microRNA155在动脉粥样硬化发生过程中的网络调控机制

动脉粥样硬化(atherosclerosis,AS)是一种慢性进行性的血管炎症性疾病,其发病机制主要包括内皮细胞损伤,脂质浸润及炎症介质分泌等。microRNA155(miR-155)是参与AS炎性调控、免疫和自噬信号等通路的微小非编码RNA。系统性研究miR-155及其靶基因的网络调控机制,能全面理解miR-155在AS中的作用,促进其在临床诊断中的应用开发。利用miRNA靶基因预测数据库miRDB、miRmap和Starbase获取miR-155的靶基因集。R语言分析基因表达综合数据库(gene expression omnibus,GEO)共享平台动脉粥样硬化斑块差异表达基因(GSE24702),筛选出18 076个差异表达基因。利用基因集富集分析(gene set enrichment analysis,GSEA)分析,观察这些差异表达基因共同富集在IL6-JAK-STAT3信号通路、炎症反应和TNFα等炎症信号通路。与miR-155靶基因交叉匹配得到371个交集mRNA,其中159个在动脉粥样硬化斑块中上调,212个在动脉粥样硬化斑块中下调。基因本体(gene ontology,GO)及基因组数据库(kyoto encyclopedia of genes and genomes,KEGG)分析研究基因功能,GO富集分析371个差异基因主要富集炎症和凋亡信号通路的负调控等功能,KEGG分析371个差异基因主要富集TGFβ等炎症信号通路。蛋白相互作用网络(protein-protein interaction networks,PPI)分析获得关键节点基因是ARRB2、FBXO11、SOCS1、FBXO22、FBXO30、KRAS、RNF19A、TRIM32、HERC4、PJA1、RCHY1和DET1。本研究表明,miR-155主要通过调控炎症反应等相关信号通路影响斑块细胞炎症、自噬及凋亡等功能,进而影响动脉粥样硬化的各个进程。     

植物发育性细胞程序死亡的发生机制

细胞程序死亡是多细胞生物体在内源发育信号或外源环境信号作用下在特定时间和空间发生的细胞死亡过程, 在植物的生长发育过程中起着重要作用。该文介绍了植物细胞程序死亡类型的几种划分方法、植物发育性细胞程序死亡研究常用的实验体系, 并着重概述有关植物发育性细胞程序死亡发生机制的研究进展。     

酵母交配过程的极性生长及其调控机制

酿酒酵母单倍体细胞能够与相反交配型的单倍体细胞发生交配。交配时酿酒酵母放弃原有出芽位点,根据信息素的浓度梯度,重新选择生长位点,向相反交配型细胞伸出突起进行极性生长。交配因子受体指导选择交配突起的位点,通过G蛋白激活Ste20p,将信号经由Ste11p、Ste7p和Fus3p组成的MAPK模块传递到Far1p和Ste12p等因子,调控相关基因的转录,抑制原有的出芽位点,选择新的生长位点,并使细胞周期停止在G1期,G蛋白与Cdc24p、Cdc42p和Bem1p等蛋白作用,聚集在细胞,使得肌协蛋白细胞骨架在交配突起处聚集,呈极性化分布,使细胞发生极性生长。     

甘草抗动脉粥样硬化机制的网络药理学研究

利用网络药理学方法探讨甘草在抗动脉粥样硬化中的分子机制。本研究利用中医药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)分析甘草中的有效活性成分,并获得有效成分的作用靶点。通过Cytoscape软件构建可视化靶点互相作用网络,对网络中的关键靶点进行基因本体(GO)富集分析和KEGG通路富集分析。结果显示甘草中40种有效活性成分的预测靶点共97个,47个靶点与动脉粥样硬化(AS)相关,其中18个是血管保护药物和脂质修饰药物的作用靶点,表明甘草可作为调控AS发展的药物。基于97个预测靶点的GO富集分析,发现甘草可参与多种生物学过程,尤其是应对外源性刺激,以及参与细胞凋亡等过程。通过构建甘草靶点与AS疾病靶点相互作用网络(PPI),确定了AKT1、MAPK3、MAPK1、JUN和CASP3等关键靶点,并对关键靶点进行KEGG富集分析,结果表明甘草主要影响调控细胞增殖、生存以及凋亡的细胞信号转导相关通路,并激活先天免疫相关信号通路,调节炎性细胞因子释放,从而发挥抗动脉粥样硬化作用。甘草具有多成分、多靶点、多途径的作用特点,主要通过PI3K-AKT信号途径、MAPK信号途径、NOD样受体信号通路调控细胞增殖和凋亡,同时发挥免疫调控作用,从而影响动脉粥样硬化的发展,由此可见,甘草可作为动脉粥样硬化疾病治疗的候选中草药。     

昆虫细胞生长之调控机制的探讨

细胞生长调控机制的探讨是近年来发育生物学中一个十分热门的研究领域。生物体内之细胞是如何得知何时该生长及分裂?何时该停止生长?何时该死亡?对生物体来说至关重大。研究显示调控细胞生长之信息传递系统出现差错,将导致生长异常,从而产生组织细胞之异常增生而诱发癌症或产生其它重大疾病。而人类也只有在充分理解细胞生长之机制的基础上,我们才能了解癌症等重大疾病发生的细胞生物学基础。在探讨细胞生长调控机制的研究中,昆虫特别是果蝇Drosophilamelanogaster一直是一个十分理想的实验材料。文章介绍了如何从昆虫看细胞之生长调控机制。     

泌乳分子机制及基因调控网络

为了提高泌乳家畜的产奶性能,使得进一步理解乳腺的功能及其调控机制变得十分必要。早期的研究倾向于从组织学和激素层面研究分析乳腺的生理功能,随着近年来分子生物学技术的发展,芯片等高通量技术被应用到乳腺泌乳机制的研究中,泌乳生物学进入了一个全新的发展时期。综述了近年来国内外关于乳腺泌乳机制方面的研究进展,如乳腺各个泌乳时期的基因调控网络、乳汁主要成分的合成调控网络、参与乳腺泌乳周期循环的信号传导通路等。     

花器官大小调控机制的研究进展

自然界中植物花的大小受到遗传因素和环境因素的双重调节。传粉者、天敌和逆境胁迫等多种因素相互制约,作为选择压力共同影响花器官形态和繁殖能力,通过选择适合的基因型,推动花器官大小的进化。近年来,对花器官大小调控机制的研究又有新的进展,已在模式植物拟南芥中分离出大量参与花器官大小调控的基因,并证实它们主要在细胞水平影响花器官的增殖和生长。本文介绍花器官大小的进化及其生物学意义,并综述了拟南芥花器官大小调控机制的研究进展。     

植物水分传输过程中的调控机制研究进展

农田土壤水分的转化利用与调控是以土壤-植物-大气连续体(SPAC)为基础,以植物为核心,其中水分在植物体内的传输与调控研究一直是国际学术研究的前沿性热点课题。本文概述了植物水分传输的驱动力和传输途径,重点从植物的气孔调节、水容调节、渗透调节、水孔蛋白调节、贮水调节、气穴和栓塞调节等方面综述了植物水分传输过程中的调控机制研究进展。通过对植物存在优化调控水分平衡的潜在能力的研究,不仅可充实SPAC系统水分传输理论,而且有助于明确植物对环境的适应机制和高效用水的潜力及其节水调控的效应,对指导干旱半干旱地区农业生产提供理论依据。     

circRNA在肿瘤中的作用及调控机制

环状RNA(circular RNA,circRNA)是一类结构上形成闭合环状的非编码RNA,在真核转录本中含量很高,具有丰富、稳定、高度保守和组织特异性等特点.近年来逐步揭示,circRNA能够与某些miRNA或蛋白质结合,参与生物发生和分子功能的调控机制,包括miRNAs分子海绵、蛋白质翻译、基因转录和RNA剪接调...     

植物体细胞胚胎发生的调控网络

植物体细胞胚胎发生是一个极其复杂而有序的过程,受到多种内外因素的影响与调控。其中基因的表达与调控是影响体细胞胚胎发生最重要和最根本的因素。这些基因包括PLANT GROWTH ACTIVATOR系列基因、LEAFYCOTYLEDON家族基因、BABY BOOM基因、SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE基因和PICKLE基因等,它们相互作用构成了一个复杂的调控网络。以下结合作者对PLANT GROWTH ACTIVATOR 37等基因的研究,对这一调控网络进行了介绍,并探讨了未来体细胞胚胎发生的研究方向。     

微小RNA-223(miR-223)在脓毒症早期诊断、炎症程度评估中的价值研究

摘要 目的：分析微小RNA-223（miR-223）在脓毒症的早期诊断、炎症严重程度评估中的检测价值。方法：通过便利抽样法选定本院2020年5月至2022年5月住院的30例脓毒症患者作为观察组,选取同期门诊体检中心30例健康体检者作为对照组,检测、比较两组外周血miR-223、血清降钙素原（PCT）、C反应蛋白（CRP）,比较脓毒症患者中轻度组、严重组外周血miR-223、血清PCT、CRP,比较脓毒症患者中死亡组、存活组外周血miR-223、血清PCT、CRP,Spearman分析miR-223与PCT、CRP的相关性,绘制ROC曲线,计算曲线下面积（AUC）,分析miR-223与PCT、CRP对脓毒症的预测价值。结果：观察组外周血miR-223、血清PCT、CRP水平均高于对照组,P＜0.05（差异均具有统计学意义）。严重组外周血miR-223、血清PCT、CRP水平均高于轻度组,P＜0.05（差异均具有统计学意义）。死亡组外周血miR-223、血清PCT、CRP水平均高于存活组,P＜0.05（差异均具有统计学意义）。miR-223与PCT、CRP均呈正相关性,P＜0.05（差异均具有统计学意义）（r值=0.796、0.785）。ROC曲线结果显示：miR-223+PCT+CRP诊断脓毒症的灵敏度（89.54%）、特异度（86.52%）明显高于miR-223（82.37%、80.44%）、PCT（78.34%、75.34%）、CRP（75.12%、74.07%）,P＜0.05（差异均具有统计学意义）。结论：脓毒症患者机体外周血miR-223水平较高,且外周血miR-223与血清PCT、CRP呈正相关性,miR-223联合PCT、CRP可提高脓毒症诊断灵敏度、特异度。     

Increased microRNA-223 in Helicobacter pylori-associated gastric cancer contributed to cancer cell proliferation and migration

Dysregulation of microRNA-223 (miR-223) was associated with gastric cancer (GC), in which Helicobacter pylori (H. pylori) played important roles. However, the mechanism of relationships between miR-223 and H. pylori-associated GC was largely undiscovered. Here, we found the overexpression of miR-223 was related with H. pylori positive infection in vivo and in vitro in GC by relative quantification of qRT-PCR. Upregulated miR-223 was responsible for the poorer prognosis of GC with H. pylori positive, also. The result indicated not only overexpression of miR-223 stimulated the proliferation by CCK-8 assays and colony formation of H. pylori associated GC cells, but also migration and invasion by scratch assay and transwell invasion assays in vitro. Above all, all our data declared H. pylori infection played an important role in developing GC according to overexpression of miR-223, which increased cancer cell proliferation and migration.     

Inhibition of microRNA-103 attenuates inflammation and endoplasmic reticulum stress in atherosclerosis through disrupting the PTEN-mediated MAPK signaling

Atherosclerosis (AS), a chronic disorder of large arteries, is the underlying pathological process of heart disease and stroke. Former researchers have found that microRNAs (miRs) are involved in the several key processes of AS. Apolipoprotein E knockout (ApoE^−/−) mice fed a high-fat-diet (HFD) to establish AS model. The expression of miR-103 was characterized in the mice model. The effects of miR-103 on inflammation and endoplasmic reticulum stress (ERS) were analyzed when the expression of miR-103 was inhibited in ApoE ^−/− mice fed an HFD and human aortic endothelial cells (HAECs) exposed to oxidized low-density lipoprotein (ox-LDL). The relationship between miR-103 and phosphatase and tensin homolog (PTEN) was identified by luciferase activity detection and real-time quantitative polymerase chain reaction (RT-qPCR). Gain- and loss-function approaches were further applied for investigating the regulatory effects of miR-103 and PTEN on ERS. Role of MAPK signaling was then analyzed using PD98059 to block this pathway. miR-103 was highly expressed in the ApoEApoE ^−/− mice fed an HFD. Downregulation of miR-103 suppressed inflammation and ERS in endothelial cells isolated from ApoE ^−/− mice fed a HFD and ox-LDL-exposed HAECs. In addition, miR-103 can target PTEN and downregulate its expression. Overexpression of PTEN reversed the miR-103-induced activation of MAPK signaling. Moreover, PTEN upregulation or MAPK signaling inhibition ease miR-103-induced inflammation and ERS in vivo and in vitro. Thus, miR-103 depletion restrains the progression of AS through blocking PTEN-mediated MAPK signaling.     

Diagnostic and mechanistic values of microRNA-130a and microRNA-203 in patients with papillary thyroid carcinoma

This research was determined to unearth the diagnostic values and the effects of microRNA (miR)-130a and miR-203 on cell proliferation and apoptosis of papillary thyroid carcinoma (PTC). Expression of miR-130a and miR-203 were evaluated and were subjected to correlation analysis. The diagnostic values of miR-130a and miR-203 and their associations with clinicopathological characteristics of patients with PTC were measured. The expression levels of miR-130a and miR-203 in K1, IHH4, TPC-1, and BCPAP cells together with Nthy-ori 3-1 cells were measured. Cells were transfected with miR-130a mimics, miR-203 mimics, and coordinate of miR-130a mimics and miR-203 mimics. Cell growth, colony formation, and apoptosis were detected by cell counting kit-8 (CCK-8) assay, colony formation assay, and flow cytometry. PTC tissues had decreased miR-130a and miR-203 relative to adjacent normal tissues and normal thyroid tissue (both P < .05). miR-130a was in positive correlation with miR-203 (r = 0.754, P < .01). miR-130a was related with tumor infiltration and tumor stage while miR-203 was implicated in tumor stage and lymph-node metastasis. The area under the curve (AUC), sensitivity, as well as specificity for miR-130 in predicting PTC was 0.839, 74.5%, and 85.0% and those for miR-203 were 0.818, 73.7%, and 84.0%, respectively. PTC cells had lower expression of miR-130a and miR-203 than that in Nthy-ori 3-1 cells. After transfected miR-130a and miR-203 mimics in BCPAP and TPC-1 cells, both cells had increased miR-130a and miR-203, promoted cell apoptosis rate and decreased cell growth rate, and colony formation ability. After coordinately transfected with miR-130a mimics and miR-203 mimics, the cell growth and colony formation ability of PTC cells were restrained, and apoptosis of PTC cells was elevated (all P < .05). This study highlights that miR-130a and miR-203 have satisfactory diagnostic value in PTC and upregulated miR-130a and miR-203 can inhibit PTC cell growth and promote cell apoptosis.     

Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe^−/−) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe^−/− mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe^−/− mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.     

Adioophilin在动脉粥样硬化中的作用机制

adipophilin是脂滴周围相关蛋白,能促进脂质蓄积和细胞内脂滴的形成,在泡沫细胞的形成中起到重要作用,是动脉粥样硬化脂质蓄积的一个标记物。但目前对其脂质蓄积机制的研究不是十分明确。本文对adipophilin在调节脂质蓄积过程中的机制做一综述,以期为动脉粥样硬化治疗提供新的理论依据和药物靶点,推动动脉粥样硬化治疗方法的发展。