es/iode’s Post

📃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.

📃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.

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 

In the tortuous folk story whereby proteins are the brain's built-in toxins, ataxin-2 is the latest casualty. Will the outcome of the Biogen and Ionis Pharmaceuticals, Inc. ALS trial help end that fable and the reliance on animal models to predict treatment responses in humans? Background: Intermediate polyQ expansions in ataxin-2 (ATXN2) are associated with amyotrophic lateral sclerosis (#ALS). https://lnkd.in/gn4jHYCW Idea: ataxin-2 may cause ALS (another long tradition: conflating correlation with causation) Animal model: reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice (https://lnkd.in/gRUzBY9P) Hypothesis: Reducing ataxin-2 will improve patients with ALS. Translation in humans: the 'ALSpire' Phase 1/2 trial of BIIB105 (an antisense oligonucleotide that binds the mRNA for ataxin-2 and mediates its degradation) on 99 ALS patients showed a significant and sustained treatment-related decrease in ataxin-2 but without impact on clinical or biomarker measures. https://lnkd.in/gbiM6yay How many more lives will we risk before we challenge our entrenched ideas about the role of proteins in neurodegenerative diseases? If proteins are abundant in our brains, might they be victims rather than villains?

🔬 ALPACAR-360 Trial: Zerlasiran as a Breakthrough in Lipoprotein(a) Management The ALPACAR-360 Trial, presented at AHA Scientific Sessions 2024 and published in JAMA, highlights the potential of zerlasiran, a short-interfering RNA (siRNA) therapy, in reducing elevated lipoprotein(a) [Lp(a)] levels—a genetic risk factor for cardiovascular disease. 🌟 Key Findings 1. Lipoprotein(a) Reduction: • Zerlasiran achieved a 90% median reduction in Lp(a) levels at 36 weeks from baseline. • These reductions were sustained through 48 weeks, demonstrating long-term efficacy. 2. Safety Profile: • Zerlasiran was well-tolerated, with no significant safety concerns reported over the 60-week trial. 3. Study Population: • 178 high-risk patients with baseline Lp(a) levels ≥125 nmol/L and high atherosclerotic cardiovascular disease (ASCVD) risk. 💡 Clinical Implications • Promising Therapeutic Option: Zerlasiran offers a novel approach for patients with elevated Lp(a), a group with limited therapeutic options until now. • Cardiovascular Risk Reduction: By effectively lowering Lp(a), zerlasiran could help mitigate ASCVD risk in genetically predisposed individuals. • Future Directions: This trial lays the foundation for larger studies focused on clinical outcomes like major cardiovascular events. ✨ Conclusion The ALPACAR-360 Trial establishes zerlasiran as a promising therapeutic advance in managing elevated Lp(a). Its robust and sustained efficacy, combined with a favorable safety profile, highlights its potential to transform care for patients at high cardiovascular risk. https://lnkd.in/djH-7xFg #AHA2024 #ALPACAR360 #LipoproteinA #Cardiology #CardiovascularInnovation #siRNAtherapy #EvidenceBasedMedicine

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)

🔬 Sickle Cell Test (Reduction Method): A Quick Overview 🔬 The Sickle Test (Reduction Method) is a simple screening test used to detect the presence of sickle hemoglobin (HbS), which is associated with sickle cell disease or sickle cell trait. Purpose of the Test The test helps diagnose: Sickle Cell Disease: A genetic disorder where red blood cells assume a sickle shape, leading to complications like anemia and organ damage. Sickle Cell Trait: A carrier state where an individual has one normal hemoglobin gene and one sickle hemoglobin gene. How the Test Works 1. Blood Sample Collection: A small amount of blood is drawn from the patient. 2. Addition of Reducing Agent: The blood is mixed with a reducing agent like sodium metabisulfite. This reduces oxygen tension, encouraging red blood cells containing HbS to sickle. 3. Observation: The sample is observed under a microscope. Sickle-shaped cells indicate the presence of HbS. Interpretation of Results Positive Test: Presence of sickle-shaped red blood cells suggests sickle cell disease or trait. Negative Test: Absence of sickle cells rules out the condition. Follow-Up Tests If the sickle test is positive, confirmatory tests are often performed, such as: Hemoglobin Electrophoresis High-Performance Liquid Chromatography (HPLC) These tests determine the exact type and proportion of hemoglobin present. Clinical Significance Early detection of sickle cell disease is crucial for managing symptoms and preventing complications like: Pain crises Stroke Infections Organ damage Limitations The sickle test is a screening tool and does not distinguish between sickle cell trait and sickle cell disease. False negatives can occur in individuals with a low percentage of HbS. #SickleCell #Diagnostics #Healthcare #Hematology #MedicalLaboratoryTechnology #Microbiology #Phlebotomy #LaboratoryTesting #DiagnosticTesting #HealthcareProfessional #MedicalTesting #ClinicalLaboratory #BiomedicalScience #HealthcareIndustry #MedicalScience #LaboratoryMedicine #ClinicalMicrobiology #InfectionControl #PhlebotomyTechnician #MedicalLabTechnician #MicrobiologyLab #ClinicalLab #HealthcareCareer #MedicalCareer #ScienceCareer #COVID19Testing #Virology #Bacteriology #Parasitology #MolecularDiagnosis #GeneticTesting #Cytology #Histopathology #Immunology #Serology

Exciting Breakthrough in IBD Research Employing Human Tissue Assays! A recent discovery by scientists at The Francis Crick Institute and University College London has unveiled a significant genetic factor contributing to inflammatory bowel disease (IBD). This groundbreaking research in functional genomics identifies a weak spot in DNA that affects the behaviour of macrophages, leading to excessive inflammation in the bowels. With Crohn’s disease and ulcerative colitis affecting millions globally, this finding marks a pivotal step towards understanding and potentially curing IBD. At REPROCELL, we are at the forefront of drug discovery, and this research aligns perfectly with our mission, by combining genomics with pharmacology. Our advanced assays, including those specifically for IBD, are designed to identify and develop targeted treatments that address the root causes of diseases. The identification of a key “regulator” gene of inflammation opens new avenues for creating more effective and personalized therapies. Using tests in ex vivo tissues from patients with IBD (as routinely done by REPROCELL), the research team found that certain existing drugs can reverse excessive inflammation, providing a head start toward developing new treatments. However, challenges remain in targeting these treatments precisely to avoid side effects and ensure they do not impair beneficial inflammation. We are excited to see such progress in the field and are committed to contributing to these advancements as we move closer to a world free from the debilitating impacts of IBD. Check out our IBD assay here: https://lnkd.in/eDhPDbUh Read more about the breakthrough in the BBC article: https://lnkd.in/e3QJ3FFb REPROCELL’s paper on functional genomics using human tissue and the use of machine learning in IBD research: https://lnkd.in/daRW7yM9

📃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