Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes.

BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity. METHODS: The study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays. RESULTS: Analysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation. CONCLUSIONS: Our present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity

Generación de información geoespacial para la evaluación estacional del agua en la cuenca de la laguna de Cajititlán mediante el modelo InVEST: una iniciativa del Proyecto Charco Bendito para la preservación ambiental

Con el fin de preservar y gestionar los recursos hídricos de manera sostenible en la cuenca de la laguna de Cajititlán, México, estudiantes del Proyecto de Aplicación Profesional del Laboratorio de Datos del Instituto Tecnológico y de Estudios Superiores de Occidente (ITESO) colaboraron con el Proyecto Charco Bendito para llevar a cabo este proyecto. Se centró en generar y analizar información geoespacial utilizando el modelo de producción estacional del agua de InVEST, un software desarrollado por la organización Natural Capital Project de la Universidad de Stanford para evaluar y cuantificar los servicios ecosistémicos proporcionados por los recursos naturales, lo que permitió tomar decisiones informadas sobre su gestión y conservación. El objetivo principal fue establecer una línea base ambiental para medir la ganancia de agua y evaluar el éxito de futuros proyectos de conservación y gestión sostenible de los recursos hídricos en la cuenca de la laguna de Cajititlán. Para lograr esto, se obtuvo y generó la información necesaria para correr el modelo de InVEST, incluyendo capas de área de interés, uso de suelo, modelo digital de elevación, hidrología, tabla de datos biofísicos, precipitación y evapotranspiración. Además, se validó la calidad de la información y se configuró el modelo, ejecutándose para analizar los resultados obtenidos y determinar la línea base ambiental en la cuenca de la laguna de Cajititlán. El proyecto también se centró en estudiar la infiltración y el escurrimiento en la cuenca de la laguna de Cajititlán, procesos clave para la regulación del ciclo hidrológico y la preservación de los recursos hídricos. Se generaron guías detalladas de cada paso del proceso para la creación de cada una de las capas con la finalidad de poder replicar el modelo en futuros años y así poder medir el progreso y la ganancia o pérdida de agua en la cuenca. Con los resultados del modelo se pudo observar que los bosques de pino y los bosques mixtos de pino-encino generan menor escurrimiento, mientras que los cambios en el uso del suelo hacia la agricultura, la urbanización y los suelos desnudos, debido a incendios agrícolas o forestales, incrementan los volúmenes de escurrimiento. La investigación también destaca la importancia de la preservación del agua y la restauración de áreas naturales para la sostenibilidad y la responsabilidad social y ambiental. Es importante destacar que los datos utilizados en este proyecto corresponden al año 2018, ya que no se contaba con datos más actualizados de evapotranspiración y precipitación para realizar ambas capas. Sin embargo, se encontró que es posible emplear datos climatológicos históricos para estimar el rendimiento estacional del agua en ausencia de datos actualizados, y que la gestión del paisaje puede afectar el flujo estacional del agua. Asimismo, se propone la inclusión de un modelo financiero en futuros estudios, que permita medir las ganancias o pérdidas económicas asociadas a la conservación y gestión sostenible de los recursos hídricos en la cuenca de la laguna de Cajititlán. De esta manera, se podrá evaluar no solo el impacto ambiental, sino también el impacto económico de las acciones efectuadas en la región.ITESO, A.C

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Curcumin differentially affects cell cycle and cell death in acute and chronic myeloid leukemia cells

Curcumin is a phytochemical with potent anti-neoplastic properties. The antitumoral effects of curcumin in cells derived from chronic or acute myeloid leukemia have been already described. However, a comparative study of the cytostatic and cytotoxic effects of curcumin on chronic and acute myeloid leukemia cells has not yet been performed. In the present study, the cellular effects of curcumin on cell lines derived from chronic or acute myeloid leukemia were examined. Dose and time-response assays were performed with curcumin on HL-60 and K562 cells. Cell viability was evaluated with trypan blue exclusion test and cell death by flow cytometry using a fluorescent molecular probe. A cell cycle profile was analyzed, and protein markers of cell cycle progression and cell death were investigated. In the present study, the K562 cells showed a higher sensitivity to the cytostatic and cytotoxic effects of curcumin compared with HL-60. In addition, curcumin induced G1 phase arrest in HL-60 cells and G2/M phase arrest in K562 cells. Furthermore, curcumin-related cell death in HL-60 was associated with the processed forms of caspases-9 and -3 proteins, whereas in K562 cells, both the processed and the unprocessed forms were present. Accordingly, activity of these caspases was significantly higher in HL-60 cells compared with that in K562. In conclusion, curcumin elicits different cellular mechanisms in chronic or acute myeloid leukemia cells and the powerful antitumoral effect was more potent in K562 compared with HL-60 cells

A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe.

Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe. Mitotic cells displayed abnormal chromatin organization, collapse of the mitotic spindle and abnormal chromosome segregation. Then, these cells died in an apoptosis dependent manner and showed diminution in the protein levels of BCL-2 and XIAP. Moreover, our results shown that a transient activation of the nuclear factor κB (NFκB) occurred early in these cells, but decreased after 6 h of the treatment, explaining in part the diminution of the anti-apoptotic proteins. Additionally, P73 was translocated to the cell nuclei, because the expression of the C/EBPα, a cognate repressor of the P73 gene, was decreased, suggesting that apoptosis is trigger by elevation of P73 protein levels acting in concert with the diminution of the two anti-apoptotic molecules. In summary, curcumin treatment might produce a P73-dependent apoptotic cell death in chronic myelogenous leukemia cells (K562), which was triggered by mitotic catastrophe, due to sustained BAX and survivin expression and impairment of the anti-apoptotic proteins BCL-2 and XIAP

Gender-Dependent Association of FTO Polymorphisms with Body Mass Index in Mexicans.

To evaluate the associations between six single-nucleotide polymorphisms (SNPs) in intron 1 of FTO and body mass index (BMI), a case-control association study of 2314 unrelated Mexican-Mestizo adult subjects was performed. The association between each SNP and BMI was tested using logistic and linear regression adjusted for age, gender, and ancestry and assuming additive, recessive, and dominant effects of the minor allele. Association analysis after BMI stratification showed that all five FTO SNPs (rs1121980, rs17817449, rs3751812, rs9930506, and rs17817449), were significantly associated with obesity class II/III under an additive model (P<0.05). Interestingly, we also documented a genetic model-dependent influence of gender on the effect of FTO variants on increased BMI. Two SNPs were specifically associated in males under a dominant model, while the remainder were associated with females under additive and recessive models (P<0.05). The SNP rs9930506 showed the highest increased in obesity risk in females (odds ratio = 4.4). Linear regression using BMI as a continuous trait also revealed differential FTO SNP contributions. Homozygous individuals for the risk alleles of rs17817449, rs3751812, and rs9930506 were on average 2.18 kg/m(2) heavier than homozygous for the wild-type alleles; rs1121980 and rs8044769 showed significant but less-strong effects on BMI (1.54 kg/m(2) and 0.9 kg/m(2), respectively). Remarkably, rs9930506 also exhibited positive interactions with age and BMI in a gender-dependent manner. Women carrying the minor allele of this variant have a significant increase in BMI by year (0.42 kg/m(2), P = 1.17 x 10(-10)). Linear regression haplotype analysis under an additive model, confirmed that the TGTGC haplotype harboring all five minor alleles, increased the BMI of carriers by 2.36 kg/m(2) (P = 1.15 x 10(-5)). Our data suggest that FTO SNPs make differential contributions to obesity risk and support the hypothesis that gender differences in the mechanisms involving these variants may contribute to disease development

Curcumin induces DNA fragmentation and cell death in K562 cells.

<p><b>A)</b> A fraction of the arrested K562 cells treated with 20 μM of curcumin showed DNA damage as indicated by the presence of TUNEL-positive cells and FACS analysis. <b>B)</b> The percentage of TUNEL-positive cells is represented by graphic bars, and <b>C)</b> production of a typical apoptotic DNA ladder is shown. <b>D)</b> Cell death was confirmed by death assays; FACS analysis, and <b>E)</b> the results are also shown as graphic bars. As positive controls of DNA fragmentation, we used cells treated with 100 nM nocodazole for 24 h. As a positive control of cell death, K562 cells were exposed to UV (40 mJ/cm²) for 2 min in a cross-linker GS Gene linker-UV chamber (Bio-Rad, Hercules CA, USA) and were recovered 24 h post-irradiation.</p

Apoptosis is produced by activation of P73.

<p><b>A)</b> Impairment of the expression of the anti-apoptotic proteins BCL-2 and XIAP is shown. <b>B</b>) The decreased expression of the anti-apoptotic proteins was caspase independent, as shown by the use of Z-VAD-FMK pancaspase inhibitor. Samples were treated with 2 pulses of 40 μM of pan-caspase inhibitor, Z-VAD-FMK (R&D, Systems), to 12 and 15 h of curcumin treatment. K562 cells were harvested after 18 h, lysed and total protein extracts were obtained for western blot analysis, using specific antibodies against of Caspase-3, PARP, BCL-2 and XIAP. <b>C</b>) The diminution of the expression of the antiapoptotic proteins was consistent with decreases in the IκBα and <b>D</b>) activation and nuclear translocation of the P73 protein, as consequence of the <b>E)</b> diminished expression of the P73 promoter repressor protein C/EBPα; M = medium, D = DMSO.</p