Article
Genetics & Heredity
Thet Fatica, Turaya Naas, Urszula Liwak, Hannah Slaa, Maryam Souaid, Brianna Frangione, Ribal Kattini, Antoine Gaudreau-Lapierre, Laura Trinkle-Mulcahy, Pranesh Chakraborty, Martin Holcik
Summary: Mitochondrial diseases are caused by dysfunctional mitochondria, and a significant portion of these diseases are associated with defects in genes responsible for tRNA metabolism. Partial loss-of-function mutations in the TRNT1 gene, which encodes the CCA-adding enzyme essential for modifying both nuclear and mitochondrial tRNAs, lead to a clinically heterogeneous disease called SIFD. Studies have found that TRNT1 deficiency results in increased sensitivity to oxidative stress and dysregulation of tRNA maturation and abundance, ultimately affecting the translation of specific proteins.
Review
Cell Biology
Tania Gupta, Mark G. Malkin, Suyun Huang
Summary: Transfer RNA (tRNA) plays a central role in protein synthesis and the epigenetic regulation of gene expression in tumors. It is also involved in cell processes such as proliferation, signaling pathways, and stress response, which are all implicated in tumorigenesis and cancer progression. Understanding tRNA function and dysregulation can lead to the development of treatments for various cancers. Additionally, tRNA modifications, including methylation, are important for tRNA folding, stability, and function. Stress-induced tRNA cleavage can form tiRNAs and short tRNA fragments (tRFs), all of which can impact a cell's fate.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Sherif Rashad, Teiji Tominaga, Kuniyasu Niizuma
Summary: Research has shown that tRNA is cleaved into tiRNA under stress, leading to repression of protein translation. The enzyme angiogenin, previously thought to be the main cleaver of tRNA, may not be required for all tiRNA generation. Mitochondrial stress plays a crucial role in regulating angiogenin-mediated tRNA cleavage.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rosanna Culurciello, Andrea Bosso, Romualdo Troisi, Valentina Barrella, Ilaria Di Nardo, Margherita Borriello, Rosa Gaglione, Valeria Pistorio, Serena Aceto, Valeria Cafaro, Eugenio Notomista, Filomena Sica, Angela Arciello, Elio Pizzo
Summary: The study found that human angiogenin (ANG) can change its subcellular localization under different cellular stresses and regulate cellular homeostasis in HaCaT cells. This research provides new insights into the potential functions of ANG in the stress response of human skin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Seokjun G. Ha, Seung-Jae Lee
Summary: Aging is characterized by a gradual decline in biological functions, leading to increased probability of diseases and deaths. Previous studies have identified non-coding RNAs (ncRNAs) as biological factors that modulate aging and lifespan. This review focuses on the relationship between tRNA-derived small RNAs (tsRNAs), ncRNAs generated from cleavage of tRNAs, and aging. It discusses age-dependent changes in tsRNA levels, their functions in age-related diseases, and their association with aging-regulating processes such as mitochondrial respiration and mRNA translation.
Article
Oncology
Litao Han, Hejing Lai, Yichen Yang, Jiaqian Hu, Zhe Li, Ben Ma, Weibo Xu, Wanlin Liu, Wenjun Wei, Duanshu Li, Yu Wang, Qiwei Zhai, Qinghai Ji, Tian Liao
Summary: In this study, a 33nt tiRNA-Gly was found to significantly increase in papillary thyroid cancer (PTC). TiRNA-Gly promotes cell proliferation and migration by directly binding to the splicing-related RNA binding protein RBM17. The expression of RBM17 in tiRNA-Gly high-expressing human PTC tissues is upregulated.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Neurosciences
Steven G. Fagan, Mark Helm, Jochen H. M. Prehn
Summary: tsRNA is a recently identified family of non-coding RNA that regulate various cellular functions in the nervous system, including stress responses, proteostasis, and neuronal survival during disease processes. Mutations to tRNA cleaving and modifying enzymes have been associated with several neurodegenerative disorders, and tsRNA levels in blood are emerging as biomarkers for neurological diseases.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Liping Luo, Ya Liu, Paul Nizigiyimana, Mingsheng Ye, Ye Xiao, Qi Guo, Tian Su, Xianghang Luo, Yan Huang, Haiyan Zhou
Summary: The study reveals the crucial role of DNA 6mA modification in the progression of nonalcoholic fatty liver disease (NAFLD). The down-regulation of ALKBH1 protein expression is associated with hepatic steatosis in NAFLD patients. It is further demonstrated that ALKBH1 protein can demethylate genes involved in fatty acid uptake and lipogenesis, resulting in reduced hepatic lipid accumulation.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Engineering, Aerospace
Hao Bai, Tongshan Zhang, Jufang Wang, Junrui Hua, Wenjun Wei
Summary: Space radiation, particularly heavy ions in cosmic rays, can cause serious DNA damage and potential carcinogenesis. Recent research identified new proteins, miRNAs, and tRNA fragments in serum as potential early biomarkers for exposure to heavy ions, which could be valuable for dose reconstruction and risk assessment in deep space exploration.
Article
Chemistry, Multidisciplinary
Eva Korytiakova, Ewelina Kaminska, Markus Mueller, Thomas Carell
Summary: The synthesis of a fluorinated fdC feeding probe allowed for the study of direct deformylation to F-dC, providing insights into the Tdg-independent removal process. The research demonstrated deformylation occurring in both stem cells and different somatic cell types. Additionally, active demethylation was investigated in a non-dividing neurogenin-inducible system of iPS cells differentiating into bipolar neurons.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Ilenia Martinelli, Mathieu Cinato, Sokhna Keita, Dimitri Marsal, Valentin Antoszewski, Junwu Tao, Oksana Kunduzova
Summary: The study found that short-term exposure to EMF did not have a significant effect on the myocardial antioxidant defense system and apoptotic cell death in cardiac cells and tissues.
Article
Biochemistry & Molecular Biology
Yasutoshi Akiyama, Yoshika Takenaka, Tomoko Kasahara, Takaaki Abe, Yoshihisa Tomioka, Pavel Ivanov
Summary: Under stress conditions, transfer RNAs (tRNAs) are cleaved to produce tiRNAs, which are negatively regulated by the RTCB ligase complex. RTCB-LC can repair tiRNAs to full-length tRNAs in vitro. Hydrogen peroxide enhances tiRNA production under stress conditions by inhibiting RTCB-LC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yosuke Tabei, Hiroko Abe, Shingo Suzuki, Nobuaki Takeda, Jun-ichiro Arai, Yoshihiro Nakajima
Summary: This study demonstrated that Sedanolide enhances cellular resistance to oxidative damage through the activation of the KEAP1-NRF2 pathway and upregulation of antioxidant enzymes. Additionally, Sedanolide attenuates cytosolic and mitochondrial ROS generation induced by H2O2, thereby exerting cytoprotective effects against H2O2-induced cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Ning Li, Meiyu Chang, Qiang Zhou, Lin Zhang, Yongheng Wang, Yi Guan, Haibin Li, Yingzheng Zhao, Chunjie Ding, Shan Hong, Sanqiao Yao
Summary: Metformin can attenuate silica-induced pulmonary fibrosis by regulating oxidative stress and the mitochondrial apoptotic pathway. Daily administration of 100 mg/kg Metformin for 21 consecutive days effectively alleviates pulmonary fibrosis through activation of AMPK signaling and relief of oxidative stress and mitochondrial apoptosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yurong Fu, Yongcheng Jin, Yue Tian, Hao Yu, Ruqi Wang, Huiyu Qi, Bo Feng, Jing Zhang
Summary: The synergistic effect of ZEA and LPS aggravates cytotoxicity by increasing the accumulation of ROS and MDA, decreasing MMP and SOD levels, and reducing GSH levels. Additionally, ZEA and LPS promote cell apoptosis by activating ER stress and suppressing anti-apoptotic proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Shintaro Nakajima, Shinichiro Sugiyama, Hidenori Oishi, Kenichi Sato, Yasushi Matsumoto, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga
Summary: The study demonstrated the usefulness of CFD analysis in diagnosing atherosclerotic changes in large CCAs, which may affect therapeutic response following flow diversion. Post-CFD visualization showed that intra-aneurysmal swirling flow prolonged blood residence time under conditions of small inlet flow rates compared to aneurysmal volume.
Article
Clinical Neurology
Dan Ozaki, Hidenori Endo, Ryosuke Tashiro, Koichiro Sugimura, Shunsuke Tatebe, Satoshi Yasuda, Yasutake Tomata, Toshiki Endo, Keita Tominaga, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga
Summary: Moyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare conditions with steno-occlusive vascular lesions, and genetic studies suggest a potential link between RNF213 polymorphism and these diseases, particularly the homozygote variant of RNF213 c.14576G>A. Surgical indications for MMD patients with PPAS should be carefully evaluated.
CEREBROVASCULAR DISEASES
(2022)
Article
Clinical Neurology
Hidenori Endo, Naoko Mori, Shunji Mugikura, Kuniyasu Niizuma, Shunsuke Omodaka, Kei Takase, Teiji Tominaga
Summary: This study aimed to evaluate new quantitative parameters of aneurysm wall enhancement (AWE) on magnetic resonance vessel wall imaging (VWI) in differentiating between stable and evolving unruptured intracranial aneurysms (UIAs). The results showed significant differences in shape features and AWE between the stable and evolving groups, indicating the effectiveness of quantitative combined analysis for distinguishing between these two conditions.
Article
Nanoscience & Nanotechnology
Khalid M. Saqr, Kiyomitsu Kano, Sherif Rashad, Kuniyasu Niizuma, Yasuhiko Kaku, Toru Iwama, Teiji Tominaga
Summary: This study explores the therapeutic hemodynamic changes after carotid artery stenting using high-resolution large eddy simulation. The study reveals that the stent can reduce velocity oscillations downstream the stenosis throat, restore the inverse kinetic energy cascade, and stabilize hemorheological fluctuations. These findings are valuable for guiding the design and optimization of carotid stents and understanding the mechanisms of vascular remodeling and carotid stenosis.
Article
Endocrinology & Metabolism
Liyin Zhang, Sherif Rashad, Yuan Zhou, Kuniyasu Niizuma, Teiji Tominaga
Summary: RNF213 gene mutations are found to be responsible for Moyamoya disease, a rare cerebrovascular occlusive disease. This study investigated the function of RNF213 in the vascular system by performing gene knockdown experiments in vascular cells. The results showed that RNF213 knockdown disrupted angiogenesis in HUVEC cells and sensitized them to inflammation. The study also revealed extensive changes in mRNA splicing and alterations in cytoskeletal organization and function in vSMCs after RNF213 knockdown. Furthermore, RNF213 knockdown disrupted endothelial-to-vSMCs communication in co-culture models.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Pharmacology & Pharmacy
Takashi Moritoyo, Naoko Nishimura, Keiko Hasegawa, Shinya Ishii, Kenji Kirihara, Munenori Takata, Akiko Kishi Svensson, Yumi Umeda-Kameyama, Shuichi Kawarasaki, Ryoko Ihara, Chie Sakanaka, Yurie Wakabayashi, Kuniyasu Niizuma, Teiji Tominaga, Tsutomu Yamazaki, Keiji Hasumi
Summary: TMS-007, a member of the SMTP family, modulates plasminogen conformation and enhances plasminogen-fibrin binding, promoting endogenous fibrinolysis. It also exhibits anti-inflammatory action through the inhibition of soluble epoxide hydrolase. The study evaluates the safety, pharmacokinetics and pharmacodynamics of TMS-007 in healthy volunteers.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Kimio Watanabe, Emiko Sato, Eikan Mishima, Mariko Miyazaki, Tetsuhiro Tanaka
Summary: Diabetic kidney disease (DKD) is the main cause of chronic kidney disease and increases the risk of cardiovascular mortality. Treatment options for DKD have advanced, but their efficacy is limited. A deeper understanding of the molecular mechanisms of DKD is necessary for the development of new treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Eikan Mishima, Adam Wahida, Tobias Seibt, Marcus Conrad
Summary: Vitamin K plays a crucial role in various physiological processes, such as blood coagulation, by serving as a cofactor for protein conversion. It also has carboxylation-independent functions, acting as an electron carrier and preventing cell death. This perspective offers an overview of the diverse functions of vitamin K, including its involvement in ferroptosis, and discusses its relationship with ferroptosis suppressor protein-1. A comparison between vitamin K and ubiquinone from an evolutionary perspective may provide further insights.
Article
Clinical Neurology
Naoya Yamazaki, Takafumi Hasegawa, Kensuke Ikeda, Ako Miyata, Shin-ichiro Osawa, Kuniyasu Niizuma, Shigenori Kanno, Teiji Tominaga, Masashi Aoki
Summary: Disturbance of smell is often associated with neurodegenerative diseases and can also be caused by head trauma, intracranial tumors, and hydrocephalus. Olfactory dysfunction is often overlooked due to the prominence of motor symptoms. This case report highlights that hydrocephalus can cause olfactory dysfunction and that it can be improved with surgical treatment.
CASE REPORTS IN NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yoshiharu Takahashi, Takumi Kajitani, Toshiki Endo, Atsushi Nakayashiki, Tomoo Inoue, Kuniyasu Niizuma, Teiji Tominaga
Summary: In this study, the potential of systemic administration of Muse cells as an effective treatment for subacute spinal cord injury (SCI) was examined. The results showed that Muse cells in CL2020 facilitated the improvement of hindlimb motor functions and reduction of cystic cavity size in a rat model of SCI. Additionally, a larger number of descending 5-HT fibers were preserved in the distal spinal cord after CL2020 treatment. The differentiation of Muse cells into neuronal and neural cells in the injured spinal cord was observed. These findings demonstrate the therapeutic potential of intravenously administered Muse cells for severe subacute SCI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Kuniyasu Niizuma, Shin-Ichiro Osawa, Hidenori Endo, Shin-Ichi Izumi, Kota Ataka, Akihiro Hirakawa, Masao Iwano, Teiji Tominaga
Summary: This randomized placebo-controlled trial demonstrated that CL2020, an allogenic Muse cell-based product, may be an effective treatment for subacute ischemic stroke, improving patients' condition and safety.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Letter
Multidisciplinary Sciences
Eikan Mishima, Toshitaka Nakamura, Jiashuo Zheng, Weijia Zhang, Andre Santos Dias Mourao, Peter Sennhenn, Marcus Conrad
Article
Multidisciplinary Sciences
Toshitaka Nakamura, Clara Hipp, Andre Santos Dias Mourao, Jan Borggraefe, Maceler Aldrovandi, Bernhard Henkelmann, Jonas Wanninger, Eikan Mishima, Elena Lytton, David Emler, Bettina Proneth, Michael Sattler, Marcus Conrad
Summary: Ferroptosis is a promising approach for treating difficult-to-treat tumors. The second ferroptosis-suppressing system, involving ferroptosis suppressor protein-1 (FSP1), has been identified, which efficiently prevents lipid peroxidation independently of the cyst(e)ine-glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis. Through a small molecule library screen, the potent FSP1 inhibitors of 3-phenylquinazolinones were identified. These inhibitors trigger subcellular relocalization of FSP1 and induce FSP1 condensation, synergistically with GPX4 inhibition, leading to ferroptosis induction. The results suggest that targeting FSP1-dependent phase separation with icFSP1 could be an efficient anti-cancer therapy.
Article
Biochemistry & Molecular Biology
Kimio Watanabe, Emiko Sato, Eikan Mishima, Shinobu Moriya, Takuma Sakabe, Atsuya Sato, Momoko Fujiwara, Takuya Fujimaru, Yugo Ito, Fumika Taki, Masahiko Nagahama, Kenichi Tanaka, Junichiro James Kazama, Masaaki Nakayama
Summary: HIF-PHIs are a new class of medications for managing renal anemia in patients with chronic kidney disease. They have multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis. This study investigated changes in plasma metabolomic profiles following the switch from an erythropoiesis-stimulating agent (ESA) to an HIF-PHI in hemodialysis patients, revealing significant changes in several compounds and decreased levels in specific metabolic pathways. These findings provide insights into the systemic biological effects of HIF-PHIs and contribute to evaluating their long-term use.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Takehiko Sugano, Nobuhiro Yoda, Toru Ogawa, Teruo Hashimoto, Kenta Shobara, Kuniyasu Niizuma, Ryuta Kawashima, Keiichi Sasaki
Summary: This study aimed to determine the optimal DTI parameters for masseter muscle fiber tractography. DTI and MRI were performed on a healthy male, and it was found that the imaging parameters significantly affected fiber length but had no significant effect on fiber orientation. The appropriate parameter combination for masseter muscle fiber tractography can be determined based on anatomical data.
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
