Perceived psychosocial stress and glucose intolerance among pregnant Hispanic women

Aim—Prior literature suggests a positive association between psychosocial stress and the risk of diabetes in non-pregnant populations, but studies during pregnancy are sparse. We evaluated the relationship between stress and glucose intolerance among 1115 Hispanic (predominantly Puerto Rican) prenatal care patients in Proyecto Buena Salud, a prospective cohort study in Western Massachusetts (2006–2011). Methods—Cohen’s Perceived Stress Scale (PSS-14) was administered in early (mean = 12.3 weeks gestation; range 4.1–18 weeks) and mid-(mean = 21.3 weeks gestation; range 18.1–26 weeks) pregnancy. Participants were classified as having a pregnancy complicated by gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance, based on the degree of abnormality on glucose tolerance testing between 24 and 28 weeks of gestation. Results—The prevalence of gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance was 4.1%, 7.2%, and 14.5%, respectively. Absolute levels of early or mid-pregnancy stress were not significantly associated with glucose intolerance. However, participants with an increase in stress from early to mid-pregnancy had a 2.6-fold increased odds of gestational diabetes mellitus (95% confidence intervals: 1.0–6.9) as compared to those with no change or a decrease in stress after adjusting for age and pre-pregnancy body mass index. In addition, every one-point increase in stress scores was associated with a 5.5 mg/dL increase in screening glucose level (β = 5.5; standard deviation = 2.8; P = 0.05), after adjusting for the same variables. Conclusion—In this population of predominantly Puerto Rican women, stress patterns during pregnancy may influence the risk of glucose intolerance

Genome-Wide Maps of Circulating miRNA Biomarkers for Ulcerative Colitis

Inflammatory Bowel Disease – comprised of Crohn's Disease and Ulcerative Colitis (UC) - is a complex, multi-factorial inflammatory disorder of the gastrointestinal tract. In this study we have explored the utility of naturally occurring circulating miRNAs as potential blood-based biomarkers for non-invasive prediction of UC incidences. Whole genome maps of circulating miRNAs in micro-vesicles, Peripheral Blood Mononuclear Cells and platelets have been constructed from a cohort of 20 UC patients and 20 normal individuals. Through Significance Analysis of Microarrays, a signature of 31 differentially expressed platelet-derived miRNAs has been identified and biomarker performance estimated through a non-probabilistic binary linear classification using Support Vector Machines. Through this approach, classifier measurements reveal a predictive score of 92.8% accuracy, 96.2% specificity and 89.5% sensitivity in distinguishing UC patients from normal individuals. Additionally, the platelet-derived biomarker signature can be validated at 88% accuracy through qPCR assays, and a majority of the miRNAs in this panel can be demonstrated to sub-stratify into 4 highly correlated intensity based clusters. Analysis of predicted targets of these biomarkers reveal an enrichment of pathways associated with cytoskeleton assembly, transport, membrane permeability and regulation of transcription factors engaged in a variety of regulatory cascades that are consistent with a cell-mediated immune response model of intestinal inflammation. Interestingly, comparison of the miRNA biomarker panel and genetic loci implicated in IBD through genome-wide association studies identifies a physical linkage between hsa-miR-941 and a UC susceptibility loci located on Chr 20. Taken together, analysis of these expression maps outlines a promising catalog of novel platelet-derived miRNA biomarkers of clinical utility and provides insight into the potential biological function of these candidates in disease pathogenesis

miR-143 Overexpression Impairs Growth of Human Colon Carcinoma Xenografts in Mice with Induction of Apoptosis and Inhibition of Proliferation

BACKGROUND: MicroRNAs (miRNAs) are aberrantly expressed in human cancer and involved in the (dys)regulation of cell survival, proliferation, differentiation and death. Specifically, miRNA-143 (miR-143) is down-regulated in human colon cancer. In the present study, we evaluated the role of miR-143 overexpression on the growth of human colon carcinoma cells xenografted in nude mice (immunodeficient mouse strain: N: NIH(s) II-nu/nu). METHODOLOGY/PRINCIPAL FINDINGS: HCT116 cells with stable miR-143 overexpression (Over-143) and control (Empty) cells were subcutaneously injected into the flanks of nude mice, and tumor growth was evaluated over time. Tumors arose ∼ 14 days after tumor cell implantation, and the experiment was ended at 40 days after implantation. miR-143 was confirmed to be significantly overexpressed in Over-143 versus Empty xenografts, by TaqMan® Real-time PCR (p<0.05). Importantly, Over-143 xenografts displayed slower tumor growth compared to Empty xenografts from 23 until 40 days in vivo (p<0.05), with final volumes of 928±338 and 2512±387 mm(3), respectively. Evaluation of apoptotic proteins showed that Over-143 versus Empty xenografts displayed reduced Bcl-2 levels, and increased caspase-3 activation and PARP cleavage (p<0.05). In addition, the incidence of apoptotic tumor cells, assessed by TUNEL, was increased in Over-143 versus Empty xenografts (p<0.01). Finally, Over-143 versus Empty xenografts displayed significantly reduced NF-κB activation and ERK5 levels and activation (p<0.05), as well as reduced proliferative index, evaluated by Ki-67 immunohistochemistry (p<0.01). CONCLUSIONS: Our results suggest that reduced tumor volume in Over-143 versus Empty xenografts may result from increased apoptosis and decreased proliferation induced by miR-143. This reinforces the relevance of miR-143 in colon cancer, indicating an important role in the control of in vivo tumor progression, and suggesting that miR-143 may constitute a putative novel therapeutic tool for colon cancer treatment that warrants further investigation

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

peer reviewe

Physical activity patterns during pregnancy in a diverse population of women

Background: Participation in physical activity during pregnancy may reduce the risk of gestational diabetes mellitus and preeclampsia and help prevent excess maternal weight gain. However, studies describing patterns and correlates of activity during pregnancy are sparse. The purpose of this cross-sectional study was to describe total physical activity (household/caregiving, occupational, leisure, sports/exercise, and transportation) and correlates of total physical activity in a racially and economically diverse sample of 233 prenatal care patients. Methods: Bilingual interviewers administered three 24-hour physical activity recalls among women in the first trimester (11%), second trimester (36%), and third trimester (53%) of pregnancy. Results: Median total energy expenditure (MET-hours/day) was similar among women in the first and second trimesters (33.4 and 33.8 MET-hours/day, respectively) and was slightly, but not statistically significantly, lower among women in the third trimester (32.6 MET-hours/day). Moderate intensity activity followed a similar pattern, being statistically significantly lower among women in the third trimester; vigorous intensity activity was low among women in each trimester of pregnancy. In terms of activity type, household/ caregiving activity was the largest contributor to both total and combined moderate and vigorous intensity energy expenditure among women in each trimester, constituting 24%–40% of total energy expenditure. Overall, total energy expenditure was highest in white non-Hispanic women and positively associated with increasing education and a history of previous live births (p < 0.01). Conclusions: Results from this study highlight the importance of including household/caregiving and occupational activities in addition to sports/exercise activities in the assessment of total energy expenditure during pregnancy