Article
Pharmacology & Pharmacy
Hongchao Jiang, Yaxue Zhao, Huirong Tang, Shixin Duan, Mengkai Li, Xinyi Yang, Jingting Liu, Xinyi Lou, Yuanyuan Cai, Wenjuan Zhao, Lei Sun, Feng Qian
Summary: DSF inhibits pulmonary fibrosis by targeting TGF-beta/SMAD signaling pathway, making it a promising therapeutic candidate for idiopathic pulmonary fibrosis (IPF).
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cell Biology
Cai-Ping Yan, Xing-Kuan Wang, Ke Jiang, Chong Yin, Chao Xiang, Yong Wang, Chaoyu Pu, Lu Chen, Yu-Ling Li
Summary: Bone defects are a global public health problem, and the available methods for inducing bone regeneration are limited. β-ecdysterone, a plant sterol similar to estrogen, has been found to promote bone regeneration by enhancing osteoblast differentiation and activating the BMP-2/Smad/Runx2/Osterix pathway. This study provides a new direction for osteogenic differentiation and offers novel therapeutic strategies for treating bone defects.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Li-Li Ren, Xiao-Jun Li, Ting-Ting Duan, Zheng-Hai Li, Jun-Zheng Yang, Ya-Mei Zhang, Liang Zou, Hua Miao, Ying-Yong Zhao
Summary: Fibrosis is the excessive deposition of extracellular matrix components in the processes of tissue repair, causing organ structural integrity and functional impairment. Transforming growth factor-beta (TGF-beta) is a key factor in promoting fibrosis by activating profibrotic signals. This review discusses the role of TGF-beta signaling in fibrotic organs, as well as potential therapeutic options for targeting tissue fibrosis through modulating TGF-beta signaling.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Kyoung Tae Lee, Yung Hyun Choi, Chang-Hee Kang, Mi-Hwa Lee, Sang-Hun Kim, Gi-Young Kim
Summary: In this study, the potential of rutin in attenuating ECM regulation and EMT caused by TGF-beta and its underlying mechanisms were investigated. Rutin was found to inhibit TGF-beta-induced ECM-related genes and EMT processes. Furthermore, rutin attenuated lung fibrosis in a mouse model. Molecular docking analyses suggest that rutin inhibits SMAD-mediated fibrotic signaling pathways. These findings highlight the potential of rutin as a therapeutic option for fibrotic and cancer-related diseases induced by TGF-beta.
Article
Biotechnology & Applied Microbiology
Wenwen Ding, Danhua Zhou, Shimeng Zhang, Jiaping Qian, Lingxia Yang, Lei Tang
Summary: This study demonstrates that Trimetazidine (TMZ) can inhibit liver fibrosis and hepatic stellate cell proliferation induced by CCl4 and TGF-beta. TMZ exerts its effects by blocking the activation of TGF beta/Smad signaling pathway. These findings provide new insights into the potential application of TMZ in the treatment of liver fibrosis.
Article
Medicine, Research & Experimental
Yun Li, Zhencheng Yu, Danyang Zhao, Dong Han
Summary: The study showed that corilagin has multiple effects on HSFs, including inhibition of collagen production, cell proliferation, cell migration, and suppression of HSF activation. Corilagin also significantly suppressed HS formation and collagen deposition in a rabbit ear scar model, as well as inhibited fibroblast proliferation and alpha-SMA expression in vivo. Additionally, western blot analysis revealed that corilagin downregulated the protein levels of TGF-beta 1 and TGF-beta receptor type I (TGF beta RI), thus affecting the levels of p-smad2/3, MMPs, and TIMP1.
Article
Biochemistry & Molecular Biology
Dan Wang, Bochuan Deng, Lu Cheng, Jieru Li, Xiaomin Guo, Jiao Zhang, Xiang Zhang, Ping Su, Guofeng Li, Xiaokang Miao, Wenle Yang, Junqiu Xie, Rui Wang
Summary: In this study, a novel peptide DR4penA was designed based on the structure-activity relationship and rational design. DR4penA showed higher anti-PF activity, antioxidant activity, and a longer half-life compared to the original peptide DR8. It was found that DR4penA attenuated bleomycin- and paraquat-induced PF, and its anti-PF activity was equivalent to that of pirfenidone. Furthermore, DR4penA suppressed the TGF-beta/Smad pathway in TGF-beta 1-induced A549 cells and paraquat-induced rats. This study suggests that DR4penA is a potential candidate for PF therapy.
Article
Medicine, Research & Experimental
Alex Boye
Summary: Early detection of cancer is crucial for cancer management and limited survival. Understanding cancer biology and key factors in cancer progression plays a significant role in cancer treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cell Biology
Daisuke Tateiwa, Takashi Kaito, Kunihiko Hashimoto, Rintaro Okada, Joe Kodama, Junichi Kushioka, Zeynep Bal, Hiroyuki Tsukazaki, Shinichi Nakagawa, Yuichiro Ukon, Hiromasa Hirai, Hongying Tian, Ivan Alferiev, Michael Chorny, Satoru Otsuru, Seiji Okada, Masahiro Iwamoto
Summary: BMPs have been used clinically for bone formation in musculoskeletal disorders, but high doses can lead to adverse events. A potent antagonist of RAR gamma was found to enhance BMP-induced bone formation, leading to increased bone volume and thickness, as well as promoting chondrogenic gene expression. This suggests potential for improving BMP-2 based bone regeneration procedures in the future.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Yangxuan Wei, Megumu Tanaka, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Hisaka Kawate, Nanqi Cui, Shinji Kakihara, Yunlu Zhao, Kohsuke Aruga, Hideki Sanjo, Takayuki Shindo
Summary: Research revealed that the reduction in adrenomedullin (AM) levels in patients with pulmonary fibrosis exacerbates the severity of the disease, while AM can attenuate fibrosis progression by suppressing TGF-beta-Smad3 signaling and microRNA-21 activity.
Article
Chemistry, Medicinal
Dali Ding, Xuebin Shen, Lizhen Yu, Yueyue Zheng, Yao Liu, Wei Wang, Li Liu, Zitong Zhao, Sihui Nian, Limin Liu
Summary: Timosaponin BII (TS BII), a main constituent of Anemarrhena asphodeloides Bunge, was found to restore lung structure, inhibit collagen deposition, and reverse abnormal expression of EMT-related marker proteins in a bleomycin-induced pulmonary fibrosis (PF) model. Furthermore, TS BII suppressed EMT by inhibiting the TGF-beta/Smad pathway both in vivo and in vitro. Therefore, TS BII may be a promising candidate for PF treatment.
PHYTOTHERAPY RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Atukuri Dorababu, Manikantha Maraswami
Summary: Pulmonary fibrosis is a condition of scarring of lung tissue caused by various factors, and currently there are no efficient drugs for its treatment. However, some chemical drugs have been found to attenuate the progression of fibrosis and improve patients' quality of life. This review summarizes the recent studies on the effects of different types of drugs and their mechanisms in treating pulmonary fibrosis, providing guidance for the development of better treatment options.
Article
Biochemistry & Molecular Biology
Beatriz Ballester, Javier Milara, Paula Montero, Julio Cortijo
Summary: The study reveals the overexpression of MUC16 in lung tissue of IPF patients and its collaboration with the TGF-beta 1 pathway to induce fibrotic processes. Repression of MUC16 expression can inhibit fibrotic processes, suggesting that targeting MUC16 may be a potential drug target for human IPF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Respiratory System
Christophe Guignabert, Marc Humbert
Summary: The TGF-beta superfamily, consisting of two major branches (TGF-beta-activin-nodal and BMP-GDF), plays a crucial role in regulating cellular processes through diverse signaling pathways, contributing to the pathogenesis of PAH.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Chun-Jung Chang, Chiou-Feng Lin, Chih-Hsin Lee, Hsiao-Chi Chuang, Fu-Chia Shih, Shu-Wen Wan, Chi Tai, Chia-Ling Chen
Summary: Abnormal activation of transforming growth factor (TGF)-beta leads to the upregulation of various signaling molecules, contributing to pulmonary lesions and collagen deposition in lung fibrosis. Interferon (IFN)-gamma signaling is significantly reduced in myofibroblasts, while treatments like BIBF 1120 can effectively inhibit TGF-beta-induced activation of myofibroblasts and attenuate fibrosis. Blockade of SHP2 enhances the anti-fibrotic efficacy of IFN-gamma in myofibroblasts.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Environmental Sciences
Ayumi Eguchi, Sayaka Mizukami, Misato Nakamura, Sousuke Masuda, Hirotada Murayama, Masashi Kawashima, Mari Inohana, Rei Nagahara, Mio Kobayashi, Risako Yamashita, Suzuka Uomoto, Emi Makino, Ryoichi Ohtsuka, Naofumi Takahashi, Shim-Mo Hayashi, Robert R. Maronpot, Makoto Shibutani, Toshinori Yoshida
Summary: The study suggests that MNZ may induce steatosis-related hepatocarcinogenesis in HFD-fed rats by inducing DNA double-strand breaks and modulating autophagy.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Hiromu Okano, Kazumi Takashima, Yasunori Takahashi, Ryota Ojiro, Qian Tang, Shunsuke Ozawa, Bunichiro Ogawa, Mihoko Koyanagi, Robert R. Maronpot, Toshinori Yoshida, Makoto Shibutani
Summary: The present study investigated the role of neuroinflammation and brain oxidative stress induced by neonatal treatment with lipopolysaccharides (LPS) on the development of autism spectrum disorder (ASD)-like behaviors and disruptive hippocampal neurogenesis in rats by exploring the chemopreventive effects of alpha-glycosyl isoquercitrin (AGIQ) as an antioxidant.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Gastroenterology & Hepatology
Mio Kobayashi, Risako Yamashita, Ryo Ichikawa, Makoto Shibutani, Toshinori Yoshida
Summary: The clumps of epithelial cells found in a mouse model of ulcerative colitis were likely derived from stem cells or their daughter progenitor cells. These clumps expressed stem cell markers and showed potential for mucosal healing.
DIGESTIVE DISEASES AND SCIENCES
(2022)
Article
Toxicology
Ryota Ojiro, Yousuke Watanabe, Hiromu Okano, Yasunori Takahashi, Kazumi Takashima, Qian Tang, Shunsuke Ozawa, Fumiyo Saito, Yumi Akahori, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
Summary: The neurotoxic patterns of VPA differ between developmental and postpubertal exposure, with developmental exposure affecting genes related to nervous system development and postpubertal exposure impacting genes related to neuronal differentiation and projection. The hippocampal dentate gyrus may be a sensitive target of developmental neurotoxicants after puberty.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Article
Environmental Sciences
Hiromu Okano, Kazumi Takashima, Yasunori Takahashi, Ryota Ojiro, Qian Tang, Shunsuke Ozawa, Xinyu Zou, Mihoko Koyanagi, Robert R. Maronpot, Toshinori Yoshida, Makoto Shibutani
Summary: In this study, the effect of LPS-induced maternal immune activation on hippocampal neurogenesis and behaviors in rat offspring was investigated. The results showed that LPS injections disrupted normal neurodevelopment, resulting in behavioral deficits in adulthood. AGIQ was found to have antioxidant effects and ameliorated most aberrations in hippocampal neurogenesis and synaptic plasticity as well as behavioral deficits.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Neurosciences
Natsuno Maeda, Saori Shimizu, Yasunori Takahashi, Reiji Kubota, Suzuka Uomoto, Keisuke Takesue, Kazumi Takashima, Hiromu Okano, Ryota Ojiro, Shunsuke Ozawa, Qian Tang, Meilan Jin, Yoshiaki Ikarashi, Toshinori Yoshida, Makoto Shibutani
Summary: The study found that developmental exposure to lead (Pb) during the young-adult stage suppresses hippocampal neurogenesis and leads to the accumulation of lead in the brain. The study also found that lead exposure induces oxidative stress and neuroinflammation, and activates specific cellular signals. Additionally, lead exposure increases the number of certain cell types, improving neurogenesis.
NEUROTOXICITY RESEARCH
(2022)
Article
Oncology
Susumu Yamashita, Miho Kojima, Nobuhiko Onda, Toshinori Yoshida, Makoto Shibutani
Summary: Near-infrared photoimmunotherapy (NIR-PIT) is a novel treatment for HER2-positive cancers, including breast cancer, using conjugates of antibody against overexpressed antigens and photoabsorber IRDye700DX. This study investigated the efficacy of HER2-targeted NIR-PIT using trastuzumab-IRDye700DX conjugate (Tra-IR700) in HER2-positive breast cancer. The results showed that NIR-PIT with Tra-IR700 induced a highly selective therapeutic effect in a HER2-positive breast cancer model.
Article
Food Science & Technology
Suzuka Uomoto, Keisuke Takesue, Saori Shimizu, Natsuno Maeda, Kanami Oshima, Emika Hara, Mio Kobayashi, Yasunori Takahashi, Makoto Shibutani, Toshinori Yoshida
Summary: We investigated the role of ER-phagy in NAFLD-related hepatocarcinogenesis in HFD-fed and/or PB-treated rats by clustering the expression levels of p62 and FAM134B in preneoplastic hepatic lesions. The results showed that PB administration increased clusters with high levels of p62, while HFD feeding increased clusters with high levels of both p62 and FAM134B. The combination of HFD feeding with PB counteracted each other's effects and the cluster composition resembled that of the control group.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Toxicology
Shunsuke Ozawa, Ryota Ojiro, Qian Tang, Xinyu Zou, Gye-Hyeong Woo, Toshinori Yoshida, Makoto Shibutani
Summary: Ochratoxin A (OTA) induces renal carcinogenicity in rats by causing karyomegaly and altering DNA methylation and gene expression. Using DNA methylation array and RNA sequencing analyses, a cluster of hypermethylated and downregulated genes associated with mitochondria and metabolic reprogramming in carcinogenesis were identified, while hypomethylated and upregulated genes related to cell cycle arrest and IL-17 production were also observed.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kazumi Takashima, Hiromu Okano, Ryota Ojiro, Qian Tang, Yasunori Takahashi, Shunsuke Ozawa, Xinyu Zou, Mihoko Koyanagi, Robert R. Maronpot, Toshinori Yoshida, Makoto Shibutani
Summary: The antioxidant alpha-glycosyl isoquercitrin (AGIQ) can ameliorate developmental neuropathy induced by polyinosinic-polycytidylic acid (PIC) and promote postnatal hippocampal neurogenesis. PIC treatment decreases the abundance of neural progenitor cells (NPCs) and suppresses the expression of related genes, while AGIQ can improve these effects and enhance the expression of signaling pathways.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Article
Biochemistry & Molecular Biology
Wen Zeng, Kazumi Takashima, Qian Tang, Xinyu Zou, Ryota Ojiro, Shunsuke Ozawa, Meilan Jin, Yujiro Ando, Toshinori Yoshida, Makoto Shibutani
Summary: The study investigated the ameliorating effects of a natural antioxidant formula (NAF) on a lipopolysaccharide (LPS)-induced cognitive dysfunction model in rats. The results showed that NAF reduced brain inflammation and increased the number of M2-type cells. Additionally, NAF facilitated fear extinction learning and restored neural progenitor cell numbers and reelin+ hilar interneurons in the hippocampus.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Article
Pathology
Naofumi Takahashi, Satoru Yamaguchi, Ryouichi Ohtsuka, Makio Takeda, Toshinori Yoshida, Tadashi Kosaka, Takanori Harada
Summary: Our study investigated the hepatotoxicity of chromated copper arsenate (CCA), a wood preservative, in female rats. We observed hepatocellular hypertrophy, hepatic dysfunction, and oxidative stress in the liver of rats exposed to CCA. Analysis of liver samples revealed changes in cell proliferation, apoptosis, and protein glutathionylation, along with alterations in gene expression related to antioxidants, GST, DNA methylation, and cell metabolism. These findings suggest that CCA-induced hepatotoxicity is mediated through decreased glutathione levels and disruption of multiple molecular pathways in the liver of female rats.
JOURNAL OF TOXICOLOGIC PATHOLOGY
(2023)
Article
Toxicology
Qian Tang, Kazumi Takashima, Wen Zeng, Hiromu Okano, Xinyu Zou, Yasunori Takahashi, Ryota Ojiro, Shunsuke Ozawa, Mihoko Koyanagi, Robert R. Maronpot, Toshinori Yoshida, Makoto Shibutani
Summary: This study investigated the role of neuroinflammation in a lipopolysaccharides (LPS)-induced cognitive dysfunction model in rats using an antioxidant, a-glycosyl isoquercitrin (AGIQ). The results showed that AGIQ treatment decreased brain proinflammatory cytokine levels and ameliorated LPS-induced adverse effects, indicating that neuroinflammation is a key factor in the development of LPS-induced impairment of fear memory acquisition.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2023)
Article
Toxicology
Ryo Ichikawa, Sosuke Masuda, Junta Nakahara, Mio Kobayashi, Risako Yamashita, Suzuka Uomoto, Ohshima Kanami, Yuko Itoi, Makoto Shibutani, Toshinori Yoshida
Summary: This study investigated the effects of autophagy inducer carbamazepine (CBZ) on early hepatocarcinogenesis induced by a high-fat diet and streptozotocin. The results showed that inhibition of autophagy and induction of NADPH oxidase subunit might contribute to the development of early hepatocellular carcinoma in this model.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2022)
Review
Pathology
Toshinori Yoshida, Mio Kobayashi, Suzuka Uomoto, Kanami Ohshima, Emika Hara, Yoshitaka Katoh, Naofumi Takahashi, Takanori Harada, Tatsuya Usui, Mohamed Elbadawy, Makoto Shibutani
Summary: The development of in vitro toxicity assessment methods using cultured cells has gained popularity for promoting animal welfare in animal experiments. This article briefly discusses the current status of hepatoxicity assessment using human and rat-derived hepatocytes, focusing on the liver organoid method. It also proposes how toxicologic pathologists should assess toxicity regarding the distribution of undifferentiated and differentiated cells in the organoid.
JOURNAL OF TOXICOLOGIC PATHOLOGY
(2022)