Exercise and prostate cancer: From basic science to clinical applications.

Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression.

The Food Environment, Preference, and Experience Modulate the Effects of Exendin-4 on Food Intake and Reward.

OBJECTIVE: The obesogenic food environment facilitates access to multiple palatable foods. Exendin-4 (EX4) is a glucagon-like peptide 1 receptor (GLP1R) agonist that inhibits food intake and has been proposed as an obesity therapy. This study tested whether the composition of the food environment and experience with palatable foods modulate the effects of EX4 on food intake and reward. METHODS: Mice fed a cafeteria (CAF) or control diet were tested for the anorectic effects of EX4 when simultaneously offered foods of varying individual preference and in a conditioned place preference (CPP) test for chocolate. Plasma glucagon-like peptide 1 (GLP1) and hypothalamic GLP1R mRNA were analyzed post mortem. RESULTS: Mice fed a CAF diet developed individual food preference patterns. Offering mice either novel or highly preferred foods decreased the potency of EX4 to inhibit food intake compared to low preference foods or chow. Compared to the control diet, CAF diet intake blocked the decrease in chocolate CPP caused by EX4 and decreased the expression of hypothalamic GLP1R mRNA without altering the plasma GLP1 concentration. CONCLUSIONS: The composition of the food environment, food preference, and experience modulate the ability of EX4 to inhibit food intake and reward. These data highlight the significance of modeling the complexity of the human food environment in preclinical obesity studies.

Heme oxygenase-1 as a target for the design of gene and pharmaceutical therapies for autoimmune diseases.

One of the major goals in the research of autoimmune diseases is to develop specific therapies to regulate the expression and function of gene products that could contribute to restoring tolerance to self-constituents and replace conventional systemic immunosuppression, which is associated with important undesired side effects. Although significant progress has been made on the understanding of the pathogenesis of autoimmunity, therapies for these ailments have not seen a change. During the last decade, different strategies such as pharmacologic or gene therapy modulation of heme oxygenase-1 (HO-1) and the administration of its metabolic product, carbon monoxide (CO), have been shown to display beneficial immunoregulatory and cytoprotective properties. In different experimental autoimmune conditions, such as Experimental autoimmune encephalomyelitis, type-1 diabetes and systemic lupus erythematosus, genetic or pharmacological modulation of HO-1, as well as delivery of CO have shown to ameliorate disease progression. Furthermore, it has been demonstrated that dendritic cell and monocyte function can be modulated by HO-1 and/or CO. In this article, recent data related to the immunoregulatory properties of HO-1/CO will be discussed, focusing on their potential therapeutic use to treat autoimmune diseases.