Clinical and Experimental Pharmacology and Physiology最新文献_第10页

Impact of noscapine on halting the progression of pentylenetetrazole induced kindling epilepsy in mice 诺斯卡平对阻止戊四唑致小鼠点燃性癫痫进展的影响

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-09-19 DOI: 10.1111/1440-1681.13825

Rishav Gupta, Divya Soni, Shubham Upadhayay, Maanvi Dhureja, Puneet Kumar

{"title":"Impact of noscapine on halting the progression of pentylenetetrazole induced kindling epilepsy in mice","authors":"Rishav Gupta, Divya Soni, Shubham Upadhayay, Maanvi Dhureja, Puneet Kumar","doi":"10.1111/1440-1681.13825","DOIUrl":"10.1111/1440-1681.13825","url":null,"abstract":"Epilepsy is caused by an excessive recurrent excitatory neuronal firing, characterized by motor, psychomotor, and sensory impairments. Current therapies fail to produce 100% outcomes because of the complexity of the disease, poor diagnosis, and upsurge to drug-resistant epilepsy. The study repurposed the drug ‘noscapine’ mainly known for its anti-tussive properties. For the management of epilepsy and its associated secondary complications. To confirm the effect of noscapine, adult mice were injected with pentylenetetrazole (PTZ) (35 mg/kg i.p.) on an alternate day for 29 days to induce epilepsy. Animals were pretreated with noscapine in three doses (5, 10, and 20 mg/kg i.p.) for 33 days. Various behavioural assessments like the open field test, Morris water maze, and tail suspension test were performed to observe animals' locomotor activity, spatial memory, and anxiety-depressive behaviour. On the 34th day, animals were sacrificed, and brains were removed for biochemical estimations. Prolonged PTZ treatment reduced locomotor, learning activity, and increased anxiety-depressive behaviour, which was further confirmed by reduced antioxidant levels such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase because of increased oxido-nitrosative stress, that is, malondialdehyde (MDA) and nitrite in the brain. In comparison, noscapine pretreatment attenuated PTZ-induced behavioural and biochemical changes in the animals. The results indicate that noscapine ameliorates the oxido-nitrosative stress. However, studies indicate that oxido-nitrosative stress is a significant concern for the GABAergic neurons and promotes the disease progression. Further studies are required to explore the molecular mechanism of noscapine, which might be a practical approach as a newer antiepileptic agent.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"50 12","pages":"984-991"},"PeriodicalIF":2.9,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10303027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Telocytes protect against lung tissue fibrosis through hexokinase 2-dependent pathway by secreting hepatocyte growth factor 远端细胞通过分泌肝细胞生长因子，通过己糖激酶2依赖性途径抑制肺组织纤维化

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-09-16 DOI: 10.1111/1440-1681.13823

Shaoyuan Zhang, Linyi Sun, Borong Chen, Siyun Lin, Jianmin Gu, Lijie Tan, Miao Lin

{"title":"Telocytes protect against lung tissue fibrosis through hexokinase 2-dependent pathway by secreting hepatocyte growth factor","authors":"Shaoyuan Zhang, Linyi Sun, Borong Chen, Siyun Lin, Jianmin Gu, Lijie Tan, Miao Lin","doi":"10.1111/1440-1681.13823","DOIUrl":"10.1111/1440-1681.13823","url":null,"abstract":"Pulmonary fibrosis (PF) is one of the common manifestations of end-stage lung disease. Chronic lung failure after lung transplantation is mainly caused by bronchiolitis obliterans syndrome (BOS) and is mainly characterized by lung tissue fibrosis. Pulmonary epithelial-mesenchymal transformation (EMT) is crucial for pulmonary fibrosis. Telocytes (TCs), a new type of mesenchymal cells, play a protective role in various acute injuries. For exploring the anti-pulmonary fibrosis effect of TCs in the BOS model in vitro and the related mechanism, rat tracheal epithelial (RTE) cells were treated with transforming growth factor-β (TGF-β) to simulate lung tissue fibrosis in vitro. The RTE cells were then co-cultured with TCs primarily extracted from rat lung tissue. Western blot, Seahorse XF Analysers and enzyme-linked immunosorbent assay were used to detect the level of EMT and aerobic respiration of RTE cells. Furthermore, anti-hepatocyte growth factor (anti-HGF) antibody was exogenously added to the cultured cells to explore further mechanisms. Moreover, hexokinase 2 (HK2) in RTE cells was knocked down to assess whether it influences the blocking effect of the anti-HGF antibody. TGF-β could induce lung tissue fibrosis in RTE cells in vitro. Nevertheless, TCs co-culture decreased the level of EMT, glucose metabolic indicators (lactate and ATP) and oxygen levels. Furthermore, TCs released hepatocyte growth factor (HGF). Therefore, the exogenous addition of anti-HGF antibody in the co-culture system blocked the anti-lung tissue fibrosis effect. However, HK2 knockdown attenuated the blocking effect of the anti-HGF antibody. In conclusion, TCs can protect against lung tissue fibrosis by releasing HGF, a process dependent on HK2.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"50 12","pages":"964-972"},"PeriodicalIF":2.9,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Circ_0002295 facilitated myocardial fibrosis progression through the miR-1287/CXCR2 axis Circ_0002295通过miR-1287/CXCR2轴促进心肌纤维化进展

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-09-09 DOI: 10.1111/1440-1681.13819

Guo-Bin Ma, Wen-Xu Chen, Fang-Jie Zhan, Wen-Jing Xie, Rong-Wei Chen, Hong Chen, Wei-Lin Ye, Yu Jiang, Jian-Ping Xu

引用次数: 0

Rosiglitazone inhibits acyl-CoA synthetase long-chain family number 4 and improves secondary brain injury in a rat model of surgical brain injury 罗格列酮抑制酰基辅酶a合成酶长链家族4并改善外科脑损伤模型大鼠继发性脑损伤

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-09-07 DOI: 10.1111/1440-1681.13815

Jinchao Shen, Min Qian, Muyao Wu, Jiafeng Tang, Yating Gong, Jie Li, Jinfen Ji, Baoqi Dang

{"title":"Rosiglitazone inhibits acyl-CoA synthetase long-chain family number 4 and improves secondary brain injury in a rat model of surgical brain injury","authors":"Jinchao Shen, Min Qian, Muyao Wu, Jiafeng Tang, Yating Gong, Jie Li, Jinfen Ji, Baoqi Dang","doi":"10.1111/1440-1681.13815","DOIUrl":"10.1111/1440-1681.13815","url":null,"abstract":"Ferroptosis is a recently discovered non-apoptotic form of cellular death. Acyl-CoA synthetase long-chain family number 4 (ACSL4) is necessary for iron-dependent cellular death, and reactive oxygen species (ROS) produced by ACSL4 are the executioners of ferroptosis. Rosiglitazone improves ferroptosis by inhibiting ACSL4. There is no research indicating whether ACSL4 plays a role in cell death after surgical brain injury (SBI). This study aimed to investigate the role of ACSL4 in SBI via the ferroptosis pathway. Ninety male Sprague–Dawley rats were examined using a model of SBI. Subsequently, the inhibitory effect of rosiglitazone on ACSL4 was assessed via western blot, real-time polymerase chain reaction (PCR), immunofluorescence, fluoro-jade C staining, Perl's staining, ROS assay, and neurological scoring. The results showed that compared with the Sham group, the protein levels of ACSL4 and transferrin were significantly increased after SBI. Administration of rosiglitazone significantly reduced neuronal necrosis, iron deposition, brain water content and ROS in brain tissue and ameliorated neurological deficits at 48 h after SBI, which was concomitant with decreased transferrin expression. These findings demonstrate that SBI-induced upregulation of ACSL4 may be partly mediated by the ferroptosis pathway, which can be reversed by rosiglitazone administration.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"50 12","pages":"927-935"},"PeriodicalIF":2.9,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction to geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1 格尔达霉素纠正通过激活热休克因子1 HSF1抑制中性粒细胞胞外网络的形成，改善脓毒症小鼠的多器官功能障碍和微血栓形成

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-31 DOI: 10.1111/1440-1681.13820

引用次数: 0

Artesunate alleviates psoriasis-like dermatitis by reducing interleukin-23 expression in tumor necrosis factor-alpha-induced HaCaT cells 青蒿琥酯通过降低肿瘤坏死因子α诱导的HaCaT细胞中白细胞介素-23的表达来缓解银屑病样皮炎

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-27 DOI: 10.1111/1440-1681.13816

Lixian Lin, Zhongzhou Huang, Ma Jianchi, Zhixuan Guo, Zhenrui Shi, Zengqi Tang, Qing Guo, Hui Xiong

{"title":"Artesunate alleviates psoriasis-like dermatitis by reducing interleukin-23 expression in tumor necrosis factor-alpha-induced HaCaT cells","authors":"Lixian Lin, Zhongzhou Huang, Ma Jianchi, Zhixuan Guo, Zhenrui Shi, Zengqi Tang, Qing Guo, Hui Xiong","doi":"10.1111/1440-1681.13816","DOIUrl":"10.1111/1440-1681.13816","url":null,"abstract":"Artesunate (ART), an antimalarial drug with a multifunctional immunomodulatory effect, reduces psoriasis disease. ART can alleviate psoriasis-like dermatitis in mice but has no effect on proinflammatory cytokines in the blood. Thus, we hypothesized that the skin might be the target tissue of ART during the treatment of psoriasis. The interleukin (IL)-23/IL-17 axis has a key role in the pathogenesis of psoriasis. However, whether and how ART manipulates the IL-23 signal during psoriasis is unknown. This study found that IL-23 is highly expressed in the epidermis of psoriasis lesions and positively correlated with histological neutrophil infiltration and clinical psoriasis area and severity index (PASI) scores. Furthermore, ART inhibits the migration and cell cycle, as well as tumor necrosis factor-alpha (TNF-α)-induced IL-23 expression in HaCaT cells in a dose-dependent manner, probably through interference with the nuclear factor kappa B (NF-κB) signalling pathway. Animal experiments in imiquimod (IMQ)-induced psoriasis-like mice model also suggested that ART dose-dependently reduces IL-23 in the epidermis and ameliorates neutrophil infiltration. These findings thus provide further molecular evidence supporting ART as a promising drug for psoriasis in clinic.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"50 11","pages":"903-913"},"PeriodicalIF":2.9,"publicationDate":"2023-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Suppression of hypothalamic–pituitary–gonadal function by linzagolix in benign prostatic hyperplasia and polycystic ovary syndrome animal models 林扎哥利对良性前列腺增生及多囊卵巢综合征动物模型下丘脑-垂体-性腺功能的抑制作用

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-25 DOI: 10.1111/1440-1681.13817

Motohiro Tezuka, Saori Yonekubo-Awaka, Yasuaki Tamai, Kumi Tsuchioka, Kaoru Kobayashi, Yu Kuramochi, Satoshi Tatemichi, Tatsuya Nagasawa, Sumiyoshi Kiguchi

{"title":"Suppression of hypothalamic–pituitary–gonadal function by linzagolix in benign prostatic hyperplasia and polycystic ovary syndrome animal models","authors":"Motohiro Tezuka, Saori Yonekubo-Awaka, Yasuaki Tamai, Kumi Tsuchioka, Kaoru Kobayashi, Yu Kuramochi, Satoshi Tatemichi, Tatsuya Nagasawa, Sumiyoshi Kiguchi","doi":"10.1111/1440-1681.13817","DOIUrl":"10.1111/1440-1681.13817","url":null,"abstract":"The hypothalamic–pituitary–gonadal (HPG) axis is an important regulatory mechanism involved primarily in the development and regulation of the reproductive systems. The suppression of the HPG axis by gonadotropin-releasing hormone (GnRH) analogues is expected to be effective for the treatment of sex hormone-dependent diseases, such as endometriosis, uterine fibroid, prostate cancer, benign prostatic hyperplasia (BPH) and polycystic ovary syndrome (PCOS). Despite the established involvement of GnRH signalling in these disorders, the therapeutic efficacy of small molecular GnRH antagonists for BPH and PCOS has not been adequately evaluated in non-clinical studies. Therefore, the purpose of the present study was to evaluate the potential of linzagolix, a small molecular GnRH antagonist, as a potential new treatment option for BPH and PCOS. Dogs and rats exhibiting normal prostates and dogs diagnosed with prostatic hyperplasia were used to evaluate the effects of linzagolix in BPH. The effects of linzagolix were also examined in a rat model of PCOS induced by repeated administration of letrozole, an aromatase inhibitor. Linzagolix reduced serum luteinizing hormone and testosterone levels in male rats and normal or BPH model dogs and suppressed prostate weight without testosterone depletion, suggesting the existence of an optimal therapeutic testosterone level for BPH treatment. In a PCOS rat model, linzagolix improved both insulin resistance and ovarian dysfunction. Treatment with linzagolix decreased follicle-stimulating hormone levels, but did not alter serum luteinizing hormone and testosterone levels. These results indicate that linzagolix may provide a new treatment option for GnRH-related disorders, such as BPH and PCOS.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"50 11","pages":"914-923"},"PeriodicalIF":2.9,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Evaluation of right atrium structure and function in a rat model of monocrotaline-induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone 大鼠肺动脉高压模型右心房结构和功能的评价:探讨胺碘酮可能的抗心律失常特性

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-23 DOI: 10.1111/1440-1681.13813

Jorge Lucas Teixeira-Fonseca, Julliane Vasconcelos Joviano-Santos, Fabiana da Silva Alcântara, Michael Ramon de Lima Conceição, Polyana Leal-Silva, Danilo Roman-Campos

{"title":"Evaluation of right atrium structure and function in a rat model of monocrotaline-induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone","authors":"Jorge Lucas Teixeira-Fonseca, Julliane Vasconcelos Joviano-Santos, Fabiana da Silva Alcântara, Michael Ramon de Lima Conceição, Polyana Leal-Silva, Danilo Roman-Campos","doi":"10.1111/1440-1681.13813","DOIUrl":"10.1111/1440-1681.13813","url":null,"abstract":"Atrial arrhythmias (AA) are common in pulmonary hypertension (PH) and are closely associated with poor clinical outcomes. One of the most studied models to investigate PH is the rat model of monocrotaline (MCT) induced PH (MCT-PH). To date, little is known about right atrium (RA) function in the MCT-PH model and the propensity of RA to develop arrhythmias. Therefore, the aim of the study was to evaluate the function of the RA of control (CTRL) and MCT treated rats, and the ability of amiodarone, a classical antiarrhythmic, to prevent the occurrence of AA in the RA in MCT-PH rats. RA function was studied in MCT-PH rats 20 days after a single subcutaneous injection of MCT 50 mg/kg. The histological results indicated the presence of RA and right ventricular hypertrophy. Surface electrocardiogram demonstrated increased P wave duration, PR wave duration and QT interval in MCT rats. RA from MCT rats were more susceptible to develop ex vivo burst pacing arrhythmias when compared to CTRL. Intriguingly, amiodarone in clinical relevant concentration was not able to prevent the occurrence arrhythmias in RA from MCT-PH animals. Hence, we conclude that the rat model of MCT-PH impairs RA structure and function, and acute exposure of RA to amiodarone in clinical relevant concentration is not able to attenuate the onset of arrhythmias in the ex vivo RA preparation.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"50 11","pages":"893-902"},"PeriodicalIF":2.9,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome 小檗碱与肠道菌群的相互作用及其对多囊卵巢综合征的潜在治疗

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-21 DOI: 10.1111/1440-1681.13814

Ting-Wei Zhu, Xue-Lian Li

引用次数: 0

Aucubin alleviates methotrexate-induced enteritis in rats by inducing autophagy Aucubin通过诱导自噬减轻甲氨蝶呤诱导的大鼠肠炎。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-15 DOI: 10.1111/1440-1681.13810

Tongao Yang, Wuying Lang, Yun Zhao, Yahan Yang, Hongli Liu, Sufen Li, Xianglong Li, Shuangqi Zhang, Haihua Zhang

{"title":"Aucubin alleviates methotrexate-induced enteritis in rats by inducing autophagy","authors":"Tongao Yang, Wuying Lang, Yun Zhao, Yahan Yang, Hongli Liu, Sufen Li, Xianglong Li, Shuangqi Zhang, Haihua Zhang","doi":"10.1111/1440-1681.13810","DOIUrl":"10.1111/1440-1681.13810","url":null,"abstract":"One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti-inflammation, anti-apoptosis and anti-oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX-induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX-induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D-lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved-caspase 1, IL-18 and IL-1β. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy-related markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX-induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX-induced enteritis. However, 3-methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX-induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX-resulted enteritis.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"50 11","pages":"855-866"},"PeriodicalIF":2.9,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10061079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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