Katarzyna Macur, Anna Roszkowska, Paulina Czaplewska, Natalia Miękus-Purwin, Ilona Klejbor, Janusz Moryś, Tomasz Bączek
{"title":"Pressure Cycling Technology Combined With MicroLC-SWATH Mass Spectrometry for the Analysis of Sex-Related Differences Between Male and Female Cerebella: A Promising Approach to Investigating Proteomics Differences in Psychiatric and Neurodegenerative Diseases.","authors":"Katarzyna Macur, Anna Roszkowska, Paulina Czaplewska, Natalia Miękus-Purwin, Ilona Klejbor, Janusz Moryś, Tomasz Bączek","doi":"10.1002/prca.202400001","DOIUrl":"10.1002/prca.202400001","url":null,"abstract":"<p><strong>Purpose: </strong>Pressure cycling technology (PCT) coupled with data-independent sequential window acquisition of all theoretical mass spectra (SWATH-MS) can be a powerful tool for identifying and quantifying biomarkers (e.g., proteins) in complex biological samples. Mouse models are frequently used in brain studies, including those focusing on different neurodevelopmental and psychiatric disorders. More and more pieces of evidence have suggested that sex-related differences in the brain impact the rates, clinical manifestations, and therapy outcomes of these disorders. However, sex-based differences in the proteomic profiles of mouse cerebella have not been widely investigated.</p><p><strong>Experimental design: </strong>In this pilot study, we evaluate the applicability of coupling PCT sample preparation with microLC-SWATH-MS analysis to map and identify differences in the proteomes of two female and two male mice cerebellum samples.</p><p><strong>Results: </strong>We identified and quantified 174 proteins in mice cerebella. A comparison of the proteomic profiles revealed that the levels of 11 proteins in the female and male mice cerebella varied significantly.</p><p><strong>Conclusions and clinical relevance: </strong>Although this study utilizes a small sample, our results indicate that the studied male and female mice cerebella possessed differing proteome compositions, mainly with respect to energy metabolism processes.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400001"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111311","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":"Correction to \"Identification of Novel Biomarkers for Frailty Diagnosis Via Serum Amino Acids Metabolomic Analysis Using UPLC-MS/MS\".","authors":"","doi":"10.1002/prca.202400084","DOIUrl":"10.1002/prca.202400084","url":null,"abstract":"","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400084"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293932","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}
Ahmed G E Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán
{"title":"A novel micropeptide, Slitharin, exerts cardioprotective effects in myocardial infarction.","authors":"Ahmed G E Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán","doi":"10.1002/prca.202300128","DOIUrl":"10.1002/prca.202300128","url":null,"abstract":"<p><strong>Purpose: </strong>Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.</p><p><strong>Experimental design: </strong>We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.</p><p><strong>Results: </strong>We identified a novel 24-amino acid micropeptide (dubbed Slitharin [Slt]) with a non-canonical leucine start codon, arising from long intergenic non-coding (LINC) RNA 2099. Neonatal rat ventricular myocytes (NRVMs) exposed to Slt were protected from hypoxic injury in vitro compared to a vehicle or scrambled control. Transcriptomic analysis of cardiomyocytes exposed to Slt reveals cytoprotective capacity, putatively through regulation of stress-induced MAPK-ERK. Slt also exerted cardioprotective effects in rats with myocardial infarction as shown by reduced infarct size 48 h post-injury. Conclusions and clinical relavance: Thus, Slt is a non-coding RNA-derived micropeptide, identified in the extracellular space, with a potential cardioprotective function.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300128"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040180","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":"Methods and clinical biomarker discovery for targeted proteomics using Olink technology.","authors":"Han Wang, Tian Zhao, Jingjing Zeng, Ruijie Zhang, Liyuan Pu, Suying Qian, Shan Xu, Yannan Jiang, Lifang Pan, Xiaoyu Dai, Xu Guo, Liyuan Han","doi":"10.1002/prca.202300233","DOIUrl":"10.1002/prca.202300233","url":null,"abstract":"<p><strong>Purpose: </strong>This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment.</p><p><strong>Experimental design: </strong>We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology.</p><p><strong>Results: </strong>Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments.</p><p><strong>Conclusions: </strong>Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300233"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899334","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}
Zhonghao Yuan, Zhizhen Lai, Yixin Zhang, Jiyun Zhang, Jinyu Zhou, Dan Li, Weihong Yu, Jiang Zhou, Zhili Li
{"title":"N-glycosylation of disease-specific haptoglobin for the early screening of diabetic retinopathy.","authors":"Zhonghao Yuan, Zhizhen Lai, Yixin Zhang, Jiyun Zhang, Jinyu Zhou, Dan Li, Weihong Yu, Jiang Zhou, Zhili Li","doi":"10.1002/prca.202300032","DOIUrl":"10.1002/prca.202300032","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR.</p><p><strong>Experimental design: </strong>Serum disease-specific haptoglobin-β (Hp-β) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry.</p><p><strong>Results: </strong>Fucosylation of Hp-β was significantly increased and sialylation of Hp-β was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p < 0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-β was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR.</p><p><strong>Conclusion: </strong>Changes in Hp-β glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300032"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060362","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}
Brandon J Harder, Annemarie N Lekkerkerker, Ellen P Casavant, Jason A Hackney, Allen Nguyen, Jacqueline M McBride, William Rodney Mathews, Veronica G Anania
{"title":"Comprehensive profiling of the human fecal proteome from IBD patients with DIA-MS enables evaluation of disease-relevant proteins.","authors":"Brandon J Harder, Annemarie N Lekkerkerker, Ellen P Casavant, Jason A Hackney, Allen Nguyen, Jacqueline M McBride, William Rodney Mathews, Veronica G Anania","doi":"10.1002/prca.202300075","DOIUrl":"10.1002/prca.202300075","url":null,"abstract":"<p><strong>Purpose: </strong>Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by chronic gastrointestinal inflammation. A high unmet need exists for noninvasive biomarkers in IBD to monitor changes in disease activity and guide treatment decisions. Stool is an easily accessed, disease proximal matrix in IBD, however the composition of the IBD fecal proteome remains poorly characterized.</p><p><strong>Experimental design: </strong>A data-independent acquisition LC-MS/MS approach was used to profile the human fecal proteome in two independent cohorts (Cohort 1: healthy n = 5, UC n = 5, CD n = 5, Cohort 2: healthy n = 20, UC n = 10, and CD n = 10) to identify noninvasive biomarkers reflective of disease activity.</p><p><strong>Results: </strong>688 human proteins were quantified, with 523 measured in both cohorts. In UC stool 96 proteins were differentially abundant and in CD stool 126 proteins were differentially abundant compared to healthy stool (absolute log2 fold change > 1, p-value < 0.05). Many of these fecal proteins are associated with infiltrating immune cells and ulceration/rectal bleeding, which are hallmarks of IBD pathobiology. Mapping the identified fecal proteins to a whole blood single-cell RNA sequencing data set revealed the involvement of various immune cell subsets to the IBD fecal proteome.</p><p><strong>Conclusions and clinical relevance: </strong>Findings from this study not only confirmed the presence of established fecal biomarkers for IBD, such as calprotectin and lactoferrin, but also revealed new fecal proteins from multiple pathways known to be dysregulated in IBD. These novel proteins could serve as potential noninvasive biomarkers to monitor specific aspects of IBD disease activity which could expedite clinical development of novel therapeutic targets.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300075"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327067","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 changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.","authors":"Xubo Yang, Hongmei Tang, Lu He, Tingting Peng, Jinling Li, Jingbo Zhang, Liru Liu, Hongyu Zhou, Zhaofang Chen, Jingyi Zhao, Yage Zhang, Mengru Zhong, Mingshan Han, Mengqing Zhang, Huiran Niu, Kaishou Xu","doi":"10.1002/prca.202300070","DOIUrl":"10.1002/prca.202300070","url":null,"abstract":"<p><strong>Purpose: </strong>The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP).</p><p><strong>Experimental design: </strong>A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting.</p><p><strong>Results: </strong>Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways.</p><p><strong>Conclusion and clinical relevance: </strong>BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300070"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060363","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}
Xian-Yan Yang, Xiao-Xia Zheng, Xue-Jia Zhai, Tao Tang, Shi-Cang Yu
{"title":"Spindle apparatus coiled-coil protein 1 (SPDL1) serves as a novel prognostic biomarker in triple-negative breast cancer.","authors":"Xian-Yan Yang, Xiao-Xia Zheng, Xue-Jia Zhai, Tao Tang, Shi-Cang Yu","doi":"10.1002/prca.202300002","DOIUrl":"10.1002/prca.202300002","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) has a poor prognosis, an ineffective diagnosis, and a high degree of aggressiveness. Therefore, novel therapeutic targets for TNBC urgently need to be identified.</p><p><strong>Methods: </strong>Through a series of bioinformatics analyses, including analysis of differential gene expression, protein-protein interaction (PPI) network, univariate cox regression, immune infiltration, pathway enrichment, etc, as well as auxiliary immunohistochemistry (IHC) and protein quantitativae analysis, to explore prognostic marker for TNBC.</p><p><strong>Results: </strong>In TNBC tissues, we found that SPDL1 (CCDC99) was considerably overexpressed at both the mRNA and protein levels compared to that in normal and non-TNBC tissues. Additionally, we found that SPDL1-high expression was strongly linked to poor prognosis in TNBC patients. Excessive SPDL1 expression was positively correlated with tumor growth and strongly linked to the cell cycle, DNA replication, and the p53 signaling pathway. In addition, CIBERSORT analysis revealed that SPDL1 can affect the tumor immune microenvironment (TME) in TNBC, encourage the development of TNBC and act as a potential prognostic biomarker for TNBC. Patients with SPDL1-high expression were more sensitive to AZD8055. Notably, we discovered that SPDL1 is highly expressed in the majority of malignancies and may have an impact on the pancancer prognosis.</p><p><strong>Conclusions: </strong>SPDL1 can serve as a novel prognostic marker for TNBC and pancancer patients.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202300002"},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692787","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}