Institute of Laboratory Animal Science

Beijing, China

Institute of Laboratory Animal Science

Beijing, China
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Bao X.,Peking Union Medical College | Feng M.,Peking Union Medical College | Wei J.,Peking Union Medical College | Han Q.,Peking Union Medical College | And 8 more authors.
European Journal of Neuroscience | Year: 2011

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. Although BMSCs-induced angiogenesis is considered important for neurological functional recovery, the neurorestorative mechanisms are not fully understood. We examined whether BMSCs-induced angiogenesis enhances cerebral tissue perfusion and creates a suitable microenvironment within the ischemic brain, which in turn accelerates endogenous neurogenesis and leads to improved functional recovery. Adult female rats subjected to 2h middle cerebral artery occlusion (MCAO) were transplanted with a subpopulation of human BMSCs from male donors (Flk-1+ hBMSCs) or saline into the ipsilateral brain parenchymal at 3days after MCAO. Flk-1+ hBMSCs-treated rats exhibited significant behavioral recovery, beginning at 2weeks after cerebral ischemia compared with controls. Moreover, rats treated with Flk-1+ hBMSCs showed increased glucose metabolic activity and reduced infarct volume. Flk-1+ hBMSCs treatment significantly increased the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, promoted angiogenesis, and facilitated cerebral blood flow in the ischemic boundary zone. Further, Flk-1+ hBMSCs treatment enhanced proliferation of neural stem/progenitor cells (NSPCs) in the subventricular zone and subgranular zone of the hippocampus. Finally, more NSPCs migrated toward the ischemic lesion and differentiated to mature neurons or glial cells with less apoptosis in Flk-1+ hBMSCs-treated rats. These data indicate that angiogenesis induced by Flk-1+ hBMSCs promotes endogenous neurogenesis, which may cause functional recovery after cerebral ischemia. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Bomsel M.,French National Center for Scientific Research | Bomsel M.,French Institute of Health and Medical Research | Bomsel M.,University of Paris Descartes | Tudor D.,French National Center for Scientific Research | And 26 more authors.
Immunity | Year: 2011

Human immunodeficiency virus (HIV)-1 is mainly transmitted mucosally during sexual intercourse. We therefore evaluated the protective efficacy of a vaccine active at mucosal sites. Macaca mulatta monkeys were immunized via both the intramuscular and intranasal routes with an HIV-1 vaccine made of gp41-subunit antigens grafted on virosomes, a safe delivery carrier approved in humans with self-adjuvant properties. Six months after 13 vaginal challenges with simian-HIV (SHIV)-SF162P3, four out of five vaccinated animals remained virus-negative, and the fifth was only transiently infected. None of the five animals seroconverted to p27. gag-SIV. In contrast, all 6 placebo-vaccinated animals became infected and seroconverted. All protected animals showed gp41-specific vaginal IgAs with HIV-1 transcytosis-blocking properties and vaginal IgGs with neutralizing and/or antibody-dependent cellular-cytotoxicity activities. In contrast, plasma IgGs totally lacked virus-neutralizing activity. The protection observed challenges the paradigm whereby circulating antiviral antibodies are required for protection against HIV-1 infection and may serve in designing a human vaccine against HIV-1-AIDS. © 2011 Elsevier Inc.

Jorns A.,Hannover Medical School | Rath K.J.,Hannover Medical School | Terbish T.,Hannover Medical School | Arndt T.,Hannover Medical School | And 4 more authors.
Endocrinology | Year: 2010

The prevention of diabetes by the immunomodulatory agent FTY720 (fingolimod) was studied in the LEW.1AR1-iddm (IDDM) rat, an animal model of human type 1 diabetes. Immune cell subtypes and cytokine profiles in pancreatic islets, secondary lymphoid tissue, and serum were analyzed for signs of immune cell activation. Animals were treated with FTY720 (1 mg/kg body weight) for 40 d starting on d 50 of life. Changes in gene and protein expression of cytokines, CD8 markers, monocyte chemoattractant protein-1, inducible NO synthase, and caspase 3 were evaluated. Treatment with FTY720 prevented diabetes manifestation and islet infiltration around d 60 of life, the usual time of spontaneous diabetes development. On d 120, 30 d after the end of FTY720 therapy, diabetes prevention persisted. However, six of 12 treated animals showed increased gene expression of IL-1β, TNF-α, and CD8 markers in pancreas-draining lymph nodes, indicating immune cell activation. In parallel, serum concentrations of these proinflammatory cytokines were increased. These six animals also showed macrophage infiltration without proinflammatory cytokine expression in a small minority (2-3%) of islets. Interestingly, regulatory T lymphocytes were significantly increased in the efferent vessels of the pancreas-draining lymph nodes only in animals without signs of immune cell activation but not in the rats with immune cell activation. This provides an indication for a lack of protective capacity in the animals with activated immune cells. Thus, FTY720 treatment prevented the manifestation of diabetes by promoting the retention of activated immune cells in the lymph nodes, thereby avoiding islet infiltration and β-cell destruction by proinflammatory cytokines. Copyright © 2010 by The Endocrine Society.

Tang T.,China Agricultural University | Zhang L.,Institute of Laboratory Animal Science | Gao R.,Institute of Laboratory Animal Science | Dai Y.,China Agricultural University | And 2 more authors.
Applied Microbiology and Biotechnology | Year: 2012

Bacterial magnetic particles (BMPs) are of interest as potential carriers of bioactive macromolecules, drugs, or liposomes. In this study, a high-pressure homogenizer was used to disrupt Magnetospirillum gryphiswaldense strain MSR-1 cells, and BMPs were purified. BMPs were labeled with fluorescence reagent 1,1'-dioctadecyl-3,3,3',3'tetramethylindocarbocianin perchlorate (DiI) and injected into the tail vein of BALB/c nude mice. Distribution of fluorescence signals of DiI-BMPs in vivo was examined using a whole-body fluorescence imaging system. The result showed that fluorescence signals were detected in liver, stomach, intestine, lungs, and spleen. However, transmission electron microscopy of ultrathin sections indicated that BMPs were mainly present in liver and lungs, but not in the other organs. BMPs could be useful as carriers for targeted drug therapy of diseases of the liver or lung. © Springer-Verlag 2012.

Memo M.,Imperial College London | Leung M.-C.,Imperial College London | Ward D.G.,University of Birmingham | Dos Remedios C.,University of Sydney | And 7 more authors.
Cardiovascular Research | Year: 2013

AimsThe pure form of familial dilated cardiomyopathy (DCM) is mainly caused by mutations in genes encoding sarcomeric proteins. Previous measurements using recombinant proteins suggested that DCM mutations in thin filament proteins decreased myofibrillar Ca2+ sensitivity, but exceptions were reported. We re-investigated the molecular mechanism of familial DCM using native proteins.Methods and resultsWe used the quantitative in vitro motility assay and native troponin and tropomyosin to study DCM mutations in troponin I, troponin T, and -tropomyosin. Four mutations reduced myofilament Ca2+ sensitivity, but one mutation (TPM1 E54K) did not alter Ca2+ sensitivity and another (TPM1 D230N) increased Ca2+ sensitivity. In thin filaments from normal human and mouse heart, protein kinase A (PKA) phosphorylation of troponin I caused a two- to three-fold decrease in myofibrillar Ca2+ sensitivity. However, Ca2+ sensitivity did not change with the level of troponin I phosphorylation in any of the DCM-mutant containing thin filaments (E40K, E54K, and D230N in -tropomyosin; R141W and ΔK210 in cardiac troponin T; K36Q in cardiac troponin I; G159D in cardiac troponin C, and E361G in cardiac -actin). This 'uncoupling' was observed with native mutant protein from human and mouse heart and with recombinant mutant protein expressed in baculovirus/Sf9 systems. Uncoupling was independent of the fraction of mutated protein present above 0.55.ConclusionWe conclude that DCM-causing mutations in thin filament proteins abolish the relationship between myofilament Ca2+ sensitivity and troponin I phosphorylation by PKA. We propose that this blunts the response to β-adrenergic stimulation and could be the cause of DCM in the long term. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.

Rosenwald M.,ETH Zurich | Perdikari A.,ETH Zurich | Rulicke T.,Institute of Laboratory Animal Science | Wolfrum C.,ETH Zurich
Nature Cell Biology | Year: 2013

Brown adipose tissue helps to maintain body temperature in hibernators, rodents and neonatal mammals by converting lipids and glucose into heat, thereby increasing energy expenditure. In addition to classical brown adipocytes, adult rodents - like adult humans - harbour brown-like adipocytes in the predominantly white adipose tissue. The formation of these brite (brown-in-white) adipocytes is a physiological response to chronic cold and their cellular origin is under debate. We show here that cold-induced formation of brite adipocytes in mice is reversed within 5 weeks of warm adaptation, but the brite adipocytes formed by cold stimulation are not eliminated. Genetic tracing and transcriptional characterization of isolated adipocytes demonstrates that they are converted into cells with the morphology and gene expression pattern of white adipocytes. Moreover, these white-typical adipocytes can convert into brite adipocytes on additional cold stimulation. Shifting the balance of this interconversion from the white towards the brite phenotype might provide a new means of counteracting obesity by increasing energy expenditure. © 2013 Macmillan Publishers Limited. All rights reserved.

Yang Y.,Institute of Laboratory Animal Science | Xiu J.,Institute of Laboratory Animal Science | Zhang X.,Institute of Laboratory Animal Science | Zhang L.,Institute of Laboratory Animal Science | And 3 more authors.
Molecules | Year: 2012

Human enterovirus 71, a member of the Picornaviridae family, is one of the major causative agent of hand, foot and mouth disease in children less than six years old. This illness has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available. In this study, antiviral effect of matrine against enterovirus 71 were evaluated in vitro and in vivo. Matrine could suppress the viral RNA copy number on rhabdomyosarcoma cells. Moreover, matrine treatment of mice challenged with a lethal dose of enterovirus 71 reduced the mortality and relieved clinical symptoms. The results showed that matrine may represent a potential therapeutic agent for enterovirus 71 infection. © 2012 by the authors.

Lu D.,Institute of Laboratory Animal Science | Ma Y.,Institute of Laboratory Animal Science | Zhang W.,Institute of Laboratory Animal Science | Bao D.,Institute of Laboratory Animal Science | And 5 more authors.
Hypertension | Year: 2012

Cytochrome P450 2E1 (CYP2E1) is a cytochrome P450 enzyme that catalyzes the metabolism of toxic substrates. CYP2E1 is upregulated in heart disease, including the dilated cardiomyopathy (DCM) mouse model. Here, knockdown of CYP2E1 significantly ameliorated the dilated left ventricle, thin wall, and dysfunctional contraction in the cTnTR141W and adriamycin-induced DCM mouse models. Interstitial fibrosis, poorly organized myofibrils, and swollen mitochondria with loss of cristae were improved in the myocardium of α-myosin heavy chain (MHC)-cTnTR141W XCYP2E1-silence double-transgenic mice when compared with the cTnTR141W transgenic mice. Oxidative stress, the activation of caspase 3 and caspase 9, the release of cytochrome c, and the apoptosis in the myocardium were significantly decreased in double-transgenic mice compared with the cTnTR141W transgenic mice. In summary, the expression of CYP2E1 is upregulated in heart disease and might be induced by hypoxemia in cardiomyopathy. The overexpression of CYP2E1 can enhance the metabolism of endogenous ketones to meet the energy demand of the heart in certain disease states, but the overexpression of CYP2E1 can also increase oxidative stress and apoptosis in the DCM heart. Knockdown or downregulation of CYP2E1 might be a therapeutic strategy to control the development of DCM after mutations of cTnTR141W or other factors, because DCM is the third most common cause of heart failure and the most frequent cause of heart transplantation. © 2012 American Heart Association, Inc.

Yang Y.,Institute of Laboratory Animal Science | Zhang L.,Institute of Laboratory Animal Science | Fan X.,Institute of Laboratory Animal Science | Qin C.,Institute of Laboratory Animal Science | Liu J.,Institute of Laboratory Animal Science
Bioorganic and Medicinal Chemistry Letters | Year: 2012

Human enterovirus 71 infection causes hand, foot and mouth disease in children under 6 years of age and has caused mortalities in large-scale outbreaks in the Asia-Pacific region. No effective vaccine or antiviral drugs currently exist against enterovirus 71 in the clinic. In this study, we investigated the antiviral effect of geraniin on enterovirus 71 both in vitro and in vivo. The results showed that geraniin effectively inhibited virus replication in rhabdomyosarcoma cells with an IC 50 of 10 μg/ml. Moreover, geraniin treatment of mice that were challenged with a lethal dose of enterovirus 71 resulted in a reduction of mortality, relieved clinical symptoms, and inhibited virus replication in muscle tissues. The results suggest that geraniin may be used as a potential drug for anti-enterovirus 71. © 2011 Elsevier Ltd. All rights reserved.

Kong Q.,Chinese Association for Laboratory Animal science CALAS | Qin C.,Institute of Laboratory Animal science | Qin C.,Chinese Association for Laboratory Animal science CALAS
ILAR Journal | Year: 2010

Laboratory animal science (LAS) advances scientific understanding of the care and use of animals that play a key role in research supporting the development of biomedicine. LAS has developed quickly in China in recent decades, and this report provides an analysis of the current status of the country's LAS policies and administration. National and provincial laws, regulations, guidelines, and standards apply to quality control and licensing, quarantine and infectious disease control, breeding and husbandry, transgenic animals, staff qualifications, animal welfare, and imports, exports, and transportation. Regulation and oversight of lab animal use are the responsibility of the national Ministry of Science and Technology, provincial departments of science and technology, and institutional animal care and use committees. We begin with an explanation of the rationale behind this paper and a brief history of policy-related activities and achievements. We then present various policies, discuss their implementation, and hypothesize about future policy developments. With the improvement of policies under an integrated, multitiered administration, the use of high-quality lab animals in Chinese scientific research is increasing and many more papers describing animal experiments performed in China are being published in international journals.

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