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ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair

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Bioactive Materials 2024年第8期38卷 438-454页

作者： Renshuai Hua Chenxi Zhao Zhengyu Xu Derong Liu Wenyuan Shen Wenlu Yuan Yan Li Jun Ma Zhishuo Wang Shiqing Feng department of Orthopedics International Science and Technology Cooperation Base of Spinal Cord InjuryTianjin Key Laboratory of Spine and Spinal Cord InjuryTianjin Medical University General Hospital154 Anshan RoadHeping DistrictTianjin300052China department of Orthopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OrthopaedicsAdvanced Medical Research InstituteCheeloo College of MedicineShandong UniversityJinanShandong250012China department of Orthopedics The Second Hospital of Shandong UniversityCheeloo College of MedicineShandong University247 Beiyuan StreetJinanShandong250033China

Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory *** is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and ferroptosis inhibitors are effective in reducing inflammation and repairing *** human umbilical cord mesenchymal stem cells(Huc-MSCs)can ameliorate inflammatory microenvironments and promote neural regeneration in SCI,their efficacy is greatly limited by the local microenvironment after ***,in this study,we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor,in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence,and combined with the reactive oxygen species(ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI ***,we also modified the classic ferroptosis inhibitor Ferrostatin-1(Fer-1)and synthesized a new prodrug Feborastatin-1(Feb-1).The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI,and promoted the recovery of neurological function in rats with *** study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.

关键词： Spinal cord injury Huc-MSCs ROS-Responsive nanoparticles Ferroptosis inhibitor

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NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4284-4304页

作者： Cheng Cheng Jie Zhang Xiaodong Li Fei Xue Lei Cao Linlin Meng Wenhai Sui Meng Zhang Yuxia Zhao Bo Xi Xiao Yu Feng Xu Jianmin Yang Yun Zhang Cheng Zhang National Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function ResearchChinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesDepartment of CardiologyQilu Hospital of Shandong UniversityJinanChina department of Cardiology Shengjing Hospital of China Medical UniversityShenyangLiaoning Province 110004China department of Traditional Chinese medicine Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012 ShandongChina department of Epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinanChina Key Laboratory Experimental Teratology of the Ministry of Education Department of PhysiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanChina department of Emergency medicine Chest Pain CenterShandong Provincial Clinical Research Center for Emergency and Critical Care MedicineQilu HospitalShandong UniversityJinanChina Cardiovascular Disease Research Center of shandong First Medical university Central Hospital Affiliated to Shandong First Medical UniversityJinanChina

Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease,but the role of natriuretic peptide receptor C(NPRC)in the pathogenesis of atherosclerosis(AS)remains *** study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress,inflammation,and apoptosis via protein kinase A(PKA)***^(−/−)mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed *** NPRC knockout mice were crossed with ApoE^(−/−)mice to generate ApoE^(−/−)NPRC^(−/−)mice,and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE^(−/−)NPRC^(−/−)versus ApoE^(−/−)*** addition,endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in *** contrast,endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in *** in vitro showed that NPRC knockdown in human aortic endothelial cells(HAECs)inhibited ROS production,pro-inflammatory cytokine expression and endothelial cell apoptosis,and increased eNOS ***,NPRC knockdown in HAECs suppressed macrophage migration,cytokine expression,and phagocytosis via its effects on endothelial *** the contrary,NPRC overexpression in endothelial cells resulted in opposite ***,the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway,leading to downstream upregulated AKT1 pathway and downregulated NF-κB *** conclusion,NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE^(−/−)mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB ***,targeting NPRC may provide a promising approach

关键词： inflammation atherosclerosis prevention

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Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

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Bone Research 2024年第2期12卷 334-348页

作者： Ziqian Xiang Pengfei Zhang Chunwang Jia Rongkun Xu Dingren Cao Zhaoning Xu Tingting Lu Jingwei Liu Xiaoxiong Wang Cheng Qiu Wenyang Fu Weiwei Li Lei Cheng Qiang Yang Shiqing Feng Lianlei Wang Yunpeng Zhao Xinyu Liu department of Orthopaedics Qilu Hospital of Shandong UniversityJinan 250012China university of Health and Rehabilitation Sciences Qingdao 226000China Xiangya School of medicine Central South UniversityChangsha 410013China School of Nursing and Rehabilitation Shandong UniversityJinan 250012China department of Pediatrics Cangzhou Central HospitalCangzhou 061011China department of Pediatric Surgery Qilu Hospital of Shandong UniversityJinan 250012China department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 30021China The Second hospital of shandong university Cheeloo College of MedicineShandong UniversityJinan 250012China

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be ***,Piezo1 channel was identified as a key iron transporter in response to mechanical ***1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron ***,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical ***,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

关键词： stress overload channel

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New insights into the suppression of inflammation and lipid accumulation by JAZF1

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Genes & Diseases 2023年第6期10卷 2457-2469页

作者： Wujun Chen Yingjie Zhong Yang Yuan Meng Zhu Wenchao Hu Ning Liu Dongming Xing Cancer Institute Department of NeurosurgeryThe Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao Cancer InstituteQingdaoShandong 266071China department of Endocrinology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdaoShandong 266035China School of Life Sciences Tsinghua UniversityBeijing 100084China

Atherosclerosis is one of the leading causes of disease and death *** identification of new therapeutic targets and agents is ***1 is expressed in many tissues and is found at particularly high levels in adipose tissue(AT).JAZF1 suppresses inflammation(including IL-1β,IL-4,IL-6,IL-8,IL-10,TNFα,IFN-γ,IAR-20,COL3A1,laminin,and MCP-1)by reducing NF-κB pathway activation and AT immune cell ***1 reduces lipid accumulation by regulating the liver X receptor response element(LXRE)of the SREBP-1c promoter,the cAMP-response element(CRE)of HMGCR,and the TR4 *** and CRE sites are present in many cytokine and lipid metabolism gene promoters,which suggests that JAZF1 regulates these genes through these ***-κB is the center of the JAZF1-mediated inhibition of the inflammatory ***1 suppresses NF-κB expression by suppressing TAK1 ***,TAK1 inhibition also decreases lipid accumulation.A dual-targeting strategy of NF-κB and TAK1 could inhibit both inflammation and lipid ***-target compounds(including prodrugs)1–5 exhibit nanomolar inhibition by targeting NF-κB and TAK1,EGFR,or ***,the NF-κB suppressing activity of these compounds is relatively low(IC50>300 nM).Compounds 6–14 suppress NF-κB expression with IC50 values ranging from 1.8 nM to 38.6 ***-276 is a highly selective,orally bioavailable TAK1 *** structural modifications of compounds using a prodrug strategy may enhance NF-κB *** review focused on the role and mechanism of JAZF1 in inflammation and lipid accumulation for the identification of new anti-atherosclerotic targets.

关键词： Atherosclerosis CRE JAZF1 LXRE NF-κB TAK1

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Emergency medicine:past,present,and future challenges

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Emergency and Critical Care medicine 2021年第2期1卷 49-52页

作者： Shujian Wei department of Emergency medicine and Chest Pain Center Qilu HospitalCheeloo College of MedicineShandong UniversityJinanShandongChina Clinical Research Center for Emergency and Critical Care medicine of shandong Province Institute of Emergency and Critical Care Medicine of Shandong UniversityQilu HospitalCheeloo College of MedicineShandong UniversityJinanShandongChina Key Laboratory of Emergency and Critical Care medicine of shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceQilu HospitalCheeloo College of MedicineShandong UniversityJinanShandongChina Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical SciencesState and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu HospitalCheeloo College of MedicineShandong UniversityJinanShandongChina qilu hospital Cheeloo College of MedicineShandong UniversityJinanShandongChina

Origin and history of emergency medicine The term“emergency,”first used in the 1630s,is derived from the Latin word emergere,meaning unforeseen events that require immediate *** term“emergency medicine”can be traced to the French Revolution(1789-1799).In 1792,Dominique Jean Larrey,a military medical surgeon,gained a position in the Army of the Rhine and left for Strasbourg,where he witnessed great mobility of the horse artillery and then suggested that General Adam Philippe de Custine have the medical staff use this method to speed up transport of the wounded.

关键词： gained horse Latin

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Eustachian tube teratoma: A case report

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World Journal of Clinical Cases 2022年第1期10卷 316-322页

作者： Jin-Ye Li Li-Xin Sun Na Hu Ge-Sheng Song Wei-Qiang Dou Ruo-Zhen Gong Chuan-Ting Li department of Radiology Shandong Provincial ENT HospitalCheeloo College of MedicineShandong UniversityJinan 250021Shandong ProvinceChina department of Radiology Shandong Province Qianfoshan HospitalJinan 250021Shandong ProvinceChina GE Healthcare MR Research ChinaBeijing 100000China Gong Ruozhen Innovation Studio Shandong Provincial ENT HospitalCheeloo College of MedicineShandong UniversityJinan 250021Shandong ProvinceChina department of Radiology Shandong Province HospitalCheeloo College of MedicineShandong UniversityJinan 250021Shandong ProvinceChina

BACKGROUND Mature teratoma composed of all three basic germ cell layers of the head and neck is a rare *** involving the temporal bone are particularly *** SUMMARY A 48-year-old male patient with a history of chronic otitis of the left ear from infancy,for which he had been operated on twice,was referred to our hospital for chronic otitis,cholesteatoma and a middle ear *** tomography(CT)scan and magnetic resonance imaging(MRI)revealed a eustachian tube teratoma,in which the anterior lower part and posterior upper part were connected by a thin membranaceous *** mass was removed completely under general anesthesia by *** of last follow-up(2 years post-surgery),the disease had not *** Pre-operative CT and MRI are necessary for eustachian tube *** surgical resection provided excellent prognosis.

关键词： Eustachian tube Teratoma Chronic otitis Computed tomography Magnetic resonance imaging Case report

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Use of the alkaline phosphatase to prealbumin ratio as an independent predictive factor for the prognosis of gastric cancer

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World Journal of Gastroenterology 2020年第44期26卷 6963-6978页

作者： Yang Li Jin-Shen Wang Yun Guo Tao Zhang Le-Ping Li departments of Gastrointestinal Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinan 250021Shandong ProvinceChina Center for Reproductive medicine Cheeloo College of MedicineJinan 250012Shandong ProvinceChina department of Biostatistics School of Public HealthShandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Gastric cancer(GC)is characterized by a low 5-year survival *** prognosis is still not satisfactory although it has significantly improved due to developments in ***,the identification of more efficient indices for the evaluation of GC prognosis is *** propose,for the first time,that the alkaline phosphatase(ALP)to prealbumin(PA)ratio(APR)can be used as an independent prognostic factor in *** To evaluate the prognostic value the APR in *** According to the exclusion strategy,we collected the preoperative serologic examination results and clinical information of 409 GC patients treated in shandong Provincial hospital from January to December,*** calculating the APR,the neutrophil and lymphocyte ratio(NLR),C-reactive protein(CRP)and albumin(ALB)ratio,platelet and lymphocyte ratio,lymphocyte and monocyte ratio,and the relationship with clinical information,we verified the role of preoperative APR ratio in the prognosis of *** addition,we used a Cox model combined with the APR and tumor stage to demonstrate its efficacy in assessing the prognosis of GC *** Preoperative APR was an independent prognostic factor for *** median age of patients in the APR-high group was greater compared with that in the APR-low *** with a higher APR had a more advanced clinical stage,higher neutrophil to lymphocyte,CRP to ALB,and platelet to lymphocyte ratios,but a lower lymphocyte to monocyte ratio(P<0.05).The APR-high group also had higher glycoprotein antigen 199 and carbohydrate antigen 125 levels than the APR-low group(P<0.05).Median overall survival and disease-free survival were significantly longer in the APR-low group than in the APR-high *** addition,a Cox model based on the APR and tumor stage was more effective in evaluating the prognosis of patients than models based on stage alone or stage plus the *** A higher APR is an independent and negative prognostic factor for *** prognosis of

关键词： Gastric cancer Prognosis Alkaline phosphatase Prealbumin Evaluating efficiency

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Imaging findings of primary pulmonary synovial sarcoma with secondary distant metastases:A case report

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World Journal of Clinical Cases 2021年第8期9卷 1893-1900页

作者： Rui Li Xin Teng Wei-Hong Han Yan Li Qing-Wei Liu department of Radiology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinan 250021Shandong ProvinceChina department of Ultrasound Qingdao Municipal HospitalShandong UniversityQingdao 266000Shandong ProvinceChina department of Ultrasound The Second HospitalCheeloo College of MedicineShandong UniversityJinan 250033Shandong ProvinceChina department of Radiology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina

BACKGROUND Synovial sarcoma(SS)accounting for 6%-10%of primary soft tissue malignancies mainly occurs in deep soft tissue adjacent to joints of the *** pulmonary SS(PPSS)is rare and has a poor *** of secondary distant metastases of PPSS occur rarely and there is a lack of corresponding imaging *** summarized the imaging findings of PPSS with multiple metastases confirmed by surgery and pathology,and shared valuable information on *** SUMMARY A 43-year-old female patient had a solid space occupying lesion in the right upper lobe of the *** results of a hemogram,erythrocyte sedimentation rate(ESR)and tumor markers were all within the normal range,tuberculin skin test(5 TU PPD)was negative(-).Chest computed tomography examination showed similar round soft tissue density in the posterior segment of the right upper ***-assisted wedge resection of the right upper lobe of the lung,right upper lobe resection and lymph node dissection were *** months after surgery,ultrasound examination showed multiple metastases on the chest wall and *** PPSS is a rare malignant lung tumor with strong invasiveness,early distant metastasis and poor *** are very few imaging *** is often manifested as irregular tumor and calcification,and the metastases have extremely low echo on ***-enhanced ultrasound indicates that the arterial phase of tumor metastases shows rapid centripetal high enhancement,manifested as“fast forward and fast regression”.

关键词： Primary pulmonary synovial sarcoma Imaging findings Contrast-enhanced ultrasound Secondary distant metastases Computed tomography Case report

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Adipocyte-derived SFRP5 inhibits breast cancer cells migration and invasion through Wnt and epithelial-mesenchymal transition signaling pathways

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Chinese Journal of Cancer Research 2020年第3期32卷 347-360页

作者： Wenzhong Zhou Chunmiao Ye Liang Li Liyuan Liu Fei Wang Lixiang Yu Fei Zhou Yujuan Xiang Yongjiu Wang Gengshen Yin Zhongbing Ma Qinye Fu Qiang Zhang Dezong Gao Shuya Huang Zhigang Yu School of medicine Cheeloo College of MedicineShandong UniversityJinan 250012China department of Breast Surgery the Second HospitalCheeloo College of MedicineShandong UniversityJinan 250033China Institute of Translational medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China

Objective:Obesity is closely associated with metastasis in breast cancer *** frizzled-related protein 5(SFRP5),one of the novel adipokines with anti-inflammatory properties,is associated with *** study aims to study the role of SFRP5 in the crosstalk between obesity and breast cancer metastasis and identify the underlying ***:3T3-L1 pre-adipocytes were differentiated to mature adipocytes and a hypertrophic adipocyte model was induced with palmitic acid(PA).Cell motility was measured in MDA-MB-231 and MCF-7 breast cancer cells co-cultured with adipocytes conditioned medium(CM)with or without SFRP5 *** and epithelialmesenchymal transition(EMT)signal pathways were investigated by western *** SFRP5 level in 218 breast cancer patients and the association with clinicopathologic characteristics of breast cancer were further *** databases ENCORI and PREDICT Plus were used to exam the link between SFRP5 and ***:Reduced SFRP5 level was detected in the hypertrophic adipocyte *** SFRP5 protein inhibited MDA-MB-231 and MCF-7 cells invasion and migration induced by PA-treated adipocyte CM,and SFRP5 inhibition by specific antibody reversed the effect of ***,SFRP5 significantly inhibited Wnt and downstream EMT in breast cancer *** circulating SFRP5 level correlated with body mass index(BMI),lymph node(LN)metastasis,TNM stage and high Ki67 expression in breast cancer *** SFRP5 level was associated with favorable predicted ***-Meier curves showed high SFRP5 level in tumor tissue was associated with better outcome of breast cancer ***:Our findings demonstrated SFRP5 is a vital adipokine that mediates the crosslink between obesity and the metastatic potential of breast *** of SFRP5 expression in the adipose microenvironment may represent a novel approach for preventing breast cancer metastasis.

关键词： Obesity adipocytes breast cancer metastasis SFRP5 EMT

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Assembly of 3D-printed Ti scaffold and free vascularized fibula using a customized Ti plate for the reconstruction of mandibular defects

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Bio-Design and Manufacturing 2022年第2期5卷 424-429页

作者： Chiyang Zhong Yixuan Zhao Hongyu Xing Qingguo Lai Runqi Xue Tianxiang Song Xiaopeng Tang Kaiwen Zhu Yanwei Deng department of Oral and Maxillofacial Surgery The Second HospitalCheeloo College of MedicineShandong UniversityJinan 250033China School of Stomatology Cheeloo College of MedicineShandong UniversityJinan 250012China School of Mechanical and Electronic Engineering Shandong Jianzhu UniversityJinan 250101China Research Center of 3D Printing in Stomatology of shandong university Jinan 250012China

Introduction Mandibular segmental defects result in significant cosmetic and functional ***,the reconstruction of both the contour and function of the mandible is a challenging *** present,autologous vascularized fibu... 详细信息

关键词： fibula mandibular defects

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