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Showing papers by "Shiro Kobayashi published in 2022"


Journal ArticleDOI
TL;DR: A new type of pH-responsive PGA-based hydrogels comprised of poly(γ-glutamic acid) modified with tyramine (PGA-Tyr) was developed through enzymatic cross-linking in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2).
Abstract: pH-responsive hydrogels are important for oral drug release applications, and they are increasingly demanded to reduce the adverse side effects of drug release and improve drug absorption. In this study, a new type of pH-responsive hydrogel comprised of poly(γ-glutamic acid) modified with tyramine (PGA-Tyr) was developed through enzymatic cross-linking in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation rate, stiffness, swelling behavior, and pore size of the resulting hydrogels were tuned by changing the concentrations of HRP and H2O2 or the degree of substitution (DS) of PGA-Tyr. The pH responsiveness of the hydrogels was evaluated by the swelling ratio in solutions with various pH values, and their pH responsiveness exhibited a good reversibility in pH 2.0 and 7.0 solutions. The degradation rate of the hydrogels in simulated intestinal fluid (SIF) was faster than that in simulated gastric fluid (SGF). Moreover, indomethacin (IM), a hydrophobic drug model, was encapsulated in the hydrogels by rapid in situ gelation, and the pH-dependent drug release of IM-loaded hydrogels was achieved in SGF and SIF. Importantly, when IM was entrapped in pluronic F-127 to form drug micelles, the burst release of the IM-micelle-loaded hydrogels with a high DS of PGA-Tyr was remarkably decreased in SGF, and sustained drug release was presented in SIF. Thus, pH-responsive PGA-based hydrogels have tremendous promise for biomedical applications, especially oral drug delivery.

6 citations


Journal ArticleDOI
TL;DR: In this article , the authors isolated a novel TBEV strain from a tick (Ixodes ovatus) collected on a dog from central Hokkaido, which was classified under a different subcluster of other Japanese isolates.

3 citations


Journal ArticleDOI
TL;DR: In this article , the role of a Y-shaped secondary structure in the pathogenicity of TBEV was analyzed using reverse genetics, and the results indicated that the secondary structure is involved in the regulation of tBEV pathogenesis.
Abstract: Tick‐borne encephalitis virus (TBEV) is a zoonotic virus that causes encephalitis in humans. Various deletions have been reported in a variable region of the 3′ untranslated region of the TBEV genome. This study analyzed the role of a Y‐shaped secondary structure in the pathogenicity of TBEV by using reverse genetics. Deletion of the structure increased the mortality rate of virus‐infected mice but did not affect the virus multiplication in cultured cells and organs. The results indicate that the secondary structure is involved in the regulation of TBEV pathogenesis.

1 citations


Journal ArticleDOI
TL;DR: In this paper , the role of autophagy in TBEV replication was investigated in mouse macrophage cell line PMJ2-R using Hypr strain of tBEV and the results showed that during an early stage of infection the viral titers were increased, while later on, at 72 hpi, the titers have declined in shAtg5 cells compared to control.

Journal ArticleDOI
TL;DR: In this paper , the authors examined neuronal degeneration and death, and activation of glial cells in mice inoculated with each strain to investigate the pathogenesis of TBEV in mice.

Journal ArticleDOI
TL;DR: In this paper , the role of autophagy in PUUV-Hok replication was examined and it was shown that autophagia was induced by infection by the Hokkaido genotype of PUUMALA orthohantavirus.

DOI
TL;DR: In this article , an orbit calculation for a probe beam is performed to verify feasibility of the heavy ion beam probe (HIBP) in the CFQS, and the required beam energy, possible ion species and the observable region in a CFQs plasma are investigated.
Abstract: The world’s first quasi-axisymmetric stellarator, CFQS, is now under construction. The CFQS will be dedicated to studies on the interaction between flow and turbulence, and confinement improvement by suppression of turbulence in connection with proof-of-principle experiment of quasi-axisymmetry. In order to conduct this experimental research, a heavy ion beam probe (HIBP) system is planned to be installed and utilized to measure the radial electric field and its fluctuation in a CFQS plasma. In this paper, an orbit calculation for a probe beam is performed to verify feasibility of the HIBP in the CFQS. The required beam energy, possible ion species, and the observable region in a CFQS plasma are investigated. The beam attenuation by a CFQS plasma is also estimated for different beam ion species. If we use 133Cs+ as a primary probe beam, the required beam energy is expected to be 30∼50 keV, which is relatively easy to handle. In this case the beam attenuation, evaluated by the ratio between the injected and detected beam currents, is 10−3∼10−2 in a CFQS plasma with a line-averaged electron density of <1.0 × 1019 m−3. For a higher density plasma, usage of 85Rb+ is better in terms of low-beam-attenuation, and a high signal-to-noise ratio. The HIBP in the CFQS will provide a great opportunity to study physics experimentally, related to the radial electric field, poloidal flow, and turbulence suppression.

Posted ContentDOI
16 Dec 2022-bioRxiv
TL;DR: In this article , the authors used siRNA screening approach and found that the ESCRT-I component TSG101 contributes to the propagation of rabies virus (RABV) and showed that the matrix protein (M) of RABV interacts with TSG 101 via the late domain containing the PY and YL motifs, which are conserved in various viral proteins.
Abstract: Viral protein assembly and virion budding are tightly regulated to enable the proper formation of progeny virions. At this late stage in the virus life cycle, some enveloped viruses take advantage of the host ESCRT (endosomal sorting complex required for transport) machinery, which contributes to the physiological functions of membrane modulation and abscission. Bullet-shaped viral particles are unique morphological characteristics of rhabdoviruses; however, the involvement of host factors in rhabdovirus infection, and specifically the molecular mechanisms underlying virion formation are not fully understood. In the present study, we used a siRNA screening approach and found that the ESCRT-I component TSG101 contributes to the propagation of rabies virus (RABV). We demonstrated that the matrix protein (M) of RABV interacts with TSG101 via the late-domain containing the PY and YL motifs, which are conserved in various viral proteins. Loss of the YL motif in the RABV M or the downregulation of host TSG101 expression resulted in the intracellular aggregation of viral proteins and abnormal virus particle formation, indicating a defect in the RABV assembly and budding processes. These results indicate that the interaction of the RABV M and TSG101 is pivotal for not only the efficient budding of progeny RABV from infected cells but also for the bullet-shaped virion morphology. Importance Enveloped-viruses bud from cells with the host lipid bilayer. Generally, the membrane modulation and abscission are mediated by host ESCRT (endosomal sorting complex required for transport) complexes. Some enveloped-viruses utilize their late (L)-domain to interact with ESCRTs, which promotes viral budding. Rhabdoviruses form characteristic bullet-shaped enveloped-virions, but the underlying molecular mechanisms involved remain elusive. Herein, we showed that TSG101, one of ESCRT components, supports rabies virus (RABV) budding and proliferation. TSG101 interacted with RABV matrix protein via L-domain, and the absence of this interaction resulted in intracellular virion accumulation and distortion of the morphology of progeny virions. Our study reveals that virion formation of RABV is highly regulated by TSG101 and the virus matrix protein.