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Injectable thermo-responsive nano-hydrogel loading triptolide for the anti-breast cancer enhancement via localized treatment based on “two strikes” effects

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2227-2245页

作者： Yaoyao Luo Jingjing Li Yichen Hu Fei Gao george pak-heng leung Funeng Geng Chaomei Fu Jinming Zhang College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Department of Pharmacology and Pharmacy University of Hong KongHongKong 999077China College of Pharmacy and Biological Engineering Chengdu UniversityChengdu 610100China Sichuan Key Laboratory of Medical American Cockroach Chengdu 615000China

The clinical application of triptolide(TPL)in tumor therapy has been greatly limited by its toxicity and inefficient ***,a localized and sustained-release thermo-sensitive hydrogel was developed for the intra-tumor administration of *** on the amphiphilic structure of poly(N-isopropylacrylamide-co-acrylic acid)-g-F68 copolymer,it was able to form nano-micelles to efficiently encapsulate TPL,and then turn into a hydrogel at ***@nano-gel exhibited a sustained drug release profile in vitro and a stronger anticancer effect caused by"two strikes".The"first strike"was its enhanced cytotoxicity compared to free TPL,due to the enhanced pro-apoptosis effect observed in both MDA-MB-231 and MCF-7 cells caused by the regulation of endogenous mitochondrial ***,TPL@nano-gel exhibited a"second-strike"through its anti-angiogenesis capabilities mediated through VEGFR-2 signaling *** expected,after intra-tumoral injection at a 0.45 mg/kg TPL-equivalent dose three times over 14 days in 4 T1 tumor-bearing mice,TPL@nano-gel led to lower systemic toxicity and higher antitumor efficacy compared to multiple injections of *** this regard,these findings indicate that this injectable thermo-responsive hydrogel carries great potential for TPL as a safe and effective cancer therapy.

关键词： Thermo-responsive hydrogel Triptolide Tumor local treatment Breast cancer Anti-angiogenesis Pro-apoptosis Micelle Survival rate

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Pharmacological efficacy of the traditional Chinese medicinal formula Kun-Tai-1A in the treatment of letrozole-induced polycystic ovary syndrome

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Traditional Medicine Research 2022年第3期7卷 44-54页

作者： Leanne Lee leung Jing Xie Ya-Cun Chen Kar-Ho Lam Hei Wan Su-Lan Yu Tzi-Bun Ng george pak-heng leung Jin Yu Ren-Min Yao Shu-Jia Sun Sydney Chi-Wai Tang Hai-Yong Chen Jia Zhao Zhang-Jin Zhang Calvin Kai-Fai Lee Kalin Yan-Bo Zhang Li-Xing Lao Yun Feng Xiang Lin Wei Meng School of Chinese Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China Workstation for Training and Research(Hong Kong Branch) Distinguished Professor Yu Jin Gynaecology of Chinese Medicine&Integrative MedicineHong Kong 999077China Shanghai Taikuntang Chinese Medicine Hospital Shanghai 200023China Department of Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China Virginia University of Integrative Medicine Virginia 22031USA Department of Ophthalmology Peking University Third HospitalBeijing 100191China Workstation of Zhu Nansun National Master of Chinese MedicineHong Kong Branch of Zhu’s School of Gynaecology of Chinese Medicine from ShanghaiHong Kong 999077China

Background:Polycystic ovary syndrome(PCOS)is an endocrine disorder that occurs in women of child-bearing ***,PCOS patients have decreased pregnancy rates and clomiphene citrate *** traditional Chinese medicine formula Kun-Tai-1S(KT1S),consisting of the seahorse species hippocampus,has been reported to elicit therapeutic effects in patients with ***,given the limited resources and global demand for wild hippocampus,whether KT1S with or without hippocampus can elicit similar therapeutic effects has not been ***:KT1S and Kun-Tai-1A(KT1A,KT1S without dry hippocampus)were used to treat a letrozole-induced rat model of PCOS with an established *** serum levels of testosterone,luteinizing hormone,anti-Müllerian hormone,and estradiol were determined,the luteinizing hormone/follicle-stimulating hormone ratio was determined,and the ovarian pathology was ***:Similar to the therapeutic effects of cyproterone acetate,both the KT1S and KT1A treatments reduced the body weight and ovarian and uterine indices in the rats with *** serum levels of testosterone,anti-Müllerian hormone,and luteinizing hormone and the luteinizing hormone/follicle-stimulating hormone ratio were significantly lower in the KT1S and KT1A treatment groups compared to the model group(P<0.01 and P<0.05,respectively).Moreover,the histopathological assessment results suggested that both the KT1S and KT1A treatments significantly ameliorated the PCOS pathology in the rats with an established disease,with a reduced number of cystic and atretic follicles and an increased number of corpora lutea being observed in the ***,there was no obvious difference in the disease outcomes between the KT1S and KT1A-treated *** pharmacology analysis revealed that 4’,7-dihydroxyflavanone,sinpemine A,quercetin,8-isopentenyl-kaempferol,and luteolin in KT1A may promote estrogen signaling;furthermore,the nitric oxide regulation pathway is also cl

关键词： polycystic ovary syndrome traditional Chinese medicine ovulation Kun-Tai-1A seahorse endocrine disease

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Icaritin Protects Cardiomyocytes from Oxidative Stress-induced Cell Injury Through Akt-Nrf2-HO-1 and Calcium Signaling Pathways

Icaritin Protects Cardiomyocytes from Oxidative Stress-induc...

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第十四届全国中药和天然药物学术研讨会

作者： Si Wan Lei Guozhen Cui Judy Yuet Wa Chan Sharon Chui Wah Luk Ken Kwok Keung Chan Ronald Adolphus Li Liang Wang Gail B.Mahady george pak heng leung Simon Ming Yuen Lee University of Macau The University of Hong Kong University of Illinois at Chicago

＜正＞Icaritin,a prenylflavonoid isolated from Herbal Epimedii,is well known for its osteoplastic and anti-tumor ***,we aimed to investigate the protective effects of icaritin against oxidative stress-induced cell injury in H9c2 cardiomyocytes and human embryonic stem cells-derived cardiomyocytes（hESC-CMs）.We found that icaritin pretreatment significantly

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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub george D.Bittner Department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

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Glycyrrhizic acid-based multifunctional nanoplatform for tumor microenvironment regulation

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Chinese Journal of Natural Medicines 2024年第12期22卷 1089-1099页

作者： XIAO Meng GUO Zhiqing YANG Yating HU Chuan Cheng Qian ZHANG Chen WU Yihan Cheng Yanfen BENSON Wui Lau Man SHAMAY Sheung Mei Ng leung george pak-heng LI Jingjing GAO Huile ZHANG Jinming State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611137China Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610072China School of Medicine Chengdu UniversityChengdu 610106China Department of Rehabilitation Sciences Faculty of Health and Social SciencesHong Kong Polytechnic UniversityHong Kong 999077China Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China The Research Centre for Chinese Medicine Innovation Hong Kong Polytechnic UniversityHong Kong 999077China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment(TME). Glycyrrhizic acid(GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid(GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles(NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.

关键词： Glycyrrhizic acid Tumor microenvironment Nanosystem Angiogenesis Self-assembly

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Impressive near-infrared brightness and singlet oxygen generation from strategic lanthanide-porphyrin double-decker complexes in aqueous solution

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Light(Science & Applications) 2019年第1期8卷 766-775页

作者： Jing-Xiang Zhang Wai-Lun Chan Chen Xie Yan Zhou Ho-Fai Chau Partha Maity george T.Harrison Aram Amassian Omar F.Mohammed Peter A.Tanner Wai-Kwok Wong Ka-leung Wong Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong S.A.R.China Hanshan Normal University ChaozhouGuangdong ProvinceChina Department of Biology Hong Kong Baptist UniversityKowloon TongHong Kong S.A.R.China KAUST Solar Center Division of Physical Science and EngineeringKing Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia

Although lanthanide double-decker complexes with hetero-macrocyclic ligands as functional luminescent and magnetic materials have promising properties,their inferior water solubility has negated their biomedical ***,four water-soluble homoleptic lanthanide(Ln=Gd,Er,Yb and La)sandwiches with diethylene-glycoldisubstituted porphyrins(DD)are reported,with their structures proven by both quantum chemical calculations and scanning tunneling *** findings demonstrate that the near-infrared emission intensity and singlet oxygen(1O2)quantum yields of YbDD and GdDD in aqueous media are higher than those of the reported capped lanthanide monoporphyrinato analogues,YbN and GdN;the brightness and luminescence lifetime in water of YbDD are greater than those of *** work provides a new dimension for the future design and development of molecular theranostics-based water-soluble double-decker lanthanide bisporphyrinates.

关键词： lanthanide porphyrin complexes

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Does Minimizing Ventricular Pacing Reduce the Incidence of Atrial Fibrillation ? A Systematic Review and Meta-analysis of Randomized Controlled Trials

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Cardiovascular Innovations and Applications 2020年第3期5卷 1-7页

作者： Ishan Lakhani Mengqi Gong Cheuk Wai Wong george Bazoukis Konstantinos PLetsas Guangping Li Khalid bin Wahleed Yunlong Xia Adrian Baranchuk Gary Tse Keith Sai Kit leung Tong Liu Dong Chang Laboratory of Cardiovascular Physiology Li Ka Shing Institute of Health SciencesHong Kong Special Administrative RegionPeople’s Republic of China Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjin 300211People’s Republic of China Li Ka Shing Faculty of Medicine The University of Hong KongHong KongSpecial Administrative RegionPeople’s Republic of China Second Department of Cardiology Laboratory of Cardiac ElectrophysiologyEvangelismos General Hospital of AthensAthensGreece Department of Cardiology First Affi liated Hospital of Dalian Medical UniversityDalianChina Division of Cardiology Kingston General HospitalQueen’s UniversityKingstonOntarioCanada Xiamen Cardiovascular Hospital Xiamen UniversityXiamenFujianPeople’s Republic of China Aston Medical School Aston UniversityBirminghamUnited Kingdom

Background:Right ventricular pacing disrupts atrioventricular synchrony and increases the risk of atrial fi brillation(AF).However,whether algorithms for minimizing ventricular pacing reduce the incidence of AF remains ***,we conducted a systematic review and meta-analysis to compare the incidence of AF between minimizing ventricular pacing and conventional pacing protocols in patients with pacemakers ***:The PubMed,Embase,and Cochrane Library databases were searched up to August 1,2017,for randomized controlled trials that reported the incidence of AF in patients with and without the use of algorithms for minimizing ventricular ***:Eleven studies comprising 5705 participants(61%males,mean age 71 years[standard deviation 11 years])were fi nally included in the *** mean follow-up duration was 24 *** of algorithms for minimizing ventricular pacing signifi cantly reduced the incidence of AF,with an odds ratio of 0.74(95%confi dence interval 0.55–1.00;P<0.05).There was moderate heterogeneity among studies(I 2=63%).Conclusions:The incidence of AF was reduced by 26%with use of algorithms for minimizing ventricular *** incorporation of such algorithms in routine clinical practice should in theory lead to a decrease in AF-related morbidity and mortality.

关键词： Atrial fibrillation minimizing ventricular pacing pacemaker

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Fatigue and Quality of Life of Women Undergoing Chemotherapy or Radiotherapy for Breast Cancer

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Clinical oncology and cancer researeh 2009年第3期6卷 179-185页

作者： Winnie K.W.So Gene Marsh W.M.Ling F.Y.leung Joe C.K.Lo Maggie Yeung george K.H.Li Department of Nursing Studies The University of Hong Kong School of Nursing University of Colorado Health Science Center Nurse Specialist Department of Clinical OncologyPamela Youde Nethersole Eastern Hospital Infection Control Unit Princess Margaret Hospital Oncology Department Princess Margaret Hospital Clinical Oncology Department Tuen Mun Hospital Department of Surgery Queen Mary Hospital

OBJECTIVE To examine fatigue and quality of life (QOL) inbreast cancer patients undergoing chemotherapy or *** A self-report survey derived from the Chineseversion of Brief Fatigue Inventory, the Functional Assessmentof Chronic Illness Therapy for Breast Cancer, and the MedicalOutcomes Study Social Support Survey. Descriptive statisticswas used to examine the intensity of fatigue and the prevalenceof severe fatigue. Multivariate analysis of variance was used todetermine factors that affect the five domains of QOL among *** The majority of the participants (n = 261) perceiveda mild level of fatigue, but 35.6% of them suffered severe *** had a significantly negative association with all domainsof QOL except social/family wellbeing. The participants whowere receiving chemotherapy, undergoing curative treatment andhaving inadequate social support were more likely to have poorerQOL in all five domains (after adjustment for age).CONCLUSION Although the majority of the participantsexperienced a mild level of fatigue, there was a substantial groupof breast cancer patients who perceived their fatigue as severe. Thefindings of this study showed that fatigue had a detrimental effecton the various aspects of the participants' QOL. Demographic andclinical characteristics of breast cancer patients who were at riskof getting poorer QOL were identified. The results of the studydemonstrate that we should enhance healthcare professionals'awareness of the importance of symptom assessment, andprovide them with information for planning effective symptom-management strategies among this study population.

关键词： breast neoplasm fatigue quality of life drug therapy.

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A microfluidic platform for continuous monitoring of dopamine homeostasis in dopaminergic cells

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Microsystems & Nanoengineering 2019年第1期5卷 593-605页

作者： Yue Yu Richard P.Sde Campos Seolim Hong Dimitar L.Krastev Siddharth Sadanand Yen leung Aaron R.Wheeler Institute for Biomaterials and Biomedical Engineering University of Toronto164 College StTorontoON M5s 3G9Canada Donnelly Centre for Cellular and Biomolecular Research 160 College St.TorontoON M5S 3E1Canada Department of Chemistry University of Toronto80 St George St.TorontoON M5S 3H6Canada Department of Human Biology University of Toronto300 Huron StreetTorontoON M5S 3J6Canada

Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal *** in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depression,and *** existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive *** response to this challenge,we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an *** used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists(cocaine,ketamine,epigallocatechin gallate,and amphetamine)and study their *** IC_(50)values of cocaine,ketamine,and epigallocatechin gallate were determined to be(average±standard deviation)3.7±1.1μM,51.4±17.9μM,and 2.6±0.8μM,***,we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from *** propose that this platform,which is the first platform to simultaneously evaluate uptake and release,could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine *** broadly,this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.

关键词： dopamine homeostasis release

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Impressive Near-infrared Brightness and Singlet Oxygen Generation from Strategic Lanthanide–porphyrin Double-decker Complexes in Aqueous Solution

Impressive Near-infrared Brightness and Singlet Oxygen Gener...

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第十一届全国化学生物学学术会议

作者： Jing-Xiang Zhang Partha Maity george T.Harrison Aram Amassian Omar F.Mohammed Peter A.Tanner Wai-Kwok Wong Ka-leung Wong Department of Chemistry Hong Kong Baptist University Hanshan Normal University KAUST Solar Center Division of Physical Science and EngineeringKing Abdullah University of Science and Technology(KAUST)

Although lanthanide double-decker complexes with hetero-macrocyclic ligands as functional luminescent and magnetic materials have promising properties, their inferior water solubility has negated their biomedical applications.[1] Herein, four water-soluble homoleptic lanthanide（Ln = Gd, Er, Yb and La） sandwiches with diethylene-glycol-disubstituted porphyrins（DD） are reported, with their structures proven by both quantum chemical calculations and scanning tunneling microscopy. Our findings demonstrate that the near-infrared emission intensity and singlet oxygen（1 O2） quantum yields of YbDD and GdDD in water are higher than those of the reported capped lanthanide monoporphyrinato analogues, YbN and GdN;the brightness and luminescence lifetime in water of YbDD are greater than those of YbN. This work provides a new dimension for the future design and development of molecular theranostics-based water-soluble double-decker lanthanide bisporphyrinates.[2]

关键词： Porphyrin-Lnthanide complex NIR-II luminescence photodynamic therapy

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