Associations between urinary glyphosate and diabetes mellitus in the US general adult: a cross-sectional study from NHANES 2013-2016.

Glyphosate-based herbicides (GBHs) are used extensively around the world and have become the leading agrochemicals. However, study about the association between glyphosate exposure and the risk of diabetes mellitus (DM) is scarce. This study used 4 years of NHANES data (2013-2016) to further investigate the association. A total of 2535 participants were enrolled in this cross-sectional study. The baseline information and urinary glyphosate levels in diabetic and non-diabetic groups were compared. Using multivariable logistic regression mode, we explored the association between both the continuous and categorical forms of urinary glyphosate and DM risk. Further subgroup analyses based on categorical covariates were also conducted. Urinary glyphosate levels were 0.42 ng/ml in participants with diabetes and 0.34 ng/ml in participants without diabetes (P < 0.05). As a continuous variable, ln-transformed urinary glyphosate was significantly associated with an increased risk of DM in the most adjusted model (OR 1.28, 95% CI 1.03-1.57). However, the association was not significant in the most adjusted categorical model (P > 0.05).In further subgroup analyses, the associations remained significant in several subgroups. This study provides new evidence that glyphosate exposure was associated with a higher risk of diabetes in the American general adult population.

Causal association between self-reported fatigue and coronary artery disease: a bidirectional two-sample Mendelian randomization analysis.

Background: Observational studies have reported the association between fatigue and coronary artery disease (CAD), but the causal association between fatigue and CAD is unclear. Method: We conducted a bidirectional Mendelian randomization (MR) study using publicly available genome-wide association studies (GWAS) data. The inverse-variance weighted (IVW) method was used as the primary analysis. We performed three complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) to evaluate the sensitivity and horizontal pleiotropy of the results. Result: Self-reported fatigue had a causal effect on coronary artery atherosclerosis (CAA) (OR 1.047, 95%CI 1.033-1.062), myocardial infarction (MI) (OR 1.027 95%CI 1.014-1.039) and coronary heart disease (CHD) (OR 1.037, 95%CI 1.021-1.053). We did not find a significant reverse causality between self-reported fatigue and CAD. Given the heterogeneity revealed by MR-Egger regression, we employed the IVW random effect model. For the examination of fatigue on CHD and the reverse analysis of CAA, and MI on fatigue, the MR-PRESSO test found horizontal pleiotropy. No significant outliers were found. Conclusion: The MR analysis reveals a causal relationship between self-reported fatigue and CAD. The results should be interpreted with caution due to horizontal pleiotropy.

Identification of the shared mechanisms and common biomarkers between Sjögren's syndrome and atherosclerosis using integrated bioinformatics analysis.

Background: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes and pathways influencing the pathophysiology of SS and AS via bioinformatic analysis of microarray data. Methods: Microarray datasets of SS (GSE40611) and AS (GSE28829) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired using R software's "limma" packages, and the functions of common DEGs were determined using Gene Ontology and Kyoto Encyclopedia analyses. The protein-protein interaction (PPI) was established using the STRING database. The hub genes were assessed via cytoHubba plug-in and validated by external validation datasets (GSE84844 for SS; GSE43292 for AS). Gene set enrichment analysis (GSEA) and immune infiltration of hub genes were also conducted. Results: Eight 8 hub genes were identified using the intersection of four topological algorithms in the PPI network. Four genes (CTSS, IRF8, CYBB, and PTPRC) were then verified as important cross-talk genes between AS and SS with an area under the curve (AUC) ≥0.7. Furthermore, the immune infiltration analysis revealed that lymphocytes and macrophages are essentially linked with the pathogenesis of AS and SS. Moreover, the shared genes were enriched in multiple metabolisms and autoimmune disease-related pathways, as evidenced by GSEA analyses. Conclusion: This is the first study to explore the common mechanism between SS and AS. Four key genes, including CTSS, CYBB, IRF8, and PTPRC, were associated with the pathogenesis of SS and AS. These hub genes and their correlation with immune cells could be a potential diagnostic and therapeutic target.

Transient ischemic attack and coronary artery disease: a two-sample Mendelian randomization analysis.

Background: Although observational studies have shown that patients who experienced transient ischemic attacks (TIAs) had a higher risk of coronary artery disease (CAD), the causal relationship is ambiguous. Methods: We conducted a two-sample Mendelian randomization (MR) study to analyze the causal relationship between TIA and CAD using data from the FinnGen genome-wide association study. Analysis was performed using the inverse-variance weighted (IVW) method. The robustness of the results was evaluated using MR-Egger regression, the weighted median, MR pleiotropy residual sum, and outlier (MR-PRESSO) and multivariable MR analysis. Results: Results from IVW random-effect model showed that TIA was associated with an increased risk of coronary artery atherosclerosis (OR 1.17, 95% CI 1.06-1.28, P = 0.002), ischemic heart disease (OR 1.15, 95% CI 1.04-1.27, P = 0.007), and myocardial infarction (OR1.15, 95% CI 1.02-1.29, P = 0.025). In addition, heterogeneity and horizontal pleiotropy were observed in the ischemic heart disease results, while the sensitivity analysis revealed no evidence of horizontal pleiotropy in other outcomes. Conclusions: This MR study demonstrated a potential causal relationship between TIA and CAD. Further research should be conducted to investigate the mechanism underlying the association.

Non-thyroidal illness syndrome and the prognosis of heart failure: a systematic review and meta-analysis.

Background: Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis. Methods: Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to 1 July 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle-Ottawa Scale. The heterogeneity of the results was assessed with I2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted. Results: A total of 626 studies were retrieved, and 18 studies were finally included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE. Conclusions: This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation.

The Refinement of Risk Stratification for Atrial Thrombus or Spontaneous Echo Contrast in Nonvalvular Atrial Fibrillation.

As for nonvalvular atrial fibrillation (NVAF) patients with left atrial thrombus or spontaneous echo contrast (LAT/SEC), we evaluated the additional predictive value of serum uric acid (SUA) and Left atrial diameter (LAD) for CHADS2 and CHA2DS2-VASc, and explored the influence from the level of SUA and LAD to LAT/SEC in moderate risk group. Thus, we put forward the concept of a borderline high risk group to guide clinical anticoagulant therapy in patients with NVAF.A total of 284 NVAF patients without the history of anticoagulant prior to hospitalization were enrolled. They were divided into LAT/SEC group or No LAT/SEC group according to transesophageal echocardiography (TEE). Then, we explored and compared the additional predictive value of serological and ultrasonic indexes after combining them to CHADS2/CHA2DS2-VASc.61 patients (21.48%) had LAT/SEC. SUA and LAD were the independent risk factors of LAT/SEC. After being added with LAD and SUA, the predictive value of CHADS2 and CHA2DS2-VASc were increased much more than others. In the moderate risk group, the incidence of LAT/SEC rose significantly when SUA or LAD was higher than cut-off values.SUA and LAD enhanced the predictive ability of CHADS2 and CHA2DS2-VASc for LAT/SEC as additional factors. For patients in moderate risk group, if SUA or LAD was higher than cut-off values, the risk of thromboembolism events would rise accompanied by the elevated risk of LAT/SEC.

PINK1 alleviates myocardial hypoxia-reoxygenation injury by ameliorating mitochondrial dysfunction.

PTEN inducible kinase-1 (PINK1) mutant induces mitochondrial dysfunction of cells, resulting in an inherited form of Parkinson's disease. However its exact role in the cardiomyocytes is unclear. The present study examined the function of PINK1 in hypoxia-reoxygenation (H/R) induced H9c2 cell damage and its potential mechanism. The H/R model in H9c2 cells was established by 6 h of hypoxia and 12 h of reoxygenation. The CCK8 and LDH assay indicated that the cell viability was obviously reduced after H/R. The expression of PINK1 was decreased in H/R-induced H9c2 cells compared with control group. The vector overexpressing PINK1 was constructed to transfect into H/R-induced H9c2 cells. Our results showed that cell viability was increased, cell apoptosis and caspase 3, cytochrome C (Cyto C) levels were decreased after LV-PINK1 transfection. Furthermore, PINK1 overexpression stabilized electron transport chain (ETC) activity, increased ATP production, mPTP opening and mitochondrial membrane potential (MMP), inhibited ROS-generating mitochondria, implying PINK1 alleviates H/R induced mitochondrial dysfunction in cardiomyocytes. In addition, the TRAP-1 siRNA was transfected into PINK1 treated H9c2 cells after H/R to detected the molecular mechanism of PINK1 protecting cardiomyocytes. The results indicated that silence of TRAP-1 reversed the effects of PINK1 in H/R-induced H9c2 cells. In conclusion, these results suggest that PINK1 overexpression alleviates H/R-induced cell damage of H9c2 cells by phosphorylation of TRAP-1, and that is a valid approach for protection from myocardial I/R injury.