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Abstract DNA methylation is a critical step in brain development, 5-Methyl-2'-deoxycytidine (5mdC) is one of the global DNA methylation markers. Arsenic and lead exposures have been associated with neurotoxicity, which may be linked to epigenetic changes. Our research sought to investigate the correlation between 5mdC and developmental delay (DD) among preschoolers. Additionally, we assessed whether 5mdC modified the impacts of blood lead and total urinary arsenic levels on DD. We analyzed the concentrations of 5mdC, blood cadmium and lead, and total urinary arsenic in 174 children with DD and 88 healthy children. Global DNA methylation levels are expressed as the ratio 5mdC/2’-dexyguanosine (dG), called 5mdC (%). In our findings, elevated levels of blood lead and total urinary arsenic were significantly associated with DD risk among preschoolers. Furthermore, high 5mdC (%) was related with reduced risk of DD, with an odds ratio (OR) and 95% confidence interval (CI) of 0.14 (0.06 – 0.32). A notable multiplicative interaction was observed between low 5mdC (%) and elevated blood lead levels to increase OR of DD, with OR and 95% CI was 9.51 (4.18 – 21.64). The findings provide evidence of the combined effects of reduced 5mdC (%) and high blood lead concentrations, increasing the OR of DD.

Abstract Myocardial ischemia–reperfusion injury (MIRI) was often observed after surgeries, causing a lot of suffering to patients. Inflammation and apoptosis were critical determinants during MIRI. We conveyed experiments to reveal the regulatory functions of circHECTD1 in MIRI development. The Rat MIRI model was established and determined by 2,3,5‐triphenyl tetrazolium chloride (TTC) staining. We analyzed cell apoptosis using TUNEL and flow cytometry. Proteins expression was evaluated by western blot. The RNA level was determined by qRT‐PCR. Secreted inflammatory factors were analyzed by ELISA assay. To predict the interaction sequences on circHECTD1, miR‐138‐5p, and ROCK2, bioinformatics analysis was performed. Dual‐luciferase assay was used to confirm these interaction sequences. CircHECTD1 and ROCK2 were upregulated in the rat MIRI model, while miR‐138‐5p was decreased. CircHECTD1 knockdown alleviated H/R‐induced inflammation in H9c2 cells. Direct interaction and regulation of circHECTD1/miR‐138‐5p and miR‐138‐5p/ROCK2 were confirmed by dual‐luciferase assay. CircHECTD1 promoted H/R‐induced inflammation and cell apoptosis by inhibiting miR‐138‐5p. miR‐138‐5p alleviated H/R‐induced inflammation, while ectopic ROCK2 antagonized such effect of miR‐138‐5p. Our research suggested that the circHECTD1‐modulated miR‐138‐5p suppressing is responsible for ROCK2 activation during H/R‐induced inflammatory response, providing a novel insight into MIRI‐associated inflammation.

DNA methylation is a critical step in brain development, 5-Methyl-2'-deoxycytidine (5mdC) is one of the global DNA methylation markers. Arsenic and lead exposures have been associated with neurotoxicity, which may be linked to epigenetic changes. Our research sought to investigate the correlation between 5mdC and developmental delay (DD) among preschoolers. Additionally, we assessed whether 5mdC modified the impacts of blood lead and total urinary arsenic levels on DD. We analyzed the concentrations of 5mdC, blood cadmium and lead, and total urinary arsenic in 174 children with DD and 88 healthy children. Global DNA methylation levels are expressed as the ratio 5mdC/2'-dexyguanosine (dG), called 5mdC (%). In our findings, elevated levels of blood lead and total urinary arsenic were significantly associated with DD risk among preschoolers. Furthermore, high 5mdC (%) was related with reduced risk of DD, with an odds ratio (OR) and 95% confidence interval (CI) of 0.14 (0.06 – 0.32). A notable multiplicative interaction was observed between low 5mdC (%) and elevated blood lead levels to increase OR of DD, with OR and 95% CI was 9.51 (4.18 – 21.64). The findings provide evidence of the combined effects of reduced 5mdC (%) and high blood lead concentrations, increasing the OR of DD. [ABSTRACT FROM AUTHOR]

Abstract Chronic inflammation is the cause of chronic kidney disease (CKD). The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the inflammation process and is associated with the regulatory effects of NLRP3 gene polymorphisms. This study evaluated the association between NLRP3 gene polymorphisms and CKD, and further explored whether the association of environmental metals with CKD varied by the NLRP3 genotypes. A total of 218 CKD patients and 427 age- and sex-matched healthy controls were recruited in this clinic-based case–control study. Patients were identified as having CKD if their estimated glomerular filtration rate (eGFR)

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of 57.58 versus 35.74 μg/dL were 1.98 and 1.17–3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45–4.56) and 2.96 (95% CI 1.67–5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.