Instituto Nacional Of Medicina Genomica

Mexico City, Mexico

Instituto Nacional Of Medicina Genomica

Mexico City, Mexico

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Garcia-Ortiz H.,Instituto Nacional Of Medicina Genomica | Velazquez-Cruz R.,Instituto Nacional Of Medicina Genomica | Jimenez-Morales S.,Instituto Nacional Of Medicina Genomica | Baca V.,Hospital Of Pediatria | Orozco L.,Instituto Nacional Of Medicina Genomica
Annals of the Rheumatic Diseases | Year: 2010

Objective: Variations in gene copy number (CNV) have been recognised as a hereditable source of susceptibility in human complex diseases. Recent studies have shown that Tlr7 gene dosage has a significant contribution in the autoimmune-enhancing effect in mouse models of systemic lupus erythematosus (SLE). A study was therefore performed to investigate whether CNVs in TLR7 contribute to the genetic component of childhood-onset SLE. Methods: A case-control association study was performed in 328 Mexican children with SLE and 403 healthy controls. Determination of CNVs of TLR7 was achieved by real-time PCR using the ΔΔCt method. Expression levels of TLR7 and interferon α (IFNα) were determined in 23 patients. In addition, a stratification analysis was performed to investigate the association of TLR7 gene copy number (CN) with lupus nephritis. Results: A significant increase was found in the relative TLR7 gene CN in females patients with SLE compared with female controls (p<0.0001). However, logistic regression analysis by gender showed a higher OR (OR 6.61, p=0.005) in male patients with >1 copy of TLR7 than in female patients with >2 copies (OR 3.07, p<0.0001). This association was not observed with lupus nephritis. TLR7 mRNA levels correlated significantly with TLR7 CN and with IFNα mRNA levels. Conclusion: These results show that an increase in TLR7 CN is a risk factor for childhood-onset SLE and provide new evidence for a role for X-linked gene dosage in SLE susceptibility. There is also evidence to suggest that TLR7 may be involved in the pathogenesis of SLE through the induction of IFNα.


Castellanos-Jankiewicz A.,Instituto Nacional Of Medicina Genomica | Castellanos-Jankiewicz A.,Mayab University | del Bosque-Plata L.,Instituto Nacional Of Medicina Genomica | Tejero M.E.,Instituto Nacional Of Medicina Genomica
Plant Foods for Human Nutrition | Year: 2014

Hypercholesterolemia is a major contributor for disease burden in both the developed and developing world and an important risk factor for cardiovascular diseases (CVD). Phytosterols (PhS) and dietary fiber (DF) act as low density lipoprotein cholesterol (LDL-C) lowering agents, offering an effective treatment against high blood cholesterol and CVD. The aim of this review was to consider clinical evidence that analyzed the combination of PhS and DF in a cereal carrier for lowering LDL-C. Electronic database searches were carried out to identify peer-reviewed journal articles, from which five intervention studies that combined both components in a cereal carrier were identified and included in the present review. LDL-C lowering effects varied widely among studies, due to large heterogeneity in study design, subject baseline characteristics, length of the interventions, PhS and DF dosage and type of DF used. In relation to a time of intake, three studies suggested a frequency or distribution of the product's consumption during the day, while two studies did not consider this factor. Overall, the selected studies found significant differences on LDL-C concentrations, although not all of them reached the expected outcomes. Future research should be conducted to explore the effect that different types of DF exert on LDL-C when combined with PhS, and to analyze the effect of the product's time of intake in order to suggest an optimal moment of the day for its consumption. © 2014 Springer Science+Business Media New York.


Martinez-Pacheco M.,National Autonomous University of Mexico | Hidalgo-Miranda A.,Instituto Nacional Of Medicina Genomica | Romero-Cordoba S.,Instituto Nacional Of Medicina Genomica | Valverde M.,National Autonomous University of Mexico | Rojas E.,National Autonomous University of Mexico
Gene | Year: 2014

Metals are a threat to human health by increasing disease risk. Experimental data have linked altered miRNA expression with exposure to some metals. MiRNAs comprise a large family of non-coding single-stranded molecules that primarily function to negatively regulate gene expression post-transcriptionally. Although several human populations are exposed to low concentrations of As, Cd and Pb as a mixture, most toxicology research focuses on the individual effects that these metals exert. Thus, this study aims to evaluate global miRNA and mRNA expression changes induced by a metal mixture containing NaAsO2, CdCl2, Pb(C2H3O2)2·3H2O and to predict possible metal-associated disease development under these conditions. Our results show that this metal mixture results in a miRNA expression profile that may be responsible for the mRNA expression changes observed under experimental conditions in which coding proteins are involved in cellular processes, including cell death, growth and proliferation related to the metal-associated inflammatory response and cancer. © 2013 Elsevier B.V.


Grosso-Becerra M.V.,National Autonomous University of Mexico | Croda-Garcia G.,National Autonomous University of Mexico | Merino E.,National Autonomous University of Mexico | Servin-Gonzalez L.,National Autonomous University of Mexico | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

In a number of bacterial pathogens, the production of virulence factors is induced at 37°C; this effect is often regulated by mRNA structures formed in the 5′ untranslated region (UTR) that block translation initiation of genes at environmental temperatures. At 37°C, the RNA structures become unstable and ribosomes gain access to their binding sites in the mRNAs. Pseudomonas aeruginosa is an important opportunistic pathogen and the expression of many of its virulence-associated traits is regulated by the quorum-sensing (QS) response, but the effect of temperature on virulence-factor expression is not well-understood. The aim of this work is the characterization of the molecular mechanism involved in thermoregulation of QS-dependent virulence-factor production. We demonstrate that traits that are dependent on the QS transcriptional regulator RhlR have a higher expression at 37°C, correlating with a higher RhlR concentration as measured by Western blot. We also determined, using gene fusions and point mutations, that RhlR thermoregulation is a posttranscriptional effect dependent on an RNA thermometer of the ROSE (Repression Of heat-Shock gene Expression) family. This RNA element regulates the expression of the rhlAB operon, involved in rhamnolipid production, and of the downstream rhlR gene. We also identified a second functional thermometer in the 5′ UTR of the lasI gene. We confirmed that these RNA thermometers are the main mechanism of thermoregulation of QS-dependent gene expression in P. aeruginosa using quantitative real-time PCR. This is the first description, to our knowledge, of a ROSE element regulating the expression of virulence traits and of an RNA thermometer controlling multiple genes in an operon through a polar effect. © 2014, National Academy of Sciences. All rights reserved.


Lopez-Leal G.,National Autonomous University of Mexico | Tabche M.L.,National Autonomous University of Mexico | Castillo-Ramirez S.,National Autonomous University of Mexico | Mendoza-Vargas A.,Instituto Nacional Of Medicina Genomica | And 2 more authors.
BMC Genomics | Year: 2014

Background: Regulation of transcription is essential for any organism and Rhizobium etli (a multi-replicon, nitrogen-fixing symbiotic bacterium) is no exception. This bacterium is commonly found in the rhizosphere (free-living) or inside of root-nodules of the common bean (Phaseolus vulgaris) in a symbiotic relationship. Abiotic stresses, such as high soil temperatures and salinity, compromise the genetic stability of R. etli and therefore its symbiotic interaction with P. vulgaris. However, it is still unclear which genes are up- or down-regulated to cope with these stress conditions. The aim of this study was to identify the genes and non-coding RNAs (ncRNAs) that are differentially expressed under heat and saline shock, as well as the promoter regions of the up-regulated loci. Results: Analysing the heat and saline shock responses of R. etli CE3 through RNA-Seq, we identified 756 and 392 differentially expressed genes, respectively, and 106 were up-regulated under both conditions. Notably, the set of genes over-expressed under either condition was preferentially encoded on plasmids, although this observation was more significant for the heat shock response. In contrast, during either saline shock or heat shock, the down-regulated genes were principally chromosomally encoded. Our functional analysis shows that genes encoding chaperone proteins were up-regulated during the heat shock response, whereas genes involved in the metabolism of compatible solutes were up-regulated following saline shock. Furthermore, we identified thirteen and nine ncRNAs that were differentially expressed under heat and saline shock, respectively, as well as eleven ncRNAs that had not been previously identified. Finally, using an in silico analysis, we studied the promoter motifs in all of the non-coding regions associated with the genes and ncRNAs up-regulated under both conditions.Conclusions: Our data suggest that the replicon contribution is different for different stress responses and that the heat shock response is more complex than the saline shock response. In general, this work exemplifies how strategies that not only consider differentially regulated genes but also regulatory elements of the stress response provide a more comprehensive view of bacterial gene regulation. © 2014 López-Leal et al.; licensee BioMed Central Ltd.


Escandon-Rivera S.,National Autonomous University of Mexico | Gonzalez-Andrade M.,Instituto Nacional Of Medicina Genomica | Bye R.,National Autonomous University of Mexico | Linares E.,National Autonomous University of Mexico | And 2 more authors.
Journal of Natural Products | Year: 2012

An aqueous extract from the aerial parts of Brickellia cavanillesii attenuated postprandial hyperglycemia in diabetic mice during oral glucose and sucrose tolerance tests. Experimental type-II DM was achieved by treating mice with streptozotocin (100 mg/kg) and β-nicotinamide adenine dinucleotide (40 mg/kg). These pharmacological results demonstrated that B. cavanillesii is effective for controlling fasting and postprandial blood glucose levels in animal models. The same aqueous extract also showed potent inhibitory activity (IC50 = 0.169 vs 1.12 mg/mL for acarbose) against yeast α-glucosidase. Bioassay-guided fractionation of the active extract using the α-glucosidase inhibitory assay led to the isolation of several compounds including two chromenes [6-acetyl-5-hydroxy-2,2-dimethyl-2H-chromene (1) and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2)], two sesquiterpene lactones [caleins B (3) and C (4)], several flavonoids [acacetin (5), genkwanin (6), isorhamnetin (7), kaempferol (8), and quercetin (9)], and 3,5-di-O-caffeoylquinic acid (10). Chromene 2 is a new chemical entity. Compounds 2, 4, 7, and 9 inhibited the activity of yeast α-glucosidase with IC50 0.42, 0.28, 0.16, and 0.53 mM, respectively, vs 1.7 mM for acarbose. Kinetic analysis revealed that compounds 4 and 7 behaved as mixed-type inhibitors with Ki values of 1.91 and 0.41 mM, respectively, while 2 was noncompetititive, with a Ki of 0.13 mM. Docking analysis predicted that these compounds, except 2, bind to the enzyme at the catalytic site. © 2012 The American Chemical Society and American Society of Pharmacognosy.


Alaez C.,Institute Diagnostico y Referencia Epidemiologicos | Alaez C.,Instituto Nacional Of Medicina Genomica | Flores-A H.,Institute Diagnostico y Referencia Epidemiologicos | Munguia A.,Institute Diagnostico y Referencia Epidemiologicos | Gorodezky C.,Institute Diagnostico y Referencia Epidemiologicos
Tissue Antigens | Year: 2015

The B*14:41N allele was identified in a The National Marrow Donor Program (NMDP) Hispanic donor typed by our Mexican Registry-DONORMO © 2015 John Wiley & Sons A/S.


Villarreal-Molina M.T.,Instituto Nacional Of Medicina Genomica | Antuna-Puente B.,Instituto Nacional Of Medicina Genomica
Biochimie | Year: 2012

Adipose tissue is an endocrine organ that plays an essential role in regulating several metabolic functions through the secretion of biological mediators called "adipokines". Dysregulation of adipokines plays a crucial role in obesity-related diseases. Adiponectin (APN) is the most abundant adipokine accounting for the 0.01% of total serum protein, and is involved in a wide variety of physiological processes including energy metabolism, inflammation, and vascular physiology. APN plasma levels are reduced in individuals with obesity, type 2 diabetes and coronary artery disease, all traits with low-grade chronic inflammation. It is has been suggested that the absence of APN anti-inflammatory effects may be a contributing factor to this inflammation. APN inhibits the expression of tumor necrosis factor-α- induced endothelial adhesion molecules, macrophage-to-foam cell transformation, tumor necrosis factor-α expression in macrophages and adipose tissue, and smooth muscle cell proliferation. It also has anti-apoptotic and anti-oxidant effects, which play a role in its cardioprotective action. This review will focus on APN as an anti-inflammatory, anti-atherogenic and cardioprotective plasma protein. © 2012 Elsevier Masson SAS. All rights reserved.


Tejero M.E.,Instituto Nacional Of Medicina Genomica | Tejero M.E.,Ibero-American University of Mexico
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2010

Cardiovascular disease is a leading cause of death and disability in adults in Latin America. Women are more affected by these diseases than by all forms of cancer. Latin American countries have experienced rapid and uneven socioeconomic changes with a significant effect on lifestyle, demographic and health-related indicators. Differences in methodological approaches make it difficult to compare studies and health statistics across countries in the region. According to available statistics, female population in Latin American countries have lower mortality rate from coronary heart disease and higher mortality rate from cerebrovascular disease than North America. Current rates of obesity and type 2 diabetes are alarming in female in some countries. The high prevalence of risk factors forecasts an increase in cardiovascular disease for the coming decades in this region of the world. More systematic and sustained efforts for research, education, surveillance, prevention, early detection and affordable treatment are required across all Latin American countries to improve health conditions for adult population and particularly for women, who are more affected by obesity and diabetes. This article reviews the available information on cardiovascular disease and related risk factors in Latin American countries with a focus on female and to provide a brief description of selected multinational and national efforts to study and prevent this threat. © 2010 Elsevier B.V.


Hernandez-Lemus E.,Instituto Nacional Of Medicina Genomica
Journal of Non-Newtonian Fluid Mechanics | Year: 2010

In this paper we will outline a proposal for an irreversible thermodynamic theory of gene regulation. This theory would allow us to have a proper integration of molecular biophysical data for both, normal and abnormal gene function within the cell, hence enabling biomedical applications. The formalism is based on ideas taken from Extended Irreversible Thermodynamics. We describe how to deal with experimental data (mRNA levels) for high throughput gene expression experiments (microarrays) in order to extract information relevant for the biological characterization of gene regulatory phenomena. We then derive explicit expressions for the gene expression intensity, the chemical potentials of transcription and their associated affinities, as well as the corresponding Maxwell relations. With the aid of these, we were able to show that a change in the expression level of a single gene may affect the expression levels of the other genes and therefore of the whole genome. © 2010 Elsevier B.V.

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