Native Mexican black bean purified anthocyanins fractionated by high-performance counter-current chromatography modulate inflammatory pathways.

In addition to their pigment properties, the potential health benefits of anthocyanins have made them a subject of interest in recent years. This study aimed to obtain purified anthocyanin fractions from native Mexican black bean cultivars using Amberlite XAD-7 resin column and HPCCC and evaluate their anti-inflammatory properties using RAW 264.7 cells. The major anthocyanins in the purified anthocyanin fractions were delphinidin 3-glucoside (61.8%), petunidin 3-glucoside (25.2%), and malvidin 3-glucoside (12.2%). Purified anthocyanin fractions at 12.5 µg/mL effectively prevented LPS-induced ERK1/ERK2 phosphorylation and reduced the protein expression of COX-2 and mRNA expression of iNOS. Results showed that purified anthocyanin fractions have the potential to modulate the inflammatory response by inhibiting the production of pro-inflammatory mediators through the ERK1/ERK2 and NF-κB pathways. This study suggests that anthocyanins from black beans could be used as a natural strategy to help modulate inflammation-associated diseases.

The potential role of apigenin in the enhancement of the antioxidant adaptation to exercise by bioactive dietary compounds

Oxidative stress (OS) occurs when the antioxidant defense system is overwhelmed by the predominance of reactive oxygen species (ROS) and pro-oxidant factors. Several diseases such as hypertension, insulin resistance, type 2 diabetes mellitus and neurodegenerative diseases are characterized by chronic OS. Physical exercise constitutes an affordable tool to prevent or ameliorate these conditions. However, during physical activity, acute ROS are produced inducing an activation in peroxisome proliferator activated receptor-Gamma Coactivator-1alpha (PGC-1α), and nuclear factor erythroid-2 related factor 2 (Nrf2), PGC-1α/Nrf2 pathway. This signaling pathway facilitates interaction with antioxidant response elements (ARE), thereby initiating an upregulation in the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and mitochondrial biogenesis. In both cases, whether involving healthy animals or individuals engaged in physical exercise, supplementation with antioxidant scavengers leads to a reduction in the expression and activity of PGC-1α, SOD, CAT, and GPX across various tissues, which is not observed with indirect antioxidants. The preventive role of physical exercise against chronic OS is avoided when executed in conjunction with supplementation of scavenger antioxidants. However, similar to exercise, the indirect antioxidant apigenin can activate the PGC1-α/Nrf2 signaling pathway. Here, we summarize evidence supporting apigenin as a non-nutritional supplement that could enhance the adaptive effects of exercise, improving the endogenous antioxidant defense. Therefore, apigenin could be an interesting supplement to enhance the endogenous antioxidant adaptation induced by exercise in healthy subjects, but also to improve the effectiveness of exercise to prevent oxidative stress-associated diseases.

El estrés oxidativo (OS) ocurre cuando el sistema de defensa antioxidante es sobrepasado por el predominio de especies reactivas de oxígeno (ROS) y factores prooxidantes. Varias enfermedades como la hipertensión, la resistencia a la insulina, la diabetes mellitus tipo 2 y enfermedades neurodegenerativas se caracterizan por un OS crónico. El ejercicio físico constituye una herramienta asequible para prevenir o mejorar estas enfermedades. Sin embargo, durante la actividad física, se producen ROS agudas que inducen una activación en la vía PGC-1α/Nrf2. Esta vía de señalización facilita la interacción con los elementos de respuesta antioxidante (ARE), iniciando así una regulación que permite la expresión de enzimas antioxidantes, incluidas SOD, CAT, GPX y biogénesis mitocondrial. En ambos casos, ya sea que se trate de animales sanos o de individuos que practican ejercicio físico, la suplementación con antioxidantes "scavengers" conduce a una reducción en la expresión y actividad de PGC-1α, SOD, CAT y GPX en varios tejidos, lo que no se observa con antioxidantes "indirectos". El papel preventivo del ejercicio físico contra el OS crónico se atenúa cuando se realiza en conjunto con la suplementación de antioxidantes "scavengers". Sin embargo, de manera similar al ejercicio, la apigenina es un antioxidante "indirecto" que puede activar la vía de señalización PGC1-α/Nrf2. Aquí, resumimos la evidencia que respalda a apigenina como un suplemento no-nutricional que podría mejorar los efectos adaptativos del ejercicio, mejorando la defensa antioxidante endógena de sujetos sanos que no tienen suficiente tiempo para hacer ejercicio.

Triple-negative breast cancer in Peru: 2000 patients and 15 years of experience.

BACKGROUND: Epidemiological studies commonly identify the clinical characteristics and survival outcomes of patients with breast cancer at five years. Our study aims to describe the sociodemographic, clinicopathological characteristics and determine the long-term event-free survival (EFS) and overall survival (OS) of a Peruvian population with triple-negative breast cancer. METHODS: We reviewed the medical records of new cases treated at a single institution in the period 2000-2014. The survival analysis included patients with stages I-IV. Survival estimates at 10 years were calculated with the Kaplan-Meier method and compared with the Log-rank test. We further used multivariate Cox regression analysis to calculate prognostic factors of recurrence and mortality. RESULTS: Among the 2007 patients included, the median age at diagnosis was 49 years (19-95 years). Most patients presented histologic grade III (68.7%), tumor stage II (34.2%), and III (51.0%) at diagnosis. Local and distant relapse was present in 31.9 and 51.4% of the patients, respectively. The most frequent sites of metastasis were the lungs (14.5%), followed by bone (9.7%), brain (9.6%), and liver (7.9%). The median follow-up was 153 months. At 3, 5, and 10 years, the EFS of the population was 55%, 49%, and 41%, respectively, while the OS was 64%, 56%, and 47%, respectively. Moreover, an N3 lymph node status was the most important prognostic factor for both disease relapse (HR: 2.54, 95% CI: 2.05-3.15) and mortality (HR: 2.51, 95% CI: 2.01-3.14) at ten years. An older age and higher T staging were associated with a worse OS, while patients who received radiotherapy and adjuvant chemotherapy had better survival rates. CONCLUSION: The sociodemographic features of Peruvian patients with TNBC are similar to those of other populations. However, our population was diagnosed at more advanced clinical stages, and thus, EFS and OS were lower than international reports while prognostic factors were similar to previous studies.

MAP1203 Promotes Mycobacterium avium Subspecies paratuberculosis Binding and Invasion to Bovine Epithelial Cells.

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease, chronic and ultimately fatal enteritis that affects ruminant populations worldwide. One mode of MAP transmission is oral when young animals ingest bacteria from the collostrum and milk of infected dams. The exposure to raw milk has a dramatic impact on MAP, resulting in a more invasive and virulent phenotype. The MAP1203 gene is upregulated over 28-fold after exposure of the bacterium to milk. In this study, the role of MAP1203 in binding and invasion of the bovine epithelial cells was investigated. By over-expressing the native MAP1203 gene and two clones of deletion mutant in the signal sequence and of missense mutations changing the integrin domain from RGD into RDE, we demonstrate that MAP1203 plays a role in increasing binding in more than 50% and invasion in 35% of bovine MDBK epithelial cells during early phase of infection. Furthermore, results obtained suggest that MAP1203 is a surface-exposed protein in MAP and the signal sequence is required for processing and expression of functional protein on the surface of the bacterium. Using the protein pull-down assay and far-Western blot, we also demonstrate that MAP1203 interacts with the host dihydropyrimidinase-related protein 2 and glyceraldehyde 3-phosphate dehydrogenase proteins, located on the membrane of epithelial cell and involved in the remodeling of the cytoskeleton. Our data suggests that MAP1203 plays a significant role in the initiation of MAP infection of the bovine epithelium.