The internal ribosome entry site (IRES) has been widely used to coexpress heterologous gene products by a message from single promoter. However, little is known about the efficiency of IRES-dependent second expression in comparison with that first expression. This study was undertaken characterize relative bicistronic vector, which derived 5′ untranslated regions encephalomyocarditis virus (EMCV). compared cap-dependent several cultured cell lines and mouse liver vivo. ranged 6 100% (in most...

Abstract Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede repair processes. Herein, an innovative ultrasound‐modulatable hydrogel platform with selenoprotein‐mediated antioxidant effects to promote injury is presented. This encapsulates oxygen‐enriched selene‐incorporated thin‐shell silicon methacrylate gelatin (O 2 ‐PSSG). The resultant construct orchestrates modulation bone‐defect microenvironment,...

Kupffer cells (KCs) rapidly remove intravenously injected adenovirus (Ad) vectors from the circulation. A better understanding of mechanisms involved could suggest strategies to improve Ad gene delivery by suppressing or evading KC uptake. We recently showed that clearance type 5 KCs does not involve interaction with well-established receptors, namely, integrins coxsackievirus and receptor (J. S. Smith, Z. Xu, J. Tian, C. Stevenson, A. P. Byrnes, Hum. Gene Ther. 19:547-554, 2008). In current...

Understanding innate immunity is key to improving the safety of adenovirus (Ad) vectors for systemic gene therapy. Ad has been shown activate complement in vitro, but activation after injection vivo not directly measured. Using protein C3a as a marker activation, we show that types 2 and 5 human Ads cause rapid intravenous mice. Unexpectedly, mechanisms were different than those vitro. Antibodies critical by antibodies required vivo. The classical pathway was whereas involved both...

Adenovirus serotype 5 (Ad5) naturally infects the liver after intravenous injection, making it a candidate for hepatocyte-directed gene transfer. While Ad5 can be efficient, most of dose is destroyed by Kupffer cells before reach hepatocytes. In contrast, bearing hexon from Ad6 (Ad5/6) evades cells. Ad5/6 dramatically increases hepatocyte transduction in BALB/c mice, has surprisingly little effect on C57BL/6 mice. To determine source this strain-specific difference, roles cells, sinusoidal...

When adenovirus (Ad) vectors are injected intravenously they rapidly taken up by Kupffer cells (KCs) in the liver. This results massive KC necrosis within minutes, followed a more gradual disappearance of KCs from It is not known how recognize Ad, or why Ad kills KCs. We used variety mutated and fiber-pseudotyped to evaluate capsid proteins influence uptake define viral that involved destruction found depletion liver was partially dependent on interactions between integrins, but independent...

ABSTRACT Natural IgM inhibits gene transfer by adenovirus type 5 (Ad5) vectors. We show that polyreactive natural antibodies bind to Ad5 and inhibition of liver transduction depends on Kupffer cells. By manipulating concentration in vivo , we demonstrate a concentration-dependent manner. further differences between BALB/c C57BL/6 mice contribute lower efficiency mice.

We previously developed single adenovirus (Ad) vectors that contained the components for a tetracycline-regulatable gene-expression system in E1 and E3 deletion regions, showed Ad containing tet-on exhibit much inferior regulation of transgene expression than those tet-off system. In many cases, may be preferable because its positive expression. To this end, present study, by introducing latest generation reverse tetracycline-responsive transcriptional activator (rtTA2s-M2 or rtTA2s-S2)...

RNA interference (RNAi) is a powerful tool for the knockdown of gene expression. Here, we report on development an adenovirus (Ad) vector-mediated doxycycline (Dox)-inducible small interfering (siRNA) expression system. We used this siRNA system to control p53 and c-Myc in human cancer cells. Coinfection Ad vectors containing under Dox-inducible H1 promoter expressing tetracycline repressor inhibited levels dose-dependent manner with both Dox viral dose. Regulated silencing was obtained....

Innate immune responses are a major barrier to safe systemic gene therapy with adenovirus (Ad) vectors. We show that intravenous (IV) injection of rats Ad5 vectors causes novel rapid shock reaction involves hypotension, hemoconcentration, tissue edema, and vasocongestion, notable pathology in the pancreas gastrointestinal system. for first time this is dependent on platelet-activating factor (PAF), lipid signaling molecule known inducer. Ad upregulated PAF within 5 minutes vivo, antagonists...

In recent years, there has been a noticeable increase in research on krill oil (KO) for its health benefits. However, the action of KO lowering blood pressure (BP) not studied yet. Therefore aim this study was to assess ability long-term supplementation lower systolic BP (SBP) spontaneously hypertensive rats (SHRs) and Sprague Dawley (SD) rats.Compared with blank control (BC) SHRs administered edible soybean oil, high-dose (500 mg kg-1 body weight (BW)) KO-supplemented 2nd, 3rd, 4th 5th...

Adenoviral vectors (AdV) activate multiple signaling pathways associated with innate immune responses, including mitogen-activated protein kinases (MAPKs). In this study, we investigated how systemically-injected AdVs two MAPK (p38 and ERK) the contribution of these to AdV-induced cytokine chemokine responses in mice. Mice were injected intravenously either a helper-dependent Ad2 vector that does not express viral genes or transgenes, mutant ts1, which is defective endosomal escape. We found...

The majority of adenovirus (Ad) vectors are based on human Ad type 5, which is a member species C. Species C also includes the closely-related types 1, 2, 6, 57 and 89. It known that coagulation factors bind to Ad5 hexon play key role in liver tropism vectors, but it unclear how affect derived from other Ads. We evaluated both vitro following intravenous injection mice. To assess impact differences, we constructed chimeric contain hypervariable regions types, including with mutations...

Objectives The aim is to discover α-glucosidase/acetylcholinesterase inhibitors as lead compounds from a traditional herbal prescription of Qi-Li-Qiang-Xin capsule (QLQX). Methods A novel strategy combining time-based fractionation, LC-QTOF-MS, enzymatic activity assay, molecular docking and component-target association analysis was performed QLQX. Time-based fractionation combined with assay used find the distribution period active in prescription. LC-QTOF-MS analyze structure compounds....

Pharmacognosy Magazine,2017,13,51,454-458.DOI:10.4103/pm.pm_205_16Published:July 2017Type:Original ArticleAuthors:Zhili Xu, Mingbo Zhang, Deqiang Dou, Xiaojun Tao, and Tingguo Kang Author(s) affiliations:Zhili Department of Pharmacology, College Pharmacy, Liaoning University Traditional Chinese Medicine, Dalian 116600, P.R. China Abstract:Background: Berberine is a natural isoquinoline alkaloid possessing various pharmacological effects, particularly apparent in the treatment diarrhea, but...

Adenovirus vectors are widely used in gene therapy clinical trials, and preclinical studies with these often conducted mice. It is therefore critical to understand whether mouse adequately predict the behavior of adenovirus humans. The most commonly-used derived from serotype 5 (Ad5). Ad5 hexon protein can bind coagulation factor X (FX), binding FX has a major impact on vector interactions other blood proteins. In serum, protects neutralization by natural antibodies complement. current...

The aims of this study were to build an IBD mouse model and further observe the effects deoxyschisandrin on visceral sensitivity evaluate relevance brain-derived neurotrophic factor (BDNF) intestinal hypersensitivity mice. results showed that could depress contraction isolated smooth muscle, modulate gastrointestinal function, efficiently decrease disease activity index (DAI) mice, which proved had antidiarrheal animals. In colorectal distention (CRD) experiment, sensibility was increased in...