Journal of Proteome Research最新文献

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Phosphoproteomic Profiling of Early-Stage Non-Small Cell Lung Cancer Provides Preliminary Evidence of Phosphorylation-Regulated Rho GTPase Signaling Driving Cytoskeletal Remodeling, Angiogenesis, and Cell Cycle Progression 早期非小细胞肺癌的磷酸化蛋白质组学分析提供了磷酸化调节的Rho GTPase信号驱动细胞骨架重塑、血管生成和细胞周期进展的初步证据
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-15 DOI: 10.1021/acs.jproteome.6c00453
Baby Rorielyn T. Dimayacyac-Esleta, Lara Beatrice L. Suñga, Lorenzo M. Zarate, Ferdinand D. Mira, Ben Joshua O. Porras, Dave Laurence A. Juntilla, Venus B. Pondevida, Eloise I. Prieto
{"title":"Phosphoproteomic Profiling of Early-Stage Non-Small Cell Lung Cancer Provides Preliminary Evidence of Phosphorylation-Regulated Rho GTPase Signaling Driving Cytoskeletal Remodeling, Angiogenesis, and Cell Cycle Progression","authors":"Baby Rorielyn T. Dimayacyac-Esleta,&nbsp;Lara Beatrice L. Suñga,&nbsp;Lorenzo M. Zarate,&nbsp;Ferdinand D. Mira,&nbsp;Ben Joshua O. Porras,&nbsp;Dave Laurence A. Juntilla,&nbsp;Venus B. Pondevida,&nbsp;Eloise I. Prieto","doi":"10.1021/acs.jproteome.6c00453","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00453","url":null,"abstract":"<p>Non-smallcell lung cancer (NSCLC) is the primary cause of cancer-relateddeaths worldwide. This can be attributed to the difficulty in earlydetection and the limited efficacy of available treatments, partlydue to an incomplete understanding of the disease biology. Identificationof key proteins involved in early-stage progression and understandingthe underlying mechanisms can greatly contribute to the developmentof diagnostic and treatment strategies for NSCLC. Quantitative phosphoproteomicanalysis was done on paired tumor tissues and adjacent normal lungtissues from early-stage NSCLC adenocarcinoma (LUAD) patients to allowfor the identification of proteins with differential phosphorylationand their associated pathways. A total of 6483 phosphoproteins wereidentified, with 1229 proteins having significantly higher phosphorylationand 701 proteins having significantly lower phosphorylation in thetumor tissues. All MS data were deposited in ProteomeXchange withthe identifier PXD071583. Function enrichment analysis showed thatthe differentially phosphorylated proteins and phosphosites were primarilyinvolved in Rho GTPase signaling and cytoskeleton remodeling. Analysisof protein interaction networks suggests that the predicted kinaseactivity likely drives malignant transformation in NSCLC LUAD, presumablythrough Rho GTPase-mediated angiogenesis and cell cycle progression.More importantly, this study identified several protein phosphositeswith differential phosphorylation and inferred kinase-phosphositeactivities that have not previously been reported in NSCLC LUAD.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4957–4972"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Selective Enrichment of Newly Synthesized Proteins Using Phos-Tag Click Tip Enables Nascent Proteome Analysis in Influenza A Virus Infection 利用Phos-Tag点击提示选择性富集新合成的蛋白质,可以在甲型流感病毒感染中进行新生蛋白质组分析
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-19 DOI: 10.1021/acs.jproteome.6c00391
Yayoi Kimura, Tomoko Akiyama, Tatsuhiro Kobashi, Maiko Hosotani, Yoko Ino, Jihye Shin, Naotoshi Nakamura, Eiji Kinoshita, Kei Miyakawa, Akihide Ryo
{"title":"Selective Enrichment of Newly Synthesized Proteins Using Phos-Tag Click Tip Enables Nascent Proteome Analysis in Influenza A Virus Infection","authors":"Yayoi Kimura,&nbsp;Tomoko Akiyama,&nbsp;Tatsuhiro Kobashi,&nbsp;Maiko Hosotani,&nbsp;Yoko Ino,&nbsp;Jihye Shin,&nbsp;Naotoshi Nakamura,&nbsp;Eiji Kinoshita,&nbsp;Kei Miyakawa,&nbsp;Akihide Ryo","doi":"10.1021/acs.jproteome.6c00391","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00391","url":null,"abstract":"<p>Profiling of newlysynthesized proteins (NSPs) provides accessto dynamic changes in protein production that accompany acute cellularresponses. Bioorthogonal noncanonical amino acid tagging (BONCAT)-basedapproaches enable selective labeling of NSPs; however, their broaderapplication remains constrained by labor-intensive enrichment workflowsand limited sensitivity for direct peptide-level analysis. Here, wedeveloped a workflow termed “Phos-tag Click Tip” byintegrating a phosphorylated variant of bicyclononyne (pBCN) withPhos-tag affinity purification to selectively capture azidohomoalanine(AHA)-labeled peptides for newly synthesized proteome analysis (NSProteomics).This approach overcomes key limitations of conventional proteomicsand BONCAT-based strategies by enabling efficient enrichment and sensitivedetection of NSP-derived peptides. Using this workflow, we performedcomprehensive NSP profiling of host cells during influenza A virusinfection. We identified dynamic changes in distinct NSP profilesassociated with viral replication, host restriction, and immune responses,many of which were not readily detected with conventional whole-cell-or phospho-proteomic analyses. Overall, the Phos-tag Click Tip workflowprovides a complementary approach for stimulus-responsive NSP profiling,offering functionally relevant insights into host–virus interactionsand cellular response mechanisms.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4888–4902"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatial Proteomics of the Human Atherosclerotic Microenvironment Reveals Heterogeneity in Intraplaque Proteomes and Extracellular Matrix Remodeling 人类动脉粥样硬化微环境的空间蛋白质组学揭示斑块内蛋白质组学和细胞外基质重塑的异质性
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-19 DOI: 10.1021/acs.jproteome.6c00011
Kathrine V. Jokumsen, Lasse G. Lorentzen, Karin Yeung, Timothy A. Resch, Jonas P. Eiberg, Michael J. Davies, Luke F. Gamon
{"title":"Spatial Proteomics of the Human Atherosclerotic Microenvironment Reveals Heterogeneity in Intraplaque Proteomes and Extracellular Matrix Remodeling","authors":"Kathrine V. Jokumsen,&nbsp;Lasse G. Lorentzen,&nbsp;Karin Yeung,&nbsp;Timothy A. Resch,&nbsp;Jonas P. Eiberg,&nbsp;Michael J. Davies,&nbsp;Luke F. Gamon","doi":"10.1021/acs.jproteome.6c00011","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00011","url":null,"abstract":"<p>Plaque heterogeneityunderlies the propensity of atheroscleroticlesions to rupture and trigger cardiovascular events. Most proteomicstudies examine <em>bulk</em> changes, obscuring key spatialdifferences in protein abundance. We report a high-resolution spatialproteomics workflow exploring the molecular landscape of human plaquesand a murine myocardium. By combining laser capture microdissectionwith high-sensitivity ion-mobility mass spectrometry, spatial profilingof cellular and extracellular matrix (ECM) proteomes was achieved.Over 2700 proteins were detected from 50,000 μm<sup>2</sup> areas,revealing substantial intraplaque heterogeneity across distinct regions(lipid-rich, media, shoulder, necrotic core, intima) and distancefrom the artery lumen. Inverse correlations between proteases (cathepsinB) and core structural ECM proteins (perlecan, HSPG2) indicated activeECM remodeling. Analysis of media layers indicated distinct proteinsignatures associated with smooth muscle contraction and cell–cellcommunication. Blood coagulation signatures, including platelet degranulationand fibrin formation, were enriched at the intima. Inflammatory (clustersof differentiation 4/68, CD4/CD68; vascular cell adhesion molecule1, VCAM1) and vascular damage markers (tenascin-C, TNC) were enrichedin shoulder regions. The necrotic core was dominated by blood proteins,consistent with intraplaque hemorrhage. This workflow resolves proteomicchanges over ∼200 μm distances, providing unprecedentedinsights into plaque morphology and offers a powerful tool for elucidatingplaque biology.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4534–4545"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Variability to Consensus: Rescoring Harmonizes Peptide Identification across Diverse Search Engines and Data Sets 从可变性到共识:在不同的搜索引擎和数据集上重新评分协调肽识别
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-19 DOI: 10.1021/acs.jproteome.6c00226
Dirk Winkelhardt, Sven Berres, Julian Uszkoreit
{"title":"From Variability to Consensus: Rescoring Harmonizes Peptide Identification across Diverse Search Engines and Data Sets","authors":"Dirk Winkelhardt,&nbsp;Sven Berres,&nbsp;Julian Uszkoreit","doi":"10.1021/acs.jproteome.6c00226","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00226","url":null,"abstract":"<p>Peptide-spectrummatch (PSM) rescoring has become standard in proteomicsworkflows, improving peptide identification accuracy across diversesearch engines. Despite the availability of multiple rescoring strategies,systematic comparisons spanning several search engines, data sets,and database configurations remain limited. Here, we benchmarked sevenpublicly available search engines, evaluating standard target-decoy-basedfalse discovery rate (FDR) estimation alongside Percolator, MS2Rescore,and Oktoberfest across four data sets acquired on different mass spectrometryplatforms in data-dependent mode and searched against protein databasesof varying size and composition. Rescoring substantially increasedidentification consensus and reduced variability between search engines,with prediction-based approaches yielding the largest gains. Whiledatabase size had limited impact for human data sets, it significantlyaffected identification rates on a metaproteomic data set. Entrapment-basedevaluation indicated generally adequate FDR control across methods,although prediction-based rescoring exhibited a higher tendency towardFDR underestimation in specific configurations. Overall, advancedrescoring strategies harmonize peptide identification outcomes acrosssearch engines, thereby enhancing robustness and comparability inproteomics analyses. However, careful feature selection and appropriatedatabase choice remain essential to ensure reliable FDR control andoptimal performance across diverse experimental settings.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4676–4687"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Translation of Organ-on-a-Chip Technology for Human-Relevant Diagnostic Biomarkers 探索器官芯片技术转化为与人类相关的诊断生物标志物
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-05 DOI: 10.1021/acs.jproteome.6c00120
Conor C. Jenkins, Priscilla E. Lee, Dylan H. Fudge, Gabrielle M. Rizzo, Allison E. Clay, Raquel L. Shortt-Jackson, Shoshanah M. Myska, Daniel J. Angelini, Elizabeth S. Dhummakupt, Tyler D. P. Goralski
{"title":"Exploring the Translation of Organ-on-a-Chip Technology for Human-Relevant Diagnostic Biomarkers","authors":"Conor C. Jenkins,&nbsp;Priscilla E. Lee,&nbsp;Dylan H. Fudge,&nbsp;Gabrielle M. Rizzo,&nbsp;Allison E. Clay,&nbsp;Raquel L. Shortt-Jackson,&nbsp;Shoshanah M. Myska,&nbsp;Daniel J. Angelini,&nbsp;Elizabeth S. Dhummakupt,&nbsp;Tyler D. P. Goralski","doi":"10.1021/acs.jproteome.6c00120","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00120","url":null,"abstract":"<p>Microphysiological systems (MPSs)are gaining tractionas a viablealternative model for toxicity studies. Further characterization isnecessary to explore the full translational potential of MPSs to humanphysiology, along with the utility of these platforms to serve asa diagnostic tool. Multiomics analyses have emerged as a key meansfor identifying host biomarkers associated with chemical and drugexposure. Correlations between published human omics and MPS technologyomics data will inform the potential of organ chips to accuratelyrepresent human responses and provide an alternative approach forimproved biomarker discovery for toxicity assessment and exposureidentification. To interrogate these potential overlaps, TissUse Chip3multiorgan chips (MOCs) seeded with kidney organoids, liver organoids,and respiratory tract tissue were exposed to low, therapeutic, andtoxic doses of acetaminophen (<em>n</em> = 4 for each condition)for 24 h and subjected to proteomic and metabolomic analysis. Thedata from our organ chips are largely consistent with biomarkers anddysregulations identified in published human omics data, in vitroand in vivo data, to include the identification of several known acetaminophenmetabolites and biotransformation products. These data suggest thatorgan chips may be a suitable surrogate for human biomarker identificationand drug or hazardous chemical exposure diagnosis.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4599–4613"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ProtPen Combines Sequence- and Structure-based Approaches to Facilitate Protein Function Predictions on a Proteome-wide Scale ProtPen结合了基于序列和结构的方法,以促进蛋白质组范围内的蛋白质功能预测。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-14 DOI: 10.1021/acs.jproteome.6c00074
Diya Mathai, Stefan Schulze
{"title":"ProtPen Combines Sequence- and Structure-based Approaches to Facilitate Protein Function Predictions on a Proteome-wide Scale","authors":"Diya Mathai,&nbsp;Stefan Schulze","doi":"10.1021/acs.jproteome.6c00074","DOIUrl":"10.1021/acs.jproteome.6c00074","url":null,"abstract":"<p>Proteins of unknown function represent a significantgap in ourunderstanding of biological processes, encompassing large portionsof the proteomes of many organisms, especially prokaryotes. Addressingthis gap is critical to understanding the biology and pathogenicityof such organisms. We introduce ProtPen, an open-source pipeline thatfacilitates protein function prediction by combining eggNOG-mapperfor sequence-based annotation with Foldseek for rapid structural similaritysearches using AlphaFold-predicted protein structures. Annotationresults from both tools are merged and enriched with UniProt metadatato produce a comprehensive output suitable for downstream analysis.The pipeline requires only a FASTA input file with UniProt identifiers,and is designed to analyze data sets on the scale of whole proteomes.Benchmarking on a curated data set of well-characterized <em>Pseudomonas aeruginosa</em> proteins demonstrated an annotationaccuracy of &gt;90%, and highlighted the complementarity of sequence-and structure-based methods. Further evaluation of ProtPen includedits application to biologically relevant data sets, comprising proteinsof unknown function that exhibited significant differential abundancesin a proteomics data set of <em>P. aeruginosa</em>, and uncharacterized glycoproteins from <em>Haloferax volcanii</em>. ProtPen is readily extensible to incorporateadditional protein function prediction tools. In summary, this pipelinefacilitates the systemwide annotation of proteins of unknown functionfrom proteomic data sets and whole proteomes.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"5000–5010"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blood Bile Acids for Inflammatory Bowel Disease Diagnosis and Disease Activity Assessment: A Metabolomics Meta-Analysis 血胆汁酸诊断炎症性肠病和疾病活动性评估:代谢组学荟萃分析。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-25 DOI: 10.1021/acs.jproteome.6c00383
Nguyen Quang Thu, Vo Thuy An, Le Hoang Bach Dat, Tran Minh Hung, Huy Truong Nguyen, Nguyen Phuoc Long
{"title":"Blood Bile Acids for Inflammatory Bowel Disease Diagnosis and Disease Activity Assessment: A Metabolomics Meta-Analysis","authors":"Nguyen Quang Thu,&nbsp;Vo Thuy An,&nbsp;Le Hoang Bach Dat,&nbsp;Tran Minh Hung,&nbsp;Huy Truong Nguyen,&nbsp;Nguyen Phuoc Long","doi":"10.1021/acs.jproteome.6c00383","DOIUrl":"10.1021/acs.jproteome.6c00383","url":null,"abstract":"<p>Alterations in circulating bile acids (BAs) have beenreportedin inflammatory bowel disease (IBD), but the consistency of thesechanges across clinically relevant comparisons remains unclear. Ourgoal was to investigate systemic BA alterations in IBD using a metabolomicsmeta-analysis with an exploratory analysis of BA-related gene expressionas a supporting context. A systematic review and meta-analysis of28 metabolomics studies examined blood BA profiles associated withIBD, IBD diagnosis, and disease activity assessment. Univariate analysisand logistic regression modeling of two independent IBD cohorts exploredthe blood BA-related genes and IBD. Across 28 studies that comprised5056 IBD patients, 1721 healthy controls, and 314 non-IBD patients,131 BAs were reported. Eight predefined clinical comparisons wereeligible for the meta-analysis. Lower secondary BA levels were consistentlyobserved in IBD patients compared with controls, between UC and CD,and in active versus remission patients. Deoxycholic acid, glycodeoxycholicacid, and taurodeoxycholic acid were frequently decreased, whereasglycocholic acid was increased in certain comparisons. Transcriptomicsanalyses revealed differential expression of several BA-related genesin blood, including <em>SLC51A</em>, <em>ABCB4</em>, and <em>ACOT8</em>, across the comparisons. Our findingsidentify consistent circulating BA alterations in IBD and highlightthe relevance of blood BA for future biomarker research in the diagnosisand disease activity assessment.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4847–4858"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
α-Ketoglutarate Promotes Ciprofloxacin Tolerance in Methicillin-Resistant Staphylococcus aureus via Glutamate-Mediated Metabolic Remodeling α-酮戊二酸通过谷氨酸介导的代谢重塑促进耐甲氧西林金黄色葡萄球菌对环丙沙星的耐受。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-07-31 DOI: 10.1021/acs.jproteome.6c00131
Qing-qiang Xu, Lv-yuan Fan, Jing-yun Wu, Ting Zhang, Zhuo-ying Cao, Wen-ting Zhang, Yu-bin Su, Jiao Fei
{"title":"α-Ketoglutarate Promotes Ciprofloxacin Tolerance in Methicillin-Resistant Staphylococcus aureus via Glutamate-Mediated Metabolic Remodeling","authors":"Qing-qiang Xu,&nbsp;Lv-yuan Fan,&nbsp;Jing-yun Wu,&nbsp;Ting Zhang,&nbsp;Zhuo-ying Cao,&nbsp;Wen-ting Zhang,&nbsp;Yu-bin Su,&nbsp;Jiao Fei","doi":"10.1021/acs.jproteome.6c00131","DOIUrl":"10.1021/acs.jproteome.6c00131","url":null,"abstract":"<p>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) is a globally significant pathogen causing severe infections.The chronicity and recurrence of its infection pose serious challengesto public health. In this study, we reported that intracellular accumulationof α-ketoglutarate (α-KG) significantly increased ciprofloxacin(CIP) tolerance in MRSA. Using integrated metabolomic and functionalgenomic approaches, we demonstrated that both exogenous α-KGand genetic knockout of α-KG dehydrogenase (Δ<em>sucA</em>, Δ<em>sucB</em>) induced CIP tolerance in MRSA. Mechanistically,elevated α-KG levels drive the accumulation of glutamate (Glu),which in turn reduced bacterial membrane potential and cellular ATPcontent. Furthermore, Glu accumulation raised intracellular osmoticpressure, leading to decreased CIP uptake. These metabolic alterationsenable MRSA to sustain high tolerance toward ciprofloxacin. Our findingsreveal a key role of the α-KG-Glu metabolic axis in drivingantibiotic tolerance and provide novel insights into the metabolicadaptations underlying drug persistence in MRSA.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4636–4650"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differential Proteomic Profiling of Responders and Non-responders to Direct-Acting Antivirals Treatment in Chronic Hepatitis C Virus Infection 慢性丙型肝炎病毒感染直接抗病毒治疗反应者和无反应者的差异蛋白质组学分析
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-08-11 DOI: 10.1021/acs.jproteome.5c01003
Shreyasi Nath, Anwesha Ghosh, Raina Das, Sagnik Bakshi, Supradip Dutta, Priya Verma, Uttaran Bhattacharjee, Upasana Baskey, Sudipta Mondal, Kaushik Kumar Dey, Provash Chandra Sadhukhan
{"title":"Differential Proteomic Profiling of Responders and Non-responders to Direct-Acting Antivirals Treatment in Chronic Hepatitis C Virus Infection","authors":"Shreyasi Nath,&nbsp;Anwesha Ghosh,&nbsp;Raina Das,&nbsp;Sagnik Bakshi,&nbsp;Supradip Dutta,&nbsp;Priya Verma,&nbsp;Uttaran Bhattacharjee,&nbsp;Upasana Baskey,&nbsp;Sudipta Mondal,&nbsp;Kaushik Kumar Dey,&nbsp;Provash Chandra Sadhukhan","doi":"10.1021/acs.jproteome.5c01003","DOIUrl":"10.1021/acs.jproteome.5c01003","url":null,"abstract":"<p>Hepatitis C Virus (HCV), particularly genotype 3 (GT-3),is highlyprevalent in India and is associated with faster progression to cirrhosis,hepatocellular carcinoma, and higher treatment failure rates. AlthoughDirect-Acting Antivirals (DAAs) have revolutionized HCV therapy, 5–10%of patients fail to achieve sustained virological response (SVR).This proteomic study aimed to identify changes in the proteomic profilebefore and after treatment of both responders and non-responders toHCV treatment. Paired plasma samples from HCV GT-3 infected patientswere collected before and 12 weeks after initiating DAAs treatment,along with healthy controls. Quantitative proteomic analysis was performedon the paired samples. Differentially expressed proteins (DEPs) wereidentified and subjected to functional analysis including gene setenrichment analysis (GSEA) and protein–protein interaction(PPI) network analysis. GSEA revealed enrichment in extracellularmatrix organization and innate immune pathways. Expression patternsof candidate proteins selected based on fold change and false discoveryrate (FDR) criteria were further evaluated in an independent cohort.Western blot confirmed key expression trends of candidate proteins.Proteins linked to extracellular matrix remodeling and angiogenesisshowed differential expression patterns. Successful validation ofthese candidate proteins in large independent cohorts holds potentialto predict therapeutic outcomes.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4448–4462"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteomic Identification of Pig Xenoantigens for Clinical Xenotransplantation 临床异种移植用猪异种抗原的蛋白质组学鉴定。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2026-09-04 Epub Date: 2026-07-30 DOI: 10.1021/acs.jproteome.5c01244
Hongyi Liu, Trung Hoàng, Yingwei Hu, Yuanwei Xu, Zhenyu Sun, Brandon J. Peiffer, Yuanyu Huang, Zhaoli Sun, Hui Zhang
{"title":"Proteomic Identification of Pig Xenoantigens for Clinical Xenotransplantation","authors":"Hongyi Liu,&nbsp;Trung Hoàng,&nbsp;Yingwei Hu,&nbsp;Yuanwei Xu,&nbsp;Zhenyu Sun,&nbsp;Brandon J. Peiffer,&nbsp;Yuanyu Huang,&nbsp;Zhaoli Sun,&nbsp;Hui Zhang","doi":"10.1021/acs.jproteome.5c01244","DOIUrl":"10.1021/acs.jproteome.5c01244","url":null,"abstract":"<p>Xenotransplantation using genetically engineered pigorgans offersa promising solution to the shortage of donor organs for life-savingtransplantations. However, human-preformed antibodies against unknownpig xenoantigens remain a significant barrier to successful xenotransplantation.Current methods for characterizing these antibodies or xenoantigensare limited to cellular-level cross-match assays. In this study, wedeveloped a novel approach to identify pig xenoantigens, includingpeptide and glycopeptide epitopes, that react with human-preformedantibodies. First, human-preformed antibodies against xenoantigenswere enriched from plasma using immobilized pig kidney proteins. Theenriched antibodies were then immobilized and used to isolate pigkidney proteins, peptides, and intact glycopeptides, followed by liquidchromatography–tandem mass spectrometry analysis. This dual-levelapproach identified 221 peptides corresponding to 153 proteins, witha significant enrichment of plasma membrane and extracellular proteins.Notably, 11 peptides were unique to pig sequences, suggesting theirpotential role in driving xenogeneic immune responses. Glycoproteomicanalysis identified 122 intact glycopeptides, predominantly complex/hybridglycoforms, and Neu5Gc-containing glycans. Our method effectivelyidentifies peptides and intact glycopeptides reactive to human-preformedantibodies, providing critical insights for discovering xenoantigens.These findings could guide genetic engineering strategies and enhancerecipient candidate screening for xenotransplantation, ultimatelyincreasing the feasibility and success of xenogeneic organ transplantation.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4511–4523"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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