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Protein translation:biological processes and therapeutic strategies for human diseases

Signal Transduction and Targeted Therapy 2024年第3期9卷 1048-1064页

作者： Xuechao Jia Xinyu He Chuntian Huang Jian Li Zigang Dong kangdong liu Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450000China China-US(Henan)Hormel Cancer Institute ZhengzhouHenan 450000China Department of Pathology and Pathophysiology Henan University of Chinese MedicineZhengzhouHenan 450000China Tianjian Laboratory of Advanced Biomedical Sciences ZhengzhouHenan 450052China Research Center for Basic Medicine Sciences Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052 HenanChina Provincial Cooperative Innovation Center for Cancer Chemoprevention Zhengzhou UniversityZhengzhouHenan 450000China State Key Laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenan 450000China The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention ZhengzhouHenan 450000China

Protein translation is a tightly regulated cellular process that is essential for gene expression and protein *** deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human *** this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease *** explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome *** translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease *** development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation ***,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular ***,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is *** conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic *** in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human ***,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.

关键词： translation offering precise

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RNA选择性剪接对肿瘤细胞放射敏感性影响的研究进展

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中华放射肿瘤学杂志 2024年第5期33卷 479-484页

作者：秦子凡郑晓丽刘康栋葛红郑州大学附属肿瘤医院河南省肿瘤医院放疗科郑州450008 郑州大学基础医学院病理生理学系郑州450000

放射治疗是恶性肿瘤最主要的治疗方式之一,放射敏感性是影响肿瘤患者放疗疗效的关键因素,也一直是研究的热点。选择性剪接是基因表达过程中转录后关键的调控步骤,选择性剪接可以使前体mRNA产生多种不同的剪接异构体,进而产生不同的蛋白... 详细信息

放射治疗是恶性肿瘤最主要的治疗方式之一,放射敏感性是影响肿瘤患者放疗疗效的关键因素,也一直是研究的热点。选择性剪接是基因表达过程中转录后关键的调控步骤,选择性剪接可以使前体mRNA产生多种不同的剪接异构体,进而产生不同的蛋白质,它们在维持机体正常生命活动中起着至关重要的作用。肿瘤细胞相对正常细胞而言,有着更高比例的剪接失调事件发生。选择性剪接的失调,可以导致基因组不稳定性、血管生成等病理过程的发生,从而导致疾病的进展。肿瘤细胞中发生的异常剪接事件,可以作为新的治疗靶点。本文将对RNA选择性剪接、剪接事件与放射敏感性相关研究,以及研究展望进行综述。

关键词：选择性剪接剪接异构体放射敏感性

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Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

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Frontiers of Medicine 2023年第2期17卷 290-303页

作者： Yubing Zhou Xinyu He Yanan Jiang Zitong Wang Yin Yu Wenjie Wu Chenyang Zhang Jincheng Li Yaping Guo Xinhuan Chen Zhicai liu Jimin Zhao kangdong liu Zigang Dong The Pathophysiology Department School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhou 450000China The China-US(Henan)Hormel Cancer Institute Zhengzhou 450000China State Key Laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou 450000China Provincial Cooperative Innovation Center for Cancer Chemoprevention Zhengzhou UniversityZhengzhou 450000China Cancer Chemoprevention International Collaboration Laboratory Zhengzhou 450000China Oncology Department The Tumor Hospital of Linzhou CityLinzhou 456500China

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine cyclin-dependent kinase 2 patient-derived xenograft esophageal squamous cell carcinoma

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Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1874-1888页

作者： Penglei Wang Xuechao Jia Bingbing Lu Han Huang Jialin liu Xuejiao liu Qiong Wu Yamei Hu Pan Li Huifang Wei Tingting liu Dengyun Zhao Lingwei Zhang Xueli Tian Yanan Jiang Yan Qiao Wenna Nie Xinli Ma Ruihua Bai Cong Peng Zigang Dong kangdong liu Department of Pathophysiology Basic Medicine Research CenterSchool of Basic Medical SciencesAMSZhengzhou University450000 ZhengzhouChina China-US(Henan)Hormel Cancer Institute 450000 ZhengzhouChina The Department of Pathology Affiliated Cancer Hospital of Zhengzhou University450000 ZhengzhouChina The Department of Dermatology Xiangya HospitalCentral South University410078 ChangshaChina The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention 450000 ZhengzhouChina State Key Laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou University450000 ZhengzhouChina Provincial Cooperative Innovation Center for Cancer Chemoprevention Zhengzhou UniversityZhengzhouChina

Constitutive activation of RAS-RAF-MEK-ERK signaling pathway(MAPK pathway)frequently occurs in many cancers harboring RAS or RAF oncogenic *** of the paradoxical activation induced by a single use of BRAF or MEK inhibitors,dual-target RAF and MEK treatment is thought to be a promising *** this work,we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases,thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS *** enzyme profiling,surface plasmon resonance(SPR),isothermal titration calorimetry(ITC),cellular thermal shift assay,computational docking,and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/*** assay,luminescent ADP detection assay,and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase ***,erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase ***,erianin attenuated melanoma and colorectal cancer in ***,we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.

关键词： MEK1/2 BRAF activation

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Novel dual inhibitor for targeting PIM1 and FGFR1 kinases inhibits colorectal cancer growth in vitro and patient-derived xenografts in vivo

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4122-4137页

作者： Fanxiang Yin Ran Zhao Dhilli Rao Gorja Xiaorong Fu Ning Lu Hai Huang Beibei Xu Hanyong Chen Jung-Hyun Shim kangdong liu Zhi Li Kyle Vaughn Laster Zigang Dong Mee-Hyun Lee Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China China-US(Henan)Hormel Cancer Institute Zhengzhou 450008China Translational Medical Center the First Affiliated Hospital of Zheng zhou UniversityZhengzhou 450052China The Hormel Institute University of MinnesotaAustinMN 55912USA Department of Biomedicine Health&Life Convergencen ScienceBK21 FourCollege of Pharmacy Mokpo National UniversityJeonnam 58554Republic of Korea The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention Zhengzhou 450001China Department of General Surgery the Affiliated Tumor Hospital of Zhengzhou UniversityZhengzhou 450008China College of Korean Medicine Dongshin UniversityNaju 58245Republic of Korea

Colorectal cancer(CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1(PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration,and apoptosis. Fibroblast growth factor receptor 1(FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration. Small molecule HCI-48 is a derivative of chalcone, a class of compounds known to possess anti-tumor, anti-inflammatory and antibacterial effects. However,the underlying mechanism of chalcones against colorectal cancer remains unclear. This study reports that HCI-48 mainly targets PIM1 and FGFR1 kinases, thereby eliciting antitumor effects on colorectal cancer growth in vitro and in vivo. HCI-48 inhibited the activity of both PIM1 and FGFR1 kinases in an ATPdependent manner, as revealed by computational docking models. Cell-based assays showed that HCI-48inhibited cell proliferation in CRC cells(HCT-15, DLD1, HCT-116 and SW620), and induced cell cycle arrest in the G2/M phase through modulation of cyclin A2. HCI-48 also induced cellular apoptosis, as evidenced by an increase in the expression of apoptosis biomarkers such as cleaved PARP, cleaved caspase 3 and cleaved caspase 7. Moreover, HCI-48 attenuated the activation of downstream components of the PIM1 and FGFR1 signaling pathways. Using patient-derived xenograft(PDX) murine tumor models,we found that treatment with HCI-48 diminished the PDX tumor growth of implanted CRC tissue expressing high protein levels of PIM1 and FGFR1. This study suggests that the inhibitory effect of HCI-48 on colorectal tumor growth is mainly mediated through the dual-targeting of PIM1 and FGFR1kinases. This work provides a theoretical basis for the future application of HCI-48 in the treatment of clinical CRC.

关键词： PIM1 FGFR1 Colorectal cancer HCI-48 Targeted therapy Small moleculecompound ofchalcone Patient-derived xenograft model ATPKinase activity

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Acetylshikonin inhibits inflammatory responses and Papain-like protease activity in murine model of COVID-19

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4028-4030页

作者： Ning Lu Tingxuan Gu Xueli Tian Simin Zhao Guoguo Jin Fredimoses Mangaladoss Yan Qiao kangdong liu Ran Zhao Zigang Dong Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou UniversityZhengzhouHenan450001P.R.China China-US(Henan)Hormel Cancer Institute No.127Dongming RoadJinshui DistrictZhengzhouHenan450008China Department of Pathology The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenan450008China The Henan Luoyang Orthopedic Hospital ZhengzhouHenanP.R.China

Dear Editor,The emerging severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant Omicron has rapidly replaced the Delta variant and presents a huge challenge to public health and health care ***-driven hyperinflammation is the leading cause of a series of COVID-19 clinical symptoms.1 Our research attempted to discover an anti-inflammatory or anti-viral small molecule agent capable of treating COVID-19 hyperinflammation.

关键词： inflammatory acute inflammation

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数控车床加工精度的改进设计分析

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现代工业经济和信息化 2019年第11期9卷 79-81页

作者：刘康东商丘技师学院

对于数控车床技术而言,最核心的一个问题便是优化零件加工精度的工艺处理,加工精度处理技术水平的高低是决定数控车床技术的重要因素。阐述了数控机床在当前各领域的应用情况,分析了影响数控机床加工精度的因素,研究了有效提高数控车床... 详细信息

对于数控车床技术而言,最核心的一个问题便是优化零件加工精度的工艺处理,加工精度处理技术水平的高低是决定数控车床技术的重要因素。阐述了数控机床在当前各领域的应用情况,分析了影响数控机床加工精度的因素,研究了有效提高数控车床加工精度的方法,希望对数控机床的发展有一定的帮助。

关键词：数控车床加工精度处理技术改进设计

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食管癌组织的蛋白组学表达谱分析

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食管疾病 2023年第3期5卷 210-213,229页

作者：李胤桦杨靖宽王云飞刘康栋郑州大学基础医学院河南郑州450001

目的通过对74对食管癌和癌旁正常组织样本进行蛋白质组学分析,探索影响食管癌发生发展的关键蛋白。方法从PRIDE数据库(编号PXD021701)和iProX数据库(编号IPX0002501000)下载74对食管癌患者癌和癌旁组织的蛋白质组学数据,根据样本肿瘤分... 详细信息

目的通过对74对食管癌和癌旁正常组织样本进行蛋白质组学分析,探索影响食管癌发生发展的关键蛋白。方法从PRIDE数据库(编号PXD021701)和iProX数据库(编号IPX0002501000)下载74对食管癌患者癌和癌旁组织的蛋白质组学数据,根据样本肿瘤分期筛选显著差异表达的关键蛋白,并利用GO富集分析和KEGG数据库进行生物信息学分析。结果蛋白质组学分析共鉴定到9300个显著差异蛋白,其中包括78个显著上调蛋白和318个显著下调蛋白(FDR≤0.05,LogFC≥1)。进一步利用GO数据库和KEGG数据库进行分析,发现PLOD1、COL10A1和COL11A1在食管癌中高表达且与食管癌患者的预后显著相关。结论PLOD1、COL10A1和COL11A1可能是食管癌潜在的治疗靶点。

关键词：食管癌蛋白质组学生物标志物

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凝血酶敏感蛋白-1对人肝癌细胞株HCCLM3生长增殖的作用

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郑州大学学报（医学版） 2009年第1期44卷 143-145页

作者：薛建锋刘康栋彭淑牖郑州大学第一附属医院普外科郑州450052 郑州大学基础医学院病理生理学教研室郑州450001 浙江大学医学院附属第二医院外科杭州310009

目的:研究凝血酶敏感蛋白-1(TSP-1)及受体CD36、CD47对人肝癌细胞株HCCLM3生长及细胞周期的作用,初步探讨TSP-1可能的作用途径。方法:根据处理因素将细胞株分为:TSP-1组(加入TSP-1蛋白,40mg/L)、空白对照组、CD36阻断组、CD47阻断组。... 详细信息

目的:研究凝血酶敏感蛋白-1(TSP-1)及受体CD36、CD47对人肝癌细胞株HCCLM3生长及细胞周期的作用,初步探讨TSP-1可能的作用途径。方法:根据处理因素将细胞株分为:TSP-1组(加入TSP-1蛋白,40mg/L)、空白对照组、CD36阻断组、CD47阻断组。阻断组细胞接种后先加入5mg/L对应的单抗,待单抗与细胞充分结合后再加入40mg/LTSP-1。用四唑盐比色法(MTT)、流式细胞术和ELISA法分别观察TSP-1及CD36、CD47单抗对细胞生长、细胞周期、增殖指数(PI)及TGF-β1分泌的影响。结果:TSP-1组、CD36阻断组、CD47阻断组细胞生长受抑,且CD36阻断组的细胞生长抑制率低于CD47阻断组。TSP-1组G0/G1期细胞数增加,S期和G2/M期细胞数减少,与对照组和CD36阻断组相比差异有统计学意义。对照组、TSP-1组、CD36阻断组及CD47阻断组PI分别为:(42.70±2.09)%、(27.85±0.71)%、(38.04±1.35)%和(31.78±0.43)%,各组之间两两比较,差异均有统计学意义(P均<0.05)。各组TGF-β1的含量差异无统计学意义。结论:TSP-1主要通过与受体CD36的结合对人肝癌细胞株HCCLM3的生长增殖有抑制作用。TSP-1对HCCLM3的抑制可能不是通过调节TGF-β1的分泌而发挥作用。

关键词：癌肝细胞 HCCLM3 凝血酶敏感蛋白-1 细胞周期 TGF-β1

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Pathological complete response to gefitinib in a10-year-old boy with EGFR-negative pulmonary mucoepidermoid carcinoma: A case report and literature review

Pathological complete response to gefitinib in a10-year-old ...

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第八届中国肿瘤学术大会暨第十三届海峡两岸肿瘤学术会议

作者： Shaomei Li Zhe Zhang Hong Tang Zhen He Yun Gao Weiguo Ma Yuxi Chang Bing Wei Jie Ma kangdong liu Qiming Wang Zhiyong Ma Department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou University Henan Cancer Hospital Department of Clinical Laboratory Affiliated Cancer Hospital of Zhengzhou University Department of Molecular Pathology Affiliated Cancer Hospital of Zhengzhou University Department of Research Service Office Affiliated Cancer Hospital of ZhengzhouUniversity Department of Pathophysiology School of Basic Medical Science Zhengzhou University

＜正＞Objective Mucoepidermoid carcinoma（MEC）of the lung is a rare form of lung cancer,accounting for 0.1 to 0.2%of all pulmonary *** can occur at any age（range,3–78years old）;nearly 50%of patients are less than ...

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