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CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta,alpha,beta,and gamma

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3142-3154页

作者： Jiejie Geng Liang chen Yufeng Yuan Ke Wang Youchun Wang Chuan Qin Guizhen Wu Ruo chen Zheng Zhang Ding Wei Peng Du Jun Zhang Peng Lin Kui Zhang Yongqiang Deng Ke Xu Jiangning Liu Xiuxuan Sun Ting Guo Xu Yang Jiao Wu Jianli Jiang Ling Li Kun Zhang Zhe Wang Jing Zhang Qingguo Yan Hua Zhu Zhaohui Zheng Jinlin Miao Xianghui Fu Fengfan Yang Xiaochun chen Hao Tang Yang Zhang Ying Shi Yumeng Zhu Zhuo Pei Fei Huo Xue Liang Yatao Wang Qingyi Wang Wen Xie Yirong Li Mingyan Shi Huijie Bian Ping Zhu zhi-nan chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi'an 710032China School of Medicine Shanghai UniversityShanghai 200444China Zhongnan Hospital of Wuhan University Wuhan 430071China Division of HIV/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)and WHO Collaborating Center for Standardization and Evaluation of BiologicalsBeijing 102629China Institute of Laboratory Animals Science Chinese Academy of Medical SciencesBeijing 100071China NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 100871China Beijing Institute of Biotechnology Beijing 100871China Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi'an 710032China Beijing Institute of Microbiology and Epidemiology Beijing 100071China School of Basic Medicine Fourth Military Medical UniversityXi'an 710032China Jiangsu Pacific Meinuoke Biopharmceutical Co.Ltd Changzhou 213022China

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing *** in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 ***,we identified CD147 as a universal receptor for SARS-CoV-2 and its ***,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,***,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and *** infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling ***,we proposed that severe COVID-19-related cytokine storm is induced by a"spike protein-CD147-CyPA signaling axis":Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK ***,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine ***,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its ***,our findings provided a new perspective for severe COVID-19-related ***,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

关键词： CD147 cytokine storm

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Surface micro-arrays enhancing electromagnetic interference shielding of polydimethylsiloxane/multiwalled carbon nanotubes nanocomposites

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nano Research 2025年第1期18卷 508-519页

作者： Ke Jiang zhi chen Ji Yu chen Zheng Shan Huang Ming Wang Chongqing Key Laboratory of Soft-Matter Material Manufacturing School of Chemistry and Chemical EngineeringSouthwest UniversityChongqing 400715China School of Mechanics Civil Engineering and ArchitecturesNorthwestern Polytechnical UniversityXi’an 710072China Jieyang Branch of Chemistry and Chemical Engineering Guangdong Laboratory(Rongjiang Laboratory) Jieyang 515200China

Herein,the electromagnetic shielding performance of surface concave-convex(SC)and zig-zag micro-arrays was studied by using a simulation prediction and a three-dimensional(3D)printing custom ***,surface stripe concaveconvex(SSC)and surface cylindrical concave-convex(SCC)micro-arrays with or without zig-zag micro-arrays are designed,and their shielding performance is simulated in multi-bands(C-,X-band).The multiwalled carbon nanotubes/polydimethylsiloxane composites(MWCNT/PDMS)with different SC structures and different electrical conductivity are molded in acrylonitrile-butadiene-styrene copolymer(ABS)molds which are printed by a 3D *** results show that the electromagnetic interference shielding effectiveness(EMI SE)of the samples can be enhanced by constructing the SC micro-arrays with zig-zag micro-arrays,and improving with the increase of conductivity and *** addition,the shielding mechanism of the SC-MWCNT/PDMS composites is investigated and discussed by an electromagnetic simulation.

关键词： surface micro-arrays electrical properties electromagnetic interference(EMI)shielding three-dimensional(3D)printing

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Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1845-1855页

作者： Huijie Bian Zhao-Hui Zheng Ding Wei Aidong Wen Zheng Zhang Jian-Qi Lian Wen-Zhen Kang Chun-Qiu Hao Jing Wang Rong-Hua Xie Ke Dong Jie-Lai Xia Jin-Lin Miao Wen Kang Guoquan Li Di Zhang Mingru Zhang Xiu-Xuan Sun Likun Ding Kui Zhang Junfeng Jia Jin Ding zhiqin Li Yanyan Jia Lin-Na Liu Zhe Zhang Zhao-Wei Gao Hong Du Na Yao Qing Wang Ke Wang Jie-Jie Geng Bin Wang Ting Guo Ruo chen Yu-Meng Zhu Li-Juan Wang Qian He Rui-Rui Yao Ying Shi Xiang-Min Yang Jian-Sheng Zhou Yi-nan Ma Ya-Tao Wang Xue Liang Fei Huo Zhe Wang Yang Zhang Xu Yang Ye Zhang Lu-Hua Gao Ling Wang Xiao-Chun chen Hao Tang Shuang-Shuang Liu Qing-Yi Wang zhi-nan chen Ping Zhu National Translational Science Center for Molecular Medicine and Department of Cell Biology Fourth Military Medical UniversityXi'anChina Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi'anChina Department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi'anChina Center for Infectious Diseases Tangdu HospitalFourth Military Medical UniversityXi'anChina Department of Nuclear Medicine Xijing HospitalFourth Military Medical UniversityXi'anChina department of Clinical Diagnosis Tangdu HospitalFourth Military Medical UniversityXKanChina College of Military Preventive Medicine Fourth Military Medical UniversityXi'anChina Department of Pharmaceutics Tangdu HospitalFourth Military Medical UniversityXi'anChina Department of Pathology Fourth Military Medical UniversityXi'anChina Jiangsu Pacific Meinuoke Biopharmaceutical Co.Ltd ChangzhouChina Department of Foreign Languages Fourth Military Medical UniversityXi'anChina

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 *** is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)***,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 *** phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was *** serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic *** obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each *** biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to *** the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent *** meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control *** results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

关键词： patients dosage phase

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星级酒店精细化管理探析

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文史博览(理论) 2008年第10期 71-73页

作者：娄丽芝湘南学院

随着科学技术的不断进步,精细化管理已成为决定未来企业竞争成败的关键。星级酒店推行精细化管理势在必行。星级酒店实行精细化管理要注重细化、量化、标准化、协调化、流程系统化、务实与严格化。

关键词：星级酒店精细化管理

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Slug upregulates CD147 expression through TGF-β promoted epithelial to mesenchymal transition in human hepatocellular carcinoma

Slug upregulates CD147 expression through TGF-β promoted ep...

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2010’全国肿瘤分子标志及应用学术研讨会暨第五届中国中青年肿瘤专家论坛

作者： Ning-Yu Ru,Jiao Wu,zhi-nan chen,Huijie Bian Cell Engineering Research Centre and Department of Cell Biology,State Key Laboratory of Cancer Biology,Fourth Military Medical University,Xi’an 710032, China

CD147 is a transmembrance glycoprotein that promotes tumor progress invasion and *** of CD147 has been observed in various types of human *** changes in cell adhesion and migration during tumour invasion are reminisce...

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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Construction of Recombinant Newcastle Disease Virus for Oncolytic Therapy of Cancer

Construction of Recombinant Newcastle Disease Virus for Onco...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Ding Wei~1,Na Sun~1,Yuan Wang~1,Gang nan~1,Zhen Ren~2,zhi-nan chen~1,Huijie Bian~1 1.Cell Engineering Research Centre and Department of Cell Biology.Fourth Military Medical University 2.Department of Microbiology,Third Military Medical University

Newcastle disease virus(NDV),a naturally oncolytic virus,is known as a potential agent for cancer ***, we constructed a reverse genetic system based on Italien strain which is an oncolytic and virulence strain of NDV. Using the reverse genetic system,two recombinant NDV carrying EGFP and firefly luciferase genes were *** the proliferation kinetic and the anti-tumor activity of recombinant viruses were evaluated in vitro and in ***:To generate the recombinant NDV,a minigenome plasmid,three helper plasmids and genome plasmid were *** complete coding sequence of EGFP or firefly luciferase was inserted into the non-coding region between HN and F *** helper plasmids and genome plasmid were co-transfected into BSR-T7/5 cells to rescue the recombinant NDV To evaluate the propagation and anti-tumor characteristics,several cell lines were infected with recombinant NDV and NDV Italien,and the viral titer and cell viability were measured in different time *** evaluate the anti-tumor activity in vivo,tumor-bearing nude mice were infected with the recombinant virus through intratumoral or intravenous injection,the exogenous gene expression were observed by living image system and the tumor volume and survival time were ***:Recombinant NDV were collected and purified at 5 day post transfection and identified by genome *** data showed the insertion of exogenous reporter gene did not affect the viral propagation efficiency,and the recombinant NDV kept the characteristics of tumor-selective replication and the sensitivity to type I interferon similar as wild-type NDV Living image showed the recombinant NDV replicated in tumor tissue of nude mice ***,the recombinant NDV prolonged the survival time of nude mice significantly by intratumoral injection(Pnant NDV with reporter gene based on NDV Italien strain for the first time which kept the propagation pr

关键词： Newcastle disease virus Reverse genetic technology Oncolytic virus Cancer

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Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells

Functional recovery in acute traumatic spinal cord injury af...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Sheng-Li HU,Hai-Shui LUO,Jiang-Tao LI,Yong-zhi XIA,Lan LI,Li-Jun ZHANG,Hui MENG,Gao-Yu CUI,zhi chen, nan WU,Jiang-Kai LIN,Gang ZHU,Hua FENG Department of Neurosurgery,Southwest Hospital,the Third Military Medical University,Chongqing 400038,China

＜正＞Objective Spinal cord injury results in loss of neurons,degen eration of axons,formation of glial scar,and severe functional immunofluorescence *** umbilical cord mesenchymal stem cells can be induced to form neural cells in ***,these cells have a significantly enhanced potential therapeutic role for treating spinal cord *** and Setting Rats were randomly divided into three groups:sham operation group,control group, and human umbilical cord mesenchymal stem cell *** groups were subjected to tures around the lesion site by weight drop device except for sham *** Thirty-six female Sprague-Dawley *** The control group received Dulbecco’s modified media/nutrient mixture F-12 injections,whereas the human umbilical cord mesenchymal stem cell group undertook human umbilical cord mesenchymal stem cells transplantation at the dorsal spinal cord 2 mm rostrally and 2 mm caudally to the injury site at 24 hrs after spinal cord *** Rats from each group were examined for neurologic function and contents of brain-derived neurotrophic factor. Survival,migration,and differentiation of glial scar were also explored by using immunohistochemistry and *** results Recovery of hindlimb locomotor function was significantly enhanced in the human umbilical cord mesenchymal stem cells grafted animals at 5 wks after *** recovery was accompanied by increased length of neurofilament positive fibers and increased numbers of growth cone-like structures around the lesion *** human umbilical cord mesenchymal stem cells survived,migrated over short distances,and produced large amounts of glial cell line-derived neurotrophic factor and neurotrophin-3 in the host spinal *** were fewer reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the human umbilical cord mesenchymal stem cell group than in the control *** Treatment with

关键词： functional recovery mesenchymal stem cells spinal cord injury transplantation umbilical cord

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Kangfuxin solution alleviates esophageal stenosis after endoscopic submucosal dissection:A natural ingredient strategy

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World Journal of Gastroenterology 2025年第1期31卷 110-125页

作者： Xin Zhou Dan Ma Yi-Xiang He Jing Jin Hong-Lian Wang Yun-Feng Wang Fan Yang Jian-Qin Liu Jie chen zhi Li Department of Spleen and Stomach Diseases the Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City The Affiliated Traditional Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Gastroenterology Changhai HospitalNaval Medical UniversityShanghai 20082China Research Center of Integrated Chinese and Western Medicine The Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina School of Integrated Traditional Chinese and Western Clinical Medicine North Sichuan Medical CollegeNanchong637100Sichuan ProvinceChina

BACKGROUND Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection(ESD).Excessive fibrotic repair is a typical pathological feature leading to stenosis after *** To examine the effectiveness and underlying mechanism of Kangfuxin solution(KFX)in mitigating excessive fibrotic repair of the esophagus *** Pigs received KFX at 0.74 mL/kg/d for 21 days after esophageal full circumferential *** examinations occurred on days 7 and 21 *** vitro,recombinant transforming growth factor(TGF)-β1(5 ng/mL)induced a fibrotic microenvironment in primary esophageal fibroblasts(pEsF).After 24 hours of KFX treatment(at 1.5%,1%,and 0.5%),expression ofα-smooth muscle actin-2(ACTA2),fibronectin(FN),and type collagen I was *** signaling was analyzed,including TGF-β1,Smad2/3,and phosphor-smad2/3(p-Smad2/3).RESULTS Compared to the Control group,the groups treated with KFX and prednisolone exhibited reduced esophageal stenosis,lower weight loss rates,and improved food tolerance 21 d after *** treatment,Masson staining revealed thinner and less dense collagen fibers in the submucosal ***,the expression of fibrotic effector molecules was notably ***,KFX downregulated the transduction levels of fibrotic functional molecules such as TGF-β1,Smad2/3,and p-Smad2/*** vitro,pEsF exposed to TGF-β1-induced fibrotic microenvironment displayed increased fibrotic activity,which was reversed by KFX treatment,leading to reduced activation of ACTA2,FN,and collagen *** 1.5%KFX treatment group showed decreased expression of p-Smad 2/3 in TGF-β1-activated *** KFX showed promise as a therapeutic option for post-full circumferential esophageal ESD strictures,potentially by suppressing fibroblast fibrotic activity through modulation of the TGF-β1/Smads signaling pathway.

关键词： Kangfuxin solution Natural component Endoscopic submucosal dissection Esophagus stricture Fibrosis

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无血清培养HAb18细胞的生长代谢与抗体分泌特征

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细胞生物学杂志 2006年第1期28卷 79-83页

作者：李玲米力谢丽刘蓉冯强徐力青陈志南第四军医大学细胞生物学教研室西安710032

通过逐步降低血清浓度,HPLC氨基酸分析及正交实验筛选研制了HAb18杂交瘤细胞的无血清培养基。对在该无血清培养条件下的细胞进行了计数,对培养上清液进行了葡萄糖、谷氨酰胺、乳酸和氨浓度以及抗体分泌量和抗原结合活性测定,并对动力学... 详细信息

通过逐步降低血清浓度,HPLC氨基酸分析及正交实验筛选研制了HAb18杂交瘤细胞的无血清培养基。对在该无血清培养条件下的细胞进行了计数,对培养上清液进行了葡萄糖、谷氨酰胺、乳酸和氨浓度以及抗体分泌量和抗原结合活性测定,并对动力学参数进行了分析,结果表明HAb18细胞在无血清培养条件下达到的最大细胞密度和抗体分泌量分别为0.91×106个/ml和43.8mg/L;细胞比生长速率较在有血清条件下稍有下降,而抗体合成速率提高(0.0207/h比0.0218/h,0.387pg/cell/h比0.218pg/cell/h,P<0.01)。无血清培养时葡萄糖和谷氨酰胺消耗无明显变化,但乳酸浓度降低,氨浓度升高;此外,分泌抗体的抗原结合活性增加。研究无血清培养条件下的HAb18细胞生长代谢和抗体分泌特征可为建立HAb18无血清悬浮流加培养工艺打下基础。

关键词：杂交瘤细胞无血清培养细胞生长细胞代谢抗体分泌

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