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Evaluation of the Pharmacokinetics and Renal Excretion of Ma-Zi-Ren-Wan in Health Subjects

World Journal of Traditional Chinese medicine 2017年第2期3卷 8-15页

作者： Dong-Dong Hu Linda Li-Dan Zhong Kun Wai Huai-Xue Mu Cheng-Yuan Lin Ling Zhao Liang Dai Tao Huang Zhao-Xiang Bian hong kong Chinese medicine Study Centre Hong Kong Baptist University School of Chinese medicine Hong Kong Baptist University hong kong Baptist University Shenzhen Research institute and Continuing Education

Background: Ma-Zi-Ren-Wan(MZRW) is a classic Chinese formula for treating human constipation. It is comprised of six *** previous studies have shown its great therapeutic effect. The absorbed compounds had been studied in rat, while there was no study about its components in human ***: To observe the components of MZRW absorbed in health subjects and study the pharmacokinetics of major compounds. At the same time, to observe the renal excretion of MZRW in health subjects based on the quantification of major ***: Health adults were randomly assigned to three dose groups(5 g, 7.5 g and 10 g q.d.) of MZRW. Blood samples were collected from the medial cubital vein just before and at 0.25, 0.5, 1, 2, 4, 8 and 12 h after administration. Urine samples were collected at 0 to 3 h, 3 to 6 h, 6 to 9 h and 9 to 12 h after MZRW administration, with the urine volume recorded for each time segment. Plasma and urine samples were analyzed by optimized LC-MSMS(Liquid chromatography-tandem mass spectrometry) method for pharmacokinetics and renal excretion study of ***: Ten compounds of MZRW were observed in 23 health subjects. Due to the low concentration in plasma at the current dose, only four compounds(Albiflorin, paeoniflorin, magnolol and rhein) were quantified in the plasma sample. Honokiol, aloe emodin and emodin could only meet the LLOQ at some time points of the high dose group. Hesperidin, naringin and amygdalin could not be detected in plasma sample. While seven compounds(Amygdalin, albiflorin, paeoniflorin, magnolol, honokiol, rhein and aloe emodin) could be quantified in urine, the renal excretion was well ***: MZRW was safe and well tolerated in this clinical study. Albiflorin, paeoniflorin, magnolol and rhein was well quantified in plasma. The renal excretion of paeoniflorin, albiflorin and rhein were dose dependent for doses ranging between 5 and 10 g.

关键词： Ma-Zi-Ren-Wan LC-MS/MS Pharmacokinetics Human plasma Renal Excretion

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Spontaneous type 1 pattern, ventricular arrhythmias and sudden cardiac death in Brugada Syndrome： an updated systematic review and meta-analysis

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Journal of Geriatric Cardiology 2017年第10期14卷 639-643页

作者： Ahmed Bayoumy Meng-Qi GONG Ka Hou Christien Li Sunny Hei Wong William KK Wu Guang-Ping LI George Bazoukis Konstantinos P Letsas Wing Tak Wong Yun-Long XIA Tong LIU Gary Tse Department of medicine and Therapeutics Faculty of Medicine Chinese University of Hong Kong Hong Kong China Li Ka Shing institute of Health Sciences Faculty of Medicine Chinese University of Hong Kong Hong Kong China Faculty of medicine University of Amsterdam The Netherlands Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of Cardiology Tianjin Institute of Cardiology Second Hospitalof Tianjin Medical University Tianjin China Faculty of medicine Newcastle University United Kingdom Department of Anaesthesia and Intensive Care Faculty of Medicine Chinese University of Hong Kong Hong Kong China Second Department of Cardiology Evangelismos General Hospital of Athens Athens Greece School of Life Sciences Chinese University of Hong Kong Hong Kong China Department of Cardiology First Affiliated Hospital of Dalian Medical University Dalian China

Brugada syndrome （BrS） is primary electrical disorder characterized by ST segment elevation with right bundle branch block morphology in patients with apparent structurally normal hearts, It predisposes affected individuals to ventricular tachycardia/fibrillation （VT/VF） and sudden cardiac death （SCD）.A number of studies have identified risk factors that are associated with a more malignant course of disease. These include male gender, syncope, a spontaneous type 1 ECG pattern, family history of SCD, family history of Brugada syndrome,

关键词： Brugada syndrome Risk stratification Spontaneous type 1 Sudden cardiac death Ventricular arrhythmia

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Neurovascular ageing:transcriptomic readout and implications on therapeutic targeting in Alzheimer’s disease

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Neural Regeneration Research 2021年第12期16卷 2411-2412页

作者： Zhongqi Li Bonaventure Ip Vincent C.T.Mok Ho Ko Division of Neurology Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong Special Administrative RegionChina Li Ka Shing institute of Health Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina(Li ZKo H)Margaret K.L.Cheung Research Centre for Management of ParkinsonismThe Chinese University of Hong KongHong Kong Special Administrative RegionChina Chow Yuk Ho Technology Centre for Innovative medicine The Chinese University of Hong KongHong Kong Special Administrative RegionChina Gerald Choa Neuroscience Centre School of Biomedical SciencesDepartment of PsychiatryPeter Hung Pain Research InstituteFaculty of MedicineThe Chinese University of Hong KongHong Kong Special Administrative RegionChina

Ageing is one of the greatest risk factors for neurodegenerative *** the complex biological changes in ageing increase the brain’s susceptibility to neurodegeneration remains incompletely *** into neurodegenerative disorders has shifted from a neuron-centric approach,to the contributing roles of age-related neurovascular and glial cell dysfunction.

关键词： incomplete susceptibility ageing

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Insights into the genetic architecture of congenital heart disease from animal modeling

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Zoological Research 2023年第3期44卷 577-590页

作者： Wenjuan Zhu Cecilia W.Lo The Chinese University of hong kong Hong Kong SARChina Department of Developmental Biology University of Pittsburgh School of MedicinePittsburghPA15201 USA Kunming institute of Zoology-The Chinese University of hong kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina

Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth *** hundreds of genes have been implicated in the genetic etiology of CHD,their role in CHD pathogenesis is still poorly *** is largely a reflection of the sporadic nature of CHD,as well as its variable expressivity and incomplete *** reviewed the monogenic causes and evidence for oligogenic etiology of CHD,as well as the role of de novo mutations,common variants,and genetic *** further mechanistic insight,we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic *** the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis,thereby facilitating early intervention to improve outcomes for patients with CHD.

关键词： Congenital heart disease Genetic modifier Single cell sequencing De novo mutation Protective variant Common copy number variant

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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

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MHC class I-LILRB3 delivers a punch to eliminate precancerous cells

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Cellular & Molecular Immunology 2022年第6期19卷 655-656页

作者： Chi Chun Wong Jun Yu institute of Digestive Disease Department of Medicine and TherapeuticsState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

In the study by Ayukawa et al.[1],the authors presented an innate defense mechanism whereby normal epithelial cells actively remove precancerous cells from the epithelium via mechanical extrusion(Fig.1).

关键词： precancerous epithelium

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Fish-on-Chips:unveiling neural processing of chemicals in small animals through precise fluidic control

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Neural Regeneration Research 2024年第11期19卷 2351-2353页

作者： Samuel K.H.Sy Ho Ko Division of Neurology Department of Medicine and TherapeuticsFaculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Li Ka Shing institute of Health Sciences Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Department of Electrical and Electronic Engineering Faculty of EngineeringThe University of Hong KongPok Fu LamHong Kong IslandHong Kong Special Administrative RegionChina Advanced Biomedical Instrumentation Center Hong Kong Science ParkPak Shek KokNew TerritoriesHong Kong Special Administrative RegionChina Margaret K.L.Cheung Research Center for Management of Parkinsonism Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Lau Tat-chuen Research Center of Brain Degenerative Diseases in Chinese Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Gerald Choa Neuroscience institute The Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina

Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in ***,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal ***,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain ***,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much *** is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.

关键词： dealing precise sizes

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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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Contrasting neuropathology and functional recovery after spinal cord injury in developing and adult rats

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Neuroscience Bulletin 2013年第4期29卷 509-516页

作者： Qiuju Yuan Huanxing Su Kin Chiu Wutian Wu Zhi-Xiu Lin Department of Anatomy The University of Hong Kong School of Chinese medicine Faculty of Science The Chinese University of Hong Kong State Key Laboratory of Quality Research in Chinese medicine and institute of Chinese Medical Sciences University of Macao State Key Laboratory of Brain and Cognitive Sciences Development and Growth Li Ka Shing Faculty of Medicine The University of Hong Kong Research Center of Reproduction Development and Growth Li Ka Shing Faculty of Medicine The University of Hong Kong GHM institute of CNS Regeneration Jinan University

Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 （PN1）, PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a 〉5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold （FG） also showed that FG did not cross the transection site in PN1 and PN7rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored.

关键词： neonatal spinal cord injury regeneration functional recovery rat

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Arabidopsis EXTRA-LARGE G PROTEIN 1(XLG1) functions together with XLG2 and XLG3 in PAMP-triggered MAPK activation and immunity

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Journal of integrative Plant Biology 2023年第3期65卷 825-837页

作者： Yiping Wang Hailei Zhang Pengxi Wang Huan Zhong Wuzhen Liu Shoudong Zhang Liming Xiong Yingying Wu Yiji Xia Department of Biology Hong Kong Baptist UniversityHong Kong 999077China institute for Research and Continuing Education Hong Kong Baptist UniversityShen Zhen 518057China State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongHong Kong 999077China State Key Laboratory of Biological and Environmental Analysis Hong Kong Baptist UniversityHong Kong 999077China

Pattern-triggered immunity(PTI) is an essential strategy used by plants to deploy broad-spectrum resistance against pathogen attacks. Heterotrimeric G proteins have been reported to contribute to *** the three non-canonical EXTRA-LARGE G PROTEINs(XLGs) in Arabidopsis thaliana, XLG2 and XLG3 were shown to positively regulate immunity,but XLG1 was not considered to function in defense,based on the analysis of a weak xlg1 *** this study, we characterized the xlg1 xlg2 xlg3 triple knockout mutants generated from an xlg1 knockout allele. The strong xlg1 xlg2 xlg3 triple mutants compromised pathogen-associated molecular pattern(PAMP)-triggered activation of mitogen-activated protein kinases(MAPKs) and resistance to pathogen infection. The three XLGs interacted with MAPK cascade proteins involved in defense signaling, including the MAPK kinase kinases MAPKKK3 and MAPKKK5, the MAPK kinases MKK4 and MKK5, and the MAPKs MPK3 and MPK6. Expressing a constitutively active form of MKK4 restored MAPK activation and partially recovered the compromised disease resistance seen in the strong xlg1 xlg2 xlg3 triple mutant. Furthermore, mutations of all three XLGs largely restored the phenotype of the autoimmunity mutant bak1-interacting receptor-like kinase 1. Our study reveals that all three XLGs function redundantly in PAMP-triggered MAPK activation and plant immunity.

关键词： Arabidopsis heterotrimeric G protein MAPK cascade plant immunity XLG1 XLG2

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