微小核糖核酸在参与缺血/再灌注过程中的研究进展

微小核糖核酸(miRNA)是一种近年来发现的存在于真核生物中的非编码调控RNA,其作用机制主要是在转录后水平上调控基因的表达。不同miRNA在炎性反应以及组织缺血/再灌注(I/R)过程中的表达水平有不同程度的变化,炎性反应是介导I/R损伤的重要因素之一,这一现象初步揭示了miRNA在I/R过程中扮演着重要的角色。深入研究将miRNA早期诊断和治疗I/R损伤有重要的临床意义。     

MicroRNA, the putative molecular control for mid-life decline

In a society experiencing an accelerating increase in the middle- and old-age population, there is an urgent need to address age-dependent frailties by a paradigm shift, i.e. a new medical strategy to combat middle-age decline at the stage before incipient old-age problems develop into full-blown diseases. We suggest that a decline in cellular health status occurs at mid-life, and that this decline may involve a universal or system-specific programmatic shift of signaling control. This decline, although sub-clinical and asymptomatic, may precipitate increased risk of late-life diseases. The putative control for this mid-life cellular decline may be governed by a recently discovered group of molecular species, the microRNAs, small RNAs of approximately 22 nucleotide bases. In general microRNAs, while themselves not coding for any protein product, negatively regulate the expression of target genes by either degrading their message or inhibiting translation by binding to their 3'-untranslated region (UTR). Thus, possible derailment of these negative regulators for gene expression in mid-life may be the putative force inducing molecular frailty in individual cell signaling, and in time leading to tissue-wide dysfunction. A challenge for future research is then to identify these dysfunctional microRNAs, in order to develop advance diagnosis and therapy to combat mid-life decline, a preventive medicine approach to block, delay or reduce the risk of old-age diseases.     

丙泊酚抗肿瘤作用及分子机制在肺癌中的研究进展

肺癌是最常见的恶性肿瘤,手术切除是治疗肺癌的主要手段,但术后仍会有术后肿瘤复发与转移的可能。丙泊酚是最常用的静脉全麻药物,近年来越来越多的文献表明,丙泊酚对肺癌患者有延长生存期的作用。本文通过检索相关文献,总结丙泊酚通过调控微小RNA(MicroRNA,miRNA)和环状RNA(circular RNA,circRNA)从而调节多种信号通路发挥直接抗肿瘤作用;丙泊酚促进T细胞分化提高免疫力,减少炎症介质间接抑制肿瘤细胞活性;丙泊酚还可以提高肿瘤细胞对化疗药物的敏感性,发挥间接抗肿瘤作用。此外,临床试验也证实,丙泊酚可能因其抗肿瘤特性与癌症患者术后生存密切相关。因此,肺癌手术麻醉中使用丙泊酚静脉全麻药可能更为适合,但仍需要大样本前瞻性临床试验去证实。     

Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis

The sequence of events associated with the development of gastric cancer has been described as “the gastric precancerous cascade”. This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context.     

MicroRNA Expression Analysis in Patients with Primary Myelofibrosis,Polycythemia vera and Essential Thrombocythemia

MicroRNAs (miRNA) are small non-coding RNA molecules that play critical roles in cell differentiation, proliferation and apoptosis and thus regulate haematopoietic stem cells and committed progenitor cells. We analyzed expressions of miRNAs associated with hematopoietic transformation of myeloid, erythroid and megakaryocytic progenitor cells during haematopoiesis (mir155, mir181a, mir221, mir222, mir223, mir451), in patients with primary myelofibrosis (PMF) (n = 22), polycythemia vera (PV) (n = 33), essential thrombocythemia (ET) (n = 49) and in healthy controls (n = 40) by quantitate/real time polymerase chain reaction. RT-PCR testing was negative for BCR–ABL1 fusion gene in all the patients. Mir155 was expressed in higher levels in all 3 disorders (p < 0.05). Mir221 was higher especially in ET and PMF group (p < 0.05). Mir222 expression was lower in PV patients (p < 0.05) and higher in ET and PMF patients compared to control group. Mir223 expression was higher in ET and PMF group than control group (p > 0.05). Mir451 levels were lower in all three groups compared to control group (p < 0.05). There was no difference in expression levels of mir181a between groups. JAK2V617F positivity, co-morbidities, drugs, and gender did not affect miRNA expressions. This study holds promise for the future application of these molecules for differential diagnosis and as therapeutic targets in Philadelphia chromosome negative myeloproliferative neoplasms.     

Kinetics of plasma microRNA-499 expression in acute myocardial infarction

Background

MicroRNA (miRNA) is reported to be present in human plasma and has been increasingly suggested as a biomarker for diseases. Our study aimed to investigate the kinetics of cardiac-specific microR-499 (miR-499) in acute myocardial infarction (AMI).

Methods

Circulating concentrations of cardiac enriched miR-499 were measured by quantitative PCR in 73 patients with acute coronary syndrome (ACS), including 53 with AMI and 20 with unstable angina (UA). Thirty healthy subjects were used as controls. Plasma samples in AMI group were obtained immediately after admission and at 12 h, 24 h, 3 d and 7 d after onset of symptoms. Plasma samples in UA and healthy control groups were collected immediately after admission. The severity and extent of coronary stenotic lesions were evaluated on the basis of coronary angiography using Gensini score.

Results

miR-499 expression levels were significantly higher in the 53 AMI patients than in the 20 UA patients and 30 healthy controls immediately after admission (P<0.01). A measurable increase in miR-499 levels was observed in AMI patients within 24 h of the last onset of chest pain and the levels returned to the baseline after 7 d. Plasma miR-499 levels in the patients with AMI were positively-correlated with cTnI (r=0.384, P<0.01) and CK-MB (r=0.402, P<0.01). In addition, miR-499 levels in AMI patients with two- and three-vessel coronary artery disease (CAD) were significantly higher than those in patients with single-vessel CAD (P<0.05). Gensini scores were used to evaluate the severity of coronary stenosis. miR-499 were positively correlated with Gensini scores (r=0.52, P<0.01). miR-499 levels at admission were significantly higher than that those 24 h after percutaneous coronary intervention (PCI) in AMI patients (P<0.01) and were negatively correlated with LVEF (r=0.36, P=0.008).

Conclusions

Cardiac-specific miRNA-499 levels were found to be linearly proportional to myocardial damage. MiRNA-499 might prove to be a new biomarker for AMI and a predictor of the risk of myocardial ischemia.     

卵巢癌患者血浆miR-205、miR-212及miR-429的水平分析及意义

目的 探讨卵巢癌患者血浆miR-205、miR-212及miR-429水平,分析3者与卵巢癌临床病理学特征的关系。方法 收集本院收治的71例上皮性卵巢癌患者未经治疗前的血浆标本（上皮性卵巢癌组）,采用实时定量RT-PCR（qRT-PCR）法检测以上标本的miR-205、miR-212及miR-429水平,收集卵巢癌患者的临床病理学参数（年龄、临床分期、分化程度、组织类型及淋巴结转移情况）,比较不同miR-205、miR-212及miR-429水平的临床病理参数分布差异,采用受试者工作特征曲线（ROC）评价血浆miR-205、miR-212及miR-429水平在卵巢癌诊断中的临床价值。同时选取同期的68例女性健康体检者（健康对照组）及66例良性卵巢肿瘤患者（良性卵巢肿瘤组）的血浆标本作对照。结果 上皮性卵巢癌组的血浆miR-205水平高于良性卵巢肿瘤组和健康对照组,但miR-212和miR-429水平低于良性卵巢肿瘤组和健康对照组,差异均有统计学意义（P<0.05）;上皮性卵巢癌组中的miR-205水平与年龄、临床分期、分化程度及淋巴结转移有关,miR-212水平与临床分期、分化程度有关,miR-429水平与临床分期、淋巴结转移有关,以上差异均有统计学意义（P<0.05）;卵巢癌患者血浆miR-205水平与miR-212及miR-429均呈负相关（r=-0.572、-0.325）,miR-212与miR-429呈正相关（r=0.473）,差异均有统计学意义（P<0.05）;血浆miR-205、miR-212及miR-429诊断卵巢癌的AUC、灵敏度和特异度分别为0.915、92.1%和86.2%,0.944,87.3%和91.0%,0.905、88.5%和83.6%。结论 卵巢癌患者血浆中miR-205呈高表达,miR-212和miR-429呈低表达,与临床病理学参数有关,且在卵巢癌诊断中有一定的价值,可用于卵巢癌的辅助诊断和病情评估。