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Exogeneous metal ions as therapeutic agents in cardiovascular disease and their delivery strategies

Regenerative Biomaterials 2024年第2期3卷 1-16页

作者： Xiaoqian Hong Geer Tian Yang Zhu Tanchen Ren Department of Cardiology of the Second Affliated Hospital and State Key Laboratory of Transvascular Implantation Devices Cardiovascular Key Laboratory of Zhejiang ProvinceZhejiang University School of MedicineHangzhou 310o09China Binjiang Institute of Zhejiang University Hangzhou 310053China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Metal ions participate in many metabolic processes in the human body,and their homeostasis is crucial for life.In cardiovascular diseases(CVDs),the equilibriums of metal ions are frequently interrupted,which are related to a variety of disturbances of physiological processes leading to abnormal cardiac functions.Exogenous supplement of metal ions has the potential to work as therapeutic strategies for the treatment of CVDs.Compared with other therapeutic drugs,metal ions possess broad availability,good stability and safety and diverse drug delivery strategies.The delivery strategies of metal ions are important to exert their ther-apeutic effects and reduce the potential toxic side effects for cardiovascular applications,which are also receiving increasing attention.Controllable local delivery strategies for metal ions based on various biomaterials are constantly being designed.In this review,we comprehensively summarized the positive roles of metal ions in the treatment of cVDs from three aspects:protecting cells from oxidative stress,inducing angiogenesis,and adjusting the functions of ion channels.In addition,we introduced the transferability of metal ions in vascular reconstruction and cardiac tissue repair,as well as the currently available engineered strategies for the precise delivery of metal ions,such as integrated with nanoparticles,hydrogels and scaffolds.

关键词： metal ions cardiovascular disease tissue engineering oxidative stress angiogenesis ion channel

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Emerging approaches to probing ion channel structure and function

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Neuroscience Bulletin 2012年第4期28卷 351-374页

作者： Wei-Guang Li Tian-Le Xu Neuroscience Division Department of Biochemistry and Molecular Cell BiologyInstitute of Medical SciencesShanghaiJiao Tong University School of MedicineShanghai 200025China

ion channels,as membrane proteins,are the sensors of the cell.They act as the first line of communication with the world beyond the plasma membrane and transduce changes in the external and internal environments into unique electrical signals to shape the responses of excitable cells.Because of their importance in cellular communication,ion channels have been intensively studied at the structural and functional levels.Here,we summarize the diverse approaches,including molecular and cellular,chemical,optical,biophysical,and computational,used to probe the structural and functional rearrangements that occur during channel activation（or sensitization）,inactivation（or desensitization）,and various forms of modulation.The emerging insights into the structure and function of ion channels by multidisciplinary approaches allow the development of new pharmacotherapies as well as new tools useful in controlling cellular activity.

关键词： ion channel structure and function mutagenesis covalent modification voltage-clamp fluorometry computational chemistry

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ion channel mechanism of gastrointestinal motility and gastric hypersensitivity in functional dyspepsia:a review

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Gastroenterology & Hepatology Research 2022年第3期4卷 23-29页

作者： Terigele Bao Feng Lan Guorui Li Xiyele Mu Ta Na Minghai Fu Yongsheng Chen School of Mongolian Medicine Inner Mongolia University for NationalitiesTongliao 028000Inner Mongolia Autonomous RegionChina School of Life Sciences Inner Mongolia University for NationalitiesTongliao 028000Inner Mongolia Autonomous RegionChina

Functional dyspepsia(FD)is a regularly diagnosed clinical gastrointestinal ailment with a high incidence rate that can considerably impact patients’health and quality of life and impose a substantial financial burden.Modern research on the pathophysiology of functional dyspepsia has not thoroughly explained the underlying reasons.The condition does not manifest any significant organ abnormalities,which raises the disease’s difficulty coefficient.Major pathogenic exceptions in FD include gastrointestinal motor dysfunction,gastrointestinal hormone secretion problem,visceral hypersensitivity,and brain-gut axis.Several ion channels have reportedly been implicated in the pathophysiological process of FD.Therefore,it is crucial to comprehend the probable activities of various ion channels in FD.This study focuses on the current state of research on the possible role of several ion channels in the pathogenesis of FD.

关键词： functional dyspepsia ion channel gastrointestinal motility gastric hypersensitivity smooth muscle

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Wave growth rate in a cylindrical metal waveguide with ion-channel guiding of a relativistic electron beam

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Chinese Physics B 2010年第12期19卷 234-241页

作者：李海容唐昌建王顺金 School of Physics Science and Technology Sichuan University College of Science University of Science and Technology Liaoning

This paper addresses the formulae and numerical issues related to the possibility that fast wave may be grown when a relativistic electron beam through an ion channel in a cylindrical metal waveguide. To derive the dispersion equations of the beam-wave interaction, it solves relativistic Lorentz equation and Maxwell＇s equations for appropriate boundary conditions. It has been found in this waveguide structure that the TM0m modes are the rational operating modes of coupling between the electromagnetic modes and the betatron modes. The interaction of the dispersion curves of the electromagnetic TM0m modes and the upper betatron modes is studied. The growth rates of the wave are obtained, and the effects of the beam radius, the beam energy, the plasma frequency, and the beam plasma frequency on the wave growth rate are numerically calculated and discussed.

关键词： relativistic electron beam plasma ion channel dispersion relations wave growth rate

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Electromagnetic dispersion characteristics of a high energy electron beam guided with an ion channel

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Plasma Science and Technology 2017年第2期19卷 20-27页

作者：肖集雄曾中王之江夏冬辉刘昌海 Institute of fusion and plasma research Huazhong University of Science and TechnologyWuhan 430074People's Republic of China

Taking self-fields into consideration, dispersion properties of two types of electromagnetic modes for a high energy electron beam guided with an ion channel are investigated by using the linear perturbation theory. The dependences of the dispersion frequencies of electromagnetic waves on the electron beam radius, betatron frequency and boundary current are revealed. It is found that the electron beam radius and betatron frequency have different influences on the electromagnetic waves dispersion behavior by compared with the previous works. As the boundary current is taken into account, the TM modes will have two branches and a lowfrequency branch emerged as the new branch in strong ion channel case. This new branch has similar dispersion behavior to the betatron modes. For TE modes, there are two branches and they have different dispersion behaviors in strong ion channel case. However, in weak ion channel case, the dispersion behaviors for both of the low frequency and high frequency branches are similar.

关键词： dispersion behavior electromagnetic eigenmodes betatron oscillation ion channel

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Highlights for the 6th International ion channel Conference:ion channel structure,function,disease and therapeutics

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Acta Pharmaceutica Sinica B 2017年第6期7卷 665-669页

作者： Limei Wang Kewei Wang Department of Pharmacology Qingdao University School of PharmacyQingdao 266021China

To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6 th International ion channel Conference(IICC-2017) was held between June 23–27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on(1) ion channel structure and function;(2) ion channel physiology and human diseases;(3) ion channels as targets for drug discovery;(4) Technological advances in ion channel research. An insightful overview was presented on the structure and function of the mechanotransduction channel Drosophila NOMPC(No mechanoreceptor potential C), a member of the transient receptor potential(TRP) channel family. Recent studies on Transmembrane protein 16 or Anoctamin-1(TMEM16A, a member of the calcium-activated chloride channel [CaCC] family) were summarized as well. In addition, topics for ion channel regulation, homeostatic feedback and brain disorders were thoroughly discussed. The presentations at the IICC-2017 offer new insights into our understanding of ion channel structures and functions, and ion channels as targets for drug discovery.

关键词： ion channel Structure Function channelopathy Drug target Mechanotransduction Voltage-gated Ca2+ channel Anoctamin-1 Calcium activated chloride channel M-type potassium channel GIRK channel Voltage-gated sodium channel

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Journal of Bio-X Research 2021年第4期4卷 145-150页

作者： Honglan Zheng Wanning Cui Zhiqiang Yan Institute of Molecular Physiology Shenzhen Bay LaboratoryShenzhenGuangdong Province State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceSchool of Life SciencesFudan UniversityShanghaiChina

Sensorineural hearing loss is the most common sensory deficit in humans,with an estimated prevalence of 1 in 500 newborns.Approximately half of childhood hearing loss is attributed to genetic factors and can be classified as syndromic or non-syndromic based on the inheritance pattern.The ion channel genesKCNQ1,KCNE1,KCNQ4,P2RX2,TMC1,KCNJ10,andCACNA1D have frequently been associated with genetic hearing loss.Because of the important roles these genes play in cochlear hair cell function and the auditory pathways,mutations in these genes that result in impaired ion channel function can lead to hereditary hearing loss.The main purpose of this review was to examine the latest research progress on the functional roles,inheritance pattern,gene expression,protein structure,clinical phenotypes,mouse models,and possible treatments of the most commonly studied ion channels associated with inherited deafness.A comprehensive summary could help highlight ion channels that should be investigated as potential drug targets for the treatment of inherited deafness.

关键词： channelopathies gene mutation genetic hearing loss ion channel therapy

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Study of the ion channel Behavior of Didodecyldimethylammonium Bromide Formed Bilayer Lipid Membrane Stimulated by PF_6^-

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Chinese Journal of Chemistry 2003年第1期21卷 62-65页

作者：佟月红韩晓军汪尔康 State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences

Bilayer lipid membranes (BLM) formed from didodecyldimethylammonium bromide were made on the freshly exposed surface of a glassy carbon (GC) and were demonstrated by the ac impedance spectroscopy. The ion channels of membrane properties induced by PF -_6 were studied by the cyclic voltammetric methods. Experimental results indicated that the ion channel of BLM was open in the presence of the PF -_6 due to the interaction of PF -_6 with the BLM, while it was switched off in the absence of PF -_6. Because the ion channel behavior was affected by the concentration of PF -_6, a sensor for PF -_6 can be developed.

关键词： ion channel bilayer lipid membrane hexafluorophos-phate anions (PF -_6) tris(2,2′-bipyridine)ruthenium(II) chloride

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The allosteric gating mechanism of the MthK channel

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National Science Review 2022年第8期9卷 35-46页

作者： Fenghui Guan Tianyu Li Wei Dong Rui Guo Hao Chai Zhiqiu Chen Zhong Ren Yang Li Sheng Ye Frontiers Science Center for Synthetic Biology (Ministry of Education) Tianjin Key Laboratory of Function and Application of Biological Macromolecular StructuresSchool of Life SciencesTianjin University National Clinical Research Center for Aging and Medicine Huashan HospitalFudan University Department of Logistics Tianjin University Department of Chemistry University of Illinois at Chicago State Key Laboratory of Drug Research and Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences The Cancer Hospital of the University of Chinese Academy of Sciences Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of Sciences Life Sciences Institute Zhejiang University University of Chinese Academy of Sciences Renz Research Inc.

Allostery is a fundamental element during channel gating in response to an appropriate stimulus by which events occurring at one site are transmitted to distal sites to regulate activity. To address how binding of the first Caion at one of the eight chemically identical subunits facilitates the other Ca-binding events in Mth K, a Ca-gated K+channel containing a conserved ligand-binding RCK domain, we analysed a large collection of Mth K structures and performed the corresponding thermodynamic and electrophysiological measurements. These structural and functional studies led us to conclude that the conformations of the Ca-binding sites alternate between two quaternary states and exhibit significant differences in Caaffinity. We further propose an allosteric model of the Mth K-gating mechanism by which a cascade of structural events connect the initial Ca-binding to the final changes of the ring structure that open the ion-conduction pore. This mechanical model reveals the exquisite design that achieves the allosteric gating and could be of general relevance for the action of other ligand-gated ion channels containing the RCK domain.

关键词： ion channel allosteric gating mechanism protein structural data analysis

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Can glial cells save neurons in epilepsy?

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Neural Regeneration Research 2023年第7期18卷 1417-1422页

作者： Weida Shen Jelena BogdanovićPristov Paola Nobili Ljiljana Nikolić Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineZhejiang University City CollegeHangzhouZhejiang ProvinceChina Department of Life Sciences University of BelgradeInstitute for Multidisciplinary ResearchBelgradeSerbia Institute of Functional Genomics(IGF) University of MontpellierCNRSINSERMMontpellierFrance Department of Neurophysiology Institute for Biological Research Siniša StankovićNational Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia

Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons.However,approximately 30%of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70%of patients can be alleviated but not completely removed by the current medications.Thus,new strategies for the treatment of epilepsy are in urgent demand.Over the past decades,with the increase in knowledge on the role of glia in the genesis and development of epilepsy,glial cells are receiving renewed attention.In a normal brain,glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function.In epilepsy,however,the supportive roles of glial cells are compromised,and their interaction with neurons is altered,which disrupts brain function.In this review,we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity,with the major focus on the dysfunction of astroglial potassium channels,water channels,gap junctions,glutamate transporters,purinergic signaling,synaptogenesis,on the roles of microglial inflammatory cytokines,microglia-astrocyte interactions in epilepsy,and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain.These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.

关键词： astrocyte cytokines glutamate ion channel microglia myelin neuron oligodendrocyte purinergic signaling seizures

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