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Morphine analgesia in male inbred genetic diversity mice recapitulates the among-individual variance in response to morphine in humans

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Animal Models and Experimental Medicine 2022年第3期5卷 288-296页

作者： Yin Yang Bowen Guan Qiang Wei Wei Wang aimin meng Key Laboratory of Human Disease Comparative Medicine Ministry of HealthBeijing Engineering Research Center for Laboratory Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)BeijingChina Department of Physiology and Neurobiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina

Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine can be explained in terms of pharmacodynamics and pharmacokinetics, genetic polymorphisms also play an important role. However, the genetic basis of different sensitivity and tolerance susceptibility to morphine remains ambiguous. Using 15 strains of inbred Genetic Diversity(GD) mice,a new resource with wide genetic and phenotypic variation, we demonstrated great variance in sensitivity to morphine analgesia and susceptibility to morphine tolerance between different GD strains. Among-i ndividual variance in response to morphine analgesia in the population can be modeled in GD mice. Two loci respectively may be associated with the among-i ndividual variance in morphine sensitivity and tolerance,confirming the role of genetic factors in among-i ndividual different responses to morphine. These results indicate that GD mice may be a potential tool for the identification of new biomarkers to improve the clinical administration of morphine.

关键词： inbred genetic diversity mice morphine analgesia morphine tolerance quantitative trait loci mapping

Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

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Animal Models and Experimental Medicine 2023年第2期6卷 146-154页

作者： Yuhang Sun Bowen Guan Xing Liu Lingyan Zhang Xinpei Wang aimin meng Ran Gao National Human Diseases Animal Model Resource Center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)National Center of Technology Innovation for Animal ModelBeijingChina

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor *** susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of *** susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary ***:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in *** urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed *** for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase *** on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU ***:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC *** GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

关键词： angiotensin I converting enzyme busulfan hematopoietic stem cell injury inbred genetic diversity mice urinary marker

The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

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Animal Models and Experimental Medicine 2022年第6期5卷 565-574页

作者： Yinping Dong YuanYang Zhang Xinyue Wang Wenxuan Li Junling Zhang Lu Lu Hui Dong Saijun Fan aimin meng Deguan Li Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Institute of Radiation MedicineChinese Academy of Medical Science&Peking Union Medical CollegeTianjinChina Key Laboratory of Human Disease Comparative Medicine Ministry of HealthBeijing Engineering Research Center for Laboratory Animal Models of Human Critical DiseasesNational Human Diseases Animal Model Resource CenterInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)BeijingChina

Background:Gastrointestinal(GI)injury is one of the most common side effects of ***,there is no ideal therapy method except for symptomatic treatment in the ***(XBJ)is a traditional Chinese medicine,used to treat sepsis by *** this study,the protective effects of XBJ on radiation-i nduced intestinal injury(RⅢ)and its mechanism were ***:The effect of XBJ on survival of irradiated C57BL/6 mice was *** changes including the number of crypts and the length of villi were evaluated by H&*** expression of Lgr5^(+)intestinal stem cells(ISCs),Ki67^(+)cells,villin and lysozymes were examined by *** expression of cytokines in the intestinal crypt was detected by *** damage and apoptosis rates in the small intestine were also evaluated by ***:In the present study,XBJ improved the survival rate of the mice after 8.0and 9.0 Gy total body irradiation(TBI).XBJ attenuated structural damage of the small intestine,maintained regenerative ability and promoted proliferation and differentiation of crypt cells,decreased apoptosis rate and reduced DNA damage in the *** of IL-6 and TNF-α was limited,but IL-1,TNF-β and IL-10 levels were increased in XBJ-treated group after *** expression of Bax and p53 were decreased after XBJ ***:Taken together,XBJ provides a protective effect on RⅢby inhibiting inflammation and blocking p53-related apoptosis pathway.

关键词： Xuebijing injection Intestinal injury Total body irradiation Inflammation Apoptosis

HMGB1 increases radiosensitivity by interacting with HDAC1

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中华放射医学与防护杂志 2015年第1期35卷 8-14页

作者： He Xin meng Qinghui meng aimin Liu Qiang Wang Haichao Fan Saijun HeXin mengQinghui mengaimin LiuQiang WangHaichao FanSaijun 100092 Tianjin Key laboratory of Radiation Medicineand Nuclear Medicine Institute of Radiation Medicine ChineseAcademy of Medical Sciences China

ObjectiveTo study the nuclear protein association of high-mobility group box-1(HMGB1) and histone deacetylase 1(HDAC1), and the effect of interaction on radiosensitivity in human breast cancer cells.MethodsThe protein-protein interaction was determined by immunoprecipitation-Western blot and glutathione-S-transferase capture assays. Cell growth was examined by MTT (methyl thiazolyl tetrazolium)assay and clonogenic assay. Histone deacetylase activity was analyzed by histone deacetylase assay.ResultsA significant increase of HMGB1 protein and radiosensitivity was observed in MDA-MB-231 and MDA-MB-468 cells transfected with a pCMV-Tag2B expression vector carrying with a full-length of HMGB1 cDNA. HMGB1 binding to HDAC1 was demonstrated as GST(glutathione S-transferase)-pull down and immunoprecipitation Western blot assay, and the association was elevated by irradiation. An LXCXE motif was required for the HMGB1-HADC1 interaction and HMGB1 radiosensitization. A significant difference of IC 50 value was observed, for example, 1.8 and 2.2 Gy(wtHMGB1 transfectants, P0.05), both compared with 3.9 and 4.1 Gy(pCMV-Tag2B transfectants) in MDA-MB-231 and MDA-MB-468 cells, respectively. A specific HDAC1 inhibitor trichostatin A markedly reduced the HMGB1-mediated radiosensitivity, 0.5 Gy in the presence of trichostatin A versus 1.8 Gy in absence of trichostatin A in MDA-MB-231 transfectants, 1.2 Gy (with trichostatin A) versus 2.2 Gy (without trichostatin A) in MDA-MB-468 transfectants, P<0.05. Histone deacetylase activity was also detected in immunoprecipitates prepared from these cells with antibodies to HMGB1, and this activity was abolished by the histone trichostatin A. ConclusionsThese results suggest a previous unanticipated role for HDAC1 in modification of HMGB1-mediated radiosensitivity by its direct interaction with HMGB1.

关键词：临床医学诊断放射医学 HMGB1

Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis

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Chinese Medical Journal 2015年第13期128卷 1787-1792页

作者： Xiao-Long Du Ling-Shang Kong Qing-You meng aimin Qian Wen-Dong Li Hong Chen Xiao-Qiang Li Cheng-Long Li Department of Vascular Surgery The Second Affiliated Hospital of Soochow University Suzhou 215000 Jiangsu China

Background： Catheter-directed thrombolysis （CDT） has been a mainstay in treating deep venous thrombosis （DVT）. However, the optimal dosage ofa thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT. Methods： A retrospective analysis was perfornaed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evahmted by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively. Results： The mean total dose of 3.34 （standard deviation [SD] 1.38） million units of urokinase was administered during a mean of 5.18 （SD 2.28） days. Prior to discharge, Grade Ⅲ （complete lysis） was achieved in 154 （36%） patients; Grade II （50-99% lysis） in 222 （52%）： and Grade I （50%~ lysis） in 51 （12%）. The major complications included one intracranial hemorrhage, one henaatochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study. Conclusions： Treatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.

关键词： Catheter-based Interventions Deep Vein Thrombosis Endovascular Treatment Thrombolysis: Venous Disease

The effects of Xuebijing Injection on the hematopoietic injury induced by irradiation in mice

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The effects of Xuebijing Injection on the hematopoietic inju...

第四届泛环渤海生物化学与分子生物学会学术交流会

作者： Deguan Li Xiao Chai Chengchengli Hongying Wu Lu Lu Xiaochun Wang Mingfeng Zhao aimin meng Institute of Radiation Medicine Chinese Academy of Medical Science and Peking Union Medical Collage Department of Hematology Tianjin First Central Hospital

Objective:Xuebijing injection(XBJ)is a traditional Chinese herbal prescription widely used in the treatment of *** this study the protective effects of Xuebijing Injection(XBJ)on the hematopoietic system damage in the radiated mice were ***:45 ICR mice were divided into three equal groups and designated as non-irradiated mice(Ctl),total body irradiated mice(IR)and IR mice administered XBJ(0.4ml/kg)by ip injection every day for 7 successive

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Study on Substation Monitor Control in Thin Coal Seam Fully Mechanized Working Face

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Study on Substation Monitor Control in Thin Coal Seam Fully ...

2008’“先进集成技术”院士论坛暨第二届仪表、自动化与先进集成技术大会

作者： Wang Wenxing Wang aimin meng Guoying (School of Mechanical,Electronic and Information Engineering in China University Mining and Technology Beijing 100083)

Geology circumstance of thin coal mine seam is extremely complicated and there are many hidden *** system of production in thin coal seam fully mechanized working face was selected independently. It is important to provide the complete sets of equipment for the thin coal seam fully mechanized working face. System structure of the powered support' communication system and hardware design,main motion flow of the monitoring equipment were pointed out in this paper based on fully mechanized mining face in thin coal seam for complete sets of electric control *** of them have completed in *** this technology can be used in working face,production will be promoted to a new step forward.

关键词： Monitoring Powered support Communication Coal mine

Expression of Nox4 in the hematopoietic cells of ATM-/- and Terc-/-mice

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Expression of Nox4 in the hematopoietic cells of ATM-/- and ...

第四届泛环渤海生物化学与分子生物学会学术交流会

作者： Deguan Li Yingying Wang Chengcheng li Hongying Wu Lu Lu Junling Zhang Xiaochun Wang Daohong Zhou aimin meng Institute of Radiation Medicine Chinese Academy of Medical Science and Peking Union Medical Collage

Non-phagocytic cell oxidase family of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase is the major sources of reactive oxygen species(ROS)in a number of non-phygocyfic *** might enhance ROS level of hematopoietic stem cells(HSC)by up-regulation of Nox4(NADPH oxidase 4),the ROS levels in HSC of ataxia-telangiectasia mutated(ATM)mice and telomerase knockout(Terc)micewere also

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To investigate the role of macrophages in the development of murine pulmonary fibrosis induced irradiation exposure

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To investigate the role of macrophages in the development of...

第十四届中国实验动物科学年会

作者： Lulu Su Deguan li Yinping Dong Yueying Wang Yuquan Wang Bowen Guan Yanhua Lu Feiyue Fan aimin meng Institute of Laboratory Animal Science Chinese Academy of Medical Science (CAMS) and Comparative Medicine Center Peking Union Medical College (PUMC) Key Laboratory of Human Diseases Comparative Medicine Ministry of Health Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases Beijing Engineering Research Center for Laboratory Animal Models of Human Critical Diseases Institute of Radiation Medicine Chinese Academy of Medical Science and Peking Union Medical College Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine

Purpose:Radiation induced pulmonary fibrosis(RIPF) is one of the severe injuries induced by irradiation exposure. The pathogenesis of RIPF is very complicated. The present study was to investigate the changes of phenotype of macrophages and genes expression, and explore the effect of irradiation on the function of macrophages in the development of RIPF. Methods: The C57 BL/6 male mice were exposed to 17 Gy X ray irradiation(IR) on the right side of the chest to establish lung fibrosis model. ABT-263 was a BCL-2 inhibitor and found to attenuate RIPF in our previous work. ABT-263 was administered at 16 weeks post IR exposure. The right lung tissues were collected at 4, 8, 16 and 23 weeks post IR to detect the alternation of phenotype of macrophages by flow cytometry. RT-PCR was used to detect genes expression level of sorted macrophages in the right lung at various time-points. Results:(1) During the development of RIPF, the ratio of macrophages in the right lung tissue had no changes between control group and IR group.(2) Compared with the control group, the MFI of M2 macrophages of IR group was significantly decreased at 8 weeks, and increased at 16 weeks and 23 weeks post IR. However, there were no significant differences in the MFI of M1 macrophages between control group and IR group at various time-points.(3) The expression level of P16 in sorted macrophages from irradiated mice significantly increased but the expression level of P21 didn’t change during lung fibrosis. As to the genes related to the function of M1 and M2 macrophage, the expression levels of TGF-α,IL-1α,IL-10, Arg-1 and Mmp14 significantly increased, especially in the late stage of fibrosis development. However, the expression level of TGF-β had no change during fibrosis, which was the most common pro-fibrotic factor.(4) ABT-263 had no function on the ratio of macrophage, macrophage polarization and genes expression at 23 weeks post IR. Discussion:In this study, we found macrophage polarization wa

关键词： Radiation induced pulmonary fibrosis Irradiation Macrophages ABT-263