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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Research Article

Fenbufen Alleviates Severe Acute Pancreatitis by Suppressing Caspase-1/Caspase-11-mediated Pyroptosis in Mice

Author(s): Shien Shen, Wenqin Xiao, Weiliang Jiang, Kai Li, Xingya Guo, Guanzhao Zong, Chuanyang Wang, Jingpiao Bao, Jiahui Chen, Zhiyuan Cheng, Jie Shen and Rong Wan*

Volume 17, 2024

Published on: 13 July, 2023

Article ID: e110523216783 Pages: 9

DOI: 10.2174/1874467217666230511095540

open_access

Abstract

Aim: In the present study, we aimed to investigate the effects of Fenbufen treatment on the SAP model induced by caerulein and lipopolysaccharide.

Background: Severe acute pancreatitis (SAP) is an extremely dangerous disease with high mortality, which is associated with inflammatory response and acinar cell death. The caspase family plays an important role in cell death, such as caspase-1 and caspase-11 in pyroptosis. In recent years, caspases have been shown to be a novel pharmacological target of Fenbufen.

Objective: Effects of Fenbufen on pancreatic tissue damage and serum levels of lipase and amylase in SAP in mice; Effect of Fenbufen on caspase-1 pathway in SAP in mice; Effect of Fenbufen on caspase-1/caspase-11-mediated pyroptosis of PACs in SAP in mice; Effect of Fenbufen on isolated PACs and caspase-1/caspase-11-mediated pyroptosis in vitro.

Methods: In vivo, eighteen female C57BL/6 mice were randomly divided into 3 groups: the NC group, the SAP group, and the Fenbufen +SAP group with 6 mice in each group. The SAP model was induced by intraperitoneal injection of caerulein and lipopolysaccharide. The pathological changes in pancreatic and the serum levels of lipase and amylase and the relative gene and protein expressions in each group were compared. In vitro, pancreatic acinar cells were assigned to 5 groups: medium group, SAP group, Fenbufen 100μM group, Fenbufen 200μM group, and Fenbufen 400μM group. The cell damage and the relative gene and protein expressions in each group were evaluated.

Results: Our results showed that Fenbufen ameliorated the severity of SAP and decreased the serum levels of lipase and amylase. Meanwhile, the in vivo and in vitro data demonstrated that Fenbufen inhibited the activation of caspase-1 and caspase-11, decreasing the levels of IL-1β, IL-18, and GSDMD. In in vitro experiments, we found that by inhibiting the activation of caspase-1 and caspase-11, Fenbufen significantly reduced lactate dehydrogenase (LDH) excretion by acinar cells.

Conclusion: In general, our data showed that Fenbufen could protect the pancreatic acinar cell from injury by inhibiting pyroptosis.

[1]
Jin, D.; Tan, J.; Jiang, J.; Philips, D.; Liu, L. The early predictive value of routine laboratory tests on the severity of acute pancreatitis patients in pregnancy: A retrospective study. Sci. Rep., 2020, 10(1), 10087.
[http://dx.doi.org/10.1038/s41598-020-66921-x] [PMID: 32572085]
[2]
Beger, H.G.; Rau, B.M. Severe acute pancreatitis: Clinical course and management. World J. Gastroenterol., 2007, 13(38), 5043-5051.
[http://dx.doi.org/10.3748/wjg.v13.i38.5043] [PMID: 17876868]
[3]
Cai, J.; Zhou, X.; Yu, H.; Xue, H.; Li, D. Effect of bone marrow mesenchymal stem cells on RhoA/ROCK signal pathway in severe acute pancreatitis. Am. J. Transl. Res., 2019, 11(8), 4809-4816.
[PMID: 31497201]
[4]
Sundar, V.; Senthil Kumar, K.A.; Manickam, V.; Ramasamy, T. Current trends in pharmacological approaches for treatment and management of acute pancreatitis-a review. J. Pharm. Pharmacol., 2020, 72(6), 761-775.
[http://dx.doi.org/10.1111/jphp.13229] [PMID: 32012276]
[5]
Fan, R.; Sui, J.; Dong, X.; Jing, B.; Gao, Z. Wedelolactone alleviates acute pancreatitis and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis. Free Radic. Biol. Med., 2021, 173, 29-40.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.07.009] [PMID: 34246777]
[6]
Zhao, S.; Li, X.; Wang; Wang, H. The role of the effects of autophagy on NLRP3 inflammasome in inflammatory nervous system diseases. Front. Cell Dev. Biol., 2021, 9, 657478.
[http://dx.doi.org/10.3389/fcell.2021.657478] [PMID: 34079796]
[7]
Wang, Z.; Gu, Z.; Hou, Q.; Chen, W.; Mu, D.; Zhang, Y.; Liu, Q.; Liu, Z.; Yang, D. Zebrafish GSDMEb cleavage-gated pyroptosis drives septic acute kidney injury in vivo. J. Immunol., 2020, 204(7), 1929-1942.
[http://dx.doi.org/10.4049/jimmunol.1901456] [PMID: 32111733]
[8]
Zasłona, Z.; Flis, E.; Wilk, M.M.; Carroll, R.G.; Palsson-McDermott, E.M.; Hughes, M.M.; Diskin, C.; Banahan, K.; Ryan, D.G.; Hooftman, A.; Misiak, A.; Kearney, J.; Lochnit, G.; Bertrams, W.; Greulich, T.; Schmeck, B.; McElvaney, O.J.; Mills, K.H.G.; Lavelle, E.C.; Wygrecka, M.; Creagh, E.M.; O’Neill, L.A.J. Caspase-11 promotes allergic airway inflammation. Nat. Commun., 2020, 11(1), 1055.
[http://dx.doi.org/10.1038/s41467-020-14945-2] [PMID: 32103022]
[9]
Yuan, B.; Zhou, X.; You, Z.; Xu, W.; Fan, J.; Chen, S.; Han, Y.; Wu, Q.; Zhang, X. Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage. Cell Death Dis., 2020, 11(1), 76.
[http://dx.doi.org/10.1038/s41419-020-2248-z] [PMID: 32001670]
[10]
Wang, J.; Wang, L.; Zhang, X.; Xu, Y.; Chen, L.; Zhang, W.; Liu, E.; Xiao, C.; Kou, Q. Cathepsin B aggravates acute pancreatitis by activating the NLRP3 inflammasome and promoting the caspase-1-induced pyroptosis. Int. Immunopharmacol., 2021, 94, 107496.
[http://dx.doi.org/10.1016/j.intimp.2021.107496] [PMID: 33639565]
[11]
Moore, R.A.; Derry, S.; McQuay, H.J. Single dose oral fenbufen for acute postoperative pain in adults. Cochrane Database Syst. Rev., 2009, 2009, CD007547.
[http://dx.doi.org/10.1002/14651858.CD007547.pub2]
[12]
Crossley, R.J. Side effect and safety data for fenbufen. Am. J. Med., 1983, 75(4), 84-90.
[http://dx.doi.org/10.1016/0002-9343(83)90334-0] [PMID: 6227235]
[13]
Husain, A.; Ahmad, A.; Alam, M.M.; Ajmal, M.; Ahuja, P. Fenbufen based 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones as safer antiinflammatory and analgesic agents. Eur. J. Med. Chem., 2009, 44(9), 3798-3804.
[http://dx.doi.org/10.1016/j.ejmech.2009.04.009] [PMID: 19457595]
[14]
Child, R.G.; Osterberg, A.C.; Sloboda, A.E.; Tomcufcik, A.S. Fenbufen, a new anti-inflammatory analgesic: synthesis and structure-activity relationships of analogs. J. Pharm. Sci., 1977, 66(4), 466-476.
[http://dx.doi.org/10.1002/jps.2600660403] [PMID: 300797]
[15]
Sloboda, A.E.; Osterberg, A.C. The pharmacology of fenbufen, 3-(4-biphenylylcarbonyl)propionic acid, and 4-biphenylacetic acid, interesting antiinflammatory-analgesic agents. Inflammation, 1976, 1(4), 415-438.
[http://dx.doi.org/10.1007/BF00920340] [PMID: 24194464]
[16]
Smith, C.E.; Soti, S.; Jones, T.A.; Nakagawa, A.; Xue, D.; Yin, H. NSAIDs are caspase inhibitors. Cell Chem. Biol., 2017, 24, 281-292.
[http://dx.doi.org/10.1016/j.chembiol.2017.02.003] [PMID: 28238723]
[17]
Lu, G.; Pan, Y.; Kayoumu, A.; Zhang, L.; Yin, T.; Tong, Z.; Li, B.; Xiao, W.; Ding, Y.; Li, W. Indomethacin inhabits the NLRP3 inflammasome pathway and protects severe acute pancreatitis in mice. Biochem. Biophys. Res. Commun., 2017, 493(1), 827-832.
[http://dx.doi.org/10.1016/j.bbrc.2017.08.060] [PMID: 28867183]
[18]
De Sarro, G.; Renne, S.; Nava, F.; De Sarro, A. Fenbufen pretreatment potentiates the anticonvulsant activity of CPPene and NBQX in DBA/2 mice. J. Pharm. Pharmacol., 2011, 46(12), 1017-1022.
[http://dx.doi.org/10.1111/j.2042-7158.1994.tb03259.x]
[19]
Chiccarelli, F.S.; Eisner, H.J.; Van Lear, G.E. Disposition and metabolism of fenbufen in several laboratory animals. Arzneimittelforschung, 1980, 30(4A), 707-715.
[PMID: 6776965]
[20]
Naora, K.; Katagiri, Y.; Ichikawa, N.; Hayashibara, M.; Iwamoto, K. A minor possibility of pharmacokinetic interaction between enoxacin and fenbufen in rats. J. Pharmacobiodyn., 1990, 13(2), 90-96.
[http://dx.doi.org/10.1248/bpb1978.13.90]
[21]
Vrolyk, V.; Schneberger, D.; Le, K.; Wobeser, B.K.; Singh, B. Mouse model to study pulmonary intravascular macrophage recruitment and lung inflammation in acute necrotizing pancreatitis. Cell Tissue Res., 2019, 378(1), 97-111.
[http://dx.doi.org/10.1007/s00441-019-03023-9]
[22]
Hu, G.; Shen, J.; Cheng, L.; Guo, C.; Xu, X.; Wang, F.; Huang, L.; Yang, L.; He, M.; Xiang, D.; Zhu, S.; Wu, M.; Yu, Y.; Han, W.; Wang, X. Reg4 protects against acinar cell necrosis in experimental pancreatitis. Gut, 2011, 60(6), 820-828.
[http://dx.doi.org/10.1136/gut.2010.215178] [PMID: 21193457]
[23]
Kang, R.; Zhang, Q.; Hou, W.; Yan, Z.; Chen, R.; Bonaroti, J.; Bansal, P.; Billiar, T.R.; Tsung, A.; Wang, Q.; Bartlett, D.L.; Whitcomb, D.C.; Chang, E.B.; Zhu, X.; Wang, H.; Lu, B.; Tracey, K.J.; Cao, L.; Fan, X.G.; Lotze, M.T.; Zeh, H.J., III; Tang, D. Intracellular Hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice. Gastroenterology, 2014, 146(4), 1097-1107.e8.
[http://dx.doi.org/10.1053/j.gastro.2013.12.015] [PMID: 24361123]
[24]
Tang, D.; Kang, R.; Berghe, T.V.; Vandenabeele, P.; Kroemer, G. The molecular machinery of regulated cell death. Cell Res., 2019, 29(5), 347-364.
[http://dx.doi.org/10.1038/s41422-019-0164-5] [PMID: 30948788]
[25]
Portelli, M.; Jones, C.D. Severe acute pancreatitis: Pathogenesis, diagnosis and surgical management. Hepatobiliary Pancreat. Dis. Int., 2017, 16(2), 155-159.
[http://dx.doi.org/10.1016/S1499-3872(16)60163-7] [PMID: 28381378]
[26]
Minkov, G.A.; Halacheva, K.S.; Yovtchev, Y.P.; Gulubova, M.V. Pathophysiological mechanisms of acute pancreatitis define inflammatory markers of clinical prognosis. Pancreas, 2015, 44(5), 713-717.
[http://dx.doi.org/10.1097/MPA.0000000000000329] [PMID: 26061557]
[27]
Gao, L.; Dong, X.; Gong, W.; Huang, W.; Xue, J.; Zhu, Q.; Ma, N.; Chen, W.; Fu, X.; Gao, X.; Lin, Z.; Ding, Y.; Shi, J.; Tong, Z.; Liu, T.; Mukherjee, R.; Sutton, R.; Lu, G.; Li, W. Acinar cell NLRP3 inflammasome and gasdermin D (GSDMD) activation mediates pyroptosis and systemic inflammation in acute pancreatitis. Br. J. Pharmacol., 2021, 178(17), 3533-3552.
[http://dx.doi.org/10.1111/bph.15499] [PMID: 33871879]
[28]
Lv, J.; Shen, X.; Shen, X.; Li, X.; Jin, Z.; Ouyang, X.; Lu, J.; Zhu, D.; Wang, J.; Shen, X. Miltefosine as a PPM1A activator improves AD-like pathology in mice by alleviating tauopathy via microglia/neurons crosstalk. Brain, Behavior, & Immunity - Health, 2022, 26, 100546.
[http://dx.doi.org/10.1016/j.bbih.2022.100546] [PMID: 36388134]
[29]
Fang, M.; Zhang, A.; Du, Y.; Lu, W.; Wang, J.; Minze, L.J.; Cox, T.C.; Li, X.C.; Xing, J.; Zhang, Z. TRIM18 is a critical regulator of viral myocarditis and organ inflammation. J. Biomed. Sci., 2022, 29(1), 55.
[http://dx.doi.org/10.1186/s12929-022-00840-z]
[30]
Xing, J.; Zhou, X.; Fang, M.; Zhang, E.; Minze, L.J.; Zhang, Z. DHX15 is required to control RNA virus-induced intestinal inflammation. Cell Rep., 2021, 35(12), 109205.
[http://dx.doi.org/10.1016/j.celrep.2021.109205] [PMID: 34161762]
[31]
Mareninova, O.A.; Sung, K.F.; Hong, P.; Lugea, A.; Pandol, S.J.; Gukovsky, I.; Gukovskaya, A.S. Cell death in pancreatitis: Caspases protect from necrotizing pancreatitis. J. Biol. Chem., 2006, 281(6), 3370-3381.
[http://dx.doi.org/10.1074/jbc.M511276200] [PMID: 16339139]

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      • 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=98) and sj.journal_id!=98 group by `j`.`nid`) as `aggregate_table`
      1.41msalphaeurekaselec_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=98) and sj.journal_id!=98 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.16msalphaeurekaselec_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=98) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.45msalphaeurekaselec_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=98) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.28msalphaeurekaselec_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` = '131700'
      280μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 131700
      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` = '131700'
      2.95msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 131700
      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` = '131700' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      4.6msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 131700
      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
      300μsalphaeurekaselec_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 = 98 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      26.02msalphaeurekaselec_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 = 98 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      9.8msalphaeurekaselec_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 = 98 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      3.93msalphaeurekaselec_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` = 131700 limit 1
      220μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 131700
      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 = 131700 and content_type = 'article' order by status desc limit 1
      250μsalphaeurekaselec_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` = 216783 limit 1
      270μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 216783
      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` = 'CMP' 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: CMP
      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 = '131700' 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) )
      420μsalphaeurekaselec_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 = '12576' 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) )
      360μsalphaeurekaselec_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 = '3428' 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) )
      340μsalphaeurekaselec_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 * from `article` where `first_page` < '1' and is_uploaded = 1 and issue_id = 12576 order by cast(first_page as SIGNED) desc limit 1
      1.03msalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1
      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` > '9' and is_uploaded = 1 and issue_id = 12576 order by cast(first_page as SIGNED) asc limit 1
      840μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 9
      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
      240μsalphaeurekaselec_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` = 131700 limit 1
      2.62msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 131700
      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` = 98 and `b`.`banner_from_date` <= 1740074955 and `b`.`banner_to_date` >= 1740074955 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.25msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 98
      • 3: 1740074955
      • 4: 1740074955
      • 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` = 98 and `b`.`banner_from_date` <= 1740074955 and `b`.`banner_to_date` >= 1740074955 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.67msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 98
      • 3: 1740074955
      • 4: 1740074955
      • 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='10a30d7d4d3d5d17619e4b99c9eea6e0'
      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#?
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        uc_cart_id
        10a30d7d4d3d5d17619e4b99c9eea6e0
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/131700" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        []
        
        response_headers
        0 of 0
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        session_attributes
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-20 18:09:15GET/article/131700514331