From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.

Importancia de un modelo de nefroprevención adaptado para Colombia

La enfermedad renal crónica es una afección que, dados sus altos niveles de incidencia y prevalencia, constituye un importante problema de salud pública a nivel mundial. Esta entidad se encuentra dentro de las principales causas de muerte tanto en Colombia como en el mundo y representa una gran carga social y económica, similar a la de otras enfermedades crónicas no trasmisibles como la hipertensión arterial y la diabetes mellitus. Actualmente, los gobiernos han realizado esfuerzos para moderar sus estadísticas; sin embargo, estos no han sido lo suficientemente sólidos para mantener bajo control el efecto que ejercen dichas patologías en la salud de las personas, por lo cual se hace imprescindible fortalecer las acciones que fomenten su prevención y control. En el presente artículo se realiza una revisión narrativa de la literatura, partiendo de la información disponible en las diferentes bases de datos, con el objetivo de resaltar la importancia de implementar un modelo de nefroprevención adaptado para Colombia que permita prevenir y detectar oportunamente los factores de riesgo cardiovasculares y renales, y que además facilite el diagnóstico precoz de la enfermedad renal crónica en aras de disminuir su progresión y sus consecuencias potencialmente letales.

Chronic kidney disease is a condition that, given its high levels of incidence and prevalence, constitutes a major public health problem worldwide. This entity is among the leading causes of death both in Colombia and in the world, and represents a great social an economic burden, similar to that of other chronic non-communicable diseases such as arterial hypertension and diabetes mellitus. Currently, governments have made efforts to moderate their statistics; however, these have not been solid enough to keep under control the effect that these pathologies have on the health of the individuals, for which it is indispensable to strengthen actions that promote their prevention and control. In the present article, a narrative literature review is carried out, based on the information available in the different databases, with the purpose of highlighting the importance of implementing a nephroprevention model adapted for Colombia that allows to timely prevent and detect the cardiovascular and renal risk factors, and also facilitate the early diagnosis of chronic kidney disease in order to slow its progression and its potentially lethal consequences.

MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis.

BACKGROUND: In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. METHODS: We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. RESULTS: We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. CONCLUSION: The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.

Concordancia de tres escalas de riesgo cardiovascular en mujeres con diabetes mellitus tipo 2 / Concordance of three scales of cardiovascular risk in women with diabetes mellitus type 2

Resumen Introducción: establecer estimadores del riesgo cardiovasculares (RCV) que permitan tener igual concordancia dentro del subconjunto de la población es importante para diseñar terapias que briden ventajas a cada subpoblación. Objetivo: comparar las escalas Framingham, SCORE/REGICOR y ACC/AHA en una corte de mujeres con diabetes. Materiales y métodos: se realizó un estudio descriptivo transversal en donde se compararon las escalas Framingham, SCORE/REGICOR y ACC/AHA para identificar los niveles de riesgo cardiovascular en mujeres con diabetes mellitus tipo 2. Los datos se recopilaron entre 2014 y 2016 en pacientes del Centro Endocrinológico del Caribe ubicado en Barranquilla, Colombia. Se consideraron variables sociodemográficas, antropométricas y clínicas. Resultados: el 100% de la muestra (n=107) eran mujeres con una edad media de 58,5±13,646 años. Según la escala Framingham el 72,9% (n=78) se clasificó como de riesgo bajo; el 21,5% (23), intermedio, y el 5,6% (n=6), alto. Con la escala SCORE/REGICOR el 57,0% (n=61) estuvo en riesgo bajo; el 42,1% (n=45), en moderado, y el 0,9% (n=1), en alto. Finalmente, mediante la escala ACC/ AHA el 35,5% (n=38) se clasificó en riesgo bajo y el 64,5% (n=69), en elevado. Conclusiones: en el presente estudio se observó una baja concordancia al comparar las escalas de riesgo cardíaco analizadas (Framingham, SCORE/REGICOR y ACC/AHA) en mujeres colombianas con diabetes mellitus tipo dos y se observó además que la edad y el colesterol total fueron los valores que más afectaron la variación entre las escalas comparadas.

Abstract Introduction: Establishing cardiovascular risk (CVR) estimators that allow for equal concordance within the subset of the population is important for establishing therapy that provide advantages for each subpopulation. In this article we focus on buying CVR scale in women with type 2 diabetes mellitus. Objective: Compare between the Framingham, SCORE/REGICOR and ACC/AHA scales in a court of women with diabetes. Methods: The data collected were between 2014 and 2016 from the population of the Caribbean Endocrinological Center, Barranquilla, Colombia, considering the sociodemographic, anthropometric, and clinical variables. In this study, it was possible to establish comparisons between the Framingham, SCORE/REGICOR and ACC/AHA scales to identify cardiovascular risk levels in women with T2DM. Results: 100% of the sample (n = 107) were women with a mean age of 58.5 ± 13,646 years, 78 (72.9%) were classified as low risk, 23 (21.5%) intermediate and 6 ( 5.6%) high with the scale The SCORE/REGICOR scale showed 61 (57.0%) at low risk, 45 (42.1%) moderate and 1 (0.9%) high; while ACC / AHA 38 (35.5%) is classified as low risk and 69 (64.5%) as high. Conclusions: In the present study, a low concordance was observed when comparing the cardiac risk scales (Framingham, SCORE/REGICOR and ACC/AHA) in Colombian women with type two diabetes and it was also observed that age and total cholesterol were the values that more affected variation between the comparative cardiovascular risk scale.

El impacto de la educación en ciencias biológicas en pacientes con enfermedad renal en un contexto de epidemia por COVID-19 / The impact of education in biological science in patients with kidney disease in the context of a covid-19 epidemic

Resumen La educación en ciencias biológicas juega un papel importante a la hora de entender los sistemas vivos y ecosistemas que nos rodea en contexto de una epidemia de tipo zoonótico como SARS-CoV-2 y cumple un papel importante para el autocuidado en pacientes con enfermedad renal que son una población en alto riesgo según datos epidemiológicos. El presente trabajo pretende describir la asociación entre la educación en ciencia biológica y la epidemia por COVID-19. La educación en ciencias biológicas es un componente importante supeditado al autocuidado para que muchos pacientes con enfermedad renal puedan entender la importancia de tener una mejor adherencia al régimen terapéutico y el régimen alimenticio, y en el caso puntual de la epidemia por COVID-19 puede permitir que ellos tomen las medidas preventivas que eviten su exposición al patógeno.

Abstract Biologic education plays an important role in understanding the living systems and ecosystems that it does not surround in the context of a zoonotic-like epidemic such as SARS-CoV-2 may have an important role for self-care in patients with kidney disease that they are a population at high risk according to epidemiological data. That is why the present work aims to describe the association between education in biological science in patients with kidney disease in the context of a covid-19 epidemic. Biological science education is an important component subject to self-care so that many patients with kidney disease allowing them to understand, the importance of having a better adhere to the therapeutic regimen, dietary regimen and in the specific case of the epidemic by COVID-19 may allow them to take preventive measures to avoid their exposure to the pathogen.

Compromiso renal y digestivo en infecciones por COVID-19 / Renal and digestive engagement in COVID-19 infections

Resumen La infección por el síndrome respiratorio agudo severo (SARS-CoV-2) ha causado una de las emergencias epidemiológicas más grandes de los últimos 10 años y sus efectos patológicos son aún estudiados. Por lo anterior, resulta importante describir los mecanismos asociados al compromiso renal y digestivo en la infección por SARS-CoV-2. Los mecanismos patológicos en tejido renal y en intestino causados por la infección por SARS-CoV-2 son propios del tropismo viral por células de estos sistemas y de los mecanismos citopáticos de etapa lítica de la infección, con una liberación continua de viriones que favorece la generación de un entorno inflamatorio con la consecuente secreción descontrolada de citoquinas proinflamatorias que conducen a la infección entérica del intestino y a las alteraciones en el riñón.

Abstract Infection with Severe Acute Respiratory Syndrome (SARS-CoV-2) has caused one of the largest epidemiological emergencies in the last 10 years and its pathological effects are still studied. Due to the aforementioned, it is important to describe the mechanisms associated with renal and digestive compromise in SARS-CoV-2 infection. The pathological mechanisms in kidney tissue and in the intestine caused by SARS-CoV-2 infection are characteristic of the viral tropism by cells of these systems and of the lymphocytic mechanisms of the lytic stage of the infection, with a continuous release of virions that favors the generation of an inflammatory environment with the consequent uncontrolled secretion of proinflammatory cytokines that lead to enteric infection of the intestine and alterations in the kidney.

Epidemiology and Toxicology of Ciguatera Poisoning in the Colombian Caribbean.

Ciguatera is a food intoxication caused by the consumption of primarily coral fish; these species exist in large numbers in the seas that surround the Colombian territory. The underreported diagnosis of this clinical entity has been widely highlighted due to multiple factors, such as, among others, ignorance by the primary care practitioner consulted for this condition as well as clinical similarity to secondary gastroenteric symptoms and common food poisonings of bacterial, parasitic or viral etiology. Eventually, it was found that people affected by ciguatoxins had trips to coastal areas hours before the onset of symptoms. Thanks to multiple studies over the years, it has been possible to identify the relation between toxigenic dinoflagellates and seagrasses, as well as its incorporation into the food chain, starting by fish primarily inhabiting reef ecosystems and culminating in the intake of these by humans. Identifying the epidemiological link, its cardinal symptoms and affected systems, such as gastrointestinal, the peripheral nervous system and, fortunately with a low frequency, the cardiovascular system, leads to a purely clinical diagnostic impression without necessitating further complementary studies; in addition, what would also help fight ciguatera poisoning is performing an adequate treatment of the symptoms right from the start, without underestimating or overlooking any associated complications.

Epigenetic Mechanisms and Posttranslational Modifications in Systemic Lupus Erythematosus.

The complex physiology of eukaryotic cells is regulated through numerous mechanisms, including epigenetic changes and posttranslational modifications. The wide-ranging diversity of these mechanisms constitutes a way of dynamic regulation of the functionality of proteins, their activity, and their subcellular localization as well as modulation of the differential expression of genes in response to external and internal stimuli that allow an organism to respond or adapt to accordingly. However, alterations in these mechanisms have been evidenced in several autoimmune diseases, including systemic lupus erythematosus (SLE). The present review aims to provide an approach to the current knowledge of the implications of these mechanisms in SLE pathophysiology.

Integrated analysis of microRNA regulation and its interaction with mechanisms of epigenetic regulation in the etiology of systemic lupus erythematosus.

The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA-disease association data from genetics, epigenetics, circulating miRNAs, and miRNA-target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p.

Cell Signaling in Neuronal Stem Cells.

The defining characteristic of neural stem cells (NSCs) is their ability to multiply through symmetric divisions and proliferation, and differentiation by asymmetric divisions, thus giving rise to different types of cells of the central nervous system (CNS). A strict temporal space control of the NSC differentiation is necessary, because its alterations are associated with neurological dysfunctions and, in some cases, death. This work reviews the current state of the molecular mechanisms that regulate the transcription in NSCs, organized according to whether the origin of the stimulus that triggers the molecular cascade in the CNS is internal (intrinsic factors) or whether it is the result of the microenvironment that surrounds the CNS (extrinsic factors).

Neurogénesis en cerebro adulto / Neurogenesis in adult brain

Resumen Las lesiones cerebrales de cualquier etiología, incluyendo traumatismos, enfermedades neurodegenerativas o accidentes cerebrovasculares, suponen alteraciones irreversibles en la función cognitiva, el sistema motor y somato sensorial, e incluso de personalidad. En la actualidad no existen tratamientos eficientes, por tanto, la búsqueda de opciones terapéuticas para aumentar la tasa de reemplazo neuronal en el sistema nervioso central es uno de las líneas de investigación más activas en la neurociencia actual. En este sentido, el descubrimiento de la reposición neuronal a partir de células madre neurales (NSC) en el sistema nervioso central (SNC) adulto ha supuesto un nuevo enfoque en el desarrollo de terapias para este tipo de lesiones cerebrales. El descubrimiento de células madre neurales (NSC) en el cerebro adulto, abrió la posibilidad del desarrollo de nuevas terapias neurorregenerativas basadas en la reposición neuronal a partir de NSC (neurogénesis). En condiciones fisiológicas, existe neurogénesis a partir de NSC en dos zonas del cerebro adulto: el hipocampo y la zona subventricular (SVZ), mientras que en el resto del cerebro adulto no existe neurogenesis o es escasa. Sin embargo, cuando hay una lesión cerebral, estas NSC son reclutadas en el perímetro donde se produjo y se puede ver como proliferan células con características de precursores neurales (NPC). En esta publicación se hace una revisión exhaustiva de los conocimientos actuales sobre la neurogénesis en cerebro adulto.

Abstract Brain injuries of any etiology including traumatic injuries, neurodegenerative diseases or strokes are very common and involve irreversible impairments in cognitive function, motor and somatosensory system, and even personality. These types of lesions lack effective curative treatments, with the search for therapeutic options being one of the most active fields of research in current neuroscience. In this sense, the discovery of neural replenishment from neural stem cells (NSC) in the adult central nervous system (CNS) has been a new approach in the development of therapies for this type of brain injury. The discovery of neural stem cells (NSCs) in the adult brain has opened up the possibility of developing new neuroregenerative therapies based on neural replenishment from neural stem cells (neurogenesis). In physiological conditions, neurogenesis exists from NSC only in two areas of the adult brain, the hippocampus and the subventricular zone (SVZ), whereas in the rest of the adult brain there is no or little neurogenesis. However, when a brain injury occurs, these NSCs are recruited into the perimeter of the lesion and cells with proliferating neural precursor (NPC) characteristics can be seen. The publication provides a comprehensive review of current knowledge on neurogenesis in adult brain.

Análisis y predición de epitopes T y B en proteínas de Helicobacter pylori: Una aproximación inicial al diseño racional de estrategias terapeuticas alternativas sin uso de antibióticos / Analysis and prediction of T and B epitopes in Helicobacter pylori proteins: An initial approach to the rational design of alternative therapeutic strategies without the use of antibiotics

Resumen Helicobacter pylori (H. pylori) es un bacteria deforma espiral gram negativa que se estima afecta a más de la mitad de la población mundial, estableciendo una infección crónica en el estómago, debido a diversos mecanismos de evasión de la respuesta inmune. Este microorganismo se ha asociado con diversos trastornos gástricos que van desde gastritis hasta cáncer, por lo que es reconocido por la Organización Mundial de la Salud (OMS) como carcinógeno clase I. Regímenes de tratamiento convencionales involucran el uso de antibióticos, y estos fracasan cada vez más en el control de la infección, debido a que H. pylori ha adquirido de forma progresiva resistencia a los compuestos utilizados, lo cual sugiere la necesidad de desarrollar nuevas estrategias terapéuticas, lo cual implica la identificación de nuevos blancos terapéuticos. Este estudio tuvo como propósito la evaluación in silico de epitopes T y B en proteínas del Helicobacter pylori. Para ello fueron identificadas 22 proteínas de membrana externas de Helicobacter pylori Cepa 26695 con número de acceso NC_000915; en la selección se empleó la herramienta web Vaxign (disponible gratis enhttp://www.violinet.org/vaxign/), en las que se predijeron 100 epítopes (60 epítopes clases I y 40 epítopes clase II), que potencialmente podrían se utilizados en el desarrollo de nuevos abordajes terapéuticos de la infección por H. pylori sin uso de antibióticos.

Abstract Helicobacter pylori (H. pylori) is a gram-negative spiral bacterium, estimated to affect more than half the world population, establishing chronic infection in the stomach, due to diverse mechanisms of immune response evasion. This microorganism has been associated with various gastric disorders ranging from gastritis to cancer, and is recognized by the World Health Organization (WHO) as a class I carcinogen. Conventional treatment regimes involve the use of antibiotics and these fail every time but in the control of the infection, because H. pylori has progressively acquired resistance to the compounds used, suggesting the need to develop new therapeutic strategies, which implies the identification of new therapeutic targets. The present study aimed at the in silico evaluation of T and B epitopes in Helicobacter pylori proteins. For this, 22 external membrane proteins of Helicobacter pylori Strain 26695 with accession number NC_000915 were identified, in the selection the web tool Vaxign (was available free athttp://www.violinet.org/vaxign/), in which they were predicted 100 epitopes (60 class I epitopes and 40 class II epitopes), which could potentially be used in the development of new therapeutic approaches to H. pylori infection without the use of antibiotics.

Profiling analysis of circulating microRNA in peripheral blood of patients with class IV lupus nephritis.

Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It's estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group) and healthy individuals (CTL group). Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2) and false discovery rate (0.05). We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p). These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of LN.