Network pharmacology, molecular docking, and experimental verification reveal the mechanism of Yi-Shen-Hua-Shi granules treating acute kidney injury.

Ethnopharmacological Relevance: Yi-Shen-Hua-Shi granules (YSHSG) have been shown to improve kidney function in various renal disorders, which are characterized by the sudden decline and impairment of kidney function.

Aim Of The Study: To investigate the precise mechanisms and targets of YSHSG in combating sepsis-induced AKI.

Materials And Methods: Through network pharmacology, the active ingredients, main target proteins, and related signaling pathways of YSHSG in the treatment of sepsis-induced AKI were predicted.

" philosophy" for the design of anticancer drug delivery nanoparticles.

Understanding the in vivo transport process provides guidelines for designing ideal nanoparticles (NPs) with higher efficacy and fewer off-target effects. Many factors, such as particle size, morphology, surface potential, structural stability, and etc., may influence the delivering process of NPs due to the existence of various physiological barriers within the body.

Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice.

Objectives: The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle knockout () mice.

Methods: The mice and littermate () mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle.

Single-cell RNA sequencing and ATAC sequencing identify novel biomarkers for bicuspid aortic valve-associated thoracic aortic aneurysm.

Introduction: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiovascular defect and known to cause thoracic aortic aneurysms (TAAs). To improve our understanding of BAV pathogenesis, we characterized the cellular composition of BAV tissues and identified molecular changes in each cell population.

Methods: Tissue samples from two patients with BAV and two heart transplant donors were analyzed using single-cell RNA sequencing, assay for transposase-accessible chromatin using sequencing, and weighted gene coexpression network analysis for differential gene analysis.

LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans.

Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C.

Investigation of a UPR-Related Gene Signature Identifies the Pro-Fibrotic Effects of Thrombospondin-1 by Activating CD47/ROS/Endoplasmic Reticulum Stress Pathway in Lung Fibroblasts.

Unfolded protein response (UPR) signaling and endoplasmic reticulum (ER) stress have been linked to pulmonary fibrosis. However, the relationship between UPR status and pulmonary function and prognosis in idiopathic pulmonary fibrosis (IPF) patients remains largely unknown. Through a series of bioinformatics analyses, we established a correlation between UPR status and pulmonary function in IPF patients.

Reduced hydrogen sulfide production contributes to adrenal insufficiency induced by hypoxia via modulation of NLRP3 inflammasome activation.

Adrenocortical responsiveness is critical for maintaining glucocorticoids production and homeostasis during stress. We sought to investigate adrenocortical responsiveness during hypoxia in mice and the mechanisms responsible for the regulation of adrenal responsiveness. (1) Adult male WT mice were randomly divided into four groups: normoxia, hypoxia (24h), hypoxia (72h), hypoxia (72h) + GYY4137(hydrogen sulfide (HS) donor, 133mmol/kg/day); (2) WT mice were randomly divided into four groups: sham, adrenalectomy (ADX), sham+hypoxia, ADX+hypoxia; (3) mice were randomly divided into two groups: , +GYY4137.

Resveratrol alleviates acute lung injury through regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in a cecal ligation and puncture model.

Sepsis is considered as a life-threatening organ dysfunction caused by a dysregulated response of the host to an infection. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition, and is the type of organ injury that is most commonly induced by sepsis. Resveratrol (RSV) has been shown to exert a wide range of therapeutic effects due to its anti-inflammatory and anti-oxidant properties.

Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes.

Hydrogen sulfide (HS) is naturally synthesized in a wide range of mammalian tissues. Whether HS is involved in the regulation of erythrocyte functions remains unknown. Using mice with a genetic deficiency in a HS natural synthesis enzyme cystathionine--lyase (CSE) and high-throughput metabolomic profiling, we found that levels of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), an erythroid-specific metabolite negatively regulating hemoglobin- (Hb-) oxygen (O) binding affinity, were increased in CSE knockout ( ) mice under normoxia.

NLRP3 inflammasome-dependent pyroptosis and apoptosis in hippocampus neurons mediates depressive-like behavior in diabetic mice.

A relatively large number of diabetic patients risk complications of clinical depression that lead to poorer quality of life, however the precise mechanisms for diabetes-associated depression are not fully understood. Links between hyperglycemia-induced oxidative stress and NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation have been reported in the pathogenesis of diabetes. The present study aimed to elucidate the contribution of NLRP3-mediated apoptotic/pyroptotic neuronal cell death to diabetes-associated depression.

[Construction of transgenic mice with specific Cre recombinase expression in the zona fasciculata in adrenal cortex].

The adrenal gland is an important endocrine organ of human body. CYP11B1 gene was specifically expressed in the zona fasciculata in adrenal cortex. In order to better study the function of genes specifically expressed in the zona fasciculata in adrenal cortex, the mice with Cre recombinase specifically expressed in the zona fasciculata in adrenal cortex were constructed.

Endogenous HS resists mitochondria-mediated apoptosis in the adrenal glands via ATP5A1 S-sulfhydration in male mice.

In a previous study, we showed that endogenous hydrogen sulfide (HS) plays a key role in the maintenance of intact adrenal cortex function via the protection of mitochondrial function during endoxemia. We further investigated whether mitochondria-mediated apoptosis is involved in HS protection of adrenal function. LPS treatment resulted in mitochondria-mediated apoptosis in the adrenal glands of male mice, and these effects were prevented by the HS donor GYY4137.

Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior.

Growing evidence suggests that inflammatory processes may be involved in depressive disorders. Inflammation is known to induce mitochondrial dysfunction in the nervous system. However, whether mitochondrial dysfunction is involved in the occurrence of inflammation-induced depressive-like behavior remains to be investigated.

H2S Attenuates LPS-Induced Acute Lung Injury by Reducing Oxidative/Nitrative Stress and Inflammation.

Background: Hydrogen sulfide (H2S), known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI) induced by endotoxemia.

Methods: Male ICR mice were divided in six groups: (1) Control group; (2) GYY4137treatment group; (3) L-NAME treatment group; (4) lipopolysaccharide (LPS) treatment group; (5) LPS with GYY4137 treatment group; and (6) LPS with L-NAME treatment group.

Protein tyrosine phosphatase SHP-1 modulates osteoblast differentiation through direct association with and dephosphorylation of GSK3β.

SHP-1, the Src homology-2 (SH2) domain-containing phosphatase 1, is a cytosolic protein-tyrosine phosphatase (PTP) predominantly expressed in hematopoietic-derived cells. Previous studies have focused on the involvement of SHP-1 in osteoclastogenesis. Using primary cultured mouse fetal calvaria-derived osteoblasts as a model, this study aims to investigate the effects of SHP-1 on differentiation and mineralization of osteoblasts and elucidate the signaling pathways responsible for these effects.

Upregulation of microRNA-22 contributes to myocardial ischemia-reperfusion injury by interfering with the mitochondrial function.

Mitochondrial oxidative damage is critically involved in cardiac ischemia reperfusion (I/R) injury. MicroRNA-22 (miR-22) has been predicted to potentially target sirtuin-1 (Sirt1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), both of which are known to provide protection against mitochondrial oxidative injury. The present study aims to investigate whether miR-22 is involved in the regulation of cardiac I/R injury by regulation of mitochondrial function.

Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress.

We have recently demonstrated that endotoxin causes oxidative stress and overproduction of nitric oxide in adrenal glands, thereby leading to adrenocortical insufficiency. The aim of this study is to investigate the effects of resveratrol, a natural plant polyphenol with anti-oxidant and anti-nitrative properties, on endotoxemia-associated adrenocortical insufficiency. Resveratrol was administered immediately before injection of lipopolysaccharide (LPS).

Rosiglitazone inhibition of calvaria-derived osteoblast differentiation is through both of PPARγ and GPR40 and GSK3β-dependent pathway.

Rosiglitazone (RSG) can cause bone loss, however the mechanisms remain largely unknown. This study aims to investigate the effects of RSG on differentiation and mineralization of osteoblasts using primary cultured mouse fetal calvaria-derived osteoblasts as a model, and elucidate the receptor and signaling pathways responsible for these effects. We found that RSG suppressed the differentiation and mineralization of calvaria-derived osteoblasts.

Overproduction of nitric oxide by endothelial cells and macrophages contributes to mitochondrial oxidative stress in adrenocortical cells and adrenal insufficiency during endotoxemia.

We have recently demonstrated that lipopolysaccharide (LPS) causes mitochondrial oxidative stress and dysfunction in adrenal glands, thereby leading to adrenocortical insufficiency. Since nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) leads to mitochondrial damage in various tissues, the present study aims to investigate whether NO contributes to mitochondrial oxidative stress in adrenal cortex and adrenocortical insufficiency during endotoxemia. Systemic administration of LPS increased iNOS expression and NO production in adrenal glands of mice.

CBS and CSE are critical for maintenance of mitochondrial function and glucocorticoid production in adrenal cortex.

Aims: Mitochondria are known to play a central role in adrenocortical steroidogenesis. Recently, hydrogen sulfide (H2S), a gaseous transmitter endogenously produced by cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE), has been found to improve mitochondrial function. The present study aimed at examining whether CBS and CSE are expressed in adrenal glands, and investigated the role of these enzymes in the maintenance of mitochondrial function and the production of glucocorticoids in adrenocortical cells.