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Background The CATSPER1 gene encodes a CATSPER channel protein that selectively permeates Ca2+ ions, and CATSPER expression in sperm is essential for flagellum hyperactivation and, thus, male fertility. Little is known regarding the transcriptional regulation of CATSPER1, but previous studies have performed in silico analyses of transcription factor binding sites, including three CRE sites designated 0–2, in which CRE0 is located near the transcription start site. Objetives We investigate if overexpression of CREB-A and CREMτ transcription factors might regulate CATSPER1 expression. Material and Methods In this study, the transcriptional regulation of the CATSPER1 gene by CREB-A and CREMτ transcriptions factors was determined by dual-luciferase assays in HEK293 and GC1-spg cells, and important CRE sites were mutated and analyzed for transcriptional regulation. Results The deletion of the CRE1 site dramatically increased the transcriptional activity of the CATSPER1 promoter in HEK293 and GC1-spg cells. In HEK293 cells, the CREB-A transcription factor positively regulated CATSPER1 gene expression, while the presence of CREB-A and CREMτ factors synergistically enhanced promoter activity in these cells. In contrast, deletion of CRE0 prevented any transcriptional activity of the CATSPER1 promoter in GC1-spg spermatogonial cells, but expression of either CREB-A or CREMτ restored such transcriptional activity. Conclusions The human CATSPER1 promoter is positively regulated in vitro by CREB-A in HEK293 and GC1-spg cells. Both lines showed differential transcriptional regulation, which was defined by the factors and coactivators present in each cell line as well as the context in which the CRE sites were found in the promoter.

Background and Aims Occupational exposure of parents to carcinogens is of great interest in the etiology of leukemias. Evidence of the impact of such exposure on infants or small children is scarce. Here we estimated whether occupational exposure of parents to carcinogens could be a risk factor for leukemias in their children. Methods Cases of acute leukemia (AL) in infants ≤24 months old diagnosed in Mexico City (1998–2013) were included in a population-based, case-control study. Each of the 195 cases was matched with at least one healthy child ( n = 369). For each of four exposure windows studied, the degree of exposure to carcinogens was determined for both parents by using a validated occupational exposure index. An unconditional logistic regression was carried out. Results Odds ratios (OR) and the 95% confidence intervals (CI) of the overall occupational exposure for parents during the four exposure windows indicated no association with risk of AL in their children. Pre-conception, the OR by the father 0.77 (0.49–1.21), by the mother 1.03 (0.50–2.11); during pregnancy, father 0.66 (0.38–1.15), mother 1.79 (0.46–6.90); during breastfeeding, father 0.75 (0.43–1.30), mother 0.96 (0.21–4.30); and after birth, father 0.74 (0.45–1.22), mother 0.90 (0.24–3.32). The statistical power of the sample size to identify an OR ≥2 and an exposure of ≥10% among controls was 78%. Conclusions These data support the idea that parents' occupational exposure during any of the periods studied was not a risk factor contributing to the etiology of AL in infants ≤24 months of age.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide. Mexican patients have high mortality rates, low frequency of good prognosis biomarkers (i.e., ETV6-RUNX1) and a high proportion is classified at the time of diagnosis with a high risk to relapse according to clinical features. In addition, very early relapses are more frequently observed than in other populations. The aim of the study was to identify new potential biomarkers associated with very early relapse in Mexican ALL children through transcriptome analysis.Microarray gene expression profiling on bone marrow samples of 54 pediatric ALL patients, collected at time of diagnosis and/or at relapse, was performed. Eleven patients presented relapse within the first 18 months after diagnosis. Affymetrix Human Transcriptome Array 2.0 (HTA 2.0) was used to perform gene expression analysis. Annotation and functional enrichment analyses were carried out using Gene Ontology, KEGG pathway analysis and Ingenuity Pathway Analysis tools.BLVRB, ZCCHC7, PAX5, EBF1, TMOD1 and BLNK were differentially expressed (fold-change2.0 and p value0.01) between relapsed and non-relapsed patients. Functional analysis of abnormally expressed genes revealed their important role in cellular processes related to the development of hematological diseases, cancer, cell death and survival and in cell-to-cell signaling interaction.Our data support previous findings showing the relevance of PAX5, EBF1 and ZCCHC7 as potential biomarkers to identify a subgroup of ALL children in high risk to relapse.

B-cell precursor acute lymphocytic leukemia (B-ALL) represents a worldwide public health issue. Particularly, Mexico is one of the countries with the highest incidence of ALL in children. Between the multiple factors involved in ALL etiology, genetic alterations are clearly one of the most relevant features. In this work, a group of 24 B-ALL patients, all negative for the four most frequent gene fusions (ETV6-RUNX1, BCR-ABL1, TCF3-PBX1 and MLL-AF4), were included in a high-resolution microarray analysis in order to evaluate genomic copy-number alterations (CNAs). The results of this preliminary report showed a broad genomic heterogeneity among the studied samples; 58% of the patients were hyperdiploid and 33% displayed a chromosome 9p deletion of variable length affecting genes CDKN2A/B, two patients displayed genomic instability with a high number of focal CNAs, three patients presented unique duplications affecting 2q, 12p and 1q, respectively, and one patient displayed no copy number imbalances. The copy-number profile of 44 genes previously related to B-ALL was heterogeneous as well. Overall results highlight the need for a detailed description of the genetic alterations in ALL cancer cells in order to understand the molecular pathogenesis of the disease and to identify any prognostic markers with clinical significance.

The parental age at conception has been reported to be a risk factor for childhood acute leukaemia (AL); however, the relationship is controversial. The aim of the present study was to investigate the association between parental age at conception and the risk of AL in Mexican children, a population with a high incidence of the disease and a high prevalence of pregnancies in adolescents and young adults.A multicentre case-control study was conducted. Incident AL cases younger than 17 years of age diagnosed between 2010 and 2015 were included. Controls were matched with cases according to age, sex, and health institution. Using logistic regression analysis, adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were calculated for each maternal stratum after adjusting for paternal age at conception of index child. The maternal age between 25 and 29.99 years was selected as the reference category.In most strata where maternal and paternal ages were assessed, no association was found with the risk of developing acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring. An increased risk for AML was observed when the mother was between 20 and 24.99 years of age and the father aged 25-29.99 years (aOR, 1.94; 95 % CI, 1.03-3.67). In addition, there was a positive association for ALL when the mother´s age was between 20 and 24.99 years and the father was20 years of age, however, a very wide confidence interval was noted (aOR, 12.26; 95 % CI, 1.41-106.83).In the present study, maternal and paternal ages assessed in different strata showed little association with risk of developing ALL and AML in children. Positive associations between risk of both types of childhood AL were observed with younger paternal and maternal ages.

A 220-kDa E. histolytica lectin is capable of downregulating some inflammatory cytokines (IL-5, IL-6, INF-gamma and TNF-alpha) and thus of inducing an overall anti-inflammatory Th-phenotype in leucocytes of selected, perhaps constitutionally predisposed, individuals irrespective of their HLA-DR3 profile (i.e., in this study patients long recovered from amebic abscess of the liver). This probably inhibited cytokine response pattern could increase the risk for developing amebic abscess of the liver in the course of invasive intestinal amebiasis.