Journal of pharmacological sciences最新文献_第5页

Deficiency of interleukin-19 exacerbates acute lung injury induced by intratracheal treatment of hydrochloric acid 白细胞介素-19 的缺乏会加重气管内盐酸治疗引起的急性肺损伤

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-04-17 DOI: 10.1016/j.jphs.2024.04.003

Kazuhiro Nishiyama , Joji Horikoshi , Toko Maehara , Miyuu Tanaka , Takashi Tanida , Koichi Kawada , Susumu Takeshita , Naoshige Ono , Takeshi Izawa , Mitsuru Kuwamura , Yasu-Taka Azuma

{"title":"Deficiency of interleukin-19 exacerbates acute lung injury induced by intratracheal treatment of hydrochloric acid","authors":"Kazuhiro Nishiyama , Joji Horikoshi , Toko Maehara , Miyuu Tanaka , Takashi Tanida , Koichi Kawada , Susumu Takeshita , Naoshige Ono , Takeshi Izawa , Mitsuru Kuwamura , Yasu-Taka Azuma","doi":"10.1016/j.jphs.2024.04.003","DOIUrl":"10.1016/j.jphs.2024.04.003","url":null,"abstract":"<div><p>Interleukin (IL-19) belongs to the IL-10 family of cytokines and plays diverse roles in inflammation, cell development, viral responses, and lipid metabolism. Acute lung injury (ALI) is a severe respiratory condition associated with various diseases, including severe pneumonia, sepsis, and trauma, lacking established treatments. However, the role of IL-19 in acute inflammation of the lungs is unknown. We reported the impact of IL-19 functional deficiency in mice crossed with an ALI model using HCl. Lungs damages, neutrophil infiltration, and pulmonary edema induced by HCl were significantly worse in IL-19 knockout (KO) mice than in wild-type (WT) mice. mRNA expression levels of C-X-C motif chemokine ligand 1 (CXCL1) and IL-6 in the lungs were significantly higher in IL-19 KO mice than in WT mice. Little apoptosis was detected in lung injury in WT mice, whereas apoptosis was observed in exacerbated area of lung injury in IL-19 KO mice. These results are the first to show that IL-19 is involved in acute inflammation of the lungs, suggesting a novel molecular mechanism in acute respiratory failures. If it can be shown that neutrophils have IL-19 receptors and that IL-19 acts directly on them, it would be a novel drug target.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 3","pages":"Pages 94-100"},"PeriodicalIF":3.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000331/pdfft?md5=1f87f3b3dbcba4297e1f78504d8e39d5&pid=1-s2.0-S1347861324000331-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140787739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons 雷马唑仑对大鼠脊髓背角神经元抑制性传导的作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-04-10 DOI: 10.1016/j.jphs.2024.04.002

Rintaro Hoshino , Nobuko Ohashi , Daisuke Uta , Masayuki Ohashi , Hiroyuki Deguchi , Hiroshi Baba

{"title":"Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons","authors":"Rintaro Hoshino , Nobuko Ohashi , Daisuke Uta , Masayuki Ohashi , Hiroyuki Deguchi , Hiroshi Baba","doi":"10.1016/j.jphs.2024.04.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.002","url":null,"abstract":"<div><p>Remimazolam is an ultra-short benzodiazepine that acts on the benzodiazepine site of γ-aminobutyric acid (GABA) receptors in the brain and induces sedation. Although GABA receptors are found localized in the spinal dorsal horn, no previous studies have reported the analgesic effects or investigated the cellular mechanisms of remimazolam on the spinal dorsal horn. Behavioral measures, immunohistochemistry, and <em>in vitro</em> whole-cell patch-clamp recordings of dorsal horn neurons were used to assess synaptic transmission. Intrathecal injection of remimazolam induced behavioral analgesia in inflammatory pain-induced mechanical allodynia (six rats/dose; p < 0.05). Immunohistochemical staining revealed that remimazolam suppressed spinal phosphorylated extracellular signal-regulated kinase activation (five rats/group, p < 0.05). <em>In vitro</em> whole-cell patch-clamp analysis demonstrated that remimazolam increased the frequency of GABAergic miniature inhibitory post-synaptic currents, prolonged the decay time (six rats; p < 0.05), and enhanced GABA currents induced by exogenous GABA (seven rats; p < 0.01). However, remimazolam did not affect miniature excitatory post-synaptic currents or amplitude of monosynaptic excitatory post-synaptic currents evoked by Aδ- and C-fiber stimulation (seven rats; p > 0.05). This study suggests that remimazolam induces analgesia by enhancing GABAergic inhibitory transmission in the spinal dorsal horn, suggesting its potential utility as a spinal analgesic for inflammatory pain.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 63-73"},"PeriodicalIF":3.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400032X/pdfft?md5=e9004f36617bcf5850b5b4c08db4c556&pid=1-s2.0-S134786132400032X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Both hemoglobin and hemin cause damage to retinal pigment epithelium through the iron ion accumulation 血红蛋白和血红素都会通过铁离子积累对视网膜色素上皮造成损伤

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-04-02 DOI: 10.1016/j.jphs.2024.04.001

Aomi Muramatsu , Shinsuke Nakamura , Tasuku Hirayama , Hideko Nagasawa , Akihiro Ohira , Takashi Kitaoka , Hideaki Hara , Masamitsu Shimazawa

{"title":"Both hemoglobin and hemin cause damage to retinal pigment epithelium through the iron ion accumulation","authors":"Aomi Muramatsu , Shinsuke Nakamura , Tasuku Hirayama , Hideko Nagasawa , Akihiro Ohira , Takashi Kitaoka , Hideaki Hara , Masamitsu Shimazawa","doi":"10.1016/j.jphs.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.001","url":null,"abstract":"<div><p>Subretinal hemorrhages result in poor vision and visual field defects. During hemorrhage, several potentially toxic substances are released from iron-based hemoglobin and hemin, inducing cellular damage, the detailed mechanisms of which remain unknown. We examined the effects of excess intracellular iron on retinal pigment epithelial (RPE) cells. A Fe<sup>2+</sup> probe, SiRhoNox-1 was used to investigate Fe<sup>2+</sup> accumulation after treatment with hemoglobin or hemin in the human RPE cell line ARPE-19. We also evaluated the production of reactive oxygen species (ROS) and lipid peroxidation. Furthermore, the protective effect of-an iron chelator, 2,2′-bipyridyl (BP), and ferrostatin-1 (Fer-1) on the cell damage, was evaluated. Fe<sup>2+</sup> accumulation increased in the hemoglobin- or hemin-treated groups, as well as intracellular ROS production and lipid peroxidation. In contrast, BP treatment suppressed RPE cell death, ROS production, and lipid peroxidation. Pretreatment with Fer-1 ameliorated cell death in a concentration-dependent manner and suppressed ROS production and lipid peroxidation. Taken together, these findings indicate that hemoglobin and hemin, as well as subretinal hemorrhage, may induce RPE cell damage and visual dysfunction via intracellular iron accumulation.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 44-51"},"PeriodicalIF":3.5,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000318/pdfft?md5=92ffa2385d8fb2f4f34d446b4ec314f2&pid=1-s2.0-S1347861324000318-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Imeglimin attenuates NLRP3 inflammasome activation by restoring mitochondrial functions in macrophages Imeglimin 通过恢复巨噬细胞中线粒体的功能来减轻 NLRP3 炎症小体的激活

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-27 DOI: 10.1016/j.jphs.2024.03.004

Ji Yeon Lee , Yup Kang , Ja Young Jeon , Hae Jin Kim , Dae Jung Kim , Kwan Woo Lee , Seung Jin Han

{"title":"Imeglimin attenuates NLRP3 inflammasome activation by restoring mitochondrial functions in macrophages","authors":"Ji Yeon Lee , Yup Kang , Ja Young Jeon , Hae Jin Kim , Dae Jung Kim , Kwan Woo Lee , Seung Jin Han","doi":"10.1016/j.jphs.2024.03.004","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.03.004","url":null,"abstract":"<div><p>Imeglimin is a novel oral antidiabetic drug for treating type 2 diabetes. However, the effect of imeglimin on NLRP3 inflammasome activation has not been investigated yet. Here, we aimed to investigate whether imeglimin reduces LPS-induced NLRP3 inflammasome activation in THP-1 macrophages and examine the associated underlying mechanisms. We analyzed the mRNA and protein expression levels of NLRP3 inflammasome components and IL-1β secretion. Additionally, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening were measured by flow cytometry. Imeglimin inhibited NLRP3 inflammasome-mediated IL-1β production in LPS-stimulated THP-1-derived macrophages. In addition, imeglimin reduced LPS-induced mitochondrial ROS production and mitogen-activated protein kinase phosphorylation. Furthermore, imeglimin restored the mitochondrial function by modulating mitochondrial membrane depolarization and mPTP opening. We demonstrated for the first time that imeglimin reduces LPS-induced NLRP3 inflammasome activation by inhibiting mPTP opening in THP-1 macrophages. These results suggest that imeglimin could be a promising new anti-inflammatory agent for treating diabetic complications.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 35-43"},"PeriodicalIF":3.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000306/pdfft?md5=f32655537aa9d4a725c45ca52ad8b69c&pid=1-s2.0-S1347861324000306-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140344223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells 蛋白酶体抑制剂通过 NADPH 氧化酶 5 在人神经母细胞瘤 SH-SY5Y 细胞中生成超氧阴离子诱导细胞凋亡

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-27 DOI: 10.1016/j.jphs.2024.03.002

Akiko Yamamuro-Tanabe, Yu Oshima, Takumi Iyama, Yuki Ishimaru, Yasuhiro Yoshioka

{"title":"Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells","authors":"Akiko Yamamuro-Tanabe, Yu Oshima, Takumi Iyama, Yuki Ishimaru, Yasuhiro Yoshioka","doi":"10.1016/j.jphs.2024.03.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.03.002","url":null,"abstract":"<div><p>The ubiquitin-proteasome system (UPS) is a major proteolytic system that plays an important role in the regulation of various cell processes, such as cell cycle, stress response, and transcriptional regulation, especially in neurons, and dysfunction of UPS is considered to be a cause of neuronal cell death in neurodegenerative diseases. However, the mechanism of neuronal cell death caused by UPS dysfunction has not yet been fully elucidated.</p><p>In this study, we investigated the mechanism of neuronal cell death induced by proteasome inhibitors using human neuroblastoma SH-SY5Y cells. Z-Leu-D-Leu-Leu-al (MG132), a proteasome inhibitor, induced apoptosis in SH-SY5Y cells in a concentration- and time-dependent manner. Antioxidants N-acetylcysteine and EUK-8 attenuated MG132-induced apoptosis. Apocynin and diphenyleneiodonium, inhibitors of NADPH oxidase (NOX), an enzyme that produces superoxide anions, also attenuated MG132-induced apoptosis. It was also found that MG132 treatment increased the expression of NOX5, a NOX family member, and that siRNA-mediated silencing of NOX5 and BAPTA-AM, which inhibits NOX5 by chelating calcium, suppressed MG132-induced apoptosis and production of reactive oxygen species in SH-SY5Y cells.</p><p>These results suggest that MG132 induces apoptosis in SH-SY5Y cells through the production of superoxide anion by NOX5.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 52-62"},"PeriodicalIF":3.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000288/pdfft?md5=b628cb33348109571b1bba490c2d7965&pid=1-s2.0-S1347861324000288-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus CSF1R 抑制剂 PLX3397 可消耗蒙古沙鼠的小胶质细胞，但不会消耗叙利亚仓鼠的小胶质细胞

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-23 DOI: 10.1016/j.jphs.2024.03.003

Ren Y. Sato, Yumin Zhang , Koki T. Kotake , Hiraku Onishi, Shiho Ito, Hiroaki Norimoto, Zhiwen Zhou

{"title":"CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus","authors":"Ren Y. Sato, Yumin Zhang , Koki T. Kotake , Hiraku Onishi, Shiho Ito, Hiroaki Norimoto, Zhiwen Zhou","doi":"10.1016/j.jphs.2024.03.003","DOIUrl":"10.1016/j.jphs.2024.03.003","url":null,"abstract":"<div><p>Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (<em>Mesocricetus auratus</em>) and Mongolian gerbils (<em>Meriones unguiculatus</em>), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 29-34"},"PeriodicalIF":3.5,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400029X/pdfft?md5=adbf8b5c2390572036d58aeb3338ba59&pid=1-s2.0-S134786132400029X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140273890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Upregulation of ATF4 mediates the cellular adaptation to pharmacologic inhibition of amino acid transporter LAT1 in pancreatic ductal adenocarcinoma cells ATF4 的上调介导了胰腺导管腺癌细胞对氨基酸转运体 LAT1 药物抑制的适应性变化

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-13 DOI: 10.1016/j.jphs.2024.03.001

Yu Ma , Suguru Okuda , Hiroki Okanishi , Minhui Xu , Chunhuan Jin , Hitoshi Endou , Ryuichi Ohgaki , Yoshikatsu Kanai

{"title":"Upregulation of ATF4 mediates the cellular adaptation to pharmacologic inhibition of amino acid transporter LAT1 in pancreatic ductal adenocarcinoma cells","authors":"Yu Ma , Suguru Okuda , Hiroki Okanishi , Minhui Xu , Chunhuan Jin , Hitoshi Endou , Ryuichi Ohgaki , Yoshikatsu Kanai","doi":"10.1016/j.jphs.2024.03.001","DOIUrl":"10.1016/j.jphs.2024.03.001","url":null,"abstract":"<div><p>L-type amino acid transporter 1 (LAT1) is recognized as a promising target for cancer therapy; however, the cellular adaptive response to its pharmacological inhibition remains largely unexplored. This study examined the adaptive response to LAT1 inhibition using nanvuranlat, a high-affinity LAT1 inhibitor. Proteomic analysis revealed the activation of a stress-induced transcription factor ATF4 following LAT1 inhibition, aligning with the known cellular responses to amino acid deprivation. This activation was linked to the GCN2-eIF2α pathway which regulates translation initiation. Our results show that ATF4 upregulation counteracts the suppressive effect of nanvuranlat on cell proliferation in pancreatic ductal adenocarcinoma cell lines, suggesting a role for ATF4 in cellular adaptation to LAT1 inhibition. Importantly, dual targeting of LAT1 and ATF4 exhibited more substantial anti-proliferative effects <em>in vitro</em> than individual treatments. This study underscores the potential of combining LAT1 and ATF4 inhibition as a therapeutic strategy in cancer treatment.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 1","pages":"Pages 14-20"},"PeriodicalIF":3.5,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000276/pdfft?md5=3ebaf9d7cc856ff4f50c85f1d9e44822&pid=1-s2.0-S1347861324000276-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140153095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression 没食子酸通过抑制 PI3K/AKT 通路和下调细胞周期蛋白 D1 的表达改善子宫内膜增生症

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-05 DOI: 10.1016/j.jphs.2024.02.015

Caijie Zheng , Yi Wang , Beilei Bi , Wencheng Zhou , Xinran Cao , Chenyang Zhang , Wentian Lu , Yang Sun , Jiao Qu , Wen Lv

{"title":"Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression","authors":"Caijie Zheng , Yi Wang , Beilei Bi , Wencheng Zhou , Xinran Cao , Chenyang Zhang , Wentian Lu , Yang Sun , Jiao Qu , Wen Lv","doi":"10.1016/j.jphs.2024.02.015","DOIUrl":"10.1016/j.jphs.2024.02.015","url":null,"abstract":"<div><h3>Background</h3><p>Gallic acid (GA) is an organic compound with phenolic properties that occurs naturally and can be found in Guizhi Fuling capsules, showcasing a wide range of biological functionalities.</p></div><div><h3>Purpose</h3><p>The objective of this study was to examine the influence of GA on endometrial hyperplasia (EH) and elucidate its underlying mechanism.</p></div><div><h3>Methods</h3><p>Initially, the induction of EH was achieved by administering estradiol to mice via continuous subcutaneous injection for a duration of 21 days. Concurrently, GA treatment was administered, and subsequently, the uterine tissue structure was assessed using hematoxylin and eosin (H&E) staining. Following this, the proliferation of human endometrial cells treated by GA was determined utilizing the CCK-8 method. Furthermore, network pharmacology and single-cell-RNA-seq data were employed to identify the target of GA action. In addition, we will employ immunofluorescence (IF), immunohistochemistry (IHC), flow cytometry, western blot and RT-qPCR methodologies to investigate the impact of GA on the expression level of cyclin D1, PI3K, p-PI3K, AKT, p-AKT.</p></div><div><h3>Results</h3><p>GA treatment ameliorated histopathological alterations in the uterus and suppress proliferation. Estradiol stimulation can activate the PI3K/AKT pathway, leading to up-regulation of cyclin D1 expression, whereas GA treatment results in down-regulation of its expression.</p></div><div><h3>Conclusions</h3><p>The expression of cyclin D1 is down-regulated by GA through the inhibition of the PI3K/AKT pathway, effectively mitigating estradiol-induced EH in mice.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 1","pages":"Pages 1-13"},"PeriodicalIF":3.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000264/pdfft?md5=420a84d4b79dcf40e2a866fa58bebee9&pid=1-s2.0-S1347861324000264-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140074878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury 局部用瑞帕舒地尔和溴莫尼定联合用药可增强小鼠视神经损伤模型的神经保护作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-29 DOI: 10.1016/j.jphs.2024.02.011

Kazuhiko Namekata , Takahiko Noro , Euido Nishijima , Akiko Sotozono , Xiaoli Guo , Chikako Harada , Youichi Shinozaki , Yoshinori Mitamura , Tadashi Nakano , Takayuki Harada

{"title":"Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury","authors":"Kazuhiko Namekata , Takahiko Noro , Euido Nishijima , Akiko Sotozono , Xiaoli Guo , Chikako Harada , Youichi Shinozaki , Yoshinori Mitamura , Tadashi Nakano , Takayuki Harada","doi":"10.1016/j.jphs.2024.02.011","DOIUrl":"10.1016/j.jphs.2024.02.011","url":null,"abstract":"<div><h3>Purpose</h3><p>To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve.</p></div><div><h3>Methods</h3><p>Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina.</p></div><div><h3>Results</h3><p>Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1β and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF).</p></div><div><h3>Conclusions</h3><p>Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 326-333"},"PeriodicalIF":3.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000227/pdfft?md5=ed158bb332fc314968c632e45fb88be8&pid=1-s2.0-S1347861324000227-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140011002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Laminar-selective spinal astrocyte population capable of converting tactile information into nociceptive in rats 能将大鼠触觉信息转化为痛觉信息的层状选择性脊髓星形胶质细胞群

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-27 DOI: 10.1016/j.jphs.2024.02.014

Daichi Sueto , Akihisa Onishi , Eriko I , Yu Yoshikawa , Makoto Tsuda

引用次数: 0