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Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo department of Pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China department of General Surgery Peking University Third HospitalBeijing 100191China department of Medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin ***1 has been identified as a critical oncogene in the progression of ***,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still *** To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA *** Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic ***-quent validations were conducted through spatial transcriptomics and *** construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data *** CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased ***5AC-high cells were found to promote CCA progression through WNT ***5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral ***13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor ***16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with *** the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple *** samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer *** Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis

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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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The Role of E3 Ligases in Macrophage-mediated Inflammation

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生物化学与生物物理进展 2024年第9期51卷 2037-2060页

作者： JIN Jia-Bei GE Yi-Dong JIN Xiao-Feng Zhejiang Key Laboratory of Pathophysiology Department of Biochemistry and Molecular BiologyHealth Science CenterNingbo UniversityNingbo 315211China

Macrophages,existed in almost all organs of the body,are responsible for detecting tissue injury,pathogens,playing a key role in host defense against a variety of invading pathogens triggering inflammatory *** evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification,which is responsible for normal immune ***,numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation,mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal ***,E3 ubiquitin ligases,responsible for recognizing the substrates,are key enzymes in the ubiquitin proteasome system(UPS)composed of ubiquitin(Ub),ubiquitin-activating E1 enzymes,ubiquitin-conjugating E2 enzymes,E3 ubiquitin ligases,26S proteasome,and deubiquitinating ***,several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation,including Toll-like receptors(TLRs),nucleotide-binding oligomerization domain(NOD)-like receptors(NLRs),RIG-I-like receptors(RLRs),C-type lectin receptors(CLRs)and the receptor for advanced glycation end products(RAGE).Herein,we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation,as well as the inhibitors and agonists targeting E3 ligases in macrophage mediated inflammation,providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.

关键词： E3 ligases macrophage NLRs/RLRs/TLRs targeted therapies

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The complex interplay between aging and cancer:unraveling the clues

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Medical Review 2024年第1期4卷 2-4页

作者： Zhengwei Xie Qimin Zhan peking university International Cancer Institute Peking University Health Science CenterPeking University38 Xueyuan LuBeijing 100191China peking university-Yunnan Baiyao International Medical Research center Peking University Health Science CenterPeking UniversityBeijing 100191China Laboratory of molecular Oncology Peking University Cancer Hospital&InstituteBeijing 100142China peking university International Cancer Institute Peking University Health Science CenterPeking UniversityBeijingChina State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterBeijingChina peking university-Yunnan Baiyao International Medical Research center Peking University Health Science CenterPeking UniversityBeijingChina

Throughout our life journey,two unstoppable forces shape our existence:the specter of aging and *** unrelated,these phenomena are more intertwined than we might think[1].The incidence and mortality rates of cancer increase exponentially with age,and their underlying causes are both related to cellular *** these commonalities is not only key to unlocking cancer therapies,but it may also inspire us to find interventions that delay the aging process itself.

关键词： cancer mortality aging

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When Glanzmann thrombasthenia encounters antithrombin defi ciency: how do we balance the risk and benefi t of antithrombotic therapy?

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World Journal of Emergency Medicine 2024年第1期15卷 67-69页

作者： Yu Wang Zhihao Liu Haoyu Weng Jianping Li department of Endocrinology Peking University First HospitalBeijing 100034China department of Cardiology Peking University First HospitalBeijing 100034China Key Laboratory of molecular Cardiovascular sciences of Ministry of Education Health Science CenterPeking UniversityBeijing 100034China

Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and *** this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic *** is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous ***,we describe a rare case of GT and antithrombin deficiency coexisting in a single *** was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).

关键词： thrombin throm bleeding

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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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DDX21 is a new player in co-transcriptional RNA modification and functions

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science China(Life sciences) 2024年第10期67卷 2291-2293页

作者： Chengqi Yi State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeijing 100871China peking-Tsinghua center for Life sciences Peking UniversityBeijing 100871China department of Chemical biology and Synthetic and Functional Biomolecules center College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Beijing Advanced center of RNA biology(BEACON) Peking UniversityBeijing 100871China

Ever since the first discovery of chemical modifications of RNA in 1951,researchers have been captivated by the diverse types of modifications,their associated enzymes and proteins(writers,erasers,or readers),and their downstream functional implications(Song and Yi,2017).Among the over 170 distinct types of RNA modifications identified thus far,N^(6)-methyladenosine(m6A)stands out as the most prevalent internal modification on mammalian messenger RNA(mRNA)(Song and Yi,2017).

关键词： modification player stands

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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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Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key Laboratory of Reproductive Medicine and Offspring health Nanjing Medical UniversityNanjing 211166China Shanghai Key Laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental *** a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and *** gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ *** maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)*** addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization *** conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

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AI for organic and polymer synthesis

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science China Chemistry 2024年第8期67卷 2461-2496页

作者： Xin Hong Qi Yang Kuangbiao Liao Jianfeng Pei Mao Chen Fanyang Mo Hua Lu Wen-Bin Zhang Haisen Zhou Jiaxiao Chen Lebin Su Shuo-Qing Zhang Siyuan Liu Xu Huang Yi-Zhou Sun Yuxiang Wang Zexi Zhang Zhunzhun Yu Sanzhong Luo Xue-Feng Fu Shu-Li You center of Chemistry for Frontier Technologies Department of ChemistryZhejiang UniversityHangzhou 310027China center of Basic molecular science Department of ChemistryTsinghua UniversityBeijing 100084China Guangzhou National Laboratory Guangzhou 510005China center for Quantitative biology Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China State Key Laboratory of molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai 200433China School of Materials science and Engineering Peking UniversityBeijing 100871China Beijing National Laboratory for molecular sciences Center for Soft Matter Science and EngineeringKey Laboratory of Polymer Chemistry and Physics of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China AI for science(AI4S)-Preferred Program Shenzhen Graduate SchoolPeking UniversityShenzhen 518055China State Key Laboratory of Chemical biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032China department of Chemical sciences National Natural Science Foundation of ChinaBeijing 100085China State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China

Recent years have witnessed the transformative impact from the integration of artificial intelligence with organic and polymer synthesis. This synergy offers innovative and intelligent solutions to a range of classic problems in synthetic chemistry. These exciting advancements include the prediction of molecular property, multi-step retrosynthetic pathway planning, elucidation of the structure-performance relationship of single-step transformation, establishment of the quantitative linkage between polymer structures and their functions, design and optimization of polymerization process, prediction of the structure and sequence of biological macromolecules, as well as automated and intelligent synthesis platforms. Chemists can now explore synthetic chemistry with unprecedented precision and efficiency, creating novel reactions, catalysts, and polymer materials under the datadriven paradigm. Despite these thrilling developments, the field of artificial intelligence(AI) synthetic chemistry is still in its infancy, facing challenges and limitations in terms of data openness, model interpretability, as well as software and hardware support. This review aims to provide an overview of the current progress, key challenges, and future development suggestions in the interdisciplinary field between AI and synthetic chemistry. It is hoped that this overview will offer readers a comprehensive understanding of this emerging field, inspiring and promoting further scientific research and development.

关键词： organic synthesis polymer synthesis machine learning prediction chemical database automated synthesis

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