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宋世雷, 陈跃平.骨质疏松症铜死亡基因的免疫浸润分析及潜在中药预测[J].湖南中医药大学学报英文版,2024,44(6):1100-1109.[Click to copy
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| 骨质疏松症铜死亡基因的免疫浸润分析及潜在中药预测 |
| 宋世雷,陈跃平 |
| (广西中医药大学, 广西 南宁 530200;广西中医药大学附属瑞康医院, 广西 南宁 530011) |
| 摘要: |
| 目的 通过分析铜死亡基因在骨质疏松症（osteoporosis，OP）免疫浸润中的作用，探索与OP相关的免疫细胞、免疫功能、生物标志物和潜在治疗中药。方法 从GEO数据库检索下载OP数据集，对其进行标准化处理和消除批次效应后合并。提取数据集中铜死亡的相关基因后，进行免疫浸润分析并构建风险模型，对铜死亡基因进行富集分析和中药预测。结果 （1）对GSE13850、GSE56116、GSE56815、GSE230665数据集合并后筛选出18个铜死亡基因；（2）树突状细胞、B细胞、CD8+T细胞等在细胞浸润中占比较高，免疫细胞功能主要表现为抗原呈递共抑制、Ⅰ型干扰素反应、Ⅱ型干扰素反应等；（3）与健康对照组相比，巨噬细胞与未成熟树突状细胞在OP患者组中呈现高表达，而滤泡辅助性T细胞在健康对照组中显著表达；（4）SLC31A1等13个铜死亡基因与OP免疫浸润相关，其中，SLC31A1最有可能是导致OP的风险因子；（5）OP的进展涉及乙酰辅酶A生物合成与代谢等生物过程，与脂肪酸代谢、三羧酸循环等通路相关；（6）共筛选出鱼鳔胶等10味重要中药，四气多属温、平，五味多属甘，归肾、脾经，功效多为补气、健脾、补肾、活血、行气和止痛。结论 铜死亡基因可能通过干预免疫细胞和功能参与OP的进展。SLC31A1等铜死亡基因可能有助于阐释OP的发病机制，并成为潜在的生物学标志物及治疗靶点，鱼鳔胶等中药可能是防治OP潜在分子药物的来源。 |
| 关键词: 铜死亡 骨质疏松症 免疫浸润 单样本基因集富集分析 中药预测 |
| DOI：10.3969/j.issn.1674-070X.2024.06.025 |
| Received:March 03, 2024 |
| 基金项目:国家自然科学基金项目（82360937）；广西中医药大学A类“桂派中医药传承创新团队”（2022A004）。 |
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| Immune infiltration analysis of cuproptosis-related genes in osteoporosis and prediction of potential Chinese medicines |
| SONG ShiLei, CHEN Yueping |
| (Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China;Ruikang Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, China) |
| Abstract: |
| Objective To analyze the role of cuproptosis-related genes in immune infiltration of osteoporosis (OP), so as to explore the immune cells, immune function, biomarkers, and potential therapeutic Chinese medicines related to OP. Methods The OP datasets were retrieved and downloaded from the GEO database, and they were standardized and merged after eliminating batch effects. After extracting the relevant cuproptosis-related genes from the datasets, the immune infiltration analysis was carried out and the risk model was constructed to perform enrichment analysis on the cuproptosis-related genes and to predict Chinese medicines with potential therapeutic effects. Results (1) Eighteen cuproptosis-related genes were screened from the merged datasets of GSE13850, GSE56116, GSE56815, and GSE230665; (2) dendritic cells, B cells, CD8+T cells, and other cells accounted for a relatively high proportion in cell infiltration, and immune cell functions mainly manifested as antigen presentation co-suppression, type I interferon response, type II interferon response, and others; (3) compared with the healthy control group, macrophages and immature dendritic cells were highly expressed in the OP group, while follicular helper T cells were significantly expressed in the healthy control group; (4) thirteen cuproptosis-related genes including SLC31A1 were associated with OP immune infiltration, among which SLC31A1 was the most likely risk factor for OP; (5) the progress of OP involved biological processes such as acetyl-CoA biosynthesis and metabolism, which were related to fatty acid metabolism, tricarboxylic acid cycle, and other pathways; (6) a total of ten important Chinese medicines, including fish bladder glue, were screened out. Most of them are warm and neutral in property, sweet in flavour, and access the kidney and spleen meridians. And their effects are mostly supplementing qi, strengthening the spleen, tonifying the kidney, circulating blood, moving qi, and alleviating pain. Conclusion Cuproptosis-related genes may be involved in the progression of OP by intervening with immune cells and functions. Those such as SLC31A1 may help elucidate the pathogenesis of OP and become potential biological markers and therapeutic targets. Moreover, Chinese medicines such as fish bladder glue may be the source of potential molecular drugs for OP prevention and treatment. |
| Key words: cuproptosis osteoporosis immune infiltration single-sample gene set enrichment analysis Chinese medicines prediction |
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