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MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2123-2140页

作者： Hong-Xia Bai Xue-Mei Qiu Chun-Hong Xu Jian-Qiang Guo Department of Gastroenterology The Second Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina Department of Gastroenterology Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina Department of Reproductive center Zaozhuang Maternal and Child Health Care HospitalZaozhuang 277000Shandong ProvinceChina

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regu

关键词： Gastric cancer MicroRNA-145-5p Serpin family E member 1 Epithelial-mesenchymal transition Proliferation Extracellular signal-regulated kinase-1/2

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Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 493-513页

作者： Ying-Qian Ma Ming Zhang Zhen-Hua Sun Hong-Yue Tang Ying Wang Jiang-Xue Liu Zhan-Xue Zhang Chao Wang Department of Oncology Hebei General HospitalShijiazhuang 050051Hebei ProvinceChina School of Graduate Studies Hebei Medical UniversityShijiazhuang 050017Hebei ProvinceChina Clinical Medical Research center Hebei General HospitalShijiazhuang 050051Hebei ProvinceChina Department of Gastrointestinal Surgery Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regula

关键词： Resveratrol Gastric cancer Network pharmacology Bioinformatics Molecular docking

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Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 518-528页

作者： Nan Sun Bi-Bo Tan Yong Li Department of blood Transfusion The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hubei ProvinceChina Third Department of General Surgery the Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this disease.LATS2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric cancer.AIM To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM staging.METHODS A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted.The patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic model.The performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision curves.RESULTS The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set.Area under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination ability.Calibration plots confirmed the high concordance between the predictions and actual survival outcomes.CONCLUSION We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery.This model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical outcomes.Further validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.

关键词： Gastric cancer LATS2 Column line graph Prognosis Advanced gastric cancer survival Molecular biomarkers Predictive analytics in oncology Survival analysis

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Automatic recognition of depression based on audio and video:A review

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World Journal of Psychiatry 2024年第2期14卷 225-233页

作者： Meng-Meng Han Xing-Yun Li Xin-Yu Yi Yun-Shao Zheng Wei-Li Xia Ya-Fei Liu Qing-Xiang Wang Shandong Mental Health center Shandong UniversityJinan 250014Shandong ProvinceChina Key Laboratory of Computing Power Network and Information Security Ministry of EducationShandong Computer Science Center(National Supercomputer Center in Jinan)Qilu University of Technology(Shandong Academy of Sciences)Jinan 250353Shandong ProvinceChina Shandong Engineering Research center of Big Data Applied Technology Faculty of Computer Science and TechnologyQilu University of Technology(Shandong Academy of Sciences)Jinan 250353Shandong ProvinceChina Shandong Provincial Key Laboratory of Computer Networks Shandong Fundamental Research Center for Computer ScienceJinan 250353Shandong ProvinceChina Department of Ward Two Shandong Mental Health CenterShandong UniversityJinan 250014Shandong ProvinceChina

Depression is a common mental health disorder.With current depression detection methods,specialized physicians often engage in conversations and physiological examinations based on standardized scales as auxiliary measures for depression assessment.Non-biological markers-typically classified as verbal or non-verbal and deemed crucial evaluation criteria for depression-have not been effectively utilized.Specialized physicians usually require extensive training and experience to capture changes in these features.Advancements in deep learning technology have provided technical support for capturing non-biological markers.Several researchers have proposed automatic depression estimation(ADE)systems based on sounds and videos to assist physicians in capturing these features and conducting depression screening.This article summarizes commonly used public datasets and recent research on audio-and video-based ADE based on three perspectives:Datasets,deficiencies in existing research,and future development directions.

关键词： Depression recognition Deep learning Automatic depression estimation System Audio processing Image processing Feature fusion Future development

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Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2610-2630页

作者： Ze-Hao Yu Lei-Ming Zhang Zhi-Qi Dai Meng-Na Zhang Si-Ming Zheng Health Science center The First Affiliated Hospital of Ningbo UniversityNingbo 315000Zhejiang ProvinceChina Health Science center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina College of Medicine The First Affiliated Hospital of Zhejiang UniversityHangzhou 310058Zhejiang ProvinceChina

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

关键词： Signet ring cell carcinoma Locally advanced gastric cancer Adjuvant chemotherapy Nomogram Epidemiology Overall survival

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Effect of navigation endoscopy combined with threedimensional printing technology in the treatment of orbital blowout fractures

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 570-576页

作者： Jin-Hai Yu Yao-Hua Wang Qi-Hua Xu Chao Xiong An-An Wang Hong-Fei Liao School of Optometry Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina The Affiliated Eye Hospital Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina Jiangxi Clinical Research center for Ophthalmic Disease Nanchang 330006Jiangxi ProvinceChina Jiangxi Research Institute of Ophthalmology and Visual Science Nanchang 330006Jiangxi ProvinceChina Jiangxi Provincial Key Laboratory for Ophthalmology Nanchang 330006Jiangxi ProvinceChina

●AIM:To explore the combined application of surgical navigation nasal endoscopy(NNE)and three-dimensional printing technology(3DPT)for the adjunctive treatment of orbital blowout fractures(OBF).●METHODS:Retrospective analysis was conducted on the data of patients with OBF who underwent surgical treatment at the Affiliated Eye Hospital of Nanchang University between July 2012 and November 2022.The control group consisted of patients who received traditional surgical treatment(n=43),while the new surgical group(n=52)consisted of patients who received NNE with 3DPT.The difference in therapeutic effects between the two groups was evaluated by comparing the duration of the operation,best corrected visual acuity(BCVA),enophthalmos difference,recovery rate of eye movement disorder,recovery rate of diplopia,and incidence of postoperative complications.●RESULTS:The study included 95 cases(95 eyes),with 63 men and 32 women.The patients’age ranged from 5 to 67y(35.21±15.75y).The new surgical group and the control group exhibited no statistically significant differences in the duration of the operation,BCVA and enophthalmos difference.The recovery rates of diplopia in the new surgical group were significantly higher than those in the control group at 1mo[OR=0.03,95%CI(0.01–0.15),P<0.0000]and 3mo[OR=0.11,95%CI(0.03–0.36),P<0.0000]postoperation.Additionally,the recovery rates of eye movement disorders at 1 and 3mo after surgery were OR=0.08,95%CI(0.03–0.24),P<0.0000;and OR=0.01,95%CI(0.00–0.18),P<0.0000.The incidence of postoperative complications was lower in the new surgical group compared to the control group[OR=4.86,95%CI(0.95–24.78),P<0.05].●CONCLUSION:The combination of NNE and 3DPT can shorten the recovery time of diplopia and eye movement disorder in patients with OBF.

关键词： orbital blowout fracture three-dimensional printing endoscopy surgical navigation

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Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

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Neural Regeneration Research 2024年第1期19卷 161-170页

作者： Guoqiang Zhang Jianan Lu Jingwei Zheng Shuhao Mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian Fang Jun Yu Department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Neurosurgery Huashan Hospital of Fudan University School of MedicineShanghaiChina Clinical Research center for Neurological Diseases of Zhejiang province HangzhouZhejiang ProvinceChina Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases HangzhouZhejiang ProvinceChina

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

关键词： intracerebral hemorrhage macrophage microglia neuroinflammation phagocytosis PI3K/AKT/mTOR signaling pathway Spi1 transcriptomics

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Analysis of the potential biological value of pyruvate dehydrogenase E1 subunitβin human cancer

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 144-181页

作者： Yao Rong Song-Hua Liu Ming-Zheng Tang Zhi-Hang Wu Guo-Rong Ma Xiao-Feng Li Hui Cai First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer.In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.METHODS Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)database.Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases.Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients.The correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also analyzed.Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)genes.The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was performed.The study also validated the level of mRNA or protein expression of PDHB in several cancers.Finally,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver cancer.RESULTS PDHB was significantly and differently expressed in most cancers.PDHB was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinoma,and brain lower grade glioma.In some cancers,P

关键词： Cuprotosis Pyruvate dehydrogenase E1 subunitβ Pan-cancer Prognosis Liver cancer

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Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

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Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang Department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina Fujian Academy of Medical Science FuzhouFujian ProvinceChina Key Testing Laboratory of Fujian province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin

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