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📃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.

🕵️♂️ Glucosylceramidase (GBA): A Key Enzyme at the Intersection of Gaucher Disease and Parkinson’s Glucosylceramidase (GBA) plays a crucial role in breaking down fatty molecules in the body. However, mutations in the GBA gene can lead to Gaucher disease—a condition with both physical and emotional impacts. What makes GBA even more intriguing is its link to Parkinson’s disease, as mutations in this enzyme increase the risk of developing this neurodegenerative disorder. 🌟 GBA’s role in regulating metabolism and lysosomal activity is vital, and disruptions in these processes are linked to both Gaucher and Parkinson’s diseases. Currently, cutting-edge studies are focused on treatments aimed at restoring GBA function, such as chaperone therapies and gene therapy. If successful, these breakthroughs could not only offer new hope for those affected by Gaucher and Parkinson’s diseases but also pave the way for innovative treatments for other neurodegenerative conditions. 🌍 #GBA #Parkinsons #GaucherDisease #NeurodegenerativeResearch #MedicalInnovation https://lnkd.in/eQv6gbUR

📃Scientific paper: The microbiome of kidney stones and urine of patients with nephrolithiasis Abstract: The incidence of nephrolithiasis is rising worldwide. Although it is a multifactorial disease, lifestyle plays a major role in its etiology. Another considerable factor could be an aberrant microbiome. In our observational single-center study, we aimed to investigate the composition of bacteria in kidney stones and urine focusing on patients with features of metabolic syndrome. Catheterized urine and kidney stones were collected prospectively from 100 consecutive patients undergoing endoscopic nephrolithotomy between 2020 and 2021 at our clinic. Microbiome composition was analyzed via 16S rRNA gene amplicon sequencing. Detection of bacteria was successful in 24% of the analyzed kidney stones. These patients had a prolonged length of stay compared to patients without verifiable bacteria in their stones (2.9 vs 1.5 days). Patients with features of metabolic syndrome were characterized by kidney stones colonized with classical gastrointestinal bacteria and displayed a significant enrichment of Enterococcaceae and Enterobacteriaceae. Stones of patients without features of metabolic syndrome characterized by Ureaplasma and Staphylococcaceae . Patients with bacteria in their kidney stones exhibit a longer length of stay, possibly due to more complex care. Patients presenting with features of metabolic syndrome displayed a distinct stone microbiome compared to metabolically fit patients. Understanding the role of bacteria in stone formation could enable targeted therap... Continued on ES/IODE ➡️ https://etcse.fr/4R ------- 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.

A new, very interesting study on #arthritis published this week describes how some individuals with rheumatoid arthritis experience pain even when they have very low inflammation levels. Researchers found 815 genes that are responsible for pain in such patients. These genes are responsible for "rewiring the sensory nerves," which is why anti-inflammatory drugs do not reduce pain in these individuals. The study was published in Science Translational Advances. → Research teams led by Zilong Bai at Weill Cornell Medicine, Dana Orange at The Rockefeller University, and Fan Zhang, PhD at the University of Colorado School of Medicine made the discovery of these genes. → Publication Bai Z, Bartelo N, Aslam M, et al. Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis. Sci Transl Med. 2024;16(742) 📖 Read on…https://lnkd.in/etNAtbgi #Genetics #AutoimmuneDisease #Inflammation #Medicine 

📃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.

📃Scientific paper: FTLD Patient–Derived Fibroblasts Show Defective Mitochondrial Function and Accumulation of p62 Ref.: Springer, 2021 Abstract: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and neuropathologically heterogeneous group of neurodegenerative syndromes, leading to progressive cognitive dysfunction and frontal and temporal atrophy. C9orf72 hexanucleotide repeat expansion (C9-HRE) is the most common genetic cause of FTLD, but pathogenic mechanisms underlying FTLD are not fully understood. Here, we compared cellular features and functional properties, especially related to protein degradation pathways and mitochondrial function, of FTLD patient–derived skin fibroblasts from C9-HRE carriers and non-carriers and healthy donors. Fibroblasts from C9-HRE carriers were found to produce RNA foci, but no dipeptide repeat proteins, and they showed unchanged levels of C9orf72 mRNA transcripts. The main protein degradation pathways, the ubiquitin–proteasome system and autophagy, did not show alterations between the fibroblasts from C9-HRE-carrying and non-carrying FTLD patients and compared to healthy controls. An increase in the number and size of p62-positive puncta was evident in fibroblasts from both C9-HRE carriers and non-carriers. In addition, several parameters of mitochondrial function, namely, basal and maximal respiration and respiration linked to ATP production, were significantly reduced in the FTLD patient–derived fibroblasts from both C9-HRE carriers and non-carriers. Our findings suggest that FTLD patient–derived fibroblasts, regardless of whether they carry the C9-HRE ... Continued on ES/IODE ➡️ https://etcse.fr/cPzr ------- 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. #amyotrophiclateralsclerosis #als #charcot

Genome Medicine 16, 120 (2024). Olink Proteomics profiling integrated with #metabolomics reveal novel #biomarkers and drug targets for #heart failure and atrial #fibrillation. #Olink measurements of 1,567 blood proteins in up to 35,559 participants, was used  to identify proteins affecting cardiac-disease associated metabolites, and cardiac outcomes. The study identified 35 plasma #metabolites involved with #cardiac diseases and linked these to 38 druggable #proteins, providing actionable leads for drug development including targets for de novo #drug development and also for drug repurposing. Title: "Integrating metabolomics and proteomics to identify novel drug targets for heart failure and atrial fibrillation" Altered metabolism plays a role in the #pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). Mendelian randomisation (MR) was used to assess the association of 174 #metabolites with cardiac diseases. Subsequently, cis MR was used to identify proteins affecting both the metabolites and the considered cardiac outcomes. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways. • 35 metabolites associating with cardiac disease were identified. Plasma #acylcarnitine (AC) values were strongly related with DCM, while #phosphatidylcholine (PC) values were important determinants of HF. • 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. • Some known associations were recapitulated , including between the drug target of digoxin (AT1B2), taurine and NICM risk. • Ten pleiotropic proteins affecting multiple cardiac traits were identified: ACES, APOC3, DNJA4, ENOB, FCG3A, IL6RA, NEC1, PLA2R, PLXB2, and RET. • The 38 drugged and druggable proteins included eleven proteins with a known cardiac indication, side-effect, or both: ACES (donepezil), AT1B2 (digoxin), CACP (levocarnitine), DPEP1 (cilastatin), ENASE (edoxaban), FA10 (apixaban), IL6RA (tocilizumab), KPCA (midostaurin), RET (regorafenib), SAT2 (trientine), and TRYB1 (arginine). • Notably, higher RET values were associated with #phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy #homeostasis in cardiac pathogenesis. The findings provide evidence for relevant metabolites and proteins in cardiac diseases, pointing to involved pathways and providing relevant target prioritisation for pre-clinical drug development. #cardiology #immunology #pathology #biomarkers #omics https://lnkd.in/gQ6pAQ2R

Congrats to Marion van Vugt (Marion V.) et. al. at Department of Cardiology, University Medical Center Utrecht, Utrecht University, Division Heart & Lungs, Utrecht, The Netherlands. Lovely job of combing metabolomics and proteomics to advance understanding in HF and AF. I always say "All the Omics" drives discovery and confirms suspicions all at one on every sample. [ 👇🏽 Checkout the use of genome wide mendelian randomization to make powerful associations between genomic mutations and phenotype ]. Thanks Tal Varsano for your lovely synopsis/summary/highlights [ I just LOVE plagiarizing you work 😁 ] ✴ The 38 drugged and druggable proteins included eleven proteins with a known cardiac indication, side-effect, or both: ACES (donepezil), AT1B2 (digoxin), CACP (levocarnitine), DPEP1 (cilastatin), ENASE (edoxaban), FA10 (apixaban), IL6RA (tocilizumab), KPCA (midostaurin), RET (regorafenib), SAT2 (trientine), and TRYB1 (arginine). #heartDisease, #protein #biomarkers combined with #metabolomics

📃Scientific paper: The first case of lipoprotein glomerulopathy complicated with collagen type III glomerulopathy and literature review Abstract: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease caused by pathogenic mutations in the APOE gene. Collagen type III glomerulopathy (CG) is a sporadic condition in adults characterized by abnormal accumulation of type III collagen in the subendothelial space and mesangium of the glomerulus. We report the first case of both LPG and CG in a 21-year-old male. A search of the literature found no confirmed reports of these two concomitant nephropathies. The patient presented with hypertension, proteinuria, hematuria and hyperlipidemia. Renal pathology showed lipid vacuoles in the enlarged glomerular capillary loops and type III collagen in the segmental mesangial area and on the inner side of the glomerular basement membrane by electron microscopy. Whole-exome sequencing revealed a heterozygous mutation (c.127C>T; p. Arg43Cys) in exon 3 of the APOE gene, known as the APOE-Kyoto of LPG. In addition, two heterozygous COL4A4 mutations (c.4715C>T in exon 47 and c.5065 T>C in exon 48) were observed, the first one was suspected pathogenic and the other one was uncertain significant. There is no special treatment for these diseases. The patient was treated with lipid-lowering agents, renin–angiotensin–aldosterone system inhibition and tripterygium glycosides. The patient received double-filtration plasmapheresis and immunoadsorption therapy when renal function deteriorated dramatically. Immunoadsorption was beneficial for this patient. Continued on ES/IODE ➡️ https://etcse.fr/hABU ------- 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.

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