Association of residential greenness with obstructive sleep apnea among Chinese old adults and the mediation role of PM2.5 and leisure-time physical activity.

Few studies have investigated the association of residential greenness with obstructive sleep apnea (OSA). This study was to comprehensively examine the association of residential greenness exposure with OSA and explore the mediating effect of leisure-time physical activity (LTPA) and PM2.5 on the association among Chinese old adults. A prospective cohort study that enrolled 2027 adults aged ≥65 was conducted between 1st July 2015 and 30th September 2019 in Southern China. OSA was ascertained by Berlin Questionnaire. Greenness exposure was measured by contemporaneous and cumulative average normalized difference vegetation index (NDVI) in the 1000 m radius around each participant's residential address. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated by Cox proportional hazards model to assess the impact of greenness exposure on the incidence of OSA after adjusting for confounders. LTPA and PM2.5 were examined as potential mediators in the aforementioned models. A total of 293, nearly 14.5 %, participants developed OSA within 59,251 person-months of follow-up. When comparing the highest with lowest tertiles, both contemporaneous NDVI (>0.351 vs. ≤0.325: HR = 0.20, 95 % CI = 0.13-0.31) and cumulative NDVI (> 0.346 vs. ≤ 0.317: HR = 0.32, 95 % CI = 0.21-0.47) were associated with a reduced risk of OSA after adjusting for confounders. LTPA and PM2.5 significantly mediated the association between greenness and OSA. In conclusion, this study indicated that exposure to higher residential greenness could decrease OSA risk, and this benefit may be achieved by promoting physical activity and decreasing PM2.5 concentration. The findings suggest to formulate targeted interventional strategies by expanding residential greenness to prevent OSA and reduce disease burden.

Hypermethylation of HIC2 is a potential prognostic biomarker and tumor suppressor of glioma based on bioinformatics analysis and experiments.

INTRODUCTION: Glioma is the most common primary tumor in the central nervous system, and prognostic biomarkers are still lacking. HIC ZBTB transcriptional repressor 2 (HIC2) is a hypermethylated gene that plays an important functional role in cardiac development. However, the actual role of HIC2 in glioma progression remains unclear. This study aimed to investigate the function of HIC2 and whether it could be a prognostic biomarker in glioma. METHODS: The DNA methylation and mRNA expression profiles of HIC2 were downloaded from public databases. The prognostic prediction ability and mechanism research of HIC2 were evaluated. RESULTS: We found that HIC2 was hypermethylated and expressed at low levels in glioma samples. Hypermethylation and low expression of HIC2 predicted poor prognosis. Multivariate Cox regression analysis suggested that HIC2 was an independent prognostic factor for gliomas. Co-IP assays demonstrated that HIC2 interacts with RNF44, and dual-luciferase reporter assays and ChIP assays revealed that HIC2 transcriptionally inhibits PTPRN2 expression. CONCLUSIONS: Our findings suggest that HIC2 represents a tumor suppressor gene and prognostic biomarker for glioma progression and that overexpression of HIC2 inhibits the proliferation of glioma in vitro and in vivo by interacting with RNF44 and PTPRN2.

Three nervous system-specific expressed genes are potential biomarkers for the diagnosis of sporadic amyotrophic lateral sclerosis through a bioinformatic analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease in adults. However, ALS, especially sporadic ALS (sALS), is difficult to diagnose due to the lack of biomarkers. RESULTS: We used the bioinformatics technology to find the potential biomarker and we found that two hundred seventy-four DEGs were identified and enrichment analysis showed DEGs were involved in nervous system activity, like axon_guidance and the neurotrophin_signaling_pathway. Five nervous system-specific expressed hub genes were further validated by three GEO datasets. APP, LRRK2, and PSEN1 might be potential diagnostic and prognostic biomarkers of sALS, and NEAT1-miR-373-3p/miR-302c-3p/miR-372-3p-APP, circ_0000002-miR-302d-3p/miR-373-3p-APP and XIST-miR-9-5p/miR-30e-5p/miR-671-5p might be potential ceRNA regulatory pathways. APP SNP analysis showed subjects harboring the minor G allele of rs463946, minor G allele of rs466433 and minor C allele of rs364048 had an increased risk of sALS development. CONCLUSIONS: Our results identified three nervous system-specific expressed hub genes that might be diagnostic and prognostic markers of sALS and APP might be a genetic susceptibility factor contributing to sALS development.

Occurrence of 2- and 3-monochloropropanediol esters (MCPDE) in infant formula products on the Canadian market between 2015 and 2019.

2- and 3-monochloropropanediol esters (MCPDEs) are most commonly formed as process-induced contaminants during the refinement of vegetable oils used for food production. 'In vivo' hydrolysis of 3-MCPDEs releases the potential carcinogen 3-monochloropropanediol (3-MCPD). Levels of MCPDEs in infant formula are of particular concern, as refined oils are commonly used as main fat ingredients. For this study, infant formula samples (powders, liquid concentrates and ready-to-feed infant formula samples) from the Canadian market were purchased and analysed in 2015 (35 samples) and 2019 (33 samples). MCPDE concentrations (expressed as free MCPD equivalents) were examined through an indirect analytical approach, applying acid-catalysed ester cleavage and using cyclohexanone as derivatising agent. Labelled diesters were used as internal standards. 2015 Survey data were analysed by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring mode (SIM). 2019 Survey data were analysed with an updated method using GC-MS/MS in multiple reaction monitoring modes (MRM). In 2015, levels in reconstituted formula ranging from 3.7 ng/g to 111 ng/g for 3-MCPD and 2.2 ng/g to 56.2 ng/g for 2-MCPD were found. In 2019, levels ranging from 3.9 ng/g to 74.8 ng/g for 3-MCPD and 1.0 ng/g to 33.9 ng/g for 2-MCPD were found. A significantly reduced mean of combined MCPDEs was observed between 2015 and 2019 data (64.5 ng/g, standard deviation (SD) 8.6 ng/g in 2015 to 31.8 ng/g, SD 5.6 ng/g in 2019, p-value = 0.024). For the majority of manufacturers, the data comparison among brand products over time shows decreased levels of MCPDEs. Occurrence data of MCPDEs, including data from previously published surveys (2012/2013), were also compared and a temporal trend was established.

Evaluation of stromal cell infiltration in the tumor microenvironment enable prediction of treatment sensitivity and prognosis in colon cancer.

Current clinical factors for screening candidates that might benefit from adjuvant chemotherapy in colon cancer are inadequate. Tumor microenvironment, especially the stromal components, has the potential to determine treatment response. However, clinical translation of the tumor-associated stromal characterization into a practical biomarker for helping treatment decision has not been established. Using machine learning, we established a novel 31-gene signature, called stromal cell infiltration intensity score (SIIS), to distinguish patients characterized by the enrichment of abundant stromal cells in five colon cancer datasets from GEO (N = 990). Patients with high-SIIS were at higher risk for recurrence and mortality, and could not benefit from adjuvant chemotherapy due to their intrinsic drug resistance; however, the opposite was reported for patients with low-SIIS. The role of SIIS in detection of patients with high stromal cell infiltration and reduced drug efficiency was consistently validated in the TCGA-COAD cohort (N = 382), Sun Yat-sen University Cancer Center cohort (N = 30), and could also be observed in TCGA pan-cancer settings (N = 4898) and four independent immunotherapy cohorts (N = 467). Based on multi-omics data analysis and the CRISPR library screen, we reported that lack of gene mutation, hypomethylation in ADCY4 promoter region, activation of WNT-PCP pathway and SIAH2-GPX3 axis were potential mechanisms responsible for the chemoresistance of patients within high-SIIS group. Our findings demonstrated that SIIS provide an important reference for those making treatment decisions for such special patients.

Pharmacological inhibition of DUSP6 suppresses gastric cancer growth and metastasis and overcomes cisplatin resistance.

Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP) is widely used as the standard GC treatment, but relapse and metastasis are common because of intrinsic or acquired drug resistance. The mitogen-activated protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK) pathway contributes to GC progression and drug resistance, but targeting the MAPK-ERK pathway is challenging in GC therapy. Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival. Knockdown DUSP6 inhibited GC proliferation, migration, invasion and induced apoptosis. (E/Z)-BCI hydrochloride (BCI), a DUSP6 small molecule inhibitor, increased the activity of ERK but interestingly decreased the expression of ERK response genes in BGC823, SGC7901 and CDDP-resistant SGC7901/DDP cells. BCI also caused cell death through the DNA damage response (DDR) pathway. Moreover, BCI inhibited cell proliferation, migration and invasion in a receptor-independent manner and enhanced CDDP cytotoxicity at pharmacological concentrations in the GC cells. In vivo experiments further showed that BCI enhances the antitumor effects of CDDP in cell-based xenografts and PDX models. In summary, our findings indicated that disruption of DUSP6 by BCI enhanced CDDP-induced cell death and apoptosis in GC may partly through ERK and DDR pathways. Thus, this study suggests that DUSP6 is a potential prognostic biomarker and a promising target for GC therapy.