48 research outputs found
Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation
上皮バリアを形成するペプチドJIPの発見 --JIPは上皮組織修復に貢献する--. 京都大学プレスリリース. 2021-11-18.Epithelial barriers that prevent dehydration and pathogen invasion are established by tight junctions (TJs), and their disruption leads to various inflammatory diseases and tissue destruction. However, a therapeutic strategy to overcome TJ disruption in diseases has not been established because of the lack of clinically applicable TJ-inducing molecules. Here, we found TJ-inducing peptides (JIPs) in mice and humans that corresponded to 35 to 42 residue peptides of the C terminus of alpha 1-antitrypsin (A1AT), an acute-phase anti-inflammatory protein. JIPs were inserted into the plasma membrane of epithelial cells, which promoted TJ formation by directly activating the heterotrimeric G protein G13. In a mouse intestinal epithelial injury model established by dextran sodium sulfate, mouse or human JIP administration restored TJ integrity and strongly prevented colitis. Our study has revealed TJ-inducing anti-inflammatory physiological peptides that play a critical role in tissue repair and proposes a previously unidentified therapeutic strategy for TJ-disrupted diseases
Longitudinal study of dental caries incidence associated with Streptococcus mutans and Streptococcus sobrinus in patients with intellectual disabilities
Serum cytokine and chemokine profiles in patients with immune-mediated necrotizing myopathy
ロウジン ホケン シセツ ニュウショシャ ノ カンケイセイ ノ ニード ト コーピング ニ カンスル ケンキュウ
本研究は、老人保健施設入所者の関係性のニードとコーピングの特徴を明らかにすることを目的とした。研究方法は、半構成的質問紙による入所者へのインタビューを行い、質的帰納的に分析した。その結果、関係性のニードを説明する概念は、職員に対しては「承認と尊敬の欲求」、「依存の欲求」であり、家族に対しては「愛情欲求」であった。また、他の入所者に対しては「親和欲求」、「個人的空間確保の欲求」であり、施設外の人々に対しては「地域社会への交流と参加の欲求」であった。老人保健施設入所者の関係性のニードに対するコーピングを説明する概念は、「ニード抑圧行動」。 「ニード温存行動」、「ニード充足行動」であった。そして、老人保健施設人所者は、「ニード抑圧行動」のコーピングパターンが多いという特徴を示した
Internal motions of actin characterized by quasielastic neutron scattering
International audienceQuasielastic neutron scattering (QENS) experiments were carried out on powders of F-actin and G-actin hydrated with D 2 O to characterize the internal dynamics on the picosecond time scale and the A ˚ ngstrom length scale. To investigate the effects of hydration, the measurements were done on samples at hydration ratio (h) of 0.4 (mg D 2 O/mg protein), containing only the first layer of hydra-tion water, and at h = 1.0, containing more layers of water. The QENS spectra, obtained from the measurements at two energy resolutions of 110 and 15 leV, indicated that the internal motions of both F-actin and G-actin have distributions of motions with distinct correlation times and amplitudes. Increasing hydration changes relative populations of these distinct motions. The effects of hydration were shown to be different between F-actin and G-actin. Elastic incoherent neutron scattering measurements provided the concerted results. The observed effects were interpreted in terms of the dynamical heterogeneity of the actin molecule: in G-actin, more surface loops become flexible and undergo diffusive motions of large amplitudes, whereas in F-actin the molecular interactions that keep the polymerized state suppress the large motions of the surface loops involved with polymerization so that the population of atoms undergoing large motions can increase only to a lesser degree
An alternative allosteric regulation mechanism of an acidophilic l-lactate dehydrogenase from Enterococcus mundtii 15-1A
A plant-derived Enterococcus mundtii 15-1A, that has been previously isolated from Brassica rapa L. subsp. nipposinica (L.H. Bailey) Hanelt var. linearifolia by our group, possesses two kinds of l-lactate dehydrogenase (l-LDH): LDH-1 and LDH-2. LDH-1 was activated under low concentration of fluctose-1,6-bisphosphate (FBP) at both pH 5.5 and 7.5. Although LDH-2 was also activated under the low concentration of FBP at pH 5.5, a high concentration of FBP is necessary to activate it at pH 7.5. The present study shows the crystal structures of the acidophilic LDH-2 in a complex with and without FBP and NADH. Although the tertiary structure of the ligands-bound LDH-2 is similar to that of the active form of other bacterial l-LDHs, the structure without the ligands is different from that of any other previously determined l-LDHs. Major structural alterations between the two structures of LDH-2 were observed at two regions in one subunit. At the N-terminal parts of the two regions, the ligands-bound form takes an α-helical structure, while the form without ligands displays more disordered and extended structures. A vacuum-ultraviolet circular dichroism analysis showed that the α-helix content of LDH-2 in solution is approximately 30% at pH 7.5, which is close to that in the crystal structure of the form without ligands. A D241N mutant of LDH-2, which was created by us to easily form an α-helix at one of the two parts, exhibited catalytic activity even in the absence of FBP at both pH 5.5 and 7.5
疾患活動性の高い重症筋無力症患者の胸腺ではプラズマブラストが増加している
Background and Objectives
To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact.
Methods
Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated.
Results
The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy.
Discussion
Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG