The association of phthalate metabolites with childhood waist circumference and abdominal obesity.

The association between phthalates exposure and childhood abdominal obesity is still unclear. This study aimed to assess phthalates (PAEs) exposure level and explore the association between PAEs metabolites exposure and the risk of abdominal obesity in Chinese students aged 7-10 years. A total of 798 students aged 7-10 years were selected from the baseline survey of the cohort of Childhood Blood Pressure and Environmental Factors (CBPEF), which was established in Xiamen City, Fujian province, East China, from August to November in 2018. Urine samples were collected from these students to analyze the concentrations of seven PAEs metabolites using the method of high-performance liquid chromatography-tandem triple quadrupole mass spectrometry. Waist circumference was used to define abdominal obesity. The logistic regression model was used to analyze the association of urinary creatinine-adjusted PAEs metabolites with childhood abdominal obesity risk. The prevalence of childhood abdominal obesity is 12.0% (96/798). Apart from mono(2-ethylhexyl) phthalate (62.5% for boys and 47.0% for girls), the detection rate of the others PAEs metabolites ranged from 82.6 to 100%. Boys had higher concentrations of PAEs metabolites than girls (P < 0.05), except for monoethyl phthalate. Compared with the Q1 group of PAEs metabolites, the risk of childhood abdominal obesity increased to 429% (OR = 5.29; 95% CI: 2.09, 13.39) and 273% (OR = 3.73; 95% CI: 1.57, 8.86) for the Q4 group of monoethyl phthalate and monoisobutyl phthalate, respectively. CONCLUSION: The detection rate of PAEs metabolites is common, and the exposure level of PAEs metabolites was associated with the risk of abdominal obesity in Chinese students aged 7-10 years. WHAT IS KNOWN: • The prevalence of childhood abdominal obesity had increased sharply from 4.9% in 1993 to 17.5% in 2014 in China. More than 80% of the Chinese children and adolescents have measurable level of several PAEs metabolites in the urine. Previous studies with limited sample had explored the association between DEHP metabolites exposure and childhood abdominal obesity risk, however, the association were inconsistent. WHAT IS NEW: • The detection rate of PAEs metabolites is common among Chinese children aged 7-10 years. Boys had higher concentrations of PAEs metabolites than girls (P < 0.05), except for monoethyl phthalate. Compared with the Q1 group of PAEs metabolites, the risk of childhood abdominal obesity increased to 429% and 273% for the Q4 group of monoethyl phthalate and monoisobutyl phthalate, respectively.

Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: a large prospective cohort study.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29-9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

Sex differences in the associations between adiposity distribution and cardiometabolic risk factors in overweight or obese individuals: a cross-sectional study.

BACKGROUND: We aimed to assess the associations between adiposity distribution and cardiometabolic risk factors among overweight and obese adults in China, and to demonstrate the sex differences in these associations. METHODS: A total of 1221 participants (455 males and 766 females) were included in this study. Percentage of body fat (PBF) of the whole body and regional areas, including arm, thigh, trunk, android, and gynoid, were measured by the dual-energy X-ray absorptiometry method. Central adiposity was measured by waist circumference. Clustered cardiometabolic risk was defined as the presence of two or more of the six cardiometabolic risk factors, namely, high triglyceride, low high density lipoprotein, elevated glucose, elevated blood pressure, elevated high sensitivity C-reactive protein, and low adiponectin. Linear regression models and multivariate logistic regression models were used to assess the associations between whole body or regional PBF and cardiometabolic risk factors. RESULTS: In females, except arm adiposity, other regional fat (thigh, trunk, android, gynoid) and whole-body PBF are significantly associated with clustered cardiometabolic risk, adjusting for age, smoking, alcohol drinking, physical activity, and whole-body PBF. One-SD increase in Z scores of the thigh and gynoid PBF were significantly associated with 80 and 78% lower odds of clustered cardiometabolic risk (OR: 0.20, 95%CI: 0.12-0.35 and OR: 0.22, 95%CI: 0.12-0.41). Trunk, android and whole-body PBF were significantly associated with higher odds of clustered risk with OR of 1.90 (95%CI:1.02-3.55), 2.91 (95%CI: 1.75-4.85), and 2.01 (95%CI: 1.47-2.76), respectively. While in males, one-SD increase in the thigh and gynoid PBF are associated with 94% (OR: 0.06, 95%CI: 0.02-0.23) and 83% lower odds (OR: 0.17, 95%CI: 0.05-0.57) of clustered cardiometabolic risk, respectively. Android and whole-body PBF were associated with higher odds of clustered cardiometabolic risk (OR: 3.39, 95%CI: 1.42-8.09 and OR: 2.45, 95%CI: 1.53-3.92), but the association for trunk PBF was not statistically significant (OR: 1.16, 95%CI: 0.42-3.19). CONCLUSIONS: Adiposity distribution plays an important role in the clustered cardiometabolic risk in participants with overweight and obese and sex differences were observed in these associations. In general, central obesity (measured by android PBF) could be the best anthropometric measurement for screening people at risk for CVD risk factors for both men and women. Upper body fat tends to be more detrimental to cardiometabolic health in women than in men, whereas lower body fat is relatively more protective in men than in women.

Association between supportive attitude and adoptive practice of control strategy against COVID-19 amosng college students in China: a cross-sectional study.

BACKGROUND: We investigated college students' attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). METHODS: We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. RESULTS: A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. CONCLUSIONS: Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.

Contact Settings and Risk for Transmission in 3410 Close Contacts of Patients With COVID-19 in Guangzhou, China : A Prospective Cohort Study.

BACKGROUND: Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated. OBJECTIVE: To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings. DESIGN: Prospective cohort study. SETTING: Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China. PARTICIPANTS: 3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected. MEASUREMENT: Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated. RESULTS: Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or critical. Compared with the household setting (10.3%), the secondary attack rate was lower for exposures in health care settings (1.0%; odds ratio [OR], 0.09 [CI, 0.04 to 0.20]) and on public transportation (0.1%; OR, 0.01 [CI, 0.00 to 0.08]). The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0% to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases. Index cases with expectoration were associated with higher risk for secondary infection (13.6% vs. 3.0% for index cases without expectoration; OR, 4.81 [CI, 3.35 to 6.93]). LIMITATION: There was potential recall bias regarding symptom onset among patients with COVID-19, and the symptoms and severity of index cases were not assessed at the time of exposure to contacts. CONCLUSION: Household contact was the main setting for transmission of SARS-CoV-2, and the risk for transmission of SARS-CoV-2 among close contacts increased with the severity of index cases. PRIMARY FUNDING SOURCE: Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme.

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

IL-17A-Induced PLET1 Expression Contributes to Tissue Repair and Colon Tumorigenesis.

This study identifies a novel mechanism linking IL-17A with colon tissue repair and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue repair of dextran sulfate sodium (DSS)-induced damage in colon epithelium and markedly reduced tumor development in an azoxymethane/DSS model of colitis-associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker involved in wound healing), was highly induced in DSS-treated colon tissues and tumors in an IL-17RC-dependent manner. PLET1 expression was induced in LGR5+ colon epithelial cells after DSS treatment. LGR5+PLET1+ marks a highly proliferative cell population with enhanced expression of IL-17A target genes. PLET1 deficiency impaired tissue repair of DSS-induced damage in colon epithelium and reduced tumor formation in an azoxymethane/DSS model of colitis-associated cancer. Our results suggest that IL-17A-induced PLET1 expression contributes to tissue repair and colon tumorigenesis.

Subnational variation of stunting, wasting and malnutrition in Chinese primary-school children between 2010 and 2014: urban-rural disparity.

OBJECTIVE: To examine urban-rural disparity in childhood stunting, wasting and malnutrition at national and subnational levels in Chinese primary-school children in 2010 and 2014. DESIGN: Data were obtained from two nationwide cross-sectional surveys conducted in 2010 and 2014. Malnutrition was classified using the Chinese national 'Screening Standard for Malnutrition of Children'. SETTING: All twenty-seven mainland provinces and four municipalities of mainland China.ParticipantsChildren aged 7-12 years (n 215 214; 107 741 in 2010 and 107 473 in 2014) from thirty-one provinces. RESULTS: Stunting, wasting and malnutrition prevalence were 1·9, 12·3 and 13·7 % in 2010, but decreased to 1·0, 9·4 and 10·2 % in 2014, respectively. The prevalence of stunting, wasting and malnutrition in both urban and rural children was higher in western provinces, while lower in eastern provinces. Although the prevalence of wasting and malnutrition was higher in rural children than their urban counterparts, the urban-rural disparity in both wasting and malnutrition decreased from 2010 to 2014 (prevalence OR: wasting, 1·35 to 1·16; malnutrition, 1·50 to 1·27). A reversal occurred in 2014 in several eastern provinces where the prevalence of wasting and malnutrition in urban children surpassed their rural peers. The urban-rural disparity was larger in western provinces than eastern provinces. CONCLUSIONS: The shrinking urban-rural disparity and the reversal in wasting and malnutrition suggest that the malnutrition situation has improved during the post-crisis period, especially in the western provinces. Region-specific policies and interventions can be useful to sustainably mitigate malnutrition in Chinese children, especially in rural areas and the western provinces.

Parental smoking and blood pressure in children and adolescents: a national cross-sectional study in China.

BACKGROUND: Current evidence on the health effects of passive smoking on childhood blood pressure is limited and inconsistent. We investigated the associations between exposure to parental smoking and blood pressure in children and adolescents. METHODS: A cross-sectional analysis was performed in a national sample of 42,745 children and adolescents (50.2% boys) aged 7-18 years from seven provinces in China. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Information on parental smoking was collected through questionnaire. Multivariable linear regression and logistic regression was used to investigate the associations of parental smoking with blood pressure and prevalent hypertension, respectively. RESULTS: The reported parental smoking rates were 49.7 and 50.2% in boys and girls, respectively. After adjustment for a range of potential confounders, exposure to parental smoking was associated with 0.44 [95% confidence interval (CI): 0.16, 0.72] mmHg and 0.26 (95% CI: 0.04, 0.47) mmHg higher SBP and DBP in girls. Girls exposed to parental smoking were also more likely to have hypertension compared with those without exposure (odds ratio = 1.11, 95% CI: 1.02, 1.20). No significant associations were found in boys. CONCLUSIONS: Exposure to parental smoking was associated with increased blood pressure and higher prevalence of hypertension in girls, but not in boys. Urgent strategies are needed for the promotion of smoking-free environment, especially for children and adolescents.

[Changes of the nutritional status of children and adolescents aged 7-17 years of Tujia ethnic minority in Hunan Province from 2010 to 2014].

OBJECTIVE: To understand the change of nutritional status of children and adolescents aged 7-17 years from Tujia ethnic minority in Hunan Province, and to provide evidence for the prevention and control policy making of improving the population's nutritional status. METHODS: A total of 4676 children and adolescents aged 7-17 years from Tujia ethnic minority in Hunan Province were included(2310 in year 2010, 2366 in year 2014), sample were recruited in the 2010 and 2014 Chinese National Survey on Students' Constitution and Health. The nutritional status of wasting and stunting was defined by a national malnutrition screening standard(WS/T 456-2014), overweight and obesity were defined by the body mass index percentile criteria developed by Chinese Working Group on Obesity for Children(WGOC). RESULTS: From 2010 to 2014, the obesity prevalence of Tujia children and adolescents from Hunan increased obviously from 3.1% to 5.7%, and the prevalence of wasting also increased, from 7.8% to 10.5%. The trend analysis of stunting showed that the stunting prevalence decreased significantly from 8.4% in 2010 to 3.5% in 2014. CONCLUSION: The stunting issue in Tujia children and adolescents has improved a lot from 2010 to 2014. But the prevalence of stunting is still high, and there is a dual burden of malnutrition and overnutrition.

Multiproteomic and Transcriptomic Analysis of Oncogenic ß-Catenin Molecular Networks.

The dysregulation of Wnt signaling is a frequent occurrence in many different cancers. Oncogenic mutations of CTNNB1/ß-catenin, the key nuclear effector of canonical Wnt signaling, lead to the accumulation and stabilization of ß-catenin protein with diverse effects in cancer cells. Although the transcriptional response to Wnt/ß-catenin signaling activation has been widely studied, an integrated understanding of the effects of oncogenic ß-catenin on molecular networks is lacking. We used affinity-purification mass spectrometry (AP-MS), label-free liquid chromatography-tandem mass spectrometry, and RNA-Seq to compare protein-protein interactions, protein expression, and gene expression in colorectal cancer cells expressing mutant (oncogenic) or wild-type ß-catenin. We generate an integrated molecular network and use it to identify novel protein modules that are associated with mutant or wild-type ß-catenin. We identify a DNA methyltransferase I associated subnetwork that is enriched in cells with mutant ß-catenin and a subnetwork enriched in wild-type cells associated with the CDKN2A tumor suppressor, linking these processes to the transformation of colorectal cancer cells through oncogenic ß-catenin signaling. In summary, multiomics analysis of a defined colorectal cancer cell model provides a significantly more comprehensive identification of functional molecular networks associated with oncogenic ß-catenin signaling.

Prevalence and risk factors of impaired fasting glucose and diabetes among Chinese children and adolescents: a national observational study.

The prevalence of impaired fasting glucose (IFG) and diabetes mellitus (DM) has reportedly increased significantly among Chinese children and adolescents. We aimed to examine the prevalence of IFG and DM, the disparities in sex and region and related risk factors among Chinese children and adolescents. A total of 16 434 Chinese children aged 6-17 years were selected from a national cross-sectional survey, and fasting glucose was measured for all participants. Overall, mean fasting plasma glucose (FPG) concentration was (4·64 (sd 0·51)) mmol/l, and the prevalence of DM and IFG was 0·10 and 1·89 %, respectively. Compared with girls, boys had higher FPG concentration (4·69 v. 4·58 mmol/l, r 0·107, P<0·001) and IFG prevalence (2·67 v. 1·07 %, r φ 0·059, P<0·001). Compared with rural children and adolescents, urban children and adolescent had higher FPG concentration (4·65 v. 4·62 mmol/l, r 0·029, P<0·001) and DM prevalence (0·15 v. 0·05 %, r φ 0·016, P<0·01). In addition, self-reported fried foods intake and overweight/obesity were positively associated with IFG, and the proportion of consuming fried foods more than or equal to once per week and overweight/obesity prevalence in boys and urban children and adolescents were significantly higher than girls and rural children and adolescents, respectively (P<0·05). Although the prevalence of IFG and DM was relatively low in Chinese children and adolescents, sex and region disparities were observed, which may be associated with differences in overweight/obesity prevalence and dietary factors.

The association between fetal-stage exposure to the China famine and risk of diabetes mellitus in adulthood: results from the China health and retirement longitudinal study.

BACKGROUND: The associations of famine exposure with diabetes risk in adulthood are still unclear. This study aimed to explore the association between famine exposure in early life and risk of diabetes in adulthood. METHODS: A total of 4138 subjects were selected from the data of the China Health and Retirement Longitudinal Study (CHARLS) 2011-2012. Diabetes was diagnosed as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated haemoglobin (HbA1C) > 6.5%, or self-reported diabetes. Birthdates of subjects were used to categorize famine exposure groups. The association of fetal-stage famine exposure with diabetes risk in adults was assessed using logistics regression model. RESULTS: The prevalence of diabetes in the non-exposed, fetal-stage exposed, infant-stage exposed, and preschool-stage exposed groups were 9.0, 13.6, 12.7 and 10.8%, respectively. Compared with the age-balanced control group, the fetal-stage exposed group was associated with the elevated risk of diabetes in later life after adjusting for covariates (OR = 1.37; 95%CI: 1.09-1.72; P = 0.008). Stratified analysis showed that the association between prenatal famine exposure and diabetes risk in adulthood was comparable between severely affected areas and less severely affected areas (P for interaction =0.153). CONCLUSIONS: Famine exposure in fetal stages was associated with the elevated diabetes risk in adults, which could be the critical periods for relative intervention.

Prevalence of excess body weight and underweight among 26 Chinese ethnic minority children and adolescents in 2014: a cross-sectional observational study.

BACKGROUND: Little is known regarding the nutritional burden in Chinese ethnic minority children. This study aimed to investigate the epidemiological characteristics of excess body weight and underweight for 26 ethnic groups. METHODS: Data on 80,821 participants aged 7-18 years across 26 minorities, with completed records from a large national cross-sectional survey, were obtained from Chinese National Survey on Students' Constitution and Health (CNSSCH) in 2014. Excess body weight, underweight and their components were classified according to Chinese national BMI references. RESULTS: The overall prevalence of excess body weight and underweight among ethnic groups were 12.0% and 14.5%, in which 4.4% and 4.1% of the participants were classified as obese and severe wasting, respectively. Compared with girls, boys showed a higher prevalence of underweight, severe wasting and obesity, but a lower prevalence of excess body weight (P < 0.05). Among 26 ethnic groups, Koreans had the highest prevalence of excess body weight (30.4%), while Bouyeis showed the highest prevalence of underweight (25.7%). The ethnic minority groups with high prevalence of excess body weight and underweight were more likely to show high burden of obesity and severe wasting, respectively. However, it is not the case for some groups, such as Miaos and Shuis. CONCLUSIONS: A worrying dual burden of excess body weight and underweight was recognized in Chinese ethnic minority children. Since various characteristics were found among different minorities, the ethnic-specific effort is warranted to improve their nutritional status.

Novel recurrently mutated genes in African American colon cancers.

We used whole-exome and targeted sequencing to characterize somatic mutations in 103 colorectal cancers (CRC) from African Americans, identifying 20 new genes as significantly mutated in CRC. Resequencing 129 Caucasian derived CRCs confirmed a 15-gene set as a preferential target for mutations in African American CRCs. Two predominant genes, ephrin type A receptor 6 (EPHA6) and folliculin (FLCN), with mutations exclusive to African American CRCs, are by genetic and biological criteria highly likely African American CRC driver genes. These previously unsuspected differences in the mutational landscapes of CRCs arising among individuals of different ethnicities have potential to impact on broader disparities in cancer behaviors.

DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer.

The cancer epigenome exhibits global loss of DNA methylation, which contributes to genomic instability and aberrant gene expression by mechanisms that are yet to be fully elucidated. We previously discovered over 3300 long non-coding (lnc)RNAs in human cells and demonstrated that specific lncRNAs regulate gene expression via interactions with chromatin-modifying complexes. Here, we tested whether lncRNAs could also associate with DNA methyltransferases to regulate DNA methylation and gene expression. Using RIP-seq, we identified a subset of lncRNAs that interact with the DNA methyltransferase DNMT1 in a colon cancer cell line, HCT116. One lncRNA, TCONS_00023265, which we named DACOR1 (DNMT1-associated Colon Cancer Repressed lncRNA 1), shows high, tissue-specific expression in the normal colon (including colon crypts) but was repressed in a panel of colon tumors and patient-derived colon cancer cell lines. We identified the genomic occupancy sites of DACOR1, which we found to significantly overlap with known differentially methylated regions (DMRs) in colon tumors. Induction of DACOR1 in colon cancer cell lines significantly reduced their ability to form colonies in vitro, suggesting a growth suppressor function. Consistent with the observed phenotype, induction of DACOR1 led to the activation of tumor-suppressor pathways and attenuation of cancer-associated metabolic pathways. Notably, DACOR1 induction resulted in down-regulation of Cystathionine ß-synthase, which is known to lead to increased levels of S-adenosyl methionine-the key methyl donor for DNA methylation. Collectively, our results demonstrate that deregulation of DNMT1-associated lncRNAs contributes to aberrant DNA methylation and gene expression during colon tumorigenesis.

Novel all-hydrocarbon stapled p110α[E545K] peptides as blockers of the oncogenic p110α[E545K]-IRS1 interaction.

To follow up on our recent discovery of the 18-amino acid all-hydrocarbon [i, i + 4]-stapled p110α[E545K] peptide 1 that was shown to potently block the intracellular p110α[E545K]-IRS1 interaction (a protein-protein interaction uniquely present in cancer cells expressing p110α[E545K]) and the growth of the xenograft tumors formed by cancers harboring this mutation, in the current study we prepared and examined six derivatives of 1, i.e. stapled peptides 2-A, 2-B, 3-A, 3-B, 4-A, 4-B. We found that 2-A, 2-B, 4-A, and 4-B had higher % α-helicity than 1; moreover, the enhanced % α-helicity also led to an enhanced proteolytic stability. When compared with 1, the structurally simplified 14-amino acid 4-A and 4-B were found to more potently deactivate the AKT phosphorylation at Ser473 in the p110α[E545K]-expressing colon cancer cells, whose activation was previously demonstrated by us to be specifically derived from the p110α[E545K]-IRS1 interaction. The preliminary findings from the current study have laid a foundation for future more extensive studies on the stapled p110α[E545K] peptides newly identified in the current study.

Fetal and infant exposure to severe Chinese famine increases the risk of adult dyslipidemia: Results from the China health and retirement longitudinal study.

BACKGROUND: To explore the associations between the Chinese famine exposure in early life and the dyslipidemia in adulthood. METHODS: We selected 2752 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011-2012 to evaluate the associations of early life the Chinese famine exposure with risk of dyslipidemia in adulthood. Dyslipidemia was defined as TC (Total Cholesterol): HDL-C (High-Density Lipoprotein Cholesterol) ratio ≥ 5.0 or use cholesterol lowering drugs. Famine exposure cohorts were categorized by birthdates of participants. Binary logistics regression model was used to examine the associations of early-life famine exposure with the risk of dyslipidemia. RESULTS: The dyslipidemia prevalence of the non-exposed cohort, fetal stage-, infant stage-, and preschool stage-exposed cohorts in adulthood was 15.7%, 23.1%, 22.0%, and 18.6%, respectively. Early-life exposure to the Chinese famine significantly increased LDL cholesterol concentrations in adulthood after adjusted for age. The risks of dyslipidemia in fetal (OR = 1.58; 95% CI: 1.23-2.03; P < 0.001) and infant (OR = 1.52; 95% CI: 1.15-2.00; P = 0.003) stage-exposed cohorts were significantly higher than the non-exposed cohort after adjusted for gender and current family economic status. Following gender stratification, we found that fetal (OR = 1.80; 95% CI: 1.26-2.57; P = 0.001), infant (OR = 1.75; 95% CI: 1.17-2.62; P = 0.006), and preschool (OR = 1.63; 95% CI: 1.10-2.42; P = 0.015) -stage exposure to severe famine aggravated the risk of dyslipidemia in female adults. However, the similar association was not observed for male adults. CONCLUSIONS: Early-life exposure to severe Chinese famine could link with the higher dyslipidemia risk in female adulthood, but not in male adulthood. This gender-specific effect might be associated with the hypothesis that parents in China prefer boys to girls traditionally or survivors' bias.

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer.

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a "driver" phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine-substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.

Infant exposure to Chinese famine increased the risk of hypertension in adulthood: results from the China Health and Retirement Longitudinal Study.

BACKGROUND: Early-life developmental adaptations in response to severe malnutrition may play a crucial role in susceptibility to hypertension. This study aimed to explore the associations between exposure to the Chinese famine (1959-1961) at fetal, infant and preschool stages during fetal life or childhood and the risk of hypertension in adulthood. METHODS: We used the data of 1,966 adults born between 1956 and 1964 in selected families from the China Health and Retirement Longitudinal Study (CHARLS) national survey. RESULTS: Prevalence of hypertension among adults in non-exposed, fetal-exposed, infant-exposed, and preschool-exposed cohorts was 18.9, 20.7, 28.7, and 23.4 %, respectively. In severely affected famine areas, only infant-exposed cohort had a significant increased risk of hypertension compared with non-exposed cohort (OR 2.12; 95 % CI 1.19, 3.79; P = 0.011), and the significance remained after adjusted gender, smoking, and drinking (OR 2.11; 95 % CI 1.18, 3.77; P = 0.012). After stratification by BMI and economic status, the risk of hypertension was higher for subjects with BMI ≥ 24 kg/m(2)(OR 2.09; 95 % CI 1.09, 4.01; P = 0.026) or high economic status(OR 2.26; 95 % CI 1.19, 4.31; P = 0.013) than those with BMI < 24 kg/m(2)(OR 1.65; 95 % CI 0.71, 3.83; P = 0.246) or low economic status (OR 2.18; 95 % CI 1.14, 4.18; P = 0.019) in infant-exposed cohort of severely affected famine areas. However, there was no consistent association observed in less severely affected area or other exposed cohorts in severely affected areas. CONCLUSIONS: Infanthood exposed to famine might increase the risk of hypertension in adulthood, and a postnatal 'rich' nutrient environment further increased the risk.