PROTEOMICS – Clinical Applications最新文献

{"title":"An Ensemble Method for Predicting and Designing of Druggable Proteins.","authors":"Shipra Jain, Srijanee Gupta, Gajendra P S Raghava","doi":"10.1002/prca.70046","DOIUrl":"https://doi.org/10.1002/prca.70046","url":null,"abstract":"<p><strong>Purpose: </strong>Over the years, several proteins and peptides with diverse therapeutic properties such as anticancer, antimicrobial, antihypertensive effects have been discovered. However, only a few hundred proteins are considered druggable with US FDA approval, while most of them failed during clinical trials.</p><p><strong>Experimental design: </strong>This study systematically investigates the compositional and physicochemical properties of FDA-approved proteins to develop predictive models for identifying druggable proteins. Our main dataset comprises of 356 FDA approved proteins as positive dataset and equal number of randomly selected proteins as negative dataset. We used 80% data as training set and 20% as independent validation data, with no protein in validation dataset having more than 40% similarity with any protein in training dataset.</p><p><strong>Result: </strong>Random forest-based model developed using SVC-L1 selected features obtained maximum performance AUC of 0.80 with MCC 0.61 on validation data. In addition to this, we performed MERCI-based motif analysis to find exclusive motifs/ patterns in druggable proteins. Finally, we proposed an ensemble-based method combining best performing machine learning model with exclusive motifs and achieved AUC 0.92 with MCC 0.83 on independent validation dataset.</p><p><strong>Conclusion and clinical relevance: </strong>In order to serve the scientific community, web server and standalone package of \"ThPPred\" facilitating prediction and designing of druggable proteins is proposed (https://webs.iiitd.edu.in/raghava/thppred/).</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 3","pages":"e70046"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Cervicovaginal Fluid for Diagnostic Endometriosis Biomarker Discovery.","authors":"Emily S J Paterson, Simon Scheck, Torsten Kleffmann, Roopi Gill, Nicholas Bedford, Simon McDowell, Jane E Girling, Claire E Henry","doi":"10.1002/prca.70044","DOIUrl":"10.1002/prca.70044","url":null,"abstract":"<p><strong>Purpose: </strong>Endometriosis is a prevalent inflammatory condition characterised by the presence of endometrial-like tissue outside the uterus and is associated with significant challenges, including diagnostic delays and continued reliance on laparoscopy. Although extensive research has investigated potential biomarkers in various biofluids, none have been validated for clinical use.</p><p><strong>Experimental design: </strong>This pilot study explored the proteome of cervicovaginal fluid to identify biomarkers of endometriosis. SWATH-MS was performed over two experiments on cervicovaginal fluid sampled via a low vaginal swab, from people with (n = 20) and without (n = 19) surgically confirmed endometriosis. STRING, OPLS-DA modelling and ingenuity pathway analysis were used to interrogate the data. ELISA was performed validate SWATH-MS findings.</p><p><strong>Results: </strong>There were 29 proteins in experiment one and 47 proteins in experiment two identified as differentially abundant between cases and controls. No proteins were identified as differentially abundant in both experiments. Legumain (LGMN) measured via ELISA was significantly increased in the cervicovaginal fluid of people with endometriosis.</p><p><strong>Conclusions and clinical relevance: </strong>Cervicovaginal fluid proteins sampled via vaginal swab may have limited biomarker potential for endometriosis. A larger and more diverse cohort would be required to confirm the promise of cervicovaginal fluid LGMN as a candidate biomarker of endometriosis.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 3","pages":"e70044"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Cerebrospinal Fluid from Severe COVID-19 Patients Reveals Prognostic Biomarkers Associated with Disease Outcome.","authors":"Harry Alexopoulos, Martina Samiotaki, Eirini Gkogkou, Sofia Mavromati, Kleopatra Bitzogli, Georgios Panagiotou, Athanasios Tzioufas, Eleni Magira, Αnastasia Kotanidou, Ioannis Trougakos","doi":"10.1002/prca.70042","DOIUrl":"10.1002/prca.70042","url":null,"abstract":"<p><strong>Purpose: </strong>Coronavirus disease 2019 (COVID-19) has highlighted significant neurological complications in severe cases. Cerebrospinal fluid (CSF) proteomics could reveal biomarkers related to clinical outcome among critically ill patients.</p><p><strong>Experimental design: </strong>We performed high-resolution proteomic analyses of CSF samples from 29 intensive care unit (ICU) patients with severe COVID-19 and 19 controls. Differentially expressed proteins and associated pathways were identified through bioinformatic and statistical analyses.</p><p><strong>Results: </strong>Proteomic analysis identified 488 significantly altered proteins between COVID-19 patients and controls. Proteins linked to coagulation, inflammation, and blood-brain barrier dysfunction (e.g., SERPINC1, KNG1, PLG) were elevated in patients who survived ICU admission. Conversely, proteins associated with metabolic disruption, cellular stress, and neuroinflammation (e.g., FABP3, PDIA4) were upregulated in non-survivors. Pathway enrichment analyses confirmed involvement of immune activation, inflammatory responses, and coagulation cascades.</p><p><strong>Conclusions and clinical relevance: </strong>CSF proteomics in severe COVID-19 patients reveals potential biomarkers predictive of patient outcomes. These findings support the involvement of systemic inflammation and blood-brain barrier disruption in COVID-19 pathophysiology, suggesting novel targets for personalized intervention strategies.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 2","pages":"e70042"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormonal Contraceptives and Depression: A Proteomic Analysis Using Neuronal Models.","authors":"Sam Thilmany, Andreas Thomas, Yvonne Reinders, Farhad Shakeri, Matthias Vogel, Albert Sickmann, Catharina Scholl, Mario Thevis","doi":"10.1002/prca.70017","DOIUrl":"10.1002/prca.70017","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Hormonal contraceptives are linked to a higher prevalence of depressive symptoms. Given their popularity in Western countries, understanding the biochemical effects on neuronal cells is crucial to minimizing mental health risks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Experimental design: &lt;/strong&gt;Neural progenitor cells were treated with ethinyl estradiol (EE) and levonorgestrel (LNG), two synthetic sex hormones commonly used in oral contraception, and S-23, a selective androgen receptor modulator developed as a potential synthetic sex hormone for male hormonal contraception. Label-based quantitative proteomics with the TMTpro 16plex tandem mass tags were used to assess protein expression changes between treated and untreated cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Treatment of human neural progenitor cells with EE, LNG, EE + LNG, and S-23 led to distinct and overlapping proteomic changes, with enrichment in pathways related to inflammation, oxidative stress, transcriptional regulation, and cell death. Disease association analyses linked these changes to neurodegenerative and psychiatric conditions, including mechanisms relevant to depression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and clinical relevance: &lt;/strong&gt;These findings suggest that hormonal compounds used in contraception and performance enhancement may influence molecular pathways implicated in mental health, particularly depression. Although not directly translatable to clinical outcomes, the results support the need for further investigation into the neuropsychiatric effects of hormonal treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This study addresses a pressing clinical need to better understand the potential mental health impacts of widely used hormonal contraceptives. While highly effective for pregnancy prevention, compounds such as ethinyl estradiol and levonorgestrel have repeatedly been associated with increased risk of depressive symptoms, highlighting the importance of investigating their molecular effects on neural systems. To explore this, we applied label-based quantitative proteomics in an undifferentiated human neural progenitor cell model treated with ethinyl estradiol, levonorgestrel, their combination, and the selective androgen receptor modulator S-23. The treatments induced distinct and overlapping changes in protein expression, with enrichment in pathways related to inflammation, oxidative stress, cell adhesion, chromatin dynamics, and programmed cell death-biological processes known to intersect with mechanisms implicated in depression. These findings offer insight into how synthetic hormones and hormone-like compounds may modulate neuronal biology, potentially contributing to adverse mental health outcomes. However, due to limitations of the in vitro model-such as the absence of systemic context, pharmacokinetics, and mature neuronal function-these results are primarily hypothesis-generating. They underscore the importance of further research to clarify the pathophysiologi","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70017"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Epicatechin Supplementation on Plasma Proteome Profiles in Obese Men and Women-An Exploratory Approach to Sexual Dimorphism.","authors":"Celso Pereira Batista Sousa-Filho, Allanis Valon Ferreira, Leo Kei Iwai, Alison Felipe Alencar Chaves, Talita Souza Siqueira, Victoria Silva, Guilherme Ribeiro Romualdo, Rosemari Otton","doi":"10.1002/prca.70027","DOIUrl":"10.1002/prca.70027","url":null,"abstract":"<p><strong>Purpose: </strong>Evidence suggests that consuming epicatechin-rich green tea can increase metabolism in the body, and this metabolic effect might be linked to weight loss in obese subjects. The precise mechanism by which epicatechin influences weight loss is still unclear. Our goal was to identify a specific signature in the plasma proteins of obese individuals, categorized or not by gender (men and women), and to investigate how epicatechin (EC) supplementation affected them. Additionally, we analyzed anthropometric data to assess the potential anti-obesity effects of EC and to identify any gender-related differences that may have emerged.</p><p><strong>Methods: </strong>In our clinical trial, we provided pure EC (90%) at a daily dosage of 200 mg, administered before the main meal, for three months. The participants were obese men and women with a body mass index (BMI) of 30 kg/m² or higher. We conducted measurements of body dimensions and performed biochemical blood tests before and after the supplementation with EC, also analyzing the proteome in the plasma samples.</p><p><strong>Findings: </strong>EC supplementation did not alter anthropometric parameters in obese subjects, but it did cause significant molecular changes in their plasma proteome, which varied between men and women. Key proteins like RPL30 were consistently regulated, indicating that EC might activate translational remodeling to adapt to metabolic stress in obesity.</p><p><strong>Conclusions: </strong>Proteomic profiling reveals early biomarkers of therapeutic efficacy, and future research should examine EC's time-dependent effects on ribosomal biogenesis and metabolic regulation.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70027"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12743591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Profiling of Lysine Ubiquitylation in the Human Hypothalamus.","authors":"Zhi-Yi Zhang, Tao Ding, Jie Kong, Qiao-Chu Wang, Xu-Tong Zhang, Chun-Mei Shi, Jun-Tao Yang, Jiang-Feng Liu","doi":"10.1002/prca.70029","DOIUrl":"10.1002/prca.70029","url":null,"abstract":"<p><strong>Purpose: </strong>Ubiquitylation is a vital post-translational modification involved in various biological processes, yet its role in the human hypothalamus remains largely unexplored. This study aims to profile the ubiquitinome of the human hypothalamus, uncovering the ubiquitylation landscape and its potential implications in hypothalamic function.</p><p><strong>Experimental design: </strong>We employed LC‒MS/MS to analyze hypothalamic tissues from six healthy elderly individuals, focusing on identifying and characterizing ubiquitinated sites and proteins. Motif analysis, functional enrichment, and protein-protein interaction (PPI) network were conducted to profile the landscape.</p><p><strong>Results: </strong>Our analysis identified 21,815 ubiquitinated sites across 5314 proteins and five types of modification motifs in the normal human hypothalamus. Ubiquitinated proteins were predominantly localized to the cell membrane. Functional enrichment related to neuronal and endocrine pathways, especially with MAPK signaling. PPI network analysis focused on five ubiquitinated proteins, including PRKACA, PRKACB, PRKCA, PRKCB, and PRKCG. Additionally, we analyzed their relationship with E3 ligases using UbiBrowser.</p><p><strong>Conclusions and clinical relevance: </strong>This study offers the first comprehensive analysis of the human hypothalamic ubiquitinome. Our work provides a reliable foundation for future research into the implications of ubiquitylation in neuroendocrine-related disorders.</p><p><strong>Summary: </strong>The human hypothalamus is crucial in regulating metabolism, stress response, and circadian rhythms. Dysfunctions in these processes are linked to various disorders, including Alzheimer's disease, obesity, and sleep disorders. Although ubiquitylation is a key protein modification that affects cellular function, its specific role within the hypothalamus remains poorly understood. This study provides the first detailed profile of lysine ubiquitylation in the human hypothalamus, identifying over 21,000 ubiquitinated sites on more than 5000 proteins. The findings provide valuable insights into the ubiquitylation landscape, highlighting key ubiquitinated proteins and pathways that may be involved in neuroendocrine diseases. This research provides a foundation for future research and highlights the potential of ubiquitylation as a therapeutic target for neurological and endocrine disorders.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70029"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Biomarkers Are Linked to QTc Interval in Patients With Chronic Heart Failure.","authors":"Mylène Barry-Loncq de Jong, Teun B Petersen, Sabrina Abou Kamar, Navin Suthahar, Nick van Boven, K Martijn Akkerhuis, Peter J van der Spek, Peter D Katsikis, Rudolf A de Boer, Victor A W M Umans, Eric Boersma, Folkert W Asselbergs, Jasper J Brugts, Sing-Chien Yap, Isabella Kardys","doi":"10.1002/prca.70020","DOIUrl":"10.1002/prca.70020","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study investigates the link between circulating proteins and rate-corrected QT (QTc) interval in patients with heart failure with reduced ejection fraction (HFrEF) and their association with cardiovascular outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and results: &lt;/strong&gt;We analyzed 197 HFrEF patients from the prospective Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis (Bio-SHiFT) study, all in sinus rhythm at baseline. Baseline QTc intervals were calculated and corrected for broad QRS complexes (&gt;120 ms) using Bogossian's formula. Using the Somalogic-SomaScan Assay, 1105 cardiovascular-related proteins were measured in baseline blood samples. Linear regression identified 11 biomarkers significantly associated with QTc interval (false discovery rate [FDR] &lt; 0.05), adjusted for age, sex, and QT-prolonging medications. These included interleukin-1 receptor-like 1 (ST2) and angiopoietin-2. An additional four biomarkers showed potential relevance (FDR &lt; 0.1). Cox regression analysis revealed that five biomarkers-ST2, angiopoietin-2, atrial natriuretic factor, insulin-like growth factor-binding protein 7 (IGFBP7), and carbonic anhydrase 4 (CA4)-were significantly associated with the composite clinical endpoint of cardiovascular death, heart transplantation, left ventricular assist device implantation, and heart failure hospitalization.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Several cardiovascular proteins are associated with the QTc interval and adverse cardiovascular events in HFrEF patients. The observed associations highlight pathways such as inflammation, fibrosis, and angiogenesis, which may contribute to QTc prolongation and adverse outcomes in HFrEF. Further research is warranted to reveal underlying mechanisms and clinical applicability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This study is the first to investigate the association between QTc interval and a broad panel of over 1000 plasma proteins in patients with heart failure with reduced ejection fraction (HFrEF). We identified 11 proteins significantly linked to QTc interval, five of which also demonstrated prognostic relevance for adverse cardiovascular outcomes. The associated biomarkers are linked to inflammation, fibrosis, and angiogenesis-related pathways. These findings provide novel insights into the multifactorial mechanisms associated with QTc prolongation, potentially due to direct or indirect effects. The results emphasize the potential of circulating biomarkers as tools for understanding the pathophysiological processes associated with QTc prolongation and arrhythmogenesis in heart failure. Moreover, the identification of interleukin-1 receptor-like 1 (ST2), angiopoietin-2, atrial natriuretic factor, IGFBP7, and carbonic anhydrase 4 (CA4) as shared markers of QTc interval prolongation and adverse outcomes underscores their clinical utility as both diagnostic and prognosti","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70020"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12743590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Insights Into the Pathogenesis of Intracerebral Hemorrhage: The Role of Blend Sign in Hematoma Expansion.","authors":"Hang Hang, Shanpeng Liu, Likun Wang, Linshan Zhang, Cuiying Liu, Baohui Xu, Heng Zhao, Guofeng Wu","doi":"10.1002/prca.70028","DOIUrl":"10.1002/prca.70028","url":null,"abstract":"<p><strong>Objective: </strong>The \"blend sign\" is a critical CT imaging marker for predicting hematoma expansion in intracerebral hemorrhage (ICH). This study aimed to elucidate its underlying pathological mechanisms by comparing proteomic profiles between hyperdense and hypodense regions within the hematoma.</p><p><strong>Methods: </strong>Hematoma samples from nine ICH patients exhibiting the blend sign were obtained via minimally invasive puncture. Isotope-labeled proteomics and bioinformatic analyses were performed to identify differentially expressed proteins (DEPs), which were further validated by Western blotting and ELISA.</p><p><strong>Results: </strong>A total of 77 DEPs were identified, including 66 upregulated and 11 downregulated in hyperdense regions compared to hypodense areas. Functional enrichment analysis revealed significant involvement of inflammatory responses, apoptosis, oxidative stress, and metabolic dysregulation. Notably, cytochrome C, growth-associated protein 43 (GAP43), and tau were markedly upregulated in hyperdense regions.</p><p><strong>Conclusions: </strong>The blend sign is associated with region-specific molecular changes involving inflammation, apoptosis, and metabolic alterations. These findings provide mechanistic insights into hematoma heterogeneity and lay a foundation for future studies exploring their role in hematoma expansion and clinical outcomes.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70028"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparison of Emotionally Stimulated and Conventionally Collected Tears Using Bottom-Up, Label-Free Quantitative Proteomic Analysis-A Pilot Study.","authors":"Campbell Bruce Mousseau, Alena R Veigl-Lunsford, Rhonda L Pitsch, Sean W Harshman","doi":"10.1002/prca.70023","DOIUrl":"10.1002/prca.70023","url":null,"abstract":"<p><p>Proteomic analysis of biofluids is central for identifying disease biomarkers. Tears have become popular targets for biomarker discovery and biosensor development, largely because they can be collected noninvasively and are rich sources of biomarkers for ocular and systemic diseases. Although basal and reflex tears have been well characterized, the proteome of psycho-emotionally stimulated tears remains largely unexplored, hindering their applicability in biomarker discovery studies and the advancement of tear-based biosensors. Comprehensive proteomic analysis across different tear types is crucial for identifying novel biomarkers and improving disease diagnosis and monitoring. In this pilot study, tears collected via conventional stimulation techniques (\"standard\") versus those elicited through emotional stimuli (\"emotional\") were purchased from single donors through two vendors. We compared the proteomic profiles of emotional (n = 6) and standard (n = 14) single donor human tears to better understand the biochemical composition and functional roles of different tear types. In total, 907 proteins were identified from all tear samples. Fifty-two tear proteins were significantly enriched in emotionally stimulated tears. Functional characterization of enriched proteins revealed that most were extracellular or secreted. Many were also involved in host defense or immune responses, including members of the S100A and neutrophil defensin protein families. SUMMARY: Although emotional tears are known to differ from basal and reflex tears in both composition and function, the specific biochemical characteristics and functional roles of emotional tears remain poorly understood. This gap in knowledge is largely due to the limited research conducted on emotional tears, despite their distinct origins. A more complete understanding of all tear types is necessary for the continuation of biomarker discovery and the development of tear fluid-based biosensors. In this exploratory study, tears collected via a conventional/standard protocol and those collected from emotional stimulus were obtained from two vendors and subjected to proteomic profiling and comparison. A bottom-up proteomic approach was utilized to analyze tear samples, facilitating a comparison between tear types and contributing to the characterization of psycho-emotional tears.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70023"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12743588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Targeted Analysis of Extracellular Vesicle-Enriched Plasma Proteome Between Early and Late Rugby Playing Career.","authors":"Abhishek Jagan, Yusuke Nishimura, Tim Donovan, Jatin G Burniston","doi":"10.1002/prca.70036","DOIUrl":"10.1002/prca.70036","url":null,"abstract":"<p><strong>Purpose: </strong>Rugby players experience high-impact collisions, potentially increasing their risk of neurodegenerative conditions. This study investigates whether the plasma proteome of extracellular vesicles (EV) provides biomarkers to indicate differential risk associated with a rugby career.</p><p><strong>Experimental design: </strong>Twenty-four males were recruited: eight academy rugby players (18 ± 1 years), eight professional rugby players (33 ± 5 years; >10-year career), and eight CrossFit athletes (32 ± 5 years; no history of collision-related injuries). EV were enriched from plasma using strong-anion exchange magnetic microparticles and digested proteins were analyzed by LC-MS/MS for label-free quantitation.</p><p><strong>Results: </strong>A total of 449 proteins were identified (false discovery rate <1%). Statistical analysis on 403 proteins quantified in at least n = 3 participants in each group highlighted 52 significant (p < 0.05, q < 0.01) differences, including 44 proteins that had abundance profiles unique to professional rugby players. Eight proteins which were depleted and three proteins which were elevated have previously recognized roles in neurodegenerative processes.</p><p><strong>Conclusions and clinical relevance: </strong>Proteins associated with neuroprotection were specifically depleted in the plasma EV proteome of long-serving professional rugby players. The proteins highlighted in professional rugby players could be used to develop biomarker panels for predicting at-risk athletes or for guiding treatment interventions.</p><p><strong>Summary: </strong>Repetitive high-impact collisions experienced by rugby players may predispose them to neurodegenerative conditions, yet the biological processes underpinning this risk remain poorly understood. This study investigates whether the proteome of plasma extracellular vesicles (EV) could serve as early, minimally invasive biomarkers of neurodegenerative risk in athletes exposed to repeated head impacts. By comparing the EV proteome of professional rugby players, younger academy athletes, and non-collision sport controls, we identified specific proteins with known neuroprotective roles that were depleted in long-serving rugby professionals. These alterations suggest systemic biological changes related to prolonged exposure to collisions. Our findings provide novel insight by highlighting the potential of EV-based proteomic profiling as a tool for early detection and monitoring of neurodegeneration-related processes in at-risk athletic populations. This approach could ultimately inform strategies for risk stratification, early intervention, and tailored clinical monitoring in collision sport athletes.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70036"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12743589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145638080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}