Obtención de nuevos genes de la hormona del crecimiento en vertebrados

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

Evaluation of skin expression profiles of patients with vitiligo treated with narrow-band UVB therapy by targeted RNA-seq

Abstract: Background: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. oBjective: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. Methods: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student’s t-test and the Mann-Whitney U-test. results: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). study liMitations: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. conclusion: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo. Keywords: Gene expression; Phototherapy; Vitilig

Circulating microRNA expression profile in B-cell acute lymphoblastic leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a highly diverse disease characterized by cytogenetic and molecularabnormalities, including altered microRNA (miRNA) expression signatures. AIM: We perform and validate a plasma miRNA expression profiling to identify potential miRNA involved in leukemogenesis METHODS: MiRNA expression profiling assay was realized in 39 B-ALL and 7 normal control plasma samples using TaqMan Low Density Array (TLDA) plates on Applied Biosystems 7900 HT Fast Real-Time PCR System. MiRNA validation was done for six miRNA differentially expressed by quantitative real-time PCR. RESULTS: Seventy-seven circulating miRNA differentially expressed: hsa-miR-511, -222, and -34a were overexpressed, whereas hsa-miR-199a-3p, -223, -221, and -26a were underexpressed (p values < 0.005 for both sets). According to operating characteristic curve analysis, hsa-miR-511 was the most valuable biomarker for distinguishing B-ALL from normal controls,with an area under curve value of 1 and 100% for sensitivity, and specificity respectively. CONCLUSIONS: Measuring circulating levels of specific miRNA implicated in regulation of cell differentiation and/or cell proliferation such as hsa-miRNA-511, offers high sensitivity and specificity in B-ALL detection and may be potentially useful for detection of disease progression, as indicator of therapeutic response, and in the assessment of biological and/or therapeutic targets for patients with B-ALL

CAPN3, DCT, MLANA and TYRP1 are overexpressed in skin of vitiligo vulgaris Mexican patients

Abstract. Vitiligo is a disorder causing skin depigmentation, in which several factors have been proposed for its pathogenesis: Environmental, genetic and biological aspects of melanocytes, even those of the surrounding keratinocytes. However, the lack of understanding of the mechanisms has complicated the task of predicting the development and progression. The present study used microarray analysis to characterize the transcriptional profile of skin from Vitiligo Vulgaris (VV) patients and the identified transcripts were validated using targeted high-throughput RNA sequencing in a broader set of patients. For microarrays, mRNA was taken from 20 skin biopsies of 10 patients with VV (pigmented and depigmented skin biopsy of each), and 5 biopsies of healthy subjects matched for age and sex were used as a control. A signature was identified that contains the expression pattern of 722 genes between depigmented vitiligo skin vs. healthy control, 1,108 between the pigmented skin of vitiligo vs. healthy controls and 1,927 between pigmented skin, depigmented vitiligo and healthy controls (P<0.05; false discovery rate, <0.1). When comparing the pigmented and depigmented skin of patients with vitiligo, which reflects the real difference between both skin types, 5 differentially expressed genes were identified and further validated in 45 additional VV patients by RNA sequencing. This analysis showed significantly higher RNA levels of calpain-3, dopachrome tautomerase, melan-A and tyrosinase-related protein-1 genes. The data revealed that the pigmented skin of vitiligo is already affected at the level of gene expression and that the main differences between pigmented and non-pigmented skin are explained by the expression of genes associated with pigment metabolism

Profiles of amino acids and acylcarnitines related with insecticide exposure in culex quinquefasciatus (Say)

Culex quinquefasciatus Say is a vector of many pathogens of humans, and both domestic and wild animals. Personal protection, reduction of larval habitats, and chemical control are the best ways to reduce mosquito bites and, therefore, the transmission of mosquito-borne pathogens. Currently, to reduce the risk of transmission, the pyrethroids, and other insecticide groups have been extensively used to control both larvae and adult mosquitoes. In this context, amino acids and acylcarnitines have never been associated with insecticide exposure and or insecticide resistance. It has been suggested that changes in acylcarnitines and amino acids profiles could be a powerful diagnostic tool for metabolic alterations. Monitoring these changes could help to better understand the mechanisms involved in insecticide resistance, complementing the strategies for managing this phenomenon in the integrated resistance management. The purpose of the study was to determine the amino acids and acylcarnitines profiles in larvae of Cx. quinquefasciatus after the exposure to different insecticides. Bioassays were performed on Cx. quinquefasciatus larvae exposed to the diagnostic doses (DD) of the insecticides chlorpyrifos (0.001 μg/mL), temephos (0.002 μg/mL) and permethrin (0.01 μg/mL). In each sample, we analyzed the profile of 12 amino acids and 31 acylcarnitines by LC-MS/MS. A t-test was used to determine statistically significant differences between groups and corrections of q-values. Results indicates three changes, the amino acids arginine (ARG), free carnitine (C0) and acetyl-carnitine (C2) that could be involved in energy production and insecticide detoxification. We confirmed that concentrations of amino acids and acylcarnitines in Cx. quinquefasciatus vary with respect to different insecticides. The information generated contributes to understand the possible mechanisms and metabolic changes occurring during insecticide exposure. © 2017 Martin-Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Integrated transcriptomic and metabolomic analysis shows that disturbances in metabolism of tumor cells contribute to poor survival of RCC patients

Purpose Cellular metabolism of renal cell carcinoma (RCC) tumors is disturbed. The clinical significance of these alterations is weakly understood. We aimed to find if changes in metabolic pathways contribute to survival of RCC patients. Material and methods 35 RCC tumors and matched controls were used for metabolite profiling using gas chromatography-mass spectrometry and transcriptomic analysis with qPCR-arrays targeting the expression of 93 metabolic genes. The clinical significance of obtained data was validated on independent cohort of 468 RCC patients with median follow-up of 43.22\ua0months. Results The levels of 31 metabolites were statistically significantly changed in RCC tumors compared with controls. The top altered metabolites included beta-alanine (+\ua04.2-fold), glucose (+\ua03.4-fold), succinate (−\ua011.0-fold), myo-inositol (−\ua04.6-fold), adenine (−\ua04.2-fold), uracil (−\ua03.7-fold), and hypoxanthine (−\ua03.0-fold). These disturbances were associated with altered expression of 53 metabolic genes. ROC curve analysis revealed that the top metabolites discriminating between tumor and control samples included succinate (AUC\ua0=\ua00.91), adenine (AUC\ua0=\ua00.89), myo-inositol (AUC\ua0=\ua00.87), hypoxanthine (AUC\ua0=\ua00.85), urea (AUC\ua0=\ua00.85), and beta-alanine (AUC\ua0=\ua00.85). Poor survival of RCC patients correlated (p\ua0<\ua00.0001) with altered expression of genes involved in metabolism of succinate (HR\ua0=\ua02.7), purines (HR\ua0=\ua02.4), glucose (HR\ua0=\ua02.4), beta-alanine (HR\ua0=\ua02.5), and myo-inositol (HR\ua0=\ua01.9). Conclusions We found that changes in metabolism of succinate, beta-alanine, purines, glucose and myo-inositol correlate with poor survival of RCC patients. © 2016 Elsevier B.V

Multivariate Radiological-Based Models for the Prediction of Future Knee Pain: Data from the OAI

In this work, the potential of X-ray based multivariate prognostic models to predict the onset of chronic knee pain is presented. Using X-rays quantitative image assessments of joint-space-width (JSW) and paired semiquantitative central X-ray scores from the Osteoarthritis Initiative (OAI), a case-control study is presented. The pain assessments of the right knee at the baseline and the 60-month visits were used to screen for case/control subjects. Scores were analyzed at the time of pain incidence (T-0), the year prior incidence (T-1), and two years before pain incidence (T-2). Multivariate models were created by a cross validated elastic-net regularized generalized linear models feature selection tool. Univariate differences between cases and controls were reported by AUC, C-statistics, and ODDs ratios. Univariate analysis indicated that the medial osteophytes were significantly more prevalent in cases than controls: C-stat 0.62, 0.62, and 0.61, at T-0, T-1, and T-2, respectively. The multivariate JSW models significantly predicted pain: AUC = 0.695, 0.623, and 0.620, at T-0, T-1, and T-2, respectively. Semiquantitative multivariate models predicted paint with C-stat = 0.671, 0.648, and 0.645 at T-0, T-1, and T-2, respectively. Multivariate models derived from plain X-ray radiography assessments may be used to predict subjects that are at risk of developing knee pain. © 2015 Jorge I. Galván-Tejada et al

SurvExpress: An Online Biomarker Validation Tool and Database for Cancer Gene Expression Data Using Survival Analysis

Validation of multi-gene biomarkers for clinical outcomes is one of the most important issues for cancer prognosis. An important source of information for virtual validation is the high number of available cancer datasets. Nevertheless, assessing the prognostic performance of a gene expression signature along datasets is a difficult task for Biologists and Physicians and also time-consuming for Statisticians and Bioinformaticians. Therefore, to facilitate performance comparisons and validations of survival biomarkers for cancer outcomes, we developed SurvExpress, a cancer-wide gene expression database with clinical outcomes and a web-based tool that provides survival analysis and risk assessment of cancer datasets. The main input of SurvExpress is only the biomarker gene list. We generated a cancer database collecting more than 20,000 samples and 130 datasets with censored clinical information covering tumors over 20 tissues. We implemented a web interface to perform biomarker validation and comparisons in this database, where a multivariate survival analysis can be accomplished in about one minute. We show the utility and simplicity of SurvExpress in two biomarker applications for breast and lung cancer. Compared to other tools, SurvExpress is the largest, most versatile, and quickest free tool available. SurvExpress web can be accessed in http://bioinformatica.mty.itesm.mx/SurvExpress (a tutorial is included). The website was implemented in JSP, JavaScript, MySQL, and R. © 2013 Aguirre-Gamboa et al

Effect of Consuming Beef with Varying Fatty Acid Compositions as a Major Source of Protein in Volunteers under a Personalized Nutritional Program

Beef is an excellent source of nutrients; unfortunately, most nutritional recommendations suggest limiting or even avoiding it. Studies have shown that the fatty acid composition of meat influences weight loss. This randomized controlled clinical trial evaluated the anthropometric and serum lipid changes after a food intervention that included frequent beef consumption (120 g consumed four days/week for four weeks). Volunteers were randomly assigned to the commercial or Wagyu-Cross beef groups, with the latter beef possessing higher fat and MUFA contents. Both groups exhibited reductions in body measurements and lipid profiles; however, the Wagyu-Cross group exhibited greater changes in weight (&minus;3.75 vs. &minus;2.90 kg) and BMI (&minus;1.49 vs. &minus;1.03) than the commercial group, without a significant difference between them. No significant group differences in lipid profiles were observed; however, the Wagyu-Cross group exhibited a more favorable change in decreasing the TC concentration (&minus;7.00 mg/dL) and LDL-C concentration (&minus;12.5 mg/dL). We suggest that high MUFA beef could be included in weight-loss programs since it does not affect weight loss and hasn&rsquo;t a negative influence on lipid metabolism