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N, N-dimethyltryptamine, a natural psychedelic, rapidly improves spatial memory and hippocampal longterm potentiation: a potential rapid-acting therapy for dementia-associated wandering

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中国药理学与毒理学杂志 2023年第7期37卷 489-490页

作者： CHENG Dan LEI Zhuogui Benjamin Chun-Kit TONG catherine kin chiu LI Ying king-Ho CHEUNG ZHANG Zhangjin School of Chinese Medicine the University of HongKong Department of Neuroscience City University of HongKong School of Chinses Medicine and Mr. and Mrs. Ko Chi Ming Centre for Parkinson’s Disease Research HongKong Baptist University Department of Psychology LKS Faculty of Medicine the University of HongKong Department of Chinese Medicine the University of Hong Kong-Shenzhen Hospital

There is no fast-acting treatment strategies against Alzheimer′s disease(AD), in particular dementia-related wandering. N, N-dimethyltryptamine(DMT) is a natural psychedelic that may have rapid-onset nootropic effects. In this study, 5 × FAD transgenic mice which recapitulated amyloid neuropathological features of AD received one single injection of 6 or 12 mg · kg-1DMT and tested at 0.5, 1, and 2 h thereafter in Y-maze for spatial memory. 5×FAD transgenic mice exhibited pronounced decreases in time spent, number entered, and distance travelled in the novel arm of Y-maze. DMT at 12 mg · kg-1partially or completely reversed the three behavioral indices at multiple time points, up to 2 h post injection. The rapid-onset behavioral improvement was consistent with pharmacokinetic analysis of DMT, showing approximately 30 min to reach the maximum concentration in the brain tissue. The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP), an electrophysiological feature of memory formation and consolidation. DMT potently enhanced LTP and restored intracellular calcium activity, expression and phosphorylation of calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ) and AMPA-type glutamate receptor1(GluR1), the two key calcium-activated mediators involved in LTP induction. Adenosine triphosphate(ATP)is purinergic signalling molecules that are involved in LTP induction and maintenance. DMT rapidly increased mitochondrial ATP dynamics in in vivo and in vitro *** results suggest that DMT rapidly improve spatial memory and hippocampal LTP by restoring the CaMKⅡ-GluR1 signaling pathway and mitochondrial ATP production. It may be served as a fast-acting nootropic agent for the treatment of AD in particular wandering.

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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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Modulation of morphological changes of microglia and neuroprotection by monocyte chemoattractant protein-1 in experimental glaucoma

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Cellular & Molecular Immunology 2010年第1期7卷 61-68页

作者： kin chiu Sze-Chun Yeung Kwok-Fai So Raymond Chuen-Chung Chang Laboratory of Neurodegenerative Diseases Department of AnatomyUniversity of Hong KongPokfulamHong KongChina State Key Laboratory of Brain and Cognitive Sciences University of HongKongPokfulamHongKongChina Research Centre of Heart BrainHormone and Healthy AgingLiKa Shing Faculty of MedicineUniversity of Hong KongPokfulamHong KongChina

Monocyte chemoattractant protein-1(MCP-1)/CCL2 is a C–C chemokine involved in the activation and recruitment of monocytic cells to injury ***-1/CCL2 can induce either neuroprotection or neurodestruction in vitro,depending on the experimental *** aim to use MCP-1/CCL2 as an experimental tool to investigate the morphological changes of microglia when loss of healthy retinal ganglion cells(RGCs)is exacerbated or attenuated in an experimental glaucoma *** a high concentration(1000 ng)of MCP-1/CCL2 and lipopolysaccharide(LPS)-exacerbated RGC loss,100 ng MCP-1/CCL2 provided neuroprotection towards *** MCP-1/CCL2(100 ng)also upregulated insulin-like growth factor-1(IGF-1)immunoreactivity in the *** neuroprotective effect of MCP-1/CCL2 was not due to the massiveinfiltration of microglia/*** together,this is the first report showing that an appropriate amount of MCP-1/CCL2 can protect RGCs in experimental glaucoma.

关键词： glaucoma IGF-1 MCP-1/CCL2 microglia neuroprotection

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CircTUBD1: A Novel Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis

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Journal of Clinical and Translational Hepatology 2022年第4期10卷 571-573页

作者： catherine Yujia Gu Terence kin Wah Lee Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic UniversityHong KongChina State Key Laboratory of Chemical Biology and Drug Discovery The Hong Kong Polytechnic UniversityHong KongChina

Citation of this article:Gu CY,Lee ***1:A Nov-el Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis.J Clin Transl Hepatol 2022;10(4):***:10.14218/*** liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer mortality worldwide.1 Liver transplantation and surgical resection are two curative therapeutic options for liver cancer patients at the early ***,most patients are diagnosed at advanced stages.

关键词： Liver Therapeutic cancer

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More than anti-malarial agents: therapeutic potential of artemisinins in neurodegeneration

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Neural Regeneration Research 2019年第9期14卷 1494-1498页

作者： Bing-Wen Lu Larry Baum Kwok-Fai So kin chiu Li-Ke Xie Department of Ophthalmology Eye HospitalChina Academy of Chinese Medical SciencesBeijingChina Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administration RegionChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Genomic Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Li Ka Shing Faculty of MedicineHong Kong Special Administration RegionChina Department of Psychiatry Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Li Ka Shing Faculty of MedicineHong Kong Special Administration RegionChina GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Funding:This

Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese *** and its derivatives(artemisinins)have been widely used for many years as anti-malarial agents,with few adverse side ***,evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria,including cancers,inflammatory diseases,and autoimmune *** is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions,whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders,including Alzheimer’s *** discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation,inflammation,and amyloid beta protein(Aβ).In this review,we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities,suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders.

关键词： artemisinin inflammation neuroinflammation neurodegeneration Alzheimer’s disease Parkinson’s disease Aβ anti-oxidation neuroprotection neural regeneration

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Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-β-induced inflammatory reactions in microglial cells

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Neural Regeneration Research 2022年第1期17卷 203-209页

作者： Zhong-Qing Sun Jin-Feng Liu Wei Luo Ching-Hin Wong Kwok-Fai So Yong Hu kin chiu Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina Guangdong-Hong Kong-Macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Orthopaedics&Traumatology The University of Hong KongHong Kong Special Administrative RegionChina

Lycium barbarum(LB)is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions,such as antioxidation,neuroprotection,and immune *** of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta(Aβ)transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding *** the present study,immortalized microglial cells were pretreated with *** extract for 1 hour and then treated with oligomeric Aβfor 23 *** results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells,downregulated the expression of M1 pro-inflammatory markers(inducible nitric oxide synthase,tumor necrosis factorα,interleukin-6,and interleukin-1β),and upregulated the expression of M2 anti-inflammatory markers(arginase-1,chitinase-like protein 3,and interleukin-4).LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factorα,interleukin-6,and interleukin-1βin microglial *** results of in vitro cytological experiments suggest that,in microglial cells,LB extract can inhibit oligomeric Aβ-induced M1 polarization and concomitant inflammatory reactions,and promote M2 polarization.

关键词： Alzheimer’s disease amyloid-β anti-inflammatory factors Lycium barbarum extract M1 microglia M2 microglia neuroinflammation proinflammatory factors

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Surface Modification of Intraocular Lenses

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Chinese Medical Journal 2016年第2期129卷 206-214页

作者： Qi Huang George Pak-Man Cheng kin chiu Gui-Qin Wang Department of Ophthalmology Navy General Hospital of PLA Beijing 100048 China Department of Ophthalmilogy Third Clinical Medical College of Southern Medical University Guangzhou Guangdong 510515 China Department of Ophthalmology Hong Kong Laser Eye Center Hong Kong 999077 China Department of Ophthalmology Laboratory of Retina Brain Research l:he Univeisity of Hong Kong Hong Kong 999077 China State Key Laboratory of Brain and Cognitive Sciences The University of Hong Kong Hong Kong 999077 China Research Centre of Heart Brain Hormone and Healthy Aging The University of Hong Kong Hong Kong 999077 China

Objective： This paper aimed to review the current literature on the surface modification ofintraocular lenses （IOLs）. Data Sources： All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect. Study Selection： The articles on the surface modification of 1OLs were included, but those on design modification and surface coating were excluded. Results： Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly （ethylene glycol）, polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO2, heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of ｜OLs had led to a better biocompatibility in both in vitro and animal experiments. Conclusion： The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.

关键词： Biocompatibility Capsule Biocompatibility Cataract Intraocular Lenses Surface Modification Uveal Biocompatibility

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Mechanisms of electrical stimulation in eye diseases:A narrative review

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Advances in Ophthalmology Practice and Research 2022年第2期2卷 1-10页

作者： Jinfeng Liu Andre K.H.Ma Kwok Fai So Vincent W.H.Lee kin chiu Department of Ophthalmology The University of Hong KongSARHong KongChina Harrow School HarrowUK The State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongSARHong KongChina Department of Psychology The University of Hong KongSARHong KongChina Guangdong-Hong Kong-Macao Institute of Central Nervous System Regeneration Jinan UniversityGuangzhouChina

Background:In the last two decades,electrical stimulation(ES)has been tested in patients with various eye diseases and shows great treatment potential in retinitis pigmentosa and optic ***,the clinical application of ES in ophthalmology is currently *** the one hand,optimization and standardization of ES protocols is still an unmet *** the other hand,poor understanding of the underlying mechanisms has hindered clinical *** Text:Numerous experimental studies have been conducted to identify the treatment potential of ES in eye diseases and to explore the related cellular and molecular *** this review,we summarized the in vitro and in vivo evidence related to cellular and tissue response to ES in eye *** highlighted several pathways that may be utilized by ES to impose its effects on the diseased ***:Therapeutic effect of ES in retinal degenerative diseases might through preventing neuronal apoptosis,promoting neuronal regeneration,increasing neurotrophic factors production in Müller cells,inhibiting microglial activation,enhancing retinal blood flow,and modulating brain *** studies are suggested to analyse changes in specific retinal cells for optimizing the treatment parameters and choosing the best fit ES delivery method in target diseases.

关键词： Electrical stimulation Eye diseases Ophthalmology Retinitis pigmentosa Optic neuropathy

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Retinal safety and toxicity study of artesunate in vitro and in vivo

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Advances in Ophthalmology Practice and Research 2023年第2期3卷 47-54页

作者： Bing-Wen Lu Yu-Xiang Liang Jin-Feng Liu Zhong-Qing Sun Kwok-Fai So kin chiu Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong KongChina Department of Psychology Faculty of Social SciencesThe University of Hong KongHong KongChina Guangdong-Hongkong-Macao(GHM)Institute of CNS Regeneration Ministry of EducationCNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouChina

Background:Artesunate(ART),a member of the artemisinin family,possesses multi-properties,including antiinflammation,anti-oxidation,and *** was recently reported to show anti-neovascularization effect on the cornea,iris,and *** to the expensive anti-VEGF treatment,this versatile,economical treatment option is attractive in the ophthalmic *** safety and toxicity profile of ART intravitreal application are in utmost ***:In this study,immortalized microglial(IMG)cells were treated with ART to determine the safe concentrations without inducing overt inflammatory *** transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART *** doses of ART were intravitreally injected into the right eyes of C57BL/6 *** function was tested by electroretinogram,and retinal ganglion cell(RGC)survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART ***:ART below 5μM was safe for IMG cells in *** 2.5 and 5μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β,IL-6,TNF-α,and *** the in vivo study,intravitreal injection of ART below 100μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes,while 1 mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC *** addition,treatment with ART of 25,50,and 100μM significantly decreased TNF-αgene expression while ART of 100μM significantly increased IL-10 in the mouse ***:Intravitreal injection of 100μM ART could downregulate TNF-αwhile upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC *** might be used as anti-inflammatory agent for retinal disorders.

关键词： Artesunate Safety Retina Microglia

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Clinical factors affecting rejection rates in liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2015年第4期14卷 367-373页

作者： kin Pan Au See-Ching Chan Kenneth Siu-Ho Chok William Wei Sharr Wing-chiu Dai Sui-Ling Sin Tiffany Cho-Lam Wong Chung-Mau Lo Department of Surgery the University of Hong Kong Medical Center Queen Mary Hospital

With improvements in survival, liver trans- plant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of re- jection. METHOD： We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cel- lular rejection （ACR） and various clinical factors. RESULTS： Multivariate analysis showed that older age （P=0.04, OR=0.982）, chronic hepatitis B virus infection （P=0.005, OR= 0.574）, living donor liver transplantation （P=0.02, OR=0.648） and use of interleukin-2 receptor antagonist on induction （P〈0.001, OR=0.401） were associated with fewer ACRs. Patients with fulminant liver failure （P=.004, OR=4.05） were more likely to develop moderate to severe grade ACR. CONCLUSIONS： Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver trans- plantation and use of interleukin-2 receptor antagonist on in- duction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.

关键词： liver transplantation acute rejection immunosuppression

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