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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao Key Laboratory of Endemic and Ethnic diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou center for disease control and prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation center for prevention and control of Endemic and Ethnic Regional diseases Co-constructed by the province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National Clinical Research center for Ocular disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of prevention and treatment of Cerebrovascular diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina henan Key Laboratory of Cerebrovascular diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for Disaster Medicine Technology TianjinChina henan Medical Key Laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina Institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

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Neural Regeneration Research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song The National Clinical Research center for Geriatric disease Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the *** NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory ***,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau *** biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced *** findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in *** that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

关键词： 5′end trimming Alzheimer's disease amyloid-beta amyloid-β-dependent transcription FUBP3 inflammasome inflammation neuron NLRP3 tau transcription factor

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-Hong Ma Department of Neurology and Clinical Research center of Neurological disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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The Survey of Cronobacter spp.(formerly Enterbacter sakazakii) in Infant and Follow-up Powdered Formula in China in 2012

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Biomedical and Environmental Sciences 2016年第2期29卷 99-106页

作者： PEI Xiao Yan YAN Lin ZHU Jiang Hui LI Ning GUO Yun Chang FU Ping JIA Hua Yun ZHANG Xiu Li YANG Xiao Rong YANG Da Jin China National center for Food Safety Risk Assessment Beijing 100022 China Hunan province center for disease control and prevention Changsha 410000 Hunan China henan province center for disease control and prevention Zhengzhou 450000 Henan China Sichuan province center for disease control and prevention Chengdu 610000 Sichuan China

Objective To determine Cronobacter spp. contamination in infant and follow-up powdered formula in China. Methods All of 2282 samples were collected from the retail markets in China from January 2012 to December 2012, and analyzed for Cronobacter spp. by the Chinese National Food Safety Standard. Characterization of the isolates was analyzed by pulsed-field gel electrophoresis（PFGE） with XbaI and Spe I restriction enzymes. Results Cronobacter spp. strains were isolated from 25 samples, and the positive rates in infant powdered formulas and follow-up powdered formulas were 0.90%（10/1011） and 1.18%（15/1271）, respectively. Analysis of variable data regarding different purchasing store formats, seasonality, and production locations as well as comparison of infant versus follow-up formulas did not reveal statistically significant factors. During the sampling period, one of six surveillance zones did exhibit a statistically significant trend towards higher positive rate. PFGE characterization of Cronobacter spp. to elucidate genetic diversity revealed only three pairs of Cronobacter spp. out of 25 having the same PFGE patterns. Conclusion The current investigation indicated a lower positive rate of Cronobacter spp. in the powdered formula in China. This evidence suggested contamination originating from multiple different sources during the manufacturing process.

关键词： Cronobacter spp Contamination PFGE Powdered formula

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Coverage of 13-Valent Pneumococcal Conjugate Vaccine Among Children 0–15 Months of Age—9 provinces,China,2019–2021

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China CDC weekly 2023年第17期5卷 379-384页

作者： Lijun Liu Zhaonan Zhang Xixi Zhang Changsha Xu Yifan Song Li Li Jiakai Ye Zhiguo Wang Hui Liang Weiyan Zhang Ling Lin Ning Li Shujun Zhang Qianli Ma Wen Du Yongzhuo Jiao Lingsheng Cao Qi Qi Lei Cao Wenzhou Yu Sichuan center for disease control and prevention Chengdu CitySichuan ProvinceChina National Immunization Program Chinese Center for Disease Control and PreventionBeijingChina Suqian center for disease control and prevention Suqian CityJiangsu ProvinceChina Jiangsu center for disease control and prevention Nanjing CityJiangsu ProvinceChina Zhejiang center for disease control and prevention Hangzhou CityZhejiang ProvinceChina Shandong center for disease control and prevention Jinan CityShandong ProvinceChina Anhui center for disease control and prevention Hefei CityAnhui ProvinceChina Hubei center for disease control and prevention Wuhan CityHubei ProvinceChina Hunan center for disease control and prevention Changsha CityHunan ProvinceChina Guizhou center for disease control and prevention Guiyang CityGuizhou ProvinceChina Gansu center for disease control and prevention Lanzhou CityGansu ProvinceChina

Summary What is already known on this topic?Limited data exist regarding the coverage of the 13-valent pneumococcal conjugate vaccine(PCV13)in China.A lack of official statistics,coupled with an insufficient body of published literature,hinders the accurate depiction of the current *** is added by this report?This study investigated the utilization of PCV13 and estimated its coverage in nine provinces across eastern,central,and western China between 2019 and *** an annual increase in PCV13 usage during this period,the overall coverage remained suboptimal.

关键词： spite coverage hinder

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Unveiling phosphofructokinase as the key target: an innovative strategy combining pull-down assays with optical imaging for snail-killing mechanism exploration

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Science China Chemistry 2025年

作者： Yuxun Lu Weisi Wang Le Yu Yuqiang Zhao Ying Chen Yunhai Guo Bingrong Luo Yuhua Liu Shizhu Li Liping Duan Ying Zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and Technology Yunnan University College of Biological and Chemical Engineering Guangxi University of Science and Technology National Institute of Parasitic diseases Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases School of Chemistry and Environment Yunnan Minzu University Dali Institute of Schistosomiasis control

The Pomacea canaliculata, also known as apple snail, is an invasive species in China, posing a serious threat to agricultural production and public health. To prevent its rampant infestation, we developed a highly efficient snail-killing lead compound, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (PBQ). However, the killing mechanism of PBQ remains unclear. To elucidate this, two novel compounds, B-PBQ and J-PBQ, were developed through structural modification of PBQ and were used, through both protein pull-down assay and confocal laser scanning microscopy imaging, to identify and confirm that phosphofructokinase(PFK) in the apple snail is the primary target protein of PBQ. Further studies revealed that PBQ successfully inhibits the activity,content, and expression of PFK in apple snail, disrupting the glycolysis pathway and leading to abnormal energy *** disruptions impair the snail’s tolerance to low oxygen, resulting in its efficient eradication. These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides. Furthermore, the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.

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Outbreak of Dengue Fever in Central China,2013

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Biomedical and Environmental Sciences 2014年第11期27卷 894-897页

作者： HUANG Xue Yong MA Hong Xia WANG Hai Feng DU Yan Hua SU Jia LI Xing Le TANG Xiao Yan MA Hong Peng ZU Bing Can ZHANG Qiao Hong CHEN Hao Min XU Bian Li henan center for disease control and prevention Yuzhou center for disease control and prevention Xuchang center for disease control and prevention

In 2013,the first dengue fever（DF） outbreak in central China was reported in the central of henan province,northern temperate regions,although they have been sequentially recorded in Southern China.106 suspected DF cases were reported and 73 patients were confirmed dengue virus type 3（DEN-3） infections.62/392（15.8%） local health persons showed DEN antibodies *** this day henan is the northernmost province in China which has been reported about outbreak of DF and what is important is that it warns us the endemic range of DF has been expanded geographically in China.

关键词： dengue henan temperate sequentially outbreak expanded endemic Fever capture hasbeen

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