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早期糖尿病肾病患者血清鸢尾素、高迁移率族蛋白Box1、神经调节蛋白4水平变化及临床意义
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作者 连艳珍 李文悌 《临床研究》 2024年第9期133-136,共4页
目的探讨早期糖尿病肾病(DKD)患者血清鸢尾素、高迁移率族蛋白B1(HMGB1)、神经调节蛋白4(NRG4)水平变化及临床意义。方法选取2022年3月至2024年3月郑州大学第一附属医院收治的80例早期DKD患者作为早期DKD组,选取同期50例健康体检人员作... 目的探讨早期糖尿病肾病(DKD)患者血清鸢尾素、高迁移率族蛋白B1(HMGB1)、神经调节蛋白4(NRG4)水平变化及临床意义。方法选取2022年3月至2024年3月郑州大学第一附属医院收治的80例早期DKD患者作为早期DKD组,选取同期50例健康体检人员作为健康对照组,对两组人口学特征、临床资料进行收集,对血清鸢尾素、HMGB1、NRG4水平进行检测,进行单因素与多因素Logistic回归分析,明确早期DKD发生的危险因素。结果两组患者年龄、性别、饮酒史、冠心病史、吸烟史、高血压史、舒张压、收缩压、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平比较差异无统计学意义(P>0.05);早期DKD组的血清鸢尾素、NRG4水平更低,HMGB1水平更高,差异均有统计学意义(P<0.05);多因素二元Logistic回归分析结果显示,血清鸢尾素(OR=0.568;95%CI:0.389~0.829)、NRG4(OR=0.456;95%CI:0.246~0.845)是影响早期DKD发生的保护性因素,差异具有统计学意义(P<0.05),HMGB1(OR=2.976;95%CI:2.664~3.325)是独立危险因素,差异具有统计学意义(P<0.05)。结论早期DKD患者血清鸢尾素、NRG4水平更低,HMGB1水平更高,临床可用血清鸢尾素、HMGB1、NRG4水平对早期DKD发生进行评估。 展开更多
关键词 早期糖尿病肾病 血清鸢尾素 高迁移率族蛋白box1 神经调节蛋白4 临床意义
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Effects of Ethyl Pyruvate on High Mobility Group Box1 gene expression in septic lung of rat
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作者 Lian Zeng Shanglong Yao Dong Liu Yuelan Wang 《Journal of Nanjing Medical University》 2005年第6期316-320,共5页
Objective: Ethyl Pyruvate (EP) has been shown to be an effective anti-inflammatory agent in a variety of model systems. The aim of this study was to investigate the effects of EP on High Mobility Group Box1(HMGB1) gen... Objective: Ethyl Pyruvate (EP) has been shown to be an effective anti-inflammatory agent in a variety of model systems. The aim of this study was to investigate the effects of EP on High Mobility Group Box1(HMGB1) genes expression and the possible mechanisms of EP protecting against acute lung injury induced by sepsis. Methods: Forty Wistar rats were randomly divided into normal controls,sham operation,acute lung injury,and EP treatment (40 mg/kg intra-peritoneally every 6 hrs) groups. At the time points of 24 hours the animals in each group were sacrificed, and the lungs were harvested. Wet/dry lung weight ratio, the protein in the bronchoalveolar lavage fluid(BALF),and pulmonary permeability index(PPI) were determined. The histological morphology of lung was observed under microscope. The expression of HMGB1 mRNA was measured using semi-quantitative RT-PCR. Results: EP treatment decreased wet/dry lung weight ratio, the protein in the BALF,and PPI (P<0.01). The histological morphology of lung injury was ameliorated. EP significantly inhibited the HMGB1 mRNA expression(P<0.01). HMGB1 mRNA expression in lungs positively correlation with wet/dry lung weight ratio, the protein in the BALF,and PPI. Conclusion: EP administered inhibits HMGB1 mRNA expression, and protects the lungs against acute injury induced by sepsis. 展开更多
关键词 Ethyl Pyruvate acute lung injury High Mobility Group Boxl
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HMGB1在类青光眼引流阀植入术后瘢痕化中的作用机制 被引量:1
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作者 刘思远 曹凡 +5 位作者 丁晶晶 王传喜 丁碧青 梁坤 蒋正轩 鲍宁 《国际眼科杂志》 2024年第1期18-23,共6页
目的:探究高迁移率族蛋白1(HMGB1)在类青光眼引流阀植入术后瘢痕组织中的动态表达,揭示HMGB1在青光眼术后瘢痕化中的作用及其可能的作用机制。方法:将60只新西兰大白兔随机分为空白对照组(n=20)、模型组(n=20,结膜囊下硅胶植入)、模型... 目的:探究高迁移率族蛋白1(HMGB1)在类青光眼引流阀植入术后瘢痕组织中的动态表达,揭示HMGB1在青光眼术后瘢痕化中的作用及其可能的作用机制。方法:将60只新西兰大白兔随机分为空白对照组(n=20)、模型组(n=20,结膜囊下硅胶植入)、模型给药组(n=20,硅胶植入联合5-氟尿嘧啶注射)。分别于术后4、8 wk取球结膜组织,采用HE染色和Masson染色检测结膜组织中成纤维细胞和胶原纤维增生及分布情况;免疫组织化学染色检测结膜组织中HMGB1、转化生长因子(TGF)-β1、Smad3、α-平滑肌肌动蛋白(α-SMA)的分布及变化情况;RT-PCR和Western blot检测结膜组织中HMGB1、TGF-β1、Smad3、α-SMA mRNA及蛋白的表达。结果:HE染色和Masson染色结果显示,4、8 wk模型组较空白对照组结膜组织中炎症细胞、成纤维细胞及胶原纤维增生明显,而4、8 wk模型给药组结膜组织中成纤维细胞及胶原纤维增生相对于同时期模型组明显减少。免疫组织化学染色结果显示,4、8 wk模型组结膜组织中可见HMGB1、TGF-β1、Smad3、α-SMA蛋白表达,呈棕褐色染色,8 wk模型组染色更深,而4、8 wk模型给药组较同时期模型组阳性染色程度下降。4、8 wk模型组结膜组织中HE染色成纤维细胞数与免疫组织化学染色HMGB1的表达水平均呈正相关(r=0.602、0.703,均P<0.05)。RT-PCR和Western blot结果显示,4、8 wk模型组结膜组织中HMGB1、TGF-β1、Smad3、α-SMA mRNA及蛋白表达量显著高于空白对照组(均P<0.05),4、8 wk模型给药组结膜组织中HMGB1、TGF-β1、Smad3、α-SMA mRNA及蛋白表达量显著低于同时期模型组(均P<0.05)。模型组和模型给药组中HMGB1与TGF-β1、Smad3的mRNA表达水平具有正相关性(均P<0.05)。结论:类青光眼引流阀植入术后随时间延长HMGB1表达升高,HMGB1在青光眼术后具有致瘢痕形成的作用,并可能通过TGF-β/Smad信号通路参与瘢痕化的发生发展。 展开更多
关键词 高迁移率族蛋白1(HMGB1) 青光眼引流阀植入术 瘢痕化 5-氟尿嘧啶 TGF-Β/SMAD信号通路
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MiR-142-3p Regulates ILC1s by Targeting HMGB1 via the NF-κB Pathway in a Mouse Model of Early Pregnancy Loss 被引量:1
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作者 Xiang-li PANG Jie LI +2 位作者 Jing WANG Si-si YAN Jing YANG 《Current Medical Science》 SCIE CAS 2024年第1期195-211,共17页
Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target... Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice. 展开更多
关键词 maternal-fetal interface group 1 innate lymphoid cells(ILCis) high mobility group box 1(HMGB1) miR-142-3p ABORTION
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Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage 被引量:1
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作者 Yue-Ying Wang Ke Li +5 位作者 Jia-Jun Wang Wei Hua Qi Liu Yu-Lan Sun Ji-Ping Qi Yue-Jia Song 《World Journal of Diabetes》 SCIE 2024年第9期1979-2001,共23页
BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patie... BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain. 展开更多
关键词 Bone marrow mesenchymal stem cells Exosome Diabetic cerebral hemorrhage Neuroinflammation MicroRNA-129-5p High mobility group box 1
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心肌缺血再灌注损伤大鼠HMGB1表达水平的Meta分析
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作者 岑团 刘燕 黄照河 《右江医学》 2024年第5期451-458,共8页
目的对心肌缺血再灌注损伤(MIRI)大鼠高迁移率族蛋白B1(HMGB1)表达水平进行Meta分析。方法在PubMed、Embase及中国国家知识基础设施(CNKI)数据库检索相关文章,最终共纳入16篇文献,从这些文章中提取假手术组、模型组、预处理组的样本量... 目的对心肌缺血再灌注损伤(MIRI)大鼠高迁移率族蛋白B1(HMGB1)表达水平进行Meta分析。方法在PubMed、Embase及中国国家知识基础设施(CNKI)数据库检索相关文章,最终共纳入16篇文献,从这些文章中提取假手术组、模型组、预处理组的样本量、均数和标准差,采用SYRCLE动物实验风险评估工具进行方法学质量评价,应用Stata12.0软件进行Meta分析。结果MIRI大鼠模型组HMGB1表达水平显著高于假手术组(SMD=8.66,95%CI:6.49~10.82,P<0.001),MIRI大鼠预处理组HMGB1表达水平明显低于模型组(SMD=-3.33,95%CI:-4.22~-2.44,P<0.001)。亚组分析表明,不同预处理方式可能导致异质性存在。敏感性分析显示Meta分析结果可信度较高,而漏斗图显示存在发表偏倚。结论MIRI大鼠HMGB1表达水平升高,通过治疗可降低MIRI大鼠HMGB1表达水平。 展开更多
关键词 心肌缺血再灌注损伤 高迁移率族蛋白B1 预处理 META分析
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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation
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作者 Hanki Kim Bum Jun Kim +4 位作者 Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi 《Neural Regeneration Research》 SCIE CAS 2025年第1期107-115,共9页
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex... High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1. 展开更多
关键词 central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 INFLAMMATION neural stem cells NEURODEVELOPMENT oligodendrocyte progenitor cells redox status REGENERATION
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N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats
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作者 Yu-Ze Zhao Xue-Ning Zhang +7 位作者 Yi Yin Pei-Lun Xiao Meng Gao Lu-Ming Zhang Shuan-Hu Zhou Shu-Na Yu Xiao-Li Wang Yan-Song Zhao 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第2期228-238,共11页
AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for a... AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease. 展开更多
关键词 retinal diseases retinal ischemia—reperfusion injury N-ACETYLSEROTONIN high mobility group box 1 receptor for advanced glycation end-products nuclear factor-κB RATS
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Glycyrrhizic acid alleviates lung injury in sepsis through SIRT1/HMGB1 pathway
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作者 BINGJIE LIN XIAOBO YING +1 位作者 CHUANLING ZHANG GUOJUN ZHANG 《BIOCELL》 SCIE 2024年第11期1613-1623,共11页
Objectives:This study explores the protective effects of glycyrrhizic acid(GA)on sepsis-induced cellular damage and inflammation in acute lung injury(ALI),specifically through the modulation of the sirtuin 1(SIRT1)and h... Objectives:This study explores the protective effects of glycyrrhizic acid(GA)on sepsis-induced cellular damage and inflammation in acute lung injury(ALI),specifically through the modulation of the sirtuin 1(SIRT1)and high mobility group box 1(HMGB1)pathway.Methods:The study employed two experimental models:lipopolysaccharide(LPS)-induced BEAS-2B human lung epithelial cells and cecal ligation and puncture(CLP)rats,to simulate sepsis conditions.The cell model involved treatments with LPS,GA,control siRNA(si-NC),and SIRT1-specific siRNA(si-SIRT1).Evaluations included cell viability,apoptosis,and cytokine production.In the rat model,treatments included GA and the SIRT1 inhibitor EX527,with assessments on lung tissue damage,inflammation,and protein expression using Western blot and co-immunoprecipitation(Co-IP)analysis.Results:LPS exposure significantly reduced SIRT1 mRNA levels and cell viability in BEAS-2B cells,which effects were reversed by cotreatment with GA and si-NC but negated by si-SIRT1.LPS also induced apoptosis and increased pro-inflammatory cytokines and HMGB1 expression,which were mitigated by GA and si-NC and exacerbated by si-SIRT1.In CLP rats,GA treatment decreased lung tissue damage,inflammatory cytokines,and HMGB1 expression,and enhanced SIRT1 levels.However,these protective effects were reversed when GA was combined with EX527.Conclusion:GA demonstrates significant protective effects against LPS-induced damage and inflammation in lung cells and tissue by modulating the SIRT1-HMGB1 pathway.This suggests that GA could be a potential therapeutic strategy for treating sepsis and related inflammatory conditions. 展开更多
关键词 Glycyrrhizin Acid SEPSIS sirtuin 1(SIRT1) high mobility group box 1(HMGB1)
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Diagnostic significance of serum levels of serum amyloid A,procalcitonin,and high-mobility group box 1 in identifying necrotising enterocolitis in newborns
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作者 Li-Ming Guo Zhi-Hui Jiang +1 位作者 Hong-Zhen Liu Lei Zhang 《World Journal of Gastrointestinal Surgery》 SCIE 2024年第7期2003-2011,共9页
BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emer... BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC. 展开更多
关键词 Serum amyloid A PROCALCITONIN High-mobility group box 1 Necrotising enterocolitis in newborns Serum biomarkers
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Autocrine IL-8 Contributes to Propionibacterium Acnes-induced Proliferation and Differentiation of HaCaT Cells via AKT/FOXO1/Autophagy
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作者 Xiu-qin YU Jin-zhu MAO +5 位作者 Shu-yun YANG Lu WANG Chang-zhi YANG Lei HUANG Qi-hong QIAN Ting-ting ZHU 《Current Medical Science》 SCIE CAS 2024年第5期1058-1065,共8页
Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the product... Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV. 展开更多
关键词 acne vulgaris Proprionibacterium acnes KERATINOCYTE INTERLEUKIN-8 C-X-C motif chemokine receptor 2 protein kinase B forkhead box O1 AUTOPHAGY
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脑胶质瘤患者围术期血清HMGB1、MMP-9水平变化及其与术后颅内感染的关系探究
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作者 王旭 《中国医药导刊》 2024年第9期863-867,共5页
目的:探究脑胶质瘤患者围术期血清高迁移率族B1蛋白(HMGB1)、基质金属蛋白酶-9(MMP-9)水平变化及其与术后颅内感染的关系。方法:选取我院2020年7月至2022年1月择期行肿瘤切除术的脑胶质瘤患者115例,根据胶质瘤分级系统分为低级别组56例(... 目的:探究脑胶质瘤患者围术期血清高迁移率族B1蛋白(HMGB1)、基质金属蛋白酶-9(MMP-9)水平变化及其与术后颅内感染的关系。方法:选取我院2020年7月至2022年1月择期行肿瘤切除术的脑胶质瘤患者115例,根据胶质瘤分级系统分为低级别组56例(Ⅰ-Ⅱ级)与高级别组59例(Ⅲ-Ⅳ级),比较两组患者围术期血清HMGB1及MMP-9水平;根据术后颅内感染情况分为感染组21例与未感染组94例,采用多因素Logistic回归分析脑胶质瘤患者术后发生颅内感染的危险因素,绘制受试者工作特征(ROC)曲线评估血清HMGB1及MMP-9水平对脑胶质瘤患者术后颅内感染的诊断价值。结果:与术前比,两组患者术后1 d、7 d血清HMGB1及MMP-9水平均升高(P<0.05),高级别组患者围术期血清HMGB1及MMP-9水平均高于低级别组(P<0.05);感染组患者年龄>65岁、合并糖尿病、病理分期Ⅲ-Ⅳ期、手术时间>6h占比均高于未感染组患者(P<0.05);经多因素Logistic回归分析显示:年龄>65岁、病理分期Ⅲ-Ⅳ期是脑胶质瘤患者术后并发颅内感染的危险因素(P<0.05);感染组患者术后1d、7d血清HMGB1及MMP-9水平均高于未感染组(P<0.05);血清HMGB1与MMP-9水平联合评估患者术后颅内感染的曲线下面积(AUC)为0.875,敏感度为90.48%、特异性为73.40%。结论:高级别脑胶质瘤患者血清HMGB1及MMP-9水平明显高于低级别患者,且术后患者血清HMGB1及MMP-9的高表达与颅内感染密切相关,临床可通过检测血清HMGB1及MMP-9水平评估患者术后颅内感染情况。 展开更多
关键词 脑胶质瘤 围术期 血清高迁移率族B1蛋白 基质金属蛋白酶-9 颅内感染
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FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury
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作者 Mi Zhou Yang-Wu-Yue Liu +11 位作者 Yu-Hang He Jing-Yu Zhang Hao Guo Hao Wang Jia-Kui Ren Yi-Xun Su Teng Yang Jia-Bo Li Wen-Hui He Peng-Jiao Ma Man-Tian Mi Shuang-Shuang Dai 《Military Medical Research》 SCIE CAS CSCD 2024年第4期521-542,共22页
Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulatio... Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI. 展开更多
关键词 Traumatic brain injury(TBI) NEUTROPHIL Forkhead box protein O1(FOXO1) Acute stage Chronic stage
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Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization
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作者 Fei Liu Jing Xiao +4 位作者 Lei-Hui Chen Yu-Yue Pan Jun-Zhang Tian Zhi-Ren Zhang Xiao-Chun Bai 《World Journal of Stem Cells》 SCIE 2024年第3期287-304,共18页
BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling ... BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies. 展开更多
关键词 Human dental pulp stem cells Prevascularized organoids Integrated analyses ANGIOGENESIS Forkhead box protein O1
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糖尿病肾病患者外周血单个核细胞miR-92b-5p水平与高迁移率族蛋白Box1/核因子κB通路的相关性
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作者 白媛媛 史嫣 《慢性病学杂志》 2022年第12期1809-1812,共4页
目的探讨糖尿病肾病(diabetic nephropathy,DN)患者外周血单个核细胞中miR-92b-5p水平与高迁移率族蛋白Box1(high mobility group protein box1,HMGB1)/核因子κB(nuclear factor-κB,NF-κB)通路的相关性。方法选择2020年3月-2021年2... 目的探讨糖尿病肾病(diabetic nephropathy,DN)患者外周血单个核细胞中miR-92b-5p水平与高迁移率族蛋白Box1(high mobility group protein box1,HMGB1)/核因子κB(nuclear factor-κB,NF-κB)通路的相关性。方法选择2020年3月-2021年2月在河南省老干部康复医院就诊的197例2型糖尿病患者作为研究对象,合并DN患者96例作为DN组,无DN患者101例作为单纯糖尿病组,选择健康受检者100例作为对照组。采用实时定量PCR检测外周血单个核细胞中miR-92b-5p相对表达量,采用酶联免疫吸附法检测血清中HMGB1、NF-κB水平。采用受试者工作特征曲线分析miR-92b-5p对DN的诊断价值。结果DN组和单纯糖尿病组患者外周血单个核细胞中miR-92b-5p相对表达量显著低于对照组,DN组患者外周血单个核细胞中miR-92b-5p相对表达量显著低于单纯糖尿病组,差异有统计学意义(P<0.05)。DN组和单纯糖尿病组患者血清中HMGB1、NF-κB水平显著高于对照组,DN组患者血清中HMGB1、NF-κB水平显著高于单纯糖尿病组,差异有统计学意义(P<0.05)。受试者工作特征曲线结果显示,曲线下面积为0.935(95%CI 0.900~0.971,P<0.01)。DN患者miR-92-5p相对表达量与血清HMGB1、NF-κB水平均成负相关(r值分别为-0.376、-0.417,P<0.05)。结论miR-92-5p参与DN的疾病调控过程,且与HMGB1/NF-κB通路表达密切相关,可作为DN潜在的诊断靶标。 展开更多
关键词 糖尿病肾病 微小RNA 高迁移率族蛋白box1 核因子ΚB
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高迁移率族蛋白B1对体外氧糖剥夺/复氧复糖后大鼠脊髓反应性星形胶质细胞不同亚型的作用 被引量:2
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作者 王丽平 李季声 +4 位作者 邓黎 王志强 刘晋明 邓晨 孙麟 《中国组织工程研究》 CAS 北大核心 2023年第24期3831-3837,共7页
背景:脊髓损伤后星形胶质细胞可以活化为A1、A2两种不同亚型的反应性星形胶质细胞,其在基因、分子和功能方面完全不同,对脊髓损伤修复的具体作用也不同。已经证明高迁移率族蛋白B1(high-mobility group box 1,HMGB1)是脊髓损伤后的重要... 背景:脊髓损伤后星形胶质细胞可以活化为A1、A2两种不同亚型的反应性星形胶质细胞,其在基因、分子和功能方面完全不同,对脊髓损伤修复的具体作用也不同。已经证明高迁移率族蛋白B1(high-mobility group box 1,HMGB1)是脊髓损伤后的重要炎症、免疫因子,可以引起细胞水肿、炎症反应及细胞凋亡等,但其对A1、A2两种反应性星形胶质细胞的影响尚不清楚。目的:观察大鼠脊髓星形胶质细胞经氧糖剥夺/复氧复糖(oxygen-glucose deprivation/restoration,OGD/R)后激活为反应性星形胶质细胞的情况,探索损伤后产生的HMGB1对反应性星形胶质细胞不同亚型的影响及作用机制。方法:培养大鼠脊髓星形胶质细胞至第3代,经过OGD/R处理后观察细胞的形态变化,划痕实验检测细胞的迁移能力,Western blot检测反应性星形胶质细胞的激活情况。抑制HMGB1表达后分为5组:正常组、OGD6 h/R6 h组、HMGB1干扰组、阴性序列组、OGD6 h/R6 h+12μmol/L HMGB1抑制剂丙酮酸乙酯组,Western blot和细胞免疫荧光法检测反应性星形胶质细胞不同亚型特征性蛋白C3、S100A10的表达,划痕实验检测细胞的迁移能力。为探究HMGB1对反应性星形胶质细胞影响的可能机制,分为正常组、OGD6 h/R6 h组、OGD6 h/R6 h+5μmol/L TLR4抑制剂CLI-095组、OGD6 h/R6 h+5μmol/L NF-κB抑制剂BAY 11-7082组,Western blot检测TLR4、NF-κB、C3和S100A10的表达。结果与结论:(1)氧糖剥夺后细胞体积减小,边缘皱缩,迁移能力增加,复氧复糖后,细胞体积增大,活化为A1、A2型反应性星形胶质细胞,OGD6 h/R6 h时S100A10表达最多,OGD6 h/R12 h时C3表达最多(P<0.05);(2)沉默或抑制HMGB1的表达对反应性星形胶质细胞的影响:与OGD6 h/R6 h组相比,抑制HMGB1使C3表达减少(P<0.05),S100A10表达增多(P<0.05),细胞的迁移能力增强;(3)与OGD6 h/R6 h组相比,OGD6 h/R6 h+CLI 095组TLR4表达减少(P<0.05),OGD6 h/R6 h+CLI 095组和OGD6 h/R6 h+BAY 11-7082组NF-κB表达减少,C3表达减少,S100A10表达增多(P<0.05);(4)结果表明,星形胶质细胞在OGD/R后可以活化为2种不同亚型的反应性星形胶质细胞,抑制HMGB1表达可以减少A1型反应性星形胶质细胞,增多A2型反应性星形胶质细胞,细胞迁移能力增加,主要是通过TLR4/NF-κB通路产生影响。 展开更多
关键词 脊髓损伤 星形胶质细胞 氧糖剥夺 复氧复糖 高迁移率族蛋白B1 A1型反应性星形胶质细胞 A2型反应性星形胶质细胞 toll样受体4 核转录因子ΚB
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Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect 被引量:1
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作者 Piao Luo Qian Zhang +10 位作者 Tian-Yu Zhong Jia-Yun Chen Jun-Zhe Zhang Ya Tian Liu-Hai Zheng Fan Yang Ling-Yun Dai Chang Zou Zhi-Jie Li Jing-Hua Liu Ji-Gang Wang 《Military Medical Research》 SCIE CAS CSCD 2023年第1期17-31,共15页
Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-infl... Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis.Methods: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide(LPS). We screened for potential protein targets of Cel using activity-based protein profiling(ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays(CETSA) and surface plasmon resonance(SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown.Results: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS(P <0.05). Cel bound to Cys424 of pyruvate kinase M2(PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis(Warburg effect). Cel also bound to Cys106 in high mobility group box 1(HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin(IL)-1β. Cel bound to the Cys residues in lactate dehydrogenase A(LDHA).Conclusions: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein. 展开更多
关键词 CELASTROL SEPSIS Pyruvate kinase M2 High mobility group box 1 Aerobic glycolysis
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2型糖尿病肾病患者血清miR-92b-5p和HMGB1水平变化及临床意义 被引量:16
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作者 陈晨 李晶 +1 位作者 叶婷 李惠 《山东医药》 CAS 2021年第16期6-10,共5页
目的观察miR-92b-5p及高迁移率族蛋白Box1(HMGB1)在2型糖尿病肾病患者血清中的水平变化,并探讨其临床意义。方法选取2型糖尿病患者203例,依据是否合并肾病将患者分为单纯糖尿病组(n=98)和糖尿病肾病组(n=105),并纳入80例同期体检健康者... 目的观察miR-92b-5p及高迁移率族蛋白Box1(HMGB1)在2型糖尿病肾病患者血清中的水平变化,并探讨其临床意义。方法选取2型糖尿病患者203例,依据是否合并肾病将患者分为单纯糖尿病组(n=98)和糖尿病肾病组(n=105),并纳入80例同期体检健康者为对照组。采用酶联免疫吸附法检测各组血清HMGB1,采用实时荧光定量PCR法检测各组血清miR-92b-5p,采用多因素Logistic回归分析2型糖尿病肾病的危险因素,采用Pearson检验进行相关性分析,采用ROC曲线评估miR-92b-5p和HMGB1对2型糖尿病肾病的预测价值。结果单纯糖尿病组和糖尿病肾病组血清HMGB1水平高于对照组,且糖尿病肾病组高于单纯糖尿病组(P均<0.05)。单纯糖尿病组和糖尿病肾病组血清miR-92b-5p水平低于对照组,且糖尿病肾病组低于单纯糖尿病组(P均<0.05)。多因素Logistic回归分析显示,血清HMGB1水平升高与miR-92b-5p水平降低均是2型糖尿病进展为2型糖尿病肾病的独立危险因素(P均<0.05)。2型糖尿病患者血清miR-92b-5p水平与HMGB1和24 h尿蛋白(24 hpro)水平均呈负相关,与估算肾小球滤过率(eGFR)水平呈正相关(P均<0.05);HMGB1和24 hpro水平呈正相关,与eGFR水平呈负相关(P均<0.05)。血清HMGB1联合miR-92b-5p预测2型糖尿病肾病的ROC曲线下面积(AUC)为0.858(95%CI:0.800~0.908),高于miR-92b-5p(AUC=0.754,95%CI:0.688~0.821)、HMGB1(AUC=0.802,95%CI:0.737~0.860)单一检查(P均<0.05)。结论血清HMGB1水平升高和miR-92b-5p水平降低是2型糖尿病患者进展为糖尿病肾病的危险因素,早期联合检测两指标可作为临床预测及诊断2型糖尿病肾病的重要生化标志物。 展开更多
关键词 2型糖尿病肾病 微小RNA 92b-5p 高迁移率族蛋白box1 尿蛋白 肾小球滤过率
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Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis
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作者 Ming-Kun Liu Ying-Jian Chen +5 位作者 Fei Chen Zhi-Xiong Lin Zi-Cheng Zhu Yu Lin Yi-Fan Fang Dian-Ming Wu 《World Journal of Gastrointestinal Surgery》 SCIE 2023年第7期1317-1330,共14页
BACKGROUND The prevention and treatment of Hirschsprung-associated enterocolitis(HAEC)is a serious challenge in pediatric surgery.Exploring the mechanism of HAEC is conducive to the prevention of this disease.AIM To e... BACKGROUND The prevention and treatment of Hirschsprung-associated enterocolitis(HAEC)is a serious challenge in pediatric surgery.Exploring the mechanism of HAEC is conducive to the prevention of this disease.AIM To explore the possible mechanism of glycyrrhizic acid(GA)and its therapeutic effect on HAEC.METHODS We developed a model of enteritis induced by trinitrobenzenesulfonic acid(TNBS)in zebrafish,and treated it with different concentrations of GA.We analyzed the effect of GA on the phenotype and inflammation of zebrafish.RESULTS After treatment with TNBS,the area of the intestinal lumen in zebrafish was significantly increased,but the number of goblet cells in the intestinal lumen was significantly reduced,but these did not increase the mortality of zebrafish,indicating that the zebrafish enteritis model was successfully developed.Different concentrations of GA protected zebrafish with enteritis.In particular,high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area,increased the number of goblet cells in the intestinal lumen,and reduced the levels of interleukin(IL)-1βand IL-8.CONCLUSION GA significantly reduced the intestinal luminal area,increased the number of intestinal goblet cells,and decreased IL-1βand IL-8 in zebrafish,and is important for prevention and control of HAEC. 展开更多
关键词 Hirschsprung-associated enterocolitis High mobility group box 1 protein Toll-like receptor 4 INTERLEUKIN-1Β INTERLEUKIN-8 Glycyrrhizic acid
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Clinical implications of forkhead box M1, cyclooxygenase-2, and glucose-regulated protein 78 in breast invasive ductal carcinoma
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作者 Jie Bai Ying Li Li Cai 《World Journal of Clinical Cases》 SCIE 2023年第30期7284-7293,共10页
BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expres... BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC. 展开更多
关键词 Diagnostic value Forkhead box M1 CYCLOOXYGENASE-2 Glucose-regulated protein 78 Clinical implications
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