Podcasts about cell death

This episode was recorded in Fort Wayne, Indiana, during the 2025 Tri-State Dairy Conference. Dr. Laporta gives an overview of her presentation, focusing on the impact of heat stress during the dry period on the cow, her daughters and her granddaughters. She covers heat stress impacts on mammary gland involution, as well as fetal programming effects on the daughter and granddaughter. (3:37)Daughters of heat-stressed cows have fewer sweat glands located deeper in the skin, thicker skin and more sebaceous glands. This was observed at birth, weaning and puberty. They sweat more than heifers who weren't heat stressed in utero, but have higher rectal temperatures during the preweaning phase. Dr. Laporta hypothesizes that if those calves were exposed to additional stress, they would be more susceptible to illness because of the higher core temperature.  (6:34)The panel discusses heat stress impacts on male fetuses and the potential for epigenetic changes to be transmitted through semen. Dr. Gerloff asks about differences in the impacts of heat stress on first-calf heifers compared to older cows. Dr. Laporta describes the survival rates of heifers who were heat-stressed in utero. Heifers are lost from the herd even before first calving, with more following in first and second lactation.  (11:00)Dr. Laporta outlines the differences between heat-stressed and cooled treatments in her experiments. They measure respiration rates and rectal temperatures to assess the physiological impacts of heat stress in the cows. Scott asks how long the heat stress period needs to be in order to observe negative effects. Dr. Gerloff asks about calf mortality rates between the two groups. Dr. Laporta estimates a 12% death loss in the heat stress groups, who seem to be more susceptible to the usual calf illnesses. It appears that gut closure might occur earlier in heat-stressed calves - maybe even before birth, which does not bode well for their immune systems. (16:49)Dr. Laporta details how heat stress impacts mammary gland involution. Early in the dry period, you want a spike in cell death to build new cells for the next lactation. In heat-stressed cows, the spike in cell death early in the dry period is diminished, not allowing those cells to die. This results in less proliferation of the mammary gland, and the cow starts her next lactation with older cells that weren't renewed in full. Thus, producing less milk. Dr. Gerloff shares some of his experiences with heat stress in his area of Illinois. (22:17)Heat stress has negative impacts on other organs as well. Heifers who experienced heat stress in utero are born with larger adrenal glands with altered microstructure. Dr. Laporta describes some of the DNA methylation that has been observed in these heifers. The panel discusses whether the response would be similar for other types of stressors, like cold stress or social stress. (26:19)What can we do to mitigate these impacts? Cooling dry cows so they can thermoregulate during gestation is critical. Altering diets to account for heat stress is also an important strategy. Unfortunately, there is no magic bullet to “fix” cows who were exposed to heat stress in utero, but these negative implications can be prevented. Dr. Laporta has also focused on what she calls perinatal programming - after the calf is born, what can we do? She has been working to develop cooling mechanisms for calves and is interested in further investigating early life mammary development. (33:41)When a dry cow experiences heat stress, she has fewer and smaller alveoli. Daughters of those cows have smaller udders with altered tissue growth. Granddaughters of those cows have fewer estrogen receptors in their udders and negative impacts on mammary proliferation. (44:30)Panelists share their take-home thoughts. (47:52)Scott invites the audience to Bourbon and Brainiacs at ADSA in Louisville - a bourbon tasting with all your favorite professors! Sign up here: https://balchem.com/anh/bourbon/ (54:31)Please subscribe and share with your industry friends to invite more people to join us at the Real Science Exchange virtual pub table.  If you want one of our Real Science Exchange t-shirts, screenshot your rating, review, or subscription, and email a picture to anh.marketing@balchem.com. Include your size and mailing address, and we'll mail you a shirt.

Send us a textShort Summary: A deep dive into the science of oxidative stress, antioxidants, aging, and neurodegenerative diseases like Alzheimer's.About the guest: Pamela Maher, PhD is a professor at the Salk Institute in San Diego, California, with a focus on neurodegenerative diseases, oxidative stress, and antioxidants.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Dr. Pamela Maher discusses her research on cell death mechanisms, including apoptosis and ferroptosis, and their roles in health and disease. They discuss how oxidative stress from reactive oxygen species can damage cells, the body's antioxidant defenses like glutathione and studies on natural compounds—fisetin, curcumin, and cannabinol (CBN)—that may protect against brain cell loss. The conversation covers CBN's mitochondrial benefits in aging mouse models and broader risk factors for dementia, like obesity and hearing loss, emphasizing early intervention.Key Takeaways:Apoptosis is a controlled cell death process vital for development, while ferroptosis, linked to oxidative stress and iron, causes cells to burst and is tied to diseases like Alzheimer's.Oxidative stress arises when reactive oxygen species overwhelm antioxidants, damaging DNA, proteins, and cell membranes, especially polyunsaturated fats.Glutathione, a key antioxidant, relies on cysteine and declines with age, but supplements like N-acetylcysteine might help, though tolerability varies.Cannabinol (CBN), a THC byproduct, protects mitochondria and improves memory in aging mice, hinting at therapeutic potential beyond cannabinoid receptors.Middle-age risk factors like visceral obesity, type 2 diabetes, and hearing loss significantly increase dementia risk, but hearing aids can reduce it.Related episode:M&M #165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet*Not medical aSupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Readwise: Organize and share what you read. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. For all the ways you can support my efforts

Walking speed is a commonly used measure for health, as it's easy to do and doesn't cost much. Now a study by Peter Abadir, a Johns Hopkins geriatrics expert, links walking speed to cell death, as measured by release of … Is walking speed linked to cell death? Elizabeth Tracey reports Read More »

Cell death in your body happens all the time, every day, and when it does DNA is released into your blood. It may be your genetic DNA or it may be from your mitochondria, and it is giving clues to … Why does increased cell death in the body increase inflammation? Elizabeth Tracey reports Read More »

Death might seem like a pure loss, the disappearance of what makes a living thing distinct from everything else on our planet. But zoom in closer, to the cellular level, and it takes on a different, more nuanced meaning. There is a challenge in simply defining what makes an individual cell alive or dead. Scientists today are working to understand the various ways and reasons that cells disappear, and what these processes mean to biological systems. In this episode, cellular biologist Shai Shaham talks to Steven Strogatz about the different forms of cell death, their roles in evolution and disease, and why the right kinds and patterns of cell death are essential to our development and well-being.

In this episode, Dr. Jessica Steier and Dr. Sarah Scheinman discuss the complexities of cancer with Dr. Joe Zundell, a cancer biologist. They explore the definition of cancer, its prevalence, and the hallmarks that characterize cancer cells. The conversation delves into the mechanisms of cancer growth, including sustaining proliferative signaling, evading growth suppression through the P53 gene, and the process of apoptosis. The discussion aims to make these complex topics accessible to a broader audience while highlighting the importance of understanding cancer biology. In this conversation, Dr. Joe Zundell discusses the complexities of cancer biology, focusing on key hallmarks such as immune response, replicative immortality, angiogenesis, and metastasis. He emphasizes the importance of early detection and the challenges of targeting cancer cells without affecting healthy cells. The discussion highlights the need for careful consideration of information regarding cancer treatment and the significance of working with healthcare professionals. All our sources from this episode are available at: https://www.unbiasedscipod.com/episodes/ (00:00) Introduction  (05:28) Understanding Cancer: Definitions and Statistics (10:15) The Hallmarks of Cancer: An Overview (15:14) Sustaining Proliferative Signaling in Cancer (20:07) Evading Growth Suppression: The Role of P53 (25:17) Apoptosis: The Controlled Cell Death Mechanism (30:21) Understanding Cancer: Immune Response and Cell Death (33:31) Replicative Immortality: The Hayflick Limit (38:27) Angiogenesis: Blood Vessel Formation in Tumors (46:32) Invasion and Metastasis: The Spread of Cancer (54:22) Final Thoughts: The Complexity of Cancer Treatment and Early Detection Interested in advertising with us? Please reach out to advertising@airwavemedia.com, with “Unbiased Science” in the subject line. PLEASE NOTE: The discussion and information provided in this podcast are for general educational, scientific, and informational purposes only and are not intended as, and should not be treated as, medical or other professional advice for any particular individual or individuals. Every person and medical issue is different, and diagnosis and treatment requires consideration of specific facts often unique to the individual. As such, the information contained in this podcast should not be used as a substitute for consultation with and/or treatment by a doctor or other medical professional. If you are experiencing any medical issue or have any medical concern, you should consult with a doctor or other medical professional. Further, due to the inherent limitations of a podcast such as this as well as ongoing scientific developments, we do not guarantee the completeness or accuracy of the information or analysis provided in this podcast, although, of course we always endeavor to provide comprehensive information and analysis. In no event may Unbiased Science or any of the participants in this podcast be held liable to the listener or anyone else for any decision allegedly made or action allegedly taken or not taken allegedly in reliance on the discussion or information in this podcast or for any damages allegedly resulting from such reliance. The information provided herein do not represent the views of our employers. Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Pascal Meier is a Professor and Group Leader at the Institute of Cancer Research in London, England. His group investigates the complex relationship between cell death, immunity, and tumorigenesis. Particularly, they are focused on the role of cell death and inflammation in adaptation to tissue stress, treatment resistance, and tumour surveillance.

The 2024 Nobel Prize in Physiology or Medicine was awarded to Victor Ambros and Gary Ruvkun for the discovery of microRNA. It's too bad we at Reefer MEDness don't know anything about microRNA. But wait…We do! Hilal Kalkan, a post-doc at Laval University, talks to us about how microRNA and cannabinoid receptors are involved in the side effect of a common cholesterol medication. Come dive deep into the molecular workings of the endocannabinoid system with us!Hilal Kalkan - LinkedInDysfunctional endocannabinoid CB1 receptor expression and signaling contribute to skeletal muscle cell toxicity induced by simvastatin, Hilal Kalkan et al. - Paper in Cell Death and Disease(Yes we got a SOCAN membership to use this song all legal and proper like)Music by:Tuğba Yurt - Benim O -YouTubeAdditional Music:Desiree Dorion desireedorion.comMarc Clement - FacebookTranscripts, papers and so much more at: reefermed.ca

In this #review, #researchers explore the intricate relationship between various cell death pathways and host immunological responses. Kuo-Cheng Lu, Kuo-Wang Tsai, Yu-Kuen Wang, and Wan-Chung Hu from Taipei Tzu Chi Hospital, Fu Jen Catholic University, Taoyuan Armed Forces General Hospital, Tri-Service General Hospital and Ming Chuan University, have delved into the literature surrounding cell death pathways and their connections to host immunological pathways. Their review was published as the cover paper of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 15, entitled, “Types of Cell Death and Their Relations to Host Immunological Pathways.” Full blog - https://aging-us.org/2024/08/exploring-links-between-cell-death-pathways-and-immune-responses/ Paper DOI - https://doi.org/10.18632/aging.206035 Corresponding author - Wan-Chung Hu - Wanchung.Hu09@tzuchi.com.tw Video short - https://www.youtube.com/watch?v=oPaevm0vpR8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206035 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, apoptosis, autophagy, ferroptosis, necroptosis, NETosis, pyroptosis 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

BUFFALO, NY- August 16, 2024 – A new #review was #published as the #cover paper of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 15, entitled, “Types of cell death and their relations to host immunological pathways”. Various immune pathways in the host, such as TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ, have been identified. While TH2 and TH9 responses primarily target multicellular parasites, host immune pathways against viruses, intracellular microorganisms (like bacteria, protozoa, and fungi), and extracellular microorganisms utilize programmed cell death mechanisms to initiate immune responses and effectively eliminate pathogens. In their review, researchers Kuo-Cheng Lu, Kuo-Wang Tsai, Yu-Kuen Wang, and Wan-Chung Hu from Taipei Tzu Chi Hospital, Fu Jen Catholic University, Taoyuan Armed Forces General Hospital, Tri-Service General Hospital and Ming Chuan University, reviewed these cell death pathways associated with the host immunological pathways. "These relationships can help us understand the host defense mechanisms against invading pathogens and provide new insights for developing better therapeutic strategies against infections or autoimmune disorders.” DOI - https://doi.org/10.18632/aging.206035 Corresponding authors - Wan-Chung Hu - Wanchung.Hu09@tzuchi.com.tw Video short - https://www.youtube.com/watch?v=oPaevm0vpR8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206035 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, apoptosis, autophagy, ferroptosis, necroptosis, NETosis, pyroptosis 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

BUFFALO, NY- August 5, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 12, 2024, entitled, “INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death.” In this study, researchers Chantal L. Duurland, Thijs de Gunst, Harm C. den Boer, Marion T.J. van den Bosch, Bryony J. Telford, Rogier M. Vos, Xiaolei Xie, Mingfa Zang, Fang Wang, Yingying Shao, Xiaoyu An, Jingjing Wang, Jie Cai, Ludovic Bourré, Laurens A.H. van Pinxteren, Roel Q.J. Schaapveld, Michel Janicot, and Sanaz Yahyanejad from InteRNA Technologies BV, Utrecht, The Netherlands, and Crown Bioscience Inc., in San Diego, examined the effect of their lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on anti-tumor immunity. “In this study, we examined the effect of our lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on animal survival, tumor microenvironment (TME) and induction of anti-tumor immune responses.” The data presented within the study demonstrates for the first time that miR-193a-3p induces long-term immunity against tumor development via modulation of the tumor microenvironment and induction of immunogenic cell death. Additionally, the data show that systemic administration of INT-1B3 to 4T1 and H22 tumor bearing immunocompetent mice prolonged animal survival by reducing metastasis compared to phosphate buffered saline (PBS) or anti-programmed death (PD) 1 treatment. DOI - https://doi.org/10.18632/oncotarget.28608 Correspondence to - Sanaz Yahyanejad - sanaz.yah@gmail.com Video short - https://www.youtube.com/watch?v=pK_Bs5vMBCQ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28608 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, miR-193a-3p, microRNA mimic, T cell mediated immunity, immunogenic cell death About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

References J Biomed Sci 2017. 24, 63. Cell Death & Disease 2014. volume 5, page e1416 Haematologica. 2022 Mar 1; 107(3):721–732 Nucleic Acids Res. 2022 Jan 7; 50(D1): D413–D420 Oncogene 2017. volume 36, pages 5593–5608 Cell. 2021 Apr 1; 184(7):1790–1803.e17. Van Zant and Collins. 1973. "Tuesday's Gone" Lynyrd Skynyrd. https://youtu.be/LJrFxnvcWhc?si=EoL42Pw72Qe_atsz Lennon-McCartney. 1967. "I am the Walrus" Beatles. [Magical Mystery Tour, lp.] https://youtu.be/Ws5klxbI87I?si=QGe84-nMLK4dqgFy Hayward, J. 1967. "Tuesday Afternoon" [Days of Future Passed lp.] Moody Blues https://youtu.be/jmMPBQ4kYKk?si=FjZfDQ6KwCNecphw Mendelsshon, F. 1842 Wedding March C major op 61. https://youtu.be/Z-yUOBft96Y?si=ldxpuxPYTlAExXez --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

References Cell.2020 Mar 19; 180(6): 1115–1129.e13. Guerra, D.J. 2024. Intellectual materials. Goffin and King. 1962. "Up on the Roof" [Drfifters] https://youtu.be/puM1k-S86nE?si=LXzWj3SqiqHnr3JB Whitfield and Strong. 1969. "War" [Edwin Starr] https://youtu.be/dQHUAJTZqF0?si=bfB-xARpa6aVDwQg Kay and Godon 1963. "Thats Life" [Frank Sinatra] https://youtu.be/TnlPtaPxXfc?si=SmFfhohympSPVKd0 Van Heusen and Cahn 1960. "Aint that a Kick in the Head" 1960 [Dean Martin] https://youtu.be/K7jgZTDLeIs?si=bAKgzzK7mWCDJmyU Marriot and Lane 1968. "Mad John" (Ogden's Nutgone Flake; Faces lp. https://youtu.be/azxDPvoMHU8?si=iX1PCCMRcp2W7sae Mozart, WA. 1791. Overture "The Magic Flute" K.620 https://youtu.be/99VWYcapgq4?si=8gc4tRjaF02vkSzw --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

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For decades, Marcus Peter, PhD, has drilled into an area of research focused on cell death and the roles of toxic and protective short RNAs, with the goal of developing a novel form of cancer treatment. Now, this same line of research has led Peter's team to uncover new insights into the cause of Alzheimer's disease. In this episode, Peter explains his pioneering work in investigating RNA interference in diseases and explains how his lab's latest novel discovery may have relevance to an array of neurodegenerative diseases beyond Alzheimer's.

References The Journal of Biological Chemistry2018  293, 19001-19011 Cell Death & Diseasevolume 10, Article number: 315 Experimental & Molecular Medicine 2019. volume 51, Article number: 80. Trends in Immunology. 2017. REVIEW| VOL. 38,Issue 4, P287-297, April 01. Gastroenterology. 2023 Feb; 164(2): 256–271.e10 Squire/ Anderson. 1971. "The South Side of the Sky. on [ Yes -Fragile; lp] https://youtu.be/hBAauFYod80?si=bTGJiM-dCEsHjRnJ Mozart, WA. 1772. Symphony No. 25 in G minor, K. 183 https://youtu.be/rNeirjA65Dk?si=I8cdCyfO_FDlaBYc --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

References Cell Death Dis. 2020 Dec; 11(12): 1065. Genome Res. 2000 Oct; 10(10): 1445–1452. https://www.genecards.org/cgi-bin/carddisp.pl?gene=NIPBL Genes Dis. 2022 Jan; 9(1): 116–127 Schubert, F. 1824. Quartet 14 in D minor, D 810, "Death and the Maiden" https://youtu.be/XF_6vSlmm4w?si=CGTn3R6Tkn6LsMLv Browne,J. 1993. "Sky Blue and Black". https://youtu.be/Ty1I6dtC2zc?si=QHuwDiQUDh-4S5VP --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Host: Andrew Wilner, MD, FACP, FAAN Guest: Marcus E. Peter, PhD Death induced by survival gene elimination (DISE) is a cell death mechanism mediated by short RNAs. And according to a recent study, there may be a correlation between toxic DISE, DNA damage, and neuronal cell death in patients with Alzheimer's disease. Learn more about the study's findings and potential implications with Dr. Andrew Wilner and Dr. Marcus Peter, Professor of Medicine in the Division of Hematology and Oncology as well as a Professor of Biochemistry and Molecular Genetics at Northwestern University Feinberg School of Medicine in Chicago.

Literature Review 1) Pericytes are critical cells that sit around the tiny blood vessels called capillaries of the body especially in the brain. They are involved in regulating blood vessel activity. They communicate directly with the endothelial cells making them super important in the activity of the blood vessel and metabolism at the local tissue interface. From the journal Cell Death and Disease we see: "Crosstalk mechanisms....And some other discussions on Cancer detection at physicals as well as the recipe of the week. Enjoy, Dr. M

BUFFALO, NY- October 23, 2023 – A new research paper was published in Oncotarget's Volume 14 on October 19, 2023, entitled, “Apoptotic cells may drive cell death in hair follicles during their regression cycle.” Intravital microscopy in live mice has shown that the elimination of epithelial cells during hair follicle regression involves supra-basal cell differentiation and basal cell apoptosis through synergistic action of TGF-β (transforming growth factor) and mesenchymal-epithelial interactions. In this process the basal epithelial cells are not internally committed to death and the mesenchymal dermal papilla (DP) plays an essential role in death induction. Given that DP cells are not necessary for completion of the cycle, only for its initiation, it is still an open question as to the mechanism that leads to the propagation of apoptosis towards the regenerative stem cell population. In their new study, researchers Bradley D. Keister, Kailin R. Mesa and Krastan B. Blagoev from the National Science Foundation, The Jane Coffin Childs Memorial Fund for Medical Research, Yale School of Medicine, Johns Hopkins University, Bulgarian Academy of Sciences, and Sorbonne Université performed a quantitative analysis of the length of hair follicles to investigate their regression cycle. “In this paper we introduced a mathematical model of the hair follicle regression cycle that postulates that the regression is initiated by the dermal papilla, but that this signal affects only the cells adjacent to it.” The data are consistent with a propagation mechanism driven by apoptotic cells inducing apoptosis in their neighboring cells. The observation that the apoptosis slows down as the apoptotic front approaches the stem cells at the end of the follicle is consistent with a gradient of a pro-survival signal sent by these stem cells. An experiment that can falsify this mechanism is proposed. “In conclusion, hair follicle regression may be governed by cell-cell induced programmed cell death, which slows down as the stem cell compartment is approached and does not affect the stem cell compartment from which the growth phase is initiated. The class of models introduced here can be used to describe the renewal kinetics of other stem cell niches like the intestinal stem cell niche [18].” DOI - https://doi.org/10.18632/oncotarget.28529 Correspondence to - Krastan B. Blagoev - kblagoev@nsf.gov Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28529 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, hair follicle, stem cells, regression cycle, mathematical model, analysis About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It is particularly challenging to treat because HCC is often diagnosed in late stage and resistant to chemotherapy and radiation. However, advancements in targeted therapies and immunotherapies have opened new avenues for the treatment of this aggressive disease. In a new editorial paper, researchers Sawako Suzuki, Divya Venkatesh, Tomoaki Tanaka, and Carol Prives from Columbia University highlight the role of a metabolic enzyme known as glutamine synthase 2 (GLS2) in regulating ferroptosis in HCC. Ferroptosis is a form of cell death that involves iron-dependent accumulation of lipid peroxides. On October 19, 2023, their editorial was published in Oncotarget, entitled, “GLS2 shapes ferroptosis in hepatocellular carcinoma.” Full blog - https://www.oncotarget.org/2023/10/19/how-a-metabolic-enzyme-can-trigger-cell-death-in-liver-cancer-cells/ Paper DOI - https://doi.org/10.18632/oncotarget.28526 Correspondence to - Carol Prives - clp3@columbia.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28526 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, ferroptosis, hepatocellular carcinoma, GLS2, p53, tumor suppression About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.16.549200v1?rss=1 Authors: Yan, J., Lan, W., Yang, Q., Yang, Q., He, X., Dong, Y., Hu, Z., Jiao, K., Paquet-Durand, F. Abstract: Inherited retinal degeneration (IRD) refers to a group of untreatable blinding diseases characterized by a progressive loss of photoreceptors. IRD pathology is often linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, whether and how exactly intracellular Ca2+ overload contributes to photoreceptor degeneration is still controversial. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes were linked to several Ca2+-signalling related pathways. To explore this further, organotypic retinal explant cultures derived from rd1 and wt mice were treated with the intracellular Ca2+-chelator BAPTA-AM and with inhibitors for different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. The overall activity of poly(ADP-ribose) polymerases (PARPs), sirtuin-type histone-deacetylases, calpains, as well as the activation of calpain-1, and -2 were analysed in situ on retinal tissue sections. Cell viability was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, the effects of Ca2+-channel blockers were ambiguous, with T-type VGCC and NCX inhibition showing protection, while blocking CNGC and CRAC was detrimental. Activity of calpains and PARPs generally followed similar trends as cell death. Remarkably, sirtuin activity and calpain-1 activation was associated with photoreceptor protection, while calpain-2 activity was linked to degeneration. Accordingly, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. Together, these results indicate that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCC in conjunction with NCX. High Ca2+-levels likely suppress the protective activity of calpain-1 and promote neurodegeneration via activation of calpain-2. Our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of identifying and targeting degenerative processes to achieve a therapeutic benefit for IRD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Are you tired of the same old cancer treatment methods that leave you feeling drained and hopeless? Look no further than the Integrative Cancer Solutions with Dr. Karlfeldt. In our latest episode, we have Dr. Stephen Iacoboni, a medical oncologist with over 40 years of experience, discussing the use of naturopathic remedies alongside chemotherapy to overcome drug resistance. Our goal is to educate and inform our listeners about alternative cancer solutions that have been successful for others. Dr. Iacoboni shares his expertise in integrative oncology and explains why he believes that academic institutions have a primary mission of research, while a doctor in the community has a primary mission of patient care. The conversation also touches on the pros and cons of chemotherapy and the emerging direction of immunotherapy. Join us as we explore the history and progress of cancer treatment, breakthroughs in oncology, and alternative tools and treatments. Don't miss out on this informative and eye-opening episode. Tune in to Integrative Cancer Solutions with Dr. Karlfeldt today.- Alternative cancer treatments- Naturopathic remedies- Integrative oncology- Evolution of medical oncology- Pros and cons of chemotherapy- Immunotherapy limitations- Insulin Potentiated Therapy- Hyperoxidative therapy- Exploiting cancer cell vulnerabilities- Antioxidants and cancer- Nutraceuticals in cancer treatment- Revolution in oncology- Telos book and purpose in life- Scientific atheism and faith- Patient-centered care- Educational purposes only- Karlfeldt Center promotionKEY POINTS[0:0:32] With integrative and holistic methods, it's possible to WIN the fight against cancer.[0:5:16] Academic institutions are dedicated to pushing the boundaries of knowledge, while doctors are devoted to providing life-saving care to their patients.[0:8:53] In the last four decades, medical oncology has seen a remarkable transformation, from primitive radiation and surgical treatments to the development of revolutionary chemotherapy and immunotherapy treatments.[0:14:22] Shockingly, traditional cancer therapies often come with debilitating side effects - but luckily, there are now alternative solutions available![0:16:44] Miraculously, over 90% of early stage cancer cases can be successfully cured – giving hope to those facing the devastating diagnosis of stage four cancer.[0:21:39] By strategically targeting the oxidative state of cancer cells with Vitamin C and K3 at a specific ratio, researchers have uncovered an incredibly empowering and overlooked vulnerability in the fight against cancer.[0:22:10] Chemotherapy is a much less lethal and more effective alternative to Cyanide for treating cancer, with the power to eradicate cancerous cells on a much larger scale.[0:26:25] Cancer cells exhibit an alarming, frenetic energy level, devouring vast amounts of energy to fuel their rapid growth.[0:27:42] By leveraging the power of Prooxidants, cancer cells can be efficiently destroyed with reduced chemo doses, effectively cutting off their crucial supply of antioxidants![0:30:20] Despite the exorbitant price of cancer medications, some physicians prioritize patient health above profit, delivering effective and accessible treatments to improve the lives of those affected.[0:36:22] By revolutionizing oncology, we could dramatically reduce Medicare costs, saving billions of dollars and dramatically improving the lives of countless patients.[0:46:24] Incredibly, nutraceuticals with hyperoxidation properties have the potential to halt the progression of pre-cancerous cells, offering a cost-effective alternative to traditional cancer prevention methods. Connect with Stephen at https://stepheniacoboni.com/ Integrative Cancer Solutions was created to instill hope and empowerment. Other people have been where you are right now and have already done the research for you. Listen to their stories and journeys and apply what they learned to achieve similar outcomes as they have, cancer remission and an even more fullness of life than before the diagnosis. Guests will discuss what therapies, supplements, and practitioners they relied on to beat cancer. Once diagnosed, time is of the essence. This podcast will dramatically reduce your learning curve as you search for your own solution to cancer. For more information about products and services discussed in this podcast, please visit www.integrativecancersolutions.com. To learn more about the cutting-edge integrative cancer therapies Dr. Karlfeldt offer at his center, please visit www.TheKarlfeldtCenter.com.

Host: Andrew Wilner, MD, Author of "The Locum Life: A Physician's Guide to Locum Tenens" Guest: Dominique Higgins, MD, PhD Glioblastoma is the most common type of brain tumor while also being one of the most aggressive cancers in adults. So what do we need to know about ferroptosis? Dive in with Dr. Andrew Wilner as he's joined by Dr. Dominique Higgins, Assistant Professor of Neurosurgery at the University of North Carolina School of Medicine.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.09.536190v1?rss=1 Authors: Wang, Y., Zhang, R., Huang, S., Valverde, P. T.-T., Lobb-Rabe, M., Ashley, J., Venkatasubramanian, L., Carrillo, R. A. Abstract: Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the cell death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their axon terminal size and activity. We termed this compensation as cross-neuron plasticity, and in this study, we demonstrated that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required in glial cells. Surprisingly, overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. Synaptic plasticity normally declines as animals age, but in our system, functional cross-neuron plasticity can be induced at different time points, whereas structural cross-neuron plasticity can only be induced at early stages. Our work uncovers a novel role for glial Draper signaling in cross-neuron plasticity that may enhance nervous system function during neurodegeneration and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Genes & Diseases Available online 26 December 2022 Int J Mol Sci. 2021 May; 22(10): 5317 Haematologia 2016. Vol. 101 No. 6 June. Blood (2005) 106 (1): 274–286 Nature Reviews Immunology 2018. volume 18, pages 617–634. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.21.529458v1?rss=1 Authors: Hom, L. M., Sun, S., Campbell, J., Liu, P., Culbert, S., Murphy, I. M., Schafer, Z. T. Abstract: In normal tissue homeostasis, bidirectional communication between different cell types can shape numerous biological outcomes. Many studies have documented instances of reciprocal communication between fibroblasts and cancer cells that functionally change cancer cell behavior. However, less is known about how these heterotypic interactions shape epithelial cell function in the absence of oncogenic transformation. Furthermore, fibroblasts are prone to undergo senescence, which is typified by an irreversible cell cycle arrest. Senescent fibroblasts are also known to secrete various cytokines into the extracellular space; a phenomenon that is termed the senescence-associated secretory phenotype (SASP). While the role of fibroblast derived SASP factors on cancer cells has been well studied, the impact of these factors on normal epithelial cells remains poorly understood. We discovered that treatment of normal mammary epithelial cells with conditioned media (CM) from senescent fibroblasts (SASP CM) results in a caspase-dependent cell death. This capacity of SASP CM to cause cell death is maintained across multiple senescence-inducing stimuli. However, the activation of oncogenic signaling in mammary epithelial cells mitigates the ability of SASP CM to induce cell death. Despite the reliance of this cell death on caspase activation, we discovered that SASP CM does not cause cell death by the extrinsic or intrinsic apoptotic pathway. Instead, these cells die by an NLRP3, caspase-1, and gasdermin D (GSDMD)-dependent induction of pyroptosis. Taken together, our findings reveal that senescent fibroblasts can cause pyroptosis in neighboring mammary epithelial cells, which has implications for therapeutic strategies that perturb the behavior of senescent cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Cancers (Basel). 2020 Aug; 12(8): 2137. Cell Death Dis. 2020 Jan 2;11(1):5 Cell. 2022. 185. 9. :521-1538.e18 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.17.528998v1?rss=1 Authors: Scholz, N., Siebzehnrubl, F. A., Licchesi, J. D. F. Abstract: Programmed cell death is a complex and tightly regulated sequence of events that determines cell fate during tissue homeostasis, development, and pathogenesis. The small protein modifier ubiquitin mediates important regulatory functions during cell death by regulating the stability and activity of checkpoint proteins and the assembly of cell death signalling complexes. The caspase family of cysteine aspartases are essential effectors of apoptotic cell death. Components of the ubiquitin system including RING ubiquitin ligases XIAP, MDM2, RBX1; RBR E3 ubiquitin ligases Parkin and LUBAC; and HECT E3 ubiquitin ligases NEDD4 and Itch are also substrates of caspase-mediated cleavage. In the case of NEDD4 and Itch, the single cleavage event occurs outside of the catalytic HECT domain and it remains unclear whether such cleavage events impact on ubiquitin ligase activity and/or function. Here, we identified the E3 ubiquitin ligase HECTD1 as the third HECT E3 cleaved by caspase-mediated cleavage during apoptotic cell death, in a manner which does not affect the integrity of the catalytic C-ter HECT domain. We mapped the single cleavage event to DFLD1664{downarrow}S and showed that the cleaved C-ter product, which contains the HECT ligase domain, is as stable as the endogenous full length protein. We also found that HECTD1 transient depletion led to reduced caspase-3 activity, but not caspase 8 nor 9. Furthermore, we also identified caspase-3 as the protease responsible for HECTD1 cleavage at Asp1664 suggesting that HECTD1 and caspase-3 might be part of a novel feedback loop mechanism during apoptotic cell death. This study highlight novel crosstalk between cell death mechanisms and the ubiquitin system and raises important questions on whether proteolytic cleavage of E3 ubiquitin ligases might represent an underappreciated mode of regulation during cell death mechanisms. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Cell Death & Differentiation 2020.27: 3374–3385 Cell Death & Differentiation 2019. 26: 1501–1515 Cancers 2020, 12(8), 2137. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.06.527237v1?rss=1 Authors: Chen, S.-H., Prakash, S., Helgason, E., Gilchrist, C. L., Kenner, L. R., Srinivasan, R., Sterne-Weiler, T., Hafner, M., Piskol, R., Dueber, E. C., Hamidi, H., Endres, N., Ye, X., Fairbrother, W. J., Wertz, I. E. Abstract: Modulation of proteolysis is an emerging therapeutic mainstay. The clinical success of thalidomide and analogs has inspired development of rationally-designed therapeutics that repurpose endogenous degradation machinery to target pathogenic proteins. However, it is unknown whether target removal is the critical effect that drives degrader-induced efficacy. Here we report that proteasome-generated peptides actively initiate degrader-induced cell death. Utilizing BET family degraders as exemplars, we find that induced proteasomal degradation of the BRD4-long isoform (BRD4-L) generates neo-amino-terminal peptides that neutralize Inhibitor of Apoptosis (IAP) proteins to precipitate cell death. Depletion of BRD4-L paradoxically suppresses caspase activation induced by numerous BET degraders. An unbiased screen revealed that other degrader compounds, including clinical CELMoDs, rely on the same mechanism to potentiate caspase activation and apoptosis. Finally, in the context of constitutive immunoglobulin proteostasis within multiple myeloma cells, we report that therapeutic proteasomal protease inhibition alters the peptide repertoire to neutralize IAPs, thus contributing to the clinical efficacy of bortezomib. Together, these findings clarify the counterintuitive clinical benefit achieved by combining thalidomide analogs with proteasome inhibitors. Our study reveals a previously unrealized pro-apoptotic function of the peptides generated by a variety of proteolysis-modulating compounds, that provide design considerations to maximize therapeutic benefit. 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/2023.02.03.526887v1?rss=1 Authors: Mancia Leon, W. R., Steffen, D. M., Dale-Huang, F., Rakela, B., Breevoort, A., Romero-Rodriguez, R., Hasenstaub, A. R., Stryker, M. P., Weiner, J. A., Alvarez-Buylla, A. Abstract: Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Previously, we showed that loss of clustered gamma protocadherins (Pcdh{gamma}), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice. Here we show that the sole deletion of the Pcdh{gamma}c4 isoform, but not of the other 21 isoforms in the Pcdh{gamma} gene cluster, increased cIN cell death in mice during the normal period of programmed cell death. Viral expression of the Pcdh{gamma}c4 isoform rescued transplanted cINs lacking Pcdh{gamma} from cell death. We conclude that Pcdh{gamma}, specifically Pcdh{gamma}c4, plays a critical role in regulating the survival of cINs during their normal period of cell death. This demonstrates a novel specificity in the role of Pcdh{gamma} isoforms in cortical development. 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/2023.02.02.526754v1?rss=1 Authors: Sharma, R. K., Chafik, A., Bertolin, G. Abstract: Cancer cells often hijack metabolic pathways to obtain the energy required to sustain their proliferation. Understanding the molecular mechanisms underlying cancer cell metabolism is key to fine-tune the metabolic preference of specific tumors, and potentially offer new therapeutic strategies. Here, we show that the pharmacological inhibition of mitochondrial Complex V delays the cell cycle by arresting breast cancer cell models in the G0/G1 phase. Under these conditions, the abundance of the multifunctional protein Aurora kinase A/AURKA is specifically lowered. We then demonstrate that AURKA directly interacts with the mitochondrial Complex V core subunits ATP5F1A and ATP5F1B. Altering the AURKA/ATPF1A/ATPF1B nexus is sufficient to trigger G0/G1 arrest, and this is accompanied by decreased glycolysis and mitochondrial respiration rates. Last, we discover that the roles of the AURKA/ATPF1A/ATPF1B nexus depend on the specific metabolic propensity of triple-negative breast cancer cell lines, where they correlate with cell fate. On one hand, the nexus induces G0/G1 arrest in cells relying on oxidative phosphorylation as the main source of energy. On the other hand, it allows to bypass cell cycle arrest and it triggers cell death in cells with a glycolytic metabolism. Altogether, we provide evidence that AURKA and mitochondrial Complex V subunits cooperate to maintain cell metabolism in breast cancer cells. Our work paves the way to novel anti-cancer therapies targeting the AURKA/ATPF1A/ATPF1B nexus to lower cancer cell metabolism and proliferation. 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/2023.01.30.526132v1?rss=1 Authors: Gomez Deza, J., Nebiyou, M., Alkaslasi, M. R., Somasundaran, P., Slavutsky, A. L., Ward, M. E., Watkins, T. A., Le Pichon, C. E. Abstract: Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we developed a robust human IPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers a wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrated that mitochondrial fission and resultant cell death is entirely dependent on phosphorylation of dynamin related protein 1 (DRP1) by dual leucine zipper kinase (DLK). Importantly, we show that CRISPR mediated Drp1 depletion protected mouse retinal ganglion neurons from mitochondrial fission and degeneration after optic nerve crush. Our results provide a powerful platform for studying degeneration of human neurons, pinpoint key early events in damage related neural death and new focus for therapeutic intervention. 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/2023.01.13.523980v1?rss=1 Authors: Reyes Gaido, O. E., Schole, K. L., Anderson, M. E., Luczak, E. D. Abstract: Ca2+ is a fundamental determinant of survival in living cells. Excessive intracellular Ca2+ causes cellular toxicity and death but the genetic pathways contributing to Ca2+ induced cell death are incompletely understood. Here, we performed genome-wide CRISPR knock-out screening in human cells challenged with the Ca2+ ionophore ionomycin and identified genes and pathways essential for cell death after Ca2+ overload. We discovered 115 protective gene knockouts, 33 of which are non-essential genes and 21 of which belong to the druggable genome. Notably, members of store operated Ca2+ entry (SOCE), very long-chain fatty acid synthesis, and SWItch/Sucrose Non-Fermentable (SWI/SNF) pathways provided marked protection against Ca2+ toxicity. These results reveal pathways previously unknown to mediate Ca2+-induced cell death and provide a resource for the development of pharmacotherapies against the sequelae of Ca2+ overload in disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A new research paper was published in Oncotarget's Volume 13 on December 29, 2022, entitled, “Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore.” Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ12,14-prostamide J2 (15d-PMJ2) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells. Additionally, 15d-PMJ2 reduces melanoma growth in vivo. To assess the chemotherapeutic potential of 15d-PMJ2, researchers Daniel A. Ladin, Margaret M. Nelson, Estefani Cota, Catherine Colonna, Colin Burns, Jacques Robidoux, Kelsey H. Fisher-Wellman, and Rukiyah Van Dross-Anderson from East Carolina University and University of North Carolina at Chapel Hill sought to uncover molecular pathways by which 15d-PMJ2 exerts its antitumor activity. B16F10 melanoma and JWF2 squamous cell carcinoma cell lines were cultured in the presence of pharmacological agents that prevent ER or oxidative stress as well as Ca2+ channel blockers to identify mechanisms of 15d-PMJ2 cell death. “Our data demonstrated the ER stress protein, PERK, was required for 15d-PMJ2-induced death.” PERK activation triggered the release of ER-resident Ca2+ through an IP3R sensitive pathway. Increased calcium mobilization led to mitochondrial Ca2+ overload followed by mitochondrial permeability transition pore (mPTP) opening and the deterioration of mitochondrial respiration. Finally, the researchers showed that the electrophilic double bond located within the cyclopentenone ring of 15d-PMJ2 was required for its activity. “The present study identifies PERK/IP3R/mPTP signaling as a mechanism of 15d-PMJ2 antitumor activity.” DOI: https://doi.org/10.18632/oncotarget.28334 Correspondence to: Rukiyah Van Dross-Anderson - vandrossr@ecu.edu Keywords: calcium, mitochondrial respiration, endoplasmic reticulum stress, cancer, prostamide About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.

Synopsis: Luba Greenwood is the CEO of Kojin Therapeutics and Managing Partner of Dana Farber Cancer Institute Venture Fund. Kojin Therapeutics harnesses groundbreaking discoveries in cell state and ferroptosis biology to create novel therapies and cures for diseases traditionally considered intractable. The Dana Farber Cancer Institute Venture Fund accelerates the development of new research and technologies to treat incurable diseases, particularly in oncology and immunology. Luba discusses the early years of her career as a lawyer and how her legal experience relates to running a biotech company, her background in big pharma at Pfizer and Roche, and the work Kojin is doing in novel biology. She also dives into the qualities that she values in a board member, the importance of company culture, and her perspective on what good leadership looks like. Biography: Luba Greenwood is a leading figure in the biotech and digital health world with vast experience as an executive, investor, and company builder in the biotech, life sciences, diagnostics, and tech sectors. Luba is the Chief Executive Officer of Kojin Therapeutics, a world leader in ferroptosis, pioneering breakthrough medicines in oncology, immunology, neuro, metabolism, and inflammation. Most recently, Luba has served as the Managing Partner of the Dana Farber Cancer Institute Venture Fund, Binney Street Capital, which she has built and launched. She has also taught at Harvard University at the School of Engineering and Applied Sciences. Previously, Ms. Greenwood served in leadership roles at Google Life Sciences, Verily, and was a VP Global Business Development and Mergers & Acquisitions at Roche, where she also established and led the East Coast Innovation Hub. Ms. Greenwood has led $5B+ in deals and investments across multiple therapeutic areas and life sciences globally. She has also co-founded companies in the oncology, AI/ML, women's health and microbiome space. Luba began her career as a lawyer, practicing at Wilmer Cutler Pickering Hale and Dorr. She is a recipient of several awards and honors for her work in the community, including the Science Club for Girls Catalyst Award for her commitment to advocating for women in science and technology.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.20.521175v1?rss=1 Authors: Monteiro Gomes, G., Bar, J., Karpova, A., Kreutz, M. Abstract: Jacob is a synapto-nuclear messenger protein that encodes and transduces the origin of synaptic and extrasynaptic NMDA receptor signals to the nucleus. The protein assembles a signalosome that differs in case of synaptic or extrasynaptic NMDAR activation. Following nuclear import Jacob docks these signalosomes to the transcription factor CREB. We have recently shown that amyloid-beta and extrasynaptic NMDAR activation triggers the translocation of a Jacob signalosome that results in inactivation of the transcription factor CREB, a phenomenon termed Jacob-induced CREB shut-off (JaCS). JaCS contributes to early Alzheimer's disease pathology and a gene knockout of nsmf, the gene encoding Jacob, protects against amyloid pathology. Given that extrasynaptic activity is also involved in acute excitotoxicity, like in stroke, we asked whether nsmf gene knockout will also protect against acute insults, like oxygen and glucose deprivation and excitotoxic NMDA stimulation. Here we show that organotypic hippocampal slices from wild-type and nsmf-/- mice display similar degrees of degeneration when exposed to either oxygen glucose deprivation or 50 uM NMDA incubation. This lack of neuroprotection indicates that JaCS is mainly relevant in conditions of low level chronic extrasynaptic NMDAR activation that results in cellular degeneration induced by alterations in gene transcription. 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/2022.12.15.520548v1?rss=1 Authors: Martinez Lagunas, K., Savcigil, D. P., Zrilic, M., Carvajal Fraile, C., Craxton, A., Self, E., Uranga, I., de Miguel, D., Arias, M., Willenborg, S., Piekarek, M., Albert, M. C., Nugraha, K., Lisewski, I., Janakova, E., Igual, N., Tonnus, W., Hilendbrandt, X., Ibrahim, M., Ballegeer, M., Saelens, X., Kueh, A. J., Meier, P., Linkermann, A., Pardo, J., Eming, S., Walczak, H., MacFarlane, M., Peltzer, N., Annibaldi, A. Abstract: Cell death coordinates repair programs following pathogen attack and tissue injury. However, aberrant cell death can interfere with such programs and cause organ failure. cFLIP is a crucial regulator of cell death and a substrate of Caspase-8. Yet, the physiological role of cFLIP cleavage by Caspase-8 remains elusive. Here, we discovered an essential role for cFLIP cleavage in restraining cell death in different pathophysiological scenarios. Mice expressing a cleavage-resistant cFLIP mutant, CflipD377A, exhibited increased sensitivity to SARS-CoV-induced lethality, impaired skin wound healing and increased tissue damage caused by Sharpin deficiency. In vitro, abrogation of cFLIP cleavage sensitizes cells to TNF-induced necroptosis and apoptosis by favoring complex-II formation. Mechanistically, the cell death-sensitizing effect of the D377A mutation depends on Gln(Q)469. These results reveal a crucial role for cFLIP cleavage in controlling the amplitude of cell death responses occurring upon tissue stress, to ensure the execution of repair programs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Ray Lee is the CEO of Teclison, focused on overcoming the limitations of existing immunotherapy for treating liver cancer in part caused by the fact that the liver is a highly immunotolerant organ. The key is to make the tumor a low-oxygen environment and delivering a drug that only works on the tumor. Ray elaborates, "First, let me explain what the TATE represents. It stands for the Trans-arterial TEC-001 Embolization. TEC-001 is the pipeline compound we've been trying to develop. This compound is a so-called prodrug. In other words, by itself, it has a low activity. But once in the low-oxygen environment, the drug is going to be activated. What we're trying to develop is to create a very innovative way to convert the tumor into an environment with low oxygen. And this low-oxygen environment is exclusive within the tumor but not in the normal liver nor in the systemic organs." "So once they have this catheter in place, they will inject our drugs, the TEC-001, directly through the catheter into the tumor and then follow by the embolization. And what I mean by embolization is injecting a special kind of material, like a block in the tumor vessel, and cutting off the blood flow. So that means the tumor is no longer able to receive any blood, so they are not getting enough nutrients or oxygen, which makes the tumor be in a very low-oxygen environment. And that is how our drug is going to be almost immediately activated within the tumor after the embolization procedure, and that's how it works." #Teclison #LiverCancer #Cancer #SolidTumors #Immunotherapy #CancerImmunotherapy #LiverMetastasis #LungCancer #ColorectalCancer Teclison.com Download the transcript here

Dr. Ray Lee is the CEO of Teclison, focused on overcoming the limitations of existing immunotherapy for treating liver cancer in part caused by the fact that the liver is a highly immunotolerant organ. The key is to make the tumor a low-oxygen environment and delivering a drug that only works on the tumor. Ray elaborates, "First, let me explain what the TATE represents. It stands for the Trans-arterial TEC-001 Embolization. TEC-001 is the pipeline compound we've been trying to develop. This compound is a so-called prodrug. In other words, by itself, it has a low activity. But once in the low-oxygen environment, the drug is going to be activated. What we're trying to develop is to create a very innovative way to convert the tumor into an environment with low oxygen. And this low-oxygen environment is exclusive within the tumor but not in the normal liver nor in the systemic organs." "So once they have this catheter in place, they will inject our drugs, the TEC-001, directly through the catheter into the tumor and then follow by the embolization. And what I mean by embolization is injecting a special kind of material, like a block in the tumor vessel, and cutting off the blood flow. So that means the tumor is no longer able to receive any blood, so they are not getting enough nutrients or oxygen, which makes the tumor be in a very low-oxygen environment. And that is how our drug is going to be almost immediately activated within the tumor after the embolization procedure, and that's how it works." #Teclison #LiverCancer #Cancer #SolidTumors #Immunotherapy #CancerImmunotherapy #LiverMetastasis #LungCancer #ColorectalCancer Teclison.com Listen to the podcast here

References PLoS One. 2019 Jan 10;14(1):e0210207 Nature Communications volume 9, Article number: 1784 (2018)) Cell Death & Disease volume 8, page e2897; 2017 Nat Cell Biol. 2013 Apr;15(4):373-84 Dev Neurobiol. 2010 Jul; 70(8): 589–603 J. Lipid Res. (2022) 63(8) 100213 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References J. Lipid Res. (2022) 63(8) 100213 Front. Cell Dev. Biol., 15 October 2019 Bortlein et al. Cell Death & Disease. 2016. volume 7, page e2488 J. Biol. Chem. 1998;273:14550-14559 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Regain your freedom from Crohn's, ulcerative colitis, constipation and more in 12 weeks or less without harmful drugs or surgeries. To book a free call and to learn more about working with Dr. Christine, visit: www.bit.ly/gutcall  To purchase Dr. Christine's custom formulations: www.OmegaDigestion.com

Dr. Joseph O'Donnell is the Chief Medical Officer at Phosplatin Therapeutics founded to develop a drug with platinum in it to kill cancer cells. Phosplatin is in clinical trials with PT-112 which is the first cancer therapy molecule that has a pyrophosphate on it and works by harnessing the immune system and causing immunogenic cell death. Dr. Joe explains, "This drug is in this space that's really burgeoning called immuno-oncology, where we're using immune agents to stimulate the immune system to actually affect the cancer, to actually knock down the cancer. And this is one that has a different mechanism than some of the other agents and lots of potential to be used in combination to produce synergy with those other agents in this very exciting space." "So, the checkpoint inhibitors are one group of drugs that seems to be interesting to combine with PT-112, and I suspect we'll see more of that in the future. But just PT-112 by itself, it has this effect called producing immunogenic cell death. That's a way in which a drug causes cancer cells to die by activating the immune system, the adaptive immune system, to actually attack the tumor and actually devour it. And so that's one of the properties that the PT-112 has." @Phosplatin #Oncology #ImmunoOncology #Cancer #CancerTherapeutics #ICD #ImmunogenicCellDeath #Chemotherapy #CheckPointInhibitors #Innovation #NYBiotech Phosplatin.com Listen to the podcast here

Dr. Joseph O'Donnell is the Chief Medical Officer at Phosplatin Therapeutics founded to develop a drug with platinum in it to kill cancer cells. Phosplatin is in clinical trials with PT-112 which is the first cancer therapy molecule that has a pyrophosphate on it and works by harnessing the immune system and causing immunogenic cell death. Dr. Joe explains, "This drug is in this space that's really burgeoning called immuno-oncology, where we're using immune agents to stimulate the immune system to actually affect the cancer, to actually knock down the cancer. And this is one that has a different mechanism than some of the other agents and lots of potential to be used in combination to produce synergy with those other agents in this very exciting space." "So, the checkpoint inhibitors are one group of drugs that seems to be interesting to combine with PT-112, and I suspect we'll see more of that in the future. But just PT-112 by itself, it has this effect called producing immunogenic cell death. That's a way in which a drug causes cancer cells to die by activating the immune system, the adaptive immune system, to actually attack the tumor and actually devour it. And so that's one of the properties that the PT-112 has." @Phosplatin #Oncology #ImmunoOncology #Cancer #CancerTherapeutics #ICD #ImmunogenicCellDeath #Chemotherapy #CheckPointInhibitors #Innovation #NYBiotech Phosplatin.com Download the transcript here

Cell fate from Either ageing associated senescence to programmed cell death OR cell proliferation is finely tuned to the splice variant expression of Cell Cycle dependent kinase inhibitors and the relative production of pro-inflammatory cytokines under the synchrony of DNA Damage Repair (DDR), telomerase expression decline, and the protective role of the Senescence Associated Secretory Phenotype (SASP). Dr. Daniel J. Guerra. 06 Dec 2021 Authentic Biochemistry Productions References: Oncotarget. 2013 Oct; 4(10): 1552–1553 Cancer Rep Rev. 2018 Mar; 2(2): 10 Nat Med. 2017 Jun; 23(6): 775–781 Cancer Genet Cytogenet. 1999 Mar;109(2):108-13. EBioMedicine 2016 830-39DOI: (10.1016/j.ebiom.2016.04.017 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Dr. Denise Montell is the Duggan Professor of Molecular, Cellular, and Developmental Biology at the University of California, Santa Barbara. She received her PhD in Neuroscience from Stanford University, and afterwards completed an American Cancer Society postdoctoral fellowship at the Carnegie Institute of Science. She served as a faculty member at the Carnegie Institute and Johns Hopkins University before joining the faculty at UC Santa Barbara. Denise is with us today to tell us about her journey through life and science.