Activity-Based Protein Profiling of RHBDL4 Reveals Proteolysis of the Enzyme and a Distinct Inhibitor Profile.

Rhomboid proteases have fascinated scientists by virtue of their membrane-embedded active sites and proposed involvement in physiological and disease pathways. The human rhomboid protease RHBDL4 has generated particular interest due to its role in endoplasmic reticulum-associated protein degradation and upregulation in several cancers; however, chemical tools for studying this enzyme are currently lacking. Here, we describe the development of an activity-based protein profiling (ABPP) assay for RHBDL4.

Chemoproteomic strategy identified p120-catenin glutathionylation regulates E-cadherin degradation and cell migration.

Identification of cysteines with high oxidation susceptibility is important for understanding redox-mediated biological processes. In this report, we report a chemical proteomic strategy that finds cysteines with high susceptibility to S-glutathionylation. Our proteomic strategy, named clickable glutathione-based isotope-coded affinity tag (G-ICAT), identified 1,518 glutathionylated cysteines while determining their relative levels of glutathionylated and reduced forms upon adding hydrogen peroxide.

Photoactive electron donor-acceptor complex platform for Ni-mediated C(sp)-C(sp) bond formation.

A dual photochemical/nickel-mediated decarboxylative strategy for the assembly of C(sp)-C(sp) linkages is disclosed. Under light irradiation at 390 nm, commercially available and inexpensive Hantzsch ester (HE) functions as a potent organic photoreductant to deliver catalytically active Ni(0) species through single-electron transfer (SET) manifolds. As part of its dual role, the Hantzsch ester effects a decarboxylative-based radical generation through electron donor-acceptor (EDA) complex activation.

Iron-Catalyzed Direct Oxidative Alkylation and Hydroxylation of Indolin-2-ones with Alkyl-Substituted N-Heteroarenes.

Presented herein is the first direct alkylation and hydroxylation reaction between two different C(sp )-H bonds, indolin-2-ones and alkyl-substituted N-heteroarenes, through an oxidative cross-coupling reaction. The reaction is catalyzed by a simple iron salt under mild ligand-free and base-free conditions. The reaction is environmentally benign, employs air (molecular oxygen) as the terminal oxidant and oxygen source for the synthesis of O-containing compounds, and produces only water as the byproduct.

TCF7L2 regulates pancreatic β-cell function through PI3K/AKT signal pathway.

Background: Transcription factor 7-like 2 (TCF7L2), which previously known as TCF-4, is a major form of transcription factor involved in the downstream WNT signaling and exhibits the strongest association to diabetes susceptibility. Although we still do not know mechanistically how TCF7L2 exerts its physiological functions on pancreatic endocrine cells, it had been suggested that TCF7L2 may directly affect β-cell function by regulating the activation of PI3K/AKT signaling pathway.

Methods: MIN6 cells were transfected with TCF7L2 knockdown virus or lenti-TCF7L2 virus for 48 h to evaluate the contribution of TCF7L2 to the PI3K/AKT signaling pathway and pancreatic β-cell function.

High-normal urinary albumin-to-creatinine ratio is independently associated with metabolic syndrome in Chinese patients with type 2 diabetes mellitus: A cross-sectional community-based study.

Aims/introduction: Microalbuminuria is positively related to metabolic syndrome (MetS). Our aim was to investigate whether urinary albumin-to-creatinine ratio (UACR) within the normal range is independently associated with MetS in Chinese community-based patients with type 2 diabetes.

Materials And Methods: A total of 514 participants (206 males and 308 females; mean age 66 years) with UACR less than 3.

An analysis of the association between a polymorphism of KCNJ11 and diabetic retinopathy in a Chinese Han population.

Background: Genome-wide association studies (GWAS) have reported that the polymorphism rs5219 of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) is associated with type 2 diabetes mellitus (T2DM). Given that diabetic retinopathy (DR) is one of the most common microvascular complications of T2DM, GWAS have identified a number of potential susceptibility genes for DR. However, only a fraction of them have been replicated in different studies and show consistent genetic associations with the occurrence of DR.

Association and interaction analysis of PPARGC1A and serum uric acid on type 2 diabetes mellitus in Chinese Han population.

Background: Peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1A/ PGC-1α) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. The activity of PGC-1α or genetic variations in the gene encoding the enzyme may contribute to individual variations in mitochondrial function and insulin resistance or diabetes. The objective of this study was to assess the extent to which PPARGC1A (rs8192678) and serum uric acid (UA) and its interaction impact on T2DM susceptibility in Chinese Han population.

IGF2BP2 and obesity interaction analysis for type 2 diabetes mellitus in Chinese Han population.

Background: The objective of this study was to systematically evaluate the contribution of the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to type 2 diabetes mellitus (T2DM) and its interaction with obesity to T2DM susceptibility.

Methods: To clarify whether IGF2BP2 is an independent risk factor for T2DM in Chinese population, we conducted a study with a total of 2,301 Chinese Han subjects, including 1,166 T2DM patients and 1,135 controls, for the genotype of a most common and widely studied polymorphism-rs4402960 of IGF2BP2. Genotyping was performed by iPLEX technology.

Deficiency of IRTKS as an adaptor of insulin receptor leads to insulin resistance.

IRTKS encodes a member of the IRSp53/MIM homology domain family, which has been shown to play an important role in the formation of plasma membrane protrusions. Although the phosphorylation of IRTKS occurs in response to insulin stimulation, the role of this protein in insulin signaling remains unknown. Here we show that IRTKS-deficient mice exhibit insulin resistance, including hyperglycemia, hyperinsulinemia, glucose intolerance, decreased insulin sensitivity, and increased hepatic glucose production.

Low-grade albuminuria is associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes.

Background: Low-grade albuminuria is associated with cardiovascular risk factors and mortality. Our aim was to investigate the association between low-grade albuminuria and carotid atherosclerotic lesions in community-based patients with type 2 diabetes.

Methods: A cross-sectional study was performed in 475 community-based patients with type 2 diabetes (190 males and 285 females) with normal urinary albumin-to-creatinine ratios (UACR) (< 3.

Glycemic control among patients in China with type 2 diabetes mellitus receiving oral drugs or injectables.

Background: The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China.

Methods: This was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China.

Glutathione prevents free fatty acids-induced oxidative stress and apoptosis in human brain vascular endothelial cells through Akt pathway.

Aims: The damage of human brain vascular endothelial cells (HBVECs) is the key pathogenesis of diabetes-associated cerebral vascular complications. The aim of this study was to elucidate the effects of glutathione (GSH) on free fatty acids (FFAs)-induced HBVECs apoptosis, oxidative stress, and the involved possible signaling pathway.

Methods: After culturing HBVECs for 72 h with GSH and FFAs, we determined cell proliferation by CCK8, detected apoptosis by caspase-3 and Annexin V-FITC/PI staining, and judged oxygen stress by determining the reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP).

Mutation of 3β-hydroxysteroid dehydrogenase (3β-HSD) at the 3'-untranslated region is associated with adrenocortical insufficiency.

In the present study, we report the mutation of the 3β-hydroxysteroid dehydrogenase (3β-HSD) gene in a family suffering from adrenocortical insufficiency. The index patient was clinically diagnosed with adrenocortical insufficiency. Peripheral venous blood (5 ml) was collected from the proband and 5 members of his family, and genomic DNA was extracted.

Calorie restriction from a young age preserves the functions of pancreatic β cells in aging rats.

Calorie restriction (CR) is a simple method for delaying aging process, extending lifespan, and preventing the onset of aging-related diseases, such as diabetes. However, the mechanism, by which CR influences β-cell functions during the aging process, still remains unclear. In this study, sixteen 8-week-old male Sprague-Dawley rats were randomized to control group with food intake ad libitum and CR group fed with 70% of food intake of the control group.

[Effect of adipose differentiation-related protein on the apoptosis of H9c2 cells by palmitic acid].

Aim: To construct a eukaryotic expression vector for expressing adipose differentiation-related protein(ADRP) protein and obtain a stable transfected H9c2 cell line.

Methods: (1)The full length DNA fragment of ADRP gene was amplified by PCR from the myocardium of adult SD rats and was inserted into pEGFP-C1 with T4 ligase. After the identification of digestion and sequencing on the recombinant pEGFP-C1-ADRP, the recombinant was transformed into E.

[Effect of FAM172A protein on apoptosis and proliferation in HEK293 cells].

Objective: To study the effect of FAM172A protein related to diabetic macroangiopathy on apoptosis and proliferation in HEK293 cells.

Methods: The pDrive-FAM172A plasmid constructed in our previous study was used as a template to amplify human FAM172A open reading frame by a polymerase chain reaction. The resulting PCR products were subcloned into the eukaryotic expression vector PDC315 to construct recombinant PDC315-FAM172A plasmid.

[Molecular cloning of a novel gene, C5orf21 gene and its roles in diabetic macroangiopathy].

Objective: To clone a novel diabetic angiopathy related protein gene-C5orf21 and study its roles in diabetic macroangiopathy.

Methods: The open reading frame (ORF) of C5orf21 gene was cloned into vector from human aortic tissues by a RT-PCR-based approach and identified by enzyme-cutting and sequencing. The structure and function of C5orf21 gene and protein were further analyzed by bioinformatics technology.

Brap2 facilitates HsCdc14A Lys-63 linked ubiquitin modification.

Protein phosphotase Cdc14 (Cell division cycle gene 14) is a key regulator of late mitotic events in Saccharomyces cerevisiae. However the function of human Cdc14 (HsCdc14A & B) and its regulatory network are still elusive. In this study, we identified a new partner of HsCdc14A named Brap2 (BRCA1 associated protein 2) using yeast two-hybrid screening assay.

Berberine inhibits the expression of TNFalpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARgamma pathway.

Macrophages are the main source of cytokines in atherosclerotic plaques. Modified low-density lipoproteins may stimulate macrophages to produce large quantities of proinflammatory cytokines that promote atherosclerosis. Berberine is the main component of the traditional Chinese medicine umbellatine, which has a widespread effect and was used to treat many diseases clinically.

Biphasic response of endothelial progenitor cell proliferation induced by high glucose and its relationship with reactive oxygen species.

In this study, the effect of high glucose (HG) on endothelial progenitor cell (EPC) proliferation and its relationship with cyclins and reactive oxygen species (ROS) were investigated. Mouse EPCs were isolated from bone marrow using a magnetic activated cell-sorting system and cultured in the presence or absence of HG (30 mmol/l). We found that in the early stage of incubation (3 days), HG promoted cell proliferation, and increased the expressions of cdk2 and cyclin E, while in the late stage of culture (7 days) it inhibited cell proliferation and decreased the expressions of cdk2, cyclin E, and proliferating cell nuclear antigen (PCNA).

[An epidemiological study on diabetic retinopathy among type 2 diabetic patients in Shanghai].

Objective: To investigate the prevalence and risk factors of diabetic retinopathy (DR) among type 2 diabetic patients aged over 30 in Shanghai central area.

Methods: 1039 patients diagnosed with type 2 diabetes mellitus (DM) aged over 30 were investigated by randomized cluster sampling in Shanghai central area and data from 767 of those patients were analyzed.

Results: (1) Among all of the 1534 digital ocular fundus images from 767 patients, 87.