African American men in the United States have higher mortality due to prostate cancer (PCa) compared to other races. One reason for this disparity is the lack of in-depth understanding of the PCa biology in African Americans. For example, hypoxia in prostate tumor microenvironment is associated with adverse prognosis; still, no hypoxia-related studies have been reported in African Americans. Here, we compared African-American and Caucasian PCa cells for exosome secretion under normoxic (21% O₂) and hypoxic (1% O₂) conditions. All cell lines showed higher exosome secretion under hypoxia but it was clearly more prominent in African-American PCa cells. Further, under hypoxia, Rab5 (a biomarker for early endosome) was clustered in perinuclear region; and CD63 (a biomarker for exosomes and multivesicular endosomes) showed greater co-localization with actin cytoskeleton especially in African American PCa cells. Importantly, exosome biogenesis inhibitors GW4869 (10–20 µM) or DMA (10–20 µg/ml) significantly decreased cell viability and clonogenicity in PCa cells. Interestingly, we also observed higher level of lactic acid loaded in exosomes secreted under hypoxia. Overall, under chronic hypoxia, PCa cells secrete more exosomes as a survival mechanism to remove metabolic waste.

Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Simultaneously, researchers have elucidated the roles that this pathway plays in the regulation of cell proliferation, tumor development, and progression. As a result, our knowledge of PDE5i and cancer biology has expanded and provides an integration that holds great promise for some, but concern for others. This review evaluates the role of PDE5i and the NO/cGMP signaling pathway in the pathogenesis and prevention of various malignancies. A literature review was performed with regard to the role of NO/cGMP pathway in tumor formation and prevention in preclinical and clinical studies. Studies that utilized PDE5i to further explore the involvement of this pathway also were included. To evaluate whether PDE5i provide a potential benefit for treating and/or preventing malignancies; or if they create potential harm leading to the development of these malignancies. The best available data suggest that the interactions between PDE5i and cancer are tumor- and tissue-specific. Currently, the effect of PDE5i use on melanoma development is being debated. Further clinical controversy lies in PDE5i use for penile rehabilitation after nerve-sparing prostate cancer surgery. Preclinical studies suggest that PDE5 inhibition could lead to a decreased risk of developing colorectal and breast cancer, leukemia, and myeloma. PDE5i also may provide an additional antitumor immune response. Finally, researchers have demonstrated a synergistic effect from combining PDE5i with current chemotherapeutic regimens. Currently, there are inadequate data to make any conclusive statements regarding the role of PDE5i in cancer pathogenesis and how to alter clinical management. In order to create appropriate clinical guidelines, further experimental and clinical evidence is required.

Hydrogen sulfide (H₂S) is an endogenous gaseous molecule formed from L-cysteine in vascular tissue. In the present study, cardiovascular responses to the H₂S donors Na₂S and NaHS were investigated in the anesthetized rat. The intravenous injections of Na₂S and NaHS 0.03–0.5 mg/kg produced dose-related decreases in systemic arterial pressure and heart rate, and at higher doses decreases in cardiac output, pulmonary arterial pressure, and systemic vascular resistance. H₂S infusion studies show that decreases in systemic arterial pressure, heart rate, cardiac output, and systemic vascular resistance are well-maintained, and responses to Na₂S are reversible. Decreases in heart rate were not blocked by atropine, suggesting that the bradycardia was independent of parasympathetic activation and was mediated by an effect on the sinus node. The decreases in systemic arterial pressure were not attenuated by hexamethonium, glybenclamide, N^w-nitro-l-arginine methyl ester hydrochloride, sodium meclofenamate, ODQ, miconazole, 5-hydroxydecanoate, or tetraethylammonium, suggesting that ATP-sensitive potassium channels, nitric oxide, arachidonic acid metabolites, cyclic GMP, p450 epoxygenase metabolites, or large conductance calcium-activated potassium channels are not involved in mediating hypotensive responses to the H₂S donors in the rat and that responses are not centrally mediated. The present data indicate that decreases in systemic arterial pressure in response to the H₂S donors can be mediated by decreases in vascular resistance and cardiac output and that the donors have an effect on the sinus node independent of the parasympathetic system. The present data indicate that the mechanism of the peripherally mediated hypotensive response to the H₂S donors is uncertain in the intact rat.

Erectile dysfunction (ED) is a common sexual disorder that affects the lives of millions of male patients and their partners. Various medical and surgical therapies exist, with the most common being oral intake of phosphodiesterase 5 inhibitors. One therapeutic strategy in preclinical development to treat ED is stem cell transplantation. To examine the studies that have investigated stem cells for the treatment of ED. A literature review was performed through PubMed focusing on stem cells and ED. An assessment of different types of stem cells and how they may be applied therapeutically in the treatment of ED. The stem cell types that have been investigated for the treatment of ED include bone marrow-derived mesenchymal, adipose-derived, muscle-derived, testes, urine-derived, neural crest, and endothelial progenitor. Depending on the cell type, research has demonstrated that with transplantation, stem cells exert a paracrine effect on penile tissue, and can differentiate into smooth muscle, endothelium, and neurons. Multiple stem cell lines are currently being studied for their potential to treat ED. To date, stem cells have proven safe and effective in both animal and human models of ED. More research is needed to understand their full therapeutic potential.