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Evaluation of varicella zoster virus specific immune response after varicella vaccine immunization in elderly patients with diabetes mellitus. - Varicella zoster virus specific immune response induced by varicella vaccine immunization in old patients with diabetes mellitus.

开始日期2010-11-01

申办/合作机构

National Institute of Biomedical Innovation

JPRN-UMIN000003639

/ Completed临床1/2期IIT

Preventio of varicella zoster virus infection by immunization in aged patients with underlying diseases. - Preventio of varicella zoster by immunization in aged underlying disease patients.

开始日期2010-04-01

申办/合作机构

National Institute of Biomedical Innovation

100 项与 National Institute of Biomedical Innovation 相关的临床结果

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0 项与 National Institute of Biomedical Innovation 相关的专利（医药）

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2,851

项与 National Institute of Biomedical Innovation 相关的文献（医药）

2025-07-01·Biomaterials

Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research

Article

作者: Ueyama-Toba, Yukiko ; Asano, Rei ; Mizuguchi, Hiroyuki ; Nagai, Wakana ; Inui, Jumpei ; Imamura, Chiharu

Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (HLCs) are expected to replace primary human hepatocytes (PHHs) as a new stable source of hepatocytes for pharmaceutical research. However, HLCs have lower hepatic functions than PHHs, require a long time for differentiation and cannot be prepared in large quantities because they do not proliferate after their terminal differentiation. To overcome these problems, we here established hepatic organoids (iHOs) from HLCs. We then showed that the iHOs could proliferate approximately 10⁵-fold by more than 3 passages and expressed most hepatic genes more highly than HLCs. In addition, to enable their widespread use for in vitro drug discovery research, we developed a two-dimensional culture protocol for iHOs. Two-dimensionally cultured iHOs (iHO-Heps) expressed most of the major hepatocyte marker genes at much higher levels than HLCs, iHOs, and even PHHs. The iHO-Heps exhibited glycogen storage capacity, the capacity to uptake and release indocyanine green (ICG), albumin and urea secretion, and the capacity for bile canaliculi formation. Importantly, the iHO-Heps had the activity of major drug-metabolizing enzymes and responded to hepatotoxic drugs, much like PHHs. Thus, iHO-Heps overcome the limitations of the current models and promise to provide robust and reproducible pharmaceutical assays.

2025-06-01·European Journal of Cell Biology

Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids

Article

作者: Mizuguchi, Hiroyuki ; Inui, Tatsuya ; Uraya, Yusei ; Ueyama-Toba, Yukiko

To evaluate the intestinal absorption and metabolism of orally administered drugs, human induced pluripotent stem (iPS) cell‑derived enterocyte‑like cells (ELCs) are expected to be useful. In a previous report, we succeeded in developing a highly functional monolayer platform (ELC-org-mono) from human iPS cell-derived ELCs through an organoid culture and demonstrated its suitability for pharmacokinetic studies. In recent years, the air-liquid interface (ALI) culture model was developed, allowing for the culture of epithelial tissue under conditions that mimic the in vivo environment. In the present study, we applied ALI culture to ELC-org-mono for further improvement of intestinal functions. ALI culture of ELC-org-mono greatly developed goblet cells and enhanced the gene expression levels of many drug-metabolizing enzymes, drug transporters and intestinal differentiation markers. However, their activities were not enhanced. RNA-seq analysis suggested that ALI culture increased the expression of genes related to metabolic processes but decreased glycolytic processes. Analysis of glycolytic capacity confirmed that ALI culture decreased glycolytic activities. Thus, there is room for some adjustment in the ALI culture model to optimize its applicability to pharmacokinetic studies using ELC-org-mono.

2025-06-01·Journal of Oral Biosciences

Identification of PilX, pilus component of Streptococcus sanguinis

Article

作者: Sumitomo, Tomoko ; Matsumoto, Airi ; Nakata, Masanobu ; Oogai, Yuichi ; Takebe, Katsuki ; Migita, Hirono ; Yamaguchi, Masaya ; Okahashi, Nobuo ; Kawabata, Shigetada ; Yixuan, Li

OBJECTIVESStreptococcus sanguinis is an oral commensal bacterium that promotes dental biofilm formation and causes infective endocarditis. S. sanguinis strain SK36 produces pili comprising PilA, PilB, and PilC. This study determined whether the ssa1635 gene adjacent to the pilus-related gene locus encodes a pilus component and its roles in biofilm formation and eukaryotic cell adhesion.METHODSUsing a series of mutant strains and antisera against PilA, PilB, PilC, and SSA1635, immunoblot analyses and immunoprecipitation assays were performed for SSA1635 characterization. Both the involvement of the deduced pilus-specific transpeptidase SrtC in pilus assembly and SSA1635 localization were examined by immunoblot analysis of various mutant strains. Furthermore, biofilm formation assays on saliva-coated surfaces and adhesion to HeLa cells were performed to assess their functions.RESULTSSSA1635, designated as PilX, formed complexes with PilA, PilB, and PilC. PilX was identified as a tip pilin incorporated into the pilus structure by SrtC. Notably, the deletion of pilX impaired the polymerization of other pilins. Furthermore, a pilX deletion mutant exhibited decreased biofilm formation compared with the wild-type and revertant strains and comparable rates of adherence to HeLa cells.CONCLUSIONSPilX is a potential pilin tip that may aid in facilitating the polymerization of other pilins. PilX contributes to biofilm formation, although it appears to be dispensable for adhesion to HeLa cells. Further characterization of PilX-binding specificities will provide valuable insights into the colonization mechanisms of S. sanguinis.

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