Amin Marashi’s Post

A phenome-wide association study involving 361,021 individuals from the UK Biobank revealed associations of MASLD with 948 unique clinical outcomes. Metabolic dysfunction-associated steatotic liver disease (MASLD) leads to multisystem impairments, with sequential comorbidities observed in circulatory, metabolic, and inflammatory diseases. Genetic data support links between MASLD and liver, metabolic, and cardio-cerebrovascular diseases. #MASLD #metabolicdysfunction #steatoticliverdisease #multisystemimpairments #comorbidities https://lnkd.in/eCrDpyS8

#AutoImmunity #mRNADiseases AWARE !... Increase of auto-immune diseases in all world in 2024 https://lnkd.in/dKQMN5BK. Whithout antivax or conspirationism theories should legitimaly post questions : Some answers : 1 ° ) Genetics expose some people to auto-immune disease depends of HLA system especially HLA DRA2 , this system naturally protect against severe forms of COVID-19 https://lnkd.in/dJHncnzT https://lnkd.in/dy6ZW68Q. HLA-DR has been linked to aberrant presentation of self-peptide to autoreactive T helper cells in the thymus22, and genetic polymorphisms in the HLA-DRB1 gene are associated with a range of autoimmune diseases, such as rheumatoid arthritis, diabetes mellitus type I or systemic lupus erythematosus2 2° ) Should was necesseraly inject those mRNA toward young people ? In this study more of 20% young people received mRNA anti-SARS-CoV-2 had auto-antibodies https://lnkd.in/dci7DQMY You can link or not

#microbiome #inflammation #medicine #medicalsciences #healthcare https://lnkd.in/gtqWvE6Z Hope for inflammatory bowel disease Several recent studies offer insights into the murky and complex causes of #inflammatory #bowel #disease (IBD). An analysis of how populations of #gut #bacteria adapt to living in inflamed tissue could help predict how bad a case of IBD might get, monitor its progression and identify which therapies might help. “Not every inflammatory bowel disease patient who walks in the door is the same,” says immunologist David Artis. “If we can map that difference to some extent, I think we’re going to be able to better treat those people.” Summary Gut bacteria are implicated in inflammatory bowel disease (IBD), but the strains driving these associations are unknown. Large-scale studies of microbiome evolution could reveal the imprint of disease on gut bacteria, thus pinpointing the strains and genes that may underlie inflammation. Here, we use stool metagenomes of thousands of IBD patients and healthy controls to reconstruct 140,000 strain genotypes, revealing hundreds of lineages enriched in IBD. We demonstrate that these strains are ancient, taxonomically diverse, and ubiquitous in humans. Moreover, disease-associated strains outcompete their healthy counterparts during inflammation, implying long-term adaptation to disease. Strain genetic differences map onto known axes of inflammation, including oxidative stress, nutrient biosynthesis, and immune evasion. Lastly, the loss of health-associated strains of Eggerthella lenta was predictive of fecal calprotectin, a biomarker of disease severity. Our work identifies reservoirs of strain diversity that may impact inflammatory disease and can be extended to other microbiome-associated diseases.

Specific #microbiota may predispose to #myeloproliferative neoplasms [#MPNs] (#polycythemia_vera, #essential_thrombocythemia, #chronic_myeloid_leukemia, etc.). [Human] [Cohort study] Notes: - Lower relative abundance of #Phascolarctobacterium in patients with MPN. - Phascolarctobacterium may protect from inflammation; thus, lower Phascolarctobacterium in MPN patients corroborates a chronic inflammatory state in this disease. - Microbiomes of MPN patients were enriched for genes involved in d-#Glucuronate metabolism. - Changes in abundances of β-d-glucuronidases are associated with colon cancer and other inflammatory diseases  - Increased Phascolarctobacterium is associated with benefits that include protection from #Clostridium_difficile infection and lower levels of #C_reactive_protein (#CRP). - Decreased abundance of #Phascolarctobacterium is observed in autoimmune diseases such as #Primary sclerosing cholangitis and ulcerative #Colitis - Phascolarctobacterium may be associated with decreases in the short-chain fatty acid #Propionate in the gut, which, in turn, can influence inflammation. - Increased plasma concentrations of tumor necrosis factor alpha (#TNF_α) and interferon gamma-inducible 10-kDa protein (IP10) in MPN patients. - TNF-α plays a critical role in MPN pathogenesis by creating an environment that is conducive to the growth of the neoplastic clone. - #Veillonella stimulates TNF-α production of peripheral blood mononuclear cells in a dose-dependent fashion. - A species of #Parabacteroides to be enriched in patients with colorectal carcinoma. - #Parabacteroides abundance was negatively correlated with intake of fruits and vegetables.

The Role of Lipoprotein in Cardiovascular Disease Lipoproteins are responsible for lipid transport in the body. One in five individuals faces a heightened risk of cardiovascular disease and aortic valve stenosis due to elevated lipoprotein concentrations. Lipoprotein levels are strongly influenced by genetics and may increase by up to 17% after menopause compared to men. In a recent review in The Lancet (September 2024), Nordesgaard and Langsted describe, among other topics, the historical, physiological, genetic, and epidemiological perspectives, as well as the role of lipoprotein in diabetes and hypercholesterolemia, and discuss drugs that reduce lipoprotein levels. https://lnkd.in/dUKF4ts4

“Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting multiple organs that is characterized by marked clinical heterogeneity, a fluctuating course with relapses and remissions, and high-titer antibodies to diverse autoantigens.” “Systemic lupus erythematosus (SLE) displays a hallmark interferon (IFN) signature and IFN-I, IFN-II, and IFN-III fluctuate significantly over time in SLE.” “Yet, clinical trials targeting type I IFN (IFN-I) have shown variable efficacy, and blocking IFN-II failed to treat SLE. The researchers show that IFN type levels in SLE vary significantly across clinical and transcriptional endotypes. Evaluating a patient’s elevated interferon combinations allows for a better understanding of how they may react to treatments, and this would allow clinicians to group them into clinical subtypes of lupus.”

✅Excessive activation of Type-2 innate lymphocyte cells (ILC2) in the lungs due to allergen exposure results in proinflammatory signalling and recruitment of other immune cells. ✅This leads to excessive inflammation and constriction of respiratory airways making breathing difficult. ✅Researchers at the Keck School of Medicine, University of Southern California, discovered an important protein—Piezo1—that regulates activation of ILC-2 and subsequent inflammation. ✅Mouse deficient in Piezo1 had more active ILC-2 leading to uncontrolled inflammation. ✅A drug known as, Yoda1, switches on Piezo1 channels thereby reducing the activity of ILC-2 and it's subsequent inflammatory effects. ✅The effects of Yoda1 was also observed in humanised mice—human immune cells (ILC-2) in mice. ✅This opens the door to studying the therapeutic applications of Yoda1 in human trials.

🔬 New Research Protocol on Potential Treatment for Crohn’s Disease! 🌿 The URNCST Journal is excited to share a new research protocol exploring an innovative combination therapy using atorvastatin and lactulose to treat Crohn’s Disease (CD) in a mouse model. CD is a chronic inflammatory bowel disease that causes significant gastrointestinal inflammation, and current treatments often fall short in their effectiveness. This study proposes that lactulose, a prebiotic, can increase beneficial anti-inflammatory bacteria, while atorvastatin may reduce inflammatory chemokine expression. Together, they could offer a more potent treatment than using either compound alone. 📊 Study Highlights: - Mice will be treated with TNBS to induce colitis, mimicking CD. - Groups will include mice treated with lactulose, atorvastatin, or a combination of both. - Key outcomes will measure inflammatory cytokine levels, Crohn’s Disease Activity Index (CDAI) scores, and colon health. 💡 Expected Results: - Combination therapy is anticipated to reduce inflammation and improve colonic health, with the treated mice displaying the closest CDAI score to healthy controls. If successful, this could pave the way for new treatment strategies for CD, with future studies focusing on optimizing dosages and identifying additional inflammatory markers. Read the full article here: https://lnkd.in/gWcsYNkT #URNCST #ResearchProtocol #CrohnsDisease #IrritableBowelSyndrome #prebiotics #statins

🔬 Groundbreaking Discovery in IBD Research 🌟 UK scientists have identified a major cause of inflammatory bowel disease (IBD), revealing a genetic vulnerability in 95% of IBD patients. This breakthrough sheds light on how immune cells overreact, triggering severe bowel inflammation. Promisingly, existing drugs have shown potential in reversing the disease in lab experiments, setting the stage for upcoming human trials. This advancement brings hope to millions battling Crohn's disease and ulcerative colitis. #IBDResearch #HealthcareInnovation #GeneticBreakthroughs

Autophagy, a cellular degradation process, and immunity and is essential for maintaining cellular homeostasis and regulating immune responses. ⏩. Types of Autophagy ▪️Macroautophagy Engulfs large cellular components like organelles for degradation. ▪️Microautophagy Lysosomes directly engulf small cytoplasmic portions. ▪️Chaperone-Mediated Autophagy Targets specific proteins for lysosomal degradation. ▪️Selective Autophagy Includes specialized forms like mitophagy (mitochondria) and xenophagy (pathogens). ⏩. Role of Autophagy in Cancer ▪️Tumor Suppression Removes damaged organelles and proteins, preventing oxidative stress and mutations. ▪️Tumor Promotion Helps cancer cells survive by providing energy during stress and protecting them from therapy. ⏩. Autophagy in Immune Function ▪️Enhances *innate immunity* by degrading pathogens and supporting cytokine production. ▪️Boosts *adaptive immunity* through better antigen presentation and pathogen clearance. ▪️Disruptions in autophagy are linked to inflammatory diseases and immune dysfunction. ⏩. Future Prospects ▪️Investigating the molecular regulation of autophagy for therapeutic opportunities. ▪️Exploring autophagy's role in aging, disease treatment, and personalized medicine. ▪️Technological advancements may allow better monitoring and manipulation of autophagy for health improvements. Honored to have participated in the Society of Pharmaceutical Sciences and Research (SPSR) webinar on 'Role of Autophagy in Human Health' on August 25, 2024. Monika Sabharwal #Pharmacy #Autophagy #Healthcare #WPD24 #Pharmacology #Precisionmedicine #Cancertherapy