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Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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World Journal of Clinical Cases 2024年第3期12卷 474-478页

作者： Yusuf Tutar Department of Basic Pharmaceutical Sciences Faculty of PharmacyDivision of BiochemistryUniversity of Health SciencesIstanbul 34668Turkey Health Sciences Faculty Recep Tayyip Erdogan UniversityRize 53350Turkey molecular Oncology Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey molecular Medicine Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):*** all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural *** methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized *** is a popular technique for collecting direct mea-surements of metabolic activity from many biological ***,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme *** annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called *** network uses an approach that emphasizes metabolite-gene consensus via biochemical *** metabolomics and genomics data is ***,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical *** The genome and metabolites of biological organisms are not fully characterized with current ***,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug *** network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical ***,clinical data may be integrated to gene expression–metabolite expression by system genetics appr

关键词： Network pharmacology Metabologenomics Genome Pathways Cancer

PARP1-DNA co-condensation:the driver of broken DNA repair

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2351-2353页

作者： Xiang Wei Fangfang Zhou Long Zhang Life Sciences Institute The Second Affiliated Hospital of the Zhejiang University School of MedicineThe MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell BiologyZhejiang UniversityHangzhouChina The First Affiliated Hospital the Institutes of Biology and Medical SciencesSuzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215123China

A recent study published by Simon Alberti1 in Cell has revealed that DNA double-strand break(DSB)sites that prevent the disjunction of broken DNA ends are formed through poly(ADPribose)(PAR)polymerase 1(PARP1)-DNA co-condensation.1(Fig.1).Here,a comprehensive and novel model was provided for the ordered assembly of PARP1-DNA condensates,which can rationally make clear broken DNA end synapses and how repair effectors are recruited to repair DSB.

关键词： PARP1 repair rational

Biallelic variants in RBM42 cause a multisystem disorder with neurological,facial,cardiac,and musculoskeletal involvement

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Protein & Cell 2024年第1期15卷 52-68页

作者： Yiyao Chen Bingxin Yang Xiaoyu Merlin Zhang Songchang Chen Minhui Wang Liya Hu Nina Pan Shuyuan Li Weihui Shi Zhenhua Yang Li Wang Yajing Tan Jian Wang Yanlin Wang Qinghe Xing Zhonghua Ma Jinsong Li He-Feng Huang Jinglan Zhang Chenming Xu institutes of Biomedical Sciences Fudan UniversityShanghai 200032China bstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China Intermational Peace Matermity and Child Health Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200030China Shanghai Key Laboratory of Embryo Original Diseases Shanghai 200030China State Key Laboratory of Cell biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China State Key Laboratory of Rice biology the Key Laboratory of Molecular Biology of Crop Pathogens and InsectsInstitute of BiotechnologyZhejiang UniversityHangzhou 310058China Verna and Marrs McLean Department of biochemistry and molecular biology Baylor College of MedicineHoustonTX 77030USA Children's hospital of Fudan University Shanghai 201102China School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024ZhejiangChina Research Units of Embryo Original Diseases Chinese Academy of Medical Sciences(No.2019RU056)Shanghai 200011China

Here,we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 *** patient is a 2-year-old female with severe central nervous system(CNs)abnormalities,hypotonia,hearing loss,congenital heart defects,and dysmorphic facial *** whole-exome sequencing(WEs)reveals that the patient has two compound heterozygous variants,c.304C>T(p.R102*)and c.1312G>A(p.A438T),in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein *** p.A438T variant is in the RRM domain which impairs RBM42 pro-tein stability in ***,p.A438T disrupts the interaction of RBM42 with hnRNP K,which is the causa-tive gene for Au-Kline syndrome with overlapping disease characteristics seen in the index *** human R102*or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout△FgRbp1 in Fusarium while it was rescued by the wild-type(WT)human RBM42.A mouse model carying Rbm42 compound heterozygous variants,c.280C>T(p.Q94*)and c.1306_1308delinsACA(p.A436T),demonstrated gross fetal develop-mental defects and most of the double mutant animals died by ***-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing(As).Overall,we present clinical,genetic,and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

关键词： RBM42 gene RNA-binding protein neurodevelopmental disorder Au-Kline syndrome alternative splicing

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

Variant PRC1 subunit RYBP/YAF2 forms condensate with RING1B and promotes H2AK119ub deposition

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Science China Life Sciences 2024年第9期67卷 2036-2038页

作者： Yanjiang Liu Gongcheng Hu Shengxiong Yang Chenghong Yan Juehan Wang Guangjin Pan Hongjie Yao State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Department of Basic Research Guangzhou National Laboratory CAS Key Laboratory of Regenerative biology Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences University of Chinese Academy of Sciences

Dear Editor,Polycomb group(Pc G) proteins represent important roles in repressing gene expression throughout development. The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes, PRC1 and ***1 catalyzes H2AK119ub and PRC2catalyzes H3K27me1/2/3(Fursova et al.,2019). PRC1 is further categorized as CBX-containing canonical PRC1(c PRC1)and RYBP/YAF2-containing variant PRC1(v PRC1)(Blackledge and Klose,2021).

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Nuclear phylogenomics of angiosperms and insights into their relationships and evolution

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Journal of Integrative Plant biology 2024年第3期66卷 546-578页

作者： Guojin Zhang Hong Ma College of Life Sciences Hunan Normal UniversityChangsha 410081China Department of biology 510 Mueller LaboratoryHuck Institutes of the Life SciencesThe Pennsylvania State UniversityUniversity ParkPA 16802USA

Angiosperms(flowering plants) are by far the most diverse land plant group with over 300,000 species. The sudden appearance of diverse angiosperms in the fossil record was referred to by Darwin as the “abominable mystery,”hence contributing to the heightened interest in angiosperm evolution. Angiosperms display wide ranges of morphological, physiological,and ecological characters, some of which have probably influenced their species richness. The evolutionary analyses of these characteristics help to address questions of angiosperm diversification and require well resolved phylogeny. Following the great successes of phylogenetic analyses using plastid sequences,dozens to thousands of nuclear genes from next-generation sequencing have been used in angiosperm phylogenomic analyses, providing well resolved phylogenies and new insights into the evolution of angiosperms. In this review we focus on recent nuclear phylogenomic analyses of large angiosperm clades, orders, families,and subdivisions of some families and provide a summarized Nuclear Phylogenetic Tree of Angiosperm Families. The newly established nuclear phylogenetic relationships are highlighted and compared with previous phylogenetic results. The sequenced genomes of Amborella,Nymphaea, Chloranthus, Ceratophyllum, and species of monocots, Magnoliids, and basal eudicots, have facilitated the phylogenomics of relationships among five major angiosperms clades. All but one of the 64 angiosperm orders were included in nuclear phylogenomics with well resolved relationships except the placements of several orders. Most families have been included with robust and highly supported placements, especially for relationships within several large and important orders and ***, we examine the divergence time estimation and biogeographic analyses of angiosperm on the basis of the nuclear phylogenomic frameworks and discuss the differences compared with previous analyses. Furthermore,we discuss the implicatio

关键词： angiosperms evolution flowering plants nuclear gene phylogenomics phylogeny

Renewable biosynthesis of isoprene from wastewater through a synthetic biology approach:the role of individual organic compounds

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 13-24页

作者： Min Yang Xianghui Li Weixiang Chao Xiang Gao Huan Wang Lu Lu State Key Laboratory of Urban Water Resource and Environment School of Civil and Environmental EngineeringHarbin Institute of TechnologyShenzhen 518055China Center for Materials Synthetic biology CAS Key Laboratory of Quantitative Engineering Biology of CASShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academic of ScienceShenzhen 518000China Institute of Urban Ecology and Environmental Technology School of Materials and Environmental EngineeringShenzhen Polytechnic UniversityShenzhen 518055China

The biosynthesis of isoprene offers a more sustainable alternative to fossil fuel-based approaches,yet its success has been largely limited to pure organic compounds and the cost remains a *** study proposes a waste-to-wealth strategy for isoprene biosynthesis utilizing genetically engineered *** bacteria to convert organic waste from real food *** impact of organic compounds present in wastewater on *** growth and isoprene production was systematically *** results demonstrated that with filtration pretreatment of wastewater,isoprene yield,and production achieved 115 mg/g COD and 7.1 mg/(L·h),***,even without pretreatment,isoprene yield only decreased by~24%,indicating promising ***,maltose,glycerol,and lactate are effective substrates for isoprene biosynthesis,whereas starch,protein,and acetate do not support *** *** optimum C/N ratio for isoprene production was found to be 8:***,augmenting essential nutrients in wastewater elevated the isoprene yield increased to 159 mg/g *** wastewater biosynthesis significantly reduced the cost(44%–53%decrease,p-value<0.01)and CO_(2)emission(46%–55%decrease,p-value<0.01)compared with both sugar fermentation and fossil fuel–based *** study introduced a more sustainable and economically viable approach to isoprene synthesis,offering an avenue for resource recovery from wastewater.

关键词： Wastewater Resource recovery Genetic engineering Biosynthesis Isoprene

TBK1:a new target for overcoming cancer immunotherapy resistance

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Science China(Life Sciences) 2024年第1期67卷 217-218页

作者： Jizhong Guan Long Zhang Fangfang Zhou institutes of biology and Medical Science Soochow UniversitySuzhou 215123China MOE Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network Life Sciences InstituteZhejiang UniversityHangzhou 310058China

In a recent study published in Nature,Sun et al.(2023)discovered that targeting TANK-binding kinase 1(TBK1)can successfully overcome resistance to immune checkpoint blockade(ICB)treatment and the study revealed its potential *** authors provided evidence that the disruption of TBK1 signal enhances the blockade of programmed cell death protein-1(PD-1)and promotes anti-tumor immunity in the tumor microenvironment(TME).Tumor cells rely on Janus kinase(JAK)and signal transducer as well as activator of transcription(STAT)signals to elicit an immune response by perceiving tumor necrosis factorα(TNF-α)and interferon-γ(IFN-γ),resulting in receptor-interacting protein kinase(RIPK)-caspase-mediated cell death in tumor cells(Figure 1).

关键词： TBK1 immunity

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field

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Zoological Research 2024年第3期45卷 478-490页

作者： Han-Xiao Chen Xin-Yu Wang Biao Yu Chuan-Lin Feng Guo-Feng Cheng Lei Zhang Jun-Jun Wang Ying Wang Ruo-Wen Guo Xin-Miao Ji Wen-Jing Xie Wei-Li Chen Chao Song Xin Zhang CAS Key Laboratory of High Magnetic Field and Ion Beam Physical biology High Magnetic Field LaboratoryHefei Institutes of Physical ScienceChinese Academy of SciencesHefeiAnhui 230031China Science Island Branch of Graduate School University of Science and Technology of ChinaHefeiAnhui 230026China institutes of Physical Science and Information Technology Anhui UniversityHefeiAnhui 230601China

Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in *** predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late *** the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery *** the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte ***,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially ***,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP *** note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.

关键词： Acetaminophen Acute liver injury Static magnetic fields Oxidative stress DNA synthesis