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Arsenic (As) is a common contaminant in drinking water in northeastern Mexico, which reduces the expression of cytochrome P450 (CYP 450). This enzyme group metabolizes numerous drugs, such as oral antidiabetic drugs such as pioglitazone (61% CYP 3A4, 49% CYP 2C8). When CYP 450's function is inadequate, it has decreased therapeutic activity in type 2 diabetes mellitus (T2DM). This study aimed to establish the effect of As on pioglitazone metabolism in patients with T2DM. METHODOLOGY: Urine, water, and plasma samples from a healthy population (n = 11) and a population with T2DM (n = 20) were obtained. Samples were analyzed by fluorescence spectroscopy/hydride generation (As) and HPLC (pioglitazone). Additionally, CYP 3A4 and CYP 2C8 were studied by density functional theory (DFT). RESULTS: The healthy and T2DM groups were exposed via drinking water to >0.010 ppm, Ka values with a factor of 4.7 higher, Cl 1.42 lower, and ABCt 1.26 times higher concerning the healthy group. In silico analysis (DFT) of CYP 3A4 and CYP 2C8 isoforms showed the substitution of the iron atom by As in the active sites of the enzymes. CONCLUSIONS: The results indicate that the substitution of Fe for As modifies the enzymatic function of CYP 3A4 and CYP 2C8 isoforms, altering the metabolic process of CYP 2D6 and CYP 3A4 in patients with T2DM. Consequently, the variation in metabolism alters the bioavailability of pioglitazone and the expected final effect.

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INTRODUCTION: We assessed selected nutritional indicators in Mexican-origin children in two low-income, rural colonias in New Mexico on the U.S.-Mexico border. These children are at higher risk for obesity and other chronic diseases linked to poor nutrition in childhood, but little is known about their diets. METHOD: We surveyed mothers of 202 children 6 to 10 years old about sociodemographic characteristics, family and child attitudes and behaviors, and the child's diet. We compared diet with dietary recommendations and used regression trees to identify significant predictors of recommended intake. RESULTS: Among families, 89.1% participated in Medicaid, and 52.5% participated in a Supplemental Nutrition Program. More children met recommendations for fruit (36.1%) than vegetables (1.5%). Greater vegetable intake was associated with a child's not thinking healthy food tasted bad, greater family activity, and younger maternal age. Only 5.0% of children met the recommendation for <10% of energy from added sugar, with the average child consuming 2.4 times that from sugar-sweetened beverages and snacks. Lower sugar intake was associated with less screen time, not having TV on during meals, and playing team sports. Family access to healthy food and child use of mobile food vendors, vending and convenience stores were not predictive of diet. CONCLUSION: Hispanic children in border colonias have poor diets that put them at risk for obesity and numerous chronic diseases. Addressing this problem will require changing family norms and attitudes toward healthy food, screen time behavior, and physical activity levels within families.

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HOX transcript antisense RNA (HOTAIR) is an oncogenic long non-coding RNA frequently overexpressed in cancer. HOTAIR can enhance the malignant behavior of tumors by sponging microRNAs with tumor suppressor functions. Vasculogenic mimicry is a hypoxia-activated process in which tumor cells form three-dimensional (3D) channel-like networks, resembling endothelial blood vessels, to obtain nutrients. However, the role of HOTAIR in vasculogenic mimicry and the underlying mechanisms are unknown in human cancers. In the current study, we investigated the relevance of HOTAIR in hypoxia-induced vasculogenic mimicry in metastatic MDA-MB-231 and invasive Hs-578t triple negative breast cancer cells. Analysis of The Cancer Genome Atlas (TCGA) database using cBioPortal confirmed that HOTAIR was upregulated in clinical breast tumors relative to normal mammary tissues. Our quantitative RT-PCR assays showed a significant increase in HOTAIR levels after 48 h hypoxia relative to normoxia in breast cancer cell lines. Remarkably, knockdown of HOTAIR significantly abolished the hypoxia-induced vasculogenic mimicry which was accompanied by a reduction in the number of 3D channel-like networks and branch points. Likewise, HOTAIR silencing leads to reduced cell migration abilities of cancer cells. Bioinformatic analysis predicted that HOTAIR has a potential binding site for tumor suppressor miR-204. Luciferase reporter assays confirmed that HOTAIR is a competitive endogenous sponge of miR-204. Congruently, forced inhibition of HOTAIR in cells resulted in augmented miR-204 levels in breast cancer cells. Further bioinformatic analysis suggested that miR-204 can bind to the 3' untranslated region of focal adhesion kinase 1 (FAK) transcript involved in cell migration. Western blot and luciferase reporter assays confirmed that FAK is a novel target of miR-204. Finally, silencing of HOTAIR resulted in low levels of cytoplasmic FAK protein and alterations in the organization of cellular cytoskeleton and focal adhesions. In summary, our results showed, for the first time, that HOTAIR mitigates cell migration and vasculogenic mimicry by targeting the miR-204/FAK axis in triple negative breast cancer cells.

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INTRODUCTION: The prevalence of obesity is 26% among Hispanic children and teenagers and 47% among Hispanic adults. One contributor to obesity is sedentary behavior, such as using electronic screen devices (ie, screens). Low-income and Hispanic youths spend more time using such devices than other youths. METHODS: We interviewed 202 parents of Mexican-origin children aged 6 to 10 years in 2 rural communities near the US-Mexico border to determine screen use among children. We tested for associations between covariates and heavy screen use (≥4 hours/day) and calculated adjusted odds ratios (AORs) to identify independent, modifiable risk factors for such use. RESULTS: More than two-thirds (68.3%) of households had an annual income of less than $24,000, 89.1% spoke primarily Spanish, and 92.1% had internet access. The percentage of children with heavy screen use was 14.9% on weekdays and 25.2% on weekends. Smartphones were used by 62.4% of children, desktops or laptops by 60.9%; homework was the most common reason for use of these devices. One in 3 children used them for social media. Increased odds of heavy screen use were associated with having a television on while the child ate (weekday AOR = 3.02; 95% confidence interval [CI], 1.08-8.45 and weekend AOR = 2.38; 95% CI, 1.04-5.40) and using electronics to entertain (weekend AOR = 2.94; 95% CI, 1.15-7.51). More than 3 family meals per week (AOR = 0.40; 95% CI, 0.17-0.94 compared with ≤3 meals) and 2 or 3 family activities per week (AOR = 0.33; 95% CI, 0.12-0.87 compared with ≤1 activity) were associated with decreased odds of heavy weekend use. CONCLUSION: Even in low-income, Spanish-speaking communities, children have access to electronic devices, social media, and the internet, and a substantial fraction of them are heavy users. Efforts to reduce screen time might focus on understanding and changing the social norms that promote it.

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Women with abusive partners use a variety of coping strategies. This study examined the correlation between spirituality, resilience, and intimate partner violence using a cross-sectional survey of 54 Mexican American women living along the U.S.-Mexico border. The meaning-making coping model provides the conceptual framework to explore how spirituality is used as a copying strategy. Multiple ordinary least squares (OLS) regression results indicate women who score higher on spirituality also report greater resilient characteristics. Poisson regression analyses revealed that an increase in level of spirituality is associated with lower number of types of abuse experienced. Clinical, programmatic, and research implications are discussed.

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