Journal of proteomics最新文献

{"title":"Development of automated proteomic workflows utilizing silicon-based coupling agents","authors":"Connor Frey ,&nbsp;Maor Arad ,&nbsp;Kenneth Ku ,&nbsp;Rhien Hare ,&nbsp;Ronald Balagtas ,&nbsp;Yuming Shi ,&nbsp;Kyung-Mee Moon ,&nbsp;Leonard J. Foster ,&nbsp;Golfam Ghafourifar","doi":"10.1016/j.jprot.2024.105215","DOIUrl":"10.1016/j.jprot.2024.105215","url":null,"abstract":"<div><p>Automated methods for enzyme immobilization <em>via</em> 4-triethoxysilylbutyraldehyde (TESB) derived silicone-based coupling agents were developed. TESB and its oxidized derivative, 4-triethoxysilylbutanoic acid (TESBA), were determined to be the most effective. The resulting immobilized enzyme particles (IEPs) displayed robustness, rapid digestion, and immobilization efficiency of 51 ± 8%. Furthermore, we automated the IEP procedure, allowing for multiple enzymes, and/or coupling agents to be fabricated at once, in a fraction of the time <em>via</em> an Agilent Bravo. The automated trypsin TESB and TESBA IEPs were shown to rival a classical in-gel digestion method. Moreover, pepsin IEPs favored cleavage at leucine (&gt;50%) over aromatic and methionine residues. The IEP method was then adapted for an <em>in-situ</em> immobilized enzyme microreactor (IMER) fabrication. We determined that TESBA could functionalize the silica capillary's inner wall while simultaneously acting as an enzyme coupler. The IMER digestion of bovine serum albumin (BSA), mirroring IEP digestion conditions, yielded a 33–40% primary sequence coverage per LC-MS/MS analysis in as little as 15 min. Overall, our findings underscore the potential of both IEP and IMER methods, paving the way for automated analysis and a reduction in enzyme waste through reuse, thereby contributing to a more cost-effective and timely study of the proteome.</p></div><div><h3>Significance</h3><p>This research introduces 4-triethoxysilylbutyraldehyde (TESB) and its derivatives as silicon-based enzyme coupling agents and an automated liquid handling method for bottom-up proteomics (BUP) while streamlining sample preparation for high-throughput processing. Additionally, immobilized enzyme particle (IEP) fabrication and digestion within the 96-well plate allows for flexibility in protocol where different enzyme-coupler combinations can be employed simultaneously. By enabling the digestion of entire microplates and reducing manual labor, the proposed method enhances reproducibility and offers a more efficient alternative to classical in-gel techniques. Furthermore, pepsin IEPs were noted to favor cleavage at leucine residues which represents an interesting finding when compared to the literature that warrants further study. The capability of immobilized enzyme microreactors (IMER) for rapid digestion (in as little as 15 min) demonstrated the system's efficiency and potential for rapid proteomic analysis. This advancement in BUP not only improves efficiency, but also opens avenues for a fully automated, mass spectrometry-integrated proteomics workflow, promising to expedite research and discoveries in complex biological studies.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874391924001477/pdfft?md5=b0fb6fc707ef6f866eb898525c01513d&pid=1-s2.0-S1874391924001477-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of phosphorylated small ORF-encoded peptides in Hep3B cells by LC/MS/MS","authors":"Mingbo Peng ,&nbsp;Yutian Zhou ,&nbsp;Cuihong Wan","doi":"10.1016/j.jprot.2024.105214","DOIUrl":"10.1016/j.jprot.2024.105214","url":null,"abstract":"<div><p>Small ORF-encoded peptides (SEPs) are a class of low molecular weight proteins and peptides comprising &lt;100 amino acids with important functions in various life activities. Although the sequence length is short, SEPs might also have post-translational modification (PTM). Phosphorylation is one of the most essential PTMs of proteins. In this work, we enriched phosphopeptides with IMAC and TiO₂ materials and analyzed the phosphorylated SEPs in Hep3B cells. A total of 24 phosphorylated SEPs were identified, and 11 SEPs were coded by ncRNA. For the sequence analysis, we found that the general characteristics of phosphorylated SEPs are roughly the same as canonical proteins. Besides, two phosphorylation SEPs have the Stathmin family signature 2 motif, which can regulate the microtubule cytoskeleton. Some SEPs have domains or signal peptides, indicating their specific functions and subcellular locations. Kinase network analysis found a small number of kinases that may be a clue to the specific functions of some SEPs. However, only one-fifth of the predicted phosphorylation sites were identified by LC/MS/MS, indicating that many SEP PTMs are hidden in the dark, waiting to be uncovered and verified. This study helps expand our understanding of SEP and provides information for further SEP function investigation.</p></div><div><h3>Significance</h3><p>Small ORF-encoded peptides (SEPs) are important in various life activities. Although the sequence length is short (&lt;100AA), SEPs might also have post-translational modification (PTM). Phosphorylation is one of the most essential PTMs of proteins. We enriched phosphopeptides and analyzed the phosphorylated SEPs in Hep3B cells. That is the first time to explore the PTM of SPEs systematically. Kinase network analysis found a small number of kinases that may be a clue to the specific functions of SEPs. More SEP PTMs are hidden in the dark and waiting to be uncovered and verified. This study helps expand our understanding of SEP and provides information for further SEP function investigation.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186708","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}

{"title":"Global proteomic analyses of lysine acetylation, malonylation, succinylation, and crotonylation in human sperm reveal their involvement in male fertility","authors":"Yan Tian ,&nbsp;Hao Wang ,&nbsp;Tingting Pan ,&nbsp;Xiaonian Hu ,&nbsp;Jing Ding ,&nbsp;Ying Chen ,&nbsp;Jia Li ,&nbsp;Houyang Chen ,&nbsp;Tao Luo","doi":"10.1016/j.jprot.2024.105213","DOIUrl":"10.1016/j.jprot.2024.105213","url":null,"abstract":"<div><p>Protein lysine modifications (PLMs) are hotspots of post-translational modifications and are involved in many diseases; however, their role in human sperm remains obscure. This study examined the presence and functional roles of a classical PLM (lysine acetylation, Kac) and three novel PLMs (lysine malonylation, Kmal; lysine succinylation, Ksucc; lysine crotonylation, Kcr) in human sperm. Immunoblotting and immunofluorescence assays revealed modified proteins (15–150 kDa) in the tails of human sperm. An immunoaffinity approach coupled with liquid chromatography/tandem mass spectrometry revealed 1423 Kac sites in 680 proteins, 196 Kmal sites in 118 proteins, 788 Ksucc sites in 251 proteins, and 1836 Kcr sites in 645 proteins. These modified proteins participate in a variety of biological processes and metabolic pathways. Crosstalk analysis demonstrated that proteins involved in the sperm energy pathways of glycolysis, oxidative phosphorylation, the citrate cycle, fatty acid oxidation, and ketone body metabolism were modified by at least one of these modifications. In addition, these modifications were found in 62 male fertility-related proteins that weave a protein-protein interaction network associated with asthenoteratozoospermia, asthenozoospermia, globozoospermia, spermatogenic failure, hypogonadotropic hypogonadism, and polycystic kidney disease. Our findings shed light on the functional role of PLMs in male reproduction.</p></div><div><h3>Significance</h3><p>Protein lysine modifications (PLMs) are hotspots of posttranslational modifications and are involved in many diseases. This study revealed the presence of a classical PLM (lysine acetylation) and three novel PLMs (lysine malonylation, lysine succinylation, and lysine crotonylation) in human sperm tails. The modified proteins participate in a variety of biological processes and metabolic pathways. In addition, these modifications were found in 62 male infertility-associated proteins and could serve as potential diagnostic markers and therapeutic targets for male infertility.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141141656","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}

{"title":"Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density","authors":"Cui Yang ,&nbsp;Yu-Ting Huang ,&nbsp;Yi-Fei Yao,&nbsp;Jun-Yi Fu,&nbsp;Yue-Sheng Long","doi":"10.1016/j.jprot.2024.105202","DOIUrl":"10.1016/j.jprot.2024.105202","url":null,"abstract":"<div><p>Deficiency in fragile X mental retardation 1 (<em>Fmr1</em>) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) <em>Fmr1</em>^−/y mice and 306 DEPs of P90 <em>Fmr1</em>^−/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders.</p></div><div><h3>Significance</h3><p>It is well known that loss of FMRP resulted from <em>Fmr1</em> deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 <em>Fmr1</em>^−/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136181","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}

{"title":"Proteomics coupled transcriptomics reveals Slc34a1 and Slc34a3 downregulation as potential features of nephrotoxin-induced acute kidney injury","authors":"Junying Zhang ,&nbsp;Tiantian Che ,&nbsp;Liting Wang ,&nbsp;Wei Sun ,&nbsp;Jing Zhao ,&nbsp;Jiajia Chen ,&nbsp;Yang Liu ,&nbsp;Qi Pu ,&nbsp;Yu Zhang ,&nbsp;Jiani Li ,&nbsp;Zhangfu Li ,&nbsp;Zhaojing Zhu ,&nbsp;Qihuan Fu ,&nbsp;Xiaoyang Wang ,&nbsp;Jiangbei Yuan","doi":"10.1016/j.jprot.2024.105203","DOIUrl":"10.1016/j.jprot.2024.105203","url":null,"abstract":"<div><p>Acute kidney injury (AKI) stands as a prevalent and economically burdensome condition worldwide, yet its complex molecular mechanisms remain incompletely understood. To address this gap, our study employs a multifaceted approach, combining mass spectrometry and RNA sequencing technologies, to elucidate the intricate molecular landscape underlying nephrotoxin-induced AKI in mice by cisplatin- and LPS-induced. By examining the protein and RNA expression profiles, we aimed to uncover novel insights into the pathogenesis of AKI and identify potential diagnostic and therapeutic targets. Our results demonstrate significant down-regulation of Slc34a1 and Slc34a3, shedding light on their crucial roles in AKI pathology and highlighting their promise as actionable targets for diagnosis and treatment. This comprehensive analysis not only enhances our understanding of AKI pathophysiology but also offers valuable avenues for the development of targeted interventions to mitigate its clinical impact.</p></div><div><h3>Significance</h3><p>Nephrotoxicity acute kidney injury (AKI) is a common clinical condition whose pathogenesis is the process by which some drugs, chemicals or other factors cause damage to the kidneys, resulting in impaired kidney function. Although it has been proved that different nephrotoxic substances can affect the kidney through different pathways, whether they have a commonality has not been registered. Here, we combined transcriptomics and proteomics to study the molecular mechanism of LPS and cisplatin-induced nephrotoxic acute kidney injury finding that the down-regulation of Slc34a1 and Slc34a3 may be a critical link in nephrotoxic acute kidney injury, which can be used as a marker for its early diagnosis.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087375","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}

{"title":"SHIP1 modulation and proteome characterization of microglia","authors":"Erpan Ahat ,&nbsp;Zanyu Shi ,&nbsp;Shaoyou Chu ,&nbsp;Hai Hoang Bui ,&nbsp;Emily R. Mason ,&nbsp;Disha M. Soni ,&nbsp;Kenneth D. Roth ,&nbsp;Michael James Chalmers ,&nbsp;Adrian L. Oblak ,&nbsp;Jie Zhang ,&nbsp;Jesus A. Gutierrez ,&nbsp;Timothy Richardson","doi":"10.1016/j.jprot.2024.105198","DOIUrl":"10.1016/j.jprot.2024.105198","url":null,"abstract":"<div><p>Understanding microglial states in the aging brain has become crucial, especially with the discovery of numerous Alzheimer's disease (AD) risk and protective variants in genes such as INPP5D and TREM2, which are essential to microglia function in AD. Here we present a thorough examination of microglia-like cells and primary mouse microglia at the proteome and transcriptome levels to illuminate the roles these genes and the proteins they encode play in various cell states. First, we compared the proteome profiles of wildtype and INPP5D (SHIP1) knockout primary microglia. Our findings revealed significant proteome alterations only in the homozygous SHIP1 knockout, revealing its impact on the microglial proteome. Additionally, we compared the proteome and transcriptome profiles of commonly used in vitro microglia BV2 and HMC3 cells with primary mouse microglia. Our results demonstrated a substantial similarity between the proteome of BV2 and mouse primary cells, while notable differences were observed between BV2 and human HMC3. Lastly, we conducted targeted lipidomic analysis to quantify different phosphatidylinositols (PIs) species, which are direct SHIP1 targets, in the HMC3 and BV2 cells. This in-depth omics analysis of both mouse and human microglia enhances our systematic understanding of these microglia models.</p></div><div><h3>Significance</h3><p>Given the growing urgency of comprehending microglial function in the context of neurodegenerative diseases and the substantial therapeutic implications associated with SHIP1 modulation, we firmly believe that our study, through a rigorous and comprehensive proteomics, transcriptomics and targeted lipidomic analysis of microglia, contributes to the systematic understanding of microglial function in the context of neurodegenerative diseases.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080419","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}

{"title":"Unveiling novel metabolic alterations in postmenopausal osteoporosis and type 2 diabetes mellitus through NMR-based metabolomics: A pioneering approach for identifying early diagnostic markers","authors":"Simran Kaur ,&nbsp;Poonam Kumari ,&nbsp;Gurvinder Singh ,&nbsp;Nainesh Joshi ,&nbsp;Takdeer Kaur ,&nbsp;Vandana Dhiman ,&nbsp;Gurpal Singh ,&nbsp;Naresh Sachdeva ,&nbsp;Dinesh Kumar ,&nbsp;Ravi Pratap Barnwal ,&nbsp;Sanjay Kumar Bhadada","doi":"10.1016/j.jprot.2024.105200","DOIUrl":"10.1016/j.jprot.2024.105200","url":null,"abstract":"<div><h3>Background and aims</h3><p>Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (¹H NMR).</p></div><div><h3>Materials and methods</h3><p>Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using ¹H NMR spectroscopy.</p></div><div><h3>Results</h3><p>Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker.</p></div><div><h3>Conclusion</h3><p>The ¹H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076148","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}

{"title":"Quantitative proteomics revealed protein biomarkers to distinguish malignant pleural effusion from benign pleural effusion","authors":"Tingyan Dong ,&nbsp;Yueming Liang ,&nbsp;Hui Chen ,&nbsp;Yanling Li ,&nbsp;Zhiping Li ,&nbsp;Xinglin Gao","doi":"10.1016/j.jprot.2024.105201","DOIUrl":"10.1016/j.jprot.2024.105201","url":null,"abstract":"<div><p>To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000，with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values.</p></div><div><h3>Significance</h3><p>We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4–12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874391924001337/pdfft?md5=6126a0743b7c1dc09ec98e259205d7b8&pid=1-s2.0-S1874391924001337-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum proteome signatures associated with ileal and colonic ulcers in Crohn's disease","authors":"Nicolas Pierre ,&nbsp;Vân Anh Huynh-Thu ,&nbsp;Dominique Baiwir ,&nbsp;Sophie Vieujean ,&nbsp;Emeline Bequet ,&nbsp;Catherine Reenaers ,&nbsp;Catherine Van Kemseke ,&nbsp;Catherine Salée ,&nbsp;Charlotte Massot ,&nbsp;Maximilien Fléron ,&nbsp;Gabriel Mazzucchelli ,&nbsp;Lisette Trzpiot ,&nbsp;Gauthier Eppe ,&nbsp;Edwin De Pauw ,&nbsp;Edouard Louis ,&nbsp;Marie-Alice Meuwis","doi":"10.1016/j.jprot.2024.105199","DOIUrl":"10.1016/j.jprot.2024.105199","url":null,"abstract":"<div><p>At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (<em>n</em> = 23), isolated ileal ulcers (<em>n</em> = 17), or isolated colonic ulcers (<em>n</em> = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (<em>p</em>-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location.</p></div><div><h3>Significance</h3><p>Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (<em>n</em> = 23); 2) isolated ileal ulcers (<em>n</em> = 17); 3) isolated colonic ulcers (<em>n</em> = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141037645","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}

{"title":"Proteomes of plasmodium knowlesi early and late ring-stage parasites and infected host erythrocytes","authors":"D.C. Anderson ,&nbsp;Mariko S. Peterson ,&nbsp;Stacey A. Lapp ,&nbsp;Mary R. Galinski","doi":"10.1016/j.jprot.2024.105197","DOIUrl":"10.1016/j.jprot.2024.105197","url":null,"abstract":"<div><p>The emerging malaria parasite <em>Plasmodium knowlesi</em> threatens the goal of worldwide malaria elimination due to its zoonotic spread in Southeast Asia. After brief <em>ex-vivo</em> culture we used 2D LC/MS/MS to examine the early and late ring stages of infected <em>Macaca mulatta</em> red blood cells harboring <em>P. knowlesi</em>. The <em>M. mulatta</em> clathrin heavy chain and T-cell and macrophage inhibitor ERMAP were overexpressed in the early ring stage; glutaredoxin 3 was overexpressed in the late ring stage; GO term differential enrichments included response to oxidative stress and the cortical cytoskeleton in the early ring stage. <em>P. knowlesi</em> clathrin heavy chain and 60S acidic ribosomal protein P2 were overexpressed in the late ring stage; GO term differential enrichments included vacuoles in the early ring stage, ribosomes and translation in the late ring stage, and Golgi- and COPI-coated vesicles, proteasomes, nucleosomes, vacuoles, ion-, peptide-, protein-, nucleocytoplasmic- and RNA-transport, antioxidant activity and glycolysis in both stages.</p></div><div><h3>Significance</h3><p>Due to its zoonotic spread, cases of the emerging human pathogen <em>Plasmodium knowlesi</em> in southeast Asia, and particularly in Malaysia, threaten regional and worldwide goals for malaria elimination. Infection by this parasite can be fatal to humans, and can be associated with significant morbidity. Due to zoonotic transmission from large macaque reservoirs that are untreatable by drugs, and outdoor biting mosquito vectors that negate use of preventive measures such as bed nets, its containment remains a challenge. Its biology remains incompletely understood. Thus we examine the expressed proteome of the early and late <em>ex-vivo</em> cultured ring stages, the first intraerythrocyte developmental stages after infection of host rhesus macaque erythrocytes. We used GO term enrichment strategies and differential protein expression to compare early and late ring stages. The early ring stage is characterized by the enrichment of <em>P. knowlesi</em> vacuoles, and overexpression of the <em>M. mulatta</em> clathrin heavy chain, important for clathrin-coated pits and vesicles, and clathrin-mediated endocytosis. The <em>M. mulatta</em> protein ERMAP was also overexpressed in the early ring stage, suggesting a potential role in early ring stage inhibition of T-cells and macrophages responding to <em>P. knowlesi</em> infection of reticulocytes. This could allow expansion of the host <em>P. knowlesi</em> cellular niche, allowing parasite adaptation to invasion of a wider age range of RBCs than the preferred young RBCs or reticulocytes, resulting in proliferation and increased pathogenesis in infected humans. Other GO terms differentially enriched in the early ring stage include the <em>M. mulatta</em> cortical cytoskeleton and response to oxidative stress. The late ring stage is characterized by overexpression of the <em>P. knowlesi</em>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958038","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}