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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Mechanism of Procyanidin B2 in the Treatment of Chronic Myeloid Leukemia Based on Integrating Network Pharmacology and Molecular Docking

Author(s): Hong-Xing Li, Yuan-Xue Jing, Yi-Hong Chai, Xiao-Hong Sun, Xiao-Xia He, Shi-Long Xue, Ya-Ming Xi* and Xiao-Ling Ma*

Volume 23, Issue 16, 2023

Published on: 15 June, 2023

Page: [1838 - 1847] Pages: 10

DOI: 10.2174/1871520623666230526122524

Price: $65

Abstract

Objective: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically.

Methods: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology.

Results: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells.

Conclusion: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.

Graphical Abstract

[1]
Jabbour, E.; Kantarjian, H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am. J. Hematol., 2020, 95(6), 691-709.
[http://dx.doi.org/10.1002/ajh.25792] [PMID: 32239758]
[2]
Höglund, M.; Sandin, F.; Simonsson, B. Epidemiology of chronic myeloid leukaemia: An update. Ann. Hematol., 2015, 94(S2), 241-247.
[http://dx.doi.org/10.1007/s00277-015-2314-2] [PMID: 25814090]
[3]
Hochhaus, A.; Baccarani, M.; Silver, R.T.; Schiffer, C.; Apperley, J.F.; Cervantes, F.; Clark, R.E.; Cortes, J.E.; Deininger, M.W.; Guilhot, F.; Hjorth-Hansen, H.; Hughes, T.P.; Janssen, J.J.W.M.; Kantarjian, H.M.; Kim, D.W.; Larson, R.A.; Lipton, J.H.; Mahon, F.X.; Mayer, J.; Nicolini, F.; Niederwieser, D.; Pane, F.; Radich, J.P.; Rea, D.; Richter, J.; Rosti, G.; Rousselot, P.; Saglio, G.; Saußele, S.; Soverini, S.; Steegmann, J.L.; Turkina, A.; Zaritskey, A.; Hehlmann, R. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia, 2020, 34(4), 966-984.
[http://dx.doi.org/10.1038/s41375-020-0776-2] [PMID: 32127639]
[4]
Cortes, J.E.; Kim, D.W.; Pinilla-Ibarz, J.; le Coutre, P.; Paquette, R.; Chuah, C.; Nicolini, F.E.; Apperley, J.F.; Khoury, H.J.; Talpaz, M.; DiPersio, J.; DeAngelo, D.J.; Abruzzese, E.; Rea, D.; Baccarani, M.; Müller, M.C.; Gambacorti-Passerini, C.; Wong, S.; Lustgarten, S.; Rivera, V.M.; Clackson, T.; Turner, C.D.; Haluska, F.G.; Guilhot, F.; Deininger, M.W.; Hochhaus, A.; Hughes, T.; Goldman, J.M.; Shah, N.P.; Kantarjian, H. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N. Engl. J. Med., 2013, 369(19), 1783-1796.
[http://dx.doi.org/10.1056/NEJMoa1306494] [PMID: 24180494]
[5]
Cortes, J.E.; Gambacorti-Passerini, C.; Deininger, M.W.; Mauro, M.J.; Chuah, C.; Kim, D.W.; Dyagil, I.; Glushko, N.; Milojkovic, D.; le Coutre, P.; Garcia-Gutierrez, V.; Reilly, L.; Jeynes-Ellis, A.; Leip, E.; Bardy-Bouxin, N.; Hochhaus, A.; Brümmendorf, T.H. Bosutinib versus Imatinib for newly diagnosed chronic myeloid leukemia: Results from the randomized before trial. J. Clin. Oncol., 2018, 36(3), 231-237.
[http://dx.doi.org/10.1200/JCO.2017.74.7162] [PMID: 29091516]
[6]
Amir, M.; Javed, S. A review on the therapeutic role of TKIs in case of CML in combination with epigenetic drugs. Front. Genet., 2021, 12, 742802.
[http://dx.doi.org/10.3389/fgene.2021.742802] [PMID: 34745216]
[7]
Wolfe, H.R.; Rein, L.A.M. The evolving landscape of frontline therapy in chronic phase chronic myeloid leukemia (CML). Curr. Hematol. Malig. Rep., 2021, 16(5), 448-454.
[http://dx.doi.org/10.1007/s11899-021-00655-z] [PMID: 34661874]
[8]
Minciacchi, V.R.; Kumar, R.; Krause, D.S. Chronic myeloid leukemia: A model disease of the past, present and future. Cells, 2021, 10(1), 117.
[http://dx.doi.org/10.3390/cells10010117] [PMID: 33435150]
[9]
Hehlmann, R. Chronic myeloid leukemia in 2020. HemaSphere, 2020, 4(5), e468.
[http://dx.doi.org/10.1097/HS9.0000000000000468] [PMID: 33134861]
[10]
Lübking, A.; Dreimane, A.; Sandin, F.; Isaksson, C.; Märkevärn, B.; Brune, M.; Ljungman, P.; Lenhoff, S.; Stenke, L.; Höglund, M.; Richter, J.; Olsson-Strömberg, U. Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era: Population-based data from the Swedish CML registry. Bone Marrow Transplant., 2019, 54(11), 1764-1774.
[http://dx.doi.org/10.1038/s41409-019-0513-5] [PMID: 30962502]
[11]
Valencia-Hernandez, L.J.; Wong-Paz, J.E.; Ascacio-Valdés, J.A.; Chávez-González, M.L.; Contreras-Esquivel, J.C.; Aguilar, C.N. Procyanidins: From agro-industrial waste to food as bioactive molecules. Foods, 2021, 10(12), 3152.
[http://dx.doi.org/10.3390/foods10123152] [PMID: 34945704]
[12]
Yang, H.; Xiao, L.; Yuan, Y.; Luo, X.; Jiang, M.; Ni, J.; Wang, N. Procyanidin B2 inhibits NLRP3 inflammasome activation in human vascular endothelial cells. Biochem. Pharmacol., 2014, 92(4), 599-606.
[http://dx.doi.org/10.1016/j.bcp.2014.10.001] [PMID: 25450671]
[13]
Chuang, C.C.; McIntosh, M.K. Potential mechanisms by which polyphenol-rich grapes prevent obesity-mediated inflammation and metabolic diseases. Annu. Rev. Nutr., 2011, 31(1), 155-176.
[http://dx.doi.org/10.1146/annurev-nutr-072610-145149] [PMID: 21548775]
[14]
Gouvêa, C.M.C.P.; Avelar, M.M. Procyanidin B2 cytotoxicity to MCF-7 human breast adenocarcinoma cells. Indian J. Pharm. Sci., 2012, 74(4), 351-355.
[http://dx.doi.org/10.4103/0250-474X.107070] [PMID: 23626391]
[15]
Chen, H.; Wang, W.; Yu, S.; Wang, H.; Tian, Z.; Zhu, S. Procyanidins and their therapeutic potential against oral diseases. Molecules, 2022, 27(9), 2932.
[http://dx.doi.org/10.3390/molecules27092932] [PMID: 35566283]
[16]
Liu, J.; Zhang, W.Y.; Kong, Z.H.; Ding, D.G. Induction of cell cycle arrest and apoptosis by grape seed procyanidin extract in human bladder cancer BIU87 cells. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(15), 3282-3291.
[PMID: 27467005]
[17]
Owczarek, K.; Hrabec, E.; Fichna, J.; Sosnowska, D. Koziołkiewicz, M.; Szymański, J.; Lewandowska, U. Flavanols from Japanese quince (Chaenomeles japonica) fruit suppress expression of cyclooxygenase-2, metalloproteinase-9, and nuclear factor-kappaB in human colon cancer cells. Acta Biochim. Pol., 2017, 64(3), 567-576.
[http://dx.doi.org/10.18388/abp.2017_1599] [PMID: 28787469]
[18]
Lee, Y. Cancer chemopreventive potential of Procyanidin. Toxicol. Res., 2017, 33(4), 273-282.
[http://dx.doi.org/10.5487/TR.2017.33.4.273] [PMID: 29071011]
[19]
Ma, Y.; Zhang, X.; Su, Z.; Li, N.; Cao, L.; Ding, G.; Wang, Z.; Xiao, W. Insight into the molecular mechanism of a herbal injection by integrating network pharmacology and in vitro. J. Ethnopharmacol., 2015, 173, 91-99.
[http://dx.doi.org/10.1016/j.jep.2015.07.016] [PMID: 26192807]
[20]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[21]
Osman, A.E.G.; Deininger, M.W. Chronic Myeloid Leukemia: Modern therapies, current challenges and future directions. Blood Rev., 2021, 49, 100825.
[http://dx.doi.org/10.1016/j.blre.2021.100825] [PMID: 33773846]
[22]
Hehlmann, R. The new ELN recommendations for treating CML. J. Clin. Med., 2020, 9(11), 3671.
[http://dx.doi.org/10.3390/jcm9113671] [PMID: 33207600]
[23]
Braun, T.P.; Eide, C.A.; Druker, B.J. Response and resistance to BCR-ABL1-targeted therapies. Cancer Cell, 2020, 37(4), 530-542.
[http://dx.doi.org/10.1016/j.ccell.2020.03.006] [PMID: 32289275]
[24]
Chen, J.; Wang, F.; Fang, J.; Nie, D.; Zhang, Y.; Chen, X.; Li, Y.; Tan, Y.; Ma, X.; Guo, Y.; Cao, P.; Liu, M.; Liu, H. Dynamic evolution of ponatinib‐resistant mutations in BCR–ABL1 ‐positive leukaemias revealed by next‐generation sequencing. Br. J. Haematol., 2020, 191(5), e113-e116.
[http://dx.doi.org/10.1111/bjh.17068] [PMID: 33460055]
[25]
Stetka, J.; Gursky, J.; Liñan Velasquez, J.; Mojzikova, R.; Vyhlidalova, P.; Vrablova, L.; Bartek, J.; Divoky, V. Role of DNA damage response in suppressing malignant progression of chronic myeloid leukemia and polycythemia vera: Impact of different oncogenes. Cancers, 2020, 12(4), 903.
[http://dx.doi.org/10.3390/cancers12040903] [PMID: 32272770]
[26]
Vetrie, D.; Helgason, G.V.; Copland, M. The leukaemia stem cell: Similarities, differences and clinical prospects in CML and AML. Nat. Rev. Cancer, 2020, 20(3), 158-173.
[http://dx.doi.org/10.1038/s41568-019-0230-9] [PMID: 31907378]
[27]
Nogales, C.; Mamdouh, Z.M.; List, M.; Kiel, C.; Casas, A.I.; Schmidt, H.H.H.W. Network pharmacology: Curing causal mechanisms instead of treating symptoms. Trends Pharmacol. Sci., 2022, 43(2), 136-150.
[http://dx.doi.org/10.1016/j.tips.2021.11.004] [PMID: 34895945]
[28]
Zeng, Y.X.; Wang, S.; Wei, L.; Cui, Y.Y.; Chen, Y.H. Proanthocyanidins: Components, pharmacokinetics and biomedical properties. Am. J. Chin. Med., 2020, 48(4), 813-869.
[http://dx.doi.org/10.1142/S0192415X2050041X] [PMID: 32536248]
[29]
Dinner, S.; Platanias, L.C. Targeting the mTOR pathway in leukemia. J. Cell. Biochem., 2016, 117(8), 1745-1752.
[http://dx.doi.org/10.1002/jcb.25559] [PMID: 27018341]
[30]
Bibi, S.; Arslanhan, M.D.; Langenfeld, F.; Jeanningros, S.; Cerny-Reiterer, S.; Hadzijusufovic, E.; Tchertanov, L.; Moriggl, R.; Valent, P.; Arock, M. Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: Possible new targets of therapy. Haematologica, 2014, 99(3), 417-429.
[http://dx.doi.org/10.3324/haematol.2013.098442] [PMID: 24598853]
[31]
Meeran, S.M.; Katiyar, S.K. Proanthocyanidins inhibit mitogenic and survival-signaling in vitro and tumor growth in vivo. Front. Biosci., 2008, 13(13), 887-897.
[http://dx.doi.org/10.2741/2729] [PMID: 17981597]
[32]
Wu, P.S.; Wang, C.Y.; Chen, P.S.; Hung, J.H.; Yen, J.H.; Wu, M.J. 8-Hydroxydaidzein downregulates JAK/STAT, MMP, oxidative phosphorylation, and PI3K/AKT pathways in K562 cells. Biomedicines, 2021, 9(12), 1907.
[http://dx.doi.org/10.3390/biomedicines9121907] [PMID: 34944720]
[33]
Luo, X.; Feng, M.; Zhu, X.; Li, Y.; Fei, J.; Zhang, Y. VEGF depletion enhances bcr-abl-specific sensitivity of arsenic trioxide in chronic myelogenous leukemia. Hematology, 2013, 18(6), 334-340.
[http://dx.doi.org/10.1179/1607845413Y.0000000083] [PMID: 24129092]
[34]
Steinbach, A.; Clark, S.M.; Clemmons, A.B. Bosutinib: A novel src/abl kinase inhibitor for chronic myelogenous leukemia. J. Adv. Pract. Oncol., 2013, 4(6), 451-455.
[PMID: 25032026]
[35]
Bertacchini, J.; Heidari, N.; Mediani, L.; Capitani, S.; Shahjahani, M.; Ahmadzadeh, A.; Saki, N. Targeting PI3K/AKT/mTOR network for treatment of leukemia. Cell. Mol. Life Sci., 2015, 72(12), 2337-2347.
[http://dx.doi.org/10.1007/s00018-015-1867-5] [PMID: 25712020]
[36]
Nakahara, F.; Kitaura, J.; Uchida, T.; Nishida, C.; Togami, K.; Inoue, D.; Matsukawa, T.; Kagiyama, Y.; Enomoto, Y.; Kawabata, K.C.; Chen-Yi, L.; Komeno, Y.; Izawa, K.; Oki, T.; Nagae, G.; Harada, Y.; Harada, H.; Otsu, M.; Aburatani, H.; Heissig, B.; Hattori, K.; Kitamura, T. Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells. Blood, 2014, 123(25), 3932-3942.
[http://dx.doi.org/10.1182/blood-2013-01-476747] [PMID: 24825862]
[37]
Zhu, X.; Wang, L.; Zhang, B.; Li, J.; Dou, X.; Zhao, R.C. TGF- 1-induced PI3K/Akt/NF- B/MMP9 signalling pathway is activated in Philadelphia chromosome-positive chronic myeloid leukaemia hemangioblasts. J. Biochem., 2011, 149(4), 405-414.
[http://dx.doi.org/10.1093/jb/mvr016] [PMID: 21288887]

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      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=132105
      700μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 1 limit 1
      820μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 1
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and sj.journal_id!=1 group by `j`.`nid`) as `aggregate_table`
      1.18msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and sj.journal_id!=1 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.46msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      3.91msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '132105'
      220μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 132105
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '132105'
      5.25msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 132105
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '132105' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      6.05msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 132105
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      330μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      700μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 1 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      49.64msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      11.73msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.91msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 132105 limit 1
      250μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 132105
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 132105 and content_type = 'article' order by status desc limit 1
      310μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 217380 limit 1
      250μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 217380
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      250μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'ACAMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      330μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: ACAMC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '132105' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      410μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '12704' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      340μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3314' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      320μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496327 and j.to_date >= 1740496327 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3314) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496327 and j.to_date >= 1740496327 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3314) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496327 and j.to_date >= 1740496327 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3314)
      92.54msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496328 and j.to_date >= 1740496328 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12704) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496328 and j.to_date >= 1740496328 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12704) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496328 and j.to_date >= 1740496328 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12704)
      10.69msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496328 and j.to_date >= 1740496328 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 132105) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496328 and j.to_date >= 1740496328 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 132105) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740496328 and j.to_date >= 1740496328 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 132105)
      860μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '1838' and is_uploaded = 1 and issue_id = 12704 order by cast(first_page as SIGNED) desc limit 1
      540μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1838
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '1847' and is_uploaded = 1 and issue_id = 12704 order by cast(first_page as SIGNED) asc limit 1
      1.38msalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1847
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      220μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      230μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 132105 limit 1
      2.4msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 132105
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 1 and `b`.`banner_from_date` <= 1740496328 and `b`.`banner_to_date` >= 1740496328 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.18msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740496328
      • 4: 1740496328
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 1 and `b`.`banner_from_date` <= 1740496328 and `b`.`banner_to_date` >= 1740496328 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740496328
      • 4: 1740496328
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='d924a3405bb44f03c3bcaed73d043be8'
      220μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
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        ClearShow all
        Date ↕MethodURLData
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