Molecular & Cellular Proteomics最新文献

{"title":"Glycoproteoforms of Osteoarthritis-associated Lubricin in Plasma and Synovial Fluid.","authors":"Ali Reza Afshari, Vincent Chang, Kristina A Thomsson, Jennifer Höglund, Elizabeth N Browne, George Karadzhov, Keira E Mahoney, Taryn M Lucas, Valentina Rangel-Angarita, Henrik Ryberg, Kamlesh Gidwani, Kim Pettersson, Ola Rolfson, Lena I Björkman, Thomas Eisler, Tannin A Schmidt, Gregory D Jay, Stacy A Malaker, Niclas G Karlsson","doi":"10.1016/j.mcpro.2025.100923","DOIUrl":"10.1016/j.mcpro.2025.100923","url":null,"abstract":"<p><p>Lubricin/proteoglycan-4 (PRG-4) is a mucinous glycoprotein that lubricates cartilage and maintains normal tissue function and cell homeostasis. Altered O-glycoproteforms of lubricin have been found in osteoarthritis (OA) synovial fluid (SF), which could ostensibly be used to diagnose early onset OA. However, SF is invasive to obtain and generally would not be surveyed from otherwise healthy individuals. Thus, a plasma-based OA screening tool focused on lubricin glycosylation could be a less invasive method to aid in early-stage OA diagnosis. In this report, we used glycomics and glycoproteomics to characterize glycoproteoforms of OA lubricin in SF and plasma. We obtained near-complete sequence coverage of lubricin's mucin domain and its glycosylation using matched SF and plasma from patients with OA (N = 5). From SF lubricin we observed a spectrum of O-glycans ranging from a single GalNAcα1-Ser/Thr monosaccharide up to branched pentasaccharides. In contrast, plasma based lubricin was predominantly decorated with sialylated Galβ1-3GalNAcα1-Ser/Thr (Sialyl T). To explain the glycosylation differences observed between SF and plasma lubricin, we present splice variant-specific peptides found within the non-glycosylated region, revealing that that the longest spliceoform of lubricin was present exclusively in SF, while additional shorter splice variants could only be detected in plasma. Based on our glycoproteomic data, we developed and validated a lectin assay for lubricin, and applied this on a larger cohort of matched SF/plasma (N = 19) to confirm the glycosylation differences between SF and plasma proteoforms. Next, we leveraged our assay to screen over 100 patient with OA samples (OA patients N = 108/controls N = 38) to probe plasma lubricin as an OA biomarker. Here, we detected a decrease in α2,6 linked sialic acid in patients with OA and further show that the extent of α2,6 and α2,3 sialylation on plasma-associated lubricin correlated with patient characteristics, especially Body Mass Index (BMI).</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100923"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374164","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":"Proteomic Diversity in Bacteria: Insights and Implications for Bacterial Identification.","authors":"Miriam Abele, Armin Soleymaniniya, Florian P Bayer, Nina Lomp, Etienne Doll, Chen Meng, Klaus Neuhaus, Siegfried Scherer, Mareike Wenning, Nina Wantia, Bernhard Kuster, Mathias Wilhelm, Christina Ludwig","doi":"10.1016/j.mcpro.2025.100917","DOIUrl":"10.1016/j.mcpro.2025.100917","url":null,"abstract":"<p><p>Mass spectrometry-based proteomics has revolutionized bacterial identification and elucidated many molecular mechanisms underlying bacterial growth, community formation, and drug resistance. However, most research has been focused on a few model bacteria, overlooking bacterial diversity. In this study, we present the most extensive bacterial proteomic resource to date, covering 303 species, 119 genera, and five phyla with over 636,000 unique expressed proteins, confirming the existence of over 38,700 hypothetical proteins. Accessible via the public resource ProteomicsDB, this dataset enables quantitative exploration of proteins within and across species. Additionally, we developed MS2Bac, a bacterial identification algorithm that queries NCBI's bacterial proteome space in two iterations. MS2Bac achieved over 99% species-level and 89% strain-level accuracy, surpassing methods like MALDI-TOF and FTIR, as demonstrated with food-derived bacterial isolates. MS2Bac also effectively identified bacteria in clinical samples, highlighting the potential of MS-based proteomics as a routine diagnostic tool.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100917"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066455","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":"Quantitative Chromatin Protein Dynamics During Replication Origin Firing in Human Cells.","authors":"Sampath Amitash Gadi, Ivo Alexander Hendriks, Christian Friberg Nielsen, Petya Popova, Ian D Hickson, Michael Lund Nielsen, Luis Toledo","doi":"10.1016/j.mcpro.2025.100915","DOIUrl":"10.1016/j.mcpro.2025.100915","url":null,"abstract":"<p><p>Accurate genome duplication requires a tightly regulated DNA replication program that relies on the fine regulation of origin firing. While the molecular steps involved in origin firing have been determined predominantly in budding yeast, the complexity of this process in human cells has yet to be fully elucidated. Here, we describe a straightforward proteomics approach to systematically analyze protein recruitment to the chromatin during induced origin firing in human cells. Using a specific inhibitor against CHK1 kinase, we induced a synchronized wave of dormant origin firing (DOF) and assessed the S phase chromatin proteome at different time points. We provide time-resolved loading dynamics of 3269 proteins, including the core replication machinery and origin firing factors. This dataset accurately represents known temporal dynamics of proteins on the chromatin during the activation of replication forks and the subsequent DNA damage due to the hyperactivation of excessive replication forks. Finally, we used our dataset to identify the condensin II subunit NCAPH2 as a novel factor required for efficient origin firing and replication. Overall, we provide a comprehensive resource to interrogate the protein recruitment dynamics of replication origin firing events in human cells.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100915"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066463","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":"Localized K63 Ubiquitin Signaling Is Regulated by VCP/p97 During Oxidative Stress.","authors":"Austin O Maduka, Sandhya Manohar, Matthew W Foster, Gustavo M Silva","doi":"10.1016/j.mcpro.2025.100920","DOIUrl":"10.1016/j.mcpro.2025.100920","url":null,"abstract":"<p><p>Under stress conditions, cells reprogram their molecular machineries to mitigate damage and promote survival. Ubiquitin signaling is globally increased during oxidative stress, controlling protein fate and supporting stress defenses at several subcellular compartments. However, the rules driving subcellular ubiquitin localization to promote concerted response mechanisms remain understudied. Here, we show that K63-linked polyubiquitin chains, known to promote proteasome-independent pathways, accumulate primarily in noncytosolic compartments during oxidative stress induced by sodium arsenite in mammalian cells. Our subcellular ubiquitin proteomic analyses of noncytosolic compartments expanded 2.5-fold the pool of proteins (2,494) and provided a comprehensive number of sites (10,157) known to be ubiquitinated during arsenite stress, suggesting their involvement in a myriad of cellular pathways. Moreover, subcellular proteome analyses revealed proteins that are recruited to noncytosolic compartments under stress, including a significant enrichment of helper ubiquitin-binding adaptors of the ATPase valosin-containing protein (VCP) that processes ubiquitinated substrates for downstream signaling. We further show that VCP recruitment to noncytosolic compartments under arsenite stress occurs in a ubiquitin-dependent manner mediated by its adaptor NPLOC4. Additionally, we show that VCP and NPLOC4 activities are critical to sustain low levels of noncytosolic K63-linked ubiquitin chains, supporting a cyclical model of ubiquitin conjugation and removal that is disrupted by reactive oxygen species. This work deepens our understanding of the role of localized ubiquitin and VCP signaling in the basic mechanisms of stress response and highlights new pathways and molecular players that are essential to reshape the composition and function of the human subcellular proteome under dynamic environments.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100920"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066179","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":"Integrated Analysis of Proteome and Transcriptome Profiling Reveals Pan-Cancer-Associated Pathways and Molecular Biomarkers.","authors":"Guo-Sheng Hu, Zao-Zao Zheng, Yao-Hui He, Du-Chuang Wang, Rui-Chao Nie, Wen Liu","doi":"10.1016/j.mcpro.2025.100919","DOIUrl":"10.1016/j.mcpro.2025.100919","url":null,"abstract":"<p><p>Understanding dysregulated genes and pathways in cancer is critical for precision oncology. Integrating mass spectrometry-based proteomic data with transcriptomic data presents unique opportunities for systematic analyses of dysregulated genes and pathways in pan-cancer. Here, we compiled a comprehensive set of datasets, encompassing proteomic data from 2404 samples and transcriptomic data from 7752 samples across 13 cancer types. Comparisons between normal or adjacent normal tissues and tumor tissues identified several dysregulated pathways including mRNA splicing, interferon pathway, fatty acid metabolism, and complement coagulation cascade in pan-cancer. Additionally, pan-cancer upregulated and downregulated genes (PCUGs and PCDGs) were also identified. Notably, RRM2 and ADH1B, two genes which belong to PCUGs and PCDGs, respectively, were identified as robust pan-cancer diagnostic biomarkers. TNM stage-based comparisons revealed dysregulated genes and biological pathways involved in cancer progression, among which the dysregulation of complement coagulation cascade and epithelial-mesenchymal transition are frequent in multiple types of cancers. A group of pan-cancer continuously upregulated and downregulated proteins in different tumor stages (PCCUPs and PCCDPs) were identified. We further constructed prognostic risk stratification models for corresponding cancer types based on dysregulated genes, which effectively predict the prognosis for patients with these cancers. Drug prediction based on PCUGs and PCDGs as well as PCCUPs and PCCDPs revealed that small molecule inhibitors targeting CDK, HDAC, MEK, JAK, PI3K, and others might be effective treatments for pan-cancer, thereby supporting drug repurposing. We also developed web tools for cancer diagnosis, pathologic stage assessment, and risk evaluation. Overall, this study highlights the power of combining proteomic and transcriptomic data to identify valuable diagnostic and prognostic markers as well as drug targets and treatments for cancer.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100919"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066048","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":"What have Data Standards ever done for us?","authors":"S E Orchard","doi":"10.1016/j.mcpro.2025.100933","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.100933","url":null,"abstract":"<p><p>The Human Proteome Organization (HUPO) Proteomics Standards Initiative (PSI) has been successfully developing guidelines, data formats, and controlled vocabularies for both the field of molecular interaction and that of mass spectrometry for more than 20 years. This review explores some of the ways that the proteomics community has benefitted from the development of community standards and takes a look at some of the tools and resources that have been improved or developed as a result of the work of the HUPO-PSI.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100933"},"PeriodicalIF":6.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537421","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":"Proteogenomic Profiling Reveals Small ORFs and Functional Microproteins in Activated T Cells.","authors":"Yang Yang, Chuangmiao Chen, Kecheng Li, Yuanliang Zhang, Lei Chen, Jue Shi, Quanhua Mu, Yang Xu, Qian Zhao","doi":"10.1016/j.mcpro.2025.100914","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.100914","url":null,"abstract":"<p><p>Noncanonical micropeptides or called novel microproteins, i.e., polypeptides mostly under 10 kDa, are encoded by genomic sequences that have been previously annotated as noncoding but now known as small open reading frames (sORFs). The recent identification of microproteins encoded by sORFs has provided evidence that many sORFs encode functional microproteins that play crucial roles in various biological processes. T cell activation is a critical biological process for adaptive immune response. Understanding key players in this process will allow us to decipher the complex mechanisms as well as develop immunotherapy for treating a wide range of diseases. Although there have been extensive studies on canonical proteins in T cell activation, the novel microproteins in T cells and their roles have been uncharted water to date. Nascent proteins are defined as newly synthesized polypeptides emerged during the translation of mRNA. In this study, we combined nascent proteomics and quantitative proteomics to identify 411 novel microproteins in primary human T cells, including 83 nascent microproteins. We activated the T cell function with either PMA/Ionomycin (distal activation) or CD3/CD28 activating antibodies (proximal activation), and obtained a comprehensive canonical protein and microprotein profiles to pinpoint common and distinct differentially expressed proteins under these two activation conditions. After experimental testing, three microproteins numbered T1, T2 and T3 were found to be functional in regulating T cell activation. Bioinformatic and proteomic analyses suggested that T1 was functional related to immune as negative feedback to T cell activation. Our study not only established an integrated approach to uncover and elucidate novel microproteins but also highlight the significant role of microproteins in regulating T cell activation.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100914"},"PeriodicalIF":6.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365507","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":"Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides.","authors":"Meng-Hsuan Hsiao, Yang Miao, Zixing Liu, Konstantin Schütze, Nathachit Limjunyawong, Daphne Chun-Che Chien, Wayne Denis Monteiro, Lee-Shin Chu, William Morgenlander, Sahana Jayaraman, Sung-Eun Jang, Jeffrey J Gray, Heng Zhu, Xinzhong Dong, Martin Steinegger, H Benjamin Larman","doi":"10.1016/j.mcpro.2024.100901","DOIUrl":"10.1016/j.mcpro.2024.100901","url":null,"abstract":"<p><p>Animal venoms, distinguished by their unique structural features and potent bioactivities, represent a vast and relatively untapped reservoir of therapeutic molecules. However, limitations associated with comprehensively constructing and expressing highly complex venom and venom-like molecule libraries have precluded their therapeutic evaluation via high-throughput screening. Here, we developed an innovative computational approach to design a highly diverse library of animal venoms and \"metavenoms\". We used programmable M13 hyperphage display to preserve critical disulfide-bonded structures for highly parallelized single-round biopanning with quantitation via high-throughput DNA sequencing. Our approach led to the discovery of Kunitz-type domain containing proteins that target the human itch receptor Mas-related G-protein coupled receptor member X4, which plays a crucial role in itch perception. Deep learning-based structural homology mining identified two endogenous human homologs, tissue factor pathway inhibitor (TFPI), and serine peptidase inhibitor, Kunitz type 2 (SPINT2), which exhibit agonist-dependent potentiation of Mas-related G-protein coupled receptor member X4. Highly multiplexed screening of animal venoms and metavenoms is therefore a promising approach to uncover new drug candidates.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100901"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922071","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":"Filter-Aided Extracellular Vesicle Enrichment (FAEVEr) for Proteomics.","authors":"Jarne Pauwels, Tessa Van de Steene, Jana Van de Velde, Freya De Muyer, Danaë De Pauw, Femke Baeke, Sven Eyckerman, Kris Gevaert","doi":"10.1016/j.mcpro.2025.100907","DOIUrl":"10.1016/j.mcpro.2025.100907","url":null,"abstract":"<p><p>Extracellular vesicles (EVs), membrane-delimited nanovesicles that are secreted by cells into the extracellular environment, are gaining substantial interest due to their involvement in cellular homeostasis and their contribution to disease pathology. The latter in particular has led to an exponential increase in interest in EVs as they are considered to be circulating packages containing potential biomarkers and are also a possible biological means to deliver drugs in a cell-specific manner. However, several challenges hamper straightforward proteome analysis of EVs as they are generally low abundant and reside in complex biological matrices. These matrices typically contain abundant proteins at concentrations that vastly exceed the concentrations of proteins found in the EV proteome. Therefore, extensive EV isolation and purification protocols are imperative and many have been developed, including (density) ultracentrifugation, size-exclusion, and precipitation methods. Here, we describe filter-aided extracellular vesicle enrichment (FAEVEr) as an approach based on 300 kDa molecular weight cutoff filtration that allows the processing of multiple samples in parallel within a reasonable time frame and at moderate cost. We demonstrate that FAEVEr is capable of quantitatively retaining EV particles on filters, while allowing extensive washing with the mild detergent Tween-20 to remove interfering non-EV proteins. The retained particles are directly lysed on the filter for a complete recovery of the EV protein cargo toward proteome analysis. Here, we validate and optimize FAEVEr on recombinant EV material and apply it on conditioned medium as well as on complex bovine serum, human plasma, and urine. Our results indicate that EVs isolated from MCF7 cells cultured with or without serum have a drastic different proteome because of nutrient deprivation.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100907"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022968","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":"Multitiered Proteome Analysis Displays the Hyperpermeability of the Rheumatoid Synovial Compartment for Plasma Proteins.","authors":"Eva Maria Stork, Sofia Kalaidopoulou Nteak, Danique M H van Rijswijck, J Mirjam A Damen, Hans Ulrich Scherer, Rene E M Toes, Albert Bondt, Tom W J Huizinga, Albert J R Heck","doi":"10.1016/j.mcpro.2024.100900","DOIUrl":"10.1016/j.mcpro.2024.100900","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction. RA affects the synovial joints, the synovial lining, and the permeability of the synovium. As the latter is of central relevance for the distribution of systemically delivered therapeutics into synovial fluid (SF), we here assessed the protein composition of paired plasma and SF of patients diagnosed with RA at three distinct levels of depth using mass spectrometric approaches: the \"total\" proteome, the \"total\" immunoglobulin G1 (IgG1) antibody repertoire, and the RA-specific anticitrullinated protein IgG1 autoantibody repertoire. The SF proteome was found to be dominated in numbers and concentration by plasma proteins, although we additionally detected several cartilage- and neutrophil-derived proteins of lower abundance. Strikingly, the plasma proteins were not only qualitatively reflected in SF but also quantitatively, independent of their size and/or other biochemical features. Also, the synovial \"total\" IgG1 and autoreactive anticitrullinated protein antibody IgG1 repertoire highly resembled the IgG1 repertoires detected in plasma within the same patient. Our comprehensive multilayer data thus reveals that the proteome, including the dominant, most abundant (auto)antibody clones, present in SF of RA patients is a direct reflection of the proteome present in blood, spiked by the local (immune) processes within the RA joint. We thus conclude that proteins directly pass from blood into SF of these joints without substantial bias. These findings thereby not only exemplify the use of in-depth multilayer proteome analyses to revisit basic concepts underlying RA pathology and to monitor the local (immune) processes destructive to cartilage but also provide evidence indicating that (protein-based) therapeutics may equally enter SF of swollen joints and that pharmacokinetic analyses of such therapeutics in blood are directly relevant to the synovial compartment.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100900"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922072","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}