Protective role of 3-mercaptopyruvate sulfurtransferase (MPST) in the development of metabolic syndrome and vascular inflammation.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that occur concurrently and increase the risk of cardiovascular disease. 3-mercaptopyruvate sulfurtransferase (MPST) is a cysteine-catabolizing enzyme that yields pyruvate and hydrogen sulfide (HS) and plays a central role in the regulation of energy homeostasis. Herein, we seek to investigate the role of MPST/HS in MetS and its cardiovascular consequences using a mouse model of the disease.

The Macrophage-Fibroblast Dipole in the Context of Cardiac Repair and Fibrosis.

Stromal and immune cells and their interactions have gained the attention of cardiology researchers and clinicians in recent years as their contribution in cardiac repair is increasingly recognized. The repair process in the heart is a particularly critical constellation of complex molecular and cellular events and interactions that characteristically fail to ensure adequate recovery following injury, insult, or exposure to stress conditions in this regeneration-hostile organ. The tremendous consequence of this pronounced inability to maintain homeostatic states is being translated in numerous ways promoting progress into heart failure, a deadly, irreversible condition requiring organ transplantation.

The phospholamban R14del generates pathogenic aggregates by impairing autophagosome-lysosome fusion.

Phospholamban (PLN) plays a crucial role in regulating sarcoplasmic reticulum (SR) Ca cycling and cardiac contractility. Mutations within the PLN gene have been detected in patients with cardiomyopathy, with the heterozygous variant c.40_42delAGA (p.

TRBP2, a Major Component of the RNAi Machinery, Is Subjected to Cell Cycle-Dependent Regulation in Human Cancer Cells of Diverse Tissue Origin.

Background: Transactivation Response Element RNA-binding Protein (TRBP2) is a double-stranded RNA-binding protein widely known for its critical contribution to RNA interference (RNAi), a conserved mechanism of gene-expression regulation mediated through small non-coding RNA moieties (ncRNAs). Nevertheless, TRBP2 has also proved to be involved in other molecular pathways and biological processes, such as cell growth, organism development, spermatogenesis, and stress response. Mutations or aberrant expression of TRBP2 have been previously associated with diverse human pathologies, including Alzheimer's disease, cardiomyopathy, and cancer, with TRBP2 playing an essential role(s) in proliferation, invasion, and metastasis of tumor cells.

LncRNA evf-2 Exacerbates Podocyte Injury in Diabetic Nephropathy by Inducing Cell Cycle Re-entry and Inflammation Through Distinct Mechanisms Triggered by hnRNPU.

Albuminuria is a hallmark of diabetic nephropathy (DN). Podocyte injury significantly contributes to proteinuria in DN. Our study found that lncRNA EVF-2 is upregulated in podocytes of DN patients, correlating with cell cycle re-entry and inflammation.

Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn's disease through IFNα pathway.

Introduction: Crohn's disease (CD) is characterized by chronic inflammation and intestinal fibrosis leading to lifelong complications. However, the disease pathogenesis remains elusive, and the therapeutic options are limited. Here, we investigated the interaction between neutrophils and intestinal fibroblasts in the development of CD immunofibrosis, a disease mechanism predisposing to inflammatory and fibrotic complications.

Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats.

Repeated administration of ketamine (KET) has been used to model schizophrenia-like symptomatology in rodents, but the psychotomimetic neurobiological and neuroanatomical underpinnings remain elusive. In parallel, the unmet need for a better treatment of schizophrenia requires the development of novel therapeutic strategies. Cannabidiol (CBD), a major non-addictive phytocannabinoid has been linked to antipsychotic effects with unclear mechanistic basis.

Cytokeratin 18 as a Novel Biomarker in Patients with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease associated with an increased risk for sudden cardiac death (SCD). Cytokeratin 18-based proteins, such as M30 and M65 antigens, are known cell-death biomarkers. M30 antigen is released from cells during apoptosis, and M65 antigen is released during cell death from any cause, such as apoptosis or necrosis.

Antihypertensive Potential of var. : Molecular Insights and Therapeutic Implications.

Hypertension poses a significant global health burden and is associated with cardiovascular morbidity. Chios mastic gum (CMG), derived from var. , shows potential as a phytotherapeutic agent, due to its multifaceted beneficial effects.

SIMOA Diagnostics on Alzheimer's Disease and Frontotemporal Dementia.

Background: Accurate diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) represents a health issue due to the absence of disease traits. We assessed the performance of a SIMOA panel in cerebrospinal fluid (CSF) from 43 AD and 33 FTD patients with 60 matching Control subjects in combination with demographic-clinical characteristics.

Methods: 136 subjects (AD: = 43, FTD: = 33, Controls: = 60) participated.

Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development.

Cancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumour microenvironment, serving diverse functions in tumour progression. However, the mechanisms via which CAFs influence the anti-tumour immunity remain poorly understood. Here, using multiple tumour models and biopsies from cancer patients, we report that α-SMA CAFs can form immunological synapses with Foxp3 regulatory T cells (Tregs) in tumours.

Are the Head and Tail Domains of Intermediate Filaments Really Unstructured Regions?

Intermediate filaments (IFs) are integral components of the cytoskeleton which provide cells with tissue-specific mechanical properties and are involved in a plethora of cellular processes. Unfortunately, due to their intricate architecture, the 3D structure of the complete molecule of IFs has remained unresolved. Even though most of the rod domain structure has been revealed by means of crystallographic analyses, the flanked head and tail domains are still mostly unknown.

Unraveling Desmin's Head Domain Structure and Function.

Understanding the structure and function of intermediate filaments (IFs) is necessary in order to explain why more than 70 related IF genes have evolved in vertebrates while maintaining such dramatically tissue-specific expression. Desmin is a member of the large multigene family of IF proteins and is specifically expressed in myocytes. In an effort to elucidate its muscle-specific behavior, we have used a yeast two-hybrid system in order to identify desmin's head binding partners.

Polycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster.

Balancing maintenance of self-renewal and differentiation is a key property of adult stem cells. The epigenetic mechanisms controlling this balance remain largely unknown. Herein, we report that the Polycomb Repressive Complex 2 (PRC2) is required for maintenance of the intestinal stem cell (ISC) pool in the adult female Drosophila melanogaster.

The Rat: A Preclinical Model of Polycystic Kidney Disease.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) stands as the most prevalent hereditary renal disorder in humans, ultimately culminating in end-stage kidney disease. Animal models carrying mutations associated with polycystic kidney disease have played an important role in the advancement of ADPKD research. The rat model, carrying an R823W mutation in the gene, is characterized by cyst formation and kidney enlargement.

Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function.

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard.

Parkin mRNA Expression Levels in Peripheral Blood Mononuclear Cells in Parkin-Related Parkinson's Disease.

Introduction: Pathogenic variants in parkin (PRKN gene) are the second most prevalent known monogenic cause of Parkinson's disease (PD). How monoallelic or biallelic pathogenic variants in the PRKN gene may affect its transcription in patient-derived biological material has not been systematically studied.

Methods: PRKN mRNA expression levels were measured with real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs).

Mirk/Dyrk1B controls ventral spinal cord development via Shh pathway.

Cross-talk between Mirk/Dyrk1B kinase and Sonic hedgehog (Shh)/Gli pathway affects physiology and pathology. Here, we reveal a novel role for Dyrk1B in regulating ventral progenitor and neuron subtypes in the embryonic chick spinal cord (SC) via the Shh pathway. Using in ovo gain-and-loss-of-function approaches at E2, we report that Dyrk1B affects the proliferation and differentiation of neuronal progenitors at E4 and impacts on apoptosis specifically in the motor neuron (MN) domain.

Mitochondrial p38 Mitogen-Activated Protein Kinase: Insights into Its Regulation of and Role in LONP1-Deficient Nematodes.

p38 Mitogen-Activated Protein Kinase (MAPK) cascades are central regulators of numerous physiological cellular processes, including stress response signaling. In , mitochondrial dysfunction activates a PMK-3/p38 MAPK signaling pathway (MAPK), but its functional role still remains elusive. Here, we demonstrate the induction of MAPK in worms deficient in the gene, which encodes the worm ortholog of mammalian mitochondrial LonP1.

Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways.

Objectives: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients.

Methods: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed.