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Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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Neural Regeneration Research 2025年第8期20卷 2181-2198页

作者： Jiali Chen Yiyang Li Xingping Quan Jinfen Chen Yan Han Li Yang Manfei Zhou greta seng peng mok Ruibing Wang Yonghua Zhao Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmacy Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan ProvinceChina Department of Electrical and Computer Engineering University of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on *** vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic ***,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery *** utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly ***,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic *** extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke *** this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification *** the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment ***,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

关键词： delivery engineering extracellular vesicles identification ischemic stroke isolation mitochondria targeting strategy therapeutic effects

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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

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SPECT和CT系列图用于放射性核素靶向治疗内照射吸收剂量的估算

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中华核医学与分子影像杂志 2018年第7期38卷 516-517页

作者：唐军 Tiantian Li Nien-Yun Wu Na Song greta S.P.mok 上海交通大学医学院附属苏州九龙医院核医学科 Biomedical Imaging Laboratory Department of Electrical and Computer EngineeringFaculty of Science and Technologyand Faculty of Health SciencesUniversity of Macau

目的在放射性核素靶向治疗（TRT）时,事先知道药物吸收剂量的分布是非常必要的。在以往研究中,作者发现用于定量计算的SPECT系列图像的非刚性配准可提高吸收剂量估算的准确性。该研究目的是评估CT系列图像能否进一步提高TRT吸收剂量估... 详细信息

目的在放射性核素靶向治疗（TRT）时,事先知道药物吸收剂量的分布是非常必要的。在以往研究中,作者发现用于定量计算的SPECT系列图像的非刚性配准可提高吸收剂量估算的准确性。该研究目的是评估CT系列图像能否进一步提高TRT吸收剂量估算的准确性。方法用一台投影机模拟配中能通用（MEGP）准直器的SPECT/CT采集;In标记的泽娃灵（Zevalin）注射后1、12、24、72及144 h的图像,在此过程中模拟了衰减、散射和准直器-探头间的响应。随后给1例神经内分泌肿瘤患者注射了222 MBq;In-DTPA-奥曲肽（DTPAOC）,注射后24、48和72 h行SPECT/CT显像。评价4种不同时间点采集图像的配准方法:基于全身显像系列图的配准（1）SPECT（***）或（2）CT（WB-CT）;基于器官的单个器官配准（3）SPECT（O-SPECT）或（4）CT（O-CT）。使用;Y基于体素的S因子（源器官或源组织对靶器官或靶组织的内照射吸收剂量贡献因子）对体素与体素的配准进行积分卷积。生成并分析靶器官的器官吸收剂量、等剂量曲线和剂量容积直方图。结果在模拟研究中,肝、脾O-SPECT、O-CT、WB-SPECT和WB-CT 4种配准方法的器官吸收剂量误差分别是（-8.66±2.83）%、（-2.51±3.69）%、（-9.23±3.28）%、（-7.17±2.53）%和（-14.81±4.91）%、（-3.60±4.37）%、（-18.13±4.44）%、（-11.34±4.22）%。对所有器官而言,O-CT配准法的结果最好。等剂量曲线和剂量容积直方图的结果与吸收剂量估算结果一致。病例研究的结果同样显示O-CT配准法的误差最小。结论对比CT和SPECT系列图,在CT系列图上进行器官配准可更有效地提高3D剂量估算的准确性,也许应把低剂量CT扫描纳入标准TRT方案中。

关键词：放射性核素靶向治疗定量SPECT CT剂量估算图像配准

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呼吸平均CT衰减校正在心肌灌注SPECT／CT显像中的作用

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中华核医学与分子影像杂志 2017年第10期37卷 673-673页

作者：顾佳唐军苏州大学医学部放射医学与防护学院 215123 苏州大学附属第二医院核医学科 215004

目的电影平均CT（CACT）和内插平均CT（IACT）已被报道可用于改善PET／CT肿瘤和心脏显像的衰减校正（AC）。该研究旨在通过计算机模拟和物理模型实验评估CACT和IACT在心肌灌注SPECT／CT显像中的有效性。方法先采用呼吸运动幅度为2、3、... 详细信息

目的电影平均CT（CACT）和内插平均CT（IACT）已被报道可用于改善PET／CT肿瘤和心脏显像的衰减校正（AC）。该研究旨在通过计算机模拟和物理模型实验评估CACT和IACT在心肌灌注SPECT／CT显像中的有效性。方法先采用呼吸运动幅度为2、3、4cm的数字XCAT模型模拟正常男性99Tcm-MIBI的分布。平均活度和衰减图分别表示静态的SPECT和CACT，而吸气末和呼气末的衰减图分别代表2个螺旋CT（HCTs）。采用平行孔分析投影仪对60个无噪声和有噪声的投影进行超过180。的模拟。将673MBq的99Tcm填人拟人躯干模型（模型有正常的心脏或有可在呼吸平台上编程的心肌灌注缺损区，以此模拟各种呼吸幅度）中，使用SPECT／CT经180。采集60个投影，同时采集CACT、标准HCT和在极端期的2个HCTs。基于以上数据，内插CT时相在使用仿射加B样条配准融合时产生，IACT通过模拟和模型实验中平均化内插CT时相和2个原始极端期而获得。采集的投影经使用CACT、IACT和HCTs衰减校正后进行重建。极坐标靶心图和17段图经过吸收相对差（RD）的分析。2个感兴趣区（ROI）分别勾画在灌注缺损区和本底区以获得强度比（IR）。结果在模拟研究中．不同衰减校正方法产生的极坐标靶心图无显著差异，而定量RD检测表明，SPECT㈨T与原始模型最相似，其次是RDmax〈8％和〈10％的spEcyl栅。SPECTHCTs的RD值偏离原始模型和各个心肌节段的SPECTCACT，RDmax在模拟实验和模型实验中分别为19．76％和16．68％。SPECTHCTs的IR值因实际更高的运动振幅而波动性高。结论，与HCT-AC相比，CACT-AC和IACT-AC均可减轻呼吸伪影并改善心肌灌注SPECT显像的定量。IACT的使用进一步降低了辐射剂量。

关键词： SPECT/CT 心肌灌注衰减校正呼吸伪影

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A Comparison of Local Infiltration Analgesia and PECS II Block for Analgesia in Mastectomy with Axillary Dissection—A Randomised Equivalence Study

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Open Journal of Anesthesiology 2021年第8期11卷 229-242页

作者： Louis Xiang Long Ng Marilyn Hui Xin Ng Chi Wei mok Wai peng Lee Su-Ming Tan Kwee Lian Woon Department of Anaesthesia and Surgical Intensive Care Changi General Hospital Singapore Department of Anaesthesiology and Surgical Intensive Care Changi General Hospital Singapore Department of Surgery Changi General Hospital Singapore Department of Anaesthesia and Surgical Intensive Care Changi General Hospital Singapore

Objective: Various analgesic techniques can be used for a mastectomy with axillary dissection with varying degrees of efficacy. In our institution, local anaesthesia infiltration (LIA) is commonly performed by surgeons. In this study, we hypothesise that the relatively novel PECS II block is equivalent to the analgesic profile of LIA. Methodology: In this single center, prospective, randomised control trial, 40 patients undergoing unilateral mastectomy with axillary dissection were randomly assigned to receive either 30 ml 0.5% ropivacaine before skin via LIA by a specialist breast surgeon during surgery or 30 ml 0.5% ropivacaine via PECS II block, before skin incision. Fentanyl was used as rescue analgesia intraoperatively, and all patients received morphine via patient-controlled analgesia (PCA) device postoperatively. The primary outcome was the difference in total morphine consumption in 24 hours between the 2 groups after surgery with equivalency set at ±1 mg. Secondary outcomes included time to rescue analgesia after block administration, post-operative pain score over 24 hours, adverse effects encountered, total intraoperative opioid usage, effect on operative time, block performance time as well as block and surgery related complications. Results: Unadjusted mean PCA morphine consumption over 24 hours post-operatively comparing local infiltration analgesia (LIA) to that of PECS II at 95% confidence interval was -1.22 mg (95% CI: -3.77, 1.33). Total IV Fentanyl use comparing LIA to PECS II was 2.53 ± 0.98 mcg/kg and 1.96 ± 0.57 mcg, P = 0.035. There were no other significant differences in the secondary outcome. Conclusion: We conclude there is a lack of equivalence between that of LIA and PECS II block, with the PECS II block providing superior analgesia.

关键词： PECS-II Mastectomy Analgesia Anaesthesia Pain Opioids

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Synthesis and Crystal Structure of N-methyl-9-(4-bromophenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione under Microwave Irradiation

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Chinese Journal of Structural Chemistry 2005年第4期24卷 399-402页

作者： HUAGuo-Ping ZHANGXiao-Jing TUShu-Jiang ZHUSong-Lei LITuan-Jie ZHUXiao-Tong ZHANGJin-peng XuzhouInstituteofArchitecturalTechnology XuzhouJiangsu221008China DepartmentofChemistry XuzhouNormalUniversityKeyLaboratoryofBiotechnologyonMedicalPlantXuzhouJiangsu221116China

The crystal structure N-methyl-9-(4-bromophenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10- decahydroacridine(C20H20BrNO2) was determined by single-crystal X-ray diffraction analysis. It belongs to P21/n space group, with a = 10.7999(18), b = 13.845(3), c = 11.4031(3) ?, β = 99.324(4)°, Dc = 1.525 g/cm3, Z = 4, λ = 0.71070 ?, μ(mokα) = 2.455 mm-1, Mr = 386.28, V = 1682.5(5) ?3, F(000) = 792, the final R = 0.0463 and wR = 0.1053. In the crystal structure, the pyridine ring adopts a boat conformation, the two six-numbered rings fused with pyridine ring adopt twisting boat con- formation.

关键词： acridine synthesis microwave irradiation crystal structure

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Synthesis and Crystal Structure of Dinuclear Cadmium Complex [Cd_2(phen)_4(fca)_2](ClO_4)_2(H_2O)_2

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Chinese Journal of Structural Chemistry 2003年第5期22卷 558-562页

作者： ZHANGZe WUJie-Ying TIANYu-peng DUpeng LIUQing-Liang FUNHoongKun C.Suchada YANGJia-Xiang DepartmentofChemistry UniversityofScienceandTechnologyofChinaHefei230026China DepartmentofChemistry AnhuiUniversityHefei230039China StateKeyLaboratoryofCoordinationChemistry NanjingUniversityNanjing210093China X-rayCrystallographyUnit SchoolofPhysicsUniversitySainsMalaysia11800USMPenangMalaysia

A novel complex [Cd2(phen)4(fca)2](ClO4)2(H2O)2 (fca = dianion of 3-ferrocenyl- 2-crotonic acid, phen = 1,10-phenanthroline) has been synthesized and characterized by X-ray single-crystal structure analysis. It crystallizes in triclinic system, space group P?with a = 11.6297(5), b = 12.5165(5), c = 13.8986(6) ? a = 63.345(1), b = 87.747(1), g = 71.862(1), V = 1706.20(1) ?, Z = 1, Dc = 1.673 g/cm3, F(000) = 868 and m(moka) = 1.185 mm-1 (l = 0.71073 ). R = 0.0800 and wR = 0.1793 for 7653 observed reflections (I > 2s(I)). The structure consists of a dinuclear cation [Cd2(phen)4(fca)2]2+, two discrete perchlorate anions and two water molecules. The cationic part of the complex shows a tetrametallic core in which two fca groups act as the (O, O) bridging ligands between two cadmium(Ⅱ) ions with a distorted octahedral environment. The Cd…Cd intradimer distance is 4.128 ?

关键词： crystal structure cadmium complex ferrocene derivative

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Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence

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World Journal of Gastroenterology 2014年第32期20卷 11384-11393页

作者： Chun-Jen Liu Juliana Chang Po-Huang Lee Deng-Yn Lin Cheng-Chung Wu Long-Bin Jeng Yih-Jyh Lin King-Tong mok Wei-Chen Lee Hong-Zen Yeh Ming-Chih Ho Sheng-Shun Yang Mei-Due Yang Ming-Chin Yu Rey-Heng Hu Cheng-Yuan peng Kuan-Lang Lai Stanley Shi-Chung Chang Pei-Jer Chen Graduate Institute of Clinical Medicine Hepatitis Research Center and Department of Internal Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Chang Gung Memorial Hospital-Linkou Medical Center and Chang Gung University Taichung Veterans General Hospital China Medical University Hospital National Cheng Kung University Hospital Kaohsiung Veterans General Hospital Medigen Biotechnology Corporation

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.

关键词： Antiangiogenesis Antimetastasis Adjuvant therapy Disease-free survival Heparanase inhibitor Hepatocellular carcinoma PI-88 Tumor recurrence

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Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5085-5095页

作者： Ye peng Lin Zhang Chris K.P.mok Jessica Y.L.Ching Shilin Zhao Matthew K.L.Wong Jie Zhu Chunke Chen Shilan Wang Shuai Yan Biyan Qin Yingzhi Liu Xi Zhang Chun Pun Cheung Pui Kuan Cheong Ka Long Ip Adrian C.H.Fung Kenneth K.Y.Wong David S.C.Hui Francis K.L.Chan Siew C.Ng Hein M.Tun Microbiota I-Center(MaglC) Hong KongChina Jockey Club School of Public Health and Primary Care The Chinese University of Hong KongHong KongChina Li Ka Shing Institute of Health Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Surgery LKS Faculty of MedicineThe University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina Centre for Gut Microbiota Research The Chinese University of Hong KongHong KongChina

The role of gut microbiota in modulating the durability of cOVID-19 vaccine immunity is yet to be *** this cohort study,we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline,1 month,and 6 months post vaccination(p.v).Neutralisation antibody,plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition.

关键词： vaccine immunity vaccines

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive *** an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)*** of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,***,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic ***,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer T cell

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