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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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Targeting collagen expression in alcoholic liver disease

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World Journal of Gastroenterology 2011年第20期17卷 2473-2481页

作者： Kyle J Thompson Iain H McKillop Laura W Schrum Department of General Sur gery Carolinas Medical Center Liver Digestive and Metabolic Disorder LaboratoryCarolinas Medical Center

Alcoholic liver disease （ALD） is a leading cause of liver disease and liver-related deaths globally, particularly in developed nations. Liver fibrosis is a consequence of ALD and other chronic liver insults, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Liver fibrosis is characterized by accumulation of excess extracellular matrix components, including type I collagen, which disrupts liver microcirculation and leads to injury. To date, there is no therapy for the treatment of liver fibrosis; thus treatments that either prevent the accumulation of type I collagen or hasten its degradation are desirable. The focus of this review is to examine the regulation of type I collagen in fibrogenic cells of the liver and to discuss current advances in therapeutics to eliminate excessive collagen deposition.

关键词： Type I collagen Fibrosis Extracellular matrix Hepatic stellate cell Alcohol Antioxidants Endoplasmic reticulum chaperones Matrix metalloproteinase microRNA

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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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Neural Regeneration Research 2025年第3期20卷 695-714页

作者： Beibei Wu Yuqing Liu Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng Department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina Yangsheng College of Traditional Chinese Medicine Guizhou University of Traditional Chinese MedicineGuiyangGuizhou ProvinceChina Qinhuangdao Shanhaiguan Pharmaceutical Co. LtdQinhuangdaoHebei ProvinceChina National Clinical Research center for Mental disorder The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary *** amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease *** abnormalities are commonly observed in patients with Alzheimer's *** liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's ***,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's *** this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol ***,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

关键词： ABCA1 Alzheimer's disease amyloid-beta apolipoprotein E cholesterol metabolism liver liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid

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Aortoesophageal fistula:A case misdiagnosed as esophageal polyp

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World Journal of Gastroenterology 2009年第47期15卷 6007-6009页

作者： Yue Jiao Ye Zong Zhong-Lin Yu Yong-Zheng Yu Shu-Tian Zhang Department of digestive Diseases and Beijing digestive Disease center Beijing Friendship Hospital Capital Medical University Beijing 100016 China

Aortoesophageal fistula(AEF)is a rare and fatal disorder. It is also a life-threatening cause of massive upper gastrointestinal *** aortic aneurysm is the most common cause of *** of a patient with this disorder requires rapid diagnosis and immediate intervention,which is considered the best way to save the patient's *** report a case of AEF misdiagnosed as esophageal polyp.

关键词： Aortoesophageal fistula Aortic aneurysm Gastrointestinal bleeding

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Validity and reliability of the Ocular Motor Nerve Palsy Scale

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Neural Regeneration Research 2018年第10期13卷 1851-1856页

作者： Ling-Yun Zhou Chang Su Tie-Juan Liu Xue-Mei Li Ocular Motility disorder Treatment & Rehabilitation center Department of AcupunctureFirst Affiliated Hospital of Harbin Medical University

Objective and accurate assessment of the degree of ocular motor nerve palsy is helpful not only in the evaluation of prognosis, but also for the screening of treatment methods. However, there is currently no comprehensive measure of its severity. In this study, we designed the Ocular Motor Nerve Palsy Scale and investigated its validity and reliability. Six experts were invited to grade and evaluate the scale. The study recruited 106 patients with a definite diagnosis of unilateral isolated ocular motor nerve palsy. Three physicians evaluated the patients using the scale. One of the three physicians evaluated the patients again after 24 hours. The content validity index（CVI） and factor analysis were used to analyze the scale＇s construct validity. The intraclass correlation coefficient and Cronbach＇s alpha were used to evaluate the inter-rater and test-retest reliability and the internal consistency. The CVI results（I-CVI = 1.0, S-CVI = 0.9, Pc = 0.016, K＊ = 1） indicated good content validity. Factor analysis extracted two common factors that accounted for 85.2% of the variance. Furthermore, the load value of each component was above 0.8, indicating good construct validity. The Ocular Motor Nerve Palsy Scale was found to be highly reliable, with an inter-rater reliability intraclass correlation coefficient of 0.965（P 0.01）, a test-retest reliability intraclass correlation coefficient of 0.976（P 0.01）, and Cronbach＇s alpha values of 0.63–0.70. In conclusion, the Ocular Motor Nerve Palsy Scale with good validity and reliability can be used to quantify the severity of ocular motor nerve palsy. This study was registered at Chinese Clinical Trial Registry（registration number： Chi CTR-OOC-17010702）.

关键词： nerve regeneration Ocular Motor Nerve Palsy Scale oculomotor nerve paralysis abducens nerve paralysis trochlear nerve paralysis validity reliability internal consistency diplopia eyeball movement disorder ptosis neural regeneration

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Have guidelines addressing physical activity been established in nonalcoholic fatty liver disease?

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World Journal of Gastroenterology 2012年第46期18卷 6790-6800页

作者： Carmine Finelli Giovanni Tarantino center of Obesity and Eating disorder Stella Maris Mediterraneum Foundation Department of Clinical and Experimental Medicine Federico Ⅱ University Medical School of Naples

The purpose of this review was to highlight, in relation to the currently accepted pathophysiology of non-alcoholic fatty liver disease (NAFLD), the known exercise habits of patients with NAFLD and to detail the benefits of lifestyle modification with exercise (and/or physical activity) on parameters of metabolic syndrome. More rigorous, controlled studies of longer duration and defined histopathological end-points comparing exercise alone and other treatment are needed before better, evidence-based physical activity modification guidelines can be established, since several questions remain unanswered.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Physical activity Diet

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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

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Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun Department of Neurology and Neuroscience center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Efficacy of intraorbital electroacupuncture for diabetic abducens nerve palsy： study protocol for a prospective single-center randomized controlled trial

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Neural Regeneration Research 2017年第5期12卷 826-830页

作者： Ling-yun Zhou Xue-mei Li Tie-juan Liu Xiao-jie Ji Ming Zhao Chang Su Ji-chao Liu Jiang-yun Sun Ocular Motility disorder Treatment & Rehabilitation center Department of Acupuncture the First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang Province China

Abducens nerve palsy（ANP） is commonly seen in patients with diabetes mellitus. The validity of acupuncture as a traditional Chinese medicine method in peripheral nerve repair is well established. However, its efficacy in randomized controlled trials remains unclear. Herein, we designed a protocol for a prospective, single-center, randomized controlled trial to investigate the effect of intraorbital electroacupuncture on diabetic ANP. We plan to recruit 60 patients with diabetic ANP, and randomly divide them into treatment and control groups. Patients in both groups will continue their glucose-lowering therapy. A neural nutrition drug will be given to both groups for six weeks. The treatment group will also receive intraorbital electroacupuncture therapy. We will assess efficacy of treatment, eyeball movement, diplopia deviation and the levels of fasting blood-glucose and glycosylated hemoglobin before treatment at 2, 4, and 6 weeks after treatment. The efficacy and recurrence will be investigated during follow-up（1 month after intervention）. This protocol was registered at Chinese Clinical Trial Registry on 16 January 2015（Chi CTR-IPR-15005836）. This study was approved by the Ethics Committee of First Affiliated Hospital of Harbin Medical University of China（approval number： 201452）. All protocols will be in accordance with Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be provided by participants. We envisage that the results of this clinical trial will provide evidence for promoting clinical use of this new therapy for management of ANP.

关键词： nerve regeneration sixth cranial nerve peripheral nerve injury electroacupuncture diabetes mellitus eyeball movement diplopia rehabilitation ocular motility disorder intervention randomized controlled trail neural regeneration

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What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?

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World Journal of Gastroenterology 2013年第6期19卷 802-812页

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western *** resistance is a key factor in the pathogenesis of NAFLD,the latter being considered as the hepatic component of insulin resistance or *** is the most abundant adipose-specific *** is evidence that adiponectin decreases hepatic and systematic insulin resistance,and attenuates liver inflammation and *** generally predicts steatosis grade and the severity of NAFLD;however,to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be *** there is no proven pharmacotherapy for the treatment of NAFLD,recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle *** this adiponectin-focused review,the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.

关键词： Non-alcoholic fatty liver disease Obesity Adiponectin Visceral fat Adipokines

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The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

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Neural Regeneration Research 2025年第11期20卷 3211-3212页

作者： Sara Mazzoleni Marta Busnelli Silvia Bassani CNR Institute of Neuroscience Vedano al LambroItaly NeuroMi Milan center for Neuroscience MilanItaly

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive *** seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

关键词： epilepsy function system

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