检索结果-南通市图书馆

HPDL deficiency causes a neuromuscular disease by impairing the mitochondrial respiration

Journal of Genetics and Genomics 2021年第8期48卷 727-736页

作者： Yu Sun Xiujuan Wei Fang Fang Yiping Shen Haiyan Wei Jiuwei Li Xianglai Ye Yongkun Zhan Xiantao Ye Xiaomin Liu Wei Yang Yuhua Li Xiangju Geng Xuelin Huang Yiyan Ruan Zailong Qin Shang Yi Jianxin Lyu Hezhi Fang Yongguo Yu Department of Pediatric Endocrinology and Genetics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai Institute for Pediatric ResearchShanghai 200092China Key Laboratory of Laboratory Medicine Ministry of EducationZhejiang Provincial Key Laboratory of Medical GeneticsSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou 325035China Department of Neurology Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region Guangxi Birth Defects Prevention and Control InstituteNanning 530000China Shanghai Children's Medical Center Shanghai Jiao Tong University School of MedicineShanghai 200127China Boston Children's Hospital Harvard Medical SchoolBostonMA 02115USA Department of Endocrinologic and Inherited Metabolic Henan Childen's HospitalZhengzhou Children's HospitalZhengzhou 450078China Department of Radiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Rehabilitation Henan Children's HospitalZhengzhou Children's HospitalZhengzhou 450018China Zhejiang Provincial People's Hospital Affiliated People's Hospital of Hangzhou Medical CollegeHangzhou 310014China Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition Shanghai 200092China

mitochondrial diseases are caused by variants in both mitochondrial and nuclear genomes.A nuclear gene HPDL(4-hydroxyphenylpyruvate dioxygenase-like),which encodes an intermembrane mitochondrial protein,has been recently implicated in causing a neurodegenerative disease characterized by pediatric-onset spastic movement phenotypes.Here,we report six Chinese patients with bi-allelic HPDL pathogenic variants from four unrelated families showing neuropathic symptoms of variable severity,including developmental delay/intellectual disability,spasm,and hypertonia.Seven different pathogenic variants are identified,of which five are novel.Both fibroblasts and immortalized lymphocytes derived from patients show impaired mitochondrial respiratory function,which is also observed in HPDL-knockdown(KD)He La cells.In these He La cells,overexpression of a wild-type HPDL gene can rescue the respiratory phenotype of oxygen consumption rate.In addition,a decreased activity of the oxidative phosphorylation(OXPHOS)complex II is observed in patient-derived lymphocytes and HPDL-KD He La cells,further supporting an essential role of HPDL in the mitochondrial respiratory chain.Collectively,our data expand the clinical and mutational spectra of this mitochondrial neuropathy and further delineate the possible disease mechanism involving the impairment of the OXPHOS complex II activity due to the bi-allelic inactivations of HPDL.

关键词： HPDL gene mitochondrial disease Respiration impairment OXPHOS Respiration chain complexⅡ

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Peroral endoscopic myotomy in a pregnant woman diagnosed with mitochondrial disease:A case report

引用

World Journal of Gastrointestinal Endoscopy 2021年第5期13卷 155-160页

作者： Alexander A Smirnov Maya M Kiriltseva Mariya E Lyubchenko Vladimir D Nazarov Anna V Botina Aleksandr N Burakov Sergey V Lapin Department of Endoscopy Pavlov First Saint Petersburg State Medical UniversitySaint Petersburg 197022Russia Center for Molecular Medicine Pavlov First Saint Petersburg State Medical UniversitySaint Petersburg 197022Russia Department of Pathology Pavlov First Saint Petersburg State Medical UniversitySaint Petersburg 197022Russia

BACKGROUND Achalasia is a primary esophageal motility disease characterized by impairment of normal esophageal peristalsis and absence of relaxation of the lower esophageal sphincter.Sometimes is can be a part of some genetic disorders.One of the causes of gastrointestinal motility disorders,including achalasia,is mitochondrial defects.CASE SUMMARY We report about a pregnant woman with a history of symptoms associated with inherited mitochondrial disease,which was confirmed by genetic tests,and who was treated via peroral endoscopic myotomy.CONCLUSION Peroral endoscopic myotomy is possible treatment option for a pregnant woman with achalasia caused by mitochondrial disease.

关键词： mitochondrial disease Pregnancy Esophagus Peroral endoscopic myotomy Achalasia Biopsy Case report

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

mitochondrial transplantation as a promising therapy for mitochondrial diseases

引用

Acta Pharmaceutica Sinica B 2023年第3期13卷 1028-1035页

作者： Tian-guang Zhang Chao-yu Miao Department of Pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China

mitochondrial diseases are a group of inherited or acquired metabolic disorders caused by mitochondrial dysfunction which may affect almost all the organs in the body and present at any age.However,no satisfactory therapeutic strategies have been available for mitochondrial diseases so far.mitochondrial transplantation is a burgeoning approach for treatment of mitochondrial diseases by recovery of dysfunctional mitochondria in defective cells using isolated functional mitochondria.Many models of mitochondrial transplantation in cells,animals,and patients have proved effective via various routes of mitochondrial delivery.This review presents different techniques used in mitochondrial isolation and delivery,mechanisms of mitochondrial internalization and consequences of mitochondrial transplantation,along with challenges for clinical application.Despite some unknowns and challenges,mitochondrial transplantation would provide an innovative approach for mitochondrial medicine.

关键词： Mitochondria mitochondrial transplantation mitochondrial disease mitochondrial isolation mitochondrial delivery mitochondrial storage mitochondrial transplantation rejection Ethical issue

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Clinical and Molecular Characteristics in 100 Chinese Pediatric Patients with m.3243A〉G Mutation in mitochondrial DNA

引用

Chinese Medical Journal 2016年第16期129卷 1945-1949页

作者： Chang-Yu Xia Yu Liu Hui Liu Yan-Chun Zhang Yi-Nan Ma Yu Qi Department of Central Laboratory Peking University First Hospital Beijing 100034 China

Background： mitochondrial diseases are a group of energy metabolic disorders with multisystem involvements. Variable clinical features present a major challenge in pediatric diagnoses. We summarized the clinical spectrum of m.3243A〉G mutation in Chinese pediatric patients, to define the common clinical manifestations and study the correlation between heteroplasmic degree of the mutation and clinical severity of the disease. Methods： Clinical data of one-hundred pediatric patients with symptomatic mitochondrial disease harboring m.3243A〉G mutation from 2007 to 2013 were retrospectively reviewed. Detection of m.3243A〉G mutation ratio was performed by polymerase chain reaction （PCR）-restriction fragment length polymorphism. Correlation between m.3243A〉G mutation ratio and age was evaluated. The differences in clinical symptom frequency of patients with low, middle, and high levels of mutation ratio were analyzed by Chi-square test. Results： Sixty-six patients （66%） had suffered a delayed diagnosis for an average of 2 years. The most frequent symptoms were seizures （76%）, short stature （73%）, elevated plasma lactate （70%）, abnormal magnetic resonance imaging/computed tomography （MRI/CT） changes （68%）, vomiting （55%）, decreased vision （52%）, headache （50%）, and muscle weakness （48%）. The mutation ratio was correlated negatively with onset age （r = -0.470, P 〈 0.001）. Myopathy was more frequent in patients with a high level of mutation ratio. However, patients with a low or middle level of m.3243A〉G mutation ratio were more likely to suffer hearing loss, decreased vision, and gastrointestinal disturbance than patients with a high level of mutation ratio. Conclusions： Our study showed that half of Chinese pediatric patients with m.3243A〉G mutation presented seizures, short stature, abnormal MRI/CT changes, elevated plasma lactate, vomiting, and headache. Pediatric patients with these recurrent symptoms should be considered for screening m.3243A〉G mutation. Clinical manifestations and laboratory abnormalities should be c

关键词： Clinical Symptom Heteroplasmy mitochondrial A3243G Mutation mitochondrial disease

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Human iPSCs derived astrocytes rescue rotenone-induced mitochondrial dysfunction and dopaminergic neurodegeneration in vitro by donating functional mitochondria

引用

Translational Neurodegeneration 2020年第2期9卷 154-167页

作者： Xiao-Yu Cheng Sangita Biswas Juan Li Cheng-Jie Mao Olga Chechneva Jing Chen Kai Li Jiao Li Jin-Ru Zhang Chun-Feng Liu Wen-Bin Deng Department of Neurology and Suzhou Clinical Research of Neurological diseases The Second Affiliated Hospital of Soochow UniversitySuzhou215004China Department of Biochemistry and Molecular Medicine University of California DavisSacramentoCA95817USA Shriners Hospital for Children of Northern California SacramentoCA95817USA School of Pharmacy Ningxia Medical UniversityYinchuan750004China Key Laboratory of Hui Medicine Modernization Ministry of EducationYinchuan750004China

Background Parkinson’s disease(PD)is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic(DA)neurons in the substantia nigra region of the brain.Substantial evidence indicates that at the cellular level mitochondrial dysfunction is a key factor leading to pathological features such as neuronal death and accumulation of misfoldedα-synuclein aggregations.Autologous transplantation of healthy purified mitochondria has shown to attenuate phenotypes in vitro and in vivo models of PD.However,there are significant technical difficulties in obtaining large amounts of purified mitochondria with normal function.In addition,the half-life of mitochondria varies between days to a few weeks.Thus,identifying a continuous source of healthy mitochondria via intercellular mitochondrial transfer is an attractive option for therapeutic purposes.In this study,we asked whether iPSCs derived astrocytes can serve as a donor to provide functional mitochondria and rescue injured DA neurons after rotenone exposure in an in vitro model of PD.Methods We generated DA neurons and astrocytes from human iPSCs and hESCs.We established an astroglial-neuronal co-culture system to investigate the intercellular mitochondrial transfer,as well as the neuroprotective effect of mitochondrial transfer.We employed immunocytochemistry and FACS analysis to track mitochondria.Results We showed evidence that iPSCs-derived astrocytes or astrocytic conditioned media(ACM)can rescue DA neurons degeneration via intercellular mitochondrial transfer in a rotenone induced in vitro PD model.Specifically,we showed that iPSCs-derived astrocytes from health spontaneously release functional mitochondria into the media.Mito-Tracker Green tagged astrocytic mitochondria were detected in the ACM and were shown to be internalized by the injured neurons via a phospho-p38 depended pathway.Transferred mitochondria were able to significantly reverse DA neurodegeneration and axonal pruning following exposure to rotenone.When rotenone injured neuron

关键词： Parkinson's disease iPSCs Dopaminergic neurons Rotenone Astrocytes mitochondrial transfer p38 Neuroprotection mitochondrial disease

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

The mitochondrial DNA Mutation at Position 11778 in Chinese Families with Leber's Hereditary Optic Neuropathy

引用

眼科学报 1994年第3期10卷 151-156页

作者： Lishan Zhang, Ying Huang, Fangyuan Li, ShijunWang, Bin Zhu Ziping Zhang, Yi Tong, Jinjuan GaoDepartment of Biology, Nanjing Railway Medical College Nanjing 210009, ChinaDepartment of Opthahalmology, Fujian Medical College Fuzhou 350005, China Department of Biology Nanjing Railway Medical College China.

We amplified the 340 bp of mitochondrial DMA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I . After amplification and digestion of SfaN I , two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I . We studied the mtDNAs of the patients with Leber's hereditary optic neur...

关键词： mitochondrial disease mitochondrial DNA Leber’s hereditary optic neuropathy (LHON) gene mutation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Stem Cell Ophthalmology Treatment Study (SCOTS)： bone marrow-derived stem cells in the treatment of Leber＇s hereditary optic neuropathy

引用

Neural Regeneration Research 2016年第10期11卷 1685-1694页

作者： Jeffrey N. Weiss Steven Levy Susan C. Benes Retina Associates of South Florida 5800 Colonial Drive Suite 300 Margate FL USA MD Stem Cells 3 Sylvan Road South Westport CT USA The Eye Center of Columbus The Ohio State University Columbus OH USA

The Stem Cell Ophthalmology Treatment Study （SCOTS） is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov （identifier： NCT01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber＇s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study （ETDRS） of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber＇s hereditary optic neuropathy may be a viable treatment option.

关键词： nerve regeneration Leber＇s hereditary optic neuropathy mitochondrial disease optic neuropathy bone marrow derived stem cells blindness visual loss neural regeneration

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

MELAS, MIDD and Beyond: m.3243A>G MT-TL1 Mutation in Adult Patients

引用

International Journal of Clinical Medicine 2016年第7期7卷 487-495页

作者： Bun Sheng Man Kei Fong Wing Kwan Ng Sammy Pak Lam Chen Chloe Miu Mak Department of Medicine & Geriatrics Princess Margaret Hospital Hong Kong China Department of Pathology Princess Margaret Hospital Hong Kong China

m.3243A>G MT-TL1 mutation is the most common mitochondrial DNA mutation that results in a wide spectrum of disorders in a maternally inherited pedigree. In adult patients, many present with symptoms and signs indistinguishable from acquired diseases and the correct diagnosis is often delayed after many years. Nevertheless, clues suggesting m.3243A>G usually exist early in the disease course but are only realized late. These hints, from the evolution of symptoms and signs, family background, investigation results, or a combination of these, enable the physician to make the correct diagnosis early, which is important for appropriate treatment and better patient care. As with other inheritable diseases, genetic counselling should be offered regarding the disease management, inheritance mode, recurrence risk, usefulness and limitations of genetic testing and reproductive options.

关键词： mitochondrial disease MELAS m.3243A>G

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

The antioxidant Trolox restores mitochondrial membrane potential and Ca2+-stimulated ATP production in human complex I deficiency

引用

世界最新医学信息文摘 2016年第11期 8-8页

作者： Felix Distelmaier Henk-Jan Visch Jan A.M.Smeitink Ertan Mayatepek Werner J.H.Koopman Peter H.G.M.Willems

Malfunction of mitochondrial complex I caused by nuclear gene mutations causes early-onset neurodegenerative diseases. Previous work using cultured fibroblasts of complex-I-deficient patients revealed elevated levels of reactive oxygen species（ros） and reductions in both total Ca2+content of the endoplasmic reticulum(ERCa) and bradykinin（Bk）-induced increases in cytosolic and mitochondrial free Ca2+([Ca2+]c; [Ca2+]M) and ATP（[ATP]C; [ATP]M） concentration. Here, we determined the mitochondrial membrane potential（Δψ） in patient skin fibroblasts and show significant correlations with cellular ros levels and ERCa, i.e., the less negative Δψ, the higher these levels and the lower ERCa. Treatment with 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid（Trolox） normalized Δψ and Bk-induced increases in [Ca2+]Mand [ATP]M. these effects were accompanied by an increase in ERCaand Bkinduced increase in [Ca2+]c. together, these results provide evidence for an integral role of increased ROS levels in complex I deficiency and point to the potential therapeutic value of antioxidant treatment.

关键词： Reactive oxygen species Oxidative stress mitochondrial membrane potential Endoplasmic reticulum Ca2+ content mitochondrial disease Antioxidant Human skin fibroblasts

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

The antioxidant Trolox restores mitochondrial membrane potential and Ca2+-stimulated ATP production in human complex Ⅰ deficiency

引用

世界最新医学信息文摘 2017年第30期 281-281页

作者： Felix Distelmaier Henk-Jan Visch Jan A.M.Smeitink Ertan Mayatepek Werner J.H.Koopman Peter H.G.M.Willems

Malfunction of mitochondrial complex I caused by nuclear gene mutations causes early-onset neurodegenerative diseases.Previous work using cultured fibroblasts of complex-I-deficient patients revealed elevated levels of reactive oxygen species(ROS) and reductions in both total Cacontent of the endoplasmic reticulum(ER) and bradykinin(Bk)-induced increases in cytosolic and mitochondrial free Ca([Ca];[Ca]) and ATP([ATP];[ATP]) concentration.Here,we determined the mitochondrial membrane potential(Aw) in patient skin fibroblasts and show significant correlations with cellular ROS levels and ER,i.e.,the less negative Aw,the higher these levels and the lower ER.Treatment with 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid(Trolox) normalized △Ψ and Bk-induced increases in[Ca]and[ATP].These effects were accompanied by an increase in ERand Bkinduced increase in[Ca].Together,these results provide evidence for an integral role of increased ROS levels in complex I deficiency and point to the potential therapeutic value of antioxidant treatment.

关键词： Reactive oxygen species Oxidative stress mitochondrial membrane potential Endoplasmic reticulum Ca2+ content mitochondrial disease Antioxidant Human skin fibroblasts

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：