Article
Microbiology
Le Liang, Yujuan Shen, Yuan Hu, Haipeng Liu, Jianping Cao
Summary: In this study, the impact of Cgas and Sting protein deficiencies on mice infected with S. japonicum was investigated, providing new insights into potential treatments for liver pathology associated with schistosomiasis.
Article
Biochemistry & Molecular Biology
Lauren C. Morehead, Brian Koss, Daniel Fil, Billie Heflin, Sarita Garg, Katherine F. Wallis, Alan J. Tackett, Isabelle R. Miousse
Summary: Immune checkpoint inhibitor therapy has significantly improved outcomes in cancer treatment, but resistance to treatment is still a challenge for melanoma patients. This study identified that resveratrol can increase MHC-I expression and enhance the efficacy of immunotherapy. The STING pathway was identified as a potential mechanism of action. Furthermore, the study showed that STING can induce MHC-I expression independently of interferon signaling, expanding the potential of STING modulation in improving immune checkpoint blockade.
MOLECULAR IMMUNOLOGY
(2023)
Article
Virology
Yuanyuan An, Xianyao Wang, Xuxian Wu, Liang Chen, Yichen Yang, Xiaojin Lin, Nianxue Wang, Jiangyao Duan, Shiqi Long, Xing Zhao
Summary: Research demonstrates that reovirus dsRNA induces apoptosis of reovirus-resistant tumor cells through the TLR3 signaling pathway.
Article
Microbiology
Lei Xu, Mengyuan Li, Yadong Yang, Chen Zhang, Zhen Xie, Jingjing Tang, Zhenkun Shi, Shukun Chen, Guangzhe Li, Yanchao Gu, Xiao Wang, Fuhua Zhang, Yao Wang, Xihui Shen
Summary: This study reveals the important role of the cytosolic surveillance pathway cGAS-STING in the activation of the type I interferon response during S. Typhimurium infection, in addition to the TLR4-dependent response. The study also highlights the significance of mtDNA release triggered by S. Typhimurium infection in the induction of type I interferon.
Article
Immunology
Brandon M. Johnson, Toru Uchimura, Matthew D. Gallovic, Madhan Thamilarasan, Wei-Chun Chou, Sara A. Gibson, Meng Deng, Jason W. Tam, Cole J. Batty, Jonathan Williams, Glenn K. Matsushima, Eric M. Bachelder, Kristy M. Ainslie, Silva Markovic-Plese, Jenny P-Y Ting
Summary: The cGAS-cGAMP-STING pathway induces a powerful IFN-I response and has potential in cancer immunotherapy and vaccines. Encapsulated cGAMP in microparticles showed protective effects in EAE models through a STING-dependent mechanism and induced both IFN-I-dependent and -independent immunosuppressive effects, suggesting a new approach for autoimmunity treatment. This study also highlights the importance of IL-27 and IL-10 in mitigating autoreactivity, and the potential of cGAMP to regulate T cell responses.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Simone Schilling, Bruno Chausse, Hasan Onur Dikmen, Fadi Almouhanna, Jan-Oliver Hollnagel, Andrea Lewen, Oliver Kann
Summary: Activation of microglia by Toll-like receptors can lead to varying levels of neuronal network dysfunction, with severe dysfunction primarily caused by reactive oxygen and nitrogen species rather than proinflammatory cytokines.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Oncology
Graham Thomas, Luca Micci, Wenjing Yang, Joseph Katakowski, Cecilia Oderup, Purnima Sundar, Xiao Wang, Kenneth G. Geles, Shobha Potluri, Shahram Salek-Ardakani
Summary: TLR agonists have shown potential as therapeutic targets for cancer immunotherapy by influencing the tumor immune microenvironment. Different TLR agonists have varying effects on immune cell composition, interferon signatures, and expression of immune checkpoint molecules. TLR3 stimulation appears to have unique effects on macrophages, monocytes, and T cells compared to TLR7 and TLR9 agonists, suggesting potential synergies with combination therapy strategies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Xiang-Hong Ran, Jia-Wu Zhu, Ya-Yun Chen, Run-Ze Ni, Dan Mu
Summary: This study reveals that the papain-like protease of newly emerged SARS-CoV-2 can suppress interferon production and signaling through multiple mechanisms. It targets key components of the signaling pathway and provides insights into the pathogenesis of SARS-CoV-2 and potential antiviral therapies for COVID-19.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sang-Uk Seo, Jae-Hyeon Jeong, Bum-Seo Baek, Je-Min Choi, Youn Soo Choi, Hyun-Jeong Ko, Mi-Na Kweon
Summary: The study demonstrated that BLM-mediated ALI in mice induced the release of double-stranded DNA, which potentiated IFN-I-dependent pulmonary viral resistance by activating the STING/TBK1/IRF3 pathway in association with pDCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Sharafuddin Khairuddin, Wei Ling Lim, Luca Aquili, Ka Chun Tsui, Anna Chung-Kwan Tse, Shehani Jayalath, Ruhani Varma, Trevor Sharp, Abdelhamid Benazzouz, Harry Steinbusch, Arjan Blokland, Yasin Temel, Lee Wei Lim
Summary: High-frequency stimulation (HFS) is a promising therapy for depression, and this study investigated the dopamine-dependent mechanism of the antidepressant-like effects of HFS of the prelimbic cortex (HFS PrL). The results showed that HFS PrL significantly increased hedonia, reduced anxiety, decreased forced swim immobility, and enhanced hippocampal dopamine and serotonin levels.
Article
Plant Sciences
Siyu Zhang, Yujie Sun, Fengli Yao, Hongju Li, Yacong Yang, Xionghao Li, Zhongyue Bai, Yu Hu, Peng Wang, Ximing Xu
Summary: Ginkgo biflavones are identified as potential p53 activators that enhance p53 protein expression by inhibiting MDM2 protein expression. They induce cell death independent of p53 transcriptional activity and induce apoptosis and G2/M phase arrest in HCT-116 cells. Ginkgo biflavones also induce ROS generation and ferroptosis. Overall, they represent a new class of p53 activators and have potential as anticancer agents.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Ajamaluddin Malik, Abdullah Alhomida, Javed Masood Khan
Summary: This study investigated the influence of a negatively charged benzene ring containing surfactant, sodium dodecylbenzene sulphonate (SDBS), on the fibrillation of bovine liver catalase (BLC). It was found that lower concentrations of SDBS promoted the native-like alpha-helical structure of BLC, while higher concentrations led to aggregation and the formation of amyloid-like structures. At pH 2.0, higher concentrations of SDBS enabled BLC to regain its native-like alpha-helical structure.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biology
Nan Jia, Guo Li, Xing Wang, Qing Cao, Wanbiao Chen, Chengliang Wang, Ling Chen, Xiaoling Ma, Xuan Zhang, Yue Tao, Jianye Zang, Xi Mo, Jinfeng Hu
Summary: The Staphylococcal superantigen like protein 10 induces necroptosis in human cells by binding to TNFR1 and activating multiple signaling pathways. It plays a role in immune evasion and cytotoxicity during S. aureus infection.
COMMUNICATIONS BIOLOGY
(2022)
Article
Polymer Science
Balint Viktor Lovasz, Gergely Berta, Edina Lempel, Gyorgy Setalo, Monika Vecsernyes, Jozsef Szalma
Summary: The study suggests that relevant concentrations of TEGDMA monomers leached from resin-based composite materials (RBCs) induce apoptosis in pulp cells through both caspase-dependent and caspase-independent mechanisms, possibly involving endoplasmic reticulum stress and the activation of caspase-independent apoptotic pathways.
Article
Biochemistry & Molecular Biology
Rana Al-Sadi, Viszwapriya Dharmaprakash, Prashant Nighot, Shuhong Guo, Meghali Nighot, Toan Do, Thomas Y. Ma
Summary: The probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway. This enhancement is sustained, and BB1 strain designated as BB1 causes a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier is mediated by the p38 kinase pathway, not the NF-kappa B signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Atsuko Wakabayashi, Masanori Yoshinaga, Osamu Takeuchi
Summary: TANK, a negative regulator of NF-kappa B signaling, plays a critical role in ameliorating fatal DAH caused by lung vascular endothelial cell death in a mouse model of systemic lupus erythematosus by suppressing TRAF6 ubiquitination and cGAS-mediated cGAMP production.
LIFE SCIENCE ALLIANCE
(2022)
Article
Microbiology
Masaaki Toyama, Koichi Watashi, Masanori Ikeda, Atsuya Yamashita, Mika Okamoto, Kohji Moriishi, Masamichi Muramatsu, Takaji Wakita, Ashoke Sharon, Masanori Baba
Summary: Novel neplanocin A derivatives have shown potency in inhibiting HBV replication in vitro, reducing HBV RNA levels and antigen production, with a mechanism of action different from clinically approved anti-HBV agents.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Tomohisa Tanaka, Akatsuki Saito, Tatsuya Suzuki, Yoichi Miyamoto, Kazuo Takayama, Toru Okamoto, Kohji Moriishi
Summary: In this study, a stable replicon system for SARS-CoV-2 was established using a bacterial artificial chromosome vector. The system allowed for the continuous production of viral proteins and sgRNAs, which could be suppressed by certain antiviral treatments. The system was found to be more effective in screening for antiviral compounds compared to the traditional transient transfection method.
ANTIVIRAL RESEARCH
(2022)
Editorial Material
Immunology
Kouji Kobiyama, Ken J. Ishii
Summary: mRNA vaccines owe their success in part to methylation, which masks the immunostimulatory properties of the mRNA. However, the immunological mechanisms of adjuvanticity are still unclear. Two new studies have revealed distinct mechanisms for the innate sensing of this hidden adjuvant.
Article
Biochemistry & Molecular Biology
Yee Kien Chong, Sarang Tartey, Yuki Yoshikawa, Koshi Imami, Songling Li, Masanori Yoshinaga, Ai Hirabayashi, Guohao Liu, Alexis Vandenbon, Fabian Hia, Takuya Uehata, Takashi Mino, Yutaka Suzuki, Takeshi Noda, Dominique Ferrandon, Daron M. Standley, Yasushi Ishihama, Osamu Takeuchi
Summary: Cyclin J reduces cytokine production in macrophages by controlling glycolysis and mitochondrial functions. In mice, macrophage-specific cyclin J limits tumor growth, protects against LPS-induced shock, but increases susceptibility to bacterial infection.
Article
Cell Biology
Ka Man Tse, Alexis Vandenbon, Xiaotong Cui, Takashi Minot, Takuya Uehata, Keiko Yasuda, Ayuko Sato, Tohru Tsujimura, Fabian Hia, Masanori Yoshinaga, Makoto Kinoshita, Tatsusada Okuno, Osamu Takeuchi
Summary: This study developed a therapeutic strategy to suppress inflammatory responses by targeting Regnase-1, a ribonuclease involved in immune reactions. By using antisense phosphorodiamidate morpholino oligonucleotides to alter Regnase-1's binding to stem-loop structures, this strategy enhanced Regnase-1 expression and reduced proinflammatory transcripts. In animal models, intratracheal administration of Regnase-1-targeting MOs improved respiratory distress and fibrosis, while intracranial treatment attenuated the development of autoimmune encephalomyelitis.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biology
Yoichi Miyamoto, Yumi Itoh, Tatsuya Suzuki, Tomohisa Tanaka, Yusuke Sakai, Masaru Koido, Chiaki Hata, Cai-Xia Wang, Mayumi Otani, Kohji Moriishi, Taro Tachibana, Yoichiro Kamatani, Yoshihiro Yoneda, Toru Okamoto, Masahiro Oka
Summary: The study reveals that SARS-CoV-2 ORF6 directly binds to STAT1 and prevents its nuclear localization, thereby interfering with the interferon-mediated antiviral signaling pathway. ORF6 also recognizes importin alpha subtypes and promotes the nuclear exclusion of STAT1. These findings provide insights into the replication and disease progression mechanisms of SARS-CoV-2.
COMMUNICATIONS BIOLOGY
(2022)
Article
Immunology
Akane Watanabe, Sumiyuki Nishida, Temizoz Burcu, Takayuki Shibahara, Takato Kusakabe, Etsushi Kuroda, Ken J. Ishii, Atsushi Kumanogoh
Summary: This study investigated the safety and immunogenicity of a seasonal influenza vaccine adjuvanted with HP-beta-CyD. The results showed that the vaccine was well tolerated and immunogenic in healthy adults, despite containing less HA antigens.
Article
Cardiac & Cardiovascular Systems
Ai Yaku, Tadakatsu Inagaki, Ryotaro Asano, Makoto Okazawa, Hiroyoshi Mori, Ayuko Sato, Fabian Hia, Takeshi Masaki, Yusuke Manabe, Tomohiko Ishibashi, Alexis Vandenbon, Yoshinari Nakatsuka, Kotaro Akaki, Masanori Yoshinaga, Takuya Uehata, Takashi Mino, Satoshi Morita, Hatsue Ishibashi-Ueda, Akio Morinobu, Tohru Tsujimura, Takeshi Ogo, Yoshikazu Nakaoka, Osamu Takeuchi
Summary: The study found that Regnase-1 maintains lung immune homeostasis by regulating IL-6 and platelet-derived growth factor in alveolar macrophages, suppressing the development of PAH. Mice lacking Regnase-1 showed severe PAH, mirroring the pathology of patients. IL-6 and PDGF are potential targets of Regnase-1 in regulating PAH in alveolar macrophages.
Article
Multidisciplinary Sciences
Masanori Yoshinaga, Kyuho Han, David W. Morgens, Takuro Horii, Ryosuke Kobayashi, Tatsuaki Tsuruyama, Fabian Hia, Shota Yasukura, Asako Kajiya, Ting Cai, Pedro H. C. Cruz, Alexis Vandenbon, Yutaka Suzuki, Yukio Kawahara, Izuho Hatada, Michael C. Bassik, Osamu Takeuchi
Summary: In this study, the authors demonstrate the essential role of RNA methyltransferase METTL16 and MTR4-nuclear exosome in maintaining erythropoiesis and regulating DNA repair in erythroblasts. METTL16 controls the expression of DNA repair-related genes by depositing N-6-methyladenosine (m(6)A) on the structured motifs of their transcripts. Additionally, the MTR4-nuclear RNA exosome complex is involved in the regulation of METTL16 substrate mRNAs in erythroblasts.
NATURE COMMUNICATIONS
(2022)
Review
Chemistry, Medicinal
Ka Man Tse, Osamu Takeuchi
Summary: Innate immunity is responsible for anti-infective response and inflammation, which can have deleterious consequences if over-exaggerated. Cytokines play a critical role in inflammation and immune defense. Post-transcriptional regulation is important in fine-tuning cytokine expression. This review focuses on pattern-recognition receptors in innate immunity, post-transcriptional regulations of inflammatory mediators by RNA-binding proteins, especially Regnase-1, and potential therapeutic strategies for chronic and autoimmune diseases.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yuxin Wang, Tatsuya Morishima, Maiko Sezaki, Ryo Sato, Gaku Nakato, Shinji Fukuda, Kouji Kobiyama, Ken J. Ishii, Yuhua Li, Hitoshi Takizawa
Summary: Bacterial infections can activate hematopoietic stem and progenitor cells to migrate from the bone marrow to the spleen, a process known as extramedullary hematopoiesis. Recent studies have shown that gut commensal bacteria not only regulate the host immune system, but also hematopoietic homeostasis. This study reveals that Akkermansia muciniphila, a mucin-degrading bacterium, can rapidly activate bone marrow myelopoiesis and induce delayed extramedullary hematopoiesis through the MYD88/TRIF innate immune signaling pathway.
Article
Biology
Kotaro Akaki, Takashi Mino, Osamu Takeuchi
Summary: This article introduces a method for detecting protein-protein interactions, which stabilizes PPI by crosslinking POI and its binding proteins, increasing the chance of detecting interacting proteins.
Article
Immunology
Shunsuke Yamada, Yuichi Kitai, Takashi Tadokoro, Runa Takahashi, Haruka Shoji, Taiga Maemoto, Marie Ishiura, Ryuta Muromoto, Jun-Ichi Kashiwakura, Ken J. Ishii, Katsumi Maenaka, Taro Kawai, Tadashi Matsuda
Summary: Damage-associated molecular patterns (DAMPs) released from cancer cells play a crucial role in activating antitumor immune responses during cancer chemotherapy. This study reveals that topotecan (TPT) inhibits the formation of preribosomal subunits by targeting RPL15, triggering the secretion of DAMPs and enhancing the antitumor immune activation. Ribosomal stress is identified as the key factor in inducing DAMP release, highlighting the potential implications for antitumor immunotherapy.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Burcu Temizoz, Kou Hioki, Shingo Kobari, Nao Jounai, Takato Kusakabe, Michelle S. J. Lee, Cevayir Coban, Etsushi Kuroda, Ken J. Ishii
Summary: Combining TLR9 and STING agonists can synergistically induce IFN-gamma, serving as an effective anti-tumor therapy, particularly important for cancers like pancreatic cancer.
INTERNATIONAL IMMUNOLOGY
(2022)