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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

The Potential Mechanism of Liujunzi Decoction in the Treatment of Breast Cancer based on Network Pharmacology and Molecular Docking Technology

Author(s): Mei Sun, Feng Lv, Chunmeng Qin, Dan Du, Wenjun Li* and Songqing Liu*

Volume 30, Issue 9, 2024

Published on: 26 February, 2024

Page: [702 - 726] Pages: 25

DOI: 10.2174/0113816128289900240219104854

Abstract

Background: Liujunzi Decoction (LJZD) is a potential clinical treatment for Breast Cancer (BC), but the active ingredients and mechanisms underlying its effectiveness remain unclear.

Objective: The study aimed to investigate the target gene of LJZD compatibility and the possible mechanism of action in the treatment of breast cancer by using network pharmacology and molecular docking.

Methods: Based on TCMSP, ETCM, and BATMAN database searching and screening to obtain the ingredients of LJZD, the related targets were obtained. Breast cancer-related targets were collected through GEO, Geencards, OMIM, and other databases, and drug-disease Venn diagrams were drawn by R. The PPI network map was constructed by using Cytoscape. The intersecting targets were imported into the STRING database, and the core targets were analyzed and screened. The intersected targets were analyzed by the DAVID database for GO and KEGG enrichment. AutoDock Vina and Gromacs were used for molecular docking and simulation of the core targets and active ingredients.

Results: 126 active ingredients of LJZD were obtained; 241 targets related to breast cancer were sought after screening, and 180 intersection targets were identified through Venn diagram analysis. The core targets were FOS and ESR1. KEGG enrichment analysis mainly involved PI3K/Akt, MAPK, and other signaling pathways.

Conclusion: This study has explored the possible targets and signaling pathways of LJZD in treating breast cancer through network pharmacology and bioinformatics analysis. Molecular docking and simulation have further validated the potential mechanism of action of LJZD in breast cancer treatment, providing essential experimental data for future studies.

Keywords: Liujunzi decoction, network pharmacology, molecular docking, breast cancer, FOS, ESR1.

« Previous
[1]
Bernstein L, Ross RK. Endogenous hormones and breast cancer risk. Epidemiol Rev 1993; 15(1): 48-65.
[http://dx.doi.org/10.1093/oxfordjournals.epirev.a036116] [PMID: 8405212]
[2]
DeSantis CE, Miller KD, Goding Sauer A, Jemal A, Siegel RL. Cancer statistics for African Americans, 2019. CA Cancer J Clin 2019; 69(3): 211-33.
[http://dx.doi.org/10.3322/caac.21555] [PMID: 30762872]
[3]
Kolak A, Kamińska M, Sygit K, et al. Primary and secondary prevention of breast cancer. Ann Agric Environ Med 2017; 24(4): 549-53.
[http://dx.doi.org/10.26444/aaem/75943] [PMID: 29284222]
[4]
Sancho-Garnier H, Colonna M. Breast cancer epidemiology. Presse Med 2019; 48(10): 1076-84.
[http://dx.doi.org/10.1016/j.lpm.2019.09.022]
[5]
Hu Z, Pan J, Wang J, Pei Y, Zhou R. Current research status of alkaloids against breast cancer. Chin J Physiol 2022; 65(1): 12-20.
[http://dx.doi.org/10.4103/cjp.cjp_89_21] [PMID: 35229748]
[6]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[7]
Liu S, Zhu J J, Li J C. The interpretation of human body in traditional Chinese medicine and its influence on the characteristics of TCM theory. Anat Rec 2021; 304(11): 2559-65.
[http://dx.doi.org/10.1002/ar.24643]
[8]
Yang Z, Zhang Q, Yu L, Zhu J, Cao Y, Gao X. The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer. J Ethnopharmacol 2021; 264: 113249.
[http://dx.doi.org/10.1016/j.jep.2020.113249] [PMID: 32810619]
[9]
Cohen I, Tagliaferri M, Tripathy D. Traditional Chinese medicine in the treatment of breast cancer. Semin Oncol 2002; 29(6): 563-74.
[http://dx.doi.org/10.1053/sonc.2002.50005] [PMID: 12516039]
[10]
Bai X, Ta N, Gong G H, et al. Effects of integrated chinese traditional medicine and conventional western medicine on the quality of life of breast cancer patients: A systematic review and meta- analysis. Evid Based Complementary Altern Med 2022; 3123878.
[http://dx.doi.org/10.1155/2022/3123878]
[11]
Xiang Y, Guo Z, Zhu P, Chen J, Huang Y. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med 2019; 8(5): 1958-75.
[http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]
[12]
Lee YC, Chen YH, Huang YC, Lee YF, Tsai MY. Effectiveness of combined treatment with traditional Chinese medicine and western medicine on the prognosis of patients with breast cancer. J Altern Complement Med 2020; 26(9): 835-42.
[http://dx.doi.org/10.1089/acm.2019.0200] [PMID: 32924556]
[13]
Xin X L, Wang G D, Han R, et al. Mechanism underlying the effect of Liujunzi decoction on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy. J Tradit Chin Med 2022; 42(1): 108-15.
[http://dx.doi.org/10.19852/j.cnki.jtcm.2022.01.007]
[14]
Wu X, Dai Y, Nie K. Research progress of Liujunzi decoction in the treatment of tumor-associated anorexia. Drug Des Devel Ther 2022; 16: 1731-41.
[http://dx.doi.org/10.2147/DDDT.S365292] [PMID: 35698654]
[15]
Han Y, Fan X, Fan L, et al. Liujunzi decoction exerts potent antitumor activity in oesophageal squamous cell carcinoma by inhibiting miR-34a/STAT3/IL-6R feedback loop, and modifies antitumor immunity. Phytomedicine 2023; 111: 154672.
[http://dx.doi.org/10.1016/j.phymed.2023.154672] [PMID: 36701994]
[16]
Dan L, Xie F, Ying C. Observation on the toxicity reduction and efficacy enhancement effect of XiangSha Liujunzi decoction on breast cancer chemotherapy patients. J Tradit Chin Med 2018; 38(4): 455-8.
[17]
Yang Z. Clinical study of Jiawei Liujunzi decoction combined with EC regimen for the treatment of spleen and stomach weakness in breast cancer. Nanjing University of Traditional Chinese Medicine 2020.
[http://dx.doi.org/10.27253/d.cnki.gnjzu.2020.000291]
[18]
Qi F, Zhao L, Zhou A, et al. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. Biosci Trends 2015; 9(1): 16-34.
[http://dx.doi.org/10.5582/bst.2015.01019] [PMID: 25787906]
[19]
Nogales C, Mamdouh ZM, List M, Kiel C, Casas AI, Schmidt HHHW. Network pharmacology: Curing causal mechanisms instead of treating symptoms. Trends Pharmacol Sci 2022; 43(2): 136-50.
[http://dx.doi.org/10.1016/j.tips.2021.11.004] [PMID: 34895945]
[20]
Chen C, Hou J, Tanner JJ, Cheng J. Bioinformatics methods for mass spectrometry-based proteomics data analysis. Int J Mol Sci 2020; 21(8): 2873.
[http://dx.doi.org/10.3390/ijms21082873] [PMID: 32326049]
[21]
Gao L, Cao M, Li JQ, Qin XM, Fang J. Traditional Chinese medicine network pharmacology in cardiovascular precision medicine. Curr Pharm Des 2021; 27(26): 2925-33.
[http://dx.doi.org/10.2174/18734286MTExhNDUh4] [PMID: 33183189]
[22]
Ru J, Li P, Wang J, et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6(1): 13.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[23]
Xu HY, Zhang YQ, Liu ZM, et al. ETCM: An encyclopaedia of traditional Chinese medicine. Nucleic Acids Res 2019; 47(D1): D976-82.
[http://dx.doi.org/10.1093/nar/gky987] [PMID: 30365030]
[24]
Liu Z, Guo F, Wang Y, et al. BATMAN-TCM: A bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine. Sci Rep 2016; 6(1): 21146.
[http://dx.doi.org/10.1038/srep21146] [PMID: 26879404]
[25]
Leucuta SE. Selecting oral bioavailability enhancing formulations during drug discovery and development. Expert Opin Drug Discov 2014; 9(2): 139-50.
[http://dx.doi.org/10.1517/17460441.2014.877881] [PMID: 24387781]
[26]
Jia CY, Li JY, Hao GF, Yang GF. A drug-likeness toolbox facilitates ADMET study in drug discovery. Drug Discov Today 2020; 25(1): 248-58.
[http://dx.doi.org/10.1016/j.drudis.2019.10.014] [PMID: 31705979]
[27]
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7(1): 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[28]
Zhang YC, Gao WC, Chen WJ, Pang DX, Mo DY, Yang M. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of fei jin sheng formula in the treatment of lung cancer. Curr Pharm Des 2023; 29(14): 1121-34.
[http://dx.doi.org/10.2174/1381612829666230503164755] [PMID: 37138492]
[29]
Bateman A, Martin M-J, Orchard S, et al. UniProt: The universal protein knowledgebase in 2023. Nucleic Acids Res 2023; 51(D1): D523-31.
[http://dx.doi.org/10.1093/nar/gkac1052] [PMID: 36408920]
[30]
Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: Archive for functional genomics data sets-update. Nucleic Acids Res 2012; 41(D1): D991-5.
[http://dx.doi.org/10.1093/nar/gks1193] [PMID: 23193258]
[31]
Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A. OMIM.org: Online mendelian inheritance in man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res 2015; 43(D1): D789-98.
[http://dx.doi.org/10.1093/nar/gku1205] [PMID: 25428349]
[32]
Whirl-Carrillo M, Huddart R, Gong L, et al. An evidence-based framework for evaluating pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2021; 110(3): 563-72.
[http://dx.doi.org/10.1002/cpt.2350] [PMID: 34216021]
[33]
Wang Y, Zhang S, Li F, et al. Therapeutic target database 2020: Enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res 2019; 48(D1): gkz981.
[http://dx.doi.org/10.1093/nar/gkz981] [PMID: 31691823]
[34]
Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res 2018; 46(D1): D1074-82.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[35]
Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D. GeneCards: Integrating information about genes, proteins and diseases. Trends Genet 1997; 13(4): 163.
[http://dx.doi.org/10.1016/S0168-9525(97)01103-7] [PMID: 9097728]
[36]
Sherman BT, Hao M, Qiu J, et al. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res 2022; 50(W1): W216-21.
[http://dx.doi.org/10.1093/nar/gkac194] [PMID: 35325185]
[37]
Shen S, Kong J, Qiu Y, Yang X, Wang W, Yan L. Identification of core genes and outcomes in hepatocellular carcinoma by bioinformatics analysis. J Cell Biochem 2019; 120(6): 10069-81.
[http://dx.doi.org/10.1002/jcb.28290] [PMID: 30525236]
[38]
Tang D, Chen M, Huang X, et al. SRplot: A free online platform for data visualization and graphing. PLoS One 2023; 18(11): e0294236.
[http://dx.doi.org/10.1371/journal.pone.0294236] [PMID: 37943830]
[39]
Szklarczyk D, Kirsch R, Koutrouli M, et al. The STRING database in 2023: Protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 2023; 51(D1): D638-46.
[http://dx.doi.org/10.1093/nar/gkac1000] [PMID: 36370105]
[40]
Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res 2019; 47(W1): W556-60.
[http://dx.doi.org/10.1093/nar/gkz430] [PMID: 31114875]
[41]
Győrffy B. Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer. Comput Struct Biotechnol J 2021; 19: 4101-9.
[http://dx.doi.org/10.1016/j.csbj.2021.07.014] [PMID: 34527184]
[42]
Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res 2000; 28(1): 235-42.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[43]
Kim S, Chen J, Cheng T, et al. PubChem 2023 update. Nucleic Acids Res 2023; 51(D1): D1373-80.
[http://dx.doi.org/10.1093/nar/gkac956] [PMID: 36305812]
[44]
Ozkan T, Hekmatshoar Y, Ertan-Bolelli T, et al. Determination of the apoptotic effect and molecular docking of benzamide derivative XT5 in K562 cells. Anticancer Agents Med Chem 2019; 18(11): 1521-30.
[http://dx.doi.org/10.2174/1871520618666171229222534] [PMID: 29298654]
[45]
Chen L, Glover JNM, Hogan PG, Rao A, Harrison SC. Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 1998; 392(6671): 42-8.
[http://dx.doi.org/10.1038/32100] [PMID: 9510247]
[46]
Blizzard TA, DiNinno F, Morgan JD II, et al. Estrogen receptor ligands. Part 9: Dihydrobenzoxathiin SERAMs with alkyl substituted pyrrolidine side chains and linkers. Bioorg Med Chem Lett 2005; 15(1): 107-13.
[http://dx.doi.org/10.1016/j.bmcl.2004.10.036] [PMID: 15582421]
[47]
Ferreira L, dos Santos R, Oliva G, Andricopulo A. Molecular docking and structure-based drug design strategies. Molecules 2015; 20(7): 13384-421.
[http://dx.doi.org/10.3390/molecules200713384] [PMID: 26205061]
[48]
Ye J, Li L, Hu Z. Exploring the molecular mechanism of action of yinchen wuling powder for the treatment of hyperlipidemia, using network pharmacology, molecular docking, and molecular dynamics simulation. BioMed Res Int 2021; 2021: 1-14.
[http://dx.doi.org/10.1155/2021/9965906] [PMID: 34746316]
[49]
Gonzalez NA, Li BA, McCully ME. The stability and dynamics of computationally designed proteins. Protein Eng Des Sel 2022; 35: gzac001.
[http://dx.doi.org/10.1093/protein/gzac001] [PMID: 35174855]
[50]
Zhang Q. Inhibition of pancreatic cancer cell proliferation and invasion through SRC by Jiawei Chai-shao Liujunzi Decoction. Liaoning University of Traditional Chinese Medicine 2023.
[51]
Gao P. Observation of chemotherapy combined with Chai Shao Liujunzi decoction for breast cancer treatment. Electr J Clin Med Lit 2020; 7(36): 151-8.
[http://dx.doi.org/10.16281/j.cnki.jocml.2020.36.136]
[52]
Vellanki SH, Cruz RGB, Richards C, et al. Antibiotic tetrocarcin-A down-regulates JAM-A, IAPs and induces apoptosis in triple-negative breast cancer models. Anticancer Res 2019; 39(3): 1197-204.
[http://dx.doi.org/10.21873/anticanres.13230] [PMID: 30842150]
[53]
Wu W, Warner M, Wang L, et al. Drivers and suppressors of triple-negative breast cancer. Proc Natl Acad Sci USA 2021; 118(33): e2104162118.
[http://dx.doi.org/10.1073/pnas.2104162118] [PMID: 34389675]
[54]
Saatci O, Huynh-Dam KT, Sahin O. Endocrine resistance in breast cancer: From molecular mechanisms to therapeutic strategies. J Mol Med 2021; 99(12): 1691-710.
[http://dx.doi.org/10.1007/s00109-021-02136-5] [PMID: 34623477]
[55]
Yadav N, Sunder R, Desai S, et al. Progesterone modulates the DSCAM-AS1/miR-130a/ESR1 axis to suppress cell invasion and migration in breast cancer. Breast Cancer Res 2022; 24(1): 97.
[http://dx.doi.org/10.1186/s13058-022-01597-x] [PMID: 36578092]
[56]
Yi J, Wang L, Hu G, et al. CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS. EMBO J 2023; 42(10): e112408.
[http://dx.doi.org/10.15252/embj.2022112408] [PMID: 37009655]
[57]
Li Z, Wu Y, Yates ME, et al. Hotspot ESR1 mutations are multimodal and contextual modulators of breast cancer metastasis. Cancer Res 2022; 82(7): 1321-39.
[http://dx.doi.org/10.1158/0008-5472.CAN-21-2576] [PMID: 35078818]
[58]
Ajji PK, Walder K, Puri M. Combination of balsamin and flavonoids induce apoptotic effects in liver and breast cancer cells. Front Pharmacol 2020; 11: 574496.
[http://dx.doi.org/10.3389/fphar.2020.574496] [PMID: 33192517]
[59]
Balakrishnan S, Bhat FA, Raja Singh P, et al. Gold nanoparticle- conjugated quercetin inhibits epithelial–mesenchymal transition, angiogenesis and invasiveness via EGFR/ VEGFR-2-mediated pathway in breast cancer. Cell Prolif 2016; 49(6): 678-97.
[http://dx.doi.org/10.1111/cpr.12296] [PMID: 27641938]
[60]
Pateliya B, Burade V, Goswami S. Combining naringenin and metformin with doxorubicin enhances anticancer activity against triple-negative breast cancer in vitro and in vivo. Eur J Pharmacol 2021; 891: 173725.
[http://dx.doi.org/10.1016/j.ejphar.2020.173725] [PMID: 33157041]
[61]
Zeng J, Xu H, Fan P, et al. Kaempferol blocks neutrophil extracellular traps formation and reduces tumour metastasis by inhibiting ROS-PAD4 pathway. J Cell Mol Med 2020; 24(13): 7590-9.
[http://dx.doi.org/10.1111/jcmm.15394] [PMID: 32427405]
[62]
Pompura SL, Dominguez-Villar M. The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function. J Leukoc Biol 2018; 103(6): 1065-76.
[http://dx.doi.org/10.1002/JLB.2MIR0817-349R] [PMID: 29357116]
[63]
Zhang T, Zhu X, Wu H, et al. Targeting the ROS/PI3K/AKT/HIF-1α/HK2 axis of breast cancer cells: Combined administration of polydatin and 2-Deoxy-d-glucose. J Cell Mol Med 2019; 23(5): 3711-23.
[http://dx.doi.org/10.1111/jcmm.14276] [PMID: 30920152]
[64]
Yan W, Ma X, Zhao X, Zhang S. Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/AKT pathway in vivo and in vitro. Drug Des Devel Ther 2018; 12: 3961-72.
[http://dx.doi.org/10.2147/DDDT.S181939] [PMID: 30510404]
[65]
Li P, Lin Z, Liu Q, et al. Enhancer RNA SLIT2 inhibits bone metastasis of breast cancer through regulating P38 MAPK/c-Fos signaling pathway. Front Oncol 2021; 11: 743840.
[http://dx.doi.org/10.3389/fonc.2021.743840] [PMID: 34722297]
[66]
Liu Q, Liu Y, Li X, et al. Perfluoroalkyl substances promote breast cancer progression via ERα and GPER mediated PI3K/Akt and MAPK/Erk signaling pathways. Ecotoxicol Environ Saf 2023; 258: 114980.
[http://dx.doi.org/10.1016/j.ecoenv.2023.114980] [PMID: 37148752]
[67]
Wen S, Hou Y, Fu L, et al. Cancer-associated fibroblast (CAF)-derived IL32 promotes breast cancer cell invasion and metastasis via integrin β3–p38 MAPK signalling. Cancer Lett 2019; 442: 320-32.
[http://dx.doi.org/10.1016/j.canlet.2018.10.015] [PMID: 30391782]
[68]
Vethakanraj HS, Sesurajan BP, Padmanaban VP, Jayaprakasam M, Murali S, Sekar AK. Anticancer effect of acid ceramidase inhibitor ceranib-2 in human breast cancer cell lines MCF-7, MDA MB-231 by the activation of SAPK/JNK, p38 MAPK apoptotic pathways, inhibition of the Akt pathway, downregulation of ERα. Anticancer Drugs 2018; 29(1): 50-60.
[http://dx.doi.org/10.1097/CAD.0000000000000566] [PMID: 29023248]
[69]
Liu W, Lu X, Shi P, et al. TNF-α increases breast cancer stem-like cells through up-regulating TAZ expression via the non-canonical NF-κB pathway. Sci Rep 2020; 10(1): 1804.
[http://dx.doi.org/10.1038/s41598-020-58642-y] [PMID: 32019974]
[70]
Cruceriu D, Baldasici O, Balacescu O, Berindan-Neagoe I. The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: Molecular insights and therapeutic approaches. Cell Oncol 2020; 43(1): 1-18.
[http://dx.doi.org/10.1007/s13402-019-00489-1] [PMID: 31900901]
[71]
Zhang HS, Zhang ZG, Du GY, et al. Nrf2 promotes breast cancer cell migration via up-regulation of G6PD/HIF-1α/Notch1 axis. J Cell Mol Med 2019; 23(5): 3451-63.
[http://dx.doi.org/10.1111/jcmm.14241] [PMID: 30809937]
[72]
Jin J, Qiu S, Wang P, et al. Cardamonin inhibits breast cancer growth by repressing HIF-1α-dependent metabolic reprogramming. J Exp Clin Cancer Res 2019; 38(1): 377.
[http://dx.doi.org/10.1186/s13046-019-1351-4] [PMID: 31455352]
[73]
van Deursen JM. The role of senescent cells in ageing. Nature 2014; 509(7501): 439-46.
[http://dx.doi.org/10.1038/nature13193] [PMID: 24848057]
[74]
Hwang HJ, Lee YR, Kang D, et al. Endothelial cells under therapy-induced senescence secrete CXCL11, which increases aggressiveness of breast cancer cells. Cancer Lett 2020; 490: 100-10.
[http://dx.doi.org/10.1016/j.canlet.2020.06.019] [PMID: 32659248]
[75]
Yang D, Guo Q, Liang Y, et al. Wogonin induces cellular senescence in breast cancer via suppressing TXNRD2 expression. Arch Toxicol 2020; 94(10): 3433-47.
[http://dx.doi.org/10.1007/s00204-020-02842-y] [PMID: 32671444]

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