Metabonomics Application on Screening Serum Biomarkers of Golden Hamsters with Nonalcoholic Steatohepatitis Induced by High-Fat Diet | Bentham Science

Combinatorial Chemistry & High Throughput Screening

Author(s): Jingjing Hu, Yueliang Shen and Yunwen Chen*

DOI: 10.2174/1386207326666230223095745

Metabonomics Application on Screening Serum Biomarkers of Golden Hamsters with Nonalcoholic Steatohepatitis Induced by High-Fat Diet

Page: [2280 - 2292] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Background: Nonalcoholic steatohepatitis (NASH) is a common liver injury which will develop into advanced fibrosis and cirrhosis. This study was designed to identify the different serum metabolites of NASH hamsters and predict the diagnosis biomarkers for NASH.

Methods: Golden hamsters were randomly divided into a control group that received a normal diet and a NASH group that received a high-fat diet (HFD). After 12 weeks of feeding, the body and liver weight of the hamsters were monitored. Serum biochemical parameters and liver histopathological changes were analyzed. Moreover, an untargeted metabolomics analysis based on a GCTOF/ MS system was performed to identify the serum differential metabolites between the NASH and control groups.

Results: The liver weight was increased in the NASH group, accompanied by significantly higher levels of serum TC, TG, ALT, AST, LDL-C, and lower HDL-C. HE, Masson, and oil red O staining showed the hepatocyte structure destroyed, lipid droplets accumulated, and fibers proliferated in the NASH group. Furthermore, 63 differential metabolites were identified by metabolomic analysis. Lipids and fatty acids were significantly up-regulated in the NASH group. The top 9 differential metabolites included cholesterol, methyl phosphate, taurine, alpha-tocopherol, aspartic acid, etc. Metabolites were mainly involved in amino acid metabolism (glycine, cysteine, taurine), spermine, fatty acid biosynthesis, urea cycle, bile acid metabolism pathways, etc.

Conclusion: Metabonomics analysis identified 63 differential metabolites in the serum of NASH hamsters; among them, lipids and fatty acids had a key role and may be used as biomarkers for the early diagnosis of NASH.

Graphical Abstract

[1]
Tu, L.N.; Showalter, M.R.; Cajka, T.; Fan, S.; Pillai, V.V.; Fiehn, O.; Selvaraj, V. Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice. Sci. Rep., 2017, 7(1), 6120.
[http://dx.doi.org/10.1038/s41598-017-05040-6] [PMID: 28733574]
[2]
Han, J.; Dzierlenga, A.L.; Lu, Z.; Billheimer, D.D.; Torabzadeh, E.; Lake, A.D.; Li, H.; Novak, P.; Shipkova, P.; Aranibar, N.; Robertson, D.; Reily, M.D.; Lehman-McKeeman, L.D.; Cherrington, N.J. Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model. Obesity, 2017, 25(6), 1069-1076.
[http://dx.doi.org/10.1002/oby.21855] [PMID: 28452429]
[3]
Ajmera, V.; Loomba, R. Imaging biomarkers of NAFLD, NASH, and fibrosis. Mol. Metab., 2021, 50, 101167.
[http://dx.doi.org/10.1016/j.molmet.2021.101167] [PMID: 33460786]
[4]
Younossi, Z.; Henry, L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology, 2016, 150(8), 1778-1785.
[http://dx.doi.org/10.1053/j.gastro.2016.03.005] [PMID: 26980624]
[5]
Cardoso, A.C.; de Figueiredo-Mendes, C.; A Villela-Nogueira, C. Current management of NAFLD/NASH. Liver Int., 2021, 41(Suppl. 1), 89-94.
[http://dx.doi.org/10.1111/liv.14869] [PMID: 34155799]
[6]
Wong, R.J.; Aguilar, M.; Cheung, R.; Perumpail, R.B.; Harrison, S.A.; Younossi, Z.M.; Ahmed, A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology, 2015, 148(3), 547-555.
[http://dx.doi.org/10.1053/j.gastro.2014.11.039] [PMID: 25461851]
[7]
Caligiuri, A.; Gentilini, A.; Marra, F. Molecular pathogenesis of NASH. Int. J. Mol. Sci., 2016, 17(9), 1575.
[http://dx.doi.org/10.3390/ijms17091575] [PMID: 27657051]
[8]
Chalasani, N.; Younossi, Z.; Lavine, J.E.; Charlton, M.; Cusi, K.; Rinella, M.; Harrison, S.A.; Brunt, E.M.; Sanyal, A.J. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the study of liver diseases. Hepatology, 2018, 67(1), 328-357.
[http://dx.doi.org/10.1002/hep.29367] [PMID: 28714183]
[9]
Younossi, Z.; Anstee, Q.M.; Marietti, M.; Hardy, T.; Henry, L.; Eslam, M.; George, J.; Bugianesi, E. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(1), 11-20.
[http://dx.doi.org/10.1038/nrgastro.2017.109] [PMID: 28930295]
[10]
Khalifa, A.; Rockey, D.C. The utility of liver biopsy in 2020. Curr. Opin. Gastroenterol., 2020, 36(3), 184-191.
[http://dx.doi.org/10.1097/MOG.0000000000000621] [PMID: 32097176]
[11]
Rowe, I.A. Decision making for liver biopsy in NASH, not so FAST? Lancet Gastroenterol. Hepatol., 2020, 5(4), 332-334.
[http://dx.doi.org/10.1016/S2468-1253(19)30406-6] [PMID: 32027859]
[12]
Mato, J.M.; Lu, S.C. Where are we in the search for noninvasive nonalcoholic steatohepatitis biomarkers? Hepatology, 2011, 54(4), 1115-1117.
[http://dx.doi.org/10.1002/hep.24642] [PMID: 21898494]
[13]
Laíns, I.; Gantner, M.; Murinello, S.; Lasky-Su, J.A.; Miller, J.W.; Friedlander, M.; Husain, D. Metabolomics in the study of retinal health and disease. Prog. Retin. Eye Res., 2019, 69, 57-79.
[http://dx.doi.org/10.1016/j.preteyeres.2018.11.002] [PMID: 30423446]
[14]
Bowers, J.; Hughes, E.; Skill, N.; Maluccio, M.; Raftery, D. Detection of hepatocellular carcinoma in hepatitis C patients: Biomarker discovery by LC–MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 966, 154-162.
[http://dx.doi.org/10.1016/j.jchromb.2014.02.043] [PMID: 24666728]
[15]
Shi, C.; Wang, L.; Zhou, K.; Shao, M.; Lu, Y.; Wu, T. Targeted metabolomics identifies differential serum and liver amino acids biomarkers in rats with alcoholic liver disease. J. Nutr. Sci. Vitaminol., 2020, 66(6), 536-544.
[http://dx.doi.org/10.3177/jnsv.66.536] [PMID: 33390395]
[16]
Elbadawy, M.; Yamanaka, M.; Goto, Y.; Hayashi, K.; Tsunedomi, R.; Hazama, S.; Nagano, H.; Yoshida, T.; Shibutani, M.; Ichikawa, R.; Nakahara, J.; Omatsu, T.; Mizutani, T.; Katayama, Y.; Shinohara, Y.; Abugomaa, A.; Kaneda, M.; Yamawaki, H.; Usui, T.; Sasaki, K. Efficacy of primary liver organoid culture from different stages of non-alcoholic steatohepatitis (NASH) mouse model. Biomaterials, 2020, 237, 119823.
[http://dx.doi.org/10.1016/j.biomaterials.2020.119823] [PMID: 32044522]
[17]
Dei Cas, M.; Casagni, E.; Arnoldi, S.; Gambaro, V.; Roda, G. Screening of new psychoactive substances (NPS) by gaschromatography/time of flight mass spectrometry (GC/MS-TOF) and application to 63 cases of judicial seizure. Forensic Sci Int Synerg, 2019, 1, 71-78.
[http://dx.doi.org/10.1016/j.fsisyn.2019.04.003] [PMID: 32411957]
[18]
Imajo, K.; Yoneda, M.; Kessoku, T.; Ogawa, Y.; Maeda, S.; Sumida, Y.; Hyogo, H.; Eguchi, Y.; Wada, K.; Nakajima, A. Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Int. J. Mol. Sci., 2013, 14(11), 21833-21857.
[http://dx.doi.org/10.3390/ijms141121833] [PMID: 24192824]
[19]
Ioannou, G.N.; Nagana Gowda, G.A.; Djukovic, D.; Raftery, D. Distinguishing NASH histological severity using a multiplatform metabolomics approach. Metabolites, 2020, 10(4), 168.
[http://dx.doi.org/10.3390/metabo10040168] [PMID: 32344559]
[20]
Carreres, L.; Jílková, Z.M.; Vial, G.; Marche, P.N.; Decaens, T.; Lerat, H. Modeling diet-induced nafld and nash in rats: A comprehensive review. Biomedicines, 2021, 9(4), 378.
[http://dx.doi.org/10.3390/biomedicines9040378] [PMID: 33918467]
[21]
Yang, Q.H.; Xu, Y.J.; Feng, G.F.; Hu, C.F.; Zhang, Y.P.; Cheng, S.B.; Wang, Y.P.; Gong, X.W. p38 Mapk signal pathway involved in anti-inflammatory effect of chaihu-shugan-san and shen-lingbai-zhu-san on hepatocyte in non-alcoholic steatohepatitis rats. Afr. J. Tradit. Complement. Altern. Med., 2013, 11(1), 213-221.
[http://dx.doi.org/10.4314/ajtcam.v11i1.34] [PMID: 24653580]
[22]
Nakatsuka, A.; Matsuyama, M.; Yamaguchi, S.; Katayama, A.; Eguchi, J.; Murakami, K.; Teshigawara, S.; Ogawa, D.; Wada, N.; Yasunaka, T.; Ikeda, F.; Takaki, A.; Watanabe, E.; Wada, J. Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. Sci. Rep., 2016, 6(1), 21721.
[http://dx.doi.org/10.1038/srep21721] [PMID: 26883167]
[23]
Kalhan, S.C.; Guo, L.; Edmison, J.; Dasarathy, S.; McCullough, A.J.; Hanson, R.W.; Milburn, M. Plasma metabolomic profile in nonalcoholic fatty liver disease. Metabolism, 2011, 60(3), 404-413.
[http://dx.doi.org/10.1016/j.metabol.2010.03.006] [PMID: 20423748]
[24]
Gauthier, M.S.; Favier, R.; Lavoie, J.M. Time course of the development of non-alcoholic hepatic steatosis in response to high-fat diet-induced obesity in rats. Br. J. Nutr., 2006, 95(2), 273-281.
[http://dx.doi.org/10.1079/BJN20051635] [PMID: 16469142]
[25]
Seike, T.; Boontem, P.; Yanagi, M.; Li, S.; Kido, H.; Yamamiya, D.; Nakagawa, H.; Okada, H.; Yamashita, T.; Harada, K.; Kikuchi, M.; Shiraishi, Y.; Ozaki, N.; Kaneko, S.; Yamashima, T.; Mizukoshi, E. Hydroxynonenal causes hepatocyte death by disrupting lysosomal integrity in nonalcoholic steatohepatitis. Cell. Mol. Gastroenterol. Hepatol., 2022, 14(4), 925-944.
[http://dx.doi.org/10.1016/j.jcmgh.2022.06.008] [PMID: 35787976]
[26]
Kwak, D.H.; Kim, J.S.; Chang, K.T.; Choo, Y.K. Aristolochia manshuriensis Kom ethyl acetate extract protects against high-fat diet-induced non-alcoholic steatohepatitis by regulating kinase phosphorylation in mouse. J. Vet. Sci., 2016, 17(3), 279-287.
[http://dx.doi.org/10.4142/jvs.2016.17.3.279] [PMID: 26726030]
[27]
Boland, M.L.; Oró, D.; Tølbøl, K.S.; Thrane, S.T.; Nielsen, J.C.; Cohen, T.S.; Tabor, D.E.; Fernandes, F.; Tovchigrechko, A.; Veidal, S.S.; Warrener, P.; Sellman, B.R.; Jelsing, J.; Feigh, M.; Vrang, N.; Trevaskis, J.L.; Hansen, H.H. Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source. World J. Gastroenterol., 2019, 25(33), 4904-4920.
[http://dx.doi.org/10.3748/wjg.v25.i33.4904] [PMID: 31543682]
[28]
Marchesini, G.; Petta, S.; Dalle Grave, R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology, 2016, 63(6), 2032-2043.
[http://dx.doi.org/10.1002/hep.28392] [PMID: 26663351]
[29]
Pierantonelli, I.; Svegliati-Baroni, G. Nonalcoholic fatty liver disease: Basic pathogenetic mechanisms in the progression from NAFLD to NASH. Transplantation, 2019, 103(1), e1-e13.
[http://dx.doi.org/10.1097/TP.0000000000002480] [PMID: 30300287]
[30]
Van Rooyen, D.; Larter, C.; Haigh, W.; Yeh, M.; Ioannou, G.; Kuver, R.; Lee, S.; Teoh, N.; Farrell, G. Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis. Gastroenterology, 2011, 141(4), 1393-1403.
[http://dx.doi.org/10.1053/j.gastro.2011.06.040]
[31]
Jia, W.; Wei, M.; Rajani, C.; Zheng, X. Targeting the alternative bile acid synthetic pathway for metabolic diseases. Protein Cell, 2021, 12(5), 411-425.
[http://dx.doi.org/10.1007/s13238-020-00804-9] [PMID: 33252713]
[32]
Chiang, J.Y.L. Targeting bile acids and lipotoxicity for NASH treatment. Hepatol. Commun., 2017, 1(10), 1002-1004.
[http://dx.doi.org/10.1002/hep4.1127] [PMID: 29404437]
[33]
Gentile, C.L.; Nivala, A.M.; Gonzales, J.C.; Pfaffenbach, K.T.; Wang, D.; Wei, Y.; Jiang, H.; Orlicky, D.J.; Petersen, D.R.; Pagliassotti, M.J.; Maclean, K.N. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2011, 301(6), R1710-R1722.
[http://dx.doi.org/10.1152/ajpregu.00677.2010] [PMID: 21957160]
[34]
Jang, E.S.; Hwang, S.H.; Kim, J.W.; Jeong, S.H. Effectiveness of 4-week oral taurine treatment for muscle cramps in patients with liver cirrhosis: A single-arm pilot study. Yonsei Med. J., 2021, 62(1), 21-28.
[http://dx.doi.org/10.3349/ymj.2021.62.1.21] [PMID: 33381931]
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      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 8 limit 1
      670μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 8
      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=8) and sj.journal_id!=8 group by `j`.`nid`) as `aggregate_table`
      1.09msalphaeurekaselec_live_10_06_2022Subject.php#198
      Backtrace
      • 16. app/Models/Subject.php:198
      • 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=8) and sj.journal_id!=8 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      870μsalphaeurekaselec_live_10_06_2022Subject.php#198
      Backtrace
      • 14. app/Models/Subject.php:198
      • 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=8) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.02msalphaeurekaselec_live_10_06_2022Subject.php#218
      Backtrace
      • 16. app/Models/Subject.php:218
      • 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=8) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.71msalphaeurekaselec_live_10_06_2022Subject.php#218
      Backtrace
      • 14. app/Models/Subject.php:218
      • 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` = '129725'
      180μsalphaeurekaselec_live_10_06_2022Keywords.php#85
      Bindings
      • 0: 129725
      Backtrace
      • 13. app/Models/Keywords.php:85
      • 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` = '129725'
      1.56msalphaeurekaselec_live_10_06_2022Article.php#1569
      Bindings
      • 0: 129725
      Backtrace
      • 13. app/Models/Article.php:1569
      • 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 , `au`.*, (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` = '129725' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      580μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 129725
      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
      210μsalphaeurekaselec_live_10_06_2022BundleOffer.php#113
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:113
      • 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
      390μsalphaeurekaselec_live_10_06_2022Article.php#1959
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1959
      • 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 = 8 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      20.5msalphaeurekaselec_live_10_06_2022Issue.php#295
      Backtrace
      • 11. app/Models/Issue.php:295
      • 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 = 8 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`last_modified` desc
      16.87msalphaeurekaselec_live_10_06_2022Article.php#527
      Backtrace
      • 13. app/Models/Article.php:527
      • 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 = 8 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`last_modified` desc
      10msalphaeurekaselec_live_10_06_2022Article.php#527
      Backtrace
      • 13. app/Models/Article.php:527
      • 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` = 129725 limit 1
      150μsalphaeurekaselec_live_10_06_2022Article.php#743
      Bindings
      • 0: 129725
      Backtrace
      • 14. app/Models/Article.php:743
      • 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 = 129725 and content_type = 'article' order by status desc limit 1
      210μsalphaeurekaselec_live_10_06_2022Article.php#750
      Backtrace
      • 11. app/Models/Article.php:750
      • 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` = 213943 limit 1
      160μsalphaeurekaselec_live_10_06_2022Meta.php#59
      Bindings
      • 0: 213943
      Backtrace
      • 14. app/Models/Meta.php:59
      • 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
      180μsalphaeurekaselec_live_10_06_2022BundleOffer.php#113
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:113
      • 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` = 'CCHTS' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      260μsalphaeurekaselec_live_10_06_2022Article.php#2024
      Bindings
      • 0: CCHTS
      Backtrace
      • 13. app/Models/Article.php:2024
      • 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 = '129725' 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) )
      300μsalphaeurekaselec_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 = '12586' 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) )
      260μsalphaeurekaselec_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 = '3324' 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) )
      230μsalphaeurekaselec_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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3324) 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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3324) 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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3324)
      570μsalphaeurekaselec_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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12586) 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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12586) 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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12586)
      510μsalphaeurekaselec_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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 129725) 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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 129725) 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 <= 316375653 and j.to_ip >=316375653 )) and ((j.from_date <= 1737154623 and j.to_date >= 1737154623 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 129725)
      510μsalphaeurekaselec_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` < '2280' and is_uploaded = 1 and issue_id = 12586 order by cast(first_page as SIGNED) desc limit 1
      400μsalphaeurekaselec_live_10_06_2022Article.php#1818
      Bindings
      • 0: 2280
      Backtrace
      • 14. app/Models/Article.php:1818
      • 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` > '2292' and is_uploaded = 1 and issue_id = 12586 order by cast(first_page as SIGNED) asc limit 1
      380μsalphaeurekaselec_live_10_06_2022Article.php#1830
      Bindings
      • 0: 2292
      Backtrace
      • 14. app/Models/Article.php:1830
      • 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'
      150μsalphaeurekaselec_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
      170μsalphaeurekaselec_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` = 129725 limit 1
      2.31msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 129725
      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` = 8 and `b`.`banner_from_date` <= 1737154623 and `b`.`banner_to_date` >= 1737154623 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.07msalphaeurekaselec_live_10_06_2022Banner.php#189
      Bindings
      • 0: 1
      • 1: J
      • 2: 8
      • 3: 1737154623
      • 4: 1737154623
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:189
      • 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='086f300e8733a36ac8fc0925730172ad'
      170μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._main_menu:13
      • 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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        ClearShow all
        Date ↕MethodURLData
        #12025-01-17 22:57:03GET/article/12972548351