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Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells

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Bone Research 2023年第4期11卷 784-802页

作者： Yu Wang Shanshan Jin Dan Luo Danqing He Min Yu Lisha Zhu Zixin Li Liyuan Chen Chengye Ding Xiaolan Wu Tianhao Wu Weiran Huang Xuelin Zhao Meng Xu Zhengwei Xie Yan Liu Laboratory of Biomimetic Nanomaterials Department of OrthodonticsPeking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials&Translational Research Center for Orocraniofacial Stem Cells and Systemic HealthBeijing 100081China CAS Center for Excellence in Nanoscience Beijing Key Laboratory of Micro-nano Energy and SensorBeijing Institute of Nanoenergy and NanosystemsChinese Academy of SciencesBeijing 101400China Peking University International Cancer Institute Health Science CenterPeking UniversityBeijing 100083China Department of Orthopedics the Fourth Medical Center of PLA General HospitalBeijing 100048China

Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness.The top-ranked candidate,prim-O-glucosylcimifugin(POG),a saposhnikovia root extract,could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans,as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs.In vivo,the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals.Mechanistically,POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy.Thus,the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.

关键词： tendon endogenous progenitor

endogenous automatic nerve discharge promotes nerve repair: an optimized animal model

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Neural Regeneration Research 2019年第2期14卷 306-312页

作者： Jing Rui Ying-Jie Zhou Xin Zhao Ji-Feng Li Yu-Dong Gu Jie Lao Department of Hand Surgery Huashan Hospital Fudan University Key Laboratory of Hand Reconstruction Ministry of Health Shanghai Key Laboratory of Peripheral Nerve and Microsurgery

Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic(phrenic nerve group), intercostal(intercostal nerve group) or thoracodorsal nerves(thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study established

关键词： nerve regeneration peripheral nerve regeneration endogenous automatic discharge side-to-side nerve anastomosis phrenic nerve intercostal nerve animal model electrical treatment rats nerve compression neural regeneration

An endogenous neuropeptide hormone assists cancer cells in escaping from immune surveillance

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Science China(Life Sciences) 2023年第6期66卷 1451-1453页

作者： Chang-Yu Yan Yan-Ping Wu Yi-Fang Li Rong-Rong He Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility Jinan UniversityGuangzhou510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhou510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou510632China School of Traditional Chinese Medicine Jinan UniversityGuangzhou510632China

Unlike tumor chemotherapy,tumor immunotherapy relies heavily on the immune system of the patients.In recent years,immunotherapeutic approaches that target the immune checkpoint(ICT)pathways,have shown promise in cancer treatment,though resistance due to tumor-induced immunosuppression remains a major hurdle in some patients(Saleh and Elkord,2020).

关键词： endogenous cancer chemotherapy

Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status

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Bone Research 2023年第4期11卷 876-894页

作者： Ananya Nandy Ron C.M.Helderman Santosh Thapa Shobana Jayapalan Alison Richards Nikita Narayani Michael P.Czech Clifford J.Rosen Elizabeth Rendina-Ruedy Department of Medicine Division of Clinical PharmacologyVanderbilt University Medical CenterNashvilleTN 37232USA Program in Molecular Medicine University of Massachusetts Chan Medical SchoolWorcesterMA 01605USA Maine Medical Center Research Institute ScarboroughMEUSA Molecular Physiology and Biophysics Vanderbilt UniversityNashvilleTN 37232USA

Bone formation is a highly energy-demanding process that can be impacted by metabolic disorders.Glucose has been considered the principal substrate for osteoblasts,although fatty acids are also important for osteoblast function.Here,we report that osteoblasts can derive energy from endogenous fatty acids stored in lipid droplets via lipolysis and that this process is critical for bone formation.As such,we demonstrate that osteoblasts accumulate lipid droplets that are highly dynamic and provide the molecular mechanism by which they serve as a fuel source for energy generation during osteoblast maturation.Inhibiting cytoplasmic lipolysis leads to both an increase in lipid droplet size in osteoblasts and an impairment in osteoblast function.The fatty acids released by lipolysis from these lipid droplets become critical for cellular energy production as cellular energetics shifts towards oxidative phosphorylation during nutrient-depleted conditions.In vivo,conditional deletion of the ATGL-encoding gene Pnpla2 in osteoblast progenitor cells reduces cortical and trabecular bone parameters and alters skeletal lipid metabolism.Collectively,our data demonstrate that osteoblasts store fatty acids in the form of lipid droplets,which are released via lipolysis to support cellular bioenergetic status when nutrients are limited.Perturbations in this process result in impairment of bone formation,specifically reducing ATP production and overall osteoblast function.

关键词： endogenous maintain osteoblast

SIRK1-QSK1 as a novel receptor complex perceiving endogenous PEP7 peptides

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Molecular Plant 2023年第2期16卷 298-300页

作者： Jakub Rzemieniewski Martin Stegmann hytopathology School of Life SciencesTechnical University of MunichFreisingGermany

endogenous peptides are important signaling molecules facilitating short-and long-distance signaling in plant growth,development,and immunity(Rzemieniewski and Stegmann,2022).Multiple plant peptides emerged to have dual regulatory functions in both growth and defense and are thus classified as phytocytokines(Rzemieniewski and Stegmann,2022).

关键词： n,2 endogenous immunity

Insights of stem cell-based endogenous repair of intervertebral disc degeneration

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World Journal of Stem Cells 2020年第4期12卷 266-276页

作者： Yang Liu Yan Li Li-Ping Nan Feng Wang Shi-Feng Zhou Xin-Min Feng Hao Liu Liang Zhang Department of Orthopedics West China Hospital of Sichuan UniversityChengdu 610000Sichuan ProvinceChina Department of Orthopedics Dalian Medical UniversityDalian 116000Liaoning ProvinceChina Department of Oncology The Affiliated Cancer HospitalSchool of MedicineUESTCChengdu 610000Sichuan ProvinceChina Department of Orthopedics Clinical Medical College of Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina

Low back pain has become more prevalent in recent years,causing enormous economic burden for society and government.Common therapies used in clinics including conservative treatment and surgery can only relieve pain.Subsequent cell-based treatment such as mesenchymal stem cell transplantation poses problems such as short duration of therapeutic effect and tumorigenesis.Recently,the discovery and identification of stem cell niche and stem/progenitor cells in intervertebral disc bring increased attention to endogenous repair strategy.Therefore,we review the studies involving endogenous repair strategy and present the characteristics and current status of this treatment.Meanwhile,we also discuss the strategy and perspective of endogenous repair strategy in future.

关键词： Low back pain Intervertebral disc degeneration Stem cell niche Stem/progenitor cell endogenous repair strategy Stem cell treatment

Competing endogenous RNA network in newly diagnosed multiple myeloma by genetic microarray

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Chinese Medical Journal 2020年第21期133卷 2619-2621页

作者： Yu-Qin He Zhi-Yao Zhang Hui-Xing Zhou Fang Ye Wen-Ming Chen Department of Emergency Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Department of Hematology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Department of Hematology Chuiyangliu Hospitalaffiliated to Tsinghua UniversityBeijing 100022China

Multiple myeloma(MM)is a blood malignancy characterized by the clonal proliferation of plasma cells,which increases the number of monoclonal immunoglobulins in blood and urine and causes target organ damage.Long non-coding RNAs(lncRNAs)have been reported to have high genetic heterogeneity and to participate in malignancy formation,progression,and metastasis in MM.[1]Furthermore,lncRNAs and circular RNAs(circRNAs)act as microRNA(miRNA)sponges,by indirectly binding miRNAs and influencing the post-transcriptional regulation of target gene expression.This phenomenon is known as the competing endogenous(ceRNA)relationship,and it may be one of the most important lncRNA mechanisms in cancers.However,the only lncRNA maternally expressed gene 3(MEG3)was reported to function as a ceRNA to regulate homeobox gene A11 mRNA expression by sponging miR-181a in MM.[2,3]Therefore,other ceRNA relationships,especially in newly diagnosed MM patients,remain to be investigated.

关键词： endogenous expression. myeloma

Macrophage-derived small extracellular vesicles promote biomimetic mineralized collagen-mediated endogenous bone regeneration

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International Journal of Oral Science 2020年第4期12卷 317-326页

作者： Anqi Liu Shanshan Jin Cuicui Fu Shengji Cui Ting Zhang Lisha Zhu Yu Wang Steve G.F.Shen Nan Jiang Yan Liu Department of Oral and Maxillofacial Surgery Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Key Laboratory of StomatologyShanghaiChina Laboratory of Biomimetic Nanomaterials Department of OrthodonticsPeking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijingChina Department of Oral Biochemistry Academic Centre for Dentistry Amsterdam(ACTA)University of Amsterdam(UvA)and Vrije Universiteit Amsterdam(VU)Gustav Mahlerlaan 3004AmsterdamThe Netherlands Shanghai University of Medicine and Health Sciences ShanghaiChina Central Laboratory Peking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijingChina

Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still unclear.Here,we evaluated intracellular communication through small extracellular vesicles(sEVs)and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen(IMC).After implantation in the bone defect area,IMC generated more neobone and recruited more mesenchymal stem cells(MSCs)than did extrafibrillarly mineralized collagen(EMC).More CD63+CD90+and CD63+CD163+cells were detected in the defect area in the IMC group than in the EMC group.To determine the functional roles of sEVs,extracellular vesicles from macrophages cultured on different mineralized collagen were isolated,and they showed no morphological differences.However,macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2,BGLAP,COL1,and OSX and calcium nodule formation.Mechanistically,sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway,and blocking sEV secretion with GW4869 significantly impaired MSC proliferative,immunomodulative and osteogenic potential.Taken together,these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.

关键词： endogenous CD63 mediated

New insights of CYP1A in endogenous metabolism: a focus on single nucleotide polymorphisms and diseases

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Acta Pharmaceutica Sinica B 2020年第1期10卷 91-104页

作者： Jian Lu Xuyang Shang Weiguo Zhong Yuan Xu Rong Shi Xin Wang Changning Maternity and Infant Health Hospital East China Normal UniversityShanghai 200051China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Pharmacology Shanghai University of Traditional Chinese MedicineShanghai 201203China

Cytochrome P4501A(CYP1A),one of the major CYP subfamily in humans,not only metabolizes xenobiotics including clinical drugs and pollutants in the environment,but also mediates the bio transformation of important endogenous substances.In particular,some single nucleotide polymorphisms(SNPs)for CYPIA genes may affect the metabolic ability of endogenous substances,leading to some physiological or pathological changes in humans.This review first summarizes the metabolism of endogenous substances by CYPIA,and then introduces the research progress of CYPIA SNPs,especially the research related to human diseases.Finally,the relationship between SNPs and diseases is discussed.In addition,potential animal models for CYPIA gene editing are summarized.In conclusion,CYP1A plays an important role in maintaining the health in the body.

关键词： CYP1A endogenous substances Xenobiotics SNPs Metabolism and disease