Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Research Article

Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines

Author(s): Abdul M. Baig*, Zohaib Rana, Mohammad M. Mannan, Areeba Khaleeq, Fizza Nazim, Preet Katyara and Farhat Abbas

Volume 20, Issue 8, 2020

Page: [1017 - 1027] Pages: 11

DOI: 10.2174/1871520620666200409142239

Price: $65

Abstract

Background: Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs.

Objectives: We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa).

Methods: Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines.

Result: We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects.

Conclusion: Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could be re-purposed after human trials in PCa.

Keywords: Microarray, gene expression, prostate cancer, PC3, DU145, anti-cancer drugs, calmodulin, the oncomine, anti-cancer drugs.

Graphical Abstract

[1]
Liu, L.; Chen, X.; Hu, C.; Zhang, D.; Shao, Z.; Jin, Q.; Yang, J.; Xie, H.; Liu, B.; Hu, M.; Ke, K. Synthetic lethality-based identification of targets for anticancer drugs in the human signaling network. Sci. Rep. May, 2018, 8(1), 8440.
[2]
Nieto Gutierrez, A.; McDonald, P.H. GPCRs: Emerging anti-cancer drug targets. Cell. Signal., 2018, 41, 65-74.
[http://dx.doi.org/10.1016/j.cellsig.2017.09.005]
[3]
Lappano, R.; Maggiolini, M. G protein-coupled receptors: novel targets for drug discovery in cancer. Nat. Rev. Drug Discov., 2011, 10(1), 47-60.
[http://dx.doi.org/10.1038/nrd3320]
[4]
Mannan Baig, A.; Khan, N.A.; Effendi, V.; Rana, Z.; Ahmad, H.R.; Abbas, F. Differential receptor dependencies: expression and significance of muscarinic M1 receptors in the biology of prostate cancer. Anticancer Drugs, 2017, 28(1), 75-87.
[5]
Govindarajan, R.; Duraiyan, J.; Kaliyappan, K.; Palanisamy, M. Microarray and its applications. J. Pharm. Bioallied Sci., 2012, 4(2), S310-S312.
[6]
Rhodes, D.R.; Kalyana, S.; Sundaram, V. The Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia, 2007, 9, 166-180.
[7]
Tym, J.E.; Mitsopoulos, C.; Coker, E.A.; Razaz, P.; Schierz, A.C.; Antolin, A.A.; Al-Lazikani, B. canSAR: an updated cancer research and drug discovery knowledgebase. Nucleic Acids Res., 2016, 44(D1), D938-D943.
[8]
Uhlén, M.; Fagerberg, L.; Hallström, B.M.; Lindskog, C.; Oksvold, P.; Mardinoglu, A.; Sivertsson, Å.; Kampf, C.; Sjöstedt, E.; Asplund, A.; Olsson, I.; Edlund, K.; Lundberg, E.; Navani, S.; Szigyarto, C.A.; Odeberg, J.; Djureinovic, D.; Takanen, J.O.; Hober, S.; Alm, T.; Edqvist, P.H.; Berling, H.; Tegel, H.; Mulder, J.; Rockberg, J.; Nilsson, P.; Schwenk, J.M.; Hamsten, M.; von Feilitzen, K.; Forsberg, M.; Persson, L.; Johansson, F.; Zwahlen, M.; von Heijne, G.; Nielsen, J.; Pontén, F. Proteomics. Tissue-based map of the human proteome. Science, 2015, 347(6220)1260419
[http://dx.doi.org/10.1126/science.1260419] [PMID: 25613900]
[9]
Kanehisa, M.; Sato, Y.; Kawashima, M.; Furumichi, M.; Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res., 2016, 44(D1), D457-D462.
[10]
Leung, W-H. Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation. J. Experim. Med., 2017, 210(12), 2675-2692.
[11]
Lee, K.J. Pharmacologic agents for chronic diarrhea. Intest. Res., 2015, 13(4), 306-312.
[http://dx.doi.org/10.5217/ir.2015.13.4.306] [PMID: 26576135]
[12]
Giagnoni, G.; Casiraghi, L.; Senini, R.; Revel, L.; Parolaro, D.; Sala, M.; Gori, E. Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci., 1983, 33(Suppl. 1), 315-318.
[http://dx.doi.org/10.1016/0024-3205(83)90506-4] [PMID: 6319884]
[13]
Brunton, L.L.; Chabner, B.A.; Knollmann, B.C. Goodman & Gilman’s: The Pharmacological basis of Therapeutics, 12th ed; Mc-Graw Hill Education: New York, 2011.
[14]
Gong, X.W.; Xu, Y.H.; Chen, X.L.; Wang, Y.X. Loperamide, an antidiarrhea drug, has antitumor activity by inducing cell apoptosis. Pharmacol. Res., 2012, 65(3), 372-378.
[http://dx.doi.org/10.1016/j.phrs.2011.11.007] [PMID: 22119769]
[15]
Awouters, F.; Megens, A.; Verlinden, M.; Schuurkes, J.; Niemegeers, C.; Janssen, P.A. Loperamide. Survey of studies on mechanism of its antidiarrheal activity. Dig. Dis. Sci., 1993, 38(6), 977-995.
[http://dx.doi.org/10.1007/BF01295711] [PMID: 8508715]
[16]
Nussinov, R.; Wang, G.; Tsai, C.J.; Jang, H.; Lu, S.; Banerjee, A.; Zhang, J.; Gaponenko, V. Calmodulin and PI3K signaling in KRAS cancers. Trends Cancer, 2017, 3(3), 214-224.
[17]
Regan, R.C.; Gogal, R.M., Jr; Barber, J.P.; Tuckfield, R.C.; Howerth, E.W.; Lawrence, J.A. Cytotoxic effects of loperamide hydrochloride on canine cancer cells. J. Vet. Med. Sci., 2014, 76(12), 1563-1568.
[18]
Zhu, Y.; Liu, C.; Nadiminty, N.; Lou, W.; Tummala, R.; Evans, C.P.; Gao, A.C. Inhibition of ABCB1 expression overcomes acquired docetaxel resistance in prostate cancer. Mol. Cancer Ther., 2013, 12(9), 1829-1836.
[19]
Yeh, C.T.; Wu, A.T.; Chang, P.M. promethazine Trifluoperazine, an antipsychotic agent, inhibits cancer stem cell growth and overcomes drug resistance of lung cancer. Am. J. Respir. Crit. Care Med., 2012, 186(11), 1180-1188.
[http://dx.doi.org/10.1164/rccm.201207-1180OC]
[20]
Grief, F.; Soroff, H.S.; Albers, K.M.; Taichman, L.B. The effect of Promethazine, a calmodulin antagonist, on the growth of normal and malignant epidermal keratinocytes in culture. Eur. J. Cancer Clin. Oncol., 1989, 25(1), 19-26.
[21]
Kimmelman, A.C. Metabolic dependencies in RAS-driven cancers. Clin. Cancer Res.: Off. J. Am. Assoc. Cancer, 2018, 21(8), 1828-1834.
[22]
Goymer, P. Genetics: Conserved by evolution, but altered in cancer. Nat. Rev. Cancer, 2007, 7, 812-813.
[http://dx.doi.org/10.1038/nrc2268]
[23]
Lu, K.P.; Means, A.R. Regulation of the cell cycle by calcium and calmodulin. Endocr. Rev., 1993, 14(1), 40-58.
[24]
Mancini, M.; Toker, A. NFAT proteins: emerging roles in cancer progression. Nat. Rev. Cancer, 2009, 9(11), 810-820.
[http://dx.doi.org/10.1038/nrc2735] [PMID: 19851316]
[25]
Abdul, M.; Hoosein, N. Potentiation of the antiproliferative activity of MKT-077 by loperamide, diltiazem and tamoxifen. Oncol. Rep., 2003, 10(6), 2023-2026.
[http://dx.doi.org/10.3892/or.10.6.2023] [PMID: 14534737]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version751msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[13:37:40] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[13:37:41] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[13:37:41] LOG.warning: strip_tags(): Passing null to parameter #1 ($string) of type string is depre...
  • warninglog[13:37:41] LOG.warning: strip_tags(): Passing null to parameter #1 ($string) of type string is depre...
  • warninglog[13:37:41] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (96.62ms)time
  • Application (654ms)time
  • 1 x Application (87.13%)
    654ms
    1 x Booting (12.87%)
    96.62ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated564ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('59620938','',1,1739972260,1739972260) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739972260
      1.64msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('59620938','/article/105748',1,1739972260,1739972260)
      220μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59620938 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59620938) limit 1
      21.35msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59620938
      • 1: 59620938
      • 2: 59620938
      • 3: 59620938
      • 4: 59620938
      • 5: 59620938
      • 6: 59620938
      • 7: 59620938
      • 8: 59620938
      • 9: 59620938
      • 10: 59620938
      • 11: 59620938
      • 12: 59620938
      • 13: 59620938
      • 14: 59620938
      • 15: 59620938
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 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=105748
      14.8msalphaeurekaselec_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
      1.02msalphaeurekaselec_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`
      1.75msalphaeurekaselec_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
      1.45msalphaeurekaselec_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`
      231msalphaeurekaselec_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
      115msalphaeurekaselec_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` = '105748'
      500μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 105748
      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` = '105748'
      2.48msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 105748
      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` = '105748' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.15msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 105748
      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
      280μsalphaeurekaselec_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
      500μsalphaeurekaselec_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
      49.16msalphaeurekaselec_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
      24.52msalphaeurekaselec_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
      23.16msalphaeurekaselec_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` = 105748 limit 1
      340μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 105748
      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 = 105748 and content_type = 'article' order by status desc limit 1
      950μsalphaeurekaselec_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 a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 465 and content_id!=105748 and cd.content_type = 'article' order by rand() limit 20
      54.47msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 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` = 180815 limit 1
      850μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 180815
      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
      320μsalphaeurekaselec_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
      410μsalphaeurekaselec_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 = '105748' 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) )
      520μsalphaeurekaselec_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 = '9906' 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) )
      490μsalphaeurekaselec_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 = '2704' 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) )
      440μsalphaeurekaselec_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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2704) 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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2704) 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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2704)
      3.36msalphaeurekaselec_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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9906) 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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9906) 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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9906)
      920μsalphaeurekaselec_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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 105748) 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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 105748) 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 <= 59620938 and j.to_ip >=59620938 )) and ((j.from_date <= 1739972261 and j.to_date >= 1739972261 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 105748)
      710μsalphaeurekaselec_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` < '1017' and is_uploaded = 1 and issue_id = 9906 order by cast(first_page as SIGNED) desc limit 1
      690μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1017
      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` > '1027' and is_uploaded = 1 and issue_id = 9906 order by cast(first_page as SIGNED) asc limit 1
      660μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1027
      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'
      250μsalphaeurekaselec_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
      280μsalphaeurekaselec_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` = 105748 limit 1
      3.97msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 105748
      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` <= 1739972261 and `b`.`banner_to_date` >= 1739972261 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.72msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1739972261
      • 4: 1739972261
      • 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` <= 1739972261 and `b`.`banner_to_date` >= 1739972261 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.6msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1739972261
      • 4: 1739972261
      • 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='f34503f08dbc0f16ce63ec9bb3e34992'
      260μsalphaeurekaselec_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
    1MultiLanguage.php#?
        _token
        QeAk6Rw4wXQ52WNdPrxqpBruHLNlMjJb7j7dPpai
        uc_cart_id
        f34503f08dbc0f16ce63ec9bb3e34992
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/105748" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/105748
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 13:37:41 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkRKV0tMVXp3NTZ3U2lHbjE4N1BUVUE9PSIsInZhbHVlIjoiaHh1VnQ5U3JMaHgwSFlUYlkyMDN0eUQxSm9aVng3V1BHWTA4cDJTTGdFYS9Sc2Z4ZzFZSTNzd3MvYkVtVnVKVzhnVHlCTkZyOEVLZ3o3T2pET3BFbnA1YnNVQ1pxUUlIL1hLWkprMEgzeW45aHdrNEtodGJLQ1R6bnhkWUNvYUsiLCJtYWMiOiJjNjQ3YjBmM2M1YzU3MGM3OWQ3MjUxMWUxNGNhYTk1YjY5ZmJjYzA4NDRlNTUzYjNmODU0M2QxNjQzZGJhNjVjIiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 01:37:41 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkRKV0tMVXp3NTZ3U2lHbjE4N1BUVUE9PSIsInZhbHVlIjoiaHh1VnQ5U3JMaHgwSFlUYlkyMDN0eUQxSm9aVng3V1BHWTA4cDJTTGdFYS9Sc2Z4ZzFZSTNzd3MvYkVtVnVKVzhnVHlCT" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjRkUlhlc21iUGMzSkFlYmtISGxBVkE9PSIsInZhbHVlIjoic29LN25aTDZuZlZvTUNXY1VJMkZVTjJ1azB2WkxuMk5LNTlxVHJnQXVNOFhRL0VaRjExNlR5Umttd2ZvSWxJYTZJM2NOZ2QzaTlWd3dnUjZIZXNYZ0JLMFNibmR6R0Vmd3VaTkt3UHVlL1BBbXIrMkk5bE94b3g0Ti90eEVWQXciLCJtYWMiOiJiNTQ3NmJmMmQ5ZjFiNjViYzY1YzVjNWM2ZWZkNTI3MzU2ZDg0MzYzOTY2MTdjNjY2YWNkNzcyZDA1YjAxNDNiIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjRkUlhlc21iUGMzSkFlYmtISGxBVkE9PSIsInZhbHVlIjoic29LN25aTDZuZlZvTUNXY1VJMkZVTjJ1azB2WkxuMk5LNTlxVHJnQXVNOFhRL0VaRjExNlR5Umt" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkRKV0tMVXp3NTZ3U2lHbjE4N1BUVUE9PSIsInZhbHVlIjoiaHh1VnQ5U3JMaHgwSFlUYlkyMDN0eUQxSm9aVng3V1BHWTA4cDJTTGdFYS9Sc2Z4ZzFZSTNzd3MvYkVtVnVKVzhnVHlCTkZyOEVLZ3o3T2pET3BFbnA1YnNVQ1pxUUlIL1hLWkprMEgzeW45aHdrNEtodGJLQ1R6bnhkWUNvYUsiLCJtYWMiOiJjNjQ3YjBmM2M1YzU3MGM3OWQ3MjUxMWUxNGNhYTk1YjY5ZmJjYzA4NDRlNTUzYjNmODU0M2QxNjQzZGJhNjVjIiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 01:37:41 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkRKV0tMVXp3NTZ3U2lHbjE4N1BUVUE9PSIsInZhbHVlIjoiaHh1VnQ5U3JMaHgwSFlUYlkyMDN0eUQxSm9aVng3V1BHWTA4cDJTTGdFYS9Sc2Z4ZzFZSTNzd3MvYkVtVnVKVzhnVHlCT" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjRkUlhlc21iUGMzSkFlYmtISGxBVkE9PSIsInZhbHVlIjoic29LN25aTDZuZlZvTUNXY1VJMkZVTjJ1azB2WkxuMk5LNTlxVHJnQXVNOFhRL0VaRjExNlR5Umttd2ZvSWxJYTZJM2NOZ2QzaTlWd3dnUjZIZXNYZ0JLMFNibmR6R0Vmd3VaTkt3UHVlL1BBbXIrMkk5bE94b3g0Ti90eEVWQXciLCJtYWMiOiJiNTQ3NmJmMmQ5ZjFiNjViYzY1YzVjNWM2ZWZkNTI3MzU2ZDg0MzYzOTY2MTdjNjY2YWNkNzcyZDA1YjAxNDNiIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjRkUlhlc21iUGMzSkFlYmtISGxBVkE9PSIsInZhbHVlIjoic29LN25aTDZuZlZvTUNXY1VJMkZVTjJ1azB2WkxuMk5LNTlxVHJnQXVNOFhRL0VaRjExNlR5Umt" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "QeAk6Rw4wXQ52WNdPrxqpBruHLNlMjJb7j7dPpai" "uc_cart_id" => "f34503f08dbc0f16ce63ec9bb3e34992" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/105748" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 13:37:41GET/article/105748514371