Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis.

Diabetic nephropathy (DN) is the major microvascular complication of diabetes mellitus and the most important cause of end-stage renal disease worldwide. Metformin is the preferred oral hypoglycaemic drug for type 2 diabetes mellitus (T2DM). Recent studies have shown that besides lowering blood glucose, metformin also has protective effects on renal function, but its mechanism is not clear. In this study, we established a diabetic rat model by high-fat feeding combined with intraperitoneal injection of streptozotocin. Their changes of renal function, oxidative stress, histopathology and structure, and autophagy were observed after 8 weeks of metformin treatment at different dose. Sirt1 inhibitor EX527 and metformin were used to observe whether the protective effect of metformin on DN kidney was achieved through the Sirt1/FoxO1 autophagic signalling pathway. The results showed that metformin could protect renal function by up-regulating autophagy level, alleviating oxidative stress level of renal tissue and pathological and structural changes of glomeruli, and inhibiting the expression of extracellular matrix. Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis. So metformin could alleviate renal injury in diabetic rats, which may be achieved by regulating Sirt1/FoxO1 autophagic signalling pathway and inducing renal autophagy.

Dexmedetomidine Promotes SH-SY5Y Cell Resistance Against Impairment of Iron Overload by Inhibiting NF-κB Pathways.

Iron overload is a common pathophysiological state underlying many diseases that has a detrimental influence on cells. The protective effects of Dexmedetomidine (Dex), a high selective alpha-2-adrenoceptor agonist, have been revealed through many experimental models, whereas no study reports its effects on an iron overload model. To elucidate these effects, we used FeCl2 with or without Dex to treat SH-SY5Y cells for 24 h and then detected indicators of oxidative stress, inflammation and apoptosis and investigated possible mechanisms further. After treatment with FeCl2 for 24 h, cell viability decreased in a dose dependent manner, and Dex promoted cell survival in FeCl2 incubation, also in a dose-dependent manner. Compared with the FeCl2 group, 20 µM Dex significantly attenuated ROS accumulation, reduced pro-inflammatory cytokine expression, and inhibited apoptosis. Furthermore, 20 µM concentration of Dex remarkably downregulated the expression of pro-apoptotic protein and activation of caspase 3 while increasing anti-apoptotic protein expression. Additionally, Dex also effectively suppressed the expression of NF-κB and its activation. In conclusion, Dex exerted anti-oxidative stress, anti-inflammation, and anti-apoptosis effects on FeCl2-treated SH-SY5Y cells, possibly by inhibiting NF-κB signaling pathway.

[Study of relation between crushed lava spectrum and magnetic susceptibility in Xiangshan uranium orefield].

Rock spectrum research is the base of the remote sensing geology. It's of great significance of exploring the relations between rock spectrum and other rock natures. In the present study, 36 fine crushed lava samples each measuring 5 cmX5 cmX 5 cm were tested for its spectrums by SVC HR-768 portable spectrometer. But before measuring each sample, white boards should be calibrated and after measuring the curves of spectrum of each sample should make a 5 nm smooth resample so that meteoric water and noise caused by external environment can be eliminated. After such smooth resample, at the spectrum scope of 1 112-1322 nm, taking band value as horizontal axis and reflectivity as vertical axis, linear equations of rock samples can be obtained. Taking the slopes as the horizontal axis and volume magnetic susceptibility as vertical axis, y= -0. 256 31n(x) + 0. 913 7 was thus obtained and its equation correlation coefficient is up to 0. 78. The result shows that volume magnetic susceptibility is mainly caused by Fe2+ , and that the amount of Fe2+ can be almost measured in the spectrum scope of 1112 approximately 1322 nm that has a good correlation with volume magnetic susceptibility.

Long non-coding RNA BX357664 inhibits gastric cancer progression by sponging miR-183a-3p to regulate the PTEN expression and PI3K/AKT pathway.

Lately, long non-coding RNA (lncRNA) is recognized as a key regulator of gastric cancer (GC) which has aroused great interest in the fields of medicine, toxicology, and functional food. Studies related to LncRNA expression microarray data indicate that BX357664 is down-regulated in GC specimens. However, the expression pattern and molecular mechanism of BX357664 in GC have not been studied so far. The purpose of this study was to investigate the expression of lncRNA BX357664 in GC and its function in GC cell lines. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of BX357664 in 50 pairs of cancer tissues and adjacent non-cancer tissues collected from GC patients. It was found that BX357664 level was lowered in cancer specimens than adjacent non-cancer tissues and correlated with tumor size and TNM stage. Also, we used cell counting kit 8 (CCK8), cell clone formation assay and transwell assay, which affirmed that up-regulation of BX357664 inhibited the proliferation, migration, and invasion of GC cells, but promoted apoptosis. In the dual-luciferase report analysis, BX357664 acted as a miR-183-3p ceRNA to target and regulate the expression of PTEN and affect the PI3K/AKT pathway. These results indicate that BX357664 can inhibit the proliferation and metastasis of GC through the miR-183-3p/PTEN/PI3K/AKT pathway, which may serve as potential targets for the treatment of GC in the future.

MiR-92a antagonized the facilitation effect of extracellular matrix protein 1 in GC metastasis through targeting its 3'UTR region.

MicroRNAs were known to play very important roles in human diseases, and have attracted great interests of research scientists in medicine, toxicology and functional foods. Gastric carcinoma (GC) remains one of the most common and lethal types of malignancy worldwide. However, the molecular mechanism of GC and the role of microRNAs in GC development remain unclear. The expression of extracellular matrix protein 1 (ECM1) is up-regulated in many cancer types, but its functional role is inconstant. In the present study, we aimed to investigate the correlation between GC development and ECM1 expression, along with its regulation by microRNAs. Immunohistochemical results showed that ECM1 was up-regulated in GC tissues and ECM1 expression level was negatively correlated with the prognosis of GC. ECM1 was found to promote gastric cancer cell metastasis in cell migration assays by facilitating the expression of proteins involved in epithelial-mesenchymal transition (EMT). MiR-92a was recognized for the first time to suppress the migration of human GC cells by directly targeting to the 3'UTR of ECM1 gene in a dual-luciferase reporter assay. These results highlighted the antagonistic roles of ECM1 and miR-92a in GC development, which may serve as a new target for gastric cancer.

Hydroxychloroquine potentiates the anti-cancer effect of bevacizumab on glioblastoma via the inhibition of autophagy.

Bevacizumab (BEV) is widely used for the treatment of patients with recurrent glioblastoma (GBM), but recent evidence demonstrated that BEV induced cytoprotective autophagy, which allows tumor cells to survive. Hydroxychloroquine (HCQ) inhibits lysosomal acidification and blocks autophagy via influencing autophagosome fusion and degradation. HCQ is often used to enhance the efficacy of chemoradiotherapy. However, whether HCQ sensitizes GBM cells to BEV and the molecular mechanism of this effect are not clear. We showed that high concentrations of BEV increased the LC3-II/LC3-I ratio and caused the degradation of Beclin1 in the LN18 and LN229 cell lines, indicating that high concentrations of BEV induced the autophagy of the LN18 and LN229 cells. However, BEV (100 µg/ml) did not influence the autophagy of the LN18 and LN229 cells, and HCQ at less than 5 µg/ml significantly accumulated LC3B-II and p62 proteins and blocked the autophagy process. Importantly, we found that HCQ (5 µg/ml) potentiated the anti-cancer effect of BEV (100 µg/ml). Therefore, HCQ is a novel strategy that may augment the efficacy of BEV for GBM via the inhibition of autophagy.