Association between exposure to organophosphate pesticides and cytokine levels in a population of flower workers in Mexico.

The ability of organophosphate pesticides to disturb immune function has been demonstrated by in vivo and in vitro studies, but evidence of such effects on humans remains scarce. To assess the association between organophosphate pesticides exposure and cytokine levels in Mexican flower workers, a cross-sectional study was carried out. A questionnaire was provided to 121 male flower workers, and urine and blood samples were collected. Using gas chromatography, urinary concentrations of dialkylphosphate metabolites were determined. The serum cytokine levels, IL-4, IL-5, IL-6, IL-8, and IL-10, were measured using multiplex analysis, and levels of INF-γ and TNF-α by ELISA. We found that a higher dialkylphosphate concentration decreased the pro-inflammatory cytokines INF-γ (ß = -0.63; 95 % CI: -1.22, -0.05), TNF-α (ß= -1.18; 95 % CI: -2.38, 0.02), and IL-6 (ß= -0.59; 95 % CI: -1.29, 0.12), and increased IL-10 (ß=0.56; 95 % CI: 0.02, 1.09), the main anti-inflammatory cytokine, suggesting an imbalance of the immune response in flower workers.

Pesticide use patterns and their association with cytokine levels in Mexican flower workers.

OBJECTIVE: Occupational exposure to pesticides is a known risk for disrupting cellular immune response in flower workers due to their use of multiple chemical products, poor work conditions, and inadequate protection. Recently, the analysis of pesticide use patterns has emerged as an alternative to studying exposure to mixtures of these products. This study aimed to evaluate the association between exposure to different patterns of pesticide use and the cytokine profile of flower workers in the State of Mexico and Morelos, Mexico. METHODS: A cross-sectional study was carried out on a population of 108 flower workers. Serum levels of IL-4, IL-5, IL-6, IL-8, IL-10 cytokines were analyzed by means of multiplex analysis, and TNF-α and IFN-γ using an ELISA test. Pesticide use patterns were generated by principal components analysis. RESULTS: The analysis revealed that certain patterns of pesticide use, combining insecticides and fungicides, were associated with higher levels of pro-inflammatory cytokines, particularly IL-6 and IFN-γ. CONCLUSION: These findings indicate that pesticides may possess immunotoxic properties, contributing to increased inflammatory response. However, further comprehensive epidemiological studies are needed to establish a causal relationship.

Interaction between Akkermansia muciniphila and Diet Is Associated with Proinflammatory Index in School-Aged Children.

BACKGROUND: Imbalance in the intestinal microbiota can lead to chronic low-grade inflammation. Diet may influence this association. In this study, we aimed to evaluate the interaction between Akkermansia muciniphila (A. muciniphila) and dietary patterns using a proinflammatory index. METHODS: We conducted a cross-sectional study with school-aged children. We quantified the relative abundance (RA) of A. muciniphila in feces using a polymerase chain reaction. We collected dietary information through employing a food frequency questionnaire and generated dietary patterns using principal component analysis. We generated a proinflammatory index from serum levels of interleukin-6, interleukin-10, tumor necrosis factor alpha, and adiponectin validated by receptor operating characteristic curves. We evaluated the association between A. muciniphila and the proinflammatory index using logistic regression, including an interaction term with dietary patterns. RESULTS: We found that children with a low RA of A. muciniphila and a high intake of simple carbohydrates and saturated fats had increased odds of being high on the proinflammatory index. However, when the consumption of this dietary pattern is low, children with a low RA of A. muciniphila had decreased odds of being high on the proinflammatory index. CONCLUSIONS: Our results suggest that the simultaneous presence of A. muciniphila and diet have a more significant impact on the presence of being high on the proinflammatory index compared to both factors separately.

Interferon-tau (IFN-τ) Has Antiproliferative Effects, Induces Apoptosis, and Inhibits Tumor Growth in a Triple-negative Breast Cancer Murine Tumor Model.

BACKGROUND/AIM: Resistant triple-negative breast cancer (TNBC) is a subtype of this disease that is resistant to conventional chemotherapy agents. IFN-τ is a cytokine that has recently been shown to have immunoregulatory and antitumor effects. The present study aimed to examine the antiproliferative and apoptosis effects of IFN-τ in breast cancer cells and the antitumor effect in a murine tumor model of TNBC. MATERIALS AND METHODS: Murine breast cancer 4T1 cells were cultured and treated with ovine IFN-τ and through MTT and Caspase-Glo 3/7 assays, viability and cell death were determined. In addition, the antitumor effect of IFN-τ was determined in a murine tumor model of TNBC. RESULTS: Ovine IFN-τ showed a concentration-dependent antiproliferative effect on 4T1 murine breast cancer cells. Also, treatment of 4T1 cells with IFN-τ induced the activation of caspase 3 and 7, which is indicative of apoptotic cell death. Moreover, we detected an increase in the expression of type I interferon receptor (IFNAR1/2) in cells treated with IFN-. The intratumoral application of IFN-τ in mice inhibited tumor growth compared to the control non-treated group, and the effect was associated with the increased expression of GM-CSF. CONCLUSION: Ovine IFN-τ may be an effective immunotherapeutic cytokine for the treatment of TNBC.

High Relative Abundance of Staphylococcus aureus and Serum Cytokines Are Associated with Cardiometabolic Abnormalities in Children.

Background: The alteration in the composition of the gut microbiota has been associated with an increased risk of developing cardiovascular and metabolic diseases. The present study evaluated the association between the relative abundance (RA) of intestinal Staphylococcus aureus and the inflammatory response with cardiometabolic alterations in children. Methods: This cross-sectional study included 1142 children (age 6-12 years), which were classified by degree of adiposity. Anthropometry, cardiometabolic markers, and RA of intestinal S. aureus were measured. Cytokine concentrations were available in 626 children. Path coefficients (PC) were estimated by path analysis. Results: RA of S. aureus was positively associated with cholesterol PC = 24.98 (95% CI 10.76 to 39.21) and negatively with triglycerides PC = -13.10 (95% CI -22.73 to -3.48). Body mass index (BMI) Z-scores had significant mediation effects on the association between RA of S. aureus with waist circumference PC = 2.87 (95% CI 0.58 to 5.16), triglycerides PC = 6.63 (95% CI 1.29 to 11.98), low-density lipoproteins (LDL) PC = 1.73 (95% CI 0.27 to 3.18), and high-density lipoproteins PC = -1.20 (95% CI -2.19 to -0.22). Interleukin 6 (IL-6) was negatively associated with glucose PC = -3.01 (95% CI -5.85 to -0.17) and LDL PC = -8.65 (95% CI -16.54 to -0.77), and interleukin 10 (IL-10) was positively associated with glucose PC = 3.37 (95% CI 0.47 to 6.26). Conclusions: It is suggested that the RA of S. aureus, IL-6, and IL-10 are associated with cardiometabolic alterations in children, where BMI Z-scores have an important mediating effect for the development of these.

BRCA1 and VDR gene polymorphisms are associated with prostate cancer risk in Mexican men.

Prostate cancer (PC) is a polygenic disease with broad differences across ethnicities. BRCA1/2 and VDR have exhibited a featured genetic contribution to PC development in European populations. Nonetheless, its contribution in Latino populations specifically among Mexican men, where 70% of PC cases are detected in advanced stages, is still unknown. The contribution of seven polymorphisms in BRCA1/2 and VDR genes to PC susceptibility was evaluated in 370 incident PC cases and 759 age-matched (±5 years) controls belonging to the Mexican population. Based on Gleason score at diagnosis, PC cases were classified as well-differentiated PC (Gleason <7) and moderate or poorly differentiated PC (Gleason ≥7). Age at diagnosis was used to divided PC cases in earlier (<60 years) and late-onset PC (≥60 years). Prostate and breast cancer family histories were obtained through interview. Our results provided evidences about the contribution of BRCA1-rs1799966 (ORCC genotype = 2.30; 95% confidence interval [CI] = 1.36-3.91) to the moderate or poorly differentiated PC risk, independently of the family history of prostate, breast or ovary cancer. Further, VDR-rs2238135-G allele was associated with early-onset PC (ORG allele = 2.05; 95% CI = 1.06-3.95), and marginally with moderate or poorly differentiated PC risk. The present study revealed the crucial role of BRCA1 in PC aggressiveness risk, outstanding the gender imbalance regarding the breast cancer risk in women.

[Unhealthy behavior associated with the development of high blood pressure in adolescents]. / Conducta no saludable asociada con el desarrollo de presión arterial elevada en adolescentes.

This article aims to evaluate the association between unhealthy behavior pattern and prevalence and incidence of high blood pressure in adolescents. Based on data from a cohort study with a baseline population of 2,813 adolescents enrolled in a public school system, the study measured the baseline prevalence and incidence of high blood pressure as a function of smoking, alcohol and illegal drug use, and physical activity. These variables were used to build a model called "unhealthy behavior pattern", and its relationship was evaluated in relation to high blood pressure in adolescents, using multiple logistic regression models. Prevalence of high blood pressure was 8.67%. Accumulated incidence of high blood pressure was 7.58%. In the multivariate analysis of high blood pressure adjusted by degree of adiposity, there was an association with the unhealthy behavior pattern in males (OR = 3.13; 95%CI: 1.67-5.84). The association between incidence of high blood pressure and unhealthy behavior pattern was observed in females (OR = 2.34; 95%CI: 1.11-4.95). In conclusion, high blood pressure is present in the adolescent population, associated with unhealthy behaviors like smoking, alcohol and illegal drug use, and physical inactivity, independently of the degree of adiposity.

Conducta no saludable asociada con el desarrollo de presión arterial elevada en adolescentes / Unhealthy behavior associated with the development of high blood pressure in adolescents / Conduta não saudável associada com o desenvolvimento da pressão arterial elevada em adolescentes

El artículo tiene como objetivo evaluar la asociación entre el patrón de conducta no saludable sobre la prevalencia y la incidencia de la presión arterial elevada en adolescentes. A partir de la información de un estudio de cohorte con una población en la medición basal de 2.813 adolescentes del sistema de educación pública, se determinó la prevalencia (basal) e incidencia de la presión arterial elevada, junto con el consumo de tabaco, alcohol, drogas ilegales y las variables de actividad física. Con estas variables, se construyó un modelo llamado "patrón de conducta no saludable" y se evaluó su relación con la presión arterial elevada en los adolescentes, utilizando modelos de regresión logística múltiple. Entre los resultados, se observa que la prevalencia de la presión arterial elevada fue 8,67%. La incidencia acumulada de la presión arterial elevada fue 7,58%. En el análisis múltiple de la prevalencia de presión arterial elevada, ajustado por grado de adiposidad, hubo asociación con un alto patrón de conducta no saludable en el grupo de los hombres (OR = 3,13; IC95%: 1,67-5,84). La asociación de la incidencia de la presión arterial elevada y alto patrón de conducta no saludable se observa en el grupo de las mujeres, (OR = 2,34; IC95%: 1,11-4,95). Se concluye que la presión arterial elevada está presente en la población adolescente, asociado a conductas no saludables en ellos, como el tabaquismo, el alcohol, las drogas ilegales y la escasa actividad física, independientemente del grado de adiposidad.

This article aims to evaluate the association between unhealthy behavior pattern and prevalence and incidence of high blood pressure in adolescents. Based on data from a cohort study with a baseline population of 2,813 adolescents enrolled in a public school system, the study measured the baseline prevalence and incidence of high blood pressure as a function of smoking, alcohol and illegal drug use, and physical activity. These variables were used to build a model called "unhealthy behavior pattern", and its relationship was evaluated in relation to high blood pressure in adolescents, using multiple logistic regression models. Prevalence of high blood pressure was 8.67%. Accumulated incidence of high blood pressure was 7.58%. In the multivariate analysis of high blood pressure adjusted by degree of adiposity, there was an association with the unhealthy behavior pattern in males (OR = 3.13; 95%CI: 1.67-5.84). The association between incidence of high blood pressure and unhealthy behavior pattern was observed in females (OR = 2.34; 95%CI: 1.11-4.95). In conclusion, high blood pressure is present in the adolescent population, associated with unhealthy behaviors like smoking, alcohol and illegal drug use, and physical inactivity, independently of the degree of adiposity.

O artigo objetivou avaliar a associação entre o padrão de conduta não saudável sobre a prevalência e incidência da pressão arterial elevada em adolescentes. A partir das informações de um estudo de coorte, com uma população na medição basal de 2.813 adolescentes do sistema de ensino público, foi determinada a prevalência (basal) e incidência da pressão arterial elevada, junto com o consumo de cigarro, bebidas alcoólicas, drogas ilegais e as variáveis de atividade física. Com estas variáveis, foi construído um modelo chamado "padrão de conduta não saudável" e foi avaliada sua relação com a pressão arterial elevada nos adolescentes, usando modelos de regressão logística múltipla. Entre os resultados, foi observado que a prevalência da pressão arterial elevada foi 8,67%. A incidência acumulada da pressão arterial elevada foi 7,58%. Na análise múltipla de prevalência da pressão arterial elevada, ajustado por graus de gordura, houve associação com um padrão alto de conduta não saudável no grupo dos homens (OR = 3,13; IC95%: 1,67-5,84). A associação da incidência da pressão arterial elevada e um alto padrão de conduta não saudável foram observados também no grupo das mulheres, (OR = 2,34; IC95%: 1,11-4,95). Concluímos que a pressão arterial elevada está presente na população adolescente, associada a condutas não saudáveis entre elas: o tabagismo, o álcool, as drogas ilegais e a insuficiente atividade física, independentemente do grau de gordura corporal.

Interferon-Tau has Antiproliferative effects, Represses the Expression of E6 and E7 Oncogenes, Induces Apoptosis in Cell Lines Transformed with HPV16 and Inhibits Tumor Growth In Vivo.

Interferon tau (IFN-τ) is a promising alternative antiviral and immunotherapeutic agent in a wide variety of diseases including infectious, neurodegenerative, autoimmune and cancer due to its low toxicity in comparison with other type I interferon´s. The objective of our study was established the effect of the bovine IFN-τ on human (SiHa) and murine (BMK-16/myc) cells transformed with HPV 16 and evaluates the antitumor effect in a murine tumor model HPV 16 positive. We determine that bovine IFN-τ has antiproliferative effects, pro-apoptotic activity and induces repression of viral E6 and E7 oncogenes (time- and dose-dependent) on human and murine cells transformed with HPV 16 similar to the effects of IFN-ß. However, IFN-τ induces greater antiproliferative effect, apoptosis and repression of both oncogenes in BMK-16/myc cells compared to SiHa cells. The differences were explained by the presence and abundance of the type I interferon receptor (IFNAR) in each cell line. On the other hand, we treated groups of tumor-bearing mice (HPV16 positive) with IFN-τ and showed the inhibition tumor growth effect in vivo. Our finding indicates that bovine IFN-τ may be a good candidate for immunotherapy against cervical cancer.

In vivo Antitumor Effect of an HPV-specific Promoter driving IL-12 Expression in an HPV 16-positive Murine Model of Cervical Cancer.

Human papillomavirus (HPV) is a DNA virus that infects epithelial cells and has been implicated in the development of cervical cancer. Few therapeutic strategies have been designed for the treatment of cervical intraepithelial neoplasia, a precursor of cervical cancer. In these early stages, the HPV E2 protein is the most important viral factor involved in viral gene expression and plays crucial roles during the vegetative viral cycle in epithelial cells. Papillomavirus E2 binds specifically to palindromic ACCN6GGT sequences, referred to as the E2 binding sites (E2BS), which are concentrated within the viral long control region, and which are responsible for regulation of the HPV protein's expression. Here, we consider E2BS as a candidate sequence to induce the expression of antiviral therapeutic genes selectively in HPV-infected cells expressing the E2 protein. This study focuses on the use of an HPV-specific promoter comprised of four E2BS to drive the expression of IL-12, leading to an antitumor effect in an HPV-positive murine tumor model. The therapeutic strategy was implemented via viral gene therapy using adenoviral vectors with recombinant E2 and IL-12 genes and E2BS-IL-12. We demonstrate that the HPV-specific promoter E2BS is functional in vitro and in vivo through transactivation of HPV E2 transcription factor.

ADIPOQ and ADIPOR2 gene polymorphisms: association with overweight/obesity in Mexican children / Polimorfismos de los genes ADIPOQ y ADIPOR2 y su asociación con sobrepeso/obesidad en niños mexicanos

Background: ENSANUT 2012 showed a combined prevalence of overweight and obesity of 34.4% in Mexican children. Single nucleotide polymorphisms (SNPs) of the ADIPOQ and ADIPOR2 genes have been reported in many populations, but their association with obesity has not been confirmed in other studies. Our aim was to determine the association of SNPs from ADIPOQ and ADIPOR2 genes with obesity in Mexican children. Methods: A total of 2,634 children from 6 to 12 years old were enrolled in the study from four IMSS Units in Mexico City. We selected 1,469 unrelated children (745 normal weight and 724 overweight/obese). Phenotype characterization included anthropometric measurements, blood pressure, biochemical parameters, insulin concentrations and presence of acanthosis nigricans (AN). Analysis of the SNPs rs182052, rs266729, rs2241766, rs822393 of ADIPOQ and rs11061971 of ADIPOR2 was carried out in the DNA samples. Results: The study showed significant differences (p <0.05) between groups in waist circumference, blood pressure, presence of AN, insulin concentrations, HOMA-IR, fasting glucose and lipid parameters, being higher in obese children. No associations in ADIPOQ variants with the presence of overweight/obesity were found. The presence of the variant rs11061971 of ADIPOR2 in children had a significant association with protection of overweight/obesity (OR 0.79, 95% CI 0.68-0.93, p = 0.003). Also, the log-additive model confirmed the association by codominant and dominant models (p <0.05). Conclusions: The presence of rs11061971 of ADIPOR2 variant confers protection against obesity and could be used as a marker in Mexican children.

Introducción: ENSANUT 2012 mostró una prevalencia combinada de sobrepeso y obesidad en el 34.4% en niños mexicanos. Se han reportado polimorfismos de un solo nucleótido (SNP) de los genes ADIPOQ y ADIPOR2 en varias poblaciones, pero su asociación con la obesidad ha sido controversial. El objetivo de este trabajo fue determinar la asociación de SNP de ADIPOQ y ADIPOR2 con obesidad en una muestra de niños mexicanos. Métodos: Un total de 2,634 niños de 6-12 años se inscribieron en el estudio en cuatro unidades del Instituto Mexicano del Seguro Social en la Ciudad de México. Se seleccionaron 1,469 niños no emparentados (745 peso normal y 724 sobrepeso/obesidad). Se les tomaron medidas antropométricas, presión arterial, parámetros bioquímicos, insulina y presencia de acantosis nigricans (AN). El análisis de los SNP (rs182052, rs266729, rs2241766, rs822393 de ADIPOQ y rs11061971 de ADIPOR2) se realizó en muestras de ADN. Resultados: Se observaron diferencias significativas (p < 0.05) entre los grupos en la circunferencia de cintura, presión arterial, AN, insulina, HOMA-IR, glucosa en ayunas y parámetros lipídicos siendo elevados en los niños obesos. No se encontró asociación en variantes ADIPOQ con la presencia de sobrepeso/obesidad. La presencia de rs11061971 de ADIPOR2 tuvo una asociación significativa con la protección de sobrepeso/obesidad (OR de 0.79; IC95% 0.68 a 0.93, p = 0.003). El modelo Log-aditivo confirmó la asociación de los modelos codominante y dominante (p < 0.05). Conclusiones: La presencia de la variante rs11061971 de ADIPOR2 confiere protección contra la obesidad, y podría utilizarse como marcador en niños mexicanos.

[Childhood obesity is associated to the interaction between firmicutes and high energy food consumption]. / La obesidad infantil como consecuencia de la interacción entre firmicutes y el consumo de alimentos con alto contenido energético.

UNLABELLED: INTRODUCTIÓN: Obesity is a serious public health problem in Mexico, the National Health and Nutrition Survey (ENSANUT 2012) reported a 34.4% prevalence of overweight, and obesity in children aged 5-11. Recent research has suggested that the gut microbiota may be a risk factor of obesity through its influence on human metabolism. AIM OF THE STUDY: To evaluate association between the intestinal microbiota profile and obesity among children and whether this association is modified depending on the feeding pattern of a sample of schoolchildren from Mexico City. METODOLOGY AND RESULTS: Cross-sectional study on 1042 children aged 6-14 years; physical activity questionnaire, personal medical history and heredofamilial of obesity and type 2 diabetes were administered to all the children. Eating patterns was performed by principal component analysis (PCA). The association between intestinal microbiota and overweight / obesity depending on diet was assessed with logistic regression models. CONCLUSION: Our results shows that the interaction between the intestinal microbiota and diet, particularly high in fats and simple carbohydrates increases the chance of developing obesity.

Introducción: La obesidad es un grave problema de salud pública en México, la Encuesta Nacional de Salud y Nutrición (ENSANUT 2012) reporta una prevalencia de sobrepeso y obesidad en niños de 5 a 11 años de 34.4%, siendo el país con mayor prevalencia a nivel mundial. Investigaciones recientes han sugerido que la microbiota intestinal puede ser factor de riesgo de la obesidad por su influencia en el metabolismo humano. Objetivo: Evaluar si existe asociación entre el perfil de la microbiota intestinal y la obesidad infantil y si esta asociación se modifica dependiendo del patrón de alimentación de una muestra de niños de edad escolar de la Ciudad de México. Metodología y Resultados: Estudio transversal en 1042 niños de 6 a 14 años, a todos se les aplicó cuestionario de actividad física, antecedentes patológicos personales y heredofamiliares de obesidad y diabetes tipo 2. La definición de los patrones de alimentación se realizó por análisis de componentes principales (ACP). La asociación entre microbiota intestinal y sobrepeso/obesidad dependiendo de la dieta se evaluó con modelos de regresión logística, ajustados por factores de confusión. Encontramos que un perfil de abundancia relativa alta de Firmicutes y una abundancia relativa baja de Bacteroidetes aunado a un consumo elevado de dietas ricas en carbohidratos y grasas saturadas se asocia con un mayor riesgo de obesidad. Conclusión: La interacción entre la microbiota intestinal y la dieta, particularmente con alto contenido de grasas y carbohidratos simples incrementa las posibilidades de presentar obesidad.

Esclerosis múltiple / Multiple sclerosis

La esclerosis múltiple es un padecimiento neurológico con participación de mecanismos fisiopatológicos de autoinmunidad e inmunodeficiencia, con rasgos variables de respuesta inmunitaria. Estos rasgos pueden generalizarse en tres grandes subgrupos: Tipo I: defecto específico de la respuesta inmunitaria: Tipo II: inmunodefíciencia que desencadena respuestas autoinmunitarias; Tipo III: respuestas mixtas, autoinmunidad concomitante con un defecto de la respuesta inmunitaria con citotoxicidad aumentada. De la comprensión de estos mecanismos de respuesta surge una explicación racional en relación con los diversos cambios inmunológicos que cursan los pacientes con esclerosis múltiple y, considerando estas hipótesis de tipo de respuesta es factible orientar la terapéutica para el logro de una mayor eficacia de la misma