start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=23 article-no= start-page=5992 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comprehensive Identification of PTI Suppressors in Type III Effector Repertoire Reveals that Ralstonia solanacearum Activates Jasmonate Signaling at Two Different Steps en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ralstonia solanacearum is the causative agent of bacterial wilt in many plants. To identify R. solanacearum effectors that suppress pattern-triggered immunity (PTI) in plants, we transiently expressed R. solanacearum RS1000 effectors in Nicotiana benthamiana leaves and evaluated their ability to suppress the production of reactive oxygen species (ROS) triggered by flg22. Out of the 61 effectors tested, 11 strongly and five moderately suppressed the flg22-triggered ROS burst. Among them, RipE1 shared homology with the Pseudomonas syringae cysteine protease effector HopX1. By yeast two-hybrid screening, we identified jasmonate-ZIM-domain (JAZ) proteins, which are transcriptional repressors of the jasmonic acid (JA) signaling pathway in plants, as RipE1 interactors. RipE1 promoted the degradation of JAZ repressors and induced the expressions of JA-responsive genes in a cysteine-protease-activity-dependent manner. Simultaneously, RipE1, similarly to the previously identified JA-producing effector RipAL, decreased the expression level of the salicylic acid synthesis gene that is required for the defense responses against R. solanacearum. The undecuple mutant that lacks 11 effectors with a strong PTI suppression activity showed reduced growth of R. solanacearum in Nicotiana plants. These results indicate that R. solanacearum subverts plant PTI responses using multiple effectors and manipulates JA signaling at two different steps to promote infection. en-copyright= kn-copyright= en-aut-name=NakanoMasahito en-aut-sei=Nakano en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiharaTakafumi en-aut-sei=Mukaihara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Biological Sciences, Okayama (RIBS) kn-affil= en-keyword=Ralstonia solanacearum kn-keyword=Ralstonia solanacearum en-keyword=type III effector kn-keyword=type III effector en-keyword=jasmonic acid kn-keyword=jasmonic acid en-keyword=salicylic acid kn-keyword=salicylic acid en-keyword=Nicotiana plants kn-keyword=Nicotiana plants END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=23 article-no= start-page=5885 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I-2) (PGI(2)), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI(2)), phosphodiesterase type-5 (PDE5) inhibitors, and endothelin receptor antagonists (ERAs), have been shown to be effective, however, PAH remains a severe clinical condition and the long-term survival of patients with PAH is still suboptimal. The full therapeutic abilities of available drugs are reduced by medication, patient non-compliance, and side effects. Nanoparticles are expected to address these problems by providing a novel drug delivery approach for the treatment of PAH. Drug-loaded nanoparticles for local delivery can optimize the efficacy and minimize the adverse effects of drugs. Prostacyclin (PGI(2)) analogue, PDE5 inhibitors, ERA, pitavastatin, imatinib, rapamycin, fasudil, and oligonucleotides-loaded nanoparticles have been reported to be effective in animal PAH models and in vitro studies. However, the efficacy and safety of nanoparticle mediated-drug delivery systems for PAH treatment in humans are unknown and further clinical studies are required to clarify these points. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsubaraHiromi en-aut-sei=Matsubara en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Cardiology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=10 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=prostaglandin I-2 kn-keyword=prostaglandin I-2 en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=endothelin kn-keyword=endothelin END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=23 article-no= start-page=6078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multipotent Neurotrophic Effects of Hepatocyte Growth Factor in Spinal Cord Injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spinal cord injury (SCI) results in neural tissue loss and so far untreatable functional impairment. In addition, at the initial injury site, inflammation induces secondary damage, and glial scar formation occurs to limit inflammation-mediated tissue damage. Consequently, it obstructs neural regeneration. Many studies have been conducted in the field of SCI; however, no satisfactory treatment has been established to date. Hepatocyte growth factor (HGF) is one of the neurotrophic growth factors and has been listed as a candidate medicine for SCI treatment. The highlighted effects of HGF on neural regeneration are associated with its anti-inflammatory and anti-fibrotic activities. Moreover, HGF exerts positive effects on transplanted stem cell differentiation into neurons. This paper reviews the mechanisms underlying the therapeutic effects of HGF in SCI recovery, and introduces recent advances in the clinical applications of HGF therapy. en-copyright= kn-copyright= en-aut-name=YamaneKentaro en-aut-sei=Yamane en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MisawaHaruo en-aut-sei=Misawa en-aut-mei=Haruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakigawaTomoyuki en-aut-sei=Takigawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoYoshihiro en-aut-sei=Ito en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Intelligent Orthopaedic System Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Nano Medical Engineering Laboratory, RIKEN kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=hepatocyte growth factor kn-keyword=hepatocyte growth factor en-keyword=spinal cord injury kn-keyword=spinal cord injury en-keyword=neural regeneration kn-keyword=neural regeneration END