BackgroundHerpes simplex virus (HSV) is a common human pathogen that causes a variety of diseases, including oral-labial, genital lesions and life-threatening encephalitis. The antiviral nucleoside analogues such as acyclovir are currently used in anti-HSV therapies; however, clinical overuse of these drugs has led to the emergence of drug-resistant viral strains. Hence, there is an urgent need to develop new anti-HSV agents.MethodsTo identify novel anti-HSV-1 compounds, we screened the LOPAC small scale library of 1280 bioactive compounds to identify inhibitors of HSV-1-induced necroptosis. Further experiments including western blot analysis, Q-PCR analysis and immunohistochemistry were performed to explore the antiviral mechanism of the compounds.ResultsHere, we identified PHA767491 as a new inhibitor of HSV. PHA767491 potently blocked the proliferation of HSV in cells, as well as HSV induced cell death. Further, we found that PHA767491 strongly inhibited HSV infection post viral entry. Moreover, PHA767491 reduced the expression of viral genes required for DNA synthesis including UL30/42 DNA polymerase and UL5/8/52 helicase-primase complex. The essential immediate early (IE) genes such as ICP4 and ICP27 are critical for the expression of the early and late genes. Of note, PHA767491 inhibited the expression of all IE genes of both HSV-1 and HSV-2. Importantly, PHA767491 reduced viral titers in the tissues from the mice infected with HSV-1. Consistently, immunohistochemistry analysis showed that PHA767491 dramatically attenuated expression of viral protein gB in the livers.ConclusionsTaken together, PHA767491 has potent anti-HSV activity by inhibiting viral replication both in vitro and in mouse model. Thus, PHA767491 could be a promising agent for the development of new anti-HSV therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2305-0) contains supplementary material, which is available to authorized users.
The development of low-cost biological materials with controlled drug release profile is of great importance but challenging in pharmaceutical industry. Recently, bacterial cellulose nanofibers have provoked intensive research interests in tissue engineering and the pharmaceutical science due to their stability, availability, sustainability, and low toxicity. Here we describe the development of a PEI (polyethylenimine)-grafted bacterial cellulose (BC) as an efficient drug delivery system. The PEI-BC aerogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and zeta potential measurements. The optimum sample exhibited enhanced mechanical strength, remarkable adsorption capacity toward aspirin, BSA, and gentamicin, prolonged and pH-dependent drug release, and low cytotoxicity. Our work has presented a rational structure design from biomass for controllable drug carrier.
BackgroundHSV-1 is a common pathogen that infects 50–90% of the human population worldwide. HSV-1 causes numerous infection-related diseases, some of which are severely life-threatening. There are antiviral medications with activity against HSV-1. However, with the emergence of drug-resistant mutant strains of HSV-1, there is an urgent need to develop new effective anti-HSV-1 agents.MethodsTherefore, we screened a chemical library of approximately 1500 compounds to identify inhibitors of HSV-1-induced toxicity for further drug development. Moreover, we performed several experiments, including western blot analysis, Q-PCR analysis and luciferase activity assay, to explore the antiviral mechanism of the candidates.ResultsHere, we identified a small molecule, mitoxantrone dihydrochloride, with potency against HSV-1-induced toxicity. Furthermore, the viral titers and expression levels of HSV-1 viral proteins were potently reduced by the presence of MD in many cell lines. Using Q-PCR analysis, we found that MD efficiently reduced the transcription of viral genes that are essential for DNA synthesis, namely, UL5, UL9, UL29, UL30, UL42 and UL52. Notably, MD also significantly inhibited the transcription of the immediate early genes ICP0, ICP22, ICP27 and ICP47, all of which are required for the expression of early and late viral gene products. Using immunofluorescence and western blot analysis, we found that the antiviral effect of MD was independent of the activation of the NF-κB and MAPK pathways. Furthermore, we found that the reduction in the transcription of viral immediate early genes was not related to the promoter activities of ICP0.ConclusionsTherefore, the identification of compound MD as an inhibitor of toxicity induced by HSV-1 highlights its potential use in the development of novel anti-HSV-1 drugs.
Circulating tumor DNA (ctDNA) represents an emerging biomarker of liquid biopsies for the development of precision cancer diagnostics and therapeutics. However, sensitive detection of ctDNA remains challenging, due to their short half-life and low concentrations in blood samples. In this study, we report a new method to address this challenge by integrating cycled enzymatic DNA amplification technique and Au nanoparticle@silicon-assisted surface-enhanced Raman scattering (SERS) technique. We have demonstrated a reproducible identification of a single-base-mutated ctDNA sequence of diffuse intrinsic pontine gliomas (DIPGs), with the limit of detection (LOD) as low as 9.1 fM in the spiked blood samples. This approach can be used to analyze trace amounts of ctDNA in translational medicine for early diagnosis, therapeutic effect monitoring, and prognosis of patients with cancer.
Correction for ‘The sensitive detection of single-cell secreted lactic acid for glycolytic inhibitor screening with a microdroplet biosensor’ by Xuyue Chen et al., Anal. Methods, 2020, 12, 3250–3259, DOI: 10.1039/D0AY00633E.
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