Proteomic dissection of biological pathways/processes through profiling protein-protein interaction networks

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.

Current status of nitrous oxide use in pediatric patients

Nitrous oxide is one of the most commonly used inhalational anesthetic agents used in practice.It is a cost-effective,pleasant,safe,and versatile anesthetic agent with many desirable properties like good quality analgesia,decreased awareness,accelerated induction and recovery from anesthesia,and reduced utilization of other expensive inhalational agents with potential cost savings.The use of nitrous oxide has been questioned by a lot of studies and case reports perceiving its adverse systemic,hematological,immune,and neurologic adverse effects.However,the literature in the recent past has tried to resolve the controversies related to its use.The concerns over an increase in cardiovascular complications and mortality following nitrous oxide use have been negated by recent data.However,its use in certain vulnerable populations like children with cobalamin and folate deficiency or defects in their metabolic pathways remains a cause of concern for its toxic effects.In this narrative review,we aim to discuss the pharmacological properties of nitrous oxide,the potential advantages and drawbacks of the use of nitrous oxide in children,address the neurodevelopmental and other systemic effects,and throw light on the evidence regarding the safety of nitrous oxide use and its current role in pediatric procedural sedation and anesthesia practice.The literature related to its use in the pediatric population for painful procedures and surgeries has been summarized.

A network pharmacology study of Sendeng-4,a Mongolian medicine

We collected the data on the Sendeng-4 chemical composition corresponding targets through the literature and from Drug Bank, SuperT arget, TTD(Therapeutic Targets Database) and other databases and the relevant signaling pathways from the KEGG(Kyoto Encyclopedia of Genes and Genomes) database and established models of the chemical composition-target network and chemical composition-target- disease network using Cytoscape software, the analysis indicated that the chemical composition had at least nine different types of targets that acted together to exert effects on the diseases, suggesting a "multi-component, multi-target" feature of the traditional Mongolian medicine. We also employed the rat model of rheumatoid arthritis induced by Collgen Type II to validate the key targets of the chemical components of Sendeng-4, and three of the key targets were validated through laboratory experiments, further confirming the anti-inflammatory effects of Sendeng-4. In all, this study predicted the active ingredients and targets of Sendeng-4, and explored its mechanism of action, which provided new strategies and methods for further research and development of Sendeng-4 and other traditional Mongolian medicines as well.

Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

Integrative analysis of gene expression profiles reveals specific signaling pathways associated with pancreatic duct adenocarcinoma

Background:Pancreatic duct adenocarcinoma(PDAC)remains a major health problem because conventional can-cer treatments are relatively ineffective against it.Microarray studies have linked many genes to pancreatic cancer,but the available data have not been extensively mined for potential insights into PDAC.This study attempted to identify PDAC-associated genes and signaling pathways based on six microarray-based profiles of gene expression in pancre-atic cancer deposited in the gene expression omnibus database.Methods:Pathway network methods were used to analyze core pathways in six publicly available pancreatic cancer gene(GSE71989,GSE15471,GSE16515,GSE32676,GSE41368 and GSE28735)expression profiles.Genes potentially linked to PDAC were assessed for potential impact on survival time based on data in The Cancer Genome Atlas and International Cancer Genome Consortium databases,and the expression of one candidate gene(CKS2)and its association with survival was examined in 102 patients with PDAC from our hospital.Effects of CKS2 knockdown were explored in the PDAC cell lines BxPC-3 and CFPAC-1.Results:The KEGG signaling pathway called“pathway in cancer”may play an important role in pancreatic cancer development and progression.Five genes(BIRC5,CKS2,ITGA3,ITGA6 and RALA)in this pathway were significantly associated with survival time in patients with PDAC.CKS2 was overexpressed in PDAC samples from our hospital,and higher CKS2 expression in these patients was associated with shorter survival time.CKS2 knockdown substantially inhibited PDAC cell proliferation in vitro.Conclusions:Analysis integrating existing microarray datasets allowed identification of the“pathway in cancer”as an important signaling pathway in PDAC.This integrative approach may be powerful for identifying genes and pathways involved in cancer.

The interaction mechanism of nickel ions with L929 cells based on integrative analysis of proteomics and metabolomics data

The aim of this article was to study the toxicity mechanism of nickel ions(Ni^(2+))on L929 cells by combining proteomics and metabolomics.First,iTRAQ-based proteomics and LC/MS metabolomics analyses were used to determine the protein and metabolite expression profiles in L929 cells after treatment with 100μMNi^(2+)for 12,24 and 48 h.A total of 177,2191 and 2109 proteins and 40,60 and 74 metabolites were found to be differentially expressed.Then,the metabolic pathways in which both differentially expressed proteins and metabolites were involved were identified,and three pathways with proteins and metabolites showing upstream and downstream relationships were affected at all three time points.Furthermore,the protein-metabolite-metabolic pathway network was constructed,and two important metabolic pathways involving 4 metabolites and 17 proteins were identified.Finally,the functions of the important screened metabolic pathways,metabolites and proteins were investigated and experimentally verified.Ni^(2+)mainly affected the expression of upstream proteins in the glutathione metabolic pathway and the arginine and proline metabolic pathway,which further regulated the synthesis of downstream metabolites,reduced the antioxidant capacity of cells,increased the level of superoxide anions and the ratio of GSSG to GSH,led to oxidative stress,affected energy metabolism and induced apoptosis.