Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

Curcumin,the medically active component from Curcuma longa(Turmeric),is widely used to treat inflammatory diseases.Protein interaction network(PIN) analysis was used to predict its mechanisms of molecular action.Targets of curcumin were obtained based on ChE MBL and STITCH databases.Protein–protein interactions(PPIs) were extracted from the String database.The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology(GO) enrichment analysis based on molecular complex detection(MCODE).A PIN of curcumin with 482 nodes and 1688 interactions was constructed,which has scale-free,small world and modular properties.Based on analysis of these function modules,the mechanism of curcumin is proposed.Two modules were found to be intimately associated with inflammation.With function modules analysis,the anti-inflammatory effects of curcumin were related to SMAD,ERG and mediation by the TLR family.TLR9 may be a potential target of curcumin to treat inflammation.

A novel lytic phage potentially effective for phage therapy against Burkholderia pseudomallei in the tropics

Background:Burkholderia pseudomallei is a tropical pathogen that causes melioidosis.Its intrinsic drug-resistance is a leading cause of treatment failure,and the few available antibiotics require prolonged use to be effective.This study aimed to assess the clinical potential of B.pseudomallei phages isolated from Hainan,China.Methods:Burkholderia pseudomallei strain(HNBPoo1)was used as the isolation host,and phages were recovered from domestic environmental sources,which were submitted to the host range determination,lytic property assays,and stability tests.The best candidate was examined via the transmission electron microscope for classification.With its genome sequenced and analyzed,its protective efficacy against B.pseudomallei infection in A549 cells and Caenorhabditis elegans was evaluated,in which cell viability and survival rates were compared using the one-way ANOVA method and the log-rank test.Results:A phage able to lyse 24/25 clinical isolates was recovered.It was classified in the Podoviridae family and was found to be amenable to propagation.Under the optimal multiplicity of infection(MOl)of o.1,an eclipse period of around 20 min and a high titer(io12 PFU/ml)produced within 1 h were demonstrated.This phage was found stabile at a wide range of temperatures(24,37,40,50,and 60 C)and pH values(3-12).After being designated as vB_BpP_HN01,it was fully sequenced,and the 71,398 bp linear genome,containing 93 open reading frames and a tRNA-Asn,displayed a low sequence similarity with known viruses.Additionally,protective effects of applications of vB_BpP_HNo1(MOl=0.1 and MOl=1)alone or in combination with antibiotics were found to improve viability of infected cells(70.6±6.8%,85.8±5.7%,91.9±1.8%,and 96.8±1.8%,respectively).A significantly reduced mortality(10%)and a decreased pathogen load were demonstrated in infected C.elegans following the addition of this phage.Conclusions:As the frst B.pseudomallei phage was isolated in Hainan,China,phage vB_BpP_HNO1 was characterized by promising lytic property,stability,and effciency of bacterial elimination during the in vitro/vivo experiments.Therefore,we can conclude that it is a potential alternative agent for combating melioidosis.