Protein disulfide isomerase is essential for spermatogenesis in mice.

Spermatogenesis requires precise posttranslational control in the endoplasmic reticulum (ER), but the mechanism remains largely unknown. The protein disulfide isomerase (PDI) family is a group of thiol oxidoreductases responsible for catalyzing the disulfide bond formation of nascent proteins. In this study, we generated 14 strains of KO mice lacking the PDI family enzymes and found that only PDI deficiency caused spermatogenesis defects.

Real-world effectiveness of GLP-1 receptor agonist-based treatment strategies on "time in range" in patients with type 2 diabetes.

Diabetes affects millions of people worldwide annually, and several methods, including medications, are used for its management; glucagon-like peptide-1 receptor agonists (GLP-1RAs) are one such class of medications. The efficacy and safety of GLP-1RAs in treating type 2 diabetes mellitus (T2DM) have been assessed and have been shown to significantly improve time in range (TIR) in several clinical trials. However, presently, there is a lack of real-world evidence on the efficacy of GLP-1RAs in improving TIR.

Clinical efficacy of plasma exchange in systemic lupus erythematosus during pregnancy.

Objective: To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy.

Methods: The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non-PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded.

The global, regional and national burden of type 2 diabetes mellitus in the past, present and future: a systematic analysis of the Global Burden of Disease Study 2019.

Aim: To report the global, regional, and national burden of type 2 diabetes mellitus (T2DM) in 2019, assess its trends in the past, and forecast its trends in the future.

Methods: The main data source was the Global Burden of Disease 2019 database. We assessed the changes in T2DM burden from 1990 to 2019 with joinpoint regression analysis.

Efficacy of polyethylene glycol loxenatide versus insulin glargine on glycemic control in patients with type 2 diabetes: a randomized, open-label, parallel-group trial.

This trial aimed to evaluate the glycemic control of polyethylene glycol loxenatide measured with continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM), with the hypothesis that participants given PEG-Loxe would spend more time in time-in-range (TIR) than participants were given insulin glargine after 24 weeks of treatment. This 24-week, randomized, open-label, parallel-group study was conducted in the Department of Endocrine and Metabolic Diseases, Longhu Hospital, Shantou, China. Participants with T2DM, who were ≥45 years of age, HbA1c of 7.

Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes.

Aim: To evaluate the treatment effect Fand pharmacoeconomic value of Dugaglutide in women with type 2 diabetes.

Methods: Women (n=96) with type 2 diabetes recruited from June 2019 to December 2021 were randomized into two equal groups. The control group was treated with Liraglutide, and the observation group was treated with Dulaglutide, both for 24 weeks.

Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study.

Objectives: Recent studies have shown that fecal microbiota transplantation (FMT) improved the metabolic profiles of patients with type 2 diabetes mellitus (T2DM), yet the effectiveness in reversing insulin resistance and increasing metformin sensitivity in T2DM patients have not been reported. In this study, we evaluated the improvements of T2DM patients and their gut microbiota by FMT alone and FMT plus metformin.

Methods: A total of 31 patients with newly diagnosed T2DM were randomized to intervention by metformin, FMT, or FMT plus metformin in the study.

Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review.

There is a strong link between fecal microbiota and the development of type 1 diabetes. As an emerging therapeutic modality, fecal microbiota transplantation has been shown to be safe and effective in the treatment of many intestinal and extraintestinal diseases. Various studies have found that fecal microbiota transplantation can treat diseases by correcting patients' immune disorders.

Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes mellitus.

Unlabelled: Type 1 diabetes mellitus (T1DM) is an autoimmune-mediated disease characterized by a reduced or absolute lack of insulin secretion and often associated with a range of vascular and neurological complications for which there is a lack of effective treatment other than lifestyle interventions and pharmacological treatments such as insulin injections. Studies have shown that the gut microbiota is involved in mediating the onset and development of many fecal and extrafecal diseases, including autoimmune T1DM. In recent years, many cases of gut microbiota transplantation for diseases of the bowel and beyond have been reported worldwide, and this approach has been shown to be safe and effective.

Gut microbiota diversity in middle-aged and elderly patients with end-stage diabetic kidney disease.

Background: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD), but the mechanism between DKD and ESRD remains unclear. Some experts have put forward the "microbial-centered ESRD development theory", believing that the bacterial load caused by gut microecological imbalance and uremia toxin transfer are the core pathogenic links. The purpose of this study was to analyze the genomic characteristics of gut microbiota in patients with ESRD, specifically DKD or non-diabetic kidney disease (NDKD).

Polyethylene Glycol Loxenatide Injection (GLP-1) Protects Vascular Endothelial Cell Function in Middle-Aged and Elderly Patients With Type 2 Diabetes by Regulating Gut Microbiota.

To evaluate the protective effect of Polyethylene Glycol Loxenatide Injection (Glucagon-like peptide-1, GLP-1) on endothelial cells from middle-aged and elderly patients with newly diagnosed or poorly controlled type 2 diabetes mellitus (T2DM). GLP-1 weekly formulation was analyzed for cardiovascular disease protection and correlated with intestinal flora. Stool samples were collected from middle-aged and elderly patients with new-onset or poorly controlled type 2 diabetes in Longhu People's Hospital and Shantou Central Hospital from June 2019 to November 2019.

Vitamin D and Lipid Profiles in Postmenopausal Women: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

It is known that hyperlipidemia and low vitamin D level are risk factors associated with cardiovascular disease (CVD). However, the effect of vitamin D administration on lipid profiles in postmenopausal women remains unclear. This study aims to evaluate the effect of vitamin D on lipid profiles in postmenopausal women based on meta-analysis and systemic review.

The disulfide bond Cys2724-Cys2774 in the C-terminal cystine knot domain of von Willebrand factor is critical for its dimerization and secretion.

Background: Type 3 von Willebrand disease (VWD) exhibits severe hemorrhagic tendency with complicated pathogenesis. The C-terminal cystine knot (CTCK) domain plays an important role in the dimerization and secretion of von Willebrand factor (VWF). The CTCK domain has four intrachain disulfide bonds including Cys2724-Cys2774, Cys2739-Cys2788, Cys2750-Cys2804 and Cys2754-Cys2806, and the single cysteine mutation in Cys2739-Cys2788, Cys2750-Cys2804 and Cys2754-Cys2806 result in type 3 VWD, demonstrating the crucial role of these three disulfide bonds in VWF biosynthesis, however, the role of the remaining disulfide bond Cys2724-Cys2774 remains unclear.

Reconstruction of intestinal microecology of type 2 diabetes by fecal microbiota transplantation: Why and how.

Type 2 diabetes (T2D) is a chronic metabolic disease characterized by hyperglycemia due to insulin resistance. Mounting evidence has correlated T2D to alterations in the composition of gut microbiota. Accordingly, targeting the gut microbiota has become an emerging strategy for T2D management.

The effect of guar gum consumption on the lipid profile in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

Dyslipidemia is a common encounter in type 2 diabetes mellitus (T2DM) and the current strategies to manage it are still suboptimal. Subsequently, identifying newer molecules with lipid-lowering effects is necessary. A great deal of attention has been given in recent years to fiber supplements, e.

Gut Bacterial Characteristics of Patients With Type 2 Diabetes Mellitus and the Application Potential.

Type 2 diabetes mellitus (T2DM) is a complex disorder comprehensively influenced by genetic and environmental risk, and research increasingly has indicated the role of microbial dysbiosis in T2DM pathogenesis. However, studies comparing the microbiome characteristics between T2DM and healthy controls have reported inconsistent results. To further identify and describe the characteristics of the intestinal flora of T2DM patients, we performed a systematic review and meta-analysis of stool microbial profiles to discern and describe microbial dysbiosis in T2DM and to explore heterogeneity among 7 studies (600 T2DM cases, 543 controls, 1143 samples in total).

Curcumin inhibits high glucose oxidative stress and apoptosis in pancreatic beta cells via CHOP/PCG-1a and pERK1/2.

Loss of pancreatic beta-cells by apoptosis appears to play an important role in the development of insulin deficiency and the onset and/or progression of the diabetes mellitus. To this end, we report that curcumin prevents high glucose (HG) induced oxidative stress and apoptosis in mouse pancreatic beta cells. Moreover, curcumin prevents HG induced increase in expression of CHOP, decrease in PCG-1a and phosphorylation of ERK1/2 (pERK1/2) without any effect on the phosphorylation levels of p38 and JNK.

Branched-Chain Amino Acid Catabolism Promotes Thrombosis Risk by Enhancing Tropomodulin-3 Propionylation in Platelets.

Background: Branched-chain amino acids (BCAAs), essential nutrients including leucine, isoleucine, and valine, serve as a resource for energy production and the regulator of important nutrient and metabolic signals. Recent studies have suggested that dysfunction of BCAA catabolism is associated with the risk of cardiovascular disease. Platelets play an important role in cardiovascular disease, but the functions of BCAA catabolism in platelets remain unknown.

Plasma kallikrein contributes to ambient particulate matter-induced lung injury.

Particulate matter (PM) is a key component of air pollutants and is associated with mortality of cardiovascular and respiratory diseases. PM-induced tissue injury involves inflammation and coagulation. Plasma prekallikrein (pKal), along with coagulation factor XII (FXII) and high-molecular-weight kininogen (HK), form the plasma kallikrein-kinin system (KKS), a component of the innate immune response that generates proinflammatory products in response to injury.

Tyro3, Axl, and Mertk receptors differentially participate in platelet activation and thrombus formation.

Background: Previously, several studies have shown that Tyro3, Axl, and Mertk (TAM) receptors participate in platelet activation and thrombosis. However, the role of individual receptors is not fully understood.

Methods: Using single receptor-deficient platelets from TAM knockout mice in the C57BL/6 J strain, we performed a knockout study using single TAM-deficient mice.

The transmembrane protein disulfide isomerase TMX1 negatively regulates platelet responses.

Secreted platelet protein disulfide isomerases, PDI, ERp57, ERp5, and ERp72, have important roles as positive regulators of platelet function and thrombosis. Thioredoxin-related transmembrane protein 1 (TMX1) was the first described transmembrane member of the protein disulfide isomerase family of enzymes. Using a specific antibody, the recombinant extracellular domain of TMX1 (rTMX1) protein, a knockout mouse model, and a thiol-labeling approach, we examined the role of TMX1 in platelet function and thrombosis.

Protein disulfide isomerase enhances tissue factor-dependent thrombin generation.

Protein disulfide isomerase (PDI) plays an important role in fibrin generation in vivo, but the underlying mechanism remains largely unknown. In this study, using thrombin generation assay (TGA), we investigated whether PDI contributes to tissue factor (TF)-mediated thrombin generation. Human peripheral blood mononuclear cells (PBMCs) were treated with 100 ng/ml lipopolysaccharide (LPS), the expression of TF on cell surface was analyzed by flow cytometry.

The Procoagulant Activity of Apoptotic Cells Is Mediated by Interaction with Factor XII.

Apoptotic cells, by externalizing phosphatidylserine (PS) as a hallmark feature, are procoagulant. However, the mechanism by which apoptotic cells activate coagulation system remains unknown. Intrinsic coagulation pathway is initiated by coagulation factor XII (FXII) of contact activation system.

The disulfide isomerase ERp72 supports arterial thrombosis in mice.

Several CGHC motif-containing disulfide isomerases support thrombosis. We here report that endoplasmic reticulum protein 72 (ERp72), with 3 CGHC redox-active sites (a, a, and a'), supports thrombosis. We generated a new conditional knockout mouse model and found that Tie2-Cre/ERp72 mice with blood and endothelial cells lacking ERp72 had prolonged tail bleeding times and decreased platelet accumulation in laser-induced cremaster arteriole injury and FeCl-induced mesenteric arterial injury.