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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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The potential mechanism and clinical application value of remote ischemic conditioning in stroke

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Neural Regeneration Research 2025年第6期20卷 1613-1627页

作者： Yajun Zhu Xiaoguo Li Xingwei Lei Liuyang Tang Daochen Wen Bo Zeng Xiaofeng Zhang Zichao Huang Zongduo Guo The first affiliated hospital of Chongqing Medical university ChongqingChina

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

关键词： Akt apoptosis autophagy cerebral perfusion cerebral vascular stenosis clinical transformation hemorrhagic stroke ischemic stroke neuroinflammation neuroprotection Notch1 PI3K remote ischemic conditioning stroke

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High quantum yield yellow emission carbon dots for the construction of blue light blocking films

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Chinese Chemical Letters 2025年第2期36卷 244-249页

作者： Liwen Wang Boyang Wang Siyu Lu Shubo Lv Xiaoli Qu Neonatal Disease Screening Unit The Third Affiliated Hospital of Zhengzhou University College of Chemistry Pingyuan Laboratory Zhengzhou University Erythrocyte Biology Laboratory School of Life Sciences Zhengzhou University

White light illumination is essential in daily life, however, the substantial amount of blue light it contains can damage human eyes. Therefore, it is important to block this high-energy blue light to protect visual health. In this study, yellow-emitting carbon dots(CDs) with a quantum yield exceeding 94% were synthesized using citric acid and urea. These CDs effectively absorb blue light. By incorporating them into polystyrene, multiple films termed CDs-based blue light blocking films(CBFs) were developed, each offering different levels of blue light absorption. These CBFs exhibited excellent transparency and efficient blue light filtering capabilities. This study highlights the potential of high quantum yield CDs, which specifically absorb blue light, as foundational materials for developing light-blocking solutions against highenergy short-wavelength light.

关键词： Blue light blocking Carbon dots Composite film Controllable preparation High quantum yield

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Swelling and erosion assisted sustained release of tea polyphenol from antibacterial ultrahigh molecular weight polyethylene for joint replacement

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Chinese Chemical Letters 2025年第2期36卷 344-348页

作者： Yue Ren Kang Li Yi-Zi Wang Shao-Peng Zhao Shu-Min Pan Haojie Fu Mengfan Jing Yaming Wang Fengyuan Yang Chuntai Liu State Key Laboratory of Structural Analysis Optimization and CAE Software for Industrial EquipmentNational Engineering Research Center for Advanced Polymer Processing TechnologyZhengzhou University Department of Stomatology The First Affiliated Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical SciencesZhengzhou University

The considerable hazard posed by periprosthetic joint infections underlines the urgent need for the rapid advancement of in-situ drug delivery systems within joint materials. However, the pursuit of sustained antibacterial efficacy remains a formidable challenge. In this context, we proposed a novel strategy that leverages swelling and erosion mechanisms to facilitate drug release of drug-loaded ultrahigh molecular weight polyethylene(UHMWPE), thereby ensuring its long-lasting antibacterial *** oxide(PEO), a hydrophilic polymer with fast hydrating ability and high swelling capacity, was incorporated in UHMWPE alongside the antibacterial tea polyphenol(epigallocatechin gallate,EGCG as representative). The swelling of PEO enhanced water infiltration into the matrix, while the erosion of PEO balanced the release of the encapsulated EGCG, resulting in a steady release. The behavior was supported by the EGCG release profiles and the corresponding fitted release kinetic *** demonstrated by segmented antibacterial assessments, the antibacterial efficiency was enhanced 2to 3 times in the PEO/EGCG/UHMWPE composite compared to that of EGCG/UHMWPE. Additionally, the PEO/EGCG/UHMWPE composite exhibited favorable biocompatibility and mechanical performance, making it a potential candidate for the development of drug-releasing joint implants to combat prosthetic bacterial infections.

关键词： Antibacterial Joint replacement PEO Tea polyphenol UHMWPE

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Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina university of Chinese Academy of Sciences BeijingChina Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

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N-Benzyl arylamide derivatives as novel and potent tubulin polymerization inhibitors against gastric cancers: Design,structure–activity relationships and biological evaluations

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Chinese Chemical Letters 2025年第2期36卷 256-261页

作者： Jian Song Shenghui Wang Qiuge Liu Xiao Wang Shuo Yuan Hongmin Liu Saiyang Zhang School of Basic Medical Sciences Zhengzhou University Children's hospital affiliated to zhengzhou university Henan Children's Hospital Zhengzhou Children's Hospital School of Pharmaceutical Sciences Institute of Drug Discovery & Development Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education) Zhengzhou University State Key Laboratory of Esophageal Cancer Prevention & Treatment

In this work,we employed a ring-opening strategy to develop a series of novel N-benzyl arylamide derivatives as tubulin polymerization ***,13n （MY-1388） exhibited remarkable antiproliferative potency on fifteen human cancer cell lines,with half maximal inhibitory concentration (IC50)values ranging from 8 nmol/L to 48 nmol/***,13n effectively suppressed tubulin polymerization by targeting the colchicine-binding site (IC50=0.62μmol/L).13n also exhibited significant inhibition of cell colony formation,as well as displayed potent effects on inducing G2/M phase cell cycle arrest and promoting ***,13n exhibited enhanced and adequate liver microsomal stability in human and rat liver microsomes,and also exhibited a moderate half-life (T1/2=0.938 h) in ***,13n demonstrated effective antitumor effects in vivo in suppressing tumor growth in the MGC-803xenograft model (tumor growth inhibition （TGI） value was 76.4%at the dosage of 30 mg kg-1day-1)with a good safety ***,these results revealed that 13n represents a promising tubulin polymerization inhibitor that deserves further investigation for its efficacy in treating gastric cancers.

关键词： Antiproliferative activities CA-4 Colchicine binding site N-Benzyl arylamide Tubulin

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Glial cell line-derived neurotrophic factor improves impaired colonic motility in experimental colitis mice through connexin 43

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World Journal of Gastroenterology 2025年第8期31卷 82-95页

作者： Wei Yang Rui Liu Feng Xu Department of Gastroenterology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Medical School Xiangyang Vocational and Technical CollegeXiangyang 441021Hubei ProvinceChina

BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of *** suggests that glial cell line-derived neurotrophic factor(GDNF)plays a role in restoring colonic *** To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43(Cx43).METHODS An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate(DSS).The measurement of colonic transit time was conducted,and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin *** mice were treated with exogenous GDNF and Gap 19,a selective Cx43 *** Cx43 and GDNF levels were detected via immunofluorescence,immunohistochemistry,and real-time polymerase chain *** levels of inflammatory markers,including interleukin-1β,tumor necrosis factor-α,interleukin-6,and C-reactive protein,were quantified using enzyme-linked immunosorbent *** Experimental colitis was successfully induced using DSS,and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group(P<0.01).GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice(P<0.05).In the UC+Gap19+GDNF group,colitis symptoms,colonic transit time,and inflammatory marker levels remained comparable to those in the UC group,indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap *** GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated *** holds promise as a therapeutic option for improving colonic motility in patients with colitis.

关键词： Glial cell line-derived neurotrophic factor Ulcerative colitis Colonic motility Connexin 43 Dextran sodium sulfate model

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Long noncoding RNA LINC01106 promotes lung adenocarcinoma progression via upregulation of autophagy

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Oncology Research 2025年第1期33卷 171-184页

作者： GENGYUN SUN YIPING ZHENG JIANFENG CAI JIE GAO LIE DONG XIANGBIN ZHANG YINGHUI HUANG Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Anhui Medical UniversityHefei230022China Department of Respiratory and Critical Care Medicine Nanping First Hospital Affiliated to Fujian Medical UniversityNanping353006China

Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain ***:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was *** cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor *** downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)***,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD ***:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell *** silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of ***,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its *** assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 ***:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.

关键词： LINC01106 TAF15 TEAD4 ATG5 Lung adenocarcinoma(LUAD) Non-small cell lung cancer(NSCLC)

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Clinical significance of Ki-67 in patients with lung adenocarcinoma in situ complicated by type 2 diabetes

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World Journal of Diabetes 2025年第2期16卷 114-122页

作者： Ke Chen Ge Wang Jing-Cheng Hu Ying-Yi Zhou Hai-Tao Ma Department of Thoracic Surgery The First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of Endocrine The First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung *** To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by *** One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the Department of Thoracic Surgery and Endocrinology of the first affiliated hospital of Soochow university from November 2021 to December 2022 were ***-67 expression was compared among the *** Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by *** K et ***67 in patients with AIS complicated by T2DM WJD https://*** 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS ***,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.

关键词： Ki-67 Type 2 diabetes mellitus Lung adenocarcinoma in situ Immunohistochemistry Prognostic marker

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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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