Abstract:
PURPOSE:Type I collagen accumulates during liver fibrosis primarily because α-complex protein-2 (αCP(2)), encoded by the poly(rC) binding protein 2 (PCBP2) gene, binds to the 3' end of the collagen mRNA and increases its half-life. This study aimed to reverse the pro-fibrogenic effect of alcohol on hepatic stellate cells (HSCs) by silencing the PCBP2 gene with siRNA. METHODS:The silencing effects of a series of predesigned PCBP2 siRNAs were evaluated in the rat hepatic stellate cell line, HSC-T6. The pro-fibrogenic effects of alcohol on the expression levels of PCBP2 and type-I collagen were examined by several methods. The effect of PCBP2 siRNA on the stability of type I collagen α1(I) mRNA was investigated by an in vitro mRNA decay assay. RESULTS:We identified one potent PCBP2 siRNA that reversed the alcohol-induced expression of PCBP2 in HSCs. The decay rate of the collagen α1(I) mRNA increased significantly in HSCs treated with the PCBP2 siRNA. CONCLUSION:This study provides the first evidence that alcohol up-regulates the expression of PCBP2, which subsequently increases the half-life of collagen α1(I) mRNA. Silencing of PCBP2 using siRNA may provide a promising strategy to reverse the alcohol-induced pro-fibrogenic effects in HSCs.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Shukla RS,Qin B,Wan YJ,Cheng Kdoi
10.1007/s11095-011-0475-9subject
Has Abstractpub_date
2011-12-01 00:00:00pages
3058-68issue
12eissn
0724-8741issn
1573-904Xjournal_volume
28pub_type
杂志文章abstract::A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycourso...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018907825281
更新日期:1994-05-01 00:00:00
abstract::Moexipril [2-[(1-ethoxycarbonyl)-3-phenylpropyl]amino-1-oxopropyl]-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (S,S,S)], an ester prodrug of an ACE inhibitor, was formulated in controlled-release preparations with a range of in vitro release rates, to provide a prolonged input of drug in vivo. Howe...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015919413103
更新日期:1989-09-01 00:00:00
abstract::Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. H...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018940122382
更新日期:1994-12-01 00:00:00
abstract:PURPOSE:The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. METHODS:Magnetic glyconanoparticl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1021-8
更新日期:2014-06-01 00:00:00
abstract:PURPOSE:The aim of this study is to extend our previous studies to investigate the TerplexDNA synthetic gene carrier system in pharmacokinetics, biodistribution, and gene expression in major organs after systemic administration. METHODS:The stability of the TerplexDNA system was analyzed in vitro with a serum incubati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1013081710135
更新日期:2001-09-01 00:00:00
abstract:PURPOSE:To investigate if gamma-Hydroxybutyrate (GHB) tolerance is mediated by alterations in GHB systemic pharmacokinetics, transport (blood brain barrier (BBB) and neuronal) or membrane fluidity. MATERIALS AND METHODS:GHB tolerance in rats was attained by repeated GHB administration (5.31 mmol/kg, s.c., QD for 5 day...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9066-6
更新日期:2006-09-01 00:00:00
abstract::Alpha- and beta-cyclodextrins and their hydroxypropyl derivatives were converted by the reaction with chlorosulfonic acid in pyridine to the corresponding sulfates. Cyclodextrin sulfates were shown by fast-atom bombardment mass spectrometry (negative ion mode, triethanolamine matrix) to be mixtures with nearly symmetr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015854402122
更新日期:1991-09-01 00:00:00
abstract::Over the last few decades, intraperitoneal (IP) local drug delivery, providing high drug concentrations with prolonged retention in the peritoneal cavity, has opened a new horizon for the management of life-threatening peritoneal disorders, such as peritoneal carcinomatosis (PC). However, clinical translation of this ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-020-02818-8
更新日期:2020-06-03 00:00:00
abstract:PURPOSE:To identify the aggregation mechanism and the stability characteristics of three different monoclonal antibodies under acidic conditions. METHODS:The aggregation kinetics is analyzed by a combination of light scattering, size exclusion chromatography and fluorescence techniques and the aggregation data are cor...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0885-3
更新日期:2013-03-01 00:00:00
abstract::Various derivatives of the C-terminal amide group in N-protected amino acid and peptide amides were synthesized to assess their suitability as prodrug forms with the aim of protecting the amide or peptide bond against cleavage by alpha-chymotrypsin. Whereas N-acetylation, N-hydroxymethylation, and N-phthalidylation di...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015854718903
更新日期:1991-12-01 00:00:00
abstract:PURPOSE:To synthesize a trifluorinated bile acid that can be used for (19)F magnetic resonance imaging (MRI) of bile acid enterohepatic circulation, characterize its in vitro transporter affinity, stability, and (19)F-MRI signal, and assess its ability to concentrate in the gallbladder of C57BL/6 mice. METHODS:Target ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0963-6
更新日期:2013-05-01 00:00:00
abstract:PURPOSE:To investigate cellular uptake pathways of novel anionic siRNA-lipoplexes as a function of formulation composition. METHODS:Anionic formulations with anionic lipid/Ca(2+)/siRNA ratio of 1.3/2.5/1 (AF1) and 1.3/0.3/1 (AF2) were utilized. Uptake mechanisms were investigated using uptake inhibition and co-localiz...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0952-9
更新日期:2013-04-01 00:00:00
abstract::The conditions under which the absorption enhancer palmitoyl L-carnitine chloride (PCC) improved the bioavailability of the poorly absorbed antibiotic cefoxitin throughout the rat intestine has been studied. Cefoxitin alone was appreciably absorbed only in the duodenum (31% vs less than 7% elsewhere). PCC solutions (3...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018977021183
更新日期:1992-02-01 00:00:00
abstract:PURPOSE:To investigate the underlying cause for the observed differences in self-associating and viscoelastic behavior between two monoclonal antibodies, MAb1, and MAb2. METHODS:Several mutants were designed by swapping charged residues in MAb1 with those present in MAb2 at their respective positions and vice versa. R...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0410-0
更新日期:2011-07-01 00:00:00
abstract:PURPOSE:The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. METHOD:Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1335-1
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:To examine whether the glass transition temperature (Tg) of freeze-dried formulations containing polymer excipients can be accurately predicted by molecular dynamics simulation using software currently available on the market. Molecular dynamics simulations were carried out for isomaltodecaose, a fragment of de...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023831102203
更新日期:2003-06-01 00:00:00
abstract:PURPOSE:Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we inv...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1324-4
更新日期:2014-09-01 00:00:00
abstract::The plasma concentration-time profiles and pharmacokinetics were characterized for nicotine and its major metabolite, cotinine, after multiple daily application of a nicotine user-activated transdermal therapeutic system (UATTS) to nine healthy smokers. The volunteers abstained from smoking 24 hr prior to and during t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015810019076
更新日期:1991-03-01 00:00:00
abstract:PURPOSE:Safe, targeted delivery of therapeutics remains a focus of drug/gene delivery, the aim being to achieve optimal efficacy while minimising off-target delivery. Dendrimers have a vast array of potential applications and have great potential as gene and drug delivery tools. We previously reported the development o...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1408-1
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:Cell-based permeability screens are widely used to identify drug-P-glycoprotein (PGP) interaction in vitro. However, their reliability in predicting the impact of PGP on human drug pharmacokinetics is poorly defined. The aim was to determine whether a quantitative relationship exists between PGP-mediated altera...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000026434.82855.69
更新日期:2004-05-01 00:00:00
abstract::Pediatric brain tumors are most common cancers in childhood and among the leading causes of death in children. Chemotherapy has been used as adjuvant (i.e. after) or neoadjuvant (i.e. before) therapy to surgery and radiotherapy for the management of pediatric brain tumors for more than four decades and gained more att...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-013-1196-z
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:The purpose of this study was to investigate the pH-dependent passive and active transport of weakly basic drugs across the human intestinal epithelium. METHODS:The bidirectional pH-dependent transport of weak bases was studied in Caco-2 cell monolayers in the physiologic pH range of the gastrointestinal tract...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1025032511040
更新日期:2003-08-01 00:00:00
abstract:PURPOSE:In vitro in vivo correlation (IVIVC) is a biopharmaceutical tool recommended for use in formulation development. When validated, IVIVC can be used to set dissolution limits and, based on the dissolution limits, as a surrogate for an in vivo study. The purpose of this paper is to study the various methods used t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1349-8
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:The heats of reaction between the enantiomers and racemates of ibuprofen and naproxen and human serum albumin (HSA) are to be measured with and without the addition of octanoic acid. The effects of octanoic acid on the free energies of interaction between the drugs and HSA is to be determined and compared to th...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016066325476
更新日期:1996-01-01 00:00:00
abstract::In this study the intestinal degradation and absorption of a synthetic pentapeptide, metkephamid, were investigated in the rat by determination of its wall permeabilities in the small and large intestine and the extent and mechanism of its intestinal degradation. The peptide was metabolized in the gut wall through con...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018962415287
更新日期:1994-04-01 00:00:00
abstract:PURPOSE:The objective of this investigation was to determine, using the Caco-2 cell culture model, the extent to which the paracellular and transcellular routes contributed to the transport of passively absorbed drugs. An effort was also made to determine the controlling factors in this process. METHODS:We selected a ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012111008617
更新日期:1997-09-01 00:00:00
abstract:PURPOSE:Adjuvants are required to ensure the efficacy of subunit vaccines. Incorporating molecular immunopotentiators within particles could overcome drawbacks of molecular adjuvants (such as solubility and toxicity), and improve adjuvanticity of particles, achieving stronger adjuvant activity. Aim of this study is to ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1666-6
更新日期:2015-09-01 00:00:00
abstract:PURPOSE:To evaluate the reaction of a large series of pharmacologically significant 1,4-dihydropyridine (1,4-DHP) compounds with superoxide (O2.-) in dimethylsulfoxide using differential pulse voltammetry and controlled potential electrolysis. METHODS:Differential pulse voltammetry was used to track the consumption of...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1022291624933
更新日期:2003-02-01 00:00:00
abstract::Knowledge Management (KM) is a key enabler for achieving quality in a lifecycle approach for production of biopharmaceuticals. Due to the important role that it plays towards successful implementation of Quality by Design (QbD), an analysis of KM solutions is needed. This work provides a comprehensive review of the in...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-016-2043-9
更新日期:2017-02-01 00:00:00
abstract:PURPOSE:To determine whether a Protected Graft Copolymer (PGC) containing fatty acid can be used as a stabilizing excipient for GLP-1 and whether PGC/GLP-1 given once a week can be an effective treatment for diabetes. METHODS:To create a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty ac...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0542-2
更新日期:2012-01-01 00:00:00