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Isolation and bioactivity screening of soy isoflavones from soybean glycolipids identifies daidzin as a promising anti-inflammatory agent

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Traditional Medicine Research 2024年第3期9卷 1-9页

作者： Xiao-Chuan Fang Xue-Mei He Yuan-Ru Zheng Wen Li Tang-Jia Yang Jing-Tao Yu Jun-Le Li Zi-Zhe Cai Yong Wang Lin-Zhong Yu Jun-Shan Liu Third Level Research Laboratory of State Administration of Traditional Chinese Medicine Guangdong Provincial Key Laboratory of Chinese Medicine PharmaceuticsSchool of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510515China guangdong Saskatchewan Oilseed Joint Laboratory Department of Food Science and EngineeringJinan UniversityGuangzhou 510632China Institute of Biomedical Engineering College of Life Science and TechnologyJinan UniversityGuangzhou 510632China Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou 510515China

Background:Soybean has long been utilized in the realm of traditional Chinese *** of its extracts,soybean glycolipids,serves as a vital by-product of soybean oil refining,but its chemical composition and pharmacological potential have yet to be fully ***:In this study,the chemical components were isolated,and the inhibitory effects of these isolates were explored in different zebrafish inflammatory models by survival rate,Histological examination assay and quantitative Real-time PCR *** cytotoxicity of daidzin in RAW264.7 cells was evaluated by cell viability assay,and the effect of daidzin on the release of inflammatory cytokines in RAW264.7 cells was detected by enzyme linked immunosorbent assay(ELISA).Western blotting,immunofluorescence assay and alpha7 nicotinic acetylcholine receptors siRNA transfection assay were used to further explore the anti-inflammatory mechanism of ***:Four compounds(verticilloside,soya-cerebroside I,soya-cerebroside II and daidzin)were firstly isolated from the soybean glycolipids,among which verticilloside and daidzin inhibited the lipopolysaccharide,CuSO4-and tail cut-stimulated zebrafish ***,daidzin exhibited anti-inflammatory activities by increasing the survival rate,alleviating the inflammatory cells infiltration,and down-regulating the expression of pro-inflammatory cytokines and nuclear factor kappa-B,NF-kappa-B inhibitor alpha,and signal transducer and activator of transcription3 in ***,daidzin decreased the secretion of IL-6 and TNF-α,inhibited the nuclear translocations of nuclear factor kappa-B p65 and p-signal transducer and activator of transcription3 as well as the NF-kappa-B inhibitor alpha phosphorylation at Ser32 in RAW 264.7 *** importantly,it elevated the expression level of alpha7 nicotinic acetylcholine receptors in both zebrafish and RAW 264.7 cells,and the inhibitory effect of daidzin was attenuated after the addition of alpha7 ni

关键词： soybean daidzin anti-inflammation zebrafish α7nAchR

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Effects of Buyang Huanwu decoction and Astragalus mongholicus on platelet activating factor receptor activity in rabbits in vitro

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Neural Regeneration Research 2006年第7期1卷 634-637页

作者： Hui Yao1, Jiping Zhang2, Zhixi Chen3, Yongjie Wu4, Zhiqiang Li3 1Department of Pharmacy, 2Department of Science Education, Foshan Second People’s Hospital, Foshan 528000, guangdong Province, China 3Laboratory of nuclear Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, guangdong Province, China 4Department of Pharmacology, College of Pharmaceutical Science, Lanzhou University, Lanzhou 730000, Gansu Province, China Department of Pharmacy Foshan Second People's Hospital Foshan 528000 Guangdong Province China Department of Science Education Foshan Second People's Hospital Foshan 528000 Guangdong Province China Labroatory of nuclear Medicine Guangzhou University of Traditional Chinese Medicien Guangzhou 510405 Guangdong Province China Department of Pharmacology College of Pharmaceutical Science Lanzhou University Lanzhou 730000 Gansu Province China

BACKGROUND: The pharmacological action of traditional Chinese medicine compound is the comprehensive effect of the various ingredients, and the interactions of various ingredients are closely correlated with the final effect. In order to reveal the compatibility mechanism of BHD's prescription in treating and preventing ischemic cerebrovascular disease, we needed explore the effect and relation of ingredients in the prescription. OBJECTIVE: To observe the effect of Buyang Huanwu decoction (BHD) and Astragalus mongholicus on the activity of platelet activating factor receptor (PAFR) in the platelet of rabbits in vitro, and investigate the mechanism of Astragalus mongholicus. DESIGN: A decomposed recipes study. SETTING: Guangzhou University of Traditional Chinese Medicine. MATERIALS: Five New Zealand rabbits, weighing 2-3 kg, both sexes, were used. BHD was composed of Sheng Huang Qi 120 g, Dang Gui Wei 6 g, Chi Shao 4.5 g, Chuan Xiong 3 g, Di Long 3 g, Tao Ren 3 g, Hong Hua 3 g. The prescription for activating blood circulation consisted of Dang Gui Wei 6 g, Chi Shao 4.5 g, Chuan Xiong 3 g, Di Long 3 g, Tao Ren 3 g and Hong Hua 3 g. The prescription for invigorating qi consisted of 120 g Sheng Huang Qi. The prepared herbal pieces were purchased from the traditional Chinese medicine Dispensary of Foshan Second People's Hospital, and appraised by Professor Xu from Science of Chinese Materia Medica College, Guangzhou University of Traditional Chinese Medicine. 3H-PAF was supplied by Amersham Co., Ltd. (specific activity: 6. 475 TBq/mmol; batch number: 200402); PAF standard by Biomol Co., Ltd. (batch number: P1318V). METHODS: The experiments were carried out in the Laboratory of nuclear Medicine, Guangzhou University of Traditional Chinese Medicine from September to December 2004. ① Injections of BHD, prescriptions for activating blood circulation and invigorating qi were prepared by the decoction and alcohol sedimentation technique. Rabbit common carotid artery blood (40

关键词： PAFR Effects of Buyang Huanwu decoction and Astragalus mongholicus on platelet activating factor receptor activity in rabbits in vitro

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Hemolysis of PM_(10) on RBCs in vitro:An indoor air study in a coal-burning lung cancer epidemic area

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Geoscience Frontiers 2022年第1期13卷 506-511页

作者： Mengyuan Zhang Longyi Shao Tim Jones Ying Hu Rachel Adams Kelly BéruBé State Key Laboratory of Coal Resources and Safe Mining and College of Geoscience and Surveying EngineeringChina University of Mining&TechnologyBeijing 100083China School of Earth and Environmental Sciences Cardiff UniversityMuseum AvenueCardiff CF103YEUK guangdong Province nuclear Industry Geological bureau Guangzhou 510800China School of Health Sciences Cardiff Metropolitan UniversityLlandaff CampusWestern AvenueCardiff CF52YBWalesUK School of Biosciences Cardiff UniversityMuseum AvenueCardiff CF103AXWalesUK

Epidemiological studies have suggested that inhalation exposure to indoor ambient air from coal-burning environments is causally associated with respiratory health *** order to explore the toxicological mechanisms behind the adverse health effects,the hemolytic activity of PM_(10)(particulate matter with an aerodynamic diameter of 10 um or less)samples collected from homes burning coal in the recognized China"cancer village"Xuanwei were evaluated and matched against their trace elemental *** results demonstrated that the hemolytic activity of indoor PM_(10) in coal-burning environments ranged from 4.28%to 5.24%,with a clear positive dose-response *** low dose samples exhibited a reduced hemolytic activity,PM_(10) could have a toxic effect upon people in a coal-burning indoor environment for extended time *** concentrations of analyzed trace elements in PM_(10) samples ranged from 6966 to 12,958 *** the analyzed elements,Zn,Ti,Ni,Cu,Pb,Ba,Mn,Cr and V were found at higher concentrations and accounted for over 95%of the total *** concentrations of total analyzed elements in the PM_(10) samples revealed a significant positive correlation with PM_(10) hemolytic *** the analyzed elements,Zn,Pb and Cs positively correlated with hemolysis,while Li,U and V negatively correlated with the hemolysis of human red blood cells(RBCs).Therefore,the heavy metal elements could be one of the main factors responsible for the hemolytic capacity of indoor PM_(10) in coal-burning environments.

关键词： Air pollution PM_(10) Coal Hemolysis Xuanwei County

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Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2124-2137页

作者： Duo Xu Fan Yang Jiayao Chen Tianxing Zhu Fen Wang Yitai Xiao Zibin Liang Lei Bi Guolong Huang Zebo Jiang Hong Shan Dan Li Center for Interventional Medicine the Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of nuclear Medicine the Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China guangdong Provincial Key Laboratory of Biomedical Imaging and guangdong Provincial Engineering Research Center of Molecular Imaging the Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China

Acute lung injury(ALI),as a common clinical emergency,is pulmonary edema and diffuse lung infiltration caused by *** lack of non-invasive alert strategy,resulting in failure to carry out preventive treatment,means high mortality and poor *** of interferon genes(STING)is a key molecular biomarker of innate immunity in response to inflammation,but there is still a lack of STING-targeted *** this study,a novel STING-targeted PET tracer,[~(18)F]FBTA,was labeled with high radiochemical yield(79.7±4.3%)and molar activity(32.5±2.9 GBq/μmol).We confirmed that[~(18)F]FBTA has a strong STING binding affinity(K_d=26.86±6.79 nmol/L)and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug *** STING-targeted strategy also reveals that[~(18)F]FBTA can trace ALI before reaching the computed tomography(CT)diagnostic criteria,and demonstrates its better specificity and distribution than[~(18)F]fluorodeoxyglucose([~(18)F]FDG).

关键词： Acute lung injury(ALI) Stimulator of interferon genes(STING) PET imaging [~(18)F]FBTA

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Effect of Marine Collagen Peptides on Markers of Metabolic nuclear Receptors in Type 2 Diabetic Patients with/without Hypertension

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Biomedical and Environmental Sciences 2010年第2期23卷 113-120页

作者： CuI-FENG ZHU GUAN-ZHI LI HONG-BIN PENG FAN ZHANG YUN CHEN YONG LI Department of Nutrition and Food Hygiene School of Public Health Peking University Beijing 10083 China Department of Nutrition Shenzhen Hospital of Peking University Shenzhen 518036 Guangdong China. Department of Endocrinology Shenzhen Hospital of Peking University Shenzhen 518036 Guangdong China. Department of Ultrasound Division Shenzhen Hospital of Peking University Shenzhen 518036 Guangdong China.

Objective To explore Effects of marine collagen peptides （MCPs） on markers of metablic nuclear receptors, i.e peroxisome proliferator-activated receptor （PPARs）, liver X receptor （LXRs） and farnesoid X receptor （FXRs） in type 2 diabetic patients with/without hypertension. Method Study population consisted of 200 type 2 diabetic patients with/without hypertension and 50 healthy subjects, all of whom were randomly assigned to MCPs-treated diabetics （n=50）, placebo-treated diabetics （n=50）, MCPs-treated diabetics with hypertension （n=50）, placebo-treated diabetics with hypertension （n=50）, and healthy controls （n=50）. MCPs or placebo （water-soluble starch） were given daily before breakfast and bedtime over three months. Levels of free fatty acid, cytochrome P450, leptin, resistin, adiponectin, bradykinin, NO, and Prostacyclin were determined before intervention, and 1.5 months, and 3 months after intervention. Hypoglycemia and the endpoint events during the study were recorded and compared among the study groups. Result At the end of the study period, MCPs-treated patients showed marked improvement compared with patients receiving placebo. The protection exerted by MCPs seemed more profound in diabetics than in diabetics with hypertension. In particular, after MCPs intervention, levels of free fatty acid, hs-CRP, resistin, Prostacyclin decreased significantly in diabetics and tended to decrease in diabetic and hypertensive patients whereas levels of cytochrome P450, leptin, NO tended to decrease in diabetics with/without hypertension. Meanwhile, levels of adiponectin and bradykinin rose markedly in diabetics following MCPs administration. Conclusion MCPs could offer protection against diabetes and hypertension by affecting levels of molecules involved in diabetic and hypertensive pathogenesis. Regulation on metabolic nuclear receptors by MCPs may be the possible underlying mechanism for its observed effects in the study. Further study into its action may shed light on

关键词： Marine collagen peptide Peroxisome proliferator-activated receptor (PPAR) Liver X receptor Famesoid X receptor Metabolic nuclear receptor

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Total polysaccharides of the Sijunzi decoction attenuate tumor necrosis factor-α-induced damage to the barrier function of a Caco-2 cell monolayer via the nuclear factor-κB-myosin light chain kinase-myosin light chain pathway

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World Journal of Gastroenterology 2018年第26期24卷 2867-2877页

作者： Yue Lu Leng Li Jin-wei Zhang Xiao-qin Zhong Jian-An wei Ling Han The Second Clinical College (guangdong Provincial Hospital of Chinese Medicine) Guangzhou University of Chinese Medicine

AIM To explore the protective effects and underlying mechanisms of total polysaccharides of the Sijunzi decoction(TPSJ) on the epithelial barriers in vitro. METHODS Caco-2 cell monolayers were treated with or without TPSJ in the presence or absence of TNF-α, and paracellular permeability and transepithelial electrical resistance(TEER) were measured to evaluate the epithelial barrier function. Immunofluorescence and western blotting were respecti-vely used to evaluate the distribution and expression of the tight junction proteins claudin 1, claudin 2, zo3, and occludin in Caco-2 cells. western blotting was also used to evaluate the cellular expression of myosin light chain(MLC), phosphorylated MLC(pM LC), MLC kinase(MLCK), and nuclear factor(NF)-κB p65. RESULTS TPSJ promoted the proliferation of Caco-2 cells and inhibited TNF-α-induced secretion of pro-inflammatory cyto-kines. Furthermore, TPSJ significantly ameliorated both the reduction of TEER and the increased paracellular permeability observed in tumor necrosis factor(TNF)-α-damaged Caco-2 monolayers. Furthermore, TPSJ remarkably attenuated TNF-α-induced morphological changes, downregulated the expression of claudin 1, claudin 2, zo3, and occludin, and markedly suppressed TNF-α-mediated upregulation of p-MLC and MLCK expression. Finally, TPSJ inhibited the activation and expression of NF-κB p65. CONCLUSION Our results demonstrate that TPSJ alleviates the TNF-α-induced impairment of the intestinal epithelial cell barrier function by suppressing NF-κB p65-mediated phosphorylation of MLCK and MLC.

关键词： Inflammatory bowel disease tight junction total polysaccharides of the Sijunzi decoction nuclear factor-κB pathway

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Zebrafish facilitates drug screening: potential of 3-deoxy-andrographoside from Chuanxinlian(Herba Andrographitis Paniculatae) as an anti-inflammatory agent

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Journal of Traditional Chinese Medicine 2022年第5期42卷 749-757页

作者： HE Xuemei XIAO Junjie FAN Chunlin LU Zibin CAO Huihui YU Linzhong ZHENG Yuanru LIU Junshan Third Level Research Laboratory of State Administration of Traditional Chinese Medicine School of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510515China guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics Guangzhou 510515China guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China School of Pharmacy Guangdong Pharmaceutical universityGuangzhou 510006China Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou 510515China

OBJECTIVE: To systematically evaluate the in vivo antiinflammatory potential of diterpene lactones from Chuanxinlian(Herba Andrographitis Paniculatae)(AP). METHODS: We firstly adopted zebrafish, a novel and ideal animal model for high-throughput drug screening, to investigate the in vivo anti-inflammatory activities of 17 diterpene lactones isolated from ***: The results showed that most of diterpene lactones displayed significant anti-inflammatory effects in lipopolysaccharide microinjection-, copper sulfate exposure-or tail transection-induced zebrafish inflammation models. Moreover, diterpene lactone 3-deoxy-andrographoside(AP-5) was firstly found to attenuate inflammatory responses, which was closely associated with the myeloid differentiation primary response 88/nuclear factor-kappa B and signal transducer and activator of transcription 3 pathways. CONCLUSION: Our research sheds light on the inestimable roles of zebrafish in high-throughput drug screening, elucidates the potent inhibitory effects of diterpene lactones against inflammation and indicates that AP-5 may serve as a potential alternative agent for the treatment of inflammatory diseases.

关键词： diterpenes lactones inflammation zebrafish myeloid differentiation factor 88 NF-kappa B STAT3 transcription factor

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Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway

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Chinese Journal of Natural Medicines 2023年第7期21卷 540-550页

作者： HUANG Yu YANG Hui YANG Biying ZHENG Yu H OU Xiaomei CHEN Guiling ZHANG Wenqi ZENG Xiang DU Baoxin Labortory of Stem Cell Clinical Reaearch The Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510006China Labortory of Stem Cell Biology and Chinese Medicine The Second Afiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510006China Labortory of Stem Cell Biology and Chinese Medicine Guangdong Provincial Academy of Chinese Medical SciencesGuangzhou 510006China Labortory of Stem Cell Clinical Research Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510006China Department of Neurology Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510006China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal *** important aspect of ALS pathogenesis is superoxide dismutase 1(SOD1)mutant-mediated mitochondrial toxicity,leading to apoptosis in *** study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1(G-Rg1)and conditioned medium(CM)on a mutational SOD1 cell model,and to explore the underlying *** found that the contents of nerve growth factor,glial cell line-derived neurotrophic factor,and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells(hUCMSCs)were exposed to neuron differentiation reagents for seven *** or G-Rg1 decreased the apoptotic rate of SOD1^(G93A)-NSC34 cell to a certain extent,but their combination brought about the least apoptosis,compared with CM or G-Rg1 *** research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment *** associated with mitochondrial apoptotic pathways,such as Bax,caspase 9(Cas-9),and cytochrome c(Cyt c),were ***,CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B(NF-κB)signaling pathway by reducing the phosphorylation of p65 and Iκ***/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid(BetA),an agonist of the NF-κB signaling *** summary,the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1^(G93A)-NSC34 cells through suppresing the NF-κB/Bcl-2 sgaling pathway(Fig.1 is a graphcal representation of the abstract).

关键词： Apoptosis Amyotrophic lateral sclerosis Conditioned medium Ginsenoside-Rg1 Umbilical cord mesenchymal stem cells

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Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway

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Chinese Journal of Natural Medicines 2023年第07期 540-550页

作者： HUANG Yu YANG Huili YANG Biying ZHENG Yu HOU Xiaomei CHEN Guiling ZHANG Wenqi ZENG Xiang DU Baoxin Labortory of Stem Cell Clinical Reaearch The Second Clinical College of Guangzhou University of Chinese Medicine Labortory of Stem Cell Biology and Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Labortory of Stem Cell Biology and Chinese Medicine Guangdong Provincial Academy of Chinese Medical Sciences Labortory of Stem Cell Clinical Research Guangdong Provincial Hospital of Chinese Medicine Department of Neurology Guangdong Provincial Hospital of Chinese Medicine

Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1(SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1(G-Rg1) and conditioned medium(CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells(hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9(Cas-9), and cytochrome c(Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B(NF-κB)signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid(BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway(Fig. 1 is a graphical representation of the abstract).

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Fargeted elimination of mutant mitochondria DNA in MELAS-iPSCs by mitoTALENs

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Protein & Cell 2018年第3期9卷 283-297页

作者： Yi Yang Han Wu Xiangjin Kang Yanhui Liang Ting Lan Tianjie Li Tao Tan Jiangyun Peng Quanjun Zhang Geng An Yali Liu Qian Yu Zhenglai Ma Ying Lian Boon Seng Soh Qingfeng Chen Ping Liu Yaoyong Chen Xiaofang Sun Rong Li Xiumei Zhen Yang Yu Xiaoping Li Yong Fan Key Laboratory for Major Obstetric Diseases of guangdong Province Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 China Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China Center of Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 China Yunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 China Disease Modeling and Therapeutics Laboratory A'STAR Institute of Molecular and Cell Biology 61 Biopolis Drive Proteos Singapore 138673 Singapore Department of Biological Sciences National University of Singapore Singapore 117543 Singapore

Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA （mtDNA） mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells （MiPSCs） that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes （MELAS）. We engineered mitochondrial-targeted transcription activator-like effector nucleases （mitoTALENs） and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.

关键词： mitochondria iPSCs TALEN MELAS

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