Enhancing Antibody-Specific Productivity: Unraveling the Impact of XBP1s Overexpression and Glutamine Availability in SP2/0 Cells.

Augmentation of glycoprotein synthesis requirements induces endoplasmic reticulum (ER) stress, activating the unfolded protein response (UPR) and triggering unconventional XBP1 splicing. As a result, XBP1s orchestrates the expression of essential genes to reduce stress and restore homeostasis. When this mechanism fails, chronic stress may lead to apoptosis, which is thought to be associated with exceeding a threshold in XBP1s levels. Glycoprotein assembly is also affected by glutamine (Gln) availability, limiting nucleotide sugars (NS), and preventing compliance with the increased demands. In contrast, increased Gln intake synthesizes ammonia as a by-product, potentially reaching toxic levels. IgA2m(1)-producer mouse myeloma cells (SP2/0) were used as the cellular mammalian model. We explored how IgA2m(1)-specific productivity (qIgA2m(1)) is affected by (i) overexpression of human XBP1s (h-XBP1s) levels and (ii) Gln availability, evaluating the kinetic behavior in batch cultures. The study revealed a two and a five-fold increase in qIgA2m(1) when lower and higher levels of XBP1s were expressed, respectively. High h-XBP1s overexpression mitigated not only ammonia but also lactate accumulation. Moreover, XBP1s overexpressor showed resilience to hydrodynamic stress in serum-free environments. These findings suggest a potential application of h-XBP1s overexpression as a feasible and cost-effective strategy for bioprocess scalability.

Desafío hospitalario: experiencia de un equipo de ginecología en el manejo integral de pacientes COVID 19 / A hospital challenge: experience of a gynecology team in the comprehensive management of patients COVID 19

INTRODUCCIÓN: La infección por el coronavirus SARS-CoV2 (COVID 19), causal de la pandemia actual, ha significado a nivel mundial la hospitalización simultánea de múltiples pacientes poniendo a prueba la infraestructura hospitalaria y la capacidad de reacción del personal de salud. Una de las estrategias para el manejo es la reconversión de camas y servicios clínicos. OBJETIVOS: presentar experiencia de un equipo ginecológico en el manejo integral de pacientes no gineco-obstétricas con COVID 19, durante el mes de junio de 2020 en un hospital público de la Región Metropolitana. MÉTODOS: Estudio de corte transversal observacional, descriptivo. Se consideró el total de pacientes adultos hombres y mujeres sin patología gineco-obstétrica con COVID 19 ingresados al puerperio del Hospital Santiago Oriente, obteniéndose datos clínicos y demográficos a través del registro interno de la unidad y del sistema de información de red asistencial. RESULTADOS: Ingresaron 82 pacientes, 32 mujeres y 50 hombres, promedio de edad 64. El promedio de días de hospitalización fue 5, con diagnóstico de ingreso principal neumonía viral por COVID-19. Las comorbilidades frecuentes fueron hipertensión arterial sistémica y diabetes mellitus. La complicación más frecuente fue el tromboembolismo pulmonar agudo. Hubo una alta cobertura de entrega de información vía telefónica a familiares. De los 82 ingresos, 54 pacientes egresaron a su domicilio. El resto a otras unidades dentro de la institución, centros de menor complejidad o residencias sanitarias. Una paciente sexo femenino de 75 años fallece a causa de descompensación de patologias de base secundario a neumonia por Staphylococus aereus. En ella, se descarta la infección por COVID 19 dado tres exámenes por reacción de polimerasa en cadena negativos realizado antes y durante su hospitalización. CONCLUSIONES: Esta experiencia constituyó un desafío para todo el equipo de salud gineco-obstétrico, considerando que nos enfrentamos a otro tipo de pacientes y a una patología nueva. Los resultados médicos son promisorios, la experiencia humana y sentido de trabajo en equipo fue extraordinario.

INTRODUCTION: The infection by the SARS-CoV2 coronavirus (COVID 19), the cause of the current pandemic we are experiencing, has meant the simultaneous hospitalization of many patients worldwide, putting the hospital infrastructure and the reaction capacity of health personnel to the test. One of the management strategies is the reconversion of clinical services. OBJECTIVES: present the experience of a gynecological team in the comprehensive management of non-gyneco-obstetric patients with COVID 19, during the month of June 2020 in a public hospital in the Metropolitan Region. METHODS: descriptive, observational cross-sectional study. The total number of patients admitted to the ex-puerperium of the Santiago Oriente Hospital was considered, obtaining clinical and demographic data through the unit's internal registry and the healthcare network information system. RESULTS: 82 patients were admitted, 32 women and 50 men, average age 64. The average number of days of hospitalization was 5, with the main admission diagnosis being viral pneumonia due to COVID-19. Frequent comorbidities were systemic arterial hypertension and diabetes mellitus. The most frequent complication was acute pulmonary thromboembolism. There was a high coverage of the delivery of information via telephone to relatives. Of the 82 admissions, 54 patients were discharged home and the rest to other units within the institution, less complex centers or health residences. One 75 years old female patient dies from concomitant pathologies, and she wasn't positive for COVID-19. CONCLUSIONS: This experience was a challenge for the entire gynecological-obstetric health team, considering that we are facing other types of patients and a new pathology. The medical results are promising, the human experience and sense of teamwork was extraordinary.

Rediseño e implementación de un curso de psicología médica desde metodología docente presencial, a una semipresencial. Curso de psicología médica en formato b-learning / Redesign and implementation of a medical psychology course from face to face to blended learning methodology

Introducción: el curso mínimo de psicología médica tiene como propósito introducir y sensibilizar a los estudiantes en temas psicológicos básicos relevantes para la comprensión y desarrollo del ejercicio de la medicina. Entre las últimas evaluaciones de estudiantes de la Pontificia Universidad Católica, destacan comentarios negativos sobre las extensas jornadas de clases y la poca flexibilidad en la entrega de material de estudio. Métodos: se propuso implementar una metodología de clases b-learning, permi-tiendo al estudiante auto gestionar su tiempo y recibir los contenidos a distancia. Se evaluó posteriormente la aceptación de la nueva metodología a través de encuestas de satisfacción y se evaluó comparativamente el efecto de metodología en las calificaciones del alumnado. Resultados: se obtuvo resultados favorables con un promedio global al curso de 6,23 ± 0,67 para el año 2016 y 6,38 ± 0,49 para el 2017, y específicamente para la metodología b-learning de 6,03 ± 0,97 para el 2016, y para el 2017 6,41 ± 0,63. Conclusión: Se concluye que la modalidad de b-learning es una metodología de aprendizaje valorada positivamente por los alumnos con repercusión favorable en sus resultados académicos.

Introduction: the minimum course of Medical Psychology aims to introduce and to make students aware of psychological issues relevant to the understanding and development of the medical practice. Between the last evaluations made by students before 2016, negative comments about the extensive class schedules stand out. Methods: It was proposed to implement a b-learning class methodology, allowing the student to self-manage their time and receive the contents remotely. We evaluated the acceptance of the new methodo-logy through satisfaction surveys, and we evaluated the effect of this methodology on the student's qualifications. Results: favorable results were obtained with a global average to the course of 6.23 ± 0.67 for the year 2016 and 6.38 ± 0.49 for 2017, and specifically for the b-learning methodology, 6.03 ± 0.97 for 2016 and 6.41 ± 0.63 for 2017. Conclusion: We conclude that the b-learning modality is a learning methodology valued positively by the students with a positive increase in their academic results

Autophagy mediates tumor necrosis factor-α-induced phenotype switching in vascular smooth muscle A7r5 cell line.

Vascular smooth muscle cells (VSMC) dedifferentiation from a contractile to a synthetic phenotype contributes to atherosclerosis. Atherosclerotic tissue has a chronic inflammatory component with high levels of tumor necrosis factor-α (TNF-α). VSMC of atheromatous plaques have increased autophagy, a mechanism responsible for protein and intracellular organelle degradation. The aim of this study was to evaluate whether TNF-α induces phenotype switching of VSMCs and whether this effect depends on autophagy. Rat aortic Vascular smooth A7r5 cell line was used as a model to examine the phenotype switching and autophagy. These cells were stimulated with TNF-α 100 ng/mL. Autophagy was determined by measuring LC3-II and p62 protein levels. Autophagy was inhibited using chloroquine and siRNA Beclin1. Cell dedifferentiation was evaluated by measuring the expression of contractile proteins α-SMA and SM22, extracellular matrix protein osteopontin and type I collagen levels. Cell proliferation was measured by [3H]-thymidine incorporation and MTT assay, and migration was evaluated by wound healing and transwell assays. Expression of IL-1ß, IL-6 and IL-10 was assessed by ELISA. TNF-α induced autophagy as determined by increased LC3-II (1.91±0.21, p<0.001) and decreased p62 (0.86±0.02, p<0.05) when compared to control. Additionally, TNF-α decreased α-SMA (0.74±0.12, p<0.05) and SM22 (0.54±0.01, p<0.01) protein levels. Consequently, TNF-α induced migration (1.25±0.05, p<0.05), proliferation (2.33±0.24, p<0.05), and the secretion of IL-6 (258±53, p<0.01), type I collagen (3.09±0.85, p<0.01) and osteopontin (2.32±0.46, p<0.01). Inhibition of autophagy prevented all the TNF-α-induced phenotypic changes. TNF-α induces phenotype switching in A7r5 cell line by a mechanism that required autophagy. Therefore, autophagy may be a potential therapeutic target for the treatment of atherosclerosis.

Transforming growth factor-beta and Forkhead box O transcription factors as cardiac fibroblast regulators.

Fibroblasts play several homeostatic roles, including electrical coupling, paracrine signaling and tissue repair after injury. Fibroblasts have low secretory activity. However, in response to injury, they differentiate to myofibroblasts. These cells have an increased extracellular matrix synthesis and secretion, including collagen fibers, providing stiffness to the tissue. In pathological conditions myofibroblasts became resistant to apoptosis, remaining in the tissue, causing excessive extracellular matrix secretion and deposition, which contributes to the progressive tissue remodeling. Therefore, increased myofibroblast content within damaged tissue is a characteristic hallmark of heart, lung, kidney and liver fibrosis. Recently, it was described that cardiac fibroblast to myofibroblast differentiation is triggered by the transforming growth factor ß1 (TGF-ß1) through a Smad-independent activation of Forkhead box O (FoxO). FoxO proteins are a transcription factor family that includes FoxO1, FoxO3, FoxO4 and FoxO6. In several cells types, they play an important role in cell cycle arrest, oxidative stress resistance, cell survival, energy metabolism, and cell death. Here, we review the role of FoxO family members on the regulation of cardiac fibroblast proliferation and differentiation.