AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on diseas...AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.展开更多
The increase in human population has led to imminent pressures to develop new edible proteins with decreased environmental footprints.The most promising approach involves the production of single cell protein(SCP)from...The increase in human population has led to imminent pressures to develop new edible proteins with decreased environmental footprints.The most promising approach involves the production of single cell protein(SCP)from yeasts,which have been utilized in a wide variety of foods for thousands of years.In this study,102 yeast strains isolated from traditional fermented pork(Nanx Wudl)were investigated for their potential as SCP producer for the first time.Based on preliminary screening,Saccharomyces cerevisiae Y70 and Candida parapsilosis H5Y13,both showing high protein content and excellent growth capability,were selected for further analysis via 4D-DIA proteomics technology.Proteomic analysis indicated that the oxidative metabolism pathways,including TCA cycle,oxidative phosphorylation and pentose phosphate pathway,may have a significant impact on global protein synthesis and production.This study provides useful information for selecting SCP-producing yeast from Chinese fermented meat products and contribute to a deeper understanding of the underlying metabolic mechanisms behind global protein synthesis in yeast.Furthermore,these findings also provide potential molecular targets for genetic engineering modifications in yeast,aimed at constructing highly efficient cell factories for protein production.展开更多
CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Althou...CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.展开更多
Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of protein...Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of proteins in lung(A549)and colon(HT29)cancer cell lines was examined by using proteomics analysis.The protein-protein interaction study of differentially expressed proteins was done by using the Search Tool for the Retrieval of Interacting Genes(STRING),and the results showed that the proteins interacting with each other belong to different pathways.展开更多
Liraglutide(Lira),a glucagon-like peptide-1(GLP-1)receptor agonist approved for diabetes and obesity,has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease(MASLD).However,...Liraglutide(Lira),a glucagon-like peptide-1(GLP-1)receptor agonist approved for diabetes and obesity,has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease(MASLD).However,its systematic molecular regulation and mechanisms remain underexplored.In this study,a mouse model of MASLD was developed using a high-fat diet(HFD),followed by Lira administration.Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry(LC-MS/MS),while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction(qPCR)and Western blotting.Our results revealed that Lira treatment significantly reduced liver weight and serum markers,including alanine aminotransferase(ALT)and others,with glycosylation changes playing a more significant role than overall protein expression.The glycoproteome identified 255 independent glycosylation sites,emphasizing the impact of Lira on amino acid,carbohydrate metabolism,and ferroptosis.Simultaneously,proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways.21 signature molecules,including 7 proteins and 14 N-glycosylation sites(N-glycosites),were identified as potential targets.A Lira hydrogel formulation(Lira@fibrin(Fib)Gel)was developed to extend drug dosing intervals,offering enhanced therapeutic efficacy in managing chronic metabolic diseases.Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD,identifying potential molecular targets and advancing its clinical application for MASLD treatment.展开更多
Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect...Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.展开更多
Low temperature(LT)in spring has become one of the principal abiotic stresses that restrict the growth and development of wheat.Diverse analyses were performed to investigate the mechanism underlying the response of w...Low temperature(LT)in spring has become one of the principal abiotic stresses that restrict the growth and development of wheat.Diverse analyses were performed to investigate the mechanism underlying the response of wheat grain development to LT stress during booting.These included morphological observation,measurements of starch synthase activity,and determination of amylose and amylopectin content of wheat grain after exposure to treatment with LT during booting.Additionally,proteomic analysis was performed using tandem mass tags(TMT).Results showed that the plumpness of wheat grains decreased after LT stress.Moreover,the activities of sucrose synthase(SuS,EC 2.4.1.13)and ADP-glucose pyrophosphorylase(AGPase,EC 2.7.7.27)exhibited a significant reduction,leading to a significant reduction in the contents of amylose and amylopectin.A total of 509 differentially expressed proteins(DEPs)were identified by proteomics analysis.The Gene Ontology(GO)enrichment analysis showed that the protein difference multiple in the nutritional repository activity was the largest among the molecular functions,and the up-regulated seed storage protein(ssP)played an active role in the response of grains to LT stress and subsequent damage.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis showed that LT stress reduced the expression of DEPs such as sucrose phosphate synthase(SPS),glucose-1-phosphate adenylyltransferase(glgC),andβ-fructofuranosidase(FFase)in sucrose and starch metabolic pathways,thus affecting the synthesis of grain starch.In addition,many heat shock proteins(HsPs)were found in the protein processing in endoplasmic reticulum pathways,which can resist some damage caused by LT stress.These findings provide a new theoretical foundation for elucidating the underlying mechanism governing wheat yield developmentafterexposuretoLTstress inspring.展开更多
OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the...OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the antidepressant effects of JD were assessed using the sucrose preference test(SPT),forced swimming test(FST),and tail suspension test(TST).Tandem mass tag(TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment.Hierarchical clustering,Gene Ontology function annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interactions(PPIs)were used to analyze differentially expressed proteins(DEPs),which were further validated using quantitative real-time polymerase chain reaction(qR T-PCR)and Western blotting.RESULTS:Behavioral tests confirmed the antidepressant effects of JD,and bioinformatics analysis revealed 59 DEPs,including 33 up-regulated and 26 down-regulated proteins,between the CUMS and JD-M groups.KEGG and PPI analyses revealed that neurofilament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression.q RTPCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light(NEFL)and medium(NEFM)and inhibited the phosphorylation of extracellular regulated kinase 1/2(ERK1/2),whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM.CONCLUSIONS:The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.展开更多
Sini Decoction(SNT)is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold.However,elucidating the mechanism of action of SNT remains challenging due to its complex m...Sini Decoction(SNT)is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold.However,elucidating the mechanism of action of SNT remains challenging due to its complex multiple components.This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis(2D-DIGE)-based drug affinity responsive target stability(DARTS)with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction.The analysis identified 590 proteins,with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group.Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments,the findings indicate that protein disulfide-isomerase A3(PDIA3)may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.展开更多
The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-deriv...The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-derived polysaccharides,named L2,on immune functions and blood lipid profiles,isobaric tags for relative and absolute quantification(iTRAQ)-based proteomic profiling of the small intestinal tissues from aged mice treated with L2 was performed.L2 reversed immune function declines and modulated the lipid metabolism of aged mice evidenced by increased levels of serum TC,HDL-C,and LDL-C,and reduced levels of serum TG.Moreover,a total of 95 differentially regulated proteins(DRPs) were identified,of which75 were up-regulated and 20 were down-regulated.Most of the DRPs were involved in intracellular and extracellular structure organization,and cellular and metabolic regulation.Particularly,approximately 16 and 9 DRPs participated in the regulation of immune functions and lipid metabolism,respectively.Furthermore,protein-protein interaction analysis highlighted that cadherin-1,plectin,cadherin-17,Ras GTPase-activating-like protein IQGAP2,and ezrin might be key proteins in response to L2 treatment.These findings provide new insights into the biological mechanisms of mushroom polysaccharides in anti-aging from a proteomic perspective.展开更多
BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from mode...BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.展开更多
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
BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,pe...BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,peripheral blood mononuclear cells(PBMCs)serve as a robust model for investigating intracellular alterations linked to SZ.AIM To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.METHODS PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes(DEGs)and differentially expressed proteins while mapping putative disease-associated signaling pathways.Key findings were validated using western blot(WB)and real-time fluorescence quantitative PCR(RT-qPCR).RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro,with subsequent verification of target gene expression via RT-qPCR.The levels of neuronal conduction proteins,including calmodulin-dependent protein kinase II(caMKII),CREB,and BDNF,were assessed through WB.Apoptosis was quantified by flow cytometry,while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.RESULTS The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes,among which 25 DEGs were significantly altered between the SZ group and healthy controls.Notably,haptoglobin(HP),lactotransferrin(LTF),and SERPING1 exhibited marked upregulation.KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis.Clinical sample validation demonstrated elevated protein and mRNA levels of HP,LTF,and SERPING1 in the SZ group compared to controls.WB analysis of all clinical samples further corroborated the significant upregulation of SERPING1.In hippocampal CA1 neurons transfected with lentivirus,reduced SERPING1 expression was accompanied by increased levels of CaMKII,CREB,and BDNF,enhanced cell viability,and reduced apoptosis.CONCLUSION SERPING1 may suppress neural cell proliferation in SZ patients via modulation of the CaMKII-CREB-BDNF signaling pathway.展开更多
With the increasing per capita demand for animal protein,there is a growing interest in the abundant abalone protein resources.Abalone proteins are known for their nutritional and functional properties that contribute...With the increasing per capita demand for animal protein,there is a growing interest in the abundant abalone protein resources.Abalone proteins are known for their nutritional and functional properties that contribute to flavor and texture.We systematically constructed the relationship between abalone protein,processing,and proteomics.This paper reviews the nutritional properties of abalone proteins and evaluates the effects of different thermal processing techniques,non-thermal processing,and freezing on abalone proteins.In addition,we synthesize published abalone proteomics studies and the use of proteomics technology to better elucidate the quality changes of abalone and its products,and as a technical basis for the study of blue food marker proteins.It is important direction to clearly explain the protein composition and meat quality mechanism of abalone in the processing and storage by proteomic.During various types of thermal processing,non-thermal processing,and freezing of abalone,the various chemical forces between protein molecules are disrupted,which in turn leads to different degrees of denaturation,aggregation,and gelation,which may have an impact on the organoleptic properties,bioavailability,and digestibility of abalone muscle.Proteomics is used in abalone biology studies to understand developmental biology,physiology,disease,stress,and species identification and can also be a powerful tool to characterize processing methods on abalone quality properties.展开更多
Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesio...Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.展开更多
BACKGROUND Myocardial infarction(MI)occupies a very high mortality and morbidity rate,and the search for effective pharmacological treatments has far-reaching implications for clinical research.AIM To explore the prot...BACKGROUND Myocardial infarction(MI)occupies a very high mortality and morbidity rate,and the search for effective pharmacological treatments has far-reaching implications for clinical research.AIM To explore the protective effects of Mongolian medicine Agari-5 on rats with MI.METHODS Sprague-Dawley rats were used,and both the Agari-5 and model groups had their coronary arteries clamped to induce MI.Proteomics was used to research the potential mechanism of action while ELISA,hematoxylin and eosin,and Masson’s staining were used to preliminarily investigate the protective impact of Agari-5 on rats with MI.RESULTS The current study has shown that Agari-5 might enhance cardiac function indicators,including echocardiography results of rats and creatine kinase,creatine kinase isoenzyme,and lactate dehydrogenase,in rats that had MI.According to the results of pathological staining,Agari-5 may lessen inflammatory cell infiltration and cardiomyocyte fibrosis,among other things.The proteome analysis revealed that there were 60 distinct proteins in total,four of which were associated with the heart.The expression of PSAT1,PDK1,SMAD4,and SDF2 proteins may be linked to the mechanism of their protective effects.CONCLUSION Potential therapeutic effects of Agari-5 for MI and its mechanism of action may be related to PSAT1,PDK1,SMAD4,and SDF2.展开更多
Per-and polyfluoroalkyl substances(PFASs)can induce a range of adverse health effects,with the precise molecularmechanisms remaining elusive.Extracellular vesicles(EVs)have demonstrated their potential to elucidate un...Per-and polyfluoroalkyl substances(PFASs)can induce a range of adverse health effects,with the precise molecularmechanisms remaining elusive.Extracellular vesicles(EVs)have demonstrated their potential to elucidate unknown molecular mechanisms.Building upon the close alignment of their biological functions with the observed health effects of PFASs,this study innovatively focuses on proteomic insights from EVs into the molecular mechanisms underlying the systemic health effects of PFASs.Through rat exposure experiments and proteomics technology,it not only demonstrated the occurrence of PFASs in EVs but also revealed the alterations in the serum EVs and the expression of their protein cargos following mixed exposure to PFASs,leading to changes in related pathways.These changes encompass various biological processes,including proteasome activity,immune response,cytoskeletal organization,oxidative stress,cell signaling,and nervous system function.Particularly noteworthy is the uncovering of the activation of the proteasome pathway,highlighting significant key contributing proteins.These novel findings provide a new perspective for exploring the molecularmechanism underlying the systemic health effects of PFASs and offer reliable screening for potential biomarkers.Additionally,comparisons with serum confirmed the potential of serum EVs as biological responders and measurable endpoints for evaluating PFASs-induced toxicity.展开更多
Renal cell carcinoma(RCC),which accounts for about 90 percent of kidney cancers,has a distinct metabolic reprogramming profile characterized by increased aerobic glycolysis(Warburg effect),abnormal accumulation of lip...Renal cell carcinoma(RCC),which accounts for about 90 percent of kidney cancers,has a distinct metabolic reprogramming profile characterized by increased aerobic glycolysis(Warburg effect),abnormal accumulation of lipids,and impaired mitochondrial function.Recent advances in high-throughput proteomic and metabolomic technologies have revolutionized our understanding of the pathophysiology of RCC,allowing for the systematic identification of disease-specific molecular signatures,elucidation of drug resistance mechanisms,and possible targets for intervention.The review focuses on the use of proteomic and metabolomic technologies in renal cell carcinoma and the research progress on related biomarkers,and is expected to provide useful information for the early detection and treatment of RCC.展开更多
BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabo...BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP.METHODS:We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP.Plasma samples were collected from 46 CAP patients(including27 with severe CAP and 19 with non-severe CAP)and 19 healthy controls upon admission.A comprehensive analysis of the combined proteomics and metabolomics data was then performed to elucidate the key pathological features associated with CAP severity.RESULTS:The proteomic and metabolic signature was markedly dif ferent between CAPs and healthy controls.Pathway analysis of changes revealed complement and coagulation cascades,ribosome,tumor necrosis factor(TNF)signaling pathway and lipid metabolic process as contributors to CAP.Furthermore,alterations in lipid metabolism,including sphingolipids and phosphatidylcholines(PCs),and dysregulation of cadherin binding were observed,potentially contributing to the development of severe CAP.Specifi cally,within the severe CAP group,sphingosine-1-phosphate(S1P)and apolipoproteins(APOC1 and APOA2)levels were downregulated,while S100P level was signifi cantly upregulated.CONCLUSION:The combined proteomic and metabolomic analysis may elucidate the complexity of CAP severity and inform the development of improved diagnostic tools.展开更多
Natural products(NPs)have long been recognized for their therapeutic potential,especially in cancer treatment,due to an ability to interact with multiple cellular pathways.The identification of molecular targets for N...Natural products(NPs)have long been recognized for their therapeutic potential,especially in cancer treatment,due to an ability to interact with multiple cellular pathways.The identification of molecular targets for NPs is a critical step in understanding anticancer mechanisms,with chemical proteomics emerging as a powerful approach.Both label-based and-free proteomic techniques have been utilized to identify these targets,each with their own advantages and limitations.While label-based methods provide high specificity through chemical tagging,the requirement for labeling can be a limitation,potentially altering NP natural properties.Conversely,label-free techniques allow for the detection of NP-protein interactions without structural modification but may struggle with transient interactions or low-abundance targets.Recent advances in artificial intelligence(AI)have further enhanced the field by improving target prediction and streamlining data analysis.AI-driven models,especially machine learning algorithms,have proven effective in processing complex proteomic data and predicting potential NP-protein interactions.The integration of AI with chemical proteomics accelerates target identification and deepens our understanding of the molecular mechanisms underlying the anticancer effects of NPs.This review explores the application of chemical proteomics and AI in the identification of cancer-related targets for NPs,highlighting current challenges and future directions for clinical translation.展开更多
基金Supported by The Eye Hospital of Wenzhou Medical University(No.KYQD20220304)The Fifth Batch of Provincial Ten Thousand Personnel Program Outstanding Talents Funding(No.474092204)+1 种基金Innovative Talents and Teams(2024)-The Fifth Batch of Funding Funds for Scientific and Technological Innovation Leading Talents Under the Provincial Ten Thousand Personnel Program(No.4240924003G)The Key R&D Program of Zhejiang(No.2022C03112).
文摘AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.
基金financial support of the National Natural Science Foundation of China(32102016)the Taishan Industrial Experts Program,Beijing Postdoctoral Research Foundation(2323ZZ122).
文摘The increase in human population has led to imminent pressures to develop new edible proteins with decreased environmental footprints.The most promising approach involves the production of single cell protein(SCP)from yeasts,which have been utilized in a wide variety of foods for thousands of years.In this study,102 yeast strains isolated from traditional fermented pork(Nanx Wudl)were investigated for their potential as SCP producer for the first time.Based on preliminary screening,Saccharomyces cerevisiae Y70 and Candida parapsilosis H5Y13,both showing high protein content and excellent growth capability,were selected for further analysis via 4D-DIA proteomics technology.Proteomic analysis indicated that the oxidative metabolism pathways,including TCA cycle,oxidative phosphorylation and pentose phosphate pathway,may have a significant impact on global protein synthesis and production.This study provides useful information for selecting SCP-producing yeast from Chinese fermented meat products and contribute to a deeper understanding of the underlying metabolic mechanisms behind global protein synthesis in yeast.Furthermore,these findings also provide potential molecular targets for genetic engineering modifications in yeast,aimed at constructing highly efficient cell factories for protein production.
基金supported by the director of Indian Council of Agricultural Research and International Rice Research Institute (ICAR-CRRI), Cuttack, Indiathe coordinator of the ICAR-sponsored project ‘C-reactive protein (CRP) in Biofortification in Selected Crops’, India
文摘CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.
文摘Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of proteins in lung(A549)and colon(HT29)cancer cell lines was examined by using proteomics analysis.The protein-protein interaction study of differentially expressed proteins was done by using the Search Tool for the Retrieval of Interacting Genes(STRING),and the results showed that the proteins interacting with each other belong to different pathways.
基金supported by the Young Scientists Fund of the National Natural Science Foundation of China(Grant No.:82204513)the Natural Science Foundation of Sichuan Province,China(Grant No.:2023NSFSC1673)+1 种基金the Innovation Guidance Foundation of the Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,China(Grant No.:SCU2023D005)the Scientific Research Staring Foundation of Sichuan University,China(Grant No.:YJ202165).
文摘Liraglutide(Lira),a glucagon-like peptide-1(GLP-1)receptor agonist approved for diabetes and obesity,has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease(MASLD).However,its systematic molecular regulation and mechanisms remain underexplored.In this study,a mouse model of MASLD was developed using a high-fat diet(HFD),followed by Lira administration.Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry(LC-MS/MS),while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction(qPCR)and Western blotting.Our results revealed that Lira treatment significantly reduced liver weight and serum markers,including alanine aminotransferase(ALT)and others,with glycosylation changes playing a more significant role than overall protein expression.The glycoproteome identified 255 independent glycosylation sites,emphasizing the impact of Lira on amino acid,carbohydrate metabolism,and ferroptosis.Simultaneously,proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways.21 signature molecules,including 7 proteins and 14 N-glycosylation sites(N-glycosites),were identified as potential targets.A Lira hydrogel formulation(Lira@fibrin(Fib)Gel)was developed to extend drug dosing intervals,offering enhanced therapeutic efficacy in managing chronic metabolic diseases.Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD,identifying potential molecular targets and advancing its clinical application for MASLD treatment.
基金supported by the Science and Technology(S&T)Program of Hebei Province,No.22377798D(to YZ).
文摘Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.
基金supported by the National Natural Science Foundation of China(32372223)the National Key Research and Development Program of China(2022YFD2301404)+1 种基金the College Students'Innovationand Entrepreneurship Training Program of Anhui Province,China(S202210364136)the Natural Science Research Project of Anhui Educational Committee,China(2023AH040133).
文摘Low temperature(LT)in spring has become one of the principal abiotic stresses that restrict the growth and development of wheat.Diverse analyses were performed to investigate the mechanism underlying the response of wheat grain development to LT stress during booting.These included morphological observation,measurements of starch synthase activity,and determination of amylose and amylopectin content of wheat grain after exposure to treatment with LT during booting.Additionally,proteomic analysis was performed using tandem mass tags(TMT).Results showed that the plumpness of wheat grains decreased after LT stress.Moreover,the activities of sucrose synthase(SuS,EC 2.4.1.13)and ADP-glucose pyrophosphorylase(AGPase,EC 2.7.7.27)exhibited a significant reduction,leading to a significant reduction in the contents of amylose and amylopectin.A total of 509 differentially expressed proteins(DEPs)were identified by proteomics analysis.The Gene Ontology(GO)enrichment analysis showed that the protein difference multiple in the nutritional repository activity was the largest among the molecular functions,and the up-regulated seed storage protein(ssP)played an active role in the response of grains to LT stress and subsequent damage.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis showed that LT stress reduced the expression of DEPs such as sucrose phosphate synthase(SPS),glucose-1-phosphate adenylyltransferase(glgC),andβ-fructofuranosidase(FFase)in sucrose and starch metabolic pathways,thus affecting the synthesis of grain starch.In addition,many heat shock proteins(HsPs)were found in the protein processing in endoplasmic reticulum pathways,which can resist some damage caused by LT stress.These findings provide a new theoretical foundation for elucidating the underlying mechanism governing wheat yield developmentafterexposuretoLTstress inspring.
基金the National Natural Science Foundation of China:Study on the Biological Basis of Jiawei Danzhi Xiaoyaosan in Treatment of Depression based on Network Pharmacology and Proteomics(No.81973739)Natural Science Excellent Youth Fund of Henan Province:the Mechanism of Baicalin Regulates the GSK3B-Mediated Axoplasmic Transport in the Treatment of Depression(No.202300410249)+1 种基金Science and Technology Research Project of Henan Province:Study on the Antidepressant Mechanism of Jiawei Danzhi Xiaoyaosan based on the NOD-like Receptor Thermal Protein Domainassociated Protein and Tripartite Motif-containing Protein 31 Ubiquitination Pathway(No.222102310233)Study on the Mechanism of Jiawei Danzhi Xiaoyaosan in the Treatment of Depression by Regulating M1/M2 Polarization and Microglia Autophagy(No.232102310419)。
文摘OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the antidepressant effects of JD were assessed using the sucrose preference test(SPT),forced swimming test(FST),and tail suspension test(TST).Tandem mass tag(TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment.Hierarchical clustering,Gene Ontology function annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interactions(PPIs)were used to analyze differentially expressed proteins(DEPs),which were further validated using quantitative real-time polymerase chain reaction(qR T-PCR)and Western blotting.RESULTS:Behavioral tests confirmed the antidepressant effects of JD,and bioinformatics analysis revealed 59 DEPs,including 33 up-regulated and 26 down-regulated proteins,between the CUMS and JD-M groups.KEGG and PPI analyses revealed that neurofilament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression.q RTPCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light(NEFL)and medium(NEFM)and inhibited the phosphorylation of extracellular regulated kinase 1/2(ERK1/2),whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM.CONCLUSIONS:The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.
基金supported by the National Natural Science Foundation of China(Nos.82073814,82122066,and 82104328)the"Dawn"Program of the Shanghai Education Commission(No.22SG34)+1 种基金the National Key Research and Development Program of the Ministry of China(No.2022YFC2704603)Shanghai Sailing Program(No.20YF1458900).
文摘Sini Decoction(SNT)is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold.However,elucidating the mechanism of action of SNT remains challenging due to its complex multiple components.This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis(2D-DIGE)-based drug affinity responsive target stability(DARTS)with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction.The analysis identified 590 proteins,with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group.Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments,the findings indicate that protein disulfide-isomerase A3(PDIA3)may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
基金supported by the Key-Area Research and Development Program of Guangdong Province (2021B0707060001)the Program for Scientific Research Start-Up Funds of Guangdong Ocean UniversityChina Postdoctoral Science Foundation (2016T90787)。
文摘The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-derived polysaccharides,named L2,on immune functions and blood lipid profiles,isobaric tags for relative and absolute quantification(iTRAQ)-based proteomic profiling of the small intestinal tissues from aged mice treated with L2 was performed.L2 reversed immune function declines and modulated the lipid metabolism of aged mice evidenced by increased levels of serum TC,HDL-C,and LDL-C,and reduced levels of serum TG.Moreover,a total of 95 differentially regulated proteins(DRPs) were identified,of which75 were up-regulated and 20 were down-regulated.Most of the DRPs were involved in intracellular and extracellular structure organization,and cellular and metabolic regulation.Particularly,approximately 16 and 9 DRPs participated in the regulation of immune functions and lipid metabolism,respectively.Furthermore,protein-protein interaction analysis highlighted that cadherin-1,plectin,cadherin-17,Ras GTPase-activating-like protein IQGAP2,and ezrin might be key proteins in response to L2 treatment.These findings provide new insights into the biological mechanisms of mushroom polysaccharides in anti-aging from a proteomic perspective.
文摘BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.
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.
基金Supported by the Key R&D Projects of Hainan Province,No.ZDYF2022SHFZ295.
文摘BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,peripheral blood mononuclear cells(PBMCs)serve as a robust model for investigating intracellular alterations linked to SZ.AIM To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.METHODS PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes(DEGs)and differentially expressed proteins while mapping putative disease-associated signaling pathways.Key findings were validated using western blot(WB)and real-time fluorescence quantitative PCR(RT-qPCR).RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro,with subsequent verification of target gene expression via RT-qPCR.The levels of neuronal conduction proteins,including calmodulin-dependent protein kinase II(caMKII),CREB,and BDNF,were assessed through WB.Apoptosis was quantified by flow cytometry,while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.RESULTS The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes,among which 25 DEGs were significantly altered between the SZ group and healthy controls.Notably,haptoglobin(HP),lactotransferrin(LTF),and SERPING1 exhibited marked upregulation.KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis.Clinical sample validation demonstrated elevated protein and mRNA levels of HP,LTF,and SERPING1 in the SZ group compared to controls.WB analysis of all clinical samples further corroborated the significant upregulation of SERPING1.In hippocampal CA1 neurons transfected with lentivirus,reduced SERPING1 expression was accompanied by increased levels of CaMKII,CREB,and BDNF,enhanced cell viability,and reduced apoptosis.CONCLUSION SERPING1 may suppress neural cell proliferation in SZ patients via modulation of the CaMKII-CREB-BDNF signaling pathway.
基金supported by the Cross-disciplinary Integration Project of Fujian Agriculture and Forestry University(71202103C)Science and Technology Projects of Fuzhou Ocean Research Institute(2022F16).
文摘With the increasing per capita demand for animal protein,there is a growing interest in the abundant abalone protein resources.Abalone proteins are known for their nutritional and functional properties that contribute to flavor and texture.We systematically constructed the relationship between abalone protein,processing,and proteomics.This paper reviews the nutritional properties of abalone proteins and evaluates the effects of different thermal processing techniques,non-thermal processing,and freezing on abalone proteins.In addition,we synthesize published abalone proteomics studies and the use of proteomics technology to better elucidate the quality changes of abalone and its products,and as a technical basis for the study of blue food marker proteins.It is important direction to clearly explain the protein composition and meat quality mechanism of abalone in the processing and storage by proteomic.During various types of thermal processing,non-thermal processing,and freezing of abalone,the various chemical forces between protein molecules are disrupted,which in turn leads to different degrees of denaturation,aggregation,and gelation,which may have an impact on the organoleptic properties,bioavailability,and digestibility of abalone muscle.Proteomics is used in abalone biology studies to understand developmental biology,physiology,disease,stress,and species identification and can also be a powerful tool to characterize processing methods on abalone quality properties.
基金funded by the National Natural Science Foundation of China(Grant No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant Nos.2023ZD0501400-2023ZD0501402)+3 种基金Beijing Hospitals Authority’s Ascent Plan(Grant No.DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(Grant No.ZLRK202325)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(Grant No.BMU2022XKQ004)the Science Foundation of Peking University Cancer Hospital(Grant Nos.BJCH2024BJ02,XKFZ2410,and 2022-27).
文摘Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.
基金Supported by XinganLeague Science and Technology Programme Project,No.MBJH2023022.
文摘BACKGROUND Myocardial infarction(MI)occupies a very high mortality and morbidity rate,and the search for effective pharmacological treatments has far-reaching implications for clinical research.AIM To explore the protective effects of Mongolian medicine Agari-5 on rats with MI.METHODS Sprague-Dawley rats were used,and both the Agari-5 and model groups had their coronary arteries clamped to induce MI.Proteomics was used to research the potential mechanism of action while ELISA,hematoxylin and eosin,and Masson’s staining were used to preliminarily investigate the protective impact of Agari-5 on rats with MI.RESULTS The current study has shown that Agari-5 might enhance cardiac function indicators,including echocardiography results of rats and creatine kinase,creatine kinase isoenzyme,and lactate dehydrogenase,in rats that had MI.According to the results of pathological staining,Agari-5 may lessen inflammatory cell infiltration and cardiomyocyte fibrosis,among other things.The proteome analysis revealed that there were 60 distinct proteins in total,four of which were associated with the heart.The expression of PSAT1,PDK1,SMAD4,and SDF2 proteins may be linked to the mechanism of their protective effects.CONCLUSION Potential therapeutic effects of Agari-5 for MI and its mechanism of action may be related to PSAT1,PDK1,SMAD4,and SDF2.
基金supported by the Key Research and Development Plan of Zhejiang Province(No.2021C03176)Zhejiang Provincial Natural Science Foundation of China(No.LY23B070001)+2 种基金the Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province(No.20230009)the National Natural Science Foundation of China(No.22106032)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0750000).
文摘Per-and polyfluoroalkyl substances(PFASs)can induce a range of adverse health effects,with the precise molecularmechanisms remaining elusive.Extracellular vesicles(EVs)have demonstrated their potential to elucidate unknown molecular mechanisms.Building upon the close alignment of their biological functions with the observed health effects of PFASs,this study innovatively focuses on proteomic insights from EVs into the molecular mechanisms underlying the systemic health effects of PFASs.Through rat exposure experiments and proteomics technology,it not only demonstrated the occurrence of PFASs in EVs but also revealed the alterations in the serum EVs and the expression of their protein cargos following mixed exposure to PFASs,leading to changes in related pathways.These changes encompass various biological processes,including proteasome activity,immune response,cytoskeletal organization,oxidative stress,cell signaling,and nervous system function.Particularly noteworthy is the uncovering of the activation of the proteasome pathway,highlighting significant key contributing proteins.These novel findings provide a new perspective for exploring the molecularmechanism underlying the systemic health effects of PFASs and offer reliable screening for potential biomarkers.Additionally,comparisons with serum confirmed the potential of serum EVs as biological responders and measurable endpoints for evaluating PFASs-induced toxicity.
基金National Natural Science Foundation of China(3236016631760321).
文摘Renal cell carcinoma(RCC),which accounts for about 90 percent of kidney cancers,has a distinct metabolic reprogramming profile characterized by increased aerobic glycolysis(Warburg effect),abnormal accumulation of lipids,and impaired mitochondrial function.Recent advances in high-throughput proteomic and metabolomic technologies have revolutionized our understanding of the pathophysiology of RCC,allowing for the systematic identification of disease-specific molecular signatures,elucidation of drug resistance mechanisms,and possible targets for intervention.The review focuses on the use of proteomic and metabolomic technologies in renal cell carcinoma and the research progress on related biomarkers,and is expected to provide useful information for the early detection and treatment of RCC.
基金supported by the National Key Research and Development Program of China(2021YFC2501800,2023YFC0872500 and 2024YFC3044600)the National Natural Science Foundation of China(82072214,82272198,82202373)+1 种基金the Science and Technology of Shanghai Committee(21MC1930400,22Y11900100 and 23Y31900100)the Shanghai Municipal Health Commission(2023ZDFC0101)。
文摘BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP.METHODS:We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP.Plasma samples were collected from 46 CAP patients(including27 with severe CAP and 19 with non-severe CAP)and 19 healthy controls upon admission.A comprehensive analysis of the combined proteomics and metabolomics data was then performed to elucidate the key pathological features associated with CAP severity.RESULTS:The proteomic and metabolic signature was markedly dif ferent between CAPs and healthy controls.Pathway analysis of changes revealed complement and coagulation cascades,ribosome,tumor necrosis factor(TNF)signaling pathway and lipid metabolic process as contributors to CAP.Furthermore,alterations in lipid metabolism,including sphingolipids and phosphatidylcholines(PCs),and dysregulation of cadherin binding were observed,potentially contributing to the development of severe CAP.Specifi cally,within the severe CAP group,sphingosine-1-phosphate(S1P)and apolipoproteins(APOC1 and APOA2)levels were downregulated,while S100P level was signifi cantly upregulated.CONCLUSION:The combined proteomic and metabolomic analysis may elucidate the complexity of CAP severity and inform the development of improved diagnostic tools.
基金supported in part by the Science and Technology Development Fund,Macao SAR(0098/2021/A2 and 0048/2023/AFJ)the Chinese Medicine Guangdong Laboratory(HQCML-C-2024006).
文摘Natural products(NPs)have long been recognized for their therapeutic potential,especially in cancer treatment,due to an ability to interact with multiple cellular pathways.The identification of molecular targets for NPs is a critical step in understanding anticancer mechanisms,with chemical proteomics emerging as a powerful approach.Both label-based and-free proteomic techniques have been utilized to identify these targets,each with their own advantages and limitations.While label-based methods provide high specificity through chemical tagging,the requirement for labeling can be a limitation,potentially altering NP natural properties.Conversely,label-free techniques allow for the detection of NP-protein interactions without structural modification but may struggle with transient interactions or low-abundance targets.Recent advances in artificial intelligence(AI)have further enhanced the field by improving target prediction and streamlining data analysis.AI-driven models,especially machine learning algorithms,have proven effective in processing complex proteomic data and predicting potential NP-protein interactions.The integration of AI with chemical proteomics accelerates target identification and deepens our understanding of the molecular mechanisms underlying the anticancer effects of NPs.This review explores the application of chemical proteomics and AI in the identification of cancer-related targets for NPs,highlighting current challenges and future directions for clinical translation.
