Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells

<p>Abstract</p> <p>Background</p> <p>Astrocytomas are the most common and aggressive brain tumors characterized by their highly invasive growth. Gain of chromosome 7 with a hot spot at 7q32 appears to be the most prominent aberration in astrocytoma. Previously reports have shown that microRNA-335 (miR-335) resided on chromosome 7q32 is deregulated in many cancers; however, the biological function of miR-335 in astrocytoma has yet to be elucidated.</p> <p>Results</p> <p>We report that miR-335 acts as a tumor promoter in conferring tumorigenic features such as growth and invasion on malignant astrocytoma. The miR-335 level is highly elevated in C6 astrocytoma cells and human malignant astrocytomas. Ectopic expression of miR-335 in C6 cells dramatically enhances cell viability, colony-forming ability and invasiveness. Conversely, delivery of antagonist specific for miR-335 (antagomir-335) to C6 cells results in growth arrest, cell apoptosis, invasion repression and marked regression of astrocytoma xenografts. Further investigation reveals that miR-335 targets disheveled-associated activator of morphogenesis 1(Daam1) at posttranscriptional level. Moreover, silencing of endogenous Daam1 (siDaam1) could mimic the oncogenic effects of miR-335 and reverse the growth arrest, proapoptotic and invasion repression effects induced by antagomir-335. Notably, the oncogenic effects of miR-335 and siDAAM1 together with anti-tumor effects of antagomir-335 are also confirmed in human astrocytoma U87-MG cells.</p> <p>Conclusion</p> <p>These findings suggest an oncogenic role of miR-335 and shed new lights on the therapy of malignant astrocytomas by targeting miR-335.</p

Maternal exposure to ambient air pollution and congenital heart defects in China

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China.Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤1 µm (PM1), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes.Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m3] increase in PM1 was associated with 1.09-fold ([95% confidence interval, 1.01-1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed.Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings

Stage 1 hypertension defined by the 2017 ACC/AHA blood pressure guideline and cardiometabolic multimorbidity in Chinese adults

Abstract The association of blood pressure (BP) classification defined by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline with cardiometabolic multimorbidity (CMM) remains unclear. The present study aimed to investigate this research gap in the Chinese adults. Cross‐sectional data were collected from a population‐based cohort conducted in Southern China. Participants were categorized as having normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension according to the 2017 ACC/AHA guideline. CMM was defined as having two or more of the following diseases: coronary heart disease, stroke, and diabetes. The relationship between the BP classifications and CMM was examined by multivariate logistic regression. A total of 95 649 participants (mean age: 54.3 ± 10.2 years, 60.7% were women) were enrolled in this study. Multivariable‐adjusted logistic regression models revealed that stage 1 hypertension (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.03–1.78) and stage 2 hypertension (OR, 3.53; 95% CI, 2.82–4.47) were significantly associated with a higher prevalence of CMM compared with normal BP. The association between stage 1 hypertension and CMM were profound in women (OR, 1.76; 95% CI, 1.17–2.67) and in the middle‐aged group (OR, 1.53; 95% CI, 1.02–2.35) compared with men and older individuals, respectively. Our study showed that among Chinese adults, stage 1 hypertension defined by the 2017 ACC/AHA guideline was already associated with higher odds of CMM compared with normal BP, particularly in women and middle‐aged participants. Managing stage 1 hypertension may be an important measure to prevent CMM in Chinese adults

The role of lifestyle in the association between long-term ambient air pollution exposure and cardiovascular disease: a national cohort study in China

Abstract Background Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes. Methods We included 7000 participants in 2011–2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0–1; intermediate, 2–4; and favorable, 5–6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 μm [PM1], ≤ 2.5 μm [PM2.5], ≤ 10 μm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed. Results After adjusting for covariates, per 10 μg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05–1.14), PM2.5 (HR: 1.04, 95% CI: 1.00–1.08), PM10 (HR: 1.05, 95% CI: 1.03–1.08), and NO2 (HR: 1.11, 95% CI: 1.05–1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56–0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32–0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was − 0.98 (− 1.52 to − 0.44) for PM1, − 0.60 (− 1.05 to − 0.14) for PM2.5, − 1.84 (− 2.59 to − 1.09) for PM10, − 1.44 (− 2.10 to − 0.79) for NO2, and − 0.60 (− 1.08, − 0.12) for O3. Conclusions Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD

Additional file 1 of The role of lifestyle in the association between long-term ambient air pollution exposure and cardiovascular disease: a national cohort study in China

Additional file 1: Method S1. Ambient air pollution exposure acquisition. Figure S1. Sampling procedure. Figure S2. Study flowchart. Figure S3. The association of different lifestyle factors. Figure S4. (a) The proportion of single ideal factor in different lifestyle groups. (b) The proportion of ideal factors in different lifestyle groups. Figure S5. Directed acyclic graph. Figure S6. The marginal effect of lifestyle on CVD and in the relationship between ambient air pollutant exposure and CVD. Table S1. The score criteria of different lifestyle factors. Table S2. The exposure level of different air pollutants among the study population. Table S3. The exposure level by quintile of air pollutant. Table S4. The HRs (95% CIs) of the associations between lifestyle and CVD with and without adjustment for ambient air pollutant exposure. Table S5. Joint effects of lifestyle and air pollutant exposure on the incidence of CVD. Table S6. The HRs (95% CIs) of incident CVD associated with each lifestyle factor at different levels of air pollutant exposure. Table S7. Subgroup analysis of the additive interactions analysis of the effect of dichotomized lifestyle on the association between ambient air pollutant exposure and CVD in high air pollutant exposure levels (Q2–Q5). Table S8. The HRs (95% CIs) of associations between air pollutant exposure (per 10 μg/m3 increase) and incident CVD, and the mediation effect of lifestyle categories on air pollution and CVD in different sensitivity analysis models. Table S9. The HRs (95% CIs) of the association between ambient air pollutant exposure (per 10 μg/m3 increase) and CVD in different lifestyle categories in different sensitivity analysis models. Table S10. Multiplicative and additive interaction analysis of the effect of dichotomized lifestyle on the association between time-varying ambient air pollutant exposure and CVD. Table S11. Multiplicative and additive interaction analysis of the effect of dichotomized lifestyle on the association between 3 years of ambient air pollutant exposure and CVD. Table S12. Multiplicative and additive interaction analysis of the effect of dichotomized lifestyle considering new categories and nighttime sleep duration on the association between ambient air pollutant exposure and CVD. Table S13. Multiplicative and additive interaction analysis of the effect of dichotomized lifestyle considering new assignment of lifestyle categories on the association between ambient air pollutant exposure and CVD. Table S14. The subdistribution HRs (sHRs, 95% CI) of the associations between ambient air pollutant exposure (per 10 μg/m3) and CVD in different lifestyle categories. Table S15. Baseline characteristics of included and excluded participants. Table S16. Baseline characteristics of included participants and those without lifestyle scores

Association between outdoor light at night and hypertension and high‐normal blood pressure: A nationwide cross‐sectional study among Chinese adults

Abstract The authors aimed to investigate the association between outdoor light at night (LAN) intensity and blood pressure. The study included 13 507 participants aged 45 and above from the 2011–2012 China Health and Retirement Longitudinal Study baseline survey. Blood pressure measurements were obtained by averaging the last two readings recorded (three measurements with an interval of 45–60 s between each measurement) during the survey. Outdoor LAN intensity was assessed using Defense Meteorological Satellite Program data. The study categorized participants based on quartiles of outdoor LAN intensity and employed statistical methods like linear regression, restricted cubic splines, and logistic models to analyze the connections. After adjusting for potential confounding factors, higher levels of outdoor LAN intensity were associated with increase in systolic blood pressure (0.592 mmHg/interquartile range [IQR], 95% confidence interval [CI]: 0.027,1.157), diastolic blood pressure (0.853 mmHg/IQR, 95% CI: 0.525,1.180) and mean arterial pressure (0.766 mmHg/IQR, 95% CI: 0.385,1.147). Interestingly, the relationship between LAN intensity and odds of hypertension followed a non‐linear pattern, resembling a reverse “L” shape on cubic splines. Participants with the highest quartile of outdoor LAN intensity had 1.31‐fold increased odds of hypertension (95% CI: 1.08–1.58) compared to the lowest quartile. Additionally, there was an observable trend of rising odds for high‐normal blood pressure with higher levels of LAN intensity in the crude model, but no statistically significant differences were observed after adjusting for confounding factors. In conclusion, this study underscores a significant connection between outdoor LAN intensity and the prevalence of hypertension

Table1_Elucidating the role of TWIST1 in ulcerative colitis: a comprehensive bioinformatics and machine learning approach.docx

Background: Ulcerative colitis (UC) is a common and progressive inflammatory bowel disease primarily affecting the colon and rectum. Prolonged inflammation can lead to colitis-associated colorectal cancer (CAC). While the exact cause of UC remains unknown, this study aims to investigate the role of the TWIST1 gene in UC.Methods: Second-generation sequencing data from adult UC patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and characteristic genes were selected using machine learning and Lasso regression. The Receiver Operating Characteristic (ROC) curve assessed TWIST1’s potential as a diagnostic factor (AUC score). Enriched pathways were analyzed, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA). Functional mechanisms of marker genes were predicted, considering immune cell infiltration and the competing endogenous RNA (ceRNA) network.Results: We found 530 DEGs, with 341 upregulated and 189 downregulated genes. TWIST1 emerged as one of four potential UC biomarkers via machine learning. TWIST1 expression significantly differed in two datasets, GSE193677 and GSE83687, suggesting its diagnostic potential (AUC = 0.717 in GSE193677, AUC = 0.897 in GSE83687). Enrichment analysis indicated DEGs associated with TWIST1 were involved in processes like leukocyte migration, humoral immune response, and cell chemotaxis. Immune cell infiltration analysis revealed higher rates of M0 macrophages and resting NK cells in the high TWIST1 expression group, while TWIST1 expression correlated positively with M2 macrophages and resting NK cell infiltration. We constructed a ceRNA regulatory network involving 1 mRNA, 7 miRNAs, and 32 long non-coding RNAs (lncRNAs) to explore TWIST1’s regulatory mechanism.Conclusion: TWIST1 plays a significant role in UC and has potential as a diagnostic marker. This study sheds light on UC’s molecular mechanisms and underscores TWIST1’s importance in its progression. Further research is needed to validate these findings in diverse populations and investigate TWIST1 as a therapeutic target in UC.</p