対外関係からみた鎌倉時代

学位の種別:課程博士University of Tokyo(東京大学

Morphological Studies on Seeds of Scrophulariaceae s.l. and Their Systematic Significance

This study employed scanning electron microscopy and light microscopy to observe seed surface micromorphology and seed coat anatomy in the Scrophulariaceae s.l. to investigate seed characters of taxonomic importance. Seeds of 41 taxa corresponding to 13 genera of the family were carefully investigated. Seeds were minute and less than or slightly larger than 1 millimeter in length except for Melampyrum and Pedicularis species. The seed shape ranged from elliptical to broad elliptical and ovoid. In the studied species the surface sculpture was predominantly reticulate-striate, regular reticulate, sometimes colliculate, and rugose, or - rarely - ribbed, as in Lindernia procumbens and Paulownia coreana. Seed coats comprised the epidermis and the endothelium. Nevertheless, in all Melampyrum and some Veronica species the seed coat was very poorly represented and only formed by a papery layer of epidermis. According to correspondence analysis (CA) and unweighted pair group method with arithmetic mean (UPGMA) based cluster analysis the close affinities among the species of Scrophularia were well supported by their proximity to one another. Similarly, the proximity of Melampyrum species and Pedicularis species cannot be denied. In contrast, Veronica species were divided into two groups in CA plots and even three in the UPGMA tree. Regardless of the limited range taxa considered we found that similarities and differences in seed morphology between different genera could help us to understand the systematic relationships involved

The Therapeutic Effect of STAT3 Signaling-Suppressed MSC on Pain and Articular Cartilage Damage in a Rat Model of Monosodium Iodoacetate-Induced Osteoarthritis

Osteoarthritis (OA) is a degenerative disease that induces pain, cartilage deformation, and joint inflammation. Mesenchymal stem cells (MSCs) are potential therapeutic agents for treatment of OA. However, MSC therapy can cause excessive inflammation. Signal transducer and activator of transcription 3 (STAT3) modulates secretion of many proinflammatory cytokines. Experimental OA was induced by intra-articular (IA) injection of monosodium iodoacetate (MIA) to the right knee of rats. MSCs from OA patients (OA-MSCs) were treated with STA21, a small molecule that blocks STAT3 signaling, by IA or intravenous (IV) injection after MIA injection. Pain severity was quantified by assessment of secondary tactile allodynia using the von Frey assessment test. Cartilage degradation was measured by microcomputed tomography image analysis, histological analysis, and the Mankin score. Protein and gene expression was evaluated by enzyme-linked immunosorbent assay, immunohistochemistry, and real-time polymerase chain reaction. MSCs increased production of proinflammatory cytokines under inflammatory conditions. STA21 significantly decreased expression of these proinflammatory molecules via inhibition of STAT3 activity but increased gene expression of molecules related to migration potential and immunomodulation in OA-MSCs. STAT3-inhibited OA-MSCs administrated by IV or IA injection decreased pain severity and cartilage damage in rats with MIA-induced OA rats by decreasing proinflammatory cytokines in the joints. Combined IA and IV-injected STAT3-inhibited OA-MSCs had an additive effect of pain relief in MIA-induced OA rats. STAT3 inhibition may optimize the therapeutic activities of MSCs for treating OA by attenuating pain and progression of MIA by inhibiting inflammation and cartilage damage

IS6110-Restriction Fragment Length Polymorphism and Spoligotyping Analysis of Mycobacterium tuberculosis Clinical Isolates for Investigating Epidemiologic Distribution in Korea

The Beijing family of Mycobacterium tuberculosis has been emerging in the world. However, there are few nationwide data of genotypic distribution in Korea. This study aimed to identify the genotypic diversity of clinical isolates of M. tuberculosis and to demonstrate the population of Beijing family in Korea. We collected 96 clinical M. tuberculosis isolates from 11 university hospitals nationwide in Korea from 2008 to 2009. We observed 24 clusters in IS6110-RFLP analysis and 19 patterns in spoligotyping. Seventy-five isolates were confirmed to be Beijing family. Two isolates of the K strain and 12 isolates of the K family strain were also found. We found that drug resistance phenotypes were more strongly associated with Beijing family than non-Beijing family (P=0.003). This study gives an overview of the distribution of genotypes of M. tuberculosis in Korea. These findings indicate that we have to pay more attention to control of M. tuberculosis strains associated with the Beijing family

Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function

IntroductionDysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolites, and SpA pathogenesis.MethodUsing 16S rRNA sequencing data derived from feces samples of 33 axSpA patients and 20 healthy controls (HCs), we examined the compositions of their gut microbiomes.ResultsAs a result, axSpA patients were found to have decreased α-diversity compared to HCs, indicating that axSpA patients have less diverse microbiomes. In particular, at the species level, Bacteroides and Streptococcus were more abundant in axSpA patients than in HCs, whereas Faecalibacterium (F). prausnitzii, a butyrate-producing bacteria, was more abundant in HCs. Thus, we decided to investigate whether F. prausnitzii was associated with health conditions by inoculating F. prausnitzii (0.1, 1, and 10 μg/mL) or by administrating butyrate (0.5 mM) into CD4+ T cells derived from axSpA patients. The levels of IL-17A and IL-10 in the CD4+ T cell culture media were then measured. We also assessed osteoclast formation by administrating butyrate to the axSpA-derived peripheral blood mononuclear cells. The CD4+ IL-17A+ T cell differentiation, IL-17A levels were decreased, whereas IL-10 was increased by F. prausnitzii inoculation. Butyrate reduced CD4+ IL-17A+ T cell differentiation and osteoclastogenesis.DiscussionWe found that CD4+ IL-17A+ T cell polarization was reduced, when F. prausnitzii or butyrate were introduced into curdlan-induced SpA mice or CD4+ T cells of axSpA patient. Consistently, butyrate treatment was associated with the reduction of arthritis scores and inflammation levels in SpA mice. Taken together, we concluded that the reduced abundance of butyrate-producing microbes, particularly F. prausnitzii, may be associated with axSpA pathogenesis

Theoretical study on the interaction between candidate drugs and Coronavirus main protease (3CLPro) for inhibiting replication of SARS-CoV-2

We theoretically investigated the interactions of drug molecules with 3C-like protease (3CLPro), to inhibit the replication of SARS-CoV-2 using molecular dynamics (MD) simulation. Lopinavir, Ritonavir, CG376 and dipeptidyl series were used at different temperatures and concentrations. The adsorption behavior of drug candidates was compared by analyzing the root mean square fluctuation (RMSF) of 3CLPro, minimum distances and interaction energies between 3CLPro and drug and radial distribution function(RDF). The drugs were mainly adsorbed on the 3CLpro by the polar interactions. In specifically, dipeptidyl 7a was effective in inhibiting 3CLPro since it shows high binding energy, high number of attached active sites 3CLPro and compared to those of dipeptidyl 6c. In specifically, alkyl groups within drugs mainly sticked to the active sites of 3CLPro. As higher concentration, the interactions between drugs and the protein were increased, which was shown by larger adsorption area of drugs on the protein, and however, average of interaction energy is lower. Meanwhile, the number of adsorbed drugs was similar in different temperature of the drug