Podcasts about epithelial

BUFFALO, NY- July 17, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 13, entitled, “Modulating in vitro lung fibroblast activation via senolysis of senescent human alveolar epithelial cells.” Idiopathic pulmonary fibrosis (IPF) is an age-related disease with poor prognosis and limited therapeutic options. Activation of lung fibroblasts and differentiation to myofibroblasts are the principal effectors of disease pathology, but damage and senescence of alveolar epithelial cells, specifically type II (ATII) cells, has recently been identified as a potential trigger event for the progressive disease cycle. Targeting ATII senescence and the senescence-associated secretory phenotype (SASP) is an attractive therapeutic strategy; however, translatable primary human cell models that enable mechanistic studies and drug development are lacking. In this new study, researchers Joseph S. Spina, Tracy L. Carr, Lucy A. Phillips, Heather L. Knight, Nancy E. Crosbie, Sarah M. Lloyd, Manisha A. Jhala, Tony J. Lam, Jozsef Karman, Meghan E. Clements, Tovah A. Day, Justin D. Crane, and William J. Housley from AbbVie Bioresearch Center and Northeastern University describe a novel system of conditioned medium (CM) transfer from bleomycin-induced senescent primary alveolar epithelial cells (AEC) onto normal human lung fibroblasts (NHLF) that demonstrates an enhanced fibrotic transcriptional and secretory phenotype compared to non-senescent AEC CM treatment or direct bleomycin damage of the NHLFs. “In the current study, we confirm the presence of senescent cell populations within the human IPF lung, as well as assess primary cell reagents for sensitivity to senescent cell targeting therapies.” In this system, the bleomycin-treated AECs exhibited classical hallmarks of cellular senescence, including SASP and a gene expression profile that resembles aberrant epithelial cells of the IPF lung. Fibroblast activation by CM transfer was attenuated by pre-treatment of senescent AECs with the senolytic Navitoclax and AD80, but not with the standard of care agent Nintedanib or senomorphic JAK-targeting drugs (e.g., ABT-317, ruxolitinib). This model provided a relevant human system for profiling novel senescence-targeting therapeutics for IPF drug development. “Taken together, the model described herein provides a physiologically relevant, primary human cell system to study the effects of alveolar epithelial cell senescence on lung fibroblasts in the context of chronic fibrotic lung disease.” DOI - https://doi.org/10.18632/aging.205994 Corresponding author - Tovah A. Day - t.day@northeastern.edu Video short - https://www.youtube.com/watch?v=rpmo2PlGDKc Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205994 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

The CARACO prospective, multi-institutional, Phase III trial, among patients with newly diagnosed advanced epithelial ovarian cancer, found that lymphadenectomy should be omitted in patients with clinically negative lymph nodes, as well as those undergoing neoadjuvant chemotherapy and interval complete surgery. This finding from the University of Nantes was reported at the 2024 ASCO Annual Meeting. The researchers noted this surgical de-escalation allows significant reduction of serious post-operative morbidity After the session, Oncology Times correspondent Peter Goodwin learned about more study details from Jean-Marc Classe, MD, PhD, Professor of Surgery in the Department of Surgical Oncology in the Institut de Cancérologie de l'Ouest and Nantes University in Western France.

Dr. Sunad Rangarajan chats with Dr. Corrine Kliment about her article, "Loss of ANT1 Increases Fibrosis and Epithelial Cell Senescence in Idiopathic Pulmonary Fibrosis." 

I read from epistemic to epithelial.     You've never heard of Griffin and Sabine? https://en.wikipedia.org/wiki/The_Griffin_and_Sabine_Saga     Here are the 2 episodes from "The Allusionist" about epitaphs and engraving. https://www.theallusionist.org/allusionist/epitaph https://www.theallusionist.org/allusionist/precious     The word of the episode is "epistemology". https://en.wikipedia.org/wiki/Epistemology     Theme music from Jonah Kraut https://jonahkraut.bandcamp.com/     Merchandising! https://www.teepublic.com/user/spejampar     "The Dictionary - Letter A" on YouTube   "The Dictionary - Letter B" on YouTube   "The Dictionary - Letter C" on YouTube   "The Dictionary - Letter D" on YouTube   "The Dictionary - Letter E" on YouTube     Featured in a Top 10 Dictionary Podcasts list! https://blog.feedspot.com/dictionary_podcasts/     Backwards Talking on YouTube: https://www.youtube.com/playlist?list=PLmIujMwEDbgZUexyR90jaTEEVmAYcCzuq     https://linktr.ee/spejampar dictionarypod@gmail.com https://www.facebook.com/thedictionarypod/ https://www.threads.net/@dictionarypod https://twitter.com/dictionarypod https://www.instagram.com/dictionarypod/ https://www.patreon.com/spejampar https://www.tiktok.com/@spejampar 917-727-5757

Dr. John Fleetham chats with Dr. Barbro N Melgert and Dr. Chris Carlsten about their articles, "Inhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation" and "Inhaled Microplastics and Airway Development: Concerning Evidence from Organoids."

Today we discuss the different characteristics of epithelial tissue within biblical anatomy and physiology. We pray that our message encourages you and that you will seek the Bible more fervently, verifying the truth God built into our design. Blessing to each of you.Academy https://community.araratphysiology.com/plans/316165?bundle_token=081501826a1e9918c48eb8c22ea650c5&utm_source=manualSocial Links YouTube (https://www.youtube.com/channel/UCnHjsFTGl9PRWCtO_8BqLgA) Tik Tok (https://www.tiktok.com/@biblicalanatomyacademy) Facebook (https://www.facebook.com/biblicalanatomyacademy) Instagram (https://www.instagram.com/biblicalanatomyacademy/) LinkedIn (https://www.linkedin.com/company/biblicalanatomyacademy/?viewAsMember=true) Rumble (https://rumble.com/user/BiblicalAnatomyAcademy) X (https://twitter.com/BiblicalAnatomy)Contact podcast@DiscipleshipConditioning.com https://sleek.bio/biblicalanatomyacademyDiscipleship Conditioning Podcast Apple Podcasts (https://podcasts.apple.com/us/podcast/discipleship-conditioning/id1674545718) Spotify Podcasts (https://open.spotify.com/show/73WIVyB9V0ptqzxfK2PX1f)Biblical Anatomy Podcast

BUFFALO, NY- October 2, 2023 – A new priority research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 18, entitled, “Gene expression signatures of human senescent corneal and conjunctival epithelial cells.” In this new study, researchers Koji Kitazawa, Akifumi Matsumoto, Kohsaku Numa, Yasufumi Tomioka, Zhixin A. Zhang, Yohei Yamashita, Chie Sotozono, Pierre-Yves Desprez, and Judith Campisi from the Buck Institute for Research on Aging, Kyoto Prefectural University of Medicine and Lawrence Berkeley National Laboratory aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. “Here, we induced cellular senescence in human corneal and conjunctival epithelium using X-irradiation, and analyzed gene expression profiles of each cell type to determine the characteristics of senescent ocular surface cells.” The team examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated. X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation. “This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.” DOI - https://doi.org/10.18632/aging.205113 Corresponding authors - Koji Kitazawa - kkitazaw@koto.kpu-m.ac.jp, and Judith Campisi - jcampisi@buckinstitute.org Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205113 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, cornea, conjunctiva, Stevens-Johnson syndrome, limbal stem cell deficiency About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551383v1?rss=1 Authors: Cohen, M. L., Brumwell, A. N., Ho, T. C., Montas, G., Golden, J. A., Jones, K. D., Wolters, P. J., Wei, Y., Chapman, H. A., Le Saux, C. J. Abstract: Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate this, we administered the fibroblast-selective TGF{beta}1 signaling inhibitor, epigallocatechin gallate (EGCG), to Interstitial Lung Disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA sequencing on spare tissue. Unexposed biopsy samples showed higher fibroblast TGF{beta}1 signaling compared to non-disease donor or end-stage ILD tissues. In vivo, EGCG significantly downregulated TGF{beta}1 signaling and several pro-inflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted Frizzle-like Receptor Protein 2 (sFRP2), an unrecognized TGF{beta}1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s). In human AEC2-fibroblast coculture organoids, sFRP2 was essential for AEC2 trans-differentiation to basal cells. Precision cut lung slices (PCLS) from normal donors demonstrated that TGF{beta}1 promoted KRT17 expression and AEC2 morphological change, while sFRP2 was necessary for KRT5 expression in AEC2-derived basaloid cells. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin-related signaling in AEC2s were required for sFRP2-induced KRT5 expression. These findings highlight stage-specific TGF{beta}1 signaling in ILD, the therapeutic potential of EGCG in reducing IPF-related transcriptional changes, and identify the TGF{beta}1-non-canonical Wnt pathway crosstalk via sFRP2 as a novel mechanism for dysfunctional epithelial signaling in Idiopathic Pulmonary Fibrosis/ILD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551943v1?rss=1 Authors: Bagley, D. C., Russell, T., Ortiz-Zapater, E., Fox, K., Redd, P. F., Joseph, M., Rice, C. D., Reilly, C. A., Parsons, M., Rosenblatt, J. Abstract: Asthma is a common disease characterized by airway constriction, excess mucus, and inflammation. Although asthma is an inflammatory disease, subclassed by different endotypes, triggers, and immune responses, the defining diagnostic symptom is mechanical bronchoconstriction from uncontrolled smooth muscle contraction. We previously discovered a conserved process that drives epithelial cell death in response to mechanical cell crowding called epithelial cell extrusion (1,2). Because modest crowding triggers extrusion to maintain constant homeostatic epithelial cell densities, we reasoned that the pathological crowding from bronchoconstriction might potentially destroy the airway epithelial barrier, causing the typical inflammatory period that follows an asthma attack. Here, using immune-primed mice, we show that the crowding of bronchoconstriction causes excess epithelial cell extrusion and damage, resulting in inflammation in distal airways, and mucus secretion in proximal airways. Surprisingly, relaxing airways following bronchoconstriction with the current rescue treatment, albuterol, did not prevent epithelial extrusion and destruction, inflammation, or mucus secretion. However, inhibiting canonical live cell extrusion signaling during bronchoconstriction with stretch-activated/TRP channel or sphingosine 1-phosphate (S1P) inhibitors blocked all downstream symptoms. Our findings propose a new etiology for asthma where the extreme mechanical crowding from a bronchoconstrictive attack causes inflammation by wounding airway epithelium. Whereas most therapies focus on modulating downstream inflammatory symptoms, our studies suggest that blocking epithelial extrusion could prevent the feed-forward asthma inflammatory cycle. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Join Kara Wada, an adult and pediatric allergy, immunology, and lifestyle medicine physician, as we discuss the epithelial barrier hypothesis. What is the epithelial barrier hypothesis? What are some of the diseases that have been linked to epithelial barrier dysfunction? What are some of the factors that can disrupt the epithelial barrier? How can we protect our epithelial barriers? What are some lifestyle changes that can help to improve epithelial barrier function? Find out the answers to these questions and more in this episode. Kara Wada is a board-certified academic adult and pediatric allergy, immunology, and lifestyle medicine physician, Sjogren's patient, certified life coach, TEDx speaker, and Dr. Midwest 2023. She can be reached at Dr. Kara Wada and on Instagram, YouTube, Facebook, and LinkedIn. She is a national expert, sought-after speaker, advisor, and host of the Becoming Immune Confident Podcast. She is CEO and founder, The Crunchy Allergist and the Virtual Sjogren's Summit, and serves as the director of clinical content for Aila Health. She discusses her KevinMD article, "How modern lifestyle changes are disrupting our immune systems." The Podcast by KevinMD is brought to you by the Nuance Dragon Ambient eXperience. With a growing physician shortage, increasing burnout, and declining patient satisfaction, a dramatic change is needed to make health care more efficient and effective and bring back the joy of practicing medicine. AI-driven ambient clinical intelligence promises to help by revolutionizing patient and provider experiences with clinical documentation that writes itself. The Nuance Dragon Ambient eXperience, or DAX for short, is a voice-enabled, ambient clinical intelligence solution that automatically captures patient encounters securely and accurately at the point of care. Physicians who use DAX have reported a 50 percent decrease in documentation time and a 70 percent reduction in feelings of burnout, and 83 percent of patients say their physician is more personable and conversational. Rediscover the joy of medicine with clinical documentation that writes itself, all within the EHR. VISIT SPONSOR → https://nuance.com/daxinaction SUBSCRIBE TO THE PODCAST → https://www.kevinmd.com/podcast RECOMMENDED BY KEVINMD → https://www.kevinmd.com/recommended GET CME FOR THIS EPISODE → https://earnc.me/UWrm6h Powered by CMEfy.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.24.550385v1?rss=1 Authors: Bramey, N., Melo-Narvaez, M. C., See, F., Ballester-Llobell, B., Steinchen, C., Jain, E., Hafner, K., Yildirim, A. O., Koenigshoff, M., Lehmann, M. Abstract: Aging is the main risk factor for chronic lung diseases including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging such as cellular senescence are increased in different cell types such as fibroblasts in the lungs of patients. However, whether the senescent phenotype of fibroblasts derived from IPF or COPD differs is still unknown. Therefore, we characterized senescence at baseline and after exposure to disease-relevant insults (H2O2, bleomycin, and TGF-{beta}1) in primary human lung fibroblasts (phLF) from control donors, IPF, and COPD patients. We found that phLF from different disease origins have a low baseline senescence. Moreover, senescence trigger and not disease origin defines their senescence phenotype. Finally, senescent fibroblasts interfere with the stem cell capacity of alveolar progenitors in vitro. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.25.550533v1?rss=1 Authors: Ceglowski, J., Hoffman, H. K., Hoff, K. J., McCurdy, B. L., Moore, J., Prekeris, R. Abstract: The primary cilium is a critical sensory organelle that is built of axonemal microtubules ensheathed by a ciliary membrane. In polarized epithelial cells, primary cilia reside on the apical surface and must extend these microtubules directly into the extracellular space and remain a stable structure. However, the factors regulating cross-talk between ciliation and cell polarization, as well as, axonemal microtubule growth and stabilization in polarized epithelia are not fully understood. In this study, we find TTLL12, a previously uncharacterized member of the Tubulin Tyrosine Ligase-Like (TTLL) family, localizes to the base of primary cilia and is required for cilia formation in polarized renal epithelial cells. We also show that TTLL12 directly binds to the tubulin heterodimer in vitro and regulates microtubule dynamics, stability, and post-translational modifications (PTMs). While all other TTLLs catalyze the addition of glutamate or glycine to microtubule C-terminal tails, TTLL12 uniquely affects tubulin PTMs by promoting both microtubule lysine acetylation and arginine methylation. Together, this work identifies a novel microtubule regulator and provides insight into the requirements for apical extracellular axoneme formation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.18.549509v1?rss=1 Authors: Cacho-Navas, C., Lopez-Pujante, C., Reglero-Real, N., Colas-Algora, N., Cuervo, A., Conesa, J. J., Barroso, S., Ciordia, S., Paradela, A., D'Agostino, G., Manzo, C., Feito, J., Andres, G., Correas, I., Carazo, J. M., Nourshargh, S., Huch, M., Millan, J. Abstract: Epithelial Intercellular Adhesion Molecule (ICAM)-1 is apically polarized, interacts with and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures (BCs). We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell-cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.22.545997v1?rss=1 Authors: DiGiovanni, G. T., Han, W., Sherrill, T., Taylor, C. J., Nichols, D. S., Geis, N. M., Singha, U. K., Calvi, C. L., McCall, A. S., Dixon, M. M., Lui, Y., Jang, J.-H., Gutor, S. S., Polosukhin, V. V., Blackwell, T. S., Kropski, J. A., Gokey, J. J. Abstract: A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ have been implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrate that Yap and Taz are normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2 to AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to a LPS injury prevented AT1 cell regeneration, led to intra-alveolar collagen deposition, and resulted in persistent innate inflammation. Together these findings establish that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.21.545896v1?rss=1 Authors: Wuenkhaus, D., Tang, R., Nyame, K., Laqtom, N. N., Schweizer, M., Rosato, A. S., Kroegsaeter, E. K., Wollnik, C., Abu-Remaileh, M., Grimm, C., Hermey, G., Kuhn, R., Gruber-Schoffnegger, D., Markmann, S. Abstract: Mutations in the lysosomal membrane protein CLN3 cause Juvenile Neuronal Ceroid Lipofuscinosis (JNCL). Activation of the lysosomal ion channel TRPML1 has previously been shown to be beneficial in several neurodegenerative disease models. Here, we tested whether TRPML1 activation rescues disease-associated phenotypes in CLN3-deficient retinal pigment epithelial (ARPE-19 CLN3-KO) cells. ARPE-19 CLN3-KO cells accumulate LAMP1 positive organelles and show lysosomal storage of mitochondrial ATPase subunit C (SubC), globotriaosylceramide (Gb3), and glycerophosphodiesters (GPDs), whereas lysosomal bis(monoacylglycero)phosphate (BMP/LBPA) lipid levels were significantly decreased. Activation of TRPML1 reduced lysosomal storage of Gb3 and SubC but failed to restore BMP levels in CLN3-KO cells. TRPML1-mediated decrease of storage was TFEB-independent, and we identified TRPML1-mediated enhanced lysosomal exocytosis as a likely mechanism for clearing storage including GPDs. Therefore, ARPE-19 CLN3-KO cells represent a human cell model for CLN3 disease showing many of the described core lysosomal deficits, some of which can be improved using TRPML1 agonists. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.05.539557v1?rss=1 Authors: Christofidou, E., Tomazou, M., Voutouri, C., Michael, C., Stylianopoulos, T., Spyrou, G. M., Strati, K. Abstract: Oct4 is a pioneer transcription factor regulating pluripotency. However, it is poorly known whether Oct4 has an impact on somatic cells. We generated OCT4 knockout clonal cell lines using immortalized human skin keratinocytes to identify a functional role for the protein. Here we report that Oct4-deficient cells transitioned into a mesenchymal-like phenotype with enlarged size and shape, exhibited accelerated migratory behavior, decreased adhesion and appeared arrested at G2/M cell cycle checkpoint. Oct4 absence had a profound impact on cortical actin organization, with loss of microfilaments from cell periphery, increased puncta deposition in the cytoplasm and stress fiber formation. E-cadherin, beta-catenin and ZO1 were almost absent from cell-cell contacts while fibronectin deposition was markedly increased in ECM. Mapping of the transcriptional and chromatin profiles of Oct4-deficient cells revealed that Oct4 controls the levels of cytoskeletal, ECM and differentiation related genes, whereas epithelial identity is preserved through transcriptional and non-transcriptional mechanisms. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.27.538411v1?rss=1 Authors: Groh, A.-C., Kleimann, S., Nedvestky, P., Behrens, M., Moeller-Kerutt, A., Hoeffken, V., Ghosh, S., Hansen, U., Krahn, M. P., Ludwig, A., Ebnet, K., Pavenstaedt, H., Weide, T. Abstract: The evolutionarily conserved Crumbs (CRB) polarity complex, which consists of the core components CRB3a, PALS1 and PATJ, plays a key role in epithelial cell-cell contact formation and cell polarization. Recently we observed that deletion of one Pals1 allele in mice results in functional haploinsufficiency characterized by renal cysts. To address the role of PALS1 at the cellular level, we generated PALS1 knockout MDCKII cell lines using the CRISPR/Cas9 system. The loss of PALS1 resulted in increased paracellular permeability indicative of an epithelial barrier defect. This barrier defect was associated with a redistribution of several tight junction-associated proteins from bicellular cell-cell contacts to tricellular junctions. The regulation of tight junction protein localization at bicellular junctions by PALS1 was dependent on its interaction with PATJ. Together, our data uncover a critical role of PALS1 in the correct positioning of tight junction proteins to bicellular junctions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.25.538235v1?rss=1 Authors: Chen, Y., Briant, K., Camus, M. D., Brodsky, F. M. Abstract: To identify functional differences between vertebrate clathrin light chains (CLCa or CLCb), phenotypes of mice lacking genes encoding either isoform were characterised. Mice without CLCa displayed 50% neonatal mortality, reduced body weight, reduced fertility, and ~40% of aged females developed uterine pyometra. Mice lacking CLCb displayed a less severe weight reduction phenotype compared to those lacking CLCa, and had no survival or reproductive system defects. Analysis of female mice lacking CLCa that developed pyometra revealed ectopic expression of epithelial differentiation markers (FOXA2 and K14) and a reduced number of endometrial glands, indicating defects in the luminal epithelium. Defects in lumen formation and polarity of epithelial cysts derived from uterine or gut cell lines were also observed when either CLCa or CLCb were depleted, with more severe effects from CLCa depletion. In cysts, the CLC isoforms had different distributions relative to each other, while they converge in tissue. Together, these findings suggest differential and cooperative roles for CLC isoforms in epithelial lumen formation, with a dominant function for CLCa. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.18.537332v1?rss=1 Authors: Massey-Harroche, D., Conte, V., Gouirand, N., Sebbagh, M., Le Bivic, A., Bazellieres, E. Abstract: Several cellular processes during morphogenesis, tissue healing or cancer progression involve epithelial to mesenchymal plasticity that leads to collective motion (plasticity?). Even though a rich variety of EMP programs exist, a major hallmark unifying them is the initial breaking of symmetry that modifies the epithelial phenotype and axis of polarity. During this process, the actin cytoskeleton and cellular junctions are extensively remodelled correlating with the build-up of mechanical forces. As the collective migration proceeds, mechanical forces generated by the actin cytoskeleton align with the direction of migration ensuring an organized and efficient collective cell behaviour, but how forces are regulated during the breaking of symmetry at the onset of EMP remains an unaddressed question. It is known that the polarity complex CRB3/PALS1/PATJ, and in particular, CRB3 regulates the organization of the actin cytoskeleton associated to the apical domain thus pointing at a potential role of CRB3 in controlling mechanical forces. Whether and how CRB3 influences epithelial biomechanics during the epithelial-mesenchymal plasticity remains, however, largely unexplored. Here, we systematically combine mechanical and molecular analyses to show that CRB3 regulates the biomechanical properties of collective epithelial cells during the initial breaking of symmetry of the EMP. CRB3 interacts with ARP2/3 and controls the remodelling of actin throughout the monolayer via the modulation of the Rho-/Rac-GTPase balance. Taken together, our results identified CRB3, a polarity protein, as a regulator of epithelial monolayer mechanics during EMP Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 7, entitled, “p21 facilitates chronic lung inflammation via epithelial and endothelial cells.” Cellular senescence is a stable state of cell cycle arrest that regulates tissue integrity and protects the organism from tumorigenesis. However, the accumulation of senescent cells during aging contributes to age-related pathologies. One such pathology is chronic lung inflammation. p21 (CDKN1A) regulates cellular senescence via inhibition of cyclin-dependent kinases (CDKs). However, its role in chronic lung inflammation and functional impact on chronic lung disease, where senescent cells accumulate, is less understood. In this new study, researchers Naama Levi, Nurit Papismadov, Julia Majewska, Lior Roitman, Noa Wigoda, Raya Eilam, Michael Tsoory, Ron Rotkopf, Yossi Ovadya, Hagay Akiva, Ofer Regev, and Valery Krizhanovsky from the Weizmann Institute of Science aimed to elucidate the role of p21 in chronic lung inflammation. “[...] we subjected p21 knockout (p21-/-) mice to repetitive inhalations of lipopolysaccharide (LPS), an exposure that leads to chronic bronchitis and accumulation of senescent cells.” The researchers utilized a lipopolysaccharide (LPS) inhalation-induced chronic bronchitis procedure to study the effects of repetitive LPS exposure on p21 knockout (p21-/-) mice. Furthermore, the team aimed to examine the specific contribution of the epithelial, endothelial and immune compartments to chronic bronchitis pathology. They found that p21 knockout led to a reduced presence of senescent cells, alleviated the pathological manifestations of chronic lung inflammation, and improved the fitness of the mice. The expression profiling of the lung cells revealed that resident epithelial and endothelial cells, but not immune cells, play a significant role in mediating the p21-dependent inflammatory response following chronic LPS exposure. “Therefore, we suggest that p21-dependent elimination of senescent cells may limit the damage induced by the pro-inflammatory presence of senescent cells, but also promote tissue regeneration. Therefore, inhibition of p21 represents a promising strategy for limiting age-related inflammatory disorders in general and obstructive lung diseases in particular.” DOI: https://doi.org/10.18632/aging.204622 Corresponding Author: Valery Krizhanovsky - valery.krizhanovsky@weizmann.ac.il Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204622 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, chronic lung inflammation, p21 (CDKN1A) About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.15.536998v1?rss=1 Authors: Assou, S., Ahmed, E., Morichon, L., Nasri, A., Foisset, F., Bourdais, C., Gros, N., Wong, S., Petit, A. F., Vachier, I., Muriaux, D., Bourdin, A., De Vos, J. Abstract: Airway-liquid interface cultures of primary epithelial cells and of induced pluripotent stem cell-derived airway epithelial cells (ALI and iALI, respectively) are physiologically relevant models for respiratory virus infection studies because they can mimic the in vivo human bronchial epithelium. Here, we investigated gene expression profiles in human airway cultures (ALI and iALI models) infected or not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using publicly available and our own bulk and single-cell transcriptome datasets. SARS-CoV-2) infection significantly increased the expression of interferon-stimulated genes (IFI44, IFIT1, IFIT3, IFI35, IRF9, MX1, OAS1, OAS3 and ISG15) and inflammatory genes (NFKBIA, CSF1, FOSL1, IL32 and CXCL10) at day 4 post-infection, indicating activation of the interferon and immune responses to the virus. Extracellular matrix genes (ITGB6, ITGB1 and GJA1) also were altered in infected cells. Single-cell RNA sequencing data revealed that SARS-CoV-2 infection damaged the respiratory epithelium, particularly mature ciliated cells. The expression of genes encoding intercellular communication and adhesion proteins also was deregulated, suggesting a mechanism to promote shedding of infected epithelial cells. These data demonstrate that ALI/iALI models help to understand the airway epithelium response to SARS-CoV-2 infection and are a key tool for developing COVID-19 treatments. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.12.536514v1?rss=1 Authors: Awatade, N. T., Reid, A. T., Nichol, K. S., Budden, K. F., Veerati, P. C., Pathinayake, P. S., Grainge, C. L., Hansbro, P. M., Wark, P. A. Abstract: Introduction: Primary air liquid interface (ALI) cultures of bronchial epithelial cells are used extensively to model airway responses. A recent advance is the development of conditional reprogramming that enhances proliferative capability. Several different media and protocols are utilized, yet even subtle differences may influence cellular responses. We compared the morphology and functional responses, including innate immune responses to rhinovirus infection in conditionally reprogrammed primary bronchial epithelial cells (pBECs) differentiated using two commonly used culture media. Methods: pBECs from healthy participants (n = 5) were CR using gamma-irradiated 3T3 fibroblasts and Rho Kinase inhibitor. CRpBECs were differentiated at ALI in either PneumaCultTM (PN-ALI) or Bronchial Epithelial Growth Medium (BEGM)-based differentiation media (BEBM:DMEM, 50:50, LonzaTM) - (AB-ALI) for 28 days. Transepithelial electrical resistance (TEER), immunofluorescence, histology, cilia activity, ion channel function, and expression of cell markers were analyzed. Viral load was assessed by RT-qPCR and anti-viral factors quantified by Legendplex following Rhinovirus-A1b (RVA1b) infection. Results: CRpBECs differentiated in PneumaCultTM were smaller and had a lower TEER and cilia beat frequency (CBF) compared to BEGM media. PneumaCultTM media cultures exhibited significantly increased FOXJ1 expression, more ciliated cells with a larger active area, increased intracellular mucins, and increased calcium-activated chloride channel current. However, there were no significant changes in viral RNA or host antiviral responses. Conclusion: There are distinct structural and functional differences in CRpBECs cultured in the two commonly used ALI differentiation media. Such factors need to be taken into consideration when designing and comparing CRpBECs ALI experiments. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.06.535853v1?rss=1 Authors: Danan, C. H., Naughton, K. E., Hayer, K. E., Vellapan, S., McMillan, E. A., Zhou, Y., Matsuda, R., Nettleford, S. K., Katada, K., Parham, L. R., Ma, X., Chowdhury, A., Wilkins, B. J., Shah, P., Weitzman, M. D., Hamilton, K. E. Abstract: The METTL3-METTL14 methyltransferase complex adds N6-methyladenosine (m6A) to mRNA with profound impacts on cell fate. Studies delete METTL3 or METTL14 interchangeably to define the role of m6A in target tissues despite a lack of data confirming that these deletions are equivalent. Intestinal epithelial METTL14 deletion triggers stem cell death in the colon with no overt phenotype in the small intestine. The effect of METTL3 deletion in the same tissues remains unknown. We report that intestinal epithelial METTL3 deletion caused unexpected severe defects in the small intestine, including crypt and villus atrophy associated with cellular senescence and death in the crypt transit amplifying zone. Ribosome profiling and m6A-sequencing demonstrated downregulated translation of hundreds of unique methylated transcripts, including genes essential to growth factor signal transduction, such as Kras. Our study suggests that METTL3 is essential for small intestinal homeostasis via enhanced translation of growth factor signaling in crypt transit amplifying cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Ryan Conder is the Director of Epithelial and Organoid Systems at STEMCELL Technologies.  He talks about the next phase in organoid research and what questions organoids can help answer. He also discusses his experience doing a postdoc in Vienna, and Vancouver as a growing biotech hub.

Learn about where you see epithelial tissues, its characteristics & classifications.

References Clin Podiatr Med Surg . 2001 Jan;18(1):35-53 Biomedicines. 2021 Nov; 9(11): 1666 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

FDA D.I.S.C.O. Burst Edition: FDA approval of Elahere (mirvetuximab soravtansine-gynx) for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Josh Rabinowitz is a Professor of Chemistry and Integrative Genomics at Princeton University, where his research focuses on developing a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. In this episode, Josh focuses the discussion on three main topics: metabolomics, NAD (and its precursors), and cancer metabolism. The metabolomics discussion starts with a broad definition of metabolism, metabolites, and fluxomics before diving deep into glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. He then gives a detailed explanation of the electron transport chain and Krebs cycle and their implications with respect to both drugs and nutrition while also explaining how NAD is central to the process of energy generation. He then discusses the age-related decline in NAD and what current literature says about efforts to increase NAD through intravenous or oral supplementation with the precursors NMN and NR, including whether doing so provides any advantage to lifespan or healthspan. Finally, Josh ends the conversation talking about cancer metabolism and how one particular intersection between cancer metabolism and immunotherapy might provide a hopeful outlook on the future of cancer treatment. We discuss: Josh's background and unique path to becoming a research scientist at Princeton [3:30]; What sparked Josh's early interest in metabolism [11:15]; Metabolomics 101: defining metabolites and how they are regulated [16:30]; Fluxomics: metabolism as a system in action [26:00]; The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation [33:30]; The important role of lactate as an alternate fuel [36:30]; Fasting lactate levels as a potential early indicator of metabolic dysfunction [48:00]; The beauty of the Krebs cycle and the role of NAD in energy production [53:15]; How the drug metformin acts on complex I of the electron transport chain [1:05:00]; The difference between NADH and NADPH [1:08:45]; NAD levels with age, and the efficacy of supplementing with intravenous NAD [1:10:45]; The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN [1:22:15]; Exploring the hypothesis that boosting NAD levels is beneficial [1:32:30]; Cancer metabolism and the intersection with immunotherapy [1:39:00]; Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more [1:46:15]; The challenge of treating pancreatic cancer [1:50:30]; Epithelial cancers that might respond to metabolic approaches to therapy [1:56:30]; Josh's hopeful outlook on the future of cancer treatment [1:59:00]; Nutritional approaches to cancer attenuation [2:00:15]; What makes Princeton University special [2:06:15]; More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with severe asthma, uncontrolled symptoms, and exacerbations are at risk of losing lung function over time. Despite the availability of numerous treatments, many patients with severe asthma remain uncontrolled. Evolving insights into the pathophysiology of severe asthma have led to the development of biologic therapies that target epithelial alarmins, and their use is not restricted by phenotype/endotype or biomarkers. In this activity, based on a recent live web broadcast, our experts will review the latest clinical data, including key insights from medical congresses up to and including ATS 2022, with respect to novel and emerging therapies and other factors that impact the selection of treatment for patients with severe asthma who continue to have uncontrolled disease despite treatment. You will achieve greater insight into the most up-to-date evidence on the pathophysiology of severe asthma, particularly with regard to the role of epithelial alarmins in the development of severe asthma. Upon completion of this activity, participants should be better able to: Discuss the rationale for the use of therapeutic options that target epithelial alarmins, including TSLP, IL-33, and IL-25, for the treatment of severe asthma, Employ the latest pathophysiologic insights into the role of epithelial alarmins to the treatment of patients with severe asthma, Develop treatment plans for patients with severe asthma, particularly those whose disease remains uncontrolled despite treatment, based on the latest clinical evidence with regard to novel and emerging therapies.

Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with severe asthma, uncontrolled symptoms, and exacerbations are at risk of losing lung function over time. Despite the availability of numerous treatments, many patients with severe asthma remain uncontrolled. Evolving insights into the pathophysiology of severe asthma have led to the development of biologic therapies that target epithelial alarmins, and their use is not restricted by phenotype/endotype or biomarkers. In this activity, based on a recent live web broadcast, our experts will review the latest clinical data, including key insights from medical congresses up to and including ATS 2022, with respect to novel and emerging therapies and other factors that impact the selection of treatment for patients with severe asthma who continue to have uncontrolled disease despite treatment. You will achieve greater insight into the most up-to-date evidence on the pathophysiology of severe asthma, particularly with regard to the role of epithelial alarmins in the development of severe asthma. Upon completion of this activity, participants should be better able to: Discuss the rationale for the use of therapeutic options that target epithelial alarmins, including TSLP, IL-33, and IL-25, for the treatment of severe asthma, Employ the latest pathophysiologic insights into the role of epithelial alarmins to the treatment of patients with severe asthma, Develop treatment plans for patients with severe asthma, particularly those whose disease remains uncontrolled despite treatment, based on the latest clinical evidence with regard to novel and emerging therapies.

Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with severe asthma, uncontrolled symptoms, and exacerbations are at risk of losing lung function over time. Despite the availability of numerous treatments, many patients with severe asthma remain uncontrolled. Evolving insights into the pathophysiology of severe asthma have led to the development of biologic therapies that target epithelial alarmins, and their use is not restricted by phenotype/endotype or biomarkers. In this activity, based on a recent live web broadcast, our experts will review the latest clinical data, including key insights from medical congresses up to and including ATS 2022, with respect to novel and emerging therapies and other factors that impact the selection of treatment for patients with severe asthma who continue to have uncontrolled disease despite treatment. You will achieve greater insight into the most up-to-date evidence on the pathophysiology of severe asthma, particularly with regard to the role of epithelial alarmins in the development of severe asthma. Upon completion of this activity, participants should be better able to: Discuss the rationale for the use of therapeutic options that target epithelial alarmins, including TSLP, IL-33, and IL-25, for the treatment of severe asthma, Employ the latest pathophysiologic insights into the role of epithelial alarmins to the treatment of patients with severe asthma, Develop treatment plans for patients with severe asthma, particularly those whose disease remains uncontrolled despite treatment, based on the latest clinical evidence with regard to novel and emerging therapies.

Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with severe asthma, uncontrolled symptoms, and exacerbations are at risk of losing lung function over time. Despite the availability of numerous treatments, many patients with severe asthma remain uncontrolled. Evolving insights into the pathophysiology of severe asthma have led to the development of biologic therapies that target epithelial alarmins, and their use is not restricted by phenotype/endotype or biomarkers. In this activity, based on a recent live web broadcast, our experts will review the latest clinical data, including key insights from medical congresses up to and including ATS 2022, with respect to novel and emerging therapies and other factors that impact the selection of treatment for patients with severe asthma who continue to have uncontrolled disease despite treatment. You will achieve greater insight into the most up-to-date evidence on the pathophysiology of severe asthma, particularly with regard to the role of epithelial alarmins in the development of severe asthma. Upon completion of this activity, participants should be better able to: Discuss the rationale for the use of therapeutic options that target epithelial alarmins, including TSLP, IL-33, and IL-25, for the treatment of severe asthma, Employ the latest pathophysiologic insights into the role of epithelial alarmins to the treatment of patients with severe asthma, Develop treatment plans for patients with severe asthma, particularly those whose disease remains uncontrolled despite treatment, based on the latest clinical evidence with regard to novel and emerging therapies.

Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with severe asthma, uncontrolled symptoms, and exacerbations are at risk of losing lung function over time. Despite the availability of numerous treatments, many patients with severe asthma remain uncontrolled. Evolving insights into the pathophysiology of severe asthma have led to the development of biologic therapies that target epithelial alarmins, and their use is not restricted by phenotype/endotype or biomarkers. In this activity, based on a recent live web broadcast, our experts will review the latest clinical data, including key insights from medical congresses up to and including ATS 2022, with respect to novel and emerging therapies and other factors that impact the selection of treatment for patients with severe asthma who continue to have uncontrolled disease despite treatment. You will achieve greater insight into the most up-to-date evidence on the pathophysiology of severe asthma, particularly with regard to the role of epithelial alarmins in the development of severe asthma. Upon completion of this activity, participants should be better able to: Discuss the rationale for the use of therapeutic options that target epithelial alarmins, including TSLP, IL-33, and IL-25, for the treatment of severe asthma, Employ the latest pathophysiologic insights into the role of epithelial alarmins to the treatment of patients with severe asthma, Develop treatment plans for patients with severe asthma, particularly those whose disease remains uncontrolled despite treatment, based on the latest clinical evidence with regard to novel and emerging therapies.

Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with severe asthma, uncontrolled symptoms, and exacerbations are at risk of losing lung function over time. Despite the availability of numerous treatments, many patients with severe asthma remain uncontrolled. Evolving insights into the pathophysiology of severe asthma have led to the development of biologic therapies that target epithelial alarmins, and their use is not restricted by phenotype/endotype or biomarkers. In this activity, based on a recent live web broadcast, our experts will review the latest clinical data, including key insights from medical congresses up to and including ATS 2022, with respect to novel and emerging therapies and other factors that impact the selection of treatment for patients with severe asthma who continue to have uncontrolled disease despite treatment. You will achieve greater insight into the most up-to-date evidence on the pathophysiology of severe asthma, particularly with regard to the role of epithelial alarmins in the development of severe asthma. Upon completion of this activity, participants should be better able to: Discuss the rationale for the use of therapeutic options that target epithelial alarmins, including TSLP, IL-33, and IL-25, for the treatment of severe asthma, Employ the latest pathophysiologic insights into the role of epithelial alarmins to the treatment of patients with severe asthma, Develop treatment plans for patients with severe asthma, particularly those whose disease remains uncontrolled despite treatment, based on the latest clinical evidence with regard to novel and emerging therapies.

In this episode, Dr Matt and Dr Mike discuss the four tissues that make up the body. These include Epithelial, Connective, Nervous and Muscle tissue. This episode is great for anyone who wants to understand how the body is put together.

Dr. Shruti Naik is an Assistant Professor of Biological Sciences at New York University Langone Medical Center. She studies immunity in the epithelial tissues that line our body to understand how environmental stimuli collaborate with genetic factors to influence health and drive disease at these interfaces. She discusses the work she's presenting at the American Association of Immunologists' annual meeting, IMMUNOLOGY2022, on trained immunity and immune-epithelial crosstalk in tissue repair.

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

Michele De Luca, MD, shares his research in gene therapy for epidermolysis bullosa and cell therapy for ocular burns. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37671]

The Journal RETINA is devoted exclusively to diseases of the retina and vitreous.  These podcasts are intended to bring to its listeners summaries of selected articles published in the current issue of this internationally acclaimed journal.

Aging-US published a Special Collection on Eye Disease which included "Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells" which reported that loss of retinal pigment epithelium (RPE) cells occurs early in AMD, and their transplant has the potential to slow disease progression. Age-related MSC changes involve loss of function and acquisition of a senescence-associated secretory phenotype (SASP). These changes can contribute to the maintenance of a chronic state of low-grade inflammation in tissues and organs. Dr. Cesare Mariotti from The Università Politecnica delle Marche said, "Age-related macular degeneration (AMD) is an eye disorder affecting the elderly which can induce an irreversible loss of central visual function." Age-related macular degeneration (AMD) is one of the most serious and debilitating forms of aging-related eye disease. Smoking, cataract surgery, high BMI and cardiovascular disease are risk factors for AMD, as well as a family history of AMD. No effective treatment is available for neovascular AMD, while anti-VEGFD is the mainstay of treatment for dry AMD. Neovascular AMD and GA are characterized by RPE dysfunction; formation of large confluent drusen and hyperpigmentation seem to be the initial insult. AMD patients show a different phenotype as well as functional changes such as altered autophagy, mitochondrial dysfunction, and susceptibility to oxidative stress. A greater understanding of the molecular pathways that are involved in the various stages of AMD would contribute to the development of innovative therapies. The Mariotti Research Team concluded in their Aging-US Research Output that RPESCs can undergo replicative senescence, which affects their proliferation and differentiation ability. In addition, they acquired the SASP, which probably compounds the inflammatory RPE microenvironment during AMD development and progression. A greater understanding of the role of RPESCs in AMD pathogenesis is needed to find means to control the disease. Full Text - https://www.aging-us.com/article/101624/text Correspondence to: Cesare Mariotti email: mariottiocul@gmail.com Keywords: AMD, RPESCs, age-related diseases, senescence, inflammation About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

Aging-US published a Special Collection on Eye Disease which included "The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells – implication in subretinal immune privilege in the aging eye" which reported that this study aimed to understand how complement expression in macrophages is regulated by retinal pigment epithelium (RPE) RPE can modulate macrophage complement expression at the retina-choroidal interface even under aging or oxidative conditions. During inflammation, they may promote the alternative pathway of complement activation through down-regulating CFH and CD59a and upregulating C3, CFB and C1INH. When BMDMs were treated with apoptotic RPE, the expression of C1qb, CFH, and CD 59a was reduced but increased in BMDM. TNF-α pre-treated RPE enhanced C1inH and CFB expression. Dr. Heping Xu from The Queen's University Belfast as well as The Central South University said, "The neuronal retina is segregated from the systemic immune system by the blood retina barriers (BRB) and is considered as an immune privileged tissue." The immune suppressive microenvironment of the eye is critical for retinal immune privilege. Despite the lack of systemic immune surveillance, the retina is well-protected by its own innate immune defence system, including innate immune cells and the complement system. During aging, the expression of complement proteins or fragments is increased in the retina, particularly at the retina-choroid interface. Subretinal macrophages in the healthy adult eyes (6 -12 months old) often have a small soma and long- fine-dendrites (Fig. 1A), whereas the cells in the aging eye (20 – 27 months) have a large cell body that often contains pigmented debris. This suggests that they are active phagocytizing debris released by stressed RPE cells. The Xu Research Team concluded in their Aging-US Research Output, "we show that RPE cells can modulate macrophage complement expression. Under normal aging conditions, RPE cells may convert macrophages into a phenotype that can suppress complement activation with enhanced phagocytosis. This immune regulatory function of RPE cells on macrophages may be lost under inflammatory conditions. Instead, inflammatory or apoptotic RPE cells promote macrophages to produce complement components necessary for the AP activation. RPE cells together with subretinal macrophages critically control complement activation at the retina-choroid interface in the ageing eye." Full Text - https://www.aging-us.com/article/101474/text Correspondence to: Heping Xu email: heping.xu@qub.ac.uk Keywords: macrophages, retinal pigment epithelial cells, complement, aging, subretinal immune privilege About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

In this episode, we review the high-yield topic of Epithelial Cell Junctions from the Dermatology section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://anchor.fm/medbulletsstep1/message

Epithelium is one of the four basic tissue types (the other three are muscle tissue, nerve tissue, and connective tissue). It is found throughout the body—covering it; lining organs, vessels, and cavities; and forming glands. It absorbs nutrients, transports electrolytes, secretes hormones, and regulates body temperature by producing sweat. We begin with some general principles of how epithelial tissue is organized, and then we describe its various components. After listening to this AudioBrick, you should be able to: List the two types of epithelium (covering/lining and glandular) and describe their functions. Describe the structure and histologic features of epithelial tissue. Explain how covering/lining epithelium is classified. Describe the histologic features of glandular epithelium. Describe the five types of epithelial intercellular junctions. You can also check out the original brick on the Histology of Epithelial Tissue from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/