Identification and analysis of core target genes of miR-29b-3p in glioma

Objective:To investigate the core target genes of miR-29b-3p,and analyze the clinical significance of the core target genes in glioma.Methods:Bioinformatics analysis was used to predict and screen the target genes of miR-29b-3p.STRING and Cytoscape software were used to analyze the protein-protein interaction(PPI)of target genes.the differences expression and survival prognosis in glioma were analyzed by GEPIA and CGGA.Independent prognostic factors analyzed by univariate and multivariate Cox proportional hazards regression model.Results:22 target genes of miR-29b-3p were predicted using LinkedOmics,miRDB,miRTarBase,TargetScan,and starbase databases.Through the construction of the PPI network,genes out of the network were removed,and a total of 16 genes were screened for further study of their clinical significance.Based on analysis of GEPIA and CGGA databases,COL2A1,DNMT3A,and DNMT3B were excluded.Through further analysis of the univariate and multivariate Cox proportional hazard regression model,finally identified three core target genes:SERPINH1,LOXL2,CDK6.Conclusion:Bioinformatics analysis showed that miR-29b-3p targeted three core genes such as SERPINH1,LOXL2,and CDK6 in glioma.The expression of these genes was different between brain normal tissues and gliomas,between different grades of tumor,IDH mutation status and 1p/19q codeletion status.Its high expression had adverse effects on overall survival and recurrence-free survival.These core target genes can be used as an independent prognostic factor.

Co-infections with Babesia microti and Plasmodium parasites along the China-Myanmar border

Background:Babesiosis is an emerging health risk in several parts of the world.However,little is known about the prevalence of Babesia in malaria-endemic countries.The area along the China-Myanmar border in Yunnan is a main endemic area of malaria in P.R.China,however,human infection with Babesia microti(B.microti)is not recognized in this region,and its profile of co-infection is not yet clear.Methods:To understand its profile of co-infections with B.microti,our investigation was undertaken in the malaria-endemic area along the China-Myanmar border in Yunnan between April 2012 and June 2013.Four parasite species,including B.microti,Plasmodium falciparum(P.falciparum),P.vivax,and P.malariae,were identified among 449 suspected febrile persons detected by nested polymerase chain reaction(PCR)assay based on small subunit ribosomal ribonucleic acid(RNA)genes of B.microti and Plasmodium spp.Results:Of all the collected samples from febrile patients,mono-infection with B.microti,P.vivax,P.falciparum,and P.malariae accounted for 1.8%(8/449),9.8%(44/449),2.9%(13/449),and 0.2%(1/449),respectively.The rate of mixed infections of B.microti with P.falciparum or P.vivax are both 0.2%(1/449),and mixed infections of P.falciparum and P.vivax accounted for 1.1%(5/449).Conclusions:This report supports the hypothesis that babesiosis caused by B.microti is emerging along the China-Myanmar border in the Yunnan province,P.R.China,but it was ignored because of low parasitemia or mixed infection with Plasmodium spp.More sensitive and specific diagnosis methods are needed to find the rapid response mechanism of emergency for babesiosis and malaria co-prevalence areas.

Study roadmap for high-throughput development of easy to use and affordable biomarkers as diagnostics for tropical diseases:a focus on malaria and schistosomiasis

Background:Interventions are currently being used against‘infectious diseases of poverty’,which remain highly debilitating and deadly in most endemic countries,especially malaria,schistosomiasis,echinococcosis and African sleeping sickness.However,major limitations of current‘traditional’methods for diagnosis are neither simple nor convenient for population surveillance,and showed low sensitivity and specificity.Access to novel technologies for the development of adequate and reliable tools are expressly needed.A collaborative project between African Network for Drugs and Diagnostics Innovation and partner institutions in Africa and China aims to screen suitable serological biomarkers for diagnostic pipelines against these‘diseases of the poor’.Methods:Parasite-specific exposed versus unexposed individuals were screened and sera or urine/stools were collected through case-control studies in China and African countries.Target genes/open reading frames were selected,then will be cloned and cell-free expressed,quantified and immuno-detected.Target antigens/epitopes will be probed and screened with sera from exposed or unexposed individuals using a high-throughput antigen screening platform as the study progresses.The specificity and sensitivity of highly immunoreactive biomarkers will be evaluated as well,using enzyme-linked immunosorbent assays or dipsticks.Discussion:This roadmap explicitly unfolds the integrated operating procedures with focus on malaria and schistosomiasis,for the identification of suitable biomarkers that will aid the prioritization of diagnostics for population use.However,there is need to further validate any new diagnostic through comparison with standard methods in field deployable tests for each region.Our expectations for the future are to seek regulatory approval and promote the use of diagnostics in endemic areas.

Whole-genome sequencing and analysis of Plasmodium falciparum isolates from China-Myanmar border area

Background:China has made progress in malaria control and aims to eliminate malaria nationwide,but implementing effective interventions along the border regions remain a huge task.The Plasmodium falciparum cases imported from Southeast Asia has frequently reported especially in the China-Myanmar border(CMB)area.Though,information is scant on P.falciparum genetic variability in this area.Methods:This study reported P.falciparum isolates genome sequence of six clinical isolates in the CMB area.Furthermore,we estimated the nucleotide diversity,Watterson’s estimator and Tajima’s D value for the whole genome mutation rate in slide window.Results:Our data were aligned onto 96.05-98.61%of the reference 3D7 genome in high fold coverages.Principal component analysis result showed that P.falciparum clustered generally according to their geographic origin.A total of 91 genes were identified as positive selection with Ka/Ks ratio significantly higher than 1,and most of them were multigene families encoding variant surface antigens(VSAs)such as var,rif and stevor.The enrichment of the positive selection on VSA genes implied that the environment complexity subjected CMB’s P.falciparum to more pressure for survival.Conclusions:Our research suggests that greater genetic diversity in CMB area and the positive selection signals in VSA genes,which allow P.falciparum to fit the host immune system well and aggravate the difficulty of treatment.Meanwhile,results obtained from this study will provide the fundamental basis for P.falciparum population genomic research in CMB area.

High multiple mutations of Plasmodium falciparum-resistant genotypes to sulphadoxine-pyrimethamine in Lagos, Nigeria

Background Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine(SP)has been largely reported among pregnant women.However,the profile of resistance markers to SP dihydrofolate reductase(dhfr)and dihydropteroate synthase(dhps)in the general population are varied and not frequently monitored.Currently,SP is used as partner drug for artemisinin combination therapy(SP-artesunate)in some sub-Saharan African countries or as a prophylactic drug in intermittent preventive treatment of malaria during pregnancy and infants and in seasonal malaria chemoprevention(SMC).Profiling of P.falciparum-resistant genotypes to SP is dynamic and critical in providing data that would be useful for malaria control programmes.This study assessed the profile of dhfr and dhps genes genotypes among individuals with malaria in Lagos,Nigeria.Methods Molecular markers of SP resistance were identified by nested PCR and sequenced among malaria positive dried blood spots(DBS)that were collected from individuals attending health facilities from January 2013 to February 2014 and during community surveys from October 2010 to September 2011 across different Local Government Areas of Lagos State,Nigeria.Results A total of 242 and 167 samples were sequenced for dhfr and dhps,respectively.Sequence analysis of dhfr showed that 95.5%(231/242),96.3%(233/242)and 96.7%(234/242)of the samples had N51I,C59R and S108N mutant alleles,respectively.The prevalence of dhps mutation at codons A437G,A613S,S436A,A581G,I431V and K540E were 95.8%(160/167),41.9%(70/167),41.3%(69/167),31.1%(52/167),25.1%(42/167),and 1.2%(2/167)respectively.The prevalence of triple mutations(CIRNI)in dhfr was 93.8%and 44.3%for the single dhps haplotype mutation(SGKAA).Partial SP-resistance due to quadruple dhfr-dhps haplotype mutations(CIRNI-SGKAA)and octuple haplotype mutations(CIRNI-VAGKGS)with rate of 42.6%and 22.0%,respectively has been reported.Conclusions There was increased prevalence in dhfr triple haplotype mutations when compared with previous reports in the same environment but aligned with high prevalence in other locations in Nigeria and other countries in Africa.Also,high prevalence of dhfr and dhps mutant alleles occurred in the study areas in Lagos,Nigeria five to eight years after the introduction of artemisinin combination therapy underscores the need for continuous monitoring.