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
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
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
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
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
Objective:To explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch.(G.uralensis)and to improve the quality of cultivated G.uralensis for both medicine and food and aid in...Objective:To explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch.(G.uralensis)and to improve the quality of cultivated G.uralensis for both medicine and food and aid in the increase in the content of effective components in G.uralensis.Methods:In this study,whole G.uralensis plants were treated with exogenous chitosan,and compre-hensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation,respectively.Effects of chitosan induction on endogenous hormones of G.uralensis were analyzed using an enzyme-linked immunosorbent assay.Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.Results:Chitosan induction significantly increased the levels of flavonoids in G.uralensis;however,the variation in triterpenoids was not substantial.Biological processes,including photosynthesis,secondary metabolism,and abiotic stress responses,were significantly enriched.Additionally,the photosynthetic pathway,photosynthesis-antenna protein pathway,and plant hormone signal transduction pathway were significantly enriched.In the flavonoid biosynthesis pathway,the upstream-related enzyme phenylalanine ammonia-lyase(PAL)and the downstream-related enzymes chalcone synthase(CHS),polyketide reductase(PKR),chalcone isomerase(CHI),and vestitone reductase(VR)were significantly upregulated.Conclusions:Our findings suggest that chitosan induction may promote the tricarboxylic acid(TCA)cycle,and the TCA cycle enhancement significantly upregulated PAL,CHS,PKR,CHI,and VR,the five key enzymes involved in flavonoid synthesis of G.uralensis,indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G.uralensis.Our findings provide a reference for improving the quality of cultivated G.uralensis from the perspective of pharmacodynamic components.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
OBJECTIVE:To observe the effects of moxibustion at Zusanli(ST36)on rats with chronic fatigue syndrome(CFS)and to analyze the mechanisms of moxibustion through hippocampal Proteomics.METHODS:Male Sprague-Dawley(SD)rats...OBJECTIVE:To observe the effects of moxibustion at Zusanli(ST36)on rats with chronic fatigue syndrome(CFS)and to analyze the mechanisms of moxibustion through hippocampal Proteomics.METHODS:Male Sprague-Dawley(SD)rats were randomly divided into three groups:control group(CON),model group(MOD),and moxibustion group(MOX),with 12 rats in each group.The MOD and MOX groups underwent chronic multi-factor stress stimulation for 35 d to establish the CFS model.After modeling,the rats in the MOX group received mild moxibustion at Zusanli(ST36)(bilateral)for 10 minutes daily for 28 d.During the treatment period,rats in both the MOD and MOX groups continued modeling,while the CON group was kept under normal breeding conditions.The general condition of the rats was monitored,and behaviors were assessed using the Open Field Test(OFT),Exhaustion Treadmill Test,and Morris Water Maze(MWM).Hematoxylin and eosin(HE)staining and transmission electron microscopy(TEM)were employed to observe morphological changes in the hippocampus.Label-free Proteomics were utilized to identify differentially expressed proteins(DEPs)in the hippocampus,followed by bioinformatics analysis.The reliability of the Proteomics results was verified using Parallel Reaction Monitoring.RESULTS:A:Moxibustion at Zusanli(ST36)significantly reduced the general condition score of CFS rats,improved their behavioral performance in OFT,treadmill and MWM,and repaired the pathological and synaptic structural damage in the hippocampus.B:We identified DEPs by applying a fold change threshold of 1.2 and a significance level of P<0.05.In the comparison between the CON and the MOD,we identified a total of 72 DEPs(31 up-regulated and 41 down-regulated)associated with the development of CFS.In the comparison between the MOX and the MOD group,we identified a total of 103 DEPs(40 up-regulated and 63 down-regulated)related to the therapeutic effects of moxibustion.Gene Ontology(GO)enrichment analysis showed that CFS and moxibustion treatment were related to multiple biological processes,molecular functions,and cellular components.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed that CFS pathogenesis was linked to base excision repair,steroid biosynthesis,and systemic lupus erythematosus,Furthermore,the treatment of CFS with moxibustion was relevant to terpenoid skeleton biosynthesis.C:Compared with the two comparison groups,we identified 16 potential biomarkers,noting that moxibustion reversed the upregulation of 14 DEPs and the down-regulation of 2 DEPs in CFS.These proteins are mainly associated with synaptic plasticity,ribosomal function,neurotransmitter secretion,glycine metabolism,and mitochondrial function.CONCLUSION:Moxibustion at Zusanli(ST36)is effective in treating CFS,the potential biomarkers identified by Proteomics confirm that the mechanisms of moxibustion involve multiple targets and pathways,which may be key to regulating the structural and functional damage in the hippocampus associated with CFS,highlighting their significant value for future research.展开更多
The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pa...The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.展开更多
AIM:To employ proteome-wide Mendelian randomization(MR)to explore novel protein and drug targets for retinal neurodegenerative diseases(RND)in individuals of European ancestry.METHODS:This study used summary data-base...AIM:To employ proteome-wide Mendelian randomization(MR)to explore novel protein and drug targets for retinal neurodegenerative diseases(RND)in individuals of European ancestry.METHODS:This study used summary data-based MR to analyze the correlation between plasma protein levels and three RND,with protein data derived from two independent large-scale proteomics datasets.Potential drug targets were identified using Bayesian colocalization,followed by MR analysis,sensitivity testing,and external validation.Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.RESULTS:The study identified six promising protein targets,each successfully replicated at least twice.The results included three proteins related to diabetic retinopathy(ICAM1,GCKR,WARS),two proteins related to age-related macular degeneration(WARS,BRD2),and two proteins related to glaucoma(SVEP1,NPTXR).Additionally,drug prediction and molecular docking indicated that five drugs(fenofibrate,trofinetide,ticagrelor,lifitegrast,acetaminophen)effectively bound to the target proteins.CONCLUSION:This study identified six potential protein targets for RND and five existing drugs with therapeutic potential.By integrating plasma proteomics with genetic data,it provides a cost-effective framework for drug discovery.展开更多
Neonatal hypoxic-ischemic encephalopathy(HIE)refers to neonatal brain damage caused by various factors during the perinatal period that lead to hypoxia and reduced cerebral blood flow[1].Globally,0.2%to 2.26%of newbor...Neonatal hypoxic-ischemic encephalopathy(HIE)refers to neonatal brain damage caused by various factors during the perinatal period that lead to hypoxia and reduced cerebral blood flow[1].Globally,0.2%to 2.26%of newborns develop HIE,with approximately 20%resulting in neonatal death and about 25%of survivors suffering from neurological impairment[2].Currently,there is a lack of highly sensitive and specific diagnostic tools for HIE,posing significant challenges to reducing HIE mortality and neurological abnormalities[3].The development of high-throughput proteomics technology based on mass spectrometry(MS)has significantly enhanced the potential to discover biomarkers in biological fluids such as plasma,cerebrospinal fluid,saliva,and urine[4].Proteomics technology has become an engine for exploring novel markers of HIE[5].This article systematically reviews the progress of proteomics technology in the study of biomarkers for the early diagnosis of HIE,elucidating its potential application value.展开更多
Background:Fufang Muji Granules is a traditional Chinese medicine of the Manchu ethnic group and is thought to treat hepatitis and liver injury by inhibiting the elevation of alpha-fetoprotein.Methods:In this investig...Background:Fufang Muji Granules is a traditional Chinese medicine of the Manchu ethnic group and is thought to treat hepatitis and liver injury by inhibiting the elevation of alpha-fetoprotein.Methods:In this investigation,tandem mass tag(TMT)-based quantitative proteomics was performed to figure out the therapeutic mechanisms of Fufang Muji Granules on liver injury caused by carbon tetrachloride(CCl_(4))in rats.Results:Biochemical analyses(alanine aminotransferase;glutamate aminotransferase;aspartate aminotransferase)and histologic analyses(hematoxylin-eosin)demonstrated that FMG was effective in ameliorating liver injury.A sum of 6,208 proteins were identified and 2,475 proteins were determined as differential abundance proteins(DAPs)in rat liver treated with Fufang Muji Granules which compared to the model group.Bioinformatics analysis indicated that the DAPs are primarily enriched in multiple pathways such as rno00280(valine,leucine,and isoleucine degradation),rno00640(Propanoate metabolism),and rno00380(Tryptophan metabolism).Western blot was employed to validate the findings from the proteomic analysis.Conclusion:This study not only provides useful information on the mechanism of Fufang Muji Granules in the treatment of liver injury but also serves as a basis for further study of Fufang Muji Granules in vivo.展开更多
Porcine reproductive and respiratory syndrome(PRRS),a highly infectious immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus(PRRSV),has led to significant economic losses in the glob...Porcine reproductive and respiratory syndrome(PRRS),a highly infectious immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus(PRRSV),has led to significant economic losses in the global swine industry.The complexity of preventing and controlling PRRS,compounded by the limited efficacy of current vaccines,underscores the urgent need to identify antiviral targets and develop effective therapeutics against PRRSV.From the perspective of virus-host interactions,the discovery of target molecules associated with PRRSV resistance offers a promising strategy for future disease management.In this study,we conduct a comprehensive proteomic analysis using data-independent acquisition(DIA)mode to investigate the host response throughout the acute phase of PRRSV infection.This approach provides critical insights into the regulation of host antiviral and immune pathways during acute infection,advancing our theoretical understanding of PRRSV-host interactions and host gene dynamics during this critical phase.Notably,we identified SCARB2,a major lysosomal membrane protein associated with cholesterol metabolism,as a potential regulator of PRRSV replication.These findings offer novel perspectives for the prevention and control of PRRSV,contributing to the development of targeted antiviral strategies.展开更多
Objectives To elucidate the potential mechanisms of electroacupuncture(EA)in restoring detrusor-bladder neck dyssynergia(DBND)following suprasacral spinal cord injury(SSCI).Methods A total of 52 specific pathogen-free...Objectives To elucidate the potential mechanisms of electroacupuncture(EA)in restoring detrusor-bladder neck dyssynergia(DBND)following suprasacral spinal cord injury(SSCI).Methods A total of 52 specific pathogen-free(SPF)grade famale Sprague-Dawley(SD)rats(10-12 weeks,250-280 g)were randomly assigned to either a sham group(n=12)or a spinal cord injury model group(n=40).In the model group,DBND was induced through Hassan Shaker spinal cord transection at T10 level,with 24 rats meeting inclusion criteria and subse-quently randomized into DBND group(n=12)and EA intervention group(DBND+EA group,n=12).After spinal shock recovery(day 19 after modeling),DBND+EA group received EA treatment at Ciliao(BL32),Zhongji(RN3),and Sanyinjiao(SP6)acupoints for 20 min per ses-sion at 10/50 Hz frequencies,once daily for 10 d.Sham and DBND groups received anesthe-sia only without EA intervention.On day 29 post-modeling,all rats underwent urodynamic assessments,followed by hematoxylin and eosin(HE)staining,tandem mass tag(TMT)pro-teomics,and Western blot(WB)analysis of detrusor and bladder neck tissues.Differentially expressed proteins(DEPs)were defined as proteins with P<0.05,unique peptides≥2,and fold change>1.2 or<0.83.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway anal-ysis was performed using KOBAS 3.0(P<0.01),and protein-protein interaction(PPI)net-works were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)11.5 and Cytoscape 3.9.1.Results Compared with sham group,DBND group showed significantly elevated leak point pressure(LPP)and maximum cystometric capacity(MCC)(both P<0.01).EA treatment sig-nificantly reduced both LPP and MCC compared with DBND group(P<0.01 and P<0.05,re-spectively).HE staining revealed that EA reduced detrusor fibrosis and improved bladder neck inflammation.TMT proteomics identified 30 overlapping DEPs in detrusor and 59 over-lapping DEPs in bladder neck when comparing DBND+EA/DBND groups with sham group.In detrusor tissue,KEGG analysis revealed 10 significantly enriched pathways(P<0.01),in-cluding mitogen-activated protein kinase(MAPK)signaling pathway.PPI analysis showed 22 of 30 DEPs were interconnected.In bladder neck tissue,14 pathways were significantly en-riched(P<0.01),including relaxin signaling pathway,with 51 of 59 DEPs showing intercon-nections.Both TMT and WB validations demonstrated that compared with sham controls,DBND rats exhibited upregulated collagen type IV alpha 2 chain(Col4a2)and downregulated guanine nucleotide-binding protein G(z)subunit alpha(Gnaz)in detrusor tissue,while EA treatment normalized both proteins(both P<0.05).In bladder neck tissue,DBND rats showed decreased expression of smoothelin(Smtn)and calcium-activated potassium chan-nel subunit beta-1(Kcnmb1)compared with sham controls(both P<0.01),which were both upregulated following EA treatment(P<0.01 and P<0.05,respectively).Conclusion EA restores detrusor-bladder neck coordination in DBND through dual-target mechanisms.In detrusor tissue,EA modulates contraction via extracellular matrix remodel-ing,cyclic adenosine monophosphate(cAMP)signaling pathway regulation,and enhanced adenosine triphosphate(ATP)biosynthesis mediated by neurotransmitters.In bladder neck tissue,EA promotes relaxation by maintaining contractile phenotypes,reducing fibrosis,sup-pressing smooth muscle excitation,and regulating presynaptic neurotransmitter release.These findings provide mechanistic insights into EA's therapeutic role in managing DBND.展开更多
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 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.
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 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.
基金supported by grants from the National Natural Science Foundation of China(81773838).
文摘Objective:To explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch.(G.uralensis)and to improve the quality of cultivated G.uralensis for both medicine and food and aid in the increase in the content of effective components in G.uralensis.Methods:In this study,whole G.uralensis plants were treated with exogenous chitosan,and compre-hensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation,respectively.Effects of chitosan induction on endogenous hormones of G.uralensis were analyzed using an enzyme-linked immunosorbent assay.Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.Results:Chitosan induction significantly increased the levels of flavonoids in G.uralensis;however,the variation in triterpenoids was not substantial.Biological processes,including photosynthesis,secondary metabolism,and abiotic stress responses,were significantly enriched.Additionally,the photosynthetic pathway,photosynthesis-antenna protein pathway,and plant hormone signal transduction pathway were significantly enriched.In the flavonoid biosynthesis pathway,the upstream-related enzyme phenylalanine ammonia-lyase(PAL)and the downstream-related enzymes chalcone synthase(CHS),polyketide reductase(PKR),chalcone isomerase(CHI),and vestitone reductase(VR)were significantly upregulated.Conclusions:Our findings suggest that chitosan induction may promote the tricarboxylic acid(TCA)cycle,and the TCA cycle enhancement significantly upregulated PAL,CHS,PKR,CHI,and VR,the five key enzymes involved in flavonoid synthesis of G.uralensis,indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G.uralensis.Our findings provide a reference for improving the quality of cultivated G.uralensis from the perspective of pharmacodynamic components.
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National Natural Science Foundation of China projects:Research on the Mechanism of Moxibustion Activating Calcium/Calmodulin-dependent Protein KinaseⅡPhosphorylation Mediating Long-term Potentiation to Regulate Synaptic Plasticity in the Treatment of Chronic Fatigue Syndrome Cognitive Impairment(No.82305394)Research on the Mechanism of Electroacupuncture Regulating Murine Double Minute 2 Ubiquitination Postsynaptic Density Protein 95 Levels to Reshape the Synaptic Structure of Hippocampal Neurons and Improve Chronic Fatigue Syndrome Cognitive Impairment(No.82074539)+7 种基金Outstanding Youth Project of Heilongjiang Provincial Natural Science Foundation:the Mechanism of Moxibustion in Improving Chronic Fatigue Syndrome Cognitive Impairment by Regulating Calcium/Calmodulin-dependent Protein Kinase II-mediated Long-Term Potentiation(No.YQ2023H019)Youth Talent Support Project of the Chinese Association of Traditional Chinese Medicine:Research on the Molecular Pathways of Moxibustion at the Zusanli(ST36)Point in Regulating Synaptic Plasticity to Improve Chronic Fatigue Syndrome Cognitive Impairment(No.2023-QNRC2-A04)China Postdoctoral Science Foundation:Research on the Mechanism of Moxibustion in Regulating Mitochondrial Autophagy Mediating Microglial Polarization to Promote Synaptic Remodeling in Chronic Fatigue Syndrome Cognitive Impairment(No.2024MD763980)Post-doctoral Program of Heilongjiang Province:based on the Calcium/Calmodulin-dependent Protein Kinase II/Parkin/NLR Family Pyrin Domain Containing 3 Signaling Axis to Explore the Mechanism of Moxibustion in Mitochondrial Autophagy Mediating Microglial Polarization to Promote Synaptic Remodeling in Chronic Fatigue Syndrome Cognitive Impairment(No.LBH-TZ2420)Study on the Mechanism of Moxibustion at the Zusanli(ST36)Regulating Long-Term Potentiation to Promote Synaptic Remodeling and Improve Cognitive Impairment in Chronic Fatigue Syndrome(No.LBH-Z23281)Chunhui Plan of the Ministry of Education:Study on the Mechanism of the Tongdu Yu Pi Tiaoshen Acupuncture in Improving Hippocampal Synaptic Plasticity of Chronic Fatigue Syndrome Cognitive Impairment(No.HZKY20220308-202201357)Youth Talent Support Project of the Heilongjiang Provincial Association of Traditional Chinese Medicine:Study on the Effect and Mechanism of Tongdu Yupi Tiaoshen Acupuncture on Improving Hippocampal Synaptic Plasticity in Chronic Fatigue Syndrome Cognitive Impairment(No.2022-QNRC1-05)Research Project of Traditional Chinese Medicine in Heilongjiang Province:Study on the Mechanism of Acupuncture in Improving Hippocampal Synaptic Plasticity of Chronic Fatigue Syndrome Cognitive Impairment(No.ZHY2022-136)。
文摘OBJECTIVE:To observe the effects of moxibustion at Zusanli(ST36)on rats with chronic fatigue syndrome(CFS)and to analyze the mechanisms of moxibustion through hippocampal Proteomics.METHODS:Male Sprague-Dawley(SD)rats were randomly divided into three groups:control group(CON),model group(MOD),and moxibustion group(MOX),with 12 rats in each group.The MOD and MOX groups underwent chronic multi-factor stress stimulation for 35 d to establish the CFS model.After modeling,the rats in the MOX group received mild moxibustion at Zusanli(ST36)(bilateral)for 10 minutes daily for 28 d.During the treatment period,rats in both the MOD and MOX groups continued modeling,while the CON group was kept under normal breeding conditions.The general condition of the rats was monitored,and behaviors were assessed using the Open Field Test(OFT),Exhaustion Treadmill Test,and Morris Water Maze(MWM).Hematoxylin and eosin(HE)staining and transmission electron microscopy(TEM)were employed to observe morphological changes in the hippocampus.Label-free Proteomics were utilized to identify differentially expressed proteins(DEPs)in the hippocampus,followed by bioinformatics analysis.The reliability of the Proteomics results was verified using Parallel Reaction Monitoring.RESULTS:A:Moxibustion at Zusanli(ST36)significantly reduced the general condition score of CFS rats,improved their behavioral performance in OFT,treadmill and MWM,and repaired the pathological and synaptic structural damage in the hippocampus.B:We identified DEPs by applying a fold change threshold of 1.2 and a significance level of P<0.05.In the comparison between the CON and the MOD,we identified a total of 72 DEPs(31 up-regulated and 41 down-regulated)associated with the development of CFS.In the comparison between the MOX and the MOD group,we identified a total of 103 DEPs(40 up-regulated and 63 down-regulated)related to the therapeutic effects of moxibustion.Gene Ontology(GO)enrichment analysis showed that CFS and moxibustion treatment were related to multiple biological processes,molecular functions,and cellular components.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed that CFS pathogenesis was linked to base excision repair,steroid biosynthesis,and systemic lupus erythematosus,Furthermore,the treatment of CFS with moxibustion was relevant to terpenoid skeleton biosynthesis.C:Compared with the two comparison groups,we identified 16 potential biomarkers,noting that moxibustion reversed the upregulation of 14 DEPs and the down-regulation of 2 DEPs in CFS.These proteins are mainly associated with synaptic plasticity,ribosomal function,neurotransmitter secretion,glycine metabolism,and mitochondrial function.CONCLUSION:Moxibustion at Zusanli(ST36)is effective in treating CFS,the potential biomarkers identified by Proteomics confirm that the mechanisms of moxibustion involve multiple targets and pathways,which may be key to regulating the structural and functional damage in the hippocampus associated with CFS,highlighting their significant value for future research.
基金supported by National Natural Science Foundation of China(32172365 and 32272513)the Central Guidance on Local Science and Technology Development Fund of Fujian Province,China(2022L3088)the Innovative Research Funding of Fujian Agriculture and Forestry University,China(CXZX2020153D)。
文摘The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.
基金Supported by the National Natural Science Foundation of China(No.82000919)Science and Technology Project of Education Department of Jilin Province(No.JJKH20201089KJ).
文摘AIM:To employ proteome-wide Mendelian randomization(MR)to explore novel protein and drug targets for retinal neurodegenerative diseases(RND)in individuals of European ancestry.METHODS:This study used summary data-based MR to analyze the correlation between plasma protein levels and three RND,with protein data derived from two independent large-scale proteomics datasets.Potential drug targets were identified using Bayesian colocalization,followed by MR analysis,sensitivity testing,and external validation.Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.RESULTS:The study identified six promising protein targets,each successfully replicated at least twice.The results included three proteins related to diabetic retinopathy(ICAM1,GCKR,WARS),two proteins related to age-related macular degeneration(WARS,BRD2),and two proteins related to glaucoma(SVEP1,NPTXR).Additionally,drug prediction and molecular docking indicated that five drugs(fenofibrate,trofinetide,ticagrelor,lifitegrast,acetaminophen)effectively bound to the target proteins.CONCLUSION:This study identified six potential protein targets for RND and five existing drugs with therapeutic potential.By integrating plasma proteomics with genetic data,it provides a cost-effective framework for drug discovery.
文摘Neonatal hypoxic-ischemic encephalopathy(HIE)refers to neonatal brain damage caused by various factors during the perinatal period that lead to hypoxia and reduced cerebral blood flow[1].Globally,0.2%to 2.26%of newborns develop HIE,with approximately 20%resulting in neonatal death and about 25%of survivors suffering from neurological impairment[2].Currently,there is a lack of highly sensitive and specific diagnostic tools for HIE,posing significant challenges to reducing HIE mortality and neurological abnormalities[3].The development of high-throughput proteomics technology based on mass spectrometry(MS)has significantly enhanced the potential to discover biomarkers in biological fluids such as plasma,cerebrospinal fluid,saliva,and urine[4].Proteomics technology has become an engine for exploring novel markers of HIE[5].This article systematically reviews the progress of proteomics technology in the study of biomarkers for the early diagnosis of HIE,elucidating its potential application value.
基金National Natural Science Foundation of China(82104532 and 82173913)Joint Program(Applied Basic Research Project)of Liaoning Provincial Science and Technology Program(2023JH2/101700074)+1 种基金High-level Talent Innovation Support Program of Dalian(2021RD10)Fundamental Research Funds for the Central Universities(2023-SWGC-0101)。
文摘Background:Fufang Muji Granules is a traditional Chinese medicine of the Manchu ethnic group and is thought to treat hepatitis and liver injury by inhibiting the elevation of alpha-fetoprotein.Methods:In this investigation,tandem mass tag(TMT)-based quantitative proteomics was performed to figure out the therapeutic mechanisms of Fufang Muji Granules on liver injury caused by carbon tetrachloride(CCl_(4))in rats.Results:Biochemical analyses(alanine aminotransferase;glutamate aminotransferase;aspartate aminotransferase)and histologic analyses(hematoxylin-eosin)demonstrated that FMG was effective in ameliorating liver injury.A sum of 6,208 proteins were identified and 2,475 proteins were determined as differential abundance proteins(DAPs)in rat liver treated with Fufang Muji Granules which compared to the model group.Bioinformatics analysis indicated that the DAPs are primarily enriched in multiple pathways such as rno00280(valine,leucine,and isoleucine degradation),rno00640(Propanoate metabolism),and rno00380(Tryptophan metabolism).Western blot was employed to validate the findings from the proteomic analysis.Conclusion:This study not only provides useful information on the mechanism of Fufang Muji Granules in the treatment of liver injury but also serves as a basis for further study of Fufang Muji Granules in vivo.
基金supported by the National Natural Science Foundation of China(grant no.:3217190296,82102755 and 32302887)Guangdong Basic and Applied Basic Research Foundation(grant no.:2023A1515012623 and 2019B1515210030)China Postdoctoral Science Foundation(grant no.:2021M703739)。
文摘Porcine reproductive and respiratory syndrome(PRRS),a highly infectious immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus(PRRSV),has led to significant economic losses in the global swine industry.The complexity of preventing and controlling PRRS,compounded by the limited efficacy of current vaccines,underscores the urgent need to identify antiviral targets and develop effective therapeutics against PRRSV.From the perspective of virus-host interactions,the discovery of target molecules associated with PRRSV resistance offers a promising strategy for future disease management.In this study,we conduct a comprehensive proteomic analysis using data-independent acquisition(DIA)mode to investigate the host response throughout the acute phase of PRRSV infection.This approach provides critical insights into the regulation of host antiviral and immune pathways during acute infection,advancing our theoretical understanding of PRRSV-host interactions and host gene dynamics during this critical phase.Notably,we identified SCARB2,a major lysosomal membrane protein associated with cholesterol metabolism,as a potential regulator of PRRSV replication.These findings offer novel perspectives for the prevention and control of PRRSV,contributing to the development of targeted antiviral strategies.
基金National Natural Science Foundation of China (General Program, 81874510)Natural Science Foundation of Hunan Province (2022JJ40301)Scientific Research Project of the Hunan Provincial Department of Education (21B0369)。
文摘Objectives To elucidate the potential mechanisms of electroacupuncture(EA)in restoring detrusor-bladder neck dyssynergia(DBND)following suprasacral spinal cord injury(SSCI).Methods A total of 52 specific pathogen-free(SPF)grade famale Sprague-Dawley(SD)rats(10-12 weeks,250-280 g)were randomly assigned to either a sham group(n=12)or a spinal cord injury model group(n=40).In the model group,DBND was induced through Hassan Shaker spinal cord transection at T10 level,with 24 rats meeting inclusion criteria and subse-quently randomized into DBND group(n=12)and EA intervention group(DBND+EA group,n=12).After spinal shock recovery(day 19 after modeling),DBND+EA group received EA treatment at Ciliao(BL32),Zhongji(RN3),and Sanyinjiao(SP6)acupoints for 20 min per ses-sion at 10/50 Hz frequencies,once daily for 10 d.Sham and DBND groups received anesthe-sia only without EA intervention.On day 29 post-modeling,all rats underwent urodynamic assessments,followed by hematoxylin and eosin(HE)staining,tandem mass tag(TMT)pro-teomics,and Western blot(WB)analysis of detrusor and bladder neck tissues.Differentially expressed proteins(DEPs)were defined as proteins with P<0.05,unique peptides≥2,and fold change>1.2 or<0.83.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway anal-ysis was performed using KOBAS 3.0(P<0.01),and protein-protein interaction(PPI)net-works were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)11.5 and Cytoscape 3.9.1.Results Compared with sham group,DBND group showed significantly elevated leak point pressure(LPP)and maximum cystometric capacity(MCC)(both P<0.01).EA treatment sig-nificantly reduced both LPP and MCC compared with DBND group(P<0.01 and P<0.05,re-spectively).HE staining revealed that EA reduced detrusor fibrosis and improved bladder neck inflammation.TMT proteomics identified 30 overlapping DEPs in detrusor and 59 over-lapping DEPs in bladder neck when comparing DBND+EA/DBND groups with sham group.In detrusor tissue,KEGG analysis revealed 10 significantly enriched pathways(P<0.01),in-cluding mitogen-activated protein kinase(MAPK)signaling pathway.PPI analysis showed 22 of 30 DEPs were interconnected.In bladder neck tissue,14 pathways were significantly en-riched(P<0.01),including relaxin signaling pathway,with 51 of 59 DEPs showing intercon-nections.Both TMT and WB validations demonstrated that compared with sham controls,DBND rats exhibited upregulated collagen type IV alpha 2 chain(Col4a2)and downregulated guanine nucleotide-binding protein G(z)subunit alpha(Gnaz)in detrusor tissue,while EA treatment normalized both proteins(both P<0.05).In bladder neck tissue,DBND rats showed decreased expression of smoothelin(Smtn)and calcium-activated potassium chan-nel subunit beta-1(Kcnmb1)compared with sham controls(both P<0.01),which were both upregulated following EA treatment(P<0.01 and P<0.05,respectively).Conclusion EA restores detrusor-bladder neck coordination in DBND through dual-target mechanisms.In detrusor tissue,EA modulates contraction via extracellular matrix remodel-ing,cyclic adenosine monophosphate(cAMP)signaling pathway regulation,and enhanced adenosine triphosphate(ATP)biosynthesis mediated by neurotransmitters.In bladder neck tissue,EA promotes relaxation by maintaining contractile phenotypes,reducing fibrosis,sup-pressing smooth muscle excitation,and regulating presynaptic neurotransmitter release.These findings provide mechanistic insights into EA's therapeutic role in managing DBND.
