Clinical proteomics最新文献

{"title":"Repair effect analysis of mesenchymal stem cell conditioned media from multiple sources on HUVECs damaged by high glucose.","authors":"Xueyan Guo, Junyan Wang, Rong Su, Dan Luo, Keli Zhao, Yan Li","doi":"10.1186/s12014-024-09521-5","DOIUrl":"https://doi.org/10.1186/s12014-024-09521-5","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic potential of mesenchymal stem cells (MSCs) may be partly attributed to their secretion growth factors, cytokines and chemokines. In various preclinical studies, the use of MSC-conditioned media (CM) has demonstrated promising potential for promoting vascular repair.</p><p><strong>Methods: </strong>To gain a comprehensive understanding of the variations in conditioned media derived from different sources of mesenchymal stem cells (MSCs) including umbilical cord, adipose and bone marrow, we investigated their reparative effects on human umbilical vein endothelial cells (HUVECs) subjected to damage induced by high glucose. Initially, the secreted proteins from the three types of MSCs were assessed using the bicinchoninic acid (BCA) method. Subsequently, we examined the influence of different type of MSC secreted proteins on the proliferation of HUVECs under high glucose conditions. Following this, transwell migration experiments were conducted to evaluate the impact of MSC source on the migration of HUVECs damaged by high glucose. We further compared the effects of adding secreted proteins from the three types of MSCs on the tube formation ability of HUVECs subjected to high glucose damage. Finally, tandem mass tag (TMT) labeling quantitative proteomics was performed to analyze differently expressed proteins in the secreted proteins of three type MSC by using LC-MS/MS.</p><p><strong>Results: </strong>In this study, we observed a significantly higher secretion of proteins from umbilical cord mesenchymal stem cells (UMSCs) compared to adipose-derived stem cells (ADSCs). Subsequently, we found that the of proliferation HUVECs was significantly improved with supplementing the three MSCs secreted proteins under high glucose medium. Notably, the reparative effects of bone marrow mesenchymal stem cells (BMSCs) and UMSCs were superior to those of ADSCs. Afterwards, UMSCs exhibited the strongest ability to repair cell migration when HUVECs damaged by high glucose. Moreover, all three MSCs' secreted proteins exhibited the ability to enhance tube formation. Importantly, the UMSCs' secretome showed the most pronounced improvement in tube formation, as evidenced by the evaluation of parameters such as the number of nodes, the number of branches, and total length. These findings suggest that the UMSCs' secretome plays a crucial role in biological processes such as vasculature development, cell adhesion, and tissue remodeling. Additionally, the BMSCs' secretome was found to promote vascular development. The results collectively indicate the diverse therapeutic potential of MSC secretomes in influencing various aspects of cellular function and tissue repair.</p><p><strong>Conclusion: </strong>In conclusion, this study offers a valuable reference for the selection of more suitable sources of mesenchymal stem cells (MSCs) in the treatment of diabetic cardiovascular disease.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"69"},"PeriodicalIF":2.8,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative site-specific N-glycosylation analysis reveals IgG glyco-signatures for pancreatic cancer diagnosis.","authors":"Yi Jin, Ran Hu, Yufan Gu, Ailin Wei, Ang Li, Yong Zhang","doi":"10.1186/s12014-024-09522-4","DOIUrl":"https://doi.org/10.1186/s12014-024-09522-4","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a highly aggressive tumor with a poor prognosis due to a low early detection rate and a lack of biomarkers. Most of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). Alterations in the N-glycosylation of plasma immunoglobulin G (IgG) have been shown to be closely associated with the onset and development of several cancers and could be used as biomarkers for diagnosis. The study aimed to explore intact N-glycosylation profile of IgG in patients with PDAC and find relation between intact N-glycosylation profile of IgG and clinical information such as diagnosis and prognosis.</p><p><strong>Methods: </strong>In this study, we employed a well-evaluated approach (termed GlycoQuant) to assess the site-specific N-glycosylation profile of human plasma IgG in both healthy individuals and patients with pancreatic ductal adenocarcinoma (PDAC). The datasets generated and analyzed during the current study are available in the ProteomeXchange Consortium ( http://www.proteomexchange.org/ ) via the iProX partner repository, with the dataset identifier PXD051436.</p><p><strong>Results: </strong>The analysis of rapidly purified IgG samples from 100 patients with different stages of PDAC, in addition to 30 healthy controls, revealed that the combination of carbohydrate antigen 19 - 9 (CA19-9), IgG1-GP05 (IgG1-TKPREEQYNSTYR-HexNAc [4]Hex [5]Fuc [1]NeuAc [1]), and IgG4-GP04 (IgG4-EEQFNSTYR- HexNAc [4]Hex [5]Fuc [1]NeuAc [1]) can be used to distinguish between PDAC patients and healthy individuals (AUC = 0.988). In addition, cross validation of the diagnosis model showed satisfactory result.</p><p><strong>Conclusions: </strong>The study demonstrated that the integrated quantitative method can be utilized for large-scale clinical N-glycosylation research to identify novel N-glycosylated biomarkers. This could facilitate the development of clinical glycoproteomics.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"68"},"PeriodicalIF":2.8,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TMT-based proteomic analysis of radiation lung injury in rats.","authors":"Jing Liu, Kuanke Gao, Xue Ren, Tong Wu, Haibo Zhang, Defu Yang, Hengjiao Wang, Ying Xu, Ying Yan","doi":"10.1186/s12014-024-09518-0","DOIUrl":"https://doi.org/10.1186/s12014-024-09518-0","url":null,"abstract":"<p><p>Radiation-induced lung injury (RILI) is a common adverse effect of radiation therapy that negatively affects treatment progression and the quality of life of patients. Identifying biomarkers for RILI can provide reference for the prevention and treatment of RILI in clinical practice. In this study, to explore key proteins related to RILI, we constructed a rat model of RILI and analyzed RILI tissues and normal lung tissues using tandem mass spectrometry labeling and quantitative proteomics technology. We used Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Gene Ontology (GO) enrichment and protein-protein interaction (PPI) networks for bioinformatics analysis of Differentially expressed proteins (DEPs). The results identified 185 differentially expressed proteins in lung tissue from the RILI group compared with the controls, including 110 up-regulated proteins and 75 down-regulated proteins. GO analysis showed that the differentially expressed proteins were involved oxidation-reduction process, cellular biosynthetic processes and extracellular matrix. KEGG results demonstrated that the differentially expressed proteins were mainly involved in the PI3K-Akt, ECM receptor interactions, arachidonic acid metabolism, glutathione metabolism and other pathways. These results on the functions and signaling pathways of the differentially expressed proteins provide a theoretical basis for further study of the mechanism of RILI.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"67"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined urine proteomics and metabolomics analysis for the diagnosis of pulmonary tuberculosis.","authors":"Jiajia Yu, Jinfeng Yuan, Zhidong Liu, Huan Ye, Minggui Lin, Liping Ma, Rongmei Liu, Weimin Ding, Li Li, Tianyu Ma, Shenjie Tang, Yu Pang","doi":"10.1186/s12014-024-09514-4","DOIUrl":"https://doi.org/10.1186/s12014-024-09514-4","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) diagnostic monitoring is paramount to clinical decision-making and the host biomarkers appears to play a significant role. The currently available diagnostic technology for TB detection is inadequate. In the present study, we aimed to identify biomarkers for diagnosis of pulmonary tuberculosis (PTB) using urinary metabolomic and proteomic analysis.</p><p><strong>Methods: </strong>In the study, urine from 40 PTB, 40 lung cancer (LCA), 40 community-acquired pneumonia (CAP) patients and 40 healthy controls (HC) was collected. Biomarker panels were selected based on random forest (RF) analysis.</p><p><strong>Results: </strong>A total of 3,868 proteins and 1,272 annotated metabolic features were detected using pairwise comparisons. Using AUC ≥ 0.80 as a cutoff value, we picked up five protein biomarkers for PTB diagnosis. The five-protein panel yielded an AUC for PTB/HC, PTB/CAP and PTB/LCA of 0.9840, 0.9680 and 0.9310, respectively. Additionally, five metabolism biomarkers were selected for differential diagnosis purpose. By employment of the five-metabolism panel, we could differentiate PTB/HC at an AUC of 0.9940, PTB/CAP of 0.8920, and PTB/LCA of 0.8570.</p><p><strong>Conclusion: </strong>Our data demonstrate that metabolomic and proteomic analysis can identify a novel urine biomarker panel to diagnose PTB with high sensitivity and specificity. The receiver operating characteristic curve analysis showed that it is possible to perform non-invasive clinical diagnoses of PTB through these urine biomarkers.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"66"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF levels of brain-derived proteins correlate with brain ventricular volume in cognitively healthy 70-year-olds.","authors":"Sofia Bergström, Sára Mravinacová, Olof Lindberg, Anna Zettergren, Eric Westman, Lars-Olof Wahlund, Kaj Blennow, Henrik Zetterberg, Silke Kern, Ingmar Skoog, Anna Månberg","doi":"10.1186/s12014-024-09517-1","DOIUrl":"10.1186/s12014-024-09517-1","url":null,"abstract":"<p><strong>Background: </strong>The effect of varying brain ventricular volume on the cerebrospinal fluid (CSF) proteome has been discussed as possible confounding factors in comparative protein level analyses. However, the relationship between CSF volume and protein levels remains largely unexplored. Moreover, the few existing studies provide conflicting findings, indicating the need for further research.</p><p><strong>Methods: </strong>Here, we explored the association between levels of 88 pre-selected CSF proteins and ventricular volume derived from magnetic resonance imaging (MRI) measurements in 157 cognitively healthy 70-year-olds from the H70 Gothenburg Birth Cohort Studies, including individuals with and without pathological levels of Alzheimer's disease (AD) CSF markers (n = 123 and 34, respectively). Both left and right lateral, the inferior horn as well as the third and the fourth ventricular volumes were measured. Different antibody-based methods were employed for the protein measurements, with most being analyzed using a multiplex bead-based microarray technology. Furthermore, the associations between the protein levels and cortical thickness, fractional anisotropy, and mean diffusivity were assessed.</p><p><strong>Results: </strong>CSF levels of many brain-derived proteins correlated with ventricular volumes in A-T- individuals, with lower levels in individuals with larger ventricles. The strongest negative correlations with total ventricular volume were observed for neurocan (NCAN) and neurosecretory protein VGF (rho = -0.34 for both). Significant negative correlations were observed also for amyloid beta (Ab) 38, Ab40, total tau (t-tau), and phosphorylated tau (p-tau), with correlation ranging between - 0.34 and - 0.28, while no association was observed between ventricular volumes and Ab42 or neurofilament light chain (NfL). Proteins with negative correlations to ventricular volumes further demonstrated negative correlations to mean diffusivity and positive correlation to fractional anisotropy. However, only weak or no correlations were observed between the CSF protein levels and cortical thickness. A + T + individuals demonstrated higher CSF protein levels compared to A-T- individuals with the most significant differences observed for neurogranin (NRGN) and synuclein beta (SNCB).</p><p><strong>Conclusions: </strong>Our findings suggest that the levels of many brain-derived proteins in CSF may be subjected to dilution effects depending on the size of the brain ventricles in healthy individuals without AD pathology. This phenomenon could potentially contribute to the inter-individual variations observed in CSF proteomic studies.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"65"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative proteomic analysis of human vitreous in rhegmatogenous retinal detachment and diabetic retinopathy reveals a common pathway and potential therapeutic target.","authors":"Tommaso Brighenti, Giuseppe Neri, Marco Mazzola, Gabriele Tomé, Mariella Scalfati, Daniele Peroni, Romina Belli, Elena Zampedri, Toma Tebaldi, Ugo Borello, Federica Romanelli, Simona Casarosa","doi":"10.1186/s12014-024-09515-3","DOIUrl":"10.1186/s12014-024-09515-3","url":null,"abstract":"<p><strong>Background: </strong>The vitreous humor serves as a window into the physiological and pathological processes of the eye, particularly the retina. Diabetic retinopathy (DR), a leading cause of blindness, involves hyperglycemia-induced damage to retinal cells, leading to ischemia and elevated nitric oxide levels, culminating in vascular proliferation. Rhegmatogenous retinal detachment (RD) results from a break in the neuroretina, triggering ischemia, photoreceptor death, and cellular proliferation. Proliferative vitreoretinopathy (PVR) further complicates these conditions through fibrous proliferation. Despite their prevalence and potential for blindness, our understanding of the molecular mechanisms underlying these vitreoretinal diseases is incomplete.</p><p><strong>Methods and results: </strong>To elucidate disease mechanisms and identify potential therapeutic targets, we conducted a comparative proteomic analysis of vitreous samples from DR, RD, and macular pucker (P) patients, which were chosen as controls. LC-MS analysis identified 988 quantifiable proteins, with distinct clustering observed among disease groups. Differential expression analysis revealed 202 proteins in RD vs. P and 167 in DR vs. P, highlighting distinct proteomic signatures. Enrichment analysis identified glucose metabolism as an altered process in both diseases, suggesting common pathways despite differing etiologies. Notably, aldo-keto reductase family 1 member B1 (AKR1B1) has emerged as a potential key player in both DR and RD, indicating its role in glucose metabolism and inflammation. In silico drug screening identified diclofenac, an approved ophthalmic non-steroidal anti-inflammatory drug (NSAID), as a potential therapeutic agent targeting AKR1B1.</p><p><strong>Conclusion: </strong>Our study revealed distinct proteomic signatures and common pathways in vitreoretinal diseases, highlighting AKR1B1 as a potential therapeutic target. Using diclofenac during diagnosis and postoperative care for diabetic retinopathy or rhegmatogenous retinal detachment may reduce complications, lower costs, and improve quality of life. Future research will focus on confirming AKR1B1's role in vitreoretinal diseases and understanding diclofenac's mechanism of action.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"63"},"PeriodicalIF":2.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of serum N-glycans signatures in three major gastrointestinal cancers by high-throughput N-glycome profiling.","authors":"Si Liu, Jianmin Huang, Yuanyuan Liu, Jiajing Lin, Haobo Zhang, Liming Cheng, Weimin Ye, Xin Liu","doi":"10.1186/s12014-024-09516-2","DOIUrl":"10.1186/s12014-024-09516-2","url":null,"abstract":"<p><strong>Background: </strong>Alternative N-glycosylation of serum proteins has been observed in colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), while comparative study among those three cancers has not been reported before. We aimed to identify serum N-glycans signatures and introduce a discriminative model across the gastrointestinal cancers.</p><p><strong>Methods: </strong>The study population was initially screened according to the exclusion criteria process. Serum N-glycans profiling was characterized by a high-throughput assay based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Diagnostic model was built by random forest, and unsupervised machine learning was performed to illustrate the differentiation between the three major gastrointestinal (GI) cancers.</p><p><strong>Results: </strong>We have found that three major gastrointestinal cancers strongly associated with significantly decreased mannosylation and mono-galactosylation, as well as increased sialylation of serum glycoproteins. A highly accurate discriminative power (> 0.90) for those gastrointestinal cancers was obtained with serum N-glycome based predictive model. Additionally, serum N-glycome profile exhibited distinct distributions across GI cancers, and several altered N-glycans were hyper-regulated in each specific disease.</p><p><strong>Conclusions: </strong>Serum N-glycome profile was differentially expressed in three major gastrointestinal cancers, providing a new clinical tool for cancer diagnosis and throwing a light upon the disease-specific molecular signatures.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"64"},"PeriodicalIF":2.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in amino acid concentrations and the gut microbiota composition are implicated in the mucosal healing of ulcerative colitis and can be used as noninvasive diagnostic biomarkers.","authors":"Jing Wu, Maojuan Li, Chan Zhou, Jiamei Rong, Fengrui Zhang, Yunling Wen, Jinghong Qu, Rui Wu, Yinglei Miao, Junkun Niu","doi":"10.1186/s12014-024-09513-5","DOIUrl":"10.1186/s12014-024-09513-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mucosal healing is the therapeutic target for ulcerative colitis (UC). While amino acids (AAs) and the gut microbiota are known to be involved in the pathogenesis of UC, their specific roles in mucosal healing have not been fully defined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To longitudinally assess the changes in AA concentrations and the gut microbiota composition in the context of mucosal healing in UC patients, with the aim of identifying new biomarkers with predictive value for mucosal healing in UC patients and providing a new theoretical basis for dietary therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 15 UC patients with infliximab-induced mucosal healing were enrolled. Serum and fecal AA concentrations before and after mucosal healing were determined via targeted metabolomics. A receiver operating characteristic (ROC) curve was plotted to evaluate the value of different AAs in predicting mucosal healing in UC patients. The changes in the composition of the fecal gut microbiota were analyzed via metagenomics, and bioinformatics was used to analyze the functional genes and metabolic pathways associated with different bacterial species. Spearman correlation analyses of fecal AAs with significantly different concentrations and the differentially abundant bacterial species before and after mucosal healing were performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;1. The fecal concentrations of alanine, aspartic acid, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine were significantly decreased after mucosal healing. The serum concentrations of alanine, cysteine and valine significantly increased, whereas that of aspartic acid significantly decreased. Glutamic acid, leucine, lysine, methionine and threonine could accurately predict mucosal healing in UC patients, and the area under the curve (AUC) was &gt; 0.9. After combining the 5 amino acids, the AUC reached 0.96. 2. There were significant differences in the gut microbiota composition before and after mucosal healing in UC, characterized by an increase in the abundance of beneficial microbiota (Faecalibacterium prausnitzii and Bacteroides fragilis) and a decrease in the abundance of harmful microbiota (Enterococcus faecalis). LEfSe analysis identified 57 species that could predict mucosal healing, and the AUC was 0.7846. 3. Amino acid metabolic pathways were enriched in samples after mucosal healing, was associated with the abundance of multiple species, such as Faecalibacterium prausnitzi, Bacteroides fragilis, Bacteroides vulgatus and Alistipes putredinis. 4. The fecal concentrations of several AAs were negatively correlated with the abundance of a variety of beneficial strains, such as Bacteroides fragilis, uncultured Clostridium sp., Firmicutes bacterium CAG:103, Adlercreutzia equolifaciens, Coprococcus comes and positively correlated with the abundance of several ha","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"62"},"PeriodicalIF":2.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum proteomics for the identification of biomarkers to flag predilection of COVID19 patients to various organ morbidities.","authors":"Madhan Vishal Rajan, Vipra Sharma, Neelam Upadhyay, Ananya Murali, Sabyasachi Bandyopadhyay, Gururao Hariprasad","doi":"10.1186/s12014-024-09512-6","DOIUrl":"10.1186/s12014-024-09512-6","url":null,"abstract":"<p><strong>Background: </strong>COVID19 is a pandemic that has affected millions around the world since March 2020. While many patients recovered completely with mild illness, many patients succumbed to various organ morbidities. This heterogeneity in the clinical presentation of COVID19 infection has posed a challenge to clinicians around the world. It is therefore crucial to identify specific organ-related morbidity for effective treatment and better patient outcomes. We have carried out serum-based proteomic experiments to identify protein biomarkers that can flag organ dysfunctions in COVID19 patients.</p><p><strong>Methods: </strong>COVID19 patients were screened and tested at various hospitals across New Delhi, India. 114 serum samples from these patients, with and without organ morbidities were collected and annotated based on clinical presentation and treatment history. Of these, 29 samples comprising of heart, lung, kidney, gastrointestinal, liver, and neurological morbidities were considered for the discovery phase of the experiment. Proteins were isolated, quantified, trypsin digested, and the peptides were subjected to liquid chromatography assisted tandem mass spectrometry analysis. Data analysis was carried out using Proteome Discoverer software. Fold change analysis was carried out on MetaboAnalyst. KEGG, Reactome, and Wiki Pathway analysis of differentially expressed proteins were carried out using the STRING database. Potential biomarker candidates for various organ morbidities were validated using ELISA.</p><p><strong>Results: </strong>254 unique proteins were identified from all the samples with a subset of 12-31 differentially expressed proteins in each of the clinical phenotypes. These proteins establish complement and coagulation cascade pathways in the pathogenesis of the organ morbidities. Validation experiments along with their diagnostic parameters confirm Secreted Protein Acidic and Rich in Cysteine, Cystatin C, and Catalase as potential biomarker candidates that can flag cardiovascular disease, renal disease, and respiratory disease, respectively.</p><p><strong>Conclusions: </strong>Label free serum proteomics shows differential protein expression in COVID19 patients with morbidity as compared to those without morbidity. Identified biomarker candidates hold promise to flag organ morbidities in COVID19 for efficient patient care.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"61"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPOT: spatial proteomics through on-site tissue-protein-labeling.","authors":"Yuanwei Xu, T Mamie Lih, Angelo M De Marzo, Qing Kay Li, Hui Zhang","doi":"10.1186/s12014-024-09505-5","DOIUrl":"10.1186/s12014-024-09505-5","url":null,"abstract":"<p><strong>Background: </strong>Spatial proteomics seeks to understand the spatial organization of proteins in tissues or at different subcellular localization in their native environment. However, capturing the spatial organization of proteins is challenging. Here, we present an innovative approach termed Spatial Proteomics through On-site Tissue-protein-labeling (SPOT), which combines the direct labeling of tissue proteins in situ on a slide and quantitative mass spectrometry for the profiling of spatially-resolved proteomics.</p><p><strong>Materials and methods: </strong>Efficacy of direct TMT labeling was investigated using seven types of sagittal mouse brain slides, including frozen tissues without staining, formalin-fixed paraffin-embedded (FFPE) tissues without staining, deparaffinized FFPE tissues, deparaffinized and decrosslinked FFPE tissues, and tissues with hematoxylin & eosin (H&E) staining, hematoxylin (H) staining, eosin (E) staining. The ability of SPOT to profile proteomes at a spatial resolution was further evaluated on a horizontal mouse brain slide with direct TMT labeling at eight different mouse brain regions. Finally, SPOT was applied to human prostate cancer tissues as well as a tissue microarray (TMA), where TMT tags were meticulously applied to confined regions based on the pathological annotations. After on-site direct tissue-protein-labeling, tissues were scraped off the slides and subject to standard TMT-based quantitative proteomics analysis.</p><p><strong>Results: </strong>Tissue proteins on different types of mouse brain slides could be directly labeled with TMT tags. Moreover, the versatility of our direct-labeling approach extended to discerning specific mouse brain regions based on quantitative outcomes. The SPOT was further applied on both frozen tissues on slides and FFPE tissues on TMAs from prostate cancer tissues, where a distinct proteomic profile was observed among the regions with different Gleason scores.</p><p><strong>Conclusions: </strong>SPOT is a robust and versatile technique that allows comprehensive profiling of spatially-resolved proteomics across diverse types of tissue slides to advance our understanding of intricate molecular landscapes.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"60"},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}