RESUMEN

Resveratrol (RES), a polyphenol compound with anti­proliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated the means by which RES enhances the anti­proliferative effects of cisplatin (CIS) on MCF­7 cells, focusing on the inhibitory effects on DNA repair of double­strand breaks (DSBs). Chemoresistant MCF­7 cells (MCF­7R) were generated by continuous exposure to low concentrations of CIS (10 µM CIS­IC40) during 5 passages, with the IC50 value increasing ~3­fold. Using an MTT assay, we estimated the changes in IC50 for CIS in MCF­7, T47­D, MDA­MB­231 and MCF­7R cells in the presence of RES. The relative transcript level of Nbs­1, Mre­11 and Rad­50 genes was assessed using RT­qPCR analysis. Rad51 and H2AX [pSer139] protein expression was determined by western blot analysis. RES at 50 and 100 µM significantly enhanced the anti­proliferative effects of CIS in both MCF­7 and MCF­7R cells, decreasing the IC50 values for CIS to one­tenth and one­sixth, respectively. A total of 100 µM RES decreased the relative transcript levels of homologous recombination (HR) initiation complex components and the Rad51 protein level in MCF­7 and MCF­7R cells. After 48 h of CIS DNA damage, the levels of Rad51 protein increased, but this effect was inhibited by 100 µM RES. RES also maintained serine 139 phosphorylation of histone H2AX, suggesting that RES prevents the repair of DSBs. It was observed that RES exerts an antagonistic effect over CIS on the activation of Rad51 and sustained phosphorylation of H2AX. The results suggest that RES in combination with DNA damage­based therapy has potential as a strategy to overcome resistance and provide much safer and more effective treatment for breast cancer.

Asunto(s)

Neoplasias de la Mama/genética , Cisplatino/farmacología , Regulación hacia Abajo , Resistencia a Antineoplásicos/efectos de los fármacos , Recombinasa Rad51/genética , Estilbenos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Histonas/metabolismo , Humanos , Células MCF-7 , Fosforilación/efectos de los fármacos , Recombinasa Rad51/metabolismo , Resveratrol

RESUMEN

Resumen OBJETIVO: determinar, mediante reacción en cadena de la polimerasa (PCR), si C. albicans y C. glabrata son causantes de las recurrencias de candidiasis vulvovaginal y si suelen colonizar la vagina de mujeres mexicanas asintomáticas en edad reproductiva. MATERIALES Y MÉTODOS: estudio analítico, transversal, prospectivo, experimental, de casos y controles, efectuado en mujeres de 18 a 45 años de edad, atendidas en el servicio de Ginecología del Centro Médico ABC de la Ciudad de México y el Cinvestav del Instituto Politécnico Nacional. Identificar C. albicans y C. glabrata en muestras vaginales por medio de reacción en cadena de la polimerasa con iniciadores específicos para cada especie. RESULTADOS: se estudiaron 93 pacientes: 46 casos y 47 controles. En los casos se encontraron: 2.17% con C. albicans, 80.4% con C. glabrata y 17.3% con coinfección por ambas especies. En los controles se encontraron: 61.7% con C. albicans, 4.2% con C. glabrata, 19.1% con coinfección por ambas especies y 14.8% con ausencia de Candida spp. CONCLUSIONES: el agente causal de la mayor parte de las candidiasis vulvovaginales recurrentes es C. glabrata. La colonización por esta especie y por C. albicans es común y no provoca síntoma alguno, por lo que para su identificación es importante utilizar métodos de diagnóstico como la reacción en cadena de la polimerasa.

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Abstract BACKGROUND: 75% of women are affected with vulvovaginal candidiasis and 10% of them will have at least 4 episodes during one year. The most common etiological agents are C. albicans and C. glabrata, which is usually the responsible of the recurrent cases when the patients have received inadequate treatment. Up to 55% of asymptomatic women can have different species of Candida spp. as vaginal commensals, but there are no recent studies that identify this yeast through molecular techniques in healthy women and with history of vulvovaginal candidiasis. OBJECTIVE: Determine using polymerase chain reaction if C. albicans and C. glabrata are responsible of recurrent vulvovaginal candidiasis and if they usually colonize Mexican asymptomatic women in reproductive age. MATERIAL AND METHODS: An analytical, transversal, prospective, experimental, case control study was carried out in women age 18 to 45 in the Gynecology Service of ABC Medical Centre of México City and IPN Cinvestav. C. albicans and C. glabrata were identified in vaginal samples using polymerase chain reaction with specific primers for each specie. RESULTS: A total of 93 patients were studied, 46 cases and 47 controls. 2.17% of the case patients were positive C. albicans, 80.43% for C. glabrata, and 17.39% for both species. 61.70% of the control patients were positive for C. albicans, 4.20% for C. glabrata, 19.14% for both species, and 14.89% were negative for Candida. CONCLUSIONS: The main etiological agent of recurrent vulvovaginal candidiasis is C. glabrata. The vaginal colonization of this specie and C. albicans is common and causes no symptoms, thus, it is important to use diagnostic tools such as polymerase chain reaction to identify them. It is relevant to investigate the factors that help this yeast to cause a symptomatic infection and stop being just a vaginal commensal.

RESUMEN

Obesity and overweight are health problems of multifactorial etiology, which may include changes in the microbiome. In Mexico, more than 30 % of the child population between 5 and 11 years of age suffer from being overweight or are obese, which makes it a public health issue in progress. The purpose of this work was to measure the short-chain fatty acid concentration by high-performance liquid chromatography (HPLC), and to characterize the bacterial diversity by ion torrent semiconductor sequencing, of 16S rDNA libraries prepared from stools collected from a sample of well-characterized Mexican children for normal weight, overweight, and obese conditions by anthropometric and biochemical criteria. We found that triglyceride levels are increased in overweight and obese children, who presented altered propionic and butyric acid concentrations in feces. In addition, although the colon microbiota did not show a clear bacterial dysbiosis among the three conditions, the abundance of some particular bacteria was changed with respect to normal controls. We conclude from our results that the imbalance in the abundance of at least nine different bacteria as well as altered short-chain fatty acid concentration in feces is associated to the overweight and obese conditions of Mexican children.

Asunto(s)

Bacterias/metabolismo , Biodiversidad , Ácidos Grasos/biosíntesis , Microbiota , Obesidad/etiología , Sobrepeso/etiología , Bacterias/clasificación , Bacterias/genética , Estudios de Casos y Controles , Niño , Heces/química , Heces/microbiología , Femenino , Humanos , Metabolismo de los Lípidos , Masculino , México , Obesidad/metabolismo , Sobrepeso/metabolismo , Fenotipo

RESUMEN

AIMS/HYPOTHESIS: We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. METHODS: We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. RESULTS: In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10(-5)) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10(-8)) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. CONCLUSIONS/INTERPRETATION: We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.

Asunto(s)

Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo/métodos , Adulto , Anciano , Femenino , Genotipo , Hispánicos o Latinos/genética , Humanos , Masculino , Americanos Mexicanos/genética , México , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Texas , Adulto Joven

RESUMEN

BACKGROUND: Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City. METHODS: We analysed the association of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARgamma, FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS. The analysis included 519 subjects with T2D defined according to the ADA criteria, 389 with MS defined according to the AHA/NHLBI criteria and 547 controls. Association was tested with the program ADMIXMAP including individual ancestry, age, sex, education and in some cases body mass index (BMI), in a logistic regression model. RESULTS: The two markers located within the TCF7L2 gene showed strong associations with T2D (rs7903146, T allele, odd ratio (OR) = 1.76, p = 0.001 and rs12255372, T allele, OR = 1.78, p = 0.002), but did not show significant association with MS. The non-synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018). Nominally significant associations were also observed between T2D and the SIRT1 rs3758391 SNP and MS and the HHEX rs5015480 polymorphism. CONCLUSIONS: Variants located within the gene TCF7L2 are strongly associated with T2D but not with MS, providing support to previous evidence indicating that polymorphisms at the TCF7L2 gene increase T2D risk. In contrast, the non-synonymous ADRB3 rs4994 polymorphism is associated with T2D and MS.

Asunto(s)

Diabetes Mellitus Tipo 2/genética , Síndrome Metabólico/genética , Polimorfismo Genético , Adulto , Factores de Edad , Glucemia/metabolismo , Presión Sanguínea/genética , Índice de Masa Corporal , Peso Corporal/genética , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/etnología , Escolaridad , Femenino , Estudios de Asociación Genética , Humanos , Insulina/sangre , Resistencia a la Insulina/genética , Masculino , Síndrome Metabólico/etnología , México , Persona de Mediana Edad , Triglicéridos/sangre