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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 945-997页

作者： Jian Sheng loh Wen Qi Mak Li Kar Stella Tan Chu Xin Ng Hong Hao Chan Shiau Hueh Yeow Jhi Biau Foo Yong Sze Ong chee Wun How Kooi Yeong Khaw School of Pharmacy Monash University MalaysiaJalan Lagoon Selatan47500 Bandar SunwaySelangorMalaysia School of Pharmacy Faculty of Health&Medical SciencesTaylor’s University1Jalan TaylorsSubang Jaya 47500 SelangorMalaysia Digital Health&Medical Advancements Taylor’s University1Jalan TaylorsSubang Jaya 47500 SelangorMalaysia School of Biosciences Faculty of Health&Medical SciencesTaylor’s University1Jalan TaylorsSubang Jaya 47500 SelangorMalaysia UCL School of Pharmacy University College London29-39 Brunswick SquareLondon WC1N 1AXUK

The human gastrointestinal tract is populated with a diverse microbial *** vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology,including health maintenance,development,aging,and *** advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome–host *** has unveiled the bidirectional communication between the gut microbiome and the central nervous system,referred to as the“microbiota–gut–brain axis”.The microbiota–gut–brain axis represents an important regulator of glial functions,making it an actionable target to ameliorate the development and progression of neurodegenerative *** this review,we discuss the mechanisms of the microbiota–gut–brain axis in neurodegenerative *** the gut microbiome provides essential cues to microglia,astrocytes,and oligodendrocytes,we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative ***,we discuss the mechanisms of the microbiota–gut–brain axis in neurodegenerative diseases using a metabolite-centric approach,while also examining the role of gut microbiota-related neurotransmitters and gut ***,we examine the potential of targeting the intestinal barrier,blood–brain barrier,meninges,and peripheral immune system to counteract glial dysfunction in ***,we conclude by assessing the pre-clinical and clinical evidence of probiotics,prebiotics,and fecal microbiota transplantation in neurodegenerative diseases.A thorough comprehension of the microbiota–gut–brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.

关键词： degenerative therapeutic diseases

Peperomia pellucida(L.) Kunth and eye diseases: A review on phytochemistry, pharmacology and toxicology

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Journal of Integrative Medicine 2022年第4期20卷 292-304页

作者： keat Lam Ho Phaik Har Yong chee Woon Wang Umah Rani Kuppusamy Chek Tung Ngo Festo Massawe Zhi Xiang Ng School of Biosciences Faculty of Science and EngineeringUniversity of Nottingham Malaysia43500 SelangorMalaysia School of Bioscience Faculty of MedicineBioscience and NursingMAHSA University42610 SelangorMalaysia Department of Biochemistry Faculty of MedicineBioscience and NursingMAHSA University42610 SelangorMalaysia Department of Biomedical Science Faculty of MedicineUniversity of Malaya50603 Kuala LumpurMalaysia Optimax Sunway Eye Specialist Centre Bandar Sunway46150 SelangorMalaysia

Peperomia pellucida(L.) Kunth is a medicinal plant used to manage inflammatory illnesses such as conjunctivitis, and gastrointestinal and respiratory tract disorders in tropical and subtropical ***, little is known about its pharmacological mechanism of action against eye diseases. This review aims to critically discuss the phytochemistry, pharmacology and toxicology of P. pellucida as well as its roles in the treatment of cataract, glaucoma and diabetic retinopathy. Recent developments in the uses of P. pellucida for healthcare and nutraceutical products by the pharmaceutical industry are also covered in this review. For this review, a literature search was performed with PubMed, ScienceDirect, SciFinder Scholar and Scopus databases, using relevant keywords. Among the various phytochemicals identified from P. pellucida, β-caryophyllene, carotol, dillapiole, ellagic acid, pellucidin A, phytol and vitexin exhibit strong pharmacological activities within the mitogen-activated protein kinase and nuclear factor-κB signalling pathways in inflammatory eye diseases. The antihypertensive, anti-inflammatory, antioxidant,antihyperglycemic and anti-angiogenic activities displayed by P. pellucida extracts in many in vitro,in vivo and clinical studies suggest its potential role in the management of inflammatory eye diseases.P. pellucida extract was non-toxic against normal cell lines but displayed mild toxicity in animal *** growing public interest in P. pellucida has inspired the nutraceutical and pharmaceutical industries to process the plant into health products. Although the potential pharmacological mechanisms against eye diseases have been summarized, further studies of the interactions among constituent phytochemicals from P. pellucida within various signalling pathways shall support the use of the plant as an alternative therapeutic source.

关键词： Peperomia pellucida Phytochemistry Pharmacology Toxicology Cataract Diabetic retinopathy Glaucoma

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Advances of macroalgae biomass for the third generation of bioethanol production

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Chinese Journal of Chemical Engineering 2020年第2期28卷 502-517页

作者： Inn Shi Tan Man Kee Lam Henry chee Yew Foo Steven Lim keat Teong Lee Department of Chemical Engineering Curtin UniversitySarawak Campus CDT 25098009 MiriSarawakMalaysia Chemical Engineering Department Universiti Teknologi PETRONAS32610 Seri IskandarPerakMalaysia Centre for Biofuel and Biochemical Research Institute of Self-Sustainable BuildingUniversiti Teknologi PETRONAS32610 Seri IskandarPerakMalaysia Department of Chemical Engineering Lee Kong Chian Faculty of Engineering and ScienceUniversiti Tunku Abdul Rahman43000SelangorMalaysia School of Chemical Engineering Universiti Sains MalaysiaEngineering CampusSeri Ampangan14300 Nibong TebalPulau PinangMalaysia

In recent years, utilization of renewable sources for biofuel production is gaining popularity due to growing greenhouse gas(GHG) emissions which causes global warming. There has been a great effort in exploring alternative feedstock for bioethanol production. In this context, the production of third-generation bioethanol from macroalgae has emerged as an alternative feedstock to food crop-based starch and lignocellulosic *** is mainly due to the fast growth rate of macroalgae, no competition with agricultural land, high carbohydrate content and relatively simple processing steps compared to lignocellulosic biomass. This review paper provides an insight of recent innovative approaches for macroalgae bioethanol production, including conventional and advanced hydrolysis process to produce fermentable sugar, various fermentation technologies, economic analysis and life cycle assessment. With the current technology maturity, efficient utilization of macroalgae as sustainable source for bioethanol and other value-added chemicals production could be achieved in the near future.

关键词： Macroalage Hydrolysis Biomass Fermentation Bioethanol

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The Thermogel Chronicle——From Rational Design of Thermogelling Copolymers to Advanced Thermogel Applications

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Accounts of Materials Research 2021年第10期2卷 881-894页

作者： Qianyu Lin Cally Owh Jason Y.C.Lim Pei Lin chee Michelle P.Y.Yew Eilis T.Y.Hor Xian Jun loh Institute of Materials Research and Engineering(IMRE) Agency for ScienceTechnology and Research(A*STAR)138634Singapore NUS Graduate School for Integrative Sciences and Engineering National University of Singapore(NUS)119077Singapore Department of Materials Science and Engineering National University of Singapore(NUS)117576Singapore School of Materials Science and Engineering Nanyang Technological University639798Singapore

CONSPECTUS:Temperature responsive supramolecular hydrogels,also known as thermogels,are produced by the self-assembly of amphiphilic copolymers in solution following temperature *** are a class of high caliber novel materials possessing highly attractive properties such as injectability,ability to undergo temperature controlled reversible sol−gel phase transitions,high biocompatibility,and tunable *** research vigor has been dedicated to designing advanced amphiphilic copolymers and investigating their molecular interactions in order to enhance the properties of the thermogelling systems and expand the scope of their *** such,thermogelling systems have since become well established in the field of sustained localized drug or protein delivery and have also been demonstrated as high potential materials for niche applications such as threedimensional cell culture,wound healing patches,and vitreous *** developments saw the advent of thermogelling systems with advanced biomedical applications ranging from enhanced cancer therapy to radiology imaging to tissue engineering,and these are usually achieved by the conjugating of biologically relevant molecules such as drugs and peptides to the thermogel copolymer or by incorporating nanoparticles into the thermogel *** developments in this field see a shift away from employing traditional synthetic polymers such as polypropylene glycol(PPG)and poly(lactic-co-glycolic acid)(PLGA)to utilizing more advanced nature-derived bioactive molecules and also introducing chiral moieties in the thermogelling copolymer backbone.

关键词： Copolymer backbone utilizing

Clinical applications, limitations and future role of transient elastography in the management of liver disease

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第1期7卷 91-106页

作者： Pik Eu Chang George Boon-Bee Goh Jing Hieng Ngu Hiang keat Tan chee Kiat Tan Department of Gastroen- terology and Hepatology Singapore General Hospital George Boon-Bee Goh Duke- NUS Graduate Medical School

Transient elastography(TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate noninvasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in-time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease.

关键词： Liver stiffness Transient elastography Non-invasive Fibrosis Chronic

The Taoism Philosophy within Traditional Chinese Medicine:The Relation between Huang Di Nei Jing(《黄帝内经》Yellow Emperor's Inner Classic)and Dao De Jing(《道德经》Tao Te Jing)

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Chinese Medicine and Culture 2019年第4期2卷 184-188页

作者： chee Hoong Lim Seng keat Lim Guo Lin Wong Linchao Qian Yun Jin Kim School of Traditional Chinese Medicine Xiamen University Malaysia

Taoism refers to an indigenous Chinese philosophical and religious tradition. For more than two and a half millennia, it has had a profound social and intellectual influence on Eastern Asia and since the 19 th century has deeply influenced Western countries. Dao De Jing(《道德经》Tao Te Jing) is still considered to be the primary text of Taoism. The Tao Te Jing is attributed to Laozi, the classical Chinese Philosopher, and describes the major doctrines of Taoism. It is most relevant to Traditional Chinese Medicine(TCM). This article offers a brief introduction to the Taoism within TCM – the relation between Huang Di Nei Jing(《黄帝内经》The Yellow Emperor’s Inner Classic) and Dao De Jing(《道德经》Tao Te Jing).

关键词： Dao De Jing (《》 Tao Te Jing) Huang Di Nei Jing (《》 The Yellow Emperorss Inner Classic) Taoism Philosophy

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri Boon Koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen loh Wei keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Genome Institute of Singapore Agency for Science Technology and Research Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： hepatocellular carcinoma intra-tumor heterogeneity phenotypic evolution tumor evolution

The Efficacy of Plant-Based Ionizers in Removing Aerosol for COVID-19 Mitigation

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Research 2021年第1期2021卷 70-80页

作者： Ady Suwardi Chin Chun Ooi Dan Daniel chee Kiang Ivan Tan Hongying Li Ou Yang Zhong Liang Yuanting Karen Tang Jing Yee chee Anton Sadovoy Shu-Ye Jiang Srinivasan Ramachandran Enyi Ye Chang Wei Kang Wun Chet Davy Cheong Keng Hui Lim Xian Jun loh Institute of Materials Research and Engineering 2 Fusionopolis WayAgency for ScienceTechnology and ResearchSingapore 138634 Institute of High Performance Computing 1 Fusionopolis WayAgency for ScienceTechnology and ResearchSingapore 138632 Temasek Life Sciences Laboratory 1 Research LinkNational University of SingaporeSingapore 117604

Small-sized droplets/aerosol transmission is one of the factors responsible for the spread of COVID-19,in addition to large droplets and surface contamination(fomites).While large droplets and surface contamination can be relatively easier to deal with(i.e.,using mask and proper hygiene measures),aerosol presents a different challenge due to their ability to remain airborne for a long *** calls for mitigation solutions that can rapidly eliminate the airborne ***-COVID-19,air ionizers have been touted as effective tools to eliminate small *** this work,we sought to evaluate the efficacy of a novel plant-based ionizer in eliminating *** was found that factors such as the ion concentration,humidity,and ventilation can drastically affect the efficacy of aerosol *** aerosol removal rate was quantified in terms of ACH(air changes per hour)and CADR-(clean air delivery rate-)equivalent unit,with ACH as high as 12 and CADR as high as 141 ft^(3)/minute being achieved by a plant-based ionizer in a small isolated *** work provides an important and timely guidance on the effective deployment of ionizers in minimizing the risk of COVID-19 spread via airborne aerosol,especially in a poorly-ventilated environment.

关键词： aerosol eliminate sized

Pilocytic astrocytoma of the cerebellum in children

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Pilocytic astrocytoma of the cerebellum in children