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Azithromycin enhances anticancer activity of TRAIL by inhibiting autophagy and up-regulating the protein levels of DR4/5 in colon cancer cells in vitro and in vivo

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Cancer Communications 2018年第1期38卷 446-458页

作者： Xinran Qiao Xiaofei Wang Yue Shang Yi Li shu-zhen chen Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050P.R.China

Background:Azithromycin is a member of macrolide antibiotics,and has been reported to inhibit the proliferation of cancer ***,the underlying mechanisms are not been fully *** necrosis factor-related apoptosis-inducing ligand(TRAIL)selectively targets tumor cells without damaging healthy *** the present study,we examined whether azithromycin is synergistic with TRAIL,and if so,the underlying mechanisms in colon ***:HCT-116,SW480,SW620 and DiFi cells were treated with azithromycin,purified TRAIL,or their combina-tion.A sulforhoddamine B assay was used to examine cell *** was examined using annexin V-FITC/PI staining,and autophagy was observed by acridine orange *** blot analysis was used to detect protein expression *** mechanistic experiments,siRNAs were used to knockdown death receptors(DR4,DR5)and *** anticancer effect of azithromycin and TRAIL was also examined in BALB/c nude mice carrying HCT-116 ***:Azithromycin decreased the proliferation of HCT-116 and SW480 cells in a dose-dependent *** of azithromycin and TRAIL inhibited tumor growth in a manner that could not be explained by additive *** increased the expressions of DR4,DR5,p62 and LC-3B proteins and potentiated induction of apoptosis by *** of DR4 and DR5 with siRNAs increased cell survival rate and decreased the expression of cleaved-PARP induced by the combination of azithromycin and ***-3B siRNA and CQ potentiated the anti-proliferation activity of TRAIL alone,and increased the expressions of DR4 and ***:The synergistic antitumor effect of azithromycin and TRAIL mainly relies on the up-regulations of DR4 and DR5,which in turn result from LC-3B-involved autophagy inhibition.

关键词： Azithromycin TRAIL Apoptosis Autophagy Colon cancer

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Detection of k-ras gene point mutation in fine needle aspiration and pancreatic juice by sequence special primer method and its clinical significance

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World Journal of Gastroenterology 2000年第6期6卷 917-919页

作者： Xun Liang Liu Cun Cai Dai Yi Miao Jing Hui Du Zhao Song Zhang shu zhen chen Department of General Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210024Jiangsu ProvinceChina The Molecular Biology Research Center of Nanjing Medical University Nanjing 210029Jiangsu ProvinceChina

INTRODUCTIONThe point mutation rate of k-ras gene at codon 12 inpancreatic adenocarcinoma is reported to be as highas 90%,and with no mutations in normalpancreas tissues or other pancreatic *** detected the presence o... 详细信息

关键词： pancreatic neoplasms/diagnosis polymerase chain reaction biopsy needle genes ras pancreatic diseases pancreatic juice gene amplification cytodiagnosis

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Arahidopsis CHLOROPHYLLASE 1 protects young leaves from long-term photodamage by facilitating FtsH-mediated D1 degradation in photosystemⅡrepair

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Molecular Plant 2021年第7期14卷 1149-1167页

作者： Ya-nan Tian Rui-hao Zhong Jun-bin Wei Hong-hui Luo Yoram Eyal Hong-lei Jin La-jie Wu Ke-ying Liang Ying-man Li shu-zhen chen Zhao-qi Zhang Xue-qun Pang State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources/Guangdong Provincial Key Laboratory of Postharvest Science of Fruits and Vegetables South China Agricultural UniversityGuangzhou 510642People's Republic of China College of Life Sciences South China Agricultural UniversityGuangzhou 510642People's Republic of China College of Horticulture South China Agricultural UniversityGuangzhou 510642People's Republic of China lnstitute of Plant Sciences The Volcani CenterAgricultural Research OrganizationBet Dagan 50250Israel lnstituteof Medical Plant Physiology and Ecology School of Pharmaceutical SciencesGuangzhou University of Chinese MedicineGuangzhou 510006People's Republic of China

The proteolytic degradation of the photodamaged D1 core subunit during the photosystemⅡ(PSⅡ)repair cycle is well understood,but chlorophyll turnover during D1 degradation remains ***,we report that Arabidopsis thaliana CHLOROPHYLLASE 1(CLH1)plays important roles in the PSII repair *** abundance of CLH1 and CLH2 peaks in young leaves and is induced by high-light *** of clh1 single and clh1-1/2-2 double mutants display increased photoinhibition after long-term high-light exposure,whereas seedlings overexpressing CLH1 have enhanced light tolerance compared with the wild ***1 is localized in the developing chloroplasts of young leaves and associates with the PSⅡ-dismantling complexes RCC1 and RC47,with a preference for the latter upon exposure to high ***,degradation of damaged D1 protein is retarded in young clh1-1/2-2 leaves after 18-h highlight exposure but is rescued by the addition of recombinant CLH1 in ***,overexpression of CLH1 in a variegated mutant(var2~2)that lacks thylakoid protease FtsH2,with which CLH1 interacts,suppresses the variegation and restores D1 degradation.A var2-2 clh1-1/2-2triple mutant shows more severe variegation and seedling *** together,these results establish CLH1 as a long-sought chlorophyll dephytylation enzyme that is involved in PSⅡrepair and functions in long-term adaptation of young leaves to high-light exposure by facilitating FtsH-mediated D1 degradation.

关键词： chlorophyllase photosystemⅡrepair young leaf D1 degradation photoprotection chlorophyll dephytylation

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在体内和体外条件下阿奇霉素通过抑制自噬和上调结肠癌细胞内DR4/5蛋白水平增强TRAIL抗癌活性

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癌症 2018年第12期37卷 545-558页

作者： Xinran Qiao Xiaofei Wang Yue Shang Yi Li shu-zhen chen 医药生物技术研究所中国医学科学院&北京协和医学院

背景与目的阿奇霉素为大环内酯抗生素,曾被报道可抑制肿瘤细胞增殖。然而,其潜在机制尚未完全阐明。肿瘤坏死因子相关凋亡诱导配体(TNF?related apoptosis inducing ligand,TRAIL)选择性地靶向肿瘤细胞而不损伤健康细胞。在本研究中,我... 详细信息

背景与目的阿奇霉素为大环内酯抗生素,曾被报道可抑制肿瘤细胞增殖。然而,其潜在机制尚未完全阐明。肿瘤坏死因子相关凋亡诱导配体(TNF?related apoptosis inducing ligand,TRAIL)选择性地靶向肿瘤细胞而不损伤健康细胞。在本研究中,我们研究阿奇霉素是否与TRAIL协同作用,如果有相互作用,进一步探究其在结肠癌中的潜在机制。方法对HCT?116、SW480、SW620和DiFi细胞进行阿奇霉素给药处理,纯化TRAIL或它们的结合物。采用磺酰罗丹明B实验检测细胞存活。凋亡检测采用了annexin V?FITC/PI染色法,自噬则通过吖啶橙染色法检测。Western blot分析用于检测蛋白表达水平。在机制实验中,siRNA用于敲低死亡受体(DR4、DR5)和LC?3B。利用携带HCT?116异种移植瘤的BALB/c裸鼠进行了阿奇霉素和TRAIL联合抗癌作用的检测。结果阿奇霉素剂量依赖性地抑制HCT?116和SW480细胞的增殖。阿奇霉素和TRAIL联合抑制肿瘤生长的行为不能通过叠加效应解释。阿奇霉素提高了DR4、DR5、p62和LC?3B蛋白的表达水平,增强了TRAIL诱导凋亡。siRNA敲低DR4和DR5后提高了细胞存活率,降低了阿奇霉素和TRAIL联合诱导的cleaved?PARP的表达。LC?3B siRNA和Chloroquine(CQ)增强了TRAIL单独的抗增殖活性,提高了DR4和DR5的表达。结论阿奇霉素和TRAIL的协同抗肿瘤作用主要依赖于DR4和DR5的上调,而这是LC?3B相关自噬抑制的结果。

关键词：阿奇霉素 TRAIL 凋亡自噬结肠癌

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A MODIFIED CEPSTRUM MELODY EXTRACTOR FOR QUERY BY HUMMING

A MODIFIED CEPSTRUM MELODY EXTRACTOR FOR QUERY BY HUMMING

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第11届国际模糊系统协会世界大会

作者： Shen Yang, shu zhen chen School of Electronic Information, Wuhan University, Wuhan 430079, Hubei, China

This paper presents a melody extractor based on cep strum for humming input. By this extractor, an adaptive double-threshold method is designed for voiced/silent decision. Then pitches of voice segments are extracted by a modified cepstrum method. Finally, the sequences of rhythm and pitch are achieved and outputted. Experiment results show that the extractor can correctly elicit melody information of humming signals.

关键词： query by humming cepstrum melody rhythm pitch contour

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Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

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Neural Regeneration Research 2025年第1期20卷 159-173页

作者： Man Han Deyang Zeng Wei Tan Xingxing chen shuyuan Bai Qiong Wu Yushan chen zhen Wei Yufei Mei Yan Zeng Brain Science and Advanced Technology Institute Wuhan University of Science and TechnologyWuhanHubei ProvinceChina Geriatric Hospital Affiliated to Wuhan University of Science and Technology WuhanHubei ProvinceChina School of Public Health Wuhan University of Science and TechnologyWuhanHubei ProvinceChina

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral *** studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and *** how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress *** this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of *** focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine *** determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic ***,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

关键词： amygdala chronic mild stress chronic social defeat stress corticolimbic system depression hippocampus medial prefrontal cortex nucleus accumbens social stress models ventral tegmental area

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稀土-铋复合氧化物体系的研究

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化学学报 1986年第2期44卷 139-144页

作者：张静筠许淑珍陈明玉刘书珍苏锵中国科学院长春应用化学研究所中国科学院长春应用化学研究所长春

本文讨论了稀土-铋复合氧化物的制备及某些性质的变化规律.稀土与三价金属的复合氧化物的制备与性质已做了大量工作,然而关于稀土-铋复合氧化物的热稳定性、磁性和反射光谱及其变化规律文献报道不多. 在1200℃空气中制备的稀土-铋复合... 详细信息

本文讨论了稀土-铋复合氧化物的制备及某些性质的变化规律.稀土与三价金属的复合氧化物的制备与性质已做了大量工作,然而关于稀土-铋复合氧化物的热稳定性、磁性和反射光谱及其变化规律文献报道不多. 在1200℃空气中制备的稀土-铋复合氧化物的晶体结构可分为三种类型,其中三价轻稀土（RE=La,Nd,Sm,Eu和Gd）-铋复合氧化物为菱形结构的固溶体,属于三方晶系,Pr6O11（Bi2O3）1.8和（Tb4O7）1.5·（Bi2O3）1.68为萤石型结构的固溶体,属立方晶系.其余的3RE2O3·nBi2O3（RE=Ce,Dy,Ho,Er,Tm,Yb,Lu和Y,n分别为0.80,1.68,1.60,1.30,0.94,0.82,0.12和1.34）复合氧化物为萤石型的固溶体和C-型RE2O3的混相.这些固溶体的晶胞参数随着原子序数的增加而减少,这种变化规律是由镧系收缩引起的. 随着稀土原子序的增加,稀土-铋复合氧化物的热稳定性降低,并在钆处出现转折,它们磁化率呈现具有两个极大值的周期变化.由于Bi-O键的存在,在它们的反射光谱中有一个宽的紫外吸收带,因此它们可能应用为着色透镜玻璃和紫外吸收材料.

关键词：复合氧化物 Bi 热稳定性三价固溶体热力学性质稀土

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结直肠癌靶向治疗的现状与未来

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世界华人消化杂志 2017年第4期25卷 307-315页

作者：陈淑珍中国医学科学院北京协和医学院医药生物技术研究所北京市100050

结直肠癌(colorectal cancer,CRC)是消化系统常见的恶性肿瘤.目前主要采用传统化疗与靶向药物联合来治疗转移性CRC患者,提高肿瘤对药物的反应率,延长患者的无病生存期和总生存期,改善患者生活质量.本文对血管内皮生长因子、表皮生长因... 详细信息

结直肠癌(colorectal cancer,CRC)是消化系统常见的恶性肿瘤.目前主要采用传统化疗与靶向药物联合来治疗转移性CRC患者,提高肿瘤对药物的反应率,延长患者的无病生存期和总生存期,改善患者生活质量.本文对血管内皮生长因子、表皮生长因子受体、环氧化酶-2、基质金属蛋白酶、受体酪氨酸激酶、PD-1/PD-L1、RAS、BRAF等C R C靶向治疗的相关分子靶点进行了阐述并说明了他们在CRC的分布情况;同时,也对CRC靶向治疗的现状进行了描述,包括抗体药物、小分子靶向药物、融合蛋白、免疫治疗等.本文将为CRC的个体化精准治疗提供参考.

关键词：结直肠癌靶向治疗血管内皮生长因子表皮生长因子受体免疫治疗

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基于CFD与最小二乘法的翼伞动力学建模

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北京理工大学学报 2017年第2期37卷 157-162,167页

作者：孙青林梁炜陶金罗淑贞陈增强贺应平南开大学计算机与控制工程学院天津300350 航宇救生装备有限公司实验部湖北襄阳441022

襟翼偏转气动计算是翼伞建模的关键问题,为提高翼伞动力学模型精度,本文引入襟翼偏转气动模型,提出CFD数值模拟与最小二乘辨识相结合的方法:数值模拟借助动网格动态捕捉翼伞外形与姿态变化,获取襟翼偏转气动数据;最小二乘法进行模型参... 详细信息

襟翼偏转气动计算是翼伞建模的关键问题,为提高翼伞动力学模型精度,本文引入襟翼偏转气动模型,提出CFD数值模拟与最小二乘辨识相结合的方法:数值模拟借助动网格动态捕捉翼伞外形与姿态变化,获取襟翼偏转气动数据;最小二乘法进行模型参数辨识,修正翼伞气动计算.研究表明襟翼偏转气动模型较好反映翼伞气动规律,对应动力学模型与空投试验数据接近,验证本文建模方法的有效性,为翼伞精确建模提供新思路.

关键词：翼伞动力学模型襟翼偏转数值模拟最小二乘法

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Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

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Neural Regeneration Research 2025年第6期20卷 1801-1815页

作者： Qing He zhen Wang Yuchen Wang Mengjie Zhu Zhile Liang Kanghong Zhang Yuge Xu Gong chen GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina

Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

关键词： aquaporin-4 Ascl1 astrocyte cortex Dlx2 gap junction glia-to-neuron conversion neural regeneration NeuroD1 reprogramming

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