Article
Oncology
Lu Lu, Yi-Xin Jiang, Xiao-Xia Liu, Jin-Mei Jin, Wen-Jie Gu, Xin Luan, Ying-Yun Guan, Li-Jun Zhang
Summary: Colorectal cancer (CRC) is a major malignant tumor with limited efficacy of existing therapies, making it necessary to explore potential combination therapy to improve immunotherapy efficacy. GW4064, a FXR agonist, has been found to induce apoptosis, block cell cycle, and mediate immunogenic cell death (ICD) of CRC cells in vitro. However, it could not suppress CRC tumor growth in vivo. Further studies showed that GW4064 upregulated PD-L1 expression in CRC cells through activating FXR and MAPK signaling pathways. Combination therapy of PD-L1 immune checkpoint blockade with FXR agonist exhibited excellent anti-tumor effects and increased CD8(+) T cells infiltration, with 33% tumor bearing mice cured.
Article
Biochemistry & Molecular Biology
Snehal N. Chaudhari, David A. Harris, Hassan Aliakbarian, James N. Luo, Matthew T. Henke, Renuka Subramaniam, Ashley H. Vernon, Ali Tavakkoli, Eric G. Sheu, A. Sloan Devlin
Summary: After bariatric surgery, levels of the endogenous bile acid cholic acid-7-sulfate (CA7S) increase in the gastrointestinal tract of both mice and humans. CA7S acts as a G-protein-coupled receptor TGR5 agonist to increase glucose tolerance during insulin resistance. This agonist remains gut-restricted, minimizing off-target effects previously observed for TGR5 agonists absorbed into the circulation.
NATURE CHEMICAL BIOLOGY
(2021)
Review
Immunology
Bei-Bei Cui, Yun-Ru Tian, Xin-Yue Ma, Geng Yin, Qibing Xie
Summary: IMNM is characterized by elevated creatinine kinase and necrotic muscle fibers, often associated with autoantibodies. Conventional therapies may have poor response, but anti-B-cell therapies show promise. In a case study and literature review, patients with anti-SRP IMNM had positive responses to belimumab and rituximab treatments.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Silvia Marchiano, Michele Biagioli, Rosalinda Roselli, Angela Zampella, Cristina Di Giorgio, Martina Bordoni, Rachele Bellini, Ginevra Urbani, Elva Morretta, Maria Chiara Monti, Eleonora Distrutti, Stefano Fiorucci
Summary: The study compared the pharmacological effects of UDCA and norUDCA in a mouse model of NAFLD/NASH, finding that both protected against liver steatosis and fibrosis development, improved lipid metabolism and insulin sensitivity, with UDCA acting as a GPBAR1 agonist, while norUDCA had no effect on GPBAR1 signaling.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Biochemistry & Molecular Biology
Wanqiu Huang, Shixuan Jiao, Siliang Chen, Ya Chen, Zhongcheng Yang, Wenxin Wang, Zhijun Cao, Zheng Li, Luyong Zhang
Summary: The prevalence of hyperuricemia is increasing, causing a burden on the public health system. Benzbromarone, a uric acid-lowering drug, was found to have anti-inflammatory effects. This study aimed to improve the effectiveness of benzbromarone using a structure-based drug design strategy and identified compound 4 as more active than benzbromarone.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ji Won Min, Yoo-Jin Shin, Hyeyoung Lee, Bo-Mi Kim, Ki Hyun Park, Kyoung Chan Doh, Tae-Min Kim, Sun Woo Lim, Chul Woo Yang, Eun-Jee Oh, Byung Ha Chung
Summary: Inhibition of BAFF can reduce HLA.A2-specific IgG, alter the proportions of B cells in the bone marrow and spleen, and decrease specific immune responses. This suggests that BAFF suppression may be a useful target for desensitization therapy research and development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Tsuneyuki Miyazaki, Yohei Shirakami, Taku Mizutani, Akinori Maruta, Takayasu Ideta, Masaya Kubota, Hiroyasu Sakai, Takashi Ibuka, Salvatore Genovese, Serena Fiorito, Vito Alessandro Taddeo, Francesco Epifano, Takuji Tanaka, Masahito Shimizu
Summary: The study showed that the novel FXR agonist nelumal A can effectively attenuate colonic inflammation and suppress colitis-related carcinogenesis by reducing bile acid synthesis and oxidative damage. This agent may have potential for treating inflammatory bowel diseases and related colorectal cancer chemoprevention.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Moritz Helmstaedter, Jan Vietor, Jana Sommer, Simone Schierle, Sabine Willems, Astrid Kaiser, Jurema Schmidt, Daniel Merk
Summary: A new FXR modulator chemotype has been discovered with tunable activity between agonism and antagonism through minor structural modifications, showing high selectivity and binding affinities. This new FXR ligand compound demonstrates good metabolic stability in cells and can serve as a novel scaffold for FXR-targeted drug discovery.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Lijun Hu, Qiang Ren, Liming Deng, Zongtao Zhou, Zongyu Cai, Bin Wang, Zheng Li
Summary: FXR, a nuclear receptor activated by bile acids, regulates bile acid and lipid metabolism and maintains internal environment stability. Compound 41, a novel series of FXR partial agonists, showed the best activity and strong interaction with the binding pocket of FXR, indicating its potential for further investigation as a promising therapeutic target for liver disorders.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yukiko Yamashita, Keigo Gohda, Yusuke Iguchi, Ko Fujimori, Keisuke Oda, Arisa Masuda, Mizuho Une, Naoki Teno
Summary: This study identified a benzimidazole compound 18 with dual partial agonistic activity for FXR and PPAR gamma, which could be a novel candidate for treating NAFLD associated with type 2 diabetes mellitus.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Lili Xi, Axi Shi, Tiantian Shen, Guoxu Wang, Yuhui Wei, Jingjing Guo
Summary: Cholestasis is a common clinical disease caused by a disruption in bile acids homeostasis, and the Farnesoid X receptor (FXR) plays a critical role in regulating this balance. This study aimed to identify potential FXR agonists for the treatment of cholestasis using a molecular docking-based virtual screening method. Six compounds were selected and evaluated, with licraside showing the most promising results. In vivo evaluation using an animal model confirmed that licraside reduced biliary and serum markers of cholestasis and had a therapeutic effect on liver injury. These findings highlight the potential of licraside as an FXR agonist for cholestasis treatment, and the study contributes valuable insights into the development of novel compounds from traditional Chinese medicine.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Dermatology
Nhung Thi My Ly, Ni Ma, Ikuko Ueda-Hayakawa, Chuyen Thi Hong Nguyen, Reiko Anada, Hiroyuki Okamoto, Manabu Fujimoto
Summary: This study aimed to identify clinical and laboratory parameters supporting cancer prediction in anti-TIF1 gamma antibody-positive DM patients. The cancer group showed a higher proportion of males, older age, and higher levels of anti-TIF1 gamma antibodies. Inflammatory cytokines, particularly TNF and TNF receptor superfamilies, were found to be elevated in cancer-associated DM patients and may serve as potential markers for cancer prediction.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Jie-ping Wang, Meng-yu Zhang, Ming Luo, Shu Qin, Xian-ming Xia
Summary: This study observed the treatment effect of the FXR agonist GW4064 in a rat model of hilar cholangiocarcinoma and explored a new therapeutic target for gene therapy. The results showed that GW4064 increased the expression of FXR in tumor tissues, suggesting that FXR may be a new therapeutic target for hilar cholangiocarcinoma.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Fusheng Guo, Yihui Gao, Xiaobao Li, Xiaoguang Lei
Summary: The natural product 2-oxokolavenol is identified as a novel and selective FXR agonist with therapeutic efficacy against APAP-induced hepatocyte damage. Mechanistically, 2-oxokolavenol forms hydrogen bonds with human FXR and selectively induces its transcriptional activity, providing a potential hit compound for the design of new FXR modulators.
Article
Oncology
Vianihuini Figueroa-Vazquez, Jonathan Ko, Christian Breunig, Anja Baumann, Nicola Giesen, Aniko Palfi, Christoph Mueller, Christian Lutz, Torsten Hechler, Michael Kulke, Carsten Mueller-Tidow, Alwin Kraemer, Hartmut Goldschmidt, Andreas Pahl, Marc S. Raab
Summary: HDP-101, an anti-BCMA antibody conjugated with an amanitin derivative, demonstrates high efficacy against multiple myeloma cells while sparing BCMA-negative cells. It induces tumor regression in animal models at low doses and shows good tolerability, suggesting a promising therapeutic approach to overcome drug resistance in this disease.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Gastroenterology & Hepatology
Zobair M. Younossi, Linda Henry, Janus P. Ong, Atsushi Tanaka, Yuichiro Eguchi, Masashi Mizokami, Young-Suk Lim, Yock Young Dan, Ming-Lung Yu, Maria Stepanova
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2019)
Article
Gastroenterology & Hepatology
Atsushi Tanaka, Mitsuru Mori, Kosuke Matsumoto, Hiromasa Ohira, Susumu Tazuma, Hajime Takikawa
HEPATOLOGY RESEARCH
(2019)
Article
Gastroenterology & Hepatology
Shuichiro Umetsu, Kenji Notohara, Takahiro Nakazawa, Tomoyuki Tsunoda, Tsuyoshi Sogo, Haruki Komatsu, Atsushi Tanaka, Susumu Tazuma, Hajime Takikawa, Ayano Inui, Tomoo Fujisawa
HEPATOLOGY RESEARCH
(2019)
Review
Gastroenterology & Hepatology
Atsushi Tanaka
Review
Gastroenterology & Hepatology
Yukifumi Sasamori, Atsushi Tanaka, Takuya Ayabe
HEPATOLOGY RESEARCH
(2020)
Article
Gastroenterology & Hepatology
Atsushi Tanaka, Mitsuru Mori, Kensuke Kubota, Itaru Naitoh, Takahiro Nakazawa, Hajime Takikawa, Michiaki Unno, Terumi Kamisawa, Shigeyuki Kawa, Kazuichi Okazaki
JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
(2020)
Article
Gastroenterology & Hepatology
Atsushi Tanaka, Junko Hirohara, Toshiaki Nakano, Kosuke Matsumoto, Olivier Chazouilleres, Hajime Takikawa, Bettina E. Hansen, Fabrice Carrat, Christophe Corpechot
Summary: The addition of bezafibrate to ursodeoxycholic acid in patients with primary biliary cholangitis was associated with improved prognosis, as evident from a large retrospective cohort study. The combination therapy showed a significant decrease in all-cause and liver-related mortality or need for liver transplantation, indicating the potential benefits of this treatment approach.
JOURNAL OF HEPATOLOGY
(2021)
Review
Gastroenterology & Hepatology
Atsushi Tanaka, Kenji Notohara
Summary: IgG4-related disease is a chronic inflammatory disease that may affect multiple organs of the body, characterized by elevated serum IgG4 levels and massive infiltration of IgG4(+) plasma cells in damaged tissues. The phenotypes of IgG4-RD in the liver, such as IgG4-AIH and IgG4-hepatopathy, along with their clinical characteristics, remain to be established due to the lack of consensus.
HEPATOLOGY RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Kensuke Kubota, Terumi Kamisawa, Takahiro Nakazawa, Atsushi Tanaka, Itaru Naitoh, Hajime Takikawa, Michiaki Unno, Shigeyuki Kawa, Atsushi Masamune, Seiji Nakamura, Kazuichi Okazaki
Summary: This study aimed to clarify the feasible duration of steroid treatment for patients with IgG4-sclerosing cholangitis (SC). The results showed that steroid therapy significantly increased the remission rate but carried a risk of relapse. Younger age, shorter disease duration, use of immunosuppressants, and discontinuation of steroid medication were identified as independent risk factors for relapse. Preemptive measures can reduce the occurrence of steroid-related complications.
JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Toshihiko Arizumi, Susumu Tazuma, Hiroyuki Isayama, Takahiro Nakazawa, Toshio Tsuyuguchi, Hajime Takikawa, Atsushi Tanaka
Summary: This study investigated the association between UDCA treatment and improved LT-free survival in a cohort of Japanese PSC patients.
JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Kensuke Kubota, Terumi Kamisawa, Takahiro Nakazawa, Atsushi Tanaka, Itaru Naitoh, Yusuke Kurita, Hajime Takikawa, Michiaki Unno, Shigeyuki Kawa, Atsushi Masamune, Seiji Nakamura, Kazuichi Okazaki
Summary: This study reviewed the data of 924 patients with IgG4-SC from a nationwide survey in Japan and found that 15% of these patients developed cancer. The risk of cancer development was significantly influenced by relapse, and most cancers occurred within 8 years after the diagnosis of IgG4-SC, with the highest risks in pancreatic and biliary cancers. Maintenance steroid treatment had a positive impact on the prognosis of these patients.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Kosuke Matsumoto, Junko Hirohara, Akihito Takeuchi, Ryo Miura, Yoshinari Asaoka, Toshiaki Nakano, Atsushi Tanaka
Summary: For patients with suboptimal responses to UDCA, combination therapy with OCA and BZF has been shown to improve long-term outcomes. However, some patients still experience death or liver transplantation despite this treatment. This study explored prognostic indicators in patients receiving combination treatment of UDCA and BZF.
HEPATOLOGY RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Atsushi Tanaka, Masanori Atsukawa, Keiji Tsuji, Kazuo Notsumata, Akari Suyama, Hiroshi Ito, Sugato Das, Robyn von Maltzahn, Megan M. McLaughlin
Summary: This study aimed to compare patient characteristics and outcomes between the overall and Japanese populations in the treatment of pruritus in patients with primary biliary cholangitis. The results showed similar demographics and baseline clinical characteristics across treatment groups and between both populations. The therapeutic responses and safety of linerixibat were consistent in both the Japanese and overall populations, indicating its effectiveness as a treatment option for cholestatic pruritus in patients with primary biliary cholangitis.
HEPATOLOGY RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Yuki Yamashita, Takeji Umemura, Takefumi Kimura, Satoru Joshita, Junko Hirohara, Toshiaki Nakano, Atsumasa Komori, Atsushi Tanaka
Summary: This study showed that baseline ALBI grade is a simple non-invasive predictor for prognosis in PBC, and it is significantly associated with histological stage and disease progression. ALBI score/grade can be used to assess liver function and predict mortality and the need for liver transplantation in PBC patients.
