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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei college of Pharmacy and First clinical Medical college Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3217-3218页

作者： Laura Huggon Emma L.Clayton UK Dementia Research Institute at King’s college London LondonUK Department of Basic and clinical Neuroscience Institute of Psychiatry Psychology&NeuroscienceKing’s College LondonLondonUK

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping *** these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly *** and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

关键词： diseases amyotrophic sclerosis

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina college of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Gut-brain axis as a bridge in obesity and depression:Mechanistic exploration and therapeutic prospects

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World Journal of Psychiatry 2025年第1期15卷 12-20页

作者： Rui-Ying Fang Xiao-Rui Pan Xin-Xing Zeng Zheng-Zheng Li Bo-Fan Chen Hai-Min Zeng Jie Peng The Second clinical Medical college The Second Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina

A recent study by Wang et al,published in the World Journal of Psychiatry,provided preventative and therapeutic strategies for the comorbidity of obesity and *** gut-brain axis,which acts as a two-way communication system between the gastrointestinal tract and the central nervous system,plays a pivotal role in the pathogenesis of these *** suggests that metabolic byproducts,such as short-chain fatty acids,lipopolysaccharide and bile acids,which are generated by the gut microbiota,along with neurotransmitters and inflammatory mediators within the gut-brain axis,modulate the host's metabolic processes,neuronal regulation,and immune responses through diverse *** interaction between obesity and depression via the gut-brain axis involves disruptions in the gut microbiota balance,inflammatory immune responses,and alterations in the neuroendocrine *** the gut-brain axis,for example,through a ketogenic diet,the use of probiotics,and the supplementation of antioxidants,offers new remedial approaches for obesity and *** research that explores the mechanisms of the gut-brain axis is needed to provide more evidence for clinical treatment.

关键词： Gut-brain axis Obesity Depression Gut microbiota Mechanism

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Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The clinical Medical college Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second clinical Medical college Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

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A new guaianolide from the roots of Pterocypsela elata

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Chinese Chemical Letters 2013年第1期24卷 55-56页

作者： Yi-Xiao Bai Jing Tan Fu-Lin Yan Ming-Ming Ding Xiang Wang Pharmacy college Xinxiang Medical University third clinical college of Xinxiang Medical University

In order to find more biologically active substances, we have carefully investigated the chemical constituents of Pterocypsela elata. One new guaianolide, （4S）-ll-methoxycarbonyl-guaiane- l（10）,5（6）,7（11）,8（9）-tetraen-6,12-olide was isolated from the EtOAc extracts of the roots of P. elata. Its structure was elucidated by various spectroscopic methods and confirmed by X-ray crystallographic analysis.

关键词： CompositaePterocypsela elataSesquiterpene lactonesGuaianolide

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Distribution and drug resistance of pathogenic bacteria in emergency patients

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World Journal of clinical Cases 2019年第20期7卷 3175-3184页

作者： Wei Huai Qing-Bian Ma Jia-Jia Zheng Yang Zhao Qiang-Rong Zhai Emergency Department Third Clinical Medical CollegePeking UniversityBeijing 100191China Laboratory Department Third Clinical Medical CollegePeking UniversityBeijing 100191China

BACKGROUND Antibiotic resistance has become a global threat for human health,calling for rational use of *** To analyze the distribution and drug resistance of the bacteria,providing the prerequisite for use of antibiotics in emergency *** A total of 2048 emergency patients from 2013 to 2017 were *** clinical examination specimens were collected,followed by isolation of *** bacterial identification and drug susceptibility testing were carried *** A total of 3387 pathogens were *** top six pathogens were Acinetobacter baumannii(660 strains),Staphylococcus aureus(436 strains),Klebsiella pneumoniae(347 strains),Pseudomonas aeruginosa(338 strains),Escherichia coli(237 strains),and Candida albicans(207 strains).The isolation rates of these pathogens decreased year by year except Klebsiella pneumoniae,which increased from 7.1%to 12.1%.Acinetobacter baumannii is a widely-resistant strain,with multiple resistances to imipenem,ciprofloxacin,minocycline and *** Staphylococcus aureus had high resistance rates to levofloxacin,penicillin G,and *** the susceptibility of it to vancomycin and tigecycline were 100%.Klebsiella pneumoniae had high resistance rates to imipenem,cefoperazone/sulbactam,amikacin,and ciprofloxacin,with the lowest resistance rate to *** resistance rates of Pseudomonas aeruginosa to cefoperazone/sulbactam and imipenem were higher,with the resistance rate to amikacin below 10%.Besides,Escherichia coli had high resistance rates to ciprofloxacin and cefoperazone/sulbactam and low resistance rates to imipenem,amikacin,and *** The pathogenic bacteria isolated from the emergency patients were mainly Acinetobacter baumannii,Staphylococcus aureus,Klebsiella pneumoniae,Pseudomonas aeruginosa,Escherichia coli,and Candida *** detection rates of drugresistant bacteria were high,with different bacteria having multiple drug resistances to commonly

关键词： Distribution Drug resistance Bacteria Emergency department

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina college of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Hemophagocytic lymphohistiocytosis complicated by polyserositis:A case report

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World Journal of clinical Cases 2019年第19期7卷 3069-3073页

作者： Ping Zhu Qing Ye Ting-Hong Li Tao Han Feng-Mei Wang Department of Hepatology and Gastroenterology Tianjin Third Central Hospital The Third Central Clinical College of Tianjin Medical University

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a rare group of disorders of immune dysregulation characterized by clinical symptoms of severe *** are basically two types of clinical scenarios:Familial HLH and sporadic *** is thought that the syndrome is implicated in the development of infections,malignancies,and autoimmune ***,whether primary or secondary,is characterized by activated macrophages in hematopoietic organs,hepatosplenomegaly,cytopenia,and fever;however,HLH complicated with polyserositis(PS)has never been *** SUMMARY We present a case of fever in a 46-year-old previously healthy Chinese woman complicated by pericardial,pleural,and abdomen *** had no contact with sick individuals,recent travel,illicit drug use,or new sexual *** did not consume alcohol or tobacco and lacked a family history of other *** were prescribed for suspected infection,and acute liver injury subsequently ***-enhanced computed tomography showed mild pericardial effusion,pleural effusion,hepatosplenomegaly,and a large amount of ascites.A full blood count revealed leukopenia and *** ferritin and triglyceride levels were *** test for Epstein-Barr(EB)virus DNA was *** suggests that EB virus replication and EB virus infection *** studies showed hemophagocytosis in bone marrow biopsy *** patient’s condition progressed *** providing symptomatic support treatment,eliminating immune stimuli,and administering comprehensive cyclosporine and dexamethasone treatment,the patient’s condition continued to progress,and the patient’s family members decided to stop treatment;the patient subsequently *** This case shows the significance of considering HLH as part of the evaluation of unexplained fever and PS of unknown origin.

关键词： Hemophagocytic lymphohistiocytosis Polyserositis Liver injury Fever Case report

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