Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium.

Impact of Curcumin on the IL-17A-Mediated p53-Fibrinolytic System: Mouse Proteomics and Integrated Human Fibrosis scRNAseq Insights.

Acute lung injury (ALI) is primarily driven by an intense inflammation in the alveolar epithelium. Key to this is the pro-inflammatory cytokine, Interleukin 17 (IL-17), which influences pulmonary immunity and modifies p53 function. The direct role of IL-17A in p53-fibrinolytic system is still unclear, it is important to evaluate this mechanism to regulate the ALI progression to idiopathic pulmonary fibrosis (IPF).

CD201 fascia progenitors choreograph injury repair.

Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation. Here we identify a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using skin injury models in mice, single-cell transcriptomics and genetic lineage tracing, ablation and gene deletion models, we demonstrate that CD201 progenitors control the pace of wound healing by generating multiple specialized cell types, from proinflammatory fibroblasts to myofibroblasts, in a spatiotemporally tuned sequence.

Neutrophils direct preexisting matrix to initiate repair in damaged tissues.

Internal organs heal injuries with new connective tissue, but the cellular and molecular events of this process remain obscure. By tagging extracellular matrix around the mesothelium lining in mouse peritoneum, liver and cecum, here we show that preexisting matrix was transferred across organs into wounds in various injury models. Using proteomics, genetic lineage-tracing and selective injury in juxtaposed organs, we found that the tissue of origin for the transferred matrix likely dictated the scarring or regeneration of the healing tissue.

RNA-Seq of Single Fish Cells - Seeking Out the Leukocytes Mediating Immunity in Teleost Fishes.

The immune system is a complex and sophisticated biological system, spanning multiple levels of complexity, from the molecular level to that of tissue. Our current understanding of its function and complexity, of the heterogeneity of leukocytes, is a result of decades of concentrated efforts to delineate cellular markers using conventional methods of antibody screening and antigen identification. In mammalian models, this led to in-depth understanding of individual leukocyte subsets, their phenotypes, and their roles in health and disease.

Grape Seed Flour Extends Longevity by Improving Multi-Organ Dysfunction and Age-Associated Oxidative Stress and Inflammation in Healthy Rat.

According to the free-radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout life span leads to impairment of the main biological macromolecules as DNA, lipids, and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains a high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anticarcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective.

Protective effect of grape seed extract and orlistat co-treatment against stroke: Effect on oxidative stress and energy failure.

Ischemic stroke is a major health concern and a leading cause of mortality worldwide. Oxidative stress is an early event in the course of stroke inducing neuro-inflammation and cell death. Grape seed extract (GSE) is a natural phytochemical mixture exhibiting antioxidant, anti-inflammatory and neuroprotective properties.

Protective effect of (Xenical+GSF) against I/R-induced blood brain barrier disruption, ionic edema, lipid deregulation and neuroinflammation.

Ischemic stroke is a leading cause of mortality worldwide that occurs following the reduction or interruption of blood brain supply, characterized by a cascade of early events as oxidative stress and ensuing neuro-inflammation, energy failure and the burst of intracellular Ca++ resulting in activation of phospholipases and large increase in FFA including arachidonic acid, ultimately leading to nervous cell death. Grape Seed Flour (GSF) is a complex polyphenolic mixture harboring antioxidant, anti-inflammatory and neuroprotective properties. Orlistat (Xenical ™,Xe) is a gastro-intestinal lipase inhibitor and an anti-obesity agent.

Alleviation of drought stress in faba bean ( L.) by exogenous application of β-aminobutyric acid (BABA).

Drought stress is one of the most prevalent environmental factors limiting faba bean ( L.) crop productivity. β-aminobutyric acid (BABA) is a non-protein amino acid that may be involved in the regulation of plant adaptation to drought stress.

Preventive and curative effects of grape seed powder on stroke using in vitro and in vivo models of cerebral ischemia/reperfusion.

Stroke is a worldwide concern. Many studies pointed out relevant preventive effect of grape seed powder (GSP) against deleterious brain ischemia/reperfusion (I/R) injury, but curative effect has been scarcely approached. The present work aimed at studying the preventive and curative effect of GSP against stroke using in-vitro and in-vivo models.

Neuroprotective effect of grape seed extract on brain ischemia: a proteomic approach.

Stroke is one of the leading causes of long-lasting disability in human and oxidative stress an important underlying cause. Molecular insights into pathophysiology of ischemic stroke are still obscure, and the present study investigated the protective effect of high dosage Grape Seed Extract (GSE 2.5 g/kg) on brain ischemia-reperfusion (I/R) injury using a proteomic approach.

Characterization, anti-oxidative effect of grape seed powder and in silico affinity profiling of polyphenolic and extra-phenolic compounds for calpain inhibition.

Vitis vinifera grape is a highly cultivated crop and solid wastes generated by the wine industry are largely under exploited. Plentiful studies have intended analyzing the polyphenolic content of grape seeds but characterization of non phenolic compounds is rather scarce. The present study aimed at the selective extraction of lipid, phenolic and aqueous phases from grape seed powder (GSP) in order to establish their intimate composition, as well as their antioxidant and chelating properties underlying partly their biological effects.

Protective effect of grape seed and skin extract against high-fat diet-induced dyshomeostasis of energetic metabolism in rat lung.

Background: Obesity is currently one of the major epidemics of this millennium and affects poeples throughout the world. It causes multiple systemic complications as it significantly interferes with respiratory function.

Objective: We aimed in the present work to study the effect of high fat diet (HFD) on lung oxidative stress and energy metabolism alterations, as well as the putative protection afforded by grape seed and skin extract (GSSE).

Protective effects of grape seed and skin extract against high-fat-diet-induced lipotoxicity in rat lung.

Background: Obesity is a public health problem characterized by increased fat accumulation in different tissues. Obesity is directly linked to breathing problems and medical complications with lung, including obstructive sleep apnea syndrome, obesity hypoventilation syndrome, chronic obstructive pulmonary disease, asthma….In the present work, we aimed to investigate the effect of high fat diet (HFD) on lung lipotoxicity, oxidative stress, fatty acid composition and proportions in lung and implication in asthma development.

Brain proteomic modifications associated to protective effect of grape extract in a murine model of obesity.

In recent years, the obesity epidemic has developed into a major health crisis worldwide. With current treatments limited to expensive, high-risk surgery and minimally efficacious pharmacotherapy, new therapeutic options are urgently needed to fight against this alarming trend. Though brain dysfunction has been studied linked to high fat diet (HFD) and grape seed and skin extract (GSSE) correction, the proteomic modifications linking the two effects on brain lipotoxicity are not well understood.

Dietary supplementation of grape seed and skin flour mitigates brain oxidative damage induced by a high-fat diet in rat: Gender dependency.

It is unknown whether gender has an impact on brain injury in obesity, and, if so, whether treatment with grape seed and skin flour could exert a protective effect. Both male and female rats were fed a standard diet (SD) or a high fat diet (HFD) during eight weeks and treated with high dosage grape seed and skin flour (GSSF). Fat-induced oxidative stress was evaluated into the brain with a special emphasis on transition metals determination.

Grape seed and skin extract protects kidney from doxorubicin-induced oxidative injury.

The study investigated the protective effect of grape seed and skin extract (GSSE) against doxorubicin-induced renal toxicity in healthy rats. Animals were treated with GSSE or not (control), for 8 days, administered with doxorubicin (20mg/kg) in the 4th day, and renal function as well as oxidative stress parameters were evaluated. Data showed that doxorubicin induced renal toxicity by affecting renal architecture and plasma creatinine.

Protective effect of grape seed and skin extract on cerebral ischemia in rat: implication of transition metals.

Ischemic stroke is a leading cause of long lasting disability in humans and oxidative stress an important underlying cause. The present study aims to determine the effect of short term (seven-days) administration of high dosage grape seed and skin extract (GSSE 2.5 g/kg) on ischemia/reperfusion (I/R) injury in a rat model of global ischemia.