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A wound evolves with variable pHs depending on the healing stage, and the maintenance of mild acidic condition can help healing by deterring the formation of a biofilm. Herein, a dual‐layer wound dressing with an acid‐responsive zeolitic imidazolate framework–8 (ZIF‐8) layer and an acid‐modulating layer is designed to control the acid‐dependent release of therapeutic agents for the improved healing process. The outer dressing layer is coated with curcumin‐incorporated ZIF‐8, where curcumin and zinc ions are released upon dissociation of ZIF‐8 in an acidic condition. The inner layer, a pH modulator, is fabricated by electrospinning polyvinylpyrrolidone with addition of acetic acid. In vitro release test shows that the outer layer dressing attains a considerably higher release of curcumin and Zn2+ under an acidic condition. Combined with the inner acidic layer, the dual layer dressing exhibits facilitated release of effective agents regardless of environmental pHs, attributed to the proper pH modulation to about 6.5. The anti‐oxidant activity of curcumin and antibacterial activity of Zn2+ are confirmed. The study highlights the novel proof‐of‐concept design of active wound dressing demonstrating the dual functions of pH regulation and the stimulus‐responsive drug delivery. [ABSTRACT FROM AUTHOR]

Screening of the antiviral and virucidal activities of ethanol extracts from plants endemic to the Republic of Korea revealed the inhibitory activity of a 70% ethanol extract of the whole plant of A. pseudoglehnii (APE) against influenza virus infection. Two chlorophyll derivatives, ethyl pheophorbides a and b, isolated as active components of APE, exerted virucidal effects with no evident cytotoxicity. These compounds were effective only under conditions of direct incubation with the virus, and exerted no effects on the influenza A virus (IAV) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Interestingly, virucidal activities of ethyl pheophorbides a and b were observed against enveloped but not non-enveloped viruses, suggesting that these compounds act by affecting the integrity of the viral membrane and reducing infectivity. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus latent infection integral membrane protein 1 (LMP1) mimics a constitutively active TNF receptor (TNFR). LMP1 has two C-terminal cytosolic domains, transformation effector sites (TES)1 and -2, that engage TNFR-associated factors (TRAFs) and the TNFR-associated death domain protein, respectively, and activate NF-[kappa]B. NF-[kappa]B activation is critical for Epstein-Barr virus-infected lymphoblast survival. TES1- and TES2-mediated NF-[kappa]B activations are IL-1 receptor-associated kinase 1 (IRAK1)-dependent. Because IRAK1 is upstream of TRAF6 in IL-1 activation of NF-[kappa]B, the potential role of IRAK1 in LMP1-mediated NF-[kappa]B activation through TRAF6 and inhibitor of [kappa]B (I[kappa]B) kinase (IKK) was initially investigated. Surprisingly, LMP1 expression activated TRAF6 ubiquitination, IKK[beta] induction of I[kappa]B[alpha] phosphorylation, and p65 nuclear translocation in both WT and IRAK1-deficient I1A 293 cells. LMP1 also induced IKK[alpha]-mediated p100 processing and p52 nuclear localization in WT and IRAK1-deficient I1A 293 cells. Further, LMP1 TES1 and TES2 induced p65, p50, and p52 NF-[kappa]B DNA binding in WT and IRAK1-deficient I1A 293 cells. However, LMP1 induced p65/ RelA S536 phosphorylation only in WT 293 cells or in IRAK1 kinase point mutant reconstituted I1A 293 cells but not in IRAK1-deficient I1A 293 cells. IRAK1 was also required for LMP1 activation of p38, one of the kinases that can mediate p65/RelA S536 phosphorylation and activate NF-[kappa]B-dependent transcription. Thus, the critical IRAK1 role in LMP1-induced NF-[kappa]B activation is in mediating p65/ReIA S536 phosphorylation through an effect on p38 or other p65 S536 kinases.

We have previously reported that seventy percent ethanol extract of Chrysanthemum indicum Linne (CIE) strongly reduces Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line (LCL) survival by inhibiting virus-encoded latent infection membrane protein 1 (LMP1)-induced NF-κB activation. To identify an active compound(s) in CIE that inhibits LMP1-induced NF-κB activation, activity-guided fractionation was employed. The CH2Cl2 fraction of CIE strongly reduced LMP1-induced NF-κB activation and LCL viability with relatively low cytotoxic effects on primary human foreskin fibroblast (HFF), HeLa or Burkitt’s lymphoma (BL41) cells. Furthermore, lupeol, a pentacyclic triterpene, was identified in the CH2Cl2 fraction of CIE to attenuate LMP1-induced NF-κB activation and LCL viability. This study demonstrates that lupeol is one of active compounds in the CH2Cl2 fraction of CIE that inhibits LMP1-induced NF-κB activation and reduces NF-κB-dependent LCL viability. [ABSTRACT FROM AUTHOR]

Silicon dioxide (SiO2) and zinc oxide (ZnO) nanoparticles are widely used in various applications, raising issues regarding the possible adverse effects of these metal oxide nanoparticles on human cells. In this study, we determined the cytotoxic effects of differently charged SiO2 and ZnO nanoparticles, with mean sizes of either 100 or 20 nm, on the U373MG human glioblastoma cell line. The overall cytotoxicity of ZnO nanoparticles against U373MG cells was significantly higher than that of SiO2 nanoparticles. Neither the size nor the surface charge of the ZnO nanoparticles affected their cytotoxicity against U373MG cells. The 20 nm SiO2 nanoparticles were more toxic than the 100 nm nanoparticles against U373MG cells, but the surface charge had little or no effect on their cytotoxicity. Both SiO2 and ZnO nanoparticles activated caspase-3 and induced DNA fragmentation in U373MG cells, suggesting the induction of apoptosis. Thus, SiO2 and ZnO nanoparticles appear to exert cytotoxic effects against U373MG cells, possibly via apoptosis.