Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and...Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center(FUSCC)for sequential high-precision proteomic profiling.Results:ARG1,NOS3,and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC.Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment.Furthermore,the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.Conclusions:The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.展开更多
Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incid...Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.展开更多
Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incid...Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.Over 650 proteins were shared among at least 50 diseases,and over 1,000 showed sex and age heterogeneity.Furthermore,proteins demonstrated promising potential in disease discrimination(area under the curve[AUC]>0.80 in 183 diseases).Finally,integrating protein quantitative trait locus data determined 474 causal proteins,providing 37 drug-repurposing opportunities and 26 promising targets with favorable safety profiles.These results provide an open-access comprehensive proteome-phenome resource(https://proteome-phenome-atlas.com/)to help elucidate the biological mechanisms of diseases and accelerate the development of disease biomarkers,prediction models,and therapeutic targets.展开更多
Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathway...Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17.Methods: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry.Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified.Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17.Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis.However, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells.Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly.Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.展开更多
Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile prote...Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.展开更多
Extreme cold environment can threaten human health and life through increasing the risk of myocardial infarction,stroke,frostbite,and hypothermia.Insufficient heat production to maintain core body temperature is a maj...Extreme cold environment can threaten human health and life through increasing the risk of myocardial infarction,stroke,frostbite,and hypothermia.Insufficient heat production to maintain core body temperature is a major cause of cold injury.To cope with cold stress,human and other mammals have developed the capacity of cold acclimatization to adapt to such a harsh environment.Adaptive non-shivering thermogenesis is a ubiquitous form of cold acclimatization.This review article systematically summarizes the role of three inducible thermogenic forms,including food intake,circadian rhythms,and cold exposure in mediating non-shivering thermogenesis under cold exposure and presents the potential interventions for minimizing the adverse health consequences of cold temperature.展开更多
Objective:Studies have shown that both short-term and long-term cold exposures disturb the biological process.The aim of the present study is to investigate the effects of intermittent cold exposure on proteomic profi...Objective:Studies have shown that both short-term and long-term cold exposures disturb the biological process.The aim of the present study is to investigate the effects of intermittent cold exposure on proteomic profiles in the hypothalamus and pituitary of female Sprague-Dawley(SD)rats.Materials and methods:The rats were exposed to-10°C in a cabin for 4 h per day,and the treatment lasted for 14 days.The comparative label-free LC-MS/MS analysis was performed to investigate the changes of proteomic profiles in the hypothalamus and pituitary.ELISA analysis was used to validate the expression of differential proteins.Results:22 differential proteins in the hypothalamus and 75 differential proteins in the pituitary were identified by the label-free proteomic analysis.Gene ontology annotation and enrichment analysis indicated that cold exposure disrupted protein phosphorylation,filopodium assembly,intracellular protein transport,peripheral nervous system neuron axonogenesis,spinal cord development,Golgi organization,positive regulation of pseudopodium assembly,and cell-cell adhesion.Three proteins(Cdc42,Ptprs,and Setd7)were down-regulated in the cold exposure group.Conclusion:The results indicate that intermittent cold exposure alters the proteomic profiles of hypothalamus and pituitary in female rats.展开更多
Exercise affects muscle metabolism and composition in the untrained muscles. The proteome of muscle tissue will be affected by exercise and resting. This is of economic importance for pork quality where transportation...Exercise affects muscle metabolism and composition in the untrained muscles. The proteome of muscle tissue will be affected by exercise and resting. This is of economic importance for pork quality where transportation relates to exercise of untrained muscles. Rest reverses exercise effects. The objective of this research was to develop potential protein biomarkers that predict the optimal resting time after exercise related to optimal pork quality. Ten litters of four female pigs were within litter allocated to the four treatment groups： exercise by running on a treadmill for 27 minutes followed by rest for 0, 1, or 3 h; control pigs without exercise. Proteome profiles and biochemical traits measuring energy metabolism and meat quality traits expected to be related to exercise were determined in the Longissimus and the Biceps femoris of the pigs. The results indicated associations between protein abundances in muscles and exercise, resting, and biochemical traits.展开更多
Glioma is difficult to treat due to the unique tumor microenvironment and bloodebrain barrier.(13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]indolizidine(PF403),a phenanthroindolizidine alkaloid,has been identified ...Glioma is difficult to treat due to the unique tumor microenvironment and bloodebrain barrier.(13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]indolizidine(PF403),a phenanthroindolizidine alkaloid,has been identified as a promising therapeutic agent for the treatment of glioma.However,the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated.Hence,a strategy without chemical modification was applied to identify the target of PF403.In this study,we identified nicotinamide phosphoribosyl transferase(NAMPT)as the target of PF403 by using thermal proteome profiling(TPP).Moreover,microscale thermophoresis(MST),surface plasmon resonance(SPR),and isothermal titration calorimetry(ITC)experiments confirmed that NAMPT exhibits good affinity for PF403.Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT,leading to a decrease in the concentration of nicotinamide adenine dinucleotide(NAD ^(+))in U87 cells.X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of piepi interactions with residue Tyr188 to maintain binding with NAMPT(PDB code 8Y55).After NAMPT was knocked down with lentivirus,PF403 lost or partially lost its antitumor activity at the cellular and animal levels.These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.展开更多
Extracting exosomes from bodily fluids offers a promising approach to overcoming inherent limitations,enabling the identification of potential biomarkers,especially those present in low abundance.^(1)PC-3 cells,known ...Extracting exosomes from bodily fluids offers a promising approach to overcoming inherent limitations,enabling the identification of potential biomarkers,especially those present in low abundance.^(1)PC-3 cells,known for their high metastatic potential compared with LNCaP cells,are widely used as a model for prostate cancer progression.^(2,3)How-ever,the mechanisms underlying their metastatic charac-teristics remain unclear.Therefore,there is a critical need to investigate diagnostic methods for prostate cancer,as current techniques have various limitations that can lead to overtreatment due to their lack of precision.展开更多
Objective:In this study,we aimed to identify novel genetic loci and protein biomarkers associated with silicosis susceptibility in Chinese workers through integrated proteomic and genomic analyses and to develop an ea...Objective:In this study,we aimed to identify novel genetic loci and protein biomarkers associated with silicosis susceptibility in Chinese workers through integrated proteomic and genomic analyses and to develop an early diagnostic prediction model.Methods:A genome-wide association study(GWAS)was conducted on 163 patients with silicosis and 183 controls,followed by Olink proteomic profiling of 92 plasma proteins.Protein quantitative trait loci(pQTL)mapping,Mendelian randomization(MR),and Bayesian co-localization were used to infer causal relationships.A causal protein risk score(CPRS)model integrating genetic and proteomic data was developed and validated using 10-fold cross-validation.Results:GWAS identified 16 novel risk loci(P<1×10^(-5)),including rs6677666(WLS)and rs2272528(COL4A4).MR analysis revealed eight plasma proteins associated with silicosis risk,with MMP12,EGF,Gal_9,GZMA,and ICOSLG showing significant differential expression(P<0.05).The CPRS model combining these proteins demonstrated a high diagnostic accuracy(AUC=0.915),outperforming traditional clinical variables.Conclusion:This multi-omics study uncovered genetic and proteomic markers linked to silicosis susceptibility and established a robust predictive model.The integration of GWAS and proteomics offers novel insights into the pathogenesis of silicosis,and supports development of early detection and prevention policies for high-risk populations.展开更多
In this study, we present a constructive algorithm for training cooperative support vector machine ensembles （CSVMEs）. CSVME combines ensemble architecture design with cooperative training for individual SVMs in ens...In this study, we present a constructive algorithm for training cooperative support vector machine ensembles （CSVMEs）. CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.展开更多
Background Alzheimer’s disease(AD)is the most prominent form of dementia worldwide.It is characterized by tau lesions that spread throughout the brain in a spatio-temporal manner.This has led to the prion-like propag...Background Alzheimer’s disease(AD)is the most prominent form of dementia worldwide.It is characterized by tau lesions that spread throughout the brain in a spatio-temporal manner.This has led to the prion-like propagation hypothesis implicating a transfer of pathological tau seeds from cell to cell.Human brain-derived extracellular vesicles(BD-EVs)isolated from the brain-derived fluid of AD patients contain seeds that contribute to this tau pathology spreading.Knowing the rich diversity of EVs,isolation of functional EV sub-populations is required to unravel their implication in the pathophysiology of AD.Methods Here,enriched-small EVs(eSEVs)and enriched-large EVs(eLEVs)were isolated from frozen tissues after collagenase enzymatic brain dissociation to guarantee the best EVs’integrity.Then proteomic profiling and tau seeding capacity testing were performed in vitro and in vivo.Results BD-EVs were stratified according to their size(eSEVs and eLEVs)and characterized to define new markers specific to EVs in AD.Both AD-derived eSEVs and eLEVs show the presence of GWAS-associated proteins and indicate a specific AD pathophysiological signature.Notably,AD eSEVs contain more proteins relative to the integrin-mediated synaptic signaling,while AD eLEVs proteins were more related to respiratory electron transport and brain immunity.Injection of these vesicles in transgenic mouse brain revealed that the AD-derived eSEVs are more prone than eLEVs to participate in the prion-like propagation and hence represent an interesting therapeutic target.Conclusion This study highlights the significant contribution of AD-derived EVs to tau propagation and provides new insights into different roles of EV sub-populations in AD.展开更多
Objective This study was mainly focused on study of the proteome profile change between exposure to 1-Bromopropane(1-BP)and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were co...Objective This study was mainly focused on study of the proteome profile change between exposure to 1-Bromopropane(1-BP)and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label展开更多
Hemp is the term commonly used to refer to the variety of Cannabis sativa L.cultivated for industrial purposes.The seeds have gained interest in recent years as functional foods due to their nutritional composition an...Hemp is the term commonly used to refer to the variety of Cannabis sativa L.cultivated for industrial purposes.The seeds have gained interest in recent years as functional foods due to their nutritional composition and high content of protein and bioactive compounds.In this study,ten hemp protein hydrolysates(HPHs)were obtained by enzymatic hydrolysis with Alcalase and Flavourzyme from hemp protein isolate(HPI)and their antioxidant properties(DPPH radical scavenging activity,beta-carotene activity and ferric ion reducing antioxidant power(FRAP))were evaluated.Shorter peptide sequences,mainly obtained with Flavourzyme,were found to react with free radicals more easily.The peptidome of all the hydrolysates was characterized,identifying,and quantifying the peptides.Furthermore,19 unique peptides were assessed by in silico tools to hypothesize those that could be responsible of the bioactivity reported for the hydrolysates.From the identified peptides,based on the molecular features and the predictions,the peptides KNAIYTPH,EERPGHF,and KNGMMAPH,among others,are proposed to be highly contributing to the antioxidant activity of the hydrolysates.展开更多
Small ubiquitin-like modifiers(SUMOs)are protein modifiers that can form polymeric chains.They are important signals in cellular processes,and their study and profiling require the development of molecular tools.Herei...Small ubiquitin-like modifiers(SUMOs)are protein modifiers that can form polymeric chains.They are important signals in cellular processes,and their study and profiling require the development of molecular tools.Herein,the authors have reported an efficient chemical protein synthesis approach for the generation of dimeric SUMO-2-based photoaffinity probes through the ligation of four readily synthesizable peptides.Proteomic studies using this diSUMO-2 probe on HeLa cell nuclear lysate found it to capture a significantly different selection of proteins compared with its monoSUMO counterparts.This resulted in the identification of several previously unknown SUMO chain-specific interacting proteins such as 40S ribosomal protein S3,which showed a significantly higher affinity for polySUMO chains than monomeric SUMO.Collectively,these results emphasize the need to develop SUMO chain-based probes in other species,and to shed light on the important role of polySUMOylation in diseases.展开更多
Daqu provides microbiota,flavor substances and enzymes for liquor fermentation.Storage after fermentation is an essential stage for the mature of Daqu.However,it is still unclear about the effect of storage on the mic...Daqu provides microbiota,flavor substances and enzymes for liquor fermentation.Storage after fermentation is an essential stage for the mature of Daqu.However,it is still unclear about the effect of storage on the microbiota structure and enzyme profile.Here,this work revealed the variation of microbiota structure and enzyme profile after storage of low-temperature Daqu using amplicon sequencing and proteomic profile analysis.Results showed that the content of acidity significantly increased by 13.79%(P<0.05).The saccharification power,liquefaction power and fermentation power significantly increased by 2.90%,17.32%and 16.04%,respectively(P<0.05).The contents of 3-methyl-1-butanol and 1-octen-3-ol increased by 147.19%and 29.12%,respectively(P<0.05).Lichtheimia,Saccharomyces,Rhizopus,Aspergillus,Pantoea,Lactiplantibacillus,Pichia,Lacticaseibacillus,Pseudo-monas,Linnemannia,Levilactobacillus,Pediococcus,Paenibacillus and Lactobacillus were the major enzyme-producing microbiota(average protein abundance>1%)using proteomic profile analysis.After storage,the relative abundances of Lactobacillus and Aspergillus increased from 2.59%to 17.63%,and 7.53%-33.67%using amplicon sequencing,respectively.The protein abundance of α-amylase produced by Aspergillus increased from 0.05%to 0.11%,and was consistent with variations of the relative abundance of Aspergillus,and the liquefaction power.The protein abundance of lactic acid dehydrogenase produced by Lactobacillus increased from 0.07%to 0.11%,and was consistent with the variation of relative abundance of Lactobacillus.This work revealed the effect of storage on microbioa and enzyme proteomic profile of low-temperature Daqu.It would be beneficial for controlling the storage stage of Daqu,and help improving the quality of Daqu.展开更多
Background:Heart failure(HF)is the leading cause of death worldwide.Myocardial infarction(MI)is a major contributor to HF.Shengmai injection(SMI)has exhibited protective efficacy in preventing HF.However,the advantage...Background:Heart failure(HF)is the leading cause of death worldwide.Myocardial infarction(MI)is a major contributor to HF.Shengmai injection(SMI)has exhibited protective efficacy in preventing HF.However,the advantages of SMI in the progression of MI-induced HF remain unclear.Objective:To reveal the advantages of SMI in the progression of MI-induced HF.Methods:The differently expressed proteins in rat models with ischemia at the 7th,14th,21st,and 28th days were obtained from PubMed.The“compound-target”network of SMI was constructed via the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine database.The protein-protein interaction relationship was constructed,and biological function was applied to evaluate the advantage effect of SMI in the progression of MI-induced HF.In addition,the prediction results were validated in rats with left anterior descending coronary artery ligation.The cardiac function and heart performance were observed via echocardiography,hematoxylin-eosin staining,and Masson staining,and the levels of procollagen type I carboxy-terminal propeptide,recombinant versican(VCAN),and collagen 1A1(COL1A1)weremeasured via enzyme-linked immunosorbent assay in rat plasma.In vitro,H9c2 cells were treated with Angiotensin II(Ang II),and the cell viability,the level of reactive oxygen species(ROS)and Ca^(2+),and the expression of ANP and connective tissue growth factor were evaluated.Furthermore,the schizandrin A was identified as one of the possible key compounds.After schizandrin A treatment,the level of ROS and Ca^(2+)and the expression of COL1A1 and VCAN were evaluated.Results:There were 189 compounds and 1612 targets involved in the“compound-target”network,and an interaction relationship was constructed.According to the top subnetwork,the Gene Ontology annotation revealed that SMI may have an antifibrotic and cardiac protective effect against MI-induced HF.In rats,SMI increased ejection fraction,left ventricular fractional shortening,and cardiac output and decreased fibrosis injury;moreover,SMI decreased the levels of procollagen type I carboxy-terminal propeptide,VCAN,and COL1A1 within 35 days.When compared with the Ang II treatment group,SMI increased cell viability and decreased cellular calcium concentration,ROS generation,and the expression of ANP and connective tissue growth factor in vitro.Furthermore,schizandrin A was discovered to be a possible compound in myocardial protection.Schizandrin A increased cell viability after Ang II treatment while decreasing COL1A1 and VCAN levels.Conclusions:This method demonstrates that SMI has an antifibrotic effect.This study provides a promising perspective on translating omics data to clinical applications,as well as an appealing approach to investigating the precise intervention of a multicomponent drug.展开更多
High-grade lung neuroendocrine carcinomas(Lu-NECs)are clinically refractory malignancies with poor prognosis and limited therapeutic advances.The biological and molecular features underlying the histological heterogen...High-grade lung neuroendocrine carcinomas(Lu-NECs)are clinically refractory malignancies with poor prognosis and limited therapeutic advances.The biological and molecular features underlying the histological heterogeneity of Lu-NECs are not fully understood.In this study,we present a multi-omics integration of whole-exome sequencing and deep proteomic profiling in 93 Chinese Lu-NECs to establish the first comprehensive proteogenomic atlas of this disease spectrum.Our analyses revealed a high degree of mutational concordance among the subtypes at the genomic level;however,distinct proteomic profiles enabled a clear differentiation of histological subtypes,unveiling subtype-specific molecular and biological features related to tumor metabolism,immunity,and proliferation.Furthermore,RB1 mutations confer divergent prognostic effects through subtype-specific cis-and trans-proteomic regulation.In addition,we identified potential protein biomarkers for histological subtype classification and risk stratification,which were validated by immunohistochemistry in an independent cohort.This study provides a valuable proteogenomic resource and insight into Lu-NEC heterogeneity.展开更多
基金supported by the National Key Research and Development Project of China(Grant No.2021YFF1201300 and 2021YFF1201302)the Shanghai Committee of Science and Technology(Grant No.24DX2800100)the Institutional Projects of SIBPT(Grant No.YZ2024-07)。
文摘Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center(FUSCC)for sequential high-precision proteomic profiling.Results:ARG1,NOS3,and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC.Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment.Furthermore,the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.Conclusions:The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.
文摘Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.
文摘Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.Over 650 proteins were shared among at least 50 diseases,and over 1,000 showed sex and age heterogeneity.Furthermore,proteins demonstrated promising potential in disease discrimination(area under the curve[AUC]>0.80 in 183 diseases).Finally,integrating protein quantitative trait locus data determined 474 causal proteins,providing 37 drug-repurposing opportunities and 26 promising targets with favorable safety profiles.These results provide an open-access comprehensive proteome-phenome resource(https://proteome-phenome-atlas.com/)to help elucidate the biological mechanisms of diseases and accelerate the development of disease biomarkers,prediction models,and therapeutic targets.
基金financially supported by the Fundamental Research Grant Scheme,(FRGS/1/2016/SKK08/MUSM/02/1)under the Ministry of Higher Education,Malaysia
文摘Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17.Methods: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry.Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified.Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17.Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis.However, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells.Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly.Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.
基金Public Welfare Re-search Fund of Huzhou City(2018GYB60).
文摘Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.
基金the National Natural Science Foundation of China(NO.82001989,NO.82030055).
文摘Extreme cold environment can threaten human health and life through increasing the risk of myocardial infarction,stroke,frostbite,and hypothermia.Insufficient heat production to maintain core body temperature is a major cause of cold injury.To cope with cold stress,human and other mammals have developed the capacity of cold acclimatization to adapt to such a harsh environment.Adaptive non-shivering thermogenesis is a ubiquitous form of cold acclimatization.This review article systematically summarizes the role of three inducible thermogenic forms,including food intake,circadian rhythms,and cold exposure in mediating non-shivering thermogenesis under cold exposure and presents the potential interventions for minimizing the adverse health consequences of cold temperature.
基金the grants of Tianjin Institute of Environmental and Operational Medicine(BWS17J025).
文摘Objective:Studies have shown that both short-term and long-term cold exposures disturb the biological process.The aim of the present study is to investigate the effects of intermittent cold exposure on proteomic profiles in the hypothalamus and pituitary of female Sprague-Dawley(SD)rats.Materials and methods:The rats were exposed to-10°C in a cabin for 4 h per day,and the treatment lasted for 14 days.The comparative label-free LC-MS/MS analysis was performed to investigate the changes of proteomic profiles in the hypothalamus and pituitary.ELISA analysis was used to validate the expression of differential proteins.Results:22 differential proteins in the hypothalamus and 75 differential proteins in the pituitary were identified by the label-free proteomic analysis.Gene ontology annotation and enrichment analysis indicated that cold exposure disrupted protein phosphorylation,filopodium assembly,intracellular protein transport,peripheral nervous system neuron axonogenesis,spinal cord development,Golgi organization,positive regulation of pseudopodium assembly,and cell-cell adhesion.Three proteins(Cdc42,Ptprs,and Setd7)were down-regulated in the cold exposure group.Conclusion:The results indicate that intermittent cold exposure alters the proteomic profiles of hypothalamus and pituitary in female rats.
文摘Exercise affects muscle metabolism and composition in the untrained muscles. The proteome of muscle tissue will be affected by exercise and resting. This is of economic importance for pork quality where transportation relates to exercise of untrained muscles. Rest reverses exercise effects. The objective of this research was to develop potential protein biomarkers that predict the optimal resting time after exercise related to optimal pork quality. Ten litters of four female pigs were within litter allocated to the four treatment groups： exercise by running on a treadmill for 27 minutes followed by rest for 0, 1, or 3 h; control pigs without exercise. Proteome profiles and biochemical traits measuring energy metabolism and meat quality traits expected to be related to exercise were determined in the Longissimus and the Biceps femoris of the pigs. The results indicated associations between protein abundances in muscles and exercise, resting, and biochemical traits.
基金supported financially by the National Natural Science Foundation of China(No.22337007).
文摘Glioma is difficult to treat due to the unique tumor microenvironment and bloodebrain barrier.(13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]indolizidine(PF403),a phenanthroindolizidine alkaloid,has been identified as a promising therapeutic agent for the treatment of glioma.However,the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated.Hence,a strategy without chemical modification was applied to identify the target of PF403.In this study,we identified nicotinamide phosphoribosyl transferase(NAMPT)as the target of PF403 by using thermal proteome profiling(TPP).Moreover,microscale thermophoresis(MST),surface plasmon resonance(SPR),and isothermal titration calorimetry(ITC)experiments confirmed that NAMPT exhibits good affinity for PF403.Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT,leading to a decrease in the concentration of nicotinamide adenine dinucleotide(NAD ^(+))in U87 cells.X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of piepi interactions with residue Tyr188 to maintain binding with NAMPT(PDB code 8Y55).After NAMPT was knocked down with lentivirus,PF403 lost or partially lost its antitumor activity at the cellular and animal levels.These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.
基金supported by grants from the National Research Foundation of Korea(NRF)(No.2022R1A2C109179013,RS-2024-00451519,RS-2024-00359310,2018R1A5A1024340)the National Research Council of Science&Technology(NST)Aging Convergence Research Center(Korea)(No.CRC22012-200)the Ministry of Health and Welfare of Korea(No.HV22C012800).
文摘Extracting exosomes from bodily fluids offers a promising approach to overcoming inherent limitations,enabling the identification of potential biomarkers,especially those present in low abundance.^(1)PC-3 cells,known for their high metastatic potential compared with LNCaP cells,are widely used as a model for prostate cancer progression.^(2,3)How-ever,the mechanisms underlying their metastatic charac-teristics remain unclear.Therefore,there is a critical need to investigate diagnostic methods for prostate cancer,as current techniques have various limitations that can lead to overtreatment due to their lack of precision.
基金Supported by the Jiangsu Provincial Social Development Program of the Key R&D Project(BE2022803)Natural Science Foundation of Jiangsu(BK20201485)+1 种基金Jiangsu Provincial Key Medical Discipline(ZDXK202249)Scientific Research Project of Jiangsu Health Commission(M2022085).
文摘Objective:In this study,we aimed to identify novel genetic loci and protein biomarkers associated with silicosis susceptibility in Chinese workers through integrated proteomic and genomic analyses and to develop an early diagnostic prediction model.Methods:A genome-wide association study(GWAS)was conducted on 163 patients with silicosis and 183 controls,followed by Olink proteomic profiling of 92 plasma proteins.Protein quantitative trait loci(pQTL)mapping,Mendelian randomization(MR),and Bayesian co-localization were used to infer causal relationships.A causal protein risk score(CPRS)model integrating genetic and proteomic data was developed and validated using 10-fold cross-validation.Results:GWAS identified 16 novel risk loci(P<1×10^(-5)),including rs6677666(WLS)and rs2272528(COL4A4).MR analysis revealed eight plasma proteins associated with silicosis risk,with MMP12,EGF,Gal_9,GZMA,and ICOSLG showing significant differential expression(P<0.05).The CPRS model combining these proteins demonstrated a high diagnostic accuracy(AUC=0.915),outperforming traditional clinical variables.Conclusion:This multi-omics study uncovered genetic and proteomic markers linked to silicosis susceptibility and established a robust predictive model.The integration of GWAS and proteomics offers novel insights into the pathogenesis of silicosis,and supports development of early detection and prevention policies for high-risk populations.
基金partly supported by the National Natural Science Foundation of China (No.60574019 and 60474045)the National Basic Research Program(973 Program)of China(No.2002CB312200)+2 种基金the Key Technologies R&D Program of Zhejiang Province (No.2005C21087)the Academician Foundation of Zhejiang Province(No.2005A1001-13)the Center for Bioinformatics Program Grant of Harvard Center of Neurodegeneration and Repair,Harvard Medical School,Boston,USA.
文摘In this study, we present a constructive algorithm for training cooperative support vector machine ensembles （CSVMEs）. CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.
基金supported by grants from the program Investissement d’Avenir LabEx(investing in the future laboratory excellence)DISTALZ(Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer’s Disease)+2 种基金France Alzheimer,Fondation pour la Recherche Medicale and ANR grants(TONIC,TauSeed)Our laboratories are also supported by LiCEND(Lille Centre of Excellence in Neurodegenerative Disorders)CNRS,Inserm,Metropole Europeenne de Lille,University of Lille,I-SITE ULNE,Region Hauts de France and FEDER.The OrganOmics platform of PRISM Inserm U1192 which is recognized and supported by the University of Lille and,the Infrastructure PROFI(https://www.profi prote omics.fr/)and the GIS IbiSA(https://www.ibisa.net/).The OrganOmics platform(Villeneuve d’Ascq,France)is also supported by Region Hauts de France and FEDER funding.
文摘Background Alzheimer’s disease(AD)is the most prominent form of dementia worldwide.It is characterized by tau lesions that spread throughout the brain in a spatio-temporal manner.This has led to the prion-like propagation hypothesis implicating a transfer of pathological tau seeds from cell to cell.Human brain-derived extracellular vesicles(BD-EVs)isolated from the brain-derived fluid of AD patients contain seeds that contribute to this tau pathology spreading.Knowing the rich diversity of EVs,isolation of functional EV sub-populations is required to unravel their implication in the pathophysiology of AD.Methods Here,enriched-small EVs(eSEVs)and enriched-large EVs(eLEVs)were isolated from frozen tissues after collagenase enzymatic brain dissociation to guarantee the best EVs’integrity.Then proteomic profiling and tau seeding capacity testing were performed in vitro and in vivo.Results BD-EVs were stratified according to their size(eSEVs and eLEVs)and characterized to define new markers specific to EVs in AD.Both AD-derived eSEVs and eLEVs show the presence of GWAS-associated proteins and indicate a specific AD pathophysiological signature.Notably,AD eSEVs contain more proteins relative to the integrin-mediated synaptic signaling,while AD eLEVs proteins were more related to respiratory electron transport and brain immunity.Injection of these vesicles in transgenic mouse brain revealed that the AD-derived eSEVs are more prone than eLEVs to participate in the prion-like propagation and hence represent an interesting therapeutic target.Conclusion This study highlights the significant contribution of AD-derived EVs to tau propagation and provides new insights into different roles of EV sub-populations in AD.
文摘Objective This study was mainly focused on study of the proteome profile change between exposure to 1-Bromopropane(1-BP)and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label
基金funded by grant P20_00661 from the Andalusian Plan for Research,Development and Innovation(PAIDI)2020by grant US-1381492 from the European Regional Development Fund(ERDF).
文摘Hemp is the term commonly used to refer to the variety of Cannabis sativa L.cultivated for industrial purposes.The seeds have gained interest in recent years as functional foods due to their nutritional composition and high content of protein and bioactive compounds.In this study,ten hemp protein hydrolysates(HPHs)were obtained by enzymatic hydrolysis with Alcalase and Flavourzyme from hemp protein isolate(HPI)and their antioxidant properties(DPPH radical scavenging activity,beta-carotene activity and ferric ion reducing antioxidant power(FRAP))were evaluated.Shorter peptide sequences,mainly obtained with Flavourzyme,were found to react with free radicals more easily.The peptidome of all the hydrolysates was characterized,identifying,and quantifying the peptides.Furthermore,19 unique peptides were assessed by in silico tools to hypothesize those that could be responsible of the bioactivity reported for the hydrolysates.From the identified peptides,based on the molecular features and the predictions,the peptides KNAIYTPH,EERPGHF,and KNGMMAPH,among others,are proposed to be highly contributing to the antioxidant activity of the hydrolysates.
基金This study was supported by the National Key R&D Program of China(nos.2017YFA0505200 and 2017YFA0505400)the National Natural Science Foundation of China(nos.91753205,21877024,21977089,81621002,and 21621003)the Fundamental Research Funds for the Central Universities(no.JZ2019HGPB0105).
文摘Small ubiquitin-like modifiers(SUMOs)are protein modifiers that can form polymeric chains.They are important signals in cellular processes,and their study and profiling require the development of molecular tools.Herein,the authors have reported an efficient chemical protein synthesis approach for the generation of dimeric SUMO-2-based photoaffinity probes through the ligation of four readily synthesizable peptides.Proteomic studies using this diSUMO-2 probe on HeLa cell nuclear lysate found it to capture a significantly different selection of proteins compared with its monoSUMO counterparts.This resulted in the identification of several previously unknown SUMO chain-specific interacting proteins such as 40S ribosomal protein S3,which showed a significantly higher affinity for polySUMO chains than monomeric SUMO.Collectively,these results emphasize the need to develop SUMO chain-based probes in other species,and to shed light on the important role of polySUMOylation in diseases.
基金supported by the 111 Project(No.111-2-06)Xining Science and Technology Planning Program(2023-Y-04).
文摘Daqu provides microbiota,flavor substances and enzymes for liquor fermentation.Storage after fermentation is an essential stage for the mature of Daqu.However,it is still unclear about the effect of storage on the microbiota structure and enzyme profile.Here,this work revealed the variation of microbiota structure and enzyme profile after storage of low-temperature Daqu using amplicon sequencing and proteomic profile analysis.Results showed that the content of acidity significantly increased by 13.79%(P<0.05).The saccharification power,liquefaction power and fermentation power significantly increased by 2.90%,17.32%and 16.04%,respectively(P<0.05).The contents of 3-methyl-1-butanol and 1-octen-3-ol increased by 147.19%and 29.12%,respectively(P<0.05).Lichtheimia,Saccharomyces,Rhizopus,Aspergillus,Pantoea,Lactiplantibacillus,Pichia,Lacticaseibacillus,Pseudo-monas,Linnemannia,Levilactobacillus,Pediococcus,Paenibacillus and Lactobacillus were the major enzyme-producing microbiota(average protein abundance>1%)using proteomic profile analysis.After storage,the relative abundances of Lactobacillus and Aspergillus increased from 2.59%to 17.63%,and 7.53%-33.67%using amplicon sequencing,respectively.The protein abundance of α-amylase produced by Aspergillus increased from 0.05%to 0.11%,and was consistent with variations of the relative abundance of Aspergillus,and the liquefaction power.The protein abundance of lactic acid dehydrogenase produced by Lactobacillus increased from 0.07%to 0.11%,and was consistent with the variation of relative abundance of Lactobacillus.This work revealed the effect of storage on microbioa and enzyme proteomic profile of low-temperature Daqu.It would be beneficial for controlling the storage stage of Daqu,and help improving the quality of Daqu.
基金supported by the national key research and development program of China(2019YFC1708900)National Natural Science Foundation of China(82204973)+2 种基金scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2021B015)the fundamental research funds for the central public welfare research institutes of Institute of Chinese Materia Medica,China Academy ofChinese Medical Sciences(ZXKT21030)special program for outstanding,young scientific and technological talents(innovation)of China Academy of ChineseMedical Sciences(ZZ15-YQ-034).
文摘Background:Heart failure(HF)is the leading cause of death worldwide.Myocardial infarction(MI)is a major contributor to HF.Shengmai injection(SMI)has exhibited protective efficacy in preventing HF.However,the advantages of SMI in the progression of MI-induced HF remain unclear.Objective:To reveal the advantages of SMI in the progression of MI-induced HF.Methods:The differently expressed proteins in rat models with ischemia at the 7th,14th,21st,and 28th days were obtained from PubMed.The“compound-target”network of SMI was constructed via the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine database.The protein-protein interaction relationship was constructed,and biological function was applied to evaluate the advantage effect of SMI in the progression of MI-induced HF.In addition,the prediction results were validated in rats with left anterior descending coronary artery ligation.The cardiac function and heart performance were observed via echocardiography,hematoxylin-eosin staining,and Masson staining,and the levels of procollagen type I carboxy-terminal propeptide,recombinant versican(VCAN),and collagen 1A1(COL1A1)weremeasured via enzyme-linked immunosorbent assay in rat plasma.In vitro,H9c2 cells were treated with Angiotensin II(Ang II),and the cell viability,the level of reactive oxygen species(ROS)and Ca^(2+),and the expression of ANP and connective tissue growth factor were evaluated.Furthermore,the schizandrin A was identified as one of the possible key compounds.After schizandrin A treatment,the level of ROS and Ca^(2+)and the expression of COL1A1 and VCAN were evaluated.Results:There were 189 compounds and 1612 targets involved in the“compound-target”network,and an interaction relationship was constructed.According to the top subnetwork,the Gene Ontology annotation revealed that SMI may have an antifibrotic and cardiac protective effect against MI-induced HF.In rats,SMI increased ejection fraction,left ventricular fractional shortening,and cardiac output and decreased fibrosis injury;moreover,SMI decreased the levels of procollagen type I carboxy-terminal propeptide,VCAN,and COL1A1 within 35 days.When compared with the Ang II treatment group,SMI increased cell viability and decreased cellular calcium concentration,ROS generation,and the expression of ANP and connective tissue growth factor in vitro.Furthermore,schizandrin A was discovered to be a possible compound in myocardial protection.Schizandrin A increased cell viability after Ang II treatment while decreasing COL1A1 and VCAN levels.Conclusions:This method demonstrates that SMI has an antifibrotic effect.This study provides a promising perspective on translating omics data to clinical applications,as well as an appealing approach to investigating the precise intervention of a multicomponent drug.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,2024-I2M-C&T-A-005).
文摘High-grade lung neuroendocrine carcinomas(Lu-NECs)are clinically refractory malignancies with poor prognosis and limited therapeutic advances.The biological and molecular features underlying the histological heterogeneity of Lu-NECs are not fully understood.In this study,we present a multi-omics integration of whole-exome sequencing and deep proteomic profiling in 93 Chinese Lu-NECs to establish the first comprehensive proteogenomic atlas of this disease spectrum.Our analyses revealed a high degree of mutational concordance among the subtypes at the genomic level;however,distinct proteomic profiles enabled a clear differentiation of histological subtypes,unveiling subtype-specific molecular and biological features related to tumor metabolism,immunity,and proliferation.Furthermore,RB1 mutations confer divergent prognostic effects through subtype-specific cis-and trans-proteomic regulation.In addition,we identified potential protein biomarkers for histological subtype classification and risk stratification,which were validated by immunohistochemistry in an independent cohort.This study provides a valuable proteogenomic resource and insight into Lu-NEC heterogeneity.
