Article
Immunology
Artur Javmen, Jun Zou, Shreeram C. Nallar, Henryk Szmacinski, Joseph R. Lakowicz, Andrew T. Gewirtz, Vladimir Y. Toshchakov
Summary: A peptide named 5R667 was found to have the strongest inhibitory effect on TLR5 signaling and could also inhibit signaling of TLR4, TLR2, and TLR9. It selectively bound to the TIR domains of TLR adapters and formed motifs that are highly conserved in vertebrate evolution. These findings suggest that 5R667 can serve as a pan-specific TLR inhibitor.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julia Maria Coronas-Serna, Elba del Val, Jonathan C. Kagan, Maria Molina, Victor J. Cid
Summary: Toll-like receptor signaling plays a key role in detecting pathogens and initiating inflammation through supramolecular organizing centers (SMOCs), which rely on protein-protein interactions involving Toll Interleukin-1 Receptor (TIR) and Death Domain (DD).
Article
Cell Biology
Richard M. Lucas, Liping Liu, James E. B. Curson, Yvette W. H. Koh, Neeraj Tuladhar, Nicholas D. Condon, Kaustav Das Gupta, Sabrina S. Burgener, Kate Schroder, Evan Ingley, Matthew J. Sweet, Jennifer L. Stow, Lin Luo
Summary: The immune-specific transmembrane adaptor SCIMP acts as a scaffold for Erk1/2 in TLR pathways, guiding the spatial and temporal recruitment of Erk2 for pro-inflammatory TLR4 signaling. SCIMP deficiency results in defects in Erk1/2 recruitment, c-Fos activation, and pro-inflammatory cytokine production, with these effects being phenocopied by Erk1/2 signaling inhibition. This highlights a specific role for SCIMP in membrane recruitment of Erk1/2 kinase to initiate TLR-mediated pro-inflammatory responses in macrophages.
Article
Agriculture, Dairy & Animal Science
Haofei Song, Jima Quan, Chang Li, Wan Liang, Lan Zhang, Shuangshuang Wang, Hongyu Lu, Keli Yang, Danna Zhou, Peng Li, Yongxiang Tian
Summary: In this study, we found that overexpression of the SLAMF1 gene significantly inhibited PRRSV replication and reduced the levels of key signaling pathways and inflammatory factors. On the other hand, knockdown of the SLAMF1 gene enhanced PRRSV replication and the levels of key signaling pathways and inflammatory factors.
Article
Multidisciplinary Sciences
Uyory Choe, Quynhchi Pham, Young S. Kim, Liangli Yu, Thomas T. Y. Wang
Summary: This study examined the expression, regulation, and function of SLAMF protein members in human monocytes and macrophages. Differentiated THP-1 macrophages showed higher levels of SLAMF7 compared to other SLAMF members, and TLR stimuli increased the expression of SLAMF7 mRNA. Importantly, SLAMF7 enhanced the TLR-mediated induction of pro-inflammatory cytokines, but had no effect on phagocytosis.
SCIENTIFIC REPORTS
(2023)
Article
Biotechnology & Applied Microbiology
LinWei Li, Jing Xia, RuTing Cui, Bin Kong
Summary: The study showed that SLC12A8 is upregulated in breast carcinoma, with high levels associated with a poorer prognosis and a positive correlation with the TLR/NLR signaling pathway. Functional experiments revealed that SLC12A8 promotes cell viability, invasiveness, and motility in breast carcinoma cells by activating the TLR/NLR signaling pathway.
Article
Oncology
Tingfeng Wu, Yongxiu Chen, Liying Yang, Xiangyu Wang, Ke'en Chen, Dianshuang Xu
Summary: RNASE2 is a novel marker associated with the diagnosis and prognosis of patients with glioma, and it promotes the malignant progression of gliomas through the PI3K/Akt signaling pathway.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Suiying Liang, Yueyang Liu, Jianhui He, Tian Gao, Lanying Li, Shanyang He
Summary: The overexpression of FAM46A in ovarian cancer patients is associated with aggressive phenotype and poor prognosis. Additionally, FAM46A overexpression leads to increased resistance to cisplatin in ovarian cancer cells. However, inhibition of FAM46A sensitizes ovarian cancer cells to cisplatin cytotoxicity. Mechanistically, upregulation of FAM46A activates TGF-beta/Smad signaling and upregulates nuclear Smad2 levels.
Article
Anatomy & Morphology
Xin Li, Sheng Xiao, Fanling Li, Ke Fang, Jie Wen, Haoli Gong
Summary: This study elucidated the mechanism underlying Th17/Treg imbalance during osteoarthritis progression. The results showed that MXI1 promoted Th17 cell differentiation and restricted Treg cell differentiation, leading to accelerated progression of osteoarthritis.
Article
Oncology
Qian Li, Mengqing Sun, Yao Meng, Mengqing Feng, Menglan Wang, Cunjie Chang, Heng Dong, Fangtian Bu, Chao Xu, Jing Liu, Qi Ling, Yiting Qiao, Jianxiang Chen
Summary: In hepatocellular carcinoma, upregulation of KIF18B is associated with hyperactivation of the mTORC1 signaling pathway, poor prognosis, and HCC recurrence. KIF18B promotes HCC cell proliferation and migration by activating mTORC1 signaling. KIF18B and γ-Actin synergistically modulate lysosome positioning and enhance mTORC1 signaling transduction.
Review
Education, Scientific Disciplines
Shupeng Liu, Yang He, Shifeng Li, Xuemin Gao, Fang Yang
Summary: Kinesin family member 3A is a crucial motor protein involved in various physiological and pathological processes. The wingless-related integration site/beta-catenin signaling pathway plays a vital role in embryonic development, organogenesis, tissue regeneration, and carcinogenesis. Recent studies have focused on the molecular mechanisms of kinesin family member 3A, particularly its interaction with the wingless-related integration site/beta-catenin signaling pathway. The upregulation and downregulation of kinesin family member 3A influence disease pathogenesis and patient outcomes through the wingless-related integration site/beta-catenin signaling pathway.
Article
Cardiac & Cardiovascular Systems
Chenyang Gao, Wangxing Hu, Feng Liu, Zhiru Zeng, Qifeng Zhu, Jiaqi Fan, Jinyong Chen, Si Cheng, Kaixiang Yu, Yi Qian, Tanchen Ren, Jing Zhao, Xianbao Liu, Jian'an Wang
Summary: This study demonstrates that inhibition of Akr1B1 can attenuate calcification degree both in vitro and in vivo. The Akr1B1 inhibitor epalrestat may be a potential treatment option for CAVD.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Enhua Shen, Jingzhi Zhang, Yujuan Lu
Summary: DEPDC1B is highly expressed in HCC cells and its knockdown inhibits cell growth and invasion, exerting an anticancer effect through activating the p53 signaling pathway.
Article
Multidisciplinary Sciences
Kuniaki Yabe, Yasuko Yamamoto, Masao Takemura, Takeshi Hara, Hisashi Tsurumi, Ginette Serrero, Toshitaka Nabeshima, Kuniaki Saito
Summary: Progranulin plays a crucial role in hematopoietic cancers, modulating cell proliferation via the TGF-β axis. Studies suggest that Progranulin could be a potential new therapeutic target for hematopoietic cancers.
Article
Biochemistry & Molecular Biology
Tomomi Hasegawa, Nonawin Lucob-Agustin, Koki Yasufuku, Takaaki Kojima, Shunsaku Nishiuchi, Atsushi Ogawa, Misuzu Takahashi-Nosaka, Mana Kano-Nakata, Mayuko Inari-Ikeda, Moeko Sato, Hiroyuki Tsuji, Cornelius Mbathi Wainaina, Akira Yamauchi, Yoshiaki Inukai
Summary: The our1 mutant exhibits accelerated seminal root elongation through promotion of cell division and elongation, reduction of short and thin lateral roots density, and increase in long and thick lateral roots density. The OUR1 gene promotes root development by suppressing auxin signaling.
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)
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
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
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
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
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
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
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)
Article
Oncology
Chikako Shibata, Motoyuki Otsuka, Takahiro Seimiya, Takahiro Kishikawa, Kazunaga Ishigaki, Mitsuhiro Fujishiro
CLINICAL AND TRANSLATIONAL MEDICINE
(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)
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
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.