Gut microbiome and clinical and lifestyle host factors associated with recurrent positive RT-PCR for SARS-CoV-2.

Background: SARS-CoV-2 and COVID-19 are still active in the population. Some patients remained PCR-positive for more than 4 weeks, called "persistently PCR-positive". Recent evidence suggests a link between the gut microbiota and susceptibility to COVID-19, although no studies have explored persistent PCR conditions.

A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure.

Study Question: Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility?

Summary Answer: Our findings revealed a significant association between SPGF and the gene and identified three novel genes (, , and ) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition.

What Is Known Already: SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants.

Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke.

Ischemic stroke is the result of a permanent or transient occlusion of a brain artery, leading to irreversible tissue injury and long-term sequelae. Despite ongoing advancements in revascularization techniques, stroke remains the second leading cause of death worldwide. A comprehensive understanding of the complex and interconnected mechanisms, along with the endogenous mediators that modulate stroke responses is essential for the development of effective interventions.

Beyond wrecking a wall: revisiting the concept of blood-brain barrier breakdown in ischemic stroke.

The blood-brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation. It tightly modulates the ion transport and nutrient influx, while restricting the entry of harmful factors, and selectively limiting the migration of immune cells, thereby maintaining brain homeostasis. Despite the well-established association between blood-brain barrier disruption and most neurodegenerative/neuroinflammatory diseases, much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.

A Novel Plant-Based Nutraceutical Combined with Exercise Can Revert Oxidative Status in Plasma and Liver in a Diet-Induced-Obesity Animal Model.

The prevalence of obesity increases alarmingly every year mostly due to external factors such as high-fat and high-refined sugar intake associated with a sedentary lifestyle. It triggers metabolic disorders such as insulin resistance, hyperlipemia, non-alcoholic fatty liver disease, chronic inflammation, oxidative stress, and gut microbiota dysbiosis. The aim of this study was to evaluate the beneficial effects of a combined intervention with caloric restriction, nutraceutical intake, and a mixed training protocol on oxidative stress, inflammation, and gut dysbiosis derived from the development of obesity in a C57BL6/J mouse experimental model of diet-induced obesity (4.

Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice.

Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown that resveratrol (RSV) is a promising molecule that can mitigate PARP1 overactivity, but its low bioavailability is a limitation for medical use. This study examined the impact of a synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), in the 661W cell line against HO oxidative stress and in rd10 mice.

Exploring the Microbiome in Human Reproductive Tract: High-Throughput Methods for the Taxonomic Characterization of Microorganisms.

Microorganisms are important due to their widespread presence and multifaceted roles across various domains of life, ecology, and industries. In humans, they underlie the proper functioning of multiple systems crucial to well-being, including immunological and metabolic functions. Emerging research addressing the presence and roles of microorganisms within human reproduction is increasingly relevant.

Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there is an urgent need to develop innovative approaches that target multifactorial underlying causes to potentially prevent or limit disease progression.

A holistic approach to understanding immune-mediated inflammatory diseases: bioinformatic tools to integrate omics data.

Immune-mediated inflammatory diseases (IMIDs) comprise a complex group of pathologies with diverse etiologies and clinical manifestations. In particular, omics technologies have remodeled our understanding of a set of IMIDs such as systemic autoimmune rheumatic diseases (SARDs), generating vast amounts of data on the genome, epigenome, transcriptome, proteome and metabolome of immune cells and SARDs patients. However, the integration of omics data to advance our knowledge of these diseases is challenging, requiring advanced bioinformatic tools.

Comparative Analysis of the Physicochemical and Biological Characteristics of Freeze-Dried PEGylated Cationic Solid Lipid Nanoparticles.

Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs).

Single-cell transcriptomic profiling reveals a pathogenic role of cytotoxic CD4 T cells in giant cell arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis mediated by an aberrant immunological response against the blood vessel wall. Although the pathogenic mechanisms that drive GCA have not yet been elucidated, there is strong evidence that CD4 T cells are key drivers of the inflammatory process occurring in this vasculitis. The aim of this study was to further delineate the role of CD4 T cells in GCA by applying single-cell RNA sequencing and T cell receptor (TCR) repertoire profiling to 114.

Novel Therapeutic Opportunities for Neurodegenerative Diseases with Mesenchymal Stem Cells: The Focus on Modulating the Blood-Brain Barrier.

Neurodegenerative disorders encompass a broad spectrum of profoundly disabling situations that impact millions of individuals globally. While their underlying causes and pathophysiology display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, is a common feature among them. Consequently, targeting the BBB has emerged as an innovative therapeutic strategy for addressing neurological disorders.

Inflammasomes NLRP3 and AIM2 in peri-implantitis: A cross-sectional study.

Background: Inflammasome components NLRP3 and AIM2 contribute to inflammation development by the activation of caspase-1 and IL-1β. They have not been yet evaluated in samples from patients with active peri-implantitis. Thus, the aim of the present study is to analyze the expression of inflammasomes NLRP3 and AIM2 and subsequent caspase 1 and IL-1β assessing the microenvironment of leukocyte subsets in samples from patients with active peri-implantitis.

Explainable artificial intelligence to predict and identify prostate cancer tissue by gene expression.

Background And Objective: Prostate cancer is one of the most prevalent forms of cancer in men worldwide. Traditional screening strategies such as serum PSA levels, which are not necessarily cancer-specific, or digital rectal exams, which are often inconclusive, are still the screening methods used for the disease. Some studies have focused on identifying biomarkers of the disease but none have been reported for diagnosis in routine clinical practice and few studies have provided tools to assist the pathologist in the decision-making process when analyzing prostate tissue.

Therapeutic Effect of a Latent Form of Cortistatin in Experimental Inflammatory and Fibrotic Disorders.

Cortistatin is a cyclic neuropeptide that recently emerged as an attractive therapeutic factor for treating inflammatory, autoimmune, fibrotic, and pain disorders. Despite of its efficiency and apparent safety in experimental preclinical models, its short half-life in body fluids and its potential pleiotropic effects, due to its promiscuity for several receptors expressed in various cells and tissues, represent two major drawbacks for the clinical translation of cortistatin-based therapies. Therefore, the design of new strategies focused on increasing the stability, bioavailability, and target specificity of cortistatin are lately demanded by the industry.

Comparison of Metagenomics and Metatranscriptomics Tools: A Guide to Making the Right Choice.

The study of microorganisms is a field of great interest due to their environmental (e.g., soil contamination) and biomedical (e.