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整合多组学和单细胞通讯分析以揭示强直性脊柱炎的发病机制。

Integrating multiomics and Single-Cell communication analysis to uncover Ankylosing spondylitis mechanisms.

机构信息

The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, Guangxi, 530021, P.R. China.

出版信息

Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113276. doi: 10.1016/j.intimp.2024.113276. Epub 2024 Oct 1.

DOI:10.1016/j.intimp.2024.113276
PMID:39357209
Abstract

BACKGROUND

Ankylosing spondylitis (AS) is a chronic inflammatory joint disorder, necessitating early diagnosis and effective treatment. The specific mechanism of action of Cassia twigs in the treatment of AS is not fully understood.

METHODS

Blood samples and clinical data from 28,458 individuals (6,101 with AS, 22,357 without AS) were collected. To construct a predictive model, we utilized logistic regressions and machine learning techniques to create a dynamic nomogram. Immune cell infiltration was evaluated using the GSE73754 dataset. Subsequently, we obtained vertebral bone marrow blood from AS patients for 10X single-cell sequencing. We also extracted and purified total RNA from hip joint ligament tissue samples from six AS patients and six non-AS patients. The genes related to the expression of AS and Cassia twigs were analyzed comprehensively, and the specific drug targets were identified by molecular docking. The interactions between immune cells through cell communication analysis were elucidated.

RESULTS

We developed a dynamic nomogram incorporating the neutrophil count (NEUT) and other variables. Neutrophil immune responses were confirmed through immune infiltration analysis utilizing GSE73754. We observed the early involvement of neutrophils in the pathology of AS. The CAT-expressing Cassia twigs gene could be used as a drug target for the treatment of AS. Moreover, comprehensive RNA analysis revealed notable CAT expression in neutrophils and various other immune cells.

CONCLUSIONS

Neutrophils play dual roles in AS, regulating inflammation and initiating differentiation signals to other cells. The CAT gene, which is expressed in Cassia twigs, has emerged as a potential therapeutic target for AS treatment.

摘要

背景

强直性脊柱炎(AS)是一种慢性炎症性关节疾病,需要早期诊断和有效治疗。桂枝治疗 AS 的具体作用机制尚不完全清楚。

方法

收集了 28458 个人的血液样本和临床数据(6101 例 AS,22357 例非 AS)。为了构建预测模型,我们利用逻辑回归和机器学习技术创建了一个动态列线图。使用 GSE73754 数据集评估免疫细胞浸润。随后,我们从 AS 患者获取了椎骨骨髓血进行 10X 单细胞测序。我们还从 6 例 AS 患者和 6 例非 AS 患者的髋关节韧带组织样本中提取和纯化了总 RNA。综合分析与 AS 和桂枝表达相关的基因,并通过分子对接确定特定的药物靶点。通过细胞通讯分析阐明免疫细胞之间的相互作用。

结果

我们开发了一个包含中性粒细胞计数(NEUT)和其他变量的动态列线图。通过 GSE73754 的免疫浸润分析,证实了中性粒细胞免疫反应。我们观察到中性粒细胞早期参与 AS 的病理学过程。表达 CAT 的桂枝基因可作为治疗 AS 的药物靶点。此外,综合 RNA 分析显示中性粒细胞和其他各种免疫细胞中 CAT 表达显著。

结论

中性粒细胞在 AS 中发挥双重作用,调节炎症并向其他细胞发出分化信号。在桂枝中表达的 CAT 基因已成为 AS 治疗的潜在治疗靶点。

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