Estudio molecular de la familia GH

Tesis (Maestría en Ciencias con Especialidad en Biología Molecular e Ingeniería Genética) UANLUANLhttp://www.uanl.mx

Healthy Exosomes and their Effects on Diabetic Cardiomyocytes

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and anti-CD81 antibodies. Further work includes concentrating exosome presence and utilizing a wider variety of exosome-specific antibodies, as well as exploring techniques for more effective exosome extraction from plasma

Estudio de la etiología de meningitis aséptica y meningoencefalitis en el Hospital Universitario Dr. José Eleuterio González, mediante estrategias de virología molecular

Antecedentes: La meningitis aséptica y la meningoencefalitis constituyen problemas de gran importancia clínica. Sus agentes etiológicos más frecuentes son los enterovirus (ECHOvirus, Coxsackievirus, Enterovirus no-polio), Togavirus, Flavivirus, Bunyavirus y otros grupos antes conocidos como ARBOvirus (Arthopod-borne viruses) y el virus del herpes humano. Objetivo: En este trabajo nos propusimos identificar, mediante la reacción en cadena de la polimerasa, los genomas virales de los virus del herpes simple (VHS tipos 1 y 2), del enterovirus y del virus del oeste del Nilo (VON) como causantes de meningitis aséptica y de meningoencefalitis. Material y métodos: Se estudiaron 30 pacientes que ingresaron al Hospital Universitario Dr. José Eleuterio González durante el período de febrero de 2005 a junio de 2008. Se analizaron muestras de líquido cefalorraquídeo (2 mL) para buscar, mediante la reacción en cadena de la polimerasa, el genoma del enterovirus, del VHS tipos 1 y 2, y del virus del oeste del Nilo, siguiendo protocolos estandarizados. Resultados: Ninguno de los pacientes estudiados fue positivo para los virus buscados mediante amplificación por la reacción en cadena de la polimerasa. Entre los datos clínicos relevantes encontramos que la presencia de estupor o el coma se relacionó significativamente con la muerte (p = 0.005). Encontramos, además, que tres muertes ocurrieron en el grupo de pacientes con meningoencefalitis (p = 0.021). Conclusiones: No encontramos el genoma de los virus analizados en el líquido cefalorraquídeo de los pacientes estudiados, probablemente debido al tamaño limitado de la muestra, a su calidad, o a diversos factores epidemiológicos en nuestra región. La información clínica y del laboratorio de los pacientes estudiados es similar a la que está publicada en estudios anteriores. Es necesario realizar estudios más amplios, incluyendo a un mayor número de pacientes que nos permitan conocer la etiología de este tipo de enfermedades en nuestra comunidad. Esto hará posible mejorar la metodología para el diagnóstico en los pacientes con patología del sistema nervioso central

Presencia del virus del oeste del Nilo en el noreste de México

Objetivo. Detectar la presencia del virus del oeste del Nilo (VON) en aves, equinos y seres humanos en el noreste de México. Material y métodos. Se buscó en diferentes localidades del noreste de México la presencia de anticuerpos antivirus del oeste del Nilo (anti-VON) en suero de 33 aves, 24 caballos y 237 personas mediante pruebas de ELISA durante el periodo de julio de 2003 a julio de 2006. En los sueros humanos se buscó también el RNA-VON mediante RT-PCR. Resultados. Se encontraron tres aves seropositivas y 15 equinos. En el hombre, 40% de los sueros fue positivo para anticuerpos IgG y ninguno para anticuerpos IgM. Conclusiones. El VON se encuentra activo en México y se suma a otras enfermedades emergentes transmitidas por vectores que representan un reto a la investigación y a los programas de prevención

Identification of a Novel Pathogenic Rearrangement Variant of the APC Gene Associated with a Variable Spectrum of Familial Cancer

Familial adenomatous polyposis (FAP) is an autosomal-dominant condition characterized by the presence of multiple colorectal adenomas, caused by germline variants in the adenomatous polyposis coli (APC) gene. More than 300 germline variants have been characterized. The detection of novel variants is important to understand the mechanisms of pathophysiology. We identified a novel pathogenic germline variant using next-generation sequencing (NGS) in a proband patient. The variant is a complex rearrangement (c.422+1123_532-577 del ins 423-1933_423-1687 inv) that generates a complete deletion of exon 5 of the APC gene. To study the variant in other family members, we designed an endpoint PCR method followed by Sanger sequencing. The variant was identified in the proband patient’s mother, one daughter, her brother, two cousins, a niece, and a second nephew. In patients where the variant was identified, we found atypical clinical symptoms, including mandibular, ovarian, breast, pancreatic, and gastric cancer. Genetic counseling and cancer prevention strategies were provided for the family. According to the American College of Medical Genetics (ACMG) guidelines, this novel variant is considered a PVS1 variant (very strong evidence of pathogenicity), and it can be useful in association with clinical data for early surveillance and suitable treatment. View Full-Tex

Biobanks: Experience of the School of Medicine and the “Dr. José Eleuterio González” University Hospital of the Universidad Autónoma de Nuevo León

Medical research has greatly beneited from molecular biology and increasingly relies on tools from the “omics” disciplines (mainly genomics, transcriptomics, proteomics and metabolomics). The availability of biological samples preserved with high quality standards is a sine qua non condition for such studies and their repositories are referred to as biobanks. Biobanks support the transportation, storage, preservation, and initial pathological and analytical examinations of biospecimens, as well as the protection of relevant information and the comparison of clinical and laboratory findings. A biobank facility is one of the most valuable tools the academic medicine organizations can offer to their researchers to improve the competitiveness of their current and future medical research. it acts as an essential bridge and an effective catalyst for research synergies between basic and clinical sciences, and it can be potentiated with efforts to raise funds for acquiring and maintaining cutting-edge analytical infrastructure to better serve its clinical, pharmaceutical and biotech clients

Disintegrins extracted from totonacan rattlesnake (Crotalus totonacus) venom and their anti-adhesive and anti-migration effects on MDA-MB-231 and HMEC-1 cells

Disintegrins are low molecular weight cysteine-rich proteins (4–14 kDa) that are isolated mainly from viperid snake venom. Due to their potential as lead compounds for binding and blocking integrin receptors, snake venom disintegrins have become one of the most studied venom protein families. The aim of this study was to obtain disintegrins from C. totonacus venom and evaluate their capability to bind and block integrin receptors. The C. totonacus disintegrin fraction (totonacin) represents two disintegrin isoforms obtained from C. totonacus venom. These disintegrins showed extracellular-matrix (ECM) protein adhesion and migration inhibitory effects on MDA-MB-231 and HMEC-1 cells. Totonacin (3 μM) inhibited MDA-MB-231 cell adhesion to the ECM proteins, fibronectin, vitronectin, and laminin by 31.2, 44.0, and 32.1, respectively. Adhesion inhibition to fibronectin, vitronectin, and laminin observed on HMEC-1 cells was 42.8, 60.8, and 51%, respectively. In addition, totonacin (3 μM) significantly inhibited MDA-MB-231 and HMEC-1 cell migration (41.4 and 48.3%, respectively). Totonacin showed more potent cell adhesion inhibitory activity toward vitronectin in both cell lines. These results suggest a major affinity of totonacin toward αVβ3, α8β1, αVβ5, αVβ1, and αIIbβ3 integrins. In addition, the inhibitory effect observed on MDA-MB-231 and HMEC-1 cell migration reinforces the evidence of an interaction between these disintegrins and αVβ3 integrin, which plays a key role in migration and angiogenesis

TOX3 rs3803662 Polymorphism Is Associated With Breast Cancer Protection In Northeastern Mexican Woman

Introduction: Low penetrance genes are involved in breast cancer (BC) and confer risk for the development of this neoplasia. Different single nucleotide polymorphisms (SNPs) associated with BC have been identified, such as rs3803662 (TOX3), which is related to estrogen receptors in European and African-American women. The contribution of this variant in the Mexican population is unknown. The objective of this study was to evaluate, through a case-control design, the association of the SNP rs3803662 (TOX3), with the risk of BC in women from northeastern Mexico. Methods: We included 434 cases and 228 controls. Genotyping was carried out using RFLPs. The SPSS 7.0 statistical program was used to determine the gene frequencies, the estimation of the relative risk (Odds ratio [OR]), and the Hardy-Weinberg equilibrium (EHW). Results: The homocygote (T/T) genotype of the SNP TOX3 rs3803662 was identified as a protective allele for BC (OR: 0.47, 95% CI: 0.29 - 0.78). Conclusions; The T allele of the SNP rs3803662 can be considered as a protective factor for BC from northeastern Mexico women

Epidemiological Algorithm and Early Molecular Testing to Prevent COVID-19 Outbreaks in a Mexican Oncologic Center

Introduction: Prevention strategies and detection of latent COVID-19 infections in oncology staff and oncologic patients are essential to prevent outbreaks in a cancer center. In this study, we used two statistical predictive models in oncology staff and patients from the radiotherapy area to prevent outbreaks and detect COVID-19 cases. Methods: Staff and patients answered a questionnaire (electronic and paper surveys, respectively) with clinical and epidemiological information. The data was collected through two online survey tools: Real-Time Tracking (R-Track) and Summary of Factors (S-Facts). According to the algorithm\u27s models, cut-off values were established. SARS-CoV-2 qRT-PCR tests confirmed the algorithm\u27s positive individuals. Results: Oncology staff members (n=142) were tested, and 14% (n=20) were positives for the R-Track algorithm; 75% (n=15) were qRT-PCR positive. The S-Facts algorithm identified 7.75% (n=11) positive oncology staff members, and 81.82% (n=9) were qRT-PCR positive. Oncology patients (n=369) were evaluated, and 1.36% (n=5) were positive for the algorithms. The 5 patients (100%) were confirmed by qRT-PCR at a very early stage. Conclusions: The proposed algorithms could prove to become an essential prevention tool in countries where qRT-PCR tests and vaccines are insufficient for the population