Molecular changes in adipocyte-derived stem cells during their interplay with cervical cancer cells.

PURPOSE: Obesity is as an important risk factor and has been associated with a worse prognosis in at least 13 distinct tumor types. This is partially due to intercellular communication between tumor cells and adipose tissue-derived stem cells (ADSCs), which are increased in obese individuals. As yet, however, little is known about the molecular changes occurring in ADSCs in these conditions. Cervical cancer has a high incidence and mortality rate in women from developing countries, particularly in those with a high body mass index (BMI). METHODS: We analyzed the expression profile of ADSCs co-cultured with cervical cancer cells through massive RNA sequencing followed by evaluation of various functional alterations resulting from the modified transcriptome. RESULTS: A total of 761 coding and non-coding dysregulated RNAs were identified in ADSCs after co-culture with HeLa cells (validation in CaSki and SiHA cells). Subsequent network analysis showed that these changes were correlated with migration, stemness, DNA repair and cytokine production. Functional experiments revealed a larger ALDHhigh subpopulation and a higher migrative capacity of ADSCs after co-culture with HeLa cells. Interestingly, CXCL3 and its intragenic long-noncoding RNA, lnc-CXCL3, were found to be co-regulated during co-culture. A loss-of-function assay revealed that lnc-CXCL3 acts as a key regulator of CXCL3 expression. CONCLUSIONS: Our results suggest that intercellular communication between ADSCs and cervical cancer cells modifies the RNA expression profile in the former, including that of lncRNAs, which in turn can regulate the expression of diverse chemokines that favor malignancy-associated capacities such as migration.

Adipose-derived mesenchymal stem cells promote the malignant phenotype of cervical cancer.

Epidemiological studies indicate that obesity negatively affects the progression and treatment of cervical-uterine cancer. Recent evidence shows that a subpopulation of adipose-derived stem cells can alter cancer properties. In the present project, we described for the first time the impact of adipose-derived stem cells over the malignant behavior of cervical cancer cells. The transcriptome of cancer cells cultured in the presence of stem cells was analyzed using RNA-seq. Changes in gene expression were validated using digital-PCR. Bioinformatics tools were used to identify the main transduction pathways disrupted in cancer cells due to the presence of stem cells. In vitro and in vivo assays were conducted to validate cellular and molecular processes altered in cervical cancer cells owing to stem cells. Our results show that the expression of 95 RNAs was altered in cancer cells as a result of adipose-derived stem cells. Experimental assays indicate that stem cells provoke an increment in migration, invasion, angiogenesis, and tumorigenesis of cancer cells; however, no alterations were found in proliferation. Bioinformatics and experimental analyses demonstrated that the NF-kappa B signaling pathway is enriched in cancer cells due to the influence of adipose-derived stem cells. Interestingly, the tumor cells shift their epithelial to a mesenchymal morphology, which was reflected by the increased expression of specific mesenchymal markers. In addition, stem cells also promote a stemness phenotype in the cervical cancer cells. In conclusion, our results suggest that adipose-derived stem cells induce cervical cancer cells to acquire malignant features where NF-kappa B plays a key role.

The Short-Term Effects of Roux-en-Y Gastric Bypass on Renal Excretion of Sodium and Its Association with Blood Pressure.

INTRODUCTION: Bariatric surgery has been shown to be effective in reducing weight and has benefits, such as lowering blood pressure. An increase in urinary sodium excretion has been suggested as a possible mechanism. This study explored changes in sodium excretion and their correlation with blood pressure after Roux-en-Y gastric bypass. MATERIALS AND METHODS: This study was conducted on 28 obese participants with body mass index (BMI) of 44.54 ± 7.81 kg/m2 who underwent gastric bypass. Before surgery and at the third and sixth months after gastric bypass, blood pressure, urinary sodium concentration, 24-hour (24-h) urinary sodium excretion, and fractional excretion of sodium were evaluated. In addition, serum sodium and potassium levels were determined. Nonparametric tests were used to analyze the data. RESULTS: Blood pressure decreased after surgery and remained at low levels over the 3- and 6-month periods. The urinary sodium concentration increased at 3 months after surgery; however, the 24-h urinary sodium excretion and urine volume decreased. Interestingly, although some associations between variables were observed, significant correlations between the 24-h urinary sodium excretion and the systolic, diastolic, and mean blood pressures were found. In addition, the urine volume was higher in the sixth month than in the third month following surgery. CONCLUSIONS: In the months immediately following surgery, a low-salt and low-volume diet favors decreases in urine volume and 24-h urinary sodium excretion. In addition, in the sixth month after surgery, an association between blood pressure and 24-h urinary sodium excretion was observed.

Expression of the growth hormone receptor isoforms and its correlation with the metabolic profile in morbidly obese subjects.

BACKGROUND AND AIM OF THE STUDY: Given the lipolytic effect of GH and its potential role in determining adipose tissue distribution, we evaluated the expression of the GH hormone receptor (GHR) isoforms in patients with morbid obesity seeking associations with metabolic parameters. METHODS: 262 morbidly obese subjects (mean age 42.5 ± 11 years, 75% women) underwent PCR-genotyping of the exon 3 GHR polymorphism. In 17 of these subjects, who proved to be heterozygous for the exon 3 genotype (+3/-3), subcutaneous and visceral adipose tissue was obtained during bariatric surgery; total RNA was extracted, reversely transcribed, and the different isoforms of the GHR (exon 3 containing and lacking flGHR as well as the trGHR) were PCR-amplified using specific primers. RESULTS: 27% were +3/+3 homozygous, 20% -3/-3 homozygous and 53% were +3/-3 heterozygous. Compared to subjects homozygous for the +3 genotype, homozygous and heterozygous carriers of the -3 genotype were significantly heavier and tended to have a higher HOMA 2-IR. Expression of the flGHR and trGHR mRNA was demonstrated in all evaluated samples of subcutaneous and visceral adipose tissue from the 17 patients. The exon 3+ isoform was expressed in all adipose tissue samples, whereas only six subjects expressed the 3- isoform as well. The only distinctive feature of these six patients was a higher HbA1c. CONCLUSIONS: The heterozygous GHR +3/-3 genotype is more prevalent in subjects with morbid obesity. Patients expressing the exon +3 and exon -3 isoforms in adipose tissue had a higher HbA1c, than those expressing only the exon -3 isoform.

[Clinical and biochemical characteristics of patients with morbid obesity at the time of hospital admission and one year after undergoing bariatric surgery]. / Características clínicas y bioquímicas de pacientes con obesidad extrema al ingreso y un año después de someterse a cirugía bariátrica.

BACKGROUND: Three percent of Mexicans suffer from morbid obesity. Comorbidities associated to this condition diminish quality of life, increase mortality and health care costs. Despite bariatric surgery has specific indications and risks, it is the only treatment with effective long-term results. The aim of the study was to evaluate biochemical and clinical patient characteristics, both preoperatively and a year after they underwent bariatric surgery. METHODS: We carried out a quasi-experimental study that evaluates a sample of patients in the Clínica de Obesidad at Hospital de Especialidades (a third level hospital) between March 2011 and October 2015. RESULTS: A total of 150 patients were analyzed (60 % were women). Mean age was 41 ± 9 years and mean body mass index (BMI) was 48 kg/m2 (42-53 kg/m2). Before surgery, type 2 diabetes mellitus (T2DM) was present in 31 %, hypertension in 60 % and 30 % of the patients were "metabolically healthy obese". A year after surgery, the percentage of excess body weight loss was 66 %, T2DM and hypertension remission was 70 % and 50 %, respectively. CONCLUSION: Bariatric surgery is an effective treatment to reduce excess weight. It improves biochemical, and clinical parameters in extreme obese patients.

Introducción: el 3 % de la población mexicana padece obesidad extrema. Sus comorbilidades disminuyen la calidad de vida, aumentan la mortalidad y los costos de atención médica. El único tratamiento con resultados a largo plazo es la cirugía bariátrica, aunque tiene indicaciones y riesgos específicos. Buscamos evaluar las características de los pacientes de cirugía bariátrica al inicio y un año después del tratamiento quirúrgico. Métodos: estudio cuasi experimental con los datos antropométricos, clínicos y bioquímicos de una muestra de pacientes operados en la Clínica de Obesidad del Hospital de Especialidades del Centro Médico Nacional de marzo del 2011 a octubre del 2015. Resultados: fueron analizados 150 pacientes (60 % mujeres), la media de edad fue de 41 ± 9 años y el índice de masa corporal (IMC) de 48 kg/m2 (42-53 kg/m2). Previo a la cirugía, 31 % tenía diabetes mellitus tipo 2 (DM2) y 62 % hipertensión arterial (HAS). El 30 % eran obesos "metabólicamente sanos". Un año después de la cirugía el porcentaje del exceso de peso perdido fue de 66 %. La remisión de DM2 y HAS fue de 70 y 50 %, respectivamente. Conclusión: la cirugía bariátrica es efectiva en la pérdida de peso y en la mejoría de parámetros bioquímicos y clínicos en pacientes con obesidad extrema.

Implementación del plan de cuidados de enfermería al paciente con cirugía bariátrica / Implementation of the nursing care plan for patients who underwent bariatric surgery

Resumen:

Introducción: la obesidad constituye una enfermedad sistémica, crónica y multicausal. En ella se involucran la susceptibilidad genética, estilos de vida y del entorno, con influencia de diversos determinantes subyacentes, como la globalización, la cultura, la condición económica, la educación, la urbanización y el entorno político y social. La atención integral de las enfermedades crónicas no transmisibles (ECNT), como la obesidad, requiere de intervenciones de alto impacto que puedan aplicarse con un enfoque de atención primaria que refuerce la detección precoz y el tratamiento oportuno. Entre las estrategias sectoriales que coadyuvan en la atención integral de la obesidad mórbida en México destaca la difusión e implementación de a) programas estratégicos para la atención del paciente con obesidad mórbida, b) guías de práctica clínica sobre el tratamiento de la obesidad mórbida y c) planes de cuidados de enfermería (PLACE) del paciente con obesidad.

Desarrollo: se describen las fases relacionadas con el proceso de diseño e implementación del PLACE al paciente con obesidad mórbida, sometido a cirugía bariátrica en una unidad médica de tercer nivel de atención del Instituto Mexicano del Seguro Social (IMSS), específicamente: a) diseño y revisión del plan de cuidados, b) difusión y capacitación del personal de enfermería sobre obesidad y el PLACE, c) utilización y d) seguimiento. Para esta implementación se involucraron intervenciones sobre los profesionales e intervenciones organizativas.

Conclusiones: las diferentes acciones que se propongan para la difusión, capacitación, implantación y seguimiento de los PLACE deben ser abordadas desde una perspectiva metodológica para garantizar resultados favorables.

Abstract:

Introduction: Obesity is a systemic, chronic and multicausal disease, which is related to genetic susceptibility, lifestyle and environment, and influenced by various underlying determinants, such as globalization, culture, economic status, education, urbanization, and the political and social environment. Comprehensive treatment of chronic non-communicable diseases (NCDs), like obesity, requires high impact interventions that can be applied by a primary care approach to strengthen early detection and timely treatment. Among the sectoral strategies that assist in the comprehensive care of morbid obesity in México, it stands out the dissemination and implementation of: a) strategic programs for the care of patients with morbid obesity, b) clinical practice guidelines on the treatment of morbid obesity, and c) nursing care plans (PLACE, in Spanish) for the obese patient.

Development: This document describes the stages related to the design and implementation of the PLACE for morbidly obese patients who underwent bariatric surgery in a tertiary care medical unit of the Instituto Mexicano del Seguro Social (IMSS), specifically: a) the design and review of the plan of care b) its dissemination and the training of nurses regarding obesity and the PLACE, c) use, and d) monitoring. For this implementation, we included interventions in regards to professionals and to organizations. Conclusions: The different actions proposed for training, dissemination, implementation, and monitoring of nursing care plans should be approached from a methodological perspective to ensure a favorable outcome.

[The current state of obesity in Mexico]. / Escenario actual de la obesidad en México.

Excess weight (overweight and obesity) is currently recognized as one of the most important challenges of public health in the world, given its size, speed of growth, and the negative effect on the population who suffers it. Overweight and obesity increases significantly the risk of chronic non-communicable diseases, and premature mortality, as well as the social cost of health. Today, Mexico has the second global prevalence of obesity in the adult population (30 %), which is ten times higher than Korea's or Japan's (4 %). Until 2012, 26 million Mexican adults were overweight, and 22 million, obese. This implies a major challenge for the health sector. Mexico needs to plan and implement strategies and cost-effective actions for the prevention and control of obesity in children, adolescents, and adults. Global experience shows that proper care of obesity and overweight demands to formulate and coordinate efficient multi-sectoral strategies for enhancing protective factors to health, particularly to modify individual behavior, family and community.

El exceso de peso corporal (sobrepeso y obesidad) es reconocido actualmente como uno de los retos más importantes de salud pública en el mundo, dada su magnitud, la rapidez de su incremento y el efecto negativo que ejerce sobre la salud de la población que lo padece. El sobrepeso y la obesidad incrementan significativamente el riesgo de padecer enfermedades crónicas no transmisibles y la mortalidad prematura, ademásdel costo social de la salud. Actualmente, México ocupa el segundo lugar de prevalencia mundial de obesidad en la población adulta (30 %), que es diez veces mayor que la de Japón o Corea (4 %). Hasta el año 2012, 26 millones de adultos mexicanos tenían sobrepeso y 22 millones, obesidad, lo que representa un reto muy importante para el sector salud.México debe planear e implementar estrategias y líneas de acción costo-efectivas, dirigidas a la prevención y el control de la obesidad del niño, el adolescente y el adulto. La experiencia global indica que la atención correcta de la obesidad y el sobrepeso requiere que se formulen y coordinen estrategias multisectoriales eficientes que permitan potenciar los factores de protección hacia la salud, particularmente para modificar el comportamiento individual, familiar y comunitario.