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.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
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
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: 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
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
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
Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies....Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.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
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
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
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
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.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support from the Shanghai Science and Technology Development Program (Grant Nos. 03DZ14024 & 07ZR14010)the 863 High Technology Foundation of China (Grant No. 2006AA02A310)+1 种基金US NIH 1R01AI064806-01A2, 5R21DK082706U.S. Department of Energy, the Office of Science (BER) (Grant No. DE-FG02- 07ER64422)
文摘Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.
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.
