8 results on '"Sun, Liangdan"'
Search Results
2. Cutaneous Calcium/Calmodulin‐Dependent Protein Kinase II‐γ–Positive Sympathetic Nerves Secreting Norepinephrine Dictate Psoriasis.
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Yu, Yafen, Chen, Weiwei, Li, Bao, Li, Zhuo, Wang, Yirui, Mao, Yiwen, Fan, Wencheng, Bai, Yuanming, Hu, Hongbo, Zhen, Qi, and Sun, Liangdan
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PROTEIN kinases ,NORADRENALINE ,PSORIASIS ,CD30 antigen ,NERVES ,SKIN inflammation - Abstract
Cutaneous sympathetic nerve is a crucial part of neuropsychiatric factors contributing to skin immune response, but its role in the psoriasis pathogenesis remains unclear. It is found that cutaneous calcium/calmodulin‐dependent protein kinase II‐γ (CAMK2γ), expressed mainly in sympathetic nerves, is activated by stress and imiquimod in mouse skin. Camk2g‐deficient mice exhibits attenuated imiquimod‐induced psoriasis‐like manifestations and skin inflammation. CaMK2γ regulates dermal γδT‐cell interleukin‐17 production in imiquimod‐treated mice, dependent on norepinephrine production following cutaneous sympathetic nerve activation. Adrenoceptor β1, the primary skin norepinephrine receptor, colocalises with γδT cells. CaMK2γ aggravates psoriasiform inflammation via sympathetic nerve–norepinephrine–γδT cell–adrenoceptor β1–nuclear factor‐κB and –p38 axis activation. Application of alcaftadine, a small‐molecule CaMK2γ inhibitor, relieves imiquimod‐induced psoriasis‐like manifestations in mice. This study reveals the mechanisms of sympathetic‐nervous‐system regulation of γδT‐cell interleukin‐17 secretion, and provides insight into neuropsychiatric factors dictating psoriasis pathogenesis and new potential targets for clinical psoriasis treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Genome wide association study and meta‐analysis identified multiple new risk loci for freckles in 4813 Chinese individuals.
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Luo, Sihan, Li, Zhuo, Wang, Minhao, Liu, Zhili, Wang, Daiyue, Bai, Yuanming, Ge, Huiyao, Yu, Yafen, Yu, Yanxia, Chen, Weiwei, Wang, Yirui, Zhang, Chang, Yu, Jing, Song, Can, Lv, Chengzhi, Zhen, Qi, Han, Yang, and Sun, Liangdan
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GENOME-wide association studies , *LOCUS (Genetics) , *LINKAGE disequilibrium - Abstract
Freckle is a prevalent pigmentary dermatosis with an obvious hereditary component. Dozens of freckles risk loci have been discovered through research on multiple traits or other diseases, rather than as an independent trait. To discover novel variants associated with freckles, we performed GWAS and meta‐analysis in 4813 Chinese individuals. We conducted GWAS and meta‐analysis of two cohorts: 197 patients and 1603 controls (Cohort I), and 336 patients and 2677 controls (Cohort II), both from China. Then we performed linkage disequilibrium (LD) analysis, eQTL study, and enrichment analysis with association results for functional implications. Finally, we discovered 59 new SNPs and 13 novel susceptibility genes associated with freckles (Pmeta <5 × 10−8), which has enriched the genetic research on freckles. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Correlation between double‐stranded DNA and acute urticaria.
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Li, Yuanyuan, Li, Zhuo, Lu, Jiayi, Qu, Guangbo, Qin, Qin, Zhang, Chang, Bai, Yuanming, Wang, Daiyue, Luo, Sihan, Li, Bao, Han, Yang, Chen, Weiwei, Zhen, Qi, and Sun, Liangdan
- Abstract
Background Methods Results Conclusions Acute urticaria is a prevalent inflammatory dermatosis characterized by fulminant wheals, often accompanied by severe pruritis. It may also cause nausea, vomiting, and abdominal pain. Numerous studies have substantiated the pivotal involvement of double‐stranded DNA (dsDNA) in autoimmunity. However, the role of dsDNA in the pathogenesis of acute urticaria is unclear.We measured serum dsDNA levels in patients and controls. The relationship between dsDNA levels and environmental exposures (temperature, ultraviolet [UV] index, and season) was investigated by correlating disease onset dates with archived meteorological data. Finally, we used quantitative PCR to determine the expressions of genes encoding dsDNA receptors, single‐stranded RNA (ssRNA) receptors, exosome formation, and type I interferon in the peripheral blood of patients and controls.Serum dsDNA levels were significantly higher in patients with acute urticaria compared with controls (mean values 1.38 and 0.94 ng/ml, respectively, P < 0.001). dsDNA levels were higher in patients exposed to higher environmental temperatures and UV indices and were higher during the summer months. We also found that the expressions of genes encoding dsDNA receptors, ssRNA receptors, absent in melanoma factor 2 (AIM2)‐related inflammatory factors, and interferon alpha were up‐regulated in patients.We demonstrated that serum dsDNA levels are elevated in acute urticaria and are influenced by climatic factors such as temperature, ultraviolet index, and season. We also found that elevated dsDNA promotes the expression of AIM2‐related factors and type I interferons. This study generates new hypotheses regarding the pathogenesis of acute urticaria and suggests novel therapeutic targets. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.
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Liu X, Zheng X, Shu Y, Qu X, Wang Q, Liu X, Hu FY, Liu J, Lian Y, He BM, Li C, Zhou D, Qiu W, Sun L, and Hong Z
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- Humans, Genome-Wide Association Study, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class II genetics, HLA-A Antigens genetics, Anti-N-Methyl-D-Aspartate Receptor Encephalitis genetics, HLA-DQ beta-Chains genetics, Interferon-Induced Helicase, IFIH1 genetics
- Abstract
Background and Objectives: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population., Methods: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls., Results: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10
-8 , OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 ( p = 1.43 × 10-12 ; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 ( p = 4.36 × 10-7 ; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 ( p = 1.28 × 10-8 ; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQβ1-126H ( p = 1.43 × 10-12 ; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R ( p = 3.40 × 10-8 ; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02., Discussion: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.- Published
- 2024
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6. Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study.
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Xu L, Zheng X, Yin S, Yang K, Fan Q, Gu Y, Yuan Y, Yin C, Zang Y, Pang C, Sun L, and Ren S
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- Humans, Female, Male, China epidemiology, Adult, Young Adult, Middle Aged, Cornea pathology, Adolescent, Genetic Loci, Corneal Topography, East Asian People, Keratoconus genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Asian People genetics, Genotype
- Abstract
Purpose: Keratoconus (KC) is a progressive corneal disease that can lead to corneal blindness if not properly managed. The purpose of this study was to identify genetic associations with KC in China and to investigate whether these genetic variants are associated with corneal thickness and corneal curvature in KC cases., Methods: A genome-wide association study was conducted on 853 patients with KC and 6248 controls. The KC cases were genotyped with the Illumina Infinium Human Asian Screening Array BeadChip, and the controls were genotyped with the Illumina Infinium Human Global Screening Array BeadChip. Genetic associations with KC, as well as correlations between the positive variants and corneal parameters including central corneal thickness (CCT) and mean keratometry (Km), were compared using PLINK version 1.90., Results: Our present study identified four single-nucleotide polymorphisms (SNPs) within four risk loci (PTGER3: rs2300163, EYA1: rs1077435, ASS1: rs141365191, and CHTF8: rs3743680) associated with KC in Chinese patients that reached genome-wide significance. Among the identified SNPs with P < 1.00 × 10-4, seven SNPs (FOSL2-PLB1: rs12622211, RXRA-COL5A1: rs3118515, rs3132306, rs1536482, rs3118520, KAT6B: rs192187772, RAP2A-IPO5: rs41361245) were observed to be associated with CCT, and one SNP (USP13: rs6767552) was found to be associated with Km., Conclusions: In the first genome-wide association study of KC with a relatively large study population in China, we identified four SNPs in four risk loci associated with the disease. The findings enriched the understanding of genetic susceptibility to KC and provided new insights into the genetic etiology of the disease.
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- 2024
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7. Effectiveness of guselkumab in patients with moderate-to-severe plaque psoriasis: a retrospective study from China.
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Huang H, Liu H, Zhu Z, Wang W, Liang B, Tang H, Yang S, Sheng Y, Sun L, and Zhang X
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- Humans, Retrospective Studies, Severity of Illness Index, China, Treatment Outcome, Antibodies, Monoclonal, Psoriasis drug therapy, Antibodies, Monoclonal, Humanized
- Abstract
Data on guselkumab as treatment for moderate-to-severe plaque psoriasis, especially in different body regions, in China is limited. This study aimed to estimate the effectiveness of guselkumab in Chinese patients with moderate-to-severe plaque psoriasis, including effectiveness at different body regions. This multicentre, observational study retrospectively enrolled patients with moderate-to-severe plaque psoriasis. Effectiveness outcome was based on Psoriasis Area and Severity Index (PASI) response and improvement in Body Surface Area (BSA) and Dermatology Life Quality Index (DLQI). A total of 51 patients were included, with a median age of 44.00 (18.00, 74.00) years and median duration of psoriasis of 10.00 (0.50, 55.00) years. After 20 weeks of treatment, PASI response with 75% improvement from baseline (PASI 75) was reported in 96.1% of patients; 72.5% of patients achieved a DLQI score of 0-1 at week 20. The percentage of affected BSA was significantly decreased at week 4 (p<0.05), week 12 (p<0.001) and week 20 (p<0.001). PASI score significantly changed from baseline after four weeks (p<0.001), 12 weeks (p<0.001) and 20 weeks of treatment (p<0.001). DLQI score significantly increased at week 4 (p<0.001), week 12 (p<0.001) and week 20 (p<0.001). PASI 75 was achieved for the upper limbs in all cases and 100% PASI improvement (PASI 100) in 89.1%. The head and lower limbs were the areas least responsive to treatment, with PASI 100 achieved in only 68.6% and 70.6%, respectively. Guselkummab provided rapid and sustained PASI improvement, especially for the skin of the upper limbs and body trunk.
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- 2024
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8. Genome-Wide Meta-Analysis Identifies 11 Susceptibility Variants of Vitiligo in the Chinese Han Population.
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Wang D, Chen W, Wang Y, Yu J, Bai Y, Luo S, Song C, Wang M, Yu Y, Li Z, Han Y, Zhen Q, and Sun L
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Vitiligo is an autoimmune disease involving loss of melanocytes. Although several genetic studies have confirmed that genetic factors play an important role, its pathogenesis remains incompletely characterized. In this study, a genome-wide meta-analysis was conducted to search for more susceptibility variants of vitiligo. Tang et al performed a GWAS for cohort I (1117 vitiligo cases and 1701 healthy controls) previously, and we conducted a GWAS for cohort II (3323 vitiligo cases and 7186 healthy controls) in this study, with the results subjected to a genome-wide meta-analysis and linkage disequilibrium analysis. We identify, to our knowledge, 11 previously unreported susceptibility variants, of which 6 variants are located in the intronic regions, and the remaining 5 variants are located within intergenic regions between genes. In addition, the results of polygenic risk score show that the best evaluated effect for target data is among significant SNVs of the base data. The susceptibility genes of vitiligo are mainly enriched in the immune-related functions and pathways. The susceptibility variants expand the role of genetic factors associated with vitiligo. The bioinformatics analysis for risk genes provides further insight into the pathogenesis of vitiligo., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
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