Abstract:
:Phosphorothioate (PS) oligodeoxynucleotides are relatively nuclease resistant, water soluble analogs of phosphodiester (PO) oligodeoxynucleotides. These molecules are chiral but still hybridize well to their RNA targets. While considered for use as in vivo anti-sense inhibitors of gene expression, their biology, especially in the anti-viral area, is dominated by non-sequence specific effects. This review discusses both the sequence and non-sequence specific biologic effects of PS oligomers, and attempts to more clearly indicate their ultimate therapeutic potential.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Stein CA,Tonkinson JL,Yakubov Ldoi
10.1016/0163-7258(91)90032-hsubject
Has Abstractpub_date
1991-12-01 00:00:00pages
365-84issue
3eissn
0163-7258issn
1879-016Xpii
0163-7258(91)90032-Hjournal_volume
52pub_type
杂志文章,评审abstract::Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium's therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurot...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2010.07.006
更新日期:2010-11-01 00:00:00
abstract::The endothelins and sarafotoxins are two structurally related families of potent vasoactive peptides. Although the physiological functions of these peptides are not entirely clear, the endothelins are probably involved in pathophysiological conditions such as hypertension and heart failure. This review summarizes the ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(92)90030-4
更新日期:1992-01-01 00:00:00
abstract::Type I signal peptidases are essential membrane-bound serine proteases that function to cleave the amino-terminal signal peptide extension from proteins that are translocated across biological membranes. The bacterial signal peptidases are unique serine proteases that utilize a Ser/Lys catalytic dyad mechanism in plac...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章
doi:10.1016/s0163-7258(00)00064-4
更新日期:2000-07-01 00:00:00
abstract::Patients of congenital diseases such as Down syndrome (DS) and Duchenne muscular dystrophy (DMD) have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Althou...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2012.02.001
更新日期:2012-06-01 00:00:00
abstract::Activation of receptors coupled to inhibitory G proteins (Galpha i/o) has opposing consequences for cyclic AMP accumulation and the activity of cyclic AMP-dependent protein kinase, depending on the duration of stimulation. Acute activation inhibits the activity of adenylate cyclase, thereby attenuating cyclic AMP accu...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2004.12.005
更新日期:2005-06-01 00:00:00
abstract::Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alt...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.03.006
更新日期:2016-05-01 00:00:00
abstract::Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Depressed patients generally display co-morbid symptoms, and depression frequently accompanies other serious disorders. Currently available drugs display limited efficacy and a pronounced delay to onset o...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.11.006
更新日期:2006-05-01 00:00:00
abstract::Conditional gene knockout represents an extremely powerful approach to study the function of single genes in the nervous system. The Cre-LoxP system is the most advanced technology for spatial and temporal control of genetic inactivation, and there is rapid progress using this methodology in neuroscience research. In ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2006.12.003
更新日期:2007-03-01 00:00:00
abstract::The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called "cardiovascular risk factors" are associated with endothelial dys...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2014.06.003
更新日期:2014-12-01 00:00:00
abstract::Pericytes and other perivascular stem cells are of growing interest in orthopedics and tissue engineering. Long regarded as simple regulators of angiogenesis and blood pressure, pericytes are now recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.08.003
更新日期:2017-03-01 00:00:00
abstract::Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormo...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.09.004
更新日期:2009-01-01 00:00:00
abstract::Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as bio...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107588
更新日期:2020-09-01 00:00:00
abstract::Hypoxia inducible factor (HIF) is an oxygen-sensitive transcription factor that enables aerobic organisms to adapt to hypoxia. This is achieved through the transcriptional activation of up to 200 genes, many of which are critical to cell survival. Under conditions of normoxia, the hydroxylation of HIF by prolyl hydrox...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2012.07.005
更新日期:2012-10-01 00:00:00
abstract::Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain. Dynorphins are members of the opioid peptide family and preferentially bind to kappa opioid receptors. In line with their localizat...
journal_title:Pharmacology & therapeutics
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.pharmthera.2009.05.006
更新日期:2009-09-01 00:00:00
abstract::Mammals dispose of cholesterol mainly through 7alpha-hydroxylated bile acids, and the enzyme catalyzing the 7alpha-hydroxylation, cholesterol 7alpha-hydroxylase (CYP7A1), has a deep impact on cholesterol homeostasis. In this review, we present the study of regulation of CYP7A1 as a good exemplification of the extraord...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.08.003
更新日期:2007-12-01 00:00:00
abstract::The selective 5-HT2C receptor agonist lorcaserin, in conjunction with lifestyle modification, was approved by the FDA in 2012 for weight management. It has been marketed in the US as Belviq® since 2013. This article provides a review of the preclinical and clinical pharmacology of lorcaserin, including its pharmacokin...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2019.107417
更新日期:2020-01-01 00:00:00
abstract::In the past 4 years, RNA interference (RNAi) has become widely used as an experimental tool to analyse the function of mammalian genes, both in vitro and in vivo. By harnessing an evolutionary conserved endogenous biological pathway, first identified in plants and lower organisms, double-stranded RNA (dsRNA) reagents ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.03.004
更新日期:2005-08-01 00:00:00
abstract::Osteoporosis is defined as a progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The clinical relevance of osteoporosis derives from the fractures that it produces. More th...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(02)00164-x
更新日期:2002-01-01 00:00:00
abstract::Pulmonary arterial hypertension is a progressive, fatal disease. Current treatments including prostanoids, endothelin-1 (ET-1) antagonists, and phosphodiesterase (PDE) inhibitors, have sought to address the pulmonary vascular endothelial dysfunction and vasoconstriction associated with the condition. These treatments ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.10.002
更新日期:2009-01-01 00:00:00
abstract::In addition to their prominent roles in the control of reproduction, estrogens are important modulators of energy balance, as evident in conditions of deficiency of estrogens, which are characterized by increased feeding and decreased energy expenditure, leading to obesity. AMP-activated protein kinase (AMPK) is a ubi...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2017.03.014
更新日期:2017-10-01 00:00:00
abstract::The tropomyosin receptor kinase (TRK) family includes TRKA, TRKB, and TRKC proteins, which are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Binding of neurotrophins to TRK proteins induces receptor dimerization, phosphorylation, and activation of the downstream signaling cascades via PI3K, RAS/MAPK/ERK, and ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2017.02.006
更新日期:2017-05-01 00:00:00
abstract::Drug candidate and toxicity screening processes currently rely on results from early-stage in vitro cell-based assays expected to faithfully represent essential aspects of in vivo pharmacology and toxicology. Several in vitro designs are optimized for high throughput to benefit screening efficiencies, allowing the ent...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2012.01.001
更新日期:2012-04-01 00:00:00
abstract::Asthma is a chronic disorder characterized by persistent inflammation of the airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells, and release of proinflammatory cytokines and lipid mediators. The natural resolution of airway inflammation is now recognized as an active host response, with hi...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.01.004
更新日期:2018-06-01 00:00:00
abstract::The pharmaceutical industry offers the world's population alleviation and cure from a variety of medical conditions, while also contributing to the economic performance of many countries. The potential importance of these characteristics have made the industry an area of intense debate, criticism and praise. This revi...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(95)00002-x
更新日期:1995-05-01 00:00:00
abstract::Macrovascular complications of diabetes, including diabetic cardiovascular disease (CVD), occur through a number of hyperglycaemia-induced mechanisms that include generation of oxidative stress, accumulation of advanced glycation end-products (AGE) and activation of protein kinase C (PKC). Cardiac oxidative stress is ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.11.013
更新日期:2017-04-01 00:00:00
abstract::Coronary microvessels play a pivotal role in determining the supply of oxygen and nutrients to the myocardium by regulating the coronary flow conductance and substance transport. Direct approaches analyzing the coronary microvessels have provided a large body of knowledge concerning the physiological and pharmacologic...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(00)00057-7
更新日期:2000-06-01 00:00:00
abstract::The PI3K/Akt/mTOR pathway is the most frequently known activated aberrant pathway in human cancers. Pathologic activation can occur at multiple levels along the signaling pathway by a variety of mechanisms, including point mutations, amplifications, and inactivation of tumor suppressor genes. This pathway is also a kn...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2014.09.006
更新日期:2015-02-01 00:00:00
abstract::The cardiovascular system is highly organised in time; blood pressure (BP), heart rate (HR), peripheral resistance, pressure and the release/activity of vasodilating hormones all display pronounced circadian variations. Pathophysiological events within the cardiovascular system are also not random, as shown for instan...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.11.008
更新日期:2006-09-01 00:00:00
abstract::Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanin...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.08.002
更新日期:2007-12-01 00:00:00
abstract::Neutrophils form an essential part of innate immunity against infection. Cancer chemotherapy-induced neutropenia (CCIN) is a condition in which the number of neutrophils in a patient's bloodstream is decreased, leading to increased susceptibility to infection. Granulocyte colony-stimulating factor (GCSF) has been the ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2019.107403
更新日期:2019-12-01 00:00:00