Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling.

Tyrosine kinase 2 (TYK2) is involved in type I interferon (IFN-I) signaling through IFN receptor 1 (IFNAR1). This signaling pathway is crucial in the early antiviral response and remains incompletely understood on B cells. Therefore, to understand the role of TYK2 in B cells, we studied these cells under homeostatic conditions and following in vitro activation using Tyk2-deficient (Tyk2-/-) mice. Splenic B cell subpopulations were altered in Tyk2-/- compared to wild type (WT) mice. Marginal zone (MZ) cells were decreased and aged B cells (ABC) were increased, whereas follicular (FO) cells remained unchanged. Likewise, there was an imbalance in transitional B cells in juvenile Tyk2-/- mice. RNA sequencing analysis of adult MZ and FO cells isolated from Tyk2-/- and WT mice in homeostasis revealed altered expression of IFN-I and Toll-like receptor 7 (TLR7) signaling pathway genes. Flow cytometry assays corroborated a lower expression of TLR7 in MZ B cells from Tyk2-/- mice. Splenic B cell cultures showed reduced proliferation and differentiation responses after activation with TLR7 ligands in Tyk2-/- compared to WT mice, with a similar response to lipopolysaccharide (LPS) or anti-CD40 + IL-4. IgM, IgG, IL-10 and IL-6 secretion was also decreased in Tyk2-/- B cell cultures. This reduced response of the TLR7 pathway in Tyk2-/- mice was partially restored by IFNα addition. In conclusion, there is a crosstalk between TYK2 and TLR7 mediated by an IFN-I feedback loop, which contributes to the establishment of MZ B cells and to B cell proliferation and differentiation.

Combining Breath Figures and Supercritical Fluids To Obtain Porous Polymer Scaffolds.

Supercritical fluids technology is a clean methodology to foam polymeric materials. However, this technique provides only the formation of inner porosity, whereas the so-called skin layer is commonly observed at the polymer surface. This article describes a new method for the preparation of outer and inner porous poly(ε-caprolactone) (PCL) scaffolds by combination of supercritical CO2 (SCCO2) foaming and the breath figures technique. In the first step, experiments with a SCCO2 reactor were performed at 35-45 °C, 100-250 bar, and 1-20 min depressurization time. The effect of these parameters in the formation of inner porosity was investigated for an adequate optimization. In a late stage, to provide also surface porosity to the polymeric samples and remove the skin layer, the breath figures technique was employed. The evaluation of porosity was determined by scanning electronic microscopy, mercury porosimetry, and micro X-ray computerized tomography scanning processing the images obtained with the ImageJ software. The results of this study using these two complementary techniques showed the existence of interconnectivity between inner and outer porosity of the samples. Furthermore, thermal transitions and crystallinity of the PCL samples have been analyzed by differential scanning calorimetry. Finally, a preliminary biological evaluation of the resulting scaffolds with mouse endothelial cells (C166-GFP) was performed to assess their biocompatibility and cellular viability.

Dinapenia y función musculo-esquelética en los pacientes mayores de 65 años / Dynapenia and musculoskeletal function in patients over 65 years of age

Objetivo: Describir la frecuencia de dinapenia en pacientes mayores de 65 años y evaluar su relación con la función musculo-esquelética, el nivel de actividad física y variables clínicas y sociodemográficas. Diseño: Estudio observacional descriptivo. Emplazamiento: Consultas de medicina de familia. Participantes: Pacientes mayores de 65 años. Fueron seleccionados 120 pacientes, correspondiendo a una prevalencia esperada de dinapenia del 25 %, un nivel de confianza del 95 % y una precisión de ±7,8 %. Mediciones Principales: Como variable dependiente se consideró la fuerza muscular en mano dominante cuantificada mediante dinamometría hidráulica. Como variables independientes se incluyeron: función musculo-esquelética (timed get up and go), caídas en últimos 3 meses, nivel de actividad física (IPAQ), autopercepción de salud (EQ-5D), medidas antropométricas, porcentaje de masa grasa, problemas de salud y datos sociodemográficos. Resultados: El valor medio de fuerza muscular fue 32,2 kg (DE: 7,6) y 19,5 kg (DE: 5,1) en hombres y mujeres respectivamente. El 41,0 % de hombres (IC95 %: 24,3-57,7) y el 51,9 % de mujeres (IC95 %: 40,2-63,5) cumplieron criterios de dinapenia. Mediante regresión logística, las variables asociadas fueron: edad de 70 o más años (OR=3,9), estados de ansiedad o depresión (OR=2,8), personas sin estudios (OR=2,8) y mayor porcentaje de masa grasa (OR=1,1). Conclusiones: Observamos elevada prevalencia de dinapenia en mayores de 65 años, guardando relación con su situación funcional. Aunque la dinapenia no es más frecuente en sujetos obesos o con pluripatología, podrían jugar un papel los estados de ansiedad o depresión y una pobre autopercepción de salud (AU)

Objective: To describe the frequency of dynapenia in patients over 65 years of age and to evaluate its relationship with musculoskeletal function, physical activity level and clinical and sociodemographic characteristics. Design: Observational, descriptive study. Location: Family Medicine consultations. Participants: Patients over 65 years of age. A total of 120 patients were selected, corresponding to an expected prevalence of dynapenia of 25 %, a confidence level of 95 % and an accuracy of ±7.8 %. Main measurements: As a dependent variable, muscular strength in the dominant hand was quantified by hydraulic dynamometry. As independent variables, we included: musculoskeletal function (timed get up and go), falls in the last 3 months, physical activity level (IPAQ), self-perception of health status (EQ-5D), anthropometric measurements, body fat percentage, health problems, and sociodemographic characteristics. Results: The mean value of muscular strength was 32.2 kg (SD: 7.6) and 19.5 kg (SD: 5.1) in men and women respectively. 41.0% of men (95% CI: 24.3-57.7) and 51.9% of women (95% CI: 40.2-63.5) met criteria for dynapenia. Using logistic regression, the associated variables were: age of 70 years or over (OR=3.9), states of anxiety or depression (OR=2.8), people without studies (OR=2.8) and a higher percentage of fat mass (OR=1.1). Conclusion: We observed a high prevalence of dynapenia in people over 65 years of age, which is related to their functional situation. Although dynapenia is not more frequent in obese subjects or in subjects with multiple pathologies, states of anxiety or depression and poor self-perception of health may play a key role (AU)