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| 1 | Punicalagin ameliorates collagen-induced arthritis by downregulating M1 macrophage and pyroptosis via NF-κB signaling pathway显示文摘Rheumatoid arthritis(RA)is a chronic inflammatory disease that eventually leads to disability.Inflammatory cell infiltration,severe joint breaking and systemic bone loss are the main clinical symptoms.In this study,we established a collagen-induced arthritis(CIA)model and found a large number of M1 macrophages and pyroptosis,which are important sources of proinflammatory cytokines.Punicalagin(PUN)is an active substance extracted from pomegranate peel.We found that it inhibited joint inflammation,cartilage damage and systemic bone destruction in CIA mice.PUN effectively alleviated the high expression of inflammatory cytokines in synovial tissue in vivo.PUN treatment shifted macrophages from the M1 phenotype to the M2 phenotype after stimulation with lipopolysaccharide(LPS)and interferon(IFN)-γ.The expression of inducible nitric oxide synthase(i NOS)and other proinflammatory cytokines released by M1 macrophages was decreased in the PUN treatment group.However,simultaneously,the expression of markers of anti-inflammatory M2 macrophages,such as arginase(Arg)-1 and interleukin(IL)-10,was increased.In addition,PUN treatment attenuated pyroptosis by downregulating the expression of NLRP3 and caspase-1,thereby preventing inflammatory cell death resulting from the release of IL-1βand IL-18.Mechanistically,PUN inhibited the activation of receptor activators of the nuclear factor-κB(NF-κB)signaling pathway,which contributes to M1 polarization and pyroptosis of macrophages.We concluded that PUN ameliorated pathological inflammation by inhibiting M1 phenotype polarization and pyroptosis and has great potential as a therapeutic treatment for human RA. | Gaoran Ge Jiaxiang Bai Qing Wang Xiaolong Liang Huaqiang Tao Hao Chen Minggang Wei Junjie Niu Huilin Yang Yaozeng Xu Yuefeng Hao Yi Xue Dechun Geng | 2022 | Science China(Life Sciences)2022，65，3： | 14 |
| 2 | ROS signaling cascades:dual regulations for osteoclast and osteoblast显示文摘Accumulating evidence indicates that intracellular reactive oxygen species(ROS)production is highly involved in bone homeostasis by intervening osteoclast or osteoblast differentiation.Interestingly,ROS that are known as oxidizing agents exert dose-dependent biphasic properties in bone remodeling,including preventing osteoblast activity but accelerating osteoclast resorption.ROS mainly composed of superoxide anion radical,hydroxyl radical,nitric oxide,and two-electron reduction product hydrogen peroxide,which are important components to regulate bone cell metabolism and function in mammal skeleton.These free radicals can be partly produced in bone and boosted in an inflammation state.Although numerous researches have emphasized the impacts of ROS on bone cell biology and verified the mechanism of ROS signaling cascades,the recapitulatory commentary is necessary.In this review article,we particularly focus on the regulation of the intracellular ROS and its potential mechanism impacting on cell-signaling transduction in osteoclast and osteoblast differentiation for preferable understanding the pathogenesis and searching for novel therapeutic protocols for human bone diseases. | Huaqiang Tao Gaoran Ge Xiaolong Liang Weicheng Zhang Houyi Sun Meng Li Dechun Geng | 2020 | Acta Biochimica et Biophysica Sinica2020，52，10： | 8 |
| 3 | Protective effects of human umbilical cord mesenchymal stem cell vein transplantation against spinal cord ischemia/reperfusion injury in rats显示文摘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, 0.2-0.3 mL bromodeoxyuridine (BrdU)-labeled hUCMSCs suspension (cell concentration 5 × 103/μL) 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: Pathological observation of rat spinal cord tissues was performed by hematoxylin-eosin staining at 6, 24, and 48 hours post-surgery. Immunohistochemistry was applied to determine hUCMSCs survival in the spinal cord. The amount of cellular apoptosis and interleukin-8 expression in spinal cord tissues was assayed utilizing the TUNEL and ELISA methods, respectively. Motor function in the hind limbs was evaluated according to Jacob's score. RESULTS: Numerous BrdU-positive cells were observed in spinal cord tissues from the transplantation group. The number of apoptotic cells and interleukin-8 levels significantly decreased in the transplantation group (P < 0.05), pathological injury was significantly ameliorated, and motor function scores significantly increased (P < 0.05) compared with the model group. CONCLUSION: Via vein transplantation, hUCMSCs were shown to reach and survive in the injury area. Results suggested that the transplanted hUCMSCs contributed to significantly improved pathological changes in the injured spinal cord, as well as motor function, following SCIRI. The protective mechanism correlated with inhibition of cellular apoptosis and reduced production of inflammatory mediators. | Jun Zou Minfeng Gan Xuesong Zhu Dechun Geng Huilin Yang | 2010 | Neural Regeneration Research2010，5，3： | 7 |
| 4 | Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy显示文摘Surgery is the final choice for most patients with intervertebral disc degeneration(IDD).Operation-caused trauma will cause inflammation in the intervertebral disc.Serious inflammation will cause tissue defects and induce tissue degeneration,IDD recurrence and the occurrence of other diseases.Therefore,we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin(ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local inflammation.ASP-liposomes(ASP-Lips)were incorporated into a photocrosslinkable gelatin-methacryloyl(GelMA)via mixing.This material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1(HMGB1)from the nucleus to the cytoplasm.We further assessed the expression of inflammatory cytokines,such as interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α),and degeneration-related factors,such as type II collagen(COL-2),Aggrecan,matrix metallopeptidases-3(MMP-3),MMP-13,a disintegrin and metalloproteinase with thrombospondin motifs-4(ADAMTS-4)and ADAMTS-5 in rat nucleus pulpous cells.The level of IDD was analyzed through H&E,safranin-O staining and immunohistochemistry in rabbit samples.In vitro,we found that ASP-Lip@GelMA treatment significantly decreased inflammatory cytokines,MMP-3 and-13,and ADAMTS-4 and-5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the nucleus.In vivo,ASP-Lip@GelMA can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue defects.This composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications. | Yu Liu Jiacheng Du Peng Peng Ruoyu Cheng Jiayi Lin Congxin Xu Huilin Yang Wenguo Cui Haiqing Mao Yuling Li Dechun Geng | 2021 | Bioactive Materials2021，6，1： | 6 |
| 5 | Protective effects of sirtuin 3 on titanium particle-induced osteogenic inhibition by regulating the NLRP3 inflammasome via the GSK-3β/β-catenin signalling pathway显示文摘Periprosthetic osteolysis(PPO)remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles.Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses.Additionally,the NLRP3 inflammasome is activated by prosthetic particles.Sirtuin3,an NAD+-dependent deacetylase of mitochondria,regulates the function of mitochondria in diverse activities.However,whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported.Therefore,we investigated the role of SIRT3 during the process of titanium(Ti)particle-induced osteolysis.We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro.Moreover,we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway.Collectively,these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation. | Kai Zheng Jiaxiang Bai Ning Li Meng Li Houyi Sun Weicheng Zhang Gaoran Ge Xiaolong Liang Huaqiang Tao Yi Xue Yuefeng Hao Chen Zhu Yaozeng Xu Dechun Geng | 2021 | Bioactive Materials2021，6，10： | 5 |
| 6 | A programmed surface on polyetheretherketone for sequentially dictating osteoimmunomodulation and bone regeneration to achieve ameliorative osseointegration under osteoporotic conditions显示文摘Polyetheretherketone(PEEK)is a desirable alternative to conventional biomedical metals for orthopedic implants due to the excellent mechanical properties.However,the inherent bioinertness of PEEK contributes to inferior osseointegration of PEEK implants,especially under pathological conditions of osteoporosis.Herein,a programmed surface is designed and fabricated on PEEK to dictate osteoimmunomodulation and bone regeneration sequentially.A degradable hybrid coating consisting of poly(lactide-co-glycolide)and alendronate(ALN)loaded nano-hydroxyapatite is deposited on PEEK and then interleukin-4(IL-4)is grafted onto the outer surface of the hybrid coating with the aid of N_(2) plasma immersion ion implantation and subsequent immersion in IL-4 solution.Dominant release of IL-4 together with ALN and Ca^(2+) during the first few days synergistically mitigates the early acute inflammatory reactions and creates an osteoimmunomodulatory microenvironment that facilitates bone regeneration.Afterwards,slow and sustained delivery of ALN and Ca^(2+) in the following weeks boosts osteogenesis and suppresses osteoclastogenesis simultaneously,consequently ameliorating bone-implant osseointegration even under osteoporotic conditions.By taking into account the different phases in bone repair,this strategy of constructing advanced bone implants with sequential functions provides customizable and clinically viable therapy to osteoporotic patients. | Yanyan Zheng Ang Gao Jiaxiang Bai Qing Liao Yuzheng Wu Wei Zhang Min Guan Liping Tong Dechun Geng Xin Zhao Paul K.Chu Huaiyu Wang | 2022 | Bioactive Materials2022，7，8： | 2 |
| 7 | Rational integration of defense and repair synergy on PEEK osteoimplants via biomimetic peptide clicking strategy显示文摘Polyetheretherketone(PEEK)has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance.However,its biological inertness,poor osteoinduction,and weak antibacterial activity make the clinical applications in a dilemma.Inspired by the mussel adhesion mechanism,here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins(Mfps)-mimic peptide with clickable azido terminal.The peptide enables mussel-like adhesion on PEEK biomaterial surfaces,leaving azido groups for the further steps of biofunctionalizations.In this study,antimicrobial peptide(AMP)and osteogenic growth peptide(OGP)were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair.Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios,an optimal PEEK surface was finally obtained in this research,which could long-term inhibit bacterial growth,stabilize bone homeostasis and facilitate interfacial bone regeneration.In a word,this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants,in particular,achieving rational integration of multiple biofunctions to match clinical requirements. | Meng Li Jiaxiang Bai Huaqiang Tao Li Hao Weiling Yin Xiaoxue Ren Ang Gao Ning Li Miao Wang Shiyuan Fang Yaozeng Xu Liang Chen Huilin Yang Huaiyu Wang Guoqing Pan Dechun Geng | 2022 | Bioactive Materials2022，7，2： | 2 |
| 8 | Targeting strategies for bone diseases:signaling pathways and clinical studies显示文摘Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago,tremendous advances have occurred in targeted therapy.From 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 diseases.As 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 tissues.Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks.With 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 horizon.In this review,we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting.We highlight targeting strategies based on bone structure and remodeling biology.For 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 exploited.For bone-targeted drug delivery,different delivery strategies targeting bone matrix,bone marrow,and specific bone cells are summarized with a comparison between different targeting ligands.Ultimately,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. | Hao Xu Wentao Wang Xin Liu Wei Huang Chen Zhu Yaozeng Xu Huilin Yang Jiaxiang Bai Dechun Geng | 2023 | Signal Transduction and Targeted Therapy2023，8，6： | 2 |
| 9 | One-pot formation and characterization of macrocyclic aromatic tetrasulfonates显示文摘 | Geng Mingwei Zhang Dechun Wu Xiangxiang | 2009 | Org Lett2009，11，4： | 1 |
| 10 | One- pot formation and characterization of macrocyclic aromatic tetrasulfonates 显示文摘 | Geng Mingwei Zhang Dechun Wu Xiangxiang | 2009 | Org Lett2009，11，4： | 1 |
| 11 | Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration显示文摘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 cells(BMSCs). | Jiaxiang Bai Gaoran Ge Qing Wang Wenming Li Kai Zheng Yaozeng Xu Huilin Yang Guoqing Pan Dechun Geng | 2023 | Research2023，，2： | 0 |
| 12 | A Full-Newton Step Feasible Interior-Point Algorithm for the Special Weighted Linear Complementarity Problems Based on a Kernel Function显示文摘In this paper,a new full-Newton step primal-dual interior-point algorithm for solving the special weighted linear complementarity problem is designed and analyzed.The algorithm employs a kernel function with a linear growth term to derive the search direction,and by introducing new technical results and selecting suitable parameters,we prove that the iteration bound of the algorithm is as good as best-known polynomial complexity of interior-point methods.Furthermore,numerical results illustrate the efficiency of the proposed method. | GENG Jie ZHANG Mingwang ZHU Dechun | 2024 | Wuhan University Journal of Natural Sciences2024，29，1： | 0 |
| 13 | Comprehensive overview of microRNA function in rheumatoid arthritis显示文摘MicroRNAs(miRNAs),a class of endogenous single-stranded short noncoding RNAs,have emerged as vital epigenetic regulators of both pathological and physiological processes in animals.They direct fundamental cellular pathways and processes by fine-tuning the expression of multiple genes at the posttranscriptional level.Growing 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 joints.This common autoimmune disorder is characterized by a complex and multifaceted pathogenesis,and its morbidity,disability and mortality rates remain consistently high.More in-depth insights into the underlying mechanisms of RA are required to address unmet clinical needs and optimize treatment.Herein,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 damage.This review also provides promising targets for innovative therapies of RA.In addition,we discuss the regulatory roles and clinical potential of extracellular mi RNAs in RA,highlighting their prospective applications as diagnostic and predictive biomarkers. | Xiaole Peng Qing Wang Wenming Li Gaoran Ge Jiachen Peng Yaozeng Xu Huilin Yang Jiaxiang Bai Dechun Geng | 2023 | Bone Research2023，11，1： | 0 |
| 14 | Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections显示文摘Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To 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 reactions.Compared 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 barrier.Meanwhile,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 tissues.The 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. | Jiaxiang Bai Yonghai Feng Wenming Li Zerui Cheng Jessica MRosenholm Huilin Yang Guoqing Pan Hongbo Zhang Dechun Geng | 2023 | Research2023，，3： | 0 |
| 15 | Nanomaterial-assisted theranosis of bone diseases显示文摘Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage destruction.Conventional approaches can regulate bone homeostasis to a certain extent.However,these therapies are still associated with some undesirable problems.Fortunately,recent advances in nanomaterials have provided unprecedented opportunities for diagnosis and therapy of bone-related diseases.This review provides a comprehensive and up-to-date overview of current advanced theranostic nanomaterials in bone-related diseases.First,the potential utility of nanomaterials for biological imaging and biomarker detection is illustrated.Second,nanomaterials serve as therapeutic delivery platforms with special functions for bone homeostasis regulation and cellular modulation are highlighted.Finally,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 functions.This review will provide scientific guidance to enhance the development of advanced nanomaterials for the diagnosis and therapy of bone-related diseases. | Kai Zheng Jiaxiang Bai Huilin Yang Yaozeng Xu Guoqing Pan Huaiyu Wang Dechun Geng | 2023 | Bioactive Materials2023，，6： | 0 |
| 16 | Osteoblastic microRNAs in skeletal diseases:Biological functions and therapeutic implications显示文摘Skeletal diseases normally represents a grievous imbalance between osteoblasts for bone formation and osteoclasts for bone resorption.A lack of osteogenic function can make it difficult to repair pathological bone erosion.Therefore,substantial efforts have been made to remedy these issues,with the aid of bioactive molecules,herbs and materials.Following recent insights,the importance of epigenetic gene regulation is increasingly evident,especially microRNAs.MicroRNAs can silence target genes by inhibiting mRNA translation or degrading mRNA molecules by binding to their 3′-untranslated region.There is accumulating evidence indicating that the miRNAs significantly involved in osteogenic gene expression,signaling pathway intervention and programmed cell death.Besides,numerous new target drugs(microRNA inhibitors or agonists)have been proposed to exploit its value in skeletal physiology and pathology.In this review,we mainly discuss the role of microRNAs in the context of skeletal disease-associated osteoblast differentiation,the applications of microRNA polymorphisms as biomarkers for diagnostic and therapeutic targets,and the challenges to meet this goal.Our summary provides novel horizon for improving the therapeutic effect of microRNAs,which may be beneficial to the further clinical translation of microRNAs in the treatments of skeletal diseases. | Lei Yu Wenming Li Peng Yang Wei Zhang Huaqiang Tao Gaoran Ge Huilin Yang Jiaxiang Bai Huaiyu Wang Dechun Geng | 2022 | Engineered Regeneration2022，3，3： | 0 |
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