Background:University students’ego-identity,an essential component of their psychological development and mental health,has widely attracted the attention of policymakers,schools,and parents.Method:A total of 298 Chi...Background:University students’ego-identity,an essential component of their psychological development and mental health,has widely attracted the attention of policymakers,schools,and parents.Method:A total of 298 Chinese vocational pathway undergraduates were recruited,and a conditional process analysis model was adopted to explore the interaction mechanism of ego-identity.Results:The results suggest that the ego-identity of Chinese vocational pathway undergraduates is significantly affected by interaction anxiousness,academic resilience,and cultural intelligence.(1)Interaction anxiousness significantly and positively predicts ego-identity.(2)Academic resilience positively and partially mediates the effect of interaction anxiousness on ego-identity.(3)Cultural intelligence significantly and positively moderates the relationship between interaction anxiousness and ego-identity.However,a similar moderating effect was not found between interaction anxiousness and academic resilience.(4)As cultural intelligence increases,the negative influence of interaction anxiousness on ego-identity gradually diminishes,whatever the cultural intelligence level.Conclusions:Interaction anxiousness,academic resilience,and cultural intelligence are essential determinants of ego-identity among Chinese vocational pathway undergraduates.Strategic interventions should be utilized to enhance their abilities to alleviate interpersonal tensions,promote their resilience in facing academic difficulties,cope with diverse cultures,and boost their sense of self-confirmation.展开更多
Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the ne...Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the network.Methods:In this research,the PNH and AA-related genes were screened through Online Mendelian Inheritance in Man(OMIM).The plugins and Cytoscape were used to search literature and build a protein-protein interaction network.Results:The protein-protein interaction network contains two molecular complexes that are five higher than the correlation integral values.The target genes of this study were obtained:CD59,STAT3,TERC,TNF,AKT1,C5AR1,EPO,IL6,IL10 and so on.We also found that many factors regulate biological behaviors:neutrophils,macrophages,vascular endothelial growth factor,immunoglobulin,interleukin,cytokine receptor,interleukin-6 receptor,tumor necrosis factor,and so on.This research provides a bioinformatics foundation for further explaining the mechanism of common development of both.Conclusion:This indicates that the PNH and AA is a complex process regulated by many cellular pathways and multiple genes.展开更多
Background:Accumulating data have suggested that long non-coding RNAs(lncRNAs)play important roles in regulating tumor cell growth.This study was designed to investigate the role of SNHG16 in hep-atocellular carcinoma...Background:Accumulating data have suggested that long non-coding RNAs(lncRNAs)play important roles in regulating tumor cell growth.This study was designed to investigate the role of SNHG16 in hep-atocellular carcinoma(HCC).Methods:SNHG16 expression was detected with real-time polymerase chain reaction(PCR).The cut-offvalue of SNHG16 for tumor-free survival(TFS)was determined with receiver operating characteristic curve analysis.Small interfering RNA was used to inhibit the expression of SNHG16 in HCC cell lines.The biologic behavior of HCC cell was determined with cell viability assay and Transwell assay in vitro.The potential predictive value of SNHG16 on prognosis was analyzed by Kaplan-Meier curves and Cox proportional hazards regression model.Results:SNHG16 expression was upregulated in tumor tissues and HCC cell lines.High expression of SNHG16 was associated with tumor recurrence and poor prognosis after surgery.Multivariate analysis revealed that SNHG16 was an independent prognostic factor for poor recurrence-free survival.Moreover,inhibition of SNHG16 in HepG2,Hep3B,and BEL-7402 cells significantly reduced cell invasiveness and proliferation.Mechanistic analyses indicated that the ECM-receptor interaction pathway was remarkably activated by SNHG16.Conclusions:SNHG16 might be a promising biomarker for predicting tumor recurrence in HCC patients after surgery and a potential therapeutic target for HCC.展开更多
To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (...To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.展开更多
Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanism...Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanisms.Methods:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in epilepsy.Through differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub genes.Results:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated genes.Enrichment analysis underscored significant alterations in immune pathways in epilepsy.Two central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and inflammation.Subsequent experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic target.Conclusion:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune system.These findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.展开更多
AIM:To understand the complex reaction of gastric inflammation induced by Helicobacter pylori(H pylori) in a systematic manner using a protein interaction network. METHODS:The expression of genes significantly changed...AIM:To understand the complex reaction of gastric inflammation induced by Helicobacter pylori(H pylori) in a systematic manner using a protein interaction network. METHODS:The expression of genes significantly changed on microarray during H pylori infection was scanned from the web literary database and translated into proteins.A network of protein interactions was constructed by searching the primary interactions of selected proteins.The constructed network was mathematically analyzed and its biological function was examined.In addition,the nodes on the network were checked to determine if they had any further functional importance or relation to other proteins by extending them. RESULTS:The scale-free network showing the relationship between inflammation and carcinogenesis was constructed.Mathematical analysis showed hub and bottleneck proteins,and these proteins were mostly related to immune response.The network contained pathways and proteins related to H pylori infection,such as the JAK-STAT pathway triggered by interleukins.Activation of nuclear factor (NF)-κB,TLR4,and other proteins known to function as core proteins of immune response were also found. These immune-related proteins interacted on the network with pathways and proteins related to the cell cycle,cell maintenance and proliferation,andtranscription regulators such as BRCA1,FOS,REL,and zinc finger proteins.The extension of nodes showed interactions of the immune proteins with cancer- related proteins.One extended network,the core network,a summarized form of the extended network, and cell pathway model were constructed. CONCLUSION:Immune-related proteins activated by H pylori infection interact with proto-oncogene proteins.The hub and bottleneck proteins are potential drug targets for gastric inflammation and cancer.展开更多
AIM: To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiv...AIM: To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiving mechanism of HBV infection.METHODS: The knowledge of HBV infection-related reactions was organized into various kinds of pathways with carefully drawn graphs in HBVPathDB. Pathway information is stored with relational database management system (DBMS), which is currently the most efficient way to manage large amounts of data and query is implemented with powerful Structured Query Language (SQL). The search engine is written using Personal Home Page (PHP) with SQL embedded and web retrieval interface is developed for searching with Hypertext Markup Language (HTML).RESULTS: We present the first version of HBVPathDB,which is a HBV infection-related molecular interaction network database composed of 306 pathways with 1050molecules involved. With carefully drawn graphs, pathway information stored in HBVPathDB can be browsed in an intuitive way. We develop an easy-to-use interface for flexible accesses to the details of database. Convenient software is implemented to query and browse the pathway information of HBVPathDB. Four search page layout options-category search, gene search, description search,unitized search-are supported by the search engine ofthe database. The database is freely available at http://www.bio-inf, net/HBVPathDB/HBV/.CONCLUSION: The conventional perspective HBVPathDB have already contained a considerable amount of pathway information with HBV infection related, which is suitable for in-depth analysis of molecular interaction network of virus and host. HBVPathDB integrates pathway data-sets with convenient software for query, browsing,visualization, that provides users more opportunity to identify regulatory key molecules as potential drug targets and to explore the possible mechanism of HBV infection based on gene expression datasets.展开更多
Almost all the cellular processes in a living system are controlled by proteins:They regulate gene expression,catalyze chemical reactions,transport small molecules across membranes,and transmit signal across membranes...Almost all the cellular processes in a living system are controlled by proteins:They regulate gene expression,catalyze chemical reactions,transport small molecules across membranes,and transmit signal across membranes.Even,a viral infection is often initiated through virus-host protein interactions.Protein-protein interactions(PPIs)are the physical contacts between two or more proteins and they represent complex biological functions.Nowadays,PPIs have been used to construct PPI networks to study complex pathways for revealing the functions of unknown proteins.Scientists have used PPIs to find the molecular basis of certain diseases and also some potential drug targets.In this review,we will discuss how PPI networks are essential to understand the molecular basis of virus-host relationships and several databases which are dedicated to virus-host interaction studies.Here,we present a short but comprehensive review on PPIs,including the experimental and computational methods of finding PPIs,the databases dedicated to virus-host PPIs,and the associated various applications in protein interaction networks of some lethal viruses with their hosts.展开更多
Female adults of the migratory locust,Locusta migratoria manilensis(Meyen),can sense seasonal photoperiod changes,which induces embryonic diapause as a key strategy to overwinter.Serine protease inhibitor genes(SPNs)w...Female adults of the migratory locust,Locusta migratoria manilensis(Meyen),can sense seasonal photoperiod changes,which induces embryonic diapause as a key strategy to overwinter.Serine protease inhibitor genes(SPNs)were thought to play key roles during diapause,while few SPNs were functionally characterized.LmSPN2 was one of those genes differentially expressed between diapause and non-diapause eggs;however,its biological function remained to be explored.So,we conducted RNAi knockdown of LmSPN2,resulting in a significant decrease of the egg diapause rate by 29.7%.Using yeast two-hybrid assays,co-immunoprecipitation,and pull-down methods,we found an interaction between LmSPN2 and LmSPN3,which was proved to be mediated by a glutamate(E331)binding site of LmSPN2.RNAi knockdown of LmSPN3 resulted in a significant increase in diapause rate by 14.6%,indicating an inverse function of LmSPN2 and LmSPN3 on diapause regulation.Double knockdown of two SPN genes resulted in a 26.4%reduction in diapause rate,indicating that LmSPN2 was the dominant regulatory signal.Moreover,we found four Toll pathway genes(easter,spätzle,pelle,and dorsal)upregulated significantly after the knockdown of LmSPN2 while downregulated after the knockdown of LmSPN3.Therefore,we speculate that two SPNs regulate diapause through the Toll pathway.Our results indicated that LmSPN2 positively regulates locust egg entry into diapause,while LmSPN3 is a negative regulator of embryonic commitment to diapause.Their interaction is mediated by the binding site of E331 and influences egg diapause through the Toll pathway.This mechanistic understanding of diapause regulation expands our understanding of insect developmental regulation and provides functional targets for developing locust management strategies.展开更多
Scurs is a horn phenotype that exhibits as small corneous structures on the skull due to the deformed development of horn tissues. Previous genome-wide association analysis of scurs in Soay sheep showed a significant ...Scurs is a horn phenotype that exhibits as small corneous structures on the skull due to the deformed development of horn tissues. Previous genome-wide association analysis of scurs in Soay sheep showed a significant association to the polled locus, relaxin-like receptor 2(RXFP2). However, the molecular mechanism underlying the development of scurs remains largely unknown. In the present study, we performed an i TRAQ-based quantitative proteomic analysis of horn tissues from both scurs and normal two-horned and four-horned individuals among Altay sheep to identify the differentially expressed proteins(DEPs) responsible for the scurs phenotype. In total, 232 proteins showed significant differential expression, and the most significant Gene ontology categories were the adhesion processes(biological adhesion(P=4.07×10–17) and cell adhesion(P=3.7×10–16)), multicellular organismal process(single-multicellular organism process(P=2.06×10–11) and multicellular organismal process(P=2.29×10–11)) and extracellular processes(extracellular matrix organization(P=4.77×10–16) and extracellular structure organization(P=4.93×10–16)). Kyoto encyclopedia of genes and genomes(KEGG) analysis showed that extracellular matrix(ECM)-receptor interactions and focal adhesion pathways were the most significant pathways. This finding is consistent with the reduced formation of extracellular matrix in scurs and the development of deformed horn tissues. Our study helps to elucidate the inheritance pattern of sheep horn traits from the perspectives of downstream expressed proteins.展开更多
Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools...Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.展开更多
Recent transcription profiling studies have revealed an unexpectedly large proportion of antisense transcripts in eukaryotic genomes. These antisense genes seem to regulate gene expression by interacting with sense ge...Recent transcription profiling studies have revealed an unexpectedly large proportion of antisense transcripts in eukaryotic genomes. These antisense genes seem to regulate gene expression by interacting with sense genes. Previ- ous studies have focused on the non-coding antisense genes, but the possible regulatory role of the antisense protein is poorly understood. In this study, we found that a protein encoded by the antisense gene ADF1 acts as a transcription suppressor, regulating the expression of sense gene MDF1 in Saccharomyces cerevisiae. Based on the evolutionary, ge- netic, cytological and biochemical evidence, we show that the protein-coding sense gene MDF1 most likely originated de novo from a previously non-coding sequence and can significantly suppress the mating efficiency of baker's yeast in rich medium by binding MATa2 and thus promote vegetative growth. These results shed new light on several im- portant issues, including a new sense-antisense interaction mechanism, the de novo origination of a functional gene, and the regulation of yeast mating pathway.展开更多
Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord ...Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.展开更多
Objective: The objective of this work is to search for a novel method to explore the disrupted pathways associated with periodontitis(PD) based on the network level.Methods: Firstly, the differential expression genes(...Objective: The objective of this work is to search for a novel method to explore the disrupted pathways associated with periodontitis(PD) based on the network level.Methods: Firstly, the differential expression genes(DEGs) between PD patients and cognitively normal subjects were inferred based on LIMMA package. Then, the proteinprotein interactions(PPI) in each pathway were explored by Empirical Bayesian(EB) coexpression program. Specifically, we determined the 100 th weight value as the threshold value of the disrupted pathways of PPI by constructing the randomly model and confirmed the weight value of each pathway. Meanwhile, we dissected the disrupted pathways under the weight value > the threshold value. Pathways enrichment analyses of DEGs were carried out based on Expression Analysis Systematic Explored(EASE) test. Finally, the better method was selected based on the more rich and significant obtained pathways by comparing the two methods. Results: After the calculation of LIMMA package, we estimated 524 DEGs in all. Then we determined 0.115222 as the threshold value of the disrupted pathways of PPI. When the weight value>0.115222, there were 258 disrupted pathways of PPI enriched in. Additionally, we observed those 524 DEGs that were enriched in 4 pathways under EASE=0.1.Conclusion: We proposed a novel network method inferring the disrupted pathway for PD. The disrupted pathways might be underlying biomarkers for treatment associated with PD.展开更多
Influenza virus contains three integral membrane proteins:haemagglutinin,neuraminidase,and matrix protein(M1 and M2).Among them,M2 protein functions as an ion channel,important for virus uncoating in endosomes of viru...Influenza virus contains three integral membrane proteins:haemagglutinin,neuraminidase,and matrix protein(M1 and M2).Among them,M2 protein functions as an ion channel,important for virus uncoating in endosomes of virus-infected cells and essential for virus replication.In an effort to explore potential new functions of M2 in the virus life cycle,we used yeast two-hybrid system to search for M2-associated cellular proteins.One of the positive clones was identified as human Hsp40/Hdj1,a DnaJ/Hsp40 family protein.Here,we report that both BM2(M2 of influenza B virus)and A/M2(M2 of influenza A virus)interacted with Hsp40 in vitro and in vivo.The region of M2-Hsp40 interaction has been mapped to the CTD1 domain of Hsp40.Hsp40 has been reported to be a regulator of PKR signaling pathway by interacting with p58^(IPK) that is a cellular inhibitor of PKR.PKR is a crucial component of the host defense response against virus infection.We therefore attempted to understand the relationship among M2,Hsp40 and p58^(IPK) by further experimentation.The results demonstrated that both A/M2 and BM2 are able to bind to p58^(IPK)in vitro and in vivo and enhance PKR autophosphorylation probably via forming a stable complex with Hsp40 and P58^(IPK),and consequently induce cell death.These results suggest that influenza virus M2 protein is involved in p58^(IPK)mediated PKR regulation during influenza virus infection,therefore affecting infected-cell life cycle and virus replication.展开更多
Integration of pathway and protein-protein interaction(PPI) data can provide more information that could lead to new biological insights. PPIs are usually represented by a simple binary model, whereas pathways are rep...Integration of pathway and protein-protein interaction(PPI) data can provide more information that could lead to new biological insights. PPIs are usually represented by a simple binary model, whereas pathways are represented by more complicated models. We developed a series of rules for transforming protein interactions from pathway to binary model, and the protein interactions from seven pathway databases, including PID, Bio Carta, Reactome, Net Path, INOH, SPIKE and KEGG, were transformed based on these rules. These pathway-derived binary protein interactions were integrated with PPIs from other five PPI databases including HPRD, Int Act, Bio GRID, MINT and DIP, to develop integrated dataset(named Path PPI). More detailed interaction type and modification information on protein interactions can be preserved in Path PPI than other existing datasets. Comparison analysis results indicate that most of the interaction overlaps values(OAB) among these pathway databases were less than 5%, and these databases must be used conjunctively. The Path PPI data was provided at http://proteomeview. hupo.org.cn/Path PPI/Path PPI.html.展开更多
Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies....Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.展开更多
Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.H...Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.Here,we identified UAT-B,a novel neoantimycin analog isolated from Streptomyces conglobatus,as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction(PPI)to overcome multi-drug resistance in colorectal cancer(CRC).The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels,triggering cell apoptosis through modulation of the Wnt/β-catenin pathway.Importantly,UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels,as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts,as well as APC^(min/+)spontaneous CRC models.Collectively,these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment,and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.展开更多
Wheat(Triticum aestivum L.) is one of the three major global food crops. Hightemperature stress can affect its yield and quality. Studies of the effect of hightemperature stress on wheat kernel development are importa...Wheat(Triticum aestivum L.) is one of the three major global food crops. Hightemperature stress can affect its yield and quality. Studies of the effect of hightemperature stress on wheat kernel development are important because they can reveal the stability of wheat quality and lead to the genetic improvement of wheat quality traits. In this study, the isobaric tags for relative and absolute quantitation(iTRAQ)method was adopted to analyze changes in the protein expression profile of wheat cultivars under high temperature stress. The protein content of wheat grain increased under heat stress, while the SDS-sedimentation value and starch content decreased.Grain filling was deficient under high temperature stress, which reduced thousandkernel weight but did not affect wheat kernel length. The 207 differentially expressed proteins identified in Gaocheng 8901 under heat stress were associated with energy metabolism, growth and development, and stress response. Gene Ontology enrichment analysis showed that the annotated proteins that were differentially expressed in Gaocheng 8901 under heat stress were involved mainly in stimulus response, abiotic stress response, stress response, and plasma membrane. A set of 78 differentially expressed proteins were assigned to 83 KEGG signaling/metabolic pathways. KEGG pathway enrichment analysis showed that this set of proteins was significantly enriched in members of 51 pathways, and the proteins participated mainly in protein synthesis in the endoplasmic reticulum, starch and sucrose metabolism, and reaction on ribosomes. Five differentially expressed proteins were involved in protein–protein interaction networks that may greatly influence the yield and quality of wheat grain. In wheat, high-temperature stress leads to a variety of effects on protein expression and may ultimately cause changes in yield and quality.展开更多
Bone morphogenetic proteins(BMPs)are a family of potent,multifunctional growth factors belonging to transforming growth factor-(TGF-).They are highly conservative in structures.Over 20 members of BMPs with varying fun...Bone morphogenetic proteins(BMPs)are a family of potent,multifunctional growth factors belonging to transforming growth factor-(TGF-).They are highly conservative in structures.Over 20 members of BMPs with varying functions such as embryogenesis,skeletal formation,hematopoiesis and neurogenesis have been identified in human body.BMPs are unique growth factors that can induce the formation of bone tissue individually.BMPs can induce the differentiation of bone marrow mesenchymal stem cells into osteoblastic lineage and promote the proliferation of osteoblasts and chondrocytes.BMPs stimulate the target cells by specific membrane-bound receptors and signal transduced through mothers against decapentaplegic(Smads)and mitogen activated protein kinase(MAPK)pathways.It has been demonstrated that BMP-2,BMP-4,BMP-6,BMP-7,and BMP-9 play an important role in bone formation.This article focuses on the molecular characterization of BMPs family members,mechanism of osteogenesis promotion,related signal pathways of osteogenic function,relationships between structure and osteogenetic activity,and the interactions among family members at bone formation.展开更多
基金the South China Normal University Teaching Reform Program(Grant No.2021263)the South China Normal University Teaching Reform Program(Grant No.2022240)the Postgraduate Innovative Research Program of the School of Education at South China Normal University(Grant No.20220309).
文摘Background:University students’ego-identity,an essential component of their psychological development and mental health,has widely attracted the attention of policymakers,schools,and parents.Method:A total of 298 Chinese vocational pathway undergraduates were recruited,and a conditional process analysis model was adopted to explore the interaction mechanism of ego-identity.Results:The results suggest that the ego-identity of Chinese vocational pathway undergraduates is significantly affected by interaction anxiousness,academic resilience,and cultural intelligence.(1)Interaction anxiousness significantly and positively predicts ego-identity.(2)Academic resilience positively and partially mediates the effect of interaction anxiousness on ego-identity.(3)Cultural intelligence significantly and positively moderates the relationship between interaction anxiousness and ego-identity.However,a similar moderating effect was not found between interaction anxiousness and academic resilience.(4)As cultural intelligence increases,the negative influence of interaction anxiousness on ego-identity gradually diminishes,whatever the cultural intelligence level.Conclusions:Interaction anxiousness,academic resilience,and cultural intelligence are essential determinants of ego-identity among Chinese vocational pathway undergraduates.Strategic interventions should be utilized to enhance their abilities to alleviate interpersonal tensions,promote their resilience in facing academic difficulties,cope with diverse cultures,and boost their sense of self-confirmation.
文摘Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the network.Methods:In this research,the PNH and AA-related genes were screened through Online Mendelian Inheritance in Man(OMIM).The plugins and Cytoscape were used to search literature and build a protein-protein interaction network.Results:The protein-protein interaction network contains two molecular complexes that are five higher than the correlation integral values.The target genes of this study were obtained:CD59,STAT3,TERC,TNF,AKT1,C5AR1,EPO,IL6,IL10 and so on.We also found that many factors regulate biological behaviors:neutrophils,macrophages,vascular endothelial growth factor,immunoglobulin,interleukin,cytokine receptor,interleukin-6 receptor,tumor necrosis factor,and so on.This research provides a bioinformatics foundation for further explaining the mechanism of common development of both.Conclusion:This indicates that the PNH and AA is a complex process regulated by many cellular pathways and multiple genes.
基金supported by grants from Science and Tech-nology Projects of Medicine and Health in Zhejiang Province(2020383364)Natural Science Foundation of Zhejiang Province(LY21H160055).
文摘Background:Accumulating data have suggested that long non-coding RNAs(lncRNAs)play important roles in regulating tumor cell growth.This study was designed to investigate the role of SNHG16 in hep-atocellular carcinoma(HCC).Methods:SNHG16 expression was detected with real-time polymerase chain reaction(PCR).The cut-offvalue of SNHG16 for tumor-free survival(TFS)was determined with receiver operating characteristic curve analysis.Small interfering RNA was used to inhibit the expression of SNHG16 in HCC cell lines.The biologic behavior of HCC cell was determined with cell viability assay and Transwell assay in vitro.The potential predictive value of SNHG16 on prognosis was analyzed by Kaplan-Meier curves and Cox proportional hazards regression model.Results:SNHG16 expression was upregulated in tumor tissues and HCC cell lines.High expression of SNHG16 was associated with tumor recurrence and poor prognosis after surgery.Multivariate analysis revealed that SNHG16 was an independent prognostic factor for poor recurrence-free survival.Moreover,inhibition of SNHG16 in HepG2,Hep3B,and BEL-7402 cells significantly reduced cell invasiveness and proliferation.Mechanistic analyses indicated that the ECM-receptor interaction pathway was remarkably activated by SNHG16.Conclusions:SNHG16 might be a promising biomarker for predicting tumor recurrence in HCC patients after surgery and a potential therapeutic target for HCC.
基金Supported by a Children Miracle Network Research Grant,No.132698 to Lin Z(P.I.)and Thomas NJ(Co-P.I.)(2011-2013)and Floros J(P.I.)(2013-2014)
文摘To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.
基金supported by the Ningxia Natural Science Foundation(Grant No.2022AAC03741)the Ningxia Medical University Scientific Research Fund(Grant No.XZ2021025).
文摘Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanisms.Methods:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in epilepsy.Through differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub genes.Results:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated genes.Enrichment analysis underscored significant alterations in immune pathways in epilepsy.Two central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and inflammation.Subsequent experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic target.Conclusion:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune system.These findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.
文摘AIM:To understand the complex reaction of gastric inflammation induced by Helicobacter pylori(H pylori) in a systematic manner using a protein interaction network. METHODS:The expression of genes significantly changed on microarray during H pylori infection was scanned from the web literary database and translated into proteins.A network of protein interactions was constructed by searching the primary interactions of selected proteins.The constructed network was mathematically analyzed and its biological function was examined.In addition,the nodes on the network were checked to determine if they had any further functional importance or relation to other proteins by extending them. RESULTS:The scale-free network showing the relationship between inflammation and carcinogenesis was constructed.Mathematical analysis showed hub and bottleneck proteins,and these proteins were mostly related to immune response.The network contained pathways and proteins related to H pylori infection,such as the JAK-STAT pathway triggered by interleukins.Activation of nuclear factor (NF)-κB,TLR4,and other proteins known to function as core proteins of immune response were also found. These immune-related proteins interacted on the network with pathways and proteins related to the cell cycle,cell maintenance and proliferation,andtranscription regulators such as BRCA1,FOS,REL,and zinc finger proteins.The extension of nodes showed interactions of the immune proteins with cancer- related proteins.One extended network,the core network,a summarized form of the extended network, and cell pathway model were constructed. CONCLUSION:Immune-related proteins activated by H pylori infection interact with proto-oncogene proteins.The hub and bottleneck proteins are potential drug targets for gastric inflammation and cancer.
基金Supported by the grant of the National High Technology R and D Program of China No. 2002AA231051the grant of the Science and Technology Program of Zhejiang Province No. 011103001
文摘AIM: To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiving mechanism of HBV infection.METHODS: The knowledge of HBV infection-related reactions was organized into various kinds of pathways with carefully drawn graphs in HBVPathDB. Pathway information is stored with relational database management system (DBMS), which is currently the most efficient way to manage large amounts of data and query is implemented with powerful Structured Query Language (SQL). The search engine is written using Personal Home Page (PHP) with SQL embedded and web retrieval interface is developed for searching with Hypertext Markup Language (HTML).RESULTS: We present the first version of HBVPathDB,which is a HBV infection-related molecular interaction network database composed of 306 pathways with 1050molecules involved. With carefully drawn graphs, pathway information stored in HBVPathDB can be browsed in an intuitive way. We develop an easy-to-use interface for flexible accesses to the details of database. Convenient software is implemented to query and browse the pathway information of HBVPathDB. Four search page layout options-category search, gene search, description search,unitized search-are supported by the search engine ofthe database. The database is freely available at http://www.bio-inf, net/HBVPathDB/HBV/.CONCLUSION: The conventional perspective HBVPathDB have already contained a considerable amount of pathway information with HBV infection related, which is suitable for in-depth analysis of molecular interaction network of virus and host. HBVPathDB integrates pathway data-sets with convenient software for query, browsing,visualization, that provides users more opportunity to identify regulatory key molecules as potential drug targets and to explore the possible mechanism of HBV infection based on gene expression datasets.
基金National Natural Science Foundation of China,No.31971180 and No.11474013.
文摘Almost all the cellular processes in a living system are controlled by proteins:They regulate gene expression,catalyze chemical reactions,transport small molecules across membranes,and transmit signal across membranes.Even,a viral infection is often initiated through virus-host protein interactions.Protein-protein interactions(PPIs)are the physical contacts between two or more proteins and they represent complex biological functions.Nowadays,PPIs have been used to construct PPI networks to study complex pathways for revealing the functions of unknown proteins.Scientists have used PPIs to find the molecular basis of certain diseases and also some potential drug targets.In this review,we will discuss how PPI networks are essential to understand the molecular basis of virus-host relationships and several databases which are dedicated to virus-host interaction studies.Here,we present a short but comprehensive review on PPIs,including the experimental and computational methods of finding PPIs,the databases dedicated to virus-host PPIs,and the associated various applications in protein interaction networks of some lethal viruses with their hosts.
基金This work was supported by the National Key R&D Program of China(2022YFD1400500)the China Agriculture Research System of MOF and MARA(CARS-34-07)+1 种基金the Publicinterest Scientific Institution Basal Research Fund,China(Y2022GH12)the Central Public-interest Scientific Institution Basal Research Fund,China(S2021XM22 and S2022XM21)。
文摘Female adults of the migratory locust,Locusta migratoria manilensis(Meyen),can sense seasonal photoperiod changes,which induces embryonic diapause as a key strategy to overwinter.Serine protease inhibitor genes(SPNs)were thought to play key roles during diapause,while few SPNs were functionally characterized.LmSPN2 was one of those genes differentially expressed between diapause and non-diapause eggs;however,its biological function remained to be explored.So,we conducted RNAi knockdown of LmSPN2,resulting in a significant decrease of the egg diapause rate by 29.7%.Using yeast two-hybrid assays,co-immunoprecipitation,and pull-down methods,we found an interaction between LmSPN2 and LmSPN3,which was proved to be mediated by a glutamate(E331)binding site of LmSPN2.RNAi knockdown of LmSPN3 resulted in a significant increase in diapause rate by 14.6%,indicating an inverse function of LmSPN2 and LmSPN3 on diapause regulation.Double knockdown of two SPN genes resulted in a 26.4%reduction in diapause rate,indicating that LmSPN2 was the dominant regulatory signal.Moreover,we found four Toll pathway genes(easter,spätzle,pelle,and dorsal)upregulated significantly after the knockdown of LmSPN2 while downregulated after the knockdown of LmSPN3.Therefore,we speculate that two SPNs regulate diapause through the Toll pathway.Our results indicated that LmSPN2 positively regulates locust egg entry into diapause,while LmSPN3 is a negative regulator of embryonic commitment to diapause.Their interaction is mediated by the binding site of E331 and influences egg diapause through the Toll pathway.This mechanistic understanding of diapause regulation expands our understanding of insect developmental regulation and provides functional targets for developing locust management strategies.
基金supported by the National Natural Science Foundations of China (31402033, U1603232)the Special Fund for Basic Scientific Research of Institute of Animal Sciences,the Chinese Academy of Agricultural Sciences (2017ywf-zd-11, Y2017JC03)the Agricultural Science and Technology Innovation Program of China (ASTIPIAS01)
文摘Scurs is a horn phenotype that exhibits as small corneous structures on the skull due to the deformed development of horn tissues. Previous genome-wide association analysis of scurs in Soay sheep showed a significant association to the polled locus, relaxin-like receptor 2(RXFP2). However, the molecular mechanism underlying the development of scurs remains largely unknown. In the present study, we performed an i TRAQ-based quantitative proteomic analysis of horn tissues from both scurs and normal two-horned and four-horned individuals among Altay sheep to identify the differentially expressed proteins(DEPs) responsible for the scurs phenotype. In total, 232 proteins showed significant differential expression, and the most significant Gene ontology categories were the adhesion processes(biological adhesion(P=4.07×10–17) and cell adhesion(P=3.7×10–16)), multicellular organismal process(single-multicellular organism process(P=2.06×10–11) and multicellular organismal process(P=2.29×10–11)) and extracellular processes(extracellular matrix organization(P=4.77×10–16) and extracellular structure organization(P=4.93×10–16)). Kyoto encyclopedia of genes and genomes(KEGG) analysis showed that extracellular matrix(ECM)-receptor interactions and focal adhesion pathways were the most significant pathways. This finding is consistent with the reduced formation of extracellular matrix in scurs and the development of deformed horn tissues. Our study helps to elucidate the inheritance pattern of sheep horn traits from the perspectives of downstream expressed proteins.
基金This work was supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership Initiative on Emerging Infectious Diseases(Project No.PE00000007,INF-ACT)。
文摘Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.
文摘Recent transcription profiling studies have revealed an unexpectedly large proportion of antisense transcripts in eukaryotic genomes. These antisense genes seem to regulate gene expression by interacting with sense genes. Previ- ous studies have focused on the non-coding antisense genes, but the possible regulatory role of the antisense protein is poorly understood. In this study, we found that a protein encoded by the antisense gene ADF1 acts as a transcription suppressor, regulating the expression of sense gene MDF1 in Saccharomyces cerevisiae. Based on the evolutionary, ge- netic, cytological and biochemical evidence, we show that the protein-coding sense gene MDF1 most likely originated de novo from a previously non-coding sequence and can significantly suppress the mating efficiency of baker's yeast in rich medium by binding MATa2 and thus promote vegetative growth. These results shed new light on several im- portant issues, including a new sense-antisense interaction mechanism, the de novo origination of a functional gene, and the regulation of yeast mating pathway.
基金supported by the State Key Program of National Natural Science Foundation of China,No.81330042(to SQF)the International Cooperation Program of the National Natural Science Foundation of China,No.81620108018(to SQF)
文摘Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.
文摘Objective: The objective of this work is to search for a novel method to explore the disrupted pathways associated with periodontitis(PD) based on the network level.Methods: Firstly, the differential expression genes(DEGs) between PD patients and cognitively normal subjects were inferred based on LIMMA package. Then, the proteinprotein interactions(PPI) in each pathway were explored by Empirical Bayesian(EB) coexpression program. Specifically, we determined the 100 th weight value as the threshold value of the disrupted pathways of PPI by constructing the randomly model and confirmed the weight value of each pathway. Meanwhile, we dissected the disrupted pathways under the weight value > the threshold value. Pathways enrichment analyses of DEGs were carried out based on Expression Analysis Systematic Explored(EASE) test. Finally, the better method was selected based on the more rich and significant obtained pathways by comparing the two methods. Results: After the calculation of LIMMA package, we estimated 524 DEGs in all. Then we determined 0.115222 as the threshold value of the disrupted pathways of PPI. When the weight value>0.115222, there were 258 disrupted pathways of PPI enriched in. Additionally, we observed those 524 DEGs that were enriched in 4 pathways under EASE=0.1.Conclusion: We proposed a novel network method inferring the disrupted pathway for PD. The disrupted pathways might be underlying biomarkers for treatment associated with PD.
基金supported by National Natural Sciences Foundation of China(NSFC)(Grant Nos.30670091 and 30599434)National Basic Research Program(Project 973)of China Ministry of Science and Technology(Grant No.2011CB504703)+1 种基金National Key Technologies R&D Program(Grant No.2006BAD06A01)GFG is a leading principal investigator of the NSFC Innovative Research Group(Grant No.81021003).
文摘Influenza virus contains three integral membrane proteins:haemagglutinin,neuraminidase,and matrix protein(M1 and M2).Among them,M2 protein functions as an ion channel,important for virus uncoating in endosomes of virus-infected cells and essential for virus replication.In an effort to explore potential new functions of M2 in the virus life cycle,we used yeast two-hybrid system to search for M2-associated cellular proteins.One of the positive clones was identified as human Hsp40/Hdj1,a DnaJ/Hsp40 family protein.Here,we report that both BM2(M2 of influenza B virus)and A/M2(M2 of influenza A virus)interacted with Hsp40 in vitro and in vivo.The region of M2-Hsp40 interaction has been mapped to the CTD1 domain of Hsp40.Hsp40 has been reported to be a regulator of PKR signaling pathway by interacting with p58^(IPK) that is a cellular inhibitor of PKR.PKR is a crucial component of the host defense response against virus infection.We therefore attempted to understand the relationship among M2,Hsp40 and p58^(IPK) by further experimentation.The results demonstrated that both A/M2 and BM2 are able to bind to p58^(IPK)in vitro and in vivo and enhance PKR autophosphorylation probably via forming a stable complex with Hsp40 and P58^(IPK),and consequently induce cell death.These results suggest that influenza virus M2 protein is involved in p58^(IPK)mediated PKR regulation during influenza virus infection,therefore affecting infected-cell life cycle and virus replication.
基金supported by the National High Technology Research and Development Program of China(2012AA020201)National Basic Research Program of China(2013CB910802,2010CB912700)+2 种基金International Science&Technology Cooperation Program of China(2014DFB30020)National Natural Science Foundation of China(31000379,31000587,31000591)Chinese State Key Project Specialized for Infectious Diseases(2012ZX10002012-006)
文摘Integration of pathway and protein-protein interaction(PPI) data can provide more information that could lead to new biological insights. PPIs are usually represented by a simple binary model, whereas pathways are represented by more complicated models. We developed a series of rules for transforming protein interactions from pathway to binary model, and the protein interactions from seven pathway databases, including PID, Bio Carta, Reactome, Net Path, INOH, SPIKE and KEGG, were transformed based on these rules. These pathway-derived binary protein interactions were integrated with PPIs from other five PPI databases including HPRD, Int Act, Bio GRID, MINT and DIP, to develop integrated dataset(named Path PPI). More detailed interaction type and modification information on protein interactions can be preserved in Path PPI than other existing datasets. Comparison analysis results indicate that most of the interaction overlaps values(OAB) among these pathway databases were less than 5%, and these databases must be used conjunctively. The Path PPI data was provided at http://proteomeview. hupo.org.cn/Path PPI/Path PPI.html.
基金support from the Shanghai Science and Technology Development Program (Grant Nos. 03DZ14024 & 07ZR14010)the 863 High Technology Foundation of China (Grant No. 2006AA02A310)+1 种基金US NIH 1R01AI064806-01A2, 5R21DK082706U.S. Department of Energy, the Office of Science (BER) (Grant No. DE-FG02- 07ER64422)
文摘Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.
基金This study was financially supported by the National Key Research and Development Program of China(2022YFC2804100,2021YFF0502400,2022YFC2804300)National Natural Science Foundation of China(82073713,22137006,82104033,82173730,81903499,32070070,82160669)Innovative research team of highlevel local universities in Shanghai(SHSMU-ZDCX20212702,China).We thank Dr.Juncheng Su from Shanghai Jiao-Tong University School of Medicine(Shanghai,China)for providing the LoVo and COLO 320DM cell lines.
文摘Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.Here,we identified UAT-B,a novel neoantimycin analog isolated from Streptomyces conglobatus,as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction(PPI)to overcome multi-drug resistance in colorectal cancer(CRC).The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels,triggering cell apoptosis through modulation of the Wnt/β-catenin pathway.Importantly,UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels,as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts,as well as APC^(min/+)spontaneous CRC models.Collectively,these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment,and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.
基金supported by the National Key Research and Development Program of China(2016YFD0100502)
文摘Wheat(Triticum aestivum L.) is one of the three major global food crops. Hightemperature stress can affect its yield and quality. Studies of the effect of hightemperature stress on wheat kernel development are important because they can reveal the stability of wheat quality and lead to the genetic improvement of wheat quality traits. In this study, the isobaric tags for relative and absolute quantitation(iTRAQ)method was adopted to analyze changes in the protein expression profile of wheat cultivars under high temperature stress. The protein content of wheat grain increased under heat stress, while the SDS-sedimentation value and starch content decreased.Grain filling was deficient under high temperature stress, which reduced thousandkernel weight but did not affect wheat kernel length. The 207 differentially expressed proteins identified in Gaocheng 8901 under heat stress were associated with energy metabolism, growth and development, and stress response. Gene Ontology enrichment analysis showed that the annotated proteins that were differentially expressed in Gaocheng 8901 under heat stress were involved mainly in stimulus response, abiotic stress response, stress response, and plasma membrane. A set of 78 differentially expressed proteins were assigned to 83 KEGG signaling/metabolic pathways. KEGG pathway enrichment analysis showed that this set of proteins was significantly enriched in members of 51 pathways, and the proteins participated mainly in protein synthesis in the endoplasmic reticulum, starch and sucrose metabolism, and reaction on ribosomes. Five differentially expressed proteins were involved in protein–protein interaction networks that may greatly influence the yield and quality of wheat grain. In wheat, high-temperature stress leads to a variety of effects on protein expression and may ultimately cause changes in yield and quality.
基金This work was supported by National Natural Science Foundation Funding(3110131631371805)Program for New Century Excellent Talents in University of Ministry of Education of China(NCET-11-0796)and Heilongjiang Province Postdoctoral Science Foundation.
文摘Bone morphogenetic proteins(BMPs)are a family of potent,multifunctional growth factors belonging to transforming growth factor-(TGF-).They are highly conservative in structures.Over 20 members of BMPs with varying functions such as embryogenesis,skeletal formation,hematopoiesis and neurogenesis have been identified in human body.BMPs are unique growth factors that can induce the formation of bone tissue individually.BMPs can induce the differentiation of bone marrow mesenchymal stem cells into osteoblastic lineage and promote the proliferation of osteoblasts and chondrocytes.BMPs stimulate the target cells by specific membrane-bound receptors and signal transduced through mothers against decapentaplegic(Smads)and mitogen activated protein kinase(MAPK)pathways.It has been demonstrated that BMP-2,BMP-4,BMP-6,BMP-7,and BMP-9 play an important role in bone formation.This article focuses on the molecular characterization of BMPs family members,mechanism of osteogenesis promotion,related signal pathways of osteogenic function,relationships between structure and osteogenetic activity,and the interactions among family members at bone formation.