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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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Role of copper in central nervous system physiology and pathology

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Neural Regeneration Research 2025年第4期20卷 1058-1068页

作者： Martina Locatelli Cinthia Farina Institute of Experimental Neurology Division of NeuroscienceIstituto di Ricovero e Cura a Carattere Scientifico(IRCCS)San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous *** copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple *** review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper ***,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

关键词： astrocytes central nervous system copper cuprizone multiple sclerosis myelin neurodegenerative disorders

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Oligodendroglial heterogeneity in health,disease,and recovery:deeper insights into myelin dynamics

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Neural Regeneration Research 2025年第11期20卷 3179-3192页

作者： Pieter-Jan Serneels Julie D.De Schutter Lies De Groef Lieve Moons Steven Bergmans KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionNeural Circuit Development&Regeneration Research GroupLeuvenBelgium KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionCellular Communication&Neurodegeneration Research GroupLeuvenBelgium

Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and ***,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing *** forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature *** new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological *** this uniform terminology will facilitate comparison and integration of data across ***,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating ***,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination ***,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.

关键词： animal models demyelination fish mammals multiple sclerosis myelin neurodegeneration oligodendrocytes oligodendroglial lineage remyelination

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Perspective on Etiology and Treatment of Bipolar disorders in China: Clinical Implications and Future Directions

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Neuroscience Bulletin 2019年第4期35卷 608-612页

作者： Zuowei Wang Chen Jun Kerning Gao Haichen Yang Yiru Fang division of Mood disorders Hongkou District Mental Health Center Shanghai 200083 China division of Mood disorders Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai 200030 China Case Western Reserve University School of Medicine Cleveland OH 44106 USA Mood and Anxiety Clinic in the Mood disorders Program of the Department of Psychiatry University Hospital Cleveland Medical Center Cleveland OH 44106 USA Department of Mood disorders Shenzhen Mental Health Centre Shenzhen 518003 China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031 China Shanghai Key Laboratory of Psychotic disorders Shanghai 201108 China

Bipolar disorder (BD) is a chronic, recurrent, disabling disease, even when given currently-available pharmacological and psychological treatments. Currently, the etiology and pathogenesis of BD remain unclear. As a consequence, patients with BD are frequently unrecognized, misdiagnosed, and inappropriately treated, which often yields a low treatment response and poor outcome.

关键词： Perspective Future Directions Bipolar disorders

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Energy metabolism homeostasis in cardiovascular diseases

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Journal of Geriatric Cardiology 2021年第12期18卷 1044-1057页

作者： Lu-Yun WANG Chen CHEN division of Cardiology Tongji HospitalTongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic DisordersHuazhong University of Science and TechnologyWuhanChina

Cardiovascular disease(CVD)is the leading cause of morbidity and mortality in the general *** metabolism disturbance is one of the early abnormalities in CVDs,such as coronary heart disease,diabetic cardiomyopathy,and heart *** explore the role of myocardial energy homeostasis disturbance in CVDs,it is important to understand myocardial metabolism in the normal heart and their function in the complex pathophysiology of *** this article,we summarized lipid metabolism/lipotoxicity and glucose metabolism/insulin resistance in the heart,focused on the metabolic regulation during neonatal and ageing heart,proposed potential metabolic mechanisms for cardiac regeneration and *** provided an overview of emerging molecular network among cardiac proliferation,regeneration,and metabolic *** novel targets promise a new era for the treatment of CVDs.

关键词： metabolism homeostasis degeneration

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Advanced non-alcoholic steatohepatitis cirrhosis: A high-risk population for pre-liver transplant portal vein thrombosis

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World Journal of Hepatology 2017年第3期9卷 139-146页

作者： Jonathan G Stine Curtis K Argo Shawn J Pelletier Daniel G Maluf Stephen H Caldwell Patrick G Northup division of Gastroenterology and Hepatology Department of Medicine Center for the Study of Coagulation Disorders in Liver Disease University of Virginia division of Transplant Department of Surgery University of Virginia

AIMTo examine if liver transplant recipients with high-risk non-alcoholic steatohepatitis (NASH) are at increased risk for pre-transplant portal venous thrombosis. METHODSData on all liver transplants in the United States from February 2002 through September 2014 were analyzed. Recipients were sorted into three distinct groups: High-risk (age > 60, body mass index > 30 kg/m2, hypertension and diabetes), low-risk and non-NASH cirrhosis. Multivariable logistic regression models were constructed. RESULTSThirty-five thousand and seventy-two candidates underwent liver transplantation and of those organ recipients, 465 were transplanted for high-risk and 2775 for low-risk NASH. Two thousand six hundred and twenty-six (7.5%) recipients had pre-transplant portal vein thrombosis; 66 (14.2%) of the high-risk NASH group had portal vein thrombosis vs 328 (11.8%) of the low-risk NASH group. In general, all NASH recipients were less likely to be male or African American and more likely to be obese. In adjusted multivariable regression analyses, high-risk recipients had the greatest risk of pre-transplant portal vein thrombosis with OR = 2.11 (95%CI: 1.60-2.76, P CONCLUSIONLiver transplant candidates with high-risk NASH are at the greatest risk for portal vein thrombosis development prior to transplantation. These candidates may benefit from interventions to decrease their likelihood of clot formation and resultant downstream hepatic decompensating events. Prospective study is needed.

关键词： Liver transplantation Non-alcoholic fatty liver disease Portal hypertension Hepatology Coagulopathy

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Immunopathogenesis and immunomodulatory therapy for myocarditis

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Science China(Life Sciences) 2023年第9期66卷 2112-2137页

作者： Wu He Ling Zhou Ke Xu Huihui Li James Jiqi Wang Chen Chen DaoWen Wang division of Cardiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyHubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersWuhan 430030China

Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis,whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.

关键词： myocarditis etiology pathogen immunopathogenesis immunomodulatory

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The double face of miR-320:cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction

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Signal Transduction and Targeted Therapy 2021年第3期6卷 950-961页

作者： Xudong Zhang Shuai Yuan Huaping Li Jiabing Zhan Feng Wang Jiahui Fan Xiang Nie Yan Wang Zheng Wen Yanghui Chen Chen Chen Dao Wen Wang division of Cardiology Tongji HospitalTongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic DisordersHuazhong University of Science and TechnologyWuhan 430030China

MicroRNAs(miRNAs)are aberrantly expressed in the pathophysiologic process of heart failure(HF).However,the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported,which might be covered by the globe effects of it on the *** the current study,Langendorff system was applied to isolate card io myocytes(CMs)and cardiac fibroblasts(CFs)from transverse aortic constriction(TAC)-induced *** increase of miR-320 expression was observed in the whole heart tissue of TAC ***,miR-320 was significantly elevated in CMs but decreased in CFs from TAC mice at different time ***,recombinant adeno-associated virus 9 with cell-type-specific promoters were used to manipulate miR-320 expressions in *** in vitro and in vivo experiments showed the miR-320 overexpression in CMs exacerbated cardiac dysfunction,whereas overexpression of miR-320 in CFs alleviated cardiac fibrosis and ***,downstream signaling pathway analyses revealed that miR-320 might induce various effects via targeting PLEKHM3 and IFITM1 in CMs and CFs,***,miR-320 mediated effects could be abolished by PLEKHM3 re-expression in CMs or IFITM1 re-expression in ***,miR-320 treated CFs were able to indirectly affect CMs function,but not vice ***,upstream signaling pathway analyses showed that miR-320 expression and decay rate were rigorously manipulated by Ago2,which was regulated by a cluster of cell-type-specific TFs distinctively expressed in CMs and CFs,***,we demonstrated that miR-320 functioned differently in various cell types of the heart during the progression of HF.

关键词： miR elevated transverse

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The Relationship Between Neuroimmunity and Bipolar Disorder:Mechanism and Translational Application

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Neuroscience Bulletin 2019年第4期35卷 595-607页

作者： Zhiang Niu Lu Yang Xiaohui Wu Yuncheng Zhu Jun Chen Yiru Fang Clinical Research Center Division of Mood Disorders Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai 200030 China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031 China Shanghai Key Laboratory of Psychotic disorders Shanghai 201108 China

Neuroimmune system may be involved in the pathological process of bipolar disorder(BD),but the essential association is not fully *** evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system(CNS).Meanwhile,neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized,such as neurotransmitter systems,neuroendocrine systems,neurotrophic factors,and oxidative ***,related genes and immune changes in peripheral blood vary with ***,neuroimmunity may play an important role in the pathogenesis of BD,and the inflammatory cytokines,especially interleukin-6 and tumor necrosis factor-alpha,have potential value for the clinical diagnosis and prognosis of BD,as well as predicting the therapeutic effects of ***-scale studies are needed to extend the evidence on neuroimmunity in BD,and to examine its clinical value for applications such as early prediction and treatment.

关键词： Neuroimmunity Inflammation Cytokines Bipolar disorder Translational application

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The effects of obesity on venous thromboembolism: A review

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Open Journal of Preventive Medicine 2012年第4期2卷 499-509页

作者： Genyan Yang Christine De Staercke W. Craig Hooper Clinical and Molecular Hemostasis Laboratory Branch Division of Blood Disorders National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention Atlanta Georgia

Obesity has emerged as a global health issue that is associated with wide spectrum of disorders, including coronary artery disease, diabetes mellitus, hypertension, stroke, and venous thromboembolism (VTE). VTE is one of the most common vascular disorders in the United States and Europe and is associated with significant mortality. Although the association between obesity and VTE appears to be moderate, obesity can interact with other environmental or genetic factors and pose a significantly greater risk of VTE among individuals who are obese and who are exposed simultaneously to several other risk factors for VTE. Therefore, identification of potential interactions between obesity and certain VTE risk factors might offer some critical points for VTE interventions and thus minimize VTE morbidity and mortality among patients who are obese. However, current obesity measurements have limitations and can introduce contradictory results in the outcome of obesity. To overcome these limitations, this review proposes several future directions and suggests some avenues for prevention of VTE associated with obesity as well.

关键词： Obesity Comorbidity Deep Vein Thrombosis Pulmonary Embolism Venous Thromboembolism Risk Factor Prevention

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