es/iode’s Post

Kudos to the team for publishing the first epigenetic map in peripheral blood of patients with Primary Sclerosing Cholangitis (PSC) and Primary Biliary Cholangitis (PBC). The study revealed unique insights, such as increased epigenetic age acceleration, distinctions in immune cell composition, and notable differences in predicted protein levels. Noteworthy associations were found in genes including vacuole membrane protein 1, SOCS3, NOD-like receptor family CARD domain containing 5, human leukocyte antigen-E, and PSMB8. The research also highlighted disease-related pathways and regulators linked to immune signaling, macrophage activation, and T-cell function, offering valuable understanding into the conditions' molecular basis. An intriguing comparison between PSC and PBC data showed limited gene-level overlap but more convergence in pathways and regulators, paving the way for potential future research and therapeutic interventions. Dive deeper into the study for comprehensive insights: [Read more](https://lnkd.in/g5_nEPVr)

Check out this tremendous study by Balaji Karthick Subramanian, Martin Pollak, and Seth Alper at Beth Israel Deaconess Medical Center that explores gain-of-function mechanisms that drive INF2-related FSGS and explain this disease's autosomal dominant inheritance. This paper has it all - GOF point mutation knock-ins, INF2 KOs, disease models, localization studies, podocyte phenotypes, FSGS patient IPSC-kidney organoids and organoid-derived podocytes, beautiful imaging... When we understand the molecular events that drive disease, we are presented with opportunities to create new therapeutics. https://lnkd.in/eGseP75N

📃Scientific paper: Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation Abstract: Intraneuronal accumulation of aggregated α-synuclein is a pathological hallmark of Parkinson’s disease. Therefore, mechanisms capable of promoting α-synuclein deposition bear important pathogenetic implications. Mutations of the glucocerebrosidase 1 (GBA) gene represent a prevalent Parkinson’s disease risk factor. They are associated with loss of activity of a key enzyme involved in lipid metabolism, glucocerebrosidase, supporting a mechanistic relationship between abnormal α-synuclein–lipid interactions and the development of Parkinson pathology. In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson’s disease and Parkinson's disease patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics. The lipid profile of PD-GBA fibroblasts differed significantly from that of control and idiopathic Parkinson’s disease cells. It was characterized by an overall increase in sphingolipid levels. It also featured a significant increase in the proportion of ceramide, sphingomyelin and hexosylceramide molecules with shorter chain length and a decrease in the percentage of longer-chain sphingolipids. The extent of this shift was correlated to the degree of reduction of fibroblast glucocerebrosidase activity. Lipid extracts from control and PD-GBA fibroblasts were added to recombinant α-synuclein solutions. The kinetics of α-synuclein aggregation were significantly accelerated afte... Continued on ES/IODE ➡️ https://etcse.fr/xMnF ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation Abstract: Intraneuronal accumulation of aggregated α-synuclein is a pathological hallmark of Parkinson’s disease. Therefore, mechanisms capable of promoting α-synuclein deposition bear important pathogenetic implications. Mutations of the glucocerebrosidase 1 (GBA) gene represent a prevalent Parkinson’s disease risk factor. They are associated with loss of activity of a key enzyme involved in lipid metabolism, glucocerebrosidase, supporting a mechanistic relationship between abnormal α-synuclein–lipid interactions and the development of Parkinson pathology. In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson’s disease and Parkinson's disease patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics. The lipid profile of PD-GBA fibroblasts differed significantly from that of control and idiopathic Parkinson’s disease cells. It was characterized by an overall increase in sphingolipid levels. It also featured a significant increase in the proportion of ceramide, sphingomyelin and hexosylceramide molecules with shorter chain length and a decrease in the percentage of longer-chain sphingolipids. The extent of this shift was correlated to the degree of reduction of fibroblast glucocerebrosidase activity. Lipid extracts from control and PD-GBA fibroblasts were added to recombinant α-synuclein solutions. The kinetics of α-synuclein aggregation were significantly accelerated afte... Continued on ES/IODE ➡️ https://etcse.fr/xMnF ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Hereditary renal amyloidosis related to a variant of the fibrinogen Aα chain (AFib): CONICET Amyloidosis is a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Hereditary amyloidosis does not respond to chemotherapy, so the identification of the amyloid subtype is essential for diagnosis, prognosis and treatment. Renal amyloidosis is characterized by the pathological acellular deposition of amyloid fibrils in glomeruli, vessels and/or interstitium. This disease manifests with intense proteinuria, nephrotic syndrome and progression to end-stage renal failure. Amyloid deposits in the kidney may arise from immunoglobulin light chains (AL amyloidosis), amyloid A, fibrinogen Aα chain, lysozyme, gelsolin, apolipoprotein AI, apolipoprotein A-II, apolipoprotein A-IV, apolipoprotein C2, apolipoprotein C3, transthyretin, and leukocyte chemotactic factor 2. Fibrinogen Aα chain amyloidosis (AFib) is an autosomal dominant inherited systemic amyloidosis caused by the deposition of amyloid fibrils comprising variants of the fibrinogen Aα chain induced by mutations in the fibrinogen Aα chain (FGA) gene. The Fib2/FGA (Fibrinogen Alpha Chain) gene encoded on 4q31.3 is an 866 amino acid protein that is a component of blood clots. In hereditary congenital dysfibrinogenemia (DYSFIBRIN), in addition to the mutation in FGA, mutations in the genes FGB (Fibrinogen Beta Chain, 4q31.3) and/or FGG (Fibrinogen Gamma Chain, 4q32.1) may be involved. FGB is cleaved by the protease thrombin to produce monomers that, together with FGA and FGG, polymerize to form an insoluble fibrin matrix. Fibrin is one of the main components of blood clots. https://lnkd.in/duRHUbU3

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

Congratulation to our metabolomics team and especially Alaa Othman for his contribution to the recent publication in Nature Communications https://lnkd.in/duy5xK92 Huge congratulation to all coauthors as well!! and especially Joanna Zaręba, PhD and Prof. Dr. Francesca Peri (https://lnkd.in/djdEu2F3) at the University of Zurich. That is the third Nature communication paper coauhored by staff in our metabolomics unit in the past couple of months, including: - The reactive pyruvate metabolite dimethylglyoxal mediates neurological consequences of diabetes https://lnkd.in/eyM6kNqH - Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target https://lnkd.in/enZG6YBC Other notable original research articles coauthored by our metabolomics unit staff in 2024: - Nature: Ancestral allele of DNA polymerase gamma modifies antiviral tolerance https://lnkd.in/eYPzTX_n - Cancer Cell: Retinoic acid receptor activation reprograms senescence response and enhances anti-tumor activity of natural killer cells https://lnkd.in/dbZGsqft We are very grateful to all of our users who trust us and give us exciting challenges in excellent world-class projects. This validates our strategy and dedication to support our users with metabolomics and lipidomics for impact. #metabolomics #lipidomics #metabolomicswithimpact #LCMS #bioinformatics #multiomics

📃Scientific paper: Correlation Analysis of Vaspin Gene Polymorphisms and Polycystic Ovary Syndrome Based on Intelligent Medicine Abstract: Polycystic ovary syndrome (PCOS) is now a common gynecological endocrine disease, also known as Stein–Leventhal syndrome. Studies have found that Vaspin gene polymorphism is significantly associated with diabetes and cardiovascular disease, and PCOS has a clear glucose metabolism abnormality. So far, because the cause of PCOS is not clear, many problems such as the etiology, diagnostic criteria, prevention, and treatment of PCOS remain unsolved. Which also makes PCOS attract the attention of academic circles. Therefore, it is urgent to clarify the pathogenesis of PCOS, in order to explore the clinical correlation between the polymorphism of the Vaspin gene and polycystic ovary syndrome. This article introduces the correlation analysis study of Vaspin gene polymorphisms and polycystic ovary syndrome based on intelligent medicine. This article first selected 40 patients with PCOS as the experimental group and then selected 40 patients without PCOS as the control group. Secondly, through the detection methods of hs-CRP level detection and oil red O fat staining and passed two sets of control experiments. Finally, intelligent medical data analysis was used to analyze the location of the Vaspin gene in the experimental group and the control group. The final result showed that the correlation reached 75%. Continued on ES/IODE ➡️ https://etcse.fr/m69M ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

This cohort study describes the clinical features, patient characteristics, and treatment of anti-melanoma differentiation–associated gene 5 (MDA5) dermatomyositis. https://ja.ma/3vMU4n9

📘 Dr. Karen English and her team at Maynooth University used MIF protein to enhance mesenchymal stromal cells (MSCs), boosting their release of VEGF, a molecule aiding lung repair through angiogenesis and other activities. In genetic mouse models, these MSCs repaired lung damage, improved healing, and reduced mucus production caused by allergens like house dust mites (HDM), offering potential new asthma treatments. RoosterBio is glad to have contributed bone marrow-derived MSCs to support this groundbreaking research. Read it here: https://lnkd.in/e8ru6776 #stemcells #stromalcells #celltherapy #stemcellresearch #celltherapyresearch #angiogenesis #lungrepair #woundhealing