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Augmenting osteoporotic bone regeneration through a hydrogel-based rejuvenating microenvironment

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Bioactive Materials 2024年第11期41卷 440-454页

作者： Xiaoting Zhang Boguang Yang Lu Feng Xiayi Xu Chenmin Wang Yuk-wai Lee Ming Wang Xuan Lu Ling Qin Sien Lin Liming Bian Gang Li Musculoskeletal Research Laboratory Department of Orthopaedics&TraumatologyThe Chinese University of Hong KongPrince of Wales HospitalHong KongChina Stem Cells and Regenerative medicine Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalHong KongChina The CUHK-ACC Space medicine Centre on Health Maintenance of Musculoskeletal System The Chinese University of Hong Kong Shenzhen Research InstituteShenzhenPR China SH Ho Scoliosis Research Laboratory Department of Orthopaedics and TraumatologyThe Chinese University of Hong KongHong KongChina Joint Scoliosis Research center of the chinese University of hong kong and Nanjing University The Chinese University of Hong KongHong KongChina Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongChina School of Biomedical Sciences and Engineering Guangzhou International CampusSouth China University of TechnologyGuangzhou511442PR China Department of Orthopaedics and Traumatology The University of Hong KongHong KongChina

Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing *** address this issue,this study introduces a hydrogel that creates a rejuvenating microenvironment,thereby facilitating efficient bone repair during the initial two weeks following bone defect *** hydrogel,named GelHFS,was created through host-guest polymerization of gelatin and acrylatedβ-*** of the human fetal mesenchymal stem cell secretome(HFS)formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell *** results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrinβ1-induced focal adhesion *** of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrinβ1-expressing cells and enhanced new bone formation and bone *** findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone *** findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.

关键词： Osteoporotic bone defects Bone regeneration Rejuvenating microenvironment Secretome Focal adhesion pathway

Chromene-based Bio AIEgens:'in-water' synthesis,regiostructure-dependent fluorescence and ER-specific imaging

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National Science Review 2023年第11期10卷 118-127页

作者： Xu-Min Cai Yuting Lin Jianyu Zhang Ying Li Zhenguo Tang Xuedan Zhang Ying Jia Wenjin Wang Shenlin Huang Parvej Alam Zheng Zhao Ben Zhong Tang Jiangsu Co-Innovation center of Efficient Processing and Utilization of Forest Resources International Innovation Center for Forest Chemicals and MaterialsCollege of Chemical EngineeringNanjing Forestry University School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen) Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionThe Hong Kong University of Science and Technology clinical Translational Research center of Aggregation-Induced Emission School of MedicineThe Second Affiliated HospitalSchool of Science and EngineeringThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)

Exploration of artificial aggregation-induced emission luminogens(AIEgens) has garnered extensive interest in the past two decades. In particular, AIEgens possessing natural characteristics(BioAIEgens) have received more attention recently due to the advantages of biocompatibility, sustainability and ***, the extremely limited number of BioAIEgens extracted from natural sources have retarded their development. Herein, a new class of Bio AIEgens based on the natural scaffold of chromene have been facilely synthesized via green reactions in a water system. These compounds show regiostructure-,polymorphism-and substituent-dependent fluorescence, which clearly illustrates the close relationship between the macroscopic properties and hierarchical structure of aggregates. Due to the superior biocompatibility of the natural scaffold, chromene-based BioAIEgens can specifically target the endoplasmic reticulum(ER) via the introduction of tosyl amide. This work has provided a new chromene scaffold for functional BioAIEgens on the basis of green and sustainable ’in-water’ synthesis, applicable regiostructure-dependent fluorescence, and effective ER-specific imaging.

关键词： chromene BioAIE ‘in-water’ chemistry regiostructure dependence ER-specific imaging

Revisiting oral fluoropyrimidine with cetuximab in metastatic colorectal cancer: Real-world data in chinese population

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 1031-1042页

作者： Ka-On Lam Man-Chi Fu Kin-Sang Lau Kam-Mo Lam Cheuk-Wai Choi Wan-Hang Chiu Cheng-Man Yuen Lai-Han Kwok Fong-Kit Tam Wing-Lok Chan Sum-Yin Chan Pui-Ying Ho To-Wai Leung Ho-Fun Lee Department of clinical Oncology LKS Faculty of MedicineThe University of Hong KongHong KongChina Department of clinical Oncology Queen Mary HospitalHong KongChina clinical Oncology Centre The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Department of Pharmacy Queen Mary HospitalHong KongChina Department of Diagnostic Radiology LKS Faculty of MedicineThe University of Hong KongHong KongChina

BACKGROUND Cetuximab in combination with oral fluoropyrimidine(FP)remains controversial in metastatic colorectal cancer(mCRC).In view of the regional variation in the tolerability of FP,we conducted a retrospective analysis to compare oral FP with infusional FP in combination with cetuximab in chinese *** To compare the efficacy and safety profile of cetuximab in combination with oral FP and infusional FP in chinese population in the real-world *** A retrospective cohort study was done to analyse consecutive patients with Kras wild-type mCRC who received first-line treatment with cetuximab and FP-based chemotherapy in our unit from January 2010 to December ***-five eligible patients were *** median follow-up of our cohort was 65.0 *** The median progression-free survival(mPFS)and median overall survival(mOS)of the entire cohort were 9.66 mo(95%CI:7.72–12.5)and 25.8 mo(95%CI:18.7–35.6),*** oral FP and infusional FP,there was no statistical significant difference in the mPFS[9.79 mo(95%CI:7.49–12.7)vs 9.63 mo(95%CI:6.34–13.4);P=0.72]and mOS[25.8 mo(95%CI:15.2–35.6)vs 26.3 mo(95%CI:18.7–41.2);P=0.63].Grade 3 or above adverse events were reported in 28.4%of patients,being similar with oral and infusional FP,and included 10.5%of neutropenia and 2.1%of diarrhoea *** The current analysis demonstrates comparable efficacy and safety profiles of cetuximab in combination with oral and infusional FP in chinese *** results expand treatment options for chinese patients and invite revision of existing treatment guidelines to incorporate oral FP-based chemotherapy plus cetuximab.

关键词： Capecitabine 5-Fluorouracil Cetuximab Metastatic colorectal cancer chinese

Exploratory use of ultrasound to determine whether demyelination following carpal tunnel syndrome co-exists with axonal degeneration

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Neural Regeneration Research 2018年第2期13卷 317-323页

作者： Xue Deng Lai-Heung Phoebe Chau Suk-Yee Chiu Kwok-Pui Leung Sheung-Wai Li Wing-Yuk Ip Department of Orthopedics & Traumatology The University of Hong Kong clinical Electro-diagnostic Unit Tung Wah Hospital Department of medicine The University of Hong Kong

Carpal tunnel syndrome （CTS） accompanied by secondary axonal degeneration cannot be clearly dis- criminated using the current cross-validated ultrasound severity classification system. This study aimed at exploring cut-off values of ultrasound parameters, including wrist cross-sectional area （W-CSA）, wrist perimeter （W-P）, ratio of cross-sectional area （R-CSA） and perimeter （R-P）, changes of CSA and P from wrist to one third distal forearm （△CSA＆AP） for differentiation. Seventy-three patients （13 male and 60 female） were assigned into group A （demyelination only, n = 40） and group B （demyelination with secondary axonal degeneration, n = 33） based on the outcomes of nerve conduction studies （NCS）. Receiver Operative Characteristics （ROC） curves were plotted to obtain sensitivity, specificity, and accuracy of cut- off values for all the ultrasound parameters. The overall identified cut-off values （W-CSA 12.0 mm2, W-P 16.27 mm, R-CSA 1.85, R-P 1.48, △CSA 6.98 mm2, △P 5.77 mm） had good sensitivity （77.1-88.6%）, fair specificity （40-62.2%） and fair-to-good accuracy （0.676-0.758）. There were also significant differences in demographics （age and severity gradation, P 〈 0.001）, NCS findings （wrist motor latency and conduction velocity, P 〈 0.0001; wrist motor amplitude, P 〈 0.05; distal sensory latency, P 〈 0.05; sensory amplitude, P 〈 0.001） and ultrasound measurements （W-CSA, W-P, R-CSA, R-P, △CSA＆△P, P 〈 0.05） between groups. These findings suggest that ultrasound can be potentially used to differentiate demyelinating CTS with sec- ondary axonal degeneration and provide better treatment guidance.

关键词： carpal tunnel syndrome nerve conduction studies ultrasound receiver operating characteristic curve peripheral nerve compression injury ultrasonography neural conduction axonal degeneration neural regeneration

Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis

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Bioactive Materials 2024年第9期39卷 255-272页

作者： Xiaobo Zhu Mingde Cao Kejia Li Yau-Tsz Chan Hon-Fai Chan Yi-Wah Mak Hao Yao Jing Sun Michael Tim-Yun Ong Kevin Ki-Wai Ho Chien-Wei Lee Oscar Kuang-Sheng Lee Patrick Shu-Hang Yung Yangzi Jiang Institute for Tissue Engineering and Regenerative medicine School of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong Special Administrative Region of ChinaChina School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongShatinHong Kong Special Administrative Region of Chin1China Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong Special Administrative Region of Chin1China center for Neuromusculoskeletal Restorative medicine Hong Kong Special Administrative Region of Chin1China Key Laboratory for Regenerative medicine Ministry of EducationSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong Special Administrative Region of Chin1China Department of Orthopaedic Surgery The First Affiliated HospitalSchool of MedicineZhejiang UniversityChina

Osteoarthritis(OA)is a major clinical challenge,and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment *** early treatments are urgently needed to prevent OA *** excessive amount of transforming growth factorβ(TGFβ)is one of the major causes of synovial fibrosis and subchondral bone sclerosis,and such pathogenic changes in early OA precede cartilage *** we report a novel strategy of intra-articular sustained-release of pirfenidone(PFD),a clinically-approved TGFβinhibitor,to achieve disease-modifying effects on early OA *** found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1(as those levels found in patients’synovial fluid).A monthly injection strategy was then designed of using poly lactic-co-glycolic acid(PLGA)microparticles and hyaluronic acid(HA)solution to enable a sustained release of PFD(the“PLGA-PFD+HA”strategy).This strategy effectively regulated OA progression in destabilization of the medial meniscus(DMM)-induced OA mice model,including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA,and reduced synovitis and pain with cartilage preservation *** finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

关键词： TGFβ1 signaling Osteoarthritis Subchondral bone Pirfenidone DMOAD

Electrocardiographic measures of repolarization dispersion and their relationships with echocardiographic indices of ventricular remodeling and premature ventricular beats in hypertension

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Journal of Geriatric Cardiology 2017年第12期14卷 717-724页

作者： Ana Ciobanu Gary Tse Tong Liu Maria V Deaconu Gabriela S Gheorghe Adriana M Iliesiu Ioan T Nanea Department of Internal medicine and Cardiology Theodor Burghele Clinical Hospital Carol Davila University of Medicine and Pharmacy Bucharest Romania Department of medicine and Therapeutics Faculty of Medicine Chinese University of Hong Kong Hong Kong China Li Ka Shing Institute of Health Sci- ences Faculty of Medicine Chinese University of Hong Kong Hong Kong China Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease Department of Cardiology Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University Tianjin China

Objective To examine the relationship between Tpeak- Tend interval （Tpe） and Tpe/QT ratio with occurrence of ventricular premature beats （VPBs） and left ventricular remodeling in hypertension. Methods A total of 52 patients with mild to moderate essential hypertension were included, undergoing echocardiography and 24-hours Holter monitoring. Ventricular remodeling was assessed by left ventricular mass index （LVMI） using the Devereux formula and diastolic fimction by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the precordial leads. The end of the T wave was set by the method of the tangent to the steepest descending slope of the T wave. Results Tpe and Tpe/QT in leads V2 （r = 0.33, P = 0.01; r = 0.27, P = 0.04 respectively） and V3 （r = 0.40, P = 0.002; r = 0.40, P = 0.003, respectively） correlated significantly with LVMI. A significant inverse relationship was observed between E/A ratio and QT （r = -0.33, P = 0.01）, Tpe in V3 （r = -0.39, P = 0.003） and Tpe/QT in V3 （r = -0.31, P = 0.02）. Tpe in V3, V5, mean Tpe and maximum Tpe with cut-offvalues of 60 ms, 59 ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular premature beats. Conclusions The repolarization parameters Tpe interval and Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic function and show better predictive values than traditional parameters such as QT interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor LV remodeling and predict occurrence of VPBs.

关键词： Hypertension Repolarization Tpeak-Tend Ventricular remodeling

Editorial:minor stroke is not minor

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Stroke & Vascular Neurology 2023年第3期8卷 175-177页

作者： Xinyi Leng David Wang medicine&Therapeutics The Chinese University of Hong KongHong KongChina Barrow Neurological Institute Petznick Stroke center PhoenixAZUSA

Defining minor stroke can be complicated.A minor stroke can be called a mini or small *** is often defined by the severity of neurological deficit,size of ischaemic lesion(s)on neuroimaging,and level of *** definition... 详细信息

关键词： minor severity transient

Tissue-based metabolite profiling and qualitative comparison of two species of Achyranthes roots by use of UHPLC-QTOF MS and laser micro-dissection

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Journal of Pharmaceutical Analysis 2018年第1期8卷 10-19页

作者： Yogini Jaiswal Zhitao Liang Alan Ho Hubiao Chen Leonard Williams Zhongzhen Zhao center for Excellence in Post-Harvest Technologies The North Carolina Research Campus School of chinese medicine Hong Kong Baptist University

Achyranthes bidentata and Achyranthes aspera are saponin and steroid rich medicinal plants, used extensively for therapeutic treatments in Traditional chinese medicine(TCM) and Ayurveda. A. bidentata is reported to be one of the rare and extensively exploited medicinal plant species that face the issue of being *** qualitative substitute with identical phyto-constituents contributing to similar composition and pharmacological benefits will help in reducing the burden of exploitation of the natural habitats of such *** the present study, a comparative metabolite analysis of the whole drug and specific tissues isolated by laser micro-dissection(LMD) was carried out for both the selected species, by use of ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-QTOF MS). The results of the study indicate that the cortex and the medullary ray tissues are rich in their content of steroidal and saponin constituents such as(25 S)-inokosterone-20,22-acetonide, ginsenoside Ro, bidentatoside II and achyranthoside *** profiling of the whole tissues of both the species indicates presence of identical constituents. Thus,it is inferred that A. bidentata and A. aspera can be used as qualitative substitutes for each other.

关键词： Achyranthes aspera Achyranthes bidentata Steroids Glycosides Saponins

Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of Basic Medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for clinical medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical Research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment