Decoding signal transducer and activator of transcription 1 across various cancers through data mining and integrative analysis.

OBJECTIVES: Using different online available databases and Bioinformatics tools, we extensively studied the role STAT1 across different cancers. METHODS: STAT1 mRNA, protein expression, and promoter methylation were analyzed and validated using UALCAN, GENT2, Human Protein Atlas (HPA), and MEXPRESS. Furthermore, the potential prognostic values were evaluated through KM plotter. Then, cBioPortal was utilized to examine the STAT1-related genetic mutations, while pathway enrichment analysis was performed using DAVID. To identify STAT1 targeted microRNAs (miRNAs) and transcription factors (TFs) we used Enricher. Moreover, a correlational analysis between STAT1 expression tumor purity and CD8+ T immune cells and a gene-drug interaction network analysis was performed using TIMER, CTD, and Cytoscape. RESULTS: In 23 major human cancers, STAT1 expression was notably up-regulated relative to corresponding controls. As well, the elevated expression of STAT1 was exclusively found to be associated with the reduced overall survival (OS) of Esophageal Carcinoma (ESCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung adenocarcinoma (LUAD) patients. This implies that STAT1 plays a significant role in the development and progression of these three cancers. Further pathway analysis indicated that STAT1 enriched genes were involved in six critical pathways, while a few interesting correlations were also documented between STAT1 expression and promoter methylation level, tumor purity, CD8+ T immune cells infiltration, and genetic alteration. In addition, we have also predicted a few miRNAs, TFs, and chemotherapeutic drugs that could regulate the STAT1 expression. CONCLUSION: The current study revealed the shared oncogenic, diagnostic, and prognostic role of STAT1 in ESCA, KIRC, and LUAD.

Effects of applying amoxicillin in juvenile mice on enamel mineralization and the expression of kallikrein­related peptidase 4 and tight junction proteins in ameloblasts.

Amoxicillin is a common pediatric drug. However, to the best of our knowledge, the role of amoxicillin in enamel hypomineralization has not yet been fully elucidated. The aim of the present study was to assess the effects of amoxicillin on enamel mineralization, the morphology of ameloblasts, as well as the expression of kallikrein­related peptidase 4 (KLK4), and the tight junction proteins, claudin 1 (CLDN1), claudin 4 (CLDN4) and occludin (OCLN), in ameloblasts of juvenile mice. A total of 36 3­day­old Kunming mice were randomly divided into three groups. The mice were administered 0, 50 or 100 mg/kg amoxicillin by intragastric administration for 19 days. The surface morphology and calcium (Ca), phosphorous (P) and carbon contents of mandibular incisors and first molars were examined by scanning electron microscopy and energy dispersive X­ray spectroscopy. Histological changes in the ameloblasts of mandibular incisors were analyzed by hematoxylin and eosin staining. The KLK4, CLDN1, CLDN4 and OCLN expression levels of ameloblasts were observed by immunohistochemical staining. The incidence of white patches in the incisor was 100% in the 100 mg/kg amoxicillin­treated groups. A greater number of enamel defects were observed in the incisal/occlusal half of mandibular incisors/molars compared with in the cervical half in the amoxicillin­treated groups. Following phosphoric­acid treatment, the enamel rod and interrod were aligned in a disorderly manner in the amoxicillin­treated groups. Amoxicillin decreased the Ca/P ratio in the enamel of mandibular incisors and molars. More intercellular spaces among maturation ameloblasts were observed in the amoxicillin­treated groups. Amoxicillin decreased KLK4 and CLDN1, CLDN4 and OCLN expression in mature ameloblasts. The administration of amoxicillin in juvenile mice induced enamel hypomineralization, and the effects of amoxicillin on enamel hypomineralization may be mediated via multiple pathways.

The ethnoepidemiology of obesity.

The prevalence of overweight and obesity varies significantly across ethnic groups and among aboriginal people in Canada and appears to be increasing overall in children and youth, which will have significant health consequences in the future. Individual health behaviours, genetic predisposition, and community-level factors all contribute to the high burden of overweight and obesity across communities in Canada. Preliminary studies indicate that individuals who live in neighbourhoods in Canada with increased walkability, fewer fast food outlets, and higher socioeconomic status have lower rates of overweight/obesity when compared with other neighbourhoods. However, more research is required to understand the impact of community level factors on overweight/obesity trends in Canadian ethnic groups, including children and youth, and aboriginal people.

Cardiovascular risk among South Asians living in Canada: a systematic review and meta-analysis.

BACKGROUND: South Asians represent about 3% of the Canadian population and have a higher burden of certain cardiovascular risk factors and cardiovascular disease (CVD) compared with white people. The objective of this study was to review the literature to compare cardiovascular risk factors and disease management practices among adult South Asian and white Canadians. METHODS: We searched MEDLINE, Embase, Cochrane and Cumulative Index to Nursing and Allied Health Literature databases from their inception through Feb. 17, 2014 and the reference lists of the selected articles. English-language studies of interventions and observational studies of biological mechanisms underlying CVD risk in South Asians conducted in Canada were eligible for inclusion. Where appropriate, we used random-effects meta-analyses to integrate results comparing the CVD risk profiles of South Asian and white Canadians. RESULTS: We included 50 articles (n = 5 805 313 individuals) in this review. Compared with white Canadians, South Asian Canadians had a higher prevalence and incidence of CVD, an increased prevalence of diabetes (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.81 to 2.80, p < 0.001) and hypertension (OR 1.11, 95% CI 1.02 to 1.22, p = 0.02), lower high-density lipoprotein cholesterol levels (mean difference -0.19 mmol/L, 95% CI -0.25 to -0.13 mmol/L, p < 0.001) and a higher percentage of body fat (men: absolute mean difference 3.23%, 95% CI 0.83% to 5.62%, p = 0.008; women: absolute mean difference 4.09%, 95% CI 3.46% to 4.72%, p < 0.001). South Asian people are also more sedentary, consume higher levels of carbohydrates and are less likely to smoke tobacco (OR 0.38, 95% CI 0.24 to 0.60, p < 0.001]) than white Canadians. No differences in access to diagnostic tests, outcomes following cardiovascular surgery or use of cardiac rehabilitation programs were apparent. INTERPRETATION: Compared with white people, South Asian people living in Canada have a higher prevalence and incidence of CVD and possess a unique cardiovascular risk profile.