血清miR-203、miR-217表达与急性髓系白血病患者预后的关系

摘要 目的：探究血清miR-203、miR-217表达与急性髓系白血病(AML)患者预后的关系。方法：选择2010年4月至2014年4月我院诊治的101例AML患者作为AML组,AML组根据治疗效果进一步分为完全缓解组和复发组,选择同期在我院体检的101例健康者作为健康组。采用荧光定量PCR检测各组的血清miR-203、miR-217表达水平,分析血清miR-203、miR-217表达水平与患者临床病理特征的关系,采用Kaplan-Meier法分析不同血清miR-203、miR-217表达水平AML患者的预后。结果：与健康组相比,AML组的血清miR-203、miR-217表达水平明显更低（P<0.05）。与完全缓解组相比,复发组的血清miR-203、miR-217表达水平明显更低（P<0.05）。血清miR-203表达水平与AML患者白细胞计数相关（P<0.05）,而血清miR-217表达水平与AML患者血小板计数相关（P<0.05）。血清miR-203相对高表达和miR-217相对高表达的AML患者5年生存率分别高于血清miR-203相对低表达和miR-217相对低表达患者（Log Rank ^miR-203 =17.870,Log Rank ^miR-217 =28.926,均P=0.000）。结论：血清miR-203、miR-217的表达水平与AML密切相关,检测血清miR-203、miR-217表达水平可能有助于评估AML患者的预后。     

Sphingosine-1-phosphate receptor agonists suppress concanavalin A-induced hepatic injury in mice

T cell-mediated immune responses play a critical role in a variety of liver injuries including autoimmune hepatitis. Injection of concanavalin A (Con A) into mice mimics the histological and pathological phenotype of T cell-mediated hepatitis. Recent advances in host immune control of organ transplantation include the development of sphingosine-1-phosphate (S1P) receptor agonists such as FTY720, which alter lymphocyte homing but do not suppress host general immunity. Herein we examined the effect of the new S1P receptor agonist KRP-203 on the Con A-induced liver damage model. In normal liver lymphocytes of BALB/c mice, both FTY720 and KRP203 promoted lymphocyte sequestering from the liver to secondary lymph nodes and significantly reduced the number of liver lymphocytes (p<0.05). Based on this observation, KRP203 was employed in the Con A-induced hepatitis model. KRP203 markedly reduced the number of CD4(+) lymphocytes that infiltrate Con A-treated liver (p<0.05) and successfully reduced serum transaminase elevation (p=0.017), therefore protecting mice from Con A-induced liver injury. Interestingly this homing modulation less occurs in natural hepatic T cell homing through the chemokine receptor, CXCR4. Therefore, S1P receptor agonists preferentially target CXCR4(+)CD4(+) peripheral blood T lymphocytes and suppress the occurrence of Con A-induced hepatitis, suggesting their therapeutic usefulness against T cell-mediated hepatic injury.     

Synthesis and stability in biological media of 1H-imidazole-1-carboxylates of ROS203, an antagonist of the histamine H3 receptor

A series of carbamate derivatives of the H(3) antagonist ROS203 (1) were prepared, and their lipophilicity and steric hindrance were modulated by introducing linear or branched alkyl chains of various lengths. In vitro stability studies were conducted to evaluate how structural modulations affect the intrinsic reactivity of the carbamoyl moiety and its recognition by metabolic enzymes. Linear alkyl carbamates were the most susceptible to enzymatic hydrolysis, with bioconversion rates being higher in rat liver and plasma. Chain ramification significantly enhanced the enzymatic stability of the set, with two derivatives (1g and 1h) being more stable by a factor of 8-40 than the ethyl carbamate 1a. Incubation with bovine serum albumin (BSA) showed a protective role of proteins on chemical and porcine-liver esterase (PLE)-catalyzed hydrolysis. Ex vivo binding data after i.v. administration of 1h revealed prolonged displacement of the labeled ligand [(3)H]-(R)-alpha-methylhistamine ([(3)H]RAMHA) from rat-brain cortical membranes, when compared to 1. However, the high rates of bioconversion in liver, as well as the chemical instability of 1h, suggest that further work is needed to optimize the enzymatic and chemical stability of these compounds.     

MPC30-DEA70载AMO-miR-222对大鼠颈总动脉球囊损伤后血管狭窄的影响

目的:阳离子磷酸胆碱聚合物(MPC30-DEA70)为非病毒类转基因载体,可与AMO-mi R-222络合,通过导管球囊系统将MPC30-DEA70/AMO-mi R-222基因复合物导入大鼠颈内动脉球囊损伤处,观察对血管平滑肌细胞增生及血管狭窄程度的影响。方法:90只雄性SD大鼠随机分为未损伤组、多聚赖氨酸(PLL组)、MPC30-DEA70/AMO-mi R-222组、PLL/AMO-mi R-222组、PLL/MPC30-DEA70组、AMO-mi R-222组、单纯损伤组、PLL载P/A=3:1组和P/A=5:1组,每组各10只。构建大鼠颈总动脉球囊损伤模型,予血管损伤段行PLL、MPC30-DEA70/AMO-mi R-222、PLL/AMO-mi R-222、PLL/MPC30-DEA70、AMO-mi R-222、PLL载P/A=3:1和P/A=5:1复合物的转运。4周后通过光学显微镜观察HE染色血管段组织形态学改变。Western blot法检测各组血管段p57Kip2、p27Kip1蛋白的表达情况。RT-PCR法检测各组血管段mi R222扩增情况。结果:光学显微镜下,多聚赖氨酸(PLL组)、裸MPC30-DEA70/AMO-mi R-222组、PLL/AMO-mi R-222组、PLL/MPC30-DEA70组、AMO-mi R-222组、MPC30-DEA70组可见内膜显著增生,新生内膜/中膜比值无组间差异,较PLL载P/A=3:1组和P/A=5:1组有组间差异,后两组比较无组间差异,未损伤组未见新生内膜增殖。Western blot法检测显示PLL载P/A=3:1组和P/A=5:1组P57kip2、P27kip1蛋白表达含量较未损伤组降低(P0.05),较余六组增高(P0.05),组间比较无显著差异(P0.05)。RT-PCR法检测显示,mi R-222表达在未损伤组很低,PLL载P/A=3:1组和P/A=5:1组增高,余六组过表达(组间比较无显著差异)。结论:MPC30-DEA70可与AMO-mi R-222络合,有效抑制球囊损伤后血管mi R222表达,从而抑制新生内膜增生及血管狭窄。     

MicroRNA-203在结直肠癌研究中的进展

结直肠癌是我国常见的消化道恶性肿瘤。目前认为结直肠癌的形成是一个多因素、多步骤的过程,其具体发病机制尚不清楚。microRNA是一类非编码小分子RNA,能在转录后水平调控靶基因的表达,参与肿瘤的增殖、侵袭和转移,甚至调节肿瘤化疗敏感性。学者普遍认为mircroRNA-203(mir-203)是抗癌小分子RNA,但与以往不同的是mir-203在结直肠癌肿的表达水平仍存在争议。本文将概述mir-203在结直肠癌的发生、发展、诊断、预后以及药物抗性中发挥的各类生物学作用。阐述mir-203在结直肠癌不同信号通路中的作用,探索其在结直肠癌研究中的全部潜能。     

胃癌组织miR-203、miR-4317的表达及临床意义

目的:探讨胃癌组织中微小核糖核酸(mi R)-203、mi R-4317的表达情况及其临床意义。方法:选择2014年1月至2016年12月我院收治的胃癌患者92例,应用实时定量荧光PCR(qRT-PCR)检测患者胃癌组织及其相应癌旁组织中mi R-203、mi R-4317的表达情况,分析mi R-203、mi R-4317表达与胃癌患者临床病理参数的关系,所有患者随访3年,根据mi R-203、mi R-4317在胃癌组织中的中位表达量将患者分为mi R-203高表达组(49例)、mi R-203低表达组(43例)、mi R-4317高表达组(51例)、mi R-4317低表达组(41例)。分析mi R-203、mi R-4317与预后的关系及预后的影响因素。结果:胃癌组织中mi R-203、mi R-4317相对表达量显著低于癌旁组织(P<0.05)。不同性别、年龄、肿瘤大小胃癌患者胃癌组织中mi R-203、mi R-4317相对表达量比较无统计学差异(P>0.05),中低分化、TNM分期为III~IV期、有淋巴结转移胃癌患者胃癌组织中mi R-203、mi R-4317相对表达量显著低于高分化、TNM分期为I~II期、无淋巴结转移胃癌患者(P<0.05)。mi R-203高表达组3年生存率显著高于mi R-203低表达组(P<0.05),mi R-4317高表达组3年生存率显著高于mi R-4317低表达组(P<0.05)。COX多因素分析显示,中低分化、TNM分期为III~IV期、有淋巴结转移、mi R-203低表达、mi R-4317低表达是影响胃癌患者预后的独立危险因素(P<0.05)。结论:胃癌组织中mi R-203、mi R-4317异常低表达,其水平与胃癌预后密切相关,且胃癌患者预后与分化程度、临床分期、淋巴结转移等相关。