亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome

自身免疫性肝炎 小桶 转录组 免疫系统 流式细胞术 生物 免疫学 小RNA 计算生物学 医学 肝炎 基因 基因表达 遗传学
作者
Fan Yang,Lei Zhou,Yi Shen,Xianglin Wang,Xiaoli Fan,Li Yang
出处
期刊:Journal of Translational Medicine [BioMed Central]
卷期号:22 (1)
标识
DOI:10.1186/s12967-024-05029-6
摘要

Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) variant syndrome (VS) exhibit a complex overlap of AIH features with PBC, leading to poorer prognoses than those with PBC or AIH alone. The biomarkers associated with drug response and potential molecular mechanisms in this syndrome have not been fully elucidated.Whole-transcriptome sequencing was employed to discern differentially expressed (DE) RNAs within good responders (GR) and poor responders (PR) among patients with PBC/AIH VS. Subsequent gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for the identified DE RNAs. Plasma metabolomics was employed to delineate the metabolic profiles distinguishing PR and GR groups. The quantification of immune cell profiles and associated cytokines was achieved through flow cytometry and immunoassay technology. Uni- and multivariable logistic regression analyses were conducted to construct a predictive model for insufficient biochemical response. The performance of the model was assessed by computing the area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity.The analysis identified 224 differentially expressed (DE) mRNAs, 189 DE long non-coding RNAs, 39 DE circular RNAs, and 63 DE microRNAs. Functional pathway analysis revealed enrichment in lipid metabolic pathways and immune response. Metabolomics disclosed dysregulated lipid metabolism and identified PC (18:2/18:2) and PC (16:0/20:3) as predictors. CD4+ T helper (Th) cells, including Th2 cells and regulatory T cells (Tregs), were upregulated in the GR group. Pro-inflammatory cytokines (IFN-γ, TNF-α, IL-9, and IL-17) were downregulated in the GR group, while anti-inflammatory cytokines (IL-10, IL-4, IL-5, and IL-22) were elevated. Regulatory networks were constructed, identifying CACNA1H and ACAA1 as target genes. A predictive model based on these indicators demonstrated an AUC of 0.986 in the primary cohort and an AUC of 0.940 in the validation cohort for predicting complete biochemical response.A combined model integrating genomic, metabolic, and cytokinomic features demonstrated high accuracy in predicting insufficient biochemical response in patients with PBC/AIH VS. Early recognition of individuals at elevated risk for insufficient response allows for the prompt initiation of additional treatments.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
2秒前
7秒前
宝贝丫头完成签到 ,获得积分10
17秒前
英姑应助背后的鞋垫采纳,获得10
26秒前
桐桐应助Benhnhk21采纳,获得10
27秒前
Dave发布了新的文献求助10
1分钟前
科研通AI2S应助科研通管家采纳,获得10
1分钟前
Aaron完成签到 ,获得积分0
2分钟前
2分钟前
4分钟前
Liufgui应助Dave采纳,获得10
4分钟前
Benhnhk21发布了新的文献求助10
4分钟前
yydragen应助yyds采纳,获得10
4分钟前
Hisam完成签到,获得积分10
4分钟前
lhy完成签到,获得积分10
5分钟前
lhy发布了新的文献求助10
5分钟前
5分钟前
积极的台灯应助Benhnhk21采纳,获得10
5分钟前
Hisam发布了新的文献求助10
5分钟前
yyds完成签到,获得积分0
5分钟前
科研通AI2S应助科研通管家采纳,获得10
5分钟前
木木完成签到 ,获得积分10
6分钟前
6分钟前
董可以发布了新的文献求助10
6分钟前
小马甲应助董可以采纳,获得10
6分钟前
6分钟前
Boren发布了新的文献求助10
6分钟前
梨子完成签到,获得积分10
6分钟前
Boren完成签到,获得积分10
7分钟前
WerWu完成签到,获得积分10
8分钟前
彭于晏应助Dc采纳,获得10
8分钟前
9分钟前
情怀应助科研通管家采纳,获得10
9分钟前
10分钟前
Dc发布了新的文献求助10
10分钟前
Dc完成签到,获得积分10
10分钟前
11分钟前
幽默平安发布了新的文献求助10
11分钟前
科研通AI2S应助科研通管家采纳,获得10
11分钟前
13分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990290
求助须知:如何正确求助?哪些是违规求助? 3532146
关于积分的说明 11256472
捐赠科研通 3271042
什么是DOI,文献DOI怎么找? 1805197
邀请新用户注册赠送积分活动 882302
科研通“疑难数据库(出版商)”最低求助积分说明 809234