ATRA

摘要： 目的:探究全反式维甲酸(ATRA)对IL-22处理后HaCaT细胞Cx43蛋白表达水平和细胞间隙连接通讯(GJIC)功能的影响,以及该过程是否与JNK通路有关,进一步阐明ATRA对GJIC功能影响的分子作用机制.方法:筛选ATRA影响IL-22处理HaCaT细胞最适处理时间;划痕标记染料示踪试验观察GJIC功能影响;免疫荧光检测ATRA和/或IL-22处理组Cx43、p-JNK、JNK表达水平的变化.结果:ATRA使HaCaT细胞的GJIC功能呈处理时间依赖性上升.ATRA作用于IL-22诱导HaCaT细胞后,Cx43蛋白表达水平增加,GJIC功能上调,p-JNK表达无明显变化.结论:ATRA可抑制IL-22介导的Cx43表达减少和GJIC下调作用,这一过程与JNK通路无关.

摘要： Objective To investigate the induction of B-cell specific phenotype in classical Hodgkin lymphoma (cHL)upon all-trans retinoic acid(ATRA)incubation. Methods To construct B-cell specific promoter(CD19, CD79a,CD79b)driven reporter plasmid with NEO cassette to realize stable transfection and selection of cHL reporter cells. To verify the intact integration by amplification of the promoter and luciferase sequences,and to functionally validate the B-cell specific promoter by ABF1 interference and luciferase assay. Repoter cells were incubated with various doses of ATRA and luciferase activity was detected at 24,48 and 72 hours. Reporter cells were treated alone or in combination with 5-Aza and ATRA followed by luciferase assay. Endogenous B-cell specific genes(CD19, CD20, CD79a and CD79b) transcription and expression levels were detected by real-time PCR and immunoblot, respectively. The expression level of CD30 antigen on Hodgkin lymphoma cell membrane upon ATRA was assessed by flow cytometry. Results ATRA treatment stimulated B-cell specific signature in cHL cells including CD19,CD79a and CD79b while down-regulated their CD30 expression. Conclusions ATRA induces B-cell phenotype deficient cHL cells to regain their B-cell transcriptional program while abolishes their Hodgkin-specific machinery.%目的 探讨全反式维甲酸(ATRA)对经典型霍奇金淋巴瘤B细胞表型的诱导作用.方法 构建含有G418抗性的B细胞特异性启动子(CD19,CD79a和CD79b)表达载体,转染霍奇金淋巴瘤细胞并筛选稳定克隆.PCR扩增启动子和荧光素酶序列验证其稳定整合,敲除ABF1后检测外源B细胞启动子活性的改变以验证其功能.检测不同浓度的ATRA在不同时间点对外源B细胞启动子活性的诱导作用,通过实时定量PCR进一步证实ATRA对B细胞特异性基因转录水平的影响;检测ATRA与去甲基化药物5-Aza联合处理对B细胞标记物表达的影响;通过流式细胞染色技术仪检测ATRA对霍奇金淋巴瘤细胞表面标记物CD30表达的影响.结果 ATRA能够诱导人经典型霍奇金淋巴瘤B细胞特异性标记物CD19、CD20、CD79a和CD79b的表达,与5-Aza具有协同诱导作用,并下调细胞表面霍奇金特异性抗原CD30的表达.结论 ATRA能够诱导B细胞表型缺失的经典型霍奇金淋巴瘤向B细胞型淋巴瘤转化.

摘要： 目的 评估全反式维甲酸(ATRA)对宫腔粘连细胞模型纤维化的影响.方法 培养原代人子宫内膜基质细胞(HESCs),ICC法鉴定细胞;用0、2.5、5、10和20 ng/mL TGF-β1诱导HESCs 48 h,qRT-PCR检测COL1A1、α-SMA的表达;以10 ng/mL TGF-β1诱导HESCs 48 h,继而0、0.1、1和10μmol/mL ATRA作用48 h,qRT-PCR、WB检测COL1A1、α-SMA、及SMAD4的表达.结果 间质细胞标记物Vimentin阳性,上皮细胞标志物CK-18阴性;与0 ng/mL TGF-β1组相比,其他组COL1A1和α-SMA的表达升高,以10 ng/mL组表达最高(P<0.01);与0μmol/mL ATRA组相比,1、10μmol/mL ATRA组COL1A1、α-SMA和SMAD4的表达下降,以1μmol/mL组下降最明显(P<0.01).结论 TGF-β1诱导HESCs发生肌成纤维细胞样改变,构建宫腔粘连细胞模型,ATRA通过TGF-β1/SMAD4信号通路改善其纤维化.

摘要： 目的 探讨AFP与PTEN在肝癌细胞中的表达情况及AFP对全反式维甲酸(ATRA)诱导肝癌细胞凋亡的影响.方法 Western Blot分析AFP和PTEN在肝癌细胞Bel7402和HLE中的表达情况,并用30 μmol/L和180 μmol/L的ATRA溶液处理细胞,观察其对AFP和PTEN表达的影响;应用免疫共沉淀技术分析PTEN和AFP的相互作用;构建AFP表达载体转染HLE细胞,观察AFP的表达对ATRA抑制癌细胞生长的影响.结果 PTEN在Bel7402和HLE细胞中均有表达,Bel7402细胞能表达AFP,HLE细胞则无AFP表达;经过180μmol/L ATRA处理24 h之后,Bel7402细胞PTEN表达水平上升,AFP表达水平下降;AFP可与PTEN相结合;当ATRA浓度为30、60、90和180 μmol/L时,通过MTT法测得HLE细胞的A490分别为1.05、0.97、0.83、0.71、0.39;HLE成功表达AFP后,ATRA对癌细胞的抑制作用消失.结论 AFP可抑制PTEN的活性;AFP可以通过与PTEN结合的方式,抑制PTEN的磷酸酯酶活性;AFP可能通过抑制PTEN的表达方式,使肝癌细胞耐受ATRA诱导的凋亡.

摘要： 目的 探讨ATO单用或联合ATRA治疗首发急性早幼粒细胞白血病临床疗效及安全性差异.方法选取收治的首发急性早幼粒细胞白血病患者150例,随机分为对照组和联合组,每组75例,分别采用ATO单用和在此基础上与ATRA联用治疗;比较2组患者完全缓解率,完全缓解所需时间,早期死亡率,随访生存率,毒副作用发生率,治疗后肝功能、心肌酶学及血脂指标水平等.结果2组患者完全缓解率比较差异无统计学意义(P>0 a.05);联合组患者完全缓解所需时间显著短于对照组,差异有统计学意义(P0.05);联合组患者随访3年生存率显著高于对照组,差异有统计学意义(P0.05);联合组患者肝功能指标水平显著高于对照组,差异有统计学意义(P0.05).结论相较于ATO单用,ATO联合ATRA治疗首发急性早幼粒细胞白血病可有效缩短完全缓解所需时间,提高远期生存率,且未增加不良反应发生风险.%Objective To investigate the therapeutic effects and safety of single -use of arsenic trioxide ( ATO) or ATO combined with all -trans retinoic acid ( ATRA) on primary acute promyelocytic leukemia .Methods One hundred and fifty patients with primary acute promyelocytic leukemia who were admitted and treated in our hospital from March 2010 to March 2013 were randomly divided into two groups:control group ( n =75) and combination treatment group ( n =75).The patients in control group were treated by ATO only , however , the patients in combination treatment group , on the basis of control group,were treated by ATRA.The complete remission rate,the time of reaching complete remission ,early death rate, follow-up survival rate ,incidence rates of toxic and side effects , liver function , levels of myocardial enzymes and blood lipid indexes after treatment were observed and compared between two groups .Results There was no significant difference in complete remission rate between two groups ( P >0.05).The time of reaching complete remission in combination treatment group was significant shorter than that in control group ( P 0.05 ).The survival rates after 3-year follow up in combination treatment group were significant higher than those in control group ( P 0.05).After treatment the levels of liver function indexes in combination group were significant higher than those in control group ( P 0.05).Conclusion The ATO combined with ATRA in the treatment of primary acute promyelocytic leukemia can effectively shorten the time of reaching complete remission , improve the long-term survival rate , moreover , which does not increase the incidence rate of adverse reactions .

摘要： 为研究全反式维甲酸(ATRA)对小鼠的急性毒性与抗感染作用,在ATRA急性毒性试验中采用最大给药量,记录小鼠给药7 d内的临床症状,然后通过剖检及病理组织学观察研究ATRA的急性毒性.将大肠杆菌经口感染小鼠建立感染模型,记录小鼠感染7 d内的临床症状,通过剖检和器官指数的测定来研究ATRA对小鼠的抗感染作用.结果表明,ATRA以最大给药量(人用剂量500倍)灌胃没有对小鼠造成明显的异常反应,体重与对照组相比差异不显著,剖检和病理组织学观察无可见病变.同时,口服高剂量ATRA的小鼠在感染后体重恢复效果好于低剂量组,口服ATRA的小鼠肝脏、肾脏、脾脏器官指数与对照组相比差异显著.说明ATRA对小鼠无急性毒性,同时具有良好的促进肝脏、肾脏、脾脏生长发育,提高机体免疫力和抗感染效果,可应用于兽医临床治疗以及疾病预防和控制.

摘要： 急性早幼粒细胞白血病是急性髓细胞白血病的一种特殊类型,2015年我院血液科收治两例早幼粒细胞白血病患者,经化疗及对症治疗后,避免了早期死亡,获得完全缓解.该病发病率较高,为提高对本病的进一步认识,现总结报到如下并探讨APL的治疗进展.

摘要： 为了研究全反式维甲酸(ATRA)对新城疫疫苗的体液免疫增强效果,本试验选取1日龄AA肉鸡作为研究对象,低剂量组和高剂量组分别灌服1 μmol/kg体重和5μmol/kg体重ATRA,在7日龄和28日龄时对药物对照组、低剂量组、高剂量组通过滴鼻、点眼的方法免疫新城疫疫苗.在7、14、21、28、35、42日龄和49日龄,每组随机取7只鸡,称重,采集胸腺、脾脏、腔上囊和血清,计算胸腺、脾脏和腔上囊免疫器官指数,利用血凝抑制(HI)试验检测血清中新城疫抗体效价.结果表明,ATRA可以促进雏鸡免疫器官生长,提高雏鸡免疫器官指数和新城疫抗体效价,表明ATRA可以增强雏鸡的体液免疫应答,且5 μg/kg体重剂量ATRA对新城疫疫苗的体液免疫增强效果更显著.

摘要： Objective To explore the effects of a novel retinoic acid ECPIRM and all-trans-retinoic acid (ATRA) on interleukin (IL)-1β expression in IL-17-stimulated human HaCaT keratinocytes.Methods Cultured HaCaT cells were classified into several groups:ECPIRM groups treated with 20-320 μmol/L ECPIRM for 24-72 hours,ATRA groups treated with 1-100 μmol/L ATRA for 24-72 hours,IL-17 group treated with 20 μg/L IL-17 for 24 hours,IL-17 + ECPIRM group cotreated with 20 μg/L IL-17 and 80 μmol/L ECPIRM for 24 hours,IL-17 + ATRA group cotreated with 20 μg/L IL-17 and 5 μmol/L ATRA for 24 hours,control group treated with the solvent solution of IL-17.Then,methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate cellular proliferative activity in these groups,enzyme-linked immunosorbent assay (ELISA) to measure the level of IL-1β protein in the culture supernatant of HaCaT cells,quantitative fluorescent PCR to detect the mRNA expression of IL-1β in HaCaT cells.Data were statistically analyzed by using one-way analysis of variance (ANOVA) followed by the least significant difference (LSD) test.Results The treatments with ECPIRM of 20 and 40 μmol/L for 24 hours could promote the proliferation of HaCaT cells.However,with the increase in treatment duration and concentrations,ECPIRM inhibited the growth of HaCaT cells in a concentration-and time-dependent manner.ATRA also decelerated the proliferation of HaCaT cells in a concentration-and time-dependent manner.The levels of supernatant IL-1β protein and intracellular IL-1β mRNA were both significantly higher in the IL-17 group than in the control group (IL-1β protein:20.312 ± 2.053 ng/L vs.11.427 ± 0.929 ng/L,P ＜ 0.05;IL-1β mRNA:4.05 ± 0.47 vs.1 ± 0.03,P ＜ 0.05),but significantly lower in the IL-17 + ECPIRM group (12.470 ± 1.897 ng/L and 0.82 ± 0.12 respectively,both P ＜ 0.05) and IL-17 + ATRA group (12.694 ± 1.478 ng/L and 0.87 ± 0.16,respectively,both P ＜ 0.05) than in the IL-17 group,and similar among the ATRA groups,ECPIRM groups and control group (both P ＞ 0.05).Conclusion IL-17 can promote the secretion of IL-1β by HaCaT cells,while ECPIRM and ATRA can significantly inhibit the IL-17-induced IL-1β secretion.%目的 探讨新型维A酸ECPIRM及全反式维A酸(ATRA)对白细胞介素17(IL-17)刺激人表皮角质形成细胞株(HaCaT细胞)IL-1β表达的影响.方法 MTT法检测不同浓度ECPIRM及ATRA与IL-17共同作用于HaCaT细胞后对其细胞增殖活力的影响;IL-17(20 μg/L)刺激HaCaT细胞或与ECPIRM(80 μmol/L)、ATRA(5 μmol/L)共培养24 h,收集细胞培养上清液并提取总RNA,分别进行酶联免疫吸附实验(ELISA)和荧光定量PCR,检测IL-1β蛋白及IL-1β mRNA水平的变化.数据处理采用单因素方差分析,组间比较采用LSD法.结果 低浓度ECPIRM可促进HaCaT细胞增殖,随着药物浓度和时间的增加,对HaCaT细胞生长出现抑制现象,并呈浓度及时间依赖性.ATRA抑制HaCaT细胞生长呈浓度及时间依赖性.IL-17刺激HaCaT细胞后细胞培养上清液中IL-1β蛋白及IL-1β mRNA水平(20.312±2.053 ng/L、4.05±0.47)与对照组(11.427土0.929 ng/L、1.00±0.03)相比明显升高,差异有统计学意义(P＜ 0.05);ECPIRM作用后IL-1β蛋白及IL-1βmRNA水平(12.470±1.897 ng/L、0.82±0.12)与IL-17刺激组(20.312±2.053 ng/L、4.05±0.47)相比降低,差异有统计学意义(P＜ 0.05);ATRA作用后IL-1β蛋白及IL-1β mRNA水平(12.694±1.478 ng/L、0.87±0.16)与IL-17刺激组(20.312±2.053 ng/L、4.05±0.47)相比明显降低,差异有统计学意义(P＜0.05),同时ECPIRM处理组、ATRA处理组与溶媒对照组比较差异无统计学意义.结论 IL-17可促进HaCaT细胞分泌IL-1β,ECPIRM及ATRA对其诱导的HaCaT细胞IL-1β的表达具有明显的抑制作用.

摘要： 本发明涉及由原子转换自由基加成聚合反应(ATRA)制备的各种聚合烷氧基胺。本发明的另一个方面是其制备方法及其作为光稳定剂、阻燃剂以及用于受控自由基聚合方法的聚合调节剂/引发剂的用途。本发明的再一个方面是也可用作聚合反应调节剂/引发剂的新型单体中间体烷氧基胺。

摘要： 本发明公开了一种ATRA‑PBAE前药共聚物及其制备方法和应用，属于药物技术领域。本发明提供的为ATRA‑PBAE前药共聚物，通过迈克尔加成反应合成具有pH敏感性的PBAE共聚物；之后通过酯化反应合成pH响应型ATRA前药共聚物。本发明公开的前药化合物对预防和治疗肿瘤具有显著效果，本发明还公开一种载药纳米粒子，为SchB/ATRA‑PBAE，由ATRA‑PBAE前药共聚物包载SchB获得，所述的前药化合物对预防和/或治疗肿瘤，尤其是乳腺肿瘤具有非常明显的效果。

摘要： 本发明公开一种Pin1抑制剂ATRA的新型可生物降解控释制剂及其制备方法和应用，包括以下步骤：a.将ATRA和PLLA溶于有机溶剂，在超临界二氧化碳的条件下，制备载ATRA的PLLA微球；b.以肝癌为模型，在体内外研究ATRA‑PLLA微球的抗癌功效及作用机制。本发明在温和的条件下，通过一步法获得ATRA‑PLLA微球，该微球的粒径均匀、包封率和产率高，能有效缓释ATRA，其主要药代动力学指标优于商品化的ATRA缓释片（该缓释片仅能用于动物）。ATRA‑PLLA微球的生物相容性好，能选择性的增强ATRA对肿瘤生长的抑制，其抗癌功效优于ATRA缓释片。ATRA通过降解Pin1和抑制多条受Pin1调控的致癌信号通路及细胞周期进展来发挥其抗癌作用。ATRA‑PLLA微球有望用于临床治疗肿瘤、炎症、关节炎、红斑狼疮、哮喘等Pin1相关疾病。

摘要： 本发明公开了一种与耐ATRA急性髓系白血病细胞特异性结合的多肽及其制备方法和应用。一种与能够与ATRA耐药性AML细胞特异性结合的多肽，命名为pepNo.5R5，其碱基序列如SEQ ID NO.1所示，其氨基酸序列如SEQ ID NO.2所示。本发明筛选得到了一种与ATRA耐药性AML细胞特异性结合的多肽，填补了目前缺乏与ATRA耐药性AML细胞结合的多肽的空白。本发明筛选得到多肽为可通过人工方法合成的小分子多肽，分子量小、活性高、穿透力强、亲和力高、特异性高、毒性低，适合作为靶向治疗的载体；本发明筛选得到的多肽具有良好的肿瘤靶向性，为该多肽的临床前深入研究奠定了坚实的基础。

摘要： 本发明涉及由原子转换自由基加成聚合反应(ATRA)制备的各种聚合烷氧基胺。本发明的另一个方面是其制备方法及其作为光稳定剂、阻燃剂以及用于受控自由基聚合方法的聚合调节剂/引发剂的用途。本发明的再一个方面是也可用作聚合反应调节剂/引发剂的新型单体中间体烷氧基胺。