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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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Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

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Neural Regeneration Research 2024年第12期19卷 2708-2722页

作者： He Fang Mengjie Li Jingchen Yang Shunping Ma Li Zhang Hongqi Yang Qiongyan Tang Jing Cao Weimin Yang Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Nutrition The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Neurology Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Department of Human Anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Neuroscience Research institute Zhengzhou University Academy of Medical SciencesZhengzhouHenan ProvinceChina

Thalamic hemorrhage can lead to the development of central post-stroke *** in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic ***,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea ***,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus *** this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central ***,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain ***,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain *** results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

关键词： central post-stroke pain hemorrhagic stroke histone deacetylase iron overload voltage-gated potassium ion channel 1.2

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In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence

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Asian Journal of pharmaceutical sciences 2024年第2期19卷 102-119页

作者： Shengnan Huang Chenyang Zhou Chengzhi Song Xiali Zhu Mingsan Miao Chunming Li Shaofeng Duan Yurong Hu Academy of Chinese medical sciences Henan University of Chinese MedicineZhengzhou 450046China School of pharmaceutical sciences Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou UniversityZhengzhou 450001China Center for Quantitative Biology Peking UniversityBeijing 100871China School of pharmaceutical sciences Henan University of Chinese MedicineZhengzhou 450046China Department of Pharmacy Chongqing University Cancer HospitalChongqing 400030China School of pharmaceutical sciences Henan UniversityZhengzhou 450046China

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

关键词： Post-sur gical tumor recurrence In situl hydrogel Immunotherapy Tumor micr oenvir onment Manganese(Ⅱ) Nitic oxide

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Copper-Free Click Chemistry-Mediated Assembly of Single Quantum Dot Nanosensor for Accurately Monitoring Locus-Specific m^(6)A in Cancer Cells

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Chinese Journal of Chemistry 2024年第5期42卷 499-504页

作者： Yue-Ying Li Ning-Ning Zhao Yi-Xuan Geng Qian Han Jian-Ge Qiu Bing-Hua Jiang Zi-Yue Wang Chun-Yang Zhang Translational Medicine Center The First Affiliated Hospital of Zhengzhou UniversityThe Academy of Medical SciencesHenan Institute of Medical and Pharmaceutical Sciences BGI CollegeZhengzhou UniversityZhengzhouHenan450052 China College of Chemistry Chemical Engineering and Materials ScienceShandong Normal UniversityJinanShandong250014 China School of Chemistry and Chemical Engineering Southeast UniversityNanjingJiangsu211189 China

N6-methyladenosine(m^(6)A)plays an important role in embryogenesis,nuclear export,transcription splicing,and protein translation ***,we demonstrate a copper-free click chemistry-mediated assembly of single quantum dot(QD)nanosensor for accurately monitoring locus-specific m^(6)A in cancer *** m^(6)A-sensitive endoribonuclease MazF can digest the unmethylated A-RNA,and the intact m^(6)A-RNA then hybridizes with DNA probes a and b to produce a sandwich hybrid,initiating the click chemistry to generate probe a–b ligation product via first tandem ligation detection reaction(LDR)***,DNA probes c and d can hybridize with the probe a–b ligation product to generate the probe c–d ligation product via second LDR *** LDR cycles can be repeated through denaturation and annealing reaction to generate abundant biotin-/fluorophore-modified probe c–d ligation products that can easily assemble on the QD surface to induce distinct fluorescence resonance energy transfer(FRET)between QD and *** assay can be homogenously performed without the involvement of copper catalyst,m^(6)A-specific antibody,radioactive labeling,ligase enzyme,enzymatic reverse transcription,and next-generation ***,it can discriminate even 0.01% m^(6)A level in complex samples and accurately measure cellular m^(6)A-RNA expression,providing a promising avenue for clinical diagnostics and biomedical research.

关键词： RNA methylation Click chemistry Förster resonance energy transfer Biosensor Cancer

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TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

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Zoological Research 2024年第4期45卷 937-950页

作者： Yi-Fu Zhu Rong-Hua Yu Shuai Zhou Pei-Pei Tang Rui Zhang Yu-Xin Wu Ran Xu Jia-Ming Wei Ying-Ying Wang Jia-Li Zhang Meng-Ke Li Xiao-Jing Shi Yu-Wei Zhang Guang-Zhi Liu Rick FThorne Xu Dong Zhang Mian Wu Song Chen School of Life sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Translational Research institute of henan Provincial People’s Hospital and People'’s Hospital of zhengzhou university Tianjian Laboratory of Advanced Biomedical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450053China institute of Medicinal Biotechnology Jiangsu College of NursingHuai’anJiangsu 223300China Laboratory Animal Center Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China henan Key Laboratory of Stem cell Differentiation and Modification Henan Provincial People’s HospitalHenan UniversityZhengzhouHenan 450053China School of Biomedical sciences and Pharmacy The University of NewcastleNSW 2308Australia

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental *** highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained ***,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in *** deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse ***,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate ***,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this ***,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO ***,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

关键词： Non-canonical autophagy TAX1BP1 FIP200 p62 Aggregates Neural stem cell

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Lactate metabolism in neurodegenerative diseases

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Neural Regeneration Research 2024年第1期19卷 69-74页

作者： Chaoguang Yang Rui-Yuan Pan Fangxia Guan Zengqiang Yuan The Brain Science Center Beijing Institute of Basic Medical SciencesBeijingChina School of Life sciences Zhengzhou UniversityZhengzhouHenan ProvinceChina

Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg *** not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological *** Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous ***,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease *** review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.

关键词： Alzheimer's disease Astrocyte-Neuron Lactate Shuttle brain central nervous system glucose metabolism glycolysis neuroinflammation Parkinson's disease protein lactylation signaling molecule

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A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

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Chinese Chemical Letters 2024年第2期35卷 295-299页

作者： Qi Fu Zhongming Lian Mengya Niu Yaru Huang Yanqiu Ai Long He Dandan Zhang Cuixia Zheng Jian-Jun Yang Lei Wang Dandan Tian Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450001China School of pharmaceutical sciences Zhengzhou UniversityZhengzhou 450001China Translational medical Center of Huaihe Hospital Henan UniversityKaifeng 475004China Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China

Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and *** concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are *** this study,we construct a near-infrared light-activated nano-therapeutic system to meet this *** detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs *** designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone ***,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone ***,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

关键词： Breast cancer bone metastasis Cancer-induced bone pain Cystine/glutamate antiporter Sorafenib Photodynamic therapy

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Effects of triaxial deformation on the fission barrier in the Z=118−120 nuclei

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Communications in Theoretical Physics 2024年第6期76卷 92-101页

作者：柴清祯王佳利刘星汉 institute of Theoretical Physics School of SciencesHenan University of TechnologyZhengzhou 450001China

By using potential energy surface(PES)calculations in the three-dimensional space(β_(2),γ,β_(4))within the framework of the macroscopic-microscopic model,the fission trajectory and fission barrier for Z=118(Og),119,120 nuclei has been systematically *** calculated PES includes macroscopic liquid-drop energy,microscopic shell correction and pairing *** the ^(294)Og176 nucleus as an example,we discuss the next closed shell after Z=82 and N=126 with the calculated Woods-Saxon single-particle ***,the results of PES in ^(294)Og is illustrated from the(X,Y)scale to the(β_(2),γ)***γdegree of freedom reveals the shape evolution clearly during the fission *** structure near the minimum and saddle point of the PES in the Z=118,119,120 nuclei is demonstrated *** on the potential energy curves,general trends of the evolution of the fission barrier heights and widths are also *** triaxial deformation in these superheavy mass regions plays a vital role in the first fission barrier,showing a significant reduction in both triaxial *** addition,the model-dependent fission barriers of proton-rich nuclei ^(295)Og,296119,and 297120 are analyzed *** studies could be valuable for synthesizing the superheavy new elements in the forthcoming HIAF and other facilities.

关键词： fission barrier potential energy surface calculation triaxiality Woods-Saxon potential superheavy new elements

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A possible probe to neutron-skin thickness by fragment parallel momentum distribution in projectile fragmentation reactions

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Nuclear Science and Techniques 2024年第6期35卷 114-119页

作者： Chun-Wang Ma Yi-Jie Duan Ya-Fei Guo Chun-Yuan Qiao Yu-Ting Wang Jie Pu Kai-Xuan Cheng Hui-Ling Wei College of Physics Henan Normal UniversityXinxiang 453007China institute of Nuclear Science and Technology Henan Academy of SciencesZhengzhou 450015China

Neutron-skin thickness is a key parameter for a neutron-rich nucleus;however,it is difficult to *** the framework of the Lanzhou Quantum Molecular Dynamics(LQMD)model,a possible probe for the neutron-skin thickness(δ_(np))of neutron-rich ^(48)Ca was studied in the 140A MeV ^(48)Ca+^(9)Be projectile fragmentation reaction based on the parallel momentum distribution(p∥)of the residual fragments.A Fermi-type density distribution was employed to initiate the neutron density distributions in the LQMD simulations.A combined Gaussian function with different width parameters for the left side(Γ_(L))and the right side(Γ_(R))in the distribution was used to describe the p∥of the residual *** neutron-rich sulfur isotopes as examples,Γ_(L) shows a sensitive correlation withδ_(np) of ^(48)Ca,and is proposed as a probe for determining the neutron skin thickness of the projectile nucleus.

关键词： Neutron-skin thickness Projectile fragmentation Parallel momentum distribution Neutron-rich nucleus Quantum molecular dynamics model

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Integrative analysis of tumor stemness and immune microenvironment deciphers novel molecular subtypes in hepatocellular carcinoma

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Genes & Diseases 2024年第5期11卷 81-84页

作者： Zhiyi Wang Shuang Chen Dongxiao Li Hui Xu Siyuan Weng Yuyuan Zhang Yuqing Ren Chunguang Guo Xiuling Li Zaoqu Liu Xinwei Han Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Gastroenterology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhouHenan 450004China Center of Reproductive Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China State Key Laboratory of medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100730China

Hepatocellular carcinoma(HCC)is a highly heterogeneous tumor,with dynamic equilibrium and complex interplay between its intricate tumor nature and ambient tumor immune microenvironment(TIME).1 Elegant research has indicated that cancer stem cells,a small subset of neoplastic cells confined within dedicated niches,display stem cell-like properties and interact with cells in TIME,thereby imparting an indelible impact on stemness regulation,tumor heterogeneity,and cancer cell plasticity.2 Previous taxonomies solely from the perspective of stemness or TIME may introduce some degree of bias in the comprehension of HCC carcinogenesis,3,4 and thus it is of paramount importance to systematically consider tumor stemness and TIME as a whole to truly portray the biological landscape of HCC.

关键词： thereby landscape stem

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