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Optical redox imaging of ANT1-de-cient muscles

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing Zhao Douglas Wallace Lin Z.Li Britton Chance Laboratory of Redox Imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA center for mitochondrial and epigenomic medicine Children's Hospital of Philadelphia Research Institute Philadelphia PA 19104USA center for Biostatistics and Epidemiology Lewis Katz School of medicine at Temple University Philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** Chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu center for Reproductive medicine Shandong University CAS Key Laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint Laboratory on Reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong Key Laboratory of Reproductive Endocrinology of the Ministry of Education Shandong University center for Reproductive medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse *** allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early ***, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-mitochondrial Pathway

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Chinese Journal of Integrative medicine 2024年第1期30卷 34-41页

作者： QI Zhi-min WANG Xia LIU Xia ZHAO Juan Medical Examination center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Experimental center for Teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(Pmitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(Pmitochondrial pathway.

关键词： asperuloside Chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis

Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie Lian Wenwu Liu Qin Hu Xiaohua Zhang Department of Neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine Department of Diving and Hyperbaric medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability *** cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain *** mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of ***,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ***,the role of succinylation modification in cell metabolism after stroke and its regulation are not well *** aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after *** also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of *** succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by *** evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic ***,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic *** between succinylation and desuccinylation has been implicated in the pathophysiology of *** agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke ***,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation

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Journal of Pharmaceutical Analysis 2024年第5期14卷 653-665页

作者： Jiani Zhong Hang Chen Qiming Liu Shenghua Zhou Zhenguo Liu Yichao Xiao Department of Cardiovascular medicine Second Xiangya HospitalCentral South UniversityChangsha410011China Xiangya School of medicine Central South UniversityChangsha410008China center for Precision medicine and Division of Cardiovascular medicine Department of MedicineSchool of MedicineUniversity of MissouriColumbiaMO65211USA

Atrial fibrillation(AF)is the most common cardiac *** medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for *** have unique metabolic characteristics to maintain adenosine triphosphate *** changes occur in myocardial metabolism in ***-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and ***-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial *** article reviews the changes in metabolic characteristics in cardiomyocytes in *** the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.

关键词： Atrial fibrillation Glucagon-like peptide-1 receptor agonists Metabolism

Role of mitochondrial dysfunction in kidney disease:Insights from the cGAS-STING signaling pathway

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Chinese Medical Journal 2024年第9期137卷 1044-1053页

作者： Lu Li Fei Liu Chunyue Feng Zhenjie Chen Nan Zhang Jianhua Mao Department of Nephrology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Pediatric Intensive Care Unit Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

Over the past decade,mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney ***,the precise molecular mechanisms linking mitochondrial damage to kidney disease remain *** recent insights into the cyclic guanosine monophosphate-adenosine monophosphate(GMP-AMP)synthetase(cGAS)-stimulator of interferon gene(STING)signaling pathway have revealed its involvement in many renal *** of these findings is that mitochondrial DNA(mtDNA)induces inflammatory responses via the cGAS-STING ***,we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage,focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney ***,we summarize the latest findings of cGAS-STING signaling pathway in cell,with a particular emphasis on its downstream signaling related to kidney *** review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway,kidney diseases,and mitochondrial dysfunction.

关键词： mitochondrial dysfunction mitochondrial DNA cGAS-STING pathway Kidney diseases Chronic kidney disease

Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu Shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng Shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China Department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China Bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The Department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in *** then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical *** detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

Shengmaisan combined with Liuwei Dihuang Decoction alleviates chronic intermittent hypoxia-induced cognitive impairment by activating the EPO/EPOR/JAK2 signaling pathway

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Chinese Journal of Natural medicines 2024年第5期22卷 426-440页

作者： SI Jianchao CHEN Xue QI Kerong LI Dongli LIU Bingbing ZHENG Yuying JI Ensheng YANG Shengchang Department of Physiology Hebei University of Chinese MedicineShijiazhuang 050000China Hebei Technology Innovation center of TCM Combined Hydrogen medicine Shijiazhuang 050000China Department of Geriatrics First People’s Hospital of XiaoganXiaogan 432000China

Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive *** evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the *** study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by *** exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH ***,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular *** function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron *** stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western *** further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 *** results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in ***,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling ***,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH *** findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.

关键词： Chronic intermittent hypoxia Cognitive impairment Shengmaisan Liuwei Dihuang Decoction Oxidative stress EPO/EPOR/JAK2 signaling pathway