Journal of pharmacological sciences最新文献_第9页

Investigation into the usefulness of cynomolgus monkeys with spontaneously elevated intraocular pressure as a model for glaucoma treatment research 将自发性眼压升高的猕猴作为青光眼治疗模型的实用性研究

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-17 DOI: 10.1016/j.jphs.2023.12.004

Tomoaki Araki , Masamitsu Shimazawa , Shinsuke Nakamura , Wataru Otsu , Yosuke Numata , Megumi Sakata , Koji Kabayama , Hideshi Tsusaki , Hideaki Hara

{"title":"Investigation into the usefulness of cynomolgus monkeys with spontaneously elevated intraocular pressure as a model for glaucoma treatment research","authors":"Tomoaki Araki , Masamitsu Shimazawa , Shinsuke Nakamura , Wataru Otsu , Yosuke Numata , Megumi Sakata , Koji Kabayama , Hideshi Tsusaki , Hideaki Hara","doi":"10.1016/j.jphs.2023.12.004","DOIUrl":"10.1016/j.jphs.2023.12.004","url":null,"abstract":"<div><p>Many glaucoma treatments focus on lowering intraocular pressure (IOP), with novel drugs continuing to be developed. One widely used model involves raising IOP by applying a laser to the trabecular iris angle (TIA) of cynomolgus monkeys to damage the trabecular meshwork. This model, however, presents challenges such as varying IOP values, potential trabecular meshwork damage, and risk of animal distress. This study investigated whether animals with naturally high IOP (>25 mmHg) could be used to effectively evaluate IOP-lowering drugs, thereby possibly replacing laser-induced models. Relationships between TIA size, IOP, and pupil diameter were also examined. Three representative IOP-lowering drugs (latanoprost, timolol, ripasudil) were administered, followed by multiple IOP measurements and assessment of corneal thickness, TIA, and pupil diameter via anterior segment optical coherence tomography (AS-OCT). There was a positive correlation was noted between IOP and corneal thickness before instillation, and a negative correlation between IOP and TIA before instillation. Our findings suggest animals with naturally high IOP could be beneficial for glaucoma research and development as a viable replacement for the laser-induced model and that measuring TIA using AS-OCT along with IOP yields a more detailed evaluation.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 52-60"},"PeriodicalIF":3.5,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000725/pdfft?md5=92f49fcdc2b8a6dc5b359320a43b5d4a&pid=1-s2.0-S1347861323000725-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691467","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

Long-lasting anti-despair and anti-anhedonia effects of (S)-norketamine in social isolation-reared mice (S)-诺基他敏对社会隔离饲养小鼠的长效抗绝望和抗失神作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-14 DOI: 10.1016/j.jphs.2023.12.005

Rei Yokoyama , Momoko Higuchi , Wataru Tanabe , Shinji Tsukada , Hisato Igarashi , Kaoru Seiriki , Takanobu Nakazawa , Atsushi Kasai , Yukio Ago , Hitoshi Hashimoto

{"title":"Long-lasting anti-despair and anti-anhedonia effects of (S)-norketamine in social isolation-reared mice","authors":"Rei Yokoyama , Momoko Higuchi , Wataru Tanabe , Shinji Tsukada , Hisato Igarashi , Kaoru Seiriki , Takanobu Nakazawa , Atsushi Kasai , Yukio Ago , Hitoshi Hashimoto","doi":"10.1016/j.jphs.2023.12.005","DOIUrl":"10.1016/j.jphs.2023.12.005","url":null,"abstract":"<div><p>Alternatives to ketamine without psychotomimetic properties for the treatment of depression have attracted much attention. Here, we examined the anti-despair and anti-anhedonia effects of the ketamine metabolites (<em>S</em>)-norketamine ((<em>S</em>)-NK), (<em>R</em>)-NK, (<em>2S,6S</em>)-hydroxynorketamine, and (<em>2R,6R</em>)-hydroxynorketamine in a mouse model of depression induced by social isolation. All ketamine metabolites examined had acute (30 min after administration) anti-despair-like effects in the forced swim test, but only (<em>S</em>)-NK showed a long-lasting (1 week) effect. Additionally, only (<em>S</em>)-NK improved reduced motivation both 30 min and 24 h after injection in the female encounter test. These results suggest that (<em>S</em>)-NK has potent and long-lasting antidepressant-like effects.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 72-76"},"PeriodicalIF":3.5,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000737/pdfft?md5=1b245c7e64b23f716e19cc9fd46c5ab8&pid=1-s2.0-S1347861323000737-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691391","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

Goreisan regulates cerebral blood flow according to barometric pressure fluctuations in female C57BL/6J mice 戈瑞森根据气压波动调节雌性 C57BL/6J 小鼠的脑血流量

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-07 DOI: 10.1016/j.jphs.2023.12.001

Yuki Kurauchi , Sumika Ryu , Risako Tanaka , Makito Haruta , Kiyotaka Sasagawa , Takahiro Seki , Jun Ohta , Hiroshi Katsuki

引用次数: 0

An ADAM17 selective inhibitor promotes glucose uptake by activating AMPK ADAM17选择性抑制剂通过激活AMPK促进葡萄糖摄取

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-01 DOI: 10.1016/j.jphs.2023.11.005

Tsugumasa Toma , Nobukazu Miyakawa , Mika Tateishi , Mikio Todaka , Tatsuya Kondo , Mikako Fujita , Masami Otsuka , Eiichi Araki , Hiroshi Tateishi

{"title":"An ADAM17 selective inhibitor promotes glucose uptake by activating AMPK","authors":"Tsugumasa Toma , Nobukazu Miyakawa , Mika Tateishi , Mikio Todaka , Tatsuya Kondo , Mikako Fujita , Masami Otsuka , Eiichi Araki , Hiroshi Tateishi","doi":"10.1016/j.jphs.2023.11.005","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.11.005","url":null,"abstract":"<div><p>AMPK activation promotes glucose and lipid metabolism. Here, we found that our previously reported ADAM17 inhibitor SN-4 activates AMPK and promotes membrane translocation and sugar uptake of GLUT4. AMPK inhibitor dorsomorphin reversed this effect of SN-4, confirming that the effect is mediated by AMPK activation. In addition, SN-4 inhibited lipid accumulation in HepG2 under high glucose conditions by promoting lipid metabolism and inhibiting lipid synthesis. Although lactic acidosis is a serious side effect of biguanides such as metformin, SN-4 did not affect lactate production. Furthermore, SN-4 was confirmed to inhibit the release of TNF-α, a causative agent of insulin resistance, from adipocytes. In diabetes treatment, it is important to not only regulate blood sugar levels but also prevent complications. Our findings reveal the therapeutic potential of SN-4 as a new antidiabetic drug that can also help prevent future complications.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 1","pages":"Pages 37-46"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000671/pdfft?md5=6af46222c2edb57117193f8f9f771b35&pid=1-s2.0-S1347861323000671-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500938","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

Transient receptor potential melastatin 2 is involved in trinitrobenzene sulfonic acid-induced acute and chronic colitis-associated fibrosis progression in mice 瞬时受体电位美拉他汀2参与三硝基苯磺酸诱导的小鼠急性和慢性结肠炎相关纤维化进展

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-11-30 DOI: 10.1016/j.jphs.2023.11.004

Tomohiro Nakamoto , Kenjiro Matsumoto , Hiroyuki Yasuda , Yasuo Mori , Shinichi Kato

{"title":"Transient receptor potential melastatin 2 is involved in trinitrobenzene sulfonic acid-induced acute and chronic colitis-associated fibrosis progression in mice","authors":"Tomohiro Nakamoto , Kenjiro Matsumoto , Hiroyuki Yasuda , Yasuo Mori , Shinichi Kato","doi":"10.1016/j.jphs.2023.11.004","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.11.004","url":null,"abstract":"<div><p>Crohn's disease, a chronic and recurrent gastrointestinal disease, frequently causes intestinal fibrosis. Transient receptor potential melastatin 2 (TRPM2), a non-selective cation channel, is activated by reactive oxygen species. This study investigated the role of TRPM2 in acute colitis and chronic colitis-associated fibrosis progression. Acute colitis and chronic colitis-associated fibrosis were induced in TRPM2-deficient (TRPM2KO) and wild-type (WT) mice through single and repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Bone marrow-derived macrophages (BMDMs) from WT and TRPM2KO mice were stimulated using H<sub>2</sub>O<sub>2</sub>. In WT mice, a single TNBS injection induced acute colitis with upregulated inflammatory cytokines/chemokines and Th1/Th17-related cytokines, while repeated TNBS injections induced chronic colitis-associated fibrosis with upregulation of fibrogenic factors and Th2-related cytokines. Acute colitis and chronic colitis-associated fibrosis with cytokines/chemokine upregulation and fibrogenic factors were considerably suppressed in TRPM2KO mice. Treating BMDMs with H<sub>2</sub>O<sub>2</sub> increased cytokine/chemokine expression and JNK, ERK, and p38 phosphorylation; however, these responses were significantly less in TRPM2KO than in WT mice. These findings suggest that TRPM2 contributes to acute colitis progression via Th1/Th17-mediated immune responses. Furthermore, TRPM2 may be directly involved in colitis-associated fibrosis induction, likely due to the regulation of Th2/TGF-β1-mediated fibrogenesis in addition to a consequence of acute colitis progression.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 1","pages":"Pages 18-29"},"PeriodicalIF":3.5,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000683/pdfft?md5=b9f714b60e7838c16b2e508de659a3cc&pid=1-s2.0-S1347861323000683-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138474599","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

Simultaneous XIAP and cIAP1/2 inhibition by a dimeric SMAC mimetic AZD5582 induces apoptosis in multiple myeloma 二聚体模拟SMAC的AZD5582同时抑制XIAP和cIAP1/2可诱导多发性骨髓瘤细胞凋亡

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-11-23 DOI: 10.1016/j.jphs.2023.11.002

Shohei Kikuchi , Yusuke Sugama , Kohichi Takada , Yusuke Kamihara , Akinori Wada , Yohei Arihara , Hajime Nakamura , Tsutomu Sato

{"title":"Simultaneous XIAP and cIAP1/2 inhibition by a dimeric SMAC mimetic AZD5582 induces apoptosis in multiple myeloma","authors":"Shohei Kikuchi , Yusuke Sugama , Kohichi Takada , Yusuke Kamihara , Akinori Wada , Yohei Arihara , Hajime Nakamura , Tsutomu Sato","doi":"10.1016/j.jphs.2023.11.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.11.002","url":null,"abstract":"<div><p>Overexpression of inhibitor of apoptosis (IAP) proteins is associated with poor prognosis. In multiple myeloma (MM), the IAP inhibitors (IAPi), LCL161, have been evaluated in preclinical and clinical settings but are not fully effective. Among IAPs, XIAP has the strongest anti-apoptotic function with direct binding activity to caspases and cIAP1 and cIAP2 are positive regulator of NF-κB signaling. Prior IAPi such as LCL161 has high affinity to cIAP1 and cIAP2 resulting in inferior inhibiting activity against XIAP. A novel dimeric IAPi, AZD5582 (C<sub>58</sub>H<sub>78</sub>N<sub>8</sub>O<sub>8</sub>), have high binding potency to XIAP with EC50 dose of 15 nM, enabling to simultaneous inhibit XIAP and cIAP1/2. AZD5582 monotherapy showed cell growth inhibition for all MM cell lines, MM1S, RPMI8226, U266 and KMS-5 and induced apoptosis. AZD5582 further showed anti-proliferation effect under the IL-6 additional condition and inhibited JAK-STAT signaling triggered by IL-6. AZD5582 combined with carfilzomib therapy showed a synergistic effect. Enhanced apoptosis was also observed in combination therapy. Synergistic effect was further observed with other conventional therapeutics. Simultaneous XIAP and cIAP1/2 inhibition by the dimeric IAPi AZD5582 is promising. This study provides a rationale of AZD5582 as a new treatment strategy in monotherapy and in combination therapy.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 1","pages":"Pages 30-36"},"PeriodicalIF":3.5,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000658/pdfft?md5=a640140a34a7ae197a134dd8fa319dda&pid=1-s2.0-S1347861323000658-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500937","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

Identification of a novel enzyme and the regulation of key enzymes in mammalian taurine synthesis 哺乳动物牛磺酸合成中一种新酶的鉴定及关键酶的调控

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-11-21 DOI: 10.1016/j.jphs.2023.11.003

Teruo Miyazaki

{"title":"Identification of a novel enzyme and the regulation of key enzymes in mammalian taurine synthesis","authors":"Teruo Miyazaki","doi":"10.1016/j.jphs.2023.11.003","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.11.003","url":null,"abstract":"<div><p>Taurine has many pharmacological roles on various tissues. The maintenance of abundant taurine content in the mammalian body through endogenous synthesis, in addition to exogenous intake, is the essential factor for morphological and functional maintenances in most tissues. The synthesis of taurine from sulfur-containing amino acids is influenced by various factors. Previous literature findings indicate the influence of the intake of proteins and sulfur-containing amino acids on the activity of the rate-limiting enzymes cysteine dioxygenase and cysteine sulfinate decarboxylase. In addition, the regulation of the activity and expression of taurine-synthesis enzymes by hormones, bile acids, and inflammatory cytokines through nuclear receptors have been reported in liver and reproductive tissues. Furthermore, flavin-containing monooxygenase subtype 1 was recently identified as the taurine-synthesis enzyme that converts hypotaurine to taurine. This review introduces the novel taurine synthesis enzyme and the nuclear receptor-associated regulation of key enzymes in taurine synthesis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 1","pages":"Pages 9-17"},"PeriodicalIF":3.5,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132300066X/pdfft?md5=749d85b000b6fb3a6ddd4535e4cb6561&pid=1-s2.0-S134786132300066X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138474600","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

Development of multifunctional pyrrole-imidazole polyamides that increase hepatocyte growth factor and suppress transforming growth factor-β1 增加肝细胞生长因子和抑制转化生长因子-β1的多功能吡咯-咪唑聚酰胺的研制

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-11-19 DOI: 10.1016/j.jphs.2023.11.001

Lan Chen , Noboru Fukuda , Takahiro Ueno , Masanori Abe , Taro Matsumoto

{"title":"Development of multifunctional pyrrole-imidazole polyamides that increase hepatocyte growth factor and suppress transforming growth factor-β1","authors":"Lan Chen , Noboru Fukuda , Takahiro Ueno , Masanori Abe , Taro Matsumoto","doi":"10.1016/j.jphs.2023.11.001","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.11.001","url":null,"abstract":"<div><h3>Purpose</h3><p>The DNA recognition peptide compounds pyrrole-imidazole (PI) polyamides bind to the minor groove and can block the binding of transcription factors to target sequences. To develop more PI polyamides as potential treatments for fibrotic diseases, including chronic renal failure, we developed multifunctional PI polyamides that increase hepatocyte growth factor (HGF) and decrease transforming growth factor (TGF)-β1.</p></div><div><h3>Methods</h3><p>We designed seven PI polyamides (HGF-1 to HGF-7) that bind to the chicken ovalbumin upstream promoter transcription factor-1 (COUP-TF1) binding site of the HGF promoter sequence. We selected PI polyamides that increase HGF and suppress TGF-β1 in human dermal fibroblasts (HDFs).</p></div><div><h3>Findings</h3><p>Gel shift assays showed that HGF-2 and HGF-4 bound the appropriate dsDNAs. HGF-2 and HGF-4 significantly inhibited the TGF-β1 mRNA expression in HDFs stimulated by phorbol 12-myristate 13-acetate. HGF-2 and HGF-4 significantly inhibited the TGF-β1 protein expression in HDFs with siRNA targeting HGF, indicating that HGF-2 and HGF-4 directly inhibited the expression of TGF-β1.</p></div><div><h3>Conclusion</h3><p>The designed and synthetic HGF PI polyamides targeting the HGF promoter, which increased the expression of HGF and suppressed the expression of TGF-β, will be a potential practical medicine for fibrotic diseases, including progressive renal diseases.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 1","pages":"Pages 1-8"},"PeriodicalIF":3.5,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000646/pdfft?md5=e696637d39f9ad3169cdc5e23ee6d349&pid=1-s2.0-S1347861323000646-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138472473","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

Catalpol ameliorates dexamethasone-induced osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via the activation of PKD1 promoter 梓醇通过激活PKD1启动子促进骨髓间充质干细胞成骨分化，从而改善地塞米松诱导的骨质疏松症

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-10-17 DOI: 10.1016/j.jphs.2023.10.002

Lei Xu , Gang Xu , Na Sun , Jialin Yao , Changyuan Wang , Wanhao Zhang , Kang Tian , Mozhen Liu , Huijun Sun

{"title":"Catalpol ameliorates dexamethasone-induced osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via the activation of PKD1 promoter","authors":"Lei Xu , Gang Xu , Na Sun , Jialin Yao , Changyuan Wang , Wanhao Zhang , Kang Tian , Mozhen Liu , Huijun Sun","doi":"10.1016/j.jphs.2023.10.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.10.002","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the effects of CA on glucocorticoid-induced osteoporosis (GIOP) and lucubrate the underlying mechanism of CA via the activation of polycystic kidney disease-1(PKD1) in bone marrow mesenchymal stem cells (BMSCs).</p></div><div><h3>Methods</h3><p>In vivo, a GIOP model in mice treated with dexamethasone (Dex) was established. Biomechanical, micro-CT, immunofluorescence staining of OCN, ALP and PKD1 and others were severally determined. qRT-PCR and Western blot methods were adopted to elucidate the particular mechanisms of CA on GIOP. In addition, BMSCs cultured in vitro were also induced by Dex to verify the effects of CA. Finally, siRNA and luciferase activity assays were performed to confirm the mechanisms.</p></div><div><h3>Results</h3><p>We found that CA could restore the destroyed bone microarchitecture and increase the bone mass in GIOP mice. CA could also upregulate PKD1 protein expression, reduce oxidative stress, and promote mRNA expression of bone formation-associated markers in GIOP mice. Furthermore, it was also observed that CA reduced oxidative stress and promoted osteogenic differentiation in Dex-induced BMSCs. Mechanically, CA could promote protein expression via increasing the activity of PKD1 promoter.</p></div><div><h3>Conclusion</h3><p>This study provides important evidences for CA in the further clinical treatment of GIOP, reveals the activation of PKD1 promoter as the underlying mechanism.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 4","pages":"Pages 221-231"},"PeriodicalIF":3.5,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49866571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses CA9和PRELID2;根据生物信息学分析，低氧反应性胰腺导管腺癌的潜在治疗靶点

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-10-17 DOI: 10.1016/j.jphs.2023.10.003

Masaki Imanishi , Takahisa Inoue , Keijo Fukushima , Ryosuke Yamashita , Ryo Nakayama , Masataka Nojima , Kosuke Kondo , Yoshiki Gomi , Honoka Tsunematsu , Kohei Goto , Licht Miyamoto , Masafumi Funamoto , Masaya Denda , Keisuke Ishizawa , Akira Otaka , Hiromichi Fujino , Yasumasa Ikeda , Koichiro Tsuchiya

{"title":"CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses","authors":"Masaki Imanishi , Takahisa Inoue , Keijo Fukushima , Ryosuke Yamashita , Ryo Nakayama , Masataka Nojima , Kosuke Kondo , Yoshiki Gomi , Honoka Tsunematsu , Kohei Goto , Licht Miyamoto , Masafumi Funamoto , Masaya Denda , Keisuke Ishizawa , Akira Otaka , Hiromichi Fujino , Yasumasa Ikeda , Koichiro Tsuchiya","doi":"10.1016/j.jphs.2023.10.003","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.10.003","url":null,"abstract":"<div><p>A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected <em>CA9</em> and <em>PRELID2</em> as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 4","pages":"Pages 232-242"},"PeriodicalIF":3.5,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49866574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0