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Ecotoxicology and Environmental Safety Jul 2024Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different...
Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Prospective Studies; Male; Female; Middle Aged; China; Metals; Adult; Aged; Environmental Pollutants; Cohort Studies; Metabolomics; Case-Control Studies; Thallium; Environmental Exposure; East Asian People
PubMed: 38772147
DOI: 10.1016/j.ecoenv.2024.116470 -
Translational Pediatrics Jan 2024Neonatal hypoxic-ischemic brain damage (HIBD) is a clinical syndrome causing brain injury in newborns with obscure etiology. Increasing evidence suggests that...
BACKGROUND
Neonatal hypoxic-ischemic brain damage (HIBD) is a clinical syndrome causing brain injury in newborns with obscure etiology. Increasing evidence suggests that ferroptosis plays a role in HIBD. This study aimed to clarify the key ferroptosis-related genes (FRGs) of HIBD, construct a long non-coding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) network, and further investigate the pathogenesis of HIBD.
METHODS
Gene expression data were downloaded from the Gene Expression Omnibus and FerrDb databases. The differentially expressed lncRNAs and FRGs were screened, and the related miRNAs and mRNAs were predicted. The obtained mRNA was intersected with the differentially expressed FRGs (DE-FRGs) to identify the key DE-FRGs. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts method was applied to analyze the immune cell infiltration level and the relationship between key genes and immune cells.
RESULTS
Gene differential expression analysis revealed that 1,178 lncRNAs, 207 miRNAs, and 647 mRNAs were differentially expressed in the blood of HIBD patients in comparison to healthy controls. The correlations of the lncRNAs, miRNAs, and mRNAs lead to the establishment of a competing endogenous RNA (ceRNA) network associated with ferroptosis in HIBD. Further validation using an external dataset and quantitative real-time polymerase chain reaction (PCR) analysis of brain tissues from hypoxic-ischemic encephalopathy rats confirmed the expression patterns of three key genes, including , and . Meanwhile, the three key genes were closely correlated with the infiltration of multiple immune cells and might affect the function of HIBD regulatory genes such as and . In addition, drug prediction suggested that four drugs, including cephaeline, emetine, mestranol, and sulmazole, might alleviate HIBD.
CONCLUSIONS
Our study established a ceRNA network, identified three key genes, and predicted four drugs that are associated with ferroptosis in HIBD, which provides new ideas for the investigation of the disease mechanisms and might facilitate the diagnosis and treatment of the disease.
PubMed: 38323182
DOI: 10.21037/tp-23-596 -
Gynecological Endocrinology : the... Dec 2023In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To... (Review)
Review
In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety. For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'. Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman. Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.
Topics: Female; Humans; Contraceptives, Oral, Combined; Progestins; Latin America; Ethinyl Estradiol; Estrogens; Women's Health
PubMed: 37857350
DOI: 10.1080/09513590.2023.2271072