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Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi Huang Xiangliang Chen Shen Liu Junshan Zhou Hongdong Zhao Ye Hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

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Non-coding RNAs in acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling Sun Xiaodan Qin Lin Zhu Teng Jiang Junshan Zhou Fuling Yan Qiwen Deng Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina General Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and *** predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain *** innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental *** expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic ***,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and *** particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic *** this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and *** from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

关键词： acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia Department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

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Neural Regeneration Research 2025年第9期20卷 2437-2453页

作者： Siyi Xu Junqiu Jia Rui Mao Xiang Cao Yun Xu Department of Neurology Nanjing Drum Tower HospitalClinical College of Jiangsu UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalChinese Academy of Medical Science&Peking Union Medical CollegeNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina nanjing Neurology Medical Center NanjingJiangsu ProvinceChina

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health *** optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent *** are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell ***,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these *** evidence has highlighted the significant role of mitophagy in acute central nervous system *** this review,we provide a comprehensive overview of the process,classification,and related mechanisms of *** also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate *** the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

关键词： autophagy intracerebral hemorrhage ischemic stroke mitochondria mitochondrial biogenesis mitochondrial quality control mitophagy spinal cord injury subarachnoid hemorrhage traumatic brain injury

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3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

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Nano-Micro Letters 2025年第2期17卷 18-45页

作者： Ke Yao Gaoying Hong Ximin Yuan Weicheng Kong Pengcheng Xia Yuanrong Li Yuewei Chen Nian Liu Jing He Jue Shi Zihe Hu Yanyan Zhou Zhijian Xie Yong He State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China Liangzhu Laboratory Zhejiang UniversityHangzhou 310027People’s Republic of China Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province College of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China stomatology hospital School of StomatologyZhejiang University School of MedicineHangzhou 310027People’s Republic of China State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin 150001People’s Republic of China Institute of Digital Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006People’s Republic of China

Hydrogel scaffolds have numerous potential applications in the tissue engineering ***,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical *** by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this ***,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent ***,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell ***,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT *** experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.

关键词： 3D printing Tough hydrogel scaffold Functional surface structure Tissue regeneration Biomaterials

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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

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Oncology Research 2025年第1期33卷 225-234页

作者： WEI ZHANG WEICHENG WANG RUI WANG XIAO HAN LIJUN ZHU WENJIE GUO YANHONG GU Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Department of Oncology The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou225300China

Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse ***,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against *** study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating *** and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against *** we employed various techniques to evaluate different aspects of the experimental *** was used to detect cell proliferation and angiogenesis in tumor *** blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor ***,immunofluorescence was employed to measure cytokine ***:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug *** was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell ***:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune *** study presents the justification for utilizing the fruquintinib and venetoclax combination in treating *** holds promise in being assimilated into anticancer medications for CRC.

关键词： Colorectal cancer(CRC) B-cell lymphoma protein 2(BCL2) Venetoclax Vascular endothelial growth factor receptor(VEGFR) Fruquintinib Anti-angiogenesis Immunotherapy

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The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

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Neural Regeneration Research 2025年第10期20卷 2741-2757页

作者： Qianzi Jin Suyu Wang Yujia Yao Qin Jiang Keran Li Department of Ophthalmology The Affiliated Eye Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina The Fourth School of Clinical Medicine Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts ***,the specific pathogenesis remains unclear,and effective early treatment options are consequently *** microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a *** intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other *** dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many *** recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the ***,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s ***,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular ***,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable *** such,the intestinal flora may play an important role in age-related macular *** the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic ***,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular ***-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the inte

关键词： age-related macular degeneration biological agents blinding eye disease dietary nutrition fecal microbial transplantation gut-eye axis intestinal flora metabolite microecology neurodegenerative disease

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Enhancing insights into Global Cancer Statistics 2022: implications for cancer control

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Science China Life Sciences 2025年第1期68卷 294-296页

作者： Jingtong Xu Runtian Wang Xiaoxiang Guan Department of Oncology the First Affiliated Hospital of Nanjing Medical University Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical University

Globally, there has been a marked escalation in tumor morbidity and mortality,cementing tumors as the predominant cause of death in numerous *** the current tumor burden across various regions is imperative to discern potential risk factors and formulate efficacious strategies for tumor ***, the International Agency for Research on Cancer(IARC) provided a status report on the global tumor burden,estimating the incidence and mortality of 36 cancers in 185 countries(Bray et al.,2024).

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Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit

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Science China Life Sciences 2025年

作者： Ruyu Wang Tianxiao Wang Ziyu Chen Jiandong Jiang Yifei Du Hua Yuan Yongchu Pan Yuli Wang Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University Department of stomatology Chongzhou People's Hospital Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular Diseases Ministry of Education International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical University Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College Department of Orthodontic The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University

Delayed tooth extraction socket(TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils(ANs), and neutrophil extracellular traps(NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium(CM) collected from berberine-treated human bone marrow mesenchymal stem cells(BBR-HB-CM) accelerated TES healing. BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2, impeded the formation of ANs and NETs, and modulated M2 macrophage efferocytosis in vivo and in vitro. Mechanistically, BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy. The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM. Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus. Overall, our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina hospital of stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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