Pharmacology最新文献

{"title":"Retraction Statement.","authors":"","doi":"10.1159/000535412","DOIUrl":"10.1159/000535412","url":null,"abstract":"","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"66"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441126","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}

{"title":"Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence.","authors":"Christoph Kuemmerli, Viviane Hess, Philipp Dutkowski, Stefanie Sinz, Ulf Kessler, Gabriel F Hess, Adrian T Billeter, Beat P Müller-Stich, Otto Kollmar, Philip C Müller","doi":"10.1159/000537887","DOIUrl":"10.1159/000537887","url":null,"abstract":"<p><strong>Background: </strong>Hepatic artery infusion chemotherapy (HAI) has been proposed as a valuable adjunct for multimodal therapy of primary and secondary liver malignancies. This review provides an overview of the currently available evidence of HAI, taking into account tumor response and long-term oncologic outcome.</p><p><strong>Summary: </strong>In colorectal liver metastases (CRLM), HAI in combination with systemic therapy leads to high response rates (85-90%) and conversion to resectablity in primary unresectable disease in up to 50%. HAI in combination with systemic therapy in CRLM in the adjuvant setting shows promising long-term outcomes with up to 50% 10-year survival in a large, non-randomized single-center cohort. For hepatocellular carcinoma patients, response rates as high as 20-40% have been reported for HAI and long-term outcomes compare well to other therapies. Similarly, survival for patients with unresectable intrahepatic cholangiocarcinoma 3 years after treatment with HAI is reported as high as 34%, which compares well to trials of systemic therapy where 3-year survival is usually below 5%. However, evidence is mainly limited by highly selected, heterogenous patient groups, and outdated chemotherapy regimens. The largest body of evidence stems from small, often non-randomized cohorts, predominantly from highly specialized single centers.</p><p><strong>Key message: </strong>In well-selected patients with primary and secondary liver malignancies, HAI might improve response rates and, possibly, long-term survival. Results of ongoing randomized trials will show whether a wider adoption of HAI is justified, particularly to increase rates of resectability in advanced malignant diseases confined to the liver.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"86-97"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11008720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription Factor 21: A Transcription Factor That Plays an Important Role in Cardiovascular Disease.","authors":"Yaqian Luo, Fangzhou He, Yifang Zhang, Shufan Li, Ruirui Lu, Xing Wei, Ji Huang","doi":"10.1159/000536585","DOIUrl":"10.1159/000536585","url":null,"abstract":"<p><strong>Background: </strong>According to the World Health Organisation's Health Report 2019, approximately 17.18 million people die from cardiovascular disease each year, accounting for more than 30% of all global deaths. Therefore, the occurrence of cardiovascular disease is still a global concern. The transcription factor 21 (TCF21) plays an important role in cardiovascular diseases. This article reviews the regulation mechanism of TCF21 expression and activity and focuses on its important role in atherosclerosis in order to contribute to the development of diagnosis and treatment of cardiovascular diseases.</p><p><strong>Summary: </strong>TCF21 is involved in the phenotypic regulation of vascular smooth muscle cells (VSMCs), promotes the proliferation and migration of VSMCs, and participates in the activation of inflammatory sequences. Increased proliferation and migration of VSMCs can lead to neointimal hyperplasia after vascular injury. Abnormal hyperplasia of neointima and inflammation are one of the main features of atherosclerosis. Therefore, targeting TCF21 may become a potential treatment for relieving atherosclerosis.</p><p><strong>Key messages: </strong>TCF21 as a member of basic helix-loop-helix transcription factors regulates cell growth and differentiation by modulating gene expression during the development of different organs and plays an important role in cardiovascular development and disease. VSMCs and cells derived from VSMCs constitute the majority of plaques in atherosclerosis. TCF21 plays a key role in regulation of VSMCs' phenotype, thus accelerating atherogenesis in the early stage. However, TCF21 enhances plaque stability in late-stage atherosclerosis. The dual role of TCF21 should be considered in the translational medicine.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"183-193"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144028","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}

{"title":"Transcription Factor MITF Inhibits the Transcription of CPT1B to Regulate Fatty Acid β-Oxidation and Thus Affects Stemness in Lung Adenocarcinoma Cells.","authors":"Weijian Tang, Hongguang Tang, Shaohua Xu, Hao Yu, Zhoumiao Chen","doi":"10.1159/000534547","DOIUrl":"10.1159/000534547","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer stem cells (CSCs) play critical roles in lung adenocarcinoma (LUAD) progression, and fatty acid oxidation is key for CSC growth and survival. Therefore, investigating the molecular mechanisms regulating fatty acid β-oxidation in LUAD is important for its treatment.</p><p><strong>Methods: </strong>Bioinformatics analysis assessed CPT1B and MITF expression and their correlation in LUAD tissues, as well as the pathways enriched by CPT1B. qRT-PCR assessed expression of CPT1B and MITF, while CCK-8 and sphere-forming assays were used to measure cell viability and stemness, respectively. Dual staining detected lipid accumulation, while kits were used to measure fatty acid β-oxidation and glycerol content. qRT-PCR was used to assay expression of lipid oxidation genes. Western blot was used to examine expression of stem cell-related markers. Dual-luciferase assay and ChIP assay were used to verify the binding relationship between MITF and CPT1B.</p><p><strong>Results: </strong>CPT1B was found to be highly expressed in LUAD and enriched in linoleic acid metabolism pathway and α-linolenic acid metabolism pathway. Functional experiments showed that CPT1B could promote stemness in LUAD cells by regulating fatty acid β-oxidation. Additionally, CPT1B was found to be regulated by the upstream transcription factor MITF, which was lowly expressed in LUAD and could downregulate CPT1B expression. Rescue experiments revealed that CPT1B/MITF axis could affect stemness in LUAD cells by regulating fatty acid β-oxidation.</p><p><strong>Conclusion: </strong>Transcription factor MITF inhibited transcription of CPT1B to regulate fatty acid β-oxidation, thereby suppressing stemness in LUAD cells. MITF and CPT1B may become new targets for LUAD.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"52-64"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452261","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}

{"title":"Negative Prognostic Associations of Selective Serotonin Reuptake Inhibitors Use in Hospitalized COVID-19 Patients and Potential Contribution of Cardiovascular Comorbidities.","authors":"Ivan Papic, Petra Bistrovic, Ivan Krecak, Maja Ortner Hadziabdic, Marko Lucijanic","doi":"10.1159/000540008","DOIUrl":"10.1159/000540008","url":null,"abstract":"<p><strong>Introduction: </strong>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of coronavirus disease 2019 (COVID-19), a very contagious systemic disease dominantly affecting the respiratory tract. Recent findings oppose earlier suggestions that selective serotonin reuptake inhibitors (SSRIs) might be protective during acute SARS-CoV-2 infection, prompting the current study.</p><p><strong>Methods: </strong>The institutional registry of a tertiary referral center was retrospectively evaluated for SSRI use and associated clinical outcomes among hospitalized COVID-19 patients with mostly severe and critical disease.</p><p><strong>Results: </strong>Among 1,558 patients, there were 78 (5%) exposed to SSRI during hospitalization. SSRI users in comparison to non-users did not significantly differ in their demographic characteristics, comorbidity profile or the severity of COVID-19 symptoms and associated inflammatory response at admission. In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher risks of death, mechanical ventilation, intensive care unit treatment, and bacteremia, whereas no significant relationship with risks of venous, arterial thrombosis, and major bleeding was present. Patients with less severe initial COVID-19 presentation, lower inflammatory burden, higher platelet count, lower cumulative comorbidity burden, presence of hyperlipidemia, atrial fibrillation, chronic heart failure and nonexposed to acetylsalicylic-acid had higher mortality associated with SSRI use.</p><p><strong>Conclusions: </strong>Findings of the current study validate findings of higher mortality but also report higher tendency for respiratory deterioration, intensive care unit treatment, and bacteremia associated with SSRI use among hospitalized COVID-19 patients. These findings also suggest the potential contribution of cardiovascular comorbidities to detrimental clinical course of SSRI exposed patients.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"357-364"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860651","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}

{"title":"M6A RNA Methylation-Mediated Dysregulation of AGAP2-AS1 Promotes Trastuzumab Resistance of Breast Cancer.","authors":"Yangjun Cai, Haihong Zheng, Dong Xu, Jingjing Xie, Weiwen Wang, Zhiwei Liu, Zhongqiu Zheng","doi":"10.1159/000539202","DOIUrl":"10.1159/000539202","url":null,"abstract":"<p><strong>Introduction: </strong>Trastuzumab is commonly used to treat human epidermal growth factor receptor-2-positive (HER2+) breast cancer, but its efficacy is often limited by chemotherapy resistance. Recent studies have indicated that long non-coding RNAs (lncRNAs) play important roles in tumor progression and response to therapy. However, the regulatory mechanisms associating lncRNAs and trastuzumab resistance remain unknown.</p><p><strong>Methods: </strong>Quantitative polymerase chain reaction was performed to detect the expression of related genes. Western blot and immunofluorescence assays were used to evaluate protein expression levels. A series of gain- or loss-of-function assays confirmed the function of AGAP2-AS1 in trastuzumab resistance, both in vitro and in vivo. RNA immunoprecipitation and pull-down analyses were conducted to verify the interaction between METTL3/YTHDF2 and lncRNA AGAP2-AS1.</p><p><strong>Results: </strong>AGAP2-AS1 was upregulated in trastuzumab-resistant cells and SKBR-3R-generated xenografts in nude mice. Silencing AGAP2-AS1 significantly decreased trastuzumab-induced cytotoxicity both in vitro and in vivo. Furthermore, m6A methylation of AGAP2-AS1 was reduced in trastuzumab-resistant cells compared to that in parental cells. In addition, METTL3 increased m6A methylation of AGAP2-AS1, which finally induced the suppressed AGAP2-AS1 expression. Moreover, YTHDF2 was essential for METTL3-mediated m6A methylation of AGAP2-AS1. Functionally, AGAP2-AS1 regulated trastuzumab resistance by inducing autophagy and increasing ATG5 expression.</p><p><strong>Conclusion: </strong>we demonstrated that METTL3/YTHDF2-mediated m6A methylation increased the expression of AGAP2-AS1, which could promote trastuzumab resistance in breast cancer. AGAP2-AS1 regulates trastuzumab resistance by inducing autophagy. Therefore, AGAP2-AS1 may be a promising predictive biomarker and therapeutic target in patients with breast cancer.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"282-292"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922573","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}

{"title":"Expression of Concern.","authors":"","doi":"10.1159/000541269","DOIUrl":"10.1159/000541269","url":null,"abstract":"","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"366"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293606","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}

{"title":"Inhalation of Spray-Dried Extract of Salvia rosmarinus Spenn Alleviates Lung Inflammatory, Oxidative, and Remodeling Changes in Asthmatic Rats.","authors":"Mohammad Amin Rajizadeh, Mohammad Abbas Bejeshk, Amirhashem Aminizadeh, Abolfazl Yari, Fahimeh Rostamabadi, Fatemeh Bagheri, Hamid Najafipour, Mohammad Hadi Nematollahi, Arian Amirkhosravi, Mehrnaz Mehrabani, Mitra Mehrabani","doi":"10.1159/000534392","DOIUrl":"10.1159/000534392","url":null,"abstract":"<p><strong>Introduction: </strong>For centuries, Salvia rosmarinus Spenn has been applied as folk medicine to cure different diseases due to its anti-inflammatory, antibacterial, antioxidant, antifungal, and antitumor effects. To find bioactive medicinal herbs exerting a protective effect on airway inflammation and remodeling, we assessed the anti-oxidative and anti-inflammatory effects of an aqueous spray-dried extract of Salvia rosmarinus Spenn. (rosemary) in an ovalbumin-induced asthmatic rat model.</p><p><strong>Methods: </strong>Rats were randomly divided into normal control (control), asthma, asthma+rosemary extract (RE) (13 mg/kg), asthma+RE (50 mg/kg), and asthma+budesonide groups. After 50 days, animals were anesthetized, and then blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for subsequent serological and pathological studies. Histopathology of lung tissues was evaluated by H&amp;E staining. The oxidative stress parameters and airway inflammation factors in BALF and lung tissue were explored.</p><p><strong>Results: </strong>Using thin layer chromatography, the presence of rosmarinic acid was confirmed in aqueous extract of rosemary. Furthermore, RE markedly decreased immunoglobulin E levels (50 mg/kg; p &lt; 0.001 vs. asthma group) and inflammatory cytokines (50 mg/kg; p &lt; 0.001 vs. asthma group) and increased antioxidant enzymes (50 mg/kg, p &lt; 0.001 vs. asthma group). Furthermore, RE at a concentration of 50 mg/kg obviously reduced the number of inflammatory cells, goblet cells, and pathological changes compared to the asthma group.</p><p><strong>Conclusion: </strong>The results showed that RE administration might prevent or alleviate allergic asthma-related pathological change, probably via antioxidant and anti-inflammatory mechanisms.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"10-21"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71426199","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}

{"title":"Erratum.","authors":"","doi":"10.1159/000538084","DOIUrl":"10.1159/000538084","url":null,"abstract":"","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"128"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028767","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}

{"title":"The Detrimental Effect of Pre-Treatment with Ivermectin on Myocardial Ischemia.","authors":"Sara Cheraghi, Shabnam Babataheri, Hamid Soraya","doi":"10.1159/000534206","DOIUrl":"10.1159/000534206","url":null,"abstract":"<p><strong>Introduction: </strong>Ivermectin (IVM) is a broad-spectrum anti-parasitic agent with potential antibacterial, antiviral, and anti-cancer effects. There are limited studies on the effects of IVM on cardiovascular diseases, so the present study sought to determine the effects of pre-treatment with IVM on myocardial ischemia in both ex vivo and in vivo.</p><p><strong>Methods: </strong>In the ex vivo part, two groups of control and treated rats with IVM (0.2 mg/kg) were examined for cardiac function and arrhythmias by isolated heart perfusion. In the in vivo part, four groups, namely, control, IVM, Iso (MI), and Iso + IVM 0.2 mg/kg were used. Subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used for the induction of myocardial infarction (MI) in male Wistar rats. Then electrocardiogram, hemodynamic factors, cardiac hypertrophy, and malondialdehyde (MDA) levels were investigated.</p><p><strong>Results: </strong>The ex vivo results showed that administration of IVM induces cardiac arrhythmia and decreases the left ventricular maximal rate of pressure increase (contractility) and maximal rate of pressure decline (relaxation). The isoproterenol-induced MI model used as an in vivo model showed that cardiac hypertrophy were increased with no improvement in the hemodynamic and electrocardiogram pattern in the IVM-treated group in comparison to MI (Iso) group. However, the MDA level was lower in the IVM-treated group.</p><p><strong>Conclusion: </strong>IVM pre-treatment demonstrates detrimental effects in cardiac ischemia through exacerbation of cardiac arrhythmia, myocardial dysfunction, and increased cardiac hypertrophy. Therefore, the use of IVM in ischemic heart patients should be done with great caution.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-9"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162631","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}