IRE1β evolves to be a guardian of respiratory and gastrointestinal mucosa.

Inositol-requiring enzyme 1 (IRE1), a mediator of the unfolded protein response, shows the highest degree of evolutionary conservation. Vertebrates express two IRE1 paralogs: IRE1α, which is universally expressed and IRE1β, which shows specific expression within mucus secreted cells in respiratory and gastrointestinal tracts. The biological properties and regulation of the two IRE1 duplicates show evolutionary differences.

Investigating the impact of empagliflozin on the retina of diabetic mice.

Background: Diabetic retinopathy (DR) frequently results in compromised visual function, with hyperglycemia-induced disruption of the blood-retinal barrier (BRB) through various pathways as a critical mechanism. Existing DR treatments fail to address early and potentially reversible microvascular alterations. This study examined the effects of empagliflozin (EMPA), a selective Sodium-glucose transporter 2 (SGLT2) inhibitor, on the retina of db/db mice.

Progress in the treatment of diabetic cardiomyopathy, a systematic review.

Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis.

UFMylation of HRD1 regulates endoplasmic reticulum homeostasis.

Ubiquitin fold modifier 1 is a small ubiquitin-like protein modifier that is essential for embryonic development of metazoans. Although UFMylation has been connected to endoplasmic reticulum homeostasis, the underlying mechanisms and the relevant cellular targets are largely unknown. Here, we show that HRD1, a ubiquitin ligase of ER-associated protein degradation (ERAD), is a novel substrate of UFM1 conjugation.

Cardioprotective and anti-inflammatory effects of Caveolin 1 in experimental diabetic cardiomyopathy.

Previous studies of the Caveolin 1 (Cav1) protein and caveolae, which are lipid raft structures found on the plasma membranes of certain cells, are associated with fat metabolism disorders, inflammation, diabetes, and cardiovascular disease. However, there have been no reports linking Cav1 to diabetic cardiomyopathy (DCM). In the present study, we established a relationship between Cav1 and the development of DCM.

The ubiquitination of CKIP-1 mediated by Src aggravates diabetic renal fibrosis (original article).

Renal chronic inflammation is an important hallmark of diabetic renal fibrosis. Casein kinase 2 interacting protein 1 (CKIP-1) performs a nephroprotective role in the pathogenesis of diabetic nephropathy (DN), which is dramatically decreased in diabetic kidneys. However, whether CKIP-1 regulates inflammation to ameliorate renal fibrosis remains unclear and it is interesting to clarify the degradation mechanism of CKIP-1.

The effects of different stress on intestinal mucosal barrier and intestinal microecology were discussed based on three typical animal models.

Recent studies have revealed that the effect of intestinal microecological disorders on organismal physiology is not limited to the digestive system, which provides new perspectives for microecological studies and new ideas for clinical diagnosis and prevention of microecology-related diseases. Stress triggers impairment of intestinal mucosal barrier function, which could be duplicated by animal models. In this paper, pathological animal models with high prevalence and typical stressors-corresponding to three major stressors of external environmental factors, internal environmental factors, and social psychological factors, respectively exemplified by burns, intestinal ischemia-reperfusion injury (IIRI), and depression models-were selected.

Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway.

Objective: To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs).

Methods: The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control.

Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway.

Purpose: Chronic inflammation plays a key role in the pathogenesis of various diseases such as diabetic nephropathy (DN). Resveratrol (RSV), a natural polyphenol, has been proven to have renoprotective effects. In this study, we used a lipopolysaccharide (LPS)-induced rat glomerular mesangial cells (RMCs) model, to elucidate the renoprotective effect of RSV on sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1P2)/NF-κB activation and the expression of downstream inflammatory mediators, such as intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and fibronectin (FN) protein expression in RMCs.

Mean arterial pressure is associated with the neurological function in patients who survived after cardiopulmonary resuscitation: A retrospective cohort study.

Background: About 18% to 40% of the survivors have moderate to severe neurological dysfunction. At present, studies on mean arterial pressure (MAP) and neurological function of patients survived after cardiopulmonary resuscitation (CPR) are limited and conflicted.

Hypothesis: The higher the MAP of the patient who survived after CPR, the better the neurological function.

Progestin and AdipoQ Receptor 3 Upregulates Fibronectin and Intercellular Adhesion Molecule-1 in Glomerular Mesangial Cells Activating NF-κB Signaling Pathway Under High Glucose Conditions.

Background: Progestin and adipoQ receptor 3 (PAQR3), is a Golgi-anchored membrane protein containing seven transmembrane helices. It has been demonstrated that PAQR3 mediates insulin resistance, glucose and lipid metabolism, and inflammation. In addition, kidney inflammatory fibrosis is an important pathological feature of diabetic nephropathy (DN).

Paeonol Ameliorates Diabetic Renal Fibrosis Through Promoting the Activation of the Nrf2/ARE Pathway via Up-Regulating Sirt1.

Diabetic nephropathy (DN) is rapidly becoming the leading cause of end-stage renal disease worldwide and a major cause of morbidity and mortality in patients of diabetes. The main pathological change of DN is renal fibrosis. Paeonol (PA), a single phenolic compound extracted from the root bark of Cortex Moutan, has been demonstrated to have many potential pharmacological activities.

CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys.

Our previous study indicated that Casein kinase 2 interacting protein-1 (CKIP-1) could promote the activation of the nuclear factor E2-related factor 2 (Nrf2)/ antioxidant response element (ARE) pathway, playing a significant role in inhibiting the fibrosis of diabetic nephropathy (DN). However, the underlying mechanism is still unknown. Here, we investigated whether CKIP-1 affects the polyubiquitination of Nrf2 and its cytosolic inhibitor kelch like ECH-associated protein 1 (Keap1) via mediating Smad ubiquitylation regulatory factor-1 (Smurf1) to promote the activation of the Nrf2/ARE signaling and resist high glucose (HG)-induced renal fibrosis in glomerular mesangial cells (GMCs) and diabetic mice kidneys.

CK2α promotes advanced glycation end products-induced expressions of fibronectin and intercellular adhesion molecule-1 via activating MRTF-A in glomerular mesangial cells.

Advanced glycation end products' (AGEs) modification of extracellular matrix proteins induces crosslinking, which results in thickening of the basement membrane and activating several intracellular signaling cascades, eventually promoting the pathological progression of diabetic nephropathy (DN). We have previously confirmed that casein kinase 2α (CK2α) activates the nuclear factor of kappaB (NF-κB) signaling pathway to enhance high glucose-induced expressions of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1) in glomerular mesangial cells (GMCs). However, to date, the mechanism by which CK2α regulates diabetic renal fibrosis is not fully understood.

Sphingosine kinase 1 mediates diabetic renal fibrosis via NF-κB signaling pathway: involvement of CK2α.

Sphingosine kinase 1 (SphK1) plays a pivotal role in regulating diabetic renal fibrotic factors such as fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1). Especially, activation of SphK1 is closely linked to the body inflammatory reaction. Casein kinase 2α subunit (CK2α), a protein kinase related to inflammatory reaction, influences diabetic renal fibrosis and expressions of FN and ICAM-1 via NF-κB pathway.

Sphingosine kinase 1 mediates AGEs-induced fibronectin upregulation in diabetic nephropathy.

Unlabelled: Activation of sphingosine kinase 1 (SphK1) signaling pathway mediates fibronectin (FN) upregulation in glomerular mesangial cells (GMCs) under high glucose (HG) condition. However, the roles of SphK1 in advanced glycation end products (AGEs)-induced DN have not been elucidated. Here we show that AGEs upregulated FN and SphK1 and SphK1 activity.

MRTF-A mediated FN and ICAM-1 expression in AGEs-induced rat glomerular mesangial cells via activating STAT5.

Advanced glycation end products (AGEs), formed at an accelerated rate under diabetes, play a role in inflammation and fibrosis in mesangial areas in diabetic nephropathy (DN). However, the transcriptional modulator that mediates the cellular response to AGEs remains largely obscure. Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, was responsible for the glomerular mesangial cells (GMCs) injury by AGEs, and, if so, how MRTF-A promoted mesangial dysfunction initiated by AGEs.

Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating CKIP-1 to resist HG-induced up-regulation of FN and ICAM-1 in GMCs and diabetic mice kidneys.

Our previous study indicated that Casein kinase 2 interacting protein-1 (CKIP-1) could promote the activation of the nuclear factor E2-related factor 2 (Nrf2)/ antioxidant response element (ARE) pathway, playing a significant role in inhibiting the fibrosis of diabetic nephropathy (DN). Polydatin (PD) has been shown to possess strong resistance effects on renal fibrosis which is closely related to activating the Nrf2/ARE pathway, too. Whereas, whether PD could resist DN through regulating CKIP-1 and consequently promoting the activation of Nrf2-ARE pathway needs further investigation.

Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway.

Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis.

Emodin self-emulsifying platform ameliorates the expression of FN, ICAM-1 and TGF-β1 in AGEs-induced glomerular mesangial cells by promoting absorption.

Emodin, a potential anti-diabetic nephropathy agent, is limited by its oral use due to the poor water solubility. The present study aimed to enhance the absorption and the suppressive effects of emodin on renal fibrosis by developing a self-microemulsifying drug delivery system (SMEDDS). Solubility studies, compatibility tests, pseudo-ternary phase diagrams analysis and central composite design were carried out to obtain the optimized formulation.

Connexin43 regulates high glucose-induced expression of fibronectin, ICAM-1 and TGF-β1 via Nrf2/ARE pathway in glomerular mesangial cells.

Nrf2/ARE signaling pathway is a crucial cellular defense system to cope with oxidative stress, which is adaptively activated, in diabetic condition that is not efficient enough to resist the oxidative stress provoked by hyperglycemia. We have previously demonstrated that Connexin43 (Cx43) attenuates renal fibrosis through c-Src. However, the underlying mechanisms need to be further clarified.

CKIP-1 ameliorates high glucose-induced expression of fibronectin and intercellular cell adhesion molecule-1 by activating the Nrf2/ARE pathway in glomerular mesangial cells.

Glucose and lipid metabolism disorders as well as oxidative stress (OSS) play important roles in diabetic nephropathy (DN). Glucose and lipid metabolic dysfunctions are the basic pathological changes of chronic microvascular complications of diabetes mellitus, such as DN. OSS can lead to the accumulation of extracellular matrix and inflammatory factors which will accelerate the progress of DN.