Abstract:
:1. An antisense oligonucleotide (ASO) is a short strand of deoxyribonucleotide analogue that hybridizes with the complementary mRNA in a sequence-specific manner via Watson-Crick base pairing. Formation of the ASO-mRNA heteroduplex either triggers RNase H activity, leading to mRNA degradation, induces translational arrest by steric hindrance of ribosomal activity, interferes with mRNA maturation by inhibiting splicing or destabilizes pre-mRNA in the nucleus, resulting in downregulation of target protein expression. 2. The ASO is not only a useful experimental tool in protein target identification and validation, but also a highly selective therapeutic strategy for diseases with dysregulated protein expression. 3. In the present review, we discuss various theoretical approaches to rational design of ASO, chemical modifications of ASO, ASO delivery systems and ASO-related toxicology. Finally, we survey ASO drugs in various current clinical studies.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Chan JH,Lim S,Wong WSdoi
10.1111/j.1440-1681.2006.04403.xsubject
Has Abstractpub_date
2006-05-01 00:00:00pages
533-40issue
5-6eissn
0305-1870issn
1440-1681pii
CEPjournal_volume
33pub_type
杂志文章,评审abstract::Agmatine, an endogenous ligand of imidazoline receptors, is reported to exhibit anti-hyperglycaemic and many other effects. It has been established that the imidazoline I3 receptor is involved in insulin secretion. The current study characterizes the role of the imidazoline I3 receptor in the protection of pancreatic ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12441
更新日期:2015-09-01 00:00:00
abstract::1. The present brief review examines some of the new developments in the area of circadian rhythm research. 2. The discovery of the mouse clock and m-per genes and their similarity to other clock genes like per and tim has provided new insight into the control of rhythms in vertebrates. In mice, these genes are expres...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1998.tb02168.x
更新日期:1998-10-01 00:00:00
abstract::1. We wished to determine whether, during pregnancy, there is reduced renal response to atrial distension, whether secretion of atrial natriuretic factor (ANF) is suppressed and whether neural input from the atrial volume receptors to the central nervous system is altered. 2. Conscious, chronically instrumented female...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1995.tb01973.x
更新日期:1995-02-01 00:00:00
abstract::1. Evidence gathered in recent years has revealed microRNAs (miRNAs) fine-tune gene expression and play an important role in various cellular processes, including cell growth, differentiation, proliferation and apoptosis. 2. The present review summarizes current knowledge of miRNA pathways in the pathogenesis of cance...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05269.x
更新日期:2010-01-01 00:00:00
abstract::1. Angiotensin (Ang) II plays a major role in vascular remodelling. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the tissue remodelling processes. The aim of the present study was to investigate whether AngII modulates TIMP-2 expression in rat aortic smooth muscle cells in vivo....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04573.x
更新日期:2007-03-01 00:00:00
abstract::1. To investigate the effect of an exercise training programme on antihypertensive drug requirements, 19 sedentary subjects (14 men and five women) with mild essential hypertension (systolic blood pressure greater than 140 mmHg but less than 180 mmHg), aged 29-55 years, were randomly assigned to 16 weeks of moderate i...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1440-1681.1991.tb01445.x
更新日期:1991-05-01 00:00:00
abstract::1. Altered calcium regulation has been observed in experimental and human hypertension. In this study erythrocyte (RBC) intracellular calcium concentration ([Ca2+]i) was compared in conscious spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) at rest and after injection of the dihydropyridine ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01068.x
更新日期:1988-04-01 00:00:00
abstract::1. Anastomosis (vasovasostomy) of epididymal and prostatic halves of vasa deferentia was carried out in rats in which unilateral or bilateral medial transection (vasectomy) had been performed 4 weeks previously. 2. Noradrenaline levels in epididymal halves of vasa deferentia, 8 weeks after anastomosis with prostatic h...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1987.tb00984.x
更新日期:1987-05-01 00:00:00
abstract::1. 125I-351A, a tyrosyl derivative of the angiotensin converting enzyme (ACE) inhibitor lisinopril, was used as a radioligand, and radioinhibitor binding and displacement assays have been established. 2. The in vitro potency of a range of ACE inhibitors against rat ACE was determined using the radioinhibitor binding d...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01053.x
更新日期:1988-02-01 00:00:00
abstract::1. Endothelin mediates its effects in a variety of renal cells via a multiplicity of intracellular signalling pathways. 2. Stimulation of phosphatidylinositol-specific phospholipase C (PI-PLC), resulting in the activation of inositol trisphosphate and diacylglycerol, can be detected even at picomolar concentrations of...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb02833.x
更新日期:1996-04-01 00:00:00
abstract::1. The present study was designed to determine the effects of ginkgolide A, ginkgolide B and quercetin on CYP3A protein expression and enzyme activity in primary cultures of human hepatocytes. 2. Hepatocytes were pretreated with ginkgolide A, ginkgolide B and quercetin (at 1, 3, 10 and 30 micromol/L) for 48 h and then...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04630.x
更新日期:2007-07-01 00:00:00
abstract::1. NBPA is a derivative of 3-n-butylpathalide isolated from Apium granolens Linn. 2. At concentrations ranging from 6 x 10(-6) to 10(-6) mol/L, NBPA inhibited the L-type calcium current in guinea-pig myocardial cells and cultured human neuroblastoma cells. 3. At 10(-6) mol/L, NBPA markedly inhibited calcium-dependent ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03144.x
更新日期:1999-10-01 00:00:00
abstract::1. In rat isolated tail arteries and atria in which transmitter stores are labelled with (3H)-noradrenaline, isoprenaline in low concentrations facilitates the stimulation-induced efflux of tritium. 2. This effect is dependent on the frequency and duration of electrical stimulation, being observed only at low frequenc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00114.x
更新日期:1980-09-01 00:00:00
abstract::Sarcopenia, defined by reduced appendicular skeletal muscle mass (ASM)/height2 (ASMI), is associated with increased arterial stiffness (brachial-ankle pulse wave velocity, baPWV) and wave reflection (augmentation index, AIx). Blood pressure (BP) responses to metaboreflex activation (post-exercise muscle ischemia, PEMI...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 信件
doi:10.1111/1440-1681.12655
更新日期:2016-12-01 00:00:00
abstract::1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm bir...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03552.x
更新日期:2001-11-01 00:00:00
abstract::1. Mast cells cultured from human peripheral blood have been used as a cell model for functional studies of human mast cells, particularly human lung mast cells. However, the beta-adrenoceptor subtype expressed by these cultured cells has not been identified. The aim of the present study was to characterize pharmacolo...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04435.x
更新日期:2006-08-01 00:00:00
abstract::1. Glucuronidation is the major route of metabolism of dihydrocodeine (DHC) and accounts for 25-30% of an oral dose in urine. The kinetics of DHC-6-glucuronide formation in liver microsomes from five human donors and the effect of a number of potential inhibitor drugs were examined using a newly developed and validate...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.t01-19-.x
更新日期:1998-03-01 00:00:00
abstract::1. Administration of 2-thiophenecarboxylic acid to rats maintained on a low calcium diet resulted in a significant depression in the serum levels of total and ionized calcium and inorganic phosphate. 2. The serum magnesium levels were not altered by the drug. ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1975.tb01828.x
更新日期:1975-03-01 00:00:00
abstract::1. In the present study, we examined whether the nuclear transcription factor (NF)-kappaB activity plays a role in the determination of sensitivity to tumour necrosis factor (TNF)-alpha or agonistic Fas antibody (Ab) in human vascular smooth muscle cells (hVSMC). 2. To inhibit agonist-induced NF-kappaB activation in h...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03817.x
更新日期:2003-03-01 00:00:00
abstract::Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of Ras and c-Myc, has been implicated in the development of multiple tumours, but its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12767
更新日期:2017-07-01 00:00:00
abstract::1. The most usual form of chronic hypoxia in humans is the intermittent hypoxia resulting from obstructive sleep apnoea (OSA). The OSA syndrome is a highly prevalent sleep breathing disorder that is considered an independent risk factor for hypertension and cardiovascular diseases. Endothelial dysfunction, oxidative s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05213.x
更新日期:2009-12-01 00:00:00
abstract::1. The object of this study was to determine whether meat protein per se is responsible for the higher blood pressures (BP) in omnivores compared with vegetarians. 2. Assessments were made by a double blind randomized control trial in 64 normotensive volunteers recruited from Royal Perth Hospital staff. 3. All volunte...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1440-1681.1987.tb00368.x
更新日期:1987-03-01 00:00:00
abstract::1. The turnover rate of inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) in noradrenaline-stimulated adult rat left atria was calculated from changes in specific activity and was found to equal 110 ct/min per mg tissue. In contrast, the isomers of inositol mono- and bisphosphates accumulated at a rate of 508 ct/min per mg....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01698.x
更新日期:1993-05-01 00:00:00
abstract::1. The present study was undertaken to elucidate the effects of parecoxib, a novel cyclo-oxygenase (COX)-2 inhibitor, on spontaneous and prostaglandin-induced contractions of uterine smooth muscle. 2. Non-pregnant adult Wistar rats were decapitated and dissected to isolate myometrial strips. The tissue was mounted in ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04632.x
更新日期:2007-08-01 00:00:00
abstract::1. One of the major causes of metabolic syndrome is elevated 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in the liver and adipose tissue. High 11β-HSD1 expression contributes significantly to the diabetic phenotype in db/db mice. The purpose of the present study was to test the effect of the pharmacological inhibiti...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05640.x
更新日期:2012-01-01 00:00:00
abstract::1. The effect of the calcium channel blocker nisoldipine on the myocardial content of lipid peroxidation products (malondialdehyde (MDA), conjugated double bonds (CDB), fluorescent end-products (RF) and mitochondrial adenine nucleotides) was investigated in conscious pigs (n = 14) subjected to 24 h of immobilization s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01258.x
更新日期:1990-01-01 00:00:00
abstract::Hypoxia-inducible factor-1 alpha (HIF-1α) and nuclear receptor related-1 (Nurr1) play pivotal roles in the development and survival of dopaminergic neurons, and deficiencies in these genes may be involved in Parkinson's disease (PD) pathogenesis. Recently, anthelminthic benzimidazoles were shown to promote HIF-1α tran...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13162
更新日期:2019-12-01 00:00:00
abstract::Preterm birth (PTB) is the single largest cause of death in infants and young children. The rate of PTB is significantly higher in male infants, particularly those that are born very preterm. Here we present evidence to suggest that the decidual renin-angiotensin system may play a role in inhibiting inflammation and m...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12734
更新日期:2017-05-01 00:00:00
abstract::1. There is mounting evidence that a wide range of antidepressants share the common feature of increasing hippocampal neurogenesis. The specificity of this association has suggested that an ability to increase neurogenesis might be a useful paradigm to screen for compounds with antidepressant activity. 2. The hope of ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2007.04608.x
更新日期:2007-05-01 00:00:00
abstract::1. The use of the isolated lung strip and single open tracheal ring for studying Schultz Dale anaphylactic contractions in both the peripheral and central airways is described. 2. This method is particularly relevant to studies of anaphylaxis because many preparations may be obtained from a single sensitized animal. 3...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1979.tb00046.x
更新日期:1979-11-01 00:00:00