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学者姓名：黄映辉
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Abstract ：
Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics. Recombinant viruses can selectivity kill cancer cells and carry therapeutic genes to tumors. Specifically, oncolytic viruses (OV) have been successfully employed for gene delivery in GB animal models and showed potential to neutralize immunosuppression at the tumor site. However, the associated systemic immunogenicity, inefficient transduction of GB cells, and inadequate distribution to metastatic tumors have been the major bottlenecks in clinical studies. Mesenchymal stem cells (MSCs), with tumor-tropic properties and immune privilege, can improve OVs targeting. Remarkably, combining the two approaches can address their individual issues. Herein, we summarize findings to advocate the reactivation of tumor suppressors p53 and PTEN in GB treatment and use MSCs as a "Trojan horse" to carry oncolytic viral cargo to disseminated tumor beds. The integration of MSCs and OVs can emerge as the new paradigm in cancer treatment.
Keyword ：
Mesenchymal stem cells Mesenchymal stem cells Targeted delivery Targeted delivery Tumor suppressors Tumor suppressors Oncolytic viruses Oncolytic viruses
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| GB/T 7714 | Ali, Sakhawat , Xia, Qin , Muhammad, Tahir et al. Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses [J]. | STEM CELL REVIEWS AND REPORTS , 2021 , 18 (2) : 523-543 . |
| MLA | Ali, Sakhawat et al. "Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses" . | STEM CELL REVIEWS AND REPORTS 18 . 2 (2021) : 523-543 . |
| APA | Ali, Sakhawat , Xia, Qin , Muhammad, Tahir , Liu, Liqun , Meng, Xinyi , Bars-Cortina, David et al. Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses . | STEM CELL REVIEWS AND REPORTS , 2021 , 18 (2) , 523-543 . |
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Abstract ：
腺病毒(Adenovirus,AdV)是常见的基因治疗载体,已有的腺病毒下游纯化工艺通常采取阴离子交换层析搭配分子筛的方式,该方法存在耗时长、成本高、难以放大并且所获得的腺病毒中具有感染性的腺病毒比例较低的问题,本研究旨在探究并优化一步层析法,纯化得到高滴度的5型腺病毒.首先在5L生物反应器中利用HEK-293.2sus细胞扩增5型腺病毒,通过对细胞沉淀的反复冻融释放病毒,利用过滤和超滤技术去除部分杂质,并通过添加核酸酶降低料液的黏稠度,最后利用新型复合填料Capto core 700或Fractogel填料进行纯化.纯化后的病毒利用50％组织细胞感染量(Median tissue culture infective dose,TCID50)测定方法测定病毒滴度,利用PCR-荧光探针法检测宿主DNA的残留以及酶联免疫法检测宿主蛋白的残留以判断除杂效果.两种一步层析法纯化腺病毒的回收率均高于传统的两步法,但在宿主蛋白和宿主DNA的去除效果上Capto core700的结果均不如Fractogel填料与超滤置换的结合,所以利用超滤和Fractogel结合的纯化方式更适合获得临床级别的腺病毒.
Keyword ：
5型腺病毒(AdV5) 5型腺病毒(AdV5) 纯化 纯化 超滤 超滤 阴离子交换层析 阴离子交换层析
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| GB/T 7714 | 马羚 , 王弘扬 , 张霖 et al. 5型腺病毒一步层析纯化方案研究 [J]. | 病毒学报 , 2020 , 36 (1) : 77-83 . |
| MLA | 马羚 et al. "5型腺病毒一步层析纯化方案研究" . | 病毒学报 36 . 1 (2020) : 77-83 . |
| APA | 马羚 , 王弘扬 , 张霖 , 胡利明 , 黄映辉 . 5型腺病毒一步层析纯化方案研究 . | 病毒学报 , 2020 , 36 (1) , 77-83 . |
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Abstract ：
Hypermethylation of gene promoter has been indicated for the contribution of gene silencing, and DNA demethylating drugs, such as 5-aza-2'-deoxycytidine (DAC), has been used clinically for cancer treatment. However, the reason why a proportion of genes with hypermethylated promoter exhibit high expression levels remains unclear and this drug is not much successful as expected in use. Furthermore, CpG islands (CGIs) are found to be located in not only promotors, but also in gene bodies. By RNA-seq and reduced representation bisulfite sequencing, we found the mismatch between the level of promoter methylation and gene expression. By chromatin Immunoprecipitation-quantitative polymerase chain reaction and luciferase reporter assay, we identified putative promoters in gene body, and proved the activities of putative promoters were affected by the methylation level of the CGI nearby. DAC can reverse the DNA hypermethylation at promoter CGIs effectively but not the CGIs in gene body. We also found that TET1 could demethylate CGIs both in promoter and gene body. Furthermore, we revealed a novel mechanism that H3K36me3 could affect the activity of putative promoter, and 5hmC recruited MeCP2 and CREB1 as a coactivator to SETD2 promoter, to enhance its gene expression and result in increased H3K36me3 in gene body. Our results concluded that putative promoters existed in the gene bodies, and TET1 could influence the transcriptional activity of putative promoters by intragenic demethylation.
Keyword ：
5hmC 5hmC DNA methylation DNA methylation TET1 TET1 gene body gene body putative promoters putative promoters
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| GB/T 7714 | Ma, Ling , Muhammad, Tahir , Wang, Hongyang et al. Putative promoters within gene bodies control exon expression via TET1-mediated H3K36 methylation [J]. | JOURNAL OF CELLULAR PHYSIOLOGY , 2020 , 235 (10) : 6711-6724 . |
| MLA | Ma, Ling et al. "Putative promoters within gene bodies control exon expression via TET1-mediated H3K36 methylation" . | JOURNAL OF CELLULAR PHYSIOLOGY 235 . 10 (2020) : 6711-6724 . |
| APA | Ma, Ling , Muhammad, Tahir , Wang, Hongyang , Du, Guangyuan , Sakhawat, Ali , Wei, Yazi et al. Putative promoters within gene bodies control exon expression via TET1-mediated H3K36 methylation . | JOURNAL OF CELLULAR PHYSIOLOGY , 2020 , 235 (10) , 6711-6724 . |
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Abstract ：
基于Q‑6XL和4FF的腺病毒载体规模化纯化方法涉及腺病毒载体纯化领域，特别设计了基于Q‑6XL和4FF串联的规模化腺病毒纯化方案, 旨在提高腺病毒载体制备的效率和纯度，最终提高腺病毒制剂的产量和质量。病毒发酵液经过离心、冻融、PEG浓缩、置换缓冲液等工艺处理后，首先采用Q‑6XL阴离子交换层析除去病毒发酵液中的宿主蛋白、宿主DNA，获得腺病毒粗纯液。然后采用4FF凝胶过滤层析(分子筛)对病毒粗纯液进行精纯，最终得到高纯度的腺病毒载体。特别的是，本方法适用于腺病毒载体规模化纯化。满足了临床阶段对于高纯度腺病毒载体用量日益增加的需求。
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| GB/T 7714 | 胡利明 , 王弘扬 , 黄映辉 et al. 基于Q-6XL和4FF的腺病毒载体规模化纯化方法 : CN202010154302.X[P]. | 2020-03-07 . |
| MLA | 胡利明 et al. "基于Q-6XL和4FF的腺病毒载体规模化纯化方法" : CN202010154302.X. | 2020-03-07 . |
| APA | 胡利明 , 王弘扬 , 黄映辉 , 马羚 , 张霖 . 基于Q-6XL和4FF的腺病毒载体规模化纯化方法 : CN202010154302.X. | 2020-03-07 . |
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Abstract ：
Purpose Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and ranked top in terms of incidence and mortality in men and women. Recently, improvements in treatment approaches for NSCLC have reported, but still, there is a need to devise innovative treatment strategies, especially to manage the advanced and metastatic stage of NSCLC. Aloperine (ALO), an herbal alkaloid, has exerted anti-cancer effects in many cancers. However, the use of any chemotherapeutic agents is dose limited due to possible adverse effects and drug-resistance issues. Therefore, a combination of chemotherapy with viral-based targeted gene therapy may provide a novel treatment strategy for NSCLC. Methods/results In this study, the results of the MTT and flow cytometry-based assays showed that Aloperine-Adbic (adenoviral vector expressing p14(ARF)/p53) combined treatment on NSCLC cells synergistically produced anti-proliferative effects, induced apoptosis, and arrested cell cycle at the G1 phase. Furthermore, the expression analysis suggested that the p53/p21 pathway might contribute to achieving aforesaid cytotoxic effects. The ALO-Adbic combined treatment prolonged the percent survival of NSCLC xenograft models. Conclusion In conclusion, ALO-Adbic combination can produce synergistic anti-cancer effects at low doses, and may offer a more effective and less toxic new treatment strategy for NSCLC.
Keyword ：
NSCLC NSCLC Aloperine Aloperine Adenoviral vectors Adenoviral vectors p53 p53 Synergy Synergy
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| GB/T 7714 | Muhammad, Tahir , Sakhawat, Ali , Khan, Aamir Ali et al. Aloperine in combination with therapeutic adenoviral vector synergistically suppressed the growth of non-small cell lung cancer [J]. | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY , 2020 , 146 (4) : 861-874 . |
| MLA | Muhammad, Tahir et al. "Aloperine in combination with therapeutic adenoviral vector synergistically suppressed the growth of non-small cell lung cancer" . | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 146 . 4 (2020) : 861-874 . |
| APA | Muhammad, Tahir , Sakhawat, Ali , Khan, Aamir Ali , Huang, Hua , Khan, Haroon Rashid , Huang, Yinghui et al. Aloperine in combination with therapeutic adenoviral vector synergistically suppressed the growth of non-small cell lung cancer . | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY , 2020 , 146 (4) , 861-874 . |
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Abstract ：
Purpose: The study aims to lay a foundational probe for the thorough application microfluidic chips in brain function research with microfluidic chips. Neuron slide culture is a common culture method in vitro, and the microfluidic chip with the artificial network pattern not only can realize neuron cells 3 D culture in vitro, but also limit the extension space of neurite outgrow. Materials and Methods: In order to analyze the differences of hippocampal cells neurite growth length between the 3 D chips and the common 2 D culture, the experiments utilized statistical analysis method analyzing the length of the hippocampus neuron neurite of 3 days, 5 days and 7 days, respectively, with the common glass slide 2 D culture method and the microfluidic chip 3 D culture in vitro. Results: The results showed that there was no significant difference in the neurite length after 3 days. However, there was a significant difference after 5 days and 7 days. It can be seen that the microfluidic chip with artificial network pattern has limitations to the growth of neurite after 5 days. Conclusions: We concluded that the growth state of hippocampal cells in the restricted 3 D space is different from that of conventional 2 D culture.It showed that the artificial network pattern design has limited the growth space of the dendrites but also affected its growth.
Keyword ：
hippocampal cells hippocampal cells artificial network pattern artificial network pattern Microfluidic chip Microfluidic chip the length of neurite the length of neurite
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| GB/T 7714 | Kong, Xianmin , Chen, Tao , Huang, Yinghui . Analysis of neurite length of hippocampal neurons cultured into 3D artificial network patterned microfluidic chips [J]. | INTERNATIONAL JOURNAL OF NEUROSCIENCE , 2020 , 131 (1) : 40-43 . |
| MLA | Kong, Xianmin et al. "Analysis of neurite length of hippocampal neurons cultured into 3D artificial network patterned microfluidic chips" . | INTERNATIONAL JOURNAL OF NEUROSCIENCE 131 . 1 (2020) : 40-43 . |
| APA | Kong, Xianmin , Chen, Tao , Huang, Yinghui . Analysis of neurite length of hippocampal neurons cultured into 3D artificial network patterned microfluidic chips . | INTERNATIONAL JOURNAL OF NEUROSCIENCE , 2020 , 131 (1) , 40-43 . |
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Abstract ：
目的:探讨TET1催化结构域(TET1-CD)基因高表达对乳腺癌细胞MDA-MB-231增殖、迁移的影响及其可能的作用机制.方法:慢病毒感染建立高表达TET1-CD的MDA-MB-231细胞系,用qPCR检测细胞中TET1-CD mRNA的表达,Transwell实验和细胞划痕实验检测细胞的迁移能力,MTT法和克隆形成实验检测细胞的增殖能力,WB实验检测MDA-MB-231细胞上皮间质转化(EMT)途径相关蛋白E-cadherin、Vimentin、MMP2以及Wnt、Hedgehog(HH)通路相关蛋白的表达水平.结果:过表达TET1-CD提高乳腺癌MDA-MB-231细胞TET1-CD的表达水平(P＜0.01),明显抑制MDA-MB-231细胞的增殖和迁移能力(均P＜0.01).过表达TET1-CD可使乳腺癌MDA-MB-231细胞E-cadherin表达上升,Vimentin、MMP2表达下调(均P＜0.05);可使β-catenin、C-myc、CyclinD1、Gli1蛋白表达水平降低(均P＜0.05).结论:过表达TET1-CD可能通过Wnt、HH信号通路抑制EMT途径进而抑制乳腺癌细胞MDA-MB-231的增殖和迁移.
Keyword ：
TET1催化结构域 TET1催化结构域 表观遗传 表观遗传 上皮间质转化 上皮间质转化 增殖 增殖 MDA-MB-231细胞 MDA-MB-231细胞 乳腺癌 乳腺癌 迁移 迁移
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| GB/T 7714 | 赵全华 , 王申森 , 马羚 et al. TET1-CD对乳腺癌细胞MDA-MB-231增殖和迁移的影响及其作用机制 [J]. | 中国肿瘤生物治疗杂志 , 2019 , 26 (6) : 644-649 . |
| MLA | 赵全华 et al. "TET1-CD对乳腺癌细胞MDA-MB-231增殖和迁移的影响及其作用机制" . | 中国肿瘤生物治疗杂志 26 . 6 (2019) : 644-649 . |
| APA | 赵全华 , 王申森 , 马羚 , 周志祥 , 黄映辉 . TET1-CD对乳腺癌细胞MDA-MB-231增殖和迁移的影响及其作用机制 . | 中国肿瘤生物治疗杂志 , 2019 , 26 (6) , 644-649 . |
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Abstract ：
Purpose: The design of pattern that limits the hippocampal cells growth is an important explore for realizing a simplified artificial neuronal network in vitro. Materials and methods: In this study, we examined the pattern in micro-fluidic chip to stipulate the hippocampal cells adhesion, growth and the formation of a functional neuronal network in vitro. Patch clamp recording technique was used to detect the growth situation and biological function of the haippocampal cells on the micro-fluidic chip which could simulate environment in vivo. Results: We showed that the number of neurons cultured was about 5000-6000 cells on the micro-fluidic chip, which was conductive to the hippocampal cells growth. The result of patch clamp recording technique showed the signals of sodium and potassium channels, meanwhile, it also revealed the signals of synaptic connection. Conclusions: These findings involve placing cells in specific locations to create organized structures, and explore the spread function of synaptic on the micro-fluidic chip.
Keyword ：
artificial neuronal network artificial neuronal network Hippocampal cells Hippocampal cells micro-fluidic chip micro-fluidic chip patch clamp recording technique patch clamp recording technique
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| GB/T 7714 | Kong, Xianmin , Tian, Shanshan , Chen, Tao et al. Functional detection of the original generation of hippocampal cells planted on to the micro-fluidic chip with artificial neuronal network using the patch clamp recording technique: a preliminary study [J]. | INTERNATIONAL JOURNAL OF NEUROSCIENCE , 2019 , 129 (5) : 430-437 . |
| MLA | Kong, Xianmin et al. "Functional detection of the original generation of hippocampal cells planted on to the micro-fluidic chip with artificial neuronal network using the patch clamp recording technique: a preliminary study" . | INTERNATIONAL JOURNAL OF NEUROSCIENCE 129 . 5 (2019) : 430-437 . |
| APA | Kong, Xianmin , Tian, Shanshan , Chen, Tao , Huang, Yinghui . Functional detection of the original generation of hippocampal cells planted on to the micro-fluidic chip with artificial neuronal network using the patch clamp recording technique: a preliminary study . | INTERNATIONAL JOURNAL OF NEUROSCIENCE , 2019 , 129 (5) , 430-437 . |
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Abstract ：
表观遗传是在指不影响遗传序列的情况下影响型状表达的方法.除了经典遗传方面,如点突变、颠换、插入与肺癌的发生有关,近年来研究显示表观遗传学对肺癌的发生也起到了重要的作用.本文主要从表观遗传学角度,简述了DNA甲基化、组蛋白修饰、非编码RNA尤其是miRNA与肺癌的关系,甲基化主要是通过抑制原癌基因,促进抑癌基因表达导致肺癌,组蛋白修饰会促进抑癌基因的表达,非编码RNA可以作为肺癌诊断的生物标记物,为肺癌的早期诊断提供依据.
Keyword ：
DNA甲基化 DNA甲基化 miRNA miRNA 组蛋白修饰 组蛋白修饰 肺癌 肺癌
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| GB/T 7714 | 刘亚茹 , 汪涛 , 马羚 et al. 表观遗传学与肺癌 [J]. | 现代生物医学进展 , 2019 , 19 (6) : 1176-1179 . |
| MLA | 刘亚茹 et al. "表观遗传学与肺癌" . | 现代生物医学进展 19 . 6 (2019) : 1176-1179 . |
| APA | 刘亚茹 , 汪涛 , 马羚 , 王申森 , 黄华 , 黄映辉 . 表观遗传学与肺癌 . | 现代生物医学进展 , 2019 , 19 (6) , 1176-1179 . |
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Abstract ：
目的初步探讨利用微流控技术体外构建三维海马神经元网络的可行性。方法设计并采用标准湿法腐蚀工艺制备网络图案化的微流控芯片。取新生SD大鼠丘脑组织,分离培养原代海马神经元后,接种于微流控芯片上进行培养。3、5、7 d时行免疫荧光染色,观察海马神经元生长情况;7 d时行海马神经元网络电生理检测。结果荧光显微镜下观察显示,随培养时间延长,海马神经元数量逐渐增加,且神经元突起亦相应增多、增长,并且均匀规则分布在微流控芯片通道,提示成功构建三维海马神经元网络。培养7 d时可以检测到海马神经元网络的单通道及多通道自发放电信号,提示神经元网络具有初步的生物学功能。结论图案化微流控芯片可以使海马神经元按照局限路...
Keyword ：
海马神经元 海马神经元 神经元网络 神经元网络 微流控芯片 微流控芯片 三维培养 三维培养
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| GB/T 7714 | 孔宪敏 , 田姗姗 , 陈涛 et al. 利用微流控技术体外构建三维海马神经元网络的初步研究 [J]. | 中国修复重建外科杂志 , 2019 , 33 (02) : 239-242 . |
| MLA | 孔宪敏 et al. "利用微流控技术体外构建三维海马神经元网络的初步研究" . | 中国修复重建外科杂志 33 . 02 (2019) : 239-242 . |
| APA | 孔宪敏 , 田姗姗 , 陈涛 , 黄映辉 . 利用微流控技术体外构建三维海马神经元网络的初步研究 . | 中国修复重建外科杂志 , 2019 , 33 (02) , 239-242 . |
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