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Yu G.,Beijing Institute of Pharmacology and Toxicology
Digestive diseases and sciences | Year: 2014

Ilaprazole is a novel proton pump inhibitor that has been marketed as an oral therapy for acid-related diseases in China and Korea. This study aimed to compare the gastroprotective effects of intravenous and enteral ilaprazole in rat models. The rats were divided into 7-8 groups receiving vehicle, esomeprazole, and different doses of intravenous and enteral ilaprazole. The rats were then exposed to indomethacin (30 mg/kg, i.g.), or water-immersion stress and gastric lesions were examined. The effects of different treatments on histamine (10 μmol/kg/h)-induced acid secretion were also observed. Intravenous ilaprazole exhibited high antiulcer activity in a dose-dependent manner. Ilaprazole at a dose of 3 mg/kg decreased ulcer number and index to the same extent as 20 mg/kg esomeprazole. Moreover, the potency of intravenous ilaprazole is superior to that of intragastric ilaprazole. In anesthetized rats, the inhibitory effect of intravenous ilaprazole on histamine-induced acid secretion is faster and longer-lasting than that of intraduodenal ilaprazole. Intravenous ilaprazole is more potent than oral ilaprazole against indomethacin- or stress-induced gastric lesions, with faster and longer inhibition of acid secretion. Source


Zhang X.,Uppsala University | Wang B.,Beijing Institute of Pharmacology and Toxicology | Li J.-P.,Uppsala University
Matrix Biology | Year: 2014

Heparan sulfate proteoglycans (HSPGs), expressed on the cell surface and in the extracellular matrix of most animal tissues, have essential functions in development and homeostasis, and have been implicated in several pathological conditions. The functions of HSPGs are mainly mediated through interactions of the heparan sulfate (HS) polysaccharide side chains with different protein ligands. The molecular structure of HS is highly diverse, expressed in a cell-type specific manner. The flexible yet controlled structure of HS is primarily generated through a strictly regulated biosynthesis process and is further modified post-synthetically, such as desulfation by endosulfatases and fragmentation by heparanase. Heparanase is an endo-glucuronidase expressed in all tissues. The enzyme has been found up-regulated in a number of pathological conditions, implying a role in diseases mainly through degradation of HS. Emerging evidence demonstrates important roles of HS and heparanase in inflammatory reactions, particularly in the regulation of leukocyte activation and extravasation. Neuroinflammation is a common feature of various central nervous system disorders, thus it is a great interest to understand the implications of HS and heparanase in neuroinflammation. © 2013 International Society of Matrix Biology. Source


Zhang Y.,Beijing University of Chinese Medicine | Wang Z.-Z.,Beijing Institute of Pharmacology and Toxicology | Sun H.-M.,Beijing University of Chinese Medicine
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2012

Previous clinical trials have evaluated the association between Parkin p.Ser167Asn (c.601G>A) variant and Parkinson's disease (PD) risk. However, the results remain conflicting rather than conclusive. Therefore, we performed this meta-analysis to assess whether pooled results show the association. We performed structured literature searches for studies addressing the association between the Parkin p.Ser167Asn variant and PD risk. We conducted analyses of study characteristics, heterogeneity, and funnel plot asymmetry in analyses analogous to additive, dominant, recessive, and general genetic models with the odds ratio (OR) as the measure of association. When 15 eligible studies (n=4,739 subjects) were pooled into the meta-analysis, there was no evidence for significant association in additive genetic model between Parkin p. Ser167Asn variant and PD risk (OR=1.02, 95% confidence interval (CI)=0.83-1.25; P=0.866). The OR for the dominant model was 1.06 (95% CI=0.80-1.41) while the OR for the recessive model was 0.90 (95% CI=0.71-1.14). The OR for the heterozygous was 1.07 (95% CI=0.80-1.43) while the OR for the homozygotes was 1.19 (95% CI=0.81-1.74). In the subgroup analysis by ethnicity, no significant association was found in any genetic model. Begg's funnel plot and Egger's test provided visual and statistical evidences for funnel plot symmetry, suggesting no presence of publication bias. In summary, the meta-analysis strongly suggests that Parkin p. Ser167Asn variant is not associated with PD risk. © 2011 Wiley Periodicals, Inc. Source


Zhang Y.,Beijing Institute of Pharmacology and Toxicology
Nano Biomedicine and Engineering | Year: 2011

All of the natural substances can be viewed as particles. According to the sizes of particles, the natural substances may be classified at six levels from small to large, and heir functional spectra can be established in the order from simple to complex. They are respectively point particles (?ppspPs), fundamental structural particles (FSPs), chemical particles (ChPs), nanoparticles (NPs), macroparticles (MPs) and celestial particles (CePs). The particles in one of these levels have their independent functional activities and interaction patterns different from those in the levels lower than them, representing a new leaping. There are very close relations between the size and functions of the particles. It is especially suitablefor biological particles. As far as the present human knowledges, the activity of the PPs is the simplest without interactions; the activities of FSPs are rather complex, their interactions result in the production of various FSPs; ChPs have more complex activities, their interactions produce inumberous sorts of ions and molecules, forming the collorful chemical world; the functional activities of NPs are much more complex than those of the ChPs, their interactions cause the production of inumberous sorts of biological NPs with the characteristics of biological phenomenon; the functional activities of MPs are the most complicated, their interactions result in the production of hundreds and southands sorts of individual living bodies with the feature of high level functional activities such as learnig, thinking and reproduction; we still know little about the functional activities of the CePs. In conclusion, the establishent of the size-function spectrum will be helpful to investigate the substance world as a whole, and reveal the interaction principles of the particles and biological essential fundamentals. © 2011 Y. Zhang, et al. Source


Jin X.-F.,Beijing Institute of Pharmacology and Toxicology | Jin X.-F.,Central South University | Wu N.,Beijing Institute of Pharmacology and Toxicology | Wang L.,Beijing Institute of Pharmacology and Toxicology | Li J.,Beijing Institute of Pharmacology and Toxicology
Cellular and Molecular Neurobiology | Year: 2013

As a class of important endogenous small noncoding RNAs that regulate gene expression at the posttranscriptional level, microRNAs (miRNAs) play a critical role in many physiological and pathological processes. It is believed that miRNAs contribute to the development, differentiation, and synaptic plasticity of the neurons, and their dysregulation has been linked to a series of diseases. MiRNAs exist in the tissues and as circulating miRNAs in several body fluids, including plasma or serum, cerebrospinal fluid, urine, and saliva. There are significant differences between the circulating miRNA expression profiles of healthy individuals and those of patients. Consequently, circulating miRNAs are likely to become a novel class of noninvasive and sensitive biomarkers. Although little is known about the origin and functions of circulating miRNAs at present, their roles in the clinical diagnosis and prognosis of diseases make them attractive markers, particularly for tumors and cardiovascular diseases. Until now, however, there have been limited data regarding the roles of circulating miRNAs in central nervous system (CNS) diseases. This review focuses on the characteristics of circulating miRNAs and their values as potential biomarkers in CNS diseases, particularly in Alzheimer's disease, Huntington's disease, multiple sclerosis, schizophrenia, and bipolar disorder. © 2013 Springer Science+Business Media New York. Source

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