Article
Cell Biology
Zefang Lin, Lixuan Huang, Qianqian Cao, Hanyue Luo, Wei Yao, Ji-chun Zhang
Summary: This study reveals that activating Nrf2 and inhibiting C/EBP beta can reduce abnormal alpha-Syn expression in Parkinson's disease and improve the degeneration of dopaminergic neurons. This suggests that activating Nrf2 and inhibiting the C/EBP beta/alpha-Syn signaling pathway may be a potential therapeutic strategy for PD.
Article
Food Science & Technology
Xiaohong Lin, Weiye Xu, Liu Liu, Shiyi Ou, Xichun Peng
Summary: The metabolites of flaxseed polysaccharide fermented by fecal bacteria were found to inhibit glucose intake and lipid accumulation, which might be a weight-loss mechanism of flaxseed polysaccharide through regulating intestinal microbiota.
FOOD RESEARCH INTERNATIONAL
(2021)
Article
Cell Biology
Han Yan, Qi Li, Mengying Li, Xiuqun Zou, Ningning Bai, Zichao Yu, Jie Zhang, Dan Zhang, Qun Zhang, Jiamin Wang, Hao Jia, Yingjie Wu, Zhaoyuan Hou
Summary: The study shows that depletion of Ajuba in 3T3-L1 cells reduces the expression of PPARγ and C/EBPα, impairing adipocyte differentiation, while overexpression increases their expression and promotes differentiation. Restoring C/EBPα or PPARγ expression in Ajuba-deficient cells improves impaired lipid accumulation. Ajuba interacts with C/EBPβ and recruits CBP to enhance binding to the promoter regions of PPARγ and C/EBPα, leading to increased gene expression.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Article
Cell Biology
Marie Christou-Kent, Sergi Cuartero, Carla Garcia-Cabau, Julia Ruehle, Julian Naderi, Julia Erber, Maria Victoria Neguembor, Marcos Plana-Carmona, Marc Alcoverro-Bertran, Luisa De Andres-Aguayo, Antonios Klonizakis, Eric Julia-Vilella, Cian Lynch, Manuel Serrano, Denes Hnisz, Xavier Salvatella, Thomas Graf, Gregoire Stik
Summary: The transcription factor CEBPA plays a role in cell identity by influencing genome architecture. It can undergo phase separation through its intrinsically disordered region, leading to the formation of specific nuclear foci and regulation of gene function.
Article
Computer Science, Artificial Intelligence
Ramon Vinas, Chaitanya K. Joshi, Dobrik Georgiev, Phillip Lin, Bianca Dumitrascu, Eric R. Gamazon, Pietro Lio
Summary: Vinas et al. propose a neural network for multi-tissue imputation of gene expression, leveraging the shared regulatory architecture of tissues. This method enhances our understanding of coordinated biological mechanisms involved in disease and homeostasis.
NATURE MACHINE INTELLIGENCE
(2023)
Article
Clinical Neurology
Yinan Yao, Seong Su Kang, Yiyuan Xia, Zhi-Hao Wang, Xia Liu, Thorsten Muller, Yi E. Sun, Keqiang Ye
Summary: The truncated APP C586-695 fragment binds directly to the inflammatory transcription factor CEBPB, enhancing its transcriptional activity and exacerbating Alzheimer's disease-related gene expression and pathogenesis.
Article
Endocrinology & Metabolism
Toshiharu Onodera, Dae-Seok Kim, Risheng Ye, May-Yun Wang, Shiuhwei Chen, Bianca C. Field, Leon Straub, Xue-Nan Sun, Chao Li, Charlotte Lee, Megan Paredes, Clair Crewe, Shangang Zhao, Christine M. Kusminski, Ruth Gordillo, Philipp E. Scherer
Summary: The disease progression of metabolic syndrome is associated with the role of adiponectin in pancreatic islets, which maintains normal pancreatic function by regulating the expression of the transcription factors PPARa and HNF4a.
MOLECULAR METABOLISM
(2023)
Article
Gastroenterology & Hepatology
Grant Elias, Michael Schonfeld, Sara Saleh, Mark Parrish, Marina Barmanova, Steven A. Weinman, Irina Tikhanovich
Summary: The mechanism of sepsis-associated ACLF was studied using a novel mouse model. The transcription factor C/EBP13 is activated in both mouse and human ACLF and may serve as a potential therapeutic target to prevent liver failure in patients with sepsis and cirrhosis.
Article
Biochemistry & Molecular Biology
Charles Antony, Subin S. George, Justin Blum, Patrick Somers, Chelsea L. Thorsheim, Dexter J. Wu-Corts, Yuxi Ali, Long Gao, Kaosheng Lv, Michel G. Tremblay, Tom Moss, Kai Tan, Jeremy E. Wilusz, Austen R. D. Ganley, Maxim Pimkin, Vikram R. Paralkar
Summary: By studying hematopoiesis, multiple potential regulators of ribosomal RNA transcription were identified, providing a template for dissecting the roles of transcription factors in this process.
Editorial Material
Endocrinology & Metabolism
Ke Zhu, Jochen Reiser
Summary: Diabetic kidney disease is affected by both genetic and environmental factors. A recent study has identified risk variants in the XOR promoter that increase its own activity in response to high blood sugar levels, which play a causative role in the development and progression of diabetic kidney disease.
Article
Biochemistry & Molecular Biology
Hui Ding, Jinjun Chen, Jingping Qin, Ruhua Chen, Zili Yi
Summary: The study confirmed that deacetylation of C/EBP beta in A549 cells successfully ameliorated TGF-beta 1-induced EMT, as shown by reduction in alpha-SMA expression and excessive collagen-I accumulation. This indicates that the EMT and fibrotic effect of TGF-beta 1 depend on acetylated C/EBP beta-mediated regulation of alpha-SMA gene activity.
MOLECULAR MEDICINE
(2021)
Editorial Material
Hematology
Karen Keeshan
Summary: The study reveals the mechanistic basis for the development of acute myeloid leukemia (AML) mediated by HoxA9 and TRIB proteins, emphasizing their crucial roles in AML oncogenic activity. Further research is needed to explore the synergistic effect of HoxA9 and TRIB proteins in AML pathogenesis, as well as the impact of TRIB proteins on different AML phenotypes.
Article
Cell Biology
Dong-mei Wu, Ji-ping Liu, Jie Liu, Wei-hong Ge, Su-zhen Wu, Chi-jia Zeng, Jia Liang, Kejian Liu, Quan Lin, Xiao-wu Hong, Yi Eve Sun, Jun Lu
Summary: This study reveals the neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury. Neurons show elevated expression of C/EBP0, followed by induction of inflammatory cytokines IL-10 and TNF-a. Silencing of C/EBP0 or IL-10 and TNF-a in neurons significantly alleviates downstream inflammatory injury responses and provides neural protection.
Article
Oncology
Miles H. Linde, Amy C. Fan, Thomas Koehnke, Aaron C. Trotman-Grant, Sarah F. Gurev, Paul Phan, Feifei Zhao, Naomi L. Haddock, Kevin A. Nuno, Eric J. Gars, Melissa Stafford, Payton L. Marshall, Christopher G. Dove, Ian L. Linde, Niklas Landberg, Lindsay P. Miller, Robbie G. Majzner, Tian Yi Zhang, Ravindra Majeti
Summary: Therapeutic cancer vaccination aims to activate tumor-reactive T cells for recognizing tumor-associated antigens (TAA) and eliminating malignant cells. The study proposes a cancer vaccination approach using myeloid-lineage reprogramming to convert cancer cells into tumor-reprogrammed antigen-presenting cells (TR-APC). The results demonstrate the effectiveness of TR-APCs in inducing clonal expansion of cancer-specific T cells, establishing immune memory, and promoting leukemia eradication.
Review
Neurosciences
Zhi-Hao Wang, Yiyuan Xia, Zhourui Wu, Seong Su Kang, Ji-chun Zhang, Pai Liu, Xia Liu, Weihong Song, Vincent Huin, Claire-Marie Dhaenens, Shan Ping Yu, Xiao-Chuan Wang, Keqiang Ye
Summary: ApoE4 activates C/EBP beta in neurons, leading to the development of AD-like pathologies such as increased expression of APP, Tau, and BACE1. Neuronal specific Thy1-ApoE4/C/EBP beta transgenic mice exhibit AD-like pathologies and cognitive disorders.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Genetics & Heredity
Takahiro Seimiya, Motoyuki Otsuka, Takuma Iwata, Eri Tanaka, Kazuma Sekiba, Chikako Shibata, Masaru Moriyama, Ryo Nakagawa, Reo Maruyama, Kazuhiko Koike
Summary: A large-scale circRNA profiling analysis was conducted in PDAC tissues using circular RNA-specific RNA sequencing, identifying over 40,000 previously unknown circRNAs, some of which were upregulated in PDAC tissues. A novel circRNA, named circPDAC RNA, was found to be upregulated in PDAC but not expressed in normal human cells, serving as a potential biomarker for cancers including PDAC.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Gastroenterology & Hepatology
Takuma Nakatsuka, Hayato Nakagawa, Yuki Hayata, Taijiro Wake, Tomoharu Yamada, Mizuki Nishibatake Kinoshita, Ryo Nakagomi, Masaya Sato, Tatsuya Minami, Koji Uchino, Kenichiro Enooku, Yotaro Kudo, Yasuo Tanaka, Takahiro Kishikawa, Motoyuki Otsuka, Ryosuke Tateishi, Kazuhiko Koike
Summary: This study found that plasma cfDNA levels in HCC patients were associated with clinical stage and high levels were linked to poor prognosis. Post-treatment increase in cfDNA levels was correlated with response to MTAs, and targeted ultra-deep sequencing of post-treatment cfDNA successfully detected various gene mutations, showing promise in predicting treatment effects.
JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Tatsunori Suzuki, Takahiro Kishikawa, Tatsuyuki Sato, Norihiko Takeda, Yuki Sugiura, Takahiro Seimiya, Kazuma Sekiba, Motoko Ohno, Takuma Iwata, Rei Ishibashi, Motoyuki Otsuka, Kazuhiko Koike
Summary: Mutational activation of the KRAS gene is an early event in the carcinogenesis of almost all PDAC. Research shows that KRAS mutation increases the dependency on glucose and glutamine and reduces intracellular levels of amino acids, necessitating higher autophagic flux for cell viability.
CANCER GENE THERAPY
(2022)
Review
Gastroenterology & Hepatology
Kazuma Sekiba, Motoyuki Otsuka, Kazuhiko Koike
Summary: Current treatments for hepatitis B virus using nucleos(t)ide analogs cannot eliminate the risk of hepatocellular carcinoma development. HBV-associated HCC can develop even in the absence of liver cirrhosis, suggesting that HBV possesses direct oncogenic potential. Multiple molecules and pathways are involved in HBx-associated HCC development, indicating that the mechanisms underlying HBx-mediated hepatocarcinogenesis are still unclear.
SEMINARS IN LIVER DISEASE
(2021)
Article
Gastroenterology & Hepatology
Katsutoshi Tokushige, Kenichi Ikejima, Masafumi Ono, Yuichiro Eguchi, Yoshihiro Kamada, Yoshito Itoh, Norio Akuta, Masato Yoneda, Motoh Iwasa, Masashi Yoneda, Motoyuki Otsuka, Nobuharu Tamaki, Tomomi Kogiso, Hiroto Miwa, Kazuaki Chayama, Nobuyuki Enomoto, Tooru Shimosegawa, Tetsuo Takehara, Kazuhiko Koike
Summary: NAFLD and NASH have become significant public health issues in both Western countries and Japan, with hepatic fibrosis being a key prognostic factor. Effective screening methods for NAFLD and urgent surveillance for HCC are necessary in Japan, where non-viral liver disease-related HCC cases are on the rise. Cardiovascular disease is the leading cause of death in NAFLD patients, emphasizing the importance of CVD monitoring in clinical practice. Several drug trials are ongoing for NAFLD/NASH therapy, with new treatments like SGLT2 inhibitors and GLP-1 analogues showing promise for future interventions.
HEPATOLOGY RESEARCH
(2021)
Review
Gastroenterology & Hepatology
Katsutoshi Tokushige, Kenichi Ikejima, Masafumi Ono, Yuichiro Eguchi, Yoshihiro Kamada, Yoshito Itoh, Norio Akuta, Masato Yoneda, Motoh Iwasa, Masashi Yoneda, Motoyuki Otsuka, Nobuharu Tamaki, Tomomi Kogiso, Hiroto Miwa, Kazuaki Chayama, Nobuyuki Enomoto, Tooru Shimosegawa, Tetsuo Takehara, Kazuhiko Koike
Summary: Nonalcoholic fatty liver disease (NAFLD) is a serious public health issue in Japan, with nonalcoholic steatohepatitis (NASH) being a progressive form that can lead to liver cirrhosis and increase the risk of hepatocellular carcinoma. The most common cause of death in NAFLD patients is cardiovascular disease.
JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Kazuma Sekiba, Motoyuki Otsuka, Kazuyoshi Funato, Yu Miyakawa, Eri Tanaka, Takahiro Seimiya, Mari Yamagami, Takeya Tsutsumi, Kazuya Okushin, Kei Miyakawa, Akihide Ryo, Kazuhiko Koike
Summary: The HBV X protein degrades the Smc5/6 complex, impairing DNA double-strand break repair and promoting cellular transformation. Nitazoxanide (NTZ) restores the function of the Smc5/6 complex, repairing HR in HBx-expressing cells and promoting colony formation.
JOURNAL OF HEPATOLOGY
(2022)
Article
Oncology
Tatsuya Minami, Ryosuke Tateishi, Naoto Fujiwara, Ryo Nakagomi, Takuma Nakatsuka, Masaya Sato, Koji Uchino, Kenichiro Enooku, Hayato Nakagawa, Hidetaka Fujinaga, Masashi Izumiya, Kazuyuki Hanajiri, Yoshinari Asaoka, Yuji Kondo, Yasuo Tanaka, Motoyuki Otsuka, Takamasa Ohki, Masahiro Arai, Atsushi Tanaka, Kiyomi Yasuda, Hideaki Miura, Itsuro Ogata, Toshiro Kamoshida, Kazuaki Inoue, Yukihiro Koike, Masatoshi Akamatsu, Hiroshi Mitsui, Hajime Fujie, Keiji Ogura, Hideo Yoshida, Tomonori Wada, Kiyohiko Kurai, Hisato Maekawa, Shuntaro Obi, Takuma Teratani, Naohiko Masaki, Kayo Nagashima, Takashi Ishikawa, Naoya Kato, Kyoji Moriya, Hiroshi Yotsuyanagi, Kazuhiko Koike
Summary: Obesity and heavy alcohol consumption are independent risk factors for the development of hepatocellular carcinoma in patients after achieving sustained virological response with antiviral therapy.
Article
Gastroenterology & Hepatology
Hiroyuki Kato, Keisuke Tateishi, Hiroaki Fujiwara, Takuma Nakatsuka, Keisuke Yamamoto, Yotaro Kudo, Yoku Hayakawa, Hayato Nakagawa, Yasuo Tanaka, Hideaki Ijichi, Motoyuki Otsuka, Dosuke Iwadate, Hiroki Oyama, Sachiko Kanai, Kensaku Noguchi, Tatsunori Suzuki, Tatsuya Sato, Ryunosuke Hakuta, Kazunaga Ishigaki, Kei Saito, Tomotaka Saito, Naminatsu Takahara, Takahiro Kishikawa, Tsuyoshi Hamada, Ryota Takahashi, Koji Miyabayashi, Suguru Mizuno, Hirofumi Kogure, Yousuke Nakai, Yoshihiro Hirata, Atsushi Toyoda, Kazuki Ichikawa, Wei Qu, Shinichi Morishita, Junichi Arita, Mariko Tanaka, Tetsuo Ushiku, Kiyoshi Hasegawa, Mitsuhiro Fujishiro, Kazuhiko Koike
Summary: Our study identified the MNX1-HNF1B axis to be biologically significant in IPMN lineages, and this axis is crucial for the regulation of genes such as MYC, SOX9, and OLFM4.
Article
Biochemistry & Molecular Biology
Kazuyoshi Funato, Motoyuki Otsuka, Kazuma Sekiba, Yu Miyakawa, Takahiro Seimiya, Chikako Shibata, Takahiro Kishikawa, Mitsuhiro Fujishiro
Summary: DNA repair processes are potential therapeutic targets for cancer treatment. This study reveals that HBV-associated HCC with a deficiency in the Smc5/6 complex is more susceptible to PARP inhibitors due to impaired homologous recombination. The findings suggest a potential treatment strategy for HBV-related HCC.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hiroaki Kanzaki, Tetsuhiro Chiba, Tatsuya Kaneko, Junjie Ao, Motoyasu Kan, Ryosuke Muroyama, Shingo Nakamoto, Tatsuo Kanda, Hitoshi Maruyama, Jun Kato, Yoh Zen, Ai Kotani, Kazuma Sekiba, Motoyuki Otsuka, Masayuki Ohtsuka, Naoya Kato
Summary: ELAVL1 protein is not only involved in the replication of hepatitis B virus, but also has an impact on the cell growth of hepatocellular carcinoma, making it a potential therapeutic target for HBV-related HCC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Chikako Shibata, Motoyuki Otsuka, Takahiro Seimiya, Takahiro Kishikawa, Kazunaga Ishigaki, Mitsuhiro Fujishiro
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Letter
Medicine, General & Internal
Elif Hindie
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Letter
Medicine, General & Internal
Motoyuki Otsuka
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Medicine, Research & Experimental
Takahiro Kishikawa, Hiroshi Higuchi, Limei Wang, Nivedita Panch, Valerie Maymi, Sachem Best, Samuel Lee, Genso Notoya, Alex Toker, Lydia E. Matesic, Gerburg M. Wulf, Wenyi Wei, Motoyuki Otsuka, Kazuhiko Koike, John G. Clohessy, Yu-Ru Lee, Pier Paolo Pandolfi
Summary: Activation of the PI3K signaling pathway in tumorigenesis is linked to PTEN inactivation, with WWP1 playing a role in PTEN dissociation from the plasma membrane and activation of PI3K signaling. Inhibition of WWP1 synergizes with PI3K inhibitors to suppress tumor growth and reduce hyperglycemia and insulin feedback, enhancing the therapeutic potential of PI3K inhibitors and opening new avenues for combination cancer therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)