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.

Bovine Interferon-Tau Activates Type I interferon-Associated Janus-signal Transducer in HPV16-positive Tumor Cell.

The mechanisms of signal transduction by interferon-tau (IFN-τ) are widely known during the gestation of ruminants. In trophoblast cells, IFN-τ involves the activation of the JAK-STAT pathway, and it can have effects on other cell types, such as tumor cells. Here we report that the HPV16-positive BMK-16/myc cell treated with ovine IFN-τ, results in the activation of the canonical JAK-STAT and non-canonical JAK-STAT pathway. The MAPK signaling pathway was activated, we detected the proteins MEK1, MEK2, Raf1, STAT3, STA4, STAT5 and STAT6. Moreover, IFN-τ induced the expression of MHC Class I, MX and IP10 in the tumor cells and this response may be associated with the viral replication and with the anti-proliferative and the immunoregulatory effects of IFN-τ.

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.

Contribution of MSMB promoter region gene polymorphism to early-onset prostate cancer risk in Mexican males.

Sexually transmitted infections and its contribution to prostate cancer (PC) development have been relevant in different populations. MSMB gene polymorphism (rs10993994) has exhibited an association both with PC as well as the susceptibility to sexually transmitted infections. Hitherto, these conditions have been not studied in Mexico yet, neither if sexually transmitted infections could modify the MSMB and PC association. Herein, socio-demographic features, sexually transmitted infections records, the reproductive backgrounds, and the genetic characterisation were analysed in 322 incident PC cases and 628 population healthy controls from Mexico City. Whole PC, early-onset PC (PC at < 60 years old), late-onset PC (≥ 60 years old), and PC aggressiveness were used to evaluate the genetic variants contribution to PC risk using unconditional logistic regression models. Overall, none associations between the allelic variants of rs10993994 polymorphisms with whole and PC aggressiveness were found. Howbeit, the TT genotype carriers presented the highest susceptibility to develop early-onset PC (OR = 2.66; 95% CI = 1.41, 5.04; p = 0.03) than CC+CT carriers, both with codominant and recessive models. Although none association between whole PC and MSMB gene polymorphism was found, our results were reinforced by prior studies in European descendent populations, suggesting a contribution between rs10993994 and early-onset PC development.

Estudio de validación de cuatro diferentes criterios para el diagnóstico de síndrome metabólico en población infantil / Validation study of four different criteria for the diagnosis of metabolic syndrome in children

Resumen Introducción: El síndrome metabólico (SM) es un problema de salud pública, el cual no cuenta con estrategias adecuadas de prevención, diagnóstico y tratamiento para población infantil. Los criterios existentes son controversiales y no son aplicables en los niños. Asimismo, varían según autores y comités de expertos; lo que podría tener importantes consecuencias en el diagnóstico de SM, impactando el tratamiento oportuno y el pronóstico del individuo. Objetivo: Validar criterios (NCEP-ATPIII; Cook, Ford y Duncan, et al; Ferranti, et al; Cruz, et al; e IDF1) para el diagnóstico de SM en niños mexicanos. Metodología: Estudio transversal de 2599 niños entre 6 y 16 años, residentes de la Ciudad de México. Se consideró SM con tres o más de los cinco componentes en los distintos criterios; y dos o más componentes con la presencia de obesidad central para IDF. Se consideró como Gold Standard la combinación de los cinco criterios diagnósticos. Para identificar el mejor valor predictivo se calculó sensibilidad, especificidad, valor predictivo positivo (VPP), valor predictivo negativo (VPN) y razón de verosimilitud. Resultados: Se observó una mayor proporción de individuos diagnosticados con SM con el criterio de Ferranti, et al. en comparación con los demás criterios evaluados. Nuestra propuesta ad hoc presentó una alta sensibilidad (0,89) y especificidad (0,90) frente al Gold Standard aplicado. Conclusión: El criterio propuesto por nosotros contiene una elección de componentes sencillos y de bajo costo, que facilitará su aplicación, permitiendo la unificación en el diagnóstico, tratamiento y pronóstico poblacional, reduciendo los índices de morbimortalidad en mexicanos.

Abstract Introduction: Metabolic syndrome (MS) is a public health problem without appropriate strategies for prevention, diagnosis and treatment in children. Existing criteria are controversial and not applicable for pediatric population, with variations according to different authors and expert committees, which could have important consequences in MS diagnosis, treatment and prognosis. Objective: To validate different definitions (NCEP-ATPIII; Cook, Ford and Duncan, et al; Ferranti, et al; Cruz, et al; and IDF1) for metabolic syndrome diagnosis in Mexican children. Methodology: Cross-sectional study of 2599 children aged between 6 and 16 years, residents of Mexico City. MS was defined as the presence of three or more of the five components in the different criteria; and two or more components with the presence of central obesity for IDF. The Gold Standard was considered as the combination of the five diagnostic criteria. To identify the best predictive value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratio were calculated. Results: A greater proportion of individuals diagnosed with the Ferranti, et al criterion was observed in comparison with the other criteria evaluated. We proposed an ad hoc criteria which showed a high sensitivity (0,89) and specificity (0,90) compared to the Gold Standard applied. Conclusion: Our diagnostic criteria contains a choice of simple and low-cost components that will facilitate its application in health institutions and will unify-diagnostic criteria, treatment, and prognosis, reducing morbidity and mortality rates in Mexican population.

High relative abundance of firmicutes and increased TNF-α levels correlate with obesity in children.

OBJECTIVE: To investigate the correlation among pro- or anti-inflammatory cytokines and the two main gut microbiota phyla in obese children. MATERIALS AND METHODS: Anthropometric data were obtained from 890 children under 14 years old to determine the degree of obesity. Serum cytokine concentration was measured by ELISA. Relative abundance of gut microbiota in feces was evaluated by quantitative RealTime PCR assays. RESULTS: Anthropometric and biochemical parameters were statistically higher in overweigth/ obese children (OW/O) than in lean (NW), Increased TNF-α levels were found in obese children that also have a high relative abundance of Firmicutes. CONCLUSIONS: Obese children have a high relative abundance of Firmicutes that correlates with increased levels of TNF-α. This is the first study that shows a relation between Firmicute abundance and TNF-α serum concentration in obese children.

High relative abundance of firmicutes and increased TNF-α levels correlate with obesity in children / Obesidad infantil y su correlación con la alta abundancia relativa de firmicutes y el aumento de los niveles de TNF-α

Abstract: Objective: To investigate the correlation among pro- or anti-inflammatory cytokines and the two main gut microbiota phyla in obese children. Materials and methods: Anthropometric data were obtained from 890 children under 14 years old to determine the degree of obesity. Serum cytokine concentration was measured by ELISA. Relative abundance of gut microbiota in feces was evaluated by quantitative Real-Time PCR assays. Results: Anthropometric and biochemical parameters were statistically higher in overweight /obese children than in lean ones. Increased TNF-α levels were found in obese children that also have a high relative abundance of Firmicutes. Conclusions: Obese children have a high relative abundance of Firmicutes that correlates with increased levels of TNF-α. This is the first study that shows a relation between Firmicute abundance and TNF-α serum concentration in obese children.

Resumen: Objetivo: Investigar la correlación entre las citocinas proinflamatorias o antiinflamatorias y los dos principales filos de la microbiota intestinal en niños obesos. Material y métodos: Se obtuvieron mediciones antropométricas de 890 niños de 6 a 14 años; posteriormente se clasificaron en normopeso y sobrepeso/obeso. Las concentraciones séricas fueron medidas por el método de ELISA. La abundancia relativa de la microbiota intestinal en heces se evaluó por PCR tiempo real. Resultados: Los parámetros bioquímicos y antropométricos fueron estadísticamente más altos en niños con sobrepeso / obesidad que en niños delgados. Se encontraron niveles más altos de FNT-α en niños obesos que también tenían una abundancia relativa alta de Firmicutes. Conclusiones: Los niños obesos tienen una alta abundancia relativa de Firmicutes, la cual se correlaciona con un incremento de los niveles de FNT-α. Este es el primer estudio que evalúa la reacción entre la abundancia de Firmicutes y la concentración sérica de FNT-α en niños obesos.

Dietary patterns in Mexican children and adolescents: Characterization and relation with socioeconomic and home environment factors.

BACKGROUND: Eating habits in children and adolescents are influenced by multiple determinants, which include socioeconomic and home environmental factors. OBJECTIVE: To characterize the dietary patterns in Mexican children and adolescents and to assess its association with socioeconomic and home environmental factors. METHODS: A cross-sectional study was conducted in 878 children and adolescents aged 5-15 years, unrelated, selected randomly from Morelos Sports Unit at north of Mexico City. Dietary, anthropometric, family, and socioeconomic information was obtained from each participant. Dietary patterns were identified through cluster analysis. The association between dietary patterns with socioeconomic and home environmental factors was assessed by a multivariate multinomial logistic regression model. RESULTS: Three major dietary patterns were identified: diverse dietary pattern (D), high fat dietary pattern (HF), and high sugar dietary pattern (HS). 87% of the participants followed the HF or HS dietary patterns (36% & 51%, respectively). Mother's occupation and the child's screen time was associated with a significant likelihood of following a HF and HS dietary patterns. CONCLUSION: A high percentage of children and adolescents reported following a HS or HF dietary pattern, which in turn were associated with socioeconomic and home environmental factors. These results suggests priority groups for prevention and control actions.

TLR9 gene polymorphism -1486T/C (rs187084) is associated with uterine cervical neoplasm in Mexican female population.

PURPOSE: The aim of this work was to evaluate the association of single nucleotide polymorphisms in TLR9 (-1486 T/C [rs187084], -1237T/C [rs5743836] and G2848A [rs352140]) with HPV infection, squamous intraepithelial lesions, and uterine cervical neoplasm in a Mexican population. Additionally, the peripheral expression of TLR9 was evaluated to evaluate the differences in the TLR9 expression associated with every genotype in the locus -1486 of the TLR9 gene. The serum concentration of TLR9 was evaluated in a randomly selected subsample. METHODS: Genotyping was performed using predesigned 5' endonuc lease assays and the association of the polymorphisms with the diagnosis groups were assessed by performing multinomial regression models. The relative expression of TLR9 in peripheral blood mononuclear cells was evaluated by real-time polymerase chain reaction and the association of the level of TLR9 expression with the diagnosis was evaluated by performing multinomial regression models. The serum concentration of TLR9 was evaluated in a subsample of patients diagnosed with uterine cervical neoplasm by ELISA. RESULTS: The results showed that genotype TT in the -1486 locus of TLR9 was significantly associated with HPV infection (OR = 3.25, 95% CI 1.12-9.46), squamous intraepithelial cervical lesion (OR = 3.76, 95% CI 1.36-10.41), and uterine cervical neoplasm (OR = 5.30, 95% CI 1.81-15.55). Moreover, the highest level of TLR9 expression was significantly associated with a greater risk for developing squamous intraepithelial cervical lesion and uterine cervical neoplasm. The serum TLR9 concentration was higher in patients with uterine cervical cancer than in controls. CONCLUSION: Our findings indicate that genotype TT in the -1486 locus of the TLR9 gene could comprise a risk genotype for HPV infection, squamous intraepithelial cervical lesion, and uterine cervical neoplasm in Mexican female population. Further studies with larger samples are needed to evaluate if the peripheral expression of TLR9 could be used as a biomarker of uterine cervical neoplasm progression.

[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.

Role of TLR9 in Oncogenic Virus-Produced Cancer.

Nucleic acid recognition by toll-like receptor 9 (TLR9) initiates signaling pathways that regulate the production of proinflammatory cytokines or type I interferons, as well as many other molecules required to initialize the immune response. The use of synthetic oligodeoxynucleotides (ODNs) has been crucial to emulate the recognition of DNA sequences by TLR9. Furthermore, ODN administration to mice has shown to confer protection against a wide range of viral, bacterial, and parasitic pathogens. In contrast, oncogenic DNA viruses like hepatitis B virus, Epstein-Barr virus, and human papilloma virus inhibit TLR9 expression, thus contributing to the establishment of chronic viral infections. In this review, we will focus on TLR9 signals initiated by ODN recognition, on the inhibition of TLR9 expression mediated by DNA oncogenic viruses, and on TLR9 expression as a relevant event in the progression to cancer, considering other functions of this receptor, aside from viral recognition.

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.

Genetic markers of inflammation may not contribute to metabolic traits in Mexican children.

BACKGROUND: Low-grade chronic inflammation is a common feature of obesity and its cardio-metabolic complications. However, little is known about a possible causal role of inflammation in metabolic disorders. Mexico is among the countries with the highest obesity rates in the world and the admixed Mexican population is a relevant sample due to high levels of genetic diversity. METHODS: Here, we studied 1,462 Mexican children recruited from Mexico City. Six genetic variants in five inflammation-related genes were genotyped: rs1137101 (leptin receptor (LEPR)), rs7305618 (hepatocyte nuclear factor 1 alpha (HNF1A)), rs1800629 (tumor necrosis factor alpha (TNFA)), rs1800896, rs1800871 (interleukin-10 (IL-10)), rs1862513 (resistin (RETN)). Ten continuous and eight binary traits were assessed. Linear and logistic regression models were used adjusting for age, sex, and recruitment centre. RESULTS: We found that one SNP displayed a nominal evidence of association with a continuous trait: rs1800871 (IL-10) with LDL (beta = -0.068 ± 1.006, P = 0.01). Subsequently, we found one nominal association with a binary trait: rs7305618 (HNF1A) with family history of hypertension (odds-ratio = 1.389 [1.054-1.829], P = 0.02). However, no P-value passed the Bonferroni correction for multiple testing. DISCUSSION: Our data in a Mexican children population are consistent with previous reports in European adults in failing to demonstrate an association between inflammation-associated single nucleotide polymorphisms (SNPs) and metabolic traits.

Androgen receptor CAG polymorphism and sporadic and early-onset prostate cancer among Mexican men.

A short CAG repeat length in the gene encoding for the androgen receptor (AR) has been associated with prostate cancer (PC) risk and aggressiveness. In Latino men, information on this association is scarce. Hence, the aim of this study was to evaluate this association in Mexican males. Using fragment analysis by capillary electrophoresis, we determined the number of CAG repeats-(CAG)n-in AR gene from 158 incident PC cases and 326 age-matched healthy controls (±5 years), residing in Mexico City, Mexico. According to Gleason scale and age at diagnosis, cases were classified as high (⩾7) and low grade (<7), as well as early onset (<60 years) or late onset PC (⩾60 years). At diagnosis, 78% of cases were classified as high-grade and 26.6% as early onset. Men with sporadic (no family history of PC) and early-onset PC presented shorter CAG repeat length than controls (18.6±2.2 vs 19.5±2.5; P=0.02). Lower number of CAG repeats (CAG)⩽19 were associated with a greater risk for early-onset PC (odds ratio: 2.31; 95% confidence interval: 1.14-4.69). CAG repeat length could increase the risk for sporadic and early-onset PC. The best cutoff point for identifying at-risk subjects was (CAG)19. However, further studies are necessary to replicate our findings in subjects with a family history of PC and also to evaluate the association between CAG repeats length and disease progression.

Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study.

Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-ß1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a ß-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When ß-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-ß1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.