On February 1,2016,the World Health Organization declared that the cluster of microcephaly cases and other neurological disorders constitute public health emergency of international concern.Furthermore,few studies dem...On February 1,2016,the World Health Organization declared that the cluster of microcephaly cases and other neurological disorders constitute public health emergency of international concern.Furthermore,few studies demonstrated that there was an increased evidence of causal relationship of Zika virus(ZIKAV)infection and microcephaly,birth abnormalities and neurological disorders such as Guillain–Barre′syndrome.ZIKAV transmission occurs mainly by the bite of infected mosquitos(Aedes species),but there are also reports that infections could occur via the placenta,breast milk,saliva,blood transfusion and sex.This article reviews the global efforts,progress in scientific research to understand the pathogenesis of ZIKAV infection&disease,clinical presentations,congenital transmission and autoimmune neurological disorders.The paper further explores the knowledge gaps,future priority research agenda for strategic response including vector control and prevention.We conducted a systematic literature review to synthesise available evidence on ZIKAV infection and its vector and host interaction from electronic databases.展开更多
Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery.Recent developments in advanced antimicrobial nanotechnologies provide num...Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery.Recent developments in advanced antimicrobial nanotechnologies provide numerous opportunities to effective remove resistant bacteria and prevent resistance from occurring through unique mechanisms.With tunable physicochemical properties,nanomaterials can be designed to be bactericidal,antifouling,immunomodulating,and capable of delivering antibacterial compounds to the infection region with spatiotemporal accuracy.Despite its substantial advancement,an important,but under-explored area,is potential microbial resistance to nanomaterials and how this can impact the clinical use of antimicrobial nanotechnologies.This review aims to provide a better understanding of nanomaterial-associated microbial resistance to accelerate bench-to-bedside translations of emerging nanotechnologies for effective control of implant associated infections.展开更多
Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive...Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337(T1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.展开更多
Chronic hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). While multiple treatment modalities are available, liver transplantation remains the sole curative treatment for adv...Chronic hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). While multiple treatment modalities are available, liver transplantation remains the sole curative treatment for advanced stages of HCC, and hence new treatment approaches are required to fulfill this unmet need of curative HCC therapy. Our first-in-man proof-of-concept adoptive T-cell immunotherapy against HBV related hepatocellular carcinoma metastases has shown promising results. Here, we review the development of T-cell immunotherapy targeting HBV antigens for the treatment of HBV-HCC and discuss the practical considerations for the safe and effective use in clinics.展开更多
Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype ...Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype having a better response.ITPA gene deficiency protects against clinically significant anaemia induced by treatment.The purpose of this study was to determine IL28B polymorphismand ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response(SVR).Methods:All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study.Blood samples for IL28B and ITPA genotyping were obtained.Medical records were reviewed for verification of treatment response,development of anaemia and if treatment reduction was required during the treatment.Results:A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin,of whom 42 agreed to participate in the study.Mean age was 45.6±12.9 years at time of treatment,and 83.3%of patients weremales.Thirty-three(78.6%)had IL28B CC genotype,of whom 25(75.8%)obtained SVR compared with only 3 of 9(33.3%)non C/C genotype patients who achieved SVR(P=0.041).Eleven(26.1%)patients had ITPA AC genotype,and 30(71.4%)had CC genotype.There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia(45.5%vs 63.3%,P=0.302).Even among patients who developed anaemia,70.8%stillmanaged to achieve SVR.Treatment reduction also had no impact on SVR.Conclusion:Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.展开更多
文摘On February 1,2016,the World Health Organization declared that the cluster of microcephaly cases and other neurological disorders constitute public health emergency of international concern.Furthermore,few studies demonstrated that there was an increased evidence of causal relationship of Zika virus(ZIKAV)infection and microcephaly,birth abnormalities and neurological disorders such as Guillain–Barre′syndrome.ZIKAV transmission occurs mainly by the bite of infected mosquitos(Aedes species),but there are also reports that infections could occur via the placenta,breast milk,saliva,blood transfusion and sex.This article reviews the global efforts,progress in scientific research to understand the pathogenesis of ZIKAV infection&disease,clinical presentations,congenital transmission and autoimmune neurological disorders.The paper further explores the knowledge gaps,future priority research agenda for strategic response including vector control and prevention.We conducted a systematic literature review to synthesise available evidence on ZIKAV infection and its vector and host interaction from electronic databases.
基金funding support from the NUS Presidential Young Professorship and NUS Technological Innovations in Infectious Diseases Translational Research.
文摘Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery.Recent developments in advanced antimicrobial nanotechnologies provide numerous opportunities to effective remove resistant bacteria and prevent resistance from occurring through unique mechanisms.With tunable physicochemical properties,nanomaterials can be designed to be bactericidal,antifouling,immunomodulating,and capable of delivering antibacterial compounds to the infection region with spatiotemporal accuracy.Despite its substantial advancement,an important,but under-explored area,is potential microbial resistance to nanomaterials and how this can impact the clinical use of antimicrobial nanotechnologies.This review aims to provide a better understanding of nanomaterial-associated microbial resistance to accelerate bench-to-bedside translations of emerging nanotechnologies for effective control of implant associated infections.
基金Ministry of Education Tier 2 grant(MOE2017-T2-1-078 and MOE-2017-T2-2-014,Singapore)National Research Foundation Competitive Research Programme(NRF-CRP21-2018-0004,Singapore)。
文摘Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337(T1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.
文摘Chronic hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). While multiple treatment modalities are available, liver transplantation remains the sole curative treatment for advanced stages of HCC, and hence new treatment approaches are required to fulfill this unmet need of curative HCC therapy. Our first-in-man proof-of-concept adoptive T-cell immunotherapy against HBV related hepatocellular carcinoma metastases has shown promising results. Here, we review the development of T-cell immunotherapy targeting HBV antigens for the treatment of HBV-HCC and discuss the practical considerations for the safe and effective use in clinics.
文摘Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype having a better response.ITPA gene deficiency protects against clinically significant anaemia induced by treatment.The purpose of this study was to determine IL28B polymorphismand ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response(SVR).Methods:All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study.Blood samples for IL28B and ITPA genotyping were obtained.Medical records were reviewed for verification of treatment response,development of anaemia and if treatment reduction was required during the treatment.Results:A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin,of whom 42 agreed to participate in the study.Mean age was 45.6±12.9 years at time of treatment,and 83.3%of patients weremales.Thirty-three(78.6%)had IL28B CC genotype,of whom 25(75.8%)obtained SVR compared with only 3 of 9(33.3%)non C/C genotype patients who achieved SVR(P=0.041).Eleven(26.1%)patients had ITPA AC genotype,and 30(71.4%)had CC genotype.There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia(45.5%vs 63.3%,P=0.302).Even among patients who developed anaemia,70.8%stillmanaged to achieve SVR.Treatment reduction also had no impact on SVR.Conclusion:Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.
