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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- 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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| 4. |
- Shen, Gulou, et al.
(författare)
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Partition and selectivity of electrolytes in cylindrical nanopores with heterogeneous surface charge
- 2021
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Ingår i: Journal of Molecular Liquids. - : Elsevier. - 0167-7322 .- 1873-3166. ; 340
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Tidskriftsartikel (refereegranskat)abstract
- In this work, ion partitioning and selectivity in cylindrical nanopores with heterogeneous surface charges at equilibrium with reservoirs are investigated by a two-dimensional (2D) classical density functional theory (DFT). We present an efficient numerical method for the large 2D system in which the fast Hankel transform and fast Fourier transform are used to calculate convolution integrals, and a hybrid method of Picard iteration and Anderson mixing is used to solve the Euler-Lagrange equations. The performance of the 2D DFT is tested by calculating the profiles of a model electrolyte in long homogeneous cylindrical nanopores. The profiles from the 2D DFT model matches well with those from a 1D DFT, and the computing time of the hybrid iteration algorithm is six times shorter than that of pure Picard iteration. We apply the model to electrolytes in cylindrical nanopores with heterogeneous surface charges. It is found that the ion adsorption and selectivity are strongly affected by the surface charge pattern, the magnitude of the surface charge, the size of charged domains on the surface, and the pore size.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- Zhang, Man, et al.
(författare)
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Highly Efficient Room-Temperature Light-Induced Synthesis of Polymer Dots: A Programming Control Paradigm of Polymer Nanostructurization from Single-Component Precursor
- 2023
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Ingår i: Journal of the American Chemical Society. - : AMER CHEMICAL SOC. - 0002-7863 .- 1520-5126. ; 145:45, s. 24657-24668
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Tidskriftsartikel (refereegranskat)abstract
- Polymer dots (PDs) have raised considerable research interest due to their advantages of designable nanostructures, high biocompatibility, versatile photoluminescent properties, and recyclability as nanophase. However, there remains a lack of in situ, real-time, and noncontact methods for synthesizing PDs. Here we report a rational strategy to synthesize PDs through a well-designed single-component precursor (an asymmetrical donor-acceptor-donor molecular structure) by photoirradiation at ambient temperature. In contrast to thermal processes that normally lack atomic economy, our method is mild and successive, based on an aggregation-promoted sulfonimidization triggered by photoinduced delocalized intrinsic radical cations for polymerization, followed by photooxidation for termination with structural shaping to form PDs. This synthetic approach excludes any external additives, rendering a conversion rate of the precursor exceeding 99%. The prepared PDs, as a single entity, can realize the integration of nanocore luminescence and precursor-transferred luminescence, showing 41.5% of the total absolute luminescence quantum efficiency, which is higher than most reported PD cases. Based on these photoluminescent properties, together with the superior biocompatibility, a unique membrane microenvironmental biodetection could be exemplified. This strategy with programming control of the single precursor can serve as a significant step toward polymer nanomanufacturing with remote control, high-efficiency, precision, and real-time operability.
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| 8. |
- Zhang, Yuehui, et al.
(författare)
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Hyperandrogenism and insulin resistance contribute to hepatic steatosis and inflammation in female rat liver.
- 2018
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:26, s. 18180-18197
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Tidskriftsartikel (refereegranskat)abstract
- Women with polycystic ovary syndrome (PCOS) are at high risk for nonalcoholic fatty liver disease (NAFLD). While insulin resistance is a common trait for both PCOS and NAFLD, hyperandrogenism is also considered to be a key factor contributing to PCOS, and the molecular mechanisms behind the interactions between insulin resistance and hyperandrogenism in the female liver remain largely unexplored. Using chronic treatment with insulin and/or human chorionic gonadotropin (hCG), we showed that all female rats with different treatments induced imbalance between de novo lipogenesis and mitochondrial β-oxidation via the Pparα/β-Srebp1/2-Acc1 axis, resulting in varying degrees of hepatic steatosis. Given the fact that hepatic lipid metabolism and inflammation are tightly linked processes, we found that hCG-induced hyperandrogenic rats had strongly aggravated hepatic inflammation. Further mechanistic investigations revealed that dysregulation of the IRS-PI3K-Akt signaling axis that integrated aberrant inflammatory, apoptotic and autophagic responses in the liver was strongly associated with hyperandrogenism itself or combined with insulin resistance. Additionally, we found that hCG-treated and insulin+hCG-induced rats developed visceral adipose tissue inflammation characterized by the presence of "crown like" structure and increased inflammatory gene expression. Because a more pronounced hepatic steatosis, inflammatory responses, and hepatocyte cell damage were observed in insulin+hCG-induced PCOS-like rats, our finding suggest that NAFLD seen in PCOS patients is dependent of hyperandrogenism and insulin resistance.
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| 9. |
- Zhang, Yuehui, et al.
(författare)
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Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus.
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells. These defects are associated with an aberration in the PI3K/Akt signaling pathway that is used as an indicator for the onset of insulin resistance in classical metabolic tissues. Concomitantly, increased GSK3β (Ser-9) phosphorylation and decreased ERK1/2 phosphorylation in rats treated with insulin and hCG were also observed. We also profiled the expression of glucose transporter (Glut) isoform genes in the uterus under conditions of insulin resistance and/or hyperandrogenism. Finally, we determined the expression pattern of glycolytic enzymes and intermediates during insulin resistance and hyperandrogenism in the uterus. These findings suggest that the PI3K/Akt and MAPK/ERK signaling pathways play a role in the onset of uterine insulin resistance, and they also suggest that changes in specific Glut isoform expression and alterations to glycolytic metabolism contribute to the endometrial dysfunction observed in PCOS patients.
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| 10. |
- Chen, Jie, et al.
(författare)
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Antioxidants, minerals and vitamins in relation to Crohn's disease and ulcerative colitis : A Mendelian randomization study
- 2023
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 57:4, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEvidence for antioxidants, minerals and vitamins in relation to the risk of Crohn's disease (CD) and ulcerative colitis (UC) is limited and inconsistent. This mendelian randomization (MR) study aimed to examine the causal associations of circulating levels of antioxidants, minerals and vitamins with CD and UC.MethodsSingle-nucleotide polymorphisms associated with antioxidants (beta-carotene, lycopene and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc and selenium), and vitamins (folate, vitamins A, B6, B12, C, D, E and K1) were employed as instrumental variables. Genetic associations with CD and UC were extracted from the UK Biobank, the FinnGen study and the International Inflammatory Bowel Disease Genetics Consortium. The inverse variance weighted method and sensitivity analyses were performed.ResultsGenetically predicted higher lycopene (OR = 0.94, 95% CI: 0.91–0.97), vitamins D (OR = 0.65, 95% CI: 0.54–0.79) and K1 (OR = 0.93, 95% CI: 0.90–0.97) levels were inversely associated with CD risk, whereas genetically predicted higher magnesium (OR = 1.53, 95% CI: 1.23–1.90) levels were positively associated with CD risk. Higher levels of genetically predicted lycopene (OR = 0.91, 95% CI: 0.88–0.95), phosphorus (OR = 0.69, 95% CI: 0.58–0.82), selenium (OR = 0.91, 95% CI: 0.85–0.97), zinc (OR = 0.91, 95% CI: 0.89–0.94), folate (OR = 0.71, 95% CI: 0.56–0.92) and vitamin E (OR = 0.78, 95% CI: 0.69–0.88) were associated with reduced UC risk, whereas genetically predicted high levels of calcium (OR = 1.46, 95% CI: 1.22–1.76) and magnesium (OR = 1.24, 95% CI: 1.03–1.49) were associated with increased risk of UC.ConclusionsOur study provided evidence that circulating levels of antioxidants, minerals and vitamins might be causally linked to the development of IBD.
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