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Mutant p53 in cancer therapy-the barrier or the path

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Journal of Molecular Cell Biology 2019年第4期11卷 293-305页

作者： Xiang Zhou Qian Hao hua lu Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences and Key Laboratory of Medical Epigenetics and Metabolism Fudan University Shanghai 200032 China Fudan University Shanghai Cancer Center Fudan University Shanghai 200032 China Department of Biochemistry & Molecular Biology and Tulane Cancer Center Tulane University School of Medicine New Orleans LA 70112 USA

Since wild-type p53 is central for maintaining genomic stability and preventing oncogenesis, its coding gene TP53 is highly mutated in ~50% of human cancers, and its activity is almost abrogated in the rest of cancers. Approximately 80% of p53 mutations are single point mutations with several hotspot mutations. Besides loss of function and dominant-negative effect on the wild-type p53 activity, the hotspot p53 mutants also acquire new oncogenic functions, so-called ‘gain-of-functions’(GOF). Because the GOF of mutant p53 is highly associated with late-stage malignance and drug resistance, these p53 mutants have become hot targets for developing novel cancer therapies. In this essay, we review some recent progresses in better understanding of the role of mutant p53 GOF in chemoresistance and the underlying mechanisms, and discuss the pros and cons of targeting mutant p53 for the development of anti-cancer therapies.

关键词： mutant p53 gain-of-function cancer therapy chemoresistance synthetic lethality

Effects of concave and convex substrate curvature on cell mechanics and the cytoskeleton

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Chinese Chemical Letters 2017年第4期28卷 818-826页

作者： Shuang-Shuang Chen Xue-Min lu Qing-hua lu School of Chemistry and Chemical Engineering State Key Laboratory of Metal Matrix Composites Shanghai Jiao Tong University Shanghai 200240 China

In order to understand how cells respond to concave and convex subcellular surface structures,colloidal crystal array and honeycomb-structured surfaces composed of highly ordered hexagonal units with completely inverse curvature were fabricated via facile self-assembly and breath figure approaches,*** influence of hexagonal surface curvature on cell fate was subsequently *** underwent more extensive spreading on the convex colloidal crystal array surface,while adhesive forces were higher on the concave honeycomb *** behaviors of cells on the different surfaces were investigated by comparing cell morphology,cellular adhesive force and cytoskeleton *** results revealed comprehensive differences in cell behavior between those on concave honeycomb surfaces and convex colloidal crystal arrays.

关键词： Colloidal crystal array Honeycomb structure Substrate curvature Cytoskeleton Adhesive force

A potential synthetic lethal strategy with PARP inhibitors:perspective on‘Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP’

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Journal of Molecular Cell Biology 2021年第9期13卷 690-692页

作者： Qian Hao hua lu Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Biochemistry&Molecular Biology and Tulane Cancer Center Tulane University School of MedicineNew OrleansLA 70112USA Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032China Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghai 200032China

The tumor suppressor p53 plays an important role in the inhibition of cancer progression,particularly in response to chemotherapy or target-specific *** or mutation of p53 often becomes a cancer’s tactic for drug *** of the clinically applied therapeutic strategies is to inhibit poly(ADP-ribose)polymerase(PARP)activity,as PARP inhibitors are widely used for subsets of tumors with homologous recombination deficiency due to mutation of BRCA1/2 or other DNA repair-associated *** has been shown that p53 deficiency or mutation enhances the cytotoxicity of PARP inhibition in various tumors(Williamson et al.,2012).

关键词： suppressor chemotherapy activation

Negative auto-regulators trap p53 in their web

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Journal of Molecular Cell Biology 2017年第1期9卷 62-68页

作者： Xiang Zhou Bo Cao hua lu Fudan University Shanghai Cancer Center and the Institutes of Biomedical Sciences Fudan University Shanghai 200032 China Department of Biochemistry & Molecular Biology and Tulane Cancer Center Tulane University School of Medicine New Orleans LA 70112 USA

The transcriptional factor p53 activates the expression of a myriad of target genes involving a complicated signalling network, resulting in various cellular outcomes, such as growth arrest, senescence, apoptosis, and metabolic changes, and leading to con- sequent suppression of tumour growth and progression. Because of the profoundly adverse effect of p53 on growth and prolifer- ation of cancer cells, several feedback mechanisms have been employed by the cells to constrain p53 activity. Two major antagonists MDM2 and MDMX （the long forms） are transcriptionally induced by p53, but in return block p53 activity, forming a negative feedback circuit and rendering chemoresistance of several cancer cells. However, they are not alone, as cancer cells also employ other proteins encoded by p53 target genes to inhibit p53 activity at transcriptional, translational, and posttransla- tional levels. This essay is thus composed to review a recent progress in understanding the mechanisms for how cancer cells hijack the p53 autoregulation by these proteins for their growth advantage and to discuss the clinical implications of these auto- regulatory loops.

关键词： p53 MDM2 NGFR transcription feedback loop chemoresistance

三维可视化助力晶体材料教学——VESTA软件

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化学教育（中英文） 2024年第8期45卷 109-116页

作者：黄亨明房正刚陆春华南京工业大学材料科学与工程学院江苏南京211816

以VESTA软件为例,探讨了三维可视化软件在晶体材料教学中的应用,强调其在抽象概念与形象认知之间的桥梁作用。VESTA的三维可视化功能有益于对晶体结构、晶格参数和对称操作等教学内容的理解,实现沉浸式教学并提升学生的参与度。电子结... 详细信息

以VESTA软件为例,探讨了三维可视化软件在晶体材料教学中的应用,强调其在抽象概念与形象认知之间的桥梁作用。VESTA的三维可视化功能有益于对晶体结构、晶格参数和对称操作等教学内容的理解,实现沉浸式教学并提升学生的参与度。电子结构教学中使用VESTA展示电荷分布,便于学生理解能级、能带和态密度等抽象概念。具体分析了将VESTA融入晶体材料教学的创新方法、潜在挑战与应对策略。总之,VESTA可视化软件通过促进交互学习、视觉理解和独立探索,有望改变晶体结构、电子结构等化学、材料学科知识点的教学方式,使学生能够有效解读晶体材料的复杂性。

关键词： VESTA 可视化晶体材料电子结构

Recent progress in Helicobacter pylori treatment

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Chinese Medical Journal 2020年第3期133卷 335-343页

作者： Yi Hu Yin Zhu Nong-hua lu Department of Gastroenterology The First Affiliated Hospital of Nancnang UniversityNanchangJiangxi 330006China.

The main challenge in the field of Helicobacter pylori(***)infection is antibiotic resistance,which influences the efficacy of eradication ***-containing quadruple therapy has been confirmed as an effective regimen for eradicating ***,especially in strains with antibiotic ***-dose proton-pump inhibitor-amoxicillin dual therapy could decrease the use of unnecessary antibiotics,which is a promising alternative *** therapy(specific probiotic or vitamin)also showed good results,although more evidence is *** *** drugs are needed,and the establishment of the *** database is an effective way to acknowledge the real-time information of *** *** review provides the recent progress of *** treatment,and further studies are needed to address the role of different regimens in improving *** eradication rate,especially in strains with antibiotics resistance.

关键词： Helicobacter pylori Bismuth,dual therapy Vonoprazan Probiotics Vitamin

Quantum information-holding single-photon router based on spontaneous emission

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Science China(Physics,Mechanics & Astronomy) 2017年第9期60卷 1-6页

作者： GuoAn Yan HaoXue Qiao hua lu AiXi Chen School of Physics and Technology Wuhan University State Key Laboratory of Magnetic Resonances and Atomic and Molecular Physics Wuhan Institute of Physics and MathematicsChinese Academy of Sciences School of Science Hubei University of Technology Key Laboratory of Quantum Information Chinese Academy of SciencesUniversity of Science and Technology of China Department of Applied Physics Zhejiang Sci-Tech University Institute for Quantum Computing University of Waterloo

In this paper, we propose a single-photon router via the use of a four-level atom system coupled with two one-dimensional coupled-resonator waveguides. A single photon can be directed from one quantum channel into another by atomic spontaneous emission. The coherent resonance and the photonic bound states lead to the perfect reflection appearing in the incident *** fidelity of the atom is related to the magnitude of the coupling strength and can reach unit when the coupling strength matches g_a = g_b. This shows that the transfer of a single photon into another quantum channel has no influence on the fidelity at special points.

关键词： quantum router quantum information quantum network couple-resonator waveguides

Quantum model for understanding protein misfolding behavior——phase diagram and manual intervention

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Science China(Physics,Mechanics & Astronomy) 2021年第6期64卷 10-16页

作者： Wen-Wen Mao Li-hua lu You-Quan Li Zhejiang Province Key Laboratory of Quantum Technology&Device and Department of Physics Zhejiang UniversityHangzhou 310027China Collaberative Innovation Center of Advanced Microstructures Nanjing UniversityNanjing 210008China

The study of protein folding is fundamental and important in the multidisciplinary field because a diversity of diseases,like Alzheimer’s and Parkinson’s are relevant to protein *** current thermodynamic and geometric approaches only phenomenologically describe but do not provide a mechanistic understanding of the competition between correct folding and *** we present a model to understand the misfolding *** the influence of dissipative strength for all possible sequences and comparing the folding time toward different compact structures,we obtain a phase diagram of the dissipative quantum phase transition that enables us to model the *** also investigate how a perturbation in the Hamiltonian affects the transition point,which motivates us to explore possible manual *** results indicate that the manual intervention may be effective for some specific sequence but not for *** approach is expected to lay a foundation for further studies on manual intervention in protein misfolding.

关键词： quantum phase diagram quantum walk mean first-passage time protein folding

尿毒清颗粒结合血液透析对尿毒症肾功能、炎症指标改善作用研究

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中华中医药学刊 2024年第4期42卷 225-229页

作者：刘倩王晶霍鹏飞刘爱翔鲁华邢台市人民医院河北邢台054000

目的评价尿毒清颗粒结合血液透析对尿毒症患者肾功能、炎症指标的改善作用。方法选择2019年1月—2022年1月医院收治的136例尿毒症病人为试验对象,随机将其分成两组。所有患者入院后均给予低盐、低蛋白饮食,控制高血压,纠正贫血和营养不... 详细信息

目的评价尿毒清颗粒结合血液透析对尿毒症患者肾功能、炎症指标的改善作用。方法选择2019年1月—2022年1月医院收治的136例尿毒症病人为试验对象,随机将其分成两组。所有患者入院后均给予低盐、低蛋白饮食,控制高血压,纠正贫血和营养不良等。对照组68例患者采用规律血液透析,选择费森4008S型血液透析机,枸橼酸盐透析液,透析血流量在260 mL/min,透析液流量500 mL/min,血液透析通道为颈内静脉,常规肝素抗凝,每周透析3次,每次4 h,连续治疗12周。治疗组68例采用尿毒清颗粒结合血液透析治疗,血液透析方法同对照组,口服尿毒清颗粒,连续治疗12周。比较两组治疗前后中医证候(神疲力乏、肢体沉重、气短懒言、腰膝酸软、脘腹胀满和肌肤甲错)积分变化,肾功能指标[血清尿素氮(Serum urea nitrogen,BUN)、血肌酐(Serum creatinine,SCr)、内生肌酐清除率(Endogenous creatinine clearance,CCr)和24 h尿蛋白定量]变化,炎症指标[转化生长因子-β(Transforming growth factor-β,TGF-β)、白细胞介素-6(interleukin-6,IL-6)和C反应蛋白(C-reactive protein,CRP)水平]变化,营养指标(血浆白蛋白、转铁蛋白和血红蛋白)变化。结果经过12周的治疗,治疗组中达到显效标准的有22例,占比32.35%,达到有效标准的有39例,占比57.35%,总有效人数为61例,占比89.70%。对照组中达到显效标准的有19例,占比27.94%,达到有效标准的有33例,占比48.53%,总有效人数为52例,占比76.47%。组间结果比较显示,治疗组治疗疗效优于对照组(P0.05)。结论尿毒清颗粒结合血液透析有助于改善尿毒病人的临床方面症状,降低其中医证候的积分,对残余的肾功能发挥保护功能,降低炎症反应,提高营养指标,其临床应用价值值得进一步研究探讨。

关键词：尿毒清颗粒血液透析尿毒症炎症因子研究