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Protective effects of Batroxobin on spinal cord injury in rats

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Neuroscience Bulletin 2013年第4期29卷 501-508页

作者： Hong Fan Xia Liu Hai-Bin Tang Peng Xiao ya-zhou wang Gong Ju Institute of Neurosciences Fourth Military Medical University Department of Rehabilitation PLA General Hospital of Air Force Department of Laboratory Medicine Xi'an Central Hospital

Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study demonstrated that, at the front of the expanding secondary injury in the spinal cord, there is an ischemic area in which many neurons can still be rescued. Therefore, enhancement of blood circulation in the cord may be helpful, and indeed, we found that a traditional Chinese medicine, shu-xue-tong, efficiently reduces the secondary injury. The aim of the present study was to investigate the effect of reducing fibrinogen with Batroxobin, a drug widely used clinically for ischemia, in rats with spinal cord contusion. We found that both 2 and 4 Batroxobin units （BU）/kg efficiently decreased the plasma fibrinogen, and 2 BU/kg significantly increased spinal blood flow, enhanced neuronal survival, mitigated astrocyte and microglia activation, and improved locomotor recovery. However, 4 BU/kg had no effect on the secondary spinal cord injury. These data suggest that Batroxobin has multiple beneficial effects on spinal cord injury, indicating a potential clinical application.

关键词： spinal cord injury secondary injury fibrinogen Batroxobin

Impact of failure mode and effects analysis-based emergency management on the effectiveness of craniocerebral injury treatment

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World Journal of Clinical Cases 2022年第2期10卷 554-562页

作者： Xiao-Lan Shao ya-zhou wang Xiong-Hui Chen Wen-Juan Ding Department of Emergency Surgery Ward 48 First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND Craniocerebral injuries encompass brain injuries,skull fractures,cranial soft tissue injuries,and similar ***,the incidence of craniocerebral injuries has increased dramatically due to the increased numbers of traffic accidents and aerial work injuries,threatening the physical and mental health of *** To investigate the impact of failure modes and effects analysis(FMEA)-based emergency management on craniocerebral injury treatment *** Eighty-four patients with craniocerebral injuries,treated at our hospital from November 2019 to March 2021,were selected and assigned,using the random number table method,to study(n=42)and control(n=42)*** in the control group received conventional management while those in the study group received FMEA theory-based emergency management,based on the control ***-and post-interventions,details regarding the emergency situation;levels of inflammatory stress indicators[Interleukin-6(IL-6),C-reactive protein(CRP),and procalcitonin(PCT)];incidence of complications;prognoses;and satisfaction regarding patient care were evaluated for both *** For the study group,the assessed parameters[pre-hospital emergency response time(9.13±2.37 min),time to receive a consultation(2.39±0.44 min),time needed to report imaging findings(1.15±4.44 min),and test reporting time(32.19±6.23 min)]were shorter than those for the control group(12.78±4.06 min,3.58±0.71 min,33.49±5.51 min,50.41±11.45 min,respectively;P0.05);post-intervention serum indicator levels were lower in both groups than pre-intervention ***,serum levels of IL-6(17.35±5.33 pg/mL),CRP(2.27±0.56 mg/L),and PCT(0.22±0.07 ng/mL)were low

关键词： Craniocerebral injury Failure modes and effects analysis theory Emergency management Treatment effect

Transient neurogenesis in ischemic cortex from Sox2^(+)astrocytes

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Neural Regeneration Research 2023年第7期18卷 1521-1526页

作者： Jia-Lei yang Hong Fan Fan-Fan Fu Bao-Lin Guo Ying Huang Li Sun Wen-Ting wang Jun-Ling Xing Xin-Tian Hu Yu-Qiang Ding Kun Zhang Ying-zhou Hu ya-zhou wang Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina China National Clinical Research Center for Neurological Diseases Department of NeurologyBeijing Tiantan HospitalBeijingChina Department of Neurology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institute of Brain ScienceFudan UniversityShanghaiChina Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan ProvinceChina

The adult cortex has long been regarded as *** injury can induce neurogenesis in the adult cortex is still ***,we report that focal ischemia stimulates a transient wave of local *** 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ***-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem *** a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new ***,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult *** addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca *** findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.

关键词： adult astrocyte cortex fate-mapping ischemia local neurogenesis neural stem cells Sox2

Characteristics of traumatic brain injury models:from macroscopic blood flow changes to microscopic mitochondrial changes

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Neural Regeneration Research 2023年第10期18卷 2268-2277页

作者： Ding-Ding yang Xiang-Dong Wan An-Di Chen Zi-Qian yan Yi-Fan Lu Jun-Chen Liu ya-zhou wang Jing wang yan Zhao Sheng-Xi Wu Guo-Hong Cai Department of Neurobiology School of Basic MedicineForth Military Medical UniversityXi’anShaanxi ProvinceChina Hebei Medical University ShijiazhuangHebei ProvinceChina College of Life Sciences&Research Center for Resource Peptide Drugs Yan’an UniversityYan’anShaanxi ProvinceChina Department of Nuclear Medicine First Affiliated Hospital of Forth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Gastroenterology First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina

Controlled cortical impingement is a widely accepted method to induce traumatic brain injury to establish a traumatic brain injury animal model.A strike depth of 1 mm at a certain speed is recommended for a moderate brain injury and a depth of>2 mm is used to induce severe brain ***,the different effects and underlying mechanisms of these two model types have not been *** study investigated the changes in cerebral blood flow,differences in the degree of cortical damage,and differences in motor function under different injury parameters of 1 and 2 mm at injury speeds of 3,4,and 5 m/*** also explored the functional changes and mitochondrial damage between the 1 and 2 mm groups in the acute(7 days)and chronic phases(30 days).The results showed that the cerebral blood flow in the injured area of the 1 mm group was significantly increased,and swelling and bulging of brain tissue,increased vascular permeability,and large-scale exudation *** the 2 mm group,the main pathological changes were decreased cerebral blood flow,brain tissue loss,and cerebral vasospasm occlusion in the injured *** motor and cognitive impairments were found on day 7 after injury in the 2 mm group;at 30 days after injury,the motor function of the 2 mm group mice recovered significantly while cognitive impairment *** sequencing showed that compared with the 1 mm group,the 2 mm group expressed more ferroptosis-related *** changes of mitochondria in the two groups on days 7 and 30 using transmission electron microscopy revealed that on day 7,the mitochondria in both groups shrank and the vacuoles became larger;on day 30,the mitochondria in the 1 mm group became larger,and the vacuoles in the 2 mm group remained *** analyzing the proportion of mitochondrial subgroups in different groups,we found that the model mice had different patterns of mitochondrial composition at different time periods,suggesting that the differenc

关键词： cerebral blood flow cognitive impairments controlled cortical impingement ferroptosis mitochondrial dysfunction motor impairments mouse model traumatic brain injury

Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis

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Journal of Pharmaceutical Analysis 2023年第10期13卷 1135-1152页

作者： Jia-Jia Zhang Chang-Geng Song Miao wang Gai-Qin Zhang Bin wang Xi Chen Peng Lin Yu-Meng Zhu Zhi-Chuan Sun ya-zhou wang Jian-Li Jiang Ling Li Xiang-Min yang Zhi-Nan Chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi'an710032China Department of Neurology Xijing HospitalFourth Military Medical UniversityXi'an710032China Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education College of Chemistry and Materials ScienceNorthwest UniversityXi'an710032China Department of Neurosurgery Xi'an Daxing HospitalXi'an710032China Department of Neurobiology and Institute of Neurosciences Collaborative Innovation Center for Brain ScienceSchool of Basic MedicineFourth Military Medical UniversityXi'an710032China

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of *** the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine *** the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular *** successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial *** of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/b-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based *** mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of *** established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic *** blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/b-arrestin2 ***,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine ***,intrathecal electroporation of silencing short hairpin RNA illustrated that the in v

关键词： Morphine tolerance Mu-opioid receptor Endocytosis Monoclonal antibody Physical dependence

Silicified collagen scaffold induces semaphorin 3A secretion by sensory nerves to improve in-situ bone regeneration

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Bioactive Materials 2022年第3期7卷 475-490页

作者： Yu-Xuan Ma Kai Jiao Qian-Qian Wan Jing Li Ming-Yi Liu Zi-Bin Zhang Wen Qin Kai-yan wang ya-zhou wang Franklin R.Tay Li-Na Niu State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxi710032China Department of Neurobiology The Fourth Military Medical UniversityXi’anShaanxi710032China The Graduate School Augusta UniversityAugustaGA30912USA

Sensory nerves promote osteogenesis through the release of ***,the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain *** present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of *** wound sites were accompanied by extensive nerve innervation and *** nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent *** of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A(Sema3A)and semaphorin 4D(Sema4D)in the dorsal root ganglion(DRG),as detected by the upregulation of signaling *** medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor *** effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing *** of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model,whereas overexpression of Sema3A promoted the silicon-induced *** of“mechanistic target of rapamycin”(mTOR)pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen *** findings support the role of silicon in inducing Sema3A production by sensory nerves,which,in turn,stimulates osteogenesis and *** together,silicon has therapeutic potential in orthopedic rehabilitation.

关键词： Distal femur defect Mechanistic target of rapamycin Semaphorin 3A Sensory nerve Silicified collagen scaffolds

Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery

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Neural Regeneration Research 2022年第8期17卷 1814-1820页

作者： Kun Zhang Wen-Can Lu Ming Zhang Qian Zhang Pan-Pan Xian Fang-Fang Liu Zhi-yang Chen Chung Sookja Kim Sheng-Xi Wu Hui-Ren Tao ya-zhou wang Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Tongji UniversityShanghaiChina Department of Spine Surgery Shenzhen University General HospitalShenzhenGuangdong ProvinceChina Department of Neurology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Department of Anesthesiology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Faculty of Medicine Macao University of Science and TechnologyMacao Special Administrative RegionChina

Neural stem cell(NSC)transplantation is a promising strategy for replacing lost neurons following spinal cord ***,the survival and differentiation of transplanted NSCs is limited,possibly owing to the neurotoxic inflammatory *** of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages,we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase(AR),a key enzyme in the polyol pathway of glucose metabolism,would provide a more beneficial microenvironment for NSC survival and ***,we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries.M2 macrophages promoted the differentiation of NSCs into neurons in *** of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional *** findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.

关键词： aldose reductase functional recovery inflammation macrophage microglia neural stem cell transplantation neuronal differentiation polarization spinal cord injury

Relationship between catecholamine level and gene polymorphism of β1 adrenergic receptor G1165C in children with EV71 infection in hand foot and mouth disease

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Asian Pacific Journal of Tropical Medicine 2017年第5期10卷 453-456页

作者： Zhi-Xian Lei Bang-Tao Li Hong-Ai Li Xiao-Ming Li Man-Fang Xie Ting Huang Qi wang ya-zhou wang Qiu-Yu Lin Li-Rong zhou Nai-Chao Feng Xin Li Dao-Mou Zhu Yuan-Ping Hai Lan Cui ya-Qin Zhang Zhi-Wen Liu Shou-Ye Wu Yong-Zhao Chen Ke-Qing Zhu Xiao-Jie He Wei Xiang Pediatric Intensive Care Unit Maternal and Child Health Care Hospital of Hainan Province (Children’s Hospital of Hainan Province) Pediatrics the Hainan Affiliated Hospital of University of South China Pediatric Nephrology the Second Xiangya Hospital of Central South University Pediatrics Maternal and Child Health Care Hospital of Hainan Province (Children’s Hospital of Hainan Province) Neonatal Maternal and Child Health Care Hospital of Hainan Province (Children’s Hospital of Hainan Province) Labway Clinical Laboratory Shanghai Ltd Pediatrics the Affiliated Hospital of Hainan Medical University

Objective:To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165 C in children with enterovirus 71(EV71) infection in hand foot and mouth disease(HFMD). Methods:The polymerase chain reaction(PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165 C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay(ELISA). Results:The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD(P0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165 C genotype and allele between EV71 infection group and healthy control group(P> 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well(P> 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group(P> 0.05),and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups(P> 0.05). Conclusions:As the disease gets worse,the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD,which is an important indicator to evaluate the progress of the disease. However,the gene polymorphism of eptor G1165 C have no significant correlation,not only with the susceptibility and severit β1 adrenergic recy of EV71 infection in hand,foot and mouth disease,but also with the levels of catecholamine.

关键词： Catecholamine β1 adrenergic receptor Gene polymorphism Enterovirus 71

Occurrence of RIP3/MLKL-mediated necroptosis in the ischemic cortex in mice

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Occurrence of RIP3/MLKL-mediated necroptosis in the ischemic...