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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Research Article

Antiglycolytic Activities of Strobilanthes crispus Active Fraction and its Bioactive Components on Triple-Negative Breast Cancer Cells In Vitro

Author(s): Siti N.H. Muhammad, Nik S. Yaacob, Nur A.M. Safuwan and Agustine N. Fauzi*

Volume 22, Issue 7, 2022

Published on: 05 January, 2022

Page: [1363 - 1369] Pages: 7

DOI: 10.2174/1871520621666210427104804

Price: $65

Abstract

Background: Survival and progression of cancer cells are highly dependent on aerobic glycolysis. Strobilanthes crispus has been shown to have promising anticancer effects on breast cancer cells. The involvement of the glycolysis pathway in producing these effects is unconfirmed, thus further investigation is required to elucidate this phenomenon.

Objective: This study aims to determine the effect of S. crispus active fraction (F3) and its bioactive components on glycolysis in triple-negative breast cancer cells (MDA-MB-231).

Methods: This study utilizes F3, lutein, β-sitosterol, and stigmasterol to be administered in MDA-MB-231 cells for measurement of antiglycolytic activities through cell poliferation, glucose uptake, and lactate concentration assays. Cell proliferation was assessed by MTT assay of MDA-MB-231 cells after treatment with F3 and its bioactive components lutein, β-sitosterol, and stigmasterol. The IC50 value in each compound was determined by MTT assay to be used in subsequent assays. The determination of glucose uptake activity and lactate concentration were quantified using fluorescence spectrophotometry.

Results: Antiproliferative activities were observed for F3 and its bioactive components, with IC50 values of 100 μg/mL (F3), 20 μM (lutein), 25 μM (β-sitosterol), and 90 μM (stigmasterol) in MDA-MB-231 cells at 48 h. The percentage of glucose uptake and lactate concentration in MDA-MB-231 cells treated with F3, lutein, or β sitosterol were significantly lower than those observed in the untreated cells in a time-dependent manner. However, treatment with stigmasterol decreased the concentration of lactate without affecting the glucose uptake in MDA-MB-231 cells.

Conclusion: The antiglycolytic activities of F3 on MDA-MB-231 cells are attributed to its bioactive components.

Keywords: Strobilanthes crispus, glucose uptake, lactate concentration, MDA-MB-231, glucose metabolism, breast cancer.

Graphical Abstract

[1]
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.
[PMID: 33538338]
[2]
Guestini, F.; McNamara, K.M.; Ishida, T.; Sasano, H. Triple negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers indentification. Expert Opin. Ther. Targets, 2016, 20(6), 705-720.
[http://dx.doi.org/10.1517/14728222.2016.1125469] [PMID: 26607563]
[3]
Telli, M.L.; Chang, E.T.; Kurian, A.W.; Keegan, T.H.; McClure, L.A.; Lichtensztajn, D.; Ford, J.M.; Gomez, S.L. Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry. Breast Cancer Res. Treat., 2011, 127(2), 471-478.
[http://dx.doi.org/10.1007/s10549-010-1173-8] [PMID: 20957431]
[4]
Pegram, M.D.; Lipton, A.; Hayes, D.F.; Weber, B.L.; Baselga, J.M.; Tripathy, D.; Baly, D.; Baughman, S.A.; Twaddell, T.; Glaspy, J.A.; Slamon, D.J. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J. Clin. Oncol., 1998, 16(8), 2659-2671.
[http://dx.doi.org/10.1200/JCO.1998.16.8.2659] [PMID: 9704716]
[5]
Wiggans, R.G.; Woolley, P.V.; Smythe, T.; Hoth, D.; Macdonald, J.S.; Green, L.; Schein, P.S. Phase-II trial of tamoxifen in advanced breat cancer. Cancer Chemother. Pharmacol., 1979, 3(1), 45-48.
[http://dx.doi.org/10.1007/BF00254419] [PMID: 535127]
[6]
Carey, L.A.; Dees, E.C.; Sawyer, L.; Gatti, L.; Moore, D.T.; Collichio, F.; Ollila, D.W.; Sartor, C.I.; Carey, L.A.; Dees, E.C.; Sawyer, L.; Gatti, L.; Moore, D.T.; Collichio, F.; Ollila, D.W.; Sartor, C.I.; Graham, M.L.; Perou, C.M. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin. Cancer Res., 2007, 13(8), 2329-2334.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1109] [PMID: 17438091]
[7]
Fridlender, M.; Kapulnik, Y.; Koltai, H. Plant derived substances with anti-cancer activity: from folklore to practice. Front. Plant Sci., 2015, 6, 799.
[http://dx.doi.org/10.3389/fpls.2015.00799] [PMID: 26483815]
[8]
Lee, M.M.L.; Chan, B.D.; Wong, W.Y.; Qu, Z.; Chan, M.S.; Leung, T.W.; Lin, Y.; Mok, D.K.W.; Chen, S.; Tai, W.C.S. Anticancer activity of centipeda minima extract in triple negative breast cancer via inhibition of AKT, NF-κB, and STAT3 signaling pathways. Front. Oncol., 2020, 10, 491.
[PMID: 32328465]
[9]
Alshaeri, H.K.; Alasmari, M.M.; Natto, Z.S.; Pino-Figueroa, A. Effects of Annona muricata extract on triple-negative breast cancer cells mediated through EGFR signaling. Cancer Manag. Res., 2020, 12, 12519-12526.
[http://dx.doi.org/10.2147/CMAR.S278647] [PMID: 33304106]
[10]
Peng, B.; He, R.; Xu, Q.; Yang, Y.; Hu, Q.; Hou, H.; Liu, X.; Li, J. Ginsenoside 20(S)-protopanaxadiol inhibits triple-negative breast cancer metastasis in vivo by targeting EGFR-mediated MAPK pathway. Pharmacol. Res., 2019, 142, 1-13.
[http://dx.doi.org/10.1016/j.phrs.2019.02.003] [PMID: 30735802]
[11]
Perry, L.M.; Metzger, J. Medicinal Plants of East and Southeast Asia: Attributed Properties and Uses; MIT Press: Cambridge, 1980.
[12]
Noraida, A. Penyembuhan semula jadi dengan herba; PTS Litera Utama, 2005.
[13]
Al-Henhena, N.; Khalifa, S.A.; Ying, R.P.Y.; Ismail, S.; Hamadi, R.; Shawter, A.N.; Idris, A.M.; Azizan, A.; Al-Wajeeh, N.S.; Abdulla, M.A.; El-Seedi, H.R. Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo. BMC Complement. Altern. Med., 2015, 15(1), 419.
[http://dx.doi.org/10.1186/s12906-015-0926-7] [PMID: 26608653]
[14]
Ghasemzadeh, A.; Jaafar, H.Z.; Rahmat, A. Phytochemical constituents and biological activities of different extracts of Strobilanthes crispus (L.) Bremek leaves grown in different locations of Malaysia. BMC Complement. Altern. Med., 2015, 15(1), 422.
[http://dx.doi.org/10.1186/s12906-015-0873-3] [PMID: 26613959]
[15]
Yaacob, N.S.; Hamzah, N.; Nik Mohamed Kamal, N.N.; Zainal Abidin, S.A.; Lai, C.S.; Navaratnam, V.; Norazmi, M.N. Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro. BMC Complement. Altern. Med., 2010, 10, 42.
[http://dx.doi.org/10.1186/1472-6882-10-42] [PMID: 20684795]
[16]
Yaacob, N.S.; Nik Mohamed Kamal, N.N.; Wong, K.K.; Norazmi, M.N. Cell cycle modulation of MCF-7 and MDA-MB-231 by a sub-fraction of Strobilanthes crispus and its combination with tamoxifen. Asian Pac. J. Cancer Prev., 2015, 16(18), 8135-8140.
[http://dx.doi.org/10.7314/APJCP.2015.16.18.8135] [PMID: 26745050]
[17]
Yankuzo, H.M.; Baraya, Y.S.; Mustapha, Z.; Wong, K.K.; Yaacob, N.S. Immunomodulatory effects of a bioactive fraction of Strobilanthes crispus in NMU-induced rat mammary tumor model. J. Ethnopharmacol., 2018, 213, 31-37.
[http://dx.doi.org/10.1016/j.jep.2017.10.024] [PMID: 29100935]
[18]
Baraya, Y.S.; Wong, K.K.; Yaacob, N.S. Strobilanthes crispus inhibits migration, invasion and metastasis in breast cancer. J. Ethnopharmacol., 2019, 233, 13-21.
[http://dx.doi.org/10.1016/j.jep.2018.12.041] [PMID: 30594607]
[19]
Yaacob, N.S.; Yankuzo, H.M.; Devaraj, S.; Wong, J.K.M.; Lai, C.S. Anti-tumor action, clinical biochemistry profile and phytochemical constituents of a pharmacologically active fraction of S. crispus in NMU-induced rat mammary tumour model. PLoS One, 2015, 10(5), e0126426.
[http://dx.doi.org/10.1371/journal.pone.0126426] [PMID: 26000968]
[20]
Weyandt, J.D.; Thompson, C.B.; Giaccia, A.J.; Rathmell, W.K. Metabolic alterations in cancer and their potential as therapeutic targets. Am. Soc. Clin. Oncol. Educ. Book, 2017, 37, 825-832.
[http://dx.doi.org/10.14694/EDBK_175561] [PMID: 28561705]
[21]
Li, N.; Tan, W.; Li, J.; Li, P.; Lee, S.; Wang, Y.; Gong, Y. Glucose metabolism in breast cancer and its implication in cancer therapy. Int. J. Clin. Med., 2011, 2, 110-128.
[http://dx.doi.org/10.4236/ijcm.2011.22022]
[22]
Choi, Y.K.; Park, K.G. Targeting glutamine metabolism for cancer treatment. Biomol. Ther. (Seoul), 2018, 26(1), 19-28.
[http://dx.doi.org/10.4062/biomolther.2017.178] [PMID: 29212303]
[23]
Warburg, O.; Wind, F.; Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol., 1927, 8(6), 519-530.
[http://dx.doi.org/10.1085/jgp.8.6.519] [PMID: 19872213]
[24]
Fantin, V.R.; St-Pierre, J.; Leder, P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell, 2006, 9(6), 425-434.
[http://dx.doi.org/10.1016/j.ccr.2006.04.023] [PMID: 16766262]
[25]
Fantin, V.R.; St-Pierre, J.; Leder, P. Metabolic therapies inhibit tumor growth in vivo and in silico. Sci. Rep., 2019, 9(1), 1-10.
[26]
Bhattacharya, B.; Mohd Omar, M.F.; Soong, R. The Warburg effect and drug resistance. Br. J. Pharmacol., 2016, 173(6), 970-979.
[http://dx.doi.org/10.1111/bph.13422] [PMID: 26750865]
[27]
Varghese, E.; Samuel, S.M.; Líšková, A.; Samec, M.; Kubatka, P.; Büsselberg, D. Targeting glucose metabolism to overcome resistance to anticancer chemotherapy in breast cancer. Cancers (Basel), 2020, 12(8), 2252.
[http://dx.doi.org/10.3390/cancers12082252] [PMID: 32806533]
[28]
Annibaldi, A.; Widmann, C. Glucose metabolism in cancer cells. Curr. Opin. Clin. Nutr. Metab. Care, 2010, 13(4), 466-470.
[http://dx.doi.org/10.1097/MCO.0b013e32833a5577] [PMID: 20473153]
[29]
Farhadi, P.; Yarani, R.; Dokaneheifard, S.; Mansouri, K. The emerging role of targeting cancer metabolism for cancer therapy. Tumour Biol., 2020, 42(10), 1010428320965284.
[http://dx.doi.org/10.1177/1010428320965284] [PMID: 33028168]
[30]
Abdel-Wahab, A.F.; Mahmoud, W.; Al-Harizy, R.M. Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy. Pharmacol. Res., 2019, 150, 104511.
[http://dx.doi.org/10.1016/j.phrs.2019.104511] [PMID: 31678210]
[31]
Fiume, L.; Vettraino, M.; Manerba, M.; Di Stefano, G. Inhibition of lactic dehydrogenase as a way to increase the anti-proliferative effect of multi-targeted kinase inhibitors. Pharmacol. Res., 2011, 63(4), 328-334.
[http://dx.doi.org/10.1016/j.phrs.2010.12.005] [PMID: 21168502]
[32]
Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100(1), 57-70.
[http://dx.doi.org/10.1016/S0092-8674(00)81683-9] [PMID: 10647931]
[33]
Lunt, S.Y.; Vander Heiden, M.G. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol., 2011, 27, 441-464.
[http://dx.doi.org/10.1146/annurev-cellbio-092910-154237] [PMID: 21985671]
[34]
Muti, P.; Quattrin, T.; Grant, B.J.; Krogh, V.; Micheli, A.; Schünemann, H.J.; Ram, M.; Freudenheim, J.L.; Sieri, S.; Trevisan, M.; Berrino, F. Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol. Biomarkers Prev., 2002, 11(11), 1361-1368.
[PMID: 12433712]
[35]
Hay, N. Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? Nat. Rev. Cancer, 2016, 16(10), 635-649.
[http://dx.doi.org/10.1038/nrc.2016.77] [PMID: 27634447]
[36]
Zhang, W.L.; Zhao, Y.N.; Shi, Z.Z.; Cong, D.; Bai, Y.S. Lutein inhibits cell growth and activates apoptosis via the PI3K/AKT/mTOR signaling pathway in A549 human non-small-cell lung cancer cells. J. Environ. Pathol. Toxicol. Oncol., 2018, 37(4), 341-350.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2018027418] [PMID: 30806240]
[37]
Mignone, L.I.; Giovannucci, E.; Newcomb, P.A.; Titus-Ernstoff, L.; Trentham-Dietz, A.; Hampton, J.M.; Willett, W.C.; Egan, K.M. Dietary carotenoids and the risk of invasive breast cancer. Int. J. Cancer, 2009, 124(12), 2929-2937.
[http://dx.doi.org/10.1002/ijc.24334] [PMID: 19330841]
[38]
Sumantran, V.N.; Zhang, R.; Lee, D.S.; Wicha, M.S. Differential regulation of apoptosis in normal versus transformed mammary epithelium by lutein and retinoic acid. Cancer Epidemiol. Biomarkers Prev., 2000, 9(3), 257-263.
[PMID: 10750663]
[39]
Gong, X.; Smith, J.R.; Swanson, H.M.; Rubin, L.P. Carotenoid lutein selectively inhibits breast cancer cell growth and potentiates the effect of chemotherapeutic agents through ROS-mediated mechanisms. Molecules, 2018, 23(4), 905.
[http://dx.doi.org/10.3390/molecules23040905] [PMID: 29662002]
[40]
Awad, A.B.; Burr, A.T.; Fink, C.S. Effect of resveratrol and β-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells. Prostaglandins Leukot. Essent. Fatty Acids, 2005, 72(3), 219-226.
[http://dx.doi.org/10.1016/j.plefa.2004.11.005] [PMID: 15664307]
[41]
Cao, Z.Q.; Wang, X.X.; Lu, L.; Xu, J.W.; Li, X.B.; Zhang, G.R.; Ma, Z.J.; Shi, A.C.; Wang, Y.; Song, Y.J. β-Sitosterol and gemcitabine exhibit synergistic anti-pancreatic cancer activity by modulating apoptosis and inhibiting epithelial-mesenchymal transition by deactivating Akt/GSK-3β signaling. Front. Pharmacol., 2019, 9, 1525.
[http://dx.doi.org/10.3389/fphar.2018.01525] [PMID: 30670971]
[42]
Vundru, S.S.; Kale, R.K.; Singh, R.P. β-Sitosterol induces G1 arrest and causes depolarization of mitochondrial membrane potential in breast carcinoma MDA-MB-231 cells. BMC Complement. Altern. Med., 2013, 13, 280.
[http://dx.doi.org/10.1186/1472-6882-13-280] [PMID: 24160369]
[43]
Awad, A.B.; Chinnam, M.; Fink, C.S.; Bradford, P.G. β-Sitosterol activates Fas signaling in human breast cancer cells. Phytomedicine, 2007, 14(11), 747-754.
[http://dx.doi.org/10.1016/j.phymed.2007.01.003] [PMID: 17350814]
[44]
Sofi, M.S.; Sateesh, M.K.; Bashir, M.; Ganie, M.A.; Nabi, S. Chemopreventive and anti-breast cancer activity of compounds isolated from leaves of Abrus precatorius L. 3 Biotech, 2018, 8(8), 371.
[http://dx.doi.org/10.1007/s13205-018-1395-8] [PMID: 30105196]
[45]
Li, K.; Yuan, D.; Yan, R.; Meng, L.; Zhang, Y.; Zhu, K. Stigmasterol exhibits potent antitumor effects in human gastric cancer cells mediated via inhibition of cell migration, cell cycle arrest, mitochondrial mediated apoptosis and inhibition of JAK/STAT signalling pathway. J. BUON, 2018, 23(5), 1420-754.
[PMID: 30570868]
[46]
Jacobo-Herrera, N.J.; Perez-Plasencia, C.; Garcia-Castillo, V.; Villanueva-Sanchez, O. Avila- Rodriguez, M.A.; Zentella-Dehesa, A. The inhibition of mTOR and LDH-A leads to tumor growth inhibition in a triple negative breast cancer xenotransplant. Int. J. Mol. Med 2015, 36 S41

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      • 0: 316548017
      • 1: 316548017
      • 2: 316548017
      • 3: 316548017
      • 4: 316548017
      • 5: 316548017
      • 6: 316548017
      • 7: 316548017
      • 8: 316548017
      • 9: 316548017
      • 10: 316548017
      • 11: 316548017
      • 12: 316548017
      • 13: 316548017
      • 14: 316548017
      • 15: 316548017
      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=115490
      950μsalphaeurekaselec_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
      1.08msalphaeurekaselec_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
      1.6msalphaeurekaselec_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`
      5.09msalphaeurekaselec_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
      4.44msalphaeurekaselec_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` = '115490'
      360μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 115490
      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` = '115490'
      2.35msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 115490
      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` = '115490' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.49msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 115490
      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
      320μsalphaeurekaselec_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
      690μsalphaeurekaselec_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
      40.38msalphaeurekaselec_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
      19.18msalphaeurekaselec_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
      18.96msalphaeurekaselec_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` = 115490 limit 1
      280μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 115490
      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 = 115490 and content_type = 'article' order by status desc limit 1
      290μsalphaeurekaselec_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` = 193046 limit 1
      220μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 193046
      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
      260μsalphaeurekaselec_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
      320μsalphaeurekaselec_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 = '115490' 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) )
      440μsalphaeurekaselec_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 = '11336' 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 = '3166' 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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166) 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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166) 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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166)
      26.39msalphaeurekaselec_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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11336) 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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11336) 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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11336)
      690μsalphaeurekaselec_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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 115490) 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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 115490) 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 <= 316548017 and j.to_ip >=316548017 )) and ((j.from_date <= 1739847360 and j.to_date >= 1739847360 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 115490)
      610μsalphaeurekaselec_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` < '1363' and is_uploaded = 1 and issue_id = 11336 order by cast(first_page as SIGNED) desc limit 1
      600μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1363
      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` > '1369' and is_uploaded = 1 and issue_id = 11336 order by cast(first_page as SIGNED) asc limit 1
      530μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1369
      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'
      200μsalphaeurekaselec_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` = 115490 limit 1
      2.41msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 115490
      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` <= 1739847360 and `b`.`banner_to_date` >= 1739847360 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.14msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1739847360
      • 4: 1739847360
      • 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` <= 1739847360 and `b`.`banner_to_date` >= 1739847360 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: 1739847360
      • 4: 1739847360
      • 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='7a84bd8202069470848a1a495613e376'
      230μsalphaeurekaselec_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
        eGYWXFMZnCVhO6Di8RVTonGqscmCGXQt0dfP2XM2
        uc_cart_id
        7a84bd8202069470848a1a495613e376
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        array:1 [ "url" => "http://alpha.eurekaselect.com/article/115490" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
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        /article/115490
        status_code
        200
        
        status_text
        OK
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        text/html; charset=UTF-8
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        []
        
        request_request
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        request_headers
        0 of 0
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        request_cookies
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        response_headers
        0 of 0
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        array:5 [ "_token" => "eGYWXFMZnCVhO6Di8RVTonGqscmCGXQt0dfP2XM2" "uc_cart_id" => "7a84bd8202069470848a1a495613e376" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/115490" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 02:56:00GET/article/115490414361