The Research Institute of St. Joe's Hamilton’s Post

In this episode (#302) of The Drive, I speak with Julia Wattacheril, M.D., M.P.H., a physician scientist and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) program at Columbia University Irving Medical Center. We delve deep into the complex world of liver health, beginning with a foundational overview of liver physiology. Julia provides an in-depth look at how alcohol impacts liver function, breaking down the metabolism of ethanol and its detrimental effects. Julia then shifts the focus to understanding liver function tests and optimal enzyme levels, providing a detailed explanation of AST and ALT and elucidating why fluctuations in these levels may or may not be concerning. Here’s a glimpse of what we discuss: - The complex and crucial functionality of the liver, its four most essential functions, and more - Methods of diagnosing liver disease and how insights guide treatment and management strategies - Potential impact of recreational drugs, statins, and other medications on liver function test results - The impact of fructose consumption on liver health and the challenges of disentangling its effects from other factors like obesity and insulin resistance - Emerging drugs and therapies for addressing fat accumulation and fibrosis related to MAFLD - More https://bit.ly/3V6pnCU

In this episode (#302) of The Drive, I speak with Julia Wattacheril, M.D., M.P.H., a physician scientist and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) program at Columbia University Irving Medical Center. We delve deep into the complex world of liver health, beginning with a foundational overview of liver physiology. Julia provides an in-depth look at how alcohol impacts liver function, breaking down the metabolism of ethanol and its detrimental effects. Julia then shifts the focus to understanding liver function tests and optimal enzyme levels, providing a detailed explanation of AST and ALT and elucidating why fluctuations in these levels may or may not be concerning. Here’s a glimpse of what we discuss: - The complex and crucial functionality of the liver, its four most essential functions, and more - Methods of diagnosing liver disease and how insights guide treatment and management strategies - Potential impact of recreational drugs, statins, and other medications on liver function test results - The impact of fructose consumption on liver health and the challenges of disentangling its effects from other factors like obesity and insulin resistance - Emerging drugs and therapies for addressing fat accumulation and fibrosis related to MAFLD - More https://bit.ly/3V6pnCU

Excited to announce that my first doctoral thesis article titled "4-Hydroxybenzoic acid rescues multisystemic disease and perinatal lethality in a mouse model of mitochondrial disease" has been published! In this study, we generated a novel model of mitochondrial disease and identified a new therapeutic option based on endogenous CoQ biosynthesis stimulation. Hopefully, this research will pave the way for future advancements in treating patients affected by this condition. #MitochondrialDisease https://lnkd.in/dWJYyEz4

Scientists have been researching senescent cells and how they work in some mammals who completely regenerate organs and live forever. These cells are the key for aging related diseases and as well contribute to anti aging if properly handled. Whereas, these scientists created a platform for selectively removing aging senescent cells without harming normal healthy cells. Thus, they have achieved a significant breakthrough in the treatment of age-related diseases comprehensively. This groundbreaking development is poised to redefine the future of health care and usher in a new era of targeted therapeutic interventions. This team designed organic molecules that selectively target receptors overexpressed in the membranes of aging cells. By leveraging the higher levels of reactive oxygen species (ROS) found in aging cells, these molecules promote the formation of disulfide bonds and create oligomers that bind together. Through self-assembly of these oligomers, the researchers successfully created artificial proteins with a stable α-helix secondary structure. These protein-like nano-assemblies exhibited strong binding affinity to the mitochondrial membranes of aging cells, leading to membrane disruption and subsequent cell self-destruction. By removing these aging senescent cells, one can define healthy aging and most probably anti-aging in the future. #healthcarecosts #healthyaging #senescentcells #diseasecomprehension

Have you heard about Barry Marshall, the scientist who drank Helicobacter pylori culture to prove his groundbreaking theory that this bacterium causes ulcers? This audacious act earned him the Nobel Prize in Physiology in 2005 alongside Robin Warren. But what drove him to such extreme measures? In the early 1980s, the medical community was skeptical of the idea that H. pylori was a pathogen responsible for causing gastritis and peptic ulcers, painful sores in the stomach lining. Marshall faced significant opposition and lacked an effective animal model to demonstrate his hypothesis. Determined to prove his point, he turned to self-experimentation, inspired by historical figures like John Hunter, who famously self-infected with gonorrhea and syphilis to understand these diseases better. In July 1984, Marshall underwent an initial endoscopy to confirm he was free of H. pylori. He then ingested a suspension of the bacteria cultured from a patient with dyspepsia. The plan was to observe if he developed an infection, thereby proving that H. pylori could cause gastritis and potentially lead to ulcers in a healthy individual. The results were dramatic. Within days, Marshall experienced symptoms including bloating, decreased appetite, and vomiting. A follow-up endoscopy revealed severe active gastritis , confirming that H. pylori was indeed pathogenic. This experiment showed that the bacteria could infect and cause significant gastrointestinal issues in a previously healthy person, reshaping the understanding of gastritis and peptic ulcer disease. Despite the risks, Marshall's self-experiment provided irrefutable evidence that changed medical perspectives and treatment approaches. Fourteen days after the initial symptoms, another endoscopy was performed, and Marshall began antibiotic treatment. While H. pylori were not detected in the final biopsy, likely due to spontaneous cure or early treatment effects, the groundbreaking nature of his work was undeniable. Barry Marshall's daring experiment is a testament to the lengths scientists sometimes go to advance medical knowledge. His story is a powerful reminder of the importance of perseverance, innovation, and the willingness to challenge established norms in the pursuit of scientific truth. #Microbiology #GutHealth

📃Scientific paper: Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a Drosophila model of Parkinson’s disease Abstract: International audience; Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein (αSyn) aggregation and associated with abnormalities in lipid metabolism. The accumulation of lipids in cytoplasmic organelles called lipid droplets (LDs) was observed in cellular models of PD. To investigate the pathophysiological consequences of interactions between αSyn and proteins that regulate the homeostasis of LDs, we used a transgenic Drosophila model of PD, in which human αSyn is specifically expressed in photoreceptor neurons. We first found that overexpression of the LD-coating proteins Perilipin 1 or 2 (dPlin1/2), which limit the access of lipases to LDs, markedly increased triacylglyclerol (TG) loaded LDs in neurons. However, dPlin-induced-LDs in neurons are independent of lipid anabolic (diacylglycerol acyltransferase 1/midway, fatty acid transport protein/dFatp) and catabolic (brummer TG lipase) enzymes, indicating that alternative mechanisms regulate neuronal LD homeostasis. Interestingly, the accumulation of LDs induced by various LD proteins (dPlin1, dPlin2, CG7900 or Klarsicht LD-BD) was synergistically amplified by the co-expression of αSyn, which localized to LDs in both Drosophila photoreceptor neurons and in human neuroblastoma cells. Finally, the accumulation of LDs increased the resistance of αSyn to proteolytic digestion, a characteristic of αSyn aggregation in human neurons. We propose that αSyn cooperates with LD... Discover the rest of the scientific article on es/iode ➡️https://etcse.fr/Fj9Py

After our first publication in Nature Metabolism showing that the engulfment of apoptotic cells by macrophages drives a metabolic switch to glycolysis, we now demonstrate that the lactate that is produced from this process stimulates proliferation of pro-resolving ("M2-like") macrophages.🧑🔬 The processes we unraveled are promising therapeutic targets to dampen inflammation and promote tissue repair, which is vital in chronic inflammatory disorders including atherosclerotic cardiovascular disease. 🩺💙 Proud of my former postdoc lab and colleague David Ngai for continuing this important line of research. 👏 Links to both Nature Metabolism publications can be found below.👇 - PFKFB2-mediated glycolysis promotes lactate-driven continual efferocytosis by macrophages: https://lnkd.in/eSmkyXzB - Efferocytosis-induced lactate enables the proliferation of pro-resolving macrophages to mediate tissue repair: https://lnkd.in/dg3fj9Q6

Extremely proud to be a part of this wonderful work! In this important work led by Isabelle Guillas and Anatol Kontush, we have introduced an innovative methodology designed to extract substantial quantities of pre-beta-HDL, enabling a comprehensive analysis of their lipidomic and proteomic constituents while evaluating their biological functions. Through the implementation of this approach, we have unveiled a distinct and exclusive lipidomic and proteomic profile in human pre-beta-HDL. Our findings reveal a remarkable enrichment of pre-beta HDL in bioactive lipids and proteins with established connections to anti-inflammatory and immune responses. This enrichment aligns perfectly with the specialized biological role of these particles. Furthermore, our investigations have demonstrated that pre-beta-HDL, in addition to its robust cholesterol efflux capabilities, exhibits potent anti-inflammatory properties. As a result, our protocol not only sheds light on the previously uncharted omic composition of pre-beta-HDL but also underscores the significance of their potent biological functions. These discoveries open up exciting possibilities for identifying novel diagnostic markers, particularly in the context of pathological alterations in lipoprotein metabolism associated with cardiovascular disease. Isabelle Guillas Marie Lhomme Maryam Darabi Philippe LESNIK Wilfried LE GOFF Maryse Guerin @Anatol Kontush #diagnosticmarkers #cardiovasculardisease #hdl #prebetahdl #lipoprotein #lipidomics #health IHU ICAN INSERM Sorbonne Université https://lnkd.in/eWQygCrS

WHY MITOCHONDRIA IS CRUCIAL FOR HEALTHY LIFE & AGING‼️💡💡 Advice you to check the article below 👇 regarding that issue

#IGFBP2 Unlocking the #Obesity Puzzle: Targeting the Adipogenesis-Hypertrophy Switch! Researchers have uncovered a promising avenue for tackling obesity: targeting the balance between fat cell creation (adipogenesis) and enlargement (hypertrophy). By honing in on this adipogenesis-hypertrophy switch, scientists aim to develop more effective therapies. This breakthrough offers hope for innovative approaches to combat obesity-related health concerns. As scientists continue to unravel the mysteries of fat cell biology, the prospects for more targeted and personalized obesity therapies are brighter than ever. https://lnkd.in/e89cUXfr Search #IGFBP2 on #dimabio.com to find the bioactive protein for this target!