a lot of mechanisms, and there are a lot of other variables, including genetics, history, exposure, and everything else in your bucket, but MOLD AND MYCOTOXINS are one of the scariest things on the planet!

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#54 Alan Cash: Using Oxaloacetate (Benagene) to support failing mitochondrial energy pathways & scavenge glutamate

Podcast for Healing Neurology

Play Episode Listen Later Nov 10, 2021 61:06

Alan Cash got curious about why our energy pathways fail us. Armed with an MS in physics, he's found himself innovating commercial production methods for oxaloacetate, a metabolite in the citric acid cycle that sits squarely within our mitochondria and are fundamental in producing the ATP that fuel every energy-requiring process in the body. In this episode, we review the nitty gritty details of energy production from the perspective of how oxaloacetate (brand names Benagene and Jubilance) can impact us from the systemic perspective. We don't typically discuss one commercial product on our show, but we have many patients using oxaloacetate and wanted to give a much more complete picture than we can in a clinic visit. Taking oxaloacetate has been shown to decrease NF-kB activation, reduce fasting glucose by ~25% (research from the late 1960's), increase NAD to NADH ratios, increase AMPK, decrease emotional symptoms of PMS (as the product Jubilance) and favorably shift cellular redox. Preliminary data from Mr Cash's current research is showing reduction in fatigue for CFS/ME patients. Remarkably, oral oxaloacetate seems to be able to cross the blood brain barrier (it's a very small molecule!) and can decrease brain glutamate levels. Most remarkably, taking exogenous oxaloacetate can mimic caloric restriction and has increased the lifespan of laboratory animals. It's been used in doses ranging from 100 to 6000mg daily (like for glioblastoma) and has been well-tolerated even at high doses. It's important to know that the commercial products Benagene and Jubilance contain the same ingredients: 100mg of oxaloacetate stabilized by 150mg of vitamin C. To answer another common question, there's no mechanism to turn oxaloacetate into the undesirable 'oxalate' compound in the human body. This tiny molecule really can pack a molecular and anti-inflammatory punch- listen in to find out more! Resources: https://benagene.com/ https://jubilance.com/ Oxaloacetate to reduce emotional symptoms in PMS: placebo-controlled, cross-over clinical trial with 48 women (2020): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073356/ Safety and target engagement profile of two oxaloacetate doses (500mg & 1000mg twice daily) in 15 Alzheimer's patients (2021) showed the higher dose increased frontal & frontoparietal brain glucose & glutathione per FDG PET scanning despite no changes in serum levels or cognitive scoring. https://pubmed.ncbi.nlm.nih.gov/32715609/ Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation & stimulates neurogenesis (2014) in mice injected with 1-2g/kg once daily dosing x 1-2 weeks. https://pubmed.ncbi.nlm.nih.gov/25027327/ Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans (roundworms) by 25% median & 13% maximal lifespan through an AMPK/FOXO-dependent pathway (2009). https://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2009.00527.x Oxaloacetate: A novel neuroprotective for acute ischemic stroke (2012) via modulation of the glutamate pathway which would also be applicable for other types of brain injury, like TBI (traumatic brain injury). https://pubmed.ncbi.nlm.nih.gov/22085530/ Neuroprotective effect of oxaloacetate in a focal brain ischemic model in the rat (2015) through pathways of glutamate scavenging. https://pubmed.ncbi.nlm.nih.gov/24807461/ Neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutatmate scavenging activity (2009). https://pubmed.ncbi.nlm.nih.gov/19543002/ Effect of alpha-ketoglutarate & oxaloacetate on brain mito DNA damage & seizures (2003). https://pubmed.ncbi.nlm.nih.gov/12749815/ Oxaloacetate acid supplementation as a mimic of caloric restriction: https://benthamopen.com/contents/pdf/TOLSJ/TOLSJ-3-22.pdf

The Gary Null Show - 07.06.21

Play Episode Listen Later Jul 6, 2021 61:01

Saw palmetto boosts testosterone synthesis Kyung Hee University (South Korea), June 30 2021. The June 2021 issue of the Journal of Medicinal Food reported the finding of a beneficial effect for saw palmetto against symptoms of andropause in rats. "Andropause, the male equivalent of menopause, is the set of symptoms caused by the age-related deficiency in male hormones that begins to occur in men in their late 40s to early 50s," Jeong Moon Yun and colleagues explained. "The symptoms of andropause include physical, psychological, and sexual problems, such as fatigue, increased body fat, decreased muscle strength and sexual function, depression, and memory loss." Dr Yun and associates evaluated the effects of an extract of saw palmetto in Leydig cells (in which testosterone biosynthesis occurs) subjected to oxidative stress and in aged rats. In Leydig cells, the administration of testosterone lowered 5 alpha-reductase (which converts testosterone to dihydrotestosterone) and increased total testosterone. In rats, one of three doses of saw palmetto extract was administered for four weeks. A control group of animals received no treatment. At the end of the treatment period, saw palmetto supplemented rats had significantly less fat tissue weight gain and total weight gain compared to the controls, without a gain in other tissue weight. Serum triglycerides, total cholesterol and the LDL to VLDL cholesterol ratio were also lower in the supplemented groups. Serum total and free testosterone and sperm counts were higher, and sex hormone binding globulin (SHBG) and 5 alpha-reductase levels were lower in all supplemented groups in comparison with the controls. In tests of muscle endurance, rats that received saw palmetto had longer swimming times compared to the control group. "We suggest that supplementation of saw palmetto may relieve the symptoms of andropause syndrome, including decreased spermatogenesis and muscle endurance and metabolic syndrome by increasing testosterone biosynthesis and bioavailability," the authors concluded. Diet rich in omega 3 fatty acids may help reduce headaches Trial provides 'grounds for optimism' for many people with persistent headaches and those who care for them University of North Carolina, July 1, 2021 Eating a diet rich in omega 3 (n-3) fatty acids reduces the frequency of headaches compared with a diet with normal intake of omega 3 and omega 6 (n-6) fatty acids, finds a study published by The BMJ today. Modern industrialised diets tend to be low in omega 3 fatty acids and high in omega 6 fatty acids. These fatty acids are precursors to oxylipins - molecules involved in regulating pain and inflammation. Oxylipins derived from omega 3 fatty acids are associated with pain-reducing effects, while oxylipins derived from omega 6 fatty acids worsen pain and can provoke migraine. But previous studies evaluating omega 3 fatty acid supplements for migraine have been inconclusive. So a team of US researchers wanted to find out whether diets rich in omega 3 fatty acids would increase levels of the pain-reducing 17-hydroxydocosahexaenoic acid (17-HDHA) and reduce the frequency and severity of headaches. Their results are based on 182 patients at the University of North Carolina, USA (88% female; average age 38 years) with migraine headaches on 5-20 days per month who were randomly assigned to one of three diets for 16 weeks. The control diet included typical levels of omega 3 and omega 6 fatty acids. Both interventional diets raised omega 3 fatty acid intake. One kept omega 6 acid intake the same as the control diet, and the other concurrently lowered omega 6 acid intake. During the trial, participants received regular dietary counseling and access to online support information. They also completed the headache impact test (HIT-6) - a questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. Over the 16 weeks, both interventional diets increased 17-HDHA levels compared with the control diet, and while HIT-6 scores improved in both interventional groups, they were not statistically significantly different from the control group. However, headache frequency was statistically significantly decreased in both intervention groups. The high omega 3 diet was associated with a reduction of 1.3 headache hours per day and two headache days per month. The high omega 3 plus low omega 6 diet group saw a reduction of 1.7 headache hours per day and four headache days per month, suggesting additional benefit from lowering dietary omega-6 fatty acid. Participants in the intervention groups also reported shorter and less severe headaches compared with those in the control group. This was a high quality, well designed trial, but the researchers do point to some limitations, such as the difficulty for patients to stick to a strict diet and the fact that most participants were relatively young women so results may not apply to children, older adults, men, or other populations. "While the diets did not significantly improve quality of life, they produced large, robust reductions in frequency and severity of headaches relative to the control diet," they write. "This study provides a biologically plausible demonstration that pain can be treated through targeted dietary alterations in humans. Collective findings suggest causal mechanisms linking n-3 and n-6 fatty acids to [pain regulation], and open the door to new approaches for managing chronic pain in humans," they conclude. These results support recommending a high omega 3 diet to patients in clinical practice, says Rebecca Burch at the Brigham and Women's Hospital, in a linked editorial. She acknowledges that interpretation of this study's findings is complex, but points out that trials of recently approved drugs for migraine prevention reported reductions of around 2-2.5 headache days per month compared with placebo, suggesting that a dietary intervention can be comparable or better. What's more, many people with migraine are highly motivated and interested in dietary changes, she adds. These findings "take us one step closer to a goal long sought by headache patients and those who care for them: a migraine diet backed up by robust clinical trial results." The Southern diet - fried foods and sugary drinks - may raise risk of sudden cardiac death University of Alabama, June 30, 2021 Regularly eating a Southern-style diet may increase the risk of sudden cardiac death, while routinely consuming a Mediterranean diet may reduce that risk, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association. The Southern diet is characterized by added fats, fried foods, eggs, organ meats (such as liver or giblets), processed meats (such as deli meat, bacon and hotdogs) and sugar-sweetened beverages. The Mediterranean diet is high in fruits, vegetables, fish, whole grains and legumes and low in meat and dairy. "While this study was observational in nature, the results suggest that diet may be a modifiable risk factor for sudden cardiac death, and, therefore, diet is a risk factor that we have some control over," said James M. Shikany, Dr.P.H., F.A.H.A., the study's lead author and professor of medicine and associate director for research in the Division of Preventive Medicine at the University of Alabama at Birmingham. "Improving one's diet - by eating a diet abundant in fruits, vegetables, whole grains and fish such as the Mediterranean diet and low in fried foods, organ meats and processed meats, characteristics of the Southern-style dietary pattern, may decrease one's risk for sudden cardiac death," he said. The study examined data from more than 21,000 people ages 45 and older enrolled in an ongoing national research project called REasons for Geographic and Racial Differences in Stroke (REGARDS), which is examining geographic and racial differences in stroke. Participants were recruited between 2003 and 2007. Of the participants in this analysis, 56% were women; 33% were Black adults; and 56% lived in the southeastern U.S., which is noteworthy as a region recognized as the Stroke Belt because of its higher stroke death rate. The Stroke Belt states included in this study were North Carolina, South Carolina, Georgia, Tennessee, Alabama, Mississippi, Arkansas and Louisiana. This study is the latest research to investigate the association between cardiovascular disease and diet - which foods have a positive vs. negative impact on cardiovascular disease risk. It may be the only study to-date to examine the association between dietary patterns with the risk of sudden cardiac death, which is the abrupt loss of heart function that leads to death within an hour of symptom onset. Sudden cardiac death is a common cause of death and accounted for 1 in every 7.5 deaths in the United States in 2016, or nearly 367,000 deaths, according to 2019 American Heart Association statistics. Researchers included participants with and without a history of coronary heart disease at the beginning of the study and assessed diets through a food frequency questionnaire completed at the beginning of the study. Participants were asked how often and in what quantities they had consumed 110 different food items in the previous year. Researchers calculated a Mediterranean diet score based on specific food groups considered beneficial or detrimental to health. They also derived five dietary patterns. Along with the Southern-style eating pattern, the analysis included a "sweets" dietary pattern, which features foods with added sugars, such as desserts, chocolate, candy and sweetened breakfast foods; a "convenience" eating pattern which relied on easy-to-make foods like mixed dishes, pasta dishes, or items likely to be ordered as take-out such as pizza, Mexican food and Chinese food; a "plant-based" dietary pattern was classified as being high in vegetables, fruits, fruit juices, cereal, bean, fish, poultry and yogurt; and an "alcohol and salad" dietary pattern, which was highly reliant on beer, wine, liquor along with green leafy vegetables, tomatoes and salad dressing. Shikany noted that the patterns are not mutually exclusive. "All participants had some level of adherence to each pattern, but usually adhered more to some patterns and less to others," he explained. "For example, it would not be unusual for an individual who adheres highly to the Southern pattern to also adhere to the plant-based pattern, but to a much lower degree." After an average of nearly 10 years of follow-up every six months to check for cardiovascular disease events, more than 400 sudden cardiac deaths had occurred among the 21,000 study participants. The study found: Overall, participants who ate a Southern-style diet most regularly had a 46% higher risk of sudden cardiac death than people who had the least adherence to this dietary pattern. Also, participants who most closely followed the traditional Mediterranean diet had a 26% lower risk of sudden cardiac death than those with the least adherence to this eating style. The American Heart Association's Diet and Lifestyle recommendations emphasize eating vegetables, fruits, whole grains, lean protein, fish, beans, legumes, nuts and non-tropical vegetable cooking oils such as olive and canola oil. Limiting saturated fats, sodium, added sugar and processed meat are also recommended. Sugary drinks are the number one source of added sugar in the U.S. diet, according to the Centers for Disease Control and Prevention, and the American Heart Association supports sugary drink taxes to drive down consumption of these products. "These findings support the notion that a healthier diet would prevent fatal cardiovascular disease and should encourage all of us to adopt a healthier diet as part of our lifestyles," said Stephen Juraschek, M.D., Ph.D., a member of the American Heart Association's Nutrition Committee of the Lifestyle and Cardiometabolic Health Council. "To the extent that they can, people should evaluate the number of servings of fruit and vegetables they consume each day and try to increase the number to at least 5-6 servings per day, as recommended by the American Heart Association. Optimal would be 8-9 servings per day. "This study also raises important points about health equity, food security and social determinants of health," he continued. "The authors describe the "Southern Diet" based on the U.S. geography associated with this dietary pattern, yet it would be a mistake for us to assume that this is a diet of choice. I think American society needs to look more broadly at why this type of diet is more common in the South and clusters among some racial, ethnic or socioeconomic groups to devise interventions that can improve diet quality. The gap in healthy eating between people with means and those without continues to grow in the U.S., and there is an incredible need to understand the complex societal factors that have led and continue to perpetuate these disparities." This current research expands on earlier studies on participants from the same national stroke project, REGARDS. In a 2018 analysis, Shikany and colleagues reported that adults ages 45 and older with heart disease who had an affinity for the Southern diet had a higher risk of death from any cause, while greater adherence to the Mediterranean diet was associated with a lower risk of death from any cause. And in a 2015 study, the Southern diet was linked to a greater risk of coronary heart disease in the same population. The large population sample and regional diversity, including a significant number of Black participants, are considered strengths of the REGARDS research project. However, potential limitations of this study include that that dietary intake was based on one-time, self-reported questionnaires, thus, it relied on the participants' memory. Self-reported diet can include inaccuracies leading to bias that could reduce the strength of the associations observed. One usual association that remains unexplained is that among individuals with a history of heart disease, those who most adhered to the sweets dietary pattern had a 51% lower risk of sudden cardiac death than participants who followed that pattern the least. Researchers note that they found "no viable explanation for the inverse association of the sweets dietary pattern with risk of sudden cardiac death in those with a history of coronary heart disease." 5-minute workout lowers blood pressure as much as exercise, drugs 'Strength training for breathing muscles' holds promise for host of health benefits University of Colorado, July 2, 2021 Working out just five minutes daily via a practice described as "strength training for your breathing muscles" lowers blood pressure and improves some measures of vascular health as well as, or even more than, aerobic exercise or medication, new CU Boulder research shows. The study, published June 29 in the Journal of the American Heart Association, provides the strongest evidence yet that the ultra-time-efficient maneuver known as High-Resistance Inspiratory Muscle Strength Training (IMST) could play a key role in helping aging adults fend off cardiovascular disease - the nation's leading killer. In the United States alone, 65% of adults over age 50 have above-normal blood pressure - putting them at greater risk of heart attack or stroke. Yet fewer than 40% meet recommended aerobic exercise guidelines. "There are a lot of lifestyle strategies that we know can help people maintain cardiovascular health as they age. But the reality is, they take a lot of time and effort and can be expensive and hard for some people to access," said lead author Daniel Craighead, an assistant research professor in the Department of Integrative Physiology. "IMST can be done in five minutes in your own home while you watch TV." Developed in the 1980s as a way to help critically ill respiratory disease patients strengthen their diaphragm and other inspiratory (breathing) muscles, IMST involves inhaling vigorously through a hand-held device which provides resistance. Imagine sucking hard through a tube that sucks back. Initially, when prescribing it for breathing disorders, doctors recommended a 30-minute-per-day regimen at low resistance. But in recent years, Craighead and colleagues have been testing whether a more time-efficient protocol--30 inhalations per day at high resistance, six days per week--could also reap cardiovascular, cognitive and sports performance improvements. For the new study, they recruited 36 otherwise healthy adults ages 50 to 79 with above normal systolic blood pressure (120 millimeters of mercury or higher). Half did High-Resistance IMST for six weeks and half did a placebo protocol in which the resistance was much lower. After six weeks, the IMST group saw their systolic blood pressure (the top number) dip nine points on average, a reduction which generally exceeds that achieved by walking 30 minutes a day five days a week. That decline is also equal to the effects of some blood pressure-lowering drug regimens. Even six weeks after they quit doing IMST, the IMST group maintained most of that improvement. "We found that not only is it more time-efficient than traditional exercise programs, the benefits may be longer lasting," Craighead said. The treatment group also saw a 45% improvement in vascular endothelial function, or the ability for arteries to expand upon stimulation, and a significant increase in levels of nitric oxide, a molecule key for dilating arteries and preventing plaque buildup. Nitric oxide levels naturally decline with age. Markers of inflammation and oxidative stress, which can also boost heart attack risk, were significantly lower after people did IMST. And, remarkably, those in the IMST group completed 95% of the sessions. "We have identified a novel form of therapy that lowers blood pressure without giving people pharmacological compounds and with much higher adherence than aerobic exercise," said senior author Doug Seals, a Distinguished Professor of Integrative Physiology. "That's noteworthy." The practice may be particularly helpful for postmenopausal women. In previous research, Seals' lab showed that postmenopausal women who are not taking supplemental estrogen don't reap as much benefit from aerobic exercise programs as men do when it comes to vascular endothelial function. IMST, the new study showed, improved it just as much in these women as in men. "If aerobic exercise won't improve this key measure of cardiovascular health for postmenopausal women, they need another lifestyle intervention that will," said Craighead. "This could be it." Preliminary results suggest MST also improved some measures of brain function and physical fitness. And previous studies from other researchers have shown it can be useful for improving sports performance. "If you're running a marathon, your respiratory muscles get tired and begin to steal blood from your skeletal muscles," said Craighead, who uses IMST in his own marathon training. "The idea is that if you build up endurance of those respiratory muscles, that won't happen and your legs won't get as fatigued." Seals said they're uncertain exactly how a maneuver to strengthen breathing muscles ends up lowering blood pressure, but they suspect it prompts the cells lining blood vessels to produce more nitric oxide, enabling them to relax. The National Institutes of Health recently awarded Seals $4 million to launch a larger follow-up study of about 100 people, comparing a 12-week IMST protocol head-to-head with an aerobic exercise program. Meanwhile, the research group is developing a smartphone app to enable people to do the protocol at home using already commercially available devices. Those considering IMST should consult with their doctor first. But thus far, IMST has proven remarkably safe, they said. "It's easy to do, it doesn't take long, and we think it has a lot of potential to help a lot of people," said Craighead. Research suggests atheroprotective role for chrysin Fu Jen Catholic University (Taiwan), July 1, 2021 According to news reporting originating from New Taipei, Taiwan, research stated, “Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis.” Our news editors obtained a quote from the research from Fu Jen Catholic University, “Kruppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries. Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin (found in mint, passionflower, honey and propolis) were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed. MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively. Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes.” According to the news editors, the research concluded: “The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role.” This research has been peer-reviewed. False-positive mammogram results linked to spike in anxiety prescriptions Penn State University, July 2, 2021 Women who experience a false-positive mammogram result are more likely to begin medication for anxiety or depression than women who received an immediate negative result, according to a study led by Penn State researcher Joel Segel. The finding highlights the importance of swift and accurate follow-up testing to rule out a breast cancer diagnosis. The study found that patients who receive a false-positive mammogram result are also prescribed anxiety or depression medication at a rate 10 to 20 percent higher than patients who receive an immediate negative result. These prescriptions are new and not continuations of previously prescribed medicines. A false-positive result is one where a suspicious finding on the screening mammogram leads to additional testing that does not end up leading to a breast cancer diagnosis. Additionally, within that group of patients who required more than one test to resolve the false-positive there was a 20 to 30 percent increase in those beginning to take anxiety or depression medications. The increase was particularly noticeable among women with commercial insurance who required multiple tests to rule out a breast cancer diagnosis. "The results suggest that efforts to quickly resolve initially positive findings including same-day follow-up tests may help reduce anxiety and even prevent initiation of anxiety or depression medication," said Segel, assistant professor of health policy and administration at Penn State. This study demonstrates that some women who experience a false-positive mammogram may need additional follow-up care to effectively handle the increased anxiety that may accompany the experience, Segel said. More importantly, from a practitioner standpoint, the study identifies sub-populations who may be most at risk of increased anxiety following a false-positive mammogram, Segel said. Specifically, women whose false-positive result requires more than one follow-up test to resolve, women with commercial insurance who undergo a biopsy, women who wait longer than one week to receive a negative result, and women who are under age 50 may all be at higher risk of experiencing clinically significant anxiety or depression. "Regular breast cancer screening is critical to early detection," Segel said. "Patients should continue to work with their providers to ensure they are receiving guideline-appropriate screening and should follow up with their providers if they experience either anxiety or depression following screening or any type of care." Researchers studied commercial- and Medicaid-claims databases to identify women ages 40 to 64 who underwent screening mammography with no prior claims for anxiety or depression medications. The findings recently appeared in Medical Care. Thymoquinone in Black Seed oil increases the expression of neuroprotective proteins while decreasing expression of pro-inflammatory cytokines Florida A&M University, June 29, 2021 According to news originating from Tallahassee, Florida, research stated, "Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines." Our news journalists obtained a quote from the research from Florida A&M University, "Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil. TQ has been shown to exhibit anti-inflammatory, anti-oxidative, and neuroprotective effects. In this study, lipopolysaccharide (LPS) and interferon gamma (IFN gamma) activated BV-2 microglial cells were treated with TQ (12.5 mu M for 24 h). We performed quantitative proteomic analysis using Orbitrap/Q-Exactive Proteomic LC-MS/MS (Liquid chromatography-mass spectrometry) to globally assess changes in protein expression between the treatment groups. Furthermore, we evaluated the ability of TQ to suppress the inflammatory response using ELISArray ™ for Inflammatory Cytokines. We also assessed TQ's effect on the gene expression of NFKB signaling targets by profiling 84 key genes via real-time reverse transcription (RT2) PCR array. Our results indicated that TQ treatment of LPS/IFN gamma-activated microglial cells significantly increased the expression of 4 antioxidant, neuroprotective proteins: glutaredoxin-3 (21 fold; p< 0.001), biliverdin reductase A (15 fold; p< 0.0001), 3-mercaptopyruvate sulfurtransferase (11 fold; p< 0.01), and mitochondria] Ion protease (> 8 fold; p< 0.001) compared to the untreated, activated cells. Furthermore, TQ treatment significantly (P < 0.0001) reduced the expression of inflammatory cytokines, IL-2 = 38%, IL-4 = 19%, IL-6 = 83%, IL-10 = 237%, and IL-17a = 29%, in the activated microglia compared to the untreated, activated which expression levels were significantly elevated compared to the control microglia: IL-2 = 127%, IL-4 = 151%, IL-6 = 670%, IL-10 = 133%, IL-17a = 127%. Upon assessing the gene expression of NFKB signaling targets, this study also demonstrated that TQ treatment of activated microglia resulted in > 7 fold down-regulation of several NFKB signaling targets genes, including interleukin 6 (IL6), complement factor B (CFB), chemokine (C-C motif) ligand 3 (CXCL3), chemokine (C-C) motif ligand 5 (CCL5) compared to the untreated, activated microglia. This modulation in gene expression counteracts the > 10-fold upregulation of these same genes observed in the activated microglia compared to the controls. Our results show that TQ treatment of LPS/IFN gamma-activated BV-2 microglial cells induce a significant increase in expression of neuroprotective proteins, a significant decrease in expression inflammatory cytokines, and a decrease in the expression of signaling target genes of the NF kappa B pathway. Our findings are the first to show that TQ treatment increased the expression of these neuroprotective proteins (biliverdin reductase-A, 3-mercaptopyruvate sulfurtransferase, glutaredoxin-3, and mitochondrial Ion protease) in the activated BV-2 microglial cells. Additionally, our results indicate that TQ treatment decreased the activation of the NF kappa B signaling pathway, which plays a key role in neuroinflammation." According to the news editors, the research concluded: "Our results demonstrate that TQ treatment reduces the inflammatory response and modulates the expression of specific proteins and genes and hence potentially reduce neuroinflammation and neurodegeneration driven by microglial activation."

united states tv women american university black health colorado chinese strength north carolina western lifestyle tennessee alabama south modern hospitals journal patients mexican diet south carolina louisiana improving mississippi arkansas alzheimer's disease collective southern taiwan birmingham prevention regular researchers parkinson chronic centers mediterranean national institutes penn state optimal limiting headaches medicaid disease control cc mir developed seals balloon herb american heart association distinguished professor lps brigham mst preliminary cns ldl serum geographic ion nf bv preventive medicine segel james m cu boulder atherosclerosis sugary yun nigella exosomes tq andropause nitric neuroinflammation ifn shbg flavonoids vldl racial differences integrative physiology pcrs black seed nf kb il6 gary null leydig imst ccl5

The Gary Null Show - 04.28.21

Mahan Health with Dr. Hanisha

Play Episode Listen Later Apr 28, 2021 59:39

Compound found in some vegetables may reduce diabetes-related kidney damage Phenethyl isothiocyanate, derived from watercress and other cruciferous vegetables, shows benefits Al-Maarefa University (Saudi Arabia), April 27, 2021 New research conducted in rats suggests a compound that gives some cruciferous vegetables their pungent taste could help to reverse kidney problems associated with diabetes. It is estimated that about one-quarter of people with diabetes will eventually develop diabetic nephropathy, a gradual loss of kidney function eventually requiring dialysis. The condition is a leading cause of chronic kidney disease in the U.S. and is also associated with a high risk of heart disease. There is currently no cure. For the new study, researchers assessed the effects of phenethyl isothiocyanate (PEITC) in rats with diabetic nephropathy. PEITC is found in several types of vegetables but is most concentrated in watercress. "Our study provides, for the first time, evidence that PEITC might be effective as a naturally occurring agent to reverse serious kidney damage in people with diabetes," said lead study author Mohamed El-Sherbiny, PhD, a postdoctoral fellow at AlMaarefa University in Riyadh, Saudi Arabia. "Our study introduces mechanistic evidence of how PEITC might manage kidney injury associated with diabetes by targeting multiple interconnected pathways involved in diabetic nephropathy, including inflammation, glycation and oxidative status." El-Sherbiny will present the research at the American Association for Anatomy annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30. Previous studies have suggested sulforaphane, a related compound in cruciferous vegetables, also helps reduce diabetes-associated kidney damage. The new study bolsters the evidence that eating more vegetables containing these compounds could help people with diabetes to stave off kidney problems. "PEITC seems to manage one of the most serious and painful diabetic complications. Luckily, PEITC is naturally present in many dietary sources, importantly watercress, broccoli, turnips and radish," said El-Sherbiny. Since the research was conducted in animal models, further studies will be needed to confirm the findings and understand how the results could translate to new treatments or dietary recommendations for people with diabetes. Eating probiotic foods helps improve bone health in women Kyung Hee University (South Korea), April 23, 2021 A recent study by researchers at Kyung Hee University (KHU) in South Korea presents a good example of how powerful probiotics are and how they can be used for medicinal purposes. The researchers examined the effects of probiotics on vaginosis caused by the bacterium, Gardnerella vaginalis, and osteoporosis induced by ovariectomy. They reported that probiotics, specifically, anti-inflammatory bacteria isolated from kimchi, caused significant improvements in female mice with the above-mentioned conditions. The researchers discussed their findings in an in an article published in the Journal of Medicinal Food. Probiotics from fermented food offer substantial benefits for women Bacterial vaginosis (BV) is a type of inflammation caused by the overgrowth of bacterialike G. vaginalis, which naturally reside in the vagina. Normally, good bacteria outnumber bad bacteria and keep them in check; but certain activities, such as frequent douching or unprotected sex, can disrupt the microbial balance in the vagina and promote the growth of bad bacteria. Osteoporosis, also called “porous bone,” is a disease characterized by either the loss of too much bone in the body, a decreased formation of bone, or both. These events cause the bones to become weak and more likely to break from a fall, a minor bump or even from sneezing. According to statistics, osteoporosis is more common in women, with one in three over the age of 50 experiencing bone fractures because of it, while only one in five men experience the same. Genetics and age can play a part in osteoporosis development, along with low calcium intake, thyroid problems, inflammatory conditions and the use of corticosteroid medications. In their study, the team from KHU noted that the excessive expression of tumor necrosis factor-a (TNF-a), a signaling protein (cytokine) secreted by inflammatory cells, is known to aggravate BV and osteoporosis. To determine if probiotics can influence the expression of TNF-a and alleviate these conditions, they isolated anti-inflammatory Lactobacillus plantarum NK3 and Bifidobacterium longum NK49 from kimchi as well as from human fecal samples. They then tested the effects of these good bacteria in female mice with BV and osteoporosis. The researchers reported that oral gavage of NK3 alone or in combination with NK49 significantly alleviated GV-induced vaginosis and decreased GV population in the vagina. The probiotics also inhibited the activation of NF-kB, a transcription factor that increases the production of inflammatory cytokines, and TNF-a expression in the vagina and uterus of the female mice. The researchers also found that treatment with NK3 alone or in combination with NK49 alleviated ovariectomy-induced osteoporosis and obesity. Moreover, it increased blood calcium, phosphorus and osteocalcin levels, as well as suppressed weight gain. NK3 and/or NK49 treatment also reduced TNF-a expression and NF-kB activation in the colon and restored optimal gut microbiota composition. Based on these findings, the researchers concluded that the probiotics present in fermented foods like kimchi can alleviate BV and osteoporosis by reducing inflammation and regulating gut microbial composition. Chronic stress may reduce lifespan in wild baboons, according to new multi-decadal study Duke University, April 21, 2021 Female baboons may not have bills to pay or deadlines to meet, but their lives are extremely challenging. They face food and water scarcity and must be constantly attuned to predators, illnesses and parasites, all while raising infants and maintaining their social status. A new study appearing April 21 in Science Advances shows that female baboons with high life-long levels of glucocorticoids, the hormones involved in the 'fight or flight' response, have a greater risk of dying than those with lower levels. Glucocorticoids are a group of hormones that help prepare the body for a challenge. While these hormones have many functions in the body, persistently high levels of glucocorticoids in the bloodstream can be a marker of stress. To understand the relationship between stress responses and survival, scientists studied 242 female baboons in Amboseli National Park, in Kenya. For more than 20 years, they measured glucocorticoid levels in the baboons' feces, a task that drew upon one of the world's largest collections of data from a wild primate population. Females with higher levels of glucocorticoids in their feces, either due to more frequent exposure to different types of challenges, or more intense stress responses, tended to die younger. The researchers then used these real values of hormone levels and risk of death to simulate a comparison between females that lived at opposite ends of the stress spectrum. The model showed that a hypothetical female whose glucocorticoid levels were kept very elevated would die 5.4 years sooner than a female whose glucocorticoid levels were kept very low. If they reach adulthood, female baboons have an expected lifespan of about 19 years, so 5.4-years represents a 25% shorter life. Five years more life can also represent enough time to raise one or two more infants. The team's simulations represent extreme values that are unlikely to be maintained throughout the females' lives, said Fernando Campos, an assistant professor at the University of Texas San Antonio and lead author of the study. Nonetheless, the link between exposure to stress-associated hormones and survival is clear. "Whether it's due to your environment or your genes or something that we are not measuring, having more glucocorticoids shortens your life," said Susan Alberts, a professor of biology and chair of evolutionary anthropology at Duke and senior author on the paper. The variation in glucocorticoid levels observed by Campos, Alberts, and their team shows that some females have it worse than others. Glucocorticoid levels may vary due to environmental factors, such as growing up in very hot and dry years, social factors, such as living in an unusually small or large group, and individual differences, such as being pregnant more often. "Those are the things we know about," said Alberts, "there's a whole bunch of horrible things that happen to animals that we just can't measure." "Whatever is exposing you to the glucocorticoids is going to shorten your life," Alberts said. "The more hits you get, the worse your outcome." Glucocorticoids play all sorts of vital roles in our bodies. They regulate our immunity, help our bodies access energy from sugars and fats, and modulate metabolic reactions to prepare the body for a challenge. But being constantly prepared for a challenge has high costs: maintenance processes get shut down, and fight or flight processes stay active for longer. Over time, these effects accumulate. "This chronic activation of the stress response leads to a caustic downstream physiological environment of not enough immune system, and not enough attention to maintenance," said Alberts. Associations between stress and survival are extremely difficult to test in a natural scenario. They require very frequent data collection for a very long period of time, in this case through the Amboseli Baboon Research Project, which was launched in 1971. Amboseli females are followed daily from birth to death, their activity is monitored, big events in their lives are recorded, and their feces are periodically collected. "In my lab we have one of the largest collections of primate behavioral data in the world," said Alberts, "and also one of the biggest primate poop collections." More than 14,000 fecal samples were used in this study. Poop is a very valuable, if slightly smelly, repository of information. By measuring hormone levels in feces rather than in blood or saliva, researchers avoid handling and stressing the animals, which could influence hormone levels. "People have long hypothesized that glucocorticoids play a role in how long you live," said Campos, "but to our knowledge this is the first direct evidence that chronic exposure to glucocorticoids strongly predicts survival in wild primates." Smoking cannabis significantly impairs vision, study finds Smoking cannabis significantly impairs vision but many users are unaware of it University of Granada (Spain), April 15, 2021 A study carried out by the University of Granada indicates that smoking cannabis significantly alters key visual functions, such as visual acuity, contrast sensitivity, three-dimensional vision (stereopsis), the ability to focus, and glare sensitivity Yet, more than 90% of users believe that using cannabis has no effect on their vision, or only a slight effect A group of researchers from the Department of Optics of the University of Granada (UGR) has studied the effects of smoking cannabis on various visual parameters compared to the effect that the users themselves perceive the drug to have on their vision. This study, led by Carolina Ortiz Herrera and Rosario González Anera, has been published in the journal Scientific Reports. Its main author, Sonia Ortiz Peregrina, explains that cannabis use is on the rise despite being an illegal drug. According to the national Survey on Alcohol, Drugs and Other Addictions in Spain 2019-2020, cannabis use nationally has increased since 2011, with 37% of Spanish adults having used this drug at some time. Approximately 10% consumed it in the last year. In this study, which had the approval of the Human Research Ethics Committee of the UGR (ref. 921/CCEIH/2019), an exhaustive visual trial was conducted on 31 cannabis users, both when they had not consumed any substance in advance and also when they were under the effect of the drug. The researchers also studied the participants' perception of the visual effects of having consumed this drug. The results showed that, following consumption, visual aspects such as visual acuity, contrast sensitivity, three-dimensional vision (stereopsis), the ability to focus, and glare sensitivity significantly worsened. Despite this, not all subjects reported a worsening of their vision after smoking cannabis. Indeed, 30% reported that their vision had not suffered at all, while 65% responded that it had worsened only slightly. The authors note that the visual parameter that could be most strongly linked to users' perception of the visual effect is contrast sensitivity. The study found a negative effect on all of the visual parameters evaluated, with the effect of cannabis on some of the parameters being analysed for the first time in this research. These results, together with the lack of awareness that the participants presented about the visual impairment caused by smoking cannabis, indicate the need to carry out awareness-raising campaigns, as this visual deterioration can pose a danger when performing everyday tasks. Poor iodine levels in pregnancy poses risks to fetal intellectual development University of South Australia, April 23, 2021 A growing number of young Australian women are at increased risk of having children born with impaired neurological conditions, due to poor iodine intake. Dietary changes, including a growing trend towards the avoidance of bread and iodised salt, as well as a reduced intake of animal products containing iodine can contribute to low iodine levels. A small pilot study undertaken by the University of South Australia (UniSA) comparing iodine levels between 31 vegan/plant-based participants and 26 omnivores has flagged the potential health risk. Urine samples showed iodine readings of 44 ug/L in the plant-based group, compared to the meat eaters' 64 ug/L level. Neither group came close to the World Health Organization's recommended 100 grams per liter. Participants from both groups who chose pink or Himalayan salt instead of iodised salt had severely deficient iodine levels, averaging 23 ug/L. The findings have been published in the International Journal of Environmental Research and Public Health. While the study was undertaken in South Australia, it builds evidence on a 2017 US study (1) that found nearly two billion people worldwide were iodine deficient, resulting in 50 million experiencing clinical side effects. UniSA research dietitian Jane Whitbread says adequate iodine is essential for fetal intellectual development. "Mild to moderate iodine deficiency has been shown to affect language development, memory and mental processing speeds," Ms Whitbread says. "During pregnancy, the need for iodine is increased and a 150mcg supplement is recommended prior to conception and throughout pregnancy. Unfortunately, most women do not take iodine supplements before conceiving. It is important to consume adequate iodine, especially during the reproductive years." Dietary sources of iodine include fortified bread, iodized salt, seafoods including seaweeds, eggs, and dairy foods. Concerns about the link between poor iodine status and impaired neurological conditions in newborns prompted the mandatory fortification of non-organic bread with iodised salt in 2009 in Australia. It has since been reported that women who consume 100g of iodine-fortified bread every day (approximately three pieces) have five times greater chance of meeting their iodine intake compared to women who don't consume that much. The average amount of bread consumed by women in this study was one piece of bread. The growing preference of Himalayan salt over iodized table salt may also be problematic, Ms Whitbread says. A quarter of women in the study reported using the pink salt which contains an insignificant level of iodine. Another issue is that plant-based milks have low levels of iodine and are not currently fortified with this nutrient. Neither group met the estimated average requirement (EAR) for calcium. The vegan/plant-based group also did not reach the recommended levels for selenium and B12 without supplementation, but their dietary intake of iron, magnesium, vitamin C, folate and fibre was higher than the meat eaters. This reflects the inclusion of iron-rich soy products, wholemeal foods, legumes, and green leafy vegetables in their diet. The researchers recommended that both new salts and plant milks be fortified with iodine as well as a campaign to raise awareness about the importance of iodine in the diet, especially for women in their reproductive years. They also called for a larger study sample to determine iodine status of Australian women. Taking vitamin D could lower heart disease risk for people with dark skin Racial disparities in heart disease may be linked to vitamin D deficiency Penn State University, April 26, 2021 New research suggests a simple step could help millions of people reduce their risk of heart disease: make sure to get enough vitamin D. Elucidating linkages between skin pigmentation, vitamin D and indicators of cardiovascular health, the new study, combined with evidence from previous research, suggests vitamin D deficiency could contribute to the high rate of heart disease among African Americans. "More darkly-pigmented individuals may be at greater risk of vitamin D deficiency, particularly in areas of relatively low sun exposure or high seasonality of sun exposure," said S. Tony Wolf, PhD, a postdoctoral fellow at the Pennsylvania State University and the study's lead author. "These findings may help to explain some of the differences that we see in the risk for developing blood vessel dysfunction, hypertension and overt cardiovascular disease between ethnic groups in the United States. Although there are many factors that contribute to the development of hypertension and cardiovascular disease, vitamin D supplementation may provide a simple and cost-effective strategy to reduce those disparities." Wolf noted that the need for vitamin D supplementation depends on a variety of factors, including where you live, how much time you spend in the sun, your skin pigmentation and your age. Wolf will present the research at the American Physiological Society annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30. Melanin, which is more concentrated in darker skin, is known to inhibit the process our bodies use to make vitamin D in the presence of sunlight. As a result, darkly pigmented people may make less vitamin D, potentially leading to vitamin D deficiency. For the study, Wolf and colleagues measured skin pigmentation, vitamin D and the activity of nitric oxide in the small blood vessels beneath the skin in 18 heathy adults of varying skin tones. Nitric oxide is important for blood vessel function, and reduced nitric oxide availability is thought to predispose an individual to the development of hypertension or cardiovascular disease. Previous studies suggest vitamin D helps to promote nitric oxide availability. Study participants with darker skin had lower levels of vitamin D and lower nitric oxide availability. In addition, the researchers found that lower levels of vitamin D were related to reduced nitric oxide-mediated blood vessel function. The results align with those of a separate study by the same research group, which found that vitamin D supplementation improved blood vitamin D levels and nitric oxide-mediated blood vessel function in otherwise healthy, young African American adults. "Vitamin D supplementation is a simple and safe strategy to ensure vitamin D sufficiency," said Wolf. "Our findings suggest that promoting adequate vitamin D status in young, otherwise healthy adults may improve nitric oxide availability and blood vessel function, and thereby serve as a prophylactic to reduce risk of future development of hypertension or cardiovascular disease." Men's loneliness linked to an increased risk of cancer University of Eastern Finland, April 27, 2021 A recent study by the University of Eastern Finland shows that loneliness among middle-aged men is associated with an increased risk of cancer. According to the researchers, taking account of loneliness and social relationships should thus be an important part of comprehensive health care and disease prevention. The findings were published in Psychiatry Research. "It has been estimated, on the basis of studies carried out in recent years, that loneliness could be as significant a health risk as smoking or overweight. Our findings support the idea that attention should be paid to this issue," Project Researcher Siiri-Liisi Kraav from the University of Eastern Finland says. The study was launched in the 1980s with 2,570 middle-aged men from eastern Finland participating. Their health and mortality have been monitored on the basis of register data up until present days. During the follow-up, 649 men, i.e. 25% of the participants, developed cancer, and 283 men (11%) died of cancer. Loneliness increased the risk of cancer by about ten per cent. This association with the risk of cancer was observed regardless of age, socio-economic status, lifestyle, sleep quality, depression symptoms, body mass index, heart disease and their risk factors. In addition, cancer mortality was higher in cancer patients who were unmarried, widowed or divorced at baseline. "Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects. This information would enable us to better alleviate loneliness and the harm caused by it, as well as to find optimal ways to target preventive measures." How exercise and the simple act of moving your body can improve mental health University of Toronto, April 26, 2021 Whether running around a track or simply stretching in your living room, physical activity can go a long way toward making you happier. Catherine Sabiston, a professor in the University of Toronto's Faculty of Kinesiology & Physical Education, says the positive impact of exercise on mental health is well-documented. "There is uncontested evidence that physical activity is conducive to mental health," she says. For example, Sabiston co-authored a study in the Journal of Sport and Exercise Psychology that adolescents who consistently participated in team sports during high school reported lower depression levels in early adulthood. A Canada Research Chair in physical activity and mental health, Sabiston directs a lab that studies the connections between physical activity and mental health, developing and evaluating interventions to promote physical activity and mental wellness among people who are at risk of inactivity and mental health problems. The lab also runs a six-week program called MoveU.HappyU that provides customized coaching and training aimed at reducing the stress and anxiety of students in the lab through physical movement. She recently spoke with U of T News about why it's important to stay active during the pandemic—and how to feel good doing it. How closely connected are physical activity and mental health? Symptoms of mental illness such as anxiety and depression can impede physical activity and vice versa. When you are experiencing symptoms, you may also encounter feelings of low self-worth and an inability to be motivated. It's very hard to find a type of physical activity that you can engage in when you lack interest in most things. Many of the symptoms tied to mental illness are also barriers to physical activity. On the flip side, there is uncontested evidence that physical activity is conducive to mental health. Physical activity prevents some forms of mental illness, and, for individuals who have been diagnosed with mental illness, physical activity can help reduce those symptoms and improve their quality of life. It holds its own weight in comparison to all other forms of treatment for mental illness, including psychotherapy and even medication. Physical activity is a potential adjunct to any other form of preventative or treatment-focused therapy. How exactly does exercise lift our mood? There are a number of mechanisms at play, including physical activity effects that are tied to our brain activity and brain chemistry. Physical activity increases our body temperature. When we are warmer, we are given the sense that we are comfortable and cared for. Also, from a historical perspective, we know that humans were naturally much more active in the past than we are now. So, physical activity brings us closer to that core level of movement that human bodies are meant to be. Moreover, physical activity can mimic mental health symptoms such as anxiety. When you exercise, you may sweat or feel your heart racing. That mimics the feeling of panic, so by engaging in exercise, you are producing a similar physical effect that can make you more accustomed to those symptoms. Exercise also provides you with an opportunity, whether for two minutes or 20, to break away from your usual routines or worries. This escape can help people better cope with their symptoms while experiencing a sense of purpose or accomplishment. In fact, feelings of mastery and accomplishment are also specific ways that physical activity impacts mental health. Small goals and activities inherent to physical activity offer plenty of opportunities for positive feedback, feeling successful and achieving, which helps stave off symptoms of mental illness. Finally, physical activity is something you can partake in outdoors, which has a potentiating effect on mental health. That allows you to see other people, even if you are not interacting with them, and feel a sense of connectedness. What are some ways people can stay active and motivated during the pandemic? We want to dispel the myth that physical activity is just running, biking and lifting weights. Physical activity can be any movement where your heart is increasing its work capacity and your body is moving. In "MoveU.HappyU," we coach students on day-to-day strategies for how to maintain a level of physical activity. Because the program is virtual now, we have trained students who are currently all over the world. Some students who had never spoken to their families about their mental health struggles are now actually having their whole families join in on the physical activities. The physical activity you are doing should be something that you enjoy. If you don't enjoy it, you're not going to continue to do it. We also want people to engage in physical activity to improve function rather than appearance. It's important to uncouple the relationship between physical activity for weight and body-size reasons and move towards physical activity for enjoyment and fun reasons. If it's fun, you are more likely to do it, and more likely to do it leads to more benefits. Do you have any tips for people looking to boost physical activity at home? There are many ways you can innovate physical activity to make it more varied, even when you are stuck in the same place. The best part of physical activity is thinking about the endless possibilities of ways your body can move. If you are purposeful about it, physical activity can be integrated into your everyday routines: Set aside time as you would if you were going to the gym or commuting. Mark it in your calendar or set an alarm to give you an actual reminder. Use your phone or a pedometer to measure your step count. Having something that measures how many steps you're taking gives you a baseline: If you know you walked a certain number of steps on day one, you can add five additional steps on day two. That way you'll have a tangible goal for increasing movement. Consciously link items or places in your home to short bouts of movement. For example, if you use the toaster oven every morning, make a habit of doing squats while you're waiting for your bread. Or when you are wheeling from one room to another, add some extra distance. When you're outside, use aspects of your environment to change up your physical activity. You can change the intensity of your walking or wheeling, for instance, each time that you pass a lamppost or see a blue car. Make it fun to change up the intensity, type, and timing of your activities. Create movement challenges for yourself and your friends, family, colleagues, or students. Set goals for taking a certain number of steps or finishing a certain number of arm raises each day. Making physical activity more like a game is a proven strategy for increasing movement—and enjoying it.

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The Inflammation Spectrum with Dr. Will Cole

Play Episode Listen Later Feb 2, 2021 48:12

What is inflammation? How can inflammation be supportive of our bodies? At what point does inflammation become a problem? What is NF-kB and what is happening biochemically when we have too much inflammation? What are diseases that may be caused directly by inflammation? What are some things that can exacerbate inflammation? What are some things that can help improve inflammation? What are some tips on fasting? Learn all this and more in this week's episode! IN THIS EPISODE: I interview my esteemed colleague, Dr. Will Cole. Dr. Will Cole, IFMCP, DNM, DC, is a leading functional medicine expert who consults people around the world via webcam and locally in Pittsburgh. Named one of the top 50 functional medicine and integrative doctors in the nation, Dr. Cole specializes in clinically investigating underlying factors of chronic disease and customizing a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. He is the bestselling author of Ketotarian and The Inflammation Spectrum. Dr. Cole has also cohosted the popular podcasts goodfellas and Keto Talk and will be hosting the new podcast, The Art of Being Well, which launches in early 2021. WHERE CAN YOU FIND DR. SOOD? - WEBSITE: https://drwillcole.com/ - INSTAGRAM: @drwillcole - FACEBOOK: @doctorwillcole - BOOKS: The Inflammation Spectrum and Intuitive Fasting WHERE CAN YOU FIND ME? Schedule a complimentary consult with me here: Mahan Health Subscribe to my newsletter for recipes, blog posts, and updates! Subscribe to my YouTube channel Follow me on Instagram Follow me on Facebook Follow me on Twitter Connect with me on LinkedIn *This podcast is not meant to serve as medical advice. Please speak to your healthcare provider before making any changes to your own personal health.

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The Actual HOW to Boost Your Immune System

Gut Check Project

Play Episode Listen Later Jan 12, 2021 54:30

0:00 Hello, everyone, welcome to the gut check project gut check project fans, KBMD health family, how are you doing? It is now time for episode number 47. I'm here with my awesome co host, Dr. Kenneth Brown. 0:13 What's up Episode 47. This is part two of our immunology. So this is I'm pretty excited. Because just this morning, you said you better check out Joe Rogan this morning because Dr. Mark Gordon is on there. And this dude was saying everything that we've been talking about, but I feel like we even have it to the next level. So we're talking to scientists that understand the whole concept of functional nutrition, functional things that I felt like he was saying, everything that we've been talking about now for quite a while like yours0:45 is no doubt the coolest thing is another thing that we'll we'll get to it in a moment. But it's it's all about eating right. having great nutrition, he used an incredible example of India, where Let's face it, a lot of people don't have the economic means that we do here in the United States. However, they're facing COVID, they have the same health issues that we do here, roughly, and they've got a large population. So when comparing apples to apples are talking about nutrition, and there's some specific things in that nutrition when you say,1:17 oh, and we're gonna get into that, in fact, I got an article here that we're gonna go over and I'll spoiler alert for you. But it's exactly what what what we're talking about right now. So we got some feedback. I apologize to everyone the last podcast we did, we were trying some unique things. And we didn't have such good sound quality, but that's what you get when your sponsor is lousy Lavalier comm so we had LousyLavalier.com Yeah, so we dropped them. And so I'm happy to announce that we got a new sponsor, which we did get a new sponsor, and this is awesome. It's actually a hot dog company. They're called diarrhea dogs. And their slogan is, we're not sure what's in the dog, but we know it will give you diarrhea. Yeah. who's who's betting our sponsor?2:05 The cool thing is, is it's a it's a host specific sponsor, so I'm looking for you to tell me how I2:11 know seriously, who in the company is? Is it Mike? is Mike getting sponsors for us, Mike, because I've already cashed a check. We got to keep talking about diarrhea dogs.2:18 It's, I can't this can't keep happening.2:20 We had lousy Lavalier as a sponsor, then we followed up with diarrhea dogs, yeah. Oh, my goodness,2:25 this is not working out.2:26 We're gonna have a little talk with Barry Weiss. How you been man?2:30 doing well, so we're into a brand new year now. What brief amount of time had a great vacation with the family? And it really just in time, right. I mean, there's, everything's kind of limited on what you can do. Yeah. But we it was, it's good to always have the older son come home spend time with him. We started building some furniture over the last couple weeks. So it's a great bonding experience with me and the boys. And of course, Maria is telling us what she wants us to look like. So trying hard to make it. Yeah. But you know, it's it's been a lot of fun. Mac is in the swing of basketball. And so life, normal life is starting to take on a new meaning. But it's it's good.3:09 Yeah. What about you? Well, for us, um, you know, the, the whole COVID lockdown, you start looking at your house a little bit. And so loida kind of convinced me that maybe we should start considering making a few little changes. And it started out with the master bath. And she's like, you know, shoot, can I do a few other things? I'm like, Yeah, absolutely. So I'm really busy with work and come back. And then you know, next thing I know, the builders or the contractors there and he's like, Look, okay, so this is what we've designed. Here's the plans, bla bla bla bla bla, and, you know, he's like, we're gonna buy the neighbor's house and we're gonna, you know, tear, tear this one down. But I mean, it was just I'm like, Whoa, we're doing a lot of work here. So I'm already in it. We're gonna be in this house for a long time. It's a great area. You notice everybody's moving to Texas. They definitely dragons bringing everybody down here. So following him. So at3:54 any point, did you have a spreadsheet that said, redo house or simply burn house?4:01 Well, then it's like one of those shows. Like once you see the plans, you're like, Oh, yeah, I want it to look like that. But you know, and oh, guess what I did today was that guess what I did? 30 seconds ago. Oh,4:12 I know what you did? Yeah, you got into crypto.4:15 So as we're setting up to do this show, we started having a conversation about cryptocurrency and Bitcoin and people have been telling me to get involved. So in a spur of the moment, while Eric was setting up the mics and everything I bought some Bitcoin Yeah, go Bitcoin.4:29 Yeah. And and we need to probably have a disclaimer that we know nothing about cryptocurrency. Oh, absolutely. Nothing nice. But yeah, it was really kind of cool to watch you do it.4:36 Yeah. So we've covered our sponsors. A little word with the person that's choosing them in the future. And so let's jump into the immune episode part two. So even if the audio is a little bit off on that last one, I encourage everyone to look at our last podcast, because I do a detailed explanation in or at least detailed for a simple country butt Dr. That's living in Texas for the innate immune system, and I actually rewatched it when we were getting the comments great information, audio bad. And at the very end, I go, so that covers the adaptive immune system. I'm like, No, I should have no it was the innate, we did not cover the adaptive yet. There's a reason why that's coming, because then we're going to lead into the vaccinations for COVID and things. Right. So that was the innate. But here's what's really cool. We're gonna talk about what Dr. Mark Gordon was talking about on Joe show. And it's super cool. Like we've been on top of this the whole time. It's been it's it's actually huge, huge news for everyone.5:36 I think a lot of people can learn a lot about what they can do just to protect themselves. And let's small preface, you don't have to just apply the knowledge that you'll pick up today to COVID. COVID actually can begin to fit into other viruses with this talk that we're going to have today.5:52 Yes. And specifically, this is not a COVID talk. We're not saying that at all. What we're saying is we're gonna talk about how to optimize a well running immune system. Yeah. And so when I talked to some of my colleagues and people discuss different things, Angie, and I were talking that she's like, have you looked at our Mendeley account? So Mendeley is where we put all our articles, and I just did a quick look. We have over 1000 articles regarding immune health and how to optimize it through nutrition and lifestyle. Yeah. So even that is science backed. Everything we're talking about here is completely science backed. In fact, one of the things I wanted to discuss because I think it's really cool is this article that just came out in 2020. It's called the antiviral functional foods and exercise, lifestyle prevention of Coronavirus. That's a very boring title. And those are the kinds of things that I read. And it was published in the Journal of nutrients. What's fascinating about this is that they discuss the things that other people are now just finally starting to talk about. Yeah, so I want to review this article really quick. Then I want to get back to the whiteboard. And hopefully sound a little bit better.7:06 We're gonna use headphones today.7:07 Yeah, we're gonna try and use headphones. I got a new mic attached to a hemorrhoid bander because I feel very comfortable holding hemorrhoid banders. Yeah, so that is dry tone right there. That is right there. 7:20 that's almost as good as the Bob Barker microphone from the remember the little skinny one that he had on7:28 the show? Yeah, when they tell you to go spay and neuter your dog.7:31 Yeah. spay and neuter your dog spin the wheel. Drive. I can't wait. I had a hard time of that. Anyway. Yeah. Yeah. Great show.7:37 So basically, on this article, it's really interesting. Not actually not interesting. For us. It was it just reiterated everything that we've kind of base talking about. What they looked into was functional foods. They called it functional foods, and physical exercise. So the exercise part was a brief part than 90% of the article was talking about functional foods, which they described as functional foods being polyphenols.8:02 Incredible.8:02 So the functional foods are polyphenols because of the various mechanisms that they do in the body. We got contacted by an author of the sirt diet. That's sirtuins. And he noticed that we've been talking about polyphenols and said, Wow, you guys are on that. So the whole thing about Adele's diet that she lost all that weight, that's called the sirtuin diet or the sirt diet. And then I've watched it on Dr. Oz. And I was like, there's something about polyphenols, polyphenols. And the reason why is you're gonna see on this whiteboard, how many different ways a functional food like a poly phenol can benefit you definitely. And so the cert diet just means that you turn on certain genes, it's an epigenetic thing. So really quick on the exercise. No big surprise, as it turns out, exercise is pretty good for you. Sure. So they looked at different aspects of it. And what it does do is it does activate natural killer cells, and will induce monocytes to become antigen presenting cells like dendritic cells. If you go I don't know what that is. We talked about that on the last episode. And we're going to get to it again here. So don't worry. That being said, super extreme exercise, which we have talked about this can actually lower your immune system. So many times when people train super hard, and we're talking about like, marathons and triathlons and marathon running. I've had so many patients that get very sick after they really train for something, they go all out, and then they get sick. And it's because I didn't even realize this, that you produce so many reactive oxygen species. This damages cells, which leads to inflammation, you're gonna hear this term over and over again. And then it actually adversely affects your white blood cells ability to fight off infections. Yeah. So the real idea is that regular exercise is really good for you. It gets rid of old immune cells that don't work very well. And you actually stimulate young healthy cells that can actually have a young, healthier immune system. It has been shown that highly conditioned athletes have a much better functioning innate immune system, as opposed to sedentary people. Yeah. So when we're sitting in a viral season, and if you're sedentary and you're overweight, and you got diabetes and high blood pressure, your immune system doesn't work as well. And there's reasons for this in this paper. So then they kind of went through that they're like, yeah, okay, so exercise is good. And then they go into 90% of the rest of the article is discussing polyphenols and the multiple areas that these functional foods benefit our immune system. Okay. And, oh, we're probably jumping ahead. What's a polyphenol?10:40 Oh, what is it polyphenol? Yeah, tell everybody what a polyphenol islittle compounds that are found. And fruits and vegetables. Generally they are what can be responsible for the coloration that's inside those fruits and vegetables. And they they're naturally occurring. Some of them are large, or small. But in essence, our bodies love them.10:59 Absolutely. So I always refer to them as mother nature's secret weapon. This particular article goes into great detail about how the flavonoids, terpenoids alkaloids in the polyphenols, so they can go into that are actually bio active, they can influence genes have peptide qualities, and are broken down by our microbiome into potent anti aging, anti inflammatory, anti cancer metabolites.11:25 Right. You know, I was thinking about this, how do we bring validation to this part of this study, or the I'm sorry, the discussion, I guess, whenever we're talking about this to people, because I started thinking about, if someone years ago when you were when you were young, and someone said, you probably need more calcium to make your bones strong, you didn't just go to the store and buy sack of calcium, you generally just started drinking more milk or something similar. Or if you were an athlete, and you knew that you needed to make sure that you didn't get cramps, you ate bananas, or ate spinach, all of that stuff, you didn't go and just buy the little element, those elements are naturally occurring in something that you're eating or drinking. That's essentially what we're trying to talk about with polyphenols is there are small little things in there that your body craves, just like your bones want calcium, the these are the vehicles, these are the foods that will deliver what your body wants to maintain health and keep you healthy 100%. And they mentioned how versatile polyphenols are.12:24 Oh yeah, meaning they function in many different ways. Number one, they can have potential influence on your gut barrier, where they improve the immune system of the gut barrier, the first portion of that, then they actually have epigenetic phenomenon. Most important is that your microbiome will break these things down to beneficial products. And that's going to be something that we've talked about post biotics before, I'm very excited. We've contacted this a PhD in Argentina, who has one of the most amazing articles describing the post biotic effect. And they actually demonstrate that the larger, more complex polyphenol is the best way to consume it. In other words, yeah, you don't want to take the one little molecule. So that's pretty much what they said about polyphenols, because we're gonna talk a lot more about that. And then it kind of like briefly go over Oh, and then there's vitamin D, which is pretty good for y'all. So vitamin D deserves its own show, because it's more like a hormone than it is like a vitamin here. And then they look at a couple other things like vitamin C and stuff, and they kind of gloss over it. And then they come back to the polyphenols. And they're like, and then they reference to the viruses. And they show how there's so much information out there about how these polyphenols actually influence the destruction of multiple viruses like influenza, Zika, virus, HSV, and Corona.13:45 And there's a mechanism to and there's13:47 a mechanism for each one of these. So the conclusion is, and this is, I hate to say Joe Rogan, for the third time in about first five minutes, it'll validate what we say. He's always said, why aren't we discussing ways to improve our immune system, prevent ourselves and do this, these guys end the whole article, and by the way, it's thick 20, some pages with references and everything they end it with the conclusion is, this is a pretty cheap and simple way to improve your immune system or optimize, get some exercise, eat some polyphenols and get a little sun. Yeah, that was the combination of it. All right. And and these people put a lot of work into that. And that that's a spoiler alert.14:31 I think I might have said though it's really, really important is that there's a lot of work. There's a lot of research, there's a lot to take in here. However the solution if you really think about it, it isn't that difficult to adhere to this to keep to keep people healthy. That's actually the coolest part. The summary of it all is polyphenol, sleep exercise. You're off to an incredible start just with that and don't i don't think you should shy away from Rogan at all. He supports tons of other podcasts gives huge mentions to other people. They're doing the same thing. When I heard Dr. Mark on this morning with him, I just I liked it because it not only was somebody else talking about the same subject, but he was doing it in such detail that we like to talk about it, that I encourage you, we're not the only ones who have this level of research and are seeing these kinds of results with people.15:22 Oh, it's so cool. And now because we're in these circles with these PhDs, I'm getting preliminary data on different studies where it's humans, where they're looking at what I'm going to talk about here. Yeah. So what I thought we could do is try and do round two, you put some headphones on, 15:37 I'm going to have to,15:38 I'm going to grab my Bob Barker mic right here. I'm going to turn this one15:46 that was kind of quiet. And now I'm going to come back like this. There he is. This is why we have headphones. This is15:52 why we have headphones. And now I'm going to switch the cameraprobably should have you looked at the computer to make sure that I'm in focus and everything. And now, let's do a recap of the last. And that's not a window of the last podcast that we did. This is a kind of quicker version of what we did. And this is to get everybody up to speed because when we talk about polyphenols, we need to make sure that you understand exactly what's going on and why there are functional food. So just to recap, the innate immune system is your response to any type of damage, whether that damage is through physical damage, whether that damage is through infection, whether that damage is through repeated poor diet choices, your body is going to try and repair itself. So let's walk through what happens. The first step, step one, let's just assume that you have an infection. If you have a virus or bacteria, what it will do is it will attack a cell. So that cell no matter what it is, sounds an alarm. And it notifies its neighbor, which is kind of its bodyguard, the mast cell. The mast cell then releases what is called braided cinan. This is really neat, because if you ever sprained an ankle or done anything, this is what's going on. The braided cinan send different proteins or cytokines to the blood vessel. First step is the blood vessel. And what it does is it actually normally the blood vessels have very tight seals, what it does is the blood vessels pull apart a little bit to allow fluid to come out. Well, the reason for that is is that you want the swelling to contain whatever's going on. You sprained an ankle, you go oh my gosh, look at my ankle, it's so swollen, well, it's there for a reason, because that fluid is trying to concentrate what your body needs in the same area. So the fluid starts coming out step to these braded cinan, and different other cytokines send up little flags, just like Velcro sticks. And these are called intercellular adhesion molecules. And what they do is they grab white blood cells that are swimming by so these white blood cells have these little hooks and they get hit and they stop and they go, Oh, what's going on all the fluids going out that way, I'm gonna go out that way. So then the white blood cells join this little party over here. This is what ends up causing redness, swelling and pain anytime you have any type of infection, anytime you have any type of injury. So now we have these white blood cells, what they do is they go, Oh, that mast cell told us to go that way. And so the white blood cells head over to what's going on. And then this allows your body to fight the intruder that's doing this. So that's step one. So now these white blood cells come around. You heard me say in that other study the antigen presenting cells. So one of these types of cells, which is a phagocyte, will actually first thing it does is it swallows the invader, bacteria, virus, fungus, whatever it is, swallows it, and the reason why does it it digests it, and then it breaks it apart and goes, Okay, this is what it looks like. So it puts wanted posters on its outside. So this guy said, I know what's attacking us now, this, this guy right here. So these antigen presenting cells, put it on the outside, and then they do something else. They release cytokines, specifically, multiple cytokines, but the important ones are TNF alpha, interleukin six, interleukin one, interleukin eight, and you're going to hear a lot more about this, because I'm talking to scientists all over the world. And people are now studying specifically how we can use functional foods to control this response. So TNF alpha, does a lot of things. It's a pro inflammatory cytokine. And so we know that TNF alpha is used in very expensive drugs block that for rheumatory arthritis for Crohn's disease for ulcerative colitis for all of that. So TNF alpha does something kind of interesting that I found unique is it actually goes to the hypothalamus and it increases your core body temperature. So when I say these are bad, they're really good for you in small amounts, it's when it becomes too much that it becomes bad. So TNF alpha hits the hypothalamus increases, and that's how you get fever, interleukin six, it goes to the bone marrow and increases the white blood cells. So this is why you have that achy feeling if you've ever had the flu, or if you're gonna get a vaccine, and you go, Oh, my gosh, I had a vaccine, that kind of hurt, I feel like I have a low level flu. It's because the bone marrow is producing more white blood cells. interleukin one goes to the liver to produce acute inflammatory reactance, which goes into something called the complement system. But that inflammation is what we measure in people. In fact, cardiologists use this all the time they look at C reactive protein, yeah, because when you have inflammation, the liver produces this. So people with coronary disease will have increased levels of that, and then interleukin eight.Fascinating, it basically produces more of those little Velcro hands. So then we come all the way back to the blood vessel. And now we've got dilation, fluid coming out. And every white blood cell that's coming through gets grabbed. So when you have the white blood cells producing here, you've got the fever, which increases the amount of blood flow heart rate is faster, everything. It's an phenomenal and just beautiful little system. Yeah, it is. And when it works great. It's exactly what we need. It's exactly what you need. In the acute phase. Definitely the innate immune system is here to protect you in the first phase. So now step three of the innate immune system out of you, but that's the antigen presenting cell, the one that we were talking about over here, sometimes they sometimes they get overwhelmed, and the virus actually wins. So the poor little guy dies. It's that's a good cartoon. Yeah, so the poor guy dies here. So the antigen presenting cell dies. So it leaves rubble, so it's comes out and the body even gets that. So reactive oxygen species are left behind, that's known as oxidative stress. That's good in small amounts, because that will kill other things around it. Assuming that this guy got overwhelmed when he dies. Maybe other cells are being overwhelmed, and then that oxidative stress will kill it. Yep. This is known as a reactive oxygen species or reactive nitrogen species. But when that goes on for a long time, that's what actually causes chronic disease, like heart disease, cancer, aging, this is actually why we age, reactive oxygen species, autoimmune disease, dementia and obesity. Nobody ever thought that you can become fat because you have low level chronic inflammation. And I've talked about this on other episodes. 22:56 Definitely.22:57 So final step here is the thing you didn't know about, which is the toll like receptors, right? Okay, so toll like receptors is just another layer of defense, where if these toll like receptors are actually activated, they do very specific things. For instance, the toll like receptor number seven, is very specific to release certain things to fight RNA viruses. You can go through these others, there are ones that are built to fight bacteria that are flageolets flageolets. Yeah, I think we're both saying that wrong, but that's okay. fragilities, flageilities. And they also do something that we have talked about before, I want to say we talked about it. On at least three episodes, I can think of the epigenetic phenomenon of nuclear factor Kappa beta NFKB. So when the toll like receptors turned on NFKB goes up. And NFKB is the one that we talked about with the broccoli episode, right? with David Roberts and john gilday. On Yeah, this is the one that actually has a what's called plio trophic phenomenon. So it affects many different things. So when NF Kappa beta is turned on, then you go through a huge surge of our old friends, TNF alpha, interleukin six, right? So he has more inflammation with inflammation, the common theme of inflammation, right? So inflammation, what does inflammation lead to? Oh, this dementia, autoimmune aging, cancer, heart attack na, so this innate immune system is here. The other thing that I did not mention was that when the toll like receptors get turned on, like this toll like receptor number seven, which is for viruses, one of the things that releases is interferons. interferons, actually, are molecules that directly destroy cells that have been infected with viruses. So if you were to get a virus, you breathe it in through your nose, let's say it goes to your lungs, a cell is being attacked, it can actually send a signal to a healthy cell says We're under attack, you need to be ready for this. And that's the little cell that waits with a gun at the door. So when the virus rings, the doorbell goes and shoots it. That's not proper technique and how you shoot it. We've25:21 seen actual footage of this going down at a microscopic level. So yeah,25:24 it's it's fascinating. Yeah, absolutely. It's like watching an old Western, just like oh, my gosh, and the. And it's totally true. Because the viruses that show up, they always wear black hats every time every time. Yeah. So that's a recap of very quick recap of what we talked about last episode. Yeah, I get it a little bit more detail. How's it? How's the sound quality?25:47 The sound is much better than last time.25:49 Okay, good. So hopefully, we'll continue with this. So how do we describe how functional foods work? Because our big thing last time was improve your immune system do this, but nobody talks about how, why?26:05 I've got a question for you. So when we look at this, and I think this is a reasonable question, you look at it, and we're talking about all the bad manifestations that happen. When there's too much TNF alpha, or aisle six or aisle one, we have too much row s, or I'm sorry, reactive oxygenation, species, ultimately, too much inflammation. But I needed all of this to happen. So, Dr. Brown, what is it that I'm missing? That would help me not have the system that I need? That keeps me alive and safe, run out of control? And basically, ultimately destroy me anyhow?26:42 Absolutely. So what we're talking about is how do you optimize? Yeah, well, running immune system. Definitely. One of the theories right now is that why do younger people not get sick with the current virus that's going around, is because they have a very good innate immune system. As we age, as I mentioned, as we age or you become sedentary, possibly, this happens. And so you go, Oh, well, I still don't get that. We'll imagine this. Imagine quietly, this attack happens, virus, bacteria, anything, and your innate immune system is kind of slow to react. And by the time it realizes, Oh, my gosh, something's going on. Many cells have been infected. Which means when these cytokines go up, it's a huge amount. If you have a really healthy innate immune system, you catch it at the first cell. Yep. So let's talk about functional foods. functional foods, functional foods, polyphenols, so I'm going to use these little brand. These little hexagons. Yeah. Demonstrate functional six added. Yes. Excited. Whatever you go.27:50 All right. Now hexagon, you're27:52 right. This is all based off of science. All based off of very detailed documented, I want to thank every PhD out there who goes through this kind of trouble and probably gets no recognition. Because this is Sony. And, you know, we're talking about so when Dr. Mark Gordon was on his show today, he didn't really understand why course it's an or why tumeric does this. Let's talk about that. Let's do that. All right, step one. So this will represent the different stages that it actually happens. Step one, intestinal gut health, intestinal gut health, that's your first barrier. Anything that comes in, you're going to make sure that you have a good healthy working gut, healthy work in gut. Step two. We know that it has potent antiviral activity. I mentioned earlier in the other article about how these functional foods can actually destroy viruses on contact.28:52 So we've got gut and the virus itself.28:54 antivirus itself step. If the virus makes it past that, inside the cell itself, is the M protease that allows the virus but bacteria do this also. It has to attach to the cell. Well, what does it do? It prevents it from attaching then, oh my gosh, this is a really tough virus and it made it through all these lines of defense already. Yeah. Well, as it turns out, bunch of foods polyphenols actually work zinc Ionafores and prevent the replication29:35 Hmm. Blocking replicase 29:37 replicase correct. Nice actually blocks the replication.29:42 So So right now we have four tags up and we're still on number one of the innate immune system. That's29:47 why it's so important to understand the innate immune system. Yes. And why nobody's talking about this. I'm going to keep going. Yeah, and this is not once again, this is not my opinion. Yeah. We've got 1000 articles to To show all of it, right? Okay, so now we got our friend, the mast cell over here and everything that I'm saying is not an on or off switch, it's the optimized way to do it. If your body needs it, these functional foods help it ramp it up. If it doesn't, it does it. Alright, so the mast cell that releases the braided cinans that go to the blood vessel, oh, the mast cell actually gets stabilized by functional foods, polyphenols, nice. So it doesn't overreact or under react, then it's almost like, really, truly Mother Nature's secret weapon, then the blood vessels which release the fluids, there's something called or I forgot what the actual enzyme is, but it actually attenuates the enzyme that creates the leakage. So it controls the amount of fluid that comes out. And in the same line, what it does is it actually controls the amount of the adhesion molecules, so all those little hooks that grab that, right, it actually does the optimum amount for that. Okay. So getting back, this is why Dr. Mark Gordon was like, Oh, we have shown that it helps with inflammation, I'm going to tell you exactly where it helps, right whole pathway. Okay, so we've now blocked the little adhesion molecules so that only the right amount of cells come out, only the right amount of cells come out. And remember, when I said that it monocytes become our antigen presenting cells, it helps them mature. Oh, it's like steroids for those guys.31:35 So it activates them. It's a growth hormone, right? So we're allowing these phagocytes to now do their role. And by having the right amount of polyphenols available, it's going to do it quicker.31:45 Exactly. So we're now heading to step two. So what does it do? Oh, yeah. It helps the antigen presenting cells, taking the vacuoles and put those different proteins on the outside quicker, because it's already made these more mature. And then we get to the real important part, it tells the antigen presenting cell, yo, be a little careful how many cytokines you send out. Hmm. So there's multiple studies looking at each one of these. And so I'll do this real quick. While you're32:19 putting those up there, I'll just add that Dr. Gordon spoke today specifically about how high circulating cytokines lead to insomnia and an inability to rest enough because it causes neural inflammation, which is just building on it. That's32:33 right. He did, he talked to specifically about that. And that's that brain gut connection and percent inflammation, that's what we always talk about. So as it turns out, it tells the antigen presenting cell, Hey, be careful what you do, then just to make sure as another safeguard, it specifically will control how much TNF alpha, how much interleukin six, how much interleukin one and how much interleukin eight is actually necessary. And these are all documented on specific studies. And I know that these are being done in humans right now, because I'm getting preliminary results. And they're showing very specific in vivo, meaning people that have this kind of situation, actually decrease these different cytokines. So it's not just a total decrease. It's the right amount. So if you need more white blood cells, then there's no reason to shut it off completely. Right. Like we just can't You can't be smarter than Mother Nature. Yeah, comes down to Okay, how am I sounding sound good. All right. Now, let's go to it's a lot better than last week. So so let's go to Step three, the antigen presenting cells that do this, also do another job, briefly, which we will get into in some other episode, or will bring a better person to do it. Some of those cells go to the lymph system, where they then activate the adaptive immune system where they form antibodies.33:56 Very, very important,33:58 relevant right now, because if everybody's running out getting a vaccine, that's what you're working on worthless unless you have this optimal.34:04 Yeah. 100%.34:06 So we won't get into that. But guess what functional foods polyphenols do?34:10 Oh, you don't even tell me that. They also work on that side. They also work on that. It's almost like your body wants polyphenols.34:16 It's almost like your body wants polyphenols. And of course, while we're at it, I mean, it's like it's almost like no, no, now he's just going overboard. No, no, I mean, it's, trust me, I read every article. It's like I feel like I'm making stuff up. Now. It helps produce interferons. It helps control the toll like receptors.34:43 So means you're just a side note. interferon if anybody's ever dealt with early stage, melanoma, I mean, there are various cancers that you actually had to end up getting injections for interferon.34:54 I did I really thought you're gonna go if anybody's ever dealt with herpes. Now I'm dead serious. Yeah, like Libya isn't interferon?35:02 Absolutely. It isn't interferon. I'm just saying I guess what I was going is, is that35:07 if you've ever dealt with herpes, you kind of looked at me like, no.35:11 That's how I felt.35:16 But this is true. So drugs do this. You're exactly right. chemo drugs and drugs like a cycle of beer. They're their interferons. Yeah, because they block viruses. So polyphenols help increase the amount of interference when it's necessary. Correct. And by blocking the toll like receptors and controlling that. They actually decrease nuclear factor Kappa beta nfkb. We had that talk with Brocelite. So polyphenols and sulforaphane block, NF Kappa beta. So35:46 I was making sure that you're making contact with the people in the room. Do you think I was I was waving over somewhere else?35:52 I thought you were having a hallucination. So all right, so we blocked NF Kappa beta, which ultimately we know does the most major thing inflammation. So we've been saying a long time that the Mediterranean diet is an anti aging, anti inflammatory diet. Yes. This is why when Adele did her sert diet, this is why it works. You decrease overall inflammation, definitely the whole process. And because, oh, I skipped a little step here. But one thing that we always talk about is the potent antioxidant effects.36:33 Yeah, I'm glad you're getting this part because we're going to augment this little section here, too.36:37 Yeah. So tell me what you got to say about antioxidant.36:39 What is it immediately takes me back because ROS is something that Joe botel and we've referenced her on the show multiple times. But when she was talking specifically about long endurance athletes and how they get injury, and how certain people who are high performance athletes get injured and have a difficult time recovering, it's often because they don't have good control of their RMS or reactive oxygenation species. you're pointing at something, but I'm not on camera. Oh, I am now. So there we go. I didn't know that. There's no red lights in here, by the way. But I find that to be a really big key aspect about rlms. And what polyphenols do because she specifically said to it to decrease healing time and increase optimal athletic performance, high polyphenol concentration, or normal amount is a must, and that our bodies are simply waiting on enough polyphenols to do this job.37:34 Yes. 100%. So now the final part here is more of a vague, you get a picture camera now to fix the camera. You can't take me by surprise anymore. I mean, we can hire Mike to find our to find our podcast sponsors, but we can't even hire a good audio visual guy.37:50 I don't think that hot dog company comes with that.37:56 Alright, so we get down to this last thing here, which is chronic disease. So what we talked about low level inflammation. This is how you can protect yourself against heart disease, cancer, aging, autoimmune dementia and obesity. And I put this one up as a general one, because we mentioned it a little bit, I want to talk about it right after this, about how large stable polyphenols I found an article that showed the more hydroxyl bonds on the outside, more beneficial is. That's why when we initially were developing Atrantil, and Dr. Bruce Burnett looked at this and said you picked the perfect poly phenol to be the most bioactive and most diverse.38:37 That's all he does. There's there's more points to do stuff. It's like more surfaces. It's more38:41 surface area. Exactly. And then in addition to that, we know that in all these articles, so if you're somebody you're like, Oh, I already take tumeric. I already take quercetin and that's awesome. Keep doing that. Yeah, keep doing that. But you have to understand something tumeric and quercetin don't get directly absorbed, they actually have to go to the microbiome where they get broken down into the metabolites. I've got articles to show what is the effective metabolite, of quercetin. So when Dr. Mark was talking about that, I want to tell him, that's awesome. But you better make sure that you have a good microbiome. So what this represents is the prebiotic ability of polyphenols to diversify your microbiome so that when you take these things, you're getting the appropriate we're gonna call them the appropriate metabolites. I call them post biotics, but we're gonna call him the appropriate metabolite.39:31 It's a honestly it's kind of like if, if you look at the way that he talked about ecgc, and, and tumeric, and trying to enforce it and etc. He broke all those down and talked about their beneficial natures as it pertains to inflammation. But what you're describing, if I can kind of put it into layman's terms, it's almost as if that is great. And you can get an Uber to have that delivered to somewhere and you hope it's a great car and you hope It gets you there comfortably. But in order for it to be effective and get there on time you want a private car you want the limousine. The limousine is the larger molecule, the all natural, larger parent molecule, if you will, kind of like what's in Atrantil and abbraccio to do that,40:17 exactly. So what you want to be able to do and what we're saying is not just supplements. Now, this is why you want to have a very colorful plate. That's why you want to have lots of fruits and vegetables. Yeah, continue to do that. Try to do every non GMO foods and vegetables. But when we're talking about polyphenols, very few things concentrate polyphenols, so when you're like, Oh, I heard Dr. Oz talked about reservatrol polyphenol. Oh, I heard someone so talk about Kirsten, polyphenol. Oh, but you know what? I drink green tea, polyphenol. Yeah. And they all get broken down. Here's what's fascinating. And I can't wait to do this. When we have Dr. Sylvia on her research is showing that you can produce quercetin egcg, which is green tea extract. You can produce the metabolites of curcumin and all these things from larger tannins. Yeah, that's what I mean, this is so fascinating, and your body knows how to do it. And you know what? I mean? Do me a favor, when you get done watching this, go to COVID? episode number two, because we did that in March. Yeah. And we were right, because we talked to scientists all the time. We're always doing this. So Sofia said, You know what, I'm gonna challenge you not to we will share the mic even though the You and I both been tested, like yesterday. Yeah, for COVID and we're negative, can you walk through and just explain what each one of these days does really quick, 41:30 I'm going to try Okay, so that a right there is going to prevent the virus itself that a if there's for the gut microbiome, that a I believe is going to prevent it from binding to that set of cells, that one is going to function as a zincionafor prevent or allowing zinc to go in and stop the replicates that is a mast cell that's going to help control the number of goodness gracious, I guess those little inflammatory markers that are going to go to the blood vessel braided cinans kind of There you go, and then be circulated which of course, we're going to regulate the amount of fluid that's going to leave the bloodstream and we're going to stop the amount of flags are gonna pop up as appropriate. Orders one, Oh, that one is a phagocytes, that's going to improve the the maturation of the phagocytes the one just below it is going to help the phagocytes since they are maturing more quickly, it's going to allow the them to display quicker and then it's going to regulate the number of cytokines which is TNF alpha, IL six, IL one and il eight. And I don't know if I'm gonna go through the mechanisms of those but that's okay. Oh, yeah, good, quick. TNF. Alpha is for the brain. IL six is for the bone and it's because of white blood cell maturation IL one is for infection and inflammatory things that come from the liver and i l eight, is what is going to basically start the cycle all over again, where the fluid is, is being summoned and redness, swelling and pain.42:55 Excellent. Stage three.42:56 Okay, that's the presenting. Yeah, it is. And that's where the cells dying, we get to oxygen a oxidative stress. Yeah, it says that. But we need to control our ros because it's not the RO S is bad. Too much ros, though, can lead to long term heart disease, cancer, aging, autoimmune dementia, obesity, and adaptive antibodies, we aren't going to go all the way through there. But essentially, aside from the innate immune system, we need help in the adaptive immune system as well.43:28 It would be fascinating to see what the antibody levels of people that are vaccinated if you're scientists out there on your on your cool study will supply you with some big polyphenols and see if people mount a better antibody response. If it lasts longer. These are all just fascinating questions. What's this?43:45 So when we get over here to TLR, we this is what is going to function as another flag zone, where we're going to signal the liver to then produce interferon, which functions to fight cancers and all kinds of different things like that. And then we have NF kb. We've talked about this extensively, whenever we had Brock elite on the show, both john and David was gonna say, Robert, but it's David Roberts on the show. And essentially, what we want to do is not have this gigantic burst of TNF alpha, and IL six because it's just going to turn into more inflammation. And again, Polly finos once again, aren't going to abandon you. They're still going to work even on that end. Okay.44:32 You're so much smarter than I thought you were. Nice job.44:36 I just remember a lot.44:38 Can you hear me on this one?44:39 Yeah, yeah, that was never good.44:41 You can probably take the headphones off now to show everybody. So did that make sense? I44:47 think it makes a lot of sense. I mean, it's a lot of information. Not everybody is going to just readily walk away, like we just did from it, but watch it several times. I think though, really what we're trying to show here is that We don't want to just say that we don't want to just say that polyphenols they'll work with with viral or bacterial infection. This is something that I wish more people would do you tell me that something works. Just explain how show me how how do you know that it's going to work? And I'm not saying that people don't have markers or blood enzymes or circulating things that they measure, they see things go down. That's important that lets you know that we're on the right track. But this kind of stuff, this kind of research that you've been sifting through with Angie, is just awesome. Because now it's almost like putting a name to the face. We can see how it's working. Exactly. So I think it's important. 45:41 And this doesn't just stop here because you know, Angie's episode, people, it's really being shared a lot. Oh, yeah, just people if you have pots or Ehlers danlos or CBOE or anything, people thousands of downloads on the podcast, by the way. Yeah. And she describes how when you have NF Kappa beta up, yeah, you're gonna have decreased acetylcholine when TNF alpha like this is all the balance in that. Yeah. The key is to see the colon whenever Yeah, but that's a whole separate conversation. This is strictly on the innate immune system, right. And so I find it fascinating. I find it fascinating that when I listen to another doctor talk about this, and I'm like that I very much like, very much like me, like, I'll listen to stuff and the patients will ask me, they're like, hey, do you know about this? And I'm like, I don't have the bandwidth and the time to do it. That's awesome, which is why I kind of tasked or I didn't task. She did it on her own, which is why Angie learned so much about dysautonomia, like I just don't have that in me right now or the time to do it. And she crushed it. Yeah. And one of the what we've been emailing, she's been emailed by so many people, she's gonna keep going, she's gonna end up writing a book and probably saving a lot of people. And so this is this is first step, innate immune system. I tell all my patients, let's exercise a little I don't care what you do, just get up off the couch and move around, right? Doesn't really matter what, don't eat highly processed foods, like high fructose corn syrup, soybean oil, anything, you're open in a package, read the label, because that breaks down that Mary, Mary Mary first step, which is gut health. All health begins and ends in the gut, definitely. And then get your polyphenols, get a little sun, get some sleep. Do you do that? That's better than what's better than most are doing.47:32 I mean, it really is. And it's, it seems complicated. And but in the end, the actionable items really aren't that complicated.47:41 I mean, when we're in some weird times, I mean, let's be honest, we're taping this episode. The day after we had that weird thing that happened last night or yesterday where47:51 you didn't get your change back at the store. I didn't47:53 get my change back. I'm still upset about that. The lady was clearly distracted, because apparently our government was overrun by48:02 Oh, yeah, that was a big deal. Yeah.48:05 And so these are stressful times. Yeah, we got to keep the inflammation down. There's nothing to cause inflammation. Yeah, don't, don't bring it upon yourself. Don't eat bad. Don't lose sleep, and make sure that you get your polyphenols.48:17 To my knowledge, polyphenols won't directly help bad politics, but maybe those politicians could use some more polyphenols and they wouldn't act so crazy.48:26 Oh my gosh, don't even get me started. Because what I want to do, and I believe that this will be the future we're gonna be sitting here 50 years from now we're gonna look the same because of the anti aging qualities of polyphenols. The 50 years from now we're gonna be like, wasn't that great that they put psilocybin in the water so that we all treat each other nice. You know? It's so you're just gonna pull up instead of Starbucks, you're gonna pull up to MDMA cafes? And I'm not kidding. Like the research on that is like, we're gonna go there also. Yeah, there. Somebody joined at baby bathwater Dr. Raven, I was reading his profile, really cool. And we're gonna I'm gonna try to bring him on here. But he's got a device called an Apollo device, which vibrates when you're not breathing appropriately, which means if and we're gonna do a whole episode on breath work, and we got our we just got all kinds of cool stuff to do. But you can't, you can't leave this hanging like, this is important. Look at all those. Look at all those one last time here. Let's just look at the amount of places.49:29 Places I'm just counting right now. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 19 20 looks like there's almost 20 things out there49:40 that I found in a guy like Bruce Burnett, sitting at home, he's like, there's 38 you're missing the critical ones. 38 on line one. I know. Well, this is this is what you get when you let a doctor try and try and try and describe this.49:54 Yeah, but seriously, I think the takeaway here is that we can put there's no Muscle behind the message there, it really does work. And this is not specific to any one virus or any one bacteria. This is what your body needs in order for your immune system to work efficiently just so happens, that it works really, really well for what a lot of people are concerned about.50:18 It does and you just came up with a whole new idea. But as we close this out I think I'm gonna attach this next time I do a hemorrhoid on a patient so we can hear50:27 the hemorrhoid. Be sure that requires some type of consent. But yeah, I think it's awesome.50:34 All right. So thank you, everyone, for listening to this. I hope that this is something that makes some sense, please share it, subscribe to the YouTube channel. Subscribe to the I guess all the other platforms, iTunes and Spotify and 50:52 we are honestly the run on Atrantil at the KBMD store has been kind of intense over the last two months. So number one, thanks for everyone for sharing all the information here recently we're doing all that we can to bring that part back online but we'll have an associated discount probably with this particular show. Just in general with with the immune system. Yeah, and as soon as that rolls out, then we'll make that available and all the show notes etc.51:15 Totally and thank you diarrhea dogs for this episode go to diarrhea dogs.com put in code Mike for a 98% discount.51:26 I can't wait to find out what people email in and say what's it diarrhea dogs.com.51:33 Remember, it's code Mike, for 98% discount.51:39 I think it's probably gonna do it for us. Thank you all for joining us on the gut check project please like and share and we will see y'all with 48 with some continuation on the immune system. Talk to you then51:49 bye bye. Thank you.

Fibroblast growth factor 9 stimulates neurite outgrowth through NF-kB signaling in striatal cell Huntington's disease models