[New development for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor beta].

Non-alcoholic fatty liver disease has now become a common hepatic metabolic disease, but there is no universally approved therapeutic drug on the market, so there is an urgent need to explore relevant therapeutic drugs. Several studies have shown that the thyroid hormone receptor ß, which is specifically expressed in the liver, plays an important role in lipid metabolism. T3 analogs and thyroid hormone receptor ß-specific agonists have been developed for thyroid hormone receptor ß. Many studies have shown that it can inhibit hepatic triglyceride synthesis, increase hepatic cholesterol clearance, reduce lipid deposition, and at the same time partly increase insulin sensitivity, promote glucose metabolism, and improve inflammation. Therefore, it has become a therapeutic drug with great potential for the treatment of non-alcoholic fatty liver disease. Herein, the mechanism, clinical research and drug development status are reviewed in order to provide new ideas for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor ß.

[Effect and mechanism of mulberry leaf polysaccharide on type 1 diabetic nephropathy in rats].

Objective: To observe the effects of mulberry leaf polysaccharide (MLP) on insulin-like growth factor 1 (IGF-1) and insulin-like growth factor blinding protein 3 (IGFBP-3) as well as the expression of IGF-1 and IGFBP-3 mRNA in the kidney of type 1 Diabetic Nephropathy (DN) rats, and to investigate its therapeutic effects and underlying mechanisms. Methods: Type 1 DN rat model was established by intraperitoneally injecting streptozocin (STZ). SD rats were randomly divided into the control, model, insulin and MLP groups, with eight rats in each group. Rats in MLP group were given orally with MLP 200 mg/kg daily for 8 weeks and insulin group rats were given subcutaneously injection of short acting insulin 1 U daily for 8 weeks. The changes in body weight, blood and urine parameters were recorded. Extracellular matrix (ECM) was calculated. The contents of IGF-1 and IGFBP-3 in blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of IGF-1 and IGFBP-3 in the kidney were evaluated by fluorescence quantitative PCR. Results: Compared with rats in control group, blood glucose, triglyceride, total cholesterol, low density lipoprotein, very low density lipoprotein, 24 h urine protein, serum creatinine and urea nitrogen in the model group rats were significantly increased (all P<0.01), and these parameters of MLP group were significantly lower than the model group (all P<0.01). The contents of IGF-1 and IGFBP-3 in the blood serum of the model group were significantly higher than those in the control group (both P<0.001), while in the MLP group they were lower than the model group[IGF-1: (0.777±0.018) ng/ml vs (0.864±0.022) ng/ml, P<0.001; IGFBP-3: (0.759±0.016) ng/ml vs (0.846±0.021) ng/ml, P<0.001]. The mRNA expressions of IGF-1 and IGFBP-3 in the kidney of the model group were significantly higher than those in the control group (both P<0.001), while in the MLP group they were lower than in the model group (IGF-1: 1.450±0.032 vs 1.810±0.090, P<0.001; IGFBP-3: 1.684±0.018 vs 1.968±0.044, P<0.001). Compared with the model group rats, there were fewer pathological changes of kidney in MLP group rats. Conclusion: MLP has a certain therapeutic effect on DN, which may be achieved by decreasing the contents of IGF-1 and IGFBP-3 in the blood serum and down-regulating the over-expression of IGF-1 and IGFBP-3 mRNA in the kidney.

Endometrial expression of telomerase, progesterone, and estrogen receptors during the implantation window in patients with recurrent implantation failure.

Telomerase plays a critical role in cell proliferation and senescence, but the exact involvement of endometrial telomerase in recurrent implantation failure (RIF) is unknown. We collected endometrial biopsies from RIF patients (N = 30) and fertile women (N = 30). Real-time PCR was performed for detecting changes in telomerase reverse transcriptase (Tert), ER alpha, and PR expression at the transcript level, and the correlation between the variable expressions of these genes was tested using regression analysis. Then, western blot and immunohistochemistry were used to analyze the expression profiles of TERT and ER alpha at the protein level. Compared to the control, Tert expression was substantially increased, whereas ER alpha expression significantly decreased in the endometrium with RIF. No change was observed in PR expression. Tert expression was inversely associated with ER alpha expression. TERT protein expression in RIF patients was also clearly elevated, and was localized to both the endometrial epithelium and stromal cells. However, the signals for ER alpha in the stromal cells were weaker than those in the control. Expression of endometrial telomerase was substantially enhanced as ER alpha decreased in RIF patients during the implantation window.

Bacterial diversity in antibiotic wastewater treatment.

The bacterial diversity of an antibiotic industrial wastewater treatment system was analyzed to provide the information required for further optimization of this process and for identification of bacterial strains that perform improved degradation of antibiotic industrial wastewater. The total bacterial DNA of samples collected at three stages (aeration, precipitation, and idle) during the sequencing batch reactor (SBR) process were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) of the 16 s rDNA V3 regions. Community analysis was conducted in terms of the richness value (S), the dominance degree and the Shannon-Wiener diversity index (H). Rich bacterial diversity was apparent in the aeration stage of the SBR process, and the number of bands in the aeration stage was more abundant than that in the precipitation and idle stages. The DGGE analysis showed 15 bands, six of which were uncultured bacteria, and included one anaerobic and five aerobic bacteria. The microbial community in the aeration stage was the most complex of the whole SBR process, while the dominant bacteria differed in each reaction stage. These results demonstrate the cyclical dynamic changes in the bacterial population during the SBR process for the treatment of antibiotic industrial wastewater.

Synthesis, antiproliferative and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors.

As a target for clinical anti-cancer treatment, epidermal growth factor receptor (EGFR) exhibits its over-expression on various tumour cells and is associated with the development of a variety of human cancers. Herein, we described the synthesis, antiproliferative activity assay and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors. Compared with Gefitinib, some of the target compounds have excellent antiproliferative activities against EGFR-expressed A431 cell line. The robust and reliable 4D-QSAR was constructed using comparative distribution detection algorithm, ordered predictors selection and genetic algorithm method, and the following acceptable statistics are shown: r2 = 0.82, Q2LOO = 0.67, Q2LMO = 0.61, r2Pred = 0.78.