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Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2998-3012页

作者： Yuan Zhao Yidan Zhang Xin Liu Jian Zhang Ya Gao Shuyue Li Cui Chang Xiang Liu Guofeng Yang department of Geriatrics Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina department of Neurosurgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease *** proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of *** this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s *** a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western *** results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease ***,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control ***,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated *** together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced n

关键词： biomarker diagnosis exosomes N-acetyl-alpha-glucosaminidase Parkinson’s disease proteomic α-synuclein

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Impact of triglyceride-glucose index on the long-term prognosis of advanced gastric cancer patients receiving immunotherapy combined with chemotherapy

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World Journal of Gastroenterology 2025年第5期31卷 68-83页

作者： Zhi-Yuan Yao Xiao Ma Yong-Zheng Cui Jie Liu Zheng-Xiang Han Jun Song department of oncology The Affiliated Hospital of Xuzhou Medical CollegeXuzhou 221000Jiangsu ProvinceChina department of oncology The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210008Jiangsu ProvinceChina department of Radiotherapy The Affiliated Hospital of Xuzhou Medical CollegeXuzhou 221000Jiangsu ProvinceChina department of Gastrointestinal Surgery The Affiliated Hospital of Xuzhou Medical CollegeXuzhou 221000Jiangsu ProvinceChina

BACKGROUND Gastric cancer(GC)is the fifth most common malignancy and the third leading cause of death *** advancements in immunotherapies,patient prognosis remains poor,necessitating the identification of key prognostic factors to optimize the treatment *** resistance,as indicated by the triglyceride glucose(TyG)index,is increasingly recognized for its impact on cancer progression and immune modulation,and its potential role in GC prognosis is of particular *** To investigate whether the TyG index,a surrogate marker of insulin resistance,can predict the prognosis of patients with advanced GC receiving immunotherapy combined with *** This retrospective study included 300 patients with advanced GC who received sintilimab combined with *** patients were categorized into two groups according to high or low TyG index,and independent prognostic factors for overall survival(OS)were determined using Cox proportional hazards regression analysis,which led to the development of a nomogram *** Of the included patients,136 had a high TyG index and 164 had a low TyG *** median progression-free survival of the high TyG index group was significantly longer than that of the low TyG index ***,the median OS of the high TyG index group was significantly longer than that of the low TyG index *** ob-jective response and disease control rates in the two groups were 18.38%vs 9.15%and 58.82%vs 46.95%,*** significant difference was noted in the incidence of adverse reactions at any level between the two groups(P>0.05).In multivariate analysis,the Eastern Cooperative oncology Group score,programmed cell death ligand 1 expression,and TyG index acted as independent prognostic factors for *** these factors,the hazard ratio of the TyG index was 0.36(95%confidence interval:0.36-0.55,P<0.001),and the nomogram model re-emphasized its importance as the main predictor of patient prognos

关键词： Triglyceride glucose index Gastric cancer Sintilimab Prognostic model Efficacy Safety

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CT whole lung radiomic nomogram:a potential biomarker for lung function evaluation and identification of COPD

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Military medical Research 2025年第1期12卷 36-47页

作者： Tao-Hu Zhou Xiu-Xiu Zhou Jiong Ni Yan-Qing Ma Fang-Yi Xu Bing Fan Yu Guan Xin-Ang Jiang Xiao-Qing Lin Jie Li Yi Xia Xiang Wang Yun Wang Wen-Jun Huang Wen-Ting Tu Peng Dong Zhao-Bin Li Shi-Yuan Liu Li Fan department of Radiology the Second Affiliated Hospital of Naval Medical UniversityShanghai 200003China School of medical Imaging Shandong Second Medical UniversityWeifang 261053ShandongChina department of Radiology School of MedicineTongji HospitalTongji UniversityShanghai 200065China department of Radiology Zhejiang Province People’s HospitalAffiliated People’s Hospital of Hangzhou Medical CollegeHangzhou 310014China department of Radiology Sir Run Run Shaw HospitalZhejiang 310018China Jiangxi Provincial People’s Hospital the First Affiliated Hospital of Nanchang Medical CollegeNanchang 330006China College of Health Sciences and Engineering University of Shanghai for Science and TechnologyShanghai 200093China department of Radiology the Second People’s Hospital of DeyangDeyang 618000SichuanChina department of Radiation oncology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

Background:Computed tomography(CT)plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease(COPD).This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD ***:This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD *** radiomic features of the whole lung volume were *** absolute shrinkage and selection operator(LASSO)logistic regression was applied for feature selection and radiomic signature construction.A radiomic nomogram was established by combining the radiomic score and clinical *** operating characteristic(ROC)curve analysis and decision curve analysis(DCA)were used to evaluate the predictive performance of the radiomic nomogram in the training,internal validation,and independent external validation ***:Eighteen radiomic features were collected from the whole lung volume to construct a radiomic *** area under the curve(AUC)of the radiomic model in the training,internal,and independent external validation cohorts were 0.888[95%confidence interval(CI)0.869–0.906],0.874(95%CI 0.844–0.904),and 0.846(95%CI 0.822–0.870),*** were higher than the clinical model(AUC were 0.732,0.714,and 0.777,respectively,P<0.001).DCA demonstrated that the nomogram constructed by combining radiomic score,age,sex,height,and smoking status was superior to the clinical factor ***:The intuitive nomogram constructed by CT-based whole-lung radiomic has shown good performance and high accuracy in identifying COPD in this multicenter study.

关键词： Chronic obstructive pulmonary disease(COPD) Computed tomography(CT) Radiomic

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Assessment of new pathological markers in early stage colon cancer:Insights and limitations

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World Journal of Gastrointestinal oncology 2025年第3期17卷 113-121页

作者： Bulent Erdogan Fatma Elif UsturalıKeskin ErkanÖzcan Ahmet Küçükarda Ali Kaan Güren Osman Köstek Bekir Muhammet Hacioglu Hilmi Kodaz department of medical oncology Division of Medical OncologyDepartment of Internal MedicineTrakya University School of MedicineEdirne 22000Türkiye department of Pathology Trakya University School of MedicineTrakya UniversityEdirne 22000Türkiye Division of medical oncology Trakya University School of MedicineEdirne 22000Türkiye Division of medical oncology Department of Internal MedicineTrakya University School of MedicineEdirne 22000Türkiye Division of medical oncology Department of Internal MedicineMarmara University School of MedicineMarmara UniversityIstanbul 34000Türkiye Division of medical oncology Department of Internal MedicineMarmara University School of MedicineIstanbul 34000Türkiye department of medical oncology Acibadem Eskisehir HospitalEskisehir 26130Türkiye

BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or ***-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being *** To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,department of medical *** divided those with and without high-risk factors into two *** examined the relationship of new pathological markers with these groups and with pathological markers in risk *** There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T *** No relationship was found between the presence of new pathological markers and high-low risk *** we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.

关键词： Colon cancer Early stage Risk factors New pathological markers Tumor-stroma ratio Tumor infiltrating lymphocytes Crohn-like reaction Desmoid reaction Poorly differentiated clusters

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HNRNPC as a pan-cancer biomarker and therapeutic target involved in tumor progression and immune regulation

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oncology Research 2025年第1期33卷 83-102页

作者： YUEZHOU ZHANG ZHAO ZHANG JINXIN DONG CHANGAN LIU department of Hepatobiliary Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing400016China department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China

Background:Aberrant expression of RNA-binding proteins(RBPs)has been linked to a variety of diseases,including hematological disorders,cardiovascular diseases,and multiple types of *** nuclear ribonucleoprotein C(HNRNPC),a member belonging to the heterogeneous nuclear ribonucleoprotein(hnRNP)family,plays a pivotal role in nucleic acid *** studies have underscored the significance of HNRNPC in tumorigenesis;however,its specific role in malignant tumor progression remains inadequately ***:We leveraged publicly available databases,including The Cancer Genome Atlas(TCGA),to explore the potential involvement of HNRNPC across various ***,we performed experimental validation studies focused on liver ***:Our analysis revealed that HNRNPC is overexpressed in a wide range of common malignancies,including liver and lung cancers,and is strongly linked to unfavorable ***,HNRNPC was observed to be closely linked to tumor *** immune checkpoint analysis and immune cell infiltration assessment,HNRNPC emerged as a potential target for modulating tumor ***,silencing of HNRNPC markedly inhibited the proliferation,metastasis,and infiltration of liver cancer ***:In summary,our findings highlight HNRNPC as a prognostic marker in various cancers,including liver cancer,and suggest its involvement in shaping the tumor immune *** insights offer potential avenues for improving clinical outcomes in tumors with elevated HNRNPC expression,particularly through immunotherapeutic strategies.

关键词： Heterogeneous nuclear ribonucleoprotein C(HNRNPC) Pan-cancer analysis Tumor immunity Prognostic biomarker Immunotherapeutic target Hepatocellular carcinoma

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Improved treatment of colorectal liver metastases by early response evaluation and regimen adjustment: a prospective study of clinical functional MR-based modeling

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Cancer Biology & Medicine 2025年第02期 166-176页

作者： Wenhua Li Huan Zhang Zhe Gong Yue Li Zhiyu Chen Xiaodong Zhu Mingzhu Huang Zhe Zhang Chenchen Wang Lixin Qiu Qirong Geng Jinjia Chang Xiaoying Zhao Xuedan Sheng Wen Zhang Tong Tong Weijian Guo department of medical oncology Fudan University Shanghai Cancer Center department of oncology Shanghai Medical College Fudan University department of Radiology Fudan University Shanghai Cancer Center department of Radiation oncology Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences

Objective: The aim of the study was to evaluate the feasibility of functional MR in predicting the clinical response to chemotherapy in patients with colorectal liver metastases(CLM).Methods: A total of 196 eligible patients were enrolled in the study between August 2016 and January 2023. Functional MR was performed at baseline and after one cycle of chemotherapy. The diffusion kurtosis radiomic texture features were extracted and a signature model was built using the R package. The initial 100 cases were designated as the training set, the following 48 cases were designated as the validation set, and the final 48 cases were designated as the intervention validation ***: Good performance for the response prediction(AUC = 0.818 in the training set and 0.755 in the validation set) was demonstrated. The objective response rates(ORRs) in the high-risk subgroup were significantly lower than the low-risk subgroup in the training and validation sets. Worse progression-free survival and overall survival rates were noted in the high-risk population. In the intervention set 22.9%(11/48) of the chemotherapy regimens for patients were changed in response to the model-predicted results and the ORR reached 77.1%(37/48), which was significantly higher than the training and validation sets [47.97%(71/148); P = 0.000].Conclusions: A functional MR signature effectively predicted the chemotherapy response and long-term survival. The adjustment of the regimen guided by the model significantly improved the ORR.

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Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

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Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu Linxi Li Yunxiang Ji Yezhong Wang Yingjia Li Yongyi Ye department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

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Combination therapy strategy based on selective internal radiation therapy as conversion therapy for inoperable giant hepatocellular carcinoma:A case report

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World Journal of Gastrointestinal oncology 2025年第3期17卷 410-417页

作者： Ming-Zhi Hao Hai-Lan Lin Yu-Bin Hu Qi-Zhong Chen Zhang-Xian Chen Lin-Bin Qiu Duan-Yu Lin Hui Zhang De-Chun Zheng Zhu-Ting Fang Jing-Feng Liu department of Tumor Interventional Radiology Clinical Ocology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of oncology and Vascular Interventional Radiology Clinical Oncology School of Fujian Medical UniversityFuzhou 350014Fujian ProvinceChina department of Nuclear Medicine Clinical Oncology School of Fujian Medical UniversityFuzhou 350014Fujian ProvinceChina department of Hepatopancreatobiliary Surgical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of Radiology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of oncology and Vascular Interventional Radiology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of Hepatobiliary Surgery Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)has become a growing health concern *** invasion and high tumor burden are key factors limiting the curative effect of selective internal radiation therapy(SIRT).CASE SUMMARY This case study reports a 49-year-old woman who was diagnosed with China Liver Cancer Staging(CNLC)IIIa HCC and>15 cm tumor ***,due to insufficient future liver remnant and vascular invasion,the tumor was unresectable;however,radical hepatectomy was performed after successful conversion therapy with SIRT using yttrium-90(90Y)resin microspheres followed by hepatic arterial infusion chemotherapy(HAIC)with tyrosine kinase inhibitor(TKI)and anti-programmed death-1(PD-1)*** using 90Y resin microspheres was given by the right hepatic artery and chemoembolization was simultaneously performed in the tumor’s feeding vessels from the right diaphragmatic *** was followed every three weeks with lenvatinib and *** 4 months post-SIRT,the tumor was downstaged to CNLC Ib and the patient successfully underwent *** histopathological examination of the resected specimen showed extensive *** This case study provides evidence for an integrated treatment strategy combining SIRT and HAIC with TKI and anti-PD-1 antibodies for patients with large HCC and microvascular *** confirmatory trials are required in the future.

关键词： Selective internal radiation therapy Hepatic arterial infusion chemotherapy Yttrium-90 resin microspheres Hepatocellular carcinoma Conversion therapy Case report

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Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

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oncology Research 2025年第1期33卷 213-224页

作者： SHIQIN JIANG YICHUN TANG FENG MA YUCHUN NIU LEI SUN department of Clinical Pharmacy Shenzhen Hospital of Integrated Traditional Chinese and Western MedicineShenzhen518104China department of Pathology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China department of Radiation oncology The First People’s Hospital of FoshanFoshan528000China department of oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China department of oncology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523721China

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer *** substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with *** the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were ***:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in *** functional role of the key gene identified in SCLC was determined both in vitro and in ***:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell ***,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in *** analysis revealed that USP1 is upregulated in *** addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune *** co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological ***,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated ***:Our study findings highlight the importance of NK cells in regulating ***1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

关键词： Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape

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NIR driven catalytic enhanced acute lung injury therapy by using polydopamine@Co nanozyme via scavenging ROS

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Chinese Chemical Letters 2025年第2期36卷 337-343页

作者： Xiaoshuai Wu Bailei Wang Yichen Li Xiaoxuan Guan Mingjing Yin Wenquan Lv Yin Chen Fei Lu Tao Qin Huyang Gao Weiqian Jin Yifu Huang Cuiping Li Ming Gao Junyu Lu Intensive Care Unit The Second Affiliated Hospital of Guangxi Medical University department of Critical Care Medicine The Ninth Affiliated Hospital of Guangxi Medical University Life Sciences Institute Guangxi Medical University department of Emergency The First Affiliated Hospital of Guangxi Medical University College & Hospital of Stomatology Guangxi Medical University Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction Guangxi Medical University

Acute lung injury(ALI) was characterized by excessive reactive oxygen species(ROS) levels and inflammatory response in the lung. Scavenging ROS could inhibit the excessive inflammatory response, further treating ALI. Herein, we designed a novel nanozyme(P@Co) comprised of polydopamine(PDA) nanoparticles(NPs) loading with ultra-small Co, combining with near infrared(NIR) irradiation, which could efficiently scavenge intracellular ROS and suppress inflammatory responses against ALI. For lipopolysaccharide(LPS) induced macrophages, P@Co + NIR presented excellent antioxidant and anti-inflammatory capacities through lowering intracellular ROS levels, decreasing the expression levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α) as well as inducing macrophage M2 directional polarization. Significantly, it displayed the outstanding activities of lowering acute lung inflammation, relieving diffuse alveolar damage, and up-regulating heat shock protein 70(HSP70) expression, resulting in synergistic enhanced ALI therapy effect. It offers a novel strategy for the clinical treatment of ROS related diseases.

关键词： Acute lung injury M2 directional polarization Nanozyme NIR driven ROS scavenging

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