Article
Urology & Nephrology
Jun Kamei, Naoki Aizawa, Takayuki Nakagawa, Shuji Kaneko, Tetsuya Fujimura, Yukio Homma, Haruki Kume, Yasuhiko Igawa
Summary: The study aimed to investigate the role of transient receptor potential melastatin 2 in bladder function and inflammation-induced hypersensitivity. Results showed that while there were minimal differences in physiological function between wild-type and transient receptor potential melastatin 2-knockout mice, the knockout mice exhibited attenuated inflammatory responses and hypersensitivity compared to their wild-type counterparts after intravesical lipopolysaccharide instillation.
INTERNATIONAL JOURNAL OF UROLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Heng Song, Xiaojuan Zhang, Ruiqing Zhai, Huoyan Liang, Gaofei Song, Yangyang Yuan, Yanan Xu, Yan Yan, Lingxiao Qiu, Tongwen Sun
Summary: This study investigated the therapeutic effects of metformin on sepsis-associated liver injury in aged mice. The results showed that metformin could alleviate liver inflammation and apoptosis, reduce liver function markers ALT and AST, and attenuate inflammatory responses by regulating the AMPK-PGC1α axis.
Article
Medicine, Research & Experimental
Sergio Lopez-Estevez, Georgia Gris, Beatriz de la Puente, Alicia Carceller, Vicente Martinez
Summary: Sigma-1 receptors play an important role in intestinal inflammation-associated referred hyperalgesia, with knockout mice showing significant attenuation in inflammation associated hypersensitivity. The absence of sigma(1)Rs had little impact on colitis generation and progression, but did show reduction in edema and down-regulation of iNOS gene expression during the chronic phase.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Zaiqi Zhang, Zhiyong Yao, Kunyang Wu, Ti Zhang, Chaoqun Xing, Xiao-Liang Xing
Summary: The neuronal transmembrane protein CNTNAP2 is correlated with pain-related hypersensitivity, and studies suggest that the hyperactive PI3K/Akt/mTOR signaling pathway could be a potential therapeutic target for this condition. Resveratrol, a widely studied polyphenol, has shown promise in alleviating pain-related hypersensitivity by suppressing the phosphorylation of S6 and attenuating nocifensive behavior duration in Cntnap2-deficient mice, possibly via the mTOR signaling pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Katelyn E. Sadler, Francie Moehring, Stephanie Shiers, Lauren J. Laskowski, Alexander R. Mikesell, Zakary R. Plautz, Allison N. Brezinski, Christina M. Mecca, Gregory Dussor, Theodore J. Price, John D. McCorvy, Cheryl L. Stucky
Summary: The study identified TRPC5 as a key contributor to tactile and spontaneous pain in multiple rodent pain models, particularly in conditions characterized by elevated LPC concentrations. 75% of human sensory neurons express TRPC5, and its activity is directly modulated by LPC.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Karim Atmani, Fabien Wuestenberghs, Maximilien Baron, Illona Boulete, Charlene Guerin, Wafa Bahlouli, David Vaudry, Jean Claude do Rego, Jean-Nicolas Cornu, Anne-Marie Leroi, Moise Coeffier, Mathieu Meleine, Guillaume Gourcerol
Summary: A new model of cross-organ visceral sensitization between the bladder and the colon was developed in mice. Intravesical injections of acetic acid induced long-lasting colorectal hypersensitivity to distension, which was mediated by neuroglial interactions, MAPK-p38 phosphorylation, and the NK1 receptor.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Immunology
Zhiwei Li, Frieder Hadlich, Klaus Wimmers, Eduard Murani
Summary: This study investigates the consequences of glucocorticoid receptor (GR) hypersensitivity during infection and provides insights into the impact of GR hypersensitivity on the fate and function of immune cells. The study found that a specific genetic variant of GR, Ala610Val, aggravates the response to endotoxemia in pigs and amplifies inflammatory responses. However, this variant also orchestrates genes involved in anti-inflammatory responses during infection, suggesting potential therapeutic applications in endotoxemia treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Shiori Kawasaki, Masahiko Soga, Yusuke Sakurai, Isamu Nanchi, Miyuki Yamamoto, Sunao Imai, Tatsuya Takahashi, Naoki Tsuno, Toshiyuki Asaki, Yasuhide Morioka, Masahide Fujita
Summary: The study suggests the involvement of TRPV4 in bladder pain in a mouse cystitis model, indicating that a TRPV4 antagonist may be useful for patients with irritable bladder pain such as those with interstitial cystitis/painful bladder syndrome.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Environmental Sciences
Rui Xiong, Wenyang Jiang, Ning Li, Bohao Liu, Ruyuan He, Bo Wang, Qing Geng
Summary: The study found that exposure to PM2.5 can increase inflammatory response, oxidative stress, and apoptosis levels in lung tissue. Knockout of macrophage-specific NLRP3 gene can mitigate these effects.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemistry & Molecular Biology
Dae Ki Hong, Yoo Seok Park, Ji Sun Woo, Ju Hee Kim, Jin Ho Beom, Sung Phil Chung, Je Sung You, Sang Won Suh
Summary: Targeted temperature management after cardiac arrest is beneficial for reducing neurological impairment, with the neuroprotective effects of TTM at 36 degrees Celsius found to be comparable to those at 33 degrees Celsius. Neuroinflammation plays a crucial role in exacerbating brain damage following sudden cardiac arrest.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Shaoping Li, Xianlong Zhou, Rong Zeng, Lian Lin, Xingnan Zou, Yu Yan, Zijun Lu, Jian Xia, Lijuan Zhang, Shaozhou Ni, Shuai Dai, Haihua Chen, Yan Zhao
Summary: Oxidative stress plays a crucial role in lung injury/fibrosis and diaphragmatic dysfunction, with YAP1 being a key regulator in this process. This study found that lung injury/fibrosis adversely affects diaphragmatic function, and YAP1 silencing treatment can alleviate lung inflammation but worsen diaphragmatic function. The difference in response to YAP1 inhibition between muscles and lungs may contribute to this disparity.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Danielle Carvalho Oliveira Coutinho, Julliane Joviano-Santos, Artur Santos -Miranda, Paulo Antonio Martins-Junior, Analina Da Silva, Robson Augusto Souza Santos, Anderson Jose Ferreira
Summary: The activation of the novel axis of the renin-angiotensin system (ACE2/Ang-(1-7)/Mas receptor) has been found to have protective effects against cardiovascular diseases. This study investigated the implications of Mas receptor knockout on cytokine profiles, energy metabolism, and electrical properties of isolated cardiomyocytes in mice.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Haruhito A. Uchida, Tetsuharu Takatsuka, Yoshiko Hada, Ryoko Umebayashi, Hidemi Takeuchi, Kenichi Shikata, Venkateswaran Subramanian, Alan Daugherty, Jun Wada
Summary: The study found that edaravone can attenuate angiotensin II-induced abdominal aortic aneurysms and atherosclerosis through its antioxidant and anti-inflammatory effects.
Article
Pharmacology & Pharmacy
Kayla Johnson, Alexis Doucette, Alexis Edwards, Aleeya Verdi, Ryan McFarland, Shelby Hulke, Amanda Fowler, Val J. Watts, Amanda H. Klein
Summary: This study found that reducing the activity or expression of adenylyl cyclase 1 can attenuate morphine tolerance and hypersensitivity, as well as provide relief for inflammatory pain.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Rishabh Sharma, Pablo M. Casillas-Espinosa, Larissa K. Dill, Sarah S. J. Rewell, Matthew R. Hudson, Terence J. O'Brien, Sandy R. Shultz, Bridgette D. Semple
Summary: Traumatic brain injury (TBI) is a leading cause of death and disability globally, especially in children. This study investigated the potential chronic impact of acute infections following pediatric TBI and found that immune challenges independently influenced chronic outcomes. Contrary to hypothesis, there was minimal synergy between TBI and infections, indicating the need for further research in preclinical modeling and patient management.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Hiroyuki Watanabe, Rinka Maekawa, Shimpei Iikuni, Masashi Kakae, Nagisa Matsuo, Hisashi Shirakawa, Shuji Kaneko, Masahiro Ono
Summary: This study characterized four diaryl oxadiazole derivatives as potential myelin-imaging probes for single photon emission computed tomography (SPECT) in multiple sclerosis (MS). The results showed that one of the derivatives, [123I]1,3,4-PODP-DM, could potentially be used as a SPECT probe for imaging myelin in MS.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Neurosciences
Hiroki Nakajima, Sayaka Fujita, Masashi Kakae, Kazuki Nagayasu, Masatsugu Oh-Hora, Hisashi Shirakawa, Shuji Kaneko
Summary: Astrocytes, glial cells in the central nervous system, play homeostatic roles but can also actively participate in CNS inflammation under pathological conditions. This study found that astrocytes upregulate inflammatory factors including PGE(2) when stimulated by TNF alpha and IL1 alpha. Knockdown or knockout of Orai2, a member of the calcium channel family, resulted in increased PGE(2) production and expression of PGE(2) synthase genes, suggesting the modulation of CNS inflammation. These findings contribute to the understanding of astrocyte involvement in inflammatory responses and potential targets for modulation of astrocytic reactivity.
Article
Neurosciences
Hikari Hatakama, Nozomi Asaoka, Kazuki Nagayasu, Hisashi Shirakawa, Shuji Kaneko
Summary: The study demonstrated that SSRI improved perseverative behavior in QNP-treated mice by modulating inhibitory inputs in the lateral OFC.
Article
Pharmacology & Pharmacy
Koki Nagaoka, Kazuki Nagayasu, Hisashi Shirakawa, Shuji Kaneko
Summary: In this study, the researchers analyzed databases to find a drug that can be used together with dopamine D2 receptor antagonists to reduce the risk of akathisia. Acetaminophen was found to be the most effective drug in suppressing tardive akathisia. Experimental validation showed that chronic treatment of rats with haloperidol caused akathisia symptoms, while acute treatment with acetaminophen significantly attenuated these symptoms.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Hiroyuki Kawai, Youcef Bouchekioua, Naoya Nishitani, Kazuhei Niitani, Shoma Izumi, Hinako Morishita, Chihiro Andoh, Yuma Nagai, Masashi Koda, Masako Hagiwara, Koji Toda, Hisashi Shirakawa, Kazuki Nagayasu, Yu Ohmura, Makoto Kondo, Katsuyuki Kaneda, Mitsuhiro Yoshioka, Shuji Kaneko
Summary: Appropriate processing of reward and aversive information is crucial for survival. Serotonergic neurons in the median raphe nucleus (MRN) of mice process reward and aversive information in opposite directions to dorsal raphe nucleus (DRN) serotonergic neurons.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Koki Nagaoka, Nozomi Asaoka, Kazuki Nagayasu, Hisashi Shirakawa, Shuji Kaneko
Summary: Repeated administration of dopamine D-2 receptor antagonists for the treatment of psychosis often leads to tardive dyskinesia. This study found that activating adenosine A2A receptors in the striatum can alleviate dyskinetic symptoms caused by TD.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Immunology
Keisuke Nozawa, Takahide Suzuki, Gen Kayanuma, Hiroki Yamamoto, Kazuki Nagayasu, Hisashi Shirakawa, Shuji Kaneko
Summary: Recent studies have found that DPP4 inhibitors increase the risk of bullous pemphigoid (BP), a common autoimmune blistering skin disease. The mechanisms behind this association are unclear, and there are currently no identified therapeutic targets for drug-induced BP. However, clinical data mining revealed that concomitant use of lisinopril, an angiotensin-converting enzyme inhibitor, significantly decreased the incidence of BP in patients receiving DPP4 inhibitors. In vitro experiments further showed that DPP4 inhibitors upregulated MMP9 and ACE2 mRNA expression, which play a role in the pathophysiology of BP, and that lisinopril and Mas receptor inhibitors could suppress this upregulation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Hiroki Yamamoto, Gen Kayanuma, Takuya Nagashima, Chihiro Toda, Kazuki Nagayasu, Shuji Kaneko
Summary: This study aimed to identify methods for the early detection of a wide range of adverse drug reactions (ADRs). A data-mining approach using large-scale medical records was used, and association rule mining (ARM) was applied to patient symptoms and medications. The results showed that ARM of claims data may be effective in the early detection of a wide range of ADR signals.
Article
Biochemistry & Molecular Biology
Shiori Yamashita, Naoki Dozono, Shota Tobori, Kazuki Nagayasu, Shuji Kaneko, Hisashi Shirakawa, Hiroshi Ueda
Summary: Abnormalities in the peripheral immune system are involved in the pathophysiology of fibromyalgia, and the activation of peripheral beta 2-adrenergic receptors plays an important role in the efferent pathway from the CNS to splenocytes in pain development. The administration of selective beta 2-blockers prevented the development but not the maintenance of pain-like behavior, and beta 2-blockade in donor mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Yuma Nagai, Yuri Kisaka, Kento Nomura, Naoya Nishitani, Chihiro Andoh, Masashi Koda, Hiroyuki Kawai, Kaoru Seiriki, Kazuki Nagayasu, Atsushi Kasai, Hisashi Shirakawa, Takanobu Nakazawa, Hitoshi Hashimoto, Shuji Kaneko
Summary: Major depressive disorder (MDD) is a common mental illness, and serotonergic neurons play a crucial role in its pathophysiology and treatment. Recalling positive memories repeatedly is effective for MDD. This study found that activating 5-HT neurons can activate specific neuronal ensembles associated with positive memories, providing insights into the antidepressive effects of serotonin.
Article
Pharmacology & Pharmacy
Zijian Zhou, Takuya Nagashima, Chihiro Toda, Mone Kobayashi, Takahide Suzuki, Kazuki Nagayasu, Hisashi Shirakawa, Satoshi Asai, Shuji Kaneko
Summary: Olanzapine is an atypical antipsychotic drug used for schizophrenia. Vitamin D has been found to reduce the risk of olanzapine-induced dyslipidemia. By analyzing clinical data and conducting experiments, it was discovered that vitamin D improves dyslipidemia by inhibiting cholesterol biosynthesis. This clinical big-data-based drug repurposing approach provides a novel treatment with high clinical predictability and a well-defined molecular mechanism.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Haruka Furuta, Mari Yamada, Takuya Nagashima, Shuichi Matsuda, Kazuki Nagayasu, Hisashi Shirakawa, Shuji Kaneko
Summary: The short-term use of dexamethasone prevents fluoroquinolone-induced and age-related tendinopathy by suppressing oxidative stress through upregulation of the antioxidant enzyme glutathione peroxidase 3 (GPX3).
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Zijian Zhou, Kazuki Nagayasu, Hisashi Shirakawa, Shuji Kaneko
Summary: Low concentrations of bortezomib (BTZ) can induce changes in peripheral nervous system cells, including dedifferentiation of Schwann cells, increased GFAP levels in satellite glial cells, and decreased expression levels of sensor and transducer ion channels in dorsal root ganglion neurons. These findings contribute to a better understanding of the mechanisms underlying BTZ-induced peripheral neuropathy.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2023)
Article
Pharmacology & Pharmacy
Kaito Takayama, Shota Tobori, Chihiro Andoh, Masashi Kakae, Masako Hagiwara, Kazuki Nagayasu, Hisashi Shirakawa, Yukio Ago, Shuji Kaneko
Summary: This study found that prenatal exposure to valproic acid in mice increased empathy-like behaviors, which were associated with hyperactivation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus (PVN). The results provide clues for further investigation of the oxytocin signaling pathway and the development of novel therapies for ASD.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Multidisciplinary Sciences
Misaki Niu, Atsushi Kasai, Masato Tanuma, Kaoru Seiriki, Hisato Igarashi, Takahiro Kuwaki, Kazuki Nagayasu, Keita Miyaji, Hiroki Ueno, Wataru Tanabe, Kei Seo, Rei Yokoyama, Jin Ohkubo, Yukio Ago, Misuzu Hayashida, Ken-Ichi Inoue, Masahiko Takada, Shun Yamaguchi, Takanobu Nakazawa, Shuji Kaneko, Hiroyuki Okuno, Akihiro Yamanaka, Hitoshi Hashimoto
Summary: This study reveals the crucial role of the claustrum in the regulation of stress-induced anxiety-related behaviors. Claustrum activation serves as a reliable marker of acute stress exposure, and its neuronal ensemble activation elicits anxiety-related behaviors while silencing attenuates such behaviors. The claustrum receives strong input from the basolateral amygdala, and selective optogenetic stimulation of the claustrum temporarily induces anxiety-related behaviors. Silencing of the claustrum ensemble increases resistance to chronic stress. The bidirectional control of stress-induced emotional responses by the claustrum suggests its potential as a target for prevention and treatment of stress-related disorders.