Melanopsin (Opn4) is an oncogene in cutaneous melanoma.

The search for new therapeutical targets for cutaneous melanoma and other cancers is an ongoing task. We expanded this knowledge by evaluating whether opsins, light- and thermo-sensing proteins, could display tumor-modulatory effects on melanoma cancer. Using different experimental approaches, we show that melanoma cell proliferation is slower in the absence of Opn4, compared to Opn4WT due to an impaired cell cycle progression and reduced melanocyte inducing transcription factor (Mitf) expression. In vivo tumor progression of Opn4KO cells is remarkably reduced due to slower proliferation, and higher immune system response in Opn4KO tumors. Using pharmacological assays, we demonstrate that guanylyl cyclase activity is impaired in Opn4KO cells. Evaluation of Tumor Cancer Genome Atlas (TCGA) database confirms our experimental data as reduced MITF and OPN4 expression in human melanoma correlates with slower cell cycle progression and presence of immune cells in the tumor microenvironment (TME). Proteomic analyses of tumor bulk show that the reduced growth of Opn4KO tumors is associated with reduced Mitf signaling, higher translation of G2/M proteins, and impaired guanylyl cyclase activity. Conversely, in Opn4WT tumors increased small GTPase and an immune-suppressive TME are found. Such evidence points to OPN4 as an oncogene in melanoma, which could be pharmacologically targeted.

Cardiovascular Risk Factors in Colombian Penitentiary Staff: An Interdisciplinary View of a High-Risk Occupation.

INTRODUCTION: Cardiovascular risk factors have been measured under different conditions, there is some missing information related to specific occupations, such as penitentiary staff which due to their characteristics could have an increased cardiovascular risk. Objective: To determine cardiovascular risk factors on military staff from penitentiary institutions in Santander-Colombia. Methods: Cross-sectional study conducted with 182 workers. Anthropometric parameters, blood pressure, serum lipid profile, and glucose levels were measured. Univariate and bivariate analyses were carried out to establish differences between individuals. Results: Anthropometric and biochemical measures showed that 71.3% participants were overweight or obese, 29.4% presented high blood pressure with increased levels of total cholesterol (27.5%), triglycerides (40.7%), glucose (9.3%), and 84.1% presented low levels of HDL cholesterol. Bivariate analysis found a negative correlation between BMI and HDL cholesterol (p < .05) and a positive correlation between BMI with triglycerides (p < .01), systolic and diastolic blood pressure (DBP) (p < .01). Conclusion: The studied military population presented increased levels of cardiovascular risk in comparison with a similar group in age, gender of nonmilitary individuals. However, it is important to carry out comparative studies between military staff in order to determine the prevalence and other risk predicting factors present in this specific population.

Aprendizaje basado en proyectos como una estrategia para la enseñanza en ciencias de la salud / Project-based learning as a teaching strategy in health sciences

Introducción: En los procesos de enseñanza-aprendizaje, los profesores deben reflexionar continuamente sobre las estrategias que se aplican directamente en el aula. Se ha estudiado el efecto de metodologías como el aprendizaje basado en problemas, el aprendizaje basado en proyectos, las simulaciones apoyadas en la tecnología, entre otras, en comparación con las metodologías tradicionales. Objetivo: Describir las fortalezas del aprendizaje basado en proyectos como estrategia educativa en el contexto de las ciencias de la salud. Desarrollo: El proceso de enseñanza-aprendizaje de las ciencias de la salud requiere de estrategias dinámicas que permitan articular los conocimientos adquiridos, con una visión práctica de las disciplinas en un contexto basado en la solución de problemas y el pensamiento crítico. Se destaca el aprendizaje basado en proyectos como una metodología que exige una participación activa, investigativa y reflexiva, para la solución de un problema; así, el conocimiento es consecuencia de la discusión, la argumentación y la toma de decisiones, que implican la construcción de dicha solución. Conclusiones: El aprendizaje basado en proyectos puede introducir mejoras y cambios con respecto a las estrategias tradicionales, al fomentar la motivación, el trabajo colaborativo, la adquisición y el afianzamiento de conocimientos en los estudiantes. Asimismo, es una metodología basada en la autoformación del estudiante que fortalece su capacidad de expresión oral y escrita, y la planificación del tiempo, por lo que se facilita la conformación y participación en equipos interdisciplinarios, competencias esenciales para el desempeño ideal de los profesionales de la salud(AU)

Introduction: In teaching-learning processes, professors must continually reflect on the strategies applied directly in the classroom. The effect of methodologies such as problem-based learning, project-based learning, technology-supported simulations, among others, has been studied in comparison with traditional methodologies. Objective: To describe the strengths of project-based learning as an educational strategy in the context of health sciences. Development: The teaching-learning process of health sciences requires dynamic strategies that allow the articulation of the acquired knowledge, with a practical vision of disciplines in a context based on problem solving and critical thinking. Project-based learning is highlighted as a methodology that requires active, investigative and reflective participation to solve a problem; thus, knowledge is the consequence of discussion, argumentation and decision-making, which imply the construction of such a solution. Conclusions: Project-based learning can introduce improvements and changes with respect to traditional strategies, by promoting motivation, collaborative work, as well as knowledge acquisition and consolidation in students. Likewise, it is a methodology based on student self-training and strengthening their capacity for oral and written expression, as well as time planning, thus facilitating the formation and participation in interdisciplinary teams, essential competences for an ideal performance of health professionals(AU)

Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema.

Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD.

An Immunometabolic Shift Modulates Cytotoxic Lymphocyte Activation During Melanoma Progression in TRPA1 Channel Null Mice.

Melanoma skin cancer is extremely aggressive with increasing incidence and mortality. Among the emerging therapeutic targets in the treatment of cancer, the family of transient receptor potential channels (TRPs) has been reported as a possible pharmacological target. Specifically, the ankyrin subfamily, representing TRPA1 channels, can act as a pro-inflammatory hub. These channels have already been implicated in the control of intracellular metabolism in several cell models, but little is known about their role in immune cells, and how it could affect tumor progression in a process known as immune surveillance. Here, we investigated the participation of the TRPA1 channel in the immune response against melanoma tumor progression in a mouse model. Using Trpa1 +/+ and Trpa1 -/- animals, we evaluated tumor progression using murine B16-F10 cells and assessed isolated CD8+ T cells for respiratory and cytotoxic functions. Tumor growth was significantly reduced in Trpa1 -/- animals. We observed an increase in the frequency of circulating lymphocytes. Using a dataset of CD8+ T cells isolated from metastatic melanoma patients, we found that TRPA1 reduction correlates with several immunological pathways. Naïve CD8+ T cells from Trpa1 +/+ and Trpa1 -/- animals showed different mitochondrial respiration and glycolysis profiles. However, under CD3/CD28 costimulatory conditions, the absence of TRPA1 led to an even more extensive metabolic shift, probably linked to a greater in vitro killling ability of Trpa1 -/- CD8+ T cells. Therefore, these data demonstrate an unprecedented role of TRPA1 channel in the metabolism control of the immune system cells during carcinogenesis.