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Epigenetics and environmental health

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

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Unveiling ferroptosis as a promising therapeutic avenue for colorectal cancer and colitis treatment

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3785-3801页

作者： Aaron T.Kaoy Christian V.Cabanlongy Kendra Padilla Xiang Xue department of biochemistry and molecular biology University of New MexicoAlbuquerqueNM 87131USA

Ferroptosis is a novel type of regulated cell death(RCD)involving iron accumulation and lipid *** its discovery in 2012,various studies have shown that ferroptosis is associated with the pathogenesis of various *** cell death has also been linked to intestinal dysfunction but can act as either a positive or negative regulator of intestinal disease,depending on the cell type and disease *** continued investigation of mechanisms underlying ferroptosis provides a wealth of potential for developing novel *** the growing prevalence of intestinal diseases,particularly colorectal cancer(CRC)and inflammatory bowel disease(IBD),this review article focuses on potential therapeutics targeting the ferroptotic pathway in relation to CRC and IBD.

关键词： Ferroptosis Colorectal cancer Inflammatory bowel disease Cell death molecular mechanisms Iron metabolism Drug therapies Targeted therapeutics

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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 Asn301);when a single site at amino acid 301 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 301 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

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Modular Synthesis of Multi-substituted Cyclobutanones Enabled by Oxyallyl Cations

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Chinese Journal of Chemistry 2024年第5期42卷 459-463页

作者： Meng Wang Zhonggui Wang Ping Lu Research center for molecular Recognition and Synthesis Department of ChemistryFudan University220 Handan LuShanghai200433 China Present address: department of cancer biology Dana-Farber Cancer Institute department of Biological Chemistry and molecular Pharmacology Harvard Medical SchoolBostonMA 02115USA

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic *** report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available *** substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic *** transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

关键词： Diastereoselectivity Modular synthesis Nucleophilic substitution Organohalides Oxyallyl cation Precision functionalization Strained molecules 1,2,3,4-Tetrasubstituted cyclobutanes

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of molecular biology for High cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical Research center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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Sciadopitysin exerts anticancer effects on HepG2 hepatocellular carcinoma cells by regulating reactive oxygen species-mediated signaling pathways

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BIOCELL 2024年第7期48卷 1055-1069页

作者： YAN-NAN LI YUN-HONG XIU YAN-JUN TANG JING-LONG CAO WEN-SHUANG HOU AN-QI WANG TIAN-ZHU LI CHENG-HAO JIN department of biochemistry and molecular biology Heilongjiang Bayi Agricultural UniversityDaqingChina Hemodialysis center Daqing Oilfield General HospitalDaqingChina department of Food Science and Engineering Heilongjiang Bayi Agricultural UniversityDaqingChina department of molecular biology Chifeng UniversityChifengChina National Coarse Cereals Engineering Research center DaqingChina

Objectives:Sciadopitysin(SP)is aﬂavonoid in Ginkgo biloba that exhibits various pharmacological *** study aimed to investigate its antitumor effects and the underlying molecular mechanism of SP in hepatocellular carcinoma(HCC)***:Network pharmacology was used for target prediction *** Counting Kit-8(CCK-8)assay was used to test the cell *** cytometry was used to test the cell cycle distribution,apoptosis status,and reactive oxygen species(ROS)*** and wound-healing assay was used to test the migration effect of SP on HepG2 *** Blot assay was used to test the expression levels of ***:Network pharmacology analysis results showed that the mitogen-activated protein kinase(MAPK)and other signaling pathways are involved in the SP anti-HCC biological ***-8 assay results demonstrated that SP showed an obvious killing effect on three types of HCC cells and low cytotoxic effect on normal *** Blot andﬂow cytometry results showed that SP regulated MAPK/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa-B(NF-κB)signaling pathway to induce mitochondrion-dependent apoptosis in HepG2 ***,SP can arrest the G0/G1 phase cell cycle via the protein kinase B(AKT)/p21/p27/cyclin-dependent kinase(CDK)/Cyclin signaling *** healing and transwell assays showed that SP inhibited cell motility and invasion through the AKT/glycogen synthase kinase3β(GSK-3β)/vimentin/β-catenin signaling ***:Theseﬁndings demonstrated that SP induced mitochondrion-dependent apoptosis,arrested cell cycle in the G0/G1 phase,and inhibited cell migration by regulating the ROS-mediated signaling pathway in HepG2 ***,SP could serve as a therapeutic agent for the treatment of human HCC.

关键词： Sciadopitysin Hepatocellular carcinoma Apoptosis Cell cycle Cell migration

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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of molecular biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China department of Clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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C19MC miRNA-520G induces SP100 antiviral gene transcription and inhibits melanin production in skin cutaneous melanoma

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Genes & Diseases 2024年第1期11卷 60-63页

作者： Goodwin G.Jinesh Marian T.Smallin Nino Mtchedlidze Isha Godwin Marco Napoli Nicole Hackel Manali S.Phadke Avani A.Deshpande Xiaobo Li John H.Lockhart Jaden R.Baldwin Suehelay Acevedo-Acevedo Yifeng Gao Michelle A.Reiser Keiran S.M.Smalley Elsa R.Flores Andrew S.Brohl department of molecular Oncology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA molecular Medicine Program H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Saveetha Medical College ChennaiTamil Nadu 602105India Tumor biology department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Sarcoma department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA

SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.

关键词： SP100 melanoma stabilization

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Simple and robust 3D MINFLUX excitation with a variable phase plate

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Light(Science & Applications) 2024年第7期13卷 1354-1363页

作者： Takahiro Deguchi Jonas Ries European molecular biology Laboratory Cell Biology and BiophysicsHeidelbergGermany. Max Perutz Labs Vienna Biocenter Campus(VBC)ViennaAustria. University of Vienna Center for Molecular BiologyDepartment of Structural and Computational BiologyViennaAustria. University of Vienna Faculty of PhysicsViennaAustria

MINFLUX has achieved extraordinary resolution in superresolution imaging and single fluorophore *** is based on localizing single fluorophores by rapid probing with a patterned beam that features a local intensity *** implementations,however,are complex and expensive and are limited in speed and ***,we show that a combination of an electro-optical modulator with a segmented birefringent element such as a spatial light modulator produces a variable phase plate for which the phase can be scanned on the MHz *** or top-hat phase patterns generate high-contrast compact excitation point-spread functions for MINFLUX localization in the x,y,and z-direction,respectively,which can be scanned across a fluorophore within a microsecond,switched within 60 microseconds and alternated among different excitation *** discuss how to compensate for non-optimal performance of the components and present a robust 3D and multi-color MINFLUX excitation module,which we envision as an integral component of a high-performance and cost-effective open-source MINFLUX.

关键词： excitation phase switched

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Targeting RAF dimers in RAS mutant tumors:From biology to clinic

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1895-1923页

作者： Huanhuan Yin Qiulin Tang Hongwei Xia Feng Bi Division of Abdominal cancer Department of Medical OncologyCancer Center and Laboratory of Molecular Targeted Therapy in OncologyWest China HospitalSichuan UniversityChengdu 610041China

RAS mutations occur in approximately 30%of tumors worldwide and have a poor prognosis due to limited *** targeting of KRAS G12C has achieved significant success in recent years,but there is still a lack of efficient therapeutic approaches for tumors with non-G12C KRAS mutations.A highly promising approach is to target the MAPK pathway downstream of RAS,with a particular focus on RAF ***-generation RAF inhibitors have been authorized to treat BRAF mutant tumors for over a ***,their use in RAS-mutated tumors is not recommended due to the paradoxical ERK activation mainly caused by RAF *** address the issue of RAF dimerization,type II RAF inhibitors have emerged as leading *** clinical studies have shown the initial effectiveness of these agents against RAS mutant ***,type II RAF inhibitors in combination with MEK or ERK inhibitors have demonstrated impressive efficacy in RAS mutant *** review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treatment in tumors with RAS mutations,as well as recent progress in therapeutic approaches to address the problem of RAF dimerization in RAS mutant tumors.

关键词： RAS mutations RAF dimerization RAF inhibitors cancer therapy Drug resistance

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