Review Article

II型糖尿病慢性并发症的预防和管理:多酚的作用(小型综述)

卷 29, 期 6, 2022

发表于: 06 January, 2022

页: [1099 - 1109] 页: 11

弟呕挨: 10.2174/0929867328666210902131021

价格: $65

摘要

糖尿病的众多并发症可能至少部分是由与持续的高血糖状态相关的氧化应激产生的。多酚是基于植物的次级代谢产物,在预防和治疗某些疾病方面具有很高的潜力,特别是那些涉及氧化应激的疾病,例如糖尿病并发症。这篇叙述性综述的目的是展示多酚在治疗和预防这些并发症中的作用的主要证据。对于书目研究,考虑了截至 2021 年 3 月 15 日发表的论文,搜索词包括与多酚、它们的类别和一些与糖尿病并发症相关的更已知化合物相关的词。有许多研究表明多酚如何有效对抗糖尿病引起的内皮损伤、氧化应激和高炎症状态,这些是糖尿病并发症的起源。黄酮类化合物以及花青素、芪或木脂素等化合物可减缓肾损伤的进展,预防缺血性事件和糖尿病肾病。许多这些研究是临床前的,在细胞或动物模型中。多酚在防治糖尿病并发症中的作用无疑是大有可为的。然而,需要进行更多的临床试验来了解这些化合物的真正有效性。

关键词: 多酚、植物化学物质、氧化应激、糖尿病、类黄酮、花青素、芪。

[1]
Pandey, K.B.; Rizvi, S.I. Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev., 2009, 2(5), 270-278.
[http://dx.doi.org/10.4161/oxim.2.5.9498] [PMID: 20716914]
[2]
Lin, S.; Zhang, G.; Liao, Y.; Pan, J.; Gong, D. Dietary flavonoids as xanthine oxidase inhibitors: Structure-affinity and structure-activity relationships. J. Agric. Food Chem., 2015, 63(35), 7784-7794.
[http://dx.doi.org/10.1021/acs.jafc.5b03386] [PMID: 26285120]
[3]
Singla, R.K.; Dubey, A.K.; Garg, A.; Sharma, R.K.; Fiorino, M.; Ameen, S.M.; Haddad, M.A.; Al-Hiary, M. Natural polyphenols: Chemical classification, definition of classes, subcategories, and structures. J. AOAC Int., 2019, 102(5), 1397-1400.
[http://dx.doi.org/10.5740/jaoacint.19-0133] [PMID: 31200785]
[4]
Aubert, C.; Chalot, G. Chemical composition, bioactive compounds, and volatiles of six table grape varieties (Vitis vinifera L.). Food Chem., 2018, 240, 524-533.
[http://dx.doi.org/10.1016/j.foodchem.2017.07.152] [PMID: 28946307]
[5]
Bars-Cortina, D.; Macià, A.; Iglesias, I.; Garanto, X.; Badiella, L.; Motilva, M.J. Seasonal variability of the phytochemical composition of new red-fleshed apple varieties compared with traditional and new white-fleshed varieties. J. Agric. Food Chem., 2018, 66(38), 10011-10025.
[http://dx.doi.org/10.1021/acs.jafc.8b03950] [PMID: 30176730]
[6]
Agati, G.; Azzarello, E.; Pollastri, S.; Tattini, M. Flavonoids as antioxidants in plants: Location and functional significance. Plant Sci., 2012, 196, 67-76.
[http://dx.doi.org/10.1016/j.plantsci.2012.07.014] [PMID: 23017900]
[7]
D’Archivio, M.; Filesi, C.; Di Benedetto, R.; Gargiulo, R.; Giovannini, C.; Masella, R. Polyphenols, dietary sources and bioavailability. Ann. Ist. Super. Sanita, 2007, 43(4), 348-361.
[PMID: 18209268]
[8]
Ozdal, T.; Sela, D.A.; Xiao, J.; Boyacioglu, D.; Chen, F.; Capanoglu, E. The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients, 2016, 8(2), 78.
[http://dx.doi.org/10.3390/nu8020078] [PMID: 26861391]
[9]
García-Conesa, M.T.; Chambers, K.; Combet, E.; Pinto, P.; Garcia-Aloy, M.; Andrés-Lacueva, C.; de Pascual-Teresa, S.; Mena, P.; Konic Ristic, A.; Hollands, W.J.; Kroon, P.A.; Rodríguez-Mateos, A.; Istas, G.; Kontogiorgis, C.A.; Rai, D.K.; Gibney, E.R.; Morand, C.; Espín, J.C.; González-Sarrías, A. Meta-analysis of the effects of foods and derived products containing ellagitannins and anthocyanins on cardiometabolic biomarkers: Analysis of factors influencing variability of the individual responses. Int. J. Mol. Sci., 2018, 19(3), E694.
[http://dx.doi.org/10.3390/ijms19030694] [PMID: 29495642]
[10]
Lewandowska, U.; Szewczyk, K.; Hrabec, E.; Janecka, A.; Gorlach, S. Overview of metabolism and bioavailability enhancement of polyphenols. J. Agric. Food Chem., 2013, 61(50), 12183-12199.
[http://dx.doi.org/10.1021/jf404439b] [PMID: 24295170]
[11]
Belguendouz, L.; Frémont, L.; Gozzelino, M.T. Interaction of transresveratrol with plasma lipoproteins. Biochem. Pharmacol., 1998, 55(6), 811-816.
[http://dx.doi.org/10.1016/S0006-2952(97)00544-3] [PMID: 9586953]
[12]
Duthie, G.G.; Gardner, P.T.; Kyle, J.A. Plant polyphenols: Are they the new magic bullet? Proc. Nutr. Soc., 2003, 62(3), 599-603.
[http://dx.doi.org/10.1079/PNS2003275] [PMID: 14692595]
[13]
Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr., 2004, 79(5), 727-747.
[http://dx.doi.org/10.1093/ajcn/79.5.727] [PMID: 15113710]
[14]
Satija, A.; Bhupathiraju, S.N.; Rimm, E.B.; Spiegelman, D.; Chiuve, S.E.; Borgi, L.; Willett, W.C.; Manson, J.E.; Sun, Q.; Hu, F.B. Plant-based dietary patterns and incidence of type 2 diabetes in US men and women: Results from three prospective cohort studies. PLoS Med., 2016, 13(6), e1002039.
[http://dx.doi.org/10.1371/journal.pmed.1002039] [PMID: 27299701]
[15]
Wang, S.; Moustaid-Moussa, N.; Chen, L.; Mo, H.; Shastri, A.; Su, R.; Bapat, P.; Kwun, I.; Shen, C.L. Novel insights of dietary polyphenols and obesity. J. Nutr. Biochem., 2014, 25(1), 1-18.
[http://dx.doi.org/10.1016/j.jnutbio.2013.09.001] [PMID: 24314860]
[16]
Baratta, F.; Pastori, D.; Bartimoccia, S.; Cammisotto, V.; Cocomello, N.; Colantoni, A.; Nocella, C.; Carnevale, R.; Ferro, D.; Angelico, F.; Violi, F.; Del Ben, M. Poor adherence to mediterranean diet and serum lipopolysaccharide are associated with oxidative stress in patients with non-alcoholic fatty liver disease. Nutrients, 2020, 12(6), E1732.
[http://dx.doi.org/10.3390/nu12061732] [PMID: 32531941]
[17]
Baratta, F.; Pastori, D.; Polimeni, L.; Bucci, T.; Ceci, F.; Calabrese, C.; Ernesti, I.; Pannitteri, G.; Violi, F.; Angelico, F.; Del Ben, M. Adherence to mediterranean diet and non-alcoholic fatty liver disease: Effect on insulin resistance. Am. J. Gastroenterol., 2017, 112(12), 1832-1839.
[http://dx.doi.org/10.1038/ajg.2017.371] [PMID: 29063908]
[18]
Guo, X.F.; Ruan, Y.; Li, Z.H.; Li, D. Flavonoid subclasses and type 2 diabetes mellitus risk: A meta-analysis of prospective cohort studies. Crit. Rev. Food Sci. Nutr., 2019, 59(17), 2850-2862.
[http://dx.doi.org/10.1080/10408398.2018.1476964] [PMID: 29768032]
[19]
Zamora-Ros, R.; Forouhi, N.G.; Sharp, S.J.; González, C.A.; Buijsse, B.; Guevara, M.; van der Schouw, Y.T.; Amiano, P.; Boeing, H.; Bredsdorff, L.; Fagherazzi, G.; Feskens, E.J.; Franks, P.W.; Grioni, S.; Katzke, V.; Key, T.J.; Khaw, K.T.; Kühn, T.; Masala, G.; Mattiello, A.; Molina-Montes, E.; Nilsson, P.M.; Overvad, K.; Perquier, F.; Redondo, M.L.; Ricceri, F.; Rolandsson, O.; Romieu, I.; Roswall, N.; Scalbert, A.; Schulze, M.; Slimani, N.; Spijkerman, A.M.; Tjonneland, A.; Tormo, M.J.; Touillaud, M.; Tumino, R. van der A, D.L.; van Woudenbergh, G.J.; Langenberg, C.; Riboli, E.; Wareham, N.J. Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations. J. Nutr., 2014, 144(3), 335-343.
[http://dx.doi.org/10.3945/jn.113.184945] [PMID: 24368432]
[20]
Guo, X.; Yang, B.; Tan, J.; Jiang, J.; Li, D. Associations of dietary intakes of anthocyanins and berry fruits with risk of type 2 diabetes mellitus: A systematic review and meta-analysis of prospective cohort studies. Eur. J. Clin. Nutr., 2016, 70(12), 1360-1367.
[http://dx.doi.org/10.1038/ejcn.2016.142] [PMID: 27530472]
[21]
Renaud, S.; de Lorgeril, M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet, 1992, 339(8808), 1523-1526.
[http://dx.doi.org/10.1016/0140-6736(92)91277-F] [PMID: 1351198]
[22]
Minutolo, F.; Sala, G.; Bagnacani, A.; Bertini, S.; Carboni, I.; Placanica, G.; Prota, G.; Rapposelli, S.; Sacchi, N.; Macchia, M.; Ghidoni, R. Synthesis of a resveratrol analogue with high ceramide-mediated proapoptotic activity on human breast cancer cells. J. Med. Chem., 2005, 48(22), 6783-6786.
[http://dx.doi.org/10.1021/jm050528k] [PMID: 16250636]
[23]
Liu, Q.; Jin, W.; Zhu, Y.; Zhou, J.; Lu, M.; Zhang, Q. Synthesis of 3′-methoxy-E-diethylstilbestrol and its analogs as tumor angiogenesis inhibitors. Steroids, 2012, 77(5), 419-423.
[http://dx.doi.org/10.1016/j.steroids.2011.12.024] [PMID: 22280958]
[24]
Mulakayala, C.; Babajan, B.; Madhusudana, P.; Anuradha, C.M.; Rao, R.M.; Nune, R.P.; Manna, S.K.; Mulakayala, N.; Kumar, C.S. Synthesis and evaluation of resveratrol derivatives as new chemical entities for cancer. J. Mol. Graph. Model., 2013, 41, 43-54.
[http://dx.doi.org/10.1016/j.jmgm.2013.01.005] [PMID: 23500626]
[25]
Hoshino, J.; Park, E.J.; Kondratyuk, T.P.; Marler, L.; Pezzuto, J.M.; van Breemen, R.B.; Mo, S.; Li, Y.; Cushman, M. Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites. J. Med. Chem., 2010, 53(13), 5033-5043.
[http://dx.doi.org/10.1021/jm100274c] [PMID: 20527891]
[26]
Lu, C.; Guo, Y.; Yan, J.; Luo, Z.; Luo, H.B.; Yan, M.; Huang, L.; Li, X. Design, synthesis, and evaluation of multitarget-directed resveratrol derivatives for the treatment of Alzheimer’s disease. J. Med. Chem., 2013, 56(14), 5843-5859.
[http://dx.doi.org/10.1021/jm400567s] [PMID: 23799643]
[27]
Tavaf, Z.; Dangolani, S.K.; Yousefi, R.; Panahi, F.; Shahsavani, M.B.; Khalafi-Nezhad, A. Synthesis of new curcumin derivatives as influential antidiabetic α-glucosidase and α-amylase inhibitors with anti-oxidant activity. Carbohydr. Res., 2020, 494, 108069.
[http://dx.doi.org/10.1016/j.carres.2020.108069] [PMID: 32563890]
[28]
Kim, J.A.; Montagnani, M.; Chandrasekran, S.; Quon, M.J. Role of lipotoxicity in endothelial dysfunction. Heart Fail. Clin., 2012, 8(4), 589-607.
[http://dx.doi.org/10.1016/j.hfc.2012.06.012] [PMID: 22999242]
[29]
Kim, J.A.; Montagnani, M.; Koh, K.K.; Quon, M.J. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation, 2006, 113(15), 1888-1904.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.563213] [PMID: 16618833]
[30]
Dauchet, L.; Ferrières, J.; Arveiler, D.; Yarnell, J.W.; Gey, F.; Ducimetière, P.; Ruidavets, J.B.; Haas, B.; Evans, A.; Bingham, A.; Amouyel, P.; Dallongeville, J. Frequency of fruit and vegetable consumption and coronary heart disease in France and Northern Ireland: the PRIME study. Br. J. Nutr., 2004, 92(6), 963-972.
[http://dx.doi.org/10.1079/BJN20041286] [PMID: 15613259]
[31]
Joshipura, K.J.; Ascherio, A.; Manson, J.E.; Stampfer, M.J.; Rimm, E.B.; Speizer, F.E.; Hennekens, C.H.; Spiegelman, D.; Willett, W.C. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA, 1999, 282(13), 1233-1239.
[http://dx.doi.org/10.1001/jama.282.13.1233] [PMID: 10517425]
[32]
Larsson, S.C.; Wolk, A. Dietary fiber intake is inversely associated with stroke incidence in healthy Swedish adults. J. Nutr., 2014, 144(12), 1952-1955.
[http://dx.doi.org/10.3945/jn.114.200634] [PMID: 25411032]
[33]
Baron, A.D. Cardiovascular actions of insulin in humans. Implications for insulin sensitivity and vascular tone. Baillieres Clin. Endocrinol. Metab., 1993, 7(4), 961-987.
[http://dx.doi.org/10.1016/S0950-351X(05)80241-1] [PMID: 8304919]
[34]
Montagnani, M.; Ravichandran, L.V.; Chen, H.; Esposito, D.L.; Quon, M.J. Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol. Endocrinol., 2002, 16(8), 1931-1942.
[http://dx.doi.org/10.1210/me.2002-0074] [PMID: 12145346]
[35]
Duarte, J.; Pérez-Palencia, R.; Vargas, F.; Ocete, M.A.; Pérez-Vizcaino, F.; Zarzuelo, A.; Tamargo, J. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br. J. Pharmacol., 2001, 133(1), 117-124.
[http://dx.doi.org/10.1038/sj.bjp.0704064] [PMID: 11325801]
[36]
Galindo, P.; Rodriguez-Gómez, I.; González-Manzano, S.; Dueñas, M.; Jiménez, R.; Menéndez, C.; Vargas, F.; Tamargo, J.; Santos-Buelga, C.; Pérez-Vizcaíno, F.; Duarte, J. Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation. PLoS One, 2012, 7(3), e32673.
[http://dx.doi.org/10.1371/journal.pone.0032673] [PMID: 22427863]
[37]
Pérez-Vizcaíno, F.; Ibarra, M.; Cogolludo, A.L.; Duarte, J.; Zaragozá-Arnáez, F.; Moreno, L.; López-López, G.; Tamargo, J. Endothelium-independent vasodilator effects of the flavonoid quercetin and its methylated metabolites in rat conductance and resistance arteries. J. Pharmacol. Exp. Ther., 2002, 302(1), 66-72.
[http://dx.doi.org/10.1124/jpet.302.1.66] [PMID: 12065701]
[38]
Anter, E.; Thomas, S.R.; Schulz, E.; Shapira, O.M.; Vita, J.A.; Keaney, J.F., Jr Activation of endothelial nitric-oxide synthase by the p38 MAPK in response to black tea polyphenols. J. Biol. Chem., 2004, 279(45), 46637-46643.
[http://dx.doi.org/10.1074/jbc.M405547200] [PMID: 15333638]
[39]
Loke, W.M.; Hodgson, J.M.; Proudfoot, J.M.; McKinley, A.J.; Puddey, I.B.; Croft, K.D. Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am. J. Clin. Nutr., 2008, 88(4), 1018-1025.
[http://dx.doi.org/10.1093/ajcn/88.4.1018] [PMID: 18842789]
[40]
Ko, F.N.; Huang, T.F.; Teng, C.M. Vasodilatory action mechanisms of apigenin isolated from Apium graveolens in rat thoracic aorta. Biochim. Biophys. Acta, 1991, 1115(1), 69-74.
[http://dx.doi.org/10.1016/0304-4165(91)90013-7] [PMID: 1659912]
[41]
Qin, C.X.; Chen, X.; Hughes, R.A.; Williams, S.J.; Woodman, O.L. Understanding the cardioprotective effects of flavonols: discovery of relaxant flavonols without antioxidant activity. J. Med. Chem., 2008, 51(6), 1874-1884.
[http://dx.doi.org/10.1021/jm070352h] [PMID: 18307286]
[42]
Chan, E.C.; Drummond, G.R.; Woodman, O.L. 3′, 4′-dihydroxyflavonol enhances nitric oxide bioavailability and improves vascular function after ischemia and reperfusion injury in the rat. J. Cardiovasc. Pharmacol., 2003, 42(6), 727-735.
[http://dx.doi.org/10.1097/00005344-200312000-00006] [PMID: 14639094]
[43]
Arredondo, F.; Echeverry, C.; Abin-Carriquiry, J.A.; Blasina, F.; Antúnez, K.; Jones, D.P.; Go, Y.M.; Liang, Y.L.; Dajas, F. After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Radic. Biol. Med., 2010, 49(5), 738-747.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.05.020] [PMID: 20554019]
[44]
Mahn, K.; Borrás, C.; Knock, G.A.; Taylor, P.; Khan, I.Y.; Sugden, D.; Poston, L.; Ward, J.P.; Sharpe, R.M.; Viña, J.; Aaronson, P.I.; Mann, G.E. Dietary soy isoflavone induced increases in antioxidant and eNOS gene expression lead to improved endothelial function and reduced blood pressure in vivo. FASEB J., 2005, 19(12), 1755-1757.
[http://dx.doi.org/10.1096/fj.05-4008fje] [PMID: 16107535]
[45]
Mann, G.E.; Rowlands, D.J.; Li, F.Y.; de Winter, P.; Siow, R.C. Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression. Cardiovasc. Res., 2007, 75(2), 261-274.
[http://dx.doi.org/10.1016/j.cardiores.2007.04.004] [PMID: 17498676]
[46]
Hong, J.; Smith, T.J.; Ho, C.T.; August, D.A.; Yang, C.S. Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues. Biochem. Pharmacol., 2001, 62(9), 1175-1183.
[http://dx.doi.org/10.1016/S0006-2952(01)00767-5] [PMID: 11705450]
[47]
Laughton, M.J.; Evans, P.J.; Moroney, M.A.; Hoult, J.R.; Halliwell, B. Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives. Relationship to antioxidant activity and to iron ion-reducing ability. Biochem. Pharmacol., 1991, 42(9), 1673-1681.
[http://dx.doi.org/10.1016/0006-2952(91)90501-U] [PMID: 1656994]
[48]
Kobuchi, H.; Roy, S.; Sen, C.K.; Nguyen, H.G.; Packer, L. Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway. Am. J. Physiol., 1999, 277(3), C403-C411.
[http://dx.doi.org/10.1152/ajpcell.1999.277.3.C403] [PMID: 10484327]
[49]
Chen, C.C.; Chow, M.P.; Huang, W.C.; Lin, Y.C.; Chang, Y.J. Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure-activity relationships. Mol. Pharmacol., 2004, 66(3), 683-693.
[PMID: 15322261]
[50]
Hämäläinen, M.; Nieminen, R.; Vuorela, P.; Heinonen, M.; Moilanen, E. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm., 2007, 2007, 45673.
[http://dx.doi.org/10.1155/2007/45673] [PMID: 18274639]
[51]
Comalada, M.; Ballester, I.; Bailón, E.; Sierra, S.; Xaus, J.; Gálvez, J.; de Medina, F.S.; Zarzuelo, A. Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship. Biochem. Pharmacol., 2006, 72(8), 1010-1021.
[http://dx.doi.org/10.1016/j.bcp.2006.07.016] [PMID: 16934226]
[52]
García-Mediavilla, V.; Crespo, I.; Collado, P.S.; Esteller, A.; Sánchez-Campos, S.; Tuñón, M.J.; González-Gallego, J. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur. J. Pharmacol., 2007, 557(2-3), 221-229.
[http://dx.doi.org/10.1016/j.ejphar.2006.11.014] [PMID: 17184768]
[53]
Kim, E.K.; Kwon, K.B.; Song, M.Y.; Han, M.J.; Lee, J.H.; Lee, Y.R.; Lee, J.H.; Ryu, D.G.; Park, B.H.; Park, J.W. Flavonoids protect against cytokine-induced pancreatic beta-cell damage through suppression of nuclear factor kappaB activation. Pancreas, 2007, 35(4), e1-e9.
[http://dx.doi.org/10.1097/mpa.0b013e31811ed0d2] [PMID: 18090225]
[54]
Jiang, F.; Guo, N.; Dusting, G.J. 3′,4′-Dihydroxyflavonol down-regulates monocyte chemoattractant protein-1 in smooth muscle: role of focal adhesion kinase and PDGF receptor signalling. Br. J. Pharmacol., 2009, 157(4), 597-606.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00199.x] [PMID: 19371329]
[55]
Kempuraj, D.; Madhappan, B.; Christodoulou, S.; Boucher, W.; Cao, J.; Papadopoulou, N.; Cetrulo, C.L.; Theoharides, T.C. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br. J. Pharmacol., 2005, 145(7), 934-944.
[http://dx.doi.org/10.1038/sj.bjp.0706246] [PMID: 15912140]
[56]
Kang, R.; Tang, D.; Schapiro, N.E.; Livesey, K.M.; Farkas, A.; Loughran, P.; Bierhaus, A.; Lotze, M.T.; Zeh, H.J. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ., 2010, 17(4), 666-676.
[http://dx.doi.org/10.1038/cdd.2009.149] [PMID: 19834494]
[57]
Yang, Y.S.; Wang, C.J.; Huang, C.N.; Chen, M.L.; Chen, M.J.; Peng, C.H. Polyphenols of Hibiscus sabdariffa improved diabetic nephropathy via attenuating renal epithelial mesenchymal transition. J. Agric. Food Chem., 2013, 61(31), 7545-7551.
[http://dx.doi.org/10.1021/jf4020735] [PMID: 23848500]
[58]
Ribaldo, P.D.; Souza, D.S.; Biswas, S.K.; Block, K.; Lopes de Faria, J.M.; Lopes de Faria, J.B. Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats. J. Nutr., 2009, 139(1), 96-100.
[http://dx.doi.org/10.3945/jn.108.095018] [PMID: 19056645]
[59]
Faria, A.M.; Papadimitriou, A.; Silva, K.C.; Lopes de Faria, J.M.; Lopes de Faria, J.B. Uncoupling endothelial nitric oxide synthase is ameliorated by green tea in experimental diabetes by re-establishing tetrahydrobiopterin levels. Diabetes, 2012, 61(7), 1838-1847.
[http://dx.doi.org/10.2337/db11-1241] [PMID: 22586583]
[60]
Peixoto, E.B.; Papadimitriou, A.; Teixeira, D.A.; Montemurro, C.; Duarte, D.A.; Silva, K.C.; Joazeiro, P.P.; Lopes de Faria, J.M.; Lopes de Faria, J.B. Reduced LRP6 expression and increase in the interaction of GSK3β with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea. J. Nutr. Biochem., 2015, 26(4), 416-430.
[http://dx.doi.org/10.1016/j.jnutbio.2014.11.012] [PMID: 25655048]
[61]
Chung, S.S.; Chung, S.K. Aldose reductase in diabetic microvascular complications. Curr. Drug Targets, 2005, 6(4), 475-486.
[http://dx.doi.org/10.2174/1389450054021891] [PMID: 16026266]
[62]
Caldwell, R.B.; Bartoli, M.; Behzadian, M.A.; El-Remessy, A.E.; Al-Shabrawey, M.; Platt, D.H.; Liou, G.I.; Caldwell, R.W. Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr. Drug Targets, 2005, 6(4), 511-524.
[http://dx.doi.org/10.2174/1389450054021981] [PMID: 16026270]
[63]
Aiello, L.P.; Bursell, S.E.; Clermont, A.; Duh, E.; Ishii, H.; Takagi, C.; Mori, F.; Ciulla, T.A.; Ways, K.; Jirousek, M.; Smith, L.E.; King, G.L. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes, 1997, 46(9), 1473-1480.
[http://dx.doi.org/10.2337/diab.46.9.1473] [PMID: 9287049]
[64]
Delmas, D.; Cornebise, C.; Courtaut, F.; Xiao, J.; Aires, V. New Highlights of Resveratrol: A Review of Properties against Ocular Diseases. Int. J. Mol. Sci., 2021, 22(3), 1295.
[http://dx.doi.org/10.3390/ijms22031295] [PMID: 33525499]
[65]
Nabavi, S.F.; Barber, A.J.; Spagnuolo, C.; Russo, G.L.; Daglia, M.; Nabavi, S.M.; Sobarzo-Sánchez, E. Nrf2 as molecular target for polyphenols: A novel therapeutic strategy in diabetic retinopathy. Crit. Rev. Clin. Lab. Sci., 2016, 53(5), 293-312.
[http://dx.doi.org/10.3109/10408363.2015.1129530] [PMID: 26926494]
[66]
Ott, C.; Jacobs, K.; Haucke, E.; Navarrete Santos, A.; Grune, T.; Simm, A. Role of advanced glycation end products in cellular signaling. Redox Biol., 2014, 2, 411-429.
[http://dx.doi.org/10.1016/j.redox.2013.12.016] [PMID: 24624331]
[67]
Asadi, S.; Gholami, M.S.; Siassi, F.; Qorbani, M.; Sotoudeh, G. Beneficial effects of nano-curcumin supplement on depression and anxiety in diabetic patients with peripheral neuropathy: A randomized, double-blind, placebo-controlled clinical trial. Phytother. Res., 2020, 34(4), 896-903.
[http://dx.doi.org/10.1002/ptr.6571] [PMID: 31788880]
[68]
Pari, L.; Murugan, P. Tetrahydrocurcumin prevents brain lipid peroxidation in streptozotocin-induced diabetic rats. J. Med. Food, 2007, 10(2), 323-329.
[http://dx.doi.org/10.1089/jmf.2006.058] [PMID: 17651069]
[69]
Ji, C.; Xu, Y.; Han, F.; Sun, D.; Zhang, H.; Li, X.; Yao, X.; Wang, H. Quercetin alleviates thermal and cold hyperalgesia in a rat neuropathic pain model by inhibiting Toll-like receptor signaling. Biomed. Pharmacother., 2017, 94, 652-658.
[http://dx.doi.org/10.1016/j.biopha.2017.07.145] [PMID: 28787700]
[70]
Basu, P.; Maier, C.; Basu, A. Effects of curcumin and its different formulations in preclinical and clinical studies of peripheral neuropathic and postoperative pain: a comprehensive review. Int. J. Mol. Sci., 2021, 22(9), 4666.
[http://dx.doi.org/10.3390/ijms22094666] [PMID: 33925121]
[71]
Hanhineva, K.; Törrönen, R.; Bondia-Pons, I.; Pekkinen, J.; Kolehmainen, M.; Mykkänen, H.; Poutanen, K. Impact of dietary polyphenols on carbohydrate metabolism. Int. J. Mol. Sci., 2010, 11(4), 1365-1402.
[http://dx.doi.org/10.3390/ijms11041365] [PMID: 20480025]
[72]
Berná, G.; Oliveras-López, M.J.; Jurado-Ruíz, E.; Tejedo, J.; Bedoya, F.; Soria, B.; Martín, F. Nutrigenetics and nutrigenomics insights into diabetes etiopathogenesis. Nutrients, 2014, 6(11), 5338-5369.
[http://dx.doi.org/10.3390/nu6115338] [PMID: 25421534]
[73]
Brownlee, M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 2005, 54(6), 1615-1625.
[http://dx.doi.org/10.2337/diabetes.54.6.1615] [PMID: 15919781]
[74]
Johnson, R.; Dludla, P.; Joubert, E.; February, F.; Mazibuko, S.; Ghoor, S.; Muller, C.; Louw, J. Aspalathin, a dihydrochalcone C-glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis. Mol. Nutr. Food Res., 2016, 60(4), 922-934.
[http://dx.doi.org/10.1002/mnfr.201500656] [PMID: 26773306]
[75]
Ortega, Á.; Berná, G.; Rojas, A.; Martín, F.; Soria, B. Gene-diet interactions in type 2 diabetes: the chicken and egg debate. Int. J. Mol. Sci., 2017, 18(6), E1188.
[http://dx.doi.org/10.3390/ijms18061188] [PMID: 28574454]
[76]
Vetterli, L.; Brun, T.; Giovannoni, L.; Bosco, D.; Maechler, P. Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism. J. Biol. Chem., 2011, 286(8), 6049-6060.
[http://dx.doi.org/10.1074/jbc.M110.176842] [PMID: 21163946]
[77]
Rouse, M.; Younès, A.; Egan, J.M. Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity. J. Endocrinol., 2014, 223(2), 107-117.
[http://dx.doi.org/10.1530/JOE-14-0335] [PMID: 25297556]
[78]
Newsholme, P.; Cruzat, V.F.; Keane, K.N.; Carlessi, R.; de Bittencourt, P.I. Jr Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem. J., 2016, 473(24), 4527-4550.
[http://dx.doi.org/10.1042/BCJ20160503C] [PMID: 27941030]
[79]
Kampmann, U.; Christensen, B.; Nielsen, T.S.; Pedersen, S.B.; Ørskov, L.; Lund, S.; Møller, N.; Jessen, N. GLUT4 and UBC9 protein expression is reduced in muscle from type 2 diabetic patients with severe insulin resistance. PLoS One, 2011, 6(11), e27854.
[http://dx.doi.org/10.1371/journal.pone.0027854] [PMID: 22114711]
[80]
Schenk, S.; McCurdy, C.E.; Philp, A.; Chen, M.Z.; Holliday, M.J.; Bandyopadhyay, G.K.; Osborn, O.; Baar, K.; Olefsky, J.M. Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction. J. Clin. Invest., 2011, 121(11), 4281-4288.
[http://dx.doi.org/10.1172/JCI58554] [PMID: 21985785]

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Request history8.2.27PHP Version543msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
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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
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
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      1.34msalphaeurekaselec_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
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      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 >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) 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 >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) 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 >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) 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 >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) 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 >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) 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 >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 314538714 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314538714) limit 1
      17.98msalphaeurekaselec_live_10_06_2022UserAccess.php#784
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      • 1: 314538714
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      • 4: 314538714
      • 5: 314538714
      • 6: 314538714
      • 7: 314538714
      • 8: 314538714
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      • 10: 314538714
      • 11: 314538714
      • 12: 314538714
      • 13: 314538714
      • 14: 314538714
      • 15: 314538714
      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=117636
      1.21msalphaeurekaselec_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` = 25 limit 1
      2.28msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 25
      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=25) and sj.journal_id!=25 group by `j`.`nid`) as `aggregate_table`
      2.21msalphaeurekaselec_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=25) and sj.journal_id!=25 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.89msalphaeurekaselec_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=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      5.47msalphaeurekaselec_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=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      3.5msalphaeurekaselec_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` = '117636'
      1.58msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 117636
      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` = '117636'
      27.48msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 117636
      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` = '117636' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      18.45msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 117636
      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
      390μsalphaeurekaselec_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
      3.47msalphaeurekaselec_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 = 25 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      53.38msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      33.68msalphaeurekaselec_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 = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      27.76msalphaeurekaselec_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` = 117636 limit 1
      280μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 117636
      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 = 117636 and content_type = 'article' order by status desc limit 1
      260μsalphaeurekaselec_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` = 196090 limit 1
      190μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 196090
      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
      210μsalphaeurekaselec_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` = 'CMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      390μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMC
      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 = '117636' 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) )
      560μsalphaeurekaselec_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 = '11305' 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) )
      480μsalphaeurekaselec_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 = '3240' 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) )
      470μsalphaeurekaselec_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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3240) 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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3240) 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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3240)
      19.77msalphaeurekaselec_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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11305) 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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11305) 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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11305)
      1msalphaeurekaselec_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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 117636) 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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 117636) 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 <= 314538714 and j.to_ip >=314538714 )) and ((j.from_date <= 1740458522 and j.to_date >= 1740458522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 117636)
      900μsalphaeurekaselec_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` < '1099' and is_uploaded = 1 and issue_id = 11305 order by cast(first_page as SIGNED) desc limit 1
      800μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1099
      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` > '1109' and is_uploaded = 1 and issue_id = 11305 order by cast(first_page as SIGNED) asc limit 1
      700μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1109
      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` = 'cn'
      270μsalphaeurekaselec_live_10_06_2022ArticleController.php#2486
      Bindings
      • 0: cn
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2486
      • 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` = 2
      310μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 2
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2487
      • 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 `multilanguage_article` where (`language_id` = 2 and `article_id` = 117636)
      9.45msalphaeurekaselec_live_10_06_2022ArticleController.php#2488
      Bindings
      • 0: 2
      • 1: 117636
      Backtrace
      • 15. app/Http/Controllers/ArticleController.php:2488
      • 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
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `keyword` from `multilanguage_keywords` where (`language_id` = 2 and `article_id` = 117636)
      5.19msalphaeurekaselec_live_10_06_2022ArticleController.php#2489
      Bindings
      • 0: 2
      • 1: 117636
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2489
      • 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 CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT_WS(' ',au.last_name, ', ', ifnull(au.initials,''), ' ', au.first_name) as authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs , `au`.*, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `multilanguage_authors` as `au` left join `multilanguage_author_affiliation` as `af` on `au`.`id` = `af`.`author_id` where `au`.`article_id` = 117636 group by `au`.`id` order by `au`.`article_id` asc, `au`.`sequence` asc
      9.94msalphaeurekaselec_live_10_06_2022MultiLangAuthor.php#30
      Bindings
      • 0: 117636
      Backtrace
      • 13. app/Models/MultiLangAuthor.php:30
      • 14. app/Http/Controllers/ArticleController.php:2493
      • 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 `multilanguage_journal`.`title` from `multilanguage_journal` where `multilanguage_journal`.`journal_id` = 25 and `language_id` = 2
      420μsalphaeurekaselec_live_10_06_2022ArticleController.php#2495
      Bindings
      • 0: 25
      • 1: 2
      Backtrace
      • 13. app/Http/Controllers/ArticleController.php:2495
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `id` from `multilanguage_article` where `article_id` = 117636 limit 1
      3.89msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 117636
      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` = 25 and `b`.`banner_from_date` <= 1740458522 and `b`.`banner_to_date` >= 1740458522 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      2.52msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740458522
      • 4: 1740458522
      • 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` = 25 and `b`.`banner_from_date` <= 1740458522 and `b`.`banner_to_date` >= 1740458522 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.89msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740458522
      • 4: 1740458522
      • 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='511f953ee4c4d64d6860fc99f13af201'
      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
    App\Models\MultiLangArticle
    2MultiLangArticle.php#?
    App\Models\MultiLanguage
    1MultiLanguage.php#?
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 04:42:02GET/article/117636/cn414403