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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong Department of spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)key laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina guangdong provincial Center for Quality Control of Minimally Invasive spine Surgery GuangzhouGuangdong ProvinceChina guangdong provincial Center for Engineering and Technology Research of Minimally Invasive spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Self-reinforced Calcium Phosphate Cement Inspired by Sea Cucumber Dermis

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 682-688页

作者：吴治文 WANG Zihao CAI Zepeng QU Liting 于涛 College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China guangdong provincial key laboratory of spine and spinal cord reconstruction The Fifth Affiliated Hospital(Heyuan Shenhe People’s Hospital)Jinan UniversityHeyuan 517000China

A composite bone cement based onα-TCP with self-reinforcing characteristics is prepared by compounding cellulose whiskers and polyvinyl alcohol in different *** this system,we are inspired by the sea cucumber,which can alter the stiffness of their inner dermis *** the formation of hydrogen bonds between the hydroxyl groups on the cellulose whiskers and PVA,the bone cement matrix can be strengthened during the curing process of *** the process of bone cement blending,there is more water,the hydrogen bond connection is destroyed,so the slurry has better fluidity at this *** the hydration of the bone cement progresses,the reduction of the water phase leads to the formation of a permeable network structure of hydrogen bond connections between the *** dual-phase action of PVA and whiskers greatly increases the mechanical strength of the bone cement system(5.5 to 23.8 MPa),while the presence of polyvinyl alcohol improves the toughness of the bone cement *** work was supposed to explore whether the chemoresponsive materials can be adapted to biomedical materials,for example,bone repair.

关键词： bone repair self-reinforce chemoresponsive hydrogen bond

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MOF-based magnetic microrobot swarms for pH-responsive targeted drug delivery

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Science China Chemistry 2024年第4期67卷 1216-1223页

作者： Qinyi Cao Yifan Zhang Yanping Tang Changjin Wu Jizhuang Wang Dan Li College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China guangdong provincial key laboratory of Functional Supramolecular Coordination Materials and Applications Jinan UniversityGuangzhou 510632China guangdong provincial key laboratory of spine and spinal cord reconstruction The Fifth Affiliated Hospital(Heyuan Shenhe People’s Hospital)Jinan UniversityHeyuan 517000China JNU-HKUST Joint laboratory for Neuroscience and Innovative Drug Research College of PharmacyJinan UniversityGuangzhou 510632China Department of Chemistry The University of Hong KongHong KongChina

Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile ***,magnetically actuated micro/nano-robots(MNRs)offer distinct advantages,such as untethered and precise *** fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug ***,we report a MOF-based magnetic microrobot swarm(MMRS)for targeted *** approach overcomes limitations associated with a single MNR,including limited drug loading and the risk of loss during *** select Zeolitic Imidazolate Framework-8(ZIF-8)as the drug vehicle for its superior loading potential and p H-sensitive *** design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8,enabling collective behaviors under *** the yaw angle of alternating magnetic fields and nanoparticles'amount,the MMRSs with controllable size achieve instantaneous transformation among different configurations,including vortex-like swarms,chain-like swarms,and elliptical swarms,facilitating adaptation to environmental *** to the subcutaneous T24 tumor site,the MMRSs with encapsulated doxorubicin(DOX)automatically degrade and release the drug,leading to a dramatic reduction of the tumor in *** investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms,ushering in new avenues for accurate and non-invasive targeted drug delivery.

关键词： magnetic microrobot swarm MOF nanoparticles magnetic propulsion pH-responsive drug release targeted drug delivery

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Is reactive oxygen species the only way for cancer inhibition over single atom nanomedicine?Autophagy regulation also works

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Chinese Chemical Letters 2024年第6期35卷 474-479页

作者： Yuanyi Zhou Ke Ma Jinfeng Liu Zirun Zheng Bo Hu Yu Meng Zhizhong Li Mingshan Zhu Postdoctoral Innovation Practice Base The First and Fifth Affiliated Hospital of Jinan UniversityGuangzhou 510632China guangdong provincial key laboratory of spine and spinal cord reconstruction The Fifth Affiliated Hospital of Jinan University(Heyuan Shenhe People’s Hospital)Heyuan 517465China School of Environment Jinan UniversityGuangzhou 511443China Department of Nephrology The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China

Exploring the therapeutic effect of single atom catalysts beyond reactive oxygen species(ROS)modulation would boost the prosperity of nanomedicine in cancer *** as a vital therapy target offers new options for the control of renal cell carcinoma(RCC)***,Fe single atom-decorated graphene oxide(Fe_(1)-GO)nanosheet is developed to be a feasible autophagy inducer in RCC *** the well-dispersed O-Fe_(1)-O active sites,Fe_(1)-GO kills ACHN cells effectively but maintains acceptable cytotoxicity to the normal podocyte and HK2 ***-depth analyses ascribe the inhibition of ACHN cells to the upregulated autophagy instead of the commonly known catalytic ROS *** in vivo therapeutic effect of Fe_(1)-GO nanomedicine is also validated by the RCC-bearing BALB/c mice model,realizing an 89% reduction of tumor weight and good *** work provides new insights into the design of autophagy regulators as well as potential therapeutic strategies for RCC treatment.

关键词： Fe single atom Autophagy Renal cell carcinoma Graphene oxide Cancer therapy

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Lkb1 orchestrates γδ T-cell metabolic and functional fitness to control IL-17-mediated autoimmune hepatitis

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Cellular & Molecular Immunology 2024年第6期21卷 546-560页

作者： Zhiqiang Xiao Shanshan Wang Liang Luo Wenkai Lv Peiran Feng Yadong Sun Quanli Yang Jun He Guangchao Cao Zhinan Yin Meixiang Yang guangdong provincial key laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai Institute of Translational MedicineZhuhai People’s Hospital Affiliated with Jinan UniversityJinan UniversityZhuhai519000China The Biomedical Translational Research Institute School of MedicineJinan UniversityGuangzhou510632China guangdong provincial key laboratory of spine and spinal cord reconstruction The Fifth Affiliated Hospital(Heyuan Shenhe People’s Hospital)Jinan UniversityHeyuan517000China key laboratory of Ministry of Education for Viral Pathogenesis&Infection Prevention and Control(Jinan University).Guangzhou key laboratory for Germ-Free Animals and Microbiota Application.Institute of laboratory Animal Science School of MedicineJinan UniversityGuangzhou510632China

γδT cells play a crucial role in immune surveillance and serve as a bridge between innate and adaptive ***,the metabolic requirements and regulation ofγδT-cell development and function remain poorly *** this study,we investigated the role of liver kinase B1(Lkb1),a serine/threonine kinase that links cellular metabolism with cell growth and proliferation,inγδT-cell *** findings demonstrate that Lkb1 is not only involved in regulatingγδT lineage commitment but also plays a critical role inγδT-cell effector ***,T-cell-specific deletion of Lkb1 resulted in impaired thymocyte development and distinct alterations inγδT-cell subsets in both the thymus and peripheral lymphoid ***,loss of Lkb1 inhibited the commitment of Vγ1 and Vγ4γδT cells,promoted the maturation of IL-17-producing Vγ6γδT cells,and led to the occurrence of fatal autoimmune hepatitis(AIH).Notably,clearance ofγδT cells or blockade of IL-17 significantly attenuated ***,Lkb1 deficiency disrupted metabolic homeostasis and AMPK activity,accompanied by increased mTORC1 activation,thereby causing overactivation ofγδT cells and enhanced ***,activation of AMPK or suppression of mTORC1 signaling effectively inhibited IL-17 levels and attenuated AIH in Lkb1-deficient *** findings highlight the pivotal role of Lkb1 in maintaining the homeostasis ofγδT cells and preventing IL-17-mediated autoimmune diseases,providing new insights into the metabolic programs governing the subset determination and functional differentiation of thymicγδT cells.

关键词： Lkb1 γδT cell Autoimmune hepatitis IL-17 Metabolic quiescence

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Pathophysiological mechanisms of chronic compressive spinal cord injury due to vascular events

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Neural Regeneration Research 2023年第4期18卷 790-796页

作者： Zhen-Xiao Ren Jing-Hui Xu Xing Cheng Gui-Xing Xu Hou-Qing Long guangdong provincial key laboratory of Orthopaedics and Traumatology/Department of spine Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurosurgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Cervical spondylotic myelopathy is the main cause of non-traumatic spinal cord injury,with chronic static and/or dynamic compressive spinal cord injury as the unique *** the progression of this condition,the microvascular network is compressed and destroyed,resulting in ischemia and *** main pathological changes are inflammation,damage to the blood spinal cord barriers,and cell apoptosis at the site of *** have confirmed that vascular regeneration and remodeling contribute to neural repair by promoting blood flow and the reconstruction of effective circulation to meet the nutrient and oxygen requirements for nerve *** decompression is the most effective clinical treatment for this condition;however,in some patients,residual neurological dysfunction remains after *** revascularization during compression and after decompression is therefore complementary to surgical *** this review,we summarize the progress in research on chronic compressive spinal cord injury,covering both physiological and pathological changes after compression and decompression,and the regulatory mechanisms of vascular injury and repair.

关键词： angiogenesis cervical spondylotic myelopathy hypoxia inflammation ischemia spinal cord injury surgical decompression

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Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo

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Journal of Materials Science & Technology 2023年第5期136卷 54-64页

作者： Bizhi Tan Naru Zhao Wei Guo Fangli Huang Hao Hu Yan Chen Jungang Li Zemin Ling Zhiyuan Zou Rongcheng Hu Chun Liu Tiansheng Zheng Gang Wang Xiao Liu Yingjun Wang Xuenong Zou guangdong provincial key laboratory of Orthopaedics and Traumatology Department of Spine SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China School of Materials Science and Engineering South China University of TechnologyGuangzhou 510641China National Engineering Research Center for Tissue Restoration and reconstruction Guangdong Province Key Laboratory of Biomedical EngineeringSouth China University of TechnologyGuangzhou 510006China Department of Orthopedics The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China

The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue *** porous architecture of the implanta-tion was essential conditions for bone ***,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate ***,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of *** in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were *** results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene ***-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular *** present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic ***,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor *** vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone *** results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.

关键词： Bioactive ceramics Hydroxyapatite coating 3D-printed porous ceramic scaffold PI3K/AKT/mTOR signaling pathway Bone regeneration

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Sustained release of hydrogen sulfide from anisotropic ferrofluid hydrogel for the repair of spinal cord injury

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Bioactive Materials 2023年第5期23卷 118-128页

作者： Ruofei Wang Xia-Xiao Wu Zhenming Tian Tian Hu Chaoyang Cai Guan-Ping Wu Gang-Biao Jiang Bin Liu Department of spine Surgery The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou510630China guangdong provincial Center for Quality Control of Minimally Invasive spine Surgery Guangzhou510630China guangdong provincial Center for Engineering and Technology Research of Minimally Invasive spine Surgery Guangzhou510630China key laboratory for Biobased Materials and Energy of Ministry of Education College of Materials and EnergySouth China Agricultural UniversityGuangzhou510642China

spinal cord injury(SCI)results in massive neuronal death,axonal disruption,and cascading inflammatory response,which causes further damage to impaired *** survived neurons with damaged function fail to form effective neuronal *** is mainly caused by the neuroinflammatory microenvironment at injury sites and regenerated axons without *** address this challenge,a ferrofluid hydrogel(FFH)was prepared with Ferric tetrasulfide(Fe3S4),carboxymethyl chitosan,and *** internal structural particles can be oriented in a magnetic field to acquire ***,Fe3S4 can release hydrogen sulfide(H2S)with anti-inflammatory effects under acidic *** in vitro experiments,0.01g/ml Fe3S4 FFH significantly reduced the inflammatory factors produced by LPS-induced BV2 *** and longer axons of the induced neural stem cells loaded on anisotropic FFH were *** vivo experiments showed that FFH reduced the activated microglia/macrophage and the expression of pro-inflammatory factors in SCI rats through the NF-κB ***,it significantly promoted directional axonal regrowth and functional recovery after *** the critical role of inhibition of neuroinflammation and directional axonal growth,anisotropic Fe3S4 FFH is a promising alternative for the treatment of SCI.

关键词： spinal cord injury Anisotropic Ferrofluid Hydrogen sulfide

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Inhibiting tau protein improves the recovery of spinal cord injury in rats by alleviating neuroinflammation and oxidative stress

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Neural Regeneration Research 2023年第8期18卷 1834-1840页

作者： Guo-Liang Chen Kai Sun Xi-Zhe Liu Kui-Leung Tong Zi-Juan Chen Lu Yu Ning-Ning Chen Shao-Yu Liu Department of Orthopedic Surgery The First Affiliated HospitalJinan UniversityGuangzhouGuangdong ProvinceChina guangdong provincial Biomedical Innovation Platform of Regeneration and Repair of spinal cord and Nerve Injury Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina guangdong provincial key laboratory of Orthopedics and Traumatology/Orthopedic Research Institute Department of Spine SurgeryThe First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery Jiujiang University Affiliated HospitalJiujiangJiangxi ProvinceChina Department of Clinical laboratory The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina

After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury *** inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's ***,whether it can play a role in the treatment of spinal cord injury remains *** this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau *** found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute ***,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model ***,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.

关键词： functional recovery MAPK pathway microglial polarization neuroinflammation neuronal regeneration oxidative stress spinal cord injury tau

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Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling

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Genes & Diseases 2024年第2期11卷 964-977页

作者： Chengzhi Wu Hengyu Liu Dongmei Zhong Xiaoming Yang Zhiheng Liao Yuyu Chen Shun Zhang Deying Su Baolin Zhang Chuan Li Liru Tian Caixia Xu Peiqiang Su guangdong provincial key laboratory of Orthopedics and Traumatology Department of Spine SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Research Center for Translational Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Precision Medicine Institute The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Orthopedics Renmin Hospital of Wuhan UniversityWuhanHubei 430060China guangdong provincial key laboratory of Proteomics and State key laboratory of Organ Failure Research School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China

Mutation of the MAPK7 gene was related to human ***7 regulated the development of limb bones and skulls in ***,the role of MAPK7 in vertebral development is still *** this study,we constructed Col2a1-cre;Mapk7 f/f transgenic mouse model to delete Mapk7 in cartilage,which displayed kyphosis and ***,Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes,which impaired chondrocyte hypertrophy and attenuated vertebral *** vivo,systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 *** study firstly clarified the mechanism by which MAPK7 was involved in vertebral development,which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.

关键词： Chondrocyte hypertrophy Growth plate Kyphosis MAPK7 MEF2C Osteopenia PI3K/AKT PTEN

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