Consenso colombiano de atención, diagnóstico y manejo de la infección por SARS-COV-2/COVID-19 en establecimientos de atención de la salud Recomendaciones basadas en consenso de expertos e informadas en la evidencia

The “Asociación Colombiana de Infectología” (ACIN) and the “Instituto de Evaluación de Nuevas Tecnologías de la Salud” (IETS) created a task force to develop recommendations for Covid 19 health care diagnosis, management and treatment informed, and based, on evidence. Theses reccomendations are addressed to the health personnel on the Colombian context of health services. © 2020 Asociacion Colombiana de Infectologia. All rights reserved

Control of immune cell function by the unfolded protein response.

Initiating and maintaining optimal immune responses requires high levels of protein synthesis, folding, modification and trafficking in leukocytes, which are processes orchestrated by the endoplasmic reticulum. Importantly, diverse extracellular and intracellular conditions can compromise the protein-handling capacity of this organelle, inducing a state of 'endoplasmic reticulum stress' that activates the unfolded protein response (UPR). Emerging evidence shows that physiological or pathological activation of the UPR can have effects on immune cell survival, metabolism, function and fate. In this Review, we discuss the canonical role of the adaptive UPR in immune cells and how dysregulation of this pathway in leukocytes contributes to diverse pathologies such as cancer, autoimmunity and metabolic disorders. Furthermore, we provide an overview as to how pharmacological approaches that modulate the UPR could be harnessed to control or activate immune cell function in disease

Impaired T cell IRE1α-XBP1 signaling directs inflammation in experimental Heart Failure with Preserved Ejection Fraction

Heart Failure with Preserved Ejection Fraction (HFpEF) is a widespread syndrome with limited therapeutic options and poorly understood immune-pathophysiology. Using a two-hit preclinical model of cardiometabolic HFpEF that induces obesity and hypertension, we found that cardiac T cell infiltration and lymphoid expansion occur concomitantly with cardiac pathology, and that diastolic dysfunction, cardiomyocyte hypertrophy and cardiac phospholamban phosphorylation are T cell-dependent. Heart-infiltrating T cells were not restricted to cardiac antigens and were uniquely characterized by impaired activation of the Inositol-requiring enzyme-1α (IRE1α)-X-box binding protein 1 (XBP1) arm of the unfolded protein response. Notably, selective ablation of XBP1 in T cells enhanced their persistence in the heart and lymphoid organs of mice with preclinical HFpEF. Furthermore, T cell IRE1α-XBP1 activation was restored after withdrawal of the two comorbidities inducing HFpEF, resulting in partial improvement of cardiac pathology. Our results demonstrate that diastolic dysfunction and cardiomyocyte hypertrophy in preclinical HFpEF are T cell-dependent, and that reversible dysregulation of the T cell IRE1α-XBP1 axis is a T cell signature of HFpEF

Depletion of dendritic cells delays ovarian cancer progression by boosting antitumor immunity

Dendritic cells (DC) and cytokines that expand myeloid progenitors are widely used to treat cancer. Here, we show that CD11c(+)DEC205(+) DCs coexpressing alpha-smooth muscle actin and VE-cadherin home to perivascular areas in the ovarian cancer microenvironment and are required for the maintenance of tumor vasculature. Consequently, depletion of DCs in mice bearing established ovarian cancer by targeting different specific markers significantly delays tumor growth and enhances the effect of standard chemotherapies. Tumor growth restriction was associated with vascular apoptosis after DC ablation followed by necrosis, which triggered an antitumor immunogenic boost. Our findings provide a mechanistic rationale for selectively eliminating tumor-associated leukocytes to promote antitumor immunity while impeding tumor vascularization and to develop more effective DC vaccines based on a better understanding of the tumor microenvironment

Depletion of dendritic cells delays ovarian cancer progression by boosting antitumor immunity

Dendritic cells (DC) and cytokines that expand myeloid progenitors are widely used to treat cancer. Here, we show that CD11c(+)DEC205(+) DCs coexpressing alpha-smooth muscle actin and VE-cadherin home to perivascular areas in the ovarian cancer microenvironment and are required for the maintenance of tumor vasculature. Consequently, depletion of DCs in mice bearing established ovarian cancer by targeting different specific markers significantly delays tumor growth and enhances the effect of standard chemotherapies. Tumor growth restriction was associated with vascular apoptosis after DC ablation followed by necrosis, which triggered an antitumor immunogenic boost. Our findings provide a mechanistic rationale for selectively eliminating tumor-associated leukocytes to promote antitumor immunity while impeding tumor vascularization and to develop more effective DC vaccines based on a better understanding of the tumor microenvironment

Consenso colombiano de atención, diagnóstico y manejo de la infección por SARS-COV-2/COVID-19 en establecimientos de atención de la salud Recomendaciones basadas en consenso de expertos e informadas en la evidencia

The “Asociación Colombiana de Infectología” (ACIN) and the “Instituto de Evaluación de Nuevas Tecnologías de la Salud” (IETS) created a task force to develop recommendations for Covid 19 health care diagnosis, management and treatment informed, and based, on evidence. Theses reccomendations are addressed to the health personnel on the Colombian context of health services. © 2020 Asociacion Colombiana de Infectologia. All rights reserved

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease