Identification of potential targets in bone destruction by Talaromyces marneffei: Insights from data-independent acquisition proteomics.

IF 2.3 3区 医学 Q3 INFECTIOUS DISEASES
Junhong Zhou, Deshuang Xi, Yilin Teng, Yanbin Feng, Baicheng Wan, Shaohui Zong, Gaofeng Zeng
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引用次数: 0

Abstract

To investigate the molecular mechanisms of Talaromyces marneffei (TM)-induced bone destruction through proteomic analysis using Data-Independent Acquisition (DIA) technology. Bone tissue samples were collected from eight patients (four TM-infected cases, four non-infectious controls). Samples underwent histopathological evaluation (Hematoxylin and Eosin Staining and Wright-Giemsa staining), DIA proteomics analysis, and protein validation through immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Comparative analysis between Control (Con) and Infected (Inf) groups showed similar demographics but significantly elevated inflammatory markers in Inf. Histopathology revealed extensive bone destruction, marked inflammatory infiltration, fibrinoid necrosis, and altered hematopoietic cell populations in Inf specimens compared to Con. DIA proteomics identified 5930 quantifiable proteins, with 509 differentially expressed proteins (DEPs) between groups. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses revealed significant enrichment of inflammation and immune response-related functions in Inf. COMMD1 was significantly downregulated while IL-17 was upregulated in Inf, as validated by immunohistochemistry and ELISA. DIA proteomics identified downregulated COMMD1 and upregulated IL-17 in TM-induced bone destruction, suggesting potential diagnostic biomarkers and therapeutic targets through inflammatory pathway modulation.

鉴定马尔尼菲Talaromyces marneffei骨破坏的潜在目标:来自数据独立获取蛋白质组学的见解。
采用数据独立采集(Data-Independent Acquisition, DIA)技术进行蛋白质组学分析,探讨Talaromyces marneffei (TM)诱导骨破坏的分子机制。采集8例患者的骨组织样本(4例tm感染病例,4例非感染对照)。样品进行组织病理学评估(苏木精和伊红染色和Wright-Giemsa染色),DIA蛋白质组学分析,并通过免疫组织化学和ELISA进行蛋白质验证。对照组(Con)和感染组(Inf)之间的比较分析显示相似的人口统计学特征,但Inf中的炎症标志物显著升高。组织病理学显示,与Con相比,Inf标本中广泛的骨破坏,明显的炎症浸润,纤维蛋白样坏死和造血细胞群的改变。DIA蛋白质组学鉴定出5930种可量化的蛋白质,组间有509种差异表达蛋白(DEPs)。GO和KEGG通路分析显示,Inf中炎症和免疫反应相关功能显著富集。免疫组织化学和ELISA证实,Inf中COMMD1显著下调,IL-17上调。DIA蛋白质组学发现COMMD1下调和IL-17上调在tm诱导的骨破坏中,提示通过炎症通路调节潜在的诊断生物标志物和治疗靶点。
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来源期刊
Medical mycology
Medical mycology 医学-兽医学
CiteScore
5.70
自引率
3.40%
发文量
632
审稿时长
12 months
期刊介绍: Medical Mycology is a peer-reviewed international journal that focuses on original and innovative basic and applied studies, as well as learned reviews on all aspects of medical, veterinary and environmental mycology as related to disease. The objective is to present the highest quality scientific reports from throughout the world on divergent topics. These topics include the phylogeny of fungal pathogens, epidemiology and public health mycology themes, new approaches in the diagnosis and treatment of mycoses including clinical trials and guidelines, pharmacology and antifungal susceptibilities, changes in taxonomy, description of new or unusual fungi associated with human or animal disease, immunology of fungal infections, vaccinology for prevention of fungal infections, pathogenesis and virulence, and the molecular biology of pathogenic fungi in vitro and in vivo, including genomics, transcriptomics, metabolomics, and proteomics. Case reports are no longer accepted. In addition, studies of natural products showing inhibitory activity against pathogenic fungi are not accepted without chemical characterization and identification of the compounds responsible for the inhibitory activity.
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