Abstract:
:The last quarter of a century has witnessed remarkable progress in the understanding of phosphoinositide 3-kinases (PI3K) signalling and their involvement in different diseases such as cancer, diabetes and inflammation. Nevertheless, many questions remain open and among these the role of genetic and epigenetic regulation of PI3K isoforms is one of the most prominent. Emerging evidence Indicates that levels of isoforms can be modulated upon stimulation or in both physiological and pathological conditions including increased gene copy number and transcription regulation. In addition, an intriguing role for epigenetic regulation of PI3K expression, caused by mechanisms other than changes in the underlying DNA sequence, are starting to get appreciated. In this review, we summarize the genetic and epigenetic regulation of PI3Ks in physiology and the role played by their alterations in different diseases.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Fyffe C,Buus R,Falasca Msubject
Has Abstractpub_date
2013-01-01 00:00:00pages
680-6issue
4eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20120926-10journal_volume
19pub_type
杂志文章,评审abstract::Our clinical observations proved that the the duodenal ulcer in patients healed without any inhibition of gastric acid secretion (1965), and the healing rates of atropine vs cimetidine vs Carbenoxolone were equal and superior to that of placebo in randomized, prospective and multiclinical study of DU patients (1978). ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796197016
更新日期:2011-01-01 00:00:00
abstract::The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190717104547
更新日期:2019-01-01 00:00:00
abstract::During the last years, mass spectrometry has revolutionised protein biochemistry and has advanced to a superior tool for the identification and detailed analysis of peptides and proteins. The high throughput allowed by some mass spectrometry platforms has enabled the important step from analysis of individual proteins...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054546932
更新日期:2005-01-01 00:00:00
abstract::Human serum albumin (HSA) is one of the major carrier proteins in the body and constitutes approximately half of the protein found in blood plasma. It plays an important role in lipid metabolism, and its ability to reversibly bind a large variety of pharmaceutical compounds makes it a crucial determinant of drug pharm...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150304163447
更新日期:2015-01-01 00:00:00
abstract::The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases ca...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797247541
更新日期:2011-01-01 00:00:00
abstract::Several lines of evidence support a mutual relationship between the nervous system and the immune system. Therefore, it is not surprising that some neuropsychiatric disorders are also characterized by immune abnormalities. In patients with phobic disorders and in patients with migraine without aura some common immune ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454234
更新日期:2003-01-01 00:00:00
abstract::Epicardial adipose tissue is not only a specific adipose tissue depot but also an active endocrine organ producing numerous substances with an important role in the development of obesity-related heart diseases. It is located between myocardium and visceral pericardium and consists predominantly of adipocytes, immunoc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180110102125
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Drugs acting on the cardiovascular and central nervous system often display relatively fast clinical responses, which may differ in neonates compared to children and adults. Introduction of bedside monitoring tools might be of additional value in the pharmacodynamic (PD) assessment of such drugs in neonates....
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170918124419
更新日期:2017-01-01 00:00:00
abstract::It is generally accepted that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are related to insulin resistance and type 2 diabetes. Mitochondria use substrates from lipid and glucose metabolism in order to generate ATP, and when mitochondrial O2 consumption is decreased due to an altered metabolism th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160209152033
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabet...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201103122813
更新日期:2020-11-03 00:00:00
abstract::The acid-base balance of cells is related to the concentration of free H⁺ ions. These are highly reactive, and their intracellular concentration must be regulated to avoid detrimental effects to the cell. H⁺ ion dynamics are influenced by binding to chelator substances ('buffering'), and by the production, diffusion a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799504920
更新日期:2012-01-01 00:00:00
abstract::In recent years, new strategies in cancer therapy have been developed targeting key signaling molecules in the receptor tyrosine kinase signal transduction pathway. In contrast, most therapeutical concepts to manipulate G protein-coupled receptors (GPCR)-mediated disorders are still limited to the use of receptor-spec...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384367
更新日期:2004-01-01 00:00:00
abstract::Parkinson's disease (PD) is a common neurodegenerative disorder characterized by cardinal features of tremor, bradykinesia, rigidity and postural instability. In addition to the motor symptoms patients experience cognitive decline eventually resulting in severe disability. Pathologically PD is characterized by neurode...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043453162
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. METHODS:This arti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666171114170642
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:A wide class of human diseases and neurodegenerative disorders, such as Alzheimer's disease, is due to the failure of a specific peptide or protein to keep its native functional conformational state and to undergo a conformational change into a misfolded state, triggering the formation of fibrillar cross-β s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160518141911
更新日期:2016-01-01 00:00:00
abstract::The antifungal agents for systemic mycoses are only a few in number. Among them amphotericin-B is still the most widely used drug, but substantial side effects including nephrotoxicity limits its clinical usefulness. Efforts to lower the toxicity are synthesis of AMPH-B analogues such as AMPH-B esters and encapsulatio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023395916
更新日期:2002-01-01 00:00:00
abstract::The skin is often introduced as the largest organ of the human body which - being uniquely exposed to external stress - faces several types of challenges, from physical, chemical, biological, and immunological origin. Therefore, the skin is also a site where inflammation, oxidative stress and cellular damage occurs re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180717155953
更新日期:2018-01-01 00:00:00
abstract::The CCN family of growth factors is composed of six structurally related proteins including the cysteine-rich 61 (Cyr61), connective tissue growth factor (CTGF), nephroblastoma overexpressed (NOV), Wnt-1 induced secreted protein-1 (WISP-1), WISP-2 and WISP-3. Each family member consists of four conserved cysteine rich...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043382567
更新日期:2004-01-01 00:00:00
abstract::Fusion proteins have been well-studied and widely applied in biopharmaceutics. Albumin fusion proteins are simple to construct, easy to purify, and stable to formulate. One main application of fusion protein is to extend the plasma half-life of therapeutic proteins and peptides. Albiglutide for diabetes treatment is t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150302120047
更新日期:2015-01-01 00:00:00
abstract::Ablation has become an important treatment for many pediatric patients with common supraventricular tachycardias (SVTs). Many multicenter studies have documented that radiofrequency (RF) catheter ablation is a safe and effective procedure for treatment of a large variety of SVTs in children and adults with a high succ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784007680
更新日期:2008-01-01 00:00:00
abstract::Free energy simulations are a powerful tool to study molecular recognition. The most rigorous variants can provide in depth understanding for a particular system, but are not suited for high throughput application to large libraries of compounds. Related, but less expensive methods are increasingly popular, including ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319230008
更新日期:2013-01-01 00:00:00
abstract::Malignant tumors aberrantly overexpress various embryonic genes and proto-oncogenes, including a variety of cancer-testis antigens (CTAs). CTAs belong to a class of testis-derived proteins which are only expressed in germ cells in the male testis, and the expression of CTA genes is entirely silenced in the adult somat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666141211154707
更新日期:2015-01-01 00:00:00
abstract::Extracellular matrix (ECM) is composed of large collagen fibrils. Glycoproteins, such as fibronectin, can bind to collagen or form their own networks. Collagen fibrils are also decorated by proteoglycans, proteins that have large glycosaminoglycan sidechains. In addition, extracellular space often contains hyaluronan,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787846720
更新日期:2009-01-01 00:00:00
abstract::Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts on motoneurons and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990341
更新日期:2013-01-01 00:00:00
abstract::Management of hypertension has evolved steadily through 25 years of major clinical trials results modifying both the definition of hypertension and clinical management strategies. Trials experience in heart failure is much less extensive given the far smaller therapeutic market and traditionally often followed on the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454504
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Sulfur mustard (SM)-induced airway injuries and chronic obstructive pulmonary disease (COPD) are characterized by chronic inflammation of the respiratory tract and share some similarities regarding the cellular and molecular mechanisms orchestrating airway destruction. Since available data regarding the immu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160307150818
更新日期:2016-01-01 00:00:00
abstract::Prion diseases are fatal neurodegenerative disorders associated with conformational conversion of the cellular prion protein (PrP(C)) into an isoform designated PrP(Sc). The pathogenic mechanism that links this conformational distortion with the development of prion diseases is unknown. PrP(C) is a GPI-anchored cell s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698873
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVES:To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. METHODS:Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy ((1)H-MRS) measurements were performed prior to...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799316163
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:New Oral Anticoagulants (NOACs) are effective and widely used to prevent and treat thromboembolic diseases, but the response to NOACs differs according to ABCB1 genotypes. OBJECTIVE:We investigated the effects of ABCB1 genotypes on the pharmacokinetics and clinical outcomes of NOACs. METHODS:We searched Pu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612824666181018153641
更新日期:2018-01-01 00:00:00
abstract::During the last decade immunomodulatory treatments have been shown to influence the natural course of multiple sclerosis (MS). However, demyelination in the central nervous system (CNS) still occurs and repair mechanisms are incomplete leading to neurological deficits. Currently, there is no therapy available to promo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206775193118
更新日期:2006-01-01 00:00:00