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Retraction Note: The teratogenic effect of pregabalin on heart, liver and kidney in rats: a light microscopic, electron microscopic and immunohistochemical study. 回缩说明:普瑞巴林对大鼠心脏、肝脏和肾脏的致畸作用:光镜、电镜和免疫组织化学研究。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-10-13 DOI: 10.1186/s40360-023-00697-4
Omnia I Ismail, Eman S Shaltout, Nora Z Abdellah, Diab F Hetta, Wael M A Abd El-Ghani, Lobna A Abdelzaher, Ahmed Mohamed Mohamed Mahmoud, Asmaa M Hasan, Noha A Rashed, Noha Esmael Ebrahem
{"title":"Retraction Note: The teratogenic effect of pregabalin on heart, liver and kidney in rats: a light microscopic, electron microscopic and immunohistochemical study.","authors":"Omnia I Ismail, Eman S Shaltout, Nora Z Abdellah, Diab F Hetta, Wael M A Abd El-Ghani, Lobna A Abdelzaher, Ahmed Mohamed Mohamed Mahmoud, Asmaa M Hasan, Noha A Rashed, Noha Esmael Ebrahem","doi":"10.1186/s40360-023-00697-4","DOIUrl":"10.1186/s40360-023-00697-4","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190495","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
Metformin alleviates adriamycin resistance of osteosarcoma by declining YY1 to inhibit MDR1 transcriptional activity. 二甲双胍通过降低YY1抑制MDR1转录活性来减轻骨肉瘤的阿霉素耐药性。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-10-12 DOI: 10.1186/s40360-023-00685-8
Bowen Wu, Peng Li, Eryue Qiu, Jian Chen
{"title":"Metformin alleviates adriamycin resistance of osteosarcoma by declining YY1 to inhibit MDR1 transcriptional activity.","authors":"Bowen Wu, Peng Li, Eryue Qiu, Jian Chen","doi":"10.1186/s40360-023-00685-8","DOIUrl":"10.1186/s40360-023-00685-8","url":null,"abstract":"<p><p>Chemotherapy resistance hinders the successful treatment of osteosarcoma (OS) to some extent. Previous studies have confirmed that metformin (Met) enhances apoptosis induced by chemotherapeutic drugs, but the underlying mechanism remains unclear. To establish adriamycin (ADM)-resistant MG-63 (MG-63/ADM) cells, the dosage of ADM was progressively increased. The results of qRT-PCR and Western blotting demonstrated that the expression level of Yin Yang 1 (YY1) and multi-drug resistance-1 (MDR1) in MG-63/ADM cells were remarkably increased compared with those in MG-63 cells. Met dramatically enhanced ADM cytotoxicity and accelerated apoptosis of MG-63/ADM cells. Moreover, Met suppressed the expressions of YY1 and MDR1 in MG-63/ADM cells. YY1 promoted its transcriptional expression by directly binding to the MDR1 promoter. Furthermore, the effects of Met on ADM sensitivity in MG-63/ADM cells was reversed due to overexpression of YY1 or MDR1. Collectively, these findings suggested that Met inhibited YY1/MDR1 pathway to reverse ADM resistance in OS, providing a new insight into the mechanism of Met in ADM resistance of OS.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190494","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
The effectiveness and safety of botulinum toxin injections for the treatment of sialorrhea with Parkinson's disease: a systematic review and meta-analysis. 肉毒杆菌毒素注射治疗帕金森病唾液溢的有效性和安全性:一项系统综述和荟萃分析。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-10-12 DOI: 10.1186/s40360-023-00694-7
Chun-Lan Yang, Jia-Peng Huang, Ying-Chao Tan, Ting-Ting Wang, Han Zhang, Yun Qu
{"title":"The effectiveness and safety of botulinum toxin injections for the treatment of sialorrhea with Parkinson's disease: a systematic review and meta-analysis.","authors":"Chun-Lan Yang, Jia-Peng Huang, Ying-Chao Tan, Ting-Ting Wang, Han Zhang, Yun Qu","doi":"10.1186/s40360-023-00694-7","DOIUrl":"10.1186/s40360-023-00694-7","url":null,"abstract":"<p><strong>Background: </strong>Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD).</p><p><strong>Methods: </strong>We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I<sup>2</sup> tests. We used the GRADE tool to assess the certainty of evidence (COE).</p><p><strong>Results: </strong>Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low).</p><p><strong>Conclusions: </strong>The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function.</p><p><strong>Trial registration: </strong>Our review protocol was registered on PROSPERO (42021288334).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190496","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: 1
Dermal effects and pharmacokinetic evaluation of the lidocaine/prilocaine cream in healthy Chinese volunteers. 利多卡因/丙胺卡因乳膏在健康中国志愿者中的皮肤作用和药代动力学评价。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-10-12 DOI: 10.1186/s40360-023-00690-x
Lingjun Li, Baole Cai, Hongyang Li, Jun Wei, Lei Tao, Pengcheng Ma
{"title":"Dermal effects and pharmacokinetic evaluation of the lidocaine/prilocaine cream in healthy Chinese volunteers.","authors":"Lingjun Li, Baole Cai, Hongyang Li, Jun Wei, Lei Tao, Pengcheng Ma","doi":"10.1186/s40360-023-00690-x","DOIUrl":"10.1186/s40360-023-00690-x","url":null,"abstract":"<p><strong>Background: </strong>EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers.</p><p><strong>Materials and methods: </strong>The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study.</p><p><strong>Results: </strong>After applied 15 g of the cream for 4 h to a 100 cm<sup>2</sup> area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated.</p><p><strong>Conclusion: </strong>The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study.</p><p><strong>Clinical trial registration: </strong>CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190493","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
Correction to: efficacy and safety of the switch of Triumeq® to generic (abacavir + lamivudine) + Tivicay®: data at 24 weeks. 更正:Triumeq®转为仿制药(阿巴卡韦)的有效性和安全性 + 拉米夫定) + Tivicay®:24周数据。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-10-06 DOI: 10.1186/s40360-023-00693-8
Julián Olalla, Javier Pérez-Stachowski, Begoña Tortajada, Alfonso Del Arco, Efrén Márquez, Javier De la Torre, Miriam Nieto, José María García de Lomas, José Luis Prada, Javier García-Alegría
{"title":"Correction to: efficacy and safety of the switch of Triumeq® to generic (abacavir + lamivudine) + Tivicay®: data at 24 weeks.","authors":"Julián Olalla, Javier Pérez-Stachowski, Begoña Tortajada, Alfonso Del Arco, Efrén Márquez, Javier De la Torre, Miriam Nieto, José María García de Lomas, José Luis Prada, Javier García-Alegría","doi":"10.1186/s40360-023-00693-8","DOIUrl":"10.1186/s40360-023-00693-8","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41153880","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
Butyrate alleviates renal inflammation and fibrosis in a rat model of polycystic ovarian syndrome by suppression of SDF-1. 丁酸通过抑制SDF-1减轻多囊卵巢综合征大鼠模型中的肾脏炎症和纤维化。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-10-03 DOI: 10.1186/s40360-023-00692-9
Al-Amin M Bashir, Kehinde S Olaniyi
{"title":"Butyrate alleviates renal inflammation and fibrosis in a rat model of polycystic ovarian syndrome by suppression of SDF-1.","authors":"Al-Amin M Bashir, Kehinde S Olaniyi","doi":"10.1186/s40360-023-00692-9","DOIUrl":"10.1186/s40360-023-00692-9","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovarian syndrome (PCOS) is a multifactorial condition with metabolic-related complications, such as diabetic nephropathy and chronic renal disorder, which are the leading cause of renal transplant globally. Protective effects of histone deacetylase (HDAC) inhibitors (HDACi) have been documented in metabolic-linked pathologies. Nonetheless, the current study investigated the restorative role of HDACi, butyrate in experimental PCOS-induced renal disorder.</p><p><strong>Materials and methods: </strong>Female Wistar rats (8-week-old) were divided into groups; control, butyrate-treated, letrozole and letrozole + butyrate-treated groups. To induce PCOS, 1 mg/kg of letrozole was given (oral gavage) for 21 days. After confirmation of PCOS, 200 mg/kg of butyrate (oral gavage) was administered for 6 weeks.</p><p><strong>Results: </strong>Rats with PCOS revealed disruption in glucose homeostasis (hyperinsulinemia and impaired glucose tolerance and insulin resistance) and presented with the phenotypes of PCOS (hyperandrogenism, multiple ovarian cysts and elevated LH/FSH ratio). Increased plasma and renal triglycerides and inflammatory (TNF-α/SDF-1/NF-κB) markers were observed with elevated levels of TGFβ-1, renal lipid peroxidation and redox imbalance (GGT, GSH, HIF-1α). Interestingly, animals with PCOS reported increased body weight as well as renal mass. Whereas, heightened levels of plasma urea, creatinine and creatine kinase indicating renal dysfunction, characterized by renal apoptosis (Caspase-6) and increased HDAC2 levels. Notwithstanding, administration of butyrate averted the alterations.</p><p><strong>Conclusion: </strong>The present investigation demonstrates that PCOS declines renal function, which is accompanied by renal inflammation, apoptosis and fibrosis. The study further suggests that butyrate, an HDAC2i restores renal function by suppressing renal SDF-1 with subsequent attenuation of renal inflammation, apoptosis and fibrosis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10548736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105059","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
Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study. 洛匹那韦在暴露于严重急性呼吸系统综合征冠状病毒2型的HIV阴性个体中的群体药代动力学分析:一项COPEP(冠状病毒暴露后预防)子研究。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-09-27 DOI: 10.1186/s40360-023-00687-6
Paul Thoueille, Margot Delfraysse, Pascal Andre, Thierry Buclin, Laurent A Decosterd, Chiara Fedeli, Pilar Ustero, Alexandra Calmy, Monia Guidi
{"title":"Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study.","authors":"Paul Thoueille, Margot Delfraysse, Pascal Andre, Thierry Buclin, Laurent A Decosterd, Chiara Fedeli, Pilar Ustero, Alexandra Calmy, Monia Guidi","doi":"10.1186/s40360-023-00687-6","DOIUrl":"10.1186/s40360-023-00687-6","url":null,"abstract":"<p><strong>Background: </strong>Lopinavir/ritonavir (LPV/r) is a drug traditionally used for the treatment of HIV that has been repurposed as a potential post-exposure prophylaxis agent against COVID-19 in the COronavirus Post-Exposure Prophylaxis (COPEP) study. The present analysis aims to evaluate LPV levels in individuals exposed to SARS-CoV-2 versus people living with HIV (PLWH) by developing a population pharmacokinetic (popPK) model, while characterizing external and patient-related factors that might affect LPV exposure along with dose-response association.</p><p><strong>Methods: </strong>We built a popPK model on 105 LPV concentrations measured in 105 HIV-negative COPEP individuals exposed to SARS-CoV-2, complemented with 170 LPV concentrations from 119 PLWH followed in our routine therapeutic drug-monitoring programme. Published LPV popPK models developed in PLWH and in COVID-19 patients were retrieved and validated in our study population by mean prediction error (MPE) and root mean square error (RMSE). The association between LPV model-predicted residual concentrations (C<sub>min</sub>) and the appearance of the COVID-19 infection in the COPEP participants was investigated.</p><p><strong>Results: </strong>A one-compartment model with linear absorption and elimination best described LPV concentrations in both our analysis and in the majority of the identified studies. Globally, similar PK parameters were found in all PK models, and provided close MPEs (from -19.4% to 8.0%, with a RMSE of 3.4% to 49.5%). No statistically significant association between C<sub>min</sub> and the occurrence of a COVID-19 infection could be detected.</p><p><strong>Conclusion: </strong>Our analysis indicated that LPV circulating concentrations were similar between COPEP participants and PLWH, and that published popPK models described our data in a comparable way.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41102811","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
Bilirubin potentiates etomidate-induced sedation by enhancing GABA-induced currents after bile duct ligation. 胆管结扎后,胆红素通过增强GABA诱导的电流来增强依托咪酯诱导的镇静作用。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-09-23 DOI: 10.1186/s40360-023-00675-w
Hao Gao, Qian Zhao, Jian-Gang Song, Guo-Xia Hu, Wei-Feng Yu, Ying-Fu Jiao, Jin-Chao Song
{"title":"Bilirubin potentiates etomidate-induced sedation by enhancing GABA-induced currents after bile duct ligation.","authors":"Hao Gao, Qian Zhao, Jian-Gang Song, Guo-Xia Hu, Wei-Feng Yu, Ying-Fu Jiao, Jin-Chao Song","doi":"10.1186/s40360-023-00675-w","DOIUrl":"10.1186/s40360-023-00675-w","url":null,"abstract":"<p><strong>Objectives: </strong>Our previous clinical trial showed that etomidate requirements to reach an appropriate level of anesthesia in patients with obstructive jaundice were reduced, which means that these patients are more sensitive to etomidate. However, the mechanism is still not completely clear. The present study was aimed to investigate the mechanism by which bilirubin facilitates etomidate induced sedation.</p><p><strong>Methods: </strong>A bile duct ligation (BDL) rat model was used to simulate obstructive jaundice. Anesthesia sensitivity to etomidate was determined by the time to loss of righting reflex (LORR). Intrathecal injection of bilirubin was used to test the effects of bilirubin on etomidate induced sedation. The modulating effects of bilirubin on GABA responses were studied using the whole-cell patch clamp technique.</p><p><strong>Results: </strong>The time to LORR induced by etomidate was significantly decreased in the BDL groups (p < 0.05), and unconjugated bilirubin in serum and cerebrospinal fluid (CSF) were markedly increased (p < 0.05). The time to LORR induced by etomidate was decreased after intrathecal injection of bilirubin (p < 0.05). A bilirubin concentration of 1.0 μM increased the GABA-induced currents of rat cortical pyramidal neurons (p < 0.05). Furthermore, 1.0 μM bilirubin enhanced GABA-induced currents modulated by etomidate (p < 0.05).</p><p><strong>Conclusions: </strong>Our results demonstrated that pathologic bilirubin in CSF could enhance etomidate induced sedation. The mechanism may be that bilirubin increase the GABA-induced currents of rat pyramidal neurons.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095731","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
Panobinostat (LBH589) combined with AM1241 induces cervical cancer cell apoptosis through autophagy pathway. 泛诺比司他(LBH589)联合AM1241通过自噬途径诱导宫颈癌症细胞凋亡。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-09-22 DOI: 10.1186/s40360-023-00686-7
Bo Sheng, Wenwen Wang, Dongyue Xia, Xiangdong Qu
{"title":"Panobinostat (LBH589) combined with AM1241 induces cervical cancer cell apoptosis through autophagy pathway.","authors":"Bo Sheng, Wenwen Wang, Dongyue Xia, Xiangdong Qu","doi":"10.1186/s40360-023-00686-7","DOIUrl":"10.1186/s40360-023-00686-7","url":null,"abstract":"<p><strong>Purpose: </strong>The study aims to investigate the apoptotic effects of combining LBH589 and AM1241 (a selective CB2 receptor agonist) on cervical cancer cells and elucidating the mechanism of this combined therapy, which may provide innovative strategies for treating this disease.</p><p><strong>Methods: </strong>The viability of the cervical cancer cells was measured by cell counting kit-8 (CCK-8) assay, and the synergistic effect was analyzed using SynergyFinder. Cell proliferation was tested by cell cloning. The apoptosis and reactive oxygen species (ROS) production in cervical cancer cells were analyzed by flow cytometry. Western blot and quantitative real-time PCR (qRT-PCR) were employed to determine changes in protein and gene levels of pathway-related factors.</p><p><strong>Results: </strong>By the results of cytotoxicity assay, SiHa cells were selected and treated with 0.1 μM LBH589 and 4 μM AM1241 for 24 h for subsequent experiments. The combination of both was synergistic as determined by bliss, ZIP, HSA and LOEWE synergy score. Plate cloning results showed that LBH589 combined with AM1241 inhibited the proliferation of cervical cancer cells compared to individual drug. Additionally, compared with LBH589 alone, the combination of LBH589 and AM1241 induced autophagy by increasing LC3II/LC3I and decreasing P62/GAPDH, leading to a significantly higher rate of apoptosis. Pharmacological inhibition of also inhibited apoptosis. Consistently, we found that the endoplasmic reticulum, DNA damage repair pathway were induced after co-administration. Furthermore, cellular ROS increased after co-administration, and apoptosis was inhibited by the addition of ROS scavenger.</p><p><strong>Conclusion: </strong>LBH589 combined with AM1241 activated the endoplasmic reticulum emergency pathway, DNA damage repair signaling pathway, oxidative stress and autophagy pathway, ultimately promoting the apoptosis of cervical cancer cells. These findings suggest that the co-administration of LBH589 and AM1241 may be a new treatment plan for the treatment of cervical cancer.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103653","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
Core decompression combined with local DFO administration loaded on polylactic glycolic acid scaffolds for the treatment of osteonecrosis of the femoral head: a pilot study. 核心减压联合负载在聚乳酸-乙醇酸支架上的局部DFO给药治疗股骨头坏死:一项初步研究。
IF 2.9 3区 医学
BMC Pharmacology & Toxicology Pub Date : 2023-09-05 DOI: 10.1186/s40360-023-00682-x
Kaveh Gharanizadeh, Ali Mohammad Sharifi, Hamed Tayyebi, Razieh Heidari, Shayan Amiri, Sajad Noorigaravand
{"title":"Core decompression combined with local DFO administration loaded on polylactic glycolic acid scaffolds for the treatment of osteonecrosis of the femoral head: a pilot study.","authors":"Kaveh Gharanizadeh,&nbsp;Ali Mohammad Sharifi,&nbsp;Hamed Tayyebi,&nbsp;Razieh Heidari,&nbsp;Shayan Amiri,&nbsp;Sajad Noorigaravand","doi":"10.1186/s40360-023-00682-x","DOIUrl":"10.1186/s40360-023-00682-x","url":null,"abstract":"<p><strong>Background: </strong>Deferoxamine (DFO) angiogenesis induction potential has been demonstrated in earlier studies, but not in the osteonecrosis of the femoral head (ONFH). In this study, we evaluated the outcome of ONFH treated with combined core decompression and local DFO administration loaded on Polylactic Glycolic Acid (PLGA).</p><p><strong>Patients and methods: </strong>In a pilot experimental study, six patients (10 hips) with early-stage non-traumatic ONFH were treated by core decompression, and concurrent injection of local DFO loaded on PLGA scaffold into the subchondral femoral head. Outcome measures were evaluated before the surgery and 12 and 24 months after the surgery and included visual analog scale (VAS) for pain, modified Merle d'Aubigné-Postel (MAP) score for hip function by MRI, and rate of osteonecrosis assessed by the modified.</p><p><strong>Results: </strong>The mean MPA score was 14.7 ± 1.16 before the surgery and 16.7 ± 1.41 one year after the surgery (P = 0.004). The mean VAS for pain was 4.7 ± 1.25 before the surgery and 1.8 ± 1.03 one year after the surgery (P = 0.005). The mean Kerboul angle was 219 ± 58.64 before the operation and 164.6 ± 41.82 one year after the operation (P < 0.001). Osteonecrosis progression or collapse was not seen in any of the patients at the final follow-up. No postoperative side effect attributed to the DFO was noticed, as well.</p><p><strong>Conclusion: </strong>In short-term follow-up, combined core decompression and local DFO administration not only prevent the progression of ONFH but also reduces the rate of osteonecrosis significantly. However, future controlled studies are required to confirm the present results.</p><p><strong>Trial registration: </strong>IRCT20161121031003N3, 16/04/2019.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10533232","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}
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