Development of a Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease Prediction in UK Biobank.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of liver-related morbidity and mortality. Although the invasive liver biopsy remains the golden standard for MASLD diagnosis, Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) is an accurate, non-invasive method for the assessment of treatment response. This study aimed at developing a Polygenic Risk Score (PRS) to improve MRI-PDFF prediction using UK Biobank data to assess an individual's genetic liability to MASLD.

Transient interactions between the fuzzy coat and the cross-β core of brain-derived Aβ42 filaments.

Several human disorders, including Alzheimer's disease (AD), are characterized by the aberrant formation of amyloid fibrils. In many cases, the amyloid core is flanked by disordered regions, known as fuzzy coat. The structural properties of fuzzy coats, and their interactions with their environments, however, have not been fully described to date.

GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2 Cerebral Organoids.

Background: The polygenic nature of autism spectrum disorder (ASD) requires the identification of converging genetic pathways during early development to elucidate its complexity and varied manifestations.

Methods: We developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the ASD risk gene.

Results: CNTNAP2 cerebral organoids displayed accelerated cell cycle, ventricular zone disorganization, and increased cortical folding.

Elimination of High-grade Gliomas Through Induced Cytolysis, Elucidated by Two Patient Cases.

Background/aim: Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant tumors in the central nervous system of adults. In practice, all patients with GBM experience relapse, and treatment options become limited following first-line therapy. We previously reported a new, successful treatment approach for a GBM patient, implemented in direct conjunction with surgical intervention.

Proteomic Changes of Glycolipid Pathways in Age-Related, Diabetic, and Post-Vitrectomy Cataracts.

: Alterations in glycolipid and glycosphingolipid pathways lead to compromised cell membranes and may be involved in cataract formation. However, the exact role of glycolipids in lens opacification is not completely understood. The aim of the current study is to investigate proteome complexity and the role of glycolipid and glycosphingolipid pathways in cataract formation.

VISTA Enhancer browser: an updated database of tissue-specific developmental enhancers.

Regulatory elements (enhancers) are major drivers of gene expression in mammals and harbor many genetic variants associated with human diseases. Here, we present an updated VISTA Enhancer Browser (https://enhancer.lbl.

Tear Proteomics in Children and Adolescents with Type 1 Diabetes: A Promising Approach to Biomarker Identification of Diabetes Pathogenesis and Complications.

The aim of the current study was to investigate the tear proteome in children and adolescents with type 1 diabetes (T1D) compared to healthy controls, and to identify differences in the tear proteome of children with T1D depending on different characteristics of the disease. Fifty-six children with T1D at least one year after diagnosis, aged 6-17 years old, and fifty-six healthy age- and sex-matched controls were enrolled in this cross-sectional study. The proteomic analysis was based on liquid chromatography tandem mass spectrometry (LC-MS/MS) enabling the identification and quantification of the protein content via Data-Independent Acquisition by Neural Networks (DIA-NN).

Exploration of isatin-based inhibitors of SARS-CoV-2 Nsp15 endoribonuclease.

The global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) urges the development of new antiviral agents with broad coronavirus coverage. Due to its key role in viral evasion from the host innate immune response, the coronavirus Nsp15 uridine-specific endoribonuclease (EndoU) is of high interest as a drug target. Considering that the isatin scaffold is well-known for its versatile pharmacological properties, we synthesized and evaluated a series of compounds carrying an isatin core.

Biomimetic CO Capture Unlocked through Enzyme Mining: Discovery of a Highly Thermo- and Alkali-Stable Carbonic Anhydrase.

Taking immediate action to combat the urgent threat of CO-driven global warming is crucial for ensuring a habitable planet. Decarbonizing the industrial sector requires implementing sustainable carbon-capture technologies, such as biomimetic hot potassium carbonate capture (BioHPC). BioHPC is superior to traditional amine-based strategies due to its eco-friendly nature.

Interplay between bone marrow adiposity and bone resorption in RANKL-mediated modelled osteoporosis.

Bone marrow adipose tissue (BMAT) accrues in osteoporosis, whereas its contribution to the progression of bone resorption remains insufficiently understood. To understand the mechanisms that promote BMAT expansion in osteoporosis, in the present study, we performed extensive analysis of the spatiotemporal pattern of BMAT expansion during the progression of bone resorption in TgRANKL transgenic mouse models of osteoporosis expressing human RANKL (receptor activator of nuclear factor-κB ligand). Our results showed that TgRANKL mice of both sexes developed dramatically increased BMAT expansion compared to wild-type (WT) littermates, that was analogous to the levels of RANKL expression and the severity of the bone loss phenotype.

A Dietary Intervention in Adults with Overweight or Obesity Leads to Weight Loss Irrespective of Macronutrient Composition.

Obesity is a critical public health issue, necessitating effective weight loss interventions. While various dietary regimens have been explored, individual responses to interventions often vary. This study involved a 3-month dietary intervention aiming at assessing the role of macronutrient composition and the potential role of genetic predisposition in weight loss among Greek adults.

drive synovial hyperplasia and arthritis by targeting cell cycle inhibitors and chromatin remodeling components.

miRNAs constitute fine-tuners of gene expression and are implicated in a variety of diseases spanning from inflammation to cancer. miRNA expression is deregulated in rheumatoid arthritis (RA); however, their specific role in key arthritogenic cells such as the synovial fibroblast (SF) remains elusive. Previous studies have shown that expression is upregulated in RA SFs.

Cyld restrains the hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis.

TNF is a potent cytokine known for its involvement in physiology and pathology. In Rheumatoid Arthritis (RA), persistent TNF signals cause aberrant activation of synovial fibroblasts (SFs), the resident cells crucially involved in the inflammatory and destructive responses of the affected synovial membrane. However, the molecular switches that control the pathogenic activation of SFs remain poorly defined.

Kidney whole-transcriptome profiling in primary antiphospholipid syndrome reveals complement, interferons and NETs-related gene expression.

Objective: Pathogenesis of antiphospholipid syndrome (APS) remains poorly elucidated. We aimed to evaluate for the first time kidney transcriptome profiles in primary APS vs systemic lupus erythematosus (SLE) and control subjects.

Methods: We performed RNA sequencing on archival formalin-fixed paraffin-embedded kidney biopsies from APS (n = 4), SLE (n = 5) and control (n = 3) individuals, differential gene expression analysis (DGEA) and enrichment analysis using gene ontology (GO) and CORUM, KEGG and Reactome pathway databases.

Longitudinal proteomics of leptin treatment in humans with acute and chronic energy deficiency-induced hypoleptinemia reveal novel, mainly immune-related, pleiotropic effects.

Background: Leptin is known for its metabolic, immunomodulatory and neuroendocrine properties, but the full spectrum of molecules downstream of leptin and relevant underlying mechanisms remain to be fully clarified. Our objective was to identify proteins and pathways influenced by leptin through untargeted proteomics in two clinical trials involving leptin administration in lean individuals.

Methods: We performed untargeted liquid chromatography-tandem mass spectrometry serum proteomics across two studies a) Short-term randomized controlled crossover study of lean male and female humans undergoing a 72-h fast with concurrent administration of either placebo or high-dose leptin; b) Long-term (36-week) randomized controlled trial of leptin replacement therapy in human females with acquired relative energy deficiency and hypoleptinemia.

Oncostatin M-driven macrophage-fibroblast circuits as a drug target in autoimmune arthritis.

Background: Recent single-cell RNA sequencing (scRNA-seq) analysis revealed the functional heterogeneity and pathogenic cell subsets in immune cells, synovial fibroblasts and bone cells in rheumatoid arthritis (RA). JAK inhibitors which ameliorate joint inflammation and bone destruction in RA, suppress the activation of various types of cells in vitro. However, the key cellular and molecular mechanisms underlying the potent clinical effects of JAK inhibitors on RA remain to be determined.

A Machine Learning-Based Web Tool for the Severity Prediction of COVID-19.

Predictive tools provide a unique opportunity to explain the observed differences in outcome between patients of the COVID-19 pandemic. The aim of this study was to associate individual demographic and clinical characteristics with disease severity in COVID-19 patients and to highlight the importance of machine learning (ML) in disease prognosis. The study enrolled 344 unvaccinated patients with confirmed SARS-CoV-2 infection.

Key Functions of the Transcription Factor BCL6 During T-Cell Differentiation.

T lymphocytes consist of several subtypes with distinct functions that help to coordinate an immune response. They are generated within the thymus through a sequential developmental pathway that produces subsets with diverse antigen specificities and functions. Naïve T cells populate peripheral lymphoid organs and are activated upon foreign antigen encounter.

Endonucleosis mediates internalization of cytoplasm into the nucleus.

Setd8 regulates transcription elongation, mitotic DNA condensation, DNA damage response and replication licensing. Here we show that, in mitogen-stimulated liver-specific Setd8-KO mice, most of the hepatocytes are eliminated by necrosis but a significant number of them survive via entering a stage exhibiting several senescence-related features. Setd8-deficient hepatocytes had enlarged nuclei, chromosomal hyperploidy and nuclear engulfments progressing to the formation of intranuclear vesicles surrounded by nuclear lamina.

Role of actin-binding proteins in cataract formation.

Introduction: Actin has been implicated in lens opacification; however, the specific actin-related pathways involved in cataracts remain unelucidated. In this study, actin-related proteome changes and signaling pathways involved in the development of cataracts were evaluated.

Methods: The anterior capsule and phacoemulsification (phaco) cassette contents were collected during cataract surgery from 11 patients with diabetic cataract (DC), 12 patients with age-related cataract (ARC), and seven patients with post-vitrectomy cataract (PVC).

Evaluation of Polygenic Risk Scores for Prediction of Coronary Artery Disease in a Greek Case-Control Study.

Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population.

The Effectiveness of Atezolizumab in Metastatic Large Cell Neuroendocrine Carcinoma of the Lungs: Insights from the LANCE Pilot Study.

Background: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC.

Methods: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone.

Fingerprinting Breast Milk; insights into Milk Exosomics.

Breast milk, often referred to as "liquid gold," is a complex biofluid that provides essential nutrients, immune factors, and developmental cues for newborns. Recent advancements in the field of exosome research have shed light on the critical role of exosomes in breast milk. Exosomes are nanosized vesicles that carry bioactive molecules, including proteins, lipids, nucleic acids, and miRNAs.