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Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

A Review on Plant Flavonoids as Potential Anticancer Agents

Author(s): Bhupinder Kapoor*, Monica Gulati, Reena Gupta, Sachin Kumar Singh, Mukta Gupta, Arshid Nabi and Pooja A. Chawla

Volume 25, Issue 6, 2021

Published on: 26 November, 2020

Page: [737 - 747] Pages: 11

DOI: 10.2174/1385272824999201126214150

Price: $65

Abstract

Flavonoids are polyphenolic compounds that are mainly derived from fruits and vegetables and constitute an essential part of plant-derived beverages such as green tea, wine and cocoa-based products. They have been shown to possess anticancer effects via different mechanisms such as carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis and differentiation, inhibition of angiogenesis, anti-oxidation and reversal of multidrug resistance or a combination of any two or more of these mechanisms. The present review summarizes the chemistry, biosynthesis and anticancer evaluation of flavonoids in both animal and human studies. A special emphasis has been placed on the flavonoids that are being screened in different phases of clinical trials for chemoprotective action against various cancers.

Keywords: Flavonoids, anticancer, chemoprotection, clinical trials, apoptosis, antiproliferation.

Graphical Abstract

[1]
Zhou, Q.; Cheng, K-W.; Xiao, J.; Wang, M. The multifunctional roles of flavonoids against the formation of advanced glycation end products (AGEs) and AGEs-induced harmful effects. Trends Food Sci. Technol., 2020, 103, 333-347.
[http://dx.doi.org/10.1016/j.tifs.2020.06.002]
[2]
Owona, B.A.; Abia, W.A.; Moundipa, P.F. Natural compounds flavonoids as modulators of inflammasomes in chronic diseases. Int. Immunopharmacol., 2020, 84106498
[http://dx.doi.org/10.1016/j.intimp.2020.106498] [PMID: 32304996]
[3]
Raffa, D.; Maggio, B.; Raimondi, M.V.; Plescia, F.; Daidone, G. Recent discoveries of anticancer flavonoids. Eur. J. Med. Chem., 2017, 142, 213-228.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.034] [PMID: 28793973]
[4]
Zhuang, C.; Zhang, W.; Sheng, C.; Zhang, W.; Xing, C.; Miao, Z. Chalcone: a privileged structure in medicinal chemistry. Chem. Rev., 2017, 117(12), 7762-7810.
[http://dx.doi.org/10.1021/acs.chemrev.7b00020] [PMID: 28488435]
[5]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: an overview. J. Nutr. Sci., 2016, 5e47
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[6]
Wang, T.Y.; Li, Q.; Bi, K.S. Bioactive flavonoids in medicinal plants: structure, activity and biological fate. Asian J. Pharm. Sci., 2018, 13(1), 12-23.
[http://dx.doi.org/10.1016/j.ajps.2017.08.004] [PMID: 32104374]
[7]
Johnson, J.; Yardily, A. Chalconoid metal chelates: spectral, biological and catalytic applications. J. Coord. Chem., 2019, 72(15), 2437-2488.
[http://dx.doi.org/10.1080/00958972.2019.1669022]
[8]
Pietta, P-G. Flavonoids as antioxidants. J. Nat. Prod., 2000, 63(7), 1035-1042.
[http://dx.doi.org/10.1021/np9904509] [PMID: 10924197]
[9]
Xiao, X.; Wang, X.; Gui, X.; Chen, L.; Huang, B. Natural flavonoids as promising analgesic candidates: a systematic review. Chem. Biodivers., 2016, 13(11), 1427-1440.
[http://dx.doi.org/10.1002/cbdv.201600060] [PMID: 27449823]
[10]
Maleki, S.J.; Crespo, J.F.; Cabanillas, B. Anti-inflammatory effects of flavonoids. Food Chem., 2019, 299125124
[http://dx.doi.org/10.1016/j.foodchem.2019.125124] [PMID: 31288163]
[11]
Huang, S.; Zhang, C-P.; Wang, K.; Li, G.Q.; Hu, F-L. Recent advances in the chemical composition of propolis. Molecules, 2014, 19(12), 19610-19632.
[http://dx.doi.org/10.3390/molecules191219610] [PMID: 25432012]
[12]
Ahangari, Z.; Naseri, M.; Vatandoost, F. Propolis: chemical composition and its applications in endodontics. Iran. Endod. J., 2018, 13(3), 285-292.
[PMID: 30083195]
[13]
Kawai, Y. Understanding metabolic conversions and molecular actions of flavonoids in vivo: toward new strategies for effective utilization of natural polyphenols in human health. J. Med. Invest., 2018, 65(34), 162-165.
[14]
Ko, E.Y.; Nile, S.H.; Sharma, K.; Li, G.H.; Park, S.W. Effect of different exposed lights on quercetin and quercetin glucoside content in onion (Allium cepa L.). Saudi J. Biol. Sci., 2015, 22(4), 398-403.
[http://dx.doi.org/10.1016/j.sjbs.2014.11.012] [PMID: 26150744]
[15]
Jeganathan, B.; Punyasiri, P.A.N.; Kottawa-Arachchi, J.D.; Ranatunga, M.A.B.; Abeysinghe, I.S.B.; Gunasekare, M.T.K.; Bandara, B.M.R. Genetic variation of flavonols quercetin, myricetin, and kaempferol in the Sri Lankan tea (Camellia sinensis L.) and their health-promoting aspects. Int. J. Food Sci., 2016.20166057434
[http://dx.doi.org/10.1155/2016/6057434] [PMID: 27366737]
[16]
Koh, E.; Wimalasiri, K.M.S.; Chassy, A.W.; Mitchell, A.E. Content of ascorbic acid, quercetin, kaempferol and total phenolics in commercial broccoli. J. Food Compos. Anal., 2009, 22(7), 637-643.
[http://dx.doi.org/10.1016/j.jfca.2009.01.019]
[17]
Thuphairo, K.; Sornchan, P.; Suttisansanee, U. Bioactive compounds, antioxidant activity and inhibition of key enzymes relevant to Alzheimer’s disease from sweet pepper (Capsicum annuum) extracts. Prev. Nutr. Food Sci., 2019, 24(3), 327-337.
[http://dx.doi.org/10.3746/pnf.2019.24.3.327] [PMID: 31608259]
[18]
Boyer, J.; Liu, R.H. Apple phytochemicals and their health benefits. Nutr. J., 2004, 3, 5.
[http://dx.doi.org/10.1186/1475-2891-3-5] [PMID: 15140261]
[19]
Falcone Ferreyra, M.L.; Rius, S.P.; Casati, P. Flavonoids: biosynthesis, biological functions, and biotechnological applications. Front. Plant Sci., 2012, 3, 222.
[http://dx.doi.org/10.3389/fpls.2012.00222] [PMID: 23060891]
[20]
Hyun, M.W.; Yun, Y.H.; Kim, J.Y.; Kim, S.H. Fungal and plant phenylalanine ammonia-lyase. Mycobiology, 2011, 39(4), 257-265.
[http://dx.doi.org/10.5941/MYCO.2011.39.4.257] [PMID: 22783113]
[21]
Winkel, B.S.J. The Biosynthesis of Flavonoids.The Science of Flavonoids; Grotewold, E., Ed.; Springer: New York, 2006, pp. 71-95.
[http://dx.doi.org/10.1007/978-0-387-28822-2_3]
[22]
Winkel-Shirley, B. Biosynthesis of flavonoids and effects of stress. Curr. Opin. Plant Biol., 2002, 5(3), 218-223.
[http://dx.doi.org/10.1016/S1369-5266(02)00256-X] [PMID: 11960739]
[23]
Abotaleb, M.; Samuel, S.M.; Varghese, E.; Varghese, S.; Kubatka, P.; Liskova, A.; Büsselberg, D. Flavonoids in cancer and apoptosis. Cancers (Basel), 2018, 11(1), 28.
[http://dx.doi.org/10.3390/cancers11010028] [PMID: 30597838]
[24]
Kuhnle, G.G.C. Nutrition epidemiology of flavan-3-ols: the known unknowns. Mol. Aspects Med., 2018, 61, 2-11.
[http://dx.doi.org/10.1016/j.mam.2017.10.003] [PMID: 29146101]
[25]
Cushnie, T.P.T.; Lamb, A.J. Antimicrobial activity of flavonoids. Int. J. Antimicrob. Agents, 2005, 26(5), 343-356.
[http://dx.doi.org/10.1016/j.ijantimicag.2005.09.002] [PMID: 16323269]
[26]
Raut, N.A.; Dhore, P.W.; Saoji, S.D.; Kokare, D.M. Selected Bioactive Natural Products for Diabetes Mellitus In: Studies in Natural Products Chemistry Atta ur, Rahman, Ed. Elsevier; , 2016; 48, pp. 287-322.
[27]
Górniak, I.; Bartoszewski, R.; Króliczewski, J. Comprehensive review of antimicrobial activities of plant flavonoids. Phytochem. Rev., 2019, 18(1), 241-272.
[http://dx.doi.org/10.1007/s11101-018-9591-z]
[28]
Farhadi, F.; Khameneh, B.; Iranshahi, M.; Iranshahy, M. Antibacterial activity of flavonoids and their structure-activity relationship: an update review. Phytother. Res., 2019, 33(1), 13-40.
[http://dx.doi.org/10.1002/ptr.6208] [PMID: 30346068]
[29]
Choy, K.W.; Murugan, D.; Leong, X-F.; Abas, R.; Alias, A.; Mustafa, M.R. Flavonoids as natural anti-inflammatory agents targeting nuclear factor-kappa B (NFκB) signaling in cardiovascular diseases: a mini review. Front. Pharmacol., 2019, 10(1295), 1295.
[http://dx.doi.org/10.3389/fphar.2019.01295] [PMID: 31749703]
[30]
Pan, M-H.; Lai, C-S.; Ho, C-T. Anti-inflammatory activity of natural dietary flavonoids. Food Funct., 2010, 1(1), 15-31.
[http://dx.doi.org/10.1039/c0fo00103a] [PMID: 21776454]
[31]
Testai, L.; Martelli, A.; Cristofaro, M.; Breschi, M.C.; Calderone, V. Cardioprotective effects of different flavonoids against myocardial ischaemia/reperfusion injury in Langendorff-perfused rat hearts. J. Pharm. Pharmacol., 2013, 65(5), 750-756.
[http://dx.doi.org/10.1111/jphp.12032] [PMID: 23600393]
[32]
Cook, N.C.; Samman, S. Flavonoids-chemistry, metabolism, cardioprotective effects, and dietary sources. J. Nutr. Biochem., 1996, 7(2), 66-76.
[http://dx.doi.org/10.1016/0955-2863(95)00168-9]
[33]
Miksicek, R.J. Commonly occurring plant flavonoids have estrogenic activity. Mol. Pharmacol., 1993, 44(1), 37-43.
[PMID: 8341277]
[34]
Resende, F.A.; de Oliveira, A.P.S.; de Camargo, M.S.; Vilegas, W.; Varanda, E.A. Evaluation of estrogenic potential of flavonoids using a recombinant yeast strain and MCF7/BUS cell proliferation assay. PLoS One, 2013, 8(10)e74881
[http://dx.doi.org/10.1371/journal.pone.0074881] [PMID: 24098354]
[35]
Obafemi, T.O.; Akinmoladun, A.C.; Olaleye, M.T.; Agboade, S.O.; Onasanya, A.A. Antidiabetic potential of methanolic and flavonoid-rich leaf extracts of Synsepalum dulcificum in type 2 diabetic rats. J. Ayurveda Integr. Med., 2017, 8(4), 238-246.
[http://dx.doi.org/10.1016/j.jaim.2017.01.008] [PMID: 28917550]
[36]
Huang, Y.; Hao, J.; Tian, D.; Wen, Y.; Zhao, P.; Chen, H.; Lv, Y.; Yang, X. Antidiabetic activity of a flavonoid-rich extract from Sophora davidii (Franch.) skeels in KK-Ay Mice via activation of AMP-activated protein kinase. Front. Pharmacol., 2018, 9, 760.
[http://dx.doi.org/10.3389/fphar.2018.00760] [PMID: 30061831]
[37]
Chahar, M.K.; Sharma, N.; Dobhal, M.P.; Joshi, Y.C. Flavonoids: a versatile source of anticancer drugs. Pharmacogn. Rev., 2011, 5(9), 1-12.
[http://dx.doi.org/10.4103/0973-7847.79093] [PMID: 22096313]
[38]
Shi, X.; Niu, L.; Zhao, L.; Wang, B.; Jin, Y.; Li, X. The antiallergic activity of flavonoids extracted from Citri Reticulatae Pericarpium. J. Food Process. Preserv., 2018, 42(4)e13588
[http://dx.doi.org/10.1111/jfpp.13588]
[39]
Cheong, H.; Ryu, S-Y.; Oak, M-H.; Cheon, S-H.; Yoo, G-S.; Kim, K-M. Studies of structure activity relationship of flavonoids for the anti-allergic actions. Arch. Pharm. Res., 1998, 21(4), 478-480.
[http://dx.doi.org/10.1007/BF02974647] [PMID: 9875480]
[40]
Raffoul, J.J.; Kucuk, O.; Sarkar, F.H.; Hillman, G.G. Dietary agents in cancer chemoprevention and treatment. J. Oncol., 2012, 2012749310
[http://dx.doi.org/10.1155/2012/749310] [PMID: 23316231]
[41]
Sak, K. Chemotherapy and dietary phytochemical agents. Chemother. Res. Pract., 2012.2012282570
[http://dx.doi.org/10.1155/2012/282570] [PMID: 23320169]
[42]
Key, T.J. Fruit and vegetables and cancer risk. Br. J. Cancer, 2011, 104(1), 6-11.
[http://dx.doi.org/10.1038/sj.bjc.6606032] [PMID: 21119663]
[43]
Bradbury, K.E.; Appleby, P.N.; Key, T.J. Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and nutrition (EPIC). Am. J. Clin. Nutr., 2014, 100(Suppl. 1), 394S-398S.
[http://dx.doi.org/10.3945/ajcn.113.071357] [PMID: 24920034]
[44]
Ren, W.; Qiao, Z.; Wang, H.; Zhu, L.; Zhang, L. Flavonoids: promising anticancer agents. Med. Res. Rev., 2003, 23(4), 519-534.
[http://dx.doi.org/10.1002/med.10033] [PMID: 12710022]
[45]
Yang, C.S.; Chung, J.Y.; Yang, G.; Chhabra, S.K.; Lee, M.J. Tea and tea polyphenols in cancer prevention. J. Nutr., 2000, 130(2S), 472S-478S.
[http://dx.doi.org/10.1093/jn/130.2.472S] [PMID: 10721932]
[46]
Lambert, J.D.; Hong, J.; Yang, G.Y.; Liao, J.; Yang, C.S. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am. J. Clin. Nutr., 2005, 81(1), 284S-291S.
[http://dx.doi.org/10.1093/ajcn/81.1.284S] [PMID: 15640492]
[47]
Kamei, H.; Koide, T.; Kojimam, T.; Hasegawa, M.; Terabe, K.; Umeda, T.; Hashimoto, Y. Flavonoid-mediated tumor growth suppression demonstrated by in vivo study. Cancer Biother. Radiopharm., 1996, 11(3), 193-196.
[http://dx.doi.org/10.1089/cbr.1996.11.193] [PMID: 10851537]
[48]
Hagiwara, A.; Yoshino, H.; Ichihara, T.; Kawabe, M.; Tamano, S.; Aoki, H.; Koda, T.; Nakamura, M.; Imaida, K.; Ito, N.; Shirai, T. Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine. J. Toxicol. Sci., 2002, 27(1), 57-68.
[http://dx.doi.org/10.2131/jts.27.57] [PMID: 11915369]
[49]
Hou, D.X.; Kai, K.; Li, J.J.; Lin, S.; Terahara, N.; Wakamatsu, M.; Fujii, M.; Young, M.R.; Colburn, N. Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure-activity relationship and molecular mechanisms. Carcinogenesis, 2004, 25(1), 29-36.
[http://dx.doi.org/10.1093/carcin/bgg184] [PMID: 14514663]
[50]
Miyagi, Y.; Om, A.S.; Chee, K.M.; Bennink, M.R. Inhibition of azoxymethane-induced colon cancer by orange juice. Nutr. Cancer, 2000, 36(2), 224-229.
[http://dx.doi.org/10.1207/S15327914NC3602_12] [PMID: 10890034]
[51]
Tanaka, T.; Makita, H.; Kawabata, K.; Mori, H.; Kakumoto, M.; Satoh, K.; Hara, A.; Sumida, T.; Tanaka, T.; Ogawa, H. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesis, 1997, 18(5), 957-965.
[http://dx.doi.org/10.1093/carcin/18.5.957] [PMID: 9163681]
[52]
Yang, M.; Tanaka, T.; Hirose, Y.; Deguchi, T.; Mori, H.; Kawada, Y. Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice. Int. J. Cancer, 1997, 73(5), 719-724.
[http://dx.doi.org/10.1002/(SICI)1097-0215(19971127)73:5<719:AID-IJC18>3.0.CO;2-0] [PMID: 9398052]
[53]
Singh, R.P.; Agarwal, R. Prostate cancer chemoprevention by silibinin: bench to bedside. Mol. Carcinog., 2006, 45(6), 436-442.
[http://dx.doi.org/10.1002/mc.20223] [PMID: 16637061]
[54]
Katiyar, S.K. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects(review). Int. J. Oncol., 2005, 26(1), 169-176.
[http://dx.doi.org/10.3892/ijo.26.1.169] [PMID: 15586237]
[55]
Caltagirone, S.; Rossi, C.; Poggi, A.; Ranelletti, F.O.; Natali, P.G.; Brunetti, M.; Aiello, F.B.; Piantelli, M. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int. J. Cancer, 2000, 87(4), 595-600.
[http://dx.doi.org/10.1002/1097-0215(20000815)87:4<595:AID-IJC21>3.0.CO;2-5] [PMID: 10918203]
[56]
Tatsuta, A.; Iishi, H.; Baba, M.; Yano, H.; Murata, K.; Mukai, M.; Akedo, H. Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats. Clin. Exp. Metastasis, 2000, 18(8), 657-662.
[http://dx.doi.org/10.1023/A:1013133803806] [PMID: 11827069]
[57]
Shukla, S.; MacLennan, G.T.; Flask, C.A.; Fu, P.; Mishra, A.; Resnick, M.I.; Gupta, S. Blockade of beta-catenin signaling by plant flavonoid apigenin suppresses prostate carcinogenesis in TRAMP mice. Cancer Res., 2007, 67(14), 6925-6935.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0717] [PMID: 17638904]
[58]
Walle, T.; Ta, N.; Kawamori, T.; Wen, X.; Tsuji, P.A.; Walle, U.K. Cancer chemopreventive properties of orally bioavailable flavonoids--methylated versus unmethylated flavones. Biochem. Pharmacol., 2007, 73(9), 1288-1296.
[http://dx.doi.org/10.1016/j.bcp.2006.12.028] [PMID: 17250812]
[59]
Deschner, E.E.; Ruperto, J.; Wong, G.; Newmark, H.L. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis, 1991, 12(7), 1193-1196.
[http://dx.doi.org/10.1093/carcin/12.7.1193] [PMID: 2070483]
[60]
Makita, H.; Tanaka, T.; Fujitsuka, H.; Tatematsu, N.; Satoh, K.; Hara, A.; Mori, H. Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin. Cancer Res., 1996, 56(21), 4904-4909.
[PMID: 8895742]
[61]
Balasubramanian, S.; Govindasamy, S. Inhibitory effect of dietary flavonol quercetin on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Carcinogenesis, 1996, 17(4), 877-879.
[http://dx.doi.org/10.1093/carcin/17.4.877] [PMID: 8625504]
[62]
Verma, A.K.; Johnson, J.A.; Gould, M.N.; Tanner, M.A. Inhibition of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res., 1988, 48(20), 5754-5758.
[PMID: 3139283]
[63]
Elangovan, V.; Sekar, N.; Govindasamy, S. Chemopreventive potential of dietary bioflavonoids against 20-methylcholanthrene-induced tumorigenesis. Cancer Lett., 1994, 87(1), 107-113.
[http://dx.doi.org/10.1016/0304-3835(94)90416-2] [PMID: 7954363]
[64]
Khan, W.A.; Wang, Z.Y.; Athar, M.; Bickers, D.R.; Mukhtar, H. Inhibition of the skin tumorigenicity of (+/-)-7 β,8 α-dihydroxy-9 α,10 α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene by tannic acid, green tea polyphenols and quercetin in Sencar mice. Cancer Lett., 1988, 42(1-2), 7-12.
[http://dx.doi.org/10.1016/0304-3835(88)90232-7] [PMID: 3141040]
[65]
Ju, J.; Lu, G.; Lambert, J.D.; Yang, C.S. Inhibition of carcinogenesis by tea constituents. Semin. Cancer Biol., 2007, 17(5), 395-402.
[http://dx.doi.org/10.1016/j.semcancer.2007.06.013] [PMID: 17686632]
[66]
Huang, M.T.; Xie, J.G.; Wang, Z.Y.; Ho, C.T.C.; Lou, Y.R.; Wang, C.X.; Hard, G.C.; Conney, A.H. Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically important constituent of tea. Cancer Res., 1997, 57(13), 2623-2629.
[PMID: 9205068]
[67]
Xu, Y.; Ho, C.T.; Amin, S.G.; Han, C.; Chung, F.L. Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res., 1992, 52(14), 3875-3879.
[PMID: 1617663]
[68]
Katiyar, S.K.; Elmets, C.A. Green tea polyphenolic antioxidants and skin photoprotection(review). Int. J. Oncol., 2001, 18(6), 1307-1313.
[http://dx.doi.org/10.3892/ijo.18.6.1307] [PMID: 11351267]
[69]
Weisburger, J.H. Tea and health: the underlying mechanisms. Proc. Soc. Exp. Biol. Med., 1999, 220(4), 271-275.
[http://dx.doi.org/10.1046/j.1525-1373.1999.d01-46.x] [PMID: 10202402]
[70]
Liu, J.D.; Chen, S.H.; Lin, C.L.; Tsai, S.H.; Liang, Y.C. Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice. J. Cell. Biochem., 2001, 83(4), 631-642.
[http://dx.doi.org/10.1002/jcb.1261] [PMID: 11746506]
[71]
Adhami, V.M.; Ahmad, N.; Mukhtar, H. Molecular targets for green tea in prostate cancer prevention. J. Nutr., 2003, 133(7), 2417S-2424S.
[http://dx.doi.org/10.1093/jn/133.7.2417S] [PMID: 12840218]
[72]
Yang, G.Y.; Liu, Z.; Seril, D.N.; Liao, J.; Ding, W.; Kim, S.; Bondoc, F.; Yang, C.S. Black tea constituents, theaflavins, inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Carcinogenesis, 1997, 18(12), 2361-2365.
[http://dx.doi.org/10.1093/carcin/18.12.2361] [PMID: 9450482]
[73]
Yang, G.; Wang, Z-Y.; Kim, S.; Liao, J.; Seril, D.N.; Chen, X.; Smith, T.J.; Yang, C.S. Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model with A/J mice. Cancer Res., 1997, 57(10), 1889-1894.
[PMID: 9157981]
[74]
Landau, J.M.; Wang, Z.Y.; Yang, G.Y.; Ding, W.; Yang, C.S. Inhibition of spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice by black and green tea. Carcinogenesis, 1998, 19(3), 501-507.
[http://dx.doi.org/10.1093/carcin/19.3.501] [PMID: 9525286]
[75]
Mimoto, J.; Kiura, K.; Matsuo, K.; Yoshino, T.; Takata, I.; Ueoka, H.; Kataoka, M.; Harada, M. (-)-Epigallocatechin gallate can prevent cisplatin-induced lung tumorigenesis in A/J mice. Carcinogenesis, 2000, 21(5), 915-919.
[http://dx.doi.org/10.1093/carcin/21.5.915] [PMID: 10783312]
[76]
Khanduja, K.L.; Gandhi, R.K.; Pathania, V.; Syal, N. Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. Food Chem. Toxicol., 1999, 37(4), 313-318.
[http://dx.doi.org/10.1016/S0278-6915(99)00021-6] [PMID: 10418948]
[77]
Akagi, K.; Hirose, M.; Hoshiya, T.; Mizoguchi, Y.; Ito, N.; Shirai, T. Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model. Cancer Lett., 1995, 94(1), 113-121.
[http://dx.doi.org/10.1016/0304-3835(95)03833-I] [PMID: 7621439]
[78]
Ohta, T.; Nakatsugi, S.; Watanabe, K.; Kawamori, T.; Ishikawa, F.; Morotomi, M.; Sugie, S.; Toda, T.; Sugimura, T.; Wakabayashi, K. Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones. Carcinogenesis, 2000, 21(5), 937-941.
[http://dx.doi.org/10.1093/carcin/21.5.937] [PMID: 10783315]
[79]
Harper, C.E.; Cook, L.M.; Patel, B.B.; Wang, J.; Eltoum, I.A.; Arabshahi, A.; Shirai, T.; Lamartiniere, C.A. Genistein and resveratrol, alone and in combination, suppress prostate cancer in SV-40 tag rats. Prostate, 2009, 69(15), 1668-1682.
[http://dx.doi.org/10.1002/pros.21017] [PMID: 19670229]
[80]
Mentor-Marcel, R.; Lamartiniere, C.A.; Eltoum, I.E.; Greenberg, N.M.; Elgavish, A. Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP). Cancer Res., 2001, 61(18), 6777-6782.
[PMID: 11559550]
[81]
Wang, J.; Eltoum, I-E.; Lamartiniere, C.A. Dietary genistein suppresses chemically induced prostate cancer in Lobund-Wistar rats. Cancer Lett., 2002, 186(1), 11-18.
[http://dx.doi.org/10.1016/S0304-3835(01)00811-4] [PMID: 12183070]
[82]
Cross, H.S.; Kállay, E.; Lechner, D.; Gerdenitsch, W.; Adlercreutz, H.; Armbrecht, H.J. Phytoestrogens and vitamin D metabolism: a new concept for the prevention and therapy of colorectal, prostate, and mammary carcinomas. J. Nutr., 2004, 134(5), 1207S-1212S.
[http://dx.doi.org/10.1093/jn/134.5.1207S] [PMID: 15113973]
[83]
Weiss, R.B.; Greene, R.F.; Knight, R.D.; Collins, J.M.; Pelosi, J.J.; Sulkes, A.; Curt, G.A. Phase I and clinical pharmacology study of intravenous flavone acetic acid (NSC 347512). Cancer Res., 1988, 48(20), 5878-5882.
[PMID: 3167843]
[84]
Ferry, D.R.; Smith, A.; Malkhandi, J.; Fyfe, D.W.; deTakats, P.G.; Anderson, D.; Baker, J.; Kerr, D.J. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer Res., 1996, 2(4), 659-668.
[PMID: 9816216]
[85]
Mulholland, P.J.; Ferry, D.R.; Anderson, D.; Hussain, S.A.; Young, A.M.; Cook, J.E.; Hodgkin, E.; Seymour, L.W.; Kerr, D.J. Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin. Ann. Oncol., 2001, 12(2), 245-248.
[http://dx.doi.org/10.1023/A:1008372017097] [PMID: 11300332]
[86]
Shapiro, G.I. Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin. Cancer Res., 2004, 10(12), 4270s-4275s.
[http://dx.doi.org/10.1158/1078-0432.CCR-040020] [PMID: 15217973]
[87]
Newcomb, E.W. Flavopiridol: pleiotropic biological effects enhance its anti-cancer activity. Anticancer Drugs, 2004, 15(5), 411-419.
[http://dx.doi.org/10.1097/01.cad.0000127332.06439.47] [PMID: 15166614]
[88]
Senderowicz, A.M. Flavopiridol: the first cyclin-dependent kinase inhibitor in human clinical trials. Invest. New Drugs, 1999, 17(3), 313-320.
[http://dx.doi.org/10.1023/A:1006353008903] [PMID: 10665481]
[90]
Wang, H.K. National Cancer Institute. Flavopiridol. Curr. Opin. Investig. Drugs, 2001, 2(8), 1149-1155.
[PMID: 11892928]
[91]
Senderowicz, A.M. Development of cyclin-dependent kinase modulators as novel therapeutic approaches for hematological malignancies. Leukemia, 2001, 15(1), 1-9.
[http://dx.doi.org/10.1038/sj.leu.2401994] [PMID: 11243375]
[92]
Gates, M.A.; Tworoger, S.S.; Hecht, J.L.; De Vivo, I.; Rosner, B.; Hankinson, S.E. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. Int. J. Cancer, 2007, 121(10), 2225-2232.
[http://dx.doi.org/10.1002/ijc.22790] [PMID: 17471564]
[93]
Peterson, J.; Lagiou, P.; Samoli, E.; Lagiou, A.; Katsouyanni, K.; La Vecchia, C.; Dwyer, J.; Trichopoulos, D. Flavonoid intake and breast cancer risk: a case--control study in Greece. Br. J. Cancer, 2003, 89(7), 1255-1259.
[http://dx.doi.org/10.1038/sj.bjc.6601271] [PMID: 14520456]
[94]
Hirose, K.; Matsuo, K.; Iwata, H.; Tajima, K. Dietary patterns and the risk of breast cancer in Japanese women. Cancer Sci., 2007, 98(9), 1431-1438.
[http://dx.doi.org/10.1111/j.1349-7006.2007.00540.x] [PMID: 17627618]
[95]
Hertog, M.G.; Bueno-de-Mesquita, H.B.; Fehily, A.M.; Sweetnam, P.M.; Elwood, P.C.; Kromhout, D. Fruit and vegetable consumption and cancer mortality in the Caerphilly study. Cancer Epidemiol. Biomarkers Prev., 1996, 5(9), 673-677.
[PMID: 8877056]
[96]
Knekt, P.; Järvinen, R.; Seppänen, R.; Hellövaara, M.; Teppo, L.; Pukkala, E.; Aromaa, A. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am. J. Epidemiol., 1997, 146(3), 223-230.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a009257] [PMID: 9247006]
[97]
Mursu, J.; Nurmi, T.; Tuomainen, T-P.; Salonen, J.T.; Pukkala, E.; Voutilainen, S. Intake of flavonoids and risk of cancer in Finnish men: the kuopio ischaemic heart disease risk factor study. Int. J. Cancer, 2008, 123(3), 660-663.
[http://dx.doi.org/10.1002/ijc.23421] [PMID: 18338754]
[98]
Messina, M.; Kucuk, O.; Lampe, J.W. An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels. J. AOAC Int., 2006, 89(4), 1121-1134.
[http://dx.doi.org/10.1093/jaoac/89.4.1121] [PMID: 16915855]
[99]
Travis, R.C.; Spencer, E.A.; Allen, N.E.; Appleby, P.N.; Roddam, A.W.; Overvad, K.; Johnsen, N.F.; Olsen, A.; Kaaks, R.; Linseisen, J.; Boeing, H.; Nöthlings, U.; Bueno-de-Mesquita, H.B.; Ros, M.M.; Sacerdote, C.; Palli, D.; Tumino, R.; Berrino, F.; Trichopoulou, A.; Dilis, V.; Trichopoulos, D.; Chirlaque, M.D.; Ardanaz, E.; Larranaga, N.; Gonzalez, C.; Suárez, L.R.; Sánchez, M.J.; Bingham, S.; Khaw, K.T.; Hallmans, G.; Stattin, P.; Rinaldi, S.; Slimani, N.; Jenab, M.; Riboli, E.; Key, T.J. Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into cancer and nutrition. Br. J. Cancer, 2009, 100(11), 1817-1823.
[http://dx.doi.org/10.1038/sj.bjc.6605073] [PMID: 19436304]
[100]
Clinicaltrials, National Library of Medicine Available from: https://clinicaltrials.gov/
[101]
Nagai, H.; Kim, Y.H. Cancer prevention from the perspective of global cancer burden patterns. J. Thorac. Dis., 2017, 9(3), 448-451.
[http://dx.doi.org/10.21037/jtd.2017.02.75] [PMID: 28449441]
[102]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[103]
Singh, S.; Dhasmana, D.C.; Bisht, M.; Singh, P.K. Pattern of adverse drug reactions to anticancer drugs: a quantitative and qualitative analysis. Indian J. Med. Paediatr. Oncol., 2017, 38(2), 140-145.
[PMID: 28900321]
[104]
Couffignal, A.L.; Lapeyre-Mestre, M.; Bonhomme, C.; Bugat, R.; Montastruc, J.L. Adverse effects of anticancer drugs: apropos of a pharmacovigilance study at a specialized oncology institution. Therapie, 2000, 55(5), 635-641.
[PMID: 11201979]
[105]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[106]
Shahidi, F.; Ambigaipalan, P. Phenolics and polyphenolics in foods, beverages and spices: antioxidant activity and health effects - a review. J. Funct. Foods, 2015, 18, 820-897.
[http://dx.doi.org/10.1016/j.jff.2015.06.018]
[107]
Hosseinzade, A.; Sadeghi, O.; Naghdipour Biregani, A.; Soukhtehzari, S.; Brandt, G.S.; Esmaillzadeh, A. Immunomodulatory effects of flavonoids: Possible induction of T CD4+ regulatory cells through suppression of mTOR pathway signaling activity. Front. Immunol., 2019, 10(51), 51.
[http://dx.doi.org/10.3389/fimmu.2019.00051] [PMID: 30766532]
[108]
Pérez-Cano, F.J.; Castell, M. Flavonoids, inflammation and immune system. Nutrients, 2016, 8(10), 659.
[http://dx.doi.org/10.3390/nu8100659] [PMID: 27775647]

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    • 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
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      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
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      230μsalphaeurekaselec_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
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      20msalphaeurekaselec_live_10_06_2022UserAccess.php#784
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      • 1: 221922387
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      • 4: 221922387
      • 5: 221922387
      • 6: 221922387
      • 7: 221922387
      • 8: 221922387
      • 9: 221922387
      • 10: 221922387
      • 11: 221922387
      • 12: 221922387
      • 13: 221922387
      • 14: 221922387
      • 15: 221922387
      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=111894
      2.18msalphaeurekaselec_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` = 19 limit 1
      1.16msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 19
      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=19) and sj.journal_id!=19 group by `j`.`nid`) as `aggregate_table`
      780μsalphaeurekaselec_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=19) and sj.journal_id!=19 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      2.61msalphaeurekaselec_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=19) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      9.29msalphaeurekaselec_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=19) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      6.46msalphaeurekaselec_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` = '111894'
      980μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 111894
      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` = '111894'
      4.85msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 111894
      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` = '111894' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.47msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 111894
      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
      400μsalphaeurekaselec_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
      720μsalphaeurekaselec_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 = 19 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      92.42msalphaeurekaselec_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 = 19 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      41.65msalphaeurekaselec_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 = 19 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      13.22msalphaeurekaselec_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` = 111894 limit 1
      260μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 111894
      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 = 111894 and content_type = 'article' order by status desc limit 1
      310μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 188445 limit 1
      230μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 188445
      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
      270μsalphaeurekaselec_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` = 'COC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      430μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: COC
      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 = '111894' 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) )
      430μsalphaeurekaselec_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 = '10500' 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) )
      370μsalphaeurekaselec_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 = '2952' 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) )
      310μsalphaeurekaselec_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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2952) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2952) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2952)
      10.85msalphaeurekaselec_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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10500) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10500) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10500)
      850μsalphaeurekaselec_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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 111894) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 111894) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1740473378 and j.to_date >= 1740473378 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 111894)
      860μsalphaeurekaselec_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` < '737' and is_uploaded = 1 and issue_id = 10500 order by cast(first_page as SIGNED) desc limit 1
      720μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 737
      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` > '747' and is_uploaded = 1 and issue_id = 10500 order by cast(first_page as SIGNED) asc limit 1
      550μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 747
      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'
      210μsalphaeurekaselec_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
      260μsalphaeurekaselec_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` = 111894 limit 1
      3.87msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 111894
      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` = 19 and `b`.`banner_from_date` <= 1740473378 and `b`.`banner_to_date` >= 1740473378 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.65msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 19
      • 3: 1740473378
      • 4: 1740473378
      • 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` = 19 and `b`.`banner_from_date` <= 1740473378 and `b`.`banner_to_date` >= 1740473378 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.73msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 19
      • 3: 1740473378
      • 4: 1740473378
      • 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='398b502a825435601361ada0d5fd21c1'
      350μsalphaeurekaselec_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
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        ClearShow all
        Date ↕MethodURLData
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