The neural mobilization technique modulates the expression of endogenous opioids in the periaqueductal gray and improves muscle strength and mobility in rats with neuropathic pain.

BACKGROUND: The neural mobilization (NM) technique is a noninvasive method that has been proven to be clinically effective in reducing pain; however, the molecular mechanisms involved remain poorly understood. The aim of this study was to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the periaqueductal gray (PAG) and improves locomotion and muscle force after chronic constriction injury (CCI) in rats. METHODS: The CCI was imposed on adult male rats followed by 10 sessions of NM every other day, starting 14 days after the CCI injury. At the end of the sessions, the PAG was analyzed using Western blot assays for opioid receptors. Locomotion was analyzed by the Sciatic functional index (SFI), and muscle force was analyzed by the BIOPAC system. RESULTS: An improvement in locomotion was observed in animals treated with NM compared with injured animals. Animals treated with NM showed an increase in maximal tetanic force of the tibialis anterior muscle of 172% (p < 0.001) compared with the CCI group. We also observed a decrease of 53% (p < 0.001) and 23% (p < 0.05) in DOR and KOR levels, respectively, after CCI injury compared to those from naive animals and an increase of 17% (p < 0.05) in KOR expression only after NM treatment compared to naive animals. There were no significant changes in MOR expression in the PAG. CONCLUSION: These data provide evidence that a non-pharmacological NM technique facilitates pain relief by endogenous analgesic modulation.

Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Beta-agonist stimulation ameliorates the phenotype of spinal and bulbar muscular atrophy mice and patient-derived myotubes.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by the loss of lower motor neurons. SBMA is caused by expansions of a polyglutamine tract in the gene coding for androgen receptor (AR). Expression of polyglutamine-expanded AR causes damage to motor neurons and skeletal muscle cells. Here we investigated the effect of ß-agonist stimulation in SBMA myotube cells derived from mice and patients, and in knock-in mice. We show that treatment of myotubes expressing polyglutamine-expanded AR with the ß-agonist clenbuterol increases their size. Clenbuterol activated the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway and decreased the accumulation of polyglutamine-expanded AR. Treatment of SBMA knock-in mice with clenbuterol, which was started at disease onset, ameliorated motor function and extended survival. Clenbuterol improved muscle pathology, attenuated the glycolytic-to-oxidative metabolic alterations occurring in SBMA muscles and induced hypertrophy of both glycolytic and oxidative fibers. These results indicate that ß-agonist stimulation is a novel therapeutic strategy for SBMA.

Biologia molecular como ferramenta no esporte de alto rendimento: possibilidades e perspectivas / Molecular biology as an instrument in the high performance sport: possibilities and perspectives / La biología molecular como una herramienta de alto ingreso deportes: posibilidades y perspectivas

Várias estratégias têm sido pensadas com o propósito de se utilizar a biologia molecular como ferramenta na pré-seleção e na seleção de talentos esportivos, na manipulação genética visando ao aumento ou à diminuição da produção de determinadas substâncias pelo organismo, na prescrição do treinamento e na recuperação de lesões. Portanto, o objetivo desta revisão é apresentar o DNA como regulador do funcionamento do organismo e de que forma alterações no perfil genético, tanto espontâneas como induzidas artificialmente, podem modular respostas fisiológicas e morfológicas por alterar a expressão de determinadas proteínas. Será dada especial atenção à descrição dos procedimentos utilizados para a manipulação genética, nos baixos riscos associados e nas estratégias que têm sido desenvolvidas com o objetivo de detectá-la. Com base em conhecimentos científicos, coerência e bom senso, diversas visões devem ser expostas e amplamente discutidas para ser definido o que é permitido e o que é proibido nas competições esportivas.

Many strategies have been thought with the purpose of to use the molecular biology as an instrument in the pre-selection and in the selection of sport talents, in the genetic manipulation to increase or to reduce the production of certain substances by the body, in the prescription of training and in the recuperation of lesions. By the way, the aim of this review is to present the DNA as regulator of the body functioning and as alterations in the genetic approach, spontaneous and artificially induced, can modulate physiological and morphological responses by changes the expression of certain proteins. It will be give special attention in the description of the proceedings used to genetic manipulation, in the small risks associated and in the strategies that have been developed with the purpose of detect them. Based in scientific knowledge, coherence and good sense, many visions have to be exposed and very discussed to be defined what is permitted and what is prohibited in the sport competitions.

Varias estrategias han sido diseñadas con el propósito de utilizar la biología molecular como una herramienta de pre-selección y selección de talentos deportivos en la manipulación genética destinada a aumentar o disminuir la producción de determinadas sustancias por el organismo en la prescripción de la formación y la recuperación de la lesión. Por lo tanto, el objetivo de esta revisión es presentar el DNA como un regulador del funcionamiento del cuerpo y cómo los cambios en el perfil genético, tanto espontáneo y artificialmente inducida, son capaces de modular las respuestas fisiológicas y morfológicas en cambio la expresión de determinadas proteínas. Se prestará especial atención en la descripción de los procedimientos utilizados para la manipulación genética, los bajos riesgos y las estrategias que se han desarrollado con el objetivo de detectar la misma. Basadas en el conocimiento científico, la coherencia y el sentido común, los diferentes puntos de vista deben ser expuestos a ser ampliamente discutidos y definidos de lo permitido y qué está prohibido en competiciones deportivas.