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Current Pharmaceutical Biotechnology

Editor-in-Chief

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

Research Article

LTBP1 Gene Expression in the Cerebral Cortex and its Neuroprotective Mechanism in Mice with Postischemic Stroke Epilepsy

Author(s): Bo Liu, Yan Wang, Dongruo He, Guochao Han, Hao Wang, Yuan Lin, Tianyu Zhang, Chao Yi and Hui Li*

Volume 24, Issue 2, 2023

Published on: 20 August, 2022

Page: [317 - 329] Pages: 13

DOI: 10.2174/1389201023666220608091511

Price: $65

Abstract

Objective: This study aimed at exploring the expression level of LTBP1 in the mouse model of epilepsy. The mechanism of LTBP1 in epileptic cerebral neural stem cells was deeply investigated to control the occurrence of epilepsy with neuroprotection.

Methods: qRT-PCR was conducted for the expression levels of LTBP1 in clinical human epileptic tissues and neural stem cells, as well as normal cerebral tissues and neural stem cells. The mouse model of postischemic stroke epilepsy (PSE) was established by the middle cerebral artery occlusion (MCAO). Then, qRT-PCR was conducted again for the expression levels of LTBP1 in mouse epileptic tissues and neural stem cells as well as normal cerebral tissues and neural stem cells. The activation and inhibitory vectors of LTBP1 were constructed to detect the effects of LTBP1 on the proliferation of cerebral neural stem cells in the PSE model combined with CCK-8. Finally, Western blot was conducted for the specific mechanism of LTBP1 affecting the development of epileptic cells.

Results: Racine score and epilepsy index of 15 mice showed epilepsy symptoms after the determination with MCAO, showing a successful establishment of the PSE model. LTBP1 expression in both diseased epileptic tissues and cells was higher than that in normal clinical epileptic tissues and cells. Meanwhile, qRT-PCR showed higher LTBP1 expression in both mouse epileptic tissues and their neural stem cells compared to that in normal tissues and cells. CCK-8 showed that the activation of LTBP1 stimulated the increased proliferative capacity of epileptic cells, while the inhibition of LTBP1 expression controlled the proliferation of epileptic cells. Western blot showed an elevated expression of TGFβ/SMAD signaling pathway-associated protein SMAD1/5/8 after activating LTBP1. The expression of molecular MMP-13 associated with the occurrence of inflammation was also activated.

Conclusion: LTBP1 can affect the changes in inflammation-related pathways by activating the TGFβ/SMAD signaling pathway and stimulate the development of epilepsy, and the inhibition of LTBP1 expression can control the occurrence of epilepsy with neuroprotection.

Keywords: LTBP1, TGFβ/SMAD, epilepsy, neuroprotection, mechanism, inflammation

Graphical Abstract

[1]
Tanaka, T.; Ihara, M. Post-stroke epilepsy. Neurochem. Int., 2017, 107, 219-228.
[http://dx.doi.org/10.1016/j.neuint.2017.02.002] [PMID: 28202284]
[2]
Zhao, Y.; Li, X.; Zhang, K.; Tong, T.; Cui, R. The progress of epilepsy after stroke. Curr. Neuropharmacol., 2018, 16(1), 71-78.
[PMID: 28606039]
[3]
Marchi, A.; Pennaroli, D.; Lagarde, S.; McGonigal, A.; Bonini, F.; Carron, R.; Lépine, A.; Villeneuve, N.; Trebuchon, A.; Pizzo, F.; Scavarda, D.; Bartolomei, F. Epileptogenicity and surgical outcome in post stroke drug resistant epilepsy in children and adults. Epilepsy Res., 2019, 155, 106155.
[http://dx.doi.org/10.1016/j.eplepsyres.2019.106155] [PMID: 31252221]
[4]
Altman, K.; Shavit-Stein, E.; Maggio, N. Post stroke seizures and epilepsy: From proteases to maladaptive plasticity. Front. Cell. Neurosci., 2019, 13, 397.
[http://dx.doi.org/10.3389/fncel.2019.00397] [PMID: 31607864]
[5]
Zhang, B.; Chen, M.; Yang, H.; Wu, T.; Song, C.; Guo, R. Evidence for involvement of the CD40/CD40L system in post-stroke epilepsy. Neurosci. Lett., 2014, 567, 6-10.
[http://dx.doi.org/10.1016/j.neulet.2014.03.003] [PMID: 24657679]
[6]
Chepurnov, S.A.; Suleĭmanova, E.M.; Guliaev, M.V.; Abbasova, K.R.; Pirogov, IuA.; Chepurnova, N.E. Neuroprotection in epilepsy. Usp. Fiziol. Nauk, 2012, 43(2), 55-71.
[PMID: 22690591]
[7]
Rana, A.; Musto, A.E. The role of inflammation in the development of epilepsy. J. Neuroinflammation, 2018, 15(1), 144.
[http://dx.doi.org/10.1186/s12974-018-1192-7] [PMID: 29764485]
[8]
Vezzani, A.; Fujinami, R.S.; White, H.S.; Preux, P.M.; Blümcke, I.; Sander, J.W.; Löscher, W. Infections, inflammation and epilepsy. Acta Neuropathol., 2016, 131(2), 211-234.
[http://dx.doi.org/10.1007/s00401-015-1481-5] [PMID: 26423537]
[9]
Dupuis, N.; Auvin, S. Inflammation and epilepsy in the developing brain: clinical and experimental evidence. CNS Neurosci. Ther., 2015, 21(2), 141-151.
[http://dx.doi.org/10.1111/cns.12371] [PMID: 25604829]
[10]
Davison, K.L.; Crowcroft, N.S.; Ramsay, M.E.; Brown, D.W.; Andrews, N.J. Viral encephalitis in England, 1989-1998: What did we miss? Emerg. Infect. Dis., 2003, 9(2), 234-240.
[http://dx.doi.org/10.3201/eid0902.020218] [PMID: 12603996]
[11]
Iyer, A.; Zurolo, E.; Spliet, W.G.; van Rijen, P.C.; Baayen, J.C.; Gorter, J.A.; Aronica, E. Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias. Epilepsia, 2010, 51(9), 1763-1773.
[http://dx.doi.org/10.1111/j.1528-1167.2010.02547.x] [PMID: 20345941]
[12]
Vezzani, A.; Aronica, E.; Mazarati, A.; Pittman, Q.J. Epilepsy and brain inflammation. Exp. Neurol., 2013, 244, 11-21.
[http://dx.doi.org/10.1016/j.expneurol.2011.09.033] [PMID: 21985866]
[13]
Nakajima, Y.; Miyazono, K.; Nakamura, H. Immunolocalization of latent transforming growth factor-beta binding protein-1 (LTBP1) during mouse development: possible roles in epithelial and mesenchymal cytodifferentiation. Cell Tissue Res., 1999, 295(2), 257-267.
[http://dx.doi.org/10.1007/s004410051232] [PMID: 9931372]
[14]
Robertson, I.B.; Horiguchi, M.; Zilberberg, L.; Dabovic, B.; Hadjiolova, K.; Rifkin, D.B. Latent TGF-β-binding proteins. Matrix Biol., 2015, 47, 44-53.
[http://dx.doi.org/10.1016/j.matbio.2015.05.005] [PMID: 25960419]
[15]
Cao, B.; Yang, L.; Rong, W.; Feng, L.; Han, N.; Zhang, K.; Cheng, S.; Wu, J.; Xiao, T.; Gao, Y. Latent transforming growth factor-beta binding protein-1 in circulating plasma as a novel biomarker for early detection of hepatocellular carcinoma. Int. J. Clin. Exp. Pathol., 2015, 8(12), 16046-16054.
[PMID: 26884881]
[16]
Fu, Y.; Wu, Z.; Guo, Z.; Chen, L.; Ma, Y.; Wang, Z.; Xiao, W.; Wang, Y. Systems-level analysis identifies key regulators driving epileptogenesis in temporal lobe epilepsy. Genomics, 2020, 112(2), 1768-1780.
[http://dx.doi.org/10.1016/j.ygeno.2019.09.020] [PMID: 31669700]
[17]
Coste de Bagneaux, P.; von Elsner, L.; Bierhals, T.; Campiglio, M.; Johannsen, J.; Obermair, G.J.; Hempel, M.; Flucher, B.E.; Kutsche, K. A homozygous missense variant in CACNB4 encoding the auxiliary calcium channel beta4 subunit causes a severe neurodevelopmental disorder and impairs channel and non-channel functions. PLoS Genet., 2020, 16(3), e1008625.
[http://dx.doi.org/10.1371/journal.pgen.1008625] [PMID: 32176688]
[18]
Saharinen, J.; Taipale, J.; Keski-Oja, J. Association of the small latent transforming growth factor-beta with an eight cysteine repeat of its binding protein LTBP-1. EMBO J., 1996, 15(2), 245-253.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00355.x] [PMID: 8617200]
[19]
Chen, Y.; Dabovic, B.; Annes, J.P.; Rifkin, D.B. Latent TGF-Beta Binding Protein-3 (LTBP-3) requires binding to TGF-beta for secretion. FEBS Lett., 2002, 517(1-3), 277-280.
[http://dx.doi.org/10.1016/S0014-5793(02)02648-0] [PMID: 12062452]
[20]
Caraci, F.; Spampinato, S.F.; Morgese, M.G.; Tascedda, F.; Salluzzo, M.G.; Giambirtone, M.C.; Caruso, G.; Munafò, A.; Torrisi, S.A.; Leggio, G.M.; Trabace, L.; Nicoletti, F.; Drago, F.; Sortino, M.A.; Copani, A.; Copani, A. Neurobiological links between depression and AD: The role of TGF-β1 signaling as a new pharmacological target. Pharmacol. Res., 2018, 130, 374-384.
[http://dx.doi.org/10.1016/j.phrs.2018.02.007] [PMID: 29438781]
[21]
Dobolyi, A.; Palkovits, M. Expression of latent transforming growth factor beta binding proteins in the rat brain. J. Comp. Neurol., 2008, 507(3), 1393-1408.
[http://dx.doi.org/10.1002/cne.21621] [PMID: 18196529]
[22]
Zhu, Y.; Culmsee, C.; Roth-Eichhorn, S.; Krieglstein, J. Beta(2)-adrenoceptor stimulation enhances latent transforming growth factor-beta-binding protein-1 and transforming growth factor-beta1 expression in rat hippocampus after transient forebrain ischemia. Neuroscience, 2001, 107(4), 593-602.
[http://dx.doi.org/10.1016/S0306-4522(01)00357-8] [PMID: 11720783]
[23]
Chen, X.; Liu, Z.; Cao, B.B.; Qiu, Y.H.; Peng, Y.P. TGF-β1 Neuroprotection via inhibition of microglial activation in a rat model of Parkinson’s disease. J. Neuroimmune Pharmacol., 2017, 12(3), 433-446.
[http://dx.doi.org/10.1007/s11481-017-9732-y] [PMID: 28429275]
[24]
Wang, X.Y.; Ba, Y.C.; Xiong, L.L.; Li, X.L.; Zou, Y.; Zhu, Y.C.; Zhou, X.F.; Wang, T.H.; Wang, F.; Tian, H.L.; Li, J.T. Erratum to: Endogenous TGFβ1 plays a crucial role in functional recovery after traumatic brain injury associated with smad3 signal in rats. Neurochem. Res., 2016, 41(5), 1209.
[http://dx.doi.org/10.1007/s11064-016-1865-5] [PMID: 26915105]
[25]
Ueki, Y.; Reh, T.A. Activation of BMP-Smad1/5/8 signaling promotes survival of retinal ganglion cells after damage in vivo. PLoS One, 2012, 7(6), e38690.
[http://dx.doi.org/10.1371/journal.pone.0038690] [PMID: 22701694]
[26]
Nishida, T.; Kubota, S.; Aoyama, E.; Takigawa, M. Impaired glycolytic metabolism causes chondrocyte hypertrophy-like changes via promotion of phospho-Smad1/5/8 translocation into nucleus. Osteoarthritis Cartilage, 2013, 21(5), 700-709.
[http://dx.doi.org/10.1016/j.joca.2013.01.013] [PMID: 23384547]
[27]
Pittayapruek, P.; Meephansan, J.; Prapapan, O.; Komine, M.; Ohtsuki, M. Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int. J. Mol. Sci., 2016, 17(6), 868.
[http://dx.doi.org/10.3390/ijms17060868] [PMID: 27271600]
[28]
Shi, G.; Cheng, Y.; Zhang, Y.; Guo, R.; Li, S.; Hong, X. Long non-coding RNA LINC00511/miR-150/MMP13 axis promotes breast cancer proliferation, migration and invasion. Biochim. Biophys. Acta Mol. Basis Dis., 2021, 1867(3), 165957.
[http://dx.doi.org/10.1016/j.bbadis.2020.165957] [PMID: 33031905]
[29]
Ji, B.; Ma, Y.; Wang, H.; Fang, X.; Shi, P. Activation of the P38/CREB/MMP13 axis is associated with osteoarthritis. Drug Des. Devel. Ther., 2019, 13, 2195-2204.
[http://dx.doi.org/10.2147/DDDT.S209626] [PMID: 31308631]
[30]
Cabrera, S.; Maciel, M.; Hernández-Barrientos, D.; Calyeca, J.; Gaxiola, M.; Selman, M.; Pardo, A. Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3). Am. J. Physiol. Lung Cell. Mol. Physiol., 2019, 316(5), L961-L976.
[http://dx.doi.org/10.1152/ajplung.00455.2017] [PMID: 30785343]
[31]
Yang, H.; Rajah, G.; Guo, A.; Wang, Y.; Wang, Q. Pathogenesis of epileptic seizures and epilepsy after stroke. Neurol. Res., 2018, 40(6), 426-432.
[http://dx.doi.org/10.1080/01616412.2018.1455014] [PMID: 29681214]
[32]
Wang, J.Z.; Vyas, M.V.; Saposnik, G.; Burneo, J.G. Incidence and management of seizures after ischemic stroke: Systematic review and meta-analysis. Neurology, 2017, 89(12), 1220-1228.
[http://dx.doi.org/10.1212/WNL.0000000000004407] [PMID: 28835405]
[33]
de Araujo Furtado, M.; Rossetti, F.; Chanda, S.; Yourick, D. Exposure to nerve agents: from status epilepticus to neuroinflammation, brain damage, neurogenesis and epilepsy. Neurotoxicology, 2012, 33(6), 1476-1490.
[http://dx.doi.org/10.1016/j.neuro.2012.09.001] [PMID: 23000013]
[34]
Doria, J.W.; Forgacs, P.B. Incidence, implications, and management of seizures following ischemic and hemorrhagic stroke. Curr. Neurol. Neurosci. Rep., 2019, 19(7), 37.
[http://dx.doi.org/10.1007/s11910-019-0957-4] [PMID: 31134438]
[35]
Reddy, D.S.; Bhimani, A.; Kuruba, R.; Park, M.J.; Sohrabji, F. Prospects of modeling poststroke epileptogenesis. J. Neurosci. Res., 2017, 95(4), 1000-1016.
[http://dx.doi.org/10.1002/jnr.23836] [PMID: 27452210]
[36]
Pitkänen, A.; Lukasiuk, K.; Dudek, F.E.; Staley, K.J. Epileptogenesis. Cold Spring Harb. Perspect. Med., 2015, 5(10), a022822.
[http://dx.doi.org/10.1101/cshperspect.a022822] [PMID: 26385090]
[37]
Lopes, R.S.; Cardoso, M.M.; Sampaio, A.O.; Barbosa, M.S., Jr; Souza, C.C.; DA Silva, M.C.; Ferreira, E.M.; Freire, M.A.; Lima, R.R.; Gomes-Leal, W. Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia. J. Biosci., 2016, 41(3), 381-394.
[http://dx.doi.org/10.1007/s12038-016-9621-1] [PMID: 27581930]
[38]
Lima, R.R.; Santana, L.N.; Fernandes, R.M.; Nascimento, E.M.; Oliveira, A.C.; Fernandes, L.M.; Dos Santos, E.M.; Tavares, P.A.; Dos Santos, I.R.; Gimarães-Santos, A.; Gomes-Leal, W. Neurodegeneration and glial response after acute striatal stroke: Histological basis for neuroprotective studies. Oxid. Med. Cell. Longev., 2016, 2016, 3173564.
[http://dx.doi.org/10.1155/2016/3173564] [PMID: 28090244]
[39]
Fluri, F.; Schuhmann, M.K.; Kleinschnitz, C. Animal models of ischemic stroke and their application in clinical research. Drug Des. Devel. Ther., 2015, 9, 3445-3454.
[PMID: 26170628]
[40]
Dallas, S.L.; Keene, D.R.; Bruder, S.P.; Saharinen, J.; Sakai, L.Y.; Mundy, G.R.; Bonewald, L.F. Role of the latent transforming growth factor beta binding protein 1 in fibrillin-containing microfibrils in bone cells in vitro and in vivo. J. Bone Miner. Res., 2000, 15(1), 68-81.
[http://dx.doi.org/10.1359/jbmr.2000.15.1.68] [PMID: 10646116]
[41]
Zhuang, X.; Zhang, H.; Li, X.; Li, X.; Cong, M.; Peng, F.; Yu, J.; Zhang, X.; Yang, Q.; Hu, G. Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1. Nat. Cell Biol., 2017, 19(10), 1274-1285.
[http://dx.doi.org/10.1038/ncb3613] [PMID: 28892080]
[42]
Saharinen, J.; Hyytiäinen, M.; Taipale, J.; Keski-Oja, J. Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF-beta action. Cytokine Growth Factor Rev., 1999, 10(2), 99-117.
[http://dx.doi.org/10.1016/S1359-6101(99)00010-6] [PMID: 10743502]
[43]
Quiñones-Pérez, B.; VanNoy, G.E.; Towne, M.C.; Shen, Y.; Singh, M.N.; Agrawal, P.B.; Smith, S.E. Three-generation family with novel contiguous gene deletion on chromosome 2p22 associated with thoracic aortic aneurysm syndrome. Am. J. Med. Genet. A., 2018, 176(3), 560-569.
[http://dx.doi.org/10.1002/ajmg.a.38590] [PMID: 29350460]
[44]
Beaufort, N.; Scharrer, E.; Kremmer, E.; Lux, V.; Ehrmann, M.; Huber, R.; Houlden, H.; Werring, D.; Haffner, C.; Dichgans, M. Cerebral small vessel disease-related protease HtrA1 processes latent TGF-β binding protein 1 and facilitates TGF-β signaling. Proc. Natl. Acad. Sci. USA, 2014, 111(46), 16496-16501.
[http://dx.doi.org/10.1073/pnas.1418087111] [PMID: 25369932]
[45]
Cai, R.; Wang, P.; Zhao, X.; Lu, X.; Deng, R.; Wang, X.; Su, Z.; Hong, C.; Lin, J. LTBP1 promotes esophageal squamous cell carcinoma progression through epithelial-mesenchymal transition and cancer-associated fibroblasts transformation. J. Transl. Med., 2020, 18(1), 139.
[http://dx.doi.org/10.1186/s12967-020-02310-2] [PMID: 32216815]
[46]
Kashima, R.; Hata, A. The role of TGF-β superfamily signaling in neurological disorders. Acta Biochim. Biophys. Sin., 2018, 50(1), 106-120.
[http://dx.doi.org/10.1093/abbs/gmx124] [PMID: 29190314]
[47]
Flanders, K.C.; Ren, R.F.; Lippa, C.F. Transforming growth factor-betas in neurodegenerative disease. Prog. Neurobiol., 1998, 54(1), 71-85.
[http://dx.doi.org/10.1016/S0301-0082(97)00066-X] [PMID: 9460794]
[48]
Zhang, X.; Huang, W.J.; Chen, W.W. TGF-β1 factor in the cerebrovascular diseases of Alzheimer’s disease. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(24), 5178-5185.
[PMID: 28051272]
[49]
Guan, J.; Miller, O.T.; Waugh, K.M.; McCarthy, D.C.; Gluckman, P.D.; Gunn, A.J. TGF beta-1 and neurological function after hypoxia-ischemia in adult rats. Neuroreport, 2004, 15(6), 961-964.
[http://dx.doi.org/10.1097/00001756-200404290-00006] [PMID: 15076715]
[50]
Higashi, T.; Kyo, S.; Inoue, M.; Tanii, H.; Saijoh, K. Novel functional single nucleotide polymorphisms in the latent transforming growth factor-beta binding protein-1L promoter: effect on latent transforming growth factor-beta binding protein-1L expression level and possible prognostic significance in ovarian cancer. J. Mol. Diagn., 2006, 8(3), 342-350.
[http://dx.doi.org/10.2353/jmoldx.2006.050133] [PMID: 16825507]
[51]
Tritschler, I.; Gramatzki, D.; Capper, D.; Mittelbronn, M.; Meyermann, R.; Saharinen, J.; Wick, W.; Keski-Oja, J.; Weller, M. Modulation of TGF-beta activity by latent TGF-beta-binding protein 1 in human malignant glioma cells. Int. J. Cancer, 2009, 125(3), 530-540.
[http://dx.doi.org/10.1002/ijc.24443] [PMID: 19431147]
[52]
Higashi, T.; Sasagawa, T.; Inoue, M.; Oka, R.; Shuangying, L.; Saijoh, K. Overexpression of latent Transforming Growth Factor-beta 1 (TGF-beta 1) binding protein 1 (LTBP-1) in association with TGF-beta 1 in ovarian carcinoma. Jpn. J. Cancer Res., 2001, 92(5), 506-515.
[http://dx.doi.org/10.1111/j.1349-7006.2001.tb01123.x] [PMID: 11376559]
[53]
Fu, X.; Zhang, P.; Song, H.; Wu, C.; Li, S.; Li, S.; Yan, C. LTBP1 plays a potential bridge between depressive disorder and glioblastoma. J. Transl. Med., 2020, 18(1), 391.
[http://dx.doi.org/10.1186/s12967-020-02509-3] [PMID: 33059753]
[54]
Chandramouli, A.; Simundza, J.; Pinderhughes, A.; Cowin, P. Choreographing metastasis to the tune of LTBP. J. Mammary Gland Biol. Neoplasia, 2011, 16(2), 67-80.
[http://dx.doi.org/10.1007/s10911-011-9215-3] [PMID: 21494784]
[55]
Troilo, H.; Steer, R.; Collins, R.F.; Kielty, C.M.; Baldock, C. Independent multimerization of Latent TGFβ Binding Protein-1 stabilized by cross-linking and enhanced by heparan sulfate. Sci. Rep., 2016, 6(1), 34347.
[http://dx.doi.org/10.1038/srep34347] [PMID: 27677855]
[56]
Oklü, R.; Hesketh, R. The latent transforming growth factor beta binding protein (LTBP) family. Biochem. J., 2000, 352(Pt 3), 601-610.
[http://dx.doi.org/10.1042/bj3520601] [PMID: 11104663]
[57]
Vehviläinen, P.; Koli, K.; Myllärniemi, M.; Lindholm, P.; Soini, Y.; Salmenkivi, K.; Kinnula, V.L.; Keski-Oja, J. Latent TGF-β Binding Proteins (LTBPs) 1 and 3 differentially regulate transforming growth factor-β activity in malignant mesothelioma. Hum. Pathol., 2011, 42(2), 269-278.
[http://dx.doi.org/10.1016/j.humpath.2010.07.005] [PMID: 21106222]
[58]
Zhao, Q.; Zheng, K.; Ma, C.; Li, J.; Zhuo, L.; Huang, W.; Chen, T.; Jiang, Y. PTPS facilitates compartmentalized LTBP1 S-Nitrosylation and promotes tumor growth under hypoxia. Mol. Cell, 2020, 77(1), 95-107.e5.
[http://dx.doi.org/10.1016/j.molcel.2019.09.018] [PMID: 31628042]
[59]
Buscemi, L.; Ramonet, D.; Klingberg, F.; Formey, A.; Smith-Clerc, J.; Meister, J.J.; Hinz, B. The single-molecule mechanics of the latent TGF-β1 complex. Curr. Biol., 2011, 21(24), 2046-2054.
[http://dx.doi.org/10.1016/j.cub.2011.11.037] [PMID: 22169532]
[60]
Sung, N.J.; Kim, N.H.; Surh, Y.J.; Park, S.A. Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway. Int. J. Mol. Sci., 2020, 21(23), 2046-5054.
[http://dx.doi.org/10.3390/ijms21239227] [PMID: 33287358]
[61]
Zhu, B.L.; Long, Y.; Luo, W.; Yan, Z.; Lai, Y.J.; Zhao, L.G.; Zhou, W.H.; Wang, Y.J.; Shen, L.L.; Liu, L.; Deng, X.J.; Wang, X.F.; Sun, F.; Chen, G.J. MMP13 inhibition rescues cognitive decline in Alzheimer transgenic mice via BACE1 regulation. Brain, 2019, 142(1), 176-192.
[http://dx.doi.org/10.1093/brain/awy305] [PMID: 30596903]
[62]
Hoogmartens, J.; Hens, E.; Engelborghs, S.; De Deyn, P.P.; van der Zee, J.; Van Broeckhoven, C.; Cacace, R. Investigation of the role of matrix metalloproteinases in the genetic etiology of Alzheimer’s disease. Neurobiol. Aging, 2021, 104, 105.e1-105.e6.
[http://dx.doi.org/10.1016/j.neurobiolaging.2021.03.011] [PMID: 33892965]
[63]
Wang, X.; Dong, C.; Li, N.; Ma, Q.; Yun, Z.; Cai, C.; An, M.; Ma, B. Modulation of TGF β activity by latent TGF-β-binding protein 1 in human osteoarthritis fibroblast-like synoviocytes. Mol. Med. Rep., 2018, 17(1), 1893-1900.
[PMID: 29257223]

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    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated194ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('59771045','',1,1740549943,1740549943) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740549943
      1.11msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('59771045','/article/124251',1,1740549943,1740549943)
      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
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) 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 >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) 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 >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) 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 >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) 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 >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) 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 >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59771045 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59771045) limit 1
      18.45msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59771045
      • 1: 59771045
      • 2: 59771045
      • 3: 59771045
      • 4: 59771045
      • 5: 59771045
      • 6: 59771045
      • 7: 59771045
      • 8: 59771045
      • 9: 59771045
      • 10: 59771045
      • 11: 59771045
      • 12: 59771045
      • 13: 59771045
      • 14: 59771045
      • 15: 59771045
      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=124251
      1.01msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 30 limit 1
      1.15msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 30
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and sj.journal_id!=30 group by `j`.`nid`) as `aggregate_table`
      1.44msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and sj.journal_id!=30 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      900μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.52msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.37msalphaeurekaselec_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` = '124251'
      1.32msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 124251
      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` = '124251'
      3.82msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 124251
      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` = '124251' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.07msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 124251
      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
      260μsalphaeurekaselec_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
      500μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 30 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      56.71msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      63.37msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      17.87msalphaeurekaselec_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` = 124251 limit 1
      280μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 124251
      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 = 124251 and content_type = 'article' order by status desc limit 1
      290μsalphaeurekaselec_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` = 205705 limit 1
      290μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 205705
      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
      320μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CPB' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      460μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPB
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '124251' 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) )
      480μsalphaeurekaselec_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 = '12001' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      360μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3326' 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) )
      350μsalphaeurekaselec_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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3326) 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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3326) 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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3326)
      7.13msalphaeurekaselec_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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12001) 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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12001) 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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12001)
      720μsalphaeurekaselec_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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 124251) 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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 124251) 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 <= 59771045 and j.to_ip >=59771045 )) and ((j.from_date <= 1740549943 and j.to_date >= 1740549943 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 124251)
      840μsalphaeurekaselec_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` < '317' and is_uploaded = 1 and issue_id = 12001 order by cast(first_page as SIGNED) desc limit 1
      690μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 317
      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` > '329' and is_uploaded = 1 and issue_id = 12001 order by cast(first_page as SIGNED) asc limit 1
      960μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 329
      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'
      230μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      240μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 124251 limit 1
      3.36msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 124251
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 30 and `b`.`banner_from_date` <= 1740549943 and `b`.`banner_to_date` >= 1740549943 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.63msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740549943
      • 4: 1740549943
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 30 and `b`.`banner_from_date` <= 1740549943 and `b`.`banner_to_date` >= 1740549943 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.63msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740549943
      • 4: 1740549943
      • 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='80cbf76d0e4f8e14f3f801400cc29cff'
      220μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        uWZI1WtzacMmY1KpFgdcO2CLX8FdHyrseKcxMalf
        uc_cart_id
        80cbf76d0e4f8e14f3f801400cc29cff
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/124251" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/124251
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
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