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Hypoxia promotes EV secretion by impairing lysosomal homeostasis in HNSCC through negative regulation of ATP6V1A by HIF-1α

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JOURNAL OF EXTRACELLULAR VESICLES 2023年第2期12卷 e12310页

作者： Wang, Xiaoning Wu, Ruoyi Zhai, Peisong liu, Zheqi Xia, Ronghui Zhang, Zhen Qin, Xing li, chuwen Chen, Wantao li, Jiang Zhang, Jianjun Shanghai Jiao Tong Univ Shanghai Peoples Hosp 9 Dept Oral Pathol Sch Med Shanghai Peoples R China Shanghai Jiao Tong Univ Peoples Hosp 9 Sch Med Dept Oral & Maxillofacial Head & Neck Oncol Shanghai Peoples R China Natl Clin Res Ctr Stomatol Shanghai Key Lab Stomatol Shanghai Peoples R China Natl Clin Res Ctr Stomatol Shanghai Res Inst Stomatol Shanghai Peoples R China Shanghai Jiao Tong Univ Peoples Hosp 9 Sch Med 639 Zhizaoju Rd Shanghai 200011 Peoples R China

Tumour cells under hypoxia tend to modulate the number and contents of extracellular vesicles (EVs) to regulate the tumour microenvironment (TME) and thus promote tumour progression. However, the mechanism of how hypoxia influences the secretion of EVs remains to be elucidated. Here, we confirm the increased production of EVs in head and neck squamous cell carcinoma (HNSCC) cells under hypoxia, where endosome-derived EVs are the main subtype affected by insufficient O-2. The accumulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) under hypoxia directly downregulates the expression of ATP6V1A, which is pivotal to maintain the homeostasis of lysosomes. Subsequently, impaired lysosomal degradation contributes to the reduced fusion of multivesicular bodies (MVBs) with lysosomes and enables the secretion of intraluminal vesicles (ILVs) as EVs. These findings establish a HIF-1 alpha-regulated lysosomal dysfunction-EV release axis and provide an exquisite framework to better understand EV biogenesis.

关键词： extracellular vesicles HIF-1 alpha hypoxia lysosomes multivesicular bodies

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NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1797-1807页

作者： Tengfei Fan Xiaoning Wang Sheng Zhang Ping Deng Yi Jiang Yidan liang Sheng Jie Qing Wang chuwen li Guocai Tian Zhen Zhang Zhenhu Ren Bo li Yanrong Chen Zhijing He Yan Luo Mingliang Chen Hanjiang Wu Zhengping Yu Huifeng Pi Zhou Zhou Zhiyuan Zhang Department of Oral and Maxillofacial-Head Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine Chinese Academy of Medical SciencesShanghaiChina Department of Oral and Maxillofacial Surgery Zhang Zhiyuan Academician WorkstationHainan Western Central HospitalShanghai Ninth People’s HospitalDanzhouHainanChina Department of Oral and Maxillofacial Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunanChina Department of Oral Pathology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Occupational Health Third Military Medical UniversityChongqingChina Department of Pathology The Second Xiangya Hospital of Central South UniversityChangshaHunanChina School of Medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Department of Oral and Maxillofacial Surgery Affiliated Hospital of Guilin Medical UniversityGuilinGuangxi Zhuang Autonomous RegionChina Institute of Pathology and Southwest Cancer Centre Southwest HospitalThird Military Medical UniversityChongqingChina and 10Department of Emergency MedicineFirst Affiliated Hospital and Department of Environmental MedicineSchool of Public HealthSchool of MedicineZhejiang UniversityHangzhouZhejiangChina

Oral squamous cell carcinoma(OSCC)is the most common type of oral malignancy,and metastasis accounts for the poor prognosis of *** is considered to facilitate OSCC development by mitigating various cellular stresses;nevertheless,the mechanisms of autophagy in OSCC cell proliferation and metastasis remain *** our study,high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1(NUPR1)as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis.

关键词： metastasis squamous prognosis

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ZnO@Bi5O7I Heterojunction Derived from ZIF-8@BiOI for Enhanced Photocatalytic Activity under Visible light

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MATERIALS 2022年第2期15卷 508页

作者： Tang, Jijun Duan, Zhengzhou Xu, Qinyun li, chuwen Hou, Dongmei Gao, Guicheng Luo, Weiqi Wang, Yujia Zhu, Yu Jiangsu Univ Sci & Technol Sch Mat Sci & Engn Zhenjiang 212003 Jiangsu Peoples R China Taizhou Univ Coll Pharm & Chem & Chem Engn Jiangsu Key Lab Chiral Pharmaceut Biomfg Taizhou 225300 Peoples R China

In the study, ZIF-8@BIOI composites were synthesized by the hydrothermal method and then calcined to acquire the ZnO@Bi5O7I composite as a novel composite for the photocatalytic deterioration of the antibiotic tetracycline (TC). The prepared ZnO@Bi5O7I composites were physically and chemically characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmet-Teller (BET) surface area, UV-Vis diffuse reflectance spectroscopy (DRS), emission fluorescence spectra, transient photocurrent response, electrochemical impedance spectra and Mott-Schottky. Among the composites formed an n-n heterojunction, which increased the separation efficiency of electrons and holes and the efficiency of charge transfer. After the photocatalytic degradation test of TC, it showed that ZnO@Bi5O7I (2:1) had the best photodegradation effect with an 86.2% removal rate, which provides a new approach to the treatment of antibiotics such as TC in wastewater.

关键词： ZnO Bi5O7I composite material photocatalytic degradation n-n heterojunction

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9-Hydroxy-8-oxypalmatine, a novel liver-mediated oxymetabolite of palmatine, alleviates hyperuricemia and kidney inflammation in hyperuricemic mice

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JOURNAL OF ETHNOPHARMACOLOGY 2024年 335卷 118606页

作者： Wu, Xiaoyan Huang, Ronglei Ai, Gaoxiang Chen, Hanbin Ma, Xingdong Zhang, Jiana Huang, Qiting Lao, Jiayi Zeng, Huiyuan li, chuwen Xie, Jianhui li, Yucui Su, Ziren Chen, Jiannan Huang, Xiaoqi Guangzhou Univ Chinese Med Sch Pharmaceut Sci 232Waihuan East Rd Guangzhou 510006 Peoples R China Guangzhou Univ Chinese Med Dongguan Inst Dongguan 523808 Peoples R China Southern Univ Sci & Technol Sch Med Dept Pharmacol Shenzhen 518055 Guangdong Peoples R China Guangzhou Med Univ Sch Pharmaceut Sci Key Lab Mol Target & Clin Pharmacol Guangzhou 511436 Peoples R China Guangzhou Univ Chinese Med Affiliated Hosp 2 Guangzhou 510120 Peoples R China Guangzhou Univ Chinese Med State Key Lab Dampness Syndrome Chinese Med Affiliated Hosp 2 Guangzhou 510120 Peoples R China

Ethnopharmacological relevance: Palmatine is a main bioactive alkaloid of Cortex Phellodendri, which has been commonly prescribed for the treatment of hyperuricemia (HUA) in China. The metabolites of palmatine were crucial to its prominent biological activity. 9-Hydroxy-8-oxypalmatine (9-OPAL) is a novel liver-mediated secondary oxymetabolite of palmatine. Aim of the study: The current study was to assess the efficacy of 9-OPAL, a novel liver-mediated secondary oxymetabolite of palmatine derived from Cortex Phellodendri, in experimental HUA mouse model and further explore its underlying mechanism. Materials and methods: An in vitro metabolic experiment with oxypalmatine was carried out using liver samples. We separated and identified a novel liver metabolite, and investigated its anti-HUA effect in mice. HUA mice were induced by potassium oxonate and hypoxanthine daily for one week. After 1 h of modeling, mice were orally administered with different doses of 9-OPAL (5, 10 and 20 mg/kg). The pathological changes of the kidneys were evaluated using hematoxylin-eosin staining (H&E). The acute toxicity of 9-OPAL was assessed. The effects of 9-OPAL on serum levels of uric acid (UA), adenosine deaminase (ADA), xanthine oxidase (XOD), creatinine (CRE), blood urea nitrogen (BUN) and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (EliSA) or biochemical method. Furthermore, Western blot, quantitative real-time PCR (qRT-PCR) and molecular docking were used to investigate the effect of 9-OPAL on the expression of renal urate transporters and NLRP3 signaling pathway in HUA mice. Results: 9-OPAL had been discovered to be a novel liver-mediated oxymetabolite of palmatine for the first time. Treatment with 9-OPAL significantly reduced the UA, CRE as well as BUN levels, and also effectively attenuated abnormal renal histopathological deterioration with favorable safety profile. Besides, 9-OPAL significantly decreased the serum and hepatic activities of XOD

关键词： 9-Hydroxy-8-oxypalmatine Hyperuricemia Anti-inflammation NLRP3 inflammasome Metabolite Nephroprotective effects

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ZIF-8-Derived ZnO and SnO2 Form ZnO@SnO2 Composites for Enhanced Photocatalysis under Visible light

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CHEMISTRYSELECT 2022年第33期7卷

作者： Tang, Jijun Duan, Zhengzhou Xv, Qinyun li, chuwen Gao, Guicheng Luo, Weiqi Hou, Dongmei Zhu, Yu Jiangsu Univ Sci & Technol Sch Mat Sci & Engn Zhenjiang 212003 Jiangsu Peoples R China Taizhou Univ Coll Pharm & Chem & Chem Engn Jiangsu Key Lab Chiral Pharmaceut Biomfg Taizhou 225300 Peoples R China

ZIF-8 was used as a precursor and was converted to ZnO by calcining at high temperature to remove the organic functional groups therein. Then ZnO@SnO2 composites were synthesized by hydrothermal method using ZnO as the carrier. All samples were characterized by XRD, SEM, EIS, Transient photocurrent test and Mott-schottky test. The photodegradation effects of pristine ZnO, SnO2 and ZnO@SnO2 composites on tetracycline (TC) were evaluated and the best results were obtained (ZnO@SnO2=2 : 1), which could remove 91.2 % of TC under visible light irradiation. The effects of pH, ionic strength, and TC concentration were researched in batch experiments. ZnO@SnO2=2 : 1 showed favorable photocatalytic activity and stability, including pH and resistance to ionic strength. The enhanced photocatalytic activity of the ZnO@SnO2=2 : 1 composite could be ascribed to the lower recombination probability of electron-hole pairs in the heterojunction and the enlarged surface area for TC adsorption during photodegradation. This study provided a reference for heterojunctions with excellent photocatalytic properties.

关键词： Heterojunction Metal organic framework Photocatalysis ZnO@SnO2 nanocomposites

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MOF composites derived BiFeO3@Bi5O7I n-n heterojunction for enhanced photocatalytic performance

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NANOTECHNOLOGY 2022年第20期33卷 205601-205601页

作者： Zhu, Yu li, chuwen Hou, Dongmei Gao, Guicheng Luo, Weiqi Duan, Zhengzhou Zhang, Tang Xv, Qinyun Wang, Yujia Tang, Jijun Taizhou Univ Coll Pharm & Chem & Chem Engn Jiangsu Key Lab Chiral Pharmaceut Biomfg Taizhou 225300 Peoples R China Jiangsu Univ Sci & Technol Sch Mat Sci & Engn Zhenjiang 212003 Jiangsu Peoples R China

BiFeO3 is a photocatalyst with excellent performance. However, its applications are limited due to its wide bandgap. In this paper, MIL-101(Fe)@BiOI composite material is synthesized by hydrothermal method and then calcined at high temperature to obtain BiFeO3@Bi5O7I composite material with high degradation capacity. Among them, an n-n heterojunction is formed, which improves the efficiency of charge transfer, and the recombination of light-generated electrons and holes promotes improved photocatalytic efficiency and stability. The result of photocatalytic degradation of tetracycline under visible light irradiation showed, BiFeO3@Bi5O7I (1:2) has the best photodegradation effect, with a degradation rate of 86.4%, which proves its potential as a photocatalyst.

关键词： BiFeO3 Bi5O7I n-n heterojunction Photocatalytic activity

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Berberine mediates root remodeling in an immature tooth with apical periodontitis by regulating stem cells from apical papilla differentiation

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International Journal of Oral Science 2020年第2期12卷 172-181页

作者： Yujia Cui Jing Xie Yujie Fu chuwen li liwei Zheng Dingming Huang Changchun Zhou Jianxun Sun Xuedong Zhou State Key Laboratory of Oral Diseases&National Clinical Center for Oral Diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Clinical Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology&National Clinical Research Center for Oral Diseases&Department of Oral and Maxillofacial-Head Neck Oncology Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghaiChina State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina and 5National Engineering Research Center for BiomaterialsSichuan UniversityChengduChina

Once pulp necrosis or apical periodontitis occurs on immature teeth,the weak root and open root apex are challenging to ***(BBR)is a potential medicine for bone disorders,therefore,we proposed to apply BBR in root canals to enhance root repair in immature *** in vivo model of immature teeth with apical periodontitis was established in rats,and root canals were filled with BBR,calcium hydroxide or sterilized saline for 3 *** shape of the roots was analyzed by micro-computed tomography and histological *** vitro,BBR was introduced into stem cells from apical papilla(SCAPs).Osteogenic differentiation of stem cells from apical papilla was investigated by alkaline phosphatase activity,mineralization ability,and gene expression of osteogenic *** signaling pathway,which regulated the osteogenesis of SCAPs was evaluated by quantitative real time PCR,Western blot analysis,and *** rats treated with BBR,more tissue was formed,with longer roots,thicker root walls,and smaller apex *** addition,we found that BBR promoted SCAPs osteogenesis in a time-dependent and concentration-dependent *** induced the expression ofβ-catenin and enhancedβ-catenin entering into the nucleus,to up-regulate more runt-related nuclear factor 2 *** enhanced root repair in immature teeth with apical periodontitis by activating the canonical Wnt/β-catenin pathway in SCAPs.

关键词： roots walls filled

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A Non-Gaussian Adaptive Importance Sampling Method for High-Dimensional and Multi-Failure-Region Yield Analysis 20

A Non-Gaussian Adaptive Importance Sampling Method for High-...

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39th IEEE/ACM International Conference On Computer Aided Design (ICCAD)

作者： Shi, Xiao Yan, Hao li, chuwen Chen, Jianli Shi, Longxing He, Lei Univ Calif Los Angeles Elect & Comp Engn Dept Los Angeles CA 90095 USA Southeast Univ Elect Engn Dept Nanjing Peoples R China Fudan Univ State Key Lab ASIC & Syst Shanghai Peoples R China

ISBN: (纸本)9781665423243

Rare-event yield analysis is challenging for high-dimensional circuit cases. In this paper, we propose a non-Gaussian adaptive importance sampling (NGAIS) method. In order to approximate the failure region in high-dimensional space, we model it as a mixture of von Mises-Fisher distributions. We formulate the parameter estimation problem as a maximum likelihood estimation problem, and then solve with expectation-maximization algorithm. Experiments on bit cell, amplifier and SRAM column circuit validate that the proposed NGAIS method outperforms other state-of-the-art approaches in terms of accuracy and efficiency.

关键词： Process Variation Failure Probability Adaptive Importance Sampling von Mises-Fisher distribution Maximum likelihood Estimation

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Zebrafish: A Promising Model for Evaluating the Toxicity of Carbon Dot-Based Nanomaterials

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ACS APPliED MATERIALS & INTERFACES 2020年第43期12卷 49012-49020页

作者： liu, Wei Huang, Gang Su, Xiaoying li, Siyi Wang, Qun Zhao, Yuying liu, Yao Luo, Jingshan li, Ye li, chuwen Yuan, Dongsheng Hong, Honghai Chen, Xiaojia Chen, Tongkai Guangzhou Univ Chinese Med Sci & Technol Innovat Ctr Guangzhou 510405 Peoples R China Guangxi Acad Sci State Key Lab Nonfood Biomass & Enzyme Technol Nanning 530007 Peoples R China Guangzhou Univ Chinese Med Sch Pharmaceut Sci Guangzhou 511400 Peoples R China Sun Yat Sen Univ Affiliated Hosp 3 Dept Pharm Guangzhou 510630 Peoples R China Guangzhou Med Univ Affiliated Hosp 3 Dept Clin Lab Guangzhou 510150 Peoples R China Univ Macau Inst Chinese Med Sci State Key Lab Qual Res Chinese Med Macau 999078 Peoples R China

Carbon dots (CDs) exhibit a wide range of desirable properties including excellent photoluminescence, photostability, and water solubility, making them ideally suitable for use in the context of drug delivery, bioimaging, and related biomedical applications. Before these CDs can be translated for use in humans, however, further research regarding their in vivo toxicity is required. Owing to their low cost, rapid growth, and significant homology to humans, zebrafish (Danio rerio) are commonly employed as in vivo model systems in the toxicity studies of nanomaterials. In the present report, our group employed a hydrothermal approach to synthesize CDs and then assessed their toxicity in zebrafish. The resultant CDs were roughly 2.4 nm spheroid particles that emitted strong blue fluorescence in response to the excitation at 365 nm. These CDs did not induce any evident embryonic toxicity or did cause any apparent teratogenic effects during hatching or development when dosed at 150 mu g/mL. However, significant effects were observed in zebrafish embryos at CD concentrations >200 mu g/mL, including pericardial and yolk sac edema, delayed growth, spinal cord flexure, and death. These high CD concentrations were further associated with the reduction in zebrafish larval locomotor activity and decreased dopamine levels, reduced frequencies of tyrosine hydroxylase-positive dopaminergic neurons, and multiple organ damage. Further studies will be required to fully understand the mechanistic basis for CD-mediated neurotoxicity, with such studies being essential to fully understand the translational potential of these unique nanomaterials.

关键词： carbon nanomaterials zebrafish (Danio rerio) nanotoxicology dopamine developmental neurotoxicity

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四氢姜黄素对大鼠C6神经胶质瘤细胞的抑制作用及机制研究

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重庆医学 2022年第24期51卷 4149-4154页

作者：任薇李晓珺张倩李楚文广东省第二中医院/广东省中医药工程技术研究院/广东省中医药研究开发重点实验室广州510095 广州医科大学药学院广州511436

目的探讨四氢姜黄素(THC)对大鼠C6神经胶质瘤细胞的抑制作用及机制。方法采用四甲基偶氮唑盐法检测不同浓度THC(12.50、25.00、50.00、100.00、200.00、400.00和800.00μmol/L)作用于大鼠C6神经胶质瘤细胞后的细胞存活率,通过Annexin V-... 详细信息

目的探讨四氢姜黄素(THC)对大鼠C6神经胶质瘤细胞的抑制作用及机制。方法采用四甲基偶氮唑盐法检测不同浓度THC(12.50、25.00、50.00、100.00、200.00、400.00和800.00μmol/L)作用于大鼠C6神经胶质瘤细胞后的细胞存活率,通过Annexin V-FITC/PI染色和caspase-3/-7活化分析检测C6细胞凋亡情况,使用DHE(二氢乙锭)-活性氧(ROS)检测试剂盒在流式细胞仪中检测ROS产生量,使用酶联免疫吸附测定试剂盒测量总抗氧化剂(TAS)和8-羟基-2′-脱氧鸟苷(8-OHdG)水平,通过定量实时逆转录-聚合酶链反应技术检测细胞核内核因子-κB(NF-κB)和过氧化物酶体增殖物激活受体γ(PPARγ)mRNA表达量。结果THC对C6细胞呈浓度和时间依赖性增殖抑制,可诱导C6细胞凋亡,THC处理降低了C6细胞中TAS水平并增加了8-OHdG水平,以剂量依赖性方式增强PPARγmRNA表达,同时下调NF-κB表达量。结论THC可通过抑制C6胶质瘤细胞NF-κB水平和增强PPARγ表达增加ROS的产生和降低TAS水平,从而促进细胞凋亡。提示THC在作为治疗神经胶质细胞瘤的新药开发方面具有一定的潜力和前景。

关键词：四氢姜黄素神经胶质瘤核因子-κB 过氧化物酶体增殖物激活受体γ 凋亡

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