Qiao Li , Yuezi Hu , Ruyi Luo , Cong Luo , Pengfei Wang , Yanjun Zhong , Shengyang He , Yanwei Luo , Ruping Dai , Zhaolan Hu
{"title":"Targeting proBDNF in neutrophil subsets: Sepsis biomarker discovery and insights into mitochondrial hyperactivation","authors":"Qiao Li , Yuezi Hu , Ruyi Luo , Cong Luo , Pengfei Wang , Yanjun Zhong , Shengyang He , Yanwei Luo , Ruping Dai , Zhaolan Hu","doi":"10.1016/j.isci.2025.113642","DOIUrl":null,"url":null,"abstract":"<div><div>Sepsis, characterized by dysregulated immune responses, necessitates biomarkers and therapies. We conducted a prospective multicentric observational study involving sepsis patients and control groups. The proportions and brain-derived neurotrophic factor precursor (proBDNF) expression of blood neutrophil subsets were detected, and their clinical value was evaluated via correlation analysis and receiver operating characteristic curve analysis. ProBDNF was significantly upregulated in immature neutrophils (CD16<sup>int</sup> Neu) in sepsis patients and slightly elevated in mature Neu (CD16<sup>hi</sup> Neu). ProBDNF expression in CD16<sup>int</sup> Neu showed promising diagnostic value for sepsis, with a specific positive correlation with disease severity, prognosis, and organ dysfunction. CD16<sup>hi</sup> Neu from sepsis patients presented hyperactivated mitochondria, as shown by their increased mitochondrial membrane potential and length, which was reversed by neutralizing proBDNF. ProBDNF expression in circulating CD16<sup>int</sup> Neu may be a promising biomarker of sepsis. Targeting proBDNF in CD16<sup>hi</sup> Neu has the potential to control mitochondrial hyperactivation during sepsis.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 11","pages":"Article 113642"},"PeriodicalIF":4.1000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225019030","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Sepsis, characterized by dysregulated immune responses, necessitates biomarkers and therapies. We conducted a prospective multicentric observational study involving sepsis patients and control groups. The proportions and brain-derived neurotrophic factor precursor (proBDNF) expression of blood neutrophil subsets were detected, and their clinical value was evaluated via correlation analysis and receiver operating characteristic curve analysis. ProBDNF was significantly upregulated in immature neutrophils (CD16int Neu) in sepsis patients and slightly elevated in mature Neu (CD16hi Neu). ProBDNF expression in CD16int Neu showed promising diagnostic value for sepsis, with a specific positive correlation with disease severity, prognosis, and organ dysfunction. CD16hi Neu from sepsis patients presented hyperactivated mitochondria, as shown by their increased mitochondrial membrane potential and length, which was reversed by neutralizing proBDNF. ProBDNF expression in circulating CD16int Neu may be a promising biomarker of sepsis. Targeting proBDNF in CD16hi Neu has the potential to control mitochondrial hyperactivation during sepsis.
期刊介绍:
Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results.
We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.