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Therapeutic effects of icarrin on amyloid-β burden in a mouse model of Alzheimer's disease

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Therapeutic effects of icarrin on amyloid-β burden in a mou...

IMMUNOHISTOCHEMICAL LOCALIZATION OF LH-RH IN HUMAN TROPHOBLAST

第二届世界天然药物和传统药物药理学学术会议

作者： Lan zhang,Jin chu,Ru-yi zhang,ying XING,Lin LI~* (Department of Pharmacology,Xuanwu Hospital of Capital Medical University,Key Laboratory for Neurodegenerative Diseases of Ministry of Education,Beijing 100053,China)

AIM To investigate the effect and pharmacological mechanism of icarrin(ICA),which is the main component extracted from a traditional Chinese epimedium herb,on Aβproduction in AD-like APP transgenic *** PDAPPV717I transgenic (Tg) mice were randomly divided into model group and ICA treated(at doses 30 and 100μmol·kg·d) *** was orally administered to Tg mice with an age range 4-10 *** burden of Aβwas measured by ELISA and *** amyloid senile plaques were detected by Congo red staining and Bielschowsky silver *** expression of APP and BACE-1 were measured by immunohistochemistry and Western *** co-expression of Aβwith amyloid fibers was detected by applying double labeled *** Orally administered ICA decreased the number of amyloid senile plaques in hippocampus of Tg *** immunohistochemical examination of brain sections stained with polyclonal anti-Aβantibody showed reduced Aβburden, and Aβlevels were also decreased in the insoluble fractions of brain homogenates,as determined by *** expression of APP and BACE-1 in hippocampus was significantly decreased in ICA treated *** ICA could reduce the Aβburden and plaque deposits in the hippocampus of APP transgenic mice through depressing the expression of APP and *** may have a promising application prospect in treatment of AD.

关键词： Alzheimer’s disease APPV717I transgenic mice β-amyloid icarrin

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Chinese Science Bulletin 1982年第10期27卷 1111-1113页

作者：朱益陶张致一 CHANG CHIH-YE Eudoerinology Department Institute of Zoology Academia Sinica Beijing Eudoerinology Department Institute of Zoology Academia Sinica Beijinghe blastocyst of mammalian species and the placenta of human being are known to produce a variety of hormones including both sex steroids and gonadotropic peptides. The human chorionic gonadotropin hCG has been detected in pregnant woman's serum as early as day 7 of gestation. Since the synthesis and the release of the pituitary gonadotropins are directly regulated by the luteinizing releasing hormone (LHRH) of the hypothalamus it would be of great interest to see if its counterpart is also

The blastocyst of mammalian species and the placenta of human being are known to produce a variety of hormones, including both sex steroids and gonadotropic peptides. The human chorionic gonadotropin, hCG, has been detected in pregnant woman’s serum as early as day 7 of gestation. Since the synthesis and the release of the pituitary gonadotropins are directly regulated by the luteinizing releasing hormone (LHRH) of the hypothalamus, it would be of great interest to see if its counterpart is

关键词： gonadotropin chorionic luteinizing pregnant placenta steroids counterpart hypothalamus releasing pituitary

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： yi zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li zhang Zheng Gang zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2982-2997页

作者： Hongli Li Jianhua Huang Di Zhao Lemei Zhu Zheyu zhang Min yi Weijun Peng Department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Metabolic Diseases ChangshaHunan ProvinceChina Hunan Academy of Chinese Medicine ChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut *** aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease *** do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of ***-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 ***,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 *** findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

关键词： Alzheimer’s disease APP/PS1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis

Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian chu Tinglin zhang Tong yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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

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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

Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development

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World Journal of Gastroenterology 2025年第2期31卷 42-51页

作者： Wen-Chong Zhen Jing Sun Xue-Ting Bai Qian zhang Zi-Han Li yi-Xin zhang Rong-Xuan Xu Wei Wu Zhi-Han Yao chun-Wen Pu Xiao-Feng Li School of Public Health Dalian Medical UniversityDalian 116044Liaoning ProvinceChina Graduate School Dalian Medical UniversityDalian 116044Liaoning ProvinceChina Dalian Public Health Clinical Center Dalian Municipal Research Institute for Public HealthDalian 116001Liaoning ProvinceChina Department of Epidemiology and Health Statistics Dalian Medical UniversityDalian 116044Liaoning ProvinceChina

BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma(HCC),a leading cause of mortality *** detection of HCC is crucial,yet *** To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio(APR)in hepatitis B progression to *** Data from 4843 patients with hepatitis B(January 2015 to January 2024)were *** incidence rates in males and females were compared using the log-rank *** were evaluated using Kaplan–Meier *** Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over ***,Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC *** The incidence of HCC was higher in *** ensure the model’s normality assumption,this study applied a logarithmic transformation to APR,yielding *** levels were higher in females(t=5.26,P<0.01).A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males(95%CI:1.653-2.431)and a 2.273-fold higher risk in females(95%CI:1.620-3.190).CONCLUSION Males are more prone to HCC,while females have higher APR *** no baseline APR link,rising APR indicates a higher HCC risk.

关键词： Alkaline phosphatase to prealbumin ratio Chronic hepatitis B patients Hepatocellular carcinoma Retrospective cohort study Linear Mixed-Effect Mode Joint Modelling of Longitudinal and Survival data

Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats

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World Journal of Gastroenterology 2025年第1期31卷 93-109页

作者： Ping zhang ying Zhu Pu Chen Tong Zhou Zhe-yi Han Jun Xiao Jian-Feng Ma Wen Ma Peng Zang ying Chen Graduate School Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina Key Laboratory of Aerospace Nutrition and Food Engineering China Astronaut Research and Training CenterBeijing 100094China Department of Gastroenterology The Air Force Medical CenterBeijing 100142China Department of Blood Transfusion Air Force Medical CenterBeijing 100142China

BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility *** pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal ***,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal *** cells are the pacemakers of gastrointestinal *** To investigate the effects of Bifidobacterium lactis(***)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit *** The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 *** tail group was given *** BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/***&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and *** fecal flora and mucosal flora of rats in each group were detected by 16S *** Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic *** microgravity reduced the expressions of SCF and c-kit,and increased the express

关键词： Simulated microgravity Rat Intestinal flora Gastrointestinal motility Stem cell factor/c-kit signaling pathway

Nomogram for overall survival in ampullary adenocarcinoma using the surveillance,epidemiology,and end results database and external validation

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World Journal of Clinical Oncology 2025年第2期16卷 36-51页

作者： Jia Yang Zi-yi Wang Jing Chen Yao zhang Lei Chen Department of Gastroenterology The First Affiliated Hospital of Army Medical UniversityChongqing 400038China Department of Epidemiology College of Preventive MedicineArmy Medical UniversityChongqing 400038China

BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal ***,only a few cases have been reported,resulting in limited information on *** To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary *** Data were sourced from the surveillance,epidemiology,and end results stat *** patients in the database were randomized in a 7:3 ratio into training and validation *** Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the *** nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical *** For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the *** area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific *** internal and external validation cohorts indicated good consistency of the *** The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.

关键词： Ampullary adenocarcinoma Dynamic nomogram Gastrointestinal tract Surveillance Epidemiology End results database Survival rate