Evaluation of testis hormonal and histopathological alterations in type I and type II diabetic rats.

BACKGROUND: Diabetes is a devastating metabolic disease that causes long-term damage to various organs. An important leading complication of diabetes is a degenerative effect on the reproductive system including infertility and gonadal dysfunction. This study aimed to evaluate the effects of experimental type I and II diabetes on the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. METHODS: Male Wistar rats were randomly divided into four separate groups: (1) type I diabetes (T1DM), (2) type II diabetes (T2DM), (3) cetrorelix acetate-treated nondiabetic control group, and (4) normal untreated group (n = 6). T1DM was experimentally induced by a single injection of alloxan (135 mg/kg) while T2DM was induced by feeding the animals with drinking water enriched with fructose (10%). Cetrorelix acetate (100 mg/kg, intraperitoneal for 1 week) treatment group was used as a positive control. All rats were killed and blood and testes were collected after 8 weeks of the study. The effects of induced diabetes on the levels of blood glucose and insulin were assessed. The levels of sex hormones and insulin were determined by radioimmunoassay. Histological staining was used to check abnormal patterns of testicular morphology, the diameter of seminiferous tubules, testicular diameter, and germinal layer thickness. RESULTS: A significant reduction in the testosterone, FSH, and LH levels were observed in T1DM, T2DM, and also in cetrorelix acetate-treated groups. Analysis of testicular histology sections revealed significantly reduced thickness of cell layer in T1DM and cetrorelix acetate-treated groups compared with the T2DM group. In T2DM, the cell numbers, the thickness of cell layer, the diameter of seminiferous tubules, and weight of testicles were slightly increased. In contrast, total tubules of empty seminiferous increased significantly in T1D and cetrorelix treated groups compared with the control group. CONCLUSION: Overall, diabetes can induce hypothalamus-pituitary-gonad axis dysfunction, affects hormonal secretion, and causes histological damage to testes, collectively leading to deleterious effects on male fertility.

Naturally occurring anti-cancer agents targeting EZH2.

Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects. In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators. Mechanisms like inhibition of histone H3K4, H3K27 and H3K36 trimethylation, down-regulation of matrix metalloproteinase expression, competitive binding to the S-adenosylmethionine binding site of EZH2 and modulation of tumor-suppressive microRNAs have been demonstrated to mediate the EZH2-inhibitory activity of the mentioned natural products. This review summarizes the pathways that are regulated by various natural products resulting in the suppression of EZH2, and provides a plausible molecular mechanism for the putative anti-cancer effects of these compounds.

Curcumin as a MicroRNA Regulator in Cancer: A Review.

Curcumin is a natural dietary polyphenol for which anti-tumor effects have been documented. Anti-inflammatory and antioxidant properties of curcumin, along with its immunomodulatory, proapoptotic, and antiangiogenic properties, are often referred to as the main mechanisms underlying the anti-tumor effects. At the molecular level, inhibition of NF-kB, Akt/PI3K, and MAPK pathways and enhancement of p53 are among the most important anticancer alterations induced by curcumin. Recent evidence has suggested that epigenetic alterations are also involved in the anti-tumor properties of curcumin. Among these curcumin-induced epigenetic alterations is modulation of the expression of several oncogenic and tumor suppressor microRNAs (miRNAs). Suppression of oncomiRs such as miR-21, miR-17-5p, miR-20a, and miR-27a and over-expression of miR-34 a/c and epithelial-mesenchymal transition-suppressor miRNAs are among the most important effects of curcumin on miRNA homeostasis. The present review will summarize the findings of in vitro and experimental studies on the impact of curcumin and its analogues on the expression of miRNAs involved in different stages of tumor initiation, growth, metastasis, and chemo-resistance.