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.

Mediation Analysis of Waist Circumference in the Association of Gut Microbiota with Insulin Resistance in Children.

BACKGROUND: Persistent gut microbiota (GM) imbalance has been associated with metabolic disease development. This study evaluated the mediating role of waist circumference in the association between GM and insulin resistance (IR) in children. METHODS: This cross-sectional study included 533 children aged between 6 and 12. The anthropometry, metabolic markers, and relative abundance (RA) of five intestinal bacterial species were measured. Path coefficients were estimated using path analysis to assess direct, indirect (mediated by waist circumference), and total effects on the association between GM and IR. RESULTS: The results indicated a positive association mediated by waist circumference between the medium and high RA of S. aureus with homeostatic model assessments for insulin resistance (HOMA-IR) and for insulin resistance adiponectin-corrected (HOMA-AD). We found a negative association mediated by waist circumference between the low and medium RA of A. muciniphila and HOMA-IR and HOMA-AD. Finally, when we evaluated the joint effect of S. aureus, L. casei, and A. muciniphila, we found a waist circumference-mediated negative association with HOMA-IR and HOMA-AD. CONCLUSIONS: Waist circumference is a crucial mediator in the association between S. aureus and A. muciniphila RA and changes in HOMA-IR and HOMA-AD scores in children.

Frecuencia de sintomatología depresiva y tratamiento en adultos mayores con acceso a servicios de salud / Frequency of depressive symptoms and treatment in older adults with access to health services / Frequência de sintomas depressivos e tratamento em idosos com acesso a serviços de saúde / Fréquence de la symptomatologie dépressive et de son traitement chez les personnes âgées ayant accès aux services de santé

Resumen Objetivo: Determinar la frecuencia de sintomatología depresiva y su tratamiento en personas adultas mayores, afiliadas a las instituciones de seguridad social de salud en México. Material y métodos: Estudio descriptivo transversal con 3,114 participantes de 7 estados del país, los cuales fueron evaluados psicológicamente, empleando la Escala de Depresión Geriátrica (GDS) de Yesavage, también se analizó su afiliación a seguridad social, funcionalidad (índices Barthel y Lawton) y estado cognoscitivo (Minimental de Folstein). El análisis de la información se realizó empleando el paquete estadístico SPSS (Statistical Package for the Social Sciences), así como los datos sociodemográficos de los participantes. Resultados: Se observó cobertura en el 88.5% de la población. La prevalencia de depresión es del 27.4% y el 96.8% de ellos no recibe tratamiento, además el 18.9% presenta dependencia funcional, el 16.2% deterioro cognoscitivo y el 7.4% ha sufrido al menos una caída con lesiones. Únicamente el 11.2% del total de enfermos fue diagnosticado en su clínica. Conclusión: La prevalencia de depresión no tratada en adultos mayores con acceso a servicios de salud es altamente significativa, es urgente la generación de protocolos, programas y capacitación de profesionales de salud que permitan identificar la patología y atender de manera integral a dicho grupo etario.

Abstract Objective: to determine the frequency of depressive symptoms and their treatment in older adults affiliated to the social health security institutions in Mexico. Material and methods: a descriptive cross-sectional study with 3,114 participants from 7 states of the country who were psychologically evaluated using the Geriatric Depression Scale (GDS) by Yesavage, also analyzed their affiliation to social security, functionality (Barthel and Lawton index) and cognitive status (Minimental State Examination of Folstein). The analysis of the information was carried out using the statistical package SPSS (Statistical Package for the Social Sciences) as well as the sociodemographic data of the participants. Results: Coverage was observed in 88.5% of the population. Prevalence of depression was 27.4% and 96.8% of them did not receive treatment. In addition 18.9% had functional dependence, 16.2% had cognitive impairment and 7.4% had suffered at least one fall with injuries. Only 11.2% of all participants were diagnosed in their clinic. Conclusion: The prevalence of untreated depression in older adults with access to health services is highly significant. It is urgent the generation of protocols, programs and training of health professionals that allow to identify the pathology and provide comprehensive care for that age group.

Sumário Objetivo: determinar a frequência dos sintomas depressivos e seu tratamento em idosos afiliados às instituições de saúde previdenciária do México. Material e métodos: estudo descritivo transversal com 3.114 participantes de 7 estados do país, avaliados psicologicamente pela Escala de Depressão Geriátrica Yesavage {GDS}, analisando também sua afiliação à seguridade social, funcionalidade (índices de Barthel e Lawton) e estado cognitivo. (Minimental de Folstein). A análise das informações foi realizada no programa estatístico SPSS (Statistical Package for the Social Sciences), além dos dados sociodemográficos dos participantes. Resultados: A cobertura foi observada em 88,5% da população. A prevalência de depressão é de 27,4% e 96,8% deles não recebem tratamento; além disso, 18,9% possuem dependência funcional, 16,2% comprometimento cognitivo e 7,4% sofreram pelo menos uma queda com lesões. Apenas 11,2% de todos os pacientes foram diagnosticados em sua clínica. Conclusão: A prevalência de depressão não tratada em idosos com acesso a serviços de saúde é altamente significativa, é urgente a geração de protocolos, programas e treinamento de profissionais de saúde para identificar a patologia e prestar assistência integral a essa faixa etária.

Résumé Objectif: Déterminer la fréquence de la symptomatologie dépressive et de son traitement chez les personnes âgées affiliées aux institutions de santé de la sécurité sociale au Mexique. Matériel et méthodes: Étude descriptive transversale avec 3 114 participants de 7 états du pays, évalués psychologiquement avec l'échelle de dépression gériatrique de Yesavage (GDS). Leur affiliation à la sécurité sociale, leur fonctionnalité (indices de Barthel et Lawton) et leur état cognitif (Folstein Minimal) ont également été évalués. L'analyse de ces informations, ainsi que des données sociodémographiques des participants, a été réalisée à l'aide du logiciel statistique SPSS (Statistical Package for the Social Sciences). Résultats: La couverture sociale a été observée chez 88,5 % de la population. La prévalence de la dépression est de 27,4% et 96,8% d'entre eux ne reçoivent pas de traitement. De plus, 18,9% présentent une dépendance fonctionnelle, 16,2% une déficience cognitive et 7,4% ont fait au moins une chute avec blessures. Seulement 11,2 % du nombre total des participants ayant une dépression ont été diagnostiqués dans leur clinique. Conclusion: La prévalence de la dépression non traitée chez les personnes âgées ayant accès aux services de santé est très importante. Il est urgent de générer des protocoles, des programmes et des formations pour les professionnels de santé qui permettent d'identifier la pathologie et de fournir une attention globale pour cette tranche d'âge.

Vitamin D receptor gene polymorphisms are associated with multiple sclerosis in Mexican adults.

BACKGROUND: Multiple sclerosis (MS) is the most prevalent autoimmune inflammatory demyelinating disease of the central nervous system (CNS) in young adults. More than 50 genomic regions have been associated with MS susceptibility. Due the important immune-modulating properties of Vitamin D, Vitamin D receptor (VDR) gene polymorphisms - which interfere with the actions of Vitamin D- could be related to increased risk of MS. METHODS: We studied 120 patients fulfilling the McDonald criteria for MS (81 females and 39 males) and 180 healthy unrelated controls, nested in a case-Control study, and were recruited from the National Institute of Neurology and Neurosurgery, Manuel Velasco Suárez in Mexico City. Genotyping of VDR gene polymorphisms BsmI (rs1544410) and TaqI (rs731236) was performed using TaqMan SNP Genotyping Assay which consists of a predesigned mix of unlabeled polymerase chain reaction (PCR) primers and the TaqMan minor groove binding group (MGB) probe (FAM dye-labeled). RESULTS: There was a statistically significant, positive association between MS and the T/T genotype of BsmI polymorphism (OR=4.15; 95%CI 1.83-9.39), showing also a significant positive trend across genotypes (p<0.01). This association was also present evaluating the recessive inheritance model of the polymorphism (OR=3.91; 95%CI 1.77-8.64). When evaluating the association by alleles, the statistically significant positive association seen by genotypes was confirmed in the T allele carriers, showing an OR of 1.83 (95%CI 1.27-2.65) for MS. CONCLUSIONS: We found a positive association of the genetic VDR polymorphisms TaqI (rs731236) and BsmI (rs1544410), with the risk of MS in a sample of Mexican adults.

Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells.

BACKGROUND: Expression of the microRNA miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA or oncomir. Due to the critical functions of its target proteins in various signaling pathways, miR-21 is an attractive target for genetic and pharmacological modulation in various cancers. Cervical cancer is the second most common cause of death from cancer in women worldwide and persistent HPV infection is the main etiologic agent. This malignancy merits special attention for the development of new treatment strategies. In the present study we analyze the role of miR-21 in cervical cancer cells. METHODS: To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression in a cervical intraepithelial neoplasia-derived cell lines using siRNAs. The effect of miR-21 on gene expression was assessed in cervical cancer cells transfected with the siRNA expression plasmid pSIMIR21. We identified the tumor suppressor gene PTEN as a target of miR-21 and determined the mechanism of its regulation throughout reporter construct plasmids. Using this model, we analyzed the expression of miR-21 and PTEN as well as functional effects such as autophagy and apoptosis induction. RESULTS: In SiHa cells, there was an inverse correlation between miR-21 expression and PTEN mRNA level as well as PTEN protein expression in cervical cancer cells. Transfection with the pSIMIR21 plasmid increased luciferase reporter activity in construct plasmids containing the PTEN-3'-UTR microRNA response elements MRE21-1 and MRE21-2. The role of miR-21 in cell proliferation was also analyzed in SiHa and HeLa cells transfected with the pSIMIR21 plasmid, and tumor cells exhibited markedly reduced cell proliferation along with autophagy and apoptosis induction. CONCLUSIONS: We conclude that miR-21 post-transcriptionally down-regulates the expression of PTEN to promote cell proliferation and cervical cancer cell survival. Therefore, it may be a potential therapeutic target in gene therapy for cervical cancer.

Utility of microRNAs and siRNAs in cervical carcinogenesis.

MicroRNAs and siRNAs belong to a family of small noncoding RNAs which bind through partial sequence complementarity to 3'-UTR regions of mRNA from target genes, resulting in the regulation of gene expression. MicroRNAs have become an attractive target for genetic and pharmacological modulation due to the critical function of their target proteins in several signaling pathways, and their expression profiles have been found to be altered in various cancers. A promising technology platform for selective silencing of cell and/or viral gene expression using siRNAs is currently in development. Cervical cancer is the most common cancer in women in the developing world and sexually transmitted infection with HPV is the cause of this malignancy. Therefore, a cascade of abnormal events is induced during cervical carcinogenesis, including the induction of genomic instability, reprogramming of cellular metabolic pathways, deregulation of cell proliferation, inhibition of apoptotic mechanisms, disruption of cell cycle control mechanisms, and alteration of gene expression. Thus, in the present review article, we highlight new research on microRNA expression profiles which may be utilized as biomarkers for cervical cancer. Furthermore, we discuss selective silencing of HPV E6 and E7 with siRNAs which represents a potential gene therapy strategy against cervical cancer.

[RNA interference: biogenesis molecular mechanisms and its applications in cervical cancer]. / RNA de interferencia: biogénesis, mecanismos moleculares y sus aplicaciones en cáncer cervical.

RNAi (RNA interference) is a natural process by which eukaryotic cells silence gene expression through small interference RNAs (siRNA) which are complementary to messenger RNA (mRNA). In this process, the siRNA that are 21-25 nucleotides long and are known as microRNA (miRNA), either associate with the RNA-induced silencing complex (RISC), which targets and cleaves the complementary mRNAs by the endonucleolytic pathway, or repress the translation. It is also possible to silence exogenous gene expression during viral infections by using DNA templates to transcribe siRNA with properties that are identical to those of bioactive microRNA. Persistent human papillomavirus (HPV) infection is the main etiological agent during cervical cancer development and the HPV E6 and E7 oncogenes, which induce cellular transformation and immortalization, represent strategic targets to be silenced with siRNA. In several in vitro and in vivo studies, it has been demonstrated that the introduction of siRNA directed against the E6 and E7 oncogenes in human tumoral cervical cells transformed by HPV, leads to the efficient silencing of HPV E6 and E7 oncogene expression, which induces the accumulation of the products of the p53 and pRb tumor suppressor genes and activates the mechanism of programmed cell death by apoptosis; thus, the progression of the tumoral growth process may be prevented. The goal of this review is to analyze the microRNA biogenesis process in the silencing of gene expression and to discuss the different protocols for the use of siRNA as a potential gene therapy strategy for the treatment of cervical cancer.

Terapia génica con citocinas contra cáncer cervicouterino / Gene therapy with cytokines against cervical cancer

La terapia génica es una excelente alternativa para el tratamiento de muchas enfermedades. La capacidad para manipular el DNA ha permitido dirigir la terapia génica para corregir la función de un gen alterado, aumentar la expresión de un gen o activar la respuesta inmune. Así, se puede proponer el uso del DNA como un medicamento capaz de controlar, corregir o curar una enfermedad. La terapia génica contra cáncer tiene un potencial enorme, y en la última década se han obtenido resultados muy alentadores del uso del DNA para controlar diversas neoplasias en modelos animales, lo cual ha permitido su aplicación en protocolos experimentales en humanos. Esta revisión concentra una reseña de los fundamentos de la terapia génica y su aplicación en cáncer cervical, desde el punto de vista de las alteraciones de la respuesta inmune enfocadas al microambiente tumoral y el uso de las citocinas como moduladores de la respuesta inmune.

[Gene therapy with cytokines against cervical cancer]. / Terapia génica con citocinas contra cáncer cervicouterino.

Gene therapy is an excellent alternative for treatment of many diseases. Capacity to manipulate the DNA has allowed direct the gene therapy to correct the function of an altered gene, to increase the expression of a gene and to favour the activation of the immune response. This way, it can intend the use of the DNA like medication able to control, to correct or to cure many diseases. Gene therapy against cancer has an enormous potential, and actually the use of the DNA has increased to control diverse cancer in animal models, with very encouraging results that have allowed its applications in experimental protocols in human. This work concentrates a review of the foundations of the gene therapy and its application on cervical cancer, from the point of view of the alterations of the immune system focused on the tumour micro-environment, and the use of the cytokines as immunomodulators.