Article
Pharmacology & Pharmacy
Fangliang Guo, Xiaolong Zheng, Ziyu He, Ruoying Zhang, Song Zhang, Minghuan Wang, Hong Chen, Wei Wang
Summary: The study found that long-term treatment with NMD helps to improve locomotion, pain-related behaviors, and spasticity-like symptoms in rats with SCI, but has less effect on open-field activity, hind limb grip strength, and bladder function. Additionally, NMD-treated rats showed greater tissue preservation, reduced lesion areas, and increased perilesional neuronal sparing, suggesting a potential therapeutic strategy for SCI treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Shiva Hashemizadeh, Zeinab Gharaylou, Saereh Hosseindoost, Maryam Sardari, Ameneh Omidi, Hassan Hosseini Ravandi, Mahmoudreza Hadjighassem
Summary: This study found that early administration of bumetanide after spinal cord injury can promote recovery of locomotor function. The results showed that bumetanide can reduce the expression of NKCC1 gene and increase GAP protein levels, thereby having neuroprotective and regenerative effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mohamed Ashmwe, Katja Posa, Alexander Ruehrnoessl, Johannes Christoph Heinzel, Patrick Heimel, Michael Mock, Barbara Schaedl, Claudia Keibl, Sebastien Couillard-Despres, Heinz Redl, Rainer Mittermayr, David Hercher
Summary: This study investigated the effects of low-energy ESWT on recovery in spinal cord injury and identified changes in miRNA expression patterns. The results showed that ESWT significantly improved motor function in both subacute and chronic experimental settings.
Article
Neurosciences
Ming-hao Ge, He Tian, Liang Mao, Dao-yong Li, Jia-quan Lin, Heng-shuo Hu, Shuo-cheng Huang, Chuan-jie Zhang, Xi-fan Mei
Summary: The study demonstrated that zinc can inhibit ferroptosis by regulating the NRF2/HO-1 and GPX4 signaling pathways, exerting a neuroprotective effect in spinal cord injury.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Chemistry, Medicinal
Haojie Zhang, Chenyu Wu, Dong-Dong Yu, Haohan Su, Yanlin Chen, Wenfei Ni
Summary: Piperine has therapeutic effects in spinal cord injury models, enhancing functional recovery, reducing inflammation and oxidative stress, and activating autophagy.
PHYTOTHERAPY RESEARCH
(2023)
Article
Neurosciences
Camila Marques Freria, Lori Graham, Ali Azimi, Paul Lu
Summary: We propose an updated model of moderately severe bilateral cervical level 6 contusive spinal cord injury (SCI) in the rat, which is more clinically relevant than previous models and allows animals to survive the lesion. This model closely mimics the most common cervical level of SCI in humans and provides a superior tool for assessing motor recovery interventions.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Cell & Tissue Engineering
Xunwei Lai, Yang Wang, Xiaokang Wang, Bin Liu, Limin Rong
Summary: Modified exosomes targeting neurotoxic astrocytes can promote neurological function recovery in spinal cord injury.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Cell Biology
Fangyi Gong, Ting Ge, Jing Liu, Jin Xiao, Xiaochuan Wu, Hehui Wang, Yingchun Zhu, Dongdong Xia, Baiwen Hu
Summary: In this study, the researchers demonstrated for the first time that trehalose reduces degeneration and iron accumulation of neurons in spinal cord injury (SCI) by inhibiting the production of reactive oxygen species (ROS) and ferroptosis caused by lipid peroxides. This promotes the survival of neurons and improves motor function recovery. The neuroprotective effect of trehalose is mediated by the activation of the NRF2/HO-1 pathway, which inhibits ferroptosis and ferroptosis-related inflammation. These findings provide valuable insights into the role of trehalose in SCI and support the hypothesis that suppressing ferroptosis plays a crucial neuroprotective role.
Article
Anesthesiology
Courtney A. Bannerman, Katya Douchant, Julia P. Segal, Mitra Knezic, Alexandra E. Mack, Caitlin Lundell-Creagh, Jaqueline R. Silva, Scott Duggan, Prameet Sheth, Nader Ghasemlou
Summary: Chronic pain is a common complication of spinal cord injury. This study developed a mouse model of spinal cord injury and observed the pain phenotype and related pathology after injury. The study also investigated the changes in the gastrointestinal microbiome.
Article
Immunology
Weiyi Zhao, Natalie Gasterich, Tim Clarner, Clara Voelz, Victoria Behrens, Cordian Beyer, Athanassios Fragoulis, Adib Zendedel
Summary: This study suggests that activation of Nrf2 in astrocytes protects against spinal cord injury by reducing oxidative damage and neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Neurosciences
Simon M. Danner, Courtney T. Shepard, Casey Hainline, Natalia A. Shevtsova, Ilya A. Rybak, David S. K. Magnuson
Summary: Thoracic spinal cord injury affects long propriospinal neurons that interconnect the cervical and lumbar enlargements, and these neurons are crucial for coordinating forelimb and hindlimb locomotor movements. Investigating locomotion over the full range of speeds can reveal otherwise hidden aspects of spinal locomotor control and post-injury recovery, which may not be fully exposed by studying recovery over a limited range of speeds.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
James W. Wiggins, Jonathan E. Sledd, Lique M. Coolen
Summary: Spinal cord injury in male rats results in decreased expression of GRP and galanin in LSt cells, with a greater impact on GRP levels. This reduction may contribute to ejaculatory dysfunction following SCI.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Li-Na Xuan, Zhen-Xin Hu, Zhen-Fu Jiang, Cong Zhang, Xiao-Wan Sun, Wen-Hua Ming, Hui-Tao Liu, Rong-Fang Qiao, Lin-Jie Shen, Shao-Bo Liu, Guan-Yu Wang, Lin Wen, Zhi-Lin Luan, Jian Yin
Summary: In this study, it was found that pregnane X receptor (PXR) is involved in the recovery of motor function after spinal cord injury (SCI) by regulating the NRF2/HO-1 pathway. Activation of PXR suppressed the NRF2/HO-1 pathway, while PXR deficiency activated this pathway and improved motor function in mice after SCI.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Connor A. Wathen, Yohannes G. Ghenbot, Ali K. Ozturk, D. Kacy Cullen, John C. O'Donnell, Dmitriy Petrov
Summary: Large animal models, particularly porcine models, of spinal cord injury are valuable for translational research and evaluation of potential therapies. The anatomical and physiological similarities to humans allow for more representative models and accurate assessment of novel treatments, including biologics. Porcine models also facilitate the collection of physiological data in a clinical-like setting. This review provides an overview of porcine spinal cord injury research, including available models and outcome measures, as well as the strengths, limitations, and alternatives.
Article
Neurosciences
Johannie Audet, Charly G. Lecomte
Summary: Tonic or phasic electrical epidural stimulation in the lumbosacral region can improve locomotion and standing in severe spinal cord injury models, but the mechanisms behind this remain largely unknown. There are limitations that currently prevent the widespread clinical implementation of this promising therapeutic approach.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Tomohiro Edamitsu, Keiko Taguchi, Ryuhei Okuyama, Masayuki Yamamoto
Summary: The skin is constantly exposed to environmental insults, which can disrupt epidermal homeostasis and lead to skin diseases. AHR and NRF2 are transcription factors that play important roles in maintaining skin homeostasis and their dysfunction may contribute to the pathogenesis of skin diseases, particularly atopic dermatitis. AHR and NRF2 may serve as potential therapeutic targets for atopic dermatitis.
Article
Multidisciplinary Sciences
Sharadha Dayalan Naidu, Takafumi Suzuki, Dina Dikovskaya, Elena Knatko, Maureen Higgins, Miu Sato, Miroslav Novak, Jose A. Villegas, Terry W. Moore, Masayuki Yamamoto, Albena T. Dinkova-Kostova
Summary: This study demonstrates that the isoquinoline compound PRL-295 increases the thermostability of Keap1, disrupts its interaction with Nrf2, and activates Nrf2-dependent transcription, thereby protecting hepatocytes.
Article
Multidisciplinary Sciences
Carla Azevedo, Gabriel Teku, Yuriy Pomeshchik, Juan F. Reyes, Margarita Chumarina, Kaspar Russ, Ekaterina Savchenko, Anna Hammarberg, Nuno Jorge Lamas, Anna Collin, Gunnar K. Gouras, Oxana Klementieva, Martin Hallbeck, Ricardo Taipa, Mauno Vihinen, Laurent Roybon
Summary: Limited evidence has revealed how aSYN proteins impact the oligodendrocyte phenotype and pathogenesis in synucleinopathies like Parkinson's disease and multiple system atrophy. The study identified early phenotypic and pathogenic changes in human oligodendrocyte lineage cells derived from patients with Parkinson's disease and multiple system atrophy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Irene F. Ugidos, Cristiana Piston, Paula Korhonen, Mireia Gomez-Buda, Valeriia Sitnikova, Pamela Klecki, Lveta Stanova, Jukka Jolkkonene, Tarja Malm
Summary: Stroke is a leading cause of death worldwide with limited therapeutic options currently available. Research has shown that sex differences play a significant role in stroke treatment and outcomes, with sexual hormones and aging being key factors influencing these differences.
Article
Ophthalmology
Akiko Hanyuda, Atsushi Goto, Masahiro Nakatochi, Yoichi Sutoh, Akira Narita, Shiori Nakano, Ryoko Katagiri, Kenji Wakai, Naoyuki Takashima, Teruhide Koyama, Kokichi Arisawa, Issei Imoto, Yukihide Momozawa, Kozo Tanno, Atsushi Shimizu, Atsushi Hozawa, Kengo Kinoshita, Taiki Yamaji, Norie Sawada, Masao Iwagami, Kenya Yuki, Kazuo Tsubota, Kazuno Negishi, Keitaro Matsuo, Masayuki Yamamoto, Makoto Sasaki, Shoichiro Tsugane, Motoki Iwasaki
Summary: This study conducted a Mendelian randomization analysis to assess the causal association between genetically predicted glycemic traits and the risk of primary open-angle glaucoma (POAG). The results did not provide strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Oncology
Kinuko Ohneda, Yohei Hamanaka, Hiroshi Kawame, Nobuo Fuse, Fuji Nagami, Yoichi Suzuki, Yumi Yamaguchi-Kabata, Muneaki Shimada, Atsushi Masamune, Yoko Aoki, Takanori Ishida, Masayuki Yamamoto
Summary: Returning individual genomic results to participants in a population-based genome cohort study is beneficial for preventing or providing early intervention for associated diseases. In this study, the majority of participants were willing to know their genomic information and did not experience remarkable negative psychological impact.
Article
Endocrinology & Metabolism
Akiko Saito-Hakoda, Atsuo Kikuchi, Tadahisa Takahashi, Yu Yokoyama, Noriko Himori, Mika Adachi, Ryoukichi Ikeda, Yuri Nomura, Jun Takayama, Junko Kawashima, Fumiki Katsuoka, Fumiyoshi Fujishima, Takehiko Yamaguchi, Akiyo Ito, Takushi Hanita, Junko Kanno, Toshimi Aizawa, Toru Nakazawa, Tetsuaki Kawase, Gen Tamiya, Masayuki Yamamoto, Ikuma Fujiwara, Shigeo Kure
Summary: This study identified a novel duplication variant of TNFRSF11A (72dup27) and suggested a broad spectrum of phenotypes in bone disorders associated with this variant.
JOURNAL OF BONE AND MINERAL METABOLISM
(2023)
Article
Genetics & Heredity
Yuka Sugawara, Yosuke Hirakawa, Hajime Nagasu, Akira Narita, Akihiro Katayama, Jun Wada, Miho Shimizu, Takashi Wada, Hiromasa Kitamura, Toshiaki Nakano, Hideki Yokoi, Motoko Yanagita, Shin Goto, Ichiei Narita, Seizo Koshiba, Gen Tamiya, Masaomi Nangaku, Masayuki Yamamoto, Naoki Kashihara
Summary: This study conducted a genome-wide association study (GWAS) in Japanese individuals to identify genetic loci related to kidney-related traits. The results identified 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among these loci, 22 have not been previously reported. The study also found that the group characterized by increased UACR had genetically distinct features from the group characterized by decreased eGFR.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Oncology
Sarang S. Talwelkar, Mikko I. Mayranpaa, Julia Schuler, Nora Linnavirta, Annabrita Hemmes, Simone Adinolfi, Matti Kankainen, Wolfgang Sommergruber, Anna-Liisa Levonen, Jari Rasanen, Aija Knuuttila, Emmy W. Verschuren, Krister Wennerberg
Summary: Treatment with ALK inhibitors improves outcome for NSCLC patients with ALK-rearranged tumors, but resistance typically develops. In this study, tumor cell cultures were generated from an ALK-rearranged tumor specimen and drug screens identified a role for PI3K beta and EGFR inhibition in enhancing ALK-inhibitor response and preventing resistance. Combinatorial treatment with ALK and PI3K beta inhibitors showed promise in targeting ALK-rearranged NSCLC.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jouni Harkonen, Petri Polonen, Ashik Jawahar Deen, Ilakya Selvarajan, Hanna-Riikka Teppo, Elitsa Y. Dimova, Thomas Kietzmann, Maarit Ahtiainen, Juha P. Vayrynen, Sara A. Vayrynen, Hanna Elomaa, Niko Tynkkynen, Tiia Eklund, Teijo Kuopio, Eva-Maria Talvitie, Pekka Taimen, Markku Kallajoki, Minna U. Kaikkonen, Merja Heinaniemi, Anna-Liisa Levonen
Summary: The NRF2 pathway is frequently activated in various cancer types, but a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and conducted a pan-cancer analysis of oncogenic NRF2 signaling using it. Our findings revealed an immunoevasive phenotype in squamous malignancies of the lung, head and neck area, cervix, and esophagus, where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression, and T cell and macrophage infiltration. These tumors have a molecular phenotype with amplification of SOX2/TP63, TP53 mutation, and CDKN2A loss, and are associated with upregulation of immunomodulatory genes NAMPT, WNT5A, SPP1, SLC7A11, SLC2A1, and PD-L1. Our functional genomics analyses suggest that these genes are candidate NRF2 targets, indicating a direct modulation of the tumor immune milieu. Single-cell mRNA data shows that cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands and increased expression of immunosuppressive ligands NAMPT, SPP1, and WNT5A involved in intercellular crosstalk. Moreover, the negative relationship between NRF2 and immune cells is explained by stromal populations of lung squamous cell carcinoma, indicating a potential effect across multiple squamous malignancies based on our molecular subtyping and deconvolution data.
Article
Biochemistry & Molecular Biology
Shu Tadaka, Junko Kawashima, Eiji Hishinuma, Sakae Saito, Yasunobu Okamura, Akihito Otsuki, Kaname Kojima, Shohei Komaki, Yuichi Aoki, Takanari Kanno, Daisuke Saigusa, Jin Inoue, Matsuyuki Shirota, Jun Takayama, Fumiki Katsuoka, Atsushi Shimizu, Gen Tamiya, Ritsuko Shimizu, Masahiro Hiratsuka, Ikuko N. Motoike, Seizo Koshiba, Makoto Sasaki, Masayuki Yamamoto, Kengo Kinoshita
Summary: Personalized medicine focuses on multi-omics data, and cohort studies from different ethnic populations contribute to understanding disease mechanisms and developing personalized medicine. The Tohoku Medical Megabank project collects biological specimens for multi-omics analysis, providing a multidimensional approach to the diversity of the Japanese population.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Liam Baird, Masayuki Yamamoto
Summary: In human cancer, abnormal activation of the NRF2 pathway can allow cancer cells to evade immune surveillance and develop into malignant tumors by reducing antigen presentation and activating signals for NK cells, which inhibits the involvement of immune effector cells.
Article
Biochemistry & Molecular Biology
Simone Adinolfi, Tommi Patinen, Ashik Jawahar Deen, Sini Pitkänen, Jouni Härkönen, Emilia Kansanen, Jenni Küblbeck, Anna-Liisa Levonen
Summary: The KEAP1-NRF2 pathway is a crucial regulator of cellular defense against oxidative and electrophilic stimuli, playing a significant role in various disease pathologies. Research focused on understanding NRF2 signaling and its downstream effects has led to the identification of novel therapeutic targets. This graphical review provides an updated overview of the KEAP1-NRF2 signaling, highlighting recent advancements in the field, including the mechanism of NRF2 activation and its potential application in cancer diagnostics and treatment.
Article
Geriatrics & Gerontology
Kota Sato, Daisuke Saigusa, Taiki Kokubun, Amane Fujioka, Qiwei Feng, Ritsumi Saito, Akira Uruno, Naomi Matsukawa, Michiko Ohno-Oishi, Hiroshi Kunikata, Yu Yokoyama, Masayuki Yasuda, Noriko Himori, Kazuko Omodaka, Satoru Tsuda, Shigeto Maekawa, Masayuki Yamamoto, Toru Nakazawa
Summary: Glaucoma is a leading cause of blindness in older people, and studying the metabolites in the aqueous humor can provide insights into its physiological and pathological conditions. This study used mass spectrometry to characterize the metabolomic profile of the aqueous humor in glaucoma patients. The findings showed that glutathione levels were significantly reduced in glaucoma patients and correlated with visual field defects. The study demonstrates the potential of aqueous humor profiling in diagnosing glaucoma and suggests that oxidative stress may be involved in its pathogenesis.
Article
Urology & Nephrology
Kazuaki Ikejiri, Takafumi Suzuki, Satsuki Muto, Hirotaka Takama, Kengo Yamawaki, Tatsuya Miyazawa, Itaru Urakawa, Yuichi Aoki, Akihito Otsuki, Fumiki Katsuoka, Kengo Kinoshita, Masaomi Nangaku, Tadao Akizawa, Masayuki Yamamoto
Summary: This study investigated the impact of the regulatory single nucleotide polymorphism, rs6721961, on the effects of bardoxolone methyl in patients with chronic kidney disease. The results showed that the efficacy and safety of bardoxolone methyl were unaffected by the rs6721961 polymorphism, indicating its positive impact on renal function in patients with various forms of CKD.
CLINICAL AND EXPERIMENTAL NEPHROLOGY
(2023)