The Role of Vitamin A-Storing Cells (Stellate Cells) in Inflammation and Tumorigenesis

Characteristic localization and distribution of vitamin A-storing cells (stellate cells) were demonstrated as hepatic stellate cells in the hepatic lobule and as subepithelial myofibroblasts in the colonic crypt. The stem cell-stem cell niche is maintained by stellate cells in the periportal area and crypt base. Periportal vitamin A-rich stellate cells decrease in patients with chronic hepatitis C who are habitual smokers. Mice fed a vitamin A-supplemented diet show reduced severity of dextran sulfate sodium (DSS)-induced colitis and development of subsequent colonic neoplasia in a model of the ulcerative colitis-dysplasia-carcinoma sequence, compared with mice fed a vitamin A-deficient diet. Decreased colonic subepithelial myofibroblasts and IgA/IgG-positive cells, and increased CD11c-positive dendritic cells in the colonic mucosa, in the vitamin A-deficient state suggest dysfunction of the stem cell niche at the colonic crypt base and colonic immunity. Accordingly, vitamin A deficiency may worsen inflammation and subsequent tumor development, indicating the possibility that vitamin A supplementation might be effective against chronic inflammation and cancer development

自然環境より単離したThibacilus ferroxidansの鉄酸化酵素及び硫化水素酸化酵素活性

It has been reported that both iron oxidase and hydrogen sulfide: ferric ion oxidoreductase (SFORase) were involved in bacterial leaching of metal ions from sulfide ores, and the amount of Cu2+ solubilized from copper ore by iron-oxidizing bacterium differed from strain. The activities of iron oxidase SFORase of iron-oxidizing bacteria isolated from the natural environments were determined. Iron-oxidizing activity and SFORase activity of 200 strains ranged from 1.20-1.65γmol/mg/min and from 0.11-2.80 γmol/mg/min, respectively. The findings that a remarkable difference was observed in the levels of SFORase activity, but not in iron-oxidizing activity, suggest that SFORase, but not iron oxidase, is the enzyme that determines the bacterial leaching activity of this bacterium.鉄酸化酵素と硫化水素酸化酵素の両方が硫化鉱石からの金属イオンのバクテリアリーチングに関与していること、銅鉱石から溶出する銅イオンの量が鉄酸化細菌の菌株間で異なることが知られている。鉄酸化酵素及び硫化水素酸化酵素活性が自然環境から単離した鉄酸化細菌に対して決定された。200株の鉄酸化細菌の鉄酸化酵素及び硫化水素酸化酵素活性は、それぞれ、1.20-1.65γmol/mg/min及び0.11-2.80γmol/mg/minの範囲にあった。これら菌株間において、鉄酸化酵素ではなく硫化水素酸化酵素活性に大きく違いがあるという発見は、前者ではなく後者がこの細菌のバクテリアリーチング活性を決定する酵素であることを示唆している

Stereodivergent Synthesis and Stereochemical Reassignment of the C79-C104 Fragment of Symbiodinolide

We have synthesized eight possible diastereoisomers 3 a-h of the C79-C97 fragment of symbiodinolide (1) in a stereodivergent manner by utilizing a dithiane addition to the aldehyde as a key step. Comparison of the 13 C NMR chemical shifts of the natural product 1 and the synthetic products 3 a-h indicated that the relative stereostructure of this fragment in symbiodinolide (1) is that represented in 3 a or f. We have stereodivergently synthesized eight possible diastereoisomers of the C94-C104 fragment 4 a-h, and we have compared their 13 C NMR chemical shifts with those of the natural product, which established the relative stereochemistry of this fragment to be that described in diastereoisomers 4 a or e. By combining the stereostructural outcomes of the C79-C97 and C94-C104 fragments, we have proposed four candidate compounds of the C79-C104 fragment 2 a-d. We also synthesized diastereoisomers 2 a and b (2 a in the preceding article; Chem. Eur. J. 2015, DOI: 10.1002/chem.201503880) by a Julia-Kocienski olefination and diastereoisomers 2 c and d by a Wittig reaction. By comparing the 13 C NMR chemical shifts of natural symbiodinolide (1) with those of the synthetic products 2 a-d, we have reassigned the stereostructure of the C79-C104 fragment of natural product 1 to be that depicted in diastereoisomer 2 b

Stereoselective Synthesis of the Proposed C79-C104 Fragment of Symbiodinolide

Stereoselective and streamlined synthesis of the proposed C79-C104 fragment 2 of symbiodinolide (1), a polyol marine natural product with a molecular weight of 2860, was achieved. In the synthetic route, the proposed C79-C104 fragment 2 was synthesized by utilizing a Julia-Kocienski olefination and subsequent Sharpless asymmetric dihydroxylation as key transformations in a convergent manner. Detailed comparison of the 13 C NMR chemical shifts between the natural product and the synthetic C79-C104 fragment 2 revealed that the stereostructure at the C91-C99 carbon chain moiety of symbiodinolide (1) should be reinvestigated

Percutaneous sclerotherapy for venous malformations using polidocanol under fluoroscopy.

This retrospective study evaluated the safety and efficacy of using polidocanol with X-ray fluoroscopy for percutaneous sclerotherapy of venous malformations of the limbs, head, and neck. The subjects were 16 of 18 patients who presented to our department with venous malformations. Two patients were excluded because they were unlikely to benefit from the treatment. Of the 16 included in the study, 1 could not be treated because of inaccessibility, and another was lost to follow-up. Among the 14 cases that we were able to follow-up, 11 cases had had pain as their primary symptom. Following treatment, this symptom remained unchanged in 1 patient, was improved in 4, and had disappeared in 6; however, there was a recurrence of pain for 3 of these patients. Two patients had sought treatment for cosmetic purposes; following treatment, the lesion disappeared in one and showed a significant reduction in the other. The remaining patient presented with a primary symptom of mouth bleeding, which disappeared following treatment. There were no critical complications. Percutaneous sclerotherapy of venous malformations using polidocanol is safe and effective, and permits repeat treatments. The efficacy is especially good for resolving pain, and complications are minor. It is desirable to use fluoroscopy for these procedures</p

酸化型HMGB-1は間葉系幹細胞/間葉系細胞を介して大腸癌の転移性を促進する

High mobility group box-1 (HMGB1) is known to be a chemotactic factor for mesenchymal stem/stromal cells (MSCs), but the effect of post-translational modification on its function is not clear. In this study, we hypothesized that differences in the oxidation state of HMGB1 would lead to differences in the function of MSCs in cancer. In human colorectal cancer, MSCs infiltrating into the stroma were correlated with liver metastasis and serum HMGB1. In animal models, oxidized HMGB1 mobilized three-fold fewer MSCs to subcutaneous tumors compared with reduced HMGB1. Reduced HMGB1 inhibited the proliferation of mouse bone marrow MSCs (BM-MSCs) and induced differentiation into osteoblasts and vascular pericytes, whereas oxidized HMGB1 promoted proliferation and increased stemness, and no differentiation was observed. When BM-MSCs pretreated with oxidized HMGB1 were co-cultured with syngeneic cancer cells, cell proliferation and stemness of cancer cells were increased, and tumorigenesis and drug resistance were promoted. In contrast, co-culture with reduced HMGB1-pretreated BM-MSCs did not enhance stemness. In an animal orthotopic transplantation colorectal cancer model, oxidized HMGB1, but not reduced HMGB1, promoted liver metastasis with intratumoral MSC chemotaxis. Therefore, oxidized HMGB1 reprograms MSCs and promotes cancer malignancy. The oxidized HMGB1–MSC axis may be an important target for cancer therapy.博士（医学）・甲第874号・令和5年3月15

Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana

Human DNA polymerase η (HsPolη) plays an important role in translesion synthesis (TLS), which allows for replication past DNA damage such as UV-induced cis-syn cyclobutane pyrimidine dimers (CPDs). Here, we characterized ApPolη from the thermophilic worm Alvinella pompejana, which inhabits deep-sea hydrothermal vent chimneys. ApPolη shares sequence homology with HsPolη and contains domains for binding ubiquitin and proliferating cell nuclear antigen. Sun-induced UV does not penetrate Alvinella's environment; however, this novel DNA polymerase catalyzed efficient and accurate TLS past CPD, as well as 7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species. In addition, we found that ApPolη is more thermostable than HsPolη, as expected from its habitat temperature. Moreover, the activity of this enzyme was retained in the presence of a higher concentration of organic solvents. Therefore, ApPolη provides a robust, human-like Polη that is more active after exposure to high temperatures and organic solvents