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Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng

Acta Pharmaceutica Sinica B 2024年第2期14卷 653-666页

作者： Shining Loo Antony Kam Bamaprasad Dutta Xiaohong Zhang Nan Feng Siu Kwan Sze Chuan-Fa Liu Xiaoliang Wang James P.Tam School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Department of Biological Sciences Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Institute of Materia Medica Chinese Academy of Medical SciencesBeijing 100050China Department of Health Sciences Brock UniversityNiagara RegionON L2S 3A1Canada

Stress and illness connection is complex and involves multiple physiological systems.Panax ginsengs,reputed for their broad-spectrum“cure-all”effect,are widely prescribed to treat stress and related illnesses.However,the identity of ginseng’s“cure-all”medicinal compounds that relieve stress remains unresolved.Here,we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress.Ginsentides are disulfide-rich,cell-penetrating and proteolytic-stable microproteins.Using affinity-enrichment mass spectrometry target identification together with in vitro,ex vivo and in vivo validations,we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway,alleviate a1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta,decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation.Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation,to prevent collagen and adrenalineinduced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice.Together,these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra-and intra-cellular proteins to reverse stress-induced damages.

关键词： Ginseng Cysteine-rich peptides Microproteins Cure-all Stress Homeostasis

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Exploiting plant transcriptomic databases:Resources,tools,and approaches

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Plant Communications 2022年第4期3卷 1-13页

作者： Peng Ken Lim Xinghai Zheng Jong Ching Goh Marek Mutwi School of Biological Sciences Nanyang Technological University60 Nanyang DriveSingapore 637551Singapore

There are now more than 300000 RNA sequencing samples available,stemming from thousands of exper-iments capturing gene expression in organs,tissues,developmental stages,and experimental treatments for hundreds of plant species.The expression data have great value,as they can be re-analyzed by others to ask and answer questions that go beyond the aims of the study that generated the data.Because gene expression provides essential clues to where and when a gene is active,the data provide powerful tools for predicting gene function,and comparative analyses allow us to study plant evolution from a new perspective.This review describes how we can gain new knowledge from gene expression profiles,expres-sion specificities,co-expression networks,differential gene expression,and experiment correlation.We also introduce and demonstrate databases that provide user-friendly access to these tools.

关键词： gene expression comparative transcriptomics gene function co-express ion differential expr ession databases

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A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong,China

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Journal of Integrative Medicine 2023年第6期21卷 550-560页

作者： Dong-jue Wei Hui-juan Li Zi-pan Lyu Ai-ping Lyu Zhao-xiang Bian Linda LD Zhong School of Chinese Medicine Hong Kong Baptist UniversityHong KongChina School of Biological Sciences Nanyang Technological University637551Singapore

Objective:Functional constipation(FC)is a common intestinal disease worldwide.Despite the presence of criteria such as Roman IV,there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches.This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients.Methods:A systematic search of the PubMed,Cochrane Library,and China National Knowledge Infrastructure databases was performed from their inception to June 30th,2022,collecting the current evidence about the efficacious integrative management for FC.We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process.Results:We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts.This pathway includes a hierarchy of recommendations for every step of the clinical process,including clinical intake,diagnostic examination,recommended labs,diagnostic flowchart,and guidance for selection of therapeutic drugs.Conclusion:This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine;it will help to provide high-quality medical services in Hong Kong for patients with FC.

关键词： Functional constipation Clinical pathway Hong Kong Integrative medicine

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Leaf morphogenesis:The multifaceted roles of mechanics

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Molecular Plant 2022年第7期15卷 1098-1119页

作者： Kexin Guo Changjin Huang Yansong Miao Daniel J.Cosgrove K.Jimmy Hsia School of Mechanical and Aerospace Engineering Nanyang Technological UniversitySingapore 639798Singapore School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Department of Biology The Pennsylvania State UniversityUniversity ParkPA 16802USA School of Chemical and Biomedical Engineering Nanyang Technological UniversitySingapore 637459Singapore

Plants produce a rich diversity of biological forms,and the diversity of leaves is especially notable.Mechanisms of leaf morphogenesis have been studied in the past two decades,with a growing focus on the interactive roles of mechanics in recent years.Growth of plant organs involves feedback by mechanical stress:growth induces stress,and stress affects growth and morphogenesis.Although much attention has been given to potential stress-sensing mechanisms and cellular responses,the mechanical principles guiding morphogenesis have not been well understood.Here we synthesize the overarching roles of mechanics and mechanical stress in multilevel and multiple stages of leaf morphogenesis,encompassing leaf primordium initiation,phyllotaxis and venation patterning,and the establishment of complex mature leaf shapes.Moreover,the roles of mechanics at multiscale levels,from subcellular cytoskeletal molecules to single cells to tissues at the organ scale,are articulated.By highlighting the role of mechanical buckling in the formation of three-dimensional leaf shapes,this review integrates the perspectives of mechanics and biology to provide broader insights into the mechanobiology of leaf morphogenesis.

关键词： leaf morphogenesis cell-wall mechanics phyllotaxis and venation patterning differential and anisotropic growth mechanical buckling

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Ancestral genome reconstruction for studies of the green lineage

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Molecular Plant 2023年第4期16卷 657-659页

作者： Marek Mutwil Alisdair R.Fernie School of Biological Sciences Nanyang Technological University60 Nanyang DriveSingapore 637551Singapore Max-Planck-Institute of Molecular Plant Physiology Am Muhlenberg 114476 Potsdam-GolmGermany

Ancestral sequence reconstruction has become a fundamental aspect of molecular evolution studies being used to trace small-scale sequence modifications through the course of the evolution of species.While first proposed in the 1960s(Zuckerkandl and Pauling,1965),it is much more recently that this discipline has attained prominence.Early studies were carried out in bacterial,followed by mammalian,systems,but more recently,the approach has additionally been used in plant studies,particularly those focused on the evolution of metabolism(Scossa and Fernie,2021).

关键词： Pauling species. attain

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The Birth of Bio-data Science:Trends,Expectations,and Applications

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Genomics, Proteomics & Bioinformatics 2020年第1期18卷 5-15页

作者： Wilson Wen Bin Goh Limsoon Wong School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Department of Computer Science National University of SingaporeSingapore 117417Singapore

Components of bio-data science Biology is becoming increasingly digitized and has now taken on the sheen of a quantitative scientific discipline.A key driving factor is the increasing pervasiveness of high-throughput technological platforms in biological research,allowing millions of data points on genes,proteins,and other biological moieties across thousands of tissues and organisms to be compiled,cleaned,stored,and integrated for the purpose of systematic studies.In this data-rich landscape.

关键词： driving becoming landscape.

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Peptide asparaginyl ligases——renegade peptide bond makers

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Science China Chemistry 2020年第3期63卷 296-307页

作者： James P.Tam Ning-Yu Chan Heng Tai Liew Shaun J.Tan Yu Chen School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Synzymes and Natural Products Center Nanyang Technological UniversitySingapore 637551Singapore NTU Institute of Structural Biology Nanyang Technological UniversitySingapore 636921Singapore

Making peptide bonds is tightly controlled by genetic code and machinery which includes cofactors,ATP,and RNAs.In this regard,the stand-alone and genetic-code-independent peptide ligases constitute a new family of renegade peptide-bond makers.A prime example is butelase-1,an Asn/Asp(Asx)-specific ligase that structurally belongs to the asparaginyl endopeptidase family.Butelase-1 specifically recognizes a C-terminal Asx-containing tripeptide motif,Asn/Asp-Xaa-Yaa(Xaa and Yaa are any amino acids),to form a site-specific Asn-Xaa peptide bond either intramolecularly as cyclic proteins or intermolecularly as modified proteins.Our work in the past five years has validated that butelase-1 is a potent and versatile ligase.Here we review the advances in ligases,with a focus on butelase-1,and their applications in engineering bioactive peptides and precision protein modifications,antibody-drug conjugates,and live-cell labeling.

关键词： asparaginyl endopeptidase Asn-specific ligation bioorthogonal ligation butelase chemoenzymatic ligation live-cell labeling protein engineering protein modification site-specific labeling tandem ligation

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Discussion on Relevance and Studies of Prescription Compatibility in Chinese Medicine

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Chinese Journal of Integrative Medicine 2021年第10期27卷 788-793页

作者： Loh Cheng Toa Steven Goh Xin Yi NTU Chinese Medicine Clinic Nanyang Technological UniversitySingapore(637551)

With Chinese medicine(CM)gaining popularity in recent years,researchers and clinicians have put in much interest and effort into the makings and effects of it,especially after the recent announcement of World Health Orgnitation's incorporation of CM into mainstream medical compendium.Individual herb has complex properties,coming from its pharmacological properties and the Chinese medical principles of organ-directed,taste and dynamic orientational behaviours.The use of individual herb in CM is rare,where various herbs/ingredients are mostly found in a prescribed formula.To fully reveal the effects of CM is a great challenge.The complexity of various herbs in combined effect,the absorption and utility rate by the body,uniqueness of individual physique,sub-types of pathological behaviors and time-line progression of the healing process add on to the complication of understanding the full effect of CM.Various theories such as pathophysiology guidance,pharmacokinetic-pharmacodynamic compatibility method,and Global Systems Biology for Integrative Genomics,Proteomics and Metabolomics,which interactively provide a wider scope,more details,with the consideration of development time-line,may shed more light to revealing the full picture of the effects of compatibility prescription.

关键词： Chinese medicine integrative effects methodologies prescription compatibility

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The small GTPase RABA2a recruits SNARE proteins to regulate the secretory pathway in parallel with the exocyst complex in Arabidopsis

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Molecular Plant 2022年第3期15卷 398-418页

作者： Lei Pang Zhiming Ma Xi Zhang Yuanzhi Huang Ruili Li Yansong Miao Ruixi Li Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes Institute of Plant and Food ScienceSchool of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore College of Biological Sciences and Technology Beijing Forestry UniversityBeijing 100083China

Delivery of proteins to the plasma membrane occurs via secretion,which requires tethering,docking,priming,and fusion of vesicles.In yeast and mammalian cells,an evolutionarily conserved RAB GTPase activation cascade functions together with the exocyst and SNARE proteins to coordinate vesicle transport with fusion at the plasma membrane.However,it is unclear whether this is the case in plants.In this study,we show that the small GTPase RABA2a recruits and interacts with the VAMP721/722-SYP121-SNAP33 SNARE ternary complex for membrane fusion.Through immunoprecipitation coupled with mass spectrometry analysis followed by the validatation with a series of biochemical assays,we identified the SNARE proteins VAMP721 and SYP121 as the interactors and downstream effectors of RABA2a.Further expreiments showed that RABA2a interacts with all members of the SNARE complex in its GTP-bound form and modulates the assembly of the VAMP721/722-SYP121-SNAP33 SNARE ternary complex.Intriguingly,we did not observe the interaction of the exocyst subunits with either RABA2a or theSNARE proteins in several different experiments.Neither RABA2a inactivation affects the subcellular localization or assembly of the exocystnor the exocyst subunit mutant exo84b shows the disrupted RABA2a-SNARE association or SNARE assembly,suggesting that the RABA2a-SNARE-and exocyst-mediated secretory pathways are largely independent.Consistently,our live imaging experiments reveal that the two sets of proteins follow non-overlapping trafficking routes,and genetic and cell biologyanalyses indicate that the two pathways select different cargos.Finally,we demonstrate that the plant-specific RABA2a-SNARE pathway is essential for the maintenance of potassium homeostasis in Arabisopsis seedlings.Collectively,our findings imply that higher plants might have generated different endomembrane sorting pathways during evolution and may enable the highly conserved endomembrane proteins to participate in plant-specific trafficking mechanisms for adaptation to the changing

关键词： exocyst RABA2a secretory process SNARE complex

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Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting

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Journal of Molecular Cell Biology 2019年第4期11卷 306-316页

作者： Yaw Sing Tan Yasmina Mhoumadi Chandra S. Verma Bioinformatics Institute Agency for Science Technology and Research Singapore 138671 School of Biological Sciences Nanyang Technological University Singapore 637551 Department of Biological Sciences National University of Singapore Singapore 117543

The transcription factor p53 plays pivotal roles in numerous biological processes, including the suppression of tumours. The rich availability of biophysical data aimed at understanding its structure–function relationships since the 1990s has enabled the application of a variety of computational modelling techniques towards the establishment of mechanistic models. Together they have provided deep insights into the structure, mechanics, energetics, and dynamics of p53. In parallel, the observation that mutations in p53 or changes in its associated pathways characterize several human cancers has resulted in a race to develop therapeutic modulators of p53, some of which have entered clinical trials. This review describes how computational modelling has played key roles in understanding structural-dynamic aspects of p53, formulating hypotheses about domains that are beyond current experimental investigations, and the development of therapeutic molecules that target the p53 pathway.

关键词： p53 structure computational modelling therapeutic targeting

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