Nitro-oleic acid (NO2-OA) ameliorates erectile dysfunction in a rat model of diabetes mellitus via modulation of fibrosis, inflammation and autophagy.

Background: Inflammation, fibrosis and autophagy represent closely related factors associated with the pathogenesis of diabetes mellitus erectile dysfunction (DMED). In this study, the therapeutic effect of nitro-oleic acid (NO2-OA) in a streptozotocin-induced rat model of DMED was evaluated. Methods: Sixty rats were randomly divided into four groups: control, DMED, DMED + Vehicle and DMED + NO2-OA. DMED was induced by intraperitoneal injection of streptozotocin in male rats. Blood glucose and body weight were measured every 2 weeks. After 4 weeks of NO2-OA treatment, erectile function was measured by electrical stimulation of cavernous nerve (CN). Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Masson's trichrome staining were used to verify the related factors and protein expression levels. Results: We found that NO2-OA could significantly increase erectile pressure in the corpus cavernosum of DMED rats. Results of western blot, confocal immunofluorescence and qRT-PCR assays revealed that NO2-OA significantly reduced inflammatory factors and the expression of nuclear factor kappa B (NF-κB). In addition, Masson staining results indicated that NO2-OA significantly reduced the display of fibrotic tissue in the corpus cavernosum. These beneficial effects may be related to reductions in the expression of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) and the increase in the expression of α-smooth muscle actin (α-SMA). Finally, NO2-OA treatment increased the expression of the autophagy marker, LC3, while P62 was decreased, effects suggesting that one of the underlying mechanisms of NO2-OA may involve an activation of the PI3K/AKT/mTOR pathway to enhance the capacity for autophagy within this tissue. Conclusions: NO2-OA enhances erectile function within a rat model of DMED by inhibiting inflammation and fibrosis along with activating autophagy.

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway.

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction (DMED) a challenging endeavor. Notable factors contributing to DMED include oxidative stress, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway activation, and apoptosis, while nitro-oleic acid (NO2-OA) has been shown to be beneficial in treating these aspects of this condition. We, herein, investigated the effects and possible mechanisms of NO2-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes. Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group. However, in response to 4 weeks of NO2-OA treatment, there was an improvement in erectile function. The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group. The expression of proapoptotic factors was increased, while that of antiapoptotic factors was decreased in the DMED group. Moreover, the cell morphology in the cavernous tissue of the DMED group also changed adversely. NO2-OA treatment significantly reversed all these changes observed in the DMED group. In conclusion, NO2-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress, activation of the NO/cGMP pathway, and a reduction in apoptosis.

N-acetylcysteine improves diabetic associated erectile dysfunction in streptozotocin-induced diabetic mice by inhibiting oxidative stress.

Oxidative stress appears to play a role in the pathogenesis of diabetes mellitus erectile dysfunction (DMED). This study aimed to investigate the effect of N-acetylcysteine (NAC) on DMED in streptozotocin-induced diabetic mice and to explore potential mechanisms. In the present study, we show that an erectile dysfunction is present in the streptozotocin-induced mouse model of diabetes as indicated by decreases in intracavernous pressure responses to electro-stimulation as well as from results of the apomorphine test of erectile function. After treatment of NAC, the intracavernous pressure was increased. In these DMED mice, oxidative stress and inflammatory responses were significantly reduced within the cavernous microenvironment, while activity of antioxidant enzymes in this cavernous tissue was enhanced after NAC treatment. These changes protected mitochondrial stress damage and a significant decreased in apoptosis within the cavernous tissue of DMED mice. This appears to involve activation of the nuclear factor erythroid 2-like-2 (Nrf2) signalling pathway, as well as suppression of the mitogen-activated protein kinase (MAPK) p38/ NF-κB pathway within cavernous tissue. In conclusion, NAC can improve erectile function through inhibiting oxidative stress via activating Nrf2 pathways and reducing apoptosis in streptozotocin-induced diabetic mice. NAC might provide a promising therapeutic strategy for individuals with DMED.

Long non-coding DANCR targets miR-185-5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3ß/snail pathway.

BACKGROUND: Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) acts as an oncogene in different cancers, although its roles in prostate cancer are not fully reported. We aimed to explore its mechanism in facilitating the malignancy of prostate cancer. METHODS: The expression of DANCR, microRNA (miR)-185-5p and LIM and SH3 protein 1 (LASP1) in 40 pairs of prostate cancer tissues and normal tissues, five prostate cancer cell lines and one epithelial cell line was assessed by a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. In transfected PC3 and C4-2 cells, cell proliferation, migration, invasion, cell cycle distribution and epithelial-mesenchymal transition (EMT) protein expression were tested via cell counting kit-8, wound healing, transwell, flow cytometry and western blot assays, respectively. The interactions between DANCR, miR-185-5p and LASP1 were verified by a dual-luciferase reporter assay. Rescue experiments were conducted to determine the roles of DANCR on the malignant properties of PC3 and C4-2 cells. The involvement of the signaling pathway was examined using a p-FAK inhibitor. RESULTS: DANCR and LASP1 expression was enhanced, whereas miR-185-5p expression was diminished in prostate cancer tissues and cell lines. Knockdown of DANCR suppressed cell proliferation, migration, invasion, G1-S transition and expression of EMT proteins of the transfected PC3 and C4-2 cells. DANCR sponged miR-185-5p to upregulate LASP1 expression. DANCR-miR-185-5p-LASP1 axis activates the FAK/PI3K/AKT/GSK3ß/Snail pathway to promote the malignant properties of PC3 and C4-2 cells. CONCLUSIONS: These findings suggest that DANCR exerts oncogenic roles in prostate cancer via the miR-185-5p/LASP1 axis activating the FAK/PI3K/AKT/GSK3ß/Snail pathway. It can be a potential biomarker in the diagnosis and monitoring of prostate cancer.