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Autophagy and beyond:Unraveling the complexity of UNC-51-like kinase 1(ULK1)from biological functions to therapeutic implications

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3743-3782页

作者： Ling Zou Minru Liao Yongqi Zhen Shiou Zhu Xiya Chen Jin Zhang Yue Hao Bo Liu School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China

UNC-51-like kinase 1(ULK1),as a serine/threonine kinase,is an autophagic initiator in mammals and a homologous protein of autophagy related protein(Atg)1 in yeast and of UNC-51 in Caenorhabditis ***1 is well-known for autophagy activation,which is evolutionarily conserved in protein transport and indispensable to maintain cell *** the direct target of energy and nutrition-sensing kinase,ULK1 may contribute to the distribution and utilization of cellular resources in response to metabolism and is closely associated with multiple pathophysiological ***,ULK1 has been widely reported to play a crucial role in human diseases,including cancer,neurodegenerative diseases,cardiovascular disease,and infections,and subsequently targeted small-molecule inhibitors or activators are also ***,the non-autophagy function of ULK1 has been emerging,indicating that non-autophagy-relevant ULK1 signaling network is also linked with diseases under some specific ***,in this review,we summarized the structure and functions of ULK1 as an autophagic initiator,with a focus on some new approaches,and further elucidated the key roles of ULK1 in autophagy and ***,we also discussed the relationships between ULK1 and human diseases,as well as illustrated a rapid progress for better understanding of the discovery of more candidate small-molecule drugs targeting ULK1,which will provide a clue on novel ULK1-targeted therapeutics in the future.

关键词： UNC-51-like kinase 1(ULK1) Autophagy Non-autophagy Biological function Small-molecule drug ULK1-targeted therapy human diseases

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Biomechanical control of lymphatic vessel physiology and functions

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Cellular & Molecular Immunology 2023年第9期20卷 1051-1062页

作者： Veronique Angeli Hwee Ying Lim Immunology Translational Research Programme Yong Loo Lin School of MedicineDepartment of Microbiology and ImmunologyNational University of SingaporeSingaporeSingapore Immunology Programme Life Sciences InstituteNational University of SingaporeSingaporeSingapore

The ever-growing research on lymphatic biology has clearly identified lymphatic vessels as key players that maintain human health through their functional roles in tissue fluid homeostasis,immunosurveillance,lipid metabolism and *** is therefore not surprising that the list of human diseases associated with lymphatic malfunctions has grown larger,including issues beyond lymphedema,a pathology traditionally associated with lymphatic drainage ***,the discovery of factors and pathways that can promote optimal lymphatic functions may offer new therapeutic *** evidence indicates that aside from biochemical factors,biomechanical signals also regulate lymphatic vessel expansion and functions ***,we review how mechanical forces induced by fluid shear stress affect the behavior and functions of lymphatic vessels and the mechanisms lymphatic vessels employ to sense and transduce these mechanical cues into biological signals.

关键词： lymphatic vessel biomechanical force mechanosensing mechanotransduction human diseases

human skin bacterial microbiota homeostasis:A delicate balance between health and disease

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微生物(英文) 2023年第2期2卷 107-120页

作者： Yibin Zhu Xi Yu Gong Cheng Tsinghua University‐Peking University Joint Center for Life Sciences School of MedicineTsinghua UniversityBeijingChina Shenzhen Bay Laboratory Institute of Infectious DiseasesShenzhenChina

As the largest organ of the body,the skin acts as a barrier to prevent diseases and harbors a variety of beneficial ***,the skin bacterial microbiota plays a vital role in health and *** of the barrier or an imbalance between symbionts and pathogens can lead to skin disorders or even systemic *** this review,we first provide an overview of research on skin bacterial microbiota and human health,including the composition of skin bacteria in a healthy state,as well as skin bacterial microbiota educating the immune system and preventing the invasion of *** then discuss the diseases that result from skin microbial dysbiosis,including atopic dermatitis,common acne,chronic wounds,psoriasis,viral transmission,cutaneous lupus,cutaneous lymphoma,and hidradenitis ***,we highlight the progress that utilizes skin microorganisms for disease therapeutics,such as bacteriotherapy and skin microbiome transplantation.A deeper knowledge of the interaction between human health and disease and the homeostasis of the skin bacterial microbiota will lead to new insights and strategies for exploiting skin bacteria as a novel therapeutic target.

关键词： homeostasis human diseases skin bacterial microbiota therapeutics

Small RNAs:An expanding world with therapeutic promises

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Fundamental Research 2023年第5期3卷 676-682页

作者： Lan-Tao Gou Qifan Zhu Mo-Fang Liu State Key Laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China

Small non-coding RNAs(sncRNAs),such as microRNAs(miRNAs),small interfering RNAs(siRNAs),PIWIinteracting RNAs(piRNAs),and transfer RNA(tRNA)-derived small RNAs(tsRNAs),play essential roles in regulating various cellular and developmental *** the past three decades,researchers have identified novel sncRNA species from various *** molecules demonstrate dynamic expression and diverse functions,and they are subject to intricate regulation through RNA modifications in both healthy and diseased ***,certain sncRNAs in gametes,particularly sperm,respond to environmental stimuli and facilitate epigenetic ***,the in-depth understanding of sncRNA functions and mechanisms has accelerated the development of small RNA-based *** this review,we present the recent advances in the field,including new sncRNA species and the regulatory influences of RNA *** also discuss the current limitations and challenges associated with using small RNAs as either biomarkers or therapeutic drugs.

关键词： Small non-coding RNAs RNA modifications human diseases RNA therapeutics Biomarkers

Era of the 4D animal model

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Animal Models and Experimental Medicine 2023年第2期6卷 178-182页

作者： Lihong Zhang Jindan Guo Jiangning Liu NHC Key Laboratory of human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical *** drawback can be overcome with animal model *** advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and *** this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D animal models over clinical studies and traditional animal models,as well as their limitations,are presented.

关键词： animal model database digitally display human diseases spatiotemporal landscapes

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Mechanopathology of red blood cell diseases—Why mechanics matters

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Theoretical & Applied Mechanics Letters 2011年第1期1卷 1-6页

作者： Chwee Teck Lim Mechanobiology Institute National University of Singapore Division of Bioengineering and Department of Mechanical Engineering National University of Singapore Singapore-MIT Alliance for Research & Technology(SMART)

During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular *** alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape,deformability and *** such,knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ***,we will present biomechanistic insights into red blood cell related diseases that manifest mechanical property changes and how they directly contribute to the pathophysiology of *** conducting cell and molecular mechanics studies,not only can we elucidate changes in the structure-property-function relationship of diseased cells,we can also exploit the new knowledge gained to develop biomechanics based devices that may better detect and diagnose these diseases as well as help identify important biomechanical targets for possible therapeutic interventions.

关键词： human diseases pathophysiology cell mechanics single molecule biomechanics

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Animal protein toxins: origins and therapeutic applications

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Biophysics Reports 2018年第5期4卷 233-242页

作者： Na Chen Siqi Xu Yuhan Zhang Feng Wang Laboratory of Protein and Peptide Drugs Institute of Biophysics Chinese Academy of Sciences

Venomous animals on the earth have been found to be valuable resources for the development of therapeutics. Enzymatic and non-enzymatic proteins and peptides are the major components of animal venoms, many of which can target various ion channels, receptors, and membrane *** to traditional small molecule drugs, natural proteins and peptides exhibit higher specificity and potency to their targets. In this review, we summarize the varieties and characteristics of toxins from a few representative venomous animals, and describe the components and applications of animal toxins as potential drug candidates in the treatment of human diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, neuropathic pain, as well as autoimmune diseases. In the meantime, there are many obstacles to translate new toxin discovery to their clinical applications. The challenges, strategies, and perspectives in the development of the protein toxin-based drugs are discussed as well.

关键词： Animal venoms Clinical applications human diseases Protein and peptides Targets

Lnc-ing RNA Processing and Function

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Lnc-ing RNA Processing and Function