| 1. |
- Chen, Jie, et al.
(författare)
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Bidirectional Mendelian Randomisation Analysis Provides Evidence for the Causal Involvement of Dysregulation of CXCL9, CCL11 and CASP8 in the Pathogenesis of Ulcerative Colitis
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:5, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Systemic inflammation is well recognised to be associated with ulcerative colitis [UC], but whether these effects are causal or consequential remains unclear. We aimed to define potential causal relationship of cytokine dysregulation with different tiers of evidence. Methods We first synthesised serum proteomic profiling data from two multicentred observational studies, in which a panel of systemic inflammatory proteins was analysed to examine their associations with UC risk. To further dissect observed associations, we then performed a bidirectional two-sample Mendelian randomisation [TSMR] analysis from both forward and reverse directions using five genome-wide association study [GWAS] summary level data for serum proteomic profiles and the largest GWAS of 28 738 European-ancestry individuals for UC risk. Results Pooled analysis of serum proteomic data identified 14 proteins to be associated with the risk of UC. Forward MR analysis using only cis-acting protein quantitative trait loci [cis-pQTLs] or trans-pQTLs further validated causal associations of two chemokines and the increased risk of UC: C-X-C motif chemokine ligand 9 [CXCL9] [OR 1.45, 95% CI 1.08, 1.95, p = 0.012] and C-C motif chemokine ligand 11 [CCL11] [OR 1.14, 95% CI 1.09, 1.18, p = 3.89 x 10(-10)]. Using both cis- and trans-acting pQTLs, an association of caspase-8 [CASP8] [OR 1.04, 95% CI 1.03, 1.05, p = 7.63 x 10(-19)] was additionally identified. Reverse MR did not find any influence of genetic predisposition to UC on any of these three inflammation proteins. Conclusion Pre-existing elevated levels of CXCL9, CCL11 and CASP8 may play a role in the pathogenesis of UC.
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| 2. |
- Sun, Yuhao, et al.
(författare)
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The Contribution of Genetic Risk and Lifestyle Factors in the Development of Adult-Onset Inflammatory Bowel Disease : A Prospective Cohort Study
- 2023
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Ingår i: American Journal of Gastroenterology. - : Lippincott Williams & Wilkins. - 0002-9270 .- 1572-0241. ; 118:3, s. 511-522
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear.METHODS: Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations.RESULTS: During the 12-year follow-up, 707 cases with CD and 1576 cases with UC were diagnosed in the UK Biobank cohort. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk with no multiplicative interaction between them. The HR of CD and UC were 2.24 (95% CI 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with a high genetic risk, respectively. The HR of CD and UC for individuals with an unfavorable lifestyle were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively. The HR of individuals with a high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI 1.58-2.66 for UC) were reduced nearly by half, compared with those with a high genetic risk but an unfavorable lifestyle (4.40, 95% CI 2.91-6.66 for CD and 4.44, 95% CI 3.34-5.91 for UC).DISCUSSION: Genetic and lifestyle factors were independently associated with susceptibility to incident CD and UC. Adherence to a favorable lifestyle was associated with a nearly 50% lower risk of CD and UC among participants at a high genetic risk.
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| 3. |
- Wang, Fang, et al.
(författare)
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Emerging contaminants: A One Health perspective
- 2024
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Ingår i: Innovation. - 2666-6758. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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| 4. |
- Yang, Zhimo, et al.
(författare)
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Facile synthesis of Fe-doped Sn4P3 anode materials for high-performance lithium-ion batteries
- 2023
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Ingår i: Solid State Sciences. - : Elsevier BV. - 1293-2558 .- 1873-3085. ; 136
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Tidskriftsartikel (refereegranskat)abstract
- Metal doping plays a momentous role in heightening the electronic conductivity of Sn4P3. This work proposes the facile synthesis of Fe-doped Sn4P3 via a solid-state reaction process. The resulting Fe-doped Sn4P3 is stacked by a great quantity of nanoparticles. As the ionic radius of Fe3+ (64.5 p.m.) is slightly smaller than that of Sn4+ (69 p.m.), Fe3+can easily dope into the structure of Sn4P3. The Sn4P3 anode with 5% Fe doping delivers a larger initial discharge capacity of 1105.1 mAh/g and coloumbic efficiency of 86.2%. After 200 cycles, a high discharge capacity of 972.4 mAh/g is reached, while the discharge capacity of un-doped Sn4P3 anode merely maintains at about 423.3 mAh/g. As an inactive matrix, Fe atoms can disperse among Sn atoms, thus inhibiting the aggregation of Sn atoms during cycling. The results display that Fe doping in Sn4P3 structure is extremely vital to heighten the architecture stability and electrochemical performance. This facile solid-state reaction process can be enlarged to the manufacture of other metal-doped Sn4P3 in the field of lithium-ion batteries.
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| 5. |
- Yuan, Shuai, et al.
(författare)
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Sleep duration and daytime napping in relation to incident inflammatory bowel disease : a prospective cohort study
- 2023
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 57:5, s. 475-485
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sleep dysregulation has been linked to gastrointestinal dysfunction and inflammation.AIMS: To explore the associations between sleep duration, daytime napping and inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC).METHODS: Exposure information was obtained from the baseline questionnaire. Sleep duration was coded as continuous and categorical (≤5, 6, 7, 8, ≥9 h/day) variables. Daytime napping was defined as yes (sometimes/usually) and no (never/rarely). Incident IBD cases were defined from primary care and hospital inpatient records. Polygenic risk scores (PRS) for the outcomes were constructed and categorised into low, intermediate and high risk. Hazard ratio (HR) and confidence interval (CI) were estimated using Cox proportional hazard regression.RESULTS: The analysis included 2604 incident IBD cases (806 CD and 1798 UC) with a median follow-up of 12.0 years. Comparing sleep duration ≤5 with 7 h/day, the HR of IBD, CD and UC was 1.36 (95% CI, 1.17-1.59), 1.53 (95% CI, 1.17-2.00) and 1.29 (95% CI, 1.07-1.56), respectively. Comparing participants with and without daytime napping, the HR of IBD, CD and UC was 1.13 (95% CI, 1.05-1.23), 1.25 (95% CI, 1.08-1.44) and 1.09 (95% CI, 0.90-1.20), respectively. No interaction of sleep duration and daytime napping with PRS was detected. However, the associations appeared stronger in individuals with high rather than low PRS.CONCLUSIONS: This study reveals positive associations between short sleep duration and daytime napping and IBD risk.
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| 6. |
- Chen, Jie, et al.
(författare)
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Plasma phospholipid arachidonic acid in relation to non-alcoholic fatty liver disease : Mendelian randomization study
- 2023
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Ingår i: Nutrition. - : Elsevier. - 0899-9007 .- 1873-1244. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The role of plasma phospholipid arachidonic acid (AA) in the development of non-alcoholic fatty liver disease (NALFD), cirrhosis, and liver cancer remains unclear. This study aimed to determine the causality of the associations of plasma phospholipid AA with NALFD, cirrhosis, and liver cancer using Mendelian ran-domization analysis.Methods: Nine independent single-nucleotide polymorphisms associated with plasma phospholipid AA at the genome-wide significance were used as instrumental variables. Summary-level data for three outcomes were obtained from 1) a genome-wide association study for NAFLD, 2) the UK Biobank study, and 3) the Finn -Gen study. The sensitivity analysis excluding the pleiotropic variant rs174547 in the FADS1 gene was per-formed. Estimates from different sources were combined using the fixed-effects meta-analysis method.Results: Per standard deviation increase in AA levels, the combined odds ratio was 1.06 (95% confidence inter-val, 1.02-1.11; P = 0.008) for NAFLD, 1.05 (95% confidence interval, 1.01-1.09; P = 0.009) for cirrhosis, and 0.99 (95% confidence interval, 0.94-1.05; P = 0.765) for liver cancer. The associations remained stable in the sensitivity analysis excluding rs174547.Conclusions: This study suggests potential causal associations of high levels of plasma phospholipid AA with the risk of NAFLD and cirrhosis.
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| 7. |
- Chen, Jie, et al.
(författare)
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Risk of incident cardiovascular disease among patients with gastrointestinal disorder : a prospective cohort study of 330,751 individuals.
- 2023
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - 2058-5225 .- 2058-1742.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The associations between gastrointestinal diseases (GIs) and cardiovascular disease (CVD) were unclear. We conducted a prospective cohort study to explore their associations.METHODS: This study included 330 751 individuals without baseline CVD from the UK Biobank cohort. Individuals with and without GIs were followed up until the ascertainment of incident CVDs, including coronary heart disease (CHD), cerebrovascular disease (CeVD), heart failure (HF) and peripheral artery disease (PAD). The diagnosis of diseases was confirmed with combination of the nationwide inpatient data, primary care data, and cancer registries. A multivariable Cox proportional hazard regression model was used to estimate the associations between GIs and the risk of incident CVD.RESULTS: During a median follow-up of 11.8 years, 31 605 incident CVD cases were diagnosed. Individuals with GIs had an elevated risk of CVD (hazard ratio 1.37; 95% confidence interval 1.34-1.41, P < 0.001). Eleven out of fifteen GIs were associated with an increased risk of CVD after Bonferroni-correction, including cirrhosis, non-alcoholic fatty liver disease, gastritis and duodenitis, irritable bowel syndrome, Barrett's esophagus, gastroesophageal reflux disease, peptic ulcer, celiac disease, diverticulum, appendicitis, and biliary disease. The associations were stronger among women, individuals aged ≤ 60 years, and those with body mass index ≥ 25 kg/m2.CONCLUSIONS: This large-scale prospective cohort study revealed the associations of GIs with an increased risk of incident CVD, in particular CHD and PAD. These findings support the reinforced secondary CVD prevention among patients with gastrointestinal disorders.
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| 8. |
- Gao, Ruichang, et al.
(författare)
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Sturgeon hydrolysates alleviate DSS-induced colon colitis in mice by modulating NF-kappa B, MAPK, and microbiota composition
- 2020
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Ingår i: Food & Function. - : ROYAL SOC CHEMISTRY. - 2042-6496 .- 2042-650X. ; 11:8, s. 6987-6999
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Tidskriftsartikel (refereegranskat)abstract
- Sturgeon muscle byproduct collected after caviar production is usually not fully utilized, and sometimes may be discarded, thus causing a lot of waste. Yet dietary protein hydrolysates, which may be derived from sturgeon muscle, have been reported to have versatile beneficial biological activities. Studying the biological activities of sturgeon muscle-derived hydrolysates holds much promise for adding value to sturgeon. The current study aimed to study the therapeutic anti-inflammatory effects of sturgeon muscle-derived hydrolysates and the underlying mechanisms. The administration of sturgeon hydrolysates (SH) significantly decreased the severity of DSS-induced damage, evidenced by increased body weight, colon length, and decreased disease activity index (DAI) and histological scores. SH also inhibited myeloperoxidase (MPO) activity and reduced the serum levels of IL-6, IL-1 beta, and TNF-alpha. Western blotting results revealed that SH suppressed DSS-induced activation of the NF-kappa B and MAPK pathways in the colon. Furthermore, SH partially restored the alteration of the gut microbiota in colitic mice. SH increased the Bacteroidetes/Firmicutes ratio and the relative abundance of Ruminococcaceae, Porphyromonadaceae, and Bacteroidetes S24-7, while decreased the abundance of potentially harmful bacteria Erysipelotrichaceae and Enterococcaceae. These results suggest that SH inhibited DSS-induced colitis by regulating the NF-kappa B and MAPK pathways and modulating microbiota composition.
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| 9. |
- Ruan, Xixian, et al.
(författare)
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Depression and 24 gastrointestinal diseases : a Mendelian randomization study
- 2023
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.
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| 10. |
- Yang, Qinsong, et al.
(författare)
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Genomic basis of the distinct biosynthesis of β-glucogallin, a biochemical marker for hydrolyzable tannin production, in three oak species
- 2024
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Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 242:6, s. 2702-2718
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Tidskriftsartikel (refereegranskat)abstract
- Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in grape wine aging, feed additives, and human healthcare. However, the limited availability of a high-quality reference genome of oaks greatly hampered the recognition of the mechanism of HT biosynthesis. Here, high-quality reference genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and Quercus dentata) that have different HT contents were generated. Multi-omics studies were carried out to identify key genes regulating HT biosynthesis. In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast one-hybrid assays were used to reveal the transcriptional regulation. Our results revealed that β-glucogallin was a biochemical marker for HT production in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme for β-glucogallin biosynthesis. The differential expression of UGT84A13, rather than enzyme activity, was the main reason for different β-glucogallin and HT accumulation. Notably, sequence variations in UGT84A13 promoters led to different trans-activating activities of WRKY32/59, explaining the different expression patterns of UGT84A13 among the three species. Our findings provide three high-quality new reference genomes for oak trees and give new insights into different transcriptional regulation for understanding β-glucogallin and HT biosynthesis in closely related oak species.
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