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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou Ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng Ying Chen Jiali Pu Baorong Zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin Chen Jinghong Xu Bin Jiang Lei Li Yawei Li Yuliang Dai Bing Wang Department of Spine Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,eIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

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Mechanisms behind elevated serum levels of plasminogen activator inhibitor-1 in frontotemporal lobar degeneration

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Neural Regeneration Research 2025年第8期20卷 2317-2318页

作者： Francesco Angelucci Jakub Hort Memory Clinic Department of NeurologySecond Faculty of MedicineCharles University and Motol University HospitalPragueCzech Republic International Clinical Research Centre St.Anne’s University HospitalBrnoCzech Republic

Frontotemporal lobar degeneration(FTLD)is a form of progressive dementia characterized by degeneration of the frontal and temporal lobes of the *** pathology involves a series of cognitive,behavioral,and neurological ... 详细信息

关键词： degeneration elevated pathology

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Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury:state of the art and future perspectives

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Neural Regeneration Research 2025年第11期20卷 3151-3171页

作者： Fatima Aldali Chunchu Deng Mingbo Nie Hong Chen Department of Rehabilitation Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal *** nerve injury results in movements or sensation impairments,and represents a serious public health *** severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain *** emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and *** stem cells,as large living cells responsive to the environment,secrete various factors and *** latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem *** have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based *** ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical *** review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying ***,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and ***,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.

关键词： clinical trials exosome extracellular vesicles mesenchymal stem cells nerve regeneration peripheral nerve injury pre-clinical experiments

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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(seVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived seVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted seVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected seVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived seVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived seVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that seVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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Combined medial patellofemoral ligament and medial patellotibial ligament reconstruction in recurrent patellar instability:A systematic review and meta-analysis

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World Journal of Clinical Cases 2023年第19期11卷 4625-4634页

作者： Ahmad Abbaszadeh Mohsen Saeedi Amir Human Hoveidaei Haleh Dadgostar Saeed Razi Mohammad Razi Department of Orthopedic Emam Khomeini Teaching HospitalAhvaz Jundishapur University of Medical SciencesAhvaz ***Iran Sports Medicine Research Center Tehran University of Medical SciencesTehran 14395-578Iran Department of Sports and exercise Medicine School of MedicineRasool Akram Medical ComplexIran University of Medical SciencesTehran ***Iran Bone and Joint Reconstruction Research Center Department of OrthopedicsSchool of MedicineIran University of Medical SciencesTehran ***Iran Department of Orthopedic Surgery Rasoul Akram HospitalIran University of Medical SciencesTehran ***Iran

BACKGROUND The medial patellofemoral ligament(MPFL),along with the medial patellotibial ligament(MPTL)and medial patellomeniscal ligament,aid in the stabilization of the patellofemoral *** the MPFL is the primary stabilizer and the MPTL is a secondary limiter,this ligament is critical in maintaining joint *** have been few studies on the combined MPFL and MPTL reconstruction and its *** To look into the outcomes of combined MPFL and MPTL reconstruction in frequent patellar *** By May 8,2022,four electronic databases were searched:Medline(PubMed),Scopus,Web of Science,and Google *** keywords such as"patellar instability,""patellar dislocation,""MPFL,""medial patellofemoral ligament,""MPTL,"and"medial patellotibial ligament"were co-searched to increase the sensitivity of the *** The pooled effects of combined MPFL and MPTL reconstruction for Kujala score(12-mo followup)and Kujala score(24-mo follow-up)were positive and incremental,according to the findings of this *** mean difference between the Cincinnati scores was also positive,but not statistically *** combination of the two surgeries reduces *** to cumulative meta-analysis,the trend of pain reduction in various studies is declining over *** The combined MPFL and MPTL reconstruction has good clinical results in knee function and,in addition to providing good control to maintain patellofemoral joint balance,the patient's pain level decreases over time,making it a valid surgical method for patella stabilization.

关键词： Medial patellofemoral ligament reconstruction Medial patellotibial ligament patella dislocation Patella instability

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A review on metastatic breast cancer in Iran

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Asian Pacific Journal of Tropical Biomedicine 2015年第6期5卷 429-433页

作者： Hamidreza Alizadeh Otaghvar Mostafa Hosseini Adnan Tizmaghz Ghazaal Shabestanipour Hamid Noori Minimally Invasive Surgery Research Center Iran University of Medical Sciences Rasool-e-akram hospital Iran University of Medical Sciences Mofid Pediatric hospital Shahid Beheshti University of Medical Sciences

Metastatic breast cancer is a disease of early breast cancer that usually occurs several years after the early breast cancer. Breast cancer is the most common cancer among Iranian women. According to the new statistics in Iran 6 160 breast cancers are diagnosed in the country each year and 1 063 cases lead to death. In this paper, epidemiology, diagnosis and treatment have been investigated. In this study, case-control clinical trials and open studies with adequate data were collected. Due to the higher risk of age group 40-49 years and the advent of advanced breast cancer in Iranian women, the early diagnosis and determination of the exact size of the tumor before surgery is important in choosing a therapy plan. The decision on the therapy of invasive breast cancer depends on several factors such as cancer stage, tumor size and type, pathological and cytological status of the tumor, the patient's opinion, the presence or absence of estrogen and progesterone receptors in the cytoplasm of tumor cells and so on.

关键词： Metastatic Breast cancer epidemiology Diagnosis Treatment

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exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Going toward Green hospital by Sustainable Healthcare Waste Management: Segregation, Treatment and Safe Disposal

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Health 2014年第19期6卷 2632-2640页

作者： Mohammad Azmal Rohollah Kalhor Nayeb Fadaei Dehcheshmeh Salimeh Goharinezhad Zohreh Asadollahi Heidari Fereshteh Farzianpour Bushehr University of Medical Sciences Bushehr Iran Health Information Management Research Center Hormozgan University of Medical Sciences Bandar Abbas Iran Health Affairs Department Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran hospital Management Research Center Iran University of Medical Sciences Tehran Iran rasoul-e-akram hospital Complex Iran University of Medical Sciences Tehran Iran Department of Health Management and economics School of Public Health Tehran University of Medical Sciences Tehran Iran

hospitals have always been the focal point of social systems identity. Thus, they acte as the mirror of the community and should be responsible for it. hospitals have been recognized as a significant source of contamination all around the world, therefore helping to endanger public health on an unintentional process. Although, the main mission of the hospital is to promote human health, it cannot be assumed as an island apart from its urban environment. “Green hospital”, as an approach to address environmental challenges and to meet communities need in health issues, has emerged recently as a try to improve the health, in line with its main mission. In this approach, all the environmental aspects of waste management are important and to be addressed. hospitals’ administrators can manage wastes disposal through composting, recycling and better supplying methods (downsizing packaging, using reusable products instead of disposables and using recycled products). This article is a review of the subject matter, in nature, using many library and online sources;it discusses about the need to move towards the green hospital approach, the administration and leadership role in its establishment, the environmental impact of hospital operations and assessment of the effects, wastes management and control, and also the methods in wastes disposal and treatment.

关键词： Green hospital Wastes Wastes Management

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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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