Gastroprotective activity of (E)-ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from Heliotropium indicum: role of nitric oxide, prostaglandins, and sulfhydryls in its mechanism of action.

CONTEXT: The gastroprotective effect of Heliotropium indicum L. (Boraginaceae), a plant traditionally used in Mexico to treat gastric ulcers, has been previously reported. However, no active compound was identified. OBJECTIVE: The current contribution aimed to isolate, through a bioassay-guided study, at least one compound from H. indicum with considerable gastroprotective activity, examine its effect on ethanol-induced gastric lesions in mice, and explore possible mechanisms of action. MATERIALS AND METHODS: Three extracts (hexane, dichloromethane, and methanol) were obtained from H. indicum leaves. Their 30 and 100 mg/kg doses were assessed on ethanol-induced gastric lesions in male CD1 mice. Since the dichloromethane extract was the most active, successive chromatographies were carried out leading to the identification of the most active compound. This compound (at 3-100 mg/kg) was compared to carbenoxolone (at 10-100 mg/kg) in biological evaluations in mice. Pre-treatments with indomethacin (10 mg/kg, s.c.), L-NAME (70 mg/kg, i.p.), and NEM (10 mg/kg, s.c.) were performed independently to determine the participation of prostaglandins, nitric oxide, and/or sulfhydryl groups, respectively, in the mechanism of action of the compound. RESULTS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from H. indicum, afforded dose-dependent gastroprotective activity. The maximum effect was observed at 100 mg/kg (90.13 ± 3.08%), with an ED50 of 5.92 ± 2.48 mg/kg. Gastroprotection was not modified by pre-treatment with indomethacin, L-NAME, or NEM. CONCLUSIONS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, isolated from H. indicum, was found to produce a substantial gastroprotective effect. Prostaglandins, nitric oxide, and non-protein sulfhydryl groups are not involved in its mechanism of action.

Apoptosis Induced by (-)-Epicatechin in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species.

(-)-Epicatechin is a phenolic compound with antioxidant activity that is present in natural food and drinks, such as cocoa and red wine. Evidence suggests that (-)-epicatechin exhibits anticancer activity; however, its mechanism of action is poorly understood. Here, we investigated the anticancer effects of (-)-epicatechin and its mechanism of action in breast cancer cells. We assessed the anticancer activity by cell proliferation assays, apoptosis by DNA fragmentation and flow cytometry. The expression of proteins associated with apoptosis was analyzed by the human apoptosis array. MitoSOXTM Red and biomarkers of oxidative damage were used to measure the effect of (-)-epicatechin on mitochondrial reactive oxygen species (ROS) and cellular damage, respectively. (-)-Epicatechin treatment caused a decreasing in the viability of MDA-MB-231 and MCF-7 cells. This cell death was associated with DNA fragmentation and an apoptotic proteomic profile. Further, (-)-epicatechin in MDA-MB-231 cells upregulated death receptor (DR4/DR5), increased the ROS production, and modulated pro-apoptotic proteins. In MCF-7 cells, (-)-epicatechin did not involve death receptor; however, an increase in ROS and the upregulation of pro-apoptotic proteins (Bad and Bax) were observed. These changes were associated with the apoptosis activation through the intrinsic pathway. In conclusion, this study shows that (-)-epicatechin has anticancer activity in breast cancer cells and provides novel insight into the molecular mechanism of (-)-epicatechin to induce apoptosis.

Lecithin-chitosan-TPGS nanoparticles as nanocarriers of (-)-epicatechin enhanced its anticancer activity in breast cancer cells.

Natural compounds such as (-)-epicatechin show a variety of biological properties including anticancer activity. Nonetheless, (-)-epicatechin's therapeutic application is limited due to its low water solubility and sensitivity to oxygen and light. Additionally, previous studies have reported that the encapsulation of flavonoids in nanoparticles might generate stable deliverable forms, which improves the availability and solubility of the bioactive compounds. The aims of this study were to generate (-)-epicatechin-loaded lecithin-chitosan nanoparticles (EC-LCT-NPs) by molecular self-assembly and to assess their cytotoxic potential against breast cancer cells. Various parameters were measured to characterize the EC-LCT-NPs including size, polydispersity index (PdI), zeta potential, morphology and entrapment efficiency. The results showed that the mean particle size of the EC-CLT-NPs was 159 ± 2.23 nm (PdI, 0.189), and the loading and entrapment efficiencies of (-)-epicatechin were 3.42 ± 0.85% and 56.1 ± 3.9%, respectively. The cytotoxic effect of the EC-CLT-NPs was greater than that of free (-)-epicatechin on breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-436 and SK-Br3). Indeed, EC-LCT-NPs showed an IC50 that was four-fold lower (85 µM) than free (-)-epicatechin (350 µM) and showed selectivity to cancerous cells. This study demonstrated that encapsulating (-)-epicatechin into lecithin-chitosan nanoparticles opens new options for breast cancer treatment.

Inserción laboral, desarrollo profesional y desempeño institucional de las (os) egresadas (os) del Plan Único de Especialización en Enfermería de la ENEO-UNAM: una experiencia de doce años / Labor market integration, professional development, and institutional performance of the graduates from the unique plan of specialization in nursing of the ENEO-UNAM: a 12 year experience

Objetivo: Analizar las características que adopta la Inserción y desempeño laboral así como el Desarrollo profesional de las egresadas(os) del Plan Único de Especialización en Enfermería (PUEE) de la ENEO-UNAM. Marco Teórico. Inserción Laboral es un término usado para referirse al proceso de incorporación de los individuos a la actividad económica. El desarrollo profesional, es el fruto de la carrera, comprende los aspectos que enriquecen a la persona con vistas hacia el logro de metas dentro de la organización. El desempeño institucional incluye acciones o comportamientos de los empleados, relevantes para con los objetivos de la organización medidos en términos de competencias y niveles de contribución. Metodología. Estudio descriptivo y transversal, las variables de la inserción laboral fueron: Centro/institución de trabajo, categoría, antigüedad, salario y funciones principales. Las dimensiones del desarrollo profesional fueron: responsabilidad, autonomía, trabajo en equipo y posicionamiento. Las del desempeño Institucional: características de la Institución empleadora, satisfacción con el desarrollo profesional del egresado, y vinculación con la ENEO. La muestra fue de 417 egresados y trece instituciones encuestadas. Para el Desempeño Institucional se aplicaron 86 cuestionarios, a personal directivo de enfermería tanto de instituciones públicas como privadas. Resultados. La Inserción laboral mostró que la actividad principal desarrollada por los egresados es la atención directa, en Desarrollo Profesional los egresados perciben que la especialidad les habilitó para actuar con responsabilidad, autonomía, y trabajar en equipo, pero en el ámbito laboral el reconocimiento es limitado. El perfil del egresado coincide con lo requerido por las instituciones empleadoras y el desempeño es percibido como bueno.

Objective: Analyze the characteristics of the processes of labor market integration and performance, as well as professional development in the graduates from the Unique Plan of Specialization in Nursing (UPSN) of the ENEO-UNAM. Theoretical Frame: Labor market integration is a term commonly used to refer the process of incorporating individuals into the economic activity. Professional development is the fruit of the career and includes the aspects which enrich the person towards the achievement of goals within the organization. Institutional development includes the actions or behaviors of the employees which are relevant to the objectives of the organization, and which can be measured in terms of competences and contribution levels. Methodology: This is a basic and descriptive study and the measured variables of labor market integration were; center/institution of work, category, seniority, salary, and principal functions; the dimensions of professional development were; responsibility, autonomy, team-work, and position; and the dimensions of institutional performance were; employer characteristics, satisfaction with the graduate's professional performance, and bonds with the ENEO. The sample included 417 graduates from the UPSN, and 13 institutions. To collect data related to institutional performance, 86 questionnaires were given to the directive nursing staff of both the public and private institutions. Results: labor market integration showed that the graduate's principal activity is direct attention. In relation to professional development, graduates perceive that their specialties enable them to perform with responsibility and autonomy, and to work in teams, but also that the acknowledgement is limited. The graduate's profile fits that required from the employer institutions, with a performance perceived as good.