Abstract：
BACKGROUND: Ulcerative colitis (UC), a recurrent inflammatory bowel disease, continues to challenge effective pharmacologic management. Disulfidptosis, a recently identified form of cell death, appears implicated in the progression of various diseases. Scientific studies have demonstrated that Modified Gegen Qinlian decoction (MGQD) alleviates UC symptoms. However, the underlying mechanisms remain inadequately elucidated.
OBJECTIVE: This study investigated the role of disulfidptosis in UC and explored the potential of MGQD to ameliorate UC by mediating disulfidptosis.
METHODS: Microarray data were utilized to identify disulfidptosis-related genes stably expressed in UC, and integrated genomic analyses were conducted to elucidate the landscape of disulfidptosis in UC. Subsequently, C57BL/6J mice were administered 3% dextran sodium sulfate (DSS) to induce experimental colitis and treated with MGQD. Quantitative real-time polymerase chain reaction and immunohistochemical analysis of colonic tissues from colitis mice were performed to validate the microarray data findings. Finally, molecular docking was employed to explore the binding interactions between MGQD components and disulfidptosis biomarkers.
RESULTS: Myosin heavy chain 10 (MYH10) and filamin A (FLNA) were identified as stably expressed in UC, demonstrating high diagnostic value for the disease. Correlation analysis indicated that disulfidptosis-related genes are associated with elevated levels of immune cells in UC. Single gene set enrichment analysis further clarified that these genes might be involved in the pathological processes of UC via immune-related pathways. Subsequent animal experiments revealed that MYH10 and FLNA were significantly upregulated in mice with colitis, a condition reversed by MGQD treatment. Molecular docking results showed that MYH10 and FLNA serve as stable binding targets for the primary components of MGQD.
CONCLUSIONS: The study identified a connection between the disulfidptosis-related landscape and immune infiltration in UC, suggesting that MGQD may modulate disulfidptosis by inhibiting MYH10 and FLNA, thereby alleviating UC.
OBJECTIVE: This study investigated the role of disulfidptosis in UC and explored the potential of MGQD to ameliorate UC by mediating disulfidptosis.
METHODS: Microarray data were utilized to identify disulfidptosis-related genes stably expressed in UC, and integrated genomic analyses were conducted to elucidate the landscape of disulfidptosis in UC. Subsequently, C57BL/6J mice were administered 3% dextran sodium sulfate (DSS) to induce experimental colitis and treated with MGQD. Quantitative real-time polymerase chain reaction and immunohistochemical analysis of colonic tissues from colitis mice were performed to validate the microarray data findings. Finally, molecular docking was employed to explore the binding interactions between MGQD components and disulfidptosis biomarkers.
RESULTS: Myosin heavy chain 10 (MYH10) and filamin A (FLNA) were identified as stably expressed in UC, demonstrating high diagnostic value for the disease. Correlation analysis indicated that disulfidptosis-related genes are associated with elevated levels of immune cells in UC. Single gene set enrichment analysis further clarified that these genes might be involved in the pathological processes of UC via immune-related pathways. Subsequent animal experiments revealed that MYH10 and FLNA were significantly upregulated in mice with colitis, a condition reversed by MGQD treatment. Molecular docking results showed that MYH10 and FLNA serve as stable binding targets for the primary components of MGQD.
CONCLUSIONS: The study identified a connection between the disulfidptosis-related landscape and immune infiltration in UC, suggesting that MGQD may modulate disulfidptosis by inhibiting MYH10 and FLNA, thereby alleviating UC.
摘要：
背景：溃疡性结肠炎（UC），复发性炎症性肠病,继续挑战有效的药物管理。二硫化物下垂，一种最近确定的细胞死亡形式，似乎与各种疾病的进展有关。科学研究表明，加味葛根芩连汤（MGQD）可以缓解UC症状。然而,潜在的机制仍未得到充分阐明。
目的：本研究探讨了二硫沉积在UC中的作用，并探讨了MGQD通过介导二硫沉积改善UC的潜力。
方法：微阵列数据用于鉴定在UC中稳定表达的双硫细胞凋亡相关基因，并进行了整合的基因组分析，以阐明UC中二硫键沉积的景观。随后，向C57BL/6J小鼠施用3%葡聚糖硫酸钠(DSS)以诱导实验性结肠炎并用MGQD治疗。进行来自结肠炎小鼠的结肠组织的定量实时聚合酶链反应和免疫组织化学分析以验证微阵列数据发现。最后,采用分子对接技术探索MGQD组分与二硫键沉积生物标志物之间的结合相互作用。
结果：肌球蛋白重链10（MYH10）和丝素A（FLNA）在UC中稳定表达，对该疾病具有很高的诊断价值。相关分析显示，双硫细胞凋亡相关基因与UC患者免疫细胞水平升高有关。单基因集富集分析进一步阐明了这些基因可能通过免疫相关途径参与UC的病理过程。随后的动物实验显示，在结肠炎小鼠中，MYH10和FLNA显著上调，通过MGQD治疗逆转的病症。分子对接结果显示MYH10和FLNA作为MGQD主要成分的稳定结合靶标。
结论：该研究确定了UC中与二硫键下垂相关的景观和免疫浸润之间的联系，提示MGQD可能通过抑制MYH10和FLNA调节二硫键凋亡，从而缓解UC。
目的：本研究探讨了二硫沉积在UC中的作用，并探讨了MGQD通过介导二硫沉积改善UC的潜力。
方法：微阵列数据用于鉴定在UC中稳定表达的双硫细胞凋亡相关基因，并进行了整合的基因组分析，以阐明UC中二硫键沉积的景观。随后，向C57BL/6J小鼠施用3%葡聚糖硫酸钠(DSS)以诱导实验性结肠炎并用MGQD治疗。进行来自结肠炎小鼠的结肠组织的定量实时聚合酶链反应和免疫组织化学分析以验证微阵列数据发现。最后,采用分子对接技术探索MGQD组分与二硫键沉积生物标志物之间的结合相互作用。
结果：肌球蛋白重链10（MYH10）和丝素A（FLNA）在UC中稳定表达，对该疾病具有很高的诊断价值。相关分析显示，双硫细胞凋亡相关基因与UC患者免疫细胞水平升高有关。单基因集富集分析进一步阐明了这些基因可能通过免疫相关途径参与UC的病理过程。随后的动物实验显示，在结肠炎小鼠中，MYH10和FLNA显著上调，通过MGQD治疗逆转的病症。分子对接结果显示MYH10和FLNA作为MGQD主要成分的稳定结合靶标。
结论：该研究确定了UC中与二硫键下垂相关的景观和免疫浸润之间的联系，提示MGQD可能通过抑制MYH10和FLNA调节二硫键凋亡，从而缓解UC。
