Oxidative stress on vessels at the maternal-fetal interface for female reproductive system disorders: Update.

Considerable evidence shows that oxidative stress exists in the pathophysiological process of female reproductive system diseases. At present, there have been many studies on oxidative stress of placenta during pregnancy, especially for preeclampsia. However, studies that directly focus on the effects of oxidative stress on blood vessels at the maternal-fetal interface and their associated possible outcomes are still incomplete and ambiguous. To provide an option for early clinical prediction and therapeutic application of oxidative stress in female reproductive system diseases, this paper briefly describes the composition of the maternal-fetal interface and the molecular mediators produced by oxidative stress, focuses on the sources of oxidative stress and the signaling pathways of oxidative stress at the maternal-fetal interface, expounds the adverse consequences of oxidative stress on blood vessels, and deeply discusses the relationship between oxidative stress and some pregnancy complications and other female reproductive system diseases.

MiR-181a Promotes Spermatogenesis by Targeting the S6K1 Pathway.

Approximately 15% of couples suffer from infertility worldwide, and male factors contribute to about 30% of total sterility cases. However, there is little progress in treatments due to the obscured understanding of underlying mechanisms. Recently microRNAs have emerged as a key player in the process of spermatogenesis. Expression profiling of miR-181a was carried out in murine testes and spermatocyte culture system. In vitro cellular and biochemical assays were used to examine the effect of miR-181a and identify its target S6K1, as well as elucidate the function with chemical inhibitor of S6K1. Human testis samples analysis was employed to validate the findings. miR-181a level was upregulated during mouse spermatogenesis and knockdown of miR-181a attenuated the cell proliferation and G1/S arrest and increased the level of S6K1, which was identified as a downstream target of miR-181a. Overexpression of S6K1 also led to growth arrest of spermatocytes while inhibitor of S6K1 rescued the miR-181a knockdown-mediated cell proliferation defect. In human testis samples of azoospermia patients, low level of miR-181a was correlated with defects in the spermatogenic process. miR-181a is identified as a new regulator and high level of miR-181a contributes to spermatogenesis via targeting S6K1.

miR-615 Inhibits Prostate Cancer Cell Proliferation and Invasion by Directly Targeting Cyclin D2.

Previous studies have reported that miR-615 exerts a tumor suppressor role in some tumors, such as esophageal squamous cell carcinoma and non-small cell lung cancer. However, the role of miR-615 in prostate cancer has not been defined. Here we found that miR-615 was downregulated in prostate cancer tissues and cell lines. Overexpression of miR-615 in PC-3 cells significantly inhibited cellular proliferation, migration, and invasion. Moreover, overexpression of miR-615 delayed tumor growth in vivo. In terms of mechanism, we found that cyclin D2 (CCND2) is a target gene of miR-615 in prostate cancer. We showed that miR-615 could bind to the 3'-UTR region of CCND2 mRNA and inhibit its expression. There was a negative correlation between the expression of miR-615 and CCND2 in prostate cancer tissues. Moreover, restoration of cyclin D2 abolished the inhibitory effects of miR-615 on the proliferation, migration, and invasion of prostate cancer cells. Taken together, our study identified miR-615 as a tumor suppressor by targeting cyclin D2 in prostate cancer.

The inhibitory effects of soybean isoflavones on testicular cell apoptosis in mice with type 2 diabetes.

The aim of the study was to investigate the inhibitory effects of soybean isoflavones (SI) on testicular cell apoptosis in mice with type-2 diabetes, as well as any possible mechanisms of action. Thirty male C57BL/6J mice were randomly divided into the control, diabetic (model), and treatment (SI) groups (n=10 each). After treatment for 20 weeks, testicular cell apoptosis was detected and evaluated using DAPI staining. The expression and distribution of caspase-3 protein in testicular tissues was detected via immunohistochemistry, while caspase-3 mRNA expression was detected using RT-PCR. Bax and Bcl-2 protein expression was detected by western blot analysis. At week 20, DAPI staining showed that SI treatment significantly decreased testicular tissue cell apoptosis in diabetic mice. Immunohistochemical staining revealed that caspase-3 expression in the SI group was significantly reduced relative to the model group. RT-PCR showed that SI treatment significantly decreased caspase-3 mRNA expression relative to the model group. Western blot analysis revealed that SI treatment significantly decreased Bax protein expression and increased Bcl-2 protein expression (P<0.01). SI exhibited an inhibitory effect on testicular tissue cell apoptosis in mice with type 2 diabetes, with this effect possibly mediated by a decreased expression of caspase-3 and Bax and increased Bcl-2 protein expression.

MiR429 expression level in renal cell cancer and its correlation with the prognosis of patients.

PURPOSE: To test the hypothesis that miR429 expression in renal cancer patients is increased and plays a role in the pathogenesis of the disease. METHODS: Twenty-seven renal cancer patients admitted to our hospital from May 2014 to May 2015 were enrolled as the study group, and 28 non-cancer patients were selected during the same period as the control group. Renal biopsy and serum samples were used to detect miR429 expression levels, and the patient histories were obtained to make relevant associations to clinical outcomes. In addition, the renal cancer cell line SK458 was used for overexpressing or knocking out miR429 in in vitro experiments to observe changes in proliferation and apoptosis rates. RESULTS: The expression levels of miR429 in renal tissues and serum of renal cancer patients were significantly higher compared with control patients (p<0.05). In addition, a correlation was found between the levels of miR429 in the serum of renal cell cancer patients and their clinical outcome after conventional treatment, with patients expressing lower miR429 levels showing better clinical outcomes. Finally, experiments with renal cancer cells revealed that the proliferation of cells overexpressing miR429 was increased and their apoptosis rate was significantly reduced, while the opposite was true in miR429-knockout cells. CONCLUSIONS: It seems that miR429 can inhibit normal apoptosis rates and lead to high proliferation rates. Accordingly, the higher serum miR429 level in renal cancer patients suggests that it plays a role in the pathogenesis of the disease, while the differential miR429 levels according to the patients' clinical outcomes after treatment suggest that miR429 may be useful as a marker for prognosis.