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Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

Neural Regeneration research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen Department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province key laboratory of Inflammation and Molecular drug target NantongJiangsu ProvinceChina Department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

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Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu Zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina key laboratory of Advanced drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

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MELK is an oncogenic kinase essential for metastasis,mitotic progression,and programmed death in lung carcinoma

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Signal Transduction and targeted Therapy 2021年第1期6卷 83-94页

作者： Qin Tang Wan Li Xiangjin Zheng Liwen Ren Jinyi Liu Sha Li Jinhua Wang Guanhua Du The State key laboratory of Bioactive Substance and Function of Natural Medicines BeijingChina key laboratory of drug target research and drug screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical College100050 BeijingChina

Lung cancer is the fastest growth rate of morbidity and mortality in nearly a decade,and remains difficult to ***,the molecular mechanisms underlying its development are still *** this study,bioinformatics analysis showed that MELK was highly expressed in lung cancer and negatively correlated to the survival of lung adenocarcinoma(LUAD).Immunohistochemistry analysis of LUAD patient tissues revealed there were a high level of MELK expression in *** of MELK expression inhibits the migration and invasion of LUAD cells,which may be mediated by Twist1,Slug,MMP7,and *** of MELK promoted the growth of LUAD cells in medium,3D Matrigel,and nude *** of MELK by OTSSP167 arrested cycle of LUAD cells at G2/M phase via PLK1-CDC25C-CDK1 pathway,and triggered apoptosis-mediated ***,these data indicate that MELK is critical for metastasis,mitotic progression,and programmed death of LUAD and may be a promising therapeutic target for LUAD.

关键词： metastasis PLK1 lung

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Tumorigenic bacteria in colorectal cancer:mechanisms and treatments

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Cancer Biology & Medicine 2022年第2期19卷 147-162页

作者： Sha Li Jinyi Liu Xiangjin Zheng Liwen Ren Yihui Yang Wan Li Weiqi Fu Jinhua Wang Guanhua Du The State key laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China key laboratory of drug target research and drug screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China

Colorectal cancer(CRC)is the third most common and the second most fatal *** recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of *** bacterial species,such as Fusobacterium nucleatum,Escherichia coli,Bacteroides fragilis,Enterococcus faecalis,and Salmonella *** been associated with CRC,based upon sequencing studies in CRC patients and functional studies in cell culture and animal *** bacteria can cause host DNA damage by genotoxic substances,including colibactin secreted by pks+Escherichia coli,*** toxin(BFT)produced by Bacteroides fragilis,and typhoid toxin(TT)from *** bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin,TLR4/MYD88/NF-κB,and SMO/RAS/p38 ***,some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function,creating a proinflammatory environment,or influencing the autophagy *** with the classical antibacterial drugs,metronidazole or erythromycin,the antibacterial active ingredients,M13@Ag(electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13),berberine,and zerumbone,were found to inhibit tumorigenic bacteria to different *** this review,we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria,as well as progress in developing effective antibacterial *** bacteria have been shown to be active in the oncogenesis and progression of CRC,and some antibacterial compounds have shown therapeutic potential in bacteria-induced *** bacteria may be useful as biomarkers or therapeutic targets for CRC.

关键词： Colorectal cancer microbiota tumorigenic mechanism genotoxicity cancer pathways tumor immunity

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Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses

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Traditional Medicine research 2025年第2期10卷 55-64页

作者： Jin-Fang Wu Yi-Sheng Chen Yu-Chun Xie Department of Rehabilitation Medicine Jiangsu Province Geriatric HospitalNanjing 210024China Fujian key laboratory of Toxicant and drug Toxicology Medical CollegeNingde Normal UniversityNingde 352100China Central laboratory Jiangsu Province Geriatric HospitalNanjing 210024China

Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise ***:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker *** visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and ***,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular ***:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius *** showed a significant presence of Olfm3+ganglion ***1 gene knockout revealed changes in SMAD family gene expression,which regulate *** stress levels were also ***:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological *** may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.

关键词： single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity

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Triterpenoid Constituents of Huperzia miyoshiana

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Chinese Journal of Chemistry 2003年第10期21卷 1364-1368页

作者：童孝田谭昌恒周慧蒋山好马晓强朱大元 State key laboratory of drug research

Thirteen triterpenoids, including three new ones, miyoshianols A (1), B (2) and C (3), were isolated from Huperzia miyoshiana . The structures of these new compounds were established as 3 O dihydroferuloyltohogenol (1) , 16 oxo 3 β ,21 β dihydroxy serrat 14 en 24 ferulate (2) and 16 oxo 3 α ,21 β dihydroxy serrat 14 en 24 ferulate (3), respectively, on the basis of their spectroscopic analysis.

关键词： Huperzia miyoshiana triterpenoids miyoshianols A B and C

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Secondary metabolites of petri-dish cultured Antrodia camphorata and their hepatoprotective activities against alcohol-induced liver injury in mice

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Chinese Journal of Natural Medicines 2019年第1期17卷 33-42页

作者： WU Yu TIAN Wen-Jing GAO Shuo LIAO Zu-Jian WANG Guang-Hui LO Jir-Mehng LIN Pei-Hsin ZENG De-Quan QIU Da-Ren LIU Xiang-Zhong ZHOU Mi LIN Ting CHEN Hai-Feng Fujian Provincial key laboratory of Innovative drug target School of Pharmaceutical SciencesXiamen University Industrial Technology research Institute

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata(PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride(TG), aspartate aminotransferase(AST), alanine aminotransferase(ALT), and malondialdehyde(MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.

关键词： Petri-dish Antrodia camphorata Hepatoprotective

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Nanoparticles targeting tumor-associated macrophages:A novel anti-tumor therapy

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Nano research 2022年第3期15卷 2177-2195页

作者： Siyuan Chen Furong Qin Manni Wang Yuquan Wei Zhiyong Qian Xiawei Wei laboratory of Aging research and Cancer drug target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

The immunosuppressive tumor microenvironment(TME)is crucial in the occurrence of tumorigenesis,metastasis,and drug *** all stromal cells,tumor-associated macrophages(TAMs)are recognized as vital components causing the TME to be favorable for cancer cells and are also main targets in cancer *** date,nanoparticle(NP)-based drug delivery systems,as new technology platforms,have exhibited considerable advantages,such as targeted drug delivery at tumor sites,enhanced drug transport efficiency,and controllable drug release profiles,which provide new approaches for cancer *** TAM-targeting nanoparticles,various therapeutic strategies have been developed by varying their design,namely,by blocking TAM recruitment,promoting TAM transformation,and directly diminishing existing *** the current review,we provide a brief overview of the role of TAMs in the tumor microenvironment and their functions and highlight strategies for TAM ***,the applications of nanoparticles in targeting TAMs to improve cancer therapeutic efficiency are summarized.

关键词： tumors immunotherapy tumor-associated macrophages nanoparticles

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The biology,function,and applications of exosomes in cancer

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2783-2797页

作者： Jinyi Liu Liwen Ren Sha Li Wan Li Xiangjin Zheng Yihui Yang Weiqi Fu Jie Yi Jinhua Wang Guanhua Du The State key laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China key laboratory of drug target research and drug screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Department of Clinical laboratory Peking Union Medical College HospitalBeijing 100730China

Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell *** can transport nucleic acids,proteins,and lipids for intercellular communication and activate signaling pathways in target *** cancers,exosomes may participate in growth and metastasis of tumors by regulating the immune response,blocking the epithelial-mesenchymal transition,and promoting *** are also involved in the development of resistance to chemotherapeutic *** in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of *** of their amphipathic structure,exosomes are natural drug delivery vehicles for cancer therapy.

关键词： Exosomes Tumor immunity Tumor metastasis drug resistance Biomarkers drug delivery

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A new and promising application of gene editing: CRISPR-controlled smart materials for tissue engineering,bioelectronics, and diagnostics

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Science China(Life Sciences) 2019年第11期62卷 1547-1549页

作者： Weiqi Hong Mengyuan Huang Yuquan Wei Xiawei Wei laboratory of Aging research and Cancer drug target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan University

A recent study published in the journal Science by Collins et *** a programmable clustered regularly interspaced short palindromic repeats(CRISPR)-responsive smart material containing the CRISPR-associated nuclease,Casl2a,and hydrogels containing DNA to deliver biological information via changes in material properties(English et al.,2019).

关键词： CRISPR smart journal

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