Protective effect of sinomenine against inflammation and oxidative stress in gestational diabetes mellitus in female rats via TLR4/MyD88/NF-κB signaling pathway.

Gestational diabetes mellitus (GDM) is a dangerous complication of pregnancy which is induced via dysfunction in glucose metabolism during pregnancy. Sinomenine (SM) has already proved an antidiabetic effect against streptozotocin (STZ)-induced diabetes mellitus (DM) in rats. In this protocol, we examined the protective effect of SM against STZ-induced GDM in rats. Wistar rats were divided into three groups and STZ (40 mg/kg) was used to induce GDM. At the end of the experimental protocol, bodyweight, pub weight, and survival rate were estimated. Blood glucose level (BGL), fasting insulin (FINS), free fatty acid (FFA), Hemoglobin A1C (HbA1c), and C-peptide were measured. Lipid, antioxidant, inflammatory cytokines, and inflammatory mediators were also determined. RT-PCR was used for estimation of the role of TLR4/MyD88/NF-κB signaling pathway. SM treatment significantly (p < .001) reduced BGL, hepatic glycogen, and improved the levels of FINS, C-peptide, FFA, and HbA1c. SM significantly (p < .001) suppressed the levels of total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), coronary artery index (CAI), very low-density lipoprotein (VLDL), atherogenic index (AI), and boosted high-density lipoprotein (HDL) levels. SM significantly (p < .001) decreased the lipid peroxidation (LPO) level and enhanced glutathione peroxidase (GPx), total antioxidant capacity (TAC), glutathione S-transferase (GST), superoxide dismutase (SOD), respectively. It reduced the levels of inflammatory cytokines including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and inflammatory mediators viz., nuclear kappa B factors (NF-κB). SM significantly (p < .001) reduced the mRNA expression of Myd88, NLRP3, TLR4, and NF-κB, which were boosted in the GDM group rats. These findings suggest that SM could be a probable drug to be used for treating GDM via inhibition of the TLR4 signaling pathway. PRACTICAL APPLICATIONS: It is well known that gestational diabetes mellitus (GDM) is a dangerous health problem during the pregnancy. SM reduced the glucose level; boosted the level of fasting insulin (FINS) and bodyweight. SM significantly improved the number of pubs and their survival rates. SM suppressed oxidative stress and inflammation via activation of TLR4/MyD88/NF-κB signaling pathway. According to our research, SM can be used as a preventive drug in the treatment of GDM during pregnancy.

Effect of ethylparaben on the growth and development of Drosophila melanogaster on preadult.

Parabens are esters of p-hydroxybenzoic acid, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and the like. This substance has estrogenic and antiandrogenic effects, and a putative role in promoting cancer through endocrine disruption. By exposing Drosophila melanogaster to different concentrations of EP (300 mg/L, 700 mg/L, and 1000 mg/L), we investigated the effect of EP on the growth and development of D. melanogaster before emergence. We found that EP prolonged the development cycle of D. melanogaster, and changed the relative expression levels of Met, Gce, EcR, Kr-h1, and Br. In addition, EP reduced the titer of juvenile hormone Ⅲ (JH Ⅲ) and 20-hydroxyecdysone (20E), and delayed the peak of hormone secretion. This study provided a more objective and thorough assessment of safety for the parabens.

Evaluation of MMP-9 and MMP-2 and their suppressor TIMP-1 and TIMP-2 in adenocarcinoma of esophagogastric junction.

OBJECTIVE: Adenocarcinoma of esophagogastric junction (AEG) is a lethal malignancy featured with early metastasis, poor prognosis, and few treatment options. Matrix metalloproteinase (MMP) and metalloproteinase suppressor (TIMP) have been considered to be associated with cancer invasion and metastasis. In our study, we evaluated expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in AEG and their correlation with clinicopathological parameters and the overall survival rate. METHODS: Expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in specimens from 120 AEGs were detected by immunohistochemistry. The correlations between expressions of these four proteins and clinicopathological characters were analyzed by chi-square test. Moreover, the prognostic value of these four biomarkers was evaluated by univariate analysis with Kaplan-Meier method and multivariate analysis with Cox regression model. RESULTS: The positive expression rate of MMP-9, MMP-2, TIMP-1, and TIMP-2 was 65%, 53%, 70%, and 49%, respectively, in the detected 120 AEG samples. MMP-9 was significantly associated with poorly histological differentiation (P=0.001), lymph node metastasis (P=0.007), and UICC stage (P=0.008). TIMP-1 showed significantly reversed correlations with histological differentiation (P=0.001), lymph node metastasis (P=0.007), and Union for International Cancer Control stage (P=0.008). Univariate analysis revealed that lymph node metastasis (P=0.002), depth of invasion (P=0.050), and MMP-9+/TIMP-1 phonotype (P<0.001) were significantly associated with the overall survival rate. Multivariate analyses demonstrated that MMP-9+/TIMP-1-phenotype was an independent prognostic factor in AEGs. CONCLUSION: Detection of MMP-9 and TIMP-1 expression allows stratification of AEG patients into different survival categories and can be useful for precise individual evaluation and survival prediction.

Transformation of acetaminophen using manganese dioxide-mediated oxidative processes: reaction rates and pathways.

This study investigates the oxidative transformation kinetics of acetaminophen (APAP) by δ-MnO2 under different conditions. APAP was rapidly oxidized by δ-MnO2 with the generation of Mn(2+). The measured APAP reaction rate considerably increased with an increase in initial δ-MnO2 and APAP concentration, but decreased as pH increased. The APAP reaction rate also increased with an increase in temperature. The addition of inorganic ions (Mn(2+), Ca(2+), and Fe(3+)) and substituted phenols (guaiacol, caffeic acid, and p-coumaric acid) as co-solutes remarkably decreased the transformation rate of APAP. The UV-Vis absorption spectra exhibited the π → π* transition, typical for aromatic rings. In addition, the intensity of the absorption peak gradually improved with increasing reaction time, suggesting that APAP can polymerize to form oligomers. Moreover, the secondary mass spectra of the dimers elucidated that the dimers were formed by the covalent bonding of phenol aromatic rings. Moreover, the higher-degree oligomers were formed by the coupling polymerization of phenolic and anilidic groups of dimers. These results are useful in understanding the fate of APAP in natural systems.