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1.
《Saudi Pharmaceutical Journal》2022,30(6):669-678
BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction. 相似文献
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3.
《Clinical lung cancer》2022,23(6):467-476
BackgroundImmune checkpoint inhibitor (ICI) monotherapy is more effective than cytotoxic chemotherapy in improving overall survival (OS) among patients with advanced-stage non-small cell lung cancer (NSCLC). Recently, chemotherapy combined with ICI has been found to yield good outcomes. However, ICI monotherapy is still considered an important treatment option. Data on long-term progression-free survival (PFS) and OS in real-world settings are limited.Patients and MethodsThis was a multicenter retrospective observational study. A total of 435 consecutive patients histologically diagnosed with advanced, metastatic, or recurrent NSCLC treated with ICI monotherapy were enrolled in this study from December 2015 to December 2018. Clinical data were collected from electronic medical records and pharmacy databases.ResultsThe PFS and OS of the patients were 3.4 and 13.0 months, respectively. The objective response and disease control rates were 22.8% and 54.9%, respectively, and the 4-year survival rate was 17.9%. Multivariate analyses revealed that elder patients (>70 years), good Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, programmed death-ligand 1 tumor proportion score (PD-L1 TPS) of ≥ 50%, absence of bone metastasis, and presence of immune-related skin toxicity, which is an immune-related adverse event, were correlated with good PFS. Moreover, good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good OS.ConclusionsThe 4-year survival rate was 17.9%. Good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good PFS and OS. 相似文献
4.
A molecular perspective for the use of type IV tyrosine kinase inhibitors as anticancer therapeutics
《Drug discovery today》2022,27(3):808-821
Tyrosine kinases are enzymes that can transfer a phosphate group from ATP to a specific protein tyrosine, serine or threonine residue within a cell, operating as a switch that can turn ‘on’ and ‘off’ causing different physiological alterations in the body. Mutated kinases have been shown to display an equilibrium shift toward the activated state. Types I–III have been studied intensively leading to drugs like imatinib (type II), cobimetinib (type III), among others. It is the same scenario for types V–VII; however, there is a lacuna in information regarding type IV inhibitors, although recently some advances have surfaced. This review aims to accumulate the knowledge gained so far about type IV inhibitors. 相似文献
5.
目的:探索甲基转移酶抑制剂DCG066对人弥漫大B细胞淋巴瘤细胞TMD-8的有效杀伤浓度,进而对其作用机制进行研究。方法:通过CCK-8实验探索DCG066对TMD-8细胞的有效杀伤浓度,通过免
疫荧光实验分析DCG066处理后TMD-8活细胞及死细胞的分布,通过流式细胞术检测DCG066对TMD-8细胞凋亡的诱导、细胞周期的抑制及胞内活性氧簇水平,Western Blot及转录组测序分析细胞凋亡及铁死亡相关基因的表达情况。结果:与对照组相比,低浓度DCG066可有效杀伤TMD-8细胞,且成剂量依赖关系。DCG066可以诱导TMD-8细胞凋亡及细胞周期抑制,Bax及DDIT等凋亡相关蛋白表达显著上调,Cyclin E1及Cyclin A2等细胞周期相关蛋白表达下调。此外,TMD-8细胞经DCG066处理后,活性氧水平升高,HOMX1及NOX2等铁死亡相关基因mRNA表达水平上调。结论:甲基转移酶抑制剂DCG066可通过诱导细胞铁死亡及凋亡、抑制细胞周期的方式,发挥杀伤弥漫大B细胞淋巴瘤的作用。 相似文献
6.
Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications. 相似文献
7.
目的基于磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)通路探究丙泊酚对七氟烷诱导大鼠神经细胞凋亡的保护作用。方法2020年1月—2021年1月于湖北省恩施土家族苗族自治州中心医院实验室进行实验,选取健康、清洁级Wistar雄性大鼠30只,随机数字表法分为对照组、七氟烷组、七氟烷+丙泊酚组(联合组),各10只。七氟烷组吸入1.5%七氟烷干预,联合组在七氟烷组基础上加丙泊酚150 mg/kg腹腔注射,对照组给予等体积的生理盐水干预,均连续干预2周。干预后各组大鼠行Morris水迷宫实验,观察大鼠海马神经细胞凋亡情况,检测氧化应激相关指标、凋亡相关因子及PI3K/Akt通路蛋白表达水平。结果逃避潜伏期、海马神经细胞凋亡率比较,七氟烷组>联合组>对照组(F/P=17.038/0.001、36.834/0.001),穿越平台次数、目标象限停留时间占比比较,七氟烷组<联合组<对照组(F/P=8.913/0.001、9.125/0.001)。LDH、MDA、Bax、Caspase-3水平比较,七氟烷组>联合组>对照组(F/P=35.166/0.001、20.773/0.001、43.896/0.001、17.462/0.001),SOD、GSH-Px、Bcl-2水平及PI3K、p-Akt表达比较,七氟烷组<联合组<对照组(F/P=12.092/0.001、16.243/0.001、15.236/0.001、28.850/0.001、28.869/0.001)。结论丙泊酚能改善七氟烷诱导的大鼠认知功能、氧化应激反应,抑制神经细胞凋亡,可能与PI3K/Akt通路有关。 相似文献
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9.
Mixed lineage leukemia 1(MLL1)是组蛋白甲基转移酶SET家族的成员之一。MLL1与WDR5、RbBP5、Ash2L和DPY-30组成MLL1甲基转移酶复合物调控组蛋白H3的第4位赖氨酸的甲基化水平,对造血系统的发育和血细胞的更新至关重要。部分白血病患者体内存在因MLL1基因易位而产生的致癌蛋白——MLL1融合蛋白,MLL1融合蛋白在发挥其致癌作用时需要功能完整的MLL1酶复合物,故靶向MLL1-WDR5的蛋白-蛋白相互作用成为治疗MLL1融合型白血病的潜在策略。本文对MLL1-WDR5蛋白-蛋白相互作用的生物学机制、结构信息以及抑制剂进行了系统的总结,并结合已报道数据对该领域进行了展望,以期为后续研究提供参考。 相似文献
10.
目的观察Ⅳ期非小细胞肺癌(NSCLC)患者应用表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI)靶向治疗后的免疫功能、肿瘤标志物水平和血清相关指标的变化。方法选取汤阴县人民医院肿瘤内科2019年2月至2020年12月收治的83例Ⅳ期NSCLC患者作为研究对象,抽签法分组,对照组41例给予传统化疗,观察组42例给予EGFR-TKI靶向治疗,对比两组的肿瘤标志物、免疫功能和血清生化指标。结果治疗后,观察组鳞状细胞癌抗原(SCC)水平为(1.10±0.22)μg/L,低于对照组的(1.82±0.27)μg/L,癌胚抗原(CEA)水平为(30.76±9.27)μg/L,低于对照组的(38.85±10.13)μg/L,细胞角蛋白19片段(CYFRA21-1)水平为(7.14±1.90)μg/L,低于对照组的(11.79±2.13)μg/L,P<0.05;观察组血管内皮生长因子(VEGF)水平为(0.28±0.04)ng/L,低于对照组的(0.44±0.06)ng/L,基质金属蛋白酶9(MMP-9)水平为(1.10±0.10)ng/L,低于对照组的(1.34±0.12)ng/L、神经元特异性烯醇化酶(NSE)水平为(12.17±2.47)ng/mL,低于对照组的(17.52±2.60)ng/mL,P<0.05;观察组表面抗原分化簇8(CD8+)水平低于对照组,表面抗原分化簇3(CD3+)、表面抗原分化簇4(CD4+)水平高于对照组,P<0.05。结论EGFR-TKI靶向治疗NSCLC临床效果佳,免疫功能、肿瘤标志物和血清相关指标均得到改善。 相似文献