Amino Acid Metabolism and Autophagy in Atherosclerotic Cardiovascular Disease.

Cardiovascular disease is the most common cause of mortality globally, accounting for approximately one out of three deaths. The main underlying pathology is atherosclerosis, a dyslipidemia-driven, chronic inflammatory disease. The interplay between immune cells and non-immune cells is of great importance in the complex process of atherogenesis.

Biological Potential of Extracts: α-Glucosidase and Antibiofilm Activities In Vitro.

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of spp.

Advances in MicroRNA Therapeutics: From Preclinical to Clinical Studies.

MicroRNAs (miRNAs) are crucial regulators of gene expression involved in various pathophysiological processes. Their ability to modulate multiple pathways simultaneously and their involvement in numerous diseases make miRNAs attractive tools and targets in therapeutic development. Significant efforts have been made to advance miRNA research in the preclinical stage, attracting considerable investment from biopharmaceutical companies.

pyTWMR: transcriptome-wide Mendelian randomization in python.

Motivation: Mendelian randomization (MR) is a widely used approach to estimate causal effect of variation in gene expression on complex traits. Among several MR-based algorithms, transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) enables the uses of multiple SNPs as instruments and multiple gene expression traits as exposures to facilitate causal inference in observational studies.

Results: Here we present a Python-based implementation of TWMR and revTWMR.

Fasting induces metabolic switches and spatial redistributions of lipid processing and neuronal interactions in tanycytes.

The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus plays a crucial role in energy balance and glucose homeostasis. It is characterized by a high functional heterogeneity and plasticity, but the underlying molecular mechanisms governing its features are not fully understood. Here, 5481 hypothalamic ependymocytes were cataloged using FACS-assisted scRNAseq from fed, 12h-fasted, and 24h-fasted adult male mice.

OTULIN-related conditions: Report of a new case and review of the literature using GenIA.

OTULIN encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections.

Exploring Asphodelus microcarpus as a source of xanthine oxidase inhibitors: Insights from in silico and in vitro studies.

Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects.

OTULIN-related conditions: Report of a new case and review of the literature using GenIA.

encodes an eponymous linear deubiquitinase (DUB), which through the regulation of M1-Ub dynamics, is essential for controlling inflammation as a negative regulator of the canonical NF-B signaling pathway. Biallelic loss-of-function (LOF) mutations in cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections.

The Antioxidant Drug Edaravone Binds to the Aryl Hydrocarbon Receptor (AHR) and Promotes the Downstream Signaling Pathway Activation.

A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS). Among drugs with free radical scavenging activity and oligodendrocyte protecting effects, Edaravone (Radicava) has recently received increasing attention because of being able to enhance remyelination in experimental in vitro and in vivo disease models. While its beneficial effects are greatly supported by experimental evidence, there is a current paucity of information regarding its mechanism of action and main molecular targets.

Genetic Deficiency of the Long Pentraxin 3 Affects Osteogenesis and Osteoclastogenesis in Homeostatic and Inflammatory Conditions.

The long pentraxin 3 (PTX3) is a soluble glycoprotein made by immune and nonimmune cells endowed with pleiotropic functions in innate immunity, inflammation, and tissue remodeling. PTX3 has recently emerged as a mediator of bone turnover in both physiological and pathological conditions, with direct and indirect effects on osteoblasts and osteoclasts. This notwithstanding, its role in bone biology, with major regard to the osteogenic potential of osteoblasts and their interplay with osteoclasts, is at present unclear.

Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman-Diamond syndrome cells.

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman-Bodian-Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation.

Pairing of single-cell RNA analysis and T cell antigen receptor profiling indicates breakdown of T cell tolerance checkpoints in atherosclerosis.

Atherosclerotic plaques form in the inner layer of arteries triggering heart attacks and strokes. Although T cells have been detected in atherosclerosis, tolerance dysfunction as a disease driver remains unexplored. Here we examine tolerance checkpoints in atherosclerotic plaques, artery tertiary lymphoid organs and lymph nodes in mice burdened by advanced atherosclerosis, via single-cell RNA sequencing paired with T cell antigen receptor sequencing.

Autophagy, innate immunity, and cardiac disease.

Autophagy is an evolutionarily conserved mechanism of cell adaptation to metabolic and environmental stress. It mediates the disposal of protein aggregates and dysfunctional organelles, although non-conventional features have recently emerged to broadly extend the pathophysiological relevance of autophagy. In baseline conditions, basal autophagy critically regulates cardiac homeostasis to preserve structural and functional integrity and protect against cell damage and genomic instability occurring with aging.

Pleiotropic effects of BAFF on the senescence-associated secretome and growth arrest.

Senescent cells release a variety of cytokines, proteases, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Sustained SASP contributes to a pattern of chronic inflammation associated with aging and implicated in many age-related diseases. Here, we investigated the expression and function of the immunomodulatory cytokine BAFF (B-cell activating factor; encoded by the gene), a SASP protein, in multiple senescence models.

The emerging landscape of non-conventional RNA functions in atherosclerosis.

Most of the human genome is transcribed into non-coding RNAs (ncRNAs), which encompass a heterogeneous family of transcripts including microRNAs (miRNAs), long ncRNAs (lncRNAs), circular RNAs (circRNAs), and others. Although the detailed modes of action of some classes are not fully elucidated, the common notion is that ncRNAs contribute to sculpting gene expression of eukaryotic cells at multiple levels. These range from the regulation of chromatin remodeling and transcriptional activity to post-transcriptional regulation of messenger RNA splicing, stability, and decay.

Anti- and Pro-Oxidant Activity of Polyphenols Extracts of Syrah and Chardonnay Grapevine Pomaces on Melanoma Cancer Cells.

The phenolic composition of Syrah and Chardonnay grape pomaces was studied to assess their antioxidant and prooxidant properties. Polyphenols were extracted by a "green" hydroalcoholic solvent (ethanol/water 1:1 /), and a detailed chemical and electrochemical characterization of the phenolic compounds was performed. The antioxidant and prooxidant capacity of the pomace was first studied by cyclic voltammetry (CV) and other reference analytical assays, then with biological tests on B16F10 metastatic melanoma cancer cells.

Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers.

The c.40_42delAGA variant in the phospholamban gene (PLN) has been associated with dilated and arrhythmogenic cardiomyopathy, with up to 70% of carriers experiencing a major cardiac event by age 70. However, there are carriers who remain asymptomatic at older ages.

Quantitative Metabolomics to Explore the Role of Plasma Polyamines in Colorectal Cancer.

Colorectal cancer (CRC) is one of the major public health and socio-economic problems, which management demands the development of non-invasive screening tests. Assessment of circulating polyamines could be a valuable tool, although analytical problems still preclude its clinical practice. We exploited ultra-high-resolution liquid chromatography and mass spectrometry, as a highly sensitive and innovative method, to profile eleven polyamines, including spermine and spermidine with their acetylated forms.

GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation.

Dissecting the pathways regulating the adaptive immune response in atherosclerosis is of particular therapeutic interest. Here we report that the lipid G-protein coupled receptor GPR55 is highly expressed by splenic plasma cells (PC), upregulated in mouse spleens during atherogenesis and human unstable or ruptured compared to stable plaques. -deficient mice developed larger atherosclerotic plaques with increased necrotic core size compared to their corresponding controls.

Targeting the MITF/APAF-1 axis as salvage therapy for MAPK inhibitors in resistant melanoma.

Melanoma is a deadly form of cancer characterized by remarkable therapy resistance. Analyzing the transcriptome of MAPK inhibitor sensitive- and resistant-melanoma, we discovered that APAF-1 is negatively regulated by MITF in resistant tumors. This study identifies the MITF/APAF-1 axis as a molecular driver of MAPK inhibitor resistance.

miR-181a/b downregulation: a mutation-independent therapeutic approach for inherited retinal diseases.

Inherited retinal diseases (IRDs) are a group of diseases whose common landmark is progressive photoreceptor loss. The development of gene-specific therapies for IRDs is hampered by their wide genetic heterogeneity. Mitochondrial dysfunction is proving to constitute one of the key pathogenic events in IRDs; hence, approaches that enhance mitochondrial activities have a promising therapeutic potential for these conditions.