A comparative study of urinary levels of multiple metals and neurotransmitter correlations between GDM and T2DM populations.

OBJECTIVE: The pathogenesis of GDM and T2DM are closely related to various metals in vivo, and changes in the concentration of these metal exposures can lead to neuropathy through the DNA damage pathway caused by the accumulation of ROS. METHOD: Urine samples were analyzed for heavy metals and trace elements by ICP-MS, neurotransmitter metabolites by HPLC, 8-OH-dG by HPLC-MS and metabolomics by UPLC-MS. RESULT: Cd and Hg were risk factors for T2DM. There was a positive correlation between 8-OH-dG and neurotransmitter metabolites in both two populations. For GDM, the metabolite with the largest down-regulation effect was desloratadine and the largest up-regulation effect was D-glycine. That tyrosine and carbon metabolites were upregulated in the GDM population and downregulated in the T2DM population. CONCLUSION: The BMI, urinary Cd and Hg endo-exposure levels correlated with elevated blood glucose, and the latter may cause changes in the DNA damage marker 8-OH-dG in both study populations and trigger common responses to neurological alterations changes in the neurotransmitter. Tyrosine, carbonin metabolites, alanine, aspartate, and glutamate were signature metabolites that were altered in both study populations. These indicators and markers have clinical implications for monitoring and prevention of neurological injury in patients with GDM and T2DM.

Study on the role of CCM3 gene and lead exposure induced neurotoxicity through neurovascular units.

This study aimed to determine the toxic effects of vascular CCM3 gene deficiency and lead (Pb) exposure on the nervous system. Lentiviral transfection was performed to generate a stable strain of brain microvascular endothelial cells with low CCM3 expression. MTT assay assessed the survival rate of cells exposed to Pb, determining the dose and duration of Pb exposure in vitro. Proteomic analysis was performed on the differentially expressed proteins in bEnd3 and HT22 cells and flow cytometry was used to detect cell apoptosis. Finally, urine samples from pregnant and postpartum women were subjected to ICP-MS to detect Pb levels and HPLC to detect neurotransmitter metabolites. Based on the proteomic analysis of bEnd3 (CCM3-/-) cells co-cultured with HT22 cells, it was determined that HT22 cells and CCM3 genes interfered with bEnd3 cell differential proteins,2 including apoptosis and ferroptosis pathways. Electron microscopy observation, ICP-MS iron ion loading detection, and WB determination of protein GPX4 expression confirmed that HT22 cells undergo apoptosis, while bEnd3 cells undergo multiple pathways of iron death and apoptosis regulation. Furthermore, a linear regression model showed the interaction between maternal urine Pb levels, the rs9818496 site of the CCM3 SNP in peripheral blood DNA, and the concentration of the neurotransmitter metabolite 5-HIAA in maternal urine (F=4.198, P < 0.05). bEnd3 cells with CCM3 gene deficiency can induce HT22 cell apoptosis through iron death and apoptosis pathways under Pb exposure in a combined cell culture Pb exposure model, and CCM3 gene deficiency in endothelial cells and Pb exposure interacts with neural cell HT22. Epidemiological studies on maternal and newborn infants further confirmed the interaction between urine Pb levels in mothers and the SNP rs9818496 site of the CCM3 gene in peripheral blood DNA.

Cooking with biomass fuels increased the risk for cognitive impairment and cognitive decline among the oldest-old Chinese adults (2011-2018): A prospective cohort study.

BACKGROUNDS: While the pernicious effects of outdoor air pollution on cognitive ability have been previously examined, evidence regarding household air pollution is scarce. METHODS: Using data from the Chinese Longitudinal Healthy Longevity Survey, we explored the relationship between cooking with biomass fuel and cognitive impairment and cognitive decline using a Cox proportional hazards model. We further assessed the correlation of biomass fuels and cognitive score using a generalized estimating equation. Cognitive ability was measured based on the Chinese version of the Mini-Mental State Examination (MMSE) and cognitive impairment was defined as MMSE < 24 points and cognitive decline was defined as a reduction of MMSE ≥ 3 points. On follow-up, we investigated the effect of switch-cooking combustibles on cognitive ability. RESULTS: The mean (SD) age of 4161 participants was 81.7 (10.0) years old. The reported cooking with biomass fuels was correlated with an elevated risk of cognitive impairment (hazard ratio (HR): 1.19, 95% confidence interval (CI): 1.04, 1.37) and cognitive decline (HR: 1.18, 95% CI: 1.04, 1.33). Besides, cooking with biomass fuels was related to a decrease in cognitive score (ß: -0.43, 95% CI: -0.73, -0.14). In comparison to persistent biomass fuel users, participants who reported changing their primary cooking fuels from biomass to clean fuels exhibited a reduced risk of cognitive impairment (HR: 0.68, 95% CI: 0.57, 0.82) and cognitive decline (HR: 0.66, 95% CI: 0.56, 0.76) and a higher cognitive score (ß: 0.72, 95% CI: 0.17, 1.26). Cooking without ventilated cookstoves was associated with a higher risk of cognitive impairment (HR: 1.31, 95% CI: 1.10, 1.58) and cognitive decline (HR: 1.18, 95% CI: 1.02, 1.38), regardless of types of cooking fuels. Interaction and stratified analyses showed relatively poor cognitive ability in participants who engaged in irregular exercise or were not living with family members. CONCLUSIONS: Cooking with biomass fuels was correlated with a higher risk of cognitive impairment and cognitive decline. Among the oldest-old population, this risk may, however, be lower for those changing their primary cooking fuels from biomass to clean fuels.

Identification of hub genes and therapeutic drugs in rheumatoid arthritis patients.

OBJECTIVES: Rheumatoid arthritis (RA) is considered a chronic autoimmune inflammatory disease that causes great morbidity and shortens life expectancy; however, the precise pathogenesis of RA remains unclear. This study aimed to select hub genes correlated with the development of RA. METHODS: Two gene expression profiles, GSE55235 and GSE12021, obtained from the Gene Expression Omnibus (GEO) were used to identify differentially expressed genes (DEGs) in control and RA samples using GEO2R, followed by other bioinformatics methods, including functional enrichment analysis, protein-protein interaction (PPI) networks, miRNA-hub gene network, and drug-hub gene interactions. In addition, qRT-PCR was finally conducted to confirm the reliability and validity of the expression level of the novel DEGs via freshly collected heparinized blood samples of healthy controls and RA patients. RESULTS: A sum of 136 upregulated and 37 downregulated DEGs were selected. Functional enrichment analysis indicated that all the upregulated DEGs were correlated with immune response, B cell receptor signalling pathway, and adaptive immune response. KEGG pathway enrichment analysis revealed that the upregulated DEGs were mostly related to cytokine-cytokine receptor interaction, primary immunodeficiency, chemokine signalling pathways, and cell adhesion molecules (CAMs). In total, 12 hub genes (IL15, KLRK1, GZMA, CXCR6, IGHV4-38-2, IGLL5, CXCL13, CXCL11, MS4A1, SDC1, SLAMF1, and PDCD1LG2) were identified and all these hub genes were upregulated, of which IGLL5 and IGHV4-38-2 were first reported to be correlated with the pathogenic mechanism and prognosis of RA. Furthermore, we also used qRT-PCR to validate the overexpression of IGLL5 and IGHV4-38-2 in RA patients compared to the healthy controls. In the miRNA-hub gene network, hsa-miR-1185-5p and hsa-miR-3679-5p might inhibit the expression of IGLL5 during the progression of RA. The 15 most promising candidate drugs, which were all approved by the Food and Drug Administration, may assist with the treatment of RA. CONCLUSIONS: Overall, these findings may assist with developing diagnostic, prognostic, and therapeutic biomarkers for RA. Key Points • IGLL5 and IGHV4-38-2 were first reported to be correlated with the pathogenic mechanism and prognosis of RA. • Besides, hsa-miR-1185-5p and hsa-miR-3679-5p may inhibit the expression of IGLL5 during the progression of RA.

Indoor solid fuel use and incident arthritis among middle-aged and older adults in rural China: A nationwide population-based cohort study.

BACKGROUND: Many households in developing countries, including China, rely on the traditional use of solid fuels for cooking and heating. Arthritis is highly prevalent in middle-aged and older adults and is a major cause of disability. However, evidence linking indoor solid fuel use with arthritis is scarce in this age group (≥45 years) in developing countries. OBJECTIVES: To investigate whether exposure to indoor solid fuel for cooking and heating is associated with arthritis in middle-aged and older adults in rural China. METHODS: Data for the present study were extracted from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal national prospective study of adults aged 45 years and older enrolled in 2010 and followed up through 2015. We included 7807 rural participants without arthritis at baseline, of whom 1548 living in a central heating area in winter were included in the heating analysis (taking the Qinling-Huaihe line as the heating boundary). Cox proportional hazards models were used to examine the association between indoor solid fuel use and arthritis, controlling for age, sex, education, marital status, smoking status, drinking status, self-reported socioeconomic status, BMI, sleep time, napping time, independent cooking, hypertension, diabetes, dyslipidemia, heart problems and stroke. We also investigated the effect of switching primary fuels and using solid fuels for both cooking and heating on arthritis risk. RESULTS: The mean (SD) age of the study participants was 59.2 (10.0) years old, and 48.0% of participants were women. A total of 64.8% and 63.0% of the participants reported primarily using solid fuel for cooking and heating, respectively. Arthritis incidence rates were lower among clean fuel users than solid fuel users. Compared to those using clean fuels, cooking and heating solid fuel users had a higher risk of arthritis, with hazard ratios (HRs) of 1.22 (95% confidence interval (CI): 1.01, 1.49) and 1.76 (95% CI: 1.07, 2.89), respectively. Switching from clean fuels to solid fuels for heating (HR: 3.28, 95% CI: 1.21, 7.91) and using solid fuels for both cooking and heating (HR, 1.71, 95% CI, 1.01-2.79) increased the risk of arthritis. CONCLUSIONS: Long-term solid fuel use for indoor cooking and heating is associated with an increased risk of arthritis events among adults aged 45 years and older in rural China. The potential benefits of reducing indoor solid fuel use in groups at high risk for arthritis merit further exploration.

Predictions of the dysregulated competing endogenous RNA signature involved in the progression of human lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer worldwide. Until now, the molecular mechanisms underlying LUAD progression have not been fully explained. This study aimed to construct a competing endogenous RNA (ceRNA) network to predict the progression in LUAD. METHODS: Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and mRNAs (DEGs) were identified from The Cancer Genome Atlas (TCGA) database with a |log2FC|> 1.0 and a false discovery rate (FDR) < 0.05. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) network, and survival analyses were performed to analyse these DEGs involved in the ceRNA network. Subsequently, the drug-gene interaction database (DGIdb) was utilized to select candidate LUAD drugs interacting with significant DEGs. Then, lasso-penalized Cox regression and multivariate Cox regression models were used to construct the risk score system. Finally, based on the correlations between DELs and DEGs involved in the risk score system, the final ceRNA network was identified. Meanwhile, the GEPIA2 database and immunohistochemical (IHC) results were utilized to validate the expression levels of selected DEGs. RESULTS: A total of 340 DELs, 29 DEMs, and 218 DEGs were selected to construct the initial ceRNA network. Functional enrichment analyses indicated that 218 DEGs were associated with the KEGG pathway terms "microRNAs in cancer", "pathways in cancer", "cell cycle", "HTLV-1 infection", and the "PI3K-Akt signalling pathway". K-M survival analysis of all differentially expressed genes involved in the ceRNA network identified 24 DELs, 4 DEMs, and 29 DEGs, all of which were significantly correlated with LUAD progression (P< 0.05). Furthermore, 15 LUAD drugs interacting with 29 significant DEGs were selected. After lasso-penalized Cox regression and multivariate Cox regression modelling, PRKCE, DLC1, LATS2, and DPY19L1 were incorporated into the risk score system, and the results suggested that LUAD patients who had the high-risk score always suffered from a poorer overall survival. Additionally, the correlation coefficients between these 4 DEGs and their corresponding DELs involved in the ceRNA network suggested that there were 2 significant DEL-DEG pairs, NAV2-AS2 - PRKCE (r= 0.430, P< 0.001) and NAV2-AS2 - LATS2 (r= 0.338, P< 0.001). And NAV2-AS2 - mir-31 - PRKCE and NAV2-SA2 - mir-31 - LATS2 were finally identified as ceRNA network involved in the progression of LUAD. CONCLUSIONS: The lncRNA-miRNA-mRNA ceRNA network plays an essential role in predicting the progression of LUAD. These results may improve our understanding and provide novel mechanistic insights to explore prognosis and therapeutic drugs for LUAD patients.

Association between biomass fuel use and risk of hypertension among Chinese older people: A cohort study.

BACKGROUNDS: Previous studies linking biomass fuel use to hypertension have been inconsistent. We investigated the association between biomass fuel use and the risk of hypertension and blood pressure measures in older Chinese people. METHODS: The prospective cohort study of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) included participants aged 65 years and older in 2011/2012 who were followed up until 2014 in 23 provinces in China. We explored the association between biomass fuel use and hypertension using the Cox proportional hazards model and examined the relationship of biomass fuel use with blood pressure measures using the generalized estimating equation. Additionally, we examined the effect of switching cooking fuels on hypertension during the follow-up. RESULTS: Among 3754 participants who were without hypertension at baseline, the mean age was 86 years old, and 47.5% of participants were men. Reported use of biomass fuel for cooking (50.2%) was associated with a higher risk of hypertension (incidence rate (IR) per 100 person-years: 13.15 versus 12.99, hazard ratio (HR) = 1.15, 95% confidence interval (CI) = 1.01-1.31). Biomass fuel use was related to systolic blood pressure (SBP) (ß 1.10 mmHg, 95% CI: 0.48-1.72), diastolic blood pressure (DBP) (ß 1.02 mmHg, 95% CI: 0.61-1.43) and mean arterial pressure (MAP) (ß 1.03 mmHg, 95% CI: 0.63-1.43) elevation. Compared with persistent clean fuel users, participants who reported switching from clean to biomass fuels for cooking had a noticeably higher risk of hypertension (IR per 100 person-years: 14.27 versus 12.81, HR 1.49, 95% CI: 1.16-1.90) and higher SBP (3.71 mmHg), DBP (2.44 mmHg) and MAP (2.86 mmHg). Interaction and stratified analyses showed greater effect estimates of SBP and MAP in the oldest oldpeople (≥85). CONCLUSIONS: The use of biomass fuel for cooking was associated with greater hypertension risk, and the risk may be higher among those who switched from clean fuels to biomass fuels in the Chinese elderly population. Biomass fuel use was associated with a statistically significant but small absolute increase in blood pressure measures.