The aim of this study was to investigate the effects of metformin supplementation on metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation and spermatogenesis in male mice with high-fat and high-cholesterol diet-induced obesity. Forty male C57BL/6 mice were fed a normal diet (NC group, n = 10) or a high-fat and high-cholesterol diet (HFC group, n = 30) for 24 weeks, and mice randomly chosen from the HFC group were later treated with metformin for the final 8 weeks of HFC feeding (HFC + Met group, n = 15). Compared with the HFC group, the obese mice supplemented with metformin exhibited improved blood cholesterol, glucose and insulin resistance. The HFC group diminishes in the sperm motility and normal sperm morphology, while the poorer maturity of testicular spermatogenesis was improved by metformin treatment. The HFC group exhibited a higher estradiol level and a lower 17β-HSD protein expression. Further analyses showed that metformin treatment increased the activities of superoxide dismutase, catalase and glutathione peroxidase and reduced lipid peroxidation. Nevertheless, both the HFC and HFC + Met groups exhibited increased expressions of apoptosis and inflammation proteins in the testis. Metformin treatment ameliorated obesity-induced poor testicular spermatogenesis and semen quality through increasing the testosterone level and antioxidant capacity.

Triple-negative breast cancer (TNBC) lacks specific therapeutic target and limits to chemotherapy and is essential to develop novel therapeutic regimens. Increasing studies indicated that tamoxifen, a selective estrogen receptor modulators (SERMs), has anti-tumor therapeutic effect in estrogen receptor α (ERα)-negative tumor. Here, we determined whether autophagy was activated by tamoxifen in TNBC cells. Moreover, CSC-3436 displayed strong and selective growth inhibition on cancer cells. Next, we investigated the anti-proliferation effect of combination of CSC-3436 plus tamoxifen on cell death in TNBC cells. Our study found that tamoxifen induces autophagy in TNBC cells. Endoplasmic reticulum stress and AMPK/mTOR contributed tamoxifen-induced autophagy. Interestingly, in combination treatment with CSC-3436 enhanced the anti-proliferative effect of tamoxifen. We found that CSC-3436 switched tamoxifen-induced autophagy to apoptosis via cleavage of ATG-5. Moreover, AMPK/mTOR pathway may involve in CSC-3436 switched tamoxifen-induced autophagy to apoptosis. The combination of tamoxifen and CSC-3436 produced stronger tumor growth inhibition compared with CSC-3436 or tamoxifen alone treatments in vivo. These data indicated that CSC-3436 combined with tamoxifen may be a potential approach for treatment TNBC.

Background: Endoscopic combined intrarenal surgery (ECIRS) adds ureteroscopic vision to percutaneous nephrolithotomy (PCNL), which can be helpful when dealing with complex renal stones. Yet, there is still no consensus on the superiority of ECIRS. We aimed to critically analyze the available evidence of studies comparing efficacy, safety, bleeding risk, and efficiency of ECIRS and PCNL. Methods: We searched for studies comparing efficacy (initial and final stone-free rate), safety (postoperative fever, overall and severe complications), efficiency (operative time and hospital stay) and bleeding risk between ECIRS and PCNL. Meta-analysis was performed. Results: Seven studies (919 patients) were identified. ECIRS provided a significantly higher initial stone-free rate, higher final stone-free rate, lower overall complications, lower severe complications, and lower rate of requiring blood transfusion. There was no difference between the two groups in terms of postoperative fever, hemoglobin drop, operative time, and hospital stay. In the subgroup analysis, both minimally invasive and conventional ECIRS were associated with a higher stone-free rate and lower complication outcomes. Conclusions: When treating complex renal stones, ECIRS has a better stone-free rate, fewer complications, and requires fewer blood transfusions compared with PCNL. Subgroups either with minimally invasive or conventional intervention showed a consistent trend.

Within the tumour microenvironment, a complex network of chemokines and their receptors affects the initiation and progression of tumours. The higher levels of tumour necrosis factor‐alpha (TNF‐α) are associated with tumour progression and an anti‐TNF‐α monoclonal antibody has been used successfully to treat patients with renal cell carcinoma (RCC). However, the role of chemokines and their receptors in the TNF‐α‐promoted progression of RCC remains unclear. In this study, TNF‐α was found to enhance the migration, invasion and epithelial‐mesenchymal transition (EMT) of RCC cells. To further investigate the molecular mechanism of TNF‐α on the progression of RCC, reverse transcription and quantitative PCR was used to screen chemokines and chemokine receptors that were associated with tumorigenesis. The results showed that TNF‐α significantly increased the expressions of CXCR2 and CXCR3 and their related ligands in RCC cells. Subsequently, we used a lentiviral shRNA system to knockdown the expression of CXCR2 and/or CXCR3 in RCC cells. CXCR2 and CXCR3 silencing inhibited the induction of Slug and ZEB‐1 with TNF‐α treatment of RCC cells. In addition, the knockdown of both CXCR2 and CXCR3 resulted in a greater decrease in cell migration, invasion and clonogenic ability compared with either CXCR2 or CXCR3 knockdown alone. Moreover, CXCR2 and CXCR3 silencing significantly reduced the sphere‐forming ability of RCC cells. High expression levels of CXCR2 and CXCR3 in cancer tissues correlated with tumour progression of renal cell carcinoma. These findings suggest that TNF‐α augments CXCR2 and CXCR3 to promote the progression of renal cell carcinoma leading to a poor prognosis.

Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti‐tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2‐overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2‐overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2‐overexpressing bladder cancer.

Excellent wound dressing is essential for effective wound repair and regeneration. However, natural polymeric skin substitutes often lack mechanical strength and hydrophilicity. One way to overcome this limitation is to use biodegradable polymers with high mechanical strength and low skin-irritation induction in wet environments. Bacterial cellulose (BC) is an attractive polymer for medical applications; unlike synthetic polymers, it is biodegradable and renewable and has a strong affinity for materials containing hydroxyl groups. Therefore, we conjugated it with resveratrol (RSV), which has a 4′-hydroxyl group and exhibits good biocompatibility and no cytotoxicity. We synthesized BC scaffolds with immobilized RSV and characterized the resulting BC/RSV scaffold with scanning electron microscopy and Fourier-transform infrared spectroscopy. We found that RSV was released from the BC in vitro after ~10 min, and immunofluorescence staining showed that BC was highly biocompatible and regenerated epithelia. Additionally, Masson’s trichrome staining showed that the scaffolds preserved the normal collagen-bundling pattern and induced re-epithelialization in defective rat epidermis. These results indicated that RSV-conjugated BC created a biocompatible environment for stem cell attachment and growth and promoted epithelial regeneration during wound healing.