miRNA-425-5P在胃癌中的表达及临床价值

目的 探讨miRNA-425-5P在胃癌中的表达及其与临床病理特征的关系。方法 利用实时荧光定量PCR(qRT-PCR)法检测90例胃癌组织及胃癌细胞(MGC-803、SGC-7901)中miRNA-425-5P的表达量,分析miRNA-425-5P与临床病理特征的关系。结果 miRNA-425-5P在胃癌组织及胃癌细胞中高表达(P<0.05),且miRNA-425-5P的表达与胃癌的浸润深度(χ²=6.106,P=0.014)、TNM分期(χ²=4.472,P=0.035)有关,但与患者年龄(χ²=0.266,P=0.606)、性别(χ²=1.593,P=0.207)、淋巴转移(χ²=1.829,P=0.176)和有无神经血管侵犯(χ²=1.029,P=0.310)无关。结论 miRNA-425-5P在胃癌组织和细胞中高表达,是胃癌预后不良的独立危险因素,有望作为胃癌诊断、治疗和评价预后的标志物。     

鞘内注射miR-212反义锁核酸对骨癌小鼠痛行为的影响

目的研究骨癌痛发展和维持过程中小鼠脊髓水平miR-212表达的变化规律及连续鞘内注射miR-212反义锁核酸LNA．anti—miR-212对骨癌痛小鼠痛行为的影响。方法本实验分为两个部分：（一）骨癌痛小鼠脊髓水平miR-212表达的变化规律：C3H／HeJ雄性小鼠36只,随机分为假手术组（sham组,n=18）和肿瘤组（T组,n=18）。sham组小鼠在右侧股骨远端骨髓腔注射不含肿瘤细胞的仪一MEM,T组小鼠在右侧股骨远端骨髓腔注射纤维肉瘤细胞NCTC2472,建立骨癌痛模型。在术前1d,术后4d、7d、10d、14d、21d,sham组和T组各随机取三只小鼠处死,取脊髓腰膨大标本,用Real-timePCR的方法检测脊髓水平miR一212的表达情况。（二）连续鞘内注射LNA—anti-miR-212对骨癌痛小鼠痛行为的影响：C3H／HeJ雄性小鼠24只,随机分为四组：L组（鞘内注射LNA-anti—miR一212,n=6）、L’组（鞘内注射LNA＇-negativecontrol,n=6）、C组（鞘内注射溶媒无核酸酶水,n=6）和S组（假手术处理,n=6）。L组、L’组和C组小鼠在右侧股骨远端注射纤维肉瘤细胞NCTC2472,S组小鼠在右侧股骨远端骨髓腔注射不含肿瘤细胞的仪一MEM。所有小鼠于术前1d、术后4d、7d、10d、14d测小鼠痛行为指标,包括自发抬足次数和机械缩足阈值（PWMT）,术后14d,L组、L’组、C组小鼠分别鞘内注射LNA—anti—miR-21212pmol／5山、LNA＇-negativecontrol12pmol／5I＊1和无核酸酶水5I＊1,连续鞘内注射7d,1次／d,每天测小鼠痛行为指标,至术后第21天。结果miR-212的表达变化表现为：与基础值相比,sham组和T组小鼠在术后第4天,脊髓水平miR一212明显升高（P〈0．05）;与基础值和sham组相比,T组小鼠脊髓水平miR-212在术后7d、10d、14d、21d均明显升高（P〈0．05）。连续鞘内注射LNA—anti—miR-212改善骨癌痛小鼠痛行为：术后19d至21d,与L’组和c组相比,L组小鼠PWMT[19d（1．07-4-0．16）g,20d（1．13±0．21）g,21d（1．27±0．21）g）]明显升高（P〈0．05）,自发抬足次数明显降低[19d（6．674-1．04）,20d（6．62±1．39）,21d（6．47±1．17）]（P〈0．05）。与14d给药前相比,L组小鼠术后19d至21d的PWMT明显升高（P〈0．05）,自发抬足次数明显降低（P〈0．05）。结论骨癌痛发展过程中,脊髓水平miR-212表达量升高。连续鞘内注射LNA-anti—miR一212可以缓解骨癌小鼠痛行为。     

miRNA-130a在肝癌组织中的表达

目的探讨肝癌组织中miRNA-130a的表达及临床意义。方法收集经病理确诊的肝癌进行外科手术切除的28例患者的肝癌组织及癌旁组织,选取16例肝外伤后肝切除患者正常肝组织作为对照,应用实时定量PCR技术检测各组织中miRNA-130a的表达。结果肝癌组织中miRNA-130a表达显著高于癌旁组织及肝外伤切除正常肝组织（P〈0.05）。miRNA-130a表达与肝癌分化程度、临床分期和是否合并肝硬化有关（P〈0.05）。结论 miRNA-130a在肝癌组织中异常高表达,可能参与肝癌的发生发展过程。     

微RNA-21在胃癌中的表达研究

目的探讨微RNA（miRNA）-21在胃癌中的表达及其与临床病理特征的关系。方法采用荧光定量聚合酶链式反应（PCR）检测胃癌组织和配对的正常胃黏膜组织中miRNA-21的表达。并分析miRNA一21表达水平与淋巴结转移及胃癌临床分期（TNM）之间的关系。结果68例胃癌组织标本中56例（82_35％）miRNA-21高表达。高于正常配对组织13例（19．11％）,差异有统计学意义（X2=54．37,P〈O．05）;在淋巴结转移阳性的胃癌组织中,miR—NA-21高表达（高于正常对照2倍）的发生率明显大于淋巴结转移阴性的胃癌组织,差异有统计学意义（X2=7．16,P〈O．05）;且T3～T4期miRNA-21高表达的发生率越高明显大于T1～T2期,差异有统计学意义（X2=4．64,P〈0．05）。结论miRNA-21在胃癌组织表达增高,与淋巴结转移及TNM分期有关,可能是胃癌诊断及治疗的分子靶标。     

Variants in the 3′UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression

Alpha-synuclein (SNCA) is a major risk gene for Parkinson''s disease (PD) and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. Regulatory regions relevant for SNCA expression include the 3′ untranslated region (UTR), which among other regulatory elements contains several micro-RNA-binding sites. Interestingly, variants located in the 3′ region of SNCA have been associated with PD in two genome-wide association studies. To test whether private mutations in this region contribute to PD, we sequenced the 3′UTR of SNCA in 1285 PD patients and 1120 age/sex-matched healthy controls. We found two rare variants, the one corresponding to the single nucleotide polymorphism rs145304567 and the novel variant c.*1004_1008delTTTTT. Although rs145304567 affects the putative-binding site of microRNA (miRNA) -433, the allele distribution was similar in PD patients and controls, and the expression of SNCA mRNA was not related to the genotype. Furthermore, a regulatory effect of miRNA-433 on SNCA expression levels was not detected.     

5‐HT2A receptor blockade and 5‐HT2C receptor activation interact to reduce cocaine hyperlocomotion and fos protein expression in the caudate‐putamen

Both the 5‐HT_2A receptor (R) antagonist M100907 and the 5‐HT_2CR agonist MK212 attenuate cocaine‐induced dopamine release and hyperlocomotion. This study examined whether these drugs interact to reduce cocaine hyperlocomotion and Fos expression in the striatum and prefrontal cortex. We first determined from dose‐effect functions a low dose of both M100907 and MK212 that failed to alter cocaine (15 mg/kg, i.p.) hyperlocomotion. Subsequently, we examined whether these subthreshold doses given together would attenuate cocaine hyperlocomotion, consistent with a 5‐HT_2A/5‐HT_2CR interaction. Separate groups of rats received two sequential drug injections 5 min apart immediately before a 1‐h locomotion test as follows: (1) saline + saline, (2) saline + cocaine, (3) 0.025 mg/kg M100907 + cocaine, (4) 0.125 mg/kg MK212 + cocaine, or (5) cocktail combination of 0.025 mg/kg M100907 and 0.125 mg/kg MK212 + cocaine. Brains were extracted for Fos immunohistochemistry 90 min after the second injection. We next examined the effects of 0.025 mg/kg M100907 and 0.125 mg/kg MK212, alone and in combination, on spontaneous locomotor activity. While neither drug given alone produced any effects, the M100907/MK212 cocktail attenuated cocaine hyperlocomotion as well as cocaine‐induced Fos expression in the dorsolateral caudate‐putamen (CPu), but had no effect on spontaneous locomotion. The findings suggest that 5‐HT_2ARs and 5‐HT_2CRs interact to attenuate cocaine hyperlocomotion and Fos expression in the CPu, and that the CPu is a potential locus of the interactive effects between these 5‐HT₂R subtypes on behavior. Further research investigating combined 5‐HT_2AR antagonism and 5‐HT_2CR agonism as a treatment for cocaine dependence is warranted. Synapse, 2012. © 2012 Wiley Periodicals, Inc.     

重型β地贫患儿珠蛋白肽链失衡的调控研究

目的 研究重型β地贫患儿外周血珠蛋白α、β、γ mRNA比例变化及miR-144基因对其平衡的调控作用.方法 分离培养患者外周血早红细胞,真核表达质粒PmiR-144-luc转染后培养72 h,运用RT-PCR分别检测重型β地贫患儿空白组、基因转染组与健康对照组外周血α、β、γ mRNA的比率变化.结果 与健康对照组比较,重型β地贫患儿外周血珠蛋白α/β 、α/β+γ 、γ/β+γ mRNA的比例水平均升高,差别有统计学意义;与重型β地贫患儿空白组比较,基因转染组珠蛋白α/β 、α/β+γ mRNA的比例水平均降低,差别有统计学意义;而γ/β+γ mRNA的比例水平变化无统计意义.结论 miR-144基因可能调控重型β地贫患儿珠蛋白α、β、γ mRNA基因比例的变化,将为重型β地贫的基因调节治疗提供新的实验依据.     

Myocardial Contraction Fraction Predicts Cardiovascular Events in Patients With Hypertrophic Cardiomyopathy and Normal Ejection Fraction

BackgroundMyocardial contraction fraction (MCF), the ratio of left ventricular stroke volume to myocardial volume, is a novel parameter that can distinguish between pathologic and physiologic hypertrophy. However, its prognostic value in hypertrophic cardiomyopathy (HCM) has never been examined. The objective was to determine if MCF is associated with functional capacity and predicts adverse cardiovascular outcomes in patients with HCM and normal left ventricular ejection fraction (LVEF).Methods and ResultsWe conducted a prospective cohort study of 137 patients with HCM and LVEF ≥55%. Patients were followed for 2.7 ± 2.5 years. We examined association of MCF with New York Heart Association (NYHA) functional class and a composite outcome of embolic stroke, heart transplantation, and cardiac death. We performed time-to-event analysis with the use of Cox proportional hazards modeling and stepwise elimination. The average age was 52 ± 18 years. The average MCF was 26 ± 11%. MCF was inversely correlated with NYHA functional class (P = .001). A total of 20 subjects experienced an outcome event with an event rate of 5.6% per patient-year. MCF independently predicted the outcome (adjusted hazard ratio 0.50 per 10% increase, 95% confidence interval 0.28–0.90, adjusted P = .02).ConclusionsIn patients with HCM and normal LVEF, MCF is associated with functional capacity and independently predicts adverse cardiovascular outcomes.