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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Molecular Mechanisms and Therapeutic Potential of Resolvins in Cancer - Current Status and Perspectives

Author(s): Amir Tajbakhsh, Fatemeh Yousefi, Najmeh Farahani, Amir Savardashtaki, Željko Reiner, Tannaz Jamialahmadi and Amirhossein Sahebkar*

Volume 31, Issue 36, 2024

Published on: 09 August, 2023

Page: [5898 - 5917] Pages: 20

DOI: 10.2174/0929867331666230727100123

Price: $65

Abstract

Resolvins are specialized pro-resolving mediators derived from omega-3 fatty acids that can suppress several cancer-related molecular pathways, including important activation of transcription parameters in the tumor cells and their microenvironment, inflammatory cell infiltration, cytokines as well as chemokines. Recently, an association between resolvins and an important anti-inflammatory process in apoptotic tumor cell clearance (efferocytosis) was shown. The inflammation status or the oncogene activation increases the risk of cancer development via triggering the transcriptional agents, including nuclear factor kappa-light-chain-enhancer of activated B cells by generating the pro-inflammatory lipid molecules and infiltrating the tumor cells along with the high level of pro-inflammatory signaling. These events can cause an inflammatory microenvironment. Resolvins might decrease the leukocyte influx into the inflamed tissues. It is widely accepted that resolvins prohibit the development of debris-triggered cancer via increasing the clearance of debris, especially by macrophage phagocytosis in tumors without any side effects. Resolvins D2, D1, and E1 might suppress tumor-growing inflammation by activation of macrophages clearance of cell debris in the tumor. Resolvin D5 can assist patients with pain during treatment. However, the effects of resolvins as anti-inflammatory mediators in cancers are not completely explained. Thus, based on the most recent studies, we tried to summarize the most recent knowledge on resolvins in cancers.

[1]
Jiang, L.; Poon, I.K.H. Methods for monitoring the progression of cell death, cell disassembly and cell clearance. Apoptosis, 2019, 24(3-4), 208-220.
[http://dx.doi.org/10.1007/s10495-018-01511-x] [PMID: 30684146]
[2]
Benish, M.; Ben-Eliyahu, S. Surgery as a double-edged sword: A clinically feasible approach to overcome the metastasis-promoting effects of surgery by blunting stress and prostaglandin responses. Cancers, 2010, 2(4), 1929-1951.
[http://dx.doi.org/10.3390/cancers2041929] [PMID: 24281210]
[3]
Magge, R.S.; DeAngelis, L.M. The double-edged sword: Neurotoxicity of chemotherapy. Blood Rev., 2015, 29(2), 93-100.
[http://dx.doi.org/10.1016/j.blre.2014.09.012] [PMID: 25445718]
[4]
Panigrahy, D.; Gartung, A.; Yang, J.; Yang, H.; Gilligan, M.M.; Sulciner, M.L.; Bhasin, S.S.; Bielenberg, D.R.; Chang, J.; Schmidt, B.A.; Piwowarski, J.; Fishbein, A.; Soler-Ferran, D.; Sparks, M.A.; Staffa, S.J.; Sukhatme, V.; Hammock, B.D.; Kieran, M.W.; Huang, S.; Bhasin, M.; Serhan, C.N.; Sukhatme, V.P. Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases. J. Clin. Invest., 2019, 129(7), 2964-2979.
[http://dx.doi.org/10.1172/JCI127282] [PMID: 31205032]
[5]
Krall, J.A.; Reinhardt, F.; Mercury, O.A.; Pattabiraman, D.R.; Brooks, M.W.; Dougan, M.; Lambert, A.W.; Bierie, B.; Ploegh, H.L.; Dougan, S.K.; Weinberg, R.A. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med., 2018, 10(436), eaan3464.
[http://dx.doi.org/10.1126/scitranslmed.aan3464] [PMID: 29643230]
[6]
de Boer, M.; van Deurzen, C.H.M.; van Dijck, J.A.A.M.; Borm, G.F.; van Diest, P.J.; Adang, E.M.M.; Nortier, J.W.R.; Rutgers, E.J.T.; Seynaeve, C.; Menke-Pluymers, M.B.E.; Bult, P.; Tjan-Heijnen, V.C.G. Micrometastases or isolated tumor cells and the outcome of breast cancer. N. Engl. J. Med., 2009, 361(7), 653-663.
[http://dx.doi.org/10.1056/NEJMoa0904832] [PMID: 19675329]
[7]
Gilroy, D.W.; Lawrence, T.; Perretti, M.; Rossi, A.G. Inflammatory resolution: New opportunities for drug discovery. Nat. Rev. Drug Discov., 2004, 3(5), 401-416.
[http://dx.doi.org/10.1038/nrd1383] [PMID: 15136788]
[8]
Nathan, C.; Ding, A. Nonresolving inflammation. Cell, 2010, 140(6), 871-882.
[http://dx.doi.org/10.1016/j.cell.2010.02.029] [PMID: 20303877]
[9]
Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F. Cancer-related inflammation. Nature, 2008, 454(7203), 436-444.
[http://dx.doi.org/10.1038/nature07205] [PMID: 18650914]
[10]
Pisco, A.O.; Huang, S. Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: ‘What does not kill me strengthens me’. Br. J. Cancer, 2015, 112(11), 1725-1732.
[http://dx.doi.org/10.1038/bjc.2015.146] [PMID: 25965164]
[11]
Brock, A.; Huang, S. Precision oncology: Between vaguely right and precisely wrong. Cancer Res., 2017, 77(23), 6473-6479.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0448] [PMID: 29162615]
[12]
Serhan, C.N. Resolution phase of inflammation: Novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu. Rev. Immunol., 2007, 25, 101-137.
[http://dx.doi.org/10.1146/annurev.immunol.25.022106.141647]
[13]
Serhan, C.N.; Brain, S.D.; Buckley, C.D.; Gilroy, D.W.; Haslett, C.; O’Neill, L.A.J.; Perretti, M.; Rossi, A.G.; Wallace, J.L. Resolution of in flammation: State of the art, definitions and terms. FASEB J., 2007, 21(2), 325-332.
[http://dx.doi.org/10.1096/fj.06-7227rev] [PMID: 17267386]
[14]
Razi, S.; Yaghmoorian Khojini, J.; Kargarijam, F.; Panahi, S.; Tahershamsi, Z.; Tajbakhsh, A.; Gheibihayat, S.M. Macrophage efferocytosis in health and disease. Cell Biochem. Funct., 2023, 41(2), 152-165.
[http://dx.doi.org/10.1002/cbf.3780] [PMID: 36794573]
[15]
Janakiram, N.B.; Mohammed, A.; Rao, C.V. Role of lipoxins, resolvins, and other bioactive lipids in colon and pancreatic cancer. Cancer Metastasis Rev., 2011, 30(3-4), 507-523.
[http://dx.doi.org/10.1007/s10555-011-9311-2] [PMID: 22015691]
[16]
Sulciner, M.L.; Serhan, C.N.; Gilligan, M.M.; Mudge, D.K.; Chang, J.; Gartung, A.; Lehner, K.A.; Bielenberg, D.R.; Schmidt, B.; Dalli, J.; Greene, E.R.; Gus-Brautbar, Y.; Piwowarski, J.; Mammoto, T.; Zurakowski, D.; Perretti, M.; Sukhatme, V.P.; Kaipainen, A.; Kieran, M.W.; Huang, S.; Panigrahy, D. Resolvins suppress tumor growth and enhance cancer therapy. J. Exp. Med., 2018, 215(1), 115-140.
[http://dx.doi.org/10.1084/jem.20170681] [PMID: 29191914]
[17]
Pirault, J.; Bäck, M. Lipoxin and resolvin receptors transducing the resolution of inflammation in cardiovascular disease. Front. Pharmacol., 2018, 9(1273), 1273.
[http://dx.doi.org/10.3389/fphar.2018.01273] [PMID: 30487747]
[18]
Sun, Y.P.; Oh, S.F.; Uddin, J.; Yang, R.; Gotlinger, K.; Campbell, E.; Colgan, S.P.; Petasis, N.A.; Serhan, C.N. Resolvin D1 and its aspirin-triggered 17R epimer. Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation. J. Biol. Chem., 2007, 282(13), 9323-9334.
[http://dx.doi.org/10.1074/jbc.M609212200] [PMID: 17244615]
[19]
Serhan, C.N.; Hong, S.; Gronert, K.; Colgan, S.P.; Devchand, P.R.; Mirick, G.; Moussignac, R.L. Resolvins. J. Exp. Med., 2002, 196(8), 1025-1037.
[http://dx.doi.org/10.1084/jem.20020760] [PMID: 12391014]
[20]
Krishnamoorthy, S.; Recchiuti, A.; Chiang, N.; Yacoubian, S.; Lee, C.H.; Yang, R.; Petasis, N.A.; Serhan, C.N. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc. Natl. Acad. Sci. USA, 2010, 107(4), 1660-1665.
[http://dx.doi.org/10.1073/pnas.0907342107] [PMID: 20080636]
[21]
Merched, A.J.; Ko, K.; Gotlinger, K.H.; Serhan, C.N.; Chan, L. Atherosclerosis: Evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J., 2008, 22(10), 3595-3606.
[http://dx.doi.org/10.1096/fj.08-112201] [PMID: 18559988]
[22]
Tajbakhsh, A.; Rezaee, M.; Kovanen, P.T.; Sahebkar, A. A. Efferocytosis in atherosclerotic lesions: Malfunctioning regulatory pathways and control mechanisms. Pharmacol. Ther., 188, 12-25.2018,
[23]
Kobayashi, N.; Karisola, P.; Peña-Cruz, V.; Dorfman, D.M.; Jinushi, M.; Umetsu, S.E.; Butte, M.J.; Nagumo, H.; Chernova, I.; Zhu, B.; Sharpe, A.H.; Ito, S.; Dranoff, G.; Kaplan, G.G.; Casasnovas, J.M.; Umetsu, D.T.; DeKruyff, R.H.; Freeman, G.J. TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity, 2007, 27(6), 927-940.
[http://dx.doi.org/10.1016/j.immuni.2007.11.011] [PMID: 18082433]
[24]
Krishnamoorthy, N.; Abdulnour, R.E.E.; Walker, K.H.; Engstrom, B.D.; Levy, B.D. Specialized proresolving mediators in innate and adaptive immune responses in airway diseases. Physiol. Rev., 2018, 98(3), 1335-1370.
[http://dx.doi.org/10.1152/physrev.00026.2017] [PMID: 29717929]
[25]
Lund, T.; Mangsbo, S.M.; Scholz, H.; Gjorstrup, P.; Tötterman, T.H.; Korsgren, O.; Foss, A. Resolvin E1 reduces proinflammatory markers in human pancreatic islets in vitro. Exp. Clin. Endocrinol. Diabetes, 2010, 118(4), 237-244.
[http://dx.doi.org/10.1055/s-0029-1241825] [PMID: 20119897]
[26]
Colotta, F.; Allavena, P.; Sica, A.; Garlanda, C.; Mantovani, A. Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability. Carcinogenesis, 2009, 30(7), 1073-1081.
[http://dx.doi.org/10.1093/carcin/bgp127] [PMID: 19468060]
[27]
Liu, X.; Yin, L.; Shen, S.; Hou, Y. Inflammation and cancer: Paradoxical roles in tumorigenesis and implications in immunotherapies. Genes Dis., 2023, 10(1), 151-164.
[http://dx.doi.org/10.1016/j.gendis.2021.09.006] [PMID: 37013041]
[28]
Malekghasemi, S.; Majidi, J.; Baghbanzadeh, A.; Abdolalizadeh, J.; Baradaran, B.; Aghebati-Maleki, L. Tumor-associated macrophages: Protumoral macrophages in inflammatory tumor microenvironment. Adv. Pharm. Bull., 2020, 10(4), 556-565.
[http://dx.doi.org/10.34172/apb.2020.066] [PMID: 33062602]
[29]
Negus, R.P.; Stamp, G.W.; Hadley, J.; Balkwill, F.R. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am. J. Pathol., 1997, 150(5), 1723-1734.
[PMID: 9137096]
[30]
Singh, N.; Baby, D.; Rajguru, J.; Patil, P.; Thakkannavar, S.; Pujari, V. Inflammation and cancer. Ann. Afr. Med., 2019, 18(3), 121-126.
[http://dx.doi.org/10.4103/aam.aam_56_18] [PMID: 31417011]
[31]
Aggarwal, B.B.; Vijayalekshmi, R.V.; Sung, B. Targeting inflammatory pathways for prevention and therapy of cancer: Short-term friend, long-term foe. Clin. Cancer Res., 2009, 15(2), 425-430.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0149] [PMID: 19147746]
[32]
Zhang, Y.; Kong, W.; Jiang, J. Prevention and treatment of cancer targeting chronic inflammation: Research progress, potential agents, clinical studies and mechanisms. Sci. China Life Sci., 2017, 60(6), 601-616.
[http://dx.doi.org/10.1007/s11427-017-9047-4] [PMID: 28639101]
[33]
Cordon-Cardo, C.; Prives, C. At the crossroads of inflammation and tumorigenesis. J. Exp. Med., 1999, 190(10), 1367-1370.
[http://dx.doi.org/10.1084/jem.190.10.1367] [PMID: 10562311]
[34]
Lee, S.H.; Cho, S.Y.; Yoon, Y.; Park, C.; Sohn, J.; Jeong, J.J.; Jeon, B.N.; Jang, M.; An, C.; Lee, S.; Kim, Y.Y.; Kim, G.; Kim, S.; Kim, Y.; Lee, G.B.; Lee, E.J.; Kim, S.G.; Kim, H.S.; Kim, Y.; Kim, H.; Yang, H.S.; Kim, S.; Kim, S.; Chung, H.; Moon, M.H.; Nam, M.H.; Kwon, J.Y.; Won, S.; Park, J.S.; Weinstock, G.M.; Lee, C.; Yoon, K.W.; Park, H. Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice. Nat. Microbiol., 2021, 6(3), 277-288.
[http://dx.doi.org/10.1038/s41564-020-00831-6] [PMID: 33432149]
[35]
Zhao, H.; Wu, L.; Yan, G.; Chen, Y.; Zhou, M.; Wu, Y.; Li, Y. Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct. Target. Ther., 2021, 6(1), 263.
[http://dx.doi.org/10.1038/s41392-021-00658-5] [PMID: 34248142]
[36]
Philip, M.; Rowley, D.A.; Schreiber, H. Inflammation as a tumor promoter in cancer induction. Semin. Cancer Biol., 2004, 14(6), 433-439.
[http://dx.doi.org/10.1016/j.semcancer.2004.06.006] [PMID: 15489136]
[37]
Lin, A.; Karin, M. NF-κB in cancer: A marked target. Semin. Cancer Biol., 2003, 13(2), 107-114.
[http://dx.doi.org/10.1016/S1044-579X(02)00128-1] [PMID: 12654254]
[38]
Balkwill, F. Tumour necrosis factor and cancer. Nat. Rev. Cancer, 2009, 9(5), 361-371.
[http://dx.doi.org/10.1038/nrc2628] [PMID: 19343034]
[39]
Micheau, O.; Tschopp, J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell, 2003, 114(2), 181-190.
[http://dx.doi.org/10.1016/S0092-8674(03)00521-X] [PMID: 12887920]
[40]
Vacca, P.; Munari, E.; Tumino, N.; Moretta, F.; Pietra, G.; Vitale, M.; Del Zotto, G.; Mariotti, F.R.; Mingari, M.C.; Moretta, L. Human natural killer cells and other innate lymphoid cells in cancer: friends or foes? Immunol. Lett., 2018, 201, 14-19.
[http://dx.doi.org/10.1016/j.imlet.2018.11.004] [PMID: 30439479]
[41]
Chrisikos, T.T.; Zhou, Y.; Slone, N.; Babcock, R.; Watowich, S.S.; Li, H.S. Molecular regulation of dendritic cell development and function in homeostasis, inflammation, and cancer. Mol. Immunol., 2019, 110, 24-39.
[http://dx.doi.org/10.1016/j.molimm.2018.01.014]
[42]
Mottola, G.; Chatterjee, A.; Wu, B.; Chen, M.; Conte, M.S. Aspirin-triggered resolvin D1 attenuates PDGF-induced vascular smooth muscle cell migration via the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway. PLoS One, 2017, 12(3), e0174936.
[http://dx.doi.org/10.1371/journal.pone.0174936] [PMID: 28362840]
[43]
Yin, C.; Argintaru, D.; Heit, B. Rab17 mediates intermixing of phagocytosed apoptotic cells with recycling endosomes. Small GTPases, 2019, 10(3), 218-226.
[http://dx.doi.org/10.1080/21541248.2017.1308852] [PMID: 28471261]
[44]
Gordon, S.; Martinez, F.O. Alternative activation of macrophages: Mechanism and functions. Immunity, 2010, 32(5), 593-604.
[http://dx.doi.org/10.1016/j.immuni.2010.05.007] [PMID: 20510870]
[45]
Ishida, T.; Yoshida, M.; Arita, M.; Nishitani, Y.; Nishiumi, S.; Masuda, A.; Mizuno, S.; Takagawa, T.; Morita, Y.; Kutsumi, H.; Inokuchi, H.; Serhan, C.N.; Blumberg, R.S.; Azuma, T. Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium–induced colitis. Inflamm. Bowel Dis., 2010, 16(1), 87-95.
[http://dx.doi.org/10.1002/ibd.21029] [PMID: 19572372]
[46]
Connor, K.M.; SanGiovanni, J.P.; Lofqvist, C.; Aderman, C.M.; Chen, J.; Higuchi, A.; Hong, S.; Pravda, E.A.; Majchrzak, S.; Carper, D.; Hellstrom, A.; Kang, J.X.; Chew, E.Y.; Salem, N., Jr; Serhan, C.N.; Smith, L.E.H. Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat. Med., 2007, 13(7), 868-873.
[http://dx.doi.org/10.1038/nm1591] [PMID: 17589522]
[47]
Serhan, C.N. Novel lipid mediators and resolution mechanisms in acute inflammation: To resolve or not? Am. J. Pathol., 2010, 177(4), 1576-1591.
[http://dx.doi.org/10.2353/ajpath.2010.100322] [PMID: 20813960]
[48]
Norris, P.C.; Libreros, S.; Serhan, C.N. Resolution metabolomes activated by hypoxic environment. Sci. Adv., 2019, 5(10), eaax4895.
[http://dx.doi.org/10.1126/sciadv.aax4895] [PMID: 31681846]
[49]
Shepelin, D.; Korzinkin, M.; Vanyushina, A.; Aliper, A.; Borisov, N.; Vasilov, R.; Zhukov, N.; Sokov, D.; Prassolov, V.; Gaifullin, N.; Zhavoronkov, A.; Bhullar, B.; Buzdin, A. Molecular pathway activation features linked with transition from normal skin to primary and metastatic melanomas in human. Oncotarget, 2016, 7(1), 656-670.
[http://dx.doi.org/10.18632/oncotarget.6394] [PMID: 26624979]
[50]
Zhong, X.; Lee, H.N.; Surh, Y.J. RvD1 inhibits TNFα-induced c-Myc expression in normal intestinal epithelial cells and destabilizes hyper-expressed c-Myc in colon cancer cells. Biochem. Biophys. Res. Commun., 2018, 496(2), 316-323.
[http://dx.doi.org/10.1016/j.bbrc.2017.12.171] [PMID: 29305860]
[51]
Polavarapu, S.; Dwarakanath, B.S.; Das, U.N. Differential action of polyunsaturated fatty acids and eicosanoids on bleomycin-induced cytotoxicity to neuroblastoma cells and lymphocytes. Arch. Med. Sci., 2018, 1(1), 207-229.
[http://dx.doi.org/10.5114/aoms.2018.72244] [PMID: 29379552]
[52]
Lu, Y.; Xu, Q.; Yin, G.; Xu, W.; Jiang, H. Resolvin D1 inhibits the proliferation of lipopolysaccharide-treated HepG2 hepatoblastoma and PLC/PRF/5 hepatocellular carcinoma cells by targeting the MAPK pathway. Exp. Ther. Med., 2018, 16(4), 3603-3610.
[http://dx.doi.org/10.3892/etm.2018.6651] [PMID: 30233715]
[53]
Prevete, N.; Liotti, F.; Illiano, A.; Amoresano, A.; Pucci, P.; de Paulis, A.; Melillo, R.M. Formyl peptide receptor 1 suppresses gastric cancer angiogenesis and growth by exploiting inflammation resolution pathways. OncoImmunology, 2017, 6(4), e1293213.
[http://dx.doi.org/10.1080/2162402X.2017.1293213] [PMID: 28507800]
[54]
Fedirko, V.; McKeown-Eyssen, G.; Serhan, C.N.; Barry, E.L.; Sandler, R.S.; Figueiredo, J.C.; Ahnen, D.J.; Bresalier, R.S.; Robertson, D.J.; Anderson, C.W.; Baron, J.A. Plasma lipoxin A4 and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas. Mol. Carcinog., 2017, 56(8), 1977-1983.
[http://dx.doi.org/10.1002/mc.22629] [PMID: 28218420]
[55]
Eritja, N.; Jové, M.; Fasmer, K.E.; Gatius, S.; Portero-Otin, M.; Trovik, J.; Krakstad, C.; Sol, J.; Pamplona, R.; Haldorsen, I.S.; Matias-Guiu, X. Tumour-microenvironmental blood flow determines a metabolomic signature identifying lysophospholipids and resolvin D as biomarkers in endometrial cancer patients. Oncotarget, 2017, 8(65), 109018-109026.
[http://dx.doi.org/10.18632/oncotarget.22558] [PMID: 29312587]
[56]
Mohri, Y.; Tanaka, K.; Imaoka, H.; Miki, C.; Fujikawa, H.; Shimura, T.; Toiyama, Y.; Araki, T.; Inoue, Y.; Kusunoki, M. DHA-enriched supplement ameliorates cancer-associated systemic inflammatory response via resolvin D1 production: A single institutional study. Biomed. Res. Ther., 2016, 1(3), 120-125.
[57]
Kuang, H.; Hua, X.; Zhou, J.; Yang, R. Resolvin D1 and E1 alleviate the progress of hepatitis toward liver cancer in long-term concanavalin A-induced mice through inhibition of NF-κB activity. Oncol. Rep., 2016, 35(1), 307-317.
[http://dx.doi.org/10.3892/or.2015.4389] [PMID: 26531230]
[58]
Liu, Y.; Yuan, X.; Li, W.; Cao, Q.; Shu, Y. Aspirin-triggered resolvin D1 inhibits TGF-β1-induced EMT through the inhibition of the mTOR pathway by reducing the expression of PKM2 and is closely linked to oxidative stress. Int. J. Mol. Med., 2016, 38(4), 1235-1242.
[http://dx.doi.org/10.3892/ijmm.2016.2721] [PMID: 27573422]
[59]
Halder, R.C.; Almasi, A.; Sagong, B.; Leung, J.; Jewett, A.; Fiala, M. Curcuminoids and omega-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon gamma production. Front Physiol., 2015, 6, 129.
[http://dx.doi.org/10.3389/fphys.2015.00129] [PMID: 26052286]
[60]
Cholkar, K.; Trinh, H.M.; Vadlapudi, A.D.; Wang, Z.; Pal, D.; Mitra, A.K. Interaction studies of resolvin E1 analog (RX-10045) with efflux transporters. J. Ocul. Pharmacol. Ther., 2015, 31(4), 248-255.
[http://dx.doi.org/10.1089/jop.2014.0144] [PMID: 25844889]
[61]
Al-Zaubai, N.; Johnstone, C.N.; Leong, M.M.; Li, J.; Rizzacasa, M.; Stewart, A.G. Resolvin D2 supports MCF-7 cell proliferation via activation of estrogen receptor. J. Pharmacol. Exp. Ther., 2014, 351(1), 172-180.
[http://dx.doi.org/10.1124/jpet.114.214403] [PMID: 25077525]
[62]
Lee, H.J.; Park, M.K.; Lee, E.J.; Lee, C.H. Resolvin D1 inhibits TGF-β1-induced epithelial mesenchymal transition of A549 lung cancer cells via lipoxin A4 receptor/formyl peptide receptor 2 and GPR32. Int. J. Biochem. Cell Biol., 2013, 45(12), 2801-2807.
[http://dx.doi.org/10.1016/j.biocel.2013.09.018] [PMID: 24120851]
[63]
Ye, Y.; Scheff, N.N.; Bernabe, D.; Salvo, E.; Ono, K.; Liu, C.; Veeramachaneni, R.; Viet, C.T.; Viet, D.T.; Dolan, J.C.; Schmidt, B.L. Anti-cancer and analgesic effects of resolvin D2 in oral squamous cell carcinoma. Neuropharmacology., 2018, 139, 182-193.
[http://dx.doi.org/10.1016/j.neuropharm.2018.07.016]
[64]
Mattoscio, D.; Ferri, G.; Miccolo, C.; Chiocca, S.; Romano, M.; Recchiuti, A. Gene expression of the D-series resolvin pathway predicts activation of anti-tumor immunity and clinical outcomes in head and neck cancer. Int. J. Mol. Sci., 2022, 23(12), 6473.
[http://dx.doi.org/10.3390/ijms23126473] [PMID: 35742918]
[65]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[66]
Grivennikov, S.I.; Greten, F.R.; Karin, M. Immunity, inflammation, and cancer. Cell, 2010, 140(6), 883-899.
[http://dx.doi.org/10.1016/j.cell.2010.01.025] [PMID: 20303878]
[67]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[68]
Baumgarten, S.C.; Frasor, J. Minireview: Inflammation: An instigator of more aggressive estrogen receptor (ER) positive breast cancers. Mol. Endocrinol., 2012, 26(3), 360-371.
[http://dx.doi.org/10.1210/me.2011-1302] [PMID: 22301780]
[69]
Kang, G.J.; Lee, H.J.; Kang, Y.P.; Kim, E.J.; Kim, H.J.; Byun, H.J.; Park, M.K.; Cho, H.; Kwon, S.W.; Lee, C.H. High-mobility group box 1 suppresses resolvin D1-induced phagocytosis via induction of resolvin D1-inactivating enzyme, 15-hydroxyprostaglandin dehydrogenase. Biochim. Biophys. Acta Mol. Basis Dis., 2015, 1852(9), 1981-1988.
[http://dx.doi.org/10.1016/j.bbadis.2015.07.005] [PMID: 26170058]
[70]
Assaraf, Y.G. The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis. Drug Resist. Updat., 2006, 9(4-5), 227-246.
[http://dx.doi.org/10.1016/j.drup.2006.09.001] [PMID: 17092765]
[71]
Robey, R.W.; Polgar, O.; Deeken, J.; To, K.W.; Bates, S.E. ABCG2: Determining its relevance in clinical drug resistance. Cancer Metastasis Rev., 2007, 26(1), 39-57.
[http://dx.doi.org/10.1007/s10555-007-9042-6] [PMID: 17323127]
[72]
Cancer IAfRo. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018. 2018. Available from: https://www.iarc.who.int/wp-content/uploads/2018/09/pr263_E.pdf
[73]
Gomes, M.; Teixeira, A.L.; Coelho, A.; Araujo, A.; Medeiros, R. The role of inflammation in lung cancer. Adv. Exp. Med. Biol., 2014, 816, 1-23.
[http://dx.doi.org/10.1007/978-3-0348-0837-8_1]
[74]
Cho, W.C.S.; Kwan, C.K.; Yau, S.; So, P.P.F.; Poon, P.C.M.; Au, J.S.K. The role of inflammation in the pathogenesis of lung cancer. Expert Opin. Ther. Targets, 2011, 15(9), 1127-1137.
[http://dx.doi.org/10.1517/14728222.2011.599801] [PMID: 21751938]
[75]
Walser, T.; Cui, X.; Yanagawa, J.; Lee, J.M.; Heinrich, E.; Lee, G.; Sharma, S.; Dubinett, S.M. Smoking and lung cancer: The role of inflammation. Proc. Am. Thorac. Soc., 2008, 5(8), 811-815.
[http://dx.doi.org/10.1513/pats.200809-100TH] [PMID: 19017734]
[76]
Kim, M.J.; Lee, Y.J.; Yoon, Y.S.; Kim, M.; Choi, J.H.; Kim, H.S.; Kang, J.L. Apoptotic cells trigger the ABCA1/STAT6 pathway leading to PPAR-γ expression and activation in macrophages. J. Leukoc. Biol., 2018, 103(5), 885-895.
[http://dx.doi.org/10.1002/JLB.2A0817-341RR] [PMID: 29603355]
[77]
Huber, M.A.; Kraut, N.; Beug, H. Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr. Opin. Cell Biol., 2005, 17(5), 548-558.
[http://dx.doi.org/10.1016/j.ceb.2005.08.001] [PMID: 16098727]
[78]
Gilligan, M.M.; Gartung, A.; Sulciner, M.L.; Norris, P.C.; Sukhatme, V.P.; Bielenberg, D.R.; Huang, S.; Kieran, M.W.; Serhan, C.N.; Panigrahy, D. Aspirin-triggered proresolving mediators stimulate resolution in cancer. Proc. Natl. Acad. Sci. USA, 2019, 116(13), 6292-6297.
[http://dx.doi.org/10.1073/pnas.1804000116] [PMID: 30862734]
[79]
Itzkowitz, S.H.; Yio, X. Inflammation and Cancer IV. Colorectal cancer in inflammatory bowel disease: The role of inflammation. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 287(1), G7-G17.
[http://dx.doi.org/10.1152/ajpgi.00079.2004] [PMID: 15194558]
[80]
Kraus, S.; Arber, N. Inflammation and colorectal cancer. Curr. Opin. Pharmacol., 2009, 9(4), 405-410.
[http://dx.doi.org/10.1016/j.coph.2009.06.006] [PMID: 19589728]
[81]
Wang, S.; Liu, Z.; Wang, L.; Zhang, X. NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell. Mol. Immunol., 2009, 6(5), 327-334.
[http://dx.doi.org/10.1038/cmi.2009.43] [PMID: 19887045]
[82]
Sitarz, R.; Skierucha, M.; Mielko, J.; Offerhaus, G.J.A.; Maciejewski, R.; Polkowski, W.P. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag. Res., 2018, 10, 239-248.
[http://dx.doi.org/10.2147/CMAR.S149619] [PMID: 29445300]
[83]
Cheng, T-Y.; Wu, M-S.; Lin, J-T.; Lin, M-T.; Shun, C-T.; Hua, K-T.; Kuo, M-L. Formyl Peptide receptor 1 expression is associated with tumor progression and survival in gastric cancer. Anticancer Res., 2014, 34(5), 2223-2229.
[PMID: 24778024]
[84]
Prevete, N.; Liotti, F.; Visciano, C.; Marone, G.; Melillo, R.M.; de Paulis, A. The formyl peptide receptor 1 exerts a tumor suppressor function in human gastric cancer by inhibiting angiogenesis. Oncogene, 2015, 34(29), 3826-3838.
[http://dx.doi.org/10.1038/onc.2014.309] [PMID: 25263443]
[85]
Blot, W.J.; McLaughlin, J.K.; Winn, D.M.; Austin, D.F.; Greenberg, R.S.; Preston-Martin, S.; Bernstein, L.; Schoenberg, J.B.; Stemhagen, A.; Fraumeni, J.F., Jr Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res., 1988, 48(11), 3282-3287.
[PMID: 3365707]
[86]
Ji, R.R.; Xu, Z.Z.; Strichartz, G.; Serhan, C.N. Emerging roles of resolvins in the resolution of inflammation and pain. Trends Neurosci., 2011, 34(11), 599-609.
[http://dx.doi.org/10.1016/j.tins.2011.08.005] [PMID: 21963090]
[87]
Serhan, C.N. Pro-resolving lipid mediators are leads for resolution physiology. Nature, 2014, 510(7503), 92-101.
[http://dx.doi.org/10.1038/nature13479] [PMID: 24899309]
[88]
Park, C.K.; Xu, Z.Z.; Liu, T.; Lü, N.; Serhan, C.N.; Ji, R.R. Resolvin D2 is a potent endogenous inhibitor for transient receptor potential subtype V1/A1, inflammatory pain, and spinal cord synaptic plasticity in mice: Distinct roles of resolvin D1, D2, and E1. J. Neurosci., 2011, 31(50), 18433-18438.
[http://dx.doi.org/10.1523/JNEUROSCI.4192-11.2011] [PMID: 22171045]
[89]
Bang, S.; Yoo, S.; Yang, T.J.; Cho, H.; Kim, Y.G.; Hwang, S.W. Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br. J. Pharmacol., 2010, 161(3), 707-720.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00909.x] [PMID: 20880407]
[90]
Katoonizadeh, A.; Poustchi, H.; Malekzadeh, R. Hepatic progenitor cells in liver regeneration: Current advances and clinical perspectives. Liver Int., 2014, 34(10), 1464-1472.
[http://dx.doi.org/10.1111/liv.12573] [PMID: 24750779]
[91]
Carbone, M.; Neuberger, J.M. Autoimmune liver disease, autoimmunity and liver transplantation. J. Hepatol., 2014, 60(1), 210-223.
[http://dx.doi.org/10.1016/j.jhep.2013.09.020] [PMID: 24084655]
[92]
Rognant, N. Acute kidney injury in patients with chronic liver disease. World J. Hepatol., 2015, 7(7), 993-1000.
[http://dx.doi.org/10.4254/wjh.v7.i7.993] [PMID: 25954481]
[93]
Sun, L.; Wang, Y.; Wang, L.; Yao, B.; Chen, T.; Li, Q.; Liu, Z.; Liu, R.; Niu, Y.; Song, T.; Liu, Q.; Tu, K. Resolvin D1 prevents epithelial-mesenchymal transition and reduces the stemness features of hepatocellular carcinoma by inhibiting paracrine of cancer-associated fibroblast-derived COMP. J. Exp. Clin. Cancer Res., 2019, 38(1), 170.
[http://dx.doi.org/10.1186/s13046-019-1163-6] [PMID: 30999932]
[94]
Park, H.J.; Carr, J.R.; Wang, Z.; Nogueira, V.; Hay, N.; Tyner, A.L.; Lau, L.F.; Costa, R.H.; Raychaudhuri, P. FoxM1, a critical regulator of oxidative stress during oncogenesis. EMBO J., 2009, 28(19), 2908-2918.
[http://dx.doi.org/10.1038/emboj.2009.239] [PMID: 19696738]
[95]
Maris, J.M. Recent advances in neuroblastoma. N. Engl. J. Med., 2010, 362(23), 2202-2211.
[http://dx.doi.org/10.1056/NEJMra0804577] [PMID: 20558371]
[96]
Brodeur, G.M. Neuroblastoma: Biological insights into a clinical enigma. Nat. Rev. Cancer, 2003, 3(3), 203-216.
[http://dx.doi.org/10.1038/nrc1014] [PMID: 12612655]
[97]
Ogo, A.; Miyake, S.; Kubota, H.; Higashida, M.; Matsumoto, H.; Teramoto, F.; Hirai, T. Synergistic effect of eicosapentaenoic acid on antiproliferative action of anticancer drugs in a cancer cell line model. Ann. Nutr. Metab., 2017, 71(3-4), 247-252.
[http://dx.doi.org/10.1159/000484618] [PMID: 29136623]
[98]
Wang, J.; Luo, T.; Li, S.; Zhao, J. The powerful applications of polyunsaturated fatty acids in improving the therapeutic efficacy of anticancer drugs. Expert Opin. Drug Deliv., 2012, 9(1), 1-7.
[http://dx.doi.org/10.1517/17425247.2011.618183] [PMID: 22171694]
[99]
Yin, P.; Wei, Y.; Wang, X.; Zhu, M.; Feng, J. Roles of specialized pro-resolving lipid mediators in cerebral ischemia reperfusion injury. Front Neurol., 2018, 9, 617.
[http://dx.doi.org/10.3389/fneur.2018.00617] [PMID: 30131754]
[100]
Dalli, J.; Serhan, C.N. Specific lipid mediator signatures of human phagocytes: Microparticles stimulate macrophage efferocytosis and pro-resolving mediators. Blood, 2012, 120(15), e60-e72.
[http://dx.doi.org/10.1182/blood-2012-04-423525] [PMID: 22904297]
[101]
Hallisey, V.; Barksdale, C.A.; Chang, J.; Sulciner, M.L.; Bielenberg, D.R.; Schmidt, B.A.; Keiran, N.; Haung, S.; Serhan, C.N.; Keiran, M.W.; Panigrahy, D. Brain cancer: Failure of resolution of inflammation? FASEB J., 2019, 33(1), 250-254.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107670] [PMID: 32891711]
[102]
Tajbakhsh, A.; Gheibi Hayat, S.M.; Movahedpour, A.; Savardashtaki, A.; Loveless, R.; Barreto, G.E.; Teng, Y.; Sahebkar, A. The complex roles of efferocytosis in cancer development, metastasis, and treatment. Biomed. Pharmacother., 2021, 140, 111776.
[http://dx.doi.org/10.1016/j.biopha.2021.111776]
[103]
Amant, F.; Moerman, P.; Neven, P.; Timmerman, D.; Van Limbergen, E.; Vergote, I. Endometrial cancer. Lancet, 2005, 366(9484), 491-505.
[http://dx.doi.org/10.1016/S0140-6736(05)67063-8] [PMID: 16084259]
[104]
Armitage, E.G.; Barbas, C. Metabolomics in cancer biomarker discovery: Current trends and future perspectives. J. Pharm. Biomed. Anal., 2014, 87, 1-11.
[http://dx.doi.org/10.1016/j.jpba.2013.08.041]
[105]
Li, D.; Xie, K.; Wolff, R.; Abbruzzese, J.L. Pancreatic cancer. Lancet, 2004, 363(9414), 1049-1057.
[http://dx.doi.org/10.1016/S0140-6736(04)15841-8] [PMID: 15051286]
[106]
Hidalgo, M. Pancreatic cancer. N. Engl. J. Med., 2010, 362(17), 1605-1617.
[http://dx.doi.org/10.1056/NEJMra0901557] [PMID: 20427809]
[107]
Jakubowska, K.; Guzińska-Ustymowicz, K.; Famulski, W.; Cepowicz, D.; Jagodzińska, D.; Pryczynicz, A. Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells. Oncol. Lett., 2016, 11(3), 1879-1884.
[http://dx.doi.org/10.3892/ol.2016.4125] [PMID: 26998093]
[108]
Taylor, P.R.; Carugati, A.; Fadok, V.A.; Cook, H.T.; Andrews, M.; Carroll, M.C.; Savill, J.S.; Henson, P.M.; Botto, M.; Walport, M.J. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J. Exp. Med., 2000, 192(3), 359-366.
[http://dx.doi.org/10.1084/jem.192.3.359] [PMID: 10934224]
[109]
Gunjal, P.M.; Schneider, G.; Ismail, A.A.; Kakar, S.S.; Kucia, M.; Ratajczak, M.Z. Evidence for induction of a tumor metastasis-receptive microenvironment for ovarian cancer cells in bone marrow and other organs as an unwanted and underestimated side effect of chemotherapy/radiotherapy. J. Ovarian Res., 2015, 8, 20.
[http://dx.doi.org/10.1186/s13048-015-0141-7] [PMID: 25887079]
[110]
Chaurio, R.; Janko, C.; Schorn, C.; Maueröder, C.; Bilyy, R.; Gaipl, U.; Schett, G.; Berens, C.; Frey, B.; Munoz, L.E. UVB-irradiated apoptotic cells induce accelerated growth of co-implanted viable tumor cells in immune competent mice. Autoimmunity, 2013, 46(5), 317-322.
[http://dx.doi.org/10.3109/08916934.2012.754433] [PMID: 23194071]
[111]
Pearson, R.M.; Casey, L.M.; Hughes, K.R.; Miller, S.D.; Shea, L.D. In vivo reprogramming of immune cells: Technologies for induction of antigen-specific tolerance. Adv. Drug Deliv. Rev., 2017, 114, 240-255.
[http://dx.doi.org/10.1016/j.addr.2017.04.005] [PMID: 28414079]
[112]
Greene, E.R.; Huang, S.; Serhan, C.N.; Panigrahy, D. Regulation of inflammation in cancer by eicosanoids. Prostaglandins Other Lipid Mediat., 2011, 96(1-4), 27-36.
[http://dx.doi.org/10.1016/j.prostaglandins.2011.08.004] [PMID: 21864702]
[113]
Rothwell, P.M.; Wilson, M.; Price, J.F.; Belch, J.F.F.; Meade, T.W.; Mehta, Z. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet, 2012, 379(9826), 1591-1601.
[http://dx.doi.org/10.1016/S0140-6736(12)60209-8] [PMID: 22440947]
[114]
Fullerton, J.N.; Gilroy, D.W. Resolution of inflammation: A new therapeutic frontier. Nat. Rev. Drug Discov., 2016, 15(8), 551-567.
[http://dx.doi.org/10.1038/nrd.2016.39] [PMID: 27020098]
[115]
Birge, R.B.; Boeltz, S.; Kumar, S.; Carlson, J.; Wanderley, J.; Calianese, D.; Barcinski, M.; Brekken, R.A.; Huang, X.; Hutchins, J.T.; Freimark, B.; Empig, C.; Mercer, J.; Schroit, A.J.; Schett, G.; Herrmann, M. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. Cell Death Differ., 2016, 23(6), 962-978.
[http://dx.doi.org/10.1038/cdd.2016.11] [PMID: 26915293]
[116]
Jing, J.; Yang, I.V.; Hui, L.; Patel, J.A.; Evans, C.M.; Prikeris, R.; Kobzik, L.; O’Connor, B.P.; Schwartz, D.A. Role of macrophage receptor with collagenous structure in innate immune tolerance. J. Immunol., 2013, 190(12), 6360-6367.
[http://dx.doi.org/10.4049/jimmunol.1202942] [PMID: 23667110]
[117]
Jacinto, R.; Hartung, T.; McCall, C.; Li, L. Lipopolysaccharide- and lipoteichoic acid-induced tolerance and cross-tolerance: Distinct alterations in IL-1 receptor-associated kinase. J. Immunol., 2002, 168(12), 6136-6141.
[http://dx.doi.org/10.4049/jimmunol.168.12.6136] [PMID: 12055225]
[118]
Getts, D.R.; McCarthy, D.P.; Miller, S.D. Exploiting apoptosis for therapeutic tolerance induction. J. Immunol., 2013, 191(11), 5341-5346.
[http://dx.doi.org/10.4049/jimmunol.1302070] [PMID: 24244028]
[119]
Francisco, L.M.; Sage, P.T.; Sharpe, A.H. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev., 2010, 236, 219-242.
[http://dx.doi.org/10.1111/j.1600-065X.2010.00923.x]
[120]
Zhang, Q.; Zhu, B.; Li, Y. Resolution of cancer-promoting inflammation: a new approach for anticancer therapy. Front Immunol., 2017, 8, 71.
[http://dx.doi.org/10.3389/fimmu.2017.00071] [PMID: 28210259]
[121]
Mickle, A.D.; Shepherd, A.J.; Mohapatra, D.P. Sensory TRP channels: The key transducers of nociception and pain. Prog. Mol. Biol. Transl. Sci., 2015, 131, 73-118.
[http://dx.doi.org/10.3389/fimmu.2017.00071] [PMID: 28210259]
[122]
Caraceni, A.; Portenoy, R.K. An international survey of cancer pain characteristics and syndromes. Pain, 1999, 82(3), 263-274.
[http://dx.doi.org/10.1016/S0304-3959(99)00073-1] [PMID: 10488677]
[123]
Lara-Solares, A.; Ahumada Olea, M.; Basantes Pinos, A.Á.; Bistre Cohén, S.; Bonilla Sierra, P.; Duarte Juárez, E.R.; Símon Escudero, O.A.; Santacruz Escudero, J.G.; Flores Cantisani, J.A. Latin-American guidelines for cancer pain management. Pain Manag., 2017, 7(4), 287-298.
[http://dx.doi.org/10.2217/pmt-2017-0006] [PMID: 28326952]
[124]
Falk, S.; Dickenson, A.H. Pain and nociception: Mechanisms of cancer-induced bone pain. J. Clin. Oncol., 2014, 32(16), 1647-1654.
[http://dx.doi.org/10.1200/JCO.2013.51.7219] [PMID: 24799469]
[125]
Elinav, E.; Nowarski, R.; Thaiss, C.A.; Hu, B.; Jin, C.; Flavell, R.A. Inflammation-induced cancer: Crosstalk between tumours, immune cells and microorganisms. Nat. Rev. Cancer, 2013, 13(11), 759-771.
[http://dx.doi.org/10.1038/nrc3611] [PMID: 24154716]
[126]
Shinko, D.; Diakos, C.I.; Clarke, S.J.; Charles, K.A. Cancer-related systemic inflammation: The challenges and therapeutic opportunities for personalized medicine. Clin. Pharmacol. Ther., 2017, 102(4), 599-610.
[http://dx.doi.org/10.1002/cpt.789] [PMID: 28699186]
[127]
Freitas, R.; Campos, M.M. Protective effects of omega-3 fatty acids in cancer-related complications. Nutrients, 2019, 11(5), 945.
[http://dx.doi.org/10.3390/nu11050945] [PMID: 31035457]
[128]
Luo, X.; Gu, Y.; Tao, X.; Serhan, C.N.; Ji, R.R. Resolvin D5 inhibits neuropathic and inflammatory pain in male but not female mice: distinct actions of D-series resolvins in chemotherapy-induced peripheral neuropathy. Front. Pharmacol., 2019, 10, 745.
[http://dx.doi.org/10.3389/fphar.2019.00745] [PMID: 31333464]
[129]
Choi, G.; Hwang, S.W. Modulation of the activities of neuronal ion channels by fatty acid-derived pro-resolvents. Front Physiol., 2016, 7, 523.
[http://dx.doi.org/10.3389/fphys.2016.00523]
[130]
Kantarci, A.; Kansal, S.; Hasturk, H.; Stephens, D.; Van Dyke, T.E. Resolvin E1 reduces tumor growth in a xenograft model of lung cancer. Am. J. Pathol., 2022, 192(10), 1470-1484.
[http://dx.doi.org/10.1016/j.ajpath.2022.07.004] [PMID: 35944728]
[131]
Choi, M.K.; Kim, J.; Park, H.M.; Lim, C.M.; Pham, T.H.; Shin, H.Y.; Kim, S.E.; Oh, D.K.; Yoon, D.Y. The DPA-derivative 11S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)- docosapentaenoic acid inhibits IL-6 production by inhibiting ROS production and ERK/NF-κB pathway in keratinocytes HaCaT stimulated with a fine dust PM(10). Ecotoxicol Environ Saf., 2022, 232, 113252.
[http://dx.doi.org/10.1016/j.ecoenv.2022.113252] [PMID: 35104780]
[132]
Blogowski, W.; Dolegowska, K.; Deskur, A.; Dolegowska, B.; Starzynska, T. Lipoxins and resolvins in patients with pancreatic cancer: A preliminary report. Front Oncol., 2021, 11, 757073.
[http://dx.doi.org/10.3389/fonc.2021.757073] [PMID: 35087747]
[133]
Bilodeau, J.F.; Gevariya, N.; Larose, J.; Robitaille, K.; Roy, J.; Oger, C.; Galano, J.M.; Bergeron, A.; Durand, T.; Fradet, Y.; Julien, P.; Fradet, V. Long chain omega-3 fatty acids and their oxidized metabolites are associated with reduced prostate tumor growth. Prostaglandins Leukot Essent Fatty Acids., 2021, 164, 102215.
[http://dx.doi.org/10.1016/j.plefa.2020.102215] [PMID: 35087747]
[134]
Khasabova, I.A.; Golovko, M.Y.; Golovko, S.A.; Simone, D.A.; Khasabov, S.G. Intrathecal administration of Resolvin D1 and E1 decreases hyperalgesia in mice with bone cancer pain: Involvement of endocannabinoid signaling. Prostaglandins Other Lipid Mediat., 2020.
[http://dx.doi.org/10.1016/j.prostaglandins.2020.106479] [PMID: 32745525]

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      • 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 ('316323591','/article/133198',1,1740526371,1740526371)
      150μsalphaeurekaselec_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 >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) 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 >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) 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 >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) 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 >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) 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 >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) 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 >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316323591 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316323591) limit 1
      11.64msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316323591
      • 1: 316323591
      • 2: 316323591
      • 3: 316323591
      • 4: 316323591
      • 5: 316323591
      • 6: 316323591
      • 7: 316323591
      • 8: 316323591
      • 9: 316323591
      • 10: 316323591
      • 11: 316323591
      • 12: 316323591
      • 13: 316323591
      • 14: 316323591
      • 15: 316323591
      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=133198
      700μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 25 limit 1
      740μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 25
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid`) as `aggregate_table`
      1.36msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.1msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.29msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.66msalphaeurekaselec_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` = '133198'
      200μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 133198
      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` = '133198'
      4.99msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 133198
      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` = '133198' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.08msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 133198
      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
      270μsalphaeurekaselec_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 = 25 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      30.47msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      33.52msalphaeurekaselec_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 = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      27.5msalphaeurekaselec_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` = 133198 limit 1
      190μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 133198
      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 = 133198 and content_type = 'article' order by status desc limit 1
      230μsalphaeurekaselec_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` = 219175 limit 1
      190μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 219175
      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
      190μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      330μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '133198' 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) )
      320μsalphaeurekaselec_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 = '13550' 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) )
      270μsalphaeurekaselec_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 = '3436' 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) )
      240μsalphaeurekaselec_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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3436) 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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3436) 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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3436)
      5.7msalphaeurekaselec_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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13550) 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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13550) 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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13550)
      580μsalphaeurekaselec_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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 133198) 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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 133198) 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 <= 316323591 and j.to_ip >=316323591 )) and ((j.from_date <= 1740526371 and j.to_date >= 1740526371 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 133198)
      570μsalphaeurekaselec_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` < '5898' and is_uploaded = 1 and issue_id = 13550 order by cast(first_page as SIGNED) desc limit 1
      450μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 5898
      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` > '5917' and is_uploaded = 1 and issue_id = 13550 order by cast(first_page as SIGNED) asc limit 1
      390μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 5917
      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'
      170μsalphaeurekaselec_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
      210μsalphaeurekaselec_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` = 133198 limit 1
      2.75msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 133198
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740526371 and `b`.`banner_to_date` >= 1740526371 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.38msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740526371
      • 4: 1740526371
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740526371 and `b`.`banner_to_date` >= 1740526371 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.4msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740526371
      • 4: 1740526371
      • 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='646fcb81127bb0d761191b6f14802248'
      230μsalphaeurekaselec_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
        bc6hol42QTuAUbtxlW33HCXIqvzFGH3plnVYPzYB
        uc_cart_id
        646fcb81127bb0d761191b6f14802248
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/133198" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/133198
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InNHdTRWNlFsZitaY1A0SU9UZ210SHc9PSIsInZhbHVlIjoiYlNZVVk1alA3N2Y0WmdVRktHVzkwYUdSV1JwNElveC9wajZyUGYzVU1rWT0iLCJtYWMiOiIzODUxZjJjMjRlZWYyZjMwMzc4YTVkNjUzNDNiOTQyN2I2YWQ3YzczMTdhZjkxM2I1ZWNlMjExNGIzNjhlMzA0IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InNHdTRWNlFsZitaY1A0SU9UZ210SHc9PSIsInZhbHVlIjoiYlNZVVk1alA3N2Y0WmdVRktHVzkwYUdSV1JwNElveC9wajZyUGYzVU1rWT0iLCJtYWMiOiIzODUxZjJjMjRlZWYy" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
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