Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Inhibition of Liver Cancer HepG2 Cell Proliferation by Enzymatically Prepared Low-molecular Citrus Pectin

Author(s): Xiao-Qian Wu, Jia-Ying Fu, Ru-Yi Mei, Xian-Jun Dai, Jun-Hui Li, Xiao-Feng Zhao* and Ming-Qi Liu*

Volume 23, Issue 6, 2022

Published on: 11 August, 2021

Page: [861 - 872] Pages: 12

DOI: 10.2174/1389201022666210729122631

Price: $65

Abstract

Background: Low-molecular citrus pectin (LCP) is a pectin polysaccharide with low molec-ular weight, low degree of crux, and no branching. It is obtained by degrading natural citrus pectin (CP) through physical, chemical and enzymatic methods. LCP has received considerable attention in recent years due to its potential applications in the medical and biological fields.

Methods: In our previous study, LCP was prepared from CP by using recombinant Bacillus subtilis pectate lyase B. Monosaccharide comparative analysis revealed that the galacturonic acid content of LCP was higher than that of CP. The cell viability effect of LCP was elucidated by using HepG2 cells and the Cell Counting Kit-8 (CCK-8) assay. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Annexin V-FITC/PI staining, and flow cytometer propidium iodide stain-ing were performed to detect the effects of LCP on apoptosis and cell cycle arrest in HepG2 cells. Mi-tochondrial membrane potential (MMP) was observed through 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine assay.

Results & Discussion: The Mw of the prepared LCP was 7.6 kDa, which was significantly lower than that of CP (140 kDa). Cell viability decreased with the increase in the concentration of LCP. The half-inhibitory concentration of 1.46 ± 0.02 mg/mL was determined. Treatment with 1.6 mg/mL LCP in-duced the apoptosis of HepG2 cells with the inhibition rate of 83.10% ± 4.72%, and the cell cycle was arrested in the S phase. Furthermore, the MMP of HepG2 cells decreased with the increase in LCP concentration.

Conclusion: The enzymatically prepared LCP could inhibit the proliferation of HepG2 cells. This study provided a partial experimental basis and reference for LCP to become a potential functional food for anti-liver cancer.

Keywords: Low-molecular citrus pectin, cell viability, HepG2, Liver cancer, cell apoptosis, cell cycle, mitochondrial mem-brane potential.

Graphical Abstract

[1]
Jin, J.; Fu, B.; Mei, X.; Yue, T.; Sun, R.; Tian, Z.; Wei, H. CD11b(-)CD27(-) NK cells are associated with the progression of lung carcinoma. PLoS One, 2013, 8(4), e61024.
[http://dx.doi.org/10.1371/journal.pone.0061024] [PMID: 23565296]
[2]
Heron, M.; Anderson, R.N. Changes in the leading cause of death: recent patterns in heart disease and cancer mortality. NCHS Data Brief, 2016, 254(254), 1-8.
[PMID: 27598767]
[3]
Yuan, S.L.; Wei, Y.Q.; Wang, X.J.; Xiao, F.; Li, S.F.; Zhang, J. Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. World J. Gastroenterol., 2004, 10(14), 2024-2028.
[http://dx.doi.org/10.3748/wjg.v10.i14.2024] [PMID: 15237427]
[4]
Chen, X.W.; Sun, J.G.; Zhang, L.P.; Liao, X.Y.; Liao, R.X. Recruitment of CD11b+Ly6C+ monocytes in non-small cell lung cancer xenografts challenged by anti-VEGF antibody. Oncol. Lett., 2017, 14(1), 615-622.
[http://dx.doi.org/10.3892/ol.2017.6236] [PMID: 28693213]
[5]
Freddie; Bray; Jacques; Ferlay; Isabelle; Soerjomataram; Rebecca; Siegel; Lindsey. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68, 394-424.
[http://dx.doi.org/10.3322/caac.21492]
[6]
Jindal, A.; Thadi, A.; Shailubhai, K. Hepatocellular carcinoma: Etiology and current and future drugs. J. Clin. Exp. Hepatol., 2019, 9(2), 221-232.
[http://dx.doi.org/10.1016/j.jceh.2019.01.004] [PMID: 31024205]
[7]
Sahu, S.K.; Chawla, Y.K.; Dhiman, R.K.; Singh, V.; Duseja, A.; Taneja, S.; Kalra, N.; Gorsi, U. Rupture of hepatocellular carcinoma: A review of literature. J. Clin. Exp. Hepatol., 2019, 9(2), 245-256.
[http://dx.doi.org/10.1016/j.jceh.2018.04.002] [PMID: 31024207]
[8]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[9]
Bruix, J.; Llovet, J.M. Major achievements in hepatocellular carcinoma. Lancet, 2009, 373(9664), 614-616.
[http://dx.doi.org/10.1016/S0140-6736(09)60381-0] [PMID: 19231618]
[10]
Abdel, B. Advances in pectin and pectinase research. Plant. ence., 2003, 165, 1169-1169.
[11]
Voragen, A.G.J.; Coenen, G.J.; Verhoef, R.P.; Schols, H.A. Pectin, a versatile polysaccharide present in plant cell walls. Struct. Chem., 2009, 20, 263-275.
[http://dx.doi.org/10.1007/s11224-009-9442-z]
[12]
Ridley, B.L.; O’Neill, M.A.; Mohnen, D. Pectins: structure, biosynthesis, and oligogalacturonide-related signaling. Phytochemistry, 2001, 57(6), 929-967.
[http://dx.doi.org/10.1016/S0031-9422(01)00113-3] [PMID: 11423142]
[13]
Caffall, K.H.; Mohnen, D. The structure, function, and biosynthesis of plant cell wall pectic polysaccharides. Carbohydr. Res., 2009, 344(14), 1879-1900.
[http://dx.doi.org/10.1016/j.carres.2009.05.021] [PMID: 19616198]
[14]
Koriem, K.M.M.; Arbid, M.S.; Emam, K.R. Therapeutic effect of pectin on octylphenol induced kidney dysfunction, oxidative stress and apoptosis in rats. Environ. Toxicol. Pharmacol., 2014, 38(1), 14-23.
[http://dx.doi.org/10.1016/j.etap.2014.04.029] [PMID: 24860957]
[15]
Popov, S.V.; Markov, P.A.; Popova, G.Y.; Nikitina, I.R.; Efimova, L.; Ovodov, Y.S. Anti-inflammatory activity of low and high methoxylated citrus pectins. Biomed. & Prev. Nutr., 2013, 3, 59-63.
[http://dx.doi.org/10.1016/j.bionut.2012.10.008]
[16]
Leclere, L.; Cutsem, P.V.; Michiels, C. Anti-cancer activities of pH- or heat-modified pectin. Front. Pharmacol., 2013, 4, 128.
[http://dx.doi.org/10.3389/fphar.2013.00128] [PMID: 24115933]
[17]
Wikiera, A.; Irla, M.; Mika, M. Health-promoting properties of pectin. Postepy Hig. Med. Dosw., 2014, 68, 590-596.
[http://dx.doi.org/10.5604/17322693.1102342] [PMID: 24864109]
[18]
Vilhena, C.; Gonçalves, M.L.; Mota, A.M. Binding of copper (II) to pectins by electrochemical methods. Electroanalysis, 2004, 16, 2065-2072.
[http://dx.doi.org/10.1002/elan.200303047]
[19]
Munarin, F.; Petrini, P.; Tanzi, M.C.; Barbosa, M.A.; Granja, P.L. Biofunctional chemically modified pectin for cell delivery. Soft Matter, 2012, 8, 4731-4739.
[http://dx.doi.org/10.1039/c2sm07260b]
[20]
Jung, J.; Arnold, R.D.; Wicker, L. Pectin and charge modified pectin hydrogel beads as a colon-targeted drug delivery carrier. Colloids Surf. B Biointerfaces, 2013, 104, 116-121.
[http://dx.doi.org/10.1016/j.colsurfb.2012.11.042] [PMID: 23298595]
[21]
Kaya, M.; Sousa, A.G.; Crépeau, M.J.; Sørensen, S.O.; Ralet, M.C. Characterization of citrus pectin samples extracted under different conditions: influence of acid type and pH of extraction. Ann. Bot., 2014, 114(6), 1319-1326.
[http://dx.doi.org/10.1093/aob/mcu150] [PMID: 25081519]
[22]
Maxwell, E.G.; Belshaw, J.N.; Waldron, W. K.; J.Morris, V. Pectin – An emerging new bioactive food polysaccharide. Trends Food. Sci. Tech. (Paris), 2012, 24, 64-73.
[23]
Ciriminna, R.; Chavarría‐Hernández, N.; Hernández, A.I.R.; Pagliaro, M. Pectin: A new perspective from the biorefinery standpoint. Biofuels Bioprod. Biorefin., 2015, 9, 368-377.
[http://dx.doi.org/10.1002/bbb.1551]
[24]
Toyoda, A.; Sato, M.; Muto, M.; Goto, T.; Miyaguchi, Y.; Inoue, E. Metabolomic analyses of plasma and liver of mice fed with immature Citrus tumida peel. Biosci. Biotechnol. Biochem., 2020, 84(6), 1098-1104.
[http://dx.doi.org/10.1080/09168451.2020.1719821] [PMID: 32019425]
[25]
White, G.W.; Katona, T.; Zodda, J.P. The use of high-performance size exclusion chromatography (HPSEC) as a molecular weight screening technique for polygalacturonic acid for use in pharmaceutical applications. J. Pharm. Biomed. Anal., 1999, 20(6), 905-912.
[http://dx.doi.org/10.1016/S0731-7085(99)00083-7] [PMID: 10746959]
[26]
Nikolic, M.V.; Mojovic, L. Hydrolysis of apple pectin by the coordinated activity of pectic enzymes. Food Chem., 2007, 101, 1-9.
[http://dx.doi.org/10.1016/j.foodchem.2005.12.053]
[27]
Yadav, S.; Yadav, P.K.; Yadav, D.; Yadav, K.D.S. Pectin lyase: A review. Process Biochem., 2009, 44, 1-10.
[http://dx.doi.org/10.1016/j.procbio.2008.09.012]
[28]
Maesen; Miranda; Babbar; Neha; Baldassarre; Stefania; Prandi; Barbara; Elst; Kathy. Enzymatic production of pectic oligosaccharides from onion skins. Carbohydr. Polym., 2016, 146, 245-252.
[http://dx.doi.org/10.1016/j.carbpol.2016.03.011]
[29]
van Alebeek, G.J.W.M.; Christensen, T.M.I.E.; Schols, H.A.; Mikkelsen, J.D.; Voragen, A.G.J. Mode of action of pectin lyase A of Aspergillus niger on differently C(6)-substituted oligogalacturonides. J. Biol. Chem., 2002, 277(29), 25929-25936.
[http://dx.doi.org/10.1074/jbc.M202250200] [PMID: 12000753]
[30]
Elboutachfaiti, R.; Delattre, C.; Michaud, P.; Courtois, B.; Courtois, J. Oligogalacturonans production by free radical depolymerization of polygalacturonan. Int. J. Biol. Macromol., 2008, 43(3), 257-261.
[http://dx.doi.org/10.1016/j.ijbiomac.2008.06.003] [PMID: 18601947]
[31]
Zhang, S.; Hu, H.; Wang, L.; Liu, F.; Pan, S. Preparation and prebiotic potential of pectin oligosaccharides obtained from citrus peel pectin. Food Chem., 2018, 244, 232-237.
[http://dx.doi.org/10.1016/j.foodchem.2017.10.071] [PMID: 29120775]
[32]
Gómez, B.; Yáñez, R.; Parajó, J.C. Production of pectin-derived oligosaccharides from lemon peels by extraction, enzymatic hydrolysis and membrane filtration. J. Chem. Technolo. Biot., 2014, 91, 234-247.
[http://dx.doi.org/10.1002/jctb.4569]
[33]
Morris, J.V.J.; Belshaw, N.W.; Waldron, K.G.; Maxwell, E. The bioactivity of modified pectin fragments. Bioactive Carbohydrates and Dietary Fibre, 2013, 1, 21-37.
[http://dx.doi.org/10.1016/j.bcdf.2013.02.001]
[34]
Wong, C.K.; Leung, K.N.; Fung, K.P.; Choy, Y.M. Immunomodulatory and anti-tumour polysaccharides from medicinal plants. J. Int. Med. Res., 1994, 22(6), 299-312.
[http://dx.doi.org/10.1177/030006059402200601] [PMID: 7895893]
[35]
Nangia-Makker, P.; Hogan, V.; Honjo, Y.; Baccarini, S.; Tait, L.; Bresalier, R.; Raz, A. Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin. J. Natl. Cancer Inst., 2002, 94(24), 1854-1862.
[http://dx.doi.org/10.1093/jnci/94.24.1854] [PMID: 12488479]
[36]
Parris, M. Kidd. A new approach to metastatic cancer prevention: Modified Citrus Pectin (MCP), a unique pectin that blocks cell surface lectins. Altern. Med. Rev., 1996, 1, 4-10.
[37]
Olano-Martin, E.; Rimbach, G.H.; Gibson, G.R.; Rastall, R.A. Pectin and pectic-oligosaccharides induce apoptosis in in vitro human colonic adenocarcinoma cells. Anticancer Res., 2003, 23(1A), 341-346.
[PMID: 12680234]
[38]
Sakurai, M.H.; Matsumoto, T.; Kiyohara, H.; Yamada, H. Detection and tissue distribution of anti-ulcer pectic polysaccharides from Bupleurum falcatum by polyclonal antibody. Planta Med., 1996, 62(4), 341-346.
[http://dx.doi.org/10.1055/s-2006-957898] [PMID: 8792667]
[39]
Eliaz, I.; Hotchkiss, A.T.; Fishman, M.L.; Rode, D. The effect of modified citrus pectin on urinary excretion of toxic elements. Phytother. Res., 2006, 20(10), 859-864.
[http://dx.doi.org/10.1002/ptr.1953] [PMID: 16835878]
[40]
Maxwell, E.G.; Belshaw, N.J.; Waldron, K.W.; Morris, V.J. Pectin e An emerging new bioactive food polysaccharide. Trends Food Sci. Technol., 2012, 24, 64-73.
[http://dx.doi.org/10.1016/j.tifs.2011.11.002]
[41]
Niture, S.K.; Refai, L. Plant pectin: A potential source for cancer suppression. J. Pharmacol. Tox. Met., 2013, 8, 9-19.
[http://dx.doi.org/10.3844/ajptsp.2013.9.19]
[42]
Yan, J.; Katz, A. PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and- independent prostate cancer cells. Integr. Cancer Ther., 2010, 9(2), 197-203.
[http://dx.doi.org/10.1177/1534735410369672] [PMID: 20462856]
[43]
Jiang, J.; Eliaz, I.; Sliva, D. Synergistic and additive effects of modified citrus pectin with two polybotanical compounds, in the suppression of invasive behavior of human breast and prostate cancer cells. Integr. Cancer Ther., 2013, 12(2), 145-152.
[http://dx.doi.org/10.1177/1534735412442369] [PMID: 22532035]
[44]
Liu, H.Y.; Huang, Z.L.; Yang, G.H.; Lu, W.Q.; Yu, N.R. Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model. World J. Gastroenterol., 2008, 14(48), 7386-7391.
[http://dx.doi.org/10.3748/wjg.14.7386] [PMID: 19109874]
[45]
Wang, S.; Li, P.; Lu, S.M.; Ling, Z.Q. Chemoprevention of low-molecular-weight citrus pectin (LCP) in gastrointestinal cancer cells. Int. J. Biol. Sci., 2016, 12(6), 746-756.
[http://dx.doi.org/10.7150/ijbs.13988] [PMID: 27194951]
[46]
Hamai-Amara, H.; Abdoun-Ouallouche, K.; Nacer-Khodja, A.; Abdelhafid, K.; Benmouloud, A.; Djefal-Kerrar, A. Optimization of the extraction of orange peel pectin and evaluation of its antiproliferative activity towards HEp2 cancer cells. Euro-Mediterranean Journal for Environmental Integration, 2020, 5, 43.
[http://dx.doi.org/10.1007/s41207-020-00179-7]
[47]
Abu-Elsaad, N.M.; Elkashef, W.F. Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells. Can. J. Physiol. Pharmacol., 2016, 94(5), 554-562.
[http://dx.doi.org/10.1139/cjpp-2015-0284] [PMID: 27010252]
[48]
Leclere, L.; Fransolet, M.; Cote, F.; Cambier, P.; Arnould, T.; Van Cutsem, P.; Michiels, C.; Tang, D. Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells. PLoS One, 2015, 10(3), e0115831.
[http://dx.doi.org/10.1371/journal.pone.0115831] [PMID: 25794149]
[49]
Huang, Z.L.; Liu, H.Y. Expression of galectin-3 in liver metastasis of colon cancer and the inhibitory effect of modified citrus pectin. Nan Fang Yi Ke Da Xue Xue Bao, 2008, 28(8), 1358-1361.
[PMID: 18753060]
[50]
Liu, M.Q.; Huo, W.K.; Dai, X.; Dang, Y.H. Preparation of low-molecular-weight citrus pectin by recombinant Bacillus subtilis pectate lyase and promotion of growth of Bifidobacterium longum. Catal. Commun., 2018, 107, 39-42.
[http://dx.doi.org/10.1016/j.catcom.2018.01.017]
[51]
Li, J.; Li, S.; Zheng, Y.; Zhang, H.; Chen, J.; Yan, L.; Ding, T.; Linhardt, R.J.; Orfila, C.; Liu, D.; Ye, X.; Chen, S. Fast preparation of rhamnogalacturonan I enriched low molecular weight pectic polysaccharide by ultrasonically accelerated metal-free Fenton reaction. Food Hydrocoll., 2019, 95, 551-561.
[http://dx.doi.org/10.1016/j.foodhyd.2018.05.025]
[52]
Deng, X.; Zhang, J.; Liu, Y.; Chen, L.; Yu, C. TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1. Sci. Rep., 2017, 7, 40256.
[http://dx.doi.org/10.1038/srep40256] [PMID: 28091531]
[53]
Kawahata, I.; Bousset, L.; Melki, R.; Fukunaga, K. Fatty acid-binding protein 3 is critical for α-synuclein uptake and MPP(+)-induced mitochondrial dysfunction in cultured dopaminergic neurons. Int. J. Mol. Sci., 2019, 20(21), 5358.
[http://dx.doi.org/10.3390/ijms20215358] [PMID: 31661838]
[54]
Omura, T.; Sasaoka, M.; Hashimoto, G.; Imai, S.; Yamamoto, J.; Sato, Y.; Nakagawa, S.; Yonezawa, A.; Nakagawa, T.; Yano, I.; Tasaki, Y.; Matsubara, K. Oxicam-derived non-steroidal anti-inflammatory drugs suppress 1-methyl-4-phenyl pyridinium-induced cell death via repression of endoplasmic reticulum stress response and mitochondrial dysfunction in SH-SY5Y cells. Biochem. Biophys. Res. Commun., 2018, 503(4), 2963-2969.
[http://dx.doi.org/10.1016/j.bbrc.2018.08.078] [PMID: 30107908]
[55]
Qingming, Y.; Xianhui, P.; Weibao, K.; Hong, Y.; Yidan, S.; Li, Z.; Yanan, Z.; Yuling, Y.; Lan, D.; Guoan, L. Antioxidant activities of malt extract from barley (Hordeum vulgare L.) toward various oxidative stress in vitro and in vivo. Food Chem., 2010, 118, 84-89.
[http://dx.doi.org/10.1016/j.foodchem.2009.04.094]
[56]
Chen, Y.; Mao, W.; Yang, Y.; Teng, X.; Zhu, W.; Qi, X.; Chen, Y.; Zhao, C.; Hou, Y.; Wang, C.; Li, N. Structure and antioxidant activity of an extracellular polysaccharide from coral-associated fungus, Aspergillus versicolor LCJ-5-4. Carbohydr. Polym., 2012, 87, 218-226.
[http://dx.doi.org/10.1016/j.carbpol.2011.07.042]
[57]
He, Y.; Zhu, Q.; Chen, M.; Huang, Q.; Wang, W.; Li, Q.; Huang, Y.; Di, W. The changing 50% inhibitory concentration (IC50) of cisplatin: a pilot study on the artifacts of the MTT assay and the precise measurement of density-dependent chemoresistance in ovarian cancer. Oncotarget, 2016, 7(43), 70803-70821.
[http://dx.doi.org/10.18632/oncotarget.12223] [PMID: 27683123]
[58]
Hazra, B.; Ghosh, S.; Kumar, A.; Pandey, B.N. The prospective role of plant products in radiotherapy of cancer: A current overview. Front. Pharmacol., 2012, 2, 94-94.
[http://dx.doi.org/10.3389/fphar.2011.00094] [PMID: 22291649]
[59]
Azemar, M.; Bernd, H.; Brigitte, H.; Heim, M.; Clemens, U. Clinical benefit in patients with advanced solid tumors treated with modified citrus pectin: a prospective pilot study. Clin. Med. Oncol., 2007, 1, 73-80.
[http://dx.doi.org/10.4137/CMO.S285]
[60]
Hayashi, A.; Gillen, A.C.; Lott, J.R. Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c mice. Altern. Med. Rev., 2000, 5(6), 546-552.
[PMID: 11134977]
[61]
Johnson, K.D.; Glinskii, O.V.; Mossine, V.V.; Turk, J.R.; Mawhinney, T.P.; Anthony, D.C.; Henry, C.J.; Huxley, V.H.; Glinsky, G.V.; Pienta, K.J.; Raz, A.; Glinsky, V.V. Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia. Neoplasia, 2007, 9(8), 662-670.
[http://dx.doi.org/10.1593/neo.07433] [PMID: 17786185]
[62]
Pienta, K.J.; Naik, H.; Akhtar, A.; Yamazaki, K.; Replogle, T.S.; Lehr, J.; Donat, T.L.; Tait, L.; Hogan, V.; Raz, A. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J. Natl. Cancer Inst., 1995, 87(5), 348-353.
[http://dx.doi.org/10.1093/jnci/87.5.348] [PMID: 7853416]
[63]
Guess, B.W.; Scholz, M.C.; Strum, S.B.; Lam, R.Y.; Johnson, H.J.; Jennrich, R.I. Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study. Prostate Cancer Prostatic Dis., 2003, 6(4), 301-304.
[http://dx.doi.org/10.1038/sj.pcan.4500679] [PMID: 14663471]
[64]
Platt, D.; Raz, A. Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J. Natl. Cancer Inst., 1992, 84(6), 438-442.
[http://dx.doi.org/10.1093/jnci/84.6.438] [PMID: 1538421]
[65]
Gunning, A.P.; Bongaerts, R.J.M.; Morris, V.J. Recognition of galactan components of pectin by galectin-3. FASEB J., 2009, 23(2), 415-424.
[http://dx.doi.org/10.1096/fj.08-106617] [PMID: 18832596]
[66]
Ahmed, H.; AlSadek, D.M.M. Galectin-3 as a potential target to prevent cancermetastasis. Clin. Med. Insights Oncol., 2015, 9, 113-121.
[http://dx.doi.org/10.4137/CMO.S29462] [PMID: 26640395]
[67]
Vayssade, M.; Sengkhamparn, N.; Verhoef, R.; Delaigue, C.; Goundiam, O.; Vigneron, P.; Voragen, A.G.; Schols, H.A.; Nagel, M.D. Antiproliferative and proapoptotic actions of okra pectin on B16F10 melanoma cells. Phytother. Res., 2010, 24(7), 982-989.
[http://dx.doi.org/10.1002/ptr.3040] [PMID: 20013817]
[68]
Chauhan, D.; Li, G.; Podar, K.; Hideshima, T.; Neri, P.; He, D.; Mitsiades, N.; Richardson, P.; Chang, Y.; Schindler, J.; Carver, B.; Anderson, K.C. A novel carbohydrate-based therapeutic GCS-100 overcomes bortezomib resistance and enhances dexamethasone-induced apoptosis in multiple myeloma cells. Cancer Res., 2005, 65(18), 8350-8358.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0163] [PMID: 16166312]
[69]
Gao, X.; Liu, J.; Liu, X.; Li, L.; Zheng, J. Cleavage and phosphorylation: important post-translational modifications of galectin-3. Cancer Metastasis Rev., 2017, 36(2), 367-374.
[http://dx.doi.org/10.1007/s10555-017-9666-0] [PMID: 28378189]
[70]
Thijssen, V.L.; Heusschen, R.; Caers, J.; Griffioen, A.W. Galectin expression in cancer diagnosis and prognosis: A systematic review. Biochim. Biophys. Acta, 2015, 1855(2), 235-247.
[PMID: 25819524]
[71]
Schöll-Naderer, M.; Helm, O.; Spencker, J.; Pfeifer, L.; Rätsch, T.; Sebens, S.; Classen, B. Plant-derived saccharides and their inhibitory potential on metastasis associated cellular processes of pancreatic ductal adenocarcinoma cells. Carbohydr. Res., 2020, 490, 107903.
[http://dx.doi.org/10.1016/j.carres.2019.107903] [PMID: 32171073]
[72]
Qi, Q.M.; Xue, Y.C.; Lv, J.; Sun, D.; Du, J.X.; Cai, S.Q.; Li, Y.H.; Gu, T.C.; Wang, M.B. Ginkgolic acids induce HepG2 cell death via a combination of apoptosis, autophagy and the mitochondrial pathway. Oncol. Lett., 2018, 15(5), 6400-6408.
[http://dx.doi.org/10.3892/ol.2018.8177] [PMID: 29725398]
[73]
P, A.; K, A.; L, S.; M, M.; K, M. Anticancer effect of fucoidan on cell proliferation, cell cycle progression, genetic damage and apoptotic cell death in HepG2 cancer cells. Toxicol. Rep., 2019, 6, 556-563.
[http://dx.doi.org/10.1016/j.toxrep.2019.06.005] [PMID: 31249789]
[74]
Zhou, L.; Wang, S.; Cao, L.; Ren, X.; Li, Y.; Shao, J.; Xu, L. Lead acetate induces apoptosis in Leydig cells by activating PPARγ/caspase-3/PARP pathway. Int. J. Environ. Health Res., 2021, 31(1), 34-44.
[http://dx.doi.org/10.1080/09603123.2019.1625034] [PMID: 31145012]
[75]
Vanwalscappel, B.; Haddad, J.G.; Almokdad, R.; Decotter, J.; Gadea, G.; Desprès, P. Zika M oligopeptide ZAMP confers cell death-promoting capability to a soluble tumor-associated antigen through caspase-3/7 activation. Int. J. Mol. Sci., 2020, 21(24), 9578.
[http://dx.doi.org/10.3390/ijms21249578] [PMID: 33339164]
[76]
Li, C.J.; Tsang, S.F.; Tsai, C.H.; Tsai, H.Y.; Chyuan, J.H.; Hsu, H.Y. Momordica charantia extract induces apoptosis in human cancer cells through caspase- and mitochondria-dependent pathways. Evid. Based Complement. Alternat. Med., 2012, 2012, 261971.
[http://dx.doi.org/10.1155/2012/261971] [PMID: 23091557]
[77]
Siriwarin, B.; Weerapreeyakul, N. Sesamol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways. Chem. Biol. Interact., 2016, 254, 109-116.
[http://dx.doi.org/10.1016/j.cbi.2016.06.001] [PMID: 27270451]
[78]
Nechiporuk, T.; Kurtz, S.E.; Nikolova, O.; Liu, T.; Jones, C.L.; D’Alessandro, A.; Culp-Hill, R.; d’Almeida, A.; Joshi, S.K.; Rosenberg, M.; Tognon, C.E.; Danilov, A.V.; Druker, B.J.; Chang, B.H.; McWeeney, S.K.; Tyner, J.W. The TP53 apoptotic network Is a primary mediator of resistance to BCL2 inhibition in AML cells. Cancer Discov., 2019, 9(7), 910-925.
[http://dx.doi.org/10.1158/2159-8290.CD-19-0125] [PMID: 31048320]
[79]
Namba, T. BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites. Sci. Adv., 2019, 5(6), eaaw1386.
[http://dx.doi.org/10.1126/sciadv.aaw1386] [PMID: 31206022]
[80]
Park, H.Y.; Kim, G.Y.; Moon, S.K.; Kim, W.J.; Yoo, Y.H.; Choi, Y.H. Fucoidan inhibits the proliferation of human urinary bladder cancer T24 cells by blocking cell cycle progression and inducing apoptosis. Molecules, 2014, 19(5), 5981-5998.
[http://dx.doi.org/10.3390/molecules19055981] [PMID: 24818577]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version516msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[04:57:57] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[04:57:57] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[04:57:57] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[04:57:57] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (151ms)time
  • Application (365ms)time
  • 1 x Application (70.7%)
    365ms
    1 x Booting (29.29%)
    151ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated255ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('51872515','',1,1740459477,1740459477) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740459477
      3.13msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('51872515','/article/116964',1,1740459477,1740459477)
      370μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51872515 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51872515) limit 1
      17.32msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51872515
      • 1: 51872515
      • 2: 51872515
      • 3: 51872515
      • 4: 51872515
      • 5: 51872515
      • 6: 51872515
      • 7: 51872515
      • 8: 51872515
      • 9: 51872515
      • 10: 51872515
      • 11: 51872515
      • 12: 51872515
      • 13: 51872515
      • 14: 51872515
      • 15: 51872515
      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=116964
      1.19msalphaeurekaselec_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` = 30 limit 1
      1.29msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 30
      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=30) and sj.journal_id!=30 group by `j`.`nid`) as `aggregate_table`
      1.62msalphaeurekaselec_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=30) and sj.journal_id!=30 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.34msalphaeurekaselec_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=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.3msalphaeurekaselec_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=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2msalphaeurekaselec_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` = '116964'
      940μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 116964
      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` = '116964'
      4.95msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 116964
      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` = '116964' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      18.82msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 116964
      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
      9.17msalphaeurekaselec_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
      740μsalphaeurekaselec_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 = 30 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      62.04msalphaeurekaselec_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 = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      20.26msalphaeurekaselec_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 = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      16.28msalphaeurekaselec_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` = 116964 limit 1
      500μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 116964
      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 = 116964 and content_type = 'article' order by status desc limit 1
      480μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 457 and content_id!=116964 and cd.content_type = 'article' order by rand() limit 20
      64.91msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 195134 limit 1
      430μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 195134
      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
      340μsalphaeurekaselec_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` = 'CPB' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      440μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPB
      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 = '116964' 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) )
      540μsalphaeurekaselec_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 = '11316' 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) )
      460μsalphaeurekaselec_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 = '3150' 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) )
      450μsalphaeurekaselec_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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3150) 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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3150) 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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3150)
      11.77msalphaeurekaselec_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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11316) 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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11316) 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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11316)
      980μsalphaeurekaselec_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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116964) 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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116964) 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 <= 51872515 and j.to_ip >=51872515 )) and ((j.from_date <= 1740459477 and j.to_date >= 1740459477 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116964)
      890μsalphaeurekaselec_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` < '861' and is_uploaded = 1 and issue_id = 11316 order by cast(first_page as SIGNED) desc limit 1
      780μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 861
      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` > '872' and is_uploaded = 1 and issue_id = 11316 order by cast(first_page as SIGNED) asc limit 1
      690μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 872
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      250μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      300μsalphaeurekaselec_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` = 116964 limit 1
      3.91msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 116964
      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` = 30 and `b`.`banner_from_date` <= 1740459477 and `b`.`banner_to_date` >= 1740459477 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.64msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740459477
      • 4: 1740459477
      • 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` = 30 and `b`.`banner_from_date` <= 1740459477 and `b`.`banner_to_date` >= 1740459477 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.58msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740459477
      • 4: 1740459477
      • 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='2af2c22eea4251bc4a9c2ec08c5cd290'
      310μsalphaeurekaselec_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
        3ysQAU8euaibYvLa4lpX9FteFbXAGAGqcqqfBKox
        uc_cart_id
        2af2c22eea4251bc4a9c2ec08c5cd290
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/116964" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/116964
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Im1IN1BSRXNNelhKak0xaitGZ1RuU0E9PSIsInZhbHVlIjoiWUhZV3RKYXBVU0dxb2JJSnM5L0VZcFRxTlJLNEdOaEJqQldDbmNaTld3az0iLCJtYWMiOiI5YjhmMGZjZjEyNmZkZmEzOTVlOGU3MmIxZTMzNWE2Y2Q5M2EyNmFlZTRkNTIwMmIwMTdhYzIyNGMwZTQwZGVmIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Im1IN1BSRXNNelhKak0xaitGZ1RuU0E9PSIsInZhbHVlIjoiWUhZV3RKYXBVU0dxb2JJSnM5L0VZcFRxTlJLNEdOaEJqQldDbmNaTld3az0iLCJtYWMiOiI5YjhmMGZjZjEyNmZk" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 04:57:57 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImVYRnBNakVTaG42Ym1MK1BQbFVwWmc9PSIsInZhbHVlIjoiVUJzR1crcHdFaUQ1L0hXZ3JLaDEydFZ0NEI1TkNidTlVcCtDaFlVaVpvWHBjRDh1ZUhQbWs0aVQyMW9iTU9kN1duUzd1N2F3VHQ4allPMUFKNjFkN2lRdTNZelhSY0M1bXZXaC9Wc2RvdlFzWkFEUFVNZzg4dlB2Tno1d2lUMWwiLCJtYWMiOiJhZTVlM2M1OTNiMGExYjlhN2I5NzUyY2ZmYjExZjI5Njc0Njc5ODhiNjQ4MWJhZmNjYTExMGEzMzc3ZjBmNzgzIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 16:57:57 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImVYRnBNakVTaG42Ym1MK1BQbFVwWmc9PSIsInZhbHVlIjoiVUJzR1crcHdFaUQ1L0hXZ3JLaDEydFZ0NEI1TkNidTlVcCtDaFlVaVpvWHBjRDh1ZUhQbWs0aVQyMW9iTU9kN1duUzd1N" 1 => "alphaeurekaselectnet_session=eyJpdiI6InJ6eWhzek0yQ1lJRldCaExXL3ZYNXc9PSIsInZhbHVlIjoiM0F4L1NjWEZnak5uR2VOSk81MHVYNEZ1QlFOemF3dnpkVUJHZVh3ZWI5Q2xjUjBoSHhNckllU0ZtcTMwNTdQOEFzZU4xZHpmNm1SR0pYYXg4d0ltQVhjaHdNMWpKM0NqL3hUMnB1aWd5TWZWOFVlVGNhOG5TTHFGWWFlV2JTcisiLCJtYWMiOiJmYzZlMjhhYmI1Nzg2OThiNjE5ZDJhMmNiZTdiZjVlNjBkYWU1OGRlNzk5NDk5NDk3YTU1ZDM1ODY2NDQ0ZWJmIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InJ6eWhzek0yQ1lJRldCaExXL3ZYNXc9PSIsInZhbHVlIjoiM0F4L1NjWEZnak5uR2VOSk81MHVYNEZ1QlFOemF3dnpkVUJHZVh3ZWI5Q2xjUjBoSHhNckllU0Z" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImVYRnBNakVTaG42Ym1MK1BQbFVwWmc9PSIsInZhbHVlIjoiVUJzR1crcHdFaUQ1L0hXZ3JLaDEydFZ0NEI1TkNidTlVcCtDaFlVaVpvWHBjRDh1ZUhQbWs0aVQyMW9iTU9kN1duUzd1N2F3VHQ4allPMUFKNjFkN2lRdTNZelhSY0M1bXZXaC9Wc2RvdlFzWkFEUFVNZzg4dlB2Tno1d2lUMWwiLCJtYWMiOiJhZTVlM2M1OTNiMGExYjlhN2I5NzUyY2ZmYjExZjI5Njc0Njc5ODhiNjQ4MWJhZmNjYTExMGEzMzc3ZjBmNzgzIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 16:57:57 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImVYRnBNakVTaG42Ym1MK1BQbFVwWmc9PSIsInZhbHVlIjoiVUJzR1crcHdFaUQ1L0hXZ3JLaDEydFZ0NEI1TkNidTlVcCtDaFlVaVpvWHBjRDh1ZUhQbWs0aVQyMW9iTU9kN1duUzd1N" 1 => "alphaeurekaselectnet_session=eyJpdiI6InJ6eWhzek0yQ1lJRldCaExXL3ZYNXc9PSIsInZhbHVlIjoiM0F4L1NjWEZnak5uR2VOSk81MHVYNEZ1QlFOemF3dnpkVUJHZVh3ZWI5Q2xjUjBoSHhNckllU0ZtcTMwNTdQOEFzZU4xZHpmNm1SR0pYYXg4d0ltQVhjaHdNMWpKM0NqL3hUMnB1aWd5TWZWOFVlVGNhOG5TTHFGWWFlV2JTcisiLCJtYWMiOiJmYzZlMjhhYmI1Nzg2OThiNjE5ZDJhMmNiZTdiZjVlNjBkYWU1OGRlNzk5NDk5NDk3YTU1ZDM1ODY2NDQ0ZWJmIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InJ6eWhzek0yQ1lJRldCaExXL3ZYNXc9PSIsInZhbHVlIjoiM0F4L1NjWEZnak5uR2VOSk81MHVYNEZ1QlFOemF3dnpkVUJHZVh3ZWI5Q2xjUjBoSHhNckllU0Z" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "3ysQAU8euaibYvLa4lpX9FteFbXAGAGqcqqfBKox" "uc_cart_id" => "2af2c22eea4251bc4a9c2ec08c5cd290" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/116964" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 04:57:57GET/article/116964414371