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: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
Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(R...Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.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
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
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
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
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
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
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
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
Proteomics is one of the most active research fields in the post-genomic era. Here we briefly introduce the scientific background of the origination of proteomics and its content, research method. The new developments...Proteomics is one of the most active research fields in the post-genomic era. Here we briefly introduce the scientific background of the origination of proteomics and its content, research method. The new developments of proteomics at the levels of individual plants, tissues, organs and organells, as well as its applications in the area of plant genetic diversity, mutant characterization, and plant physiology, etc are reviewed. At last, the challenge and prospect of proteomics are discussed.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
Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immunoresponse and chemoresistance. Abnormal expression in sugar mo...Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immunoresponse and chemoresistance. Abnormal expression in sugar moieties can impact the function of various glycoproteins, including mucins, surface receptors, adhesive proteins, proteoglycans, as well as their effectors and binding ligands, resulting in an increase in pancreatic cancer invasiveness and a cancerfavored microenvironment. Recent advance in glycoproteomics, glycomics and other chemical biology techniques have been employed to better understand the complex mechanism of glycosylation events and how they orchestrate molecular activities in genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A variety of strategies have been demonstrated targeting protein glycosylation and polysaccharides for diagnostic and therapeutic development.展开更多
Urine has become one of the most attractive biofluids in clinical proteomics,for its procurement is easy and noninvasive and it contains sufficient proteins and peptides. Urinary proteomics has thus rapidly developed ...Urine has become one of the most attractive biofluids in clinical proteomics,for its procurement is easy and noninvasive and it contains sufficient proteins and peptides. Urinary proteomics has thus rapidly developed and has been extensively applied to biomarker discovery in clinical diseases,especially kidney diseases. In this review,we discuss two important aspects of urinary proteomics in detail,namely,sample preparation and proteomic tech-nologies. In addition,data mining in urinary proteomics is also briefly introduced. At last,we present several successful examples on the application of urinary proteomics for biomarker discovery in kidney diseases,including diabetic nephropathy,IgA nephropathy,lupus nephritis,renal Fanconi syndrome,acute kidney injury,and renal allograft rejection.展开更多
Fruit ripening has been reported to be related to calcium(Ca),but the underlying mechanisms by which Ca regulates this process remain largely unknown.In order to study the changes of proteins and enriched phosphopepti...Fruit ripening has been reported to be related to calcium(Ca),but the underlying mechanisms by which Ca regulates this process remain largely unknown.In order to study the changes of proteins and enriched phosphopeptides,we conducted TMT labeling,bio-material-based PTM enrichment based on mass spectrometry in Ca-treated‘Golden Delicious’(GD)apple fruit(Malus×domestica).This dataset presents a comprehensive overview of the critical pathways involved in fruit ripening.A total of 47 proteins and 124 phosphoproteins significantly changed in Ca-treated fruit,which are crucial for regulating the cell wall and cytoskeleton,Ca-mediated signaling and transport,ethylene production,protein fate,especially ubiquitination-based protein degradation,and primary and secondary metabolisms.Our results indicated that Ca inhibited the abundance of polygalacturonase(PG)activity and increased the phosphorylation level of CSLD3.PG and phosphorylation were involved in cell wall degradation,thereby delaying fruit softening.As a secondary messenger,Ca-mediated signaling subsequently triggered downstream mitogen-activated protein kinases(MAPK)cascades and activated the membrane,transport,and ROS signaling.Moreover,MdEIN2,a key enzyme involved in the ubiquitin of protein modification,increased at Ser753 and Ser758 in Ca-treated fruit.Furthermore,diverse primary and secondary metabolisms including glycolysis,fatty acid metabolism,and oxidation respiratory chain were modulated to prevent fruit softening.These results provide basic information from protein and phosphorylation levels for apple fruit ripening during storage,which may be helpful for apple fruit storage control.展开更多
Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is relatively underdeveloped b...Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is relatively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.展开更多
Objective: To find new potential biomarkers and establish the patterns for the detection of ovarian cancer. Methods: Sixty one serum samples including 32 ovarian cancer patients and 29 healthy people were detected by ...Objective: To find new potential biomarkers and establish the patterns for the detection of ovarian cancer. Methods: Sixty one serum samples including 32 ovarian cancer patients and 29 healthy people were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The protein fingerprint data were analyzed by bioinformatics tools. Ten folds cross-validation support vector machine (SVM) was used to establish the diagnostic pattern. Results: Five potential bio- markers were found (2085 Da, 5881 Da, 7564 Da, 9422 Da, 6044 Da), combined with which the diagnostic pattern separated the ovarian cancer from the healthy samples with a sensitivity of 96.7%, a specificity of 96.7% and a positive predictive value of 96.7%. Conclusions: The combination of SELDI with bioinformatics tools could find new biomarkers and establish patterns with high sensitivity and specificity for the detection of ovarian cancer.展开更多
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 grants from the National Key Research and Development Program of China(2019YFA0802704)the National Natural Science Foundation of China(31771620)+2 种基金the Natural Science Foundation of Chongqing,China(CSTB2022NSCQMSX1424)Research Startup Fund of Southwest University(SWU117064)Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention&Henan Key Laboratory of Population Defects Prevention(ZD202302)。
文摘Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.
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.
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 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.
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(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.
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.
文摘Proteomics is one of the most active research fields in the post-genomic era. Here we briefly introduce the scientific background of the origination of proteomics and its content, research method. The new developments of proteomics at the levels of individual plants, tissues, organs and organells, as well as its applications in the area of plant genetic diversity, mutant characterization, and plant physiology, etc are reviewed. At last, the challenge and prospect of proteomics are discussed.
基金supported by the National Key Research and Development Project of China(Grant No.2021YFF1201300 and 2021YFF1201302)the Shanghai Committee of Science and Technology(Grant No.24DX2800100)the Institutional Projects of SIBPT(Grant No.YZ2024-07)。
文摘Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center(FUSCC)for sequential high-precision proteomic profiling.Results:ARG1,NOS3,and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC.Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment.Furthermore,the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.Conclusions:The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.
文摘Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immunoresponse and chemoresistance. Abnormal expression in sugar moieties can impact the function of various glycoproteins, including mucins, surface receptors, adhesive proteins, proteoglycans, as well as their effectors and binding ligands, resulting in an increase in pancreatic cancer invasiveness and a cancerfavored microenvironment. Recent advance in glycoproteomics, glycomics and other chemical biology techniques have been employed to better understand the complex mechanism of glycosylation events and how they orchestrate molecular activities in genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A variety of strategies have been demonstrated targeting protein glycosylation and polysaccharides for diagnostic and therapeutic development.
基金Project supported by the National Natural Science Foundation of China (No. 30500598)the Medical Health Science Research Foundation of Zhejiang Province, China (No. 2007B102)
文摘Urine has become one of the most attractive biofluids in clinical proteomics,for its procurement is easy and noninvasive and it contains sufficient proteins and peptides. Urinary proteomics has thus rapidly developed and has been extensively applied to biomarker discovery in clinical diseases,especially kidney diseases. In this review,we discuss two important aspects of urinary proteomics in detail,namely,sample preparation and proteomic tech-nologies. In addition,data mining in urinary proteomics is also briefly introduced. At last,we present several successful examples on the application of urinary proteomics for biomarker discovery in kidney diseases,including diabetic nephropathy,IgA nephropathy,lupus nephritis,renal Fanconi syndrome,acute kidney injury,and renal allograft rejection.
基金supported by the National Natural Science Foundation of China (Grant Nos. 31722047, 31801848)LiaoNing Revitalization Talents Program (Grant No. XLYC1802019)
文摘Fruit ripening has been reported to be related to calcium(Ca),but the underlying mechanisms by which Ca regulates this process remain largely unknown.In order to study the changes of proteins and enriched phosphopeptides,we conducted TMT labeling,bio-material-based PTM enrichment based on mass spectrometry in Ca-treated‘Golden Delicious’(GD)apple fruit(Malus×domestica).This dataset presents a comprehensive overview of the critical pathways involved in fruit ripening.A total of 47 proteins and 124 phosphoproteins significantly changed in Ca-treated fruit,which are crucial for regulating the cell wall and cytoskeleton,Ca-mediated signaling and transport,ethylene production,protein fate,especially ubiquitination-based protein degradation,and primary and secondary metabolisms.Our results indicated that Ca inhibited the abundance of polygalacturonase(PG)activity and increased the phosphorylation level of CSLD3.PG and phosphorylation were involved in cell wall degradation,thereby delaying fruit softening.As a secondary messenger,Ca-mediated signaling subsequently triggered downstream mitogen-activated protein kinases(MAPK)cascades and activated the membrane,transport,and ROS signaling.Moreover,MdEIN2,a key enzyme involved in the ubiquitin of protein modification,increased at Ser753 and Ser758 in Ca-treated fruit.Furthermore,diverse primary and secondary metabolisms including glycolysis,fatty acid metabolism,and oxidation respiratory chain were modulated to prevent fruit softening.These results provide basic information from protein and phosphorylation levels for apple fruit ripening during storage,which may be helpful for apple fruit storage control.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant Nos.:82030099,30700397 Detail)the National Key R&D Program of China(Grant No.:2022YFD2101500)+5 种基金the Science and Technology Commission of Shanghai Municipality,China(Grant No.:22DZ2303000)the Shanghai Municipal Science and Technology Commission“Science and Technology Innovation Action Plan”Technical Standard Project,China(Grant No.:21DZ2201700)the Shanghai Municipal Science and Technology Commission“Science and Technology Innovation Action Plan”Natural Science Foundation Project,China(Grant No.:23ZR1435800)the Strategic Priority Research Program of the Chinese Academy of Sciences,China(Grant No.:XDB32060000)the Basic Frontier Scientific Research Program of Chinese Academy of Sciences(Grant No.:ZDBS-LY-SM019)the Yangfan Project of Shanghai Science and Technology Commission,China(Grant No.:22YF1454100),and the Innovative Research Team of High-level Local Universities in Shanghai,China.
文摘Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is relatively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.
基金Project (No. G1998051200) supported by the National Basic Research Program (973) of China
文摘Objective: To find new potential biomarkers and establish the patterns for the detection of ovarian cancer. Methods: Sixty one serum samples including 32 ovarian cancer patients and 29 healthy people were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The protein fingerprint data were analyzed by bioinformatics tools. Ten folds cross-validation support vector machine (SVM) was used to establish the diagnostic pattern. Results: Five potential bio- markers were found (2085 Da, 5881 Da, 7564 Da, 9422 Da, 6044 Da), combined with which the diagnostic pattern separated the ovarian cancer from the healthy samples with a sensitivity of 96.7%, a specificity of 96.7% and a positive predictive value of 96.7%. Conclusions: The combination of SELDI with bioinformatics tools could find new biomarkers and establish patterns with high sensitivity and specificity for the detection of ovarian cancer.
