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The effects of leuprorelin acetate, a luteinizing hormonereleasing hormone agonist (LHRH-A), on prostate carcinogenesis in probasin/SV40 Tag transgenic rat was investigated. Fifteen weeks after administration of 0.28 and 2.8 mg/kg leuprorelin, prostate weights and serum testosterone levels were significantly decreased compared to values for transgenic controls. Histopathological findings revealed that the incidence of prostatic adenocarcinomas was significantly reduced in ventral, dorsal and lateral lobes of the prostate, correlating with decreased expression of SV40 Tag P rostate cancer has become the most commonly diagnosed malignancy in men, and the second commonest cause of cancer death after lung neoplasms in the USA.(1)Initial treatment of prostate cancer is usually androgen-ablative therapy, radiotherapy or radical prostatectomy, and patients with early stage disease respond well. However, in many patients the therapy eventually fails and death occurs from recurrent androgen-independent prostate cancer and metastasis.Luteinizing hormone-releasing hormone (LHRH), which is synthesized in hypothalamic neurons and secreted directly into the hypophyseal-portal blood circulation in a pulsatile manner, binds to high-affinity receptors (LHRH-R) on the gonadotrophic cells in the pituitary, stimulating the synthesis and release of luteinizing hormone (LH) and folliclestimulating hormone (FSH), which in turn stimulate the synthesis of sex steroids by the testes. Based on the hypothalamuspituitary-gonad hormonal relationship, LHRH analogs have been developed and used to treat prostate cancer through suppression of the pituitary release of gonadotropins to achieve a chemical castration effect. The mechanism of action is presumed to result from desensitization or downregulation of LHRH receptors in the pituitary gonadotrophs after chronic exposure to LHRH agonists and a consequent decline of gonadotropin secretion and subsequent gonadal atrophy. (2,3) However, the molecular mechanisms involved in the inhibition of prostatic carcinomas by LHRH agonists are poorly defined.Various studies have demonstrated that LHRH analogs inhibit the proliferation of human prostate cancer cell lines and prostate cancer xenografts, and also reduce the growth of androgen-dependent and independent rat Dunning tumors, suggesting that their effects are mediated by specific LHRH receptors. This has been confirmed by detection of LHRH receptor mRNA expression in human prostate cancer cell lines and prostate cancer tissues. Therefore, activation of LHRH receptors at the prostate tumor level may represent an additional and more direct mechanism of action for antitumoral LHRH agonists. (4,5) Leuprorelin acetate is a highly superactive agonistic analog of LHRH which is reported to inhibit pituitary gonadotropin secretion and suppress testicular steroidogenesis when administered chronically in therapeutic doses.(6,7) Leuprorelin treatment is an established effective palliative measure in men with previously untreated advanced prostatic cancer, and...

Aim: we aimed to construct a bioinformatics-based co-regulatory network of mRNAs and non coding RNAs (ncRNAs), which is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), followed by its validation in a NAFLD animal model. Materials and Methods: The mRNAs–miRNAs–lncRNAs regulatory network involved in NAFLD was retrieved and constructed utilizing bioinformatics tools. Then, we validated this network using an NAFLD animal model, high sucrose and high fat diet (HSHF)-fed rats. Finally, the expression level of the network players was assessed in the liver tissues using reverse transcriptase real-time polymerase chain reaction. Results: in-silico constructed network revealed six mRNAs (YAP1, FOXA2, AMOTL2, TEAD2, SMAD4 and NF2), two miRNAs (miR-650 and miR-1205), and two lncRNAs (RPARP-AS1 and SRD5A3-AS1) that play important roles as a co-regulatory network in NAFLD pathogenesis. Moreover, the expression level of these constructed network–players was significantly different between NAFLD and normal control. Conclusion and future perspectives: this study provides new insight into the molecular mechanism of NAFLD pathogenesis and valuable clues for the potential use of the constructed RNA network in effective diagnostic or management strategies of NAFLD.

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The main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin-induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.5% solution, four times/day) or orally (100 mg/kg b.w.). Cataract formation was monitored biweekly and scored into four stages. After 12 weeks of treatment, rats were subjected to ophthalmological examination, and then, their blood and lenses were prepared for biochemical analysis of glucose, insulin, reduced glutathione, total antioxidant capacity, malondialdehyde, hydrogen peroxide, caspase-12, and lenticular total proteins. In addition, tertiary structure and conformational changes of lenticular soluble proteins were analyzed using SDS-PAGE and UV absorption while changes in lenticular α-crystallin structure were investigated using intrinsic tryptophan fluorescence. Results demonstrated that both local and oral UDCA restored the normal levels of lens T-AOC, MDA, H O , and caspase-12 and improved noticeably the levels of the lens GSH and total proteins. In addition, conformational and tertiary structure changes of soluble lens proteins were significantly reduced in UDCA-treated groups. Morphological examination of lenses revealed decreased score of cataract progression in UDCA-treated groups compared to DM animals. It was concluded that UDCA decreased the incidence of diabetic cataract by maintaining the antioxidant status, reducing the endoplasmic reticulum stress, and suppressing the structural changes of soluble lens proteins.