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MAP4K inhibition as a potential therapy for amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第8期19卷 1639-1640页

作者： Shuaipeng Ma Chun-Li Zhang Department of molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTXUSA

Amyotrophic lateral sclerosis(ALS)is a rare neurological disease,featuring gradual loss of muscle controls due to degeneration of motor ***,there is currently no cure for *** available therapies only offer a limited e... 详细信息

关键词： degeneration sclerosis MAP4

N-glycosylation of Wnt3.regulates the progression of hepatocellular carcinoma by affecting Wnt/β-catenin signal pathway

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2769-2780页

作者： Xin-Zhan Zhang Xiao-Chuan Mo Zhu-Ting Wang Rong Sun Da-Quan Sun Department of Biochemistry and molecular Biology&Research center for Basic medical Sciences Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina

BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90%of hepatocellular carcinoma(HCC)cell *** a well-known secretory glycoprotein,Wnt3.can interact with FZD receptors on the cell surface,thereby activating the Wnt/β-catenin signaling ***,the N-glycosylation modification site of Wnt3.and the effect of this modification on the biological function of the protein are still *** To investigate the effect of Wnt3.N-glycosylation on the biological function of HCC *** Site-directed mutagenesis was used to verify the Wnt3.N-glycosylation sites,actinomycin D treatment was used to detect the stability of Wnt3.after site-directed mutation,the binding of the N-glycosylation site-directed mutant Wnt3.to FZD7 was observed by laser confocal microscopy,and the effects of the N-glycosylation site-directed mutation of Wnt3.on the Wnt/β-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function *** Wnt3.has two N-glycosylation-modified sites(Asn90 and Asn3.1);when a single site at amino acid 3.1 is mutated,the stability of Wnt3.is weakened;the binding ability of Wnt3.to FZD7 decreases when both sites are mutated simultaneously;and the level of proteins related to the Wnt/β-catenin signaling pathway is *** proliferation,migration and invasion are also weakened in the case of single 3.1 site and double-site *** These results indicate that by inhibiting the N-glycosylation of Wnt3.the proliferation,migration,invasion and colony formation abilities of liver cancer cells can be weakened,which might provide new therapeutic strategies for clinical liver cancer in the future.

关键词： Wnt3 N-glycosylation Hepatocellular carcinoma Liver cancer Wnt/β-catenin FZD7

Apoer2/Lrp8:the undercover cop of synaptic homeostasis

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Neural Regeneration Research 2024年第12期19卷 2563-2564页

作者： Gordon C.Werthmann Joachim Herz Department of molecular Genetics and center for Translational Neurodegeneration Research University of Texas Southwestern Medical Center at DallasDallasTXUSA Department of Neuroscience Department of Neurology University of Texas Southwestern medical center at Dallas DallasTXUSA

Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric *** this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.

关键词： homeostasis ApoE Alzheimer

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National Translational Science center for molecular Medicine & Department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor ***147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism ***,the relationship between the PTMs of CD147 and apoptosis has not been *** our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent ***1 was identified as the methyltransferase catalyzing CD147 to generate ***-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)***,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p3.,leading to tumor cell *** vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell *** together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Epigenetics and environmental health

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Frontiers of Medicine 2024年第4期18卷 571-596页

作者： Min Zhang Ting Hu Tianyu Ma Wei Huang Yan Wang Key Laboratory of Cancer and Microbiome State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Beijing Key Laboratory of Cancer Invasion and Metastasis Research Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCapital Medical UniversityBeijing100069China

Epigenetic modifications including DNA methylation,histone modifications,chromatin remodeling,and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological *** recent years,accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth,development,and diseases of individuals by affecting chromatin activity and regulating gene *** exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders,aging,cardiovascular disease,Alzheimer's disease,cancers,and so ***,epigenetic modifications are *** use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease ***,we provide an overview of the role of epigenetics in various ***,we summarize the mechanism of epigenetic alterations induced by different environmental exposures,the influence of different environmental exposures,and the crosstalk between environmental variation epigenetics,and genes that are implicated in the body's ***,the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical *** discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.

关键词： epigenetics environmental exposure health prevention and therapy

A Blood Hepatocellular Carcinoma Signature Recognizes Very Small Tumor Nodules with Metastatic Traits

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 551-561页

作者： Kun Chen Junxiao Wang Liping Jiang Fei Zhao Ruochan Zhang Zhiyuan Wu Dongmei Wang Yuchen Jiao Hui Xie Chunfeng Qu State Key Lab of molecular Oncology Department of ImmunologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Oncology Fifth Medical Center of Chinese PLA General HospitalBeijingChina Aerospace medical center/Aerospace center Hospital Peking University Aerospace Clinical CollegeBeijingChina State Key Lab of molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background and Aims:Hepatocellular carcinoma(HCC)cases with small nodules are commonly treated with radi-ofrequency ablation(RFA),but the recurrence rate remains *** study aimed to establish a blood signature for identifying HCC with metastatic traits ***:Data from HCC patients treated between 2010 and 2017 were retrospectively collected.A blood signature for meta-static HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin,cell-free DNA(cfDNA)mutations,and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA *** HCC blood signature was validated in patients prospectively enrolled ***:Of 251 HCC patients in the retrospective study,3..9% experienced recurrence within 1 year *** HCC blood signature identified from these patients included des-γ-carboxy-prothrombin≥40mAU/mL with cfDNA mutation score,where cfDNA mutations occurred in the genes of TP53.CTNNB1,and TERT *** signature effectively predicted 1-year post-RFArecurrence of HCC with 92% specificity and 91% sensitivity in the retrospective dataset,and with 87% specificity and 76% sensitivity in the prospective dataset(n=3. patients).Among 14 cases in the prospective study with biopsy tissues available,positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and ***:This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease’s early recurrence post-RFA.

关键词： Liquid biopsy Liver dysplastic nodules Radiofrequency ablation Hepatocellular carcinoma Recurrence prediction Metastatic nodules

Chimeric Monkey Born Alive with a High Contribution of Donor Cells

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Neuroscience Bulletin 2024年第6期40卷 849-851页

作者： Jia Huang Jun Wu Department of molecular Biology University of Texas Southwestern Medical CenterDallasTX75390USA Hamon center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTX75390USA Cecil H.and Ida Green center for Reproductive Biology Sciences University of Texas Southwestern Medical CenterDallasTX75390USA

Chimeras,which consist of cells from different individuals or different species,represent an important tool in biological *** in the early twentieth century,studies on chimeras have been focusing on understanding fundamental genetic and cellular developmental *** the advances in genetic engineering and embryonic stem cell(ESC)technology,chimeras have become an important tool for the generation of transgenic animals.

关键词： mechanisms advances developmental

The E3.ubiquitin ligase TRAF6 controls CTLA-4 turnover and promotes T-cell-mediated antitumor immunity

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Cellular & molecular Immunology 2024年第1期21卷 97-99页

作者： Xiao-Liang Jie Hua Guo Guang-Biao Zhou State Key Laboratory of molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BejingChina

Yu et al.[1]reported that the tumor necrosis factor(TNF)receptor OX40(CD13.)-TNF receptor-associated factor 6(TRAF6)axis mediates Lys63.linked ubiquitination and subsequent lysosomal degradation of cytotoxic T-lymphocyte antigen 4(CTLA-4),leading to the enhancement of CD8^(+)T-cell-mediated antitumor *** findings unveil a previously unknown mechanism in controlling the stability of the immune checkpoint CTLA-4 and provide a potential therapeutic target for the improvement of Tcell-based immunotherapy.

关键词： immunity OX40 ubiquitin