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IR780/Gemcitabine-conjugated metal-phenolic network enhanced photodynamic cancer therapy

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Chinese Chemical Letters 2024年第1期35卷 305-309页

作者： Songtao Zhou Hao Tian Jie Yan Zhan Zhang Guohao Wang Xinying Yu Wei Sang Bei Li Greta S.P.Mok Jie Song Yunlu Dai Cancer Center and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao 999078China MoE Frontiers science Center for Precision Oncology University of MacaoMacao 999078China Institute of Basic Medicine and Cancer(IBMC) Chinese Academy of SciencesThe Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China Biomedical Imaging Laboratory(BIG) Department of Electrical and Computer EngineeringFaculty of Science and TechnologyUniversity of MacaoMacao 999078China

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses energy of light to generate active substances that cause damage to the cancer. Photosensitizers are employed to absorb light and generate toxic reactive oxygen species (ROS) to damage biomolecules like DNA. At the same time, some chemotherapy drugs like nucleotide analogues can provide mechanism-guided promotion in the treatment efficacy of PDT. However, the photosensitizer and chemotherapy drugs used in PDT is usually organic molecules, which suffers from bad solubility, fast clearance, and acute toxicity. To achieve targeted treatment, a reasonable delivery system is necessary. Therefore, we reported a metal-phenolic network where IR780 and gemcitabine were coupled chemically to overcome these shortcomings. The enhanced PDT effects can be realized by the promoted cell death both in vitro and in vivo. Moreover, the synergistic therapy also induced T-cell mediated anti-tumor immune response, which was significant for the inhibition of distant tumor growth. This work expanded the biomedical application of metal-phenolic materials and contribute to the wider application of photodynamic cancer therapy.

关键词： Metal phenolic network IR780 Photodynamic therapy Breast cancer Gemcitabine

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

Effective and Sustainable Flood and Landslide Risk Reduction Measures:An Investigation of Two Assessment Frameworks

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International Journal of Disaster Risk science 2016年第4期7卷 374-392页

作者： Yvonne Andersson-Skld Lars Nyberg Swedish National Road and Transport Research Institute(VTI) Centre for Climate and Safety Karlstad University

Natural events such as floods and landslides can have severe *** risks are expected to increase,both as a consequence of climate change and due to increased vulnerabilities,especially in urban *** preventive measures are often cost-effective,some measures are beneficial to certain values,while some may have negative impacts on other *** aim of the study presented here was to investigate two frameworks used for assessing the effectiveness and sustainability of physical and nonphysical flood and landslide risk reduction *** study is based on literature,available information from authorities and municipalities,expert knowledge and experience,and stakeholder views and *** results indicate that the risks for suboptimization or maladaptation are reduced if many aspects are included and a broad spectrum of stakeholders are *** sustamability assessment tools applied here can contribute to a more transparent and sustainable risk management process by assessing strategies and interventions with respect to both short- and long-term perspectives,including local impacts and wider environmental impacts caused by climate change,for *** tools can also cover social and economic *** assessment tools provide checklists that can support decision processes,thus allowing for more transparent decisions.

关键词： Flood risk Landslide risk Risk reduction measures Sustainability assessment tools Sweden

A"three musketeers"tactic for inclining interferon-γ as a comrade-in-arm to reinforce the synergistic-tumoricidal therapy

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Nano Research 2022年第4期15卷 3458-3470页

作者： Wenxi Li Lisi Xie Yi Ju Zhan Zhang Bei Li Jie Li Wei Sang Guohao Wang Hao Tian Yunlu Dai Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao 999078China MOE Frontiers science Center for Precision Oncology University of MacaoMacao 999078China School of health and Biomedical sciences RMIT UniversityBundooraVictoria 3083Australia

Interferon-γ(IFN-γ),secreted by activated T cells predominantly,plays a crucial performance in the tumoricidal immune ***,a high level of IFN-γseverely ignites the immunosuppressive response,especially by increasing the expression of immune checkpoint programmed death-ligand 1(PD-L1)and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1(IDO-1).Herein,we have explored a versatile IFN-γ-nano-integrator(aPD-L1-SH@Ce6@NLG919-PEG,simplified as CNDP)to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal *** this nanointegrator,photosensitizer chlorin e6(Ce6)mediates photodynamic therapy(PDT)to re-shape immunogenicity and activate the adaptive immune response,followed by the secretion of high-level IFN-γto struggle tumor ***-1 inhibitor(NLG919)afterwards mitigates the immunosuppressive behavior of IFN-γby neutralizing the function of *** turn“waste”into wealth,anti-PD-L1(aPD-L1)antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 ***,this“three musketeers”nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.

关键词： interferon-γ(IFN-γ) anti-PD-L1(aPD-L1) IDO-1 inhibitor(NLG919) neutralization tumoricidal positive anti-tumor feedback loop

A platinum@polymer-catechol nanobraker enables radio-immunotherapy for crippling melanoma tumorigenesis, angiogenesis, and radioresistance

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Bioactive Materials 2023年第4期22卷 34-46页

作者： Wenxi Li Jie Yan Hao Tian Bei Li Guohao Wang Wei Sang Zhan Zhang Xuanjun Zhang Yunlu Dai Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR999078China MOE Frontiers science Center for Precision Oncology University of MacaoMacao SAR999078China

Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent *** melanoma intrinsic growth signals,including the blockade of PD-L1 and mTOR signaling concurrently,cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor ***,we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody(aPD-L1)for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma *** aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1:PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling;corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis,***,high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal ***,the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic *** an ingenious tactic may provide substantial benefits to clinical melanoma patients.

关键词： platinum@polymer-catechol nanobrakers Melanoma PD-1:PD-L1 interaction blockade Radio-sensitization effect Anti-tumorigenesis Anti-angiogenesis

Etiological roles of core promoter variation in triple-negative breast cancer

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Genes & Diseases 2023年第1期10卷 228-238页

作者： Teng Huang Jiaheng Li San Ming Wang Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesMinistry of Education Frontiers Science Center for Precision OncologyUniversity of MacaoTaipaMacao SAR 999078China

Abnormal geneexpression playskeyrole in *** is located around the transcriptional start *** interaction between core promoter sequences and transcriptional factors,core promoter controls transcriptional *** hypothesized that in cancer,core promoter sequences could be mutated to interfere the interaction with transcriptional factors,resulting in altered transcriptional initiation and abnormal gene expression and cancer *** used triple-negative breast cancer(TNBC)as a model to test our *** collected genome-wide core promoter variants from 279 TNBC *** extensive filtering of normal genomic polymorphism,we identified 19,427 recurrent somatic variants in 1,238 core promoters of 1,274 genes and 1,694 recurrent germline variants in 272 core promoters of 294 *** of the affected genes were oncogenes and tumor *** of RNA-seq data from the same patient cohort identified increased or decreased gene expression in 439 somatic and 85 germline variantsaffected genes,and the results were validated by luciferase reporter *** comparing with the core promoter variation data from 610 unclassified breast cancer,we observed that core promoter variants in TNBC were highly *** further identified the drugs targeting the genes with core promoter *** study demonstrates that core promoter is highly mutable in cancer,and can play etiological roles in TNBC and other types of cancer through influencing transcriptional initiation.

关键词： Core promoter RNA-seq Triple-negative breast cancer Variation Whole exome sequencing

NIR-Ⅱ-absorbing conjugated polymer-based theranostic agent for NIR-Ⅱfluorescence imaging-guided photothermal therapy acting synergistically with tumor microenvironment-responsive nitric oxide therapy

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ChemPhysMater 2022年第1期1卷 51-55页

作者： Jie Li Lisi Xie Wei Sang Wenxi Li Guohao Wang Hao Tian Zhan Zhang Jianhua Liu Quli Fan Yunlu Dai Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR 999078China Department of Radiology The Second Hospital of Jilin UniversityChangchun 130041China Key Laboratory for Organic Electronics and Information Displays&Institute of Advanced Materials(IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials(SICAM)Nanjing University of Posts&TelecommunicationsNanjing 210023China MoE Frontiers science Center for Precision Oncology University of MacaoMacao SAR 999078China

Despite tremendous advances in gas therapy,there are major concerns about the inevitable concentration of toxicity and the ability to perform real-time tracking of drug *** near-infrared(NIR-Ⅱ)window absorbing nanoplatforms hold great promise for precision medicine because of their excellent tissue penetration of light and non-invasive *** this study,we engineered an NIR-Ⅱlaser-activated theranostic agent(named CP-bF@PEG)that was composed of amphiphilic polymers(Pluronic F127,with polyethylene glycol,PEG,moieties)coated with an NIR-Ⅱ-absorbing conjugated polymer(PTTBBT,CP)and nitric oxide(NO)donor(benzofuroxan,bF),which served as an NIR-Ⅱphotothermal inducer and NO *** deep tissue penetration of NIR-Ⅱlaser irradiation,CP-bF@PEG was found to possess fluorescence imaging ability to accurately identify tumor and excellent photothermal ***,CP-bF@PEG could generate NO via glutathione activation in the tumor microenvironment in a controllable *** NIR-Ⅱ-absorbing polymer for high-contrast NIR-Ⅱfluorescence imaging-guided precision photothermal therapy achieved synergistic effects with NO therapy,as evidenced by pronounced tumor therapeutic efficacy and few side *** nanotheranostic agent is a highly promising candidate for high-contrast NIR-Ⅱimaging-guided precision photothermal therapy combined with gas therapy against cancer.

关键词： Conjugated polymer NIR-II fluorescence Photothermal therapy Tumor environment response Nitric oxide therapy

Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice

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Acta Pharmaceutica Sinica B 2023年第8期13卷 1164-1179页

作者： Xiaoqing Fan Chutian Mai Ling Zuo Jumin Huang Chun Xie Zebo Jiang Runze Li Xiaojun Yao Xingxing Fan Qibiao Wu Peiyu Yan Liang Liu Jianxin Chen Ying Xie Elaine Lai-Han Leung Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyTaipaMacao 999078China Beijing university of Chinese Medicine Beijing 100029China Cancer Center Faculty of Health Science、MOE Frontiers Science Center for Precision OncologyUniversity of MacaoMacao 999078China Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging the Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China State Key Laboratory of Dampness Syndrome of Chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine)Guangzhou 510120China

Sepsis-induced liver injury(SILI)is an important cause of septicemia ***(BWBDS)was extracted from a formula of Panax ginseng ***,Lilium brownie *** ex Miellez *** Baker,Polygonatum sibiricum *** Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)***.,and Cortex ***,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut *** protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal *** selectively promoted the growth of Lactobacillus johnsonii(***)in cecal ligation and puncture treated *** microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis ***,*** significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal ***,heat inactivation ***(***)treatment promoted macrophage anti-inflammatory activity and alleviated *** findings revealed BWBDS and gut microbiota *** as novel prebiotic and probiotic that may be used to treat *** potential underlying mechanism was at least in part,via ***-dependent immune regulation and interleukin-10+M2 macrophage production.

关键词： BaWeiBaiDuSan Sepsis-induced liver injury Network pharmacology 16S PacBio SMRT sequencing Lactobacillus johnsonii Macrophages Interleukin-10

Surface properties of bacteria from activated sludge in relation to bioflocculation

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Journal of Environmental sciences 2010年第12期22卷 1840-1845页

作者： Bing Xie Jidong Gu Jun Lu Key Laboratory of Urbanization and Ecological Restoration of Shanghai Department of Environmental Science & Technology East China Normal University Shanghai 200062 China Laboratory of Environmental Toxicology Department of Ecology & Biodiversity The University of Hong Kong Pokfulam Road Hong Kong SAR China Department of Interdisciplinary Studies Faculty of Health & Environmental Sciences Auckland University of Technology Auckland 1142 New Zealand School of Biological sciences Faculty of Science University of Auckland Auckland 1142 New Zealand

Two bacterial stains were isolated from the activated sludge and identified as Leucobacter sp. and Alcaligenesfaecalis by 16S rDNA sequencing. Pure cultures of these two strains, representing well or poorly settled bacteria, were used to investigate the mechanism of bioflocculation in activated sludge. Based on the analyses of the characteristics of cells hydrophobicity, ζ-potential, flocculation ability and extracellular polymeric substance （EPS） composition under different growth stages, it was found that the ratio of cell EPS protein had the highly influence on ζ-potential and hydrophobicity, which were important factors to bioflocculation. Cellulase and Proteinase K could destroy the extracellular biopolymer and resulted in a decrease in the hydrophobicity and ζ-potential. However, in our study, the flocculation characteristics exhibited differently in relation to cellulase and Proteinase K. Flocculation of cells treated with cellulase and Proteinase K decreased sharply, and then recovered quickly in cellulase treatment, while cells treated with Proteinase K showed no sign of recovery. This reveals that the presence of protein in extracellular biopolymer plays an important role to the bioflocculation of cells.

关键词： activated sludge hydrophobicity ζ-potential bioflocculation pure culture