| 1. |
- Furuta, Shunsuke, et al.
(författare)
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Comparison of phenotype and outcome in microscopic polyangiitis between europe and Japan.
- 2014
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 41:2, s. 325-333
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Tidskriftsartikel (refereegranskat)abstract
- There are differences between Europe and Japan in the incidence and antineutrophil cytoplasmic antibody (ANCA) serotype of patients with microscopic polyangiitis (MPA). However, differences in phenotype or outcome have not been explored. We aimed to identify differences in phenotype and outcome of MPA between Europe and Japan.
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| 2. |
- Shoda, Jumpei, et al.
(författare)
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Semaphorin 3G exacerbates joint inflammation through the accumulation and proliferation of macrophages in the synovium
- 2022
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Ingår i: Arthritis Research & Therapy. - : BioMed Central (BMC). - 1478-6362. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA). However, the precise mechanisms by which MTX stalls RA progression and alleviates the ensuing disease effects remain unknown. The aim of the present study was to identify novel therapeutic target molecules, the expression patterns of which are affected by MTX in patients with RA. Methods CD4(+) T cells from 28 treatment-naive patients with RA before and 3 months after the initiation of MTX treatment were subjected to DNA microarray analyses. The expression levels of semaphorin 3G, a differentially expressed gene, and its receptor, neuropilin-2, were evaluated in the RA synovium and collagen-induced arthritis synovium. Collagen-induced arthritis and collagen antibody-induced arthritis were induced in semaphorin3G-deficient mice and control mice, and the clinical score, histological score, and serum cytokines were assessed. The migration and proliferation of semaphorin 3G-stimulated bone marrow-derived macrophages were analyzed in vitro. The effect of local semaphorin 3G administration on the clinical score and number of infiltrating macrophages during collagen antibody-induced arthritis was evaluated. Results Semaphorin 3G expression in CD4(+) T cells was downregulated by MTX treatment in RA patients. It was determined that semaphorin 3G is expressed in RA but not in the osteoarthritis synovium; its receptor neuropilin-2 is primarily expressed on activated macrophages. Semaphorin3G deficiency ameliorated collagen-induced arthritis and collagen antibody-induced arthritis. Semaphorin 3G stimulation enhanced the migration and proliferation of bone marrow-derived macrophages. Local administration of semaphorin 3G deteriorated collagen antibody-induced arthritis and increased the number of infiltrating macrophages. Conclusions Upregulation of semaphorin 3G in the RA synovium is a novel mechanism that exacerbates joint inflammation, leading to further deterioration, through macrophage accumulation.
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| 3. |
- Tsuchiya, Maiko, et al.
(författare)
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A Novel, Tumor-Induced Osteoclastogenesis Pathway Insensitive to Denosumab but Interfered by Cannabidiol
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 20:24
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Tidskriftsartikel (refereegranskat)abstract
- Bone metabolism is strictly regulated, and impaired regulation caused by hormonal imbalances induces systemic bone loss. Local bone loss caused by tumor invasion into bone is suggested to be induced by the generation of cytokines, which affect bone metabolism, by tumor cells. The major cause of systemic and local bone losses is excess bone resorption by osteoclasts, which differentiate from macrophages by receptor activator of nuclear factor kappa-B ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha). We previously found a novel pathway for tumor-induced osteoclastogenesis targeting osteoclast precursor cells (OPCs). Tumor-induced osteoclastogenesis was resistant to RANKL and TNF-alpha inhibitors. In the present study, we confirmed that exosomes derived from oral squamous cell carcinoma (OSCC) cells induced osteoclasts from OPCs. We also showed that the depletion of exosomes from culture supernatants of OSCC cells partially interfered with osteoclastogenesis, and cannabidiol, an innoxious cannabinoid without psychotropic effects, almost completely suppressed tumor-induced osteoclastogenesis. Osteoclastogenesis and its interference by cannabidiol were independent of the expression of nuclear factor of T cell c1 (NFATc1). These results show that osteoclastogenesis induced by OSCC cells targeting OPCs is a novel osteoclastogenic pathway independent of NFATc1 expression that is partially caused by tumor-derived exosomes and suppressed by cannabidiol.
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| 4. |
- Yabuta, Hikaru, et al.
(författare)
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Macromolecular organic matter in samples of the asteroid (162173) Ryugu
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 379:6634
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Tidskriftsartikel (refereegranskat)abstract
- Samples of the carbonaceous asteroid (162173) Ryugu were collected and brought to Earth by the Hayabusa2 spacecraft. We investigated the macromolecular organic matter in Ryugu samples and found that it contains aromatic and aliphatic carbon, ketone, and carboxyl functional groups. The spectroscopic features of the organic matter are consistent with those in chemically primitive carbonaceous chondrite meteorites that experienced parent-body aqueous alteration (reactions with liquid water). The morphology of the organic carbon includes nanoglobules and diffuse carbon associated with phyllosilicate and carbonate minerals. Deuterium and/or nitrogen-15 enrichments indicate that the organic matter formed in a cold molecular cloud or the presolar nebula. The diversity of the organic matter indicates variable levels of aqueous alteration on Ryugus parent body.
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