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Protective effects of human umbilical cord mesenchymal stem cell vein transplantation against spinal cord ischemia/reperfusion injury in rats

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Neural Regeneration Research 2010年第3期5卷 171-177页

作者： Jun Zou Minfeng Gan Xuesong Zhu dechun geng Huilin Yang Department of Orthopedics First Affiliated Hospital of Soochow University Suzhou 215006 Jiangsu Province China

BACKGROUND： The majority of studies addressing spinal cord ischemia/reperfusion injury （SCIRI） have focused on drugs, proteins, cytokines, and various surgical techniques. A recent study reports that human umbilical cord mesenchymal stem cell （hUCMSC） transplantation achieves good therapeutic effects, but the mechanisms underlying nerve protection remain poorly understood. OBJECTIVE： To observe survival of transplanted hUCMSCs in SCIRI rat models and the influence on motor function in the hind limbs, to determine interleukin-8 expression and cellular apoptosis in spinal cord tissues, and to verify the hypothesis that hUCMSC transplantation exhibits protective effects on SCIRI. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of the Department of Orthopedics in the First Affiliated Hospital of Soochow University, China between January 2007 and December 2008. MATERIALS： hUCMSCs were harvested from umbilical cord blood of healthy pregnant women after parturition in the Obstetrical Department of the First Affiliated Hospital of Soochow University, China. Rabbit anti-human BrdU monoclonal antibody was provided by DAKO, USA. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） Kit and enzyme-linked immunosorbent assay （ELISA） Kit were purchased by Wuhan Boster, China. METHODS： A total of 72 healthy, Wistar, adult rats were randomly assigned to three groups： sham-surgery, model, and transplantation, with 24 rats in each group. SCIRI was induced in the model and transplantation groups via the abdominal aorta block method. The infrarenal abdominal aorta was not blocked in the sham-surgery group. Prior to abdominal aorta occlusion, 0.2 03 mL bromodeoxyuridine （BrdU）-Iabeled hUCMSCs suspension （cell concentration 5 × 10 3/uL） was injected through the great saphenous vein of the hind limb, and an equal volume of physiological saline was administered to the model and sham-surgery groups. MAIN OUTCOME MEASURES：

关键词： human umbilical cord mesenchymal stem cells spinal cord ischemia/reperfusion injury protective effect apoptosis inflammatory mediators neural regeneration

利格列汀调控巨噬细胞极化和破骨细胞形成缓解磨损颗粒诱导的骨质溶解

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中国组织工程研究 2025年第12期29卷 2421-2428页

作者：杨鹏张巍李文明李文豪吴泽彬周军耿德春苏州大学附属第一医院骨科江苏省苏州市215006

背景:研究发现,在利格列汀的干预下,巨噬细胞更多的由M1转向M2极化,降低了相关炎性因子的释放,缓解了局部炎症。目的:探讨利格列汀对巨噬细胞极化、破骨细胞活化及磨损颗粒诱导炎性骨溶解的影响。方法:(1)细胞实验:①巨噬细胞极化:将RAW... 详细信息

背景:研究发现,在利格列汀的干预下,巨噬细胞更多的由M1转向M2极化,降低了相关炎性因子的释放,缓解了局部炎症。目的:探讨利格列汀对巨噬细胞极化、破骨细胞活化及磨损颗粒诱导炎性骨溶解的影响。方法:(1)细胞实验:①巨噬细胞极化:将RAW264.7细胞分4组培养,对照组细胞加入高糖培养基;M1诱导组加入M1诱导培养基(含脂多糖100 ng/mL和干扰素γ20 ng/mL的高糖培养基)模拟炎症环境;利格列汀低、高剂量组分别加入50,200 nmol/L利格列汀处理4 h后加入M1诱导培养基。巨噬细胞极化诱导24 h后,分别进行巨噬细胞极化免疫荧光染色和RT-PCR检测。②破骨细胞活化:将RAW264.7细胞分为4组培养,对照组使用高糖培养基培养,破骨细胞诱导组、利格列汀低剂量组及高剂量组进行破骨细胞诱导,待微小破骨细胞成形后,用利格列汀(50,200 nmol/L)分别干预细胞3 d,进行细胞抗酒石酸酸性磷酸酶染色和RT-PCR检测。(2)动物实验:将24只雄性C57BL/6J小鼠随机分为4组,即假手术组、模型组、利格列汀低剂量组及高剂量组,后3组通过将钛颗粒悬浊液注射至颅骨表面建立颅骨骨溶解模型,从造模后第2天开始,利格列汀低、高剂量组分别灌胃利格列汀(2,10 mg/kg),每天1次,造模3周后,检测血清巨噬细胞极化标志蛋白及炎性因子水平,收集颅骨进行micro-CT扫描、骨参数分析及苏木精-伊红染色评估骨溶解及形态学变化。结果与结论:①细胞实验:与M1诱导组比较,利格列汀低、高剂量组可显著抑制巨噬细胞的M1极化、促进M2极化(P<0.01),且以高剂量组效果更显著(P<0.01)。与破骨诱导组比较,利格列汀低、高剂量组可抑制破骨细胞的活化及骨质吸收,且以高剂量组抑制更显著。与对照组比较,M1诱导组炎性因子mRNA表达升高(P<0.01),而与M1诱导组相比较,利格列汀低、高剂量组炎性因子mRNA表达显著降低(P<0.01)。与对照组比较,破骨诱导组破骨功能标志物的mRNA表达升高(P<0.01);与破骨诱导组比较,利格列汀低、高剂量组破骨功能标志物的mRNA表达降低(P<0.01),且以高剂量组降低更明显。②动物实验:钛颗粒植入导致小鼠颅骨骨溶解破坏,利格列汀可抑制钛颗粒诱导的骨溶解,其中以高剂量组抑制作用更显著。结果表明利格列汀具有调节巨噬细胞极化、抑制破骨细胞活化及对骨骼系统的保护作用。

关键词：利格列汀巨噬细胞极化破骨细胞活化磨损颗粒无菌性假体松动假体周围骨溶解

Nanomaterial-assisted theranosis of bone diseases

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Bioactive Materials 2023年第6期24卷 263-312页

作者： Kai Zheng Jiaxiang Bai Huilin Yang Yaozeng Xu Guoqing Pan Huaiyu Wang dechun geng Department of Orthopedics The First Affiliated Hospital of Soochow University188 Shizi RoadSuzhou215006JiangsuChina Center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518055China Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiang212013JiangsuChina

Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage *** approaches can regulate bone homeostasis to a certain ***,these therapies are still associated with some undesirable ***,recent advances in nanomaterials have provided unprecedented opportunities for diagnosis and therapy of bone-related *** review provides a comprehensive and up-to-date overview of current advanced theranostic nanomaterials in bone-related ***,the potential utility of nanomaterials for biological imaging and biomarker detection is ***,nanomaterials serve as therapeutic delivery platforms with special functions for bone homeostasis regulation and cellular modulation are ***,perspectives in this field are offered,including current key bottlenecks and future directions,which may be helpful for exploiting nanomaterials with novel properties and unique *** review will provide scientific guidance to enhance the development of advanced nanomaterials for the diagnosis and therapy of bone-related diseases.

关键词： Nanomaterials Delivery Diagnosis Therapy Bone-related diseases

Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration

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Research 2023年第2期2022卷 305-318页

作者： Jiaxiang Bai Gaoran Ge Qing Wang Wenming Li Kai Zheng Yaozeng Xu Huilin Yang Guoqing Pan dechun geng Department of Orthopaedics The First Affiliated Hospital of Soochow University188 Shizi StreetSuzhouJiangsu 215006China Institute for Advanced Materials Schoolof Materials Science and EngineeringJiangsu University301 Xuefu RoadZhenjiang Jiangsu 212013China

For patients with osteoporosis,the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation,migration,and osteogenic differentiation abilities of bone marrow mesenchymal stem cell... 详细信息

关键词： impaired osteoporosis Mimics

Metal ion metabolism and osteoporosis:possible implications for pharmaceutical biotechnology and tissue engineering

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Science China(Life Sciences) 2024年第8期67卷 1763-1765页

作者： Huaqiang Tao Qiufei Wang Kai Chen Pengfei Zhu Ye Gu dechun geng Department of Orthopedics The First Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Orthopedics Changshu Hospital Affiliated to Soochow UniversityFirst People’s Hospital of Changshu CityChangshu 215506China Department of Orthopedics Hai’an People’s HospitalHai’an 226600China

Osteoporosis(OP)is a systemic metabolic bone disease characterized by low bone mass,damage to bone microstructure and increased bone *** imbalance of functional coupling between osteoblasts and osteoclasts contributes to the pathological progression of the disease(Rachner et al.,2011).The pathogenesis of OP is precisely controlled by the complex regulatory network of the bone *** elements,although present in small amounts in the body,are essential for their influence on the physiological activities of *** ions act as effective catalysts and have applications in all stages of cell biochemical evolution(Qian et al.,2021).Bone tissue contains various metal elements,and metal ions play indispensable roles in bone metabolism at the molecular and cellular levels(Luo et al.,2023).However,it is important to note that these metal ions can also contribute to the progression of OP by influencing multiple cellular pathways either directly or indirectly.

关键词： metabolism biotechnology indispensable

Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections

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Research 2023年第3期6卷 409-421页

作者： Jiaxiang Bai Yonghai Feng Wenming Li Zerui Cheng Jessica MRosenholm Huilin Yang Guoqing Pan Hongbo Zhang dechun geng Department of Orthopedic Surgery Orthopedic InstituteThe First Affiliated HospitalMedical CollegeSoochow UniversitySuzhouJiangsu 215006P.R.China Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiangJiangsu 212013P.R.China Pharmaceutical Sciences Laboratory Faculty of Science and EngineeringÅbo Akademi UniversityTurku 20520Finland Turku Bioscience Centre University of Turku andÅbo Akademi UniversityTurku 20520Finland

Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of *** address this issue,here,we report a copper and silk fibroin(Cu-SF)complex strategy to synthesize alternative copper single-atom nanozymes(SAzymes)with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets(CuN_(x)-CNS)and tunable N coordination numbers in the CuN_(x) sites(x=2 or 4).The CuN_(x)-CNS SAzymes inherently possess triple peroxidase(POD)-,catalase(CAT)-,and oxidase(OXD)-like activities,facilitating the conversion of H_(2)O_(2)and O_(2)into reactive oxygen species(ROS)through parallel POD-and OXD-like or cascaded CAT-and OXD-like *** to CuN_(2)-CNS,tailoring the N coordination number from 2 to 4 endows the SAzyme(CuN_(4)-CNS)with higher multienzyme activities due to its superior electron structure and lower energy ***,CuN_(x)-CNS display strong absorption in the second near-infrared(NIR-II)biowindow with deeper tissue penetration,offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep *** in vitro and in vivo results demonstrate that the optimal CuN_(4)-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms,thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.

关键词： copper offering eliminate

Comprehensive overview of microRNA function in rheumatoid arthritis

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Bone Research 2023年第1期11卷 65-88页

作者： Xiaole Peng Qing Wang Wenming Li Gaoran Ge Jiachen Peng Yaozeng Xu Huilin Yang Jiaxiang Bai dechun geng Department of Orthopedics The First Affiliated Hospital of Soochow University188 Shizi StreetSuzhou215006JiangsuP.R.China Department of Orthopedics Affiliated Hospital of Zunyi Medical University563000ZunyiP.R.China

MicroRNAs(miRNAs),a class of endogenous single-stranded short noncoding RNAs,have emerged as vital epigenetic regulators of both pathological and physiological processes in *** direct fundamental cellular pathways and processes by fine-tuning the expression of multiple genes at the posttranscriptional *** evidence suggests that mi RNAs are implicated in the onset and development of rheumatoid arthritis(RA).RA is a chronic inflammatory disease that mainly affects synovial *** common autoimmune disorder is characterized by a complex and multifaceted pathogenesis,and its morbidity,disability and mortality rates remain consistently *** in-depth insights into the underlying mechanisms of RA are required to address unmet clinical needs and optimize ***,we comprehensively review the deregulated mi RNAs and impaired cellular functions in RA to shed light on several aspects of RA pathogenesis,with a focus on excessive inflammation,synovial hyperplasia and progressive joint *** review also provides promising targets for innovative therapies of *** addition,we discuss the regulatory roles and clinical potential of extracellular mi RNAs in RA,highlighting their prospective applications as diagnostic and predictive biomarkers.

关键词： impaired endogenous function

Targeting strategies for bone diseases:signaling pathways and clinical studies

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2714-2748页

作者： Hao Xu Wentao Wang Xin Liu Wei Huang Chen Zhu Yaozeng Xu Huilin Yang Jiaxiang Bai dechun geng Department of Orthopedics The First Affiliated Hospital of Soochow University188 Shizi StreetSuzhouJiangsu215006P.R.China Department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230031AnhuiChina Orthopaedic Institute Medical CollegeSoochow UniversitySuzhou215006JiangsuChina

Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago,tremendous advances have occurred in targeted *** the initial selective antibody,antitoxin to targeted drug delivery that emerged in the past decades,more precise therapeutic efficacy is realized in specific pathological sites of clinical *** a highly pyknotic mineralized tissue with lessened blood flow,bone is characterized by a complex remodeling and homeostatic regulation mechanism,which makes drug therapy for skeletal diseases more challenging than other ***-targeted therapy has been considered a promising therapeutic approach for handling such *** the deepening understanding of bone biology,improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the *** this review,we provide a panoramic summary of recent advances in therapeutic strategies based on bone *** highlight targeting strategies based on bone structure and remodeling *** bone-targeted therapeutic agents,in addition to improvements of the classic denosumab,romosozumab,and PTH1R ligands,potential regulation of the remodeling process targeting other key membrane expressions,cellular crosstalk,and gene expression,of all bone cells has been *** bone-targeted drug delivery,different delivery strategies targeting bone matrix,bone marrow,and specific bone cells are summarized with a comparison between different targeting ***,this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area.

关键词： clinical Ehrlich deepening

Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 513-528页

作者： Miao CHU Guangdong CHEN Kai CHEN Pengfei ZHU Zhen WANG Zhonglai QIAN Huaqiang TAO Yaozeng XU dechun geng Department of Orthopedics the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Orthopedics Yixing People’s HospitalYixing 214200China Department of Orthopedics Hai’an People’s HospitalHai’an 226600China Department of Orthopedics Suzhou Kowloon HospitalShanghai Jiao Tong University School of MedicineSuzhou 215028China

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the *** activation plays a crucial role in the occurrence of subchondral bone loss in early ***,the specific mechanism of osteoclast differentiation in OA remains *** our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)***2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral ***,fourteen DEGs that are associated with oxidative stress were *** first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further *** results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of *** was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in ***,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in *** research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of *** HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

关键词： Osteoclast Oxidative stress Osteoarthritis(OA) Heme oxygenase 1(HMOX1) Carnosol