Search

Objective. Several clinical studies have reported the application of dipeptidyl peptidase-4 (DPP-4) inhibitors as treatments for type 1 diabetes mellitus (T1DM). This study aims to review the outcomes of these existing studies and to discuss the therapeutic effects of DPP-4 inhibitors on T1DM. Methods. We thoroughly searched the Medline, Embase, PubMed, and Cochrane Library databases and ClinicalTrials.gov for studies concerning the use of DPP-4 inhibitors in patients with T1DM. Results. In preclinical trials, DPP-4 inhibitors improved the pathogenesis of T1DM. However, only a portion of the studies showed potential efficacy regarding clinical glycemic control and other clinical parameters. From this meta-analysis, pooled data from 5 randomized controlled trials revealed that the additional use of DPP-4 inhibitors resulted in a greater decrease in glycated hemoglobin A1c (HbA1c) levels (0.07%, 95% CI (−0.37%–0.23%)) than insulin monotherapy, although the decrease was not significant. A small decrease in postprandial glucose or insulin consumption was confirmed. Conclusion. Although DPP-4 inhibitors may be beneficial for T1DM, existing studies do not strongly support these positive effects in clinical practice. Further optimized clinical trials are needed. [ABSTRACT FROM AUTHOR]

Endocrine disruptors in marine environments represented by estrogens lead to reverse health phenomena. To obtain a more effective way to reflect and detect environmental estrogens pollution, a method was developed to obtain the full-length cDNA coding vitellogenin gene in B. sinensis, induced by 17β-estradiol (E2) solution. We have downloaded 16 fish gene sequences from the NCBI database and designed PCR primers accordingly. Based on the quantitative real-time PCR method (qRT-PCR), we analyze the differences in gene expression under the conditions of different E2 exposure times in the low, middle, and high-dose groups. The full-length cDNA consists of 4738 nucleotides with a reading frame encoding 1540 amino acid residues. In vitro recombinant plasmids were constructed and transferred to E. coli BL21 for vitellogenin expression. Efficient fusion expression was obtained by IPTG at 16°C, and the expressed target protein (680 amino acids, 75 kDa) existed in a soluble state, accounting for more than 25% of the total soluble protein. We prepared monoclonal antibodies using established immunohistochemistry to detect vitellogenin expression sites in sexually mature female fish. Our study shows that the expression sites of Vg in sexually mature female fish are mainly distributed in the fishtail, hepatopancreas, intestine, muscle, ovary, and pronephric kidney. In conclusion, the vitellogenin from B. sinensis could be used as a biomarker of environmental estrogens to achieve rapid detection in the marine environment and the subsequent experiments of development in colloidal gold strips after this research would be established to provide a highly efficient and convenient detection method for environment pollution. [ABSTRACT FROM AUTHOR]

Background. Diaphanous related formin 1 (DIAPH1) is a novel component of advanced glycation end product (AGE) signal transduction that was recently found to participate in diabetes-related disorders, obesity, and androgen hormones. We investigated whether plasma DIAPH1 levels were a potential prognostic predictor for polycystic ovary syndrome (PCOS). Methods. The levels of circulating plasma DIAPH1 and indicators of glucose, insulin, lipid metabolism, liver enzymes, kidney function, sex hormones, and inflammation were measured in 75 patients with PCOS and 77 healthy participants. All of the participants were divided into normal-weight (NW) and overweight/obese (OW) subgroups. Statistical analyses were performed with R studio. Results. PCOS patients manifested hyperandrogenism, increased luteinizing hormone/follicle-stimulating hormone (LH/FSH), and accumulated body fat and insulin resistance. Plasma DIAPH1 levels were significantly decreased in women with PCOS compared to control participants, and DIAPH1 levels were distinctly reduced in OW PCOS compared to OW control subjects (P < 0.001). DIAPH1 levels correlated with fasting blood glucose (FBG), total cholesterol (TC), the homeostasis model assessment of β-cell function (HOMA-β), and LH/FSH in all participants (FBG: r = 0.351 , P < 0.0001 ; TC: r = 0.178 , P = 0.029 ; HOMA-β: r = − 0.211 , P = 0.009 ; LH/FSH: r = − 0.172 , P = 0.040). Multivariate logistic regression analysis revealed that plasma DIAPH1 levels were an independent risk factor for PCOS. A model containing DIAPH1, BMI, FBG, and testosterone was constructed to predict the risk of PCOS, with a sensitivity of 92.0% and a specificity of 80.9%. A nomogram was constructed to facilitate clinical diagnosis. Conclusions. These findings suggest the association of plasma DIAPH1 with glucose metabolism, insulin resistance, and sex hormones and support DIAPH1 as a potential predictive factor for PCOS. [ABSTRACT FROM AUTHOR]

Purpose. Hyperoside, a flavonoid isolated from conventional medicinal herbs, has been demonstrated to exert a significant protective effect in diabetic nephropathy. This study aimed to determine the underlying mechanisms, by which hyperoside inhibits high glucose-(HG-) induced proliferation in mouse renal mesangial cells. Methods. Mouse glomerular mesangial cells line (SV40-MES13) was used to study the inhibitory effect of hyperoside on cell proliferation induced by 30 mM glucose, which was used to simulate a diabetic condition. Viable cell count was assessed using the Cell Counting Kit-8 and by the 5-ethynyl-20-deoxyuridine incorporation assay. The underlying mechanism involving miRNA-34a was further investigated by quantitative RT-PCR and transfection with miRNA-34a agomir. The phosphorylation levels of extracellular signal-regulated kinases (ERKs) and cAMP-response element-binding protein (CREB) were measured by Western blotting. The binding region and the critical binding sites of CREB in the miRNA-34a promoter were investigated by the chromatin immunoprecipitation assay and luciferase reporter assay, respectively. Results. We found that hyperoside could significantly decrease HG-induced proliferation of SV40-MES13 cells in a dose-dependent manner, without causing obvious cell death. In addition, hyperoside inhibited the activation of ERK pathway and phosphorylation of its downstream transcriptional factor CREB, as well as the miRNA-34a expression. We further confirmed that CREB-mediated regulation of miRNA-34a is dependent on the direct binding to specific sites in the promoter region of miRNA-34a. Conclusion. Our cumulative results suggested that hyperoside inhibits the proliferation of SV40-MES13 cells through the suppression of the ERK/CREB/miRNA-34a signaling pathway, which provides new insight to the current investigation on therapeutic strategies for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Asprosin is a white adipose tissue-derived hormone that increases abnormally in mammals with insulin resistance. However, the role of asprosin in polycystic ovary syndrome (PCOS), a disease partly characterized by insulin resistance, and its potential connection with type 2 diabetes mellitus (T2DM) and PCOS has not been thoroughly elucidated to date. To investigate the association of asprosin with metabolic profiles, sex-related hormones, or inflammation in females with T2DM or PCOS, plasma asprosin and metabolic indicators were measured in 66 healthy females, 53 female patients with T2DM, and 41 patients with PCOS. Spearman’s correlation analysis and binary logistic regression analysis models were used. Plasma asprosin was significantly higher in T2DM females than in healthy subjects (P<0.001) and was positively correlated with fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and HOMA-IR (P<0.05). Asprosin in PCOS subjects was also higher than in healthy subjects (P<0.001) but lower than in T2DM subjects (P<0.05), and it was positively correlated with FBG, HbA1c, HOMA-IR, LDL-c, APOB, APOE, and testosterone (P<0.05). The BMI-categorized subgroups of PCOS subjects also showed correlations of asprosin with metabolic profiles and sex-related hormones. Binary logistic regression analysis revealed that plasma asprosin level acted as an independent risk factor for T2DM or PCOS. These findings suggest the correlation of plasma asprosin level with glucose metabolism, lipid metabolism, sex-related hormones, and inflammation in females, supporting asprosin as a potential predictive factor for females with metabolic-related diseases. This trial is registered with ChiCTR-ROC-17010719. [ABSTRACT FROM AUTHOR]

A neutral polysaccharide (DIP‐1) from Duchesnea indica (Andr.) Focke was obtained by hot water extraction, ethanol precipitation and chromatographic separation (DEAE‐52 cellulose anion‐exchange column and Sephadex G‐100 gel column). The physicochemical properties of DIP‐1 were elucidated by gel permeation chromatography, monosaccharide composition, Fourier transform infrared spectrometry, UV–visible spectrophotometry, scanning electron microscope and Congo red test. The results indicated that DIP‐1 was consisted of mannose, glucosamine, glucose, galactose and arabinose in a ratio of 1.00:0.42:18.36:14.17:0.81, and its molecular weight was 218.3 kDa. Meanwhile, DIP‐1 presented a straight hexahedron structure, but no triple‐helical conformation. In antioxidant activity tests, DIP‐1 exhibited powerful scavenging activities on hydroxyl, DPPH, ABTS radicals and reducing power in a dose‐dependent manner. Especially, DIP‐1 demonstrated high inhibitory activities against SKOV‐3 and Hep‐G2 cells in vitro, with IC50 values of 1.42 and 1.23 mg/ml, respectively. Practical applications: D. indica has been used for a long time as a Chinese medicine for therapy of many diseases, including cancer, inflammation, leprosy, fever, bleeding and so on. At present, polysaccharides have attracted comprehensive attention because of a large range of pharmacological and biological properties, including antitumor, antidiabetic, antioxidant and immunomodulatory activity. In the present study, we purified and characterized a neutral polysaccharide from D. indica for the first time. Moreover, the neutral polysaccharide exhibits significant antioxidant and antitumor activities. Therefore, the present study laid a foundation for the high‐value application of D. indica polysaccharides in functional food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]