AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide...AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.展开更多
OBJECTIVE:To analyze the effect and molecular mechanism of Gehua Jiejiu Dizhi decoction(葛花解酒涤脂汤,GJDD)on alcoholic fatty live disease(AFLD)by using proteomic methods.METHODS:The male C57BL/6J mouse were randomly...OBJECTIVE:To analyze the effect and molecular mechanism of Gehua Jiejiu Dizhi decoction(葛花解酒涤脂汤,GJDD)on alcoholic fatty live disease(AFLD)by using proteomic methods.METHODS:The male C57BL/6J mouse were randomly divided into four groups:control group,model group,GJDD group and resveratrol group.After the AFLD model was successfully prepared by intragastric administration of alcohol once on the basis of the Lieber-DeCarli classical method,the GJDD group and resveratrol group were intragastrically administered with GJDD(4900 mg/kg)and resveratrol(400 mg/kg)respectively,once a day for 9 d.The fat deposition of liver tissue was observed and evaluated by oil red O(ORO)staining.4DLabel-free quantitative proteome method was used to determine and quantify the protein expression in liver tissue of each experimental group.The differentially expressed proteins were screened according to protein expression differential multiples,and then analyzed by Gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.Finally,expression validation of the differentially co-expressed proteins from control group,model group and GJDD group were verified by targeted proteomics quantification techniques.RESULTS:In semiquantitative analyses of ORO,all kinds of steatosis(ToS,MaS,and MiS)were evaluated higher in AFLD mice compared to those in GJDD or resveratroltreated mice.4DLabel-free proteomics analysis results showed that a total of 4513 proteins were identified,of which 3763 proteins were quantified and 946 differentially expressed proteins were screened.Compared with the control group,145 proteins were up-regulated and 148 proteins were down-regulated in the liver tissue of model group.In addition,compared with the model group,92 proteins were up-regulated and 135 proteins were downregulated in the liver tissue of the GJDD group.15 differentially co-expressed proteins were found between every two groups(model group vs control group,GJDD group vs model group and GJDD group vs control group),which were involved in many biological processes.Among them,11 differentially co-expressed key proteins(Aox3,H1-5,Fabp5,Ces3a,Nudt7,Serpinb1a,Fkbp11,Rpl22l1,Keg1,Acss2 and Slco1a1)were further identified by targeted proteomic quantitative technology and their expression patterns were consistent with the results of 4D label-free proteomic analysis.CONCLUSIONS:Our study provided proteomics-based evidence that GJDD alleviated AFLD by modulating liver protein expression,likely through the modulation of lipid metabolism,bile acid metabolism and with exertion of antioxidant stress.展开更多
Adenine is commonly used to establish the animal models for chronic kidney injury and its renal interstitial fibrosis. As an endogenous substance, adenine-induced kidney damage has not yet been fully studied and eluci...Adenine is commonly used to establish the animal models for chronic kidney injury and its renal interstitial fibrosis. As an endogenous substance, adenine-induced kidney damage has not yet been fully studied and elucidated, except for inflammatory reaction. Here we analyzed the proteomics of kidney of rats after adenine overloading using LS-MS/MS assay, and observed the role of anemoside B4(B4). The results showed that adenine could down-regulate 285 proteins and up-regulate 164 proteins in rat kidney tissue compared with the normal group. Down-regulated proteins mainly affected related pathways, such as energy metabolism, while up-regulated proteins affected inflammatory response pathways and metabolic pathways. B4 could significantly reverse the down-regulation of about 40 proteins, which were involved in mitochondria, redox processes, extracellular exosomes, acetylation and other signaling pathways. Simultaneously, B4 could inhibit the up-regulation of five proteins caused by adenine, which were involved in cell cycle, oocyte meiosis, PI3 K-Akt and other signaling pathways. Further experimental results of mRNA expression using real-time PCR assay supported the proteomic analysis. Therefore, we proposed that the damage of rat kidney caused by adenine was more complicated, not only with an inflammatory reaction, but also with extensive effects to various metabolic processes in the body. This work provided a valuable clue for comprehensive understanding of adenine-induced renal damage.展开更多
AIM:To identify metabolites,proteins,and related pathways involved in the etiology of rhegmatogenous retinal detachment(RRD)for use as biomarkers in diagnosing and treating RRD.METHODS:Vitreous specimens were collecte...AIM:To identify metabolites,proteins,and related pathways involved in the etiology of rhegmatogenous retinal detachment(RRD)for use as biomarkers in diagnosing and treating RRD.METHODS:Vitreous specimens were collected and liquid chromatography-tandem mass spectrometry analysis was per formed using the four-dimensional label-free technique.Statistically significant differentially expressed proteins,gene ontology(GO)terms,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representations,and protein interactions were analyzed.RESULTS:Nine specimens were subjected to proteomic analysis.In total,161 proteins were identified as differentially expressed proteins(DEPs),including 53 upregulated proteins and 108 downregulated proteins.GO functional analysis revealed that some DEPs were enriched in neuron-related terms and membrane protein terms.Moreover,KEGG analysis indicated that the cell adhesion molecule metabolic pathway was associated with the greatest number of DEPs.Finally,the evaluation of protein-protein interaction network revealed that DEPs were clustered in neuronal adhesion,apoptosis,inflammation and immune responses,correct protein folding,and glycolysis.CONCLUSION:Proteomic profiling is useful for the exploration of molecular mechanisms that underlie RRD.This study reveals increased expression levels of proteins related to heat shock protein content,glycolysis,and inflammatory responses in RRD.Knowledge regarding biomarkers of RRD pathogenesis may help to prevent the occurrence of RRD in the future.展开更多
Apis mellifera filamentous virus(Am FV)is a large DNA virus that is endemic in honeybee colonies.The genome sequence of the Am FV Swiss isolate(Am FV CH–C05)has been reported,but so far very few molecular studies hav...Apis mellifera filamentous virus(Am FV)is a large DNA virus that is endemic in honeybee colonies.The genome sequence of the Am FV Swiss isolate(Am FV CH–C05)has been reported,but so far very few molecular studies have been conducted on this virus.In this study,we isolated and purified Am FV(Am FV CN)from Chinese honeybee(Apis mellifera)colonies and elucidated its genomics and proteomics.Electron microscopy showed ovoid purified virions with dimensions of 300–500×210–285 nm,wrapping a 3165×40 nm filamentous nucleocapsid in three figure-eight loops.Unlike Am FV CH–C05,which was reported to have a circular genome,our data suggest that Am FV CN has a linear genome of approximately 493 kb.A total of 197 ORFs were identified,among which36 putative genes including 18 baculoviral homologs were annotated.The overall nucleotide similarity between the CN and CH–C05 isolates was 96.9%.Several ORFs were newly annotated in Am FV CN,including homologs of per os infectivity factor 4(PIF4)and a putative integrase.Phylogenomic analysis placed Am FVs on a separate branch within the newly proposed virus class Naldaviricetes.Proteomic analysis revealed 47 Am FV virionassociated proteins,of which 14 had over 50%sequence coverage,suggesting that they are likely to be main structural proteins.In addition,all six of the annotated PIFs(PIF-0–5)were identified by proteomics,suggesting that they may function as entry factors in Am FV infection.This study provides fundamental information regarding the molecular biology of Am FV.展开更多
AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.A...AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.After acteoside administration in DBA/2J mice,anterior segment observation,intraocular pressure(IOP)monitoring,electrophysiology examination,and hematoxylin and eosin staining were used to analyze any potential effects.Immunohistochemistry(IHC)assays were used to verify the proteomics results.Furthermore,retinal ganglion cell 5(RGC5)cell proliferation was assessed with cell counting kit-8(CCK-8)assays.Serta domain-containing protein 4(Sertad4)mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis,respectively.RESULTS:Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein.Compared with the saline group,the acteoside treatment group showed decreased IOP,improved N1-P1 wave amplitudes,thicker retina,and larger numbers of cells in the ganglion cell layer(GCL).The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group.Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury.CONCLUSION:Sertad4 is differentially expressed in DBA/2J mice.Acteoside can protect RGCs from damage,possibly through the downregulation of Sertad4,and has a potential use in glaucoma treatment.展开更多
In plants,heteromorphic self-incompatibility(HetSI)is a strategy for avoiding self-pollination and promoting outcrossing,and during this process,numerous protein-protein interaction events occur between the pistil and...In plants,heteromorphic self-incompatibility(HetSI)is a strategy for avoiding self-pollination and promoting outcrossing,and during this process,numerous protein-protein interaction events occur between the pistil and pollen.Previous studies in Primula and Fagopyrum that focused on HetSI systems have provided interesting insights;however,the molecular mechanism underlying HetSI remains largely unknown.In this study,we profiled the proteome of Plumbago auriculata stigmas before and after self-incompatible(SI)and self-compatible(SC)pollination.Comparative analyses were conducted by 4D-DIA(Four-dimensional data independent acquisition),a promising technology that increases the sensitivity and reduces the spectral complexity of proteomic analysis by adding a fourth dimension,ion mobility.The results revealed 33387 peptides and 5311 proteins in all samples.The pathways in which the differentially expressed proteins(DEPs)identified in the P×P(Pin style self-pollinated with pin pollen)vs.PS(Pin style)and T×T(Thrum style self-pollinated with thrum pollen)vs.TS(Thrum style)comparisons were significantly enriched were biosynthesis of secondary metabolites and pentose and glucuronate interconversions.In the P×T(Pin style cross-pollinated with thrum pollen)vs.PS and T×P(Thrum style cross-pollinated with pin pollen)vs.TS comparison,the top three pathways were biosynthesis of secondary metabolites,pentose and glucuronate interconversions,and phenylpropanoid biosynthesis.The phenylpropanoid biosynthesis,cutin,suberine and wax biosynthesis,and flavonoid biosynthesis pathways were enriched in the P×T vs.P×P comparison,and starch and sucrose metabolism,glycerophospholipid metabolism,and alpha-linolenic acid metabolism were abundant in the T×T vs.T×P comparison.The enriched pathways between PS and TS were the biosynthesis of secondary metabolites,phenylpropanoid biosynthesis,and pentose and glucuronate interconversion.Self-incompatibility protein S1(SI S1),Mitogen-activated protein kinase 3/4(MPK3/4),Mitogen-activated protein kinase kinase 2/3(M2K2/3),Exocyst complex component EXO70A1(E70A1)and Thioredoxin H1/2(TRXH1/2)were found to be HetSI-related candidates,and O-fucosyltransferase 23(OFT23),3-ketoacyl-CoA synthase 6(KCS6),Receptor-like protein kinase FERONIA(FERON),Fimbrin-5(FIMB5),Pollen-specific leucine-rich repeat extensin-like protein 4(PLRX4),Transcription initiation factor IIB-2(TF2B2)and Pectinesterase 1(AL11A),etc.,were identified as other regulatory transducers.These findings combined with our morphological and reactive oxygen species(ROS)intensity analyses indicate that P.auriculata has typical dry-stigmas and that the HetSI mechanism might differ between the pin and thrum.SI S1 might be the key factor in HetSI,and ROS are overexpressed during SC pollination to rapidly activate the mitogen-activated protein kinase(MAPK)-mediated phosphorylation of E70A1 to maintain stigma receptivity in plants with HetSI.展开更多
Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes ...Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes of diabetes classified by the international World Health Organization standards.Although GDM patients constitute a small proportion of the total number of diabetes cases,the incidence of GDM has risen significantly over the past decade,posing substantial risk to pregnant women and infants.Therefore,it warrants considerable attention.The pathogenesis of GDM is generally considered to resemble that of type II diabetes,though it may have distinct characteristics.Analyzing blood biochemical proteins in the context of GDM can help elucidate its pathogenesis,thereby facilitating more effective prevention and management strategies.This article reviews this critical clinical issue to enhance the medical community's sufficient understanding of GDM.展开更多
The study by Cao et al aimed to identify early second-trimester biomarkers that could predict gestational diabetes mellitus(GDM)development using advanced proteomic techniques,such as Isobaric tags for relative and ab...The study by Cao et al aimed to identify early second-trimester biomarkers that could predict gestational diabetes mellitus(GDM)development using advanced proteomic techniques,such as Isobaric tags for relative and absolute quantitation isobaric tags for relative and absolute quantitation and liquid chromatography-mass spectrometry liquid chromatography-mass spectrometry.Their analysis revealed 47 differentially expressed proteins in the GDM group,with retinol-binding protein 4 and angiopoietin-like 8 showing significantly elevated serum levels compared to controls.Although these findings are promising,the study is limited by its small sample size(n=4 per group)and lacks essential details on the reproducibility and reliability of the protein quantification methods used.Furthermore,the absence of experimental validation weakens the interpretation of the protein-protein interaction network identified through bioinformatics analysis.The study's focus on second-trimester biomarkers raises concerns about whether this is a sufficiently early period to implement preventive interventions for GDM.Predicting GDM risk during the first trimester or pre-conceptional period may offer more clinical relevance.Despite its limitations,the study presents valuable insights into potential GDM biomarkers,but larger,well-validated studies are needed to establish their predictive utility and generalizability.展开更多
基金Supported by Tianjin Key Medical Discipline Specialty Construction Project(No.TJYXZDXK-016A)Henan Provincial Department of Science and Technology(No.LHGJ20200802).
文摘AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.
基金National Science Foundation-funded Project:the Study on the Changes of Energy Metabolism and Molecular Regulation Mechanism of Alcoholic Fatty Liver based on Sirtuins1-Adenosine Monophosphate-Activated Protein Kinase Signal System and the Intervention of Gehua Jiejiu dizhi decoction(No.81660752)Basic Research Project of Guizhou Provincial Science and Technology Plan:Study on the Mechanism of Sirtuins1 Mediated Deacetylation in the Regulation of Alcoholic Fatty Liver Metabolism and the Intervention of Gehua Jiejiu Dizhi Tang[QianKeHe Fundamentals-ZK[2023]General 410]。
文摘OBJECTIVE:To analyze the effect and molecular mechanism of Gehua Jiejiu Dizhi decoction(葛花解酒涤脂汤,GJDD)on alcoholic fatty live disease(AFLD)by using proteomic methods.METHODS:The male C57BL/6J mouse were randomly divided into four groups:control group,model group,GJDD group and resveratrol group.After the AFLD model was successfully prepared by intragastric administration of alcohol once on the basis of the Lieber-DeCarli classical method,the GJDD group and resveratrol group were intragastrically administered with GJDD(4900 mg/kg)and resveratrol(400 mg/kg)respectively,once a day for 9 d.The fat deposition of liver tissue was observed and evaluated by oil red O(ORO)staining.4DLabel-free quantitative proteome method was used to determine and quantify the protein expression in liver tissue of each experimental group.The differentially expressed proteins were screened according to protein expression differential multiples,and then analyzed by Gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.Finally,expression validation of the differentially co-expressed proteins from control group,model group and GJDD group were verified by targeted proteomics quantification techniques.RESULTS:In semiquantitative analyses of ORO,all kinds of steatosis(ToS,MaS,and MiS)were evaluated higher in AFLD mice compared to those in GJDD or resveratroltreated mice.4DLabel-free proteomics analysis results showed that a total of 4513 proteins were identified,of which 3763 proteins were quantified and 946 differentially expressed proteins were screened.Compared with the control group,145 proteins were up-regulated and 148 proteins were down-regulated in the liver tissue of model group.In addition,compared with the model group,92 proteins were up-regulated and 135 proteins were downregulated in the liver tissue of the GJDD group.15 differentially co-expressed proteins were found between every two groups(model group vs control group,GJDD group vs model group and GJDD group vs control group),which were involved in many biological processes.Among them,11 differentially co-expressed key proteins(Aox3,H1-5,Fabp5,Ces3a,Nudt7,Serpinb1a,Fkbp11,Rpl22l1,Keg1,Acss2 and Slco1a1)were further identified by targeted proteomic quantitative technology and their expression patterns were consistent with the results of 4D label-free proteomic analysis.CONCLUSIONS:Our study provided proteomics-based evidence that GJDD alleviated AFLD by modulating liver protein expression,likely through the modulation of lipid metabolism,bile acid metabolism and with exertion of antioxidant stress.
基金National Innovative Drugs 13th Five-Year Major Special Project of China(Grant No.2018ZX09301030-002)
文摘Adenine is commonly used to establish the animal models for chronic kidney injury and its renal interstitial fibrosis. As an endogenous substance, adenine-induced kidney damage has not yet been fully studied and elucidated, except for inflammatory reaction. Here we analyzed the proteomics of kidney of rats after adenine overloading using LS-MS/MS assay, and observed the role of anemoside B4(B4). The results showed that adenine could down-regulate 285 proteins and up-regulate 164 proteins in rat kidney tissue compared with the normal group. Down-regulated proteins mainly affected related pathways, such as energy metabolism, while up-regulated proteins affected inflammatory response pathways and metabolic pathways. B4 could significantly reverse the down-regulation of about 40 proteins, which were involved in mitochondria, redox processes, extracellular exosomes, acetylation and other signaling pathways. Simultaneously, B4 could inhibit the up-regulation of five proteins caused by adenine, which were involved in cell cycle, oocyte meiosis, PI3 K-Akt and other signaling pathways. Further experimental results of mRNA expression using real-time PCR assay supported the proteomic analysis. Therefore, we proposed that the damage of rat kidney caused by adenine was more complicated, not only with an inflammatory reaction, but also with extensive effects to various metabolic processes in the body. This work provided a valuable clue for comprehensive understanding of adenine-induced renal damage.
文摘AIM:To identify metabolites,proteins,and related pathways involved in the etiology of rhegmatogenous retinal detachment(RRD)for use as biomarkers in diagnosing and treating RRD.METHODS:Vitreous specimens were collected and liquid chromatography-tandem mass spectrometry analysis was per formed using the four-dimensional label-free technique.Statistically significant differentially expressed proteins,gene ontology(GO)terms,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representations,and protein interactions were analyzed.RESULTS:Nine specimens were subjected to proteomic analysis.In total,161 proteins were identified as differentially expressed proteins(DEPs),including 53 upregulated proteins and 108 downregulated proteins.GO functional analysis revealed that some DEPs were enriched in neuron-related terms and membrane protein terms.Moreover,KEGG analysis indicated that the cell adhesion molecule metabolic pathway was associated with the greatest number of DEPs.Finally,the evaluation of protein-protein interaction network revealed that DEPs were clustered in neuronal adhesion,apoptosis,inflammation and immune responses,correct protein folding,and glycolysis.CONCLUSION:Proteomic profiling is useful for the exploration of molecular mechanisms that underlie RRD.This study reveals increased expression levels of proteins related to heat shock protein content,glycolysis,and inflammatory responses in RRD.Knowledge regarding biomarkers of RRD pathogenesis may help to prevent the occurrence of RRD in the future.
基金the Open Research Fund Program of the State Key Laboratory of Virology of China(Grant No.2019IOV004)the key Research Program of Frontier Sciences of Chinese Academy of Sciences(Grant No.QYZDJ-SSW-SMC021)the National Natural Science Foundation of China(Grant No.31900154 and 31572471)。
文摘Apis mellifera filamentous virus(Am FV)is a large DNA virus that is endemic in honeybee colonies.The genome sequence of the Am FV Swiss isolate(Am FV CH–C05)has been reported,but so far very few molecular studies have been conducted on this virus.In this study,we isolated and purified Am FV(Am FV CN)from Chinese honeybee(Apis mellifera)colonies and elucidated its genomics and proteomics.Electron microscopy showed ovoid purified virions with dimensions of 300–500×210–285 nm,wrapping a 3165×40 nm filamentous nucleocapsid in three figure-eight loops.Unlike Am FV CH–C05,which was reported to have a circular genome,our data suggest that Am FV CN has a linear genome of approximately 493 kb.A total of 197 ORFs were identified,among which36 putative genes including 18 baculoviral homologs were annotated.The overall nucleotide similarity between the CN and CH–C05 isolates was 96.9%.Several ORFs were newly annotated in Am FV CN,including homologs of per os infectivity factor 4(PIF4)and a putative integrase.Phylogenomic analysis placed Am FVs on a separate branch within the newly proposed virus class Naldaviricetes.Proteomic analysis revealed 47 Am FV virionassociated proteins,of which 14 had over 50%sequence coverage,suggesting that they are likely to be main structural proteins.In addition,all six of the annotated PIFs(PIF-0–5)were identified by proteomics,suggesting that they may function as entry factors in Am FV infection.This study provides fundamental information regarding the molecular biology of Am FV.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.After acteoside administration in DBA/2J mice,anterior segment observation,intraocular pressure(IOP)monitoring,electrophysiology examination,and hematoxylin and eosin staining were used to analyze any potential effects.Immunohistochemistry(IHC)assays were used to verify the proteomics results.Furthermore,retinal ganglion cell 5(RGC5)cell proliferation was assessed with cell counting kit-8(CCK-8)assays.Serta domain-containing protein 4(Sertad4)mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis,respectively.RESULTS:Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein.Compared with the saline group,the acteoside treatment group showed decreased IOP,improved N1-P1 wave amplitudes,thicker retina,and larger numbers of cells in the ganglion cell layer(GCL).The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group.Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury.CONCLUSION:Sertad4 is differentially expressed in DBA/2J mice.Acteoside can protect RGCs from damage,possibly through the downregulation of Sertad4,and has a potential use in glaucoma treatment.
基金Scientific Research Foundation of Science&Technology Department of Sichuan Province(2021YJ0497).
文摘In plants,heteromorphic self-incompatibility(HetSI)is a strategy for avoiding self-pollination and promoting outcrossing,and during this process,numerous protein-protein interaction events occur between the pistil and pollen.Previous studies in Primula and Fagopyrum that focused on HetSI systems have provided interesting insights;however,the molecular mechanism underlying HetSI remains largely unknown.In this study,we profiled the proteome of Plumbago auriculata stigmas before and after self-incompatible(SI)and self-compatible(SC)pollination.Comparative analyses were conducted by 4D-DIA(Four-dimensional data independent acquisition),a promising technology that increases the sensitivity and reduces the spectral complexity of proteomic analysis by adding a fourth dimension,ion mobility.The results revealed 33387 peptides and 5311 proteins in all samples.The pathways in which the differentially expressed proteins(DEPs)identified in the P×P(Pin style self-pollinated with pin pollen)vs.PS(Pin style)and T×T(Thrum style self-pollinated with thrum pollen)vs.TS(Thrum style)comparisons were significantly enriched were biosynthesis of secondary metabolites and pentose and glucuronate interconversions.In the P×T(Pin style cross-pollinated with thrum pollen)vs.PS and T×P(Thrum style cross-pollinated with pin pollen)vs.TS comparison,the top three pathways were biosynthesis of secondary metabolites,pentose and glucuronate interconversions,and phenylpropanoid biosynthesis.The phenylpropanoid biosynthesis,cutin,suberine and wax biosynthesis,and flavonoid biosynthesis pathways were enriched in the P×T vs.P×P comparison,and starch and sucrose metabolism,glycerophospholipid metabolism,and alpha-linolenic acid metabolism were abundant in the T×T vs.T×P comparison.The enriched pathways between PS and TS were the biosynthesis of secondary metabolites,phenylpropanoid biosynthesis,and pentose and glucuronate interconversion.Self-incompatibility protein S1(SI S1),Mitogen-activated protein kinase 3/4(MPK3/4),Mitogen-activated protein kinase kinase 2/3(M2K2/3),Exocyst complex component EXO70A1(E70A1)and Thioredoxin H1/2(TRXH1/2)were found to be HetSI-related candidates,and O-fucosyltransferase 23(OFT23),3-ketoacyl-CoA synthase 6(KCS6),Receptor-like protein kinase FERONIA(FERON),Fimbrin-5(FIMB5),Pollen-specific leucine-rich repeat extensin-like protein 4(PLRX4),Transcription initiation factor IIB-2(TF2B2)and Pectinesterase 1(AL11A),etc.,were identified as other regulatory transducers.These findings combined with our morphological and reactive oxygen species(ROS)intensity analyses indicate that P.auriculata has typical dry-stigmas and that the HetSI mechanism might differ between the pin and thrum.SI S1 might be the key factor in HetSI,and ROS are overexpressed during SC pollination to rapidly activate the mitogen-activated protein kinase(MAPK)-mediated phosphorylation of E70A1 to maintain stigma receptivity in plants with HetSI.
基金Supported by National Natural Science Foundation of China,No.32060182Qiannan Prefecture Science and Technology Plan Project in China:Qiannan Kehe She Zi[2022]No.1.
文摘Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes of diabetes classified by the international World Health Organization standards.Although GDM patients constitute a small proportion of the total number of diabetes cases,the incidence of GDM has risen significantly over the past decade,posing substantial risk to pregnant women and infants.Therefore,it warrants considerable attention.The pathogenesis of GDM is generally considered to resemble that of type II diabetes,though it may have distinct characteristics.Analyzing blood biochemical proteins in the context of GDM can help elucidate its pathogenesis,thereby facilitating more effective prevention and management strategies.This article reviews this critical clinical issue to enhance the medical community's sufficient understanding of GDM.
文摘The study by Cao et al aimed to identify early second-trimester biomarkers that could predict gestational diabetes mellitus(GDM)development using advanced proteomic techniques,such as Isobaric tags for relative and absolute quantitation isobaric tags for relative and absolute quantitation and liquid chromatography-mass spectrometry liquid chromatography-mass spectrometry.Their analysis revealed 47 differentially expressed proteins in the GDM group,with retinol-binding protein 4 and angiopoietin-like 8 showing significantly elevated serum levels compared to controls.Although these findings are promising,the study is limited by its small sample size(n=4 per group)and lacks essential details on the reproducibility and reliability of the protein quantification methods used.Furthermore,the absence of experimental validation weakens the interpretation of the protein-protein interaction network identified through bioinformatics analysis.The study's focus on second-trimester biomarkers raises concerns about whether this is a sufficiently early period to implement preventive interventions for GDM.Predicting GDM risk during the first trimester or pre-conceptional period may offer more clinical relevance.Despite its limitations,the study presents valuable insights into potential GDM biomarkers,but larger,well-validated studies are needed to establish their predictive utility and generalizability.
