Diet-derived circulating antioxidants and risk of inflammatory bowel disease: a Mendelian randomization study and meta-analysis.

Background: Previous studies have shown conflicting results regarding the impact of circulating antioxidants on the risk of inflammatory bowel disease (IBD). In this study, our intent was to investigate the causal relationship between circulating antioxidants and IBD using Mendelian randomization (MR). Methods: Instrumental variables for absolute circulating antioxidants (ascorbate, retinol, lycopene, and ß-carotene) and circulating antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbate, and retinol) were screened from published studies. We obtained outcome data from two genome-wide association study (GWAS) databases, including the international inflammatory bowel disease genetics consortium (IIBDGC, 14,927 controls and 5,956 cases for Crohn's disease (CD), 20,464 controls and 6,968 cases for ulcerative colitis (UC), and 21,770 controls and 12,882 cases for IBD) and the FinnGen study (375,445 controls and 1,665 cases for CD, 371,530 controls and 5,034 cases for UC, and 369,652 controls and 7,625 cases for IBD). MR analysis was performed in each of the two databases and those results were pooled using meta-analysis to assess the overall effect of exposure on each phenotype. In order to confirm the strength of the findings, we additionally conducted a replication analysis using the UK Biobank. Results: In the meta-analysis of the IIBDGC and FinnGen, we found that each unit increase in absolute circulating level of retinol was associated with a 72% reduction in the risk of UC (OR: 0.28, 95% CI: 0.10 to 0.78, P=0.015). The UC GWAS data from the UK Biobank also confirmed this causal relationship (OR: 0.99, 95% CI: 0.97 to 1.00, P=0.016). In addition, there was suggestive evidence that absolute retinol level was negatively associated with IBD (OR: 0.41, 95% CI: 0.18 to 0.92, P=0.031). No other causal relationship was found. Conclusion: Our results provide strong evidence that the absolute circulating level of retinol is associated with a reduction in the risk of UC. Further MR studies with more instrumental variables on circulating antioxidants, especially absolute circulating antioxidants, are needed to confirm our results.

Force and Torque Model of Magnetically Levitated System with 2D Halbach Array and Printed Circuit Board Coils.

Precision machining fields often require worktables with different stroke sizes. To address the need for scalability and facilitate manufacturing, this study proposes a novel infinite expansion magnetically levitated planar motor (MLPM) based on PCB stator coils. Different from existing magnetic levitation systems that use PCB coils, the design presented in this paper utilizes smaller coil units, with each coil being independent of one another. The coils are structured in a spiral pattern on a 16-layer PCB, comprising 15 layers of coils, while the last layer is dedicated to wiring and other circuits. Magnetic field modeling is conducted for both the stator coil and the 2D Halbach array structure employed in the system. A simple table lookup method is employed to accurately account for the prevalent end effects observed during system motion. Additionally, the decoupling effect of magnetic force and torque is evaluated by solving for the current vector at different points along a specific trajectory. To verify the accuracy of the proposed system's modeling, a prototype is developed and tested. Experimental results demonstrate that compared to traditional harmonic model methods, the proposed approach improves the calculation accuracy of magnetic force by 50.31% and torque by 70.65%. This study presents a new MLPM system with vast potential applications in precision manufacturing and robotics. The innovative design and improved performance characteristics make it a promising technology for enhancing the capabilities of worktables in precision machining fields.

Causal association between dietary factors and esophageal diseases: A Mendelian randomization study.

BACKGROUND: Using Mendelian randomization (MR) approach, our objective was to determine whether there was a causal association between dietary factors and gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), or esophageal cancer (EC). METHODS: Genome-wide association study (GWAS) data for eighteen types of dietary intake were obtained from the UK Biobank. GWAS data for GERD, BE, and EC were sourced from the FinnGen consortium. We performed univariable and multivariable MR analysis to assess the cause effect between dietary factors and esophageal diseases. MR results were expressed as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Raw vegetable intake was associated with a lower risk of GERD (OR = 0.478; P = 0.011). On the contrary, cooked vegetable intake increased the risk of GERD (OR = 1.911; P = 0.024). Bread intake was associated with increased odds of BE (OR = 6.754; P = 0.007), while processed meat intake was associated with reduced risk of BE (OR = 0.210; P = 0.035). We also observed evidence that increased consumption of dried fruit (OR = 0.087; P = 0.022) and salt added to food (OR = 0.346; P = 0.045) could prevent EC. The results of multivariable MR showed that the protective effect of consumption of salt added to food on EC was no longer significant after adjusting for the consumption of dried fruit. CONCLUSION: Vegetable consumption was associated with GERD, whereas consumption of bread and processed meat was associated with BE. Dried fruit intake was associated with a lower risk of EC, and the protective effect of consumption of salt added food on EC may also be mediated by consumption of dried fruit. Future research should be performed to investigate the mechanisms behind these cause-and-effect relationships to reduce the burden of disease caused by dietary habits.

Endoplasmic reticulum stress related genome-wide Mendelian randomization identifies therapeutic genes for ulcerative colitis and Crohn's disease.

Background: Endoplasmic reticulum stress (ERS) is an important pathophysiological mechanism in ulcerative colitis (UC) and Crohn's disease (CD). ERS-related genes may be influenced by genetic factors and intestinal inflammation. However, the role of ERS as a trigger or potential etiological factor for UC and CD is unclear, as the expression of ERS-related genes in UC and CD may be the cause or subsequent changes in intestinal inflammation. Here, we used a three-step summary data-based Mendelian randomization (SMR) approach integrating multi-omics data to identify putative causal effects of ERS-related genes in UC and CD. Methods: Genome-wide association study (GWAS) summary data for UC (6,968 cases and 20,464 controls) and CD (5,956 cases and 14,927 controls) were extracted as outcome, and DNA methylation quantitative trait loci (mQTL, 1,980 participants) data and expression QTL data (eQTL, 31,684 participants) from the blood were obtained as exposure. The ERS-related genes were extracted from the GeneCards database, and then the GWAS summary data were integrated with the mQTL and eQTL data associated with ERS genes by SMR. Sensitivity analysis included two-sample MR analysis, power calculations, Bayesian co-localization analysis, and phenotype scanning were performed to evaluate the robustness of the results. Results: A total of 1,193 ERS-related genes were obtained. The three-step SMR analysis showed that cg24011261 CpG site regulating GPX1 expression was associated with a low risk of UC, whereas GPX1 expression regulated by a combination of cg05055782, cg24011261, and cg05551922 CpG sites was associated with a low risk of CD. Sensitivity analysis further supports these findings. Conclusion: This multi-omics integration study identifies a causal relationship between the role of ERS in UC and CD and suggests potential new therapeutic targets for clinical practice.

Identification of 6 cuproptosis-related genes for active ulcerative colitis with both diagnostic and therapeutic values.

Cuproptosis has been reported to affect a variety of diseases. Therefore, we aimed to examine the role of cuproptosis-related genes in active ulcerative colitis (UC). We acquired 2 datasets of active UC from the Gene Expression Omnibus database and created immune cell infiltrations to research immune cell dysregulation. Based on the cuproptosis gene set and differentially expressed genes (DEGs), we identified the differentially expressed genes of cuproptosis (CuDEGs). We then used 2 machine learning methods to screen hub CuDEGs. Subsequently, we performed validation on additional datasets and investigated the relationship between hub CuDEGs and drug treatments. Thirty-five controls with inactive UC and 90 patients with active UC were obtained from the training sets. A total of 9157 DEGs and 27 CuDEGs were identified, respectively. Immune cell infiltration analysis revealed that patients with active UC exhibited higher levels of activated dendritic cells and neutrophils as well as lower levels of CD8+ T cells, regulatory T cells (Tregs), and macrophage M2. A six-gene cuproptosis signature was identified using machine learning algorithms. We further validated that the 6 hub CuDEGs showed a strong correlation with active UC and acted as cuproptosis-related biomarkers of active UC. Moreover, the expression of ATOX1 was downregulated, and SUMF1, MT1G, ATP7B, FDX1, and LIAS expression was upregulated in the colonic mucosa of active UC patients who responded to golimumab or vedolizumab therapy. With the exception of ATP7B, the expression patterns of hub CuDEGs before and after infliximab treatment of patients with active UC were similar to those of golimumab and vedolizumab. Cuproptosis and active UC have a complex relationship, as illustrated in our study. ATOX1, SUMF1, MT1G, ATP7B, FDX1, and LIAS are cuproptosis-related hub genes of active UC. Our study opens new avenues for investigating UC progression and developing novel therapeutic potential targets for the disease.

Causal association between inflammatory bowel disease and herpes virus infections: a two-sample bidirectional Mendelian randomization study.

Background: Previous observational or retrospective studies have suggested an association between inflammatory bowel disease (IBD) and herpes virus infections. Using Mendelian randomization (MR) approach, our objective was to determine whether there was a causal association between IBD and herpes virus infections. Methods: In genome-wide association study (GWAS) datasets of the International Inflammatory Bowel Disease Genetics Consortium, we obtained genetic instrumental variables for three phenotypes from 34,652 participants (12,882 IBD cases and 21,770 controls), 27,432 participants [6,968 ulcerative colitis (UC) cases and 20,464 controls], and 20,883 participants [5,956 Crohn's disease (CD) cases and 14,927 controls], respectively. Summary statistics for herpes virus infections (chickenpox, herpes zoster, and mononucleosis) were obtained from the FinnGen database. MR results were expressed as odds ratio (OR) with 95% confidence interval (CI). Results: Our study found no evidence of a causal effect of genetically predicted IBD on herpes virus infections [P value for inverse variance weighting (IVW): 0.063 to 0.652]. For the subtypes of IBD, UC had a suggestive association with mononucleosis (P value for IVW: 0.023). It appeared that CD was also weakly associated with mononucleosis (P value for IVW: 0.058; P value for Weighted median: 0.036). In addition, we found a suggestive causality for CD on chickenpox (P value for IVW: 0.038). Neither UC (P value for IVW: 0.574) nor CD (P value for IVW: 0.168) has a causal effect on herpes zoster. The results of the bidirectional MR analysis did not indicate that herpes virus infections were associated with IBD, UC or CD (P value for IVW: 0.239 to 0.888). Conclusion: This study showed a suggestive causality for both CD-chickenpox and UC-mononucleosis, despite no associations reaching a statistical significance value after corrections for multiple testing. There was no evidence of a causal association between IBD and its two subtypes on herpes zoster.

Major depressive disorder plays a vital role in the pathway from gastroesophageal reflux disease to chronic obstructive pulmonary disease: a Mendelian randomization study.

Background: Observational studies have shown a bidirectional association between chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), but it is not clear whether this association is causal. In our previous study, we found that depression was a hot topic of research in the association between COPD and GERD. Is major depressive disorder (MDD) a mediator of the association between COPD and GERD? Here, we evaluated the causal association between COPD, MDD, and GERD using Mendelian randomization (MR) study. Methods: Based on the FinnGen, United Kingdom Biobank, and Psychiatric Genomics Consortium (PGC) databases, we obtained genome-wide association study (GWAS) summary statistics for the three phenotypes from 315,123 European participants (22,867 GERD cases and 292,256 controls), 462,933 European participants (1,605 COPD cases and 461,328 controls), and 173,005 European participants (59,851 MDD cases and 113,154 controls), respectively. To obtain more instrumental variables to reduce bias, we extracted relevant single-nucleotide polymorphisms (SNPs) for the three phenotypes from published meta-analysis studies. Bidirectional MR and expression quantitative trait loci (eQTL)-MR were performed using the inverse variance weighting method to assess the causal association between GERD, MDD, and COPD. Results: There was no evidence of a causal effect between GERD and COPD in the bidirectional MR analysis [forward MR for GERD on COPD: odds ratios (OR) = 1.001, p = 0.270; reverse MR for COPD on GERD: OR = 1.021, p = 0.303]. The causal effect between GERD and MDD appeared to be bidirectional (forward MR for GERD on MDD: OR = 1.309, p = 0.006; reverse MR for MDD on GERD: OR = 1.530, p < 0.001), while the causal effect between MDD and COPD was unidirectional (forward MR for MDD on COPD: OR = 1.004, p < 0.001; reverse MR for COPD on MDD: OR = 1.002, p = 0.925). MDD mediated the effect of GERD on COPD in a unidirectional manner (OR = 1.001). The results of the eQTL-MR were consistent with those of the bidirectional MR. Conclusion: MDD appears to play a vital role in the effect of GERD on COPD. However, we have no evidence of a direct causal association between GERD and COPD. There is a bidirectional causal association between MDD and GERD, which may accelerate the progression from GERD to COPD.

Relationship Between COPD and GERD: A Bibliometrics Analysis.

Purpose: A growing body of evidence links chronic obstructive pulmonary disease (COPD) to gastroesophageal reflux disease (GERD). In spite of the lack of understanding of the specific cause-effect relationship between COPD and GERD, GERD has been shown to be a significant predictor of acute exacerbations of COPD. In this study, we examined the evolution of the relationship between COPD and GERD over the past decades and provided valuable insights into this topic. Methods: The Web of Science Core Collection (WoSCC) was searched since its inception until 19 August 2022 to obtain publications related to COPD and GERD. The data was analyzed in Microsoft Excel (version 2021), HisCite (version 2.1), Scimago Graphica (version 1.0.23), VOSviewer (1.6.17), and CiteSpace (version 5.8.R3). Results: We extracted 545 documents from the WoSCC database. Since 2002, there have been rapid increases in publications. Among countries and institutions, the United States and the University of Manchester were most prolific. The most cited journal was Chest, while Respiratory Medicine had the most publications. Among 2870 related authors, Hasenfuss, Gerd, Lange, Peter, and Martinez, Gerd were the top 3 contributing authors in this field. Aside from "gastroesophageal reflux disease" and "chronic obstructive pulmonary disease", the terms "quality of life", "cough", and "inflammation" were frequently occurred in the title and abstract of articles. Keywords co-occurrence overlay visualization indicated that "refractory chronic cough" was hot topics in recent years. Conclusion: Research on COPD and GERD has flourished, and its content topics have become more in-depth over time. In the future, this hot topic deserves more attention.

Exploring the Molecular Mechanism of Tong Xie Yao Fang in Treating Ulcerative Colitis Using Network Pharmacology and Molecular Docking.

Objective: The purpose of this study was to investigate the mechanisms of action of Tong Xie Yao Fang (TXYF) against ulcerative colitis (UC) by employing a network pharmacology approach. Methods: The network pharmacology approach, including screening of the active ingredients and targets, construction of the active ingredient-drug target network, the active ingredient-diseasetarget network, the protein-protein interaction (PPI) network, enrichment analyses, molecular docking, and targets validation, was used to explore the mechanisms of TXYF against UC. Results: 34 active ingredients and 129 and 772 targets of TXYF and UC, respectively, were identified. The intersection of the active ingredient-drug target network, the active ingredient-disease target network, and the PPI network suggested that kaempferol, beta-sitosterol, wogonin, and naringenin were the core ingredients and prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target. Enrichment analyses showed that regulation of exogenous protein binding and other functions were of great significance. Nuclear factor-kappa B (NF-κB) signaling pathway, interleukin-17 (IL-17) signaling pathway, and tumor necrosis factor (TNF) signaling pathway were important pathways. Results of molecular docking indicated that the core ingredients and the target molecule had strong binding affinities. We have validated the high levels of expression of PTGS2 in UC by analyzing three additional datasets from the Gene Expression Omnibus (GEO) database. Conclusions: There are multiple ingredients, targets, and pathways involved in TXYF's effectiveness against UC, and these findings will promote further research and clinical applications.

Coronary heart disease and gut microbiota: A bibliometric and visual analysis from 2002 to 2022.

Background: Existing studies have indicated that gut microbiota is closely related to the occurrence and development of coronary heart disease(CHD). Gut microbiota and its metabolites may be important diagnostic markers for CHD in the future and are expected to become new targets for the prevention and treatment of CHD. However, the current studies exploring the link between CHD and gut microbiota are miscellaneous and poorly targeted, without bibliometric analysis available. Objective: The purpose of this research was to perform a bibliometric and visual analysis of published papers on the relationship between CHD and gut microbiota. The study also sought to identify principal authors, institutions, and countries to analyze the research status and trends of gut microbiota research in the field of CHD. Methods: The Web of Science Core Collection (WoSCC) database was searched for publications on CHD and gut microbiota between 2002 and 2022. CiteSpace 5.8. R1, VOSviewer 1.6.16, and Microsoft Excel 2019 software tools were utilized to perform this bibliometric analysis and visualization. Results: There were 457 qualified publications found in total, with the annual number of publications increasing. The United States dominated in this field. Hazen, Stanley l was the author of the most papers. Cleveland Clinic published the most papers of any institution. The six main clusters' specific characteristics were discovered through analysis of the co-occurrence of keywords: inflammation, diet, trimethylamine n-oxide, metabolism, cardiovascular disease, and myocardial infarction. Newly emerging research has focused predominantly on gut microbiota metabolites and recent strategies for intervention in coronary atherosclerosis. Conclusion: These results provided a useful perspective on current research and future prospects for the research on the link between CHD and gut microbiota, which may help researchers to select suitable collaborators and facilitate their research to elucidate the underlying molecular mechanisms of CHD, including the causes, prevention, and treatment.