Regulatory mechanisms of microRNAs involvement in cancer

MicroRNAs (miRNAs) are 19-24 nucleotide noncoding RNAs that regulate the translation and degradation of target mRNAs and are extensively involved in human cancers. One unexpected conclusion of the profiling and functional studies in tumourigenesis is that some miRNAs behave in cancer cells in a dual mode, resembling the 'Dr Jekyll and Mr Hyde' story, which centers on a conception of humanity as dual in nature. The authors and others have found that onco-miRNAs and suppressor-miRNAs can represent two different looks of the same gene, behaving as oncogenes or tumour suppressors depending on tissue type and specific targets. In this review, the authors analyse the regulatory mechanisms of the main miRNA genes involved in human tumourigenesis.     

Regulatory mechanisms of microRNAs involvement in cancer

MicroRNAs (miRNAs) are 19 – 24 nucleotide noncoding RNAs that regulate the translation and degradation of target mRNAs and are extensively involved in human cancers. One unexpected conclusion of the profiling and functional studies in tumourigenesis is that some miRNAs behave in cancer cells in a dual mode, resembling the ‘Dr Jekyll and Mr Hyde’ story, which centers on a conception of humanity as dual in nature. The authors and others have found that onco-miRNAs and suppressor-miRNAs can represent two different looks of the same gene, behaving as oncogenes or tumour suppressors depending on tissue type and specific targets. In this review, the authors analyse the regulatory mechanisms of the main miRNA genes involved in human tumourigenesis.     

Regulatory mechanisms of NK cell functions

Natural Killer (NK) cells discriminate self from non-self in a manner distinct from T cells. NK cells exhibit cytotoxicity against "missing-self" by killing any cells in principle except normal self-cells. Cells expressing low levels of self MHC class I molecules such as tumor cells and foreign cells are killed, whereas normal self cells are neglected by NK cells. Although identities of activation receptors triggering NK activity are still unclear, recent studies have revealed molecules inhibiting cytotoxicity against normal self cells. In this review, we summarize current understanding of molecular basis for missing-self hypothesis and control mechanisms of NK cell activation.     

Molecular and cellular mechanisms of myocardial remodeling in heart failure

The apoptosis of smooth muscle cells, the translocation, structural and functional impairments of remaining cardiomyocytes, ventricular dilatation, and the altered extracellular matrix underlie myocardial remodeling in chronic heart failure (CHF). Among the above factors, apoptosis, which is a membrane-dependent process of programmed cell death, and cytokine derangement are of primary importance. To recognize the cytokine concept of the pathogenesis of CHF permits the clinical application of cytokine synthesis inhibitors and their functional activity.     

Regulatory mechanisms of hemoglobin oxygen affinity in acidosis and alkalosis

The recent reports of the effect of 2,3-diphosphoglycerate (2,3-DPG) on hemoglobin affinity for oxygen suggested that this substance may play a role in man's adaptation to acidosis and alkalosis.     

高尿酸对大鼠肾小球足细胞的损害作用

目的:探讨高尿酸对大鼠足细胞的损害作用及其可能机制。方法:40只雄性SD大鼠随机平均分为4组,即对照组、轻微高尿酸组、高尿酸组、别嘌醇干预组。饲养24周后处死大鼠,心脏取血检测肌酐、尿酸水平,左肾切除后行病理检查,并检测血管紧张素Ⅱ(AngⅡ)、白细胞介素6(IL-6)、超氧化物歧化酶(SOD)、nephrin、podocin在肾组织中的表达情况。结果:各组大鼠血肌酐水平差异无统计学意义;对照组、轻微高尿酸组、高尿酸组、别嘌醇干预组血尿酸水平分别为(65.04±5.26)、(106.87±11.00)、(147.23±25.75)、(89.78±11.67)μmol/L,每两组间差异有统计学意义(P0.05)。苏木精-伊红(H-E)染色显示轻微高尿酸组、高尿酸组肾小球系膜区有核细胞数略增多,但各组大鼠肾组织病理学改变均不明显。电镜显示:轻微高尿酸组、高尿酸组存在不同程度足突融合及足突细胞病理改变。免疫组化染色显示:AngⅡ主要表达于肾小球系膜区,少量表达于肾小管上皮细胞,组间差异有统计学意义(P0.05);IL-6主要表达于肾小管上皮细胞,少量表达于肾小球,组间差异有统计学意义(P0.05);SOD在肾小球及小管内均表达,组间差异有统计学意义(P0.05)。Western印迹及RT-PCR显示,每两组大鼠肾组织nephrin、podocin蛋白及mRNA表达差异均有统计学意义(P0.05)。血尿酸水平与肾组织nephrin、podocin、SOD表达负相关(P0.05),与肾组织AngⅡ及IL-6的表达正相关(P0.05);肾组织AngⅡ、IL-6的表达与nephrin、podocin的表达负相关(P0.05);肾组织SOD的表达与nephrin、podocin的表达正相关(P0.05)。结论:高尿酸血症可导致肾小球足细胞病变,其可能机制包括诱发氧化应激、激活RAS系统及微炎症反应;别嘌醇可通过降低血尿酸水平或通过减轻氧化应激反应、调控RAS活性及微炎症反应来减轻足细胞损伤。     

Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH.     

Regulatory mechanisms of neural stem cell and strategies for therapy

Neural stem cells(NSCs) are multipotential progenitor cells that can generate neurons, astrocytes, and oligodendrocytes, the three major cell types in the central nervous system. Due to their self-renewal activities, NSCs can proliferate in an undifferentiated state in vitro, allowing them to be expanded mitotically and harvested in bulk. Recent advances in stem cell biology have led us to investigate methods for the regenerative manipulation of the damaged CNS. However, there is much that is still not known about regulatory mechanisms of the differentiation and self-renewal of NSCs. In this article, we review some of the basic notions regarding the extracellular factors and signal transduction cascades involved in the differentiation and maintenance of NSCs.     

间充质干细胞分化的调控机制及其影响因素

背景:随着人们对间充质干细胞认识的深入,该细胞目前广泛应用于组织工程研究,例如缺血性脑血管病,肢体缺血等疾病的治疗等.目的:综述影响骨髓间充质干细胞分化能力因素的研究进展.方法:应用计算机检索2003-08/2009-08 PubMed数据库相关文章,检索词为mesenchymal stem cell differentiation,Wnt,β-catenin,bone morphogenetic protein,vascular endothelial growth factor,共收集到213篇相关文献.纳入与间充质干细胞分化调控机制及其影响因素相关文章,排除重复研究及Meta分析,最后纳入15篇文献进行总结.结果与结论:随着生物工程等学科的发展,人们对间充质干细胞分化的调控及其影响因素有了进一步的认识.在间充质干细胞的生存微环境内发现了许多因了如骨形态发生蛋白、血管内皮生长因子等,它们在调节细胞的分化上发挥了重要作用.相应对外界因素如何产生效应的认识也越来越多,如对细胞膜电位作用的认识.间充质干细胞的某些自身因素影响到了其分化能力,细胞的衰老就是其中的一种.     

PI3K/AKT信号通路在急性白血病中调控机制的初步研究

本研究探讨PI3K/AKT通路中的PTEN、CCND1、mTOR、RICTOR、FOXO1基因在急性髓系白血病(AML)、急性淋巴细胞白血病(ALL)患者中与正常人中表达的差异,以期查明PI3K/AKT通路在白血病中是否存在通路失调。随机收集16例骨髓标本,其中白血病12例(AML 6例,ALL 6例),正常骨髓标本4例。用实时定量RT-PCR方法检测PI3K/AKT通路中的PTEN、CCND1、mTOR、RICTOR、FOXO1基因的表达变化;以管家基因GAPDH为内参,按2-△△Ct法计算目的基因相对表达量。结果表明:PTEN、mTOR、RICTOR在AML、ALL中总体呈低表达趋势,PTEN在12例标本中有10例低表达,mTOR在12例标本中9例低表达,RICTOR在12例标本中7例低表达;FOXO1,CCND1在AML、ALL中则呈高表达趋势,FOXO1在12例标本中有9例高表达,CCND1在12例标本中7例高表达。结论:PI3K/AKT信号通路基因在白血病细胞中被激活。     

ADAM33基因调控哮喘患儿气道重塑的机制进展

小儿支气管哮喘（哮喘）的病理生理机制尚未完全清楚。气道重塑是其中重要的病理生理改变,参与了哮喘的发生、发展过程。解整合素-金属蛋白酶33（ADAM33）基因为哮喘的易感性基因,研究表明其与气道重塑密切相关。该文就 ADAM33在哮喘气道重塑中的作用机制进行阐述,以阐明哮喘发生的基因机制。     

Thromboxane mediates glomerular haemodynamics in a model of chronic glomerular disease

In order to evaluate a possible haemodynamic role of cyclooxygenase products in chronic renal disease, a model of chronic glomerular injury was induced in nephritic rats by unilateral nephrectomy and high dietary protein intake. Eight weeks after induction of an in situ immune complex glomerulonephritis (CGN), rats subjected to high protein (HP) intake (42% protein) and uninephrectomy revealed a significantly lower glomerular filtration rate (GFR; 485 +/- 53 microliters min-1 100 g-1 body weight (BW)) compared with uninephrectomized rats with ICGN which were on low protein (LP) diet (6% protein) (825 +/- 155 microliters min-1 100 g-1 BW) (P less than 0.01). The glomerular thromboxane B2 (TxB2) formation in uninephrectomized rats with ICGN on either LP or HP intake was not significantly different (HP: 473 +/- 61; LP: 493 +/- 63 pg mg-1 min-1), but was significantly higher when compared with non-nephritic controls on either diet. Glomerular prostaglandin E2 (PGE2) production in rats on HP diet was higher compared with rats with LP intake (HP: 617 +/- 67; LP: 351 +/- 76 pg mg-1 min-1) (P less than 0.01). The thromboxane receptor blocker daltroban significantly elevated suppressed GFR in ICGN rats on HP diet (ICGN+vehicle: 426 +/- 69; ICGN+daltro: 689 +/- 66 microliters min-1 100 g-1 BW) (P less than 0.01). Thromboxane receptor blockade had no effect on glomerular haemodynamics in ICGN animals receiving LP diet (ICGN+vehicle: 771 +/- 24; ICGN+daltro: 684 +/- 85 microliters min-1 100 g-1 BW).(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines

Interleukin 17 (IL-17) family consists of six cytokines in mammals. Among them, IL-17 and IL-17F are expressed by a novel subset of CD4+ helper T (Th) cells and play critical function in inflammation and autoimmunity. On the other hand, IL-17E, also called IL-25, has been associated with allergic responses. Here we summarize recent work by us as well as other investigators in understanding the regulation and function of these three cytokines. From these studies, IL-17 family cytokines may serve as novel targets for pharmaceutical intervention of immune and inflammatory diseases.