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Staphylococcus aureus is a Gram-positive bacterial pathogen of global concern and a leading cause of bacterial infections worldwide. Asymptomatic carriage of S . aureus on the skin and in the anterior nares is common and recognized as a predisposing factor to invasive infection. Transition of S . aureus from the carriage state to that of invasive infection is often accompanied by a temperature upshift from approximately 33°C to 37°C. Such a temperature shift is known in other pathogens to influence gene expression, often resulting in increased production of factors that promote survival or virulence within the host. One mechanism by which bacteria modulate gene expression in response to temperature is by the regulatory activity of RNA-based thermosensors, cis- acting riboregulators that control translation efficiency. This study was designed to identify and characterize RNA-based thermosensors in S . aureus . Initially predicted by in silico analyses of the S . aureus USA300 genome, reporter-based gene expression analyses and site-specific mutagenesis were performed to demonstrate the presence of a functional thermosensor within the 5’ UTR of cidA , a gene implicated in biofilm formation and survival of the pathogen. The nucleic sequence composing the identified thermosensor are sufficient to confer temperature-dependent post-transcriptional regulation, and activity is predictably altered by the introduction of site-specific mutations designed to stabilize or destabilize the structure within the identified thermosensor. The identified regulator is functional in both the native bacterial host S . aureus and in the distally related species Escherichia coli , suggesting that its regulatory activity is independent of host-specific factors. Interestingly, unlike the majority of bacterial RNA-based thermosensors characterized to date, the cidA thermosensor facilitates increased target gene expression at lower temperatures. In addition to the characterization of the first RNA-based thermosensor in the significant pathogen S . aureus , it highlights the diversity of function within this important class of ribo-regulators.

Aim: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated. Methods: HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement. Results: α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression. Conclusion: Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.

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Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

Diabetes Mellitus is one of the most important health problems worldwide, indicating high prevalence and mortality. In recent years, Ginkgo biloba extract has become a subject of interest because of its beneficial effects on human health, also camel milk has a good nutritive value, in addition to its antigenotoxic and anticytotoxic effects. Therefore the purpose of the present study was to investigate the protective and curative effects of camel milk and Ginkgo biloba extract against alloxan-induced diabetes in rats.Rats were either pre-treated with camel milk, Ginkgo biloba extract or both, for 10 days before alloxan administration, or treated with both camel milk and Ginkgo biloba extract after induction of diabetes using alloxan.Pre-treatment of rats with either camel milk or Ginkgo biloba extract significantly prevented the alloxan-induced elevation of blood glucose levels. The combination of camel milk and Ginkgo biloba extract before and after induction of diabetes prevented and improved blood glucose levels respectively.