Graviton Bioscience’s Post

🔬 Exciting Insights into Apoptosis: The Cell's Silent Symphony of Self-Destruction 🎵 Apoptosis, often called "programmed cell death," is a crucial process in maintaining the delicate balance of life within our bodies. Unlike necrosis, which is a chaotic and inflammatory form of cell death, apoptosis is a highly ordered and controlled process that plays a pivotal role in development, immune system function, and cancer prevention. 🧬 Key Pathways of Apoptosis: 1. Intrinsic Pathway (Mitochondrial Pathway): - Triggered by internal signals such as DNA damage or oxidative stress. - Involves the release of cytochrome c from mitochondria, leading to the activation of caspases, the enzymes that orchestrate the breakdown of cellular components. 2. Extrinsic Pathway (Death Receptor Pathway): - Initiated by external signals, such as the binding of Fas ligand or TNF (Tumor Necrosis Factor) to death receptors on the cell surface. - This activates a cascade that ultimately leads to apoptosis through caspase activation. 🔍 Understanding these pathways not only provides insight into how cells maintain homeostasis but also opens doors for therapeutic strategies in treating diseases where apoptosis is dysregulated, such as cancer and neurodegenerative disorders. By exploring the mysteries of apoptosis, researchers continue to uncover potential targets for innovative treatments, offering hope for effective interventions and paving the way towards a healthier future. #Apoptosis #CellBiology #Biotechnology #HealthcareInnovation #MolecularBiology #ResearchAndDevelopment

#liverdisease #fibrosis #medicine #medicalsciences #healthcare https://lnkd.in/g5P4-d5y Summary Chronic liver diseases, primarily #metabolic #dysfunction-associated steatotic liver disease (MASLD), harmful use of #alcohol, or viral #hepatitis, may result in #liver #fibrosis, cirrhosis, and #cancer. Hepatic fibrogenesis is a complex process with interactions between different resident and non-resident heterogeneous liver cell populations, ultimately leading to deposition of extracellular matrix and organ failure. Shifts in cell phenotypes and functions involve pronounced transcriptional and protein synthesis changes that require metabolic adaptations in cellular substrate metabolism, including glucose and lipid metabolism, resembling changes associated with the Warburg effect in cancer cells. Cell activation and metabolic changes are regulated by metabolic stress responses, including the unfolded protein response, endoplasmic reticulum stress, autophagy, ferroptosis, and nuclear receptor signaling. These metabolic adaptations are crucial for inflammatory and fibrogenic activation of macrophages, lymphoid cells, and hepatic stellate cells. Modulation of these pathways, therefore, offers opportunities for novel therapeutic approaches to halt or even reverse liver fibrosis progression.

Role of alternative splicing in liver fibrosis A healthy liver filters all the blood in your body, breaks down toxins and digests fats. It produces collagen to repair damaged cells when the liver is injured. However, a liver can produce too much collagen when an excess accumulation of fat causes chronic inflammation, a condition called metabolic dysfunction-associated steatohepatitis (MASH). In an advanced state, MASH can lead to cirrhosis, liver cancer and liver-related death. The scientists carried out their investigations in organoids — tiny little livers in a dish made from three types of liver cells fed a MASH cocktail of fatty acids, fructose and sugars. They found that in normal livers, the first component of the pathway, a nuclear seven-transmembrane protein called TM7SF3, inhibits a splicing factor called hnRNPU. hnRNPU refrains from splicing out an inhibitory exon in the messenger RNA (mRNA) of TEAD1, a transcription factor that controls the genes that produce collagen. The inhibitory exon, exon 5, keeps TEAD1 from turning on the collagen-producing genes. In the MASH-fed organoids, TM7SF3 is reduced and does not inhibit the splicing factor. The active splicing factor splices out the inhibitory exon in the transcription factor, which turns on the genes that produce collagen. This is called alternative splicing. Furthering their investigations, they designed an ASO to keep hnRNPU from splicing out exon 5. “It had the sequence that would put it just upstream of exon 5 where hnRPU binds. The ASO prevented the splicing factor from binding to the TEAD mRNA, so it couldn’t ultimately splice it out. We got pretty much only inactive TEAD when we treated MASH mice with the ASO,” said the author. With TEAD inactivated, collagen wasn’t produced. Neither was fibrosis. #ScienceMission #sciencenewshighlights https://lnkd.in/geSgCkU2

𝗜𝗻𝘃𝗲𝘀𝘁𝗶𝗴𝗮𝘁𝗶𝗻𝗴 𝗠𝗶𝘁𝗼𝗰𝗵𝗼𝗻𝗱𝗿𝗶𝗮𝗹 𝗠𝗲𝗺𝗯𝗿𝗮𝗻𝗲 𝗖𝗵𝗮𝗻𝗻𝗲𝗹𝘀 🔬 Mitochondria, the cellular powerhouses, rely critically on ion homeostasis for their proper function. Any disruption in this delicate balance can lead to abnormal cell behavior. 🧪 Why are mitochondrial ion channels important? These channels play a pivotal role in regulating the ionic permeability of the mitochondrial membrane. Understanding them is crucial since they could serve as potential therapeutic targets for several diseases, including cardiovascular, neurodegenerative, metabolic disorders, and cancer. In this flyer, you’ll discover an overview of the different ion channels found in mitochondria, along with the methods available to study them. Dive into the world of bioenergetics. Download your copy of the flyer: https://ow.ly/pt1Y50QA7ve #IonChannels #Mitochondria #DrugDiscovery #Bioenergetics #APC #MembraneBiophysics #Electrophysiology

🌌 PCSK9 Inhibitors Redefine the Future of Plaque Stability with Innovative miRNA Approach 🧬 🔍 Through meticulous experiments on ApoE−/− mice, researchers revealed a fascinating mechanism: PCSK9 inhibitors downregulated the expression of miR-186-5p and miR-375-3p while simultaneously increasing the expression of Wipf2, Pdk1, and Yap1 - key factors for plaque stabilization. 💥 💡 This visionary approach offers a glimpse into the future of cardiovascular therapy, harnessing the power of miRNA modulation to effectively combat AS progression. 🌟 https://lnkd.in/eXsTudG6 #FutureOfMedicine #ASPlaqueStability #PCSK9Inhibitors #miRNA #InnovativeResearch #RevolutionaryFindings 🚀

Very interesting study congratulations to the authors Peng, H., Xin, S., Pfeiffer, S. et al. ”Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia” Fatty Acid-Binding Protein 5 (FABP5) has been identified as a potential biomarker for ferroptosis, a death process associated with iron-catalyzed reactive species and lipid peroxidation in degenerative and hypoxic/ischemic diseases. Through surface protein dynamics analysis, FABP5 was found to be elevated in ferroptotic cell death, driving the redistribution of redox-sensitive lipids and increasing sensitivity to cell death in a positive-feedback loop. Immunodetection of FABP5 in hypoxic postmortem patients and stroke penumbra suggests its association with hypoxically damaged neurons, offering a novel means for detecting ferroptosis in tissue and supporting its role in human pathophysiology.

Alteration in alternative splicing

📢 Review paper Sharing-Vol. 29 No. 4 💕 Title: Progenitor Cell Function and Cardiovascular Remodelling Induced by SGLT2 Inhibitors 🤵 Authors: Theodora M. Stougiannou,*, Konstantinos C. Christodoulou, Theocharis Koufakis, Fotios Mitropoulos, Dimitrios Mikroulis, Cyril David Mazer4, Dimos Karangelis 🔔 Full Text: https://lnkd.in/geJFgEG3 🔑 Keywords: cardiac remodelling; heart failure; endothelial progenitor; hemopoietic stem cells; 😎Welcome to your reading! #Bioscience #biomedicalscience #biochem #medicalscience #ScienceCommunication #Biochemistry #StemCell #Virology #CancerResearch #immunology #Genetics #MolecularBiology #Microbiology #medicine #health #CellularHealth #CellCancer

New research alert! We've posted our latest manuscript on BioRxiv: "Foamy microglia link oxylipins to disease progression in multiple sclerosis." https://lnkd.in/eK27cqzF Our study sheds light on mechanisms driving chronic lesion growth in progressive #MultipleSclerosis. Understanding these molecular pathways is critical for developing new therapies. We conducted the most comprehensive multi-omics study to date, analyzing 110 human brain samples. Our datasets cover transcriptomics, proteomics, lipidomics and ABPP, integrated with single-cell data and histology to identify key drivers of lesion expansion. Key finding: Foamy microglia expressing GPNMB in active MS lesions accumulate lipids and oxylipins, contributing to lesion expansion. These cells lack pro-inflammatory signatures but show signs of dysregulation of lysosomal function and lipid metabolism. Our findings suggest that targeting monoacylglycerol lipase could slow MS lesion progression. We also propose oxylipins in cerebrospinal fluid as potential biomarkers for monitoring MS progression.  A wonderful PhD-project led by #DaanvanderVliet @LED3hub in collaboration with labs @LeidenScience and #IngeHuitinga, #AlbertHeck and Roche. Funded by the gravitation program Institute of Chemical Immunology. 6/6

Using its in silico peptide design platform, VincoAI has successfully generated peptides that specifically target the NAD+ binding sites of SARM1, a key player in axonal degeneration and neurodegenerative disease pathogenesis. #generativeai #ai #vincogen #sarm1 #neurodegenerativediseases #peptides