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Inhibitory Effect of Ouabain on Resistance to Imatinib in Chronic Myeloid Leukemia K562/G01 Cells 瓦巴因对慢性髓系白血病K562/G01细胞对伊马替尼耐药的抑制作用
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.1129
Chang-Quan Sun, J. Liu, Shiqi Zhai, H. Liu, L. Peng, Jing Hu
Ouabain has shown powerful anti-proliferation activities in various cancers, but its effect on imatinib-resistant chronic myeloid leukemia and toxicity on normal mice has not been investigated. Cell Counting Kit-8 assay was used to detect cytotoxicity and reversal effect of ouabain with different concentration (0.01 µM, 0.1 µM, 1.0 µM, 10 µM) on drug resistance of imatinib-resistant cell line of chronic myeloid leukemia (K562/G01 cell line). Flow cytometry was used to detect the apoptosis effect and cell cycle arrest. Hematological examination, biochemical examination and histological examination were used to detect sub-chronic toxicity of ouabain on healthy mice. In our present study, ouabain showed greatly inhibitory effect and significantly reduced half minimal inhibitory concentration of imatinib in K562/ G01 cells, an imatinib-resistant cell line of chronic myeloid leukemia, in a dose-and time-dependent manner, which implied that ouabain increased cell sensitivity to imatinib. Ouabain enhanced apoptosis induced by imatinib in K562/G01 cells not through cell cycle arrest. Animal experiments showed that there were no significant variances in hematological, liver function, kidney function parameters and organ histopathology of all mice groups. These data suggested that ouabain could be a potential agent to treat imatinib-resistant chronic myeloid leukemia for its powerful cytotoxicity as well as reversal effect, but further study is needed to find out its specific mechanism.
瓦巴因在多种癌症中显示出强大的抗增殖活性,但其对伊马替尼耐药慢性髓系白血病的作用和对正常小鼠的毒性尚未研究。采用细胞计数试剂盒-8检测不同浓度(0.01µM、0.1µM、1.0µM、10µM)的瓦巴因对慢性髓系白血病伊马替尼耐药细胞株(K562/G01细胞株)耐药的细胞毒性及逆转作用。流式细胞术检测细胞凋亡效应和细胞周期阻滞。采用血液学检查、生化检查和组织学检查检测乌阿巴因对健康小鼠的亚慢性毒性。在本研究中,瓦巴因对慢性髓性白血病耐伊马替尼细胞系K562/ G01细胞表现出明显的抑制作用,显著降低伊马替尼最低抑制浓度的一半,且呈剂量和时间依赖关系,表明瓦巴因增加了细胞对伊马替尼的敏感性。瓦巴因增强伊马替尼诱导的K562/G01细胞凋亡,但不通过细胞周期阻滞。动物实验结果显示,各组小鼠血液学、肝功能、肾功能参数及器官组织病理学均无显著差异。这些数据提示,瓦巴因具有强大的细胞毒性和逆转作用,可能成为治疗伊马替尼耐药慢性髓系白血病的潜在药物,但其具体机制有待进一步研究。
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引用次数: 0
Role of Calponin 2 as a Tumor Inhibitor in Esophageal Cancer 钙钙蛋白2在食管癌中的肿瘤抑制作用
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.1137
M. Gan, Yuhui Xia, Yixiao Pan, Qingxin Yu, Yiqing Guo, Yuyi Feng, J. Zheng
Calponin is an actin filament-associated regulatory protein that can inhibit the activity of myosin-ATPase and stabilize the dynamics of the actin cytoskeleton. Although calponin 2 has been reported to play roles in several cancers, whether it takes part in the progression of esophageal cancer still remains unknown. To explore the pathologic significance of calponin 2 in esophageal squamous cell carcinoma, the expression level of calponin 2 proteins in the tumor tissue of 190 esophageal squamous cell carcinoma patients was examined with immunohistochemistry while the expression level of calponin 2 messenger ribonucleic acid was analyzed by using the data from The Cancer Genome Atlas database. Both the calponin 2 messenger ribonucleic acid and protein level were increasingly expressed in the tumor tissues of esophageal squamous cell carcinoma patients compared with the adjacent non-tumor tissue and correlated negatively with the tumor grade. Patients with higher calponin 2 in the tumor tissue were found to have longer overall survival time. Calponin 2 was shown to be an independent factor influencing the overall survival of the esophageal squamous cell carcinoma patients. Methylation analysis based on MethSurv database revealed a methylation site in the body of calponin 2 gene, which was associated with a better prognosis. Further, in esophageal cancer tumor tissue, calponin 2 gene was found to co-express with genes associated with tight junction and the expression level of calponin 2 was observed to correlate significantly with the number of infiltrating immune cells. These results supported the idea that calponin 2 is involved in esophageal cancer and may function as a tumor inhibitor probably through modulating cancer cells tight junction and tumor immunity.
钙钙蛋白是肌动蛋白丝相关的调节蛋白,可以抑制肌球蛋白- atp酶的活性,稳定肌动蛋白细胞骨架的动力学。尽管钙钙蛋白2已被报道在几种癌症中发挥作用,但它是否参与食管癌的进展仍不清楚。为探讨钙钙蛋白2在食管鳞状细胞癌中的病理意义,采用免疫组化方法检测190例食管鳞状细胞癌患者肿瘤组织中钙钙蛋白2蛋白的表达水平,并利用the Cancer Genome Atlas数据库的数据分析钙钙蛋白2信使核糖核酸的表达水平。食管鳞状细胞癌患者肿瘤组织中钙钙蛋白2信使核糖核酸及蛋白表达水平均高于癌旁非肿瘤组织,且与肿瘤分级呈负相关。肿瘤组织中钙钙蛋白2含量较高的患者总体生存时间较长。钙钙蛋白2是影响食管鳞状细胞癌患者总生存率的独立因素。基于MethSurv数据库的甲基化分析显示,calponin 2基因在体内存在一个甲基化位点,与较好的预后相关。此外,在食管癌肿瘤组织中,calponin 2基因与紧密连接相关基因共表达,calponin 2的表达水平与浸润免疫细胞的数量显著相关。这些结果支持了钙钙蛋白2参与食管癌的观点,并可能通过调节癌细胞紧密连接和肿瘤免疫发挥肿瘤抑制剂的作用。
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引用次数: 0
Total Flavones of Selaginella uncinata (Desv.) Spring Inhibits Breast Cancer Cell Proliferation and Induces Apoptosis via Regulating microRNA-1269 卷柏总黄酮(Desv.)Spring通过调控microRNA-1269抑制乳腺癌细胞增殖和诱导凋亡
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.1149
Lideng Ni, Xu-lin Wang, J. Gu, Shuai Hao, Liyang Sun
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引用次数: 0
Formulation and Evaluation of Self-Emulsifying Drug Delivery Systems of Larotaxel for Oral Administration 口服Larotaxel自乳化给药系统的研制与评价
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.1150
J. Shan, Yuan Tian, G. Jingxin, H. Haibing, W. Yanjiao, YU Z, T. Xing
The objective of the present study was to develop a self-emulsifying drug delivery system of larotaxel and evaluate its in vitro and in vivo performance. The prepared larotaxel loaded self-emulsifying drug delivery system spontaneously formed microemulsion with a mean particle size of 115.4 nm when mixed with 100-fold water under gentle agitation. In vivo pharmacokinetics study of larotaxel loaded self-emulsifying drug delivery system demonstrated 5.19-fold enhancement in oral bioavailability compared to larotaxel-Sol. Furthermore, intestinal bio-distribution studies revealed that the intestinal residence time of larotaxel loaded self-emulsifying drug delivery system was dramatically extended in comparison to larotaxel-Sol. Lymphatic transport studies showed that cycloheximide, a chylomicron secretion blocker, would impede oral absorption of larotaxel loaded self-emulsifying drug delivery system, which confirmed that lymphatic route was involved in the absorption of larotaxel loaded self-emulsifying drug delivery system. What is more, in vivo antitumor experiment proved that the antitumor activity of oral larotaxel loaded self-emulsifying drug delivery system was significantly superior to oral larotaxel-Sol, which was close to intravenous larotaxel-Sol. In conclusion, self-emulsifying drug delivery system is a promising vehicle for the oral delivery of larotaxel.
本研究的目的是建立larotaxel的自乳化给药系统,并评价其体外和体内性能。制备的负载紫杉醇的自乳化给药系统在100倍水的搅拌下自发形成平均粒径为115.4 nm的微乳液。负载larotaxel自乳化给药系统的体内药代动力学研究表明,与larotaxel- sol相比,口服生物利用度提高了5.19倍。此外,肠道生物分布研究表明,与larotaxel- sol相比,负载larotaxel自乳化给药系统的肠道停留时间显着延长。淋巴转运研究表明,乳糜微粒分泌阻滞剂环己亚胺会阻碍负载larotaxel自乳化给药系统的口服吸收,这证实了负载larotaxel自乳化给药系统的吸收参与淋巴途径。此外,体内抗肿瘤实验证明口服larotaxel负载自乳化给药系统的抗肿瘤活性明显优于口服larotaxel- sol,接近静脉注射larotaxel- sol。综上所述,自乳化给药系统是一种很有前途的口服给药载体。
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引用次数: 0
TGF-β/Smad/ADAMTS-7 Axis Regulates the Process of Curcumin in Promoting the Cartilage Cells Proliferation TGF-β/Smad/ADAMTS-7轴调控姜黄素促进软骨细胞增殖的过程
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.1151
X. B. Niu, Jiangying Zhang, Y. C. Wang, Lei Guo, Y. X. Liu, W. Liu, XU Y.S.
To explore the function of curcumin on the cartilage cells, the cell proliferation and apoptosis by transforming growth factor-beta/suppressor of mothers against decapentaplegic/a disintegrin and metalloproteinase with thrombospondin motifs-7 axis was the objective of the study. The cell viability was detected by cell counting kit-8. The expression of transforming growth factor-beta, suppressor of mothers against decapentaplegic protein, a disintegrin and metalloproteinase with thrombospondin motifs-7, caspase-9, B-cell lymphoma 2, Bcl-2-associated X protein was determined by Western blot. The cartilage cells were treated with 1 mmol/l sodium nitroprusside for 24 h. Then, the cells were treated with different concentration of curcumin for 24 h. We found that 1 μmol/l curcumin could recover the cartilage cells proliferation. The transforming growth factor-beta and suppressor of mothers against decapentaplegic protein show high expression and a disintegrin and metalloproteinase with thrombospondin motifs-7 was low in the curcumin treatment group. Meanwhile, the apoptosis pathway was also detected. The caspase-9 and B-cell lymphoma 2 was higher in the curcumin treatment group than without curcumin group. However, the Bcl-2-associated X protein was lower. The cell viability, a disintegrin and metalloproteinase with thrombospondin motifs-7, caspase-9, B-cell lymphoma 2 and Bcl-2-associated X proteins also show no changes with or without curcumin when the transforming growth factor-beta was inhibited. We found that a disintegrin and metalloproteinase with thrombospondin motifs-7 show over expression, the transforming growth factor-beta and suppressor of mothers against decapentaplegic protein show high expression in the curcumin treatment group, the cell viability, caspase-9, B-cell lymphoma 2 and Bcl-2-associated X proteins show no changes with or without curcumin. Curcumin can promote the cartilage cells proliferation via transforming growth factor-beta/suppressor of mothers against decapentaplegic/a disintegrin and metalloproteinase with thrombospondin motifs-7 axis and inhibit the cell apoptosis.
本研究旨在探讨姜黄素通过转化生长因子- β /抑制因子抗十肢瘫痪/a崩解素和具有血小板反应蛋白-7轴的金属蛋白酶对软骨细胞增殖和凋亡的影响。采用细胞计数试剂盒-8检测细胞活力。Western blot检测转化生长因子- β、母亲抗十肢瘫痪蛋白抑制因子、具有血栓反应蛋白基序的崩解素和金属蛋白酶-7、caspase-9、b细胞淋巴瘤2、bcl -2相关X蛋白的表达。用1 mmol/l硝普钠处理软骨细胞24 h,然后用不同浓度的姜黄素处理24 h,发现1 μmol/l姜黄素能恢复软骨细胞的增殖。姜黄素治疗组转化生长因子- β和抗十足瘫痪蛋白抑制因子高表达,具有血栓反应蛋白基序的崩解素和金属蛋白酶-7低表达。同时检测细胞凋亡通路。姜黄素治疗组的caspase-9和b细胞淋巴瘤2高于未治疗组。而bcl -2相关的X蛋白则较低。当转化生长因子- β被抑制时,细胞活力、具有血栓反应蛋白基序-7、caspase-9、崩解素和金属蛋白酶、b细胞淋巴瘤2和bcl -2相关X蛋白也没有显示姜黄素或没有姜黄素的变化。我们发现,姜黄素治疗组的崩解素和具有血栓反应蛋白基序-7的金属蛋白酶呈高表达,转化生长因子- β和母亲抗十足瘫蛋白的抑制因子呈高表达,细胞活力、caspase-9、b细胞淋巴瘤2和bcl -2相关的X蛋白在姜黄素治疗组或不治疗组均无变化。姜黄素可通过转化生长因子- β /抗十肢瘫痪/a崩解素抑制因子和血小板反应蛋白-7轴金属蛋白酶促进软骨细胞增殖,抑制细胞凋亡。
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引用次数: 0
Evaluation of Adverse Reactions and Effects of Triamcinolone Acetonide Combined with Compound Betamethasone in Keloid 曲安奈德联合复方倍他米松治疗瘢痕疙瘩的不良反应及疗效评价
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.spl.689
W. Zhang, Jincui Shen, B. Zeng
Zhang et al. : Effects of Triamcinolone Acetonide Combined with Compound Betamethasone in Keloid To explore the drug effect and adverse reaction of triamcinolone acetonide combined with compound betamethasone in keloid is the objective of the study. 100 patients were randomly divided into study group and control group (50 patients in each group). The research group received sequential treatment with triamcinolone acetonide injection combined with compound betamethasone injection and the control group received compound betamethasone injection. Both groups had 3 courses of treatment and each course of treatment lasted for 3 w. The Vancouver scar scale score, treatment effect and adverse reactions were compared between the two groups and the recurrence rate was followed up for 1 y after the end of medication. Before treatment, there was no significant difference in Vancouver scar scale scores between the two groups but after medication, the study group was better than that of the control group (p<0.05). The total effective rate of the study group (82 %) was higher than that of the control group (54 %, p<0.05). The total incidence of adverse drug reactions in the study group was 8 % while in the control group it was 6 % and the comparison between the two groups was not statistically significant. The recurrence rates of the study group and the control group were 28 % and 34 % 6 mo after the end of medication and 32 % and 42 % after 12 mo. There was a significant difference between the two groups. The sequential injection of triamcinolone acetonide combined with compound betamethasone is effective in the treatment of keloids, with high safety and low recurrence rate, which is worthy of clinical recommendation.
Zhang等:曲安奈德联合复方倍他米松治疗瘢痕疙瘩的疗效探讨曲安奈德联合复方倍他米松治疗瘢痕疙瘩的疗效及不良反应是本研究的目的。100例患者随机分为研究组和对照组(每组50例)。研究组采用曲安奈德注射液联合复方倍他米松注射液序贯治疗,对照组采用复方倍他米松注射液。两组均治疗3个疗程,每个疗程持续3w。比较两组温哥华疤痕评分、治疗效果及不良反应,并在用药结束后随访1 y复发率。治疗前,两组温哥华疤痕评分差异无统计学意义,治疗后,研究组优于对照组(p<0.05)。研究组总有效率(82%)高于对照组(54%,p<0.05)。研究组药物不良反应总发生率为8%,对照组为6%,两组比较无统计学意义。研究组和对照组在停药6个月后复发率分别为28%和34%,停药12个月后复发率分别为32%和42%,两组比较差异有统计学意义。序贯注射曲安奈德联合复方倍他米松治疗瘢痕疙瘩有效,安全性高,复发率低,值得临床推荐。
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引用次数: 0
Association between Lung Microbiota Dysbiosis and Sepsis Induced Acute Respiratory Distress Syndrome 肺微生物群失调与败血症引起的急性呼吸窘迫综合征的关系
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.spl.692
Jingkun Ye, Zhuandi Lin, Yuxia He, Shan Li
Ye et al. : Microbiota Dysbiosis in Sepsis Induced Acute Respiratory Distress Syndrome Sepsis is associated with acute respiratory distress syndrome, which has a significant impact on the prognosis of patients. Several studies have shown that the microbiota plays a significant role in sepsis-induced acute respiratory distress syndrome, but the relationship between the microbiota and sepsis-induced acute respiratory distress syndrome is not fully understood. We conducted a case-control and single-center study in 19 sepsis-induced acute respiratory distress syndrome patients and 36 sepsis-non-induced acute respiratory distress syndrome patients to investigate the clinical features and microbiota expression. There were 55 subjects enrolled, 19 of whom suffered acute respiratory distress syndrome due to sepsis. A significant increase in the abundance of Pseudomonas aeruginosa , leptospiral virus, Cytomegalovirus , Klebsiella pneumoniae , Streptococcus pneumoniae , Candida albicans , Escherichia coli , Epstein-Barr virus and Staphylococcus aureus . Besides, expressions of peripheral T lymphocytes (cluster of differentiation 3 + , cluster of differentiation 4 + and cluster of differentiation 3 + , cluster of differentiation 8 + ) was much higher in the sepsis-induced acute respiratory distress syndrome group than that in the sepsis non-induced acute respiratory distress syndrome group. The acute physiology and chronic health evaluation II scores, duration of mechanical ventilation and mortality with 28 d and 90 d were much higher in the sepsis-induced acute respiratory distress syndrome group. Patients with sepsis-induced acute respiratory distress syndrome had worse clinical outcomes and a higher expression of peripheral T lymphocytes, as well as the relative abundance of microbiota dysbiosis.
脓毒症与急性呼吸窘迫综合征相关,对患者预后有显著影响。多项研究表明微生物群在脓毒症急性呼吸窘迫综合征中起着重要作用,但微生物群与脓毒症急性呼吸窘迫综合征之间的关系尚不完全清楚。我们对19例脓毒症致急性呼吸窘迫综合征患者和36例脓毒症非致急性呼吸窘迫综合征患者进行病例对照和单中心研究,探讨其临床特征和菌群表达。共纳入55名受试者,其中19人因败血症而出现急性呼吸窘迫综合征。铜绿假单胞菌、细螺旋体病毒、巨细胞病毒、肺炎克雷伯菌、肺炎链球菌、白色念珠菌、大肠杆菌、爱泼斯坦-巴尔病毒和金黄色葡萄球菌的丰度显著增加。此外,脓毒症诱导的急性呼吸窘迫综合征组外周血T淋巴细胞(分化簇3 +、分化簇4 +、分化簇3 +、分化簇8 +)表达明显高于非脓毒症诱导的急性呼吸窘迫综合征组。脓毒症急性呼吸窘迫综合征组的急性生理和慢性健康评估II评分、机械通气持续时间、28 d和90 d死亡率均显著高于对照组。脓毒症引起的急性呼吸窘迫综合征患者临床预后较差,外周血T淋巴细胞表达较高,微生物群失调相对丰富。
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引用次数: 0
Analysis of Heart Rate Variability in Obstructive Sleep Apnea Hypoventilation Syndrome 阻塞性睡眠呼吸暂停低通气综合征患者心率变异性分析
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.spl.682
Yanling Hong, Yan Kou, Mingli Xie, Yong Wan, Yuyan Zhang
NN50 and high frequency in group C were lower than A and B (p<0.05) and the low frequency was higher than the proportion of NN50 and high frequency in group C were lower than A and B (p<0.05) and the low frequency was higher than group A, group B and control group (p<0.05). Holter-monitoring is a non-invasive test, the price is not high and it can be a regular test for testing the autonomic nervous function in patients with obstructive sleep apnea hypopnea syndrome.
C组NN50和高频低于A、B组(p<0.05),低频高于C组NN50和高频比例低于A、B组(p<0.05),低频高于A、B组和对照组(p<0.05)。Holter-monitoring是一种无创检测,价格不高,可作为检测阻塞性睡眠呼吸暂停低通气综合征患者自主神经功能的常规检测。
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引用次数: 0
Oxymatrine Suppresses Colon Cancer by reducing microRNA-21 and microRNA-141 and Targets Epithelial-Mesenchymal Transition 氧化苦参碱通过降低microRNA-21和microRNA-141抑制结肠癌并靶向上皮-间质转化
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.spl.621
Yifeng Zhao, Mingxia Li, Chao Zhang, Xiaomin Hu, Xiong Wang, T. Zhao
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引用次数: 0
Ginsenoside Rd Attenuates Lung Ischemia/Reperfusion Injury in Mice via Regulating Mitochondrial Function 人参皂苷Rd通过调节线粒体功能减轻小鼠肺缺血再灌注损伤
IF 0.5 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.36468/pharmaceutical-sciences.spl.624
Si-Fei Yu, Qiong Song
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引用次数: 0
期刊
Indian Journal of Pharmaceutical Sciences
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