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Timp1 Deletion Induces Anxiety-like Behavior in Mice

Neuroscience Bulletin 2024年第6期40卷 732-742页

作者： Xiaotong Wang Wei Zheng Ziyi Zhu Biyu Xing Weijie Yan Ke Zhu Lingli Xiao Chaojuan Yang Mengping Wei Lei Yang Zi-Bing Jin Xueyun Bi Chen Zhang State Key Laboratory of Neurology and Oncology Drug Development Nanjing210000China School of Basic Medical Sciences Wenzhou Medical UniversityWenzhou325035China School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and RepairAdvanced Innovation Center for Human Brain ProtectionBeijing Laboratory of Oral HealthCapital Medical UniversityBeijing100069China Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing100005China Chinese Institute for Brain Research Beijing102206China Key Laboratory for Biomechanics and Mechanobiology of the Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Engineering MedicineBeihang UniversityBeijing100191China

The hippocampus is essential for learning and memory,but it also plays an important role in regulating emotional behavior,as hippocampal excitability and plasticity affect anxiety and *** synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1(TIMP1),a known protein inhibitor of extracellular matrix(ECM),and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various ***,the involvement of Timp1 in fear learning,anxiety,and hippocampal synaptic function remains to be *** study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear *** results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region,but the basic synaptic transmission and plasticity were normal in the Schaffer collateral *** together,our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors,but that Timp1 is not crucial for fear learning.

关键词： Timp1 Anxiety Fear Synaptic transmission Synaptic plasticity

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Expression and function of WNT4 involved in larvae development and limb regeneration in Portunus trituberculatus

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Journal of Oceanology and Limnology 2021年第1期39卷 306-316页

作者： Zhiming REN Yuanyuan FU Lei LIU Xiao LIU Chunlin WANG Key Laboratory of Applied Marine Biotechnology Ministry of EducationNingbo UniversityNingbo 315832China collaborative innovation center for Zhejiang Marine High-effi ciency and Healthy Aquaculture Ningbo UniversityNingbo 315832China

The wingless-related integration site(WNT)proteins are a family of secreted glycoproteins that are evolutionarily conserved and are believed to be involved in evolution in vertebrates and *** signaling pathways may be associated with limb regeneration and development in ***,the detail mechanisms remain ***,the distribution of WNT4 in the hepatopancreas,muscle,hemocyte,ganglion,heart,eyestalk,gill tissue,and diff erent larvae development stages of the swimming crab(Portunus trituberculatus)were characterized using immunofl uorescence,real-time PCR,and Western *** cant PtWNT4 expression was detected in heart and *** addition,PtWNT4 was expressed in all larval stages of *** with a dynamic expression pattern,especially in the eyestalk and other organs in the carapace *** injection of WNT4 dsRNA into regenerative limbs signifi cantly decreased PtWNT4 mRNA levels in the eyestalk,heart,and muscle,resulting in 1.9-fold,2.2-fold,and 2.7-fold decreases compared with those detected in the group injected with crab saline(Pregeneration in *** results not only demonstrated the requirement for WNT4 in limb regeneration of Crustaceans,but also suggested its ability to promote larval development at specifi c stages.

关键词： wingless-type MMTV integration site family member-4(WNT4) limb regeneration larvae development Portunus trituberculatus expression pattern RNAi

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Materials and extracellular matrix rigidity highlighted in tissue damages and diseases:Implication for biomaterials design and therapeutic targets

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Bioactive Materials 2023年第2期20卷 381-403页

作者： Jae Hee Park Seung Bin Jo Jung-Hwan Lee Hae-Hyoung Lee Jonathan CKnowles Hae-Won Kim Institute of tissue regeneration Engineering(ITREN) Dankook UniversityCheonan31116Republic of Korea Department of Nanobiomedical Science and BK21 NBM Global Research center for Regenerative medicine Dankook UniversityCheonan31116Republic of Korea Department of Biomaterials Science College of DentistryDankook UniversityCheonan31116Republic of Korea Cell&Matter Institute Dankook UniversityCheonan31116Republic of Korea Mechanobiology Dental medicine Research center Dankook UniversityCheonan31116Republic of Korea UCL Eastman-Korea Dental medicine innovation Centre Dankook UniversityCheonan31116Republic of Korea Division of Biomaterials and tissue Engineering UCL Eastman Dental InstituteUniversity College LondonRoyal Free HospitalRowland Hill StreetLondonNW32PFUnited Kingdom

Rigidity(or stiffness)of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors,such as contractility,motility,and spreading,and the resultant pathophysiological *** 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events,including migration,lineage specification,and mechanical ***,the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control,tissue repair,and disease ***,here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors,with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems,further discussion of the events and considerations in tissue-mimicking 3D conditions,and then examination of the in vivo findings that concern material/matrix *** current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues.

关键词： Matrix rigidity Biophysical cue Cell and tissue engineering 3D biomaterials conditions Therapeutic targets

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Isoquercitrin promotes peripheral nerve regeneration following sciatic crush injury in rats

Isoquercitrin promotes peripheral nerve regeneration followi...

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中国解剖学会2019年年会

作者： Jiaying Qiu Li Wei Xiaoming Yang Lai Xu Fei Ding Hualin Sun Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury RepairCo-Innovation Center of NeuroregenerationNantong University

＜正＞Oxidative stress and inflammation have been recognized to play a crucial role in the pathogenesis of peripheral nerve *** has potent anti-inflammatory and anti-oxidative *** our study,we demonstrated that

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TGF-β1-supplemented decellularized annulus fibrosus matrix hydrogels promote annulus fibrosus repair

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Bioactive Materials 2023年第1期19卷 581-593页

作者： Qiang Wei Dachuan Liu Genglei Chu Qifan Yu Zhao Liu Jiaying Li Qingchen Meng Weishan Wang Fengxuan Han Bin Li Department of Orthopaedic Surgery Orthopaedic InstituteThe First Affiliated HospitalSuzhou Medical CollegeSoochow UniversitySuzhouJiangsuChina Department of Orthopaedic Surgery The First Affiliated HospitalShihezi University School of MedicineShiheziXinjiangChina collaborative innovation center of Hematology Soochow UniversitySuzhouJiangsuChina

Annulus fibrosus(AF)repair remains a challenge because of its limited self-healing *** repair strategies combining scaffolds and growth factors show great promise in AF *** the unique and beneficial characteristics of decellularized extracellular matrix(ECM)in tissue repair have been demonstrated,the poor mechanical property of ECM hydrogels largely hinders their applications in tissue *** the present study,we combined polyethylene glycol diacrylate(PEGDA)and decellularized annulus fibrosus matrix(DAFM)to develop an injectable,photocurable hydrogel for AF *** found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous *** growth factor-β1(TGF-β1)was further incorporated into PEGDA/DAFM hydrogels,and it could be continuously released from the *** in vitro experiments showed that TGF-β1 facilitated the migration of AF ***,PEGDA/DAFM/TGF-β1 hydrogels supported the adhesion,proliferation,and increased ECM production of AF *** vivo repair performance of the hydrogels was assessed using a rat AF defect *** results showed that the implantation of PEGDA/DAFM/TGF-β1 hydrogels effectively sealed the AF defect,prevented nucleus pulposus atrophy,retained disc height,and partially restored the biomechanical properties of *** addition,the implanted hydrogel was infiltrated by cells resembling AF cells and well integrated with adjacent AF *** summary,findings from this study indicate that TGF-β1-supplemented DAFM hydrogels hold promise for AF repair.

关键词： Decellularized matrix Annulus fibrosus Hydrogel TGF-β1 tissue repair

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Biomaterials as carrier, barrier and reactor for cell-based regenerative medicine

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Protein & Cell 2015年第9期6卷 638-653页

作者： Chunxiao Qi Xiaojun Yan Chenyu Huang Alexander Melerzanov Yanan Du Department of Biomedical Engineering School of Medicine Tsinghua University Beijing 100084 China collaborative innovation center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310003 China Department of Plastic and Reconstructive Surgery Beijing Tsinghua Changgung Hospital. Medical CenterTsinghua University Beijing 102218 China Cellular and Molecular Technologies Laboratory MIPT Dolgoprudny 141701 Russia

Cell therapy has achieved tremendous success in regenerative medicine in the past several decades. However, challenges such as cell loss, death and immune-rejection after transplantation still persist. Bio- materials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation. With the assistance of bio- materials, improvement in treatment efficiency has been demonstrated in numerous animal models of degener- ative diseases compared with routine free cell-based therapy. Emerging clinical applications of biomaterial assisted cell therapies further highlight their great pro- mise in regenerative therapy and even cure for complex diseases, which have been failed to realize by conven- tional therapeutic approaches.

关键词： carrier barrier reactor biomaterial-assisted therapy regenerative medicine

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Mechanogrowth Factor Promotes Mechanical Response in Ligament Fibroblasts of Knee Osteoarthritis via Activating ATF-2

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医用生物力学 2019年第A1期34卷 54-55页

作者： Yu Ma Yang Song Linhao Li Lili Dong Li Yang '111’Project Laboratory of Biomechanics and tissue repair Bioengineering CollegeChongqing UniversityChongqing400044China Beijing Advanced innovation center for Biomedical Engineering Beihang UniversityBeijing100083China Department of Bioengineering University of California Los AngelesLos Angeles90095USA

Background&Objective Knee osteoarthritis(OA)is a degenerative disease,which not only induces superficial cartilage defects and full-thickness cartilage defects,but also exacerbates the microenvironment of the knee joint and affects the mechano-chemical responses of the *** a growth/repair factor,mechanical growth factor(MGF)has the function of preventing OA,promoting cartilage regeneration and repairing damaged *** transcription factor 2(ATF-2),a transcription factor,has the property of binding to cytokines,which makes it involved in the transcriptional regulation of various pathways in response to cellular stress,inflammatory cytokine and growth *** present,little is known about the effect of MGF on human osteoarthritis ligament fibroblasts(OA-LFs),and whether the approach can promote OA-LFs timely response to the mechanical injury and initiate signaling pathway for cell ***,the purpose of this study is to investigate whether MGF promotes mechanical response to ligament fibroblasts in osteoarthritis knee cavity via *** OA-LFs were seeded onto six-cell BioFlex plates and suffered from 12%static mechanical stretch[60 cycles/minute(1 Hz)]for 12 hours to mimic mechanical force mediated ligament ***,OA-LFs were treated with MGF before and during mechanical *** reactive oxygen species(ROS)and GRP78 mRNA expression were investigated to detect the cellular stress response of *** scratch test was performed to detect the migration ability of cells,gelatin zymography was used to examine the effect of MGF on the activity of matrix metalloproteinase 2(MMP-2)in OA-LFs,and cell deformation was detected by phalloidin-FITC staining after *** real-time polymerase chain reaction(qRT-PCR)was used to screen the messenger RNA(mRNA)expression of ATF family members after OALFs treatment with *** blotting further proved that MGF is capable to activate the ***

关键词： Mechanogrowth Factor Mechanical Response Knee Osteoarthritis via Activating ATF-2 ATF

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Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing

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Chinese Chemical Letters 2023年第4期34卷 122-126页

作者： Guiting Liu Yuan Zhou Zejun Xu Ziting Bao Li Zheng Jun Wu The State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial Hospital Sun Yat-sen UniversityGuangzhou 510120China School of Biomedical Engineering Sun Yat-sen UniversityGuangzhou 510006China Guangxi Engineering center in Biomedical Materials for tissue and Organ regeneration Life Science InstitutesGuangxi Medical UniversityNanning 530021China collaborative innovation Centre of Regenerative medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China

Anti-infection and neovascularization at the wound site are two vital factors that accelerate diabetic wound healing. However, for a wound healing dressing, the two functions need to work at different sites(inner and outer), giving big challenges for dressing design. In this study, we fabricated a novel sodium alginate/chitosan(SA/CS) Janus hydrogel dressing by the assembly of SA hydrogel loaded with silver nanoparticles(Ag NPs) and CS hydrogel impregnated with L-arginine loaded sodium alginate microspheres(Arg MSs) based on electrostatic interactions to combine the two functions. The outer SA-Ag NP hydrogel could prevent infection while avoiding the deposition of Ag NPs in the wound site, and the inner CS-Arg MS hydrogel on the wound surface could realize the sustained release of L-arginine and promote vascular regeneration. The composition, morphology and swelling/degradation of the SA-Ag NP/CS-Arg MS hydrogel were characterized systematically. L-Arginine release behavior has been tested and SA-Ag NP/CSArg MS hydrogel has been confirmed for excellent biocompatibility. Antibacterial and angiogenesis assays demonstrated the antibacterial and angiogenesis characteristics of the SA-Ag NP/CS-Arg MS hydrogel. Finally, in vivo diabetic wound healing assay demonstrated that the SA-Ag NP/CS-Arg MS hydrogel could significantly accelerate re-epithelialization, granulation tissue formation, collagen deposition and angiogenesis, thereby resulting in enhanced diabetic wound healing。

关键词： Janus hydrogel Antibacterial Angiogenesis Diabetic wound Wound healing

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Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics

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Bioactive Materials 2022年第2期7卷 267-295页

作者： Amal George Kurian Rajendra KSingh Kapil DPatel Jung-Hwan Lee Hae-Won Kim Institute of tissue regeneration Engineering(ITREN) Dankook UniversityCheonan31116Republic of Korea Department of Nanobiomedical Science&BK21 NBM Global Research center for Regenerative medicine Dankook UniversityCheonan31116Republic of Korea Biomaterials and tissue Engineering UCL Eastman Dental InstituteLondonWC1X8LDUK Department of Biomaterials Science School of DentistryDankook UniversityCheonan31116Republic of Korea UCL Eastman-Korea Dental medicine innovation Centre Dankook UniversityCheonan31116Republic of Korea Cell&Matter Institute Dankook UniversityCheonan31116Republic of Korea Department of Regenerative Dental medicine College of DentistryDankook UniversityCheonan31116Republic of Korea Mechanobiology Dental medicine Research center Dankook UniversityCheonan31116Republic of Korea

Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and *** others,methacrylated gelatin(GelMA)has become a representative hydrogel formulation,finding various biomedical *** efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials,aiming to provide enhanced physicochemical and biological properties to *** benefits of this approach are multiple:i)reinforcing mechanical properties,ii)modulating viscoelastic property to allow 3D printability of bio-inks,iii)rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues(e.g.,muscle,nerve),iv)providing stimuli-responsiveness to actively deliver therapeutic molecules,and v)endowing therapeutic capacity in tissue repair process(e.g.,antioxidant effects).The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues(bone,skin,cardiac,and nerve)that are rarely observable with *** we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue *** approaches used in GelMA can also apply to other existing polymeric hydrogel systems.

关键词： GelMA hydrogel Nanomaterials Multifunctional Therapeutics tissue repair

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Autocatalytic bifunctional supramolecular hydrogels for osteoporotic bone repair

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National Science Review 2024年第7期11卷 263-278页

作者： Zhihui Han Xiang Gao Yuanjie Wang Cheng Huang Hao Song Shuning Cheng Xiaoyuan Yang Xiaoliang Cui Jie Wu Kailu Wei Liang Cheng Institute of Functional Nano&Soft Materials(FUNSOM) Collaborative Innovation Center of Suzhou Nano Science and TechnologySoochow University Department of Orthopedics The Second Affiliated Hospital of Soochow University Macao Institute of Materials Science and Engineering Macau University of Science and Technology

Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels(Ce–Aln gel) consisting of alendronate(Aln) and cerium(Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce–Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce–Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid(RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling,hypoxia metabolism and tumor necrosis factor-alpha(TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce–Aln gel. In vivo experiments showed that the clinical drug-based Ce–Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.

关键词： autocatalysis supramolecular hydrogel anti-inflammation osteoporosis bone defect

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