Thymic Innervation Impairment in Experimental Autoimmune Encephalomyelitis.

Introduction: The thymus is the primary lymphoid organ responsible for normal T-cell development. Yet, in abnormal metabolic conditions as well as an acute infection, the organ exhibits morphological and cellular alterations. It is well established that the immune system is in a tidy connection and dependent on the central nervous system (CNS), which regulates thymic function by means of innervation and neurotransmitters.

Vertical sleeve gastrectomy improves glucose-insulin homeostasis by enhancing β-cell function and survival via FGF15/19.

Vertical sleeve gastrectomy (VSG) restores glucose homeostasis in obese mice and humans. In addition, the increased fibroblast growth factor (FGF)15/19 circulating level postsurgery has been implicated in this effect. However, the impact of FGF15/19 on pancreatic islets remains unclear.

Antioxidant effects of LEDT in dystrophic muscle cells: involvement of PGC-1α and UCP-3 pathways.

Purpose: Reactive oxygen species and mitochondrial dysfunction play a crucial role in the pathophysiology of Duchenne muscular dystrophy (DMD). The light-emitting diode therapy (LEDT) showed beneficial effects on the dystrophic muscles. However, the mechanisms of this therapy influence the molecular pathways in the dystrophic muscles, particularly related to antioxidant effects, which still needs to be elucidated.

Endocrine FGFs and their signaling in the brain: Relevance for energy homeostasis.

Since their discovery in 2000, there has been a continuous expansion of studies investigating the physiology, biochemistry, and pharmacology of endocrine fibroblast growth factors (FGFs). FGF19, FGF21, and FGF23 comprise a subfamily with attributes that distinguish them from typical FGFs, as they can act as hormones and are, therefore, referred to as endocrine FGFs. As they participate in a broad cross-organ endocrine signaling axis, endocrine FGFs are crucial lipidic, glycemic, and energetic metabolism regulators during energy availability fluctuations.

Association between protein undernutrition and diabetes: Molecular implications in the reduction of insulin secretion.

Undernutrition is still a recurring nutritional problem in low and middle-income countries. It is directly associated with the social and economic sphere, but it can also negatively impact the health of the population. In this sense, it is believed that undernourished individuals may be more susceptible to the development of non-communicable diseases, such as diabetes mellitus, throughout life.

Hypothalamic free fatty acid receptor-1 regulates whole-body energy balance.

Objective: Free fatty acid receptor-1 (FFAR1) is a medium- and long-chain fatty acid sensing G protein-coupled receptor that is highly expressed in the hypothalamus. Here, we investigated the central role of FFAR1 on energy balance.

Methods: Central FFAR1 agonism and virogenic knockdown were performed in mice.

A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection.

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage.

CETP Expression in Bone-Marrow-Derived Cells Reduces the Inflammatory Features of Atherosclerosis in Hypercholesterolemic Mice.

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of an increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL-receptor-deficient mice.

Physical exercise elicits UPR in the skeletal muscle: The role of c-Jun N-terminal kinase.

Objective: The mitochondrial unfolded protein response (UPR) is an adaptive cellular response to stress to ensure mitochondrial proteostasis and function. Here we explore the capacity of physical exercise to induce UPR in the skeletal muscle.

Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinformatics analyses.

LED therapy plus idebenone treatment targeting calcium and mitochondrial signaling pathways in dystrophic muscle cells.

Intracellular calcium dysregulation, oxidative stress, and mitochondrial dysfunction are some of the main pathway contributors towards disease progression in Duchenne muscular dystrophy (DMD). This study is aimed at investigating the effects of light emitting diode therapy (LEDT) and idebenone antioxidant treatment, applied alone or together in dystrophic primary muscle cells from mdx mice, the experimental model of DMD. Mdx primary muscle cells were submitted to LEDT and idebenone treatment and evaluated for cytotoxic effects and calcium and mitochondrial signaling pathways.

Hypothalamic α7 nicotinic acetylcholine receptor (α7nAChR) is downregulated by TNFα-induced Let-7 overexpression driven by fatty acids.

The α7nAChR is crucial to the anti-inflammatory reflex, and to the expression of neuropeptides that control food intake, but its expression can be decreased by environmental factors. We aimed to investigate whether microRNA modulation could be an underlying mechanism in the α7nAchR downregulation in mouse hypothalamus following a short-term exposure to an obesogenic diet. Bioinformatic analysis revealed Let-7 microRNAs as candidates to regulate Chrna7, which was confirmed by the luciferase assay.

SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood.

A nitroalkene derivative of salicylate alleviates diet-induced obesity by activating creatine metabolism and non-shivering thermogenesis.

Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethenyl)salicylic acid (SANA), a molecule with unprecedented beneficial effects in diet-induced obesity (DIO).

The early impact of diets enriched with saturated and unsaturated fatty acids on intestinal inflammation and tight junctions.

The gut has been suggested as the first organ to be affected by unbalanced diets contributing to the obesogenic process. This study aimed to test a short time-course exposition model to a known pro- or anti-inflammatory enriched fatty diet to understand the early gut alterations. Male mice were exposed to the chow diet (CT), high-fat (HF) diet, or a high-fat diet partially replaced on flaxseed oil (FS), rich in omega-3 (ω3), for 14 days.

Butyrate restores the fat/lean mass ratio balance and energy metabolism and reinforces the tight junction-mediated intestinal epithelial barrier in prediabetic mice independently of its anti-inflammatory and epigenetic actions.

Tissue/cellular actions of butyrate on energy metabolism and intestinal barrier in normal metabolic conditions or prediabetes are still unclear. In this work, we investigated the beneficial effect of dietary supplementation with sodium butyrate on energy metabolism, body mass composition, and intestinal epithelial barrier mediated by tight junction (TJ) in chow diet-fed normal and high-fat diet (HF)-fed prediabetic mice, considering the well-known butyrate action as an epigenetic and inflammatory regulator. Butyrate significantly reduced the fat/lean mass ratio, slightly ameliorated dyslipidemia, restored oral glucose tolerance, and increased basal energy expenditure in prediabetic HF-fed mice but had no effect on control animals.

Dopaminergic modulation by quercetin: In silico and in vivo evidence using Caenorhabditis elegans as a model.

Quercetin is a flavonol widely distributed in plants and has various described biological functions. Several studies have reported on its ability to restore neuronal function in a wide variety of disease models, including animal models of neurodegenerative disorders such as Parkinson's disease. Quercetin per se can act as a neuroprotector/neuromodulator, especially in diseases related to impaired dopaminergic neurotransmission.

The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s.

Hypusine amino acid [N-(4-amino-2-hydroxybutyl)-lysine] was first isolated in 1971 from bovine brain extracts. Hypusine originates from a post-translational modification at the eukaryotic translation initiation factor 5A (eIF5A), a protein produced by archaebacteria and eukaryotes. The eIF5A protein is the only one described containing the hypusine residue, which is essential for its activity.

The Transcriptomic Landscape of Age-Induced Changes in Human Visceral Fat and the Predicted Omentum-Liver Connectome in Males.

Aging causes alterations in body composition. Specifically, visceral fat mass increases with age and is associated with age-related diseases. The pathogenic potential of visceral fat accumulation has been associated with its anatomical location and metabolic activity.

Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging.

Disruption of mitochondrial function and protein homeostasis plays a central role in aging. However, how these processes interact and what governs their failure in aging remain poorly understood. Here, we showed that ceramide biosynthesis controls the decline in mitochondrial and protein homeostasis during muscle aging.

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production.

Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium.

Background: The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans.

Interaction between poly(A)-binding protein PABPC4 and nuclear receptor corepressor NCoR1 modulates a metabolic stress response.

Mitochondria are organelles known primarily for generating ATP via the oxidative phosphorylation process. Environmental signals are sensed by whole organisms or cells and markedly affect this process, leading to alterations in gene transcription and, consequently, changes in mitochondrial function and biogenesis. The expression of mitochondrial genes is finely regulated by nuclear transcription factors, including nuclear receptors and their coregulators.