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      Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study

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          Abstract

          Background

          Aspiration pneumonia (AP), which is a major cause of death in the elderly, does present with typical symptoms in the early stages of onset, thus it is difficult to detect and treat at an early stage. In this study, we identified biomarkers that are useful for the detection of AP and focused on salivary proteins, which may be collected non-invasively. Because expectorating saliva is often difficult for elderly people, we collected salivary proteins from the buccal mucosa.

          Methods

          We collected samples from the buccal mucosa of six patients with AP and six control patients (no AP) in an acute-care hospital. Following protein precipitation using trichloroacetic acid and washing with acetone, the samples were analyzed by liquid chromatography and tandem mass spectrometry (LC–MS/MS). We also determined the levels of cytokines and chemokines in non-precipitated samples from buccal mucosa.

          Results

          Comparative quantitative analysis of LC–MS/MS spectra revealed 55 highly ( P values < 0.10) abundant proteins with high FDR confidence ( q values < 0.01) and high coverage (> 50%) in the AP group compared with the control group. Among the 55 proteins, the protein abundances of four proteins (protein S100-A7A, eukaryotic translation initiation factor 1, Serpin B4, and peptidoglycan recognition protein 1) in the AP group showed a negative correlation with the time post-onset; these proteins are promising AP biomarker candidates. In addition, the abundance of C-reactive protein (CRP) in oral samples was highly correlated with serum CRP levels, suggesting that oral CRP levels may be used as a surrogate to predict serum CRP in AP patients. A multiplex cytokine/chemokine assay revealed that MCP-1 tended to be low, indicating unresponsiveness of MCP-1 and its downstream immune pathways in AP.

          Conclusion

          Our findings suggest that oral salivary proteins, which are obtained non-invasively, can be utilized for the detection of AP.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12014-023-09398-w.

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          Most cited references46

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            The Gene Ontology resource: enriching a GOld mine

            Abstract The Gene Ontology Consortium (GOC) provides the most comprehensive resource currently available for computable knowledge regarding the functions of genes and gene products. Here, we report the advances of the consortium over the past two years. The new GO-CAM annotation framework was notably improved, and we formalized the model with a computational schema to check and validate the rapidly increasing repository of 2838 GO-CAMs. In addition, we describe the impacts of several collaborations to refine GO and report a 10% increase in the number of GO annotations, a 25% increase in annotated gene products, and over 9,400 new scientific articles annotated. As the project matures, we continue our efforts to review older annotations in light of newer findings, and, to maintain consistency with other ontologies. As a result, 20 000 annotations derived from experimental data were reviewed, corresponding to 2.5% of experimental GO annotations. The website (http://geneontology.org) was redesigned for quick access to documentation, downloads and tools. To maintain an accurate resource and support traceability and reproducibility, we have made available a historical archive covering the past 15 years of GO data with a consistent format and file structure for both the ontology and annotations.
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              Monocyte chemoattractant protein-1 (MCP-1): an overview.

              Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.
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                Author and article information

                Contributors
                sokamoto@mhs.mp.kanazawa-u.ac.jp
                Journal
                Clin Proteomics
                Clin Proteomics
                Clinical Proteomics
                BioMed Central (London )
                1542-6416
                1559-0275
                9 March 2023
                9 March 2023
                2023
                : 20
                : 9
                Affiliations
                [1 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Advanced Health Care Science Research Unit, , Institute for Frontier Science Initiative, Kanazawa University, ; 5-11-80 Kodatsuno, Kanazawa, Ishikawa 9200942 Japan
                [2 ]GRID grid.471500.7, ISNI 0000 0004 0649 1576, Nursing Department, , Fujita Health University Hospital, ; 1-98 Dengakugakubo, Kutsukake-Cho, Toyoake, Aichi 4701192 Japan
                [3 ]GRID grid.416605.0, ISNI 0000 0004 0595 3863, Department of Oral and Maxillofacial Surgery, , Noto General Hospital, ; 6-4 Fujibashi, Nanao, Ishikawa 9260816 Japan
                [4 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Division of Immunology and Molecular Biology, Cancer Research Institute, , Kanazawa University. Kakuma-Cho, ; Kanazawa, Ishikawa 9201164 Japan
                [5 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Division of Functional Genomics, Advanced Science Research Center, , Kanazawa University, ; Kanazawa, Ishikawa 9200934 Japan
                [6 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Division of Functional Genomics, , Cancer Research Institute, Kanazawa University. Kakuma-Cho, ; Kanazawa, Ishikawa 9201164 Japan
                [7 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Institute of Medical, Pharmaceutical and Health Sciences, , AI Hospital/Macro Signal Dynamics Research and Development Center, Kanazawa University, ; 5-11-80 Kodatsuno, Kanazawa, Ishikawa 9200942 Japan
                [8 ]GRID grid.443808.3, ISNI 0000 0000 8741 9859, Ishikawa Prefectural Nursing University, ; 1-1 Gakuendai, Kahoku, Ishikawa 929-1210 Japan
                [9 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, , Kanazawa University, ; 5−11-80 Kodatsuno, Kanazawa, Ishikawa 9200942 Japan
                [10 ]GRID grid.256115.4, ISNI 0000 0004 1761 798X, Research Center for Implementation Nursing Science Initiative, Innovation Promotion Division, , Fujita Health University, ; 1-98 Dengakugakubo, Kutsukake-Cho, Toyoake, Aichi 4701192 Japan
                Article
                9398
                10.1186/s12014-023-09398-w
                9996945
                36894881
                a4005ea8-a052-4f0c-9a89-12f5f334748c
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 15 June 2022
                : 21 February 2023
                Funding
                Funded by: Japan Society for the Promotion of Science,Japan
                Award ID: 20H00560
                Categories
                Research
                Custom metadata
                © The Author(s) 2023

                Molecular medicine
                aspiration pneumonia,biomarker,proteomics,buccal mucosa
                Molecular medicine
                aspiration pneumonia, biomarker, proteomics, buccal mucosa

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