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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

塞来昔布在炎症和癌症疾病中的应用

卷 19, 期 1, 2019

页: [5 - 16] 页: 12

弟呕挨: 10.2174/1568009618666180430125201

价格: $65

摘要

背景:非甾体抗炎药,特别是选择性环氧合酶-2(cox-2)抑制剂,如塞来昔布(Cxb),被认为是一种很有前途的抗癌药物。乳癌,前列腺癌,肺癌和皮肤癌。然而,临床在预防方面的应用受到了对安全性、严重毒性(主要是针对健康个体)的担忧的限制,疗效及最佳治疗方案。与传统的NSAID相比,CXB具有较强的抗炎和胃肠耐受性等优点。最近的研究表明皮肤病Cal制剂在皮肤癌等皮肤病的治疗中比口服CXB更适合。到目前为止,人们对高层的探索越来越乐观。临床应用CXB(在预防皮肤癌和治疗皮肤炎症)或经皮途径减少系统性副作用的风险。 目的:本文简要综述了Cxb作为抗炎药物(外用或透皮贴剂)的皮肤制剂或给药系统的发展现状。它的化学预防作用主要集中在皮肤癌上。 结论:从日益增长的知识中出现了新的观点,将CXB的作用与其他物质或药剂结合起来,以不同的方式发挥作用,但却起到了补充作用。提高药效,降低毒性。

关键词: 塞来昔布,皮肤炎症,UVB诱发的癌症,化学预防,配方,非甾体抗炎药物(NSAID)。

图形摘要

[1]
Hilal-Dandan, R.; Brunton, L. Goodman and Gilman’s Manual of Pharmacology and Therapeutics, 2nd ed; Mc Graw Hill Education, 2014, pp. 879-913.
[2]
Sakamoto, C.; Soen, S. Efficacy and safety of the selective cyclooxygenase-2 inhibitor celecoxib in the treatment of rheumatoid arthritis and osteoarthritis in japan. Digestion, 2011, 83, 108-123.
[3]
Jarupongprapa, S.; Ussavasodhi, P.; Katchamart, W. Comparison of gastrointestinal adverse effects between cyclooxygenase-2 inhibitors and non- selective, non-steroidal anti-inflammatory drugs plus proton pump inhibitors: a systemic review and meta-analysis. J. Gastroenterol., 2013, 48(7), 830-838.
[4]
Chauhan, A.S.; Sridevi, S.; Chalsani, K.B.; Jain, A.K.; Jain, S.K.; Jain, N.K.; Diwan, P.V. Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin. J. Control. Release, 2003, 90(3), 335-343.
[5]
Lichtenberger, L.M. Where is the evidence that cyclooxigenase inhibition is the primary cause of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal injury? Topical injury revisited. Biochem. Pharmacol., 2001, 61, 631-637.
[6]
Fischer, S.M.; Hawk, E.T.; Lubet, R.A. Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention. Cancer Prev. Res. (Phila.), 2011, 4, 1728-1735.
[7]
Mennini, N.; Furlanetto, S.; Cirri, M.; Mura, P. Quality by design approach for developing chitosan-Ca-alginate microspheres for colon delivery of celecoxib-hydroxypropyl-β-cyclodextrin-PVP complex. Eur. J. Pharm. Biopharm., 2011, 80(1), 67-75.
[8]
Margulis-Goshen, K.; Kesselman, E.; Danino, D.; Magdassi, S. Formation of celecoxib nanoparticles from volatile microemulsions. Int. J. Pharm., 2010, 393, 230-237.
[9]
Soliman, S.M.; Abdel-Malak, N.S.; El-Gazayerley, O.N.; Abdel Rehim, A.A. Formulation of microemulsion gel systems for transdermal delivery of celecoxib: In vitro permeation, anti-inflammatory activity and skin irritation test. Drug Discov. Ther., 2010, 4(6), 459-471.
[10]
Shakeel, F.; Baboota, S.; Ahuja, A.; Ali, J.; Shafiq, S. Celecoxib nanoemulsion: Skin permeation mechanism and biovailability assesment. J. Drug Target., 2008, 16(10), 733-740.
[11]
Shakeel, F.; Baboota, S.; Ahuja, A.; Ali, J.; Shafiq, S. Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion. J. Nanobiotechnology, 2008, 6, 8.
[12]
Garti, N.; Avrahami, M.; Aserin, A. Improved solubilization of celecoxib in U-type nonionic microemulsions and their structural transitions with progressive aqueous dilution. J. Colloid Interface Sci., 2009, 299(1), 352-365.
[13]
Subramanian, N.; Ghosal, S.K.; Moulik, S.P. Topical delivery of celecoxib using microemulsion. Acta Pol. Pharm., 2004, 61(5), 335-341.
[14]
Margulis-Goshen. Weitman, M.; Major, D.T.; Magdassi, S. Inhibition of crystallization and growth of celecoxib nanoparticles formed from volatile microemulsions. J. Pharm. Sci., 2011, 100(10), 4390-4400.
[15]
Deniz, A.; Sade, A.; Severcan, F.; Keskin, D.; Tezcaner, A.; Banerjee, S. Celecoxib-loaded liposomes: effect of cholesterol on encapsulation and in vitro release characteristics. Biosci. Rep., 2010, 30(5), 365-373.
[16]
Nasr, M. In vitro and in vivo evaluation of proniosomes containing celecoxib for oral adminitration. AAPS PharmSciTech, 2010, 11(1), 85-89.
[17]
Paulson, S.K.; Hribar, J.D.; Liu, N.W.; Hajdu, E.; Bible, R.H.; Piergies, A.; Karim, A. Metabolism and excretion of [14C]celecoxib in healthy male volunteers. Drug Metab. Dispos., 2000, 28(3), 308-314.
[18]
Malik, P.; Kadam, R.S.; Cheruvu, N.P.; Kompella, U.B. Hidrophilic produg approach for reduced pigment binding and enhanced transscleral retinal delivery of celecoxib. Mol. Pharm., 2012, 9(3), 605-614.
[19]
Yener, G.; Gönüllü, U.; Uner, M.; Değim, T.; Araman, A. Effects of vehicles and penetration enhancers on the in vitro percutaneous absorption of celecoxib through human skin. Pharmazie, 2003, 58(5), 330-333.
[20]
Bachar, M.; Mandelbaum, A.; Portnaya, I.; Perlstein, H.; Even-Chen, S.; Barenholz, Y.; Danino, D. Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles. J. Control. Release, 2012, 160(2), 164-171.
[21]
Subramanian, N.; Ghosal, S.K.; Moulik, S.P. Enhanced in vitro percutaneous absorption and in vivo anti-inflamatory effect of a selective cyclooxygenase inhibitor using microemulsion. Drug Dev. Ind. Pharm., 2005, 31, 405-416.
[22]
Thakkar, H.; Kumar-Sharma, R.; Murthy, R.S. Enhanced retention of celecoxib-loaded solid lipid nanoparticles after intra-articular administration. Drugs R D., 2007, 8(5), 275-285.
[23]
Rao, C.V.; Reddy, B.S. NSAIDs and Chemoprevention. Curr. Cancer Drug Targets, 2004, 4(1), 29-42.
[24]
Haroutiunian, S.; Drennan, D.A.; Lipman, G.A. Topical NSAID therapy for musculoskeletal pain. Pain Med., 2010, 11, 535-549.
[25]
Okyar, A.; Ozsoy, Y.; Gungor, S. Novel formulation approaches for dermal and transdermal delivery of non-steroidal antiinflammatory drugs, rheumatoid arthritis - treatment, intech, 2012; available from. http://www.intechopen.com/books/rheumatoid-arthritis-treatment/novel-formulation-approaches-for-dermaland-transdermal-delivery-of-non-steroidal-anti-inflammatory
[26]
Loh, T.Y.; Cohen, P.R. Ketoprofen-induced photoallergic dermatitis. Indian J. Med. Res., 2016, 144(6), 803-806.
[27]
Wu, X.; Patterson, S.; Hawk, E. Chemoprevention-history and general principles. Best Pract. Res. Clin. Gastroenterol., 2011, 25, 445-459.
[28]
Cahoon, E.K.; Rajaraman, P.; Alexander, B.H.; Doody, M.M.; Linet, M.S.; Freedman, D.M. Use of nonesteroidal anti-inflammatory drugs and risk of basal cell carcinoma in the united states radiologic technologist study. Int. J. Cancer, 2012, 130(12), 2939-2948.
[29]
Khan, Z.; Khan, N.; Tiwari, R.P.; Sah, N.K.; Prasad, G.B.; Bisen, P.S. Biology of COX-2: An application in cancer therapeutics. Curr. Drug Targets, 2011, 12(7), 1082-1093.
[30]
Kim, T.H.; Jeong, Y.I.; Jin, S.G.; Pei, J.; Jung, T.Y.; Moon, K.S.; Kim, I.Y.; Kang, S.S.; Jung, S. Preparation of polylactide-co-glycolide nanoparticles incorparating celecoxib and their antitumor activity against brain tumor cells. Int. J. Nanomedicine, 2011, 6, 2621-2631.
[31]
Shamsher, A.A.; Charoo, N.A.; Rahman, Z.; Pillai, K.K.; Kohli, K. Tulsi oil as a potencial penetration enhancer for celecoxib transdermal gel formulations. Pharm. Dev. Technol., 2014, 19(1), 21-30.
[32]
Zhao, P.; Jiang, H.; Jiang, T.; Zhi, Z.; Wu, C.; Sun, C.; Zhang, J.; Wang, S. Inclusion of celecoxib into fibrous ordered mesoporous carbon for enhanced oral bioavailability and reduced gastric irritancy. Eur. J. Pharm. Sci., 2012, 45(5), 639-647.
[33]
Wan, F.; Bohr, A.; Maltesen, M.J.; Bjerregaard, S.; Foged, C.; Rantanen, J.; Yang, M. Critical solvent properties affecting the particle formation process and characteristics of celecoxib-loaded PLGA microparticles via spray-drying. Pharm. Res., 2013, 30(4), 1065-1076.
[34]
Abu-Diak, O.A.; Jones, D.S.; Andrews, G.P. An investigation into the dissolution properties of celecoxib melt extrudates: understanding the role of polymer type and concentration in stabilizing supersaturated drug concentrations. Mol. Pharm., 2011, 8(4), 1362.
[35]
Cheng, S.Y.; Yuen, M.C.; Lam, P.L.; Gambari, R.; Wong, R.S.; Cheng, G.Y.; Lia, P.B.; Tong, S.W.; Chan, K.W.; Lau, F.Y.; Kok, S.H.; Lam, K.H.; Chui, C.H. Synthesis, characterization and preliminary analysis of in vivo biological activity of chitosan/celecoxib micropsules. Bioorg. Med. Chem. Lett., 2010, 20(14), 4147-4151.
[36]
Nasr, M. Influence of microcrystal formulation on in vivo absorption of celecoxib in rats. AAPS PharmSciTech, 2013, 14(2), 719-726.
[37]
Patlolla, R.R.; Chougule, M.; Patel, A.R.; Jackson, T.; Tata, P.N.; Singh, M. Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers. J. Control. Release, 2010, 144(2), 233-241.
[38]
Ibrahim, M.M.; Abd-Elgawad, A.E.; Soliman, O.A.; Jablonski, M.M. Nanoparticle-based topical ophthalmic formulations for sustained celecoxib release. J. Pharm. Sci., 2013, 102(3), 1036-1053.
[39]
Amrite, A.C.; Edelhauser, H.F.; Singh, S.R.; Kompella, U.B. Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration. Mol. Vis., 2008, 14, 150-160.
[40]
Thakkar, H.P.; Murthy, R.R. Effect of cross-linking on the characteristics of the celecoxib loaded chitosan microspheres. Asian J. Pharm, 2008, 2, 246-251.
[41]
Quiñones, O.G.; Mata dos Santos, H.A.; Kibwila, D.M.; Leitão, A.; dos Santos Pyrrho, A.; Pádula, M.; Rosas, E.C.; Lara, M.G.; Pierre, M.B.R. In vitro and in vivo influence of penetration enhancers in the topical application of celecoxib. Drug Dev. Ind. Pharm., 2014, 40(9), 1180-1189.
[42]
Sharma, R.; Mehra, G.R. Preparation, characterization, in vitro and in vivo evaluation of transdermal matrix films of celecoxib. Acta Pharm. Sci, 2011, 53, 67-76.
[43]
Alam, M.I.; Baboota, S.; Kohli, K.; Ali, J.; Ahuja, A. Pharmacodymanic evaluation of proniosomal transdermal therapeutic gel containing celecoxib. Sci. Asia, 2010, 36, 305-311.
[44]
Joshi, M.; Patravale, V. Nanostructured lipid carrier (NLC) based gel of celecoxib. Int. J. Pharm., 2008, 346, 124-132.
[45]
Baboota, S.; Shakeel, F.; Ahuja, A.; Ali, J.; Shafiq, S. Design, devolepment and evaluation of novel nanoemulsion formulations for transdermal potencial of celecoxib. Acta Pharm., 2007, 57, 315-332.
[46]
Desai, P.R.; Shah, P.P.; Patlolla, R.R.; Singh, M. Dermal microdialysis technique to evaluate the trafficking of surface-modified lipid nanoparticles upon topical application. Pharm. Res., 2012, 29(9), 2587-2600.
[47]
Sharma, P.K.; Bajpai, M. Enhancement of solubility and stability of celecoxib using microemulsion based topical formulation. J. Pharm. Res., 2011, 4(7), 2216-2220.
[48]
Begum, M.Y.; Abbulu, K.; Sudhakar, M.; Jayaprakash, S. Studies on the development of celecoxib transdermal patches. Int. J. Pharm. Tech. Res., 2011, 3(3), 1609-1615.
[49]
Moreira, T.S.; de Sousa, V.P.; Pierre, M.B.R. A novel transdermal delivery system for the anti–inflamatory Lumiracoxib: Influence of Oleic Acid on in vitro percutaneous absorption and in vivo potencial cutaneous irritation. AAPS PharmSciTech, 2010, 11(2), 621-629.
[50]
Gibson, M. Pharmaceutical Preformulation and Formulation: A Practical Guide from Candidate Drug Selection to Comercial Dosage Form. Volume 199, 2nd ed; Drugs and the Pharmaceuticals Sciences, 2009.
[51]
Khurana, S.; Bedi, P.M.; Jain, N.K. Preparation and evaluation of solid lipid nanoparticles based nanogel for dermal delivery of meloxicam. Chem. Phys. Lipids, 2013, 176, 65-72.
[52]
Manconi, M.; Caddeo, C.; Sinico, C.; Valenti, D.; Mostallino, M.C.; Biggio, G.; Fadda, A.M. Ex vivo skin delivery of diclofenac by transcutol containing liposomes. Eur. J. Pharm. Biopharm., 2011, 78(1), 27-35.
[53]
Nokhodchi, A.; Sharabiani, K.; Rashidi, M.R.; Ghafourian, T. The effect of terpene concentrations on the skin penetration of diclofenac sodium. Int. J. Pharm., 2007, 335, 97-105.
[54]
Fetih, G.; Fathalla, D.; El-Badry, M. Liposomal gels for site-specific, sustained delivery of celecoxib: in vitro and in vivo evaluation. Drug Dev. Res., 2014, 75(4), 257-266.
[55]
Venkatesan, P.; Puwada, N.; Dash, R.; Prashanth Kumar, B.N.; Sarkar, D.; Azab, B.; Pathak, A.; Kundu, S.C.; Fisher, P.B.; Mandal, M. The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer. Biomaterials, 2011, 32(15), 3794-3806.
[56]
Bijman, M.N.; Hermelink, C.A.; van Berkel, P.A.; Laan, A.C.; Janmaat, M.L.; Peters, G.J.; Boven, E. Interaction between celecoxib and docetaxel or cisplatin in human cell lines of ovarian cancer and colon cancer is independent of COX-2 expression levels. Biochem. Pharmacol., 2008, 75(2), 427-437.
[57]
Steinbach, G.; Lynch, P.M.; Phillips, R.K.; Wallace, M.H.; Hawk, E.; Gordon, G.B.; Wakabayashi, N.; Saunders, B.; Shen, Y.; Fujimura, T.; Su, L.K.; Levin, B.; Godio, L.; Patterson, S.; Rodriguez-Bigas, M.A.; Jester, S.L.; King, K.L.; Schumacher, M.; Abbruzzese, J.; DuBois, R.N.; Hittelman, W.N.; Zimmerman, S.; Sherman, J.W.; Kelloff, G. The effect of celecoxib, a cyclooxigenase–2 inhibitors, in familial adenomatous polyposis. N. Engl. J. Med., 2000, 342(26), 1946-1952.
[58]
Kawamori, T.; Rao, C.V.; Seibert, K.; Reddy, B.S. Chemopreventive activity of celecoxib, a especific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res., 1998, 58(3), 409-412.
[59]
Saba, N.F.; Hurwitz, S.J.; Kono, S.A.; Yang, C.S.; Zhao, Y.; Chen, Z.; Sica, G.; Müller, S.; Moreno-Williams, R.; Lewis, M.; Grist, W.; Chen, A.Y.; Moore, C.E.; Owonikoko, T.K.; Ramalingam, S.; Beitler, J.J.; Nannapaneni, S.; Shin, H.J.; Grandis, J.R.; Khuri, F.R.; Chen, Z.G.; Shin, D.M. Chemoprevention of head and neck cancer with celecoxib and erlotinib: results of a phase ib and pharmacokinetic study. Cancer Prev. Res. (Phila.), 2014, 7(3), 283-291.
[60]
Abrahão, A.C.; Giudice, F.S.; Sperandio, F.F.; Pinto Junior Ddos, S. Effects of celecoxib treatment over the AKT pathway in head and neck squamous cell carcinoma. J. Oral Pathol. Med., 2013, 42(10), 793-798.
[61]
Kilic, A.; Schuchert, M.J.; Luketich, J.D.; Landreneau, R.J.; El-Hefnawy, T. Efficacy of signal pathway inhibitors alone and combination with cisplatin varies between human non–small cell lung cancer lines. J. Surg. Res., 2009, 154(1), 9-12.
[62]
Okada, T.; Takigawa, N.; Kishino, D.; Katayama, H.; Kuyama, S.; Sato, K.; Mimoto, J.; Ueoka, H.; Tanimoto, M.; Kiura, K. Selective cyclooxigenase-2 inhibitor prevents cisplatin-induced tmorigenesis in A/J Mice. Acta Med. Okayama, 2012, 66(3), 245-251.
[63]
Buckstein, R.; Kerbel, R.S.; Shaked, Y.; Nayar, R.; Foden, C.; Turner, R.; Lee, C.R.; Taylor, D.; Zhang, L.; Man, S.; Baruchel, S.; Stempak, D.; Bertolini, F.; Crump, M. High-dose celecoxib and metro- nomic “Low-dose” cyclophosphamide is an effective and safe therapy in patients with relapse and refractory agressive histology Non-Hodgkins lymphoma. Clin. Cancer Res., 2006, 12(17), 5190-5198.
[64]
Kim, S.H.; Kim, S.H.; Song, Y.C.; Song, Y.S. Celecoxib potentiates the anticancer effects of cisplastin on vulvar cancer cells independently of cyclooxigenase. Ann. N. Y. Acad. Sci., 2009, 1171, 635-641.
[65]
Chen, J.; Ran, Y.; Hong, C.; Chen, Z.; You, Y. Anti-cancer effects of celecoxib on nasopharyngeal carcinoma HNE-1 cells expression COX-2 oncoprotein. Cytotchenology, 2010, 62(5), 431-438.
[66]
Li, W.Z.; Wang, X.Y.; Li, Z.G.; Zhang, J.H.; Ding, Y.Q. Celecoxib enhances the inhibitory effect of cispalstin on Tca8113 cells in human tongue squamous cell carcinoma in vivo and in vitro. J. Oral Pathol. Med., 2010, 39(7), 579-584.
[67]
Yu, L.; Chen, M.; Li, Z.; Wen, J.; Fu, J.; Guo, D.; Jiang, Y.; Wu, S.; Cho, C.H.; Liu, S. Celecoxib antagonizes the cytotoxicity of cisplatin in human esophageal squamous cell carcinoma by reducing intracellular cisplatin accumulation. Mol. Pharmacol., 2011, 79(3), 608-617.
[68]
Mohammadianpanah, M.; Razmjou-Ghalaei, S.; Shafizad, A.; Ashouri-Taziani, Y.; Khademi, B.; Ahmadloo, N.; Ansari, M.; Omidvari, S.; Mosalaei, A.; Mosleh-Shirazi, M.A. Efficacy and safety of current chemoradiation with weekly cisplatin ± low–dose celecoxib in locally advanced un- differentiated nasopharygeal carcinoma: A phase II–III clinical trial. J. Cancer Res. Ther., 2011, 7(4), 442-447.
[69]
Cohen, S.; Efraim, A.N.; Levi-Schaffer, F.; Eliashar, R. The effect of hypoxia and cyclooxigenase inhibitors on nasal polyp derived fibroblasts. Am. J. Otolaryngol., 32, 564-573. 2011
[70]
Huang, K.H.; Kuo, K.L.; Chen, S.C.; Weng, T.I.; Chuang, Y.T.; Tsai, Y.C.; Pu, Y.S.; Chiang, C.K.; Liu, S.H. Down–regulation of glucose–regulated protein (GRP) 78 potentiates cytotoxic effects of celecoxib in human urothelial carcinoma cells. PLoS One, 2012, 7(3), e33615.
[71]
Sareddy, G.R.; Geeviman, K.; Ramulu, C.; Babu, P.P. The nonsteroidal anti-inflammatory drug celecoxib suppresses the growth and induces apoptosis of human glioblastoma cells via the NF-κB pathway. J. Neurooncol., 2012, 106(1), 99-109.
[72]
Chiu, L.C.; Tong, K.F.; Ooi, V.E. Cytostatic and cytotoxic effects of cyclooxigenase inhbitors and their synergy with docosahexaenoic acid on the growth of human skin melanoma A-375 cells. Biomed. Pharmacother., 2005, 59(Suppl. 2), S293-S297.
[73]
Gogas, H.; Polyzos, A.; Stavrinidis, I.; Frangia, K.; Tsoutsos, D.; Panagiotou, P.; Markopoulos, C.; Papadopoulos, O.; Pectasides, D.; Mantzourani, M.; Middleton, M.; Vaiopoulos, G.; Fountzilas, G. Temozolomide in combination with celecoxib in patients with advanced melanoma. a phase ii study of the Hellenic Cooperative Oncology Group. Ann. Oncol., 2006, 17(12), 1835-1841.
[74]
Pagliarulo, V.; Ancona, P.; Niso, M.; Colabufo, N.A.; Contino, M.; Cormio, L.; Azzariti, A.; Pagliarulo, A. The interaction of celecoxib with MDR transporters enhances the activity of mitomycin C in a bladder cancer cell line. Mol. Cancer, 2013, 12, 47.
[75]
Kim, C.H.; Chung, C.W.; Lee, H.M. Kim do, H.; Kwak, T.W.; Jeong, Y.I.; Kang, D.H. Synergistic effects of 5-aminolevulinic acid based photodynamic therapy and celecoxib via oxidative stress in human cholangiocarcinoma cells. Int. J. Nanomedicine, 2013, 8, 2173-2186.
[76]
Song, J.; Chen, Q.; Xing, D. Enhanced apoptotic effects by downregulating Mcl-1: Evidence for the improvement of photodynamic therapy with Celecoxib. Exp. Cell Res., 2013, 319(10), 1491-1504.
[77]
Hyter, S.; Indra, A.K. Nuclear hormone receptor functions in keratinocyte and melanocyte homeostasis, epidermal carcinogenesis and melanomagenesis. FEBS Lett., 2013, 587(6), 529-541.
[78]
Lee, J.L.; Mukhtar, H.; Bickers, D.R.; Kopelovich, L.; Athar, M. Cyclooxygenase in the skin: pharmacological and toxicological implications. Toxicol. Appl. Pharmacol., 2003, 192(3), 294-306.
[79]
Hatton, J.L.; Parent, A.; Tober, K.L.; Hoppes, T.; Wulff, B.C.; Duncan, F.J.; Kusewitt, D.F.; VanBuskirk, A.M.; Oberyszyn, T.M. Depletion of CD4+ cells exacerbates the cutaneous response to acute and chronic UVB exposure. J. Invest. Dermatol., 2007, 127(6), 1507-1515.
[80]
Wilgus, T.A.; Koki, A.T.; Zweifel, B.S.; Kusewitt, D.F.; Rubal, P.A.; Oberyszyn, T.M. Inhbition of cutaneous ultraviolet light B–mediated inflamation and tumor formation with topical celecoxib treatment. Mol. Carcinog., 2003, 38(2), 49-58.
[81]
Cocoş, R.; Schipor, S.; Nicolae, I.; Thomescu, C.; Raicu, F. Role of COX-2 activity and CRP levels in patients with non–melanoma skin cancer. –765GC PTGS2 polymorphism and NMSC risk. Arch. Dermatol. Res., 2012, 304(5), 335-342.
[82]
Chun, K.S.; Langenbach, R. The prostaglandin E2 receptor, EP2, regulates survivin expression via an EGFR/STAT3 pathway in UVB-exposed mouse skin. Mol. Carcinog., 2011, 5D(6), 439-448.
[83]
Buckman, S.Y.; Gresham, A.; Hale, P.; Hruza, G.; Anast, J.; Masferrer, J.; Pentland, A.P. COX-2 expression is induced by UVB exposure in human skin: Implications for the development of skin cancer. Carcinogenesis, 1998, 19(5), 723-729.
[84]
Tober, K.L.; Wilgus, T.A.; Kusewitt, D.F. Thomas-Ahner, J.M.; Maruyama, T.; Oberyszyn, T.M. Importance of the EP1 receptor in cutaneuos UVB–Induced inflamation and tumor development. J. Invest. Dermatol., 2006, 126(1), 205-211.
[85]
Singh, T.; Katiyar, S.K. Green tea catechins reduce invasive potencial of human melanoma cells by targeting COX-2, PGE2 Receptors and Epithelial to Mesenchymal Transition. PLoS One, 2011, 6(10), e25224.
[86]
Singh, T.; Vaid, M.; Katiyar, N.; Sharma, S.; Katiyar, S.K. Berberine, an isoquinoline alkaloid, inhibits melanoma cancer cell migration by reducing the espressions of cyclooxygenase-2, prostaglandin E2 and prostaglandin E2 receptors. Carcinogenesis, 2011, 32(1), 86-92.
[87]
Maglio, D.H.G.; Paz, M.L.; Cela, E.M.; Leoni, J. Cyclooxygenase-2 overexpression in non-melanoma skin cancer: molecular pathways involved as targets for prevention and treatment. skin cancers - risk factors, prevention and therapy, 2011, Prof. Caterina La Porta (Ed.), ISBN: 978- 953-307-722-2, InTech, Available from:. http://www.intechopen.com/books/skin-cancers-risk-factorsprevention-and-therapy/cyclooxygenase-2-overexpression-in-non-melanoma-skin-cancer-molecularpathways-involved-as-targets-f
[88]
Wilgus, T.A.; Ross, M.S.; Parrett, M.L.; Oberyszyn, T.M. Topical application of a selective cyclooxygenase inhibitor suppresses UVB mediated cutaneous inflammation. Prostaglandins Other Lipid, 2000, 62(4), 367-384.
[89]
Elmets, C.A.; Viner, J.L.; Pentland, A.P.; Cantrell, W.; Lin, H.Y.; Bailey, H.; Kang, S.; Linden, K.G.; Heffernan, M.; Duvic, M.; Richmond, E.; Elewski, B.E.; Umar, A.; Bell, W.; Gordon, G.B. Chemoprevention of nonmelanoma skin cancer with celecoxib: A randomized, double-blind, placebo-controlled trial. J. Natl. Cancer Inst., 2010, 102(24), 1835-1844.
[90]
Wulff, B.C.; Thomas-Ahner, J.M.; Schick, J.S.; Oberyszyn, T.M. Celecoxib reduces the effects of acute and chronic UVB exposure in mice treated with therapeutically relevant immunosupresive drugs. Int. J. Cancer, 2010, 126(1), 11-18.
[91]
Karagece Yalçin, U.; Seçkın, S. The expression of p53 and cox-2 in basal cell csarcinoma, squamous cell carcinoma and actinic keratosis cases. Turk Patoloji Derg., 2012, 28(2), 119-127.
[92]
Bundscherer, A.; Hafner, C.; Maisch, T.; Becker, B.; Landthaler, M.; Vogt, T. Antiproliferative and proapoptotic effect of rapamycin and celecoxib in malignant melanoma cell lines. Oncol. Rep., 2008, 19, 547-553.
[93]
Bhatt, R.S.; Merchan, J.; Parker, R.; Wu, H.K.; Zhang, L.; Seery, V.; Heymach, J.V.; Atkins, M.B.; McDermott, D.; Sukhatme, V.P. A phase 2 pilot trial of low-dose, continuos infusion, or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma. Cancer, 2010, 116(7), 1751-1756.
[94]
Fegn, L.; Wang, Z. Topical chemoprevention of skin cancer in mice, using combined inhibitors of 5-lipoxygenase and ciclo-oxygenase-2. J. Laryngol. Otol., 2009, 123(8), 880-884.
[95]
Amini, S.; Viera, M.H.; Valins, W.; Berman, B. Nonsurgical innovations in the treatment of nonmelanoma skin cancer. J. Clin. Aesthet. Dermatol., 2010, 3(6), 20-34.
[96]
Clarke, P. Nonmelanoma skin cancers – treatment options. Aust. Fam. Physician, 2012, 41(7), 476-480.
[97]
Feng, X.; Vyas, D.; Guan, B. Novel Target Therapy and Immunotherapy for Skin Cancer., US Pharm., 2012, 37(11) Suppl., 7-11.
[98]
Zanon, M.; Piris, A.; Bersani, I.; Vegetti, C.; Molla, A.; Scarito, A.; Anichini, A. Apoptosis protease activator protein-1 expression is dispensable for response of human cells to distinct proapoptotic agents. Cancer Res., 2004, 64(20), 7386-7394.
[99]
Simões, M.C.F.; Sousa, J.J.S.; Pais, A.A.C.C. Skin cancer and new treatment perspectives: A review. Cancer Lett., 2015, 357, 8-42.
[100]
Chakraborty, R.; Wieland, C.N.; Comfere, N.I. Molecular targeted therapies in metastatic melanoma. Pharm. Pers. Med., 2013, 6, 49-56.
[101]
Khan, M.H.; Alam, M.; Yoo, S. Epidermal growth factor receptor inhibitors in the treatment of nonmelanoma skin cancers. Dermatol. Surg., 2011, 37(9), 1199-1209.
[102]
Heath, C.H.; Deep, N.L. Nabell, l.; Carroll, W.R.; Desmond, R.; Clemons, L. Phase 1 study of erlotinib plus radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Int. J. Radiat. Oncol. Biol. Phys., 2013, 85(5), 1275-1281.
[103]
Bahner, J.D.; Bordeaux, J.S. Non-melanoma skin cancers: photodynamic therapy, cryotherapy, 5-fluorouracil, imiquimod, diclofenac, or what? Facts and controversies. Clin. Dermatol., 2013, 31(6), 792-798.
[104]
Mandala, M.; Massi, D.; De Giorgi, V. Cutaneous toxicities of BRAF inhibitors: clinical and pathological challenges and call to action. Crit. Rev. Oncol. Hematol., 2013, 88(2), 318-337.
[105]
Kawczyk-Krupka, A.; Bugaj, A.M.; Latos, W.; Zaremba, K.; Sieron, A. Photodynamic therapy in treatment of cutaneous and choroidal melanoma. Photodiagn. Photodyn. Ther., 2013, 10(4), 503-509.
[106]
Rodust, P.M.; Fecker, L.F.; Stockfleth, E.; Eberle, J. Activation of mithocondrial apoptosis pathway in cutaneous squamous cell carcinoma cells by di- clofenac/hyaluronic acid is related to upregulation of Bad as well as downregulation of Mcl-1 and Bcl-w. Exp. Dermatol., 2012, 21(7), 520-525.
[107]
Kim, S.R.; Park, J.H.; Lee, M.E.; Park, J.S.; Park, S.C.; Han, J.A. Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblast in a catalytic activity-independent manner. Mech. Ageing Dev., 2008, 129(12), 706-713.
[108]
Li, F.; Liu, S.; Ouyang, Y.; Fan, C.; Wang, T.; Zhang, C.; Zeng, B.; Chai, Y.; Wang, X. Effect of celecoxib on proliferation, collagen expresion, ERK1/2 and SMAD2/3 phosphorylation in NIH/3T3 fibroblasts. Eur. J. Pharmacol., 2012, 678, 1-5.
[109]
DeCicco-Skinner, K.L.; Nolan, S.J.; Deshpande, M.M.; Trovato, E.L.; Dempsey, T.A.; Wiest, J.S. Altered prostanoid signaling contributes to increased skin tumorigenesis in Tpl2 knockout mice. PLoS One, 2013, 8(2), e56212.
[110]
Escuin-Ordinas, H.; Atefi, M.; Fu, Y.; Cass, A.; Ng, C.; Huang, R.R.; Yashar, S.; Comin-Anduix, B.; Avramis, E.; Cochran, A.J.; Marais, R.; Lo, R.S.; Graeber, T.G.; Herschman, H.R.; Ribas, A. COX-2 inhibition prevents the apparence of cutaneous squamous cell carcinoma acelerated by BRAF inhibitors. Mol. Oncol., 2014, 8(2), 250-260.
[111]
Tang, J.Y.; Aszterbaum, M.; Athar, M.; Barsanti, F.; Cappola, C.; Estevez, N.; Hebert, J.; Hwang, J.; Khaimskiy, Y.; Kim, A.; Lu, Y.; So, P.L.; Tang, X.; Kohn, M.A.; McCulloch, C.E.; Kopelovich, L.; Bickers, D.R.; Epstein, E.H., Jr Basal cell carcinoma chemoprevention with nonsteroidal anti-inflammatory drugs in genetically predisposed PTCH1*(+/−) humans and mice. Cancer Prev. Res. (Phila.), 2010, 3(1), 25-34.
[112]
Wilgus, T.A.; Koki, A.T.; Zweifel, B.S.; Rubal, P.A.; Oberyszyn, T.M. Chemotherapeutic efficacy of topical celecoxib in a murine model of Ultraviolet Light B-Induced skin cancer. Mol. Carcinog., 2003, 38(1), 33-39.
[113]
Pentland, A.P.; Schoggins, J.W.; Scott, G.A.; Khan, K.N.; Han, R. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis, 1999, 20(10), 1939-1944.
[114]
Fischer, S.M.; Conti, C.J.; Viner, J.; Aldaz, C.M.; Lubet, R.A. Celecoxib and difluoromethylornithine in combination have strong therapeutic activity against UV-induced skin tumors in mice. Carcinogenesis, 2003, 24(5), 945-952.
[115]
Bragagni, M.; Mennini, N.; Maestrelli, F.; Cirri, M.; Mura, P. Comparative study of liposomes, transfersomes and ethosomes as carriers for improving topical delivery of celecoxib. Drug Deliv., 2012, 19(7), 345-361.
[116]
Simonetti, L.D.; Gelfuso, G.M.; Barbosa, J.C.; Lopez, R.F. Assesment of the percutaneous penetration of cisplastin: The effect of monoolein and the drug skin penetration pathway. Eur. J. Pharm. Biopharm., 2009, 73(1), 90-94.
[117]
Tennenbaum, T.; Lowry, D.; Darwiche, N.; Morgan, D.L.; Gartsbein, M.; Hansen, L.; De Luca, L.M.; Hennings, H.; Yuspa, S.H. Topical retinoic acid reduces skin papilloma formation but resistant papillomas are at high risk for malignant conversion. Cancer Res., 1998, 58(7), 1435-1443.
[118]
Chun, K.S.; Kundu, J.K.; Park, K.K.; Chung, W.Y.; Surh, Y.J. Inhibition of phorbol ester–induced mouse skin tumor promotion and COX–2 expression by celecoxib: C/EPB as a potencial molecular target. Cancer Res. Treat., 2006, 38(3), 1252-1258.
[119]
Ochalek, M.; Podhaisky, H.; Ruettinger, H.H.; Neubert, R.H.; Wohlrab, J. SC lipid model membranes designed for studying impact of ceramides species on drug diffusion and permeation, part iii: influence of penetration enhancer on diffusion and permeation of models drugs. Int. J. Pharm., 2012, 436, 206-213.
[120]
Patlolla, R.R.; Desai, P.R.; Belay, K.; Singh, M.S. Translocation of cell penetrating peptide engrafted nanoparticles across skin layers. Biomaterials, 2010, 31(21), 5598-5607.
[121]
Ventura, C.A.; Tommasini, S.; Falcone, A.; Giannone, I.; Paolino, D.; Sdrafkakis, V.; Mondello, M.R.; Puglisi, G. Influence of modified cyclodextrins on solubility and percutaneous absorption of celecoxib through human skin. Int. J. Pharm., 2006, 314(1), 37-45.
[122]
Engelbrecht, T.N.; Schroeter, A.; Hauss, T.; Neubert, R.H. Lipophilic penetration enhancers and their impact to the bilayer structure of stratum corneum lipid model membranes: Neutron diffraction studies based on the example Oleic Acid. Biochim. Biophys. Acta, 2011, 1808(12), 2798-2806.
[123]
Mélot, M.; Pudney, P.D.; Williamson, A.M.; Caspers, P.J.; Van Der Pol, A.; Puppels, G.J. Studying the effectiveness of penetration enhancers to deliver retinol through the stratum corneum by in vivo confocal raman spectroscopy. J. Control. Release, 2009, 138(1), 32-39.
[124]
Herai, H.; Gratieri, T.; Thomazine, J.A.; Bentley, M.V.; Lopez, R.F. Doxorubicin skin penetration from monolein–containing propylene glycol formulations. Int. J. Pharm., 2007, 329, 88-93.
[125]
Kreilgaard, M. Influence of microemulsions on cutaneous drug delivery. Adv. Drug Deliv. Rev., 2002, 54(Suppl. 1), S77-S98.
[126]
Pierre, M.B.; Dos Santos Miranda Costa, I. Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Arch. Dermatol. Res., 2011, 303, 607-621.
[127]
Srisuk, P.; Thongnopnua, P.; Raktanonchai, U.; Kanokpanont, S. Physico-chemical characteristics of methotrexate-entrapped oleic acid- containing deformable liposomes for in vitro transepidermal delivery targeting treatment. Int. J. Pharm., 2012, 427(2), 426-434.
[128]
Tan, A.; Simovic, S.; Davey, A.K.; Rades, T.; Boyd, B.J.; Prestidge, C.A. Silica nanoparticles to control the lipase-mediated digestion of lipid- based oral delivery systems. Mol. Pharm., 2010, 7(2), 522-532.
[129]
McCarron, P.A.; Marouf, W.M.; Donnelly, R.F.; Scott, C. Enhanced surface attachment of protein-type targeting ligands to poly(lactide-co-glycolide) nanoparticles using variable expression of polimeric acid functionality. J. Biomed. Mater. Res., 2008, 87(4), 873-884.
[130]
Schneider, M.; Stracke, F.; Hansen, S.; Schaefer, U.F. Nanoparticles and their interactions with the dermal barrier. Dermatoendocrinol, 2009, 1(4), 197-206.
[131]
Batheja, P.; Sheihet, L.; Kohn, J.; Singer, A.J.; Michniak-Kohn, B. Topical drug delivery by a polimeric nanosphere gel: formulation optimization and in vitro and in vivo skin distribution studies. J. Control. Release, 2011, 149(2), 159-167.
[132]
Mehnert, W.; Mäder, K. Solid lipid nanoparticles production, characterization and applications. Adv. Drug Deliv. Rev., 2001, 47, 165-196.
[133]
Hussain, Z.; Katas, H.; Mohd Amin, M.C.; Kumolosasi, E.; Buang, F.; Sahudin, S. Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: An ex vivo and in vivo study using an NC/Nga mouse model. Int. J. Pharm., 2013, 444(1-2), 109-119.
[134]
Estracanholli, E.A.; Praça, F.S.G.; Cintra, A.B.; Pierre, M.B.R.; Lara, M.G. Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies. AAPS PharmSciTech, 2014, 15(6), 1468-1475.
[135]
Dante, M.C.L.; Borgheti-Cardoso, L.N.; Fantini, M.C.A.; Praça, F.S.G.; Medina, W.S.G.; Pierre, M.B.R.; Lara, M.G. Liquid crystalline systems based on glyceryl monooleate and penetration enhancers for skin delivery of celecoxib: characterization, In Vitro drug release, and in vivo studies. J. Pharm. Sci., 2017, pii: S0022- 3549(17), 30778-30785

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      • 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
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      • 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
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      • 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
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      • 11: 316582179
      • 12: 316582179
      • 13: 316582179
      • 14: 316582179
      • 15: 316582179
      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
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      1.06msalphaeurekaselec_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
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      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
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      1.41msalphaeurekaselec_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=7) and sj.journal_id!=7 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.17msalphaeurekaselec_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=7) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.31msalphaeurekaselec_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=7) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.07msalphaeurekaselec_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` = '90075'
      330μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 90075
      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` = '90075'
      3.78msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 90075
      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` = '90075' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.22msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 90075
      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
      250μsalphaeurekaselec_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
      480μsalphaeurekaselec_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 = 7 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      28.77msalphaeurekaselec_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 = 7 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      14.52msalphaeurekaselec_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 = 7 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      12.58msalphaeurekaselec_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` = 90075 limit 1
      360μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 90075
      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 = 90075 and content_type = 'article' order by status desc limit 1
      490μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 490 and content_id!=90075 and cd.content_type = 'article' order by rand() limit 20
      35.02msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 161688 limit 1
      490μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 161688
      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
      220μsalphaeurekaselec_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` = 'CCDT' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      370μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CCDT
      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 = '90075' 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) )
      420μsalphaeurekaselec_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 = '8762' 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 = '2548' 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) )
      330μsalphaeurekaselec_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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2548) 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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2548) 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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2548)
      10.03msalphaeurekaselec_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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 8762) 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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 8762) 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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 8762)
      660μsalphaeurekaselec_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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 90075) 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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 90075) 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 <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988107 and j.to_date >= 1739988107 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 90075)
      620μsalphaeurekaselec_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` < '5' and is_uploaded = 1 and issue_id = 8762 order by cast(first_page as SIGNED) desc limit 1
      530μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 5
      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` > '16' and is_uploaded = 1 and issue_id = 8762 order by cast(first_page as SIGNED) asc limit 1
      470μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 16
      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'
      190μsalphaeurekaselec_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
      230μsalphaeurekaselec_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` = 90075)
      5.68msalphaeurekaselec_live_10_06_2022ArticleController.php#2488
      Bindings
      • 0: 2
      • 1: 90075
      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` = 90075)
      2.52msalphaeurekaselec_live_10_06_2022ArticleController.php#2489
      Bindings
      • 0: 2
      • 1: 90075
      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` = 90075 group by `au`.`id` order by `au`.`article_id` asc, `au`.`sequence` asc
      4.33msalphaeurekaselec_live_10_06_2022MultiLangAuthor.php#30
      Bindings
      • 0: 90075
      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` = 7 and `language_id` = 2
      200μsalphaeurekaselec_live_10_06_2022ArticleController.php#2495
      Bindings
      • 0: 7
      • 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` = 90075 limit 1
      1.34msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 90075
      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` = 7 and `b`.`banner_from_date` <= 1739988107 and `b`.`banner_to_date` >= 1739988107 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.6msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 7
      • 3: 1739988107
      • 4: 1739988107
      • 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` = 7 and `b`.`banner_from_date` <= 1739988107 and `b`.`banner_to_date` >= 1739988107 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.52msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 7
      • 3: 1739988107
      • 4: 1739988107
      • 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='c1371b217be111d628e1e037cf9e9516'
      280μsalphaeurekaselec_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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        []
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        ClearShow all
        Date ↕MethodURLData
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