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Neoplasms

Skin and Musculoskeletal Diseases

Small molecule drug

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Disease Domain	Count

Neoplasms	1

Top 5 Drug Type	Count

Small molecule drug	1

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GLI1 x GLI2	1

Targeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remains challenging. We previously reported that redox maps showing the reduction power per unit time of implanted tumor tissues via non-invasive redox imaging using a novel, compact, and portable electron paramagnetic resonance imaging (EPRI) device could be compared with tumor tissue sections. This study aimed to apply the EPRI technique to the in vivo detection of ferroptosis. Notably, redox maps reflecting changes in the redox status of tumors induced by the ferroptosis-inducing agent imidazole ketone erastin (IKE) were compared with the immunohistochemical images of 4-hydroxynonenal (4-HNE) in tumor tissue sections. Our comparison revealed a negative correlation between the reducing power of tumor tissue and the number of 4-HNE-positive cells. Furthermore, the control and IKE-treated groups exhibited significantly different distributions on the correlation map. Therefore, redox imaging using EPRI may contribute to the non-invasive detection of ferroptosis in vivo.

01 Dec 2025·Histochemistry and Cell Biology

Polycomb protein Bmi1 promotes odontoblast differentiation by accelerating Wnt and BMP signaling pathways

Article

Author: Ninomiya, Tadashi ; Hosoya, Akihiro ; Kitamura, Chiaki ; Seki-Kishimoto, Yuri ; Yukita, Akira ; Nakamura, Hiroaki ; Takebe, Hiroaki ; Iijima, Masahiro ; Noguchi, Yukiko ; Yoshiba, Nagako ; Washio, Ayako ; Morotomi, Takahiko

Bmi1 is a polycomb protein localized in stem cells and maintains their stemness. This protein is also reported to regulate the expression of various differentiation genes. In this study, to analyze the role of Bmi1 during dentinogenesis, we examined the immunohistochemical localization of Bmi1 during rat tooth development as well as after cavity preparation. Bmi1 localization was hardly detected in the dental mesenchyme at the bud and cap stages. After the bell stage, however, this protein became detectable in preodontoblasts and early odontoblasts just beginning dentin matrix secretion. As dentin formation progressed, Bmi1 immunoreactivity in the odontoblasts decreased in intensity. After cavity preparation, cells lining the dentin and some pulp cells under the cavity were immunopositive for Bmi1 at 4 days. Odontoblast-like cells forming reparative dentin were immunopositive for Bmi1 at 1 week, whereas their immunoreactivity was not detected after 8 weeks. We further analyzed the function of Bmi1 using KN-3 cells, a dental mesenchymal cell line. Overexpression of Bmi1 in KN-3 cells promoted mineralized tissue formation. In contrast, siRNA knockdown of Bmi1 in KN-3 cells reduced alkaline phosphatase activity and the expression of odontoblast differentiation marker genes such as Runx2, osterix, and osteocalcin. Additionally, KN-3 cells transfected with siRNA against Bmi1 showed reduced nuclear transition of β-catenin and expression of phosphorylated-Smad1/5/8. Taken together, these findings suggest that Bmi1 was localized in the odontoblast-lineage cells in their early differentiation stages. Bmi1 might positively regulate their differentiation by accelerating Wnt and BMP signaling pathways.

01 Jul 2025·Environmental Research

Associations between urinary phthalate metabolites and reproductive, adrenal, and gonadotropic hormones in peripubertal children: the Hokkaido study

Article

Author: Nakamura, Akie ; Kon, Masafumi ; Manabe, Atsushi ; Kishi, Reiko ; Yasuda, Ayaka ; Kitta, Takeya ; Ikenaka, Yoshinori ; Ikeda, Atsuko ; Yamaguchi, Takeshi ; Kojima, Hiroyuki ; Marsela, Megasari ; Zeng, Yi ; Ait Bamai, Yu ; Ketema, Rahel Mesfin

Phthalates have raised concerns regarding the disruption of hormone synthesis and signaling. The purpose of this study was to investigate the associations between urinary phthalate metabolites and 18 hormones, including reproductive, adrenal, and gonadotropic hormones, in peripubertal children. The study comprised a cross-sectional analysis of participants in the Hokkaido Birth Cohort Study. We collected data from 429 school children aged 9-12 living in Sapporo, Japan. Ten phthalate metabolites and 14 steroid hormones were analyzed using LC-MS/MS, whereas four peptide hormones were detected using immunoassays. Multivariable linear regression, quantile-based g-computation (qg-computation), and Bayesian kernel machine regression (BKMR) were used to investigate the associations between the individual phthalate metabolites and the phthalate mixtures with hormone levels, as well as with puberty based on hormone levels. In girls, we found that higher phthalate metabolite levels, as well as phthalate mixtures, were significantly associated with lower dehydroepiandrostenedione-sulfate (DHEA-S) and higher (androstenedione + testosterone)/DHEA-S. The higher phthalate mixture showed lower levels of LH, FSH, and cortisol levels among girls, whereas higher 11-deoxycortisol levels. In boys, a higher phthalates mixture was significantly associated with a higher estradiol/testosterone ratio, whereas lower levels of insulin-like factor-3 (INSL3), testosterone, (androstenedione + testosterone)/DHEA-S, testosterone/androstenedione, and cortisol/cortisone. Higher phthalate mixtures were associated with lower prevalence of puberty in girls. These findings indicate that phthalate exposure may disrupt the hormones in children during puberty.

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Pipeline

Pipeline Snapshot as of 08 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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