Correlation of dehydroepiandrosterone with diabetic nephropathy and its clinical value in early detection.

AIMS/INTRODUCTION: This study was carried out to assess the association of dehydroepiandrosterone (DHEA) with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus to better predict the progression of diabetic nephropathy. MATERIALS AND METHODS: A total of 1,082 patients with type 2 diabetes mellitus in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital were enrolled in this study, and grouped for comparison. The effect of serum DHEA on DN was evaluated by multivariate logistic regression analysis, and receiver operating characteristic curves were established to explore the optimal concentration of DHEA in patients with DN and non-DN. RESULTS: DHEA was significantly decreased in patients with DN (P < 0.001). The prevalence of DN was significantly higher in the low DHEA quartile than in the other quartiles (P < 0.001). Spearman-related analysis showed that DHEA levels were negatively correlated with patient age, course of diabetes, systolic blood pressure, blood creatinine, uric acid, urine albumin-to-creatinine ratio, 24-h urine microalbumin, 24-h urine protein quantification and glomerular filtration rate, and positively correlated with body mass index, total cholesterol and low density lipoprotein. Logistic regression analysis showed that the effect of DHEA on DN was statistically significant (P < 0.001). The receiver operating characteristic curve showed that the sensitivity was 81.4%, the specificity was 70% and the area under the curve was 0.812 when the optimal cut-off value was 1,640 (pg/mL). CONCLUSION: DHEA is significantly associated with DN and might be a protective factor for DN, and is important for the prediction of DN.

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ).

The Sublethal Effects of ß-Ecdysterone, a Highly Active Compound from Achyranthes bidentata Blume, on Grape Phylloxera, Daktulosphaira vitifoliae Fitch.

Grape phylloxera, Daktulosphaira vitifoliae (Fitch) (Hemiptera, Phylloxeridae), is a very destructive insect pest of grapevines. Intercropping of Achyranthes bidentata Blume (f. Amaranthaceae) and Vitis spp. grapevines can be useful to control this pest. In the present study, the toxicity of 22 compounds, known to be present in A. bidentata, to grape phylloxera was evaluated. All treatments were toxic towards grape phylloxera but the degree of toxicity differed between treatments. Among the 22 tested compounds, several of which proved toxic towards grape phylloxera. However ß-ecdysterone had higher toxic effects against grape phylloxera, with LC50 values of 175.73 mg a.i. liter-1. In addition, we assessed the sublethal effects of LC10, LC20 and LC40 of ß-ecdysterone on grape phylloxera. The fourth instar and adult developmental periods and total life span were significantly prolonged by LC40 of ß-ecdysterone. Fecundity decreased when grape phylloxera were exposed to LC20 and LC40 of ß-ecdysterone. In addition, LC40 of ß-ecdysterone decreased the intrinsic rate of increase (rm) and the finite rate of increase (λ) and prolonged the population doubling time (DT). The net reproductive rate (R0) was significantly reduced by both the LC20 and LC40 ß-ecdysterone treatments. Our results demonstrated that ß-ecdysterone had higher toxic effects and significant sublethal effects on grape phylloxera, and showed potential control of grape phylloxera.

Inhibitory effects of O-methylated isoflavone glycitein on human breast cancer SKBR-3 cells.

Glycitein is an O-methylated isoflavone which accounts for 5-10% of the total isoflavones in soy food products. Cell proliferation studies on the dietary phytoestrogen, glycitein against human breast carcinoma SKBR-3 cells showed that glycitein exhibits biphasic regulation on SKBR-3 cells. At concentrations of less than 10 mg/mL, cells respond to glycitein by increasing cell growth and de novo DNA synthesis whereas the addition of glycitein at concentrations greater than 30 mg/mL significantly inhibited cell growth and DNA synthesis in a dose-dependent manner. Cells treated with 60 mg/mL of glycitein did not regain normal growth after treatment was stopped. Glycitein was found to be cytostatic at low concentrations and cytotoxic at higher concentrations. Treatment with 100 mg/mL of glycitein severely altered the cell morphology. Collective results showed that glycitein damaged the cell membranes by increasing membrane permeability and suggested possible mechanisms of the action of dietary phytoestrogens on human breast carcinoma SKBR-3 cells.

The Efficacy of Chinese Medicinal Herbs towards Grape Phylloxera (Daktulosphaira vitifoliae Fitch) (Hemiptera, Phylloxeridae).

Bio-insecticidal effects of seven Chinese medicinal herbs on mortality, fecundity, developmental periods and life table parameters of the grape phylloxera were investigated. In an excised root bioassay experiment aqueous extracts from seven Chinese medicinal herbs increased grape phylloxera first instar mortality (26.00-38.50%) compared to other instars. The intrinsic rate of increase (rm), finite rate of increase (λ), fecundity rate and net reproductive rate (R0) were significantly reduced by A. bidentata, A. tataricus, O. basilicum, P. frutescens and N. cataria. In a glasshouse pot trial, eggs, nymphs, adults and total population were significantly reduced before population establishment compared to those after its population established, by A. bidentata, A. tataricus and O. basilicum. Overall, A. bidentata, A. tataricus and O. basilicum can be used to suppress all life-stages of grape phylloxera.

Identification of Henosepilachna vigintioctomaculata (Coleoptera: Coccinellidae) midgut putative receptor for Bacillus thuringiensis insecticidal Cry7Ab3 toxin.

Bt WZ-9 strain, containing a single Cry7Ab3 toxin, had effective insecticidal activity against larvae of Henosepilachna vigintioctomaculata. By incubation with larvae midgut homogenate and trypsin in vitro, 130 kDa Cry7Ab3 protoxin was degraded into the ∼75 kDa proteinase-resistant fragments. In vivo analysis, 130 kDa Cry7Ab3 protoxin was also processed into ∼75 kDa fragment. Histopathological observations indicated that Cry7Ab3 ingestion by H. vigintioctomaculata larvae causes acceleration in the blebbing of the midgut epithelium cells into the gut lumen and eventual lysis of the epithelium cells resulting in larval death. A ligand blotting experiment demonstrated that Cry7Ab3 toxin bound a 220 kDa BBMV protein. This receptor protein was identified as cadherin by matrix assisted laser desorption-time of flight-mass spectrometry (MALDI-TOF-MS). The cadherin protein may be the receptor of Cry7Ab3. The data obtained may contribute to a better understanding of the mechanism of Cry7Ab3 toxin against H. vigintioctomaculata larvae.