The effect of human umbilical cord mesenchymal stem cells conditioned medium combined with tamoxifen drug on BRCA1 and BRCA2 expression in breast cancer mouse models.

BACKGROUND: A growing number of studies has indicated that the expression of Breast Cancer Susceptibility Genes 1 (BRCA1) and BRCA2 contribute to the resistance to DNA-damaging chemotherapies. Tamoxifen induces tumor cell death by suppressing estrogen receptor (ER) signaling and inducing DNA damage, and BRCA1 upregulation causes Tamoxifen chemoresistance in breast cancer cells. Consequently, this research study aimed to investigate the possible therapeutic effect of Human Umbilical Cord Mesenchymal Stem Cells Conditioned Medium (UCMSCs-CM) on sensitizing breast cancer cells to Tamoxifen by regulating BRCA1 and BRCA2 expression in vivo. METHODS: Forty female mice, 4-8 weeks old, with weight of 150 g, were used for this study. Mouse 4T1 breast tumor models were established and then treated with UCMSCs-CM and Tamoxifen alone or in combination. After 10 days, the tumor masses were collected and the expression levels of BRCA1 and BRCA2 were evaluated using qRT-PCR assay. RESULTS: The results obtained from qRT-PCR assay illustrated that UCMSCs-CM, either alone or in combination with Tamoxifen, significantly downregulated the mRNA expression levels of BRCA1 in breast cancer mouse models. However, both UCMSCs-CM and Tamoxifen indicated no statistically significant impact on BRCA2 mRNA expression compared to controls. CONCLUSION: Our findings evidenced that UCMSCs-CM could be considered as a potential therapeutic option to modulate Tamoxifen chemosensitivity by regulating BRCA1 in breast cancer.

Regulatory role of microRNAs in cancer through Hippo signaling pathway.

Cancer is the major cause of death worldwide in countries of all income levels. The Hippo signaling pathway is a Drosophila kinase gene that was identified to regulate organ size, cell regeneration, and contribute to tumorigenesis. A huge variety of extrinsic and intrinsic signals regulate the Hippo signaling pathway. The Hippo signaling pathway consists of a wide array of components that merge numerous signals such as mechanical signals to address apoptosis resistance, cell proliferation, cellular outputs of growth, cell death and survival at cellular and tissue level. Recent studies have shed new light on the regulatory role of microRNAs in Hippo signaling and how they contribute to cancer progression. MicroRNAs influence various cancer-related processes such as, apoptosis, proliferation, migration, cell cycle and metabolism. Inhibition and overexpression of miRNAs via miRNA mimics and miRNA inhibitors, respectively, can uncover a hopeful and reliable insight for treatment and early diagnosis of cancer patients. In this review we will discuss our current understanding of regulatory role of miRNAs in Hippo signaling pathway.

Salvia officinalis hydroalcoholic extract improved reproduction capacity and behavioral activity in rats exposed to immobilization stress.

This study was conducted to evaluate the Salvia officinalis hydroalcoholic extract on fertility capacity and behavioral features in rats exposed to immobilization stress. Male rats were randomly divided into five groups; Control; Stressed rats; and Stressed rats received 50, 100 and/or 200 mg/kg bw S. officinalis hydroalcoholic extract. To induce stress, rats were immobilized for 49 days and received S. officinalis extract orally. On day 56, we analyzed behavioral tests and evaluated reproduction capacity by measuring LH, FSH, and testosterone. Sperm parameters such as motility, viability, and total count were also determined. Bodyweight changes were also calculated on day 56. Male rats from different groups were mated with healthy female rats. Data showed that the use of 100 and 200 mg/kg bw S. officinalis extract in stressed rats increased bodyweight gain and improved behavioral disorders compared to control-matched groups (p < .05). Besides, administration of 100 and 200 mg/kg bw S. officinalis extract had the potential to improve sperm parameters and fertility capacity in stressed rats (p < .05). Decreased testosterone levels were blunted in the stressed rats that received plant extract coincided with the reduction of LH and FSH compared to control-matched stressed rats (p < .05). We found neutral effects in stressed rats that received 50 mg/kg bw plant extract. Collectively, the hydroalcoholic extract of S. officinalis could improve the fertility capacity and behavioral features under stressful conditions in a dose-dependent manner.

Upregulation of FSHR and PCNA by administration of coenzyme Q10 on cyclophosphamide-induced premature ovarian failure in a mouse model.

Cyclophosphamide (CTX) has been broadly used in the clinic for the treatment of autoimmune disorders and ovarian cancer. The process of chemotherapy has significant toxicity in the reproductive system as it has detrimental effects on folliculogenesis, which leads to an irreversible premature ovarian failure (POF). Coenzyme Q10 (CoQ10) has positive impacts on the reproductive system due to its antioxidant properties, protecting the cells from free-radical oxidative damage and apoptosis. However, little is known about the possible synergistic effect of CTX and CoQ10 on the expression of genes involved in folliculogenesis, such as proliferation cell nuclear antigen (PCNA) and follicle-stimulating hormone receptor (FSHR). A total of 32 NMRI mice were applied and divided into four groups, including healthy control, CTX, CTX + CoQ10, and CoQ10 groups. The effects of CoQ10 on CTX-induced ovarian injury and folliculogenesis were examined by histopathological and real-time quantitative reverse transcription-polymerase chain reaction analyses. The rates of fertilization (in vitro fertilization), embryo development, as well as the level of reactive oxygen species (ROS) in metaphase II (MII) mouse oocytes after PMSG/HCC treatment were also assessed. Results showed that the treatment with CTX decreased the mRNA expression of PCNA and FSHR, IVF rate, and embryo development whereas the application of CoQ10 successfully reversed those factors. CoQ10 administration significantly enhanced histological morphology and decreased ROS levels and the number of atretic follicles in the ovary of CTX-treated mice. In conclusion, it seems that the protective effect of CoQ10 is exerted via the antioxidant and proliferative properties of this substance on CTX-induced ovarian damage.

Comparison of the Effects of Clofibrate and Silafibrate on Sperm Parameters Quality and Sex Hormones in Male Rats.

PURPOSE: Fibrates are drugs widely used for the treatment of hyperlipidemic disorders. Previous studies on a novel analogue of clofibrate, called silafibrate, have shown good lipid lowering effects. This study was designed to assess the role of silafibrate as a peroxisome proliferator-activated receptors (PPARs) agonist on sperm health and spermatogenesis in adult male rats. MATERIAL AND METHODS: Seventy male Wistar rats were randomly allocated into 7 groups: Cl-10, Cl-20, and Cl-40 mg/kg/day (clofibrate); Si-10, Si-20, and Si-40 mg/kg/day (silafibrate); and C, control. After a 28-day treatment, all rats were euthanized. Blood samples were taken for determination of testosterone, total antioxidant capacity, levels of malondialdehyde, and oxidized low-density lipoprotein. Reproductive organs were dissected and spermatozoa collected from the epididymis for analysis. RESULT: Sperm parameters (count, motility, viability, and morphology) and total serum testosterone decreased significantly in clofibrate-treated (20 and 40 mg/kg) rats (P < 0.05) as compared with normal rats. CONCLUSION: We conclude that PPARs agonists have significant adverse effect on sperm viability, motility, and total serum testosterone, and could be harmful for sperm parameters and male reproductive function in rats.