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Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing the release of microparticles

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Frontiers of Medicine 2022年第6期16卷 919-931页

作者： Han Guo Yuncong Zhang Yaxin Chu Shuo Yang Jie Zhang Rui Qiao Laboratory Medicine Peking University Third HospitalBeijing100191China Department of Clinical Laboratory Peking University International HospitalBeijing102206China

Preeclampsia(PE)is characterized by placenta-mediated pregnancy complication.The only effective treatment for PE is the delivery of the placenta.However,this treatment may cause preterm birth and neonatal death.Therefore,preventing PE is needed.The mechanism of PE involves abnormal placentation,which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation.These mediators contribute to systemic vascular dysfunction,inflammatory responses,and excessive thrombin generation.microparticles(MPs)are reportedly involved in PE by promoting the thromboinflammatory response.This study describes a strategy to prevent PE by reducing MP release using the recombinant protein,diannexin.Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation.Additionally,diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells.Moreover,in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice.Furthermore,diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro.These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.

关键词： preeclampsia recombinant protein diannexin microparticle NLRP3 inflammasome phosphatidylserin

Programmed nanoparticle-loaded microparticles for effective antigen/adjuvant delivery

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Particuology 2022年第1期20卷 77-89页

作者： Rong Xu Ying Dong Yajing Zhang Xiaoli Wang Chuangnian Zhang Yanjun Jiang Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences&1 Peking Union Medical CollegeTianjin 300192China School of Chemical Engineering and Technology.Hebei University of Technology.Tianjin.300130 China NHC Key Laboratory of Hormones and Development Tianjin Key Laboratory of Metabolic DiseasesChu Hsien-I Memorial Hospital&Tianjin Institute of EndocrinologyTianjin Medical UniversityTianjin 300134China

A microscale vaccine containing SiO_(2)nanoparticles loaded in CaC〇3 microparticles was constructed using the co-precipitation method.The antigen ovalbumin(OVA)was covalently conjugated with SiO_(2)nanoparticles,and these nanoparticles and CpG were co-encapsulated into CaCO_(3)microparticles,generating a vaccine with a size of approximately 5.2μm.Scanning electron microscopy(SEM),energy-dispersive X-ray(EDX),elemental mapping,and Fourier transform infrared(FTIR)analyses confirmed the successful preparation of the microscale vaccine;the vaccine had good storage stability without sustained antigen release,and negligible cytotoxicity to dendritic cells(DCs)and macrophages.Compared to SiO_(2)nanoparticles,the microscale vaccine can significantly improve antigen/adjuvant uptake.DCs internalized the entire microscale vaccine into lysosomes via macropinocytosis,and an increase in antigen endo/lysosomal escape was observed by confocal User scanning microscopy(CLSM).Specifically,DCs pulsed with the vaccine were fully mature,expressing high levels of costimulatory molecules(CD40,CD80,and CD86),MHCⅡ,and MHCⅠand secreting high levels of proinflammatory cytokines(IL-12,TNF-α,IL-1β,and IL-6).In addition,the vaccine had good in vivo biocompatibility,could protect the antigen from rapid degradation,and increased the retention time in lymph nodes.SiO_(2)nanoparticles-in-CaCO_(3)microparticles were an excellent carrier for antigen and adjuvant delivery.Hopefully,this study can provide some information on the design of microscale carriers for vaccine delivery systems.

关键词： Antigen delivery Cross-presentation microparticle Silica nanoparticle Bone marrow dendritic cell

Temperature/pH dual-responsive reversible morphology evolution of block copolymer microparticles under three-dimensional confinement

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Science China Chemistry 2023年第12期66卷 3587-3593页

作者： Mengmeng Zhang Zaiyan Hou Simeng Liu Guoqiang Han Meirong Tian Jintao Zhu Jiangping Xu Key Laboratory of Materials Chemistry for Energy Conversion and Storage of Ministry of Education School of Chemistry and Chemical EngineeringHuazhong University of Science and TechnologyWuhan 430074China

Development of block copolymer(BCP)microparticles with switchable morphology in response to external stimuli is important for exploiting new intelligent materials.In this work,thermo/p H dual-responsive nanoparticles(NPs)were employed as a cosurfactant to modulate the self-assembly morphology of polystyrene-b-poly(2-vinylpyridine)(PS-b-P2VP)microparticles within confined emulsion droplets.The co-surfactant was synthesized by grafting poly(acrylic acid)-b-poly(N-isopropylacrylamide)onto the surface of Fe3O4NP.The introduction of the dual-responsive co-surfactant enabled thermo/p H dual-responsive reversible morphology transition of the PS-b-P2VP microparticles by tailoring the hydrophobicity and interfacial affinity of the cosurfactant.By using this strategy,the thermo-inert PS-b-P2VP self-assembled into pupa-like microparticles at T=10℃ and p H7.5,which could transform into tulip-like microparticles when T was increased to 50℃.When the p H value was increased to 11,the pupa-like particles turned into onion-like microparticles although the PS-b-P2VP was inert to alkali.However,the pupa-like microparticles remained unchanged when both T and p H were simultaneously increased.The PAA-b-PNIPAM-grafted Fe3O4NP surfactants showed obvious advantages over the linear PAA-b-PNIPAM surfactants in modulating the morphology transition,since the linear PAA-b-PNIPAM could not induce the reversible shape transition of microparticles.Our work provides an efficient strategy to achieve reversible shape transformation of BCP microparticles while the internal phase structure is preserved,which may be utilized to switch the structural color properties of BCP microparticles.

关键词： block copolymer self-assembly stimuli-responsiveness lower critical solution temperature microparticle

A micro-sized vaccine based on recombinant Lactiplantibacillus plantarum fights against SARS-CoV-2 infection via intranasal immunization

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药学学报:英文版 2023年第7期13卷 3168-3176页

作者： Letian Li Jiayi Hao Yuhang Jiang Pengfei Hao Yuwei Gao Jing Chen Guoqing Zhang Ningyi Jin Maopeng Wang Chang Li Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses Chinese Academy of Medical SciencesChangchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchun 130122China Wenzhou Key Laboratory for Virology and Immunology Institute of VirologyWenzhou UniversityWenzhou 325035China

COVID-19 has globally spread to burden the medical system.Even with a massive vaccination,a mucosal vaccine offering more comprehensive and convenient protection is imminent.Here,a micro-sized vaccine based on recombinant Lactiplantibacillus plantarum(rLP)displaying spike or receptor-binding domain(RBD)was characterized as microparticles,and its safety and protective effects against SARS-CoV-2 were evaluated.We found a 66.7%mortality reduction and 100%protection with rLP against SARS-CoV-2 in a mouse model.The histological analysis showed decreased hemorrhage symptoms and increased leukocyte infiltration in the lung.Especially,rLP:RBD significantly decreased pulmonary viral loads.For the first time,our study provides a L.plantarum-vectored vaccine to prevent COVID-19 progress and transmission via intranasal vaccination.

关键词： COVID-19 Mucosal vaccines Lactiplantibacillus plantarum microparticle Intranasal administration Viral challenge Mice Lung targeting delivery system

Graphene-tuned threshold gain to achieve optical pulling force on microparticle

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Chinese Physics B 2021年第6期30卷 306-310页

作者：陈鸿莉黄杨 School of Science Nantong UniversityNantong 226019China School of Science Jiangsu Provincial Research Center of Light Industrial Optoelectronic Engineering and TechnologyJiangnan UniversityWuxi 214122China

We investigate optical force on a graphene-coated gain microparticle by adopting the Maxwell's stress tensor method.It is found that there exists a threshold gain in obtaining the Fano-profile optical force which indicates the reversal of optical pushing and pulling force. And giant pushing/pulling force can be achieved if the gain value of the material is in the proximity of the threshold gain. Our results show that the threshold gain is more sensitive to the relaxation time than to the Fermi energy of the graphene. We further study the optical force on larger microparticle to demonstrate the pulling force occurring at octupole resonance with small gain value and then it will appear at quadrupole resonance by increasing gain value. Our work provides an in-depth insight into the interaction between light and gain material and gives the additional degree of freedom to optical manipulation of microparticle.

关键词： pulling force threshold gain graphene microparticle

Microfluidic Generation of Multicomponent Soft Biomaterials

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Engineering 2022年第6期8卷 128-143页

作者： Yuetong Wang Luoran Shang Yuanjin Zhao Lingyun Sun Department of Rheumatology and Immunology Nanjing Drum Tower Hospital&School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China School of Food Science and Pharmaceutical Engineering Nanjing Normal UniversityNanjing 210046China Shanghai Xuhui Central Hospital&Zhongshan-Xuhui Hospital&Shanghai Key Laboratory of Medical Epigenetics&International Co-Laboratory of Medical Epigenetics and Metabolism of Ministry of Science and Technology Institutes of Biomedical SciencesFudan UniversityShanghai 200032China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001China

Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-materials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions.Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents,in that it can manipu-late multiphasic flows precisely on the micron scale.In recent decades,much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery,three-dimensional(3D)cell culture,flexible devices and wearable electronics,and biosensing for molecules.In the paper,we summarize current pro-gress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields.We also provide an outlook of the remaining challenges and future trends in this field.

关键词： Soft biomaterial Microfluidics Multicomponent microparticle Microfiber

A CALCULATION METHOD OF XQMA FOR IRREGULAR-SHAPED SUPER-microparticle SPECIMENS BY MONTE CARLO DIRECT SIMULATION

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Science in China,Ser.A 1988年第7期 870-878页

作者：何延才王心磊陈家光

An X-ray quantitative microanalysis （XQMA） calculation method for irregular-shaped super-microparticle specimens has been established. Using the Monte Carlo direct simulation the complex calculation method of separating Z. A. F coefficient can be avoided. The calculation formulae of regular-shaped particle specimens can be extended to those of irregularshaped by using the concept of ’equivalent geometric shape’. This method has been proved by the experiments of X-ray quantitative microanalysis on super-microparticle specimens.

关键词： microparticle Monte Carlo direct simulation XQMA.

microparticles as Novel Biomarkers and Therapeutic Targets in Coronary Heart Disease

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Chinese Medical Journal 2015年第2期128卷 267-272页

作者： Bo-Da Zhou Ge Guo Le-Min Zheng Ling-Yun Zu Wei Gao Department of Cardiology Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health Peking University Third Hospital Beijing 100191 China Institute of Cardiovascular Sciences and Institute of Systems Biomedicine School of Basic Medical Sciences Peking University Health Science Center Beijing 100191 China

INTRODUCTION microparticles （MPs） were increased in patients with coronary heart disease （CHD）,with the subtypes and quantity of MPs variate in different types of CHD.There were emerging reports indicating that MPs may play important roles in the pathogenesis of CHD.Here in this review we summarized the pro-inflammation,pro-coagulation effects of MPs,as well as their impacts on endothelial function and angiogenesis.MPs have the potential of being powerful diagnostic biomarkers and therapeutic tools in CHD patients in the future.

关键词： Coagulation Coronary Heart Disease Endothelial Function： hlflanlmation microparticle

Inflammation induced-endothelial cells release angiogenesis associated-microRNAs into circulation by microparticles

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Chinese Medical Journal 2014年第12期127卷 2212-2217页

作者： Zhang Jing Ren Jingyi Chen Hong Geng Qiang Department of Cardiology Peking University Peoples HospitalBeijing 100044China

Background Endothelial cells derived microRNAs can be detected in plasma and serum and there is evidence that inflammatory disease states may affect the levels of circulating microRNAs.However,there is no direct proof that inflammation induces endothelial cells to release microRNAs into circulation.This study aimed to explore whether inflammation could induce endothelial cells to release microRNAs into circulation and to investigate whether these released microRNAs derived from endothelial cells were transported in microparticles.Methods microparticles were isolated from human atherosclerotic plaques with an active inflammatory phenotype and normal vascular tissue.Flow cytometry and real-time PCR were used to detect the levels of microparticles and microRNAs.Human umbilical vein endothelial cells （HUVEC） was treated with tumour necrosis factor α （TNF-α,10 ng/ml） for 24 hours,and then HUVEC and the culture medium were respectively collected.Results By comparing microparticles isolated from human atherosclerotic plaques with an active inflammatory phenotype （n=9） and those from normal vascular tissues （n-9）,we found levels of annexin V＋ microparticles and annexin V＋ CD144＋ microparticles were significantly increased in plaques and angiogenesis associated microRNAs （106b,25,92a and 21） were also significantly increased in microparticles from plaques.After exposure to TNF-α at a concentration of 10 ng/ml （TNF-α group,n=3） or DMEM （control group,n=3） for 24 hours,counts of microparticles and expressions of microRNAs 106b,25,92a and 21 in microparticles isolated from medium significantly increased.However,there were no differences in the intracellular levels of microRNAs 25,92a or 21 isolated from HUVEC between TNF-α group and control group,while microRNA 106b decreased in TNF-α group.Conclusion Inflammation could induce endothelial cells to release angiogenesis associated microRNAs into circulation,causing higher levels of circulating endothelial cells derived microRNAs in atherosclerosis.

关键词： microRNAs atherosclerosis inflammation microparticle