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Bevacizumab and Paclitaxel in Advanced,Hormone Receptor-Positive Breast Cancer:Multifactor Dimensionality Reduction Methodology to Identify Best Overall Survival 认领 引用
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作者 Luigi Coltelli Paola Orlandi +34 位作者 Chiara Finale Gianna Musettini Luna Chiara Masini Marco Scalese Giulia Soria Elena Sartori Ylenia Nodari Giada Arrighi Arianna Bandini Marta Banchi Costanza Tacchi Donghao Tang Barbara Salvadori Lucia Tanganelli Simona Giovannelli Mirco Pistelli Samanta Cupini Maurizio Lucchesi Alessandro Cosimi Giulia Lorenzini Elisa Biasco Chiara Caparello Giulia Acconci Eloise Fontana Eleonora Bona Azzurra Farnesi Antonio Pellino Andrea Marini Ermelinda De Maio Irene Stasi Cecilia Barbara Enrico Sammarco Javier Rosada Giacomo Allegrini Guido Bocci 《Oncology Research》 SCIE 2026年第5期324-341,共18页
Background:The treatment of advanced hormone receptor-positive(HR+)breast cancer has seen relevant changes in last years.However,bevacizumab remains an option when combined with paclitaxel,but no certified pharmacogen... Background:The treatment of advanced hormone receptor-positive(HR+)breast cancer has seen relevant changes in last years.However,bevacizumab remains an option when combined with paclitaxel,but no certified pharmacogenetic profiles are now usable for the prediction of its response in breast cancer patients.This study aimed to explore the pharmacogenetic interactions among single nucleotide polymorphisms(SNPs)of genes involved in the angiogenic process and their impact on progression-free survival(PFS)and overall survival(OS)in hormone receptor-positive(HR+)metastatic breast cancer subjects administered with bevacizumab plus paclitaxel,or with paclitaxel alone(clinicaltrial.gov identifier NCT01935102).Methods:Germline DNA extracted from blood samples was analyzed using real-time polymerase chain reaction to investigate SNPs.The multifactor dimensionality reduction(MDR)analysis was employed to assess interactions between these genetic variants.A total of 168 eligible patients were analyzed.Among these,106 patients received both paclitaxel and bevacizumab,while 62 received paclitaxel alone.Results:In the combination therapy group,MDR analysis identified two pharmacogenetic interaction profiles involving specific genotypes of vascular endothelial growth factor-A(VEGF-A)rs833061 and vascular endothelial growth factor receptor-2(VEGFR-2)rs1870377.Patients with a favorable genetic profile had a median PFS(mPFS)of 22.9 months,compared to 8.7 months in those with an unfavorable profile(p=0.001).Cox proportional hazards analysis displayed an adjusted hazard ratio of 0.443(95%CI:0.284-0.691;p<0.0001).The median OS(mOS)was 50.2 months for the favorable profile vs.23.5 months for the unfavorable(p=0.003),with an adjusted hazard ratio(HR)of 0.404(95%CI:0.249-0.657;p<0.0001).In the 62 subjects administered with just paclitaxel,no significant differences in PFS(p=0.820)or OS(p=0.143)were observed between favorable and unfavorable genetic profiles.Conclusions:The MDR analysis of VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes can detect a subgroup of bevacizumab-administered+metastatic breast cancer patients with improved PFS and OS. 展开更多
关键词 Single nucleotide polymorphisms vascular endothelial growth factor-A VEGF receptor-2 bevacizumab paclitaxel advanced breast cancer angiogenesis pharmacogenetic interaction analysis
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Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients 认领 引用
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作者 Raouia ElFihry Mohcine Elmessaoudi-Idrissi +10 位作者 Fatima-Zahra Jadid Imane Zaidane Hajar Chihab Mohamed Tahiri Mostafa Kabine Wafaa Badre Isabelle Chemin Agnes Marchio Pascal Pineau Sayeh Ezzikouri Soumaya Benjelloun 《Virologica Sinica》 SCIE CAS CSCD 2020年第5期566-574,共9页
Hepatitis C virus(HCV)is still one of the main causes of liver disease worldwide.Metabolic disorders,including nonalcoholic fatty liver disease(NAFLD),induced by HCV have been shown to accelerate the progression of fi... Hepatitis C virus(HCV)is still one of the main causes of liver disease worldwide.Metabolic disorders,including nonalcoholic fatty liver disease(NAFLD),induced by HCV have been shown to accelerate the progression of fibrosis to cirrhosis and to increase the risk of hepatocellular carcinoma.An optimal peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A)activity is crucial to prevent NAFLD installation.The present study aims to investigate the associations between two common PPARGC1A polymorphisms(rs8192678 and rs12640088)and the outcomes of HCV infection in a North African context.A series of 592 consecutive Moroccan subjects,including 292 patients with chronic hepatitis C(CHC),100 resolvers and 200 healthy controls were genotyped using a TaqMan allelic discrimination assay.PPARGC1A variations at rs8192678 and rs12640088 were not associated with spontaneous clearance of HCV infection(adjusted ORs=0.76 and 0.79 respectively,P[0.05,for both).Furthermore,multivariable logistic regression analysis showed that both SNPs were not associated with fibrosis progression(OR=0.71;95%CI 0.20–2.49;P=0.739;OR=1.28;95%CI 0.25–6.54;P=0.512,respectively).We conclude that,in the genetic context of South Mediterranean patients,rs8192678 and rs12640088 polymorphisms of PPARGC1 A are neither associated with spontaneous clearance nor with disease progression in individuals infected with HCV. 展开更多
关键词 Chronic hepatitis C Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A) Polymorphisms Disease progression
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Mechanism of acupuncture in attenuating cerebral ischaemia-reperfusion injury based on nuclear receptor coactivator 4 mediated ferritinophagy 认领 引用 被引量：11
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作者 ZHANG Xinchang HUANG Zheng +3 位作者 HUANG Peiyan YANG Mengning ZHANG Zhihui NI Guangxia 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2024年第2期345-352,共8页
OBJECTIVE:To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury(CIRI)and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4(NCOA4)mediated ferritino... OBJECTIVE:To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury(CIRI)and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4(NCOA4)mediated ferritinophagy.METHODS:Sprague-Dawley male rats were divided into four groups:the sham group,model group,acupuncture group,and sham acupuncture group.After 2 h of middle cerebral artery occlusion(MCAO),reperfusion was performed for 24 h to induce CIRI.The rats were treated with acupuncture at the Neiguan(PC6)and Shuigou(GV26)acupoints.Their neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after reperfusion.Triphenyltetrazolium chloride staining was applied to assess the cerebral infarct volume at 24 h after reperfusion.The malondialdehyde(MDA)and ferrous iron(Fe2+)levels were observed after 24 h of reperfusion using an assay kit.Western blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1(FTH1)at 24 h after reperfusion.Moreover,the colocalization of ferritin with neurons,NCOA4 with microtubule-associated protein 1 light chain 3(LC3),and NCOA4 with ferritin was visualized using immunofluorescence staining.RESULTS:Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture group.Following CIRI,the expression of NCOA4,LC3 and FTH1 was increased,which enhanced ferritinophagy and induced an inappropriate accumulation of Fe2+and MDA in the ischaemic brain.However,acupuncture dramatically downregulated the expression of NCOA4,LC3 and FTH1,inhibited the overactivation of ferritinophagy,and decreased the levels of MDA and Fe2+.CONCLUSIONS:Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model. 展开更多
关键词 acupuncture ferritinophagy ferroptosis ferritin nuclear receptor coactivator 4 cerebral ischaemia-reperfusion injury
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The transcriptional coactivator CmMBF1c is required for waterlogging tolerance in Chrysanthemum morifolium 认领 引用 被引量：1
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作者 Nan Zhao Chuanwei Li +5 位作者 Yajun Yan Haibin Wang Likai Wang Jiafu Jiang Sumei Chen Fadi Chen 《Horticulture Research》 SCIE CSCD 2022年第1期3847-3858,共12页
Waterlogging is one of the most serious abiotic stressors affecting Chrysanthemum morifolium during its lifespan.However,the molecular mechanisms underlying the waterlogging tolerance of chrysanthemum remain unclear.I... Waterlogging is one of the most serious abiotic stressors affecting Chrysanthemum morifolium during its lifespan.However,the molecular mechanisms underlying the waterlogging tolerance of chrysanthemum remain unclear.In this study,we discovered that the transcriptional coactivator MULTIPROTEIN BRIDGING FACTOR 1c(CmMBF1c)was significantly induced by waterlogging stress in chrysanthemums.Promoter sequence analysis and transient dual-luciferase assay using chrysanthemum protoplasts showed that the waterlogging-tolerant cultivar‘Nannongxuefeng’carried more response elements involved in waterlogging and hypoxia stress compared with the waterlogging-sensitive cultivar‘Qinglu’,conferring on‘Nannongxuefeng’a stronger hypoxia responsive activity and higher CmMBF1c expression under waterlogging conditions.Subcellular localization and transcriptional activity assays showed that CmMBF1c protein was localized to the nucleus and had no transcriptional activation activity.Overexpression of CmMBF1c in‘Qinglu’enhanced its waterlogging tolerance by promoting its reactive oxygen species(ROS)scavenging ability and maintaining low ROS levels.However,RNAi-mediated knockdown of CmMBF1c in cultivar‘Nannongxuefeng’resulted in the opposite tendency.Yeast twohybrid screening and tobacco bimolecular f luorescence complementation assays revealed that CmHRE2,a pivotal regulator of hypoxia response,could interact with CmMBF1c.In summary,this study demonstrates that CmMBF1c improves chrysanthemum waterlogging tolerance by regulating its ROS signaling pathway and interacting with CmHRE2.These findings together offer,to our knowledge,new mechanistic insights into chrysanthemum waterlogging tolerance and provide a rational foundation for future research on the genetic improvement of horticultural crops for waterlogging stress tolerance. 展开更多
关键词 molecular mechanisms chrysanthemumspromoter sequence analysis multiprotein bridging factor c chrysanthemum protoplasts abiotic stressors chrysanthemum morifolium transcriptional coactivator waterlogging tolerance
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The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA PolⅡfrom Binding to HIV-1 LTR 认领 引用 被引量：2
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作者 Ling Ma Shumin Chen +11 位作者 Zhen Wang Saisai Guo Jianyuan Zhao Dongrong Yi Quanjie Li Zhenlong Liu Fei Guo Xiaoyu Li Pingping Jia Jiwei Ding Chen Liang Shan Cen 《Virologica Sinica》 SCIE CAS CSCD 2021年第4期796-809,共14页
The CREB-regulated transcriptional co-activators(CRTCs),including CRTC1,CRTC2 and CRTC3,enhance transcription of CREB-targeted genes.In addition to regulating host gene expression in response to cAMP,CRTCs also increa... The CREB-regulated transcriptional co-activators(CRTCs),including CRTC1,CRTC2 and CRTC3,enhance transcription of CREB-targeted genes.In addition to regulating host gene expression in response to cAMP,CRTCs also increase the infection of several viruses.While human immunodeficiency virus type 1(HIV-1)long terminal repeat(LTR)promoter harbors a cAMP response element and activation of the cAMP pathway promotes HIV-1 transcription,it remains unknown whether CRTCs have any effect on HIV-1 transcription and HIV-1 infection.Here,we reported that CRTC2 expression was induced by HIV-1 infection,but CRTC2 suppressed HIV-1 infection and diminished viral RNA expression.Mechanistic studies revealed that CRTC2 inhibited transcription from HIV-1 LTR and diminished RNA PolⅡoccupancy at the LTR independent of its association with CREB.Importantly,CRTC2 inhibits the activation of latent HIV-1.Together,these data suggest that in response to HIV-1 infection,cells increase the expression of CRTC2 which inhibits HIV-1 gene expression and may play a role in driving HIV-1 into latency. 展开更多
关键词 Human immunodeficiency virus(HIV) RNA polymeraseⅡ(RNA PolⅡ) Viral transcription Infection Virology CREB regulated transcription coactivator 2(CRTC2) Long terminal repeat(LTR) Latency
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Distinct expression profiles of transcriptional coactivators for thyroid hormone receptors during Xenopus laevis metamorphosis 认领 引用
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作者 BINDU D PAUL YUN-Bo SHI 《Cell Research》 SCIE CAS 2003年第6期459-464,共6页
The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orches... The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orchestrated developmental changes, which ultimately result in the conversion of an aquatic herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to TRs, which in turn recruit coactivators, leading to gene activation. The best-studied coactivators belong to the p160 or SRC family. Members of this family include SRC1/NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-1/RAC-3/TRAM-1. These SRCs interact directly with liganded TR and function as adapter molecules to recruit other coactivators such as p300/CBP. Here, we studied the expression patterns of these coactivators during various stages of development. Amongst the coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are expressed throughout postembryonic development with little change in their expression levels. These results support the view that these coactivators participate in gene regulation by TR during metamorphosis. 展开更多
关键词 transcription coactivators thyroid hormone receptor Xenopus laevis metamorphosis histone acetylation.
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Role of Neuropeptide Y and Peroxisome Proliferator-activated Receptor γ Coactivator-1α in Stress Cardiomyopathy 认领 引用 被引量：2
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作者 阿兰达 王云云 +9 位作者 朱少华 王荣帅 周小伟 卓荦 孙婷怡 任亮 刘茜 董红梅 刘艳 刘良 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2012年第6期823-828,共6页
Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via a... Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases. 展开更多
关键词 stress cardiomyopathy peroxisome proliferator-activated receptor γ coactivator-1alpha neuropeptide Y sudden death forensic pathology
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Down-regulated expressions of PPAR_γ and its coactivator PGC-1 are related to gastric carcinogenesis and Lauren's classification in gastric carcinoma 认领 引用 被引量：3
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作者 Han Yu Yan Xin 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2013年第6期704-714,共11页
Objective： To explore the relationship between peroxisome proliferator activated receptor-gamma （PPARγ） and peroxisome proliferator-activated receptor-gamma coactivator-1 （PGC-1） expression in gastric carcinoma ... Objective： To explore the relationship between peroxisome proliferator activated receptor-gamma （PPARγ） and peroxisome proliferator-activated receptor-gamma coactivator-1 （PGC-1） expression in gastric carcinoma （GC）, and analyze their correlations with clinicopathological features and clinical outcomes of patients. Methods：The two-step immunohistochemical method was used to detect the expression of PPARγ and PGC-1 in 179 cases of GC, and 108 cases of matched normal gastric mucosa. Besides, 16 cases of fresh GC specimens and corresponding normal gastric mucosa were detected for PGC-1 expression with Western blotting. Results： The positive rates of PPART and PGC-1 expression were significantly lower in GC （54.75%, 49.16%） than in normal gastric mucosa （70.37%, 71.30%）, respectively （P〈0.05）. The decreased expression of PGC-1 in GC was confirmed ha our Western blot analysis （P=0.004）. PPAR7 and PGC-1 expressions were related to Lauren＇s types ofGC （P〈0.05）. Positive correlation was found between PPART and PGC-1 expression in GC （rk=0.422, P〈0.001）. The survival time of PPART negative and positive patients was 36.6±3.0 vs. 38.5_＋2.7 months, and no statistical difference was found between the 5-year survival rates of two groups （34.4% vs. 44.1%, P=0.522, log-rank test）; the survival time of PGC-1 negative and positive patients was 36.2±2.8 vs. 39.9±2.9 months, while no statistical difference was found between the 5-year survival rates of the two groups （32.0% vs. 48.2%, P=0.462, log-rank test） Conclusions＇. Decreased expression of PPARγand PGC-1 in GC was related to the Lauren＇s classification. Their expressions in GC were positively correlated, indicating that their fimctions in gastric carcinogenesis may be closely related. 展开更多
关键词 Peroxisome proliferator activated receptor-gamma （PPARγ） peroxisome proliferator-activatedreceptor-gamma coactivator-1 （PGC-I） gastric carcinoma （GC） clinicopathological feature
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Inhibitory roles of protein kinase B and peroxisome proliferator-activated receptor gamma coactivator on hepatic HMG-CoA reductase promoter activity 认领 引用
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作者 Gene C. Ness Jeffrey L. Edelman 《Advances in Bioscience and Biotechnology》 CAS 2013年第10期1-5,共5页
Since we had previously demonstrated that siRNAs to tristetraprolin (TTP) markedly inhibited insulin stimulation of hepatic HMG-CoA reductase (HMGR) transcription, we investigated the effects of transfecting rat liver... Since we had previously demonstrated that siRNAs to tristetraprolin (TTP) markedly inhibited insulin stimulation of hepatic HMG-CoA reductase (HMGR) transcription, we investigated the effects of transfecting rat liver with TTP constructs. We found that transfecting diabetic rats with TTP did not increase HMGR transcription but rather led to modest inhibition. We then investigated whether co-transfection with protein kinase B, hepatic form (AKT2), might lead to phosphorylation and result in activation of HMGR transcription. We found that this treatment resulted in near complete inhibition of transcription. Transfection with peroxisome proliferator-activated receptor g coactivator (PGC-1a) also inhibited HMGR transcription. These results show that although TTP is needed for activation of HMGR transcription, it cannot by itself activate this process. AKT2 and PGC-1a, which mediate the activation of gluconeogenic genes by insulin, exert the opposite effect on HMGR. 展开更多
关键词 In Vivo Electroporation HMG-CoA Reductase Insulin Protein Kinase B Peroxisome Proliferator-Activated Receptor γ Coactivator Tristetraprolin
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Moxibustion alleviates autophagy and inhibits ferroptosis to improve cardiac function in rats with post-myocardial infarction heart failure 认领 引用
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作者 GAO Bing LIU Pan +7 位作者 LI Lan GONG Tiantian ZHU Ling LI Lingji XIA Ran MA Qiang HU Jing WANG Jing 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2026年第2期339-349,共11页
OBJECTIVE:To explore the mechanism by which moxibustion alleviates autophagy and inhibits ferroptosis,thereby improving myocardial fibrosis in rats with postmyocardial infarction heart failure(post-MI HF).METHODS:We u... OBJECTIVE:To explore the mechanism by which moxibustion alleviates autophagy and inhibits ferroptosis,thereby improving myocardial fibrosis in rats with postmyocardial infarction heart failure(post-MI HF).METHODS:We used a rat model of post-MI HF rats.Interventions included moxibustion and intraperitoneal injection of rapamycin(RAPA)along with assessing echocardiography,cardiac pathology,myocardial mitochondrial morphology,co-immunofluorescence,transmission electron microscope,Western blotting,and reverse transcriptase-quantitative polymerase chain reaction.RESULTS:Moxibustion improves the left ventricular ejection fraction and fractional shortening,myocardial cell morphology,and myocardial fibrosis levels induced by post-MI HF.In addition,it reduces the immunofluorescence co-localization intensity of nuclear receptor coactivator 4(NCOA4)and microtubuleassociated protein 1A/1B light chain 3 and decreases the level of intracellular free iron.It suppresses autophagy and ferroptosis-related indicators,downregulates NCOA4 expression,upregulates glutathione peroxidase 4 expression,and decreases lipid peroxidation levels.The activation of autophagy increases NCOA4 expression and promotes ferroptosis.Furthermore,moxibustion counteracts the effects of RAPA.CONCLUSIONS:Moxibustion can alleviate myocardial fibrosis and exert cardioprotective effects by regulating autophagy and inhibiting ferroptosis.Our findings indicate that targeting autophagy-induced ferroptosis may serve as a novel therapeutic approach for the treatment of postMI HF. 展开更多
关键词 moxibustion nuclear receptor coactivator 4 ferroptosis autophagy heart failure myocardial fibrosis
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老年缺血性脑梗死后血管性认知功能障碍患者血清SRC-3、Netrin-4水平及其临床意义 认领 引用 被引量：1
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作者 窦海玲 李世泽 +4 位作者 赵松耀 杨硕 李佳佳 吕慧君 张越 《中华神经外科疾病研究杂志》 CAS 2026年第2期67-71,共5页
目的探讨老年缺血性脑梗死后血管性认知功能障碍(VCI)患者血清类固醇受体辅助激活因子3(SRC-3)、轴突生长诱向因子4(Netrin-4)水平及其临床意义。方法选取2021年11月至2024年12月郑州大学附属郑州中心医院收治的102例老年缺血性脑梗死后... 目的探讨老年缺血性脑梗死后血管性认知功能障碍(VCI)患者血清类固醇受体辅助激活因子3(SRC-3)、轴突生长诱向因子4(Netrin-4)水平及其临床意义。方法选取2021年11月至2024年12月郑州大学附属郑州中心医院收治的102例老年缺血性脑梗死后VCI患者作为VCI组,另选择同期的102例老年缺血性脑梗死后无VCI患者作为非VCI组。比较两组血清SRC-3、Netrin-4水平差异;采用受试者工作特征(ROC)曲线分析血清SRC-3、Netrin-4水平对老年脑梗死患者发生VCI的预测价值;采用多因素Logistic逐步回归分析老年脑梗死患者发生VCI的独立影响因素。结果VCI组老年脑梗死患者血清SRC-3、Netrin-4水平显著低于非VCI组(均P<0.05)。ROC分析显示,血清SRC-3、Netrin-4联合(串联)预测老年脑梗死后发生VCI的曲线下面积为0.904,显著高于血清SRC-3、Netrin-4单独预测的0.761、0.815(Z=13.584、10.231,P<0.001)。VCI组年龄、合并高血压占比、合并糖尿病占比、梗死病灶多发占比高于非VCI组,蒙特利尔认知评估量表评分低于非VCI组(P<0.05)。多因素分析显示:高年龄、合并高血压、合并糖尿病、SRC-3≤0.53 ng/mL、Netrin-4≤49.60 ng/mL是老年脑梗死后发生VCI的独立危险因素(P<0.05)。结论老年脑梗死后VCI患者血清SRC-3、Netrin-4水平均降低,且二者联合检测对老年脑梗死后发生VCI具有较好的预测价值。 展开更多
关键词 脑梗死 血管性认知功能障碍 类固醇受体辅助激活因子3 轴突生长诱向因子4 老年
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人参总次苷调控PGC1α信号通路改善心梗后大鼠心肌能量代谢 认领 引用 被引量：1
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作者 李彬 肖悦 +6 位作者 李佳 张爱群 朱明军 高尚先 谢世阳 高原 王新陆 《中药药理与临床》 CAS CSCD 北大核心 2026年第1期68-76,共9页
目的:探讨人参总次苷通过调节过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC1α)信号通路对心梗后大鼠心肌能量代谢的影响和潜在机制。方法:选取100只SD大鼠行冠状动脉左前降支结扎术建立心肌梗死模型,心电图观察大鼠造模成功后,随机... 目的:探讨人参总次苷通过调节过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC1α)信号通路对心梗后大鼠心肌能量代谢的影响和潜在机制。方法:选取100只SD大鼠行冠状动脉左前降支结扎术建立心肌梗死模型,心电图观察大鼠造模成功后,随机分为模型对照组、人参总次苷11.6、23.3 mg/kg组、辅酶Q1010 mg/kg组,假手术对照组在冠状动脉左前降支下仅穿线不结扎。各组灌胃给予相应药物,治疗4 w。HE染色和Masson染色观察心肌组织损伤;比色法试剂盒检测心肌羟脯氨酸(HYP)、三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)含量;流式细胞仪检测心肌线粒体膜电位水平;实时荧光定量法(RT-PCR)检测心肌线粒体转录因子A(Tfam)、Pgc1α、雌激素相关受体α(Errα)、核呼吸因子1(Nrf1)、核呼吸因子2(Nrf2)、过氧化物酶体增殖物激活受体α(Pparα)mRNA表达;Western blot法检测心肌钠-钾-ATP酶(Na+-K+-ATPase)、解偶联蛋白2(UCP2)、腺苷酸转位酶(ANT)、TFAM、PGC-1α、ERRα、NRF-1、NRF-2、PPARα的蛋白表达。结果:与假手术对照组比较,心梗造模组大鼠的心电图ST段抬高幅度显著增加(P<0.01),提示心肌梗死模型造模成功,模型对照组大鼠心肌组织损伤明显加重,胶原容积分数、心肌HYP含量显著升高(P<0.01),ATP含量明显降低,ADP和AMP含量显著升高(P<0.01),ANT和Na+-K+-ATPase蛋白表达下调、UCP2蛋白表达上调(P<0.01),心肌线粒体膜电位显著下降(P<0.01),心肌Tfam、Pgc1α、Errα、Nrf1、Nrf2、Pparα的mRNA与蛋白表达显著下调(P<0.01);与模型对照组比较,人参总次苷11.65、23.3 mg/kg组和辅酶Q1010 mg/kg组心肌组织损伤明显减轻,胶原容积分数、HYP含量显著下降(P<0.01),心肌ATP含量显著升高,ADP和AMP含量显著下降(P<0.01),人参总次苷11.6 mg/kg组ANT蛋白表达上调,UCP2蛋白表达下调(P<0.01),线粒体膜电位明显升高(P<0.01),TFAM的蛋白表达上调(P<0.01),Pgc1α、Errα、Nrf1、Nrf2、Pparα的mRNA和蛋白表达明显上调(P<0.05或P<0.01),人参总次苷23.3 mg/kg组和辅酶Q1010 mg/kg组Na+-K+-ATPas和ANT蛋白表达上调,UCP2蛋白表达下调(P<0.01),线粒体膜电位明显升高(P<0.01),Tfam、Pgc1α、Errα、Nrf1、Nrf2、Pparα的mRNA和蛋白表达均显著上调(P<0.01)。结论:人参总次苷可改善心梗后心肌损伤,平衡心肌高能磷酸盐代谢及相关转运蛋白的表达,提高心肌线粒体膜电位水平,具有改善心肌能量代谢的作用,其作用机制可能与提高PGC1α信号通路相关因子表达有关。 展开更多
关键词 人参总次苷 心肌梗死 过氧化物酶体增殖物激活受体α 心肌钠-钾-ATP酶 解偶联蛋白2 腺苷酸转位酶 心肌线粒体转录因子A 雌激素相关受体α 核呼吸因子
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基于铁死亡探讨艾灸“肺俞”“心俞”改善慢性心力衰竭心肌纤维化的机制 认领 引用
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作者 高兵 贾学昭 +6 位作者 曹宇翔 刘攀 张文轩 李澜 夏冉 丁焕章 王茎 《针刺研究》 CAS CSCD 北大核心 2026年第1期48-58,共11页
目的:观察艾灸“肺俞”“心俞”对慢性心力衰竭(CHF)大鼠心肌核受体共激活因子4(NCOA4)、二价金属转运蛋白1(DMT1)及Ⅲ型胶原蛋白(CollagenⅢ)的影响,探讨艾灸改善CHF大鼠心肌纤维化的机制。方法:从50只大鼠中随机选取10只作为正常组,其... 目的:观察艾灸“肺俞”“心俞”对慢性心力衰竭(CHF)大鼠心肌核受体共激活因子4(NCOA4)、二价金属转运蛋白1(DMT1)及Ⅲ型胶原蛋白(CollagenⅢ)的影响,探讨艾灸改善CHF大鼠心肌纤维化的机制。方法:从50只大鼠中随机选取10只作为正常组,其余40只为造模组,以左前降支冠状动脉结扎进行造模。将造模成功的大鼠随机分为模型组(n=5)、艾灸组(n=7)、雷帕霉素组(n=4)、艾灸+雷帕霉素组(n=5)。艾灸组、艾灸+雷帕霉素组于大鼠背部双侧“肺俞”“心俞”给予艾灸,每日1次,连续4周;雷帕霉素组、艾灸+雷帕霉素组大鼠给予腹腔注射雷帕霉素溶液(1 mg/kg),每日1次,连续4周。干预结束后观察大鼠行为学情况,以超声心动仪检测大鼠射血分数(EF)和左室缩短率(FS),Masson染色法和透射电镜观察大鼠心脏结构形态,免疫荧光染色法检测NCOA4和自噬微管相关蛋白轻链3B(LC3B)共定位情况,实时荧光定量PCR法检测各组大鼠心肌组织NCOA4、DMT1和CollagenⅢmRNA表达,Western blot法检测各组大鼠心肌组织DMT1和CollagenⅢ的蛋白表达。结果:与正常组比较,模型组大鼠EF和FS值降低(P<0.01),心肌细胞线粒体嵴断裂甚至消失,心肌纤维蓝染面积增大(P<0.01),NCOA4与LC3B共定位增加(P<0.01),NCOA4、DMT1、CollagenⅢmRNA表达水平及DMT1、CollagenⅢ蛋白表达水平升高(P<0.01)。与模型组比较,艾灸组EF和FS值升高(P<0.05,P<0.01),线粒体形态好转,心肌纤维蓝染面积缩小(P<0.01),NCOA4和LC3B的共定位减少(P<0.01),NCOA4、DMT1、CollagenⅢmRNA表达水平及DMT1、CollagenⅢ蛋白表达水平降低(P<0.01);雷帕霉素组心肌纤维蓝染面积增大(P<0.01),NCOA4和LC3B共定位增加(P<0.01),NCOA4、DMT1、Collagen mRNA表达水平及DMT1、CollagenⅢ蛋白表达水平升高(P<0.01)。与艾灸组比较,雷帕霉素组EF和FS值下降(P<0.01),线粒体损伤更为严重;雷帕霉素组、艾灸+雷帕霉素组心肌纤维蓝染面积增大(P<0.01),NCOA4和LC3B共定位增加(P<0.01),NCOA4、DMT1、CollagenⅢmRNA表达水平及DMT1、CollagenⅢ蛋白表达水平升高(P<0.01)。结论:艾灸“肺俞”“心俞”可降低心肌组织NCOA4、DMT1表达,抑制NCOA4与LC3B的结合,从而拮抗铁蛋白自噬,改善铁代谢紊乱,抑制铁死亡,并能下调CollagenⅢ表达,最终减缓CHF心肌纤维化进程。 展开更多
关键词 慢性心力衰竭 艾灸 核受体共激活因子4 二价金属转运蛋白1 心肌纤维化
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神经元区室化线粒体生物发生机制的研究进展 认领 引用
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作者 黄佳 杨雨 +1 位作者 周胜强 刘芳 《解放军医学杂志》 CAS CSCD 北大核心 2026年第3期443-452,共10页
神经元区室化线粒体生物发生是一个复杂而精细的生物学过程,涉及线粒体在神经元不同区室(如胞体、轴突和突触)的动态生成。线粒体作为神经元的能量工厂和代谢中心,其生物发生过程受到严格的时空调控,以满足神经元不同功能区室的能量需... 神经元区室化线粒体生物发生是一个复杂而精细的生物学过程,涉及线粒体在神经元不同区室(如胞体、轴突和突触)的动态生成。线粒体作为神经元的能量工厂和代谢中心,其生物发生过程受到严格的时空调控,以满足神经元不同功能区室的能量需求和信号传递。近年来的研究显示,线粒体生物发生与神经元的存活、神经突可塑性及部分神经系统疾病的发病机制密切相关。通过调控区室化线粒体生物发生的关键信号通路,可以改善神经元的能量代谢和功能,为神经系统疾病的治疗提供潜在的干预策略。本文综述了在神经元胞体、轴突中线粒体生物发生的机制及其在多种神经系统疾病中作用的相关研究进展。 展开更多
关键词 神经元 区室化 线粒体生物发生 过氧化物酶体增殖物激活受体γ共激活因子-1α 哺乳动物雷帕霉素靶蛋白
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通脉养心丸通过增强PGC-1α介导的线粒体功能减轻心肌缺血再灌注损伤 认领 引用
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作者 于鲁 王旭 +3 位作者 刘雨桐 高杉 于春泉 李琳 《中草药》 CAS CSCD 北大核心 2026年第3期925-934,共10页
目的阐明通脉养心丸通过调节过氧化物酶体增殖物激活受体γ共激活因子-1α(peroxisome proliferator-activated receptor gamma coactivator-1α,PGC-1α)介导的线粒体功能从而发挥心肌缺血/再灌注损伤(myocardial ischemia-reperfusion... 目的阐明通脉养心丸通过调节过氧化物酶体增殖物激活受体γ共激活因子-1α(peroxisome proliferator-activated receptor gamma coactivator-1α,PGC-1α)介导的线粒体功能从而发挥心肌缺血/再灌注损伤(myocardial ischemia-reperfusion injury,MI/RI)保护作用的机制。方法构建缺氧复氧(hypoxia-reoxygenation,H/R)心肌细胞模型,给予通脉养心丸干预后,采用DCFH-DA和MitoSOXTM Red荧光探针检测细胞内活性氧(reactive oxygen species,ROS)水平;采用增强型三磷酸腺苷(adenosine triphosphate,ATP)检测试剂盒检测ATP水平;JC-1染色观察线粒体膜电位变化;采用Seahorse XF细胞线粒体压力测试分析线粒体呼吸功能;Mitotracker与透射电镜观察线粒体的形态与结构变化;采用Western blotting与qRTPCR检测线粒体融合分裂[线粒体融合素1(mitofusin 1,Mfn1)、线粒体融合素2(mitofusin 2,Mfn2)、线粒体分裂蛋白1(fission 1,Fis1)、动力相关蛋白1(dynamin-related protein 1,Drp1)]、生物合成[核呼吸因子1(nuclear respiratory factor1,Nrf1)、线粒体转录因子A(mitochondrial transcription factor A,TFAM)、线粒体DNA(mitochondrial DNA,mtDNA)拷贝数]及自噬[Beclin1、PTEN诱导激酶1(PTEN-induced putative kinase 1,PINK1)、帕金蛋白(Parkin)、p62]相关蛋白和基因的表达水平。通过PGC-1αsiRNA转染实验进一步观察通脉养心丸对PGC-1α沉默表达后H9c2细胞上述功能的影响。结果与模型组比较,通脉养心丸显著增强线粒体ATP合成(P<0.01),改善线粒体膜电位(P<0.01),减少氧化应激(P<0.01),并促进线粒体自噬(P<0.05、0.01)。沉默PGC-1α后,通脉养心丸对线粒体功能的保护作用显著削弱(P<0.05、0.01)。结论通脉养心丸能够通过PGC-1α调控线粒体的生物合成、动态平衡及自噬,从而有效改善MI/RI引发的线粒体功能紊乱与形态结构变化。揭示了PGC-1α作为线粒体功能调控的核心因子,其在MI/RI中的潜在治疗价值,为MI/RI的治疗提供了新的思路。 展开更多
关键词 通脉养心丸 心肌缺血/再灌注损伤 线粒体功能 心肌细胞损伤 过氧化物酶体增殖物激活受体γ共激活因子-1α
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恩格列净对阿霉素诱导大鼠心脏损伤模型的改善作用及其机制 认领 引用
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作者 李佳蔚 阿地力江 +1 位作者 吴莉 姜芸 《吉林大学学报（医学版）》 CAS CSCD 北大核心 2026年第1期105-115,共11页
目的:探讨恩格列净(EMPA)对阿霉素(DOX)诱导大鼠心脏损伤(HI)模型的改善作用,并阐明其作用机制。方法:24只6-7周龄雄性Wistar大鼠随机分为对照组(正常健康大鼠维持饲养)、HI组(建立DOX诱导的大鼠HI模型)和HI+EMPA组(在建立DOX诱导的大... 目的:探讨恩格列净(EMPA)对阿霉素(DOX)诱导大鼠心脏损伤(HI)模型的改善作用,并阐明其作用机制。方法:24只6-7周龄雄性Wistar大鼠随机分为对照组(正常健康大鼠维持饲养)、HI组(建立DOX诱导的大鼠HI模型)和HI+EMPA组(在建立DOX诱导的大鼠HI模型6周后,每日给予大鼠灌胃10 mg·kg-1EMPA,连续灌胃14 d),每组8只。采用心脏超声心动图检测各组大鼠左室收缩末内径(LVIDs)、左室射血分数(LVEF)和左室短轴缩短率(LVFS),HE染色和Masson染色观察各组大鼠心肌组织病理形态表现和心肌组织中胶原纤维沉积情况,脱氧核糖核苷酸末端转移酶介导的dUTP缺口末端标记(TUNEL)法分析各组大鼠心肌细胞凋亡情况,酶联免疫吸附试验(ELISA)法检测各组大鼠血清中乳酸脱氢酶(LDH)和肌酸激酶(CK)水平。采用大鼠心肌细胞H9c2进行体外实验。体外建立DOX诱导的大鼠心肌细胞损伤模型(DOX组)。细胞实验分组-1分为对照组(H9c2细胞正常培养不做任何处理)、DOX组(H9c2细胞培养液中加入0.1μmol·L-1DOX处理48 h,诱导心肌细胞损伤)、DOX+EMPA组(H9c2细胞培养液中加入0.1μmol·L-1DOX和500 nmol·L-1EMPA,处理48 h)和DOX+EMPA+EX527[沉默信息调节因子相关酶1(SIRT1)抑制剂]组(H9c2细胞培养液中加入10μmol·L-1EX527预处理1 h,然后加入0.1μmol·L-1DOX和500 nmol·L-1EMPA,处理48 h)。细胞实验分组-2分为对照组(H9c2细胞正常培养不做任何处理)、DOX组(H9c2细胞培养液中加入0.1μmol·L-1DOX处理48 h,诱导心肌细胞损伤)和DOX+动力学相关蛋白1(Drp-1)抑制剂组(H9c2细胞培养液中加入75μmol·L-1Drp-1抑制剂Mdivi-1预处理2 h,然后0.1μmol·L-1DOX处理48 h)。采用Western blotting法检测各组细胞中自噬相关蛋白微管相关蛋白1轻链3(LC3)、自噬关键分子酵母Atg6同系物BECLIN1、泛素结合蛋白P62、SIRT1、过氧化物酶体增殖物激活受体γ辅激活子1α(PGC-1α)、Drp-1、线粒体裂变1蛋白(Fis-1)和线粒体裂变因子(MFF)蛋白表达水平。结果:对照组大鼠心脏心肌纤维排列整齐,间质未见明显炎症细胞浸润和胶原纤维沉积;与对照组比较,HI组大鼠心肌纤维排列紊乱,心肌间质扩大,可见炎症细胞浸润和胶原纤维沉积;与HI组比较,HI+EMPA组大鼠心肌纤维排列较为规整,间质未见明显炎症细胞浸润,可见少量胶原纤维沉积。与对照组比较,HI组大鼠心肌组织TUNEL阳性细胞数和LVIDs升高(P<0.05),LVEF和LVFS降低(P<0.05),血清中LDH和CK水平升高(P<0.05)。与HI组比较,HI+EMPA组大鼠心肌组织TUNEL阳性细胞数和LVIDs降低(P<0.05),LVEF和LVFS均升高(P<0.05),血清中LDH和CK水平降低(P<0.05)。与对照组比较,DOX组H9c2细胞中BECLIN1蛋白表达水平和LC3-Ⅰ/LC3-Ⅱ比值升高(P<0.05),P62、SIRT1和PGC-1α蛋白表达水平降低(P<0.05),Drp-1蛋白表达水平升高(P<0.05)。与DOX组比较,DOX+EMPA组H9c2细胞中BECLIN1蛋白表达水平和LC3-Ⅰ/LC3-Ⅱ比值降低(P<0.05),P62、SIRT1和PGC-1α蛋白表达水平升高(P<0.05),Drp-1蛋白表达水平降低(P<0.05)。与DOX+EMPA组比较,DOX+EMPA+EX527组H9c2细胞中BECLIN1蛋白表达水平和LC3-Ⅰ/LC3-Ⅱ比值升高(P<0.05),P62和Drp-1蛋白表达水平降低(P<0.05)。与对照组比较,DOX组H9c2细胞中Drp-1、Fis-1和MFF蛋白表达水平升高(P<0.05);与DOX组比较,DOX+Drp-1抑制剂组H9c2细胞中Fis-1和MFF蛋白表达水平降低(P<0.05)。结论:EMPA可减轻DOX诱导的大鼠心肌病变和心脏功能异常,降低心肌细胞凋亡和自噬,其机制可能与EMPA上调SIRT1和PGC-1α蛋白表达、降低Drp1蛋白表达有关。 展开更多
关键词 阿霉素 心脏毒性 恩格列净 线粒体裂变 沉默信息调节因子相关酶1 过氧化物酶体增殖物激活受体γ辅激活子1α 动力学相关蛋白1
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TAp63对MPTP诱导的帕金森病小鼠模型氧化应激反应的影响及其机制 认领 引用
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作者 任继文 窦凯昕 +2 位作者 陶明珠 王泽晨 谢安木 《青岛大学学报（医学版）》 CAS 2026年第1期6-10,共5页
目的探讨TAp63对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病小鼠模型氧化应激的影响,并探究其潜在机制。方法将36只小鼠随机分为对照组、MPTP组、TAp63NC组、TAp63NC+MPTP组、TAp63过表达组、TAp63过表达+MPTP组,利用转棒实... 目的探讨TAp63对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病小鼠模型氧化应激的影响,并探究其潜在机制。方法将36只小鼠随机分为对照组、MPTP组、TAp63NC组、TAp63NC+MPTP组、TAp63过表达组、TAp63过表达+MPTP组,利用转棒实验、爬杆实验检测神经运动功能,利用免疫组织化学染色、Western blotting实验检测相关蛋白表达量变化,并进行活性氧(ROS)、脂质过氧化物丙二醛(MDA)和抗氧化物还原型谷胱甘肽(GSH)含量检测。结果6组小鼠行为学实验结果差异有显著意义(F=11.09、52.70,P<0.01),与对照组相比,MPTP组小鼠转棒时间明显缩短、爬杆时间明显延长(P<0.05);与TAp63NC+MPTP组相比,TAp63过表达+MPTP组小鼠转棒时间明显增加、爬杆时间明显减少(P<0.05)。6组脑组织中TAp63、酪氨酸羟化酶(TH)、沉默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体-γ共激活剂1α(PGC-1α)含量存在明显差异(F=11.16~85.39,P<0.05),与对照组相比,MPTP组4种蛋白含量显著下降(P<0.01);与TAp63NC+MPTP组相比,TAp63过表达+MPTP组小鼠4种蛋白含量明显升高(P<0.05)。6组氧化应激指标存在差异(F=33.71~58.38,P<0.001),与对照组相比,MPTP组脑组织中MDA、ROS含量显著升高,GSH水平明显降低(P<0.001);与TAp63NC+MPTP组相比,TAp63过表达+MPTP组MDA、ROS含量显著降低,GSH水平明显升高(P<0.05)。结论TAp63可能通过SIRT1/PGC-1α信号通路,抑制MPTP诱导的帕金森病小鼠模型的氧化应激反应,从而发挥神经保护作用。 展开更多
关键词 帕金森病 TAp63 过氧化物酶体增殖物激活受体γ共激活因子1α 抗衰老酶1 信号传导 氧化性应激
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血清PGC-1α、NFATc1水平与颅脑损伤患者病情、预后的关系 认领 引用
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作者 唐斌 郭效东 +1 位作者 王本瀚 姚安会 《中国临床神经外科杂志》 2026年第2期89-93,共5页
目的探讨颅脑损伤患者血清过氧化物酶体增殖物激活受体γ辅助激活因子-1α(PGC-1α)及活化T细胞核因子c1(NFATc1)水平的变化及其与病情严重程度和预后的关系。方法2021年4月至2025年4月解放军联勤保障部队第九八八医院前瞻性收治颅脑损... 目的探讨颅脑损伤患者血清过氧化物酶体增殖物激活受体γ辅助激活因子-1α(PGC-1α)及活化T细胞核因子c1(NFATc1)水平的变化及其与病情严重程度和预后的关系。方法2021年4月至2025年4月解放军联勤保障部队第九八八医院前瞻性收治颅脑损伤患者152例,根据入院时GCS分为轻型组(13~15分,51例)、中型组(9~12分,64例)和重型组(3~8分,37例);根据伤后28 d GOS评分分为预后良好组(4~5分,107例)和预后不良组(1~3分,45例)。另选取同期97例体检者为对照组。采用酶联免疫吸附法检测血清PGC-1α、NFATc1水平。采用多因素logistic回归模型分析预后影响因素;绘制ROC曲线评估血清PGC-1α、NFATc1预测患者预后的价值。结果与对照组相比,颅脑损伤组血清PGC-1α水平显著降低,NFATc1水平显著升高,且随着病情加重,变化趋势更明显(P<0.05)。相关性分析显示,血清PGC-1α水平与病情严重程度呈明显负相关(r=-0.748,P<0.001),NFATc1水平与病情严重程度呈明显正相关(r=0.602,P<0.001)。多因素logistic回归分析显示,血清NFATc1水平升高(OR=2.867,95%CI:1.614~5.091,P<0.001)是颅脑损伤患者预后不良的独立危险因素,血清PGC-1α水平升高(OR=0.619,95%CI:0.463~0.827,P=0.001)是其保护因素(P<0.05)。ROC曲线分析显示,血清PGC-1α、NFATc1二者联合预测患者预后不良的曲线下面积为0.934,显著高于二者单独预测的0.826和0.833(P<0.05)。结论颅脑损伤患者血清PGC-1α水平降低、NFATc1水平升高,二者与病情严重程度密切相关,且均为患者短期预后的独立影响因素。联合检测血清PGC-1α与NFATc1可显著提升对颅脑损伤患者预后不良的预测效能。 展开更多
关键词 颅脑损伤 过氧化物酶体增殖物激活受体γ辅助激活因子-1α 活化T细胞核因子c1 预后 血清标志物
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自噬通过核受体共激活因子4调控代谢相关脂肪性肝病中肝细胞铁死亡的分子机制 认领 引用 被引量：1
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作者 高天 曹宇萌 +2 位作者 张瑞昕 李倩倩 刘立新 《中国医科大学学报》 CAS 北大核心 2026年第1期9-14,共6页
目的探讨自噬能否通过核受体共激活因子4(NCOA4)调控代谢相关脂肪性肝病(MAFLD)中肝细胞铁死亡。方法使用1 mmol/L游离脂肪酸(FFA)干预L02肝细胞,建立MAFLD体外细胞模型,将L02肝细胞分为对照组、模型组和氯喹组。采用油红O染色以及甘油... 目的探讨自噬能否通过核受体共激活因子4(NCOA4)调控代谢相关脂肪性肝病(MAFLD)中肝细胞铁死亡。方法使用1 mmol/L游离脂肪酸(FFA)干预L02肝细胞,建立MAFLD体外细胞模型,将L02肝细胞分为对照组、模型组和氯喹组。采用油红O染色以及甘油三酯(TG)、总胆固醇(TC)、天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)检测评估模型效果。采用Western blotting和实时定量PCR检测各组肝细胞中SLC7A11、GPX4、FTH1、TFR1、LC3B、LC3-Ⅱ/LC3-Ⅰ、ATG7、NCOA4的表达。将12只C57BL/6小鼠随机分为对照组(WT组)和模型组(HFCFD组),通过高脂肪/胆固醇/果糖饲料喂养建立小鼠MAFLD模型。采用免疫组织化学染色检测各组小鼠肝组织中LC3B、NCOA4、FTH1、SLC7A11的表达。结果FFA干预后,肝细胞中脂滴聚集,TG、TC、AST、ALT含量增加(均P<0.0001)。与对照组相比,模型组肝细胞中SLC7A11、GPX4、FTH1表达水平降低(均P<0.05),TFR1、LC3-Ⅱ/LC3-Ⅰ、ATG7、NCOA4表达水平升高(均P<0.05);与模型组相比,氯喹组肝细胞中SLC7A11、GPX4、FTH1表达水平降低(均P<0.05),TFR1、LC3-Ⅱ/LC3-Ⅰ、ATG7、NCOA4表达水平升高(均P<0.05)。与WT组相比,HFCFD组小鼠肝组织中LC3B、NCOA4表达水平升高(均P<0.05),FTH1、SLC7A11表达水平降低(均P<0.05)。结论自噬能通过抑制NCOA4蛋白表达,减少FTH1降解,进而抑制MAFLD中肝细胞铁死亡。 展开更多
关键词 肝细胞 铁死亡 自噬 核受体共激活因子4 代谢相关脂肪性肝病
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Coactive design of explainable agent-based task planning and deep reinforcement learning for human-UAVs teamwork 认领 引用 被引量：20
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作者 Chang WANG Lizhen WU +3 位作者 Chao YAN Zhichao WANG Han LONG Chao YU 《Chinese Journal of Aeronautics》 SCIE EI CAS CSCD 2020年第11期2930-2945,共16页
Unmanned Aerial Vehicles(UAVs)are useful in dangerous and dynamic tasks such as search-and-rescue,forest surveillance,and anti-terrorist operations.These tasks can be solved better through the collaboration of multipl... Unmanned Aerial Vehicles(UAVs)are useful in dangerous and dynamic tasks such as search-and-rescue,forest surveillance,and anti-terrorist operations.These tasks can be solved better through the collaboration of multiple UAVs under human supervision.However,it is still difficult for human to monitor,understand,predict and control the behaviors of the UAVs due to the task complexity as well as the black-box machine learning and planning algorithms being used.In this paper,the coactive design method is adopted to analyze the cognitive capabilities required for the tasks and design the interdependencies among the heterogeneous teammates of UAVs or human for coherent collaboration.Then,an agent-based task planner is proposed to automatically decompose a complex task into a sequence of explainable subtasks under constrains of resources,execution time,social rules and costs.Besides,a deep reinforcement learning approach is designed for the UAVs to learn optimal policies of a flocking behavior and a path planner that are easy for the human operator to understand and control.Finally,a mixed-initiative action selection mechanism is used to evaluate the learned policies as well as the human’s decisions.Experimental results demonstrate the effectiveness of the proposed methods. 展开更多
关键词 Coactive design Deep reinforcement learning Human-robot teamwork Mixed-initiative Multi-agent system Task planning UAV
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