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转录组学鉴定糖尿病足溃疡感染中表达的基因。

Transcriptomic identification of genes expressed in invasive diabetic foot ulcer infection.

机构信息

Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT, United States.

Division of Life Science, Gyeongsang National University, Jinju, Republic of Korea.

出版信息

Front Cell Infect Microbiol. 2023 Jun 26;13:1198115. doi: 10.3389/fcimb.2023.1198115. eCollection 2023.

DOI:10.3389/fcimb.2023.1198115
PMID:37434783
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10332306/
Abstract

INTRODUCTION

Infection in diabetic foot ulcers (DFUs) is one of the major complications associated with patients with diabetes. is the most common offending pathogen in patients with infected DFU. Previous studies have suggested the application of species-specific antibodies against for diagnosis and monitoring treatment response. Early and accurate identification of the main pathogen is critical for management of DFU infection. Understanding the host immune response against species-specific infection may facilitate diagnosis and may suggest potential intervention options to promote healing infected DFUs. We sought to investigate evolving host transcriptome associated with surgical treatment of - infected DFU.

METHODS

This study compared the transcriptome profile of 21 patients with - infected DFU who underwent initial foot salvage therapy with irrigation and debridement followed by intravenous antibiotic therapy. Blood samples were collected at the recruitment (0 weeks) and 8 weeks after therapy to isolate peripheral blood mononuclear cells (PBMCs). We analyzed the PBMC expression of transcriptomes at two different time points (0 versus 8 weeks). Subjects were further divided into two groups at 8 weeks: healed (n = 17, 80.95%) versus non-healed (n = 4, 19.05%) based on the wound healing status. DESeq2 differential gene analysis was performed.

RESULTS AND DISCUSSION

An increased expression of , , , , and was noted during active infection at 0 weeks compared with that at 8 weeks. Lysine- and arginine-rich histones (, , , , and ) were upregulated at the initial phase of active infection at 0 weeks. and were also upregulated at the initial phase of active infection (0 weeks) compared with that at 8 weeks of follow-up. Genes of heat shock protein members (, , and ) were high in not healed patients compared with that in healed patients 8 weeks after therapy. The outcome of our study suggests that the identification of genes evolution based on a transcriptomic profiling could be a useful tool for diagnosing infection and assessing severity and host immune response to therapies.

摘要

简介

糖尿病足溃疡(DFU)感染是糖尿病患者的主要并发症之一。金黄色葡萄球菌是感染 DFU 患者最常见的致病病原体。先前的研究表明,针对 的种特异性抗体在诊断和监测治疗反应方面具有应用价值。早期、准确地识别主要病原体对于 DFU 感染的管理至关重要。了解宿主针对种特异性感染的免疫反应可能有助于诊断,并可能提示促进感染性 DFU 愈合的潜在干预选择。我们试图研究与 - 感染的 DFU 手术治疗相关的宿主转录组的演变。

方法

本研究比较了 21 例接受初始足挽救治疗(冲洗和清创,随后静脉用抗生素治疗)的 - 感染 DFU 患者的转录组谱。在招募时(0 周)和治疗后 8 周采集血样以分离外周血单核细胞(PBMC)。我们分析了两个不同时间点(0 周与 8 周)PBMC 转录组的表达。根据伤口愈合情况,将患者在 8 周时进一步分为愈合组(n = 17,80.95%)和未愈合组(n = 4,19.05%)。采用 DESeq2 差异基因分析。

结果与讨论

与 8 周时相比,在 0 周的活跃感染期, 、 、 、 和 表达增加。在 0 周活跃感染的初始阶段,赖氨酸和精氨酸丰富的组蛋白( 、 、 、 和 )上调。与 8 周随访相比,在活跃感染的初始阶段(0 周), 和 也上调。与治疗 8 周后的愈合患者相比,热休克蛋白成员( 、 、 和 )的基因在未愈合患者中较高。我们的研究结果表明,基于转录组谱识别基因演变可能是诊断感染以及评估严重程度和宿主对治疗的免疫反应的有用工具。

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