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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang Sonata S Y Yau Kwok-Fai So li Zhang Haining Ou Department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Monosialoganglioside 1 may alleviate neurotoxicity induced by propofol combined with remifentanil in neural stem cells

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Neural Regeneration Research 2017年第6期12卷 945-952页

作者： Jiang Lu Xue-qin Yao Xin Luo Yu Wang Sookja Kim Chung He-xin Tang Chi Wai Cheung Xian-yu Wang Chen Meng Qing li Anesthesiology Research institute of Hubei University of Medicine Department of Anesthesiology Taihe Hospital Hubei University of Medicine Department of Anesthesiology Li Ka Shing Faculty of Medicine The University of Hong Kong Laboratory and Clinical Research institute for Pain Li Ka Shing Faculty of Medicine The University of Hong Kong Department of Anatomy Li Ka Shing Faculty of Medicine The University of Hong Kong

Monosialoganglioside 1（GM1） is the main ganglioside subtype and has neuroprotective properties in the central nervous system. In this study, we aimed to determine whether GM1 alleviates neurotoxicity induced by moderate and high concentrations of propofol combined with remifentanil in the immature central nervous system. Hippocampal neural stem cells were isolated from newborn Sprague-Dawley rats and treated with remifentanil（5, 10, 20 ng/m L） and propofol（1.0, 2.5, 5.0 μg/m L）, and/or GM1（12.5, 25, 50 μg/m L）. GM1 reversed combined propofol and remifentanil-induced decreases in the percentage of 5-bromodeoxyuridine（＋） cells and also reversed the increase in apoptotic cell percentage during neural stem cell proliferation and differentiation. However, GM1 with combined propofol and remifentanil did not affect β-tubulin（＋） or glial fibrillary acidic protein（＋） cell percentage during neural stem cell differentiation. In conclusion, we show that GM1 alleviates the damaging effects of propofol combined with remifentanil at moderate and high exposure concentrations in neural stem cells in vitro, and exerts protective effects on the immature central nervous system.

关键词： propofol alleviate tubulin anesthesia moderate newborn protective fibrillary glial aimed

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Commentary on:“Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation”

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Neural Regeneration Research 2025年第10期20卷 3040-3040页

作者： Kwok-Fai So Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina State Key Laboratory of Brain and Cognitive science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Neuroscience and Neurorehabilitation institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).

关键词： neural Becker Human

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Size-Dependent Gold Nanoparticle Interaction at Nano–Micro Interface Using Both Monolayer and Multilayer(Tissue-like) Cell Models

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Nano-Micro Letters 2016年第1期8卷 44-53页

作者： Darren Yohan Charmainne Cruje Xiaofeng Lu Devika B.Chithrani Department of Physics Ryerson University Keenan Research Centre Li Ka Shing Knowledge InstituteSt. Michael’s Hospital

Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy. However,the success of GNP-based therapeutics depends on their ability to penetrate tumor tissue. GNPs of 20 and 50 nm diameters were used to elucidate the effects of size on the GNP interaction with tumor cells at monolayer and multilayer level. At monolayer cell level, smaller NPs had a lower uptake compared to larger NPs at monolayer cell level. However, the order was reversed at tissue-like multilayer level. The smaller NPs penetrated better compared to larger NPs in tissue-like *** on our study using tissue-like materials, we can predict that the smaller NPs are better for future therapeutics due to their greater penetration in tumor tissue once leaving the leaky blood vessels. In this study, tissue-like multilayer cellular structures(MLCs) were grown to model the post-vascular tumor environment. The MLCs exhibited a much more extensive extracellular matrix than monolayer cell cultures. The MLC model can be used to optimize the nano–micro interface at tissue level before moving into animal models. This would accelerate the use of NPs in future cancer therapeutics.

关键词： Gold nanoparticles Multilayer cellular structures Tissue penetration Hyper spectral imaging Size dependence

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Elucidating the Uptake and Distribution of Nanoparticles in Solid Tumors via a Multilayered Cell Culture Model

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Nano-Micro Letters 2015年第2期7卷 127-137页

作者： Darren Yohan Charmainne Cruje Xiaofeng Lu Devika Chithrani Department of Physics Ryerson University Keenan Research Centre Li Ka Shing Knowledge Institute St. Michael’s Hospital

Multicellular layers(MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell lines. It is not known how nanoparticles(NPs) navigate through the tumor microenvironment once they leave the tumor blood *** this study, we used the MCL model to study the uptake and penetration dynamics of NPs. Gold nanoparticles(GNPs)were used as a model system to map the NP distribution within tissue-like structures. Our results show that NP uptake and transport are dependent on the tumor cell type. MDA-MB-231 tissue showed deeper penetration of GNPs as compared to MCF-7 one. Intracellular and extracellular distributions of NPs were mapped using Cyto Viva imaging. The ability of MCLs to mimic tumor tissue characteristics makes them a useful tool in assessing the efficacy of particle distribution in solid tumors.

关键词： Gold nanoparticles Tumor Multicellular cell layers Tissue

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The association of diet, gut microbiota and colorectal cancer： what we eat may imply what we get

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Protein & Cell 2018年第5期9卷 474-487页

作者： Jia Yang Jun Yu State Key Laboratory of Digestive Disease Department of Medicine and Therapeutics Li Ka Shing Institute of Health Sciences CUHK Shenzhen Research Institute The Chinese University of Hong Kong Sha Tin Hong Kong

Despite the success of colonoscopy screening and recent advances in cancer treatment, colorectal cancer （CRC） still remains one of the most commonly diagnosed and deadly cancers, with a significantly increased incidence in developing countries where people are adapting to Western life- style. Diet has an important impact on risk of CRC. Multiple epidemiological studies have suggested that excessive animal protein and fat intake, especially red meat and processed meat, could increase the risk of developing CRC while fiber could protect against colorectal tumorigenesis. Mechanisms have been investigated by animal studies. Diet could re-shape the community structure of gut microbiota and influence its function by modulating the production of metabolites. Butyrate, one of the short-chain fatty acids （SCFAs）, which act as a favorable source for colonocytes, could protect colonic epithelial cells from tumorigenesis via anti-inflammatory and antineoplastic properties through cell metabolism, microbiota homeostasis, antiproliferative, immunomodulatory and genetic/epigenetic regulation ways. In contrast, protein fermentation and bile acid deconjugation, which cause damage to colonic cells through proinflammatory and proneoplastic ways, lead to increased risk of developing CRC. In conclusion, a balanced diet with an increased abundance of fiber should be adopted to reduce the risk and prevent CRC.

关键词： colorectal cancer gut microbiota fiber protein fat metabolites

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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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Therapeutic approaches to non-alcoholic fatty liver disease: past achievements and future challenges

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Hepatobiliary & Pancreatic Diseases International 2013年第2期12卷 125-135页

作者： Jia Xiao Rui Guo Man Lung Fung Emily C liong George L Tipoe Departments of Anatomy Li Ka Shing Faculty of Medicine The University of Hong Kong Gene and Cell Engineering Research Center Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Departments of Physiology Li Ka Shing Faculty of Medicine The University of Hong Kong Research Centre of Heart Brain Hormone and Healthy Aging CentreLi Ka Shing Faculty of Medicine The University of Hong Kong

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver injury and mortality in Western countries and China. However, as to date, there is no direct and effective therapy for this disease. The aim of this review is to analyze the key progress and challenges of main current therapeutic approaches in NAFLD. DATA SOURCE: We carried out a PubMed search of English-language articles relevant to NAFLD therapy. RESULTS: There are two major therapeutic strategies for NAFLD treatment: (1) lifestyle interventions (including weight reduction, dietary modification and physical exercise) and (2) pharmaceutical therapies. lifestyle interventions, particularly chronic and moderate intensity exercise, are the most effective and recognized clinical therapies for NAFLD. For pharmaceutical therapies, although their effects and mechanisms have been extensively investigated in laboratory studies, they still need further tests and investigations in clinical human trials. CONCLUSION: Future advancement of NAFLD therapy should focus on the mechanistic studies on cell based and animal models and human clinical trials of exercise, as well as the combination of lifestyle intervention and pharmaceutical therapy specifically targeting main signaling pathways related to lipid metabolism, oxidative stress and inflammation.

关键词： non-alcoholic fatty liver disease therapy pharmaceuticals exercise

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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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Gut Microbiome in Colorectal Cancer:Clinical Diagnosis and Treatment

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Genomics, Proteomics & Bioinformatics 2023年第1期21卷 84-96页

作者： Yali liu Harry Cheuk-Hay Lau Wing Yin Cheng Jun Yu institute of Digestive Disease and The Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong Kong Special Administrative Region 999077China

Colorectal cancer(CRC)is one of the most frequently diagnosed cancers and the leading cause of cancer-associated *** studies have shown that both genetic and environmental risk factors contribute to the development of *** metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal *** enormous efforts and substantial progresses have been made in understanding the relationship between human gut microbiome and CRC,the precise mechanisms involved remain *** data have shown a direct causative role of the gut microbiome in DNA damage,inflammation,and drug resistance in CRC,suggesting that modulation of gut microbiome could act as a powerful tool in CRC prevention and ***,we provide an overview of the relationship between gut microbiome and CRC,and explore relevant mechanisms of colorectal *** next highlight the potential of bacterial species as clinical biomarkers,as well as their roles in therapeutic *** limiting the clinical translation of gut microbiome and strategies for resolving current challenges are further discussed.

关键词： Gut microbiome Colorectal cancer Diagnostic biomarker Immunotherapy Chemotherapy

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