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.

High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers of Kidney Damage in Patients with Systemic Lupus Erythematosus.

Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage.

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.