lncRNA­miRNA­mRNA network in female offspring born from obese dams.

Maternal obesity is associated with disturbance of lipid metabolism and obesity in offspring; however, the pathogenesis is still unclear. The present study elucidated the role of potential lipid metabolism-associated long non-coding RNA (lncRNA) and identified the pathways involved in mice born to obese dams. In the present study, maternal obesity was induced by feeding a high-fat diet for 10 weeks in female C57/BL6 mice, whereas control mice were fed a standard diet. All female mice mated with healthy male mice and were allowed to deliver spontaneously. The results demonstrated that female offspring from obese dams presented a tendency to become overweight in the first 8 weeks after birth; however, maternal obesity did not significantly alter the body weight of male offspring. RNA-sequencing analysis was performed on female offspring liver at 3 weeks old. Significantly dysregulated lncRNAs and downstream targets in female offspring liver were identified using bioinformatics analysis. lncRNA, microRNA (miRNA or miR) and mRNA expression levels in liver and AML12 cells were assessed using reverse transcription-quantitative PCR. A total of 8 upregulated and 17 downregulated lncRNAs were demonstrated in offspring from obese dams and lncRNA Lockd was indicated to be a key dysregulated lncRNA. Competing endogenous RNA (ceRNA) models suggested that the lncRNA Lockd/miR-582-5p/Elovl5 pathway was key for lipid metabolism in the liver of offspring from obese dams. Finally, small interfering RNA and miRNA inhibitor transfection was used to evaluate the ceRNA models in AML12 cells. Taken together, the results of the present study indicated that lncRNA Lockd-miR-582-5p-Elovl5 network may be disrupted in lipid metabolism and lead to obesity in the offspring of obese dams. This research will provide new insights into the molecular mechanism of obesity and lipid metabolism disorder.

FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. METHODS: qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. RESULTS: LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-ß. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83-123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612-727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel-Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells. CONCLUSIONS: In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.

Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology.

Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.

Association of Adverse Childhood Experiences with Health Risk Behaviors Among College Students in Zambia.

BACKGROUND: Adverse childhood experiences (ACEs) have been linked to long-term health outcomes, while the impact of such experience has not been investigated among Zambian youth. This study examined the associations of ACEs with individual and clusters of health risk behavior among college students in Zambia. METHOD: A total of 624 college students participated in this cross-sectional study. A self-administered questionnaire was used to collect information on their ACEs and health risk behaviors. RESULTS: There were 58.3% (364) reporting some forms of ACEs, with 27.6% (172), 16.3% (102), and 14.4% (90) being exposed to 1, 2, and ≥ 3 ACEs, respectively. The prevalence of health risk behaviors ranged from 6.0 to 34.2%. Overall, ACEs were associated with increased risk of smoking, binge drinking, suicide attempt, risky sexual behaviors, and illicit drug use. Logistic regression suggested that participants with ≥ 3 ACEs (OR, 3.62; 95% CI, 2.14-6.13) were more likely to engage in the unhealthy cluster, characterized by the presence of any health risk behavior, than those without ACE. CONCLUSION: ACEs were associated with individual and clustering of health risk behaviors among Zambia college students. Our study suggests that early intervention is needed to prevent long-term adverse health consequences in this population.

Improving the Metabolic and Mental Health of Children with Obesity: A School-Based Nutrition Education and Physical Activity Intervention in Wuhan, China.

This study aimed to evaluate the effectiveness of a school-based nutrition education and physical activity intervention on cardiovascular risk profile and mental health outcomes among Chinese children with obesity. Two primary schools were randomly allocated to the control group (CG) and the intervention group (IG). We selected children with obesity from 1340 students in the third and fourth grades as participants. The IG received 8 months of nutrition education and physical activity intervention, while the CG was waitlisted. A generalized estimating equation model was applied to assess repeated variables over time. A total of 171 children with obesity (99 IG and 72 CG) aged 9.8 ± 0.7 years completed the post-intervention stage. Compared with baseline, significant reductions were observed within the IG for depression and fasting plasma glucose at post-intervention. After adjusting for confounders, group and time interaction effects showed that the IG achieved improvements in the risk of poor well-being (p = 0.051) and social anxiety (p = 0.029), had decreased diastolic blood pressure (p = 0.020) and fasting plasma glucose (p < 0.001), and had significantly increased high-density lipoprotein (p < 0.001) from baseline to post-intervention relative to the CG. The effects of school-based nutrition education and physical activity intervention on children with obesity are diverse, including not only the improvement of metabolic health but also mental health promotion.

Identification of key transcription factors in endometrial cancer by systems bioinformatics analysis.

Endometrial cancer (EC) is one of the most common malignant diseases worldwide. Although many studies have been performed on EC, a systems analysis between transcription factors (TFs) and EC relationship remains poorly characterized. Here, we present a systems bioinformatics analysis of TFs in EC patient samples to identify key TFs in EC. First, dysregulated and survival-related TFs were identified in EC using data from The Cancer Genome Atlas database and Gene Expression Omnibus. Second, we investigated the mechanisms of dysregulated TFs and tested whether their expression is correlated with prognosis of EC. Finally, we addressed new perspectives in EC biomarker research, including comprehensive knowledge of previously suggested candidate biomarkers in conjunction with novel mass spectrometry-based proteomic technologies with enhanced sensitivity and specificity not yet applied to EC studies, enabling a directed clinical perspective of the study design. Our study identified three promising TFs, E2F1, HMGA1, and PGR, which closely correlate with EC. Although treatments targeting TFs are not always efficient, these TFs may be useful as biomarkers for the diagnosis and prognosis of EC. Furthermore, we found that these dysregulated TFs and their target genes are primarily involved in the cell cycle and may promote endometrial carcinoma occurrence and development. Using integrated bioinformatic analysis, we identified candidate genes and pathways in EC, which could improve our understanding of the etiology and underlying molecular events of EC. Furthermore, these candidate genes and pathways could be therapeutic targets for EC.

Cigarette smoking as a risk factor for type 2 diabetes in women compared with men: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Few studies have investigated the effect of smoking on type 2 diabetes in women compared with men, even though several epidemiological studies provided a clear picture of the risk among the entire population. METHODS: We systematically searched PubMed and Embase up to August 2017 for prospective studies that were stratified by sex with measures of the relative risk (RR) for type 2 diabetes and current smoking compared with non-smoking. The sex-specific RRs and their ratios (RRRs), comparing women with man, were pooled using random-effects models. RESULTS: Seventeen articles were identified including 20 prospective cohorts with 5 077 289 participants and 223 084 incident cases of type 2 diabetes. The pooled RRR suggested a similar risk of type 2 diabetes associated with smoking in women compared with men (RRR: 0.98, 95% confidence interval [CI]: 0.96-1.01). Furthermore, no significant sex difference in the RR was found between former smokers and those who had never smoked (RRR: 0.98, 95% CI: 0.92-1.04). CONCLUSIONS: The findings of this meta-analysis indicate that female smokers had similar risk of type 2 diabetes with male smokers.

Associations of physical activity and fruit and vegetable intake with well-being and depressive symptoms among obese schoolchildren in Wuhan, China: a cross-sectional study.

BACKGROUND: The prevalence of childhood obesity is increasing and psychological disorder is a common comorbidity of obesity. We investigated the associations of physical activity (PA) and fruit and vegetable (FV) intake with well-being and depressive symptoms among obese schoolchildren. METHODS: Participants included 188 obese children aged 9.8 ± 0.7 years living in Wuhan, China. Self-administered questionnaires were used to collect the children's PA and FV intake information. PA was considered to be high if the child participated in sport and/or vigorous free play at least 3 days per week with 60 min per day, while sufficient FV intake was defined as consuming FV 5 times per day. Children's well-being and depressive symptoms were assessed by standard questionnaires. Multiple logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of the relationships of PA and FV intake with well-being and depressive symptoms. RESULTS: High PA and sufficient FV intake were independently associated with significantly decreased risks for depressive symptoms (for PA, OR: 0.39, 95% CI: 0.16-0.92; for FV, OR: 0.21, 95% CI: 0.08-0.55) and poor well-being (for PA, OR: 0.35, 95% CI: 0.16-0.74), respectively. Furthermore, interactive inverse associations were observed between combined high PA and sufficient FV intake with poor well-being and depressive symptoms. Compared to their counterparts, children with high PA and sufficient FV intake had significantly reduced risk for poor well-being (OR: 0.16, 95%CI: 0.05-0.55) and depressive symptoms (OR: 0.12, 95% CI: 0.03-0.48). CONCLUSIONS: High PA and sufficient FV intake are inversely associated with the risks of poor well-being and depressive symptoms among obese Chinese schoolchildren.

Association between fruit and vegetable intake and the risk of hypertension among Chinese adults: a longitudinal study.

PURPOSE: Fruit and vegetable intake has been inversely associated with the risk of hypertension; however, there is inconsistent evidence on the long-term association. Given this gap in the literature, it is necessary to identify evidence from large prospective studies, especially in China, where insufficient evidence exists. Thus, we examined the association of fruit and vegetable intake with incident hypertension in Chinese adults. METHODS: We conducted analyses among 5659 Chinese adults aged 18-64 years, free of cardiovascular disease, cancer, and hypertension in the 2006 wave of the China Health and Nutrition Survey. Fruit and vegetable intake was assessed using consecutive 24-h recalls. Incident hypertension was identified from the 2011 wave of the survey. RESULTS: A total of 866 participants developed incident hypertension. The relative risks (RRs) and 95% confidence intervals (CIs) of hypertension were 0.74 (0.55-0.99), 0.65 (0.48-0.88), 0.68 (0.50-0.92), and 0.73 (0.53-0.99) comparing each quintile group of fruit and vegetable intake with the lowest quintile group. These associations attenuated for the change of intake but remained significant for the fourth quintile, of which the RR (95% CI) was 0.65 (0.47-0.89). The magnitude of association was stronger among those who were younger, female, overweight and had prehypertension. When examined separately, fruit intake was more strongly and significantly associated with lowering BP than vegetable intake. Adding body mass index to the models attenuated all associations. CONCLUSIONS: Greater long-term intake and increased intake of fruit and vegetables may reduce the risk of developing hypertension in Chinese adults.

Combined effects of fruit and vegetables intake and physical activity on the risk of metabolic syndrome among Chinese adults.

BACKGROUND: Unbalanced dietary intake and insufficient physical activity (PA) have been recognized as risk factors for metabolic syndrome (MetS). We aimed to examine the independent and combined effects of fruit and vegetables (FV) intake and PA on MetS. METHODS AND FINDINGS: A cross-sectional survey was conducted among residents of China in 2009, with fasting blood samples collected. Participants were divided into sufficient/insufficient FV intake and adequate/ inadequate PA groups according to self-reported questionnaires. MetS was defined using the NCEP-ATPIII criteria. The difference of individual MetS components was compared across different PA or FV groups. Multivariable logistic regression was used to assess association between FV/PA and the risk of MetS. A total of 7424 adults were included in the current study. MetS was prevalent in 28.7% of participants, with 24.7% and 32.9% in male and female, respectively. Compared with those with inadequate PA and insufficient FV intake, participants with the combination of adequate PA and sufficient FV intake had the lowest risk of MetS (OR = 0.69,95%CI: 0.59-0.82), following by the group with adequate PA time but insufficient FV intake (OR = 0.74, 95%CI:0.65-0.83). CONCLUSION: Findings of the current study show that the combination of sufficient FV intake and adequate PA was significantly associated with reduced MetS risk among adult residents of China.

MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC. AIMS: To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. MATERIALS & METHODS: In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue-specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase. RESULTS: A variety of tissue-specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA-derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC. CONCLUSION: MiRNAs have emerged as non-coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC.

miR-134: A Human Cancer Suppressor?

MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations.

Social Smoking and Mental Health Among Chinese Male College Students.

PURPOSE: China has a high prevalence of smoking, but the characteristics of social smoking in Chinese college students have not been investigated. We examined the pattern of social smoking and explored the association between social smoking and personal cessation efforts and mental health factors among Chinese male college students. DESIGN: Study design was a cross-sectional survey. SETTING: P. R. China was the setting of the study. SUBJECTS: Participants were a random sample of 1327 male college students. MEASURES: All participants completed a self-administered questionnaire that examined their smoking behaviors and a group of specific mental health factors (loneliness, self-harm, suicide, depression, and anxiety). ANALYSIS: Analysis was conducted using descriptive statistics, χ2 analysis, and multivariate logistic regression. RESULTS: Of a total of 207 current smokers, 102 (49.3%) were identified as social smokers. Compared with nonsmokers, social smokers had increased risks for depression (odds ratio, 1.74; 95% confidence interval, 1.15-2.65). Among daily smokers, social smokers were less likely to have an intention to quit smoking than nonsocial smokers (odds ratio, .08; 95% confidence interval, .01-.57). CONCLUSION: This study reveals unique psychologic characteristics related to social smoking. College students are a particular group of interest because unhealthy behaviors initiated during adolescence may continue through adulthood. Our findings provide evidence for future tobacco control intervention among this population.

Associations between multiple health risk behaviors and mental health among Chinese college students.

Although there is substantial evidence that health risk behaviors increase risks of premature morbidity and mortality, little is known about the multiple health risk behaviors in Chinese college students. Here, we investigated the prevalence of multiple health risk behaviors and its relation to mental health among Chinese college students. A cross-sectional study was conducted in Wuhan, China from May to June 2012. The students reported their health risk behaviors using self-administered questionnaires. Depression and anxiety were assessed using the self-rating depression scale and self-rating anxiety scale, respectively. A total of 2422 college students (1433 males) aged 19.7 ± 1.2 years were participated in the study. The prevalence of physical inactivity, sleep disturbance, poor dietary behavior, Internet addiction disorder (IAD), frequent alcohol use and current smoking was 62.0, 42.6, 29.8, 22.3, 11.6 and 9.3%, respectively. Significantly increased risks for depression and anxiety were found among students with frequent alcohol use, sleep disturbance, poor dietary behavior and IAD. Two-step cluster analysis identified two different clusters. Participants in the cluster with more unhealthy behaviors showed significantly increased risk for depression (odds ratio (OR): 2.21; 95% confidence interval (CI): 1.83, 2.67) and anxiety (OR: 2.32; 95% CI: 1.85, 2.92). This study indicates that a relatively high prevalence of multiple health risk behaviors was found among Chinese college students. Furthermore, the clustering of health risk behaviors was significantly associated with increased risks for depression and anxiety.

Passive smoking and risk of type 2 diabetes: a meta-analysis of prospective cohort studies.

BACKGROUNDS/OBJECTIVE: The prevalence of diabetes is increasing rapidly all over the world. However, studies on passive smoking and type 2 diabetes have not been systematically assessed. Therefore, we conducted a meta-analysis to explore whether an association exists between passive smoking and risk of type 2 diabetes. METHODS: We searched PubMed, EMBASE, Cochrane library and Web of Science up to April 9(th), 2013, to identify prospective cohort studies that assessed passive smoking and risk of type 2 diabetes. The fixed-effect model was used to calculate the overall relative risk (RR). RESULT: 4 prospective cohort studies were included for analysis, with a total of 112,351 participants involved. The pooled RR was 1.28 (95% confidence interval (CI) 1.14 to 1.44) comparing those who were exposed to passive smoking with those who were not. Subgroup, sensitivity analysis and publication bias test suggested the overall result of this analysis was robust. CONCLUSIONS: Passive smoking is associated with a significantly increased risk of type 2 diabetes. Further well-designed studies are warranted to confirm this association.

Chronic effects of ambient air pollution on lung function among Chinese children.

OBJECTIVES: To examine the association between long-term exposure to air pollution and lung function among Chinese schoolchildren in Southern China (Hong Kong). METHODS: We conducted a cross-sectional study among 3168 schoolchildren (aged 8-10 years) in 3 districts in Hong Kong. Annual means of ambient PM10 (particulate matter <10 µm), SO2, NO2 and O3 from 1996 to 2003 were used to estimate the individual exposure of the subjects. Children's lung function was measured for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow between 25% and 75% of FVC (FEF(25-75)) and forced expiratory flow at 75% of FVC (FEF75). Analysis of covariance was performed separately by gender to estimate the impact of air pollution on lung function, with adjustment for socioeconomic characteristics, respiratory morbidities, height and weight, physical activity level, indoor air contaminants and short-term exposure to the air pollutants. RESULTS: After controlling for potential confounding factors, FEV1, FEF(25-75) and FEF75 for boys in a high-pollution district (HPD) were significantly lower than those in a low-pollution district (LPD) by 3.0%, 7.6% and 8.4%, respectively. No significant differences were found for girls. Results from the comparison between a moderate-pollution district (MPD) and the HPD were similar. There were no differences between children in the LPD and MPD, except that a higher FEF75 was found in boys in the MPD. PM10 is the primary pollutant responsible for the lung function deficit. Asthmatic children were more vulnerable to exposure to air pollution. CONCLUSIONS: Long-term exposure to higher ambient air pollution levels was associated with lower lung function in Chinese schoolchildren, especially among boys. Adverse effects were observed on large and small airways, with a stronger effect on the latter.