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Current Pharmaceutical Biotechnology

Editor-in-Chief

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

Review Article

Application of Hairy Root Culture for Bioactive Compounds Production in Medicinal Plants

Author(s): Caili Li and Meizhen Wang*

Volume 22, Issue 5, 2021

Published on: 16 May, 2020

Page: [592 - 608] Pages: 17

DOI: 10.2174/1389201021666200516155146

Price: $65

Abstract

Medicinal plants are rich sources of natural bioactive compounds used to treat many diseases. With the development of the health industry, the market demands for Chinese medicine have been rapidly increasing in recent years. However, over-utilization of herbal plants would cause serious ecological problems. Therefore, an effective approach should be developed to produce the pharmaceutically important natural drugs. Hairy root culture induced by Agrobacterium rhizogenes has been considered to be an effective tool to produce secondary metabolites that are originally biosynthesized in the roots or even in the aerial organs of mature plants. This review aims to summarize current progress on medicinal plant hairy root culture for bioactive compounds production. It presents the stimulating effects of various biotic and abiotic elicitors on the accumulation of secondary metabolites. Synergetic effects by combination of different elicitors or with other strategies are also included. Besides, the transgenic system has promising prospects to increase bioactive compounds content by introducing their biosynthetic or regulatory genes into medicinal plant hairy root. It offers great potential to further increase secondary metabolites yield by the integration of manipulating pathway genes with elicitors and other strategies. Then advances on two valuable pharmaceuticals production in the hairy root cultures are illustrated in detail. Finally, successful production of bioactive compounds by hairy root culture in bioreactors are introduced.

Keywords: Bioactive compounds, hairy root, medicinal plant, elicitor, regulatory genes, metabolic engineering.

Graphical Abstract

[1]
World Health Organization. In: In: The Promotion and Development of Traditional Medicine: Technical Report Series, November 28- December 21977;
[2]
Harvey, A.L. Natural products in drug discovery. Drug Discov. Today, 2008, 13(19-20), 894-901.
[http://dx.doi.org/10.1016/j.drudis.2008.07.004] [PMID: 18691670]
[3]
Koehn, F.E.; Carter, G.T. The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov., 2005, 4(3), 206-220.
[http://dx.doi.org/10.1038/nrd1657] [PMID: 15729362]
[4]
Montinari, M.R.; Minelli, S.; De Caterina, R. The first 3500 years of aspirin history from its roots-A concise summary. Vasc. Pharmacol., 2018, 113, 1-8.
[PMID: 30391545]
[5]
Tu, Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat. Med., 2011, 17(10), 1217-1220.
[http://dx.doi.org/10.1038/nm.2471] [PMID: 21989013]
[6]
Chandra, S.; Chandra, R. Engineering secondary metabolite production in hairy roots. Phytochem. Rev., 2011, 10, 371-395.
[http://dx.doi.org/10.1007/s11101-011-9210-8]
[7]
Shoeb, M. Anti-cancer agents from medicinal plants. Bangladesh J. Pharmacol., 2006, 1(2), 35-41.
[8]
Kim, Y.J.; Wyslouzil, B.E.; Weathers, P.J. Invited review: secondary metabolism of hairy root cultures in bioreactors. In Vitro Cell. Dev. Biol. Plant, 2002, 38, 1-10.
[http://dx.doi.org/10.1079/IVP2001243]
[9]
Strobel, G.A.; Hess, W.M.; Ford, E.; Sidhu, R.S.; Yang, X. Taxol from fungal endophytes and the issue of biodiversity. J. Ind. Microbiol. Biotechnol., 1996, 17(5-6), 417-423.
[http://dx.doi.org/10.1007/BF01574772]
[10]
de Brito Francisco, R.; Martinoia, E. The vacuolar transportome of plant specialized metabolites. Plant Cell Physiol., 2018, 59(7), 1326-1336.
[http://dx.doi.org/10.1093/pcp/pcy039] [PMID: 29452376]
[11]
Mukundan, U.; Dawda, H.G.; Ratnaparkhi, S. Hairy root culture and secondary metabolite production: Agrobacterium rhizogenes mediated transformed root cultures (No. 2); Agro Botanica, 1997.
[12]
Balandrin, M.F.; Klocke, J.A.; Wurtele, E.S.; Bollinger, W.H. Natural plant chemicals: sources of industrial and medicinal materials. Science, 1985, 228(4704), 1154-1160.
[http://dx.doi.org/10.1126/science.3890182] [PMID: 3890182]
[13]
DiCosmo, F.; Misawa, M. Plant cell and tissue culture: alternatives for metabolite production. Biotechnol. Adv., 1995, 13(3), 425-453.
[http://dx.doi.org/10.1016/0734-9750(95)02005-N] [PMID: 14536096]
[14]
Smetanska, I. Production of Secondary Metabolites Using Plant Cell Cultures.Advances in Biochemical Engineering Biotechnology; Stahl, U.; Donalies, U.E; Nevoigt, E., Ed.; Springer: Berlin, Heidelberg, 2008, Vol. 111, pp. 187-228.
[15]
Shilpa, K.; Varun, K.; Lakshmi, B.S. An alternate method of natural drug production: Elciting secondary metabolite production using plant cell culture. J. Plant Sci., 2010, 5(3), 222-247.
[http://dx.doi.org/10.3923/jps.2010.222.247]
[16]
Kolewe, M.E.; Gaurav, V.; Roberts, S.C. Pharmaceutically active natural product synthesis and supply via plant cell culture technology. Mol. Pharm., 2008, 5(2), 243-256.
[http://dx.doi.org/10.1021/mp7001494] [PMID: 18393488]
[17]
Verpoorte, R.; Van Der Heijden, R.; Ten Hoopen, H.J.G.; Memelink, J. Metabolic engineering of plant secondary metabolite pathways for the production of fine chemicals. Biotechnol. Lett., 1999, 21(6), 467-479.
[http://dx.doi.org/10.1023/A:1005502632053]
[18]
Karuppusamy, S. A review on trends in production of secondary metabolites from higher plants by in vitro tissue, organ and cell cultures. J. Med. Plants Res., 2009, 3, 1222-1239.
[19]
West-jr, F.R.; Mika, E.S. Synthesis of atropine by isolated roots and root-callus cultures of Belladonna. Bot. Gaz., 1957, 119, 50-54.
[http://dx.doi.org/10.1086/335961]
[20]
Kieran, P.M.; MacLoughlin, P.F.; Malone, D.M. Plant cell suspension cultures: some engineering considerations. J. Biotechnol., 1997, 59(1-2), 39-52.
[http://dx.doi.org/10.1016/S0168-1656(97)00163-6] [PMID: 9487717]
[21]
Berlin, J.; Beier, H.; Fecker, L.; Forche, E.; Noe, W.; Sasse, F.; Schiel, O.; Wray, V. Conventional and New Approaches to Increase the Alkaloid Production of Plant Cell Cultures.Primary and Secondary Metabolism of Plant Cell Cultures; Neumann, K.H.; Barz, W; Reinhard, E., Ed.; Springer: Berlin, Heidelberg, 1985, pp. 272-280.
[http://dx.doi.org/10.1007/978-3-642-70717-9_26]
[22]
Charlwood, B.V.; Charlwood, K.A. Terpenoid production in plant cell culture. Ecological Chemistry and Biochemistry of Plant Terpenoids; Harborne, J.B.; Tomas-Barberan, F., Eds.; Clarendon Press: Oxford, 1991. pp. 95-132.
[23]
Rokem, J.S.; Goldberg, I. Secondary Metabolites From Plant Cell Suspension Cultures: Methods for Yield Improvement.Advances in Biotechnological Processes; Alan R. Liss Inc.: New York, 1985, pp. 241-274.
[24]
Facchini, P.J.; St-Pierre, B. Synthesis and trafficking of alkaloid biosynthetic enzymes. Curr. Opin. Plant Biol., 2005, 8(6), 657-666.
[http://dx.doi.org/10.1016/j.pbi.2005.09.008] [PMID: 16182601]
[25]
Mugnier, J. Establishment of new axenic hairy root lines by inoculation with Agrobacterium rhizogenes. Plant Cell Rep., 1988, 7(1), 9-12.
[http://dx.doi.org/10.1007/BF00272966] [PMID: 24241404]
[26]
Giri, A.; Narasu, M.L. Transgenic hairy roots. Recent trends and applications. Biotechnol. Adv., 2000, 18(1), 1-22.
[http://dx.doi.org/10.1016/S0734-9750(99)00016-6] [PMID: 14538116]
[27]
Sharma, P.; Padh, H.; Shrivastava, N. Hairy root cultures: a suitable biological system for studying secondary metabolic pathways in plants. Eng. Life Sci., 2013, 13(1), 62-75.
[http://dx.doi.org/10.1002/elsc.201200030]
[28]
Banerjee, S.; Rahman, L.; Uniyal, G.C.; Ahuja, P.S. Enhanced production of valepotriates by Agrobacterium rhizogenes induced hairy root cultures of Valeriana wallichii DC. Plant Sci., 1998, 131, 203-208.
[http://dx.doi.org/10.1016/S0168-9452(97)00237-9]
[29]
Olsson, M.E.; Olofsson, L.M.; Lindahl, A.L.; Lundgren, A.; Brodelius, M.; Brodelius, P.E. Localization of enzymes of artemisinin biosynthesis to the apical cells of glandular secretory trichomes of Artemisia annua L. Phytochemistry, 2009, 70(9), 1123-1128.
[http://dx.doi.org/10.1016/j.phytochem.2009.07.009] [PMID: 19664791]
[30]
Liu, C.Z.; Wang, Y.C.; Ouyang, F.; Ye, H.C.; Li, G.F. Production of artemisinin by hairy root cultures of Artemisia annua L. Biotechnol. Lett., 1997, 19(9), 927-929.
[http://dx.doi.org/10.1023/A:1018362309677]
[31]
Georgiev, M.I.; Agostini, E.; Ludwig-Müller, J.; Xu, J. Genetically transformed roots: from plant disease to biotechnological resource. Trends Biotechnol., 2012, 30(10), 528-537.
[http://dx.doi.org/10.1016/j.tibtech.2012.07.001] [PMID: 22906523]
[32]
Hu, Z.B.; Du, M. Hairy root and its application in plant genetic engineering. J. Integr. Plant Biol., 2006, 48, 121-127.
[http://dx.doi.org/10.1111/j.1744-7909.2006.00121.x]
[33]
Goel, M.K.; Mehrotra, S.; Kukreja, A.K. Elicitor-induced cellular and molecular events are responsible for productivity enhancement in hairy root cultures: an insight study. Appl. Biochem. Biotechnol., 2011, 165(5-6), 1342-1355.
[http://dx.doi.org/10.1007/s12010-011-9351-7] [PMID: 21909631]
[34]
Zhao, J.; Davis, L.C.; Verpoorte, R. Elicitor signal transduction leading to production of plant secondary metabolites. Biotechnol. Adv., 2005, 24(3), 283-333.
[http://dx.doi.org/10.1016/j.biotechadv.2005.01.003] [PMID: 15848039]
[35]
Eilert, U. Elicitation: Methodology and Aspects of Application.Cell Culture and Somatic Cell Genetics of Plants; Constabel, F; Vasil, I.K., Ed.; Academic Press: San Diego, 1987, Vol. 4, pp. 153-196.
[36]
Nishi, A. Effect of Elicitors on the Production of Secondary Metabolites.Advances in Plant Biotechnology; Ryu, D.D.Y; Furasaki, S., Ed.; Elsevier Science: Amsterdam, 1994, pp. 135-151.
[http://dx.doi.org/10.1016/B978-0-444-89939-2.50014-0]
[37]
Benhamou, N. Elicitor-induced plant defence pathways. Trends Plant Sci., 1996, 1(7), 233-240.
[http://dx.doi.org/10.1016/S1360-1385(96)86901-0]
[38]
Shirasu, K.; Nakajima, H.; Rajasekhar, V.K.; Dixon, R.A.; Lamb, C. Salicylic acid potentiates an agonist-dependent gain control that amplifies pathogen signals in the activation of defense mechanisms. Plant Cell, 1997, 9(2), 261-270.
[PMID: 9061956]
[39]
Wang, J.W.; Wu, J.Y. Effective Elicitors and Process Strategies for Enhancement of Secondary Metabolite Production in Hairy Root Cultures.Biotechnology of Hairy Root Systems; Doran, P.M., Ed.; Springer: Berlin, Heidelberg, 2013, pp. 55-89.
[http://dx.doi.org/10.1007/10_2013_183]
[40]
Chen, H.; Chena, F.; Chiu, F.C.K.; Lo, C.M.Y. The effect of yeast elicitor on the growth and secondary metabolism of hairy root cultures of Salvia miltiorrhiza. Enzyme Microb. Technol., 2001, 28(1), 100-105.
[http://dx.doi.org/10.1016/S0141-0229(00)00284-2] [PMID: 11118603]
[41]
Mukundan, U.; Hjortso, M.A. Effect of fungal elicitor on thiophene production in hairy root cultures of Tayetes patula. Appl. Microbiol. Biotechnol., 1990, 33, 145-147.
[http://dx.doi.org/10.1007/BF00176515]
[42]
Liu, C.; Xu, Y.W.X.; Ouyang, F.; Ye, H.; Li, G. Improvement of artemisinin accumulation in hairy root cultures of Artemisia annua L by fungal elicitor. Bioprocess Eng., 1999, 20(2), 161-164.
[http://dx.doi.org/10.1007/PL00009041]
[43]
Bais, H.P.; Walker, T.S.; Schweizer, H.P.; Vivanco, J.M. Root specific elicitation and antimicrobial activity of rosmarinic acid in hairy root cultures of Ocimum basilicum. Plant Physiol. Biochem., 2002, 40(11), 983-995.
[http://dx.doi.org/10.1016/S0981-9428(02)01460-2]
[44]
Zhao, J.L.; Zhou, L.G.; Wu, J.Y. Promotion of Salvia miltiorrhiza hairy root growth and tanshinone production by polysaccharide-protein fractions of plant growth-promoting rhizobacterium Bacillus cereus. Process Biochem., 2010, 45(9), 1517-1522.
[http://dx.doi.org/10.1016/j.procbio.2010.05.034]
[45]
Zhou, L.; Cao, X.; Zhang, R.; Peng, Y.; Zhao, S.; Wu, J. Stimulation of saponin production in Panax ginseng hairy roots by two oligosaccharides from Paris polyphylla var. yunnanensis. Biotechnol. Lett., 2007, 29(4), 631-634.
[http://dx.doi.org/10.1007/s10529-006-9273-6] [PMID: 17216538]
[46]
Wang, J.W.; Zheng, L.P.; Zhang, B.; Zou, T. Stimulation of artemisinin synthesis by combined cerebroside and nitric oxide elicitation in Artemisia annua hairy roots. Appl. Microbiol. Biotechnol., 2009, 85(2), 285-292.
[http://dx.doi.org/10.1007/s00253-009-2090-9] [PMID: 19562334]
[47]
Stojakowska, A.; Burczyk, J.; Kisiel, W.; Zych, M.; Banas, A.; Duda, T. Effects of various elicitors on the accumulation and secretion of spiroketal enol ether diacetylenes in feverfew hairy root culture. Acta Soc. Bot. Pol., 2008, 77(1), 17-21.
[http://dx.doi.org/10.5586/asbp.2008.002]
[48]
Malarz, J.; Kisiel, W. Effect of pectinase on the production of sesquiterpene lactones in the hairy root culture of Lactuca virosa L. Acta Soc. Bot. Pol., 2000, 69(2), 115-117.
[http://dx.doi.org/10.5586/asbp.2000.014]
[49]
Rijhwani, S.K.; Shanks, J.V. Effect of elicitor dosage and exposure time on biosynthesis of indole alkaloids by Catharanthus roseus hairy root cultures. Biotechnol. Prog., 1998, 14(3), 442-449.
[http://dx.doi.org/10.1021/bp980029v] [PMID: 9622525]
[50]
Khalili, M.; Hasanloo, T.; Kazemi Tabar, S.K.; Rahnama, H. Influence of exogenous salicylic acid on flavonolignans and lipoxygenase activity in the hairy root cultures of Silybum marianum. Cell Biol. Int., 2009, 33(9), 988-994.
[http://dx.doi.org/10.1016/j.cellbi.2009.06.003] [PMID: 19524695]
[51]
Pitta-Alvarez, S.I.; Spollansky, T.C.; Giulietti, A.M. The influence of different biotic and abiotic elicitors on the production and profile of tropane alkaloids in hairy root cultures of Brugmansia candida. Enzyme Microb. Technol., 2000, 26(2-4), 252-258.
[http://dx.doi.org/10.1016/S0141-0229(99)00137-4] [PMID: 10689085]
[52]
Sivanandhan, G.; Dev, G.K.; Jeyaraj, M.; Rajesh, M.; Arjunan, A.; Muthuselvam, M.; Manickavasagam, M.; Selvaraj, N.; Ganapathi, A. Increased production of withanolide A, withanone, and withaferin A in hairy root cultures of Withania somnifera (L.) Dunal elicited with methyl jasmonate and salicylic acid. Plant Cell Tissue Organ Cult., 2013, 114(1), 121-129.
[http://dx.doi.org/10.1007/s11240-013-0297-z]
[53]
Malarz, J.; Stojakowska, A.; Kisiel, W. Effect of methyl jasmonate and salicylic acid on sesquiterpene lactone accumulation in hairy roots of Cichorium intybus. Acta Physiol. Plant., 2007, 29(2), 127-132.
[http://dx.doi.org/10.1007/s11738-006-0016-z]
[54]
Creelman, R.A.; Mullet, J.E. Jasmonic acid distribution and action in plants: regulation during development and response to biotic and abiotic stress. Proc. Natl. Acad. Sci. USA, 1995, 92(10), 4114-4119.
[http://dx.doi.org/10.1073/pnas.92.10.4114] [PMID: 11607536]
[55]
Hao, X.; Shi, M.; Cui, L.; Xu, C.; Zhang, Y.; Kai, G. Effects of methyl jasmonate and salicylic acid on tanshinone production and biosynthetic gene expression in transgenic Salvia miltiorrhiza hairy roots. Biotechnol. Appl. Biochem., 2015, 62(1), 24-31.
[http://dx.doi.org/10.1002/bab.1236] [PMID: 24779358]
[56]
Xiao, Y.; Gao, S.; Di, P.; Chen, J.; Chen, W.; Zhang, L. Methyl jasmonate dramatically enhances the accumulation of phenolic acids in Salvia miltiorrhiza hairy root cultures. Physiol. Plant., 2009, 137(1), 1-9.
[http://dx.doi.org/10.1111/j.1399-3054.2009.01257.x] [PMID: 19570133]
[57]
Kim, O.T.; Bang, K.H.; Shin, Y.S.; Lee, M.J.; Jung, S.J.; Hyun, D.Y.; Kim, Y.C.; Seong, N.S.; Cha, S.W.; Hwang, B. Enhanced production of asiaticoside from hairy root cultures of Centella asiatica (L.) Urban elicited by methyl jasmonate. Plant Cell Rep., 2007, 26(11), 1941-1949.
[http://dx.doi.org/10.1007/s00299-007-0400-1] [PMID: 17632725]
[58]
Gundlach, H.; Müller, M.J.; Kutchan, T.M.; Zenk, M.H. Jasmonic acid is a signal transducer in elicitor-induced plant cell cultures. Proc. Natl. Acad. Sci. USA, 1992, 89(6), 2389-2393.
[http://dx.doi.org/10.1073/pnas.89.6.2389] [PMID: 11607285]
[59]
Sharmila, R.; Subburathinam, K.M. Effect of signal compounds on andrographolide in the hairy root cultures of Andrographis paniculata. Int. J. Pharm. Sci. Res., 2013, 4(5), 1773.
[60]
Cadiz, N.M.; Vivanco, J.M.; Flores, H.E. Coculture of Pachyrhizus erosus (L.) hairy roots with Rhizobium spp. In Vitro Cell. Dev. Biol. Plant, 2000, 36(4), 238-242.
[http://dx.doi.org/10.1007/s11627-000-0044-0]
[61]
Able, A.J.; Guest, D.I.; Sutherland, M.W. Relationship between transmembrane ion movements, production of reactive oxygen species and the hypersensitive response during the challenge of tobacco suspension cells by zoospores of Phytophthora nicotianae. Physiol. Mol. Plant Pathol., 2001, 58(5), 189-198.
[http://dx.doi.org/10.1006/pmpp.2001.0328]
[62]
Able, A.J.; Sutherland, M.W.; Guest, D.I. Production of reactive oxygen species during non-specific elicitation, non-host resistance and field resistance expression in cultured tobacco cells. Funct. Plant Biol., 2003, 30(1), 91-99.
[http://dx.doi.org/10.1071/FP02123]
[63]
Keppler, L.D.; Baker, C.J.; Atkinson, M.M. Active oxygen production during a bacteria-induced hypersensitive reaction in tobacco suspension cells. Phytopathology, 1989, 79(9), 974-978.
[http://dx.doi.org/10.1094/Phyto-79-974]
[64]
Atkinson, M.M.; Huang, J.S.; Knopp, J.A. The hypersensitive reaction of tobacco to Pseudomonas syringae pv. pisi: Activation of a plasmalemma K+/H+ exchange mechanism. Plant Physiol., 1985, 79(3), 843-847.
[http://dx.doi.org/10.1104/pp.79.3.843] [PMID: 16664502]
[65]
Atkinson, M.M.; Keppler, L.D.; Orlandi, E.W.; Baker, C.J.; Mischke, C.F. Involvement of plasma membrane calcium influx in bacterial induction of the k/h and hypersensitive responses in tobacco. Plant Physiol., 1990, 92(1), 215-221.
[http://dx.doi.org/10.1104/pp.92.1.215] [PMID: 16667249]
[66]
Wu, J.Y.; Ng, J.; Shi, M.; Wu, S.J. Enhanced secondary metabolite (tanshinone) production of Salvia miltiorrhiza hairy roots in a novel root-bacteria coculture process. Appl. Microbiol. Biotechnol., 2007, 77(3), 543-550.
[http://dx.doi.org/10.1007/s00253-007-1192-5] [PMID: 17882415]
[67]
Wang, Y.; Zhang, H.; Zhao, B.; Yuan, X. Improved growth of Artemisia annua L hairy roots and artemisinin production under red light conditions. Biotechnol. Lett., 2001, 23(23), 1971-1973.
[http://dx.doi.org/10.1023/A:1013786332363]
[68]
Kuźma, Ł.; Skrzypek, Z.; Wysokińska, H. Diterpenoids and triterpenoids in hairy roots of Salvia sclarea. Plant Cell Tissue Organ Cult., 2006, 84(2), 171-179.
[http://dx.doi.org/10.1007/s11240-005-9018-6]
[69]
Yu, K.W.; Murthy, H.N.; Hahn, E.J.; Paek, K.Y. Ginsenoside production by hairy root cultures of Panax ginseng: influence of temperature and light quality. Biochem. Eng. J., 2005, 23(1), 53-56.
[http://dx.doi.org/10.1016/j.bej.2004.07.001]
[70]
Abbasi, B.H.; Tian, C.L.; Murch, S.J.; Saxena, P.K.; Liu, C.Z. Light-enhanced caffeic acid derivatives biosynthesis in hairy root cultures of Echinacea purpurea. Plant Cell Rep., 2007, 26(8), 1367-1372.
[http://dx.doi.org/10.1007/s00299-007-0344-5] [PMID: 17396238]
[71]
Sauerwein, M.; Yamazaki, T.; Shimomura, K. Hernandulcin in hairy root cultures of Lippia dulcis. Plant Cell Rep., 1991, 9(10), 579-581.
[http://dx.doi.org/10.1007/BF00232336] [PMID: 24220716]
[72]
Yoshimatsu, K.; Satake, M.; Shimomura, K.; Sawada, J.I.; Terao, T. Determination of cardenolides in hairy root cultures of Digitalis lanata by enzyme-linked immunosorbent assay. J. Nat. Prod., 1990, 53(6), 1498-1502.
[http://dx.doi.org/10.1021/np50072a015] [PMID: 2089119]
[73]
Sauerwein, M.; Yoshimatsu, K.; Shimomura, K. Further approaches in the production of secondary metabolites by plant tissue cultures. Plant Tiss. Cult. Lett., 1992, 9, 1-9.
[http://dx.doi.org/10.5511/plantbiotechnology1984.9.1]
[74]
Ikenaga, T.; Oyama, T.; Muranaka, T. Growth and steroidal saponin production in hairy root cultures of Solanum aculeatissimum. Plant Cell Rep., 1995, 14(7), 413-417.
[http://dx.doi.org/10.1007/BF00234045] [PMID: 24185447]
[75]
Berkov, S.; Pavlov, A.; Georgiev, V.; Bastida, J.; Burrus, M.; Ilieva, M.; Codina, C. Alkaloid synthesis and accumulation in Leucojum aestivum in vitro cultures. Nat. Prod. Commun., 2009, 4(3), 359-364.
[http://dx.doi.org/10.1177/1934578X0900400328] [PMID: 19413113]
[76]
Georgiev, V.; Ivanov, I.; Berkov, S.; Ilieva, M.; Georgiev, M.; Gocheva, T.; Pavlov, A. Galanthamine production by Leucojum aestivum L.shoot culture in a modified bubble column bioreactor with internal sections. Eng. Life Sci., 2012, 12, 534-543.
[http://dx.doi.org/10.1002/elsc.201100177]
[77]
Diop, M.F.; Hehn, A.; Ptak, A.; Chretien, F.; Doerper, S.; Gontier, E.; Bourgaud, F.; Henry, M.; Chapleur, Y.; Laurain-Mattar, D. Hairy root and tissue cultures of Leucojum aestivum L.-relationships to galanthamine content. Phytochem. Rev., 2007, 1, 137-141.
[http://dx.doi.org/10.1007/s11101-006-9043-z]
[78]
Binder, B.Y.; Peebles, C.A.; Shanks, J.V.; San, K.Y. The effects of UV-B stress on the production of terpenoid indole alkaloids in Catharanthus roseus hairy roots. Biotechnol. Prog., 2009, 25(3), 861-865.
[http://dx.doi.org/10.1002/btpr.97] [PMID: 19479674]
[79]
Gai, Q.Y.; Jiao, J.; Luo, M.; Wang, W.; Zhao, C.J.; Fu, Y.J.; Ma, W. UV elicitation for promoting astragaloside production in Astragalus membranaceus hairy root cultures with transcriptional expression of biosynthetic genes. Ind. Crops Prod., 2016, 84, 350-357.
[http://dx.doi.org/10.1016/j.indcrop.2016.02.010]
[80]
Huang, X.; Yao, J.; Zhao, Y.; Xie, D.; Jiang, X.; Xu, Z. Efficient rutin and quercetin biosynthesis through flavonoids-related gene expression in Fagopyrum tataricum Gaertn. hairy root cultures with UV-B irradiation. Front. Plant Sci., 2016, 7, 63.
[http://dx.doi.org/10.3389/fpls.2016.00063] [PMID: 26870075]
[81]
Qin, B.; Ma, L.; Wang, Y.; Chen, M.; Lan, X.; Wu, N.; Liao, Z. Effects of acetylsalicylic acid and UV-B on gene expression and tropane alkaloid biosynthesis in hairy root cultures of Anisodus luridus. Plant Cell Tissue Organ Cult., 2014, 117(3), 483-490.
[http://dx.doi.org/10.1007/s11240-014-0454-z]
[82]
Threlfall, D.R.; Whitehead, I.M. The Use of Metal Ions to Induce the Formation of Secondary Products in Plant Tissue Cultures.Manipulating Secondary Metabolism in Culture; Robins, R.J; Rhodes, M.J.C., Ed.; Cambridge University Press: Cambridge, 1988, pp. 51-56.
[83]
Choi, H.K.; Yun, J.H.; Kim, S.I.; Son, J.S.; Kim, H.R.; Kim, J.H.; Choi, H.J.; Hong, S.S. Enhanced production of paclitaxel by semi-continuous batch process (SCBP) in suspension culture of Taxus chinensis. Enzyme Microb. Technol., 2001, 29(10), 583-586.
[http://dx.doi.org/10.1016/S0141-0229(01)00427-6]
[84]
Khalili, M.; Hasanloo, T.; Kazemi Tabar, S.K. Ag{+} Enhanced Silymarin Production in Hairy Root Cultures of Silybum Marianum (L.) Gaertn. Plant Omics, 2010, 3(4), 109.
[85]
Zhang, C.; Yan, Q.; Cheuk, W.K.; Wu, J. Enhancement of tanshinone production in Salvia miltiorrhiza hairy root culture by Ag+ elicitation and nutrient feeding. Planta Med., 2004, 70(2), 147-151.
[http://dx.doi.org/10.1055/s-2004-815492] [PMID: 14994193]
[86]
Ge, X.C.; Wu, J.Y. Tanshinone production and isoprenoid pathways in Salvia miltiorrhiza hairy roots induced by Ag+ and yeast elicitor. Plant Sci., 2005, 168, 487-491.
[http://dx.doi.org/10.1016/j.plantsci.2004.09.012]
[87]
Zhang, B.; Zheng, L.P.; Li, Y.W. Wen Wang, J. Stimulation of artemisinin production in Artemisia annua hairy roots by Ag-SiO2 core-shell nanoparticles. Curr. Nanosci., 2013, 9(3), 363-370.
[http://dx.doi.org/10.2174/1573413711309030012]
[88]
Furze, J.M.; Rhodes, M.J.; Parr, A.J.; Robins, R.J.; Withehead, I.M.; Threlfall, D.R. Abiotic factors elicit sesquiterpenoid phytoalexin production but not alkaloid production in transformed root cultures of Datura stramonium. Plant Cell Rep., 1991, 10(3), 111-114.
[http://dx.doi.org/10.1007/BF00232039] [PMID: 24221487]
[89]
Olmos, E.; Martínez-Solano, J.R.; Piqueras, A.; Hellín, E. Early steps in the oxidative burst induced by cadmium in cultured tobacco cells (BY-2 line). J. Exp. Bot., 2003, 54(381), 291-301.
[http://dx.doi.org/10.1093/jxb/erg028] [PMID: 12493856]
[90]
Gangopadhyay, M.; Dewanjee, S.; Bhattacharya, S. Enhanced plumbagin production in elicited Plumbago indica hairy root cultures. J. Biosci. Bioeng., 2011, 111(6), 706-710.
[http://dx.doi.org/10.1016/j.jbiosc.2011.02.003] [PMID: 21382748]
[91]
Yaoya, S.; Kanho, H.; Mikami, Y.; Itani, T.; Umehara, K.; Kuroyanagi, M. Umbelliferone released from hairy root cultures of Pharbitis nil treated with copper sulfate and its subsequent glucosylation. Biosci. Biotechnol. Biochem., 2004, 68(9), 1837-1841.
[http://dx.doi.org/10.1271/bbb.68.1837] [PMID: 15388957]
[92]
Bhagwath, S.G.; Hjortsø, M.A. Statistical analysis of elicitation strategies for thiarubrine A production in hairy root cultures of Ambrosia artemisiifolia. J. Biotechnol., 2000, 80(2), 159-167.
[http://dx.doi.org/10.1016/S0168-1656(00)00256-X] [PMID: 10908796]
[93]
Palazón, J.; Cusidó, R.M.; Bonfill, M.; Mallol, A.; Moyano, E.; Morales, C.; Piñol, M.T. Elicitation of different Panax ginseng transformed root phenotypes for an improved ginsenoside production. Plant Physiol. Biochem., 2003, 41, 1019-1025.
[http://dx.doi.org/10.1016/j.plaphy.2003.09.002]
[94]
Jeong, G.T.A.; Park, D.H. Enhanced secondary metabolite biosynthesis by elicitation in transformed plant root system: effect of abiotic elicitors. Appl. Biochem. Biotechnol., 2006, 129-132(30), 436-446.
[http://dx.doi.org/10.1385/ABAB:130:1:436] [PMID: 16915660]
[95]
Toivonen, L.; Laakso, S.; Rosenqvist, H. The effect of temperature on hairy root cultures of Catharanthus roseus: Growth, indole alkaloid accumulation and membrane lipid composition. Plant Cell Rep., 1992, 11(8), 395-399.
[http://dx.doi.org/10.1007/BF00234368] [PMID: 24201540]
[96]
Thakore, D.; Srivastava, A.K.; Sinha, A. Enhanced Production of Antihypertensive Drug Ajmalicine in Transformed Hairy Root Culture of Catharanthus roseus by Application of Stress Factors in Statistically Optimized Medium.Chemistry of Phytopotentials: Health, Energy and Environmental Perspectives; Srivastava, M.M.; Khemani, L.D; Srivastava, S., Ed.; Springer: Berlin, Heidelberg, 2012, pp. 39-42.
[http://dx.doi.org/10.1007/978-3-642-23394-4_8]
[97]
Shi, M.; Kwok, K.W.; Wu, J.Y. Enhancement of tanshinone production in Salvia miltiorrhiza Bunge (red or Chinese sage) hairy-root culture by hyperosmotic stress and yeast elicitor. Biotechnol. Appl. Biochem., 2007, 46(Pt 4), 191-196.
[http://dx.doi.org/10.1042/BA20060147] [PMID: 17014425]
[98]
Khelifi, L.; Zarouri, B.; Amdoun, R.; Harfi, B.; Morsli, A.; Khelifi-Slaoui, M. Effects of elicitation and permeabilization on hyoscyamine content in Datura stramonium hairy roots. Adv. Environ. Biol., 2011, 5, 329-334.
[99]
Rudrappa, T.; Neelwarne, B.; Kumar, V.; Lakshmanan, V.; Venkataramareddy, S.R.; Aswathanarayana, R.G. Peroxidase production from hairy root cultures of red beet (Beta vulgaris). Electron. J. Biotechnol., 2005, 8, 185-196.
[http://dx.doi.org/10.2225/vol8-issue2-fulltext-12]
[100]
Talano, M.A.; Agostini, E.; Medina, M.I.; De Forchetti, S.M.; Tigier, H.A. Tomato (Lycopersicon esculentum cv. Pera) hairy root cultures: characterization and changes in peroxidase activity under NaCl treatment. In Vitro Cell. Dev. Biol. Plant, 2003, 39, 354-359.
[http://dx.doi.org/10.1079/IVP2002410]
[101]
Uozumi, N.; Kato, Y.; Nakashimada, Y.; Kabayashi, T. Excretion of peroxidase from horseradish hairy root in combination with ion supplementation. Appl. Microbiol. Biotechnol., 1992, 37, 560-565.
[http://dx.doi.org/10.1007/BF00240725]
[102]
Georgiev, M.I.; Ludwig-Muller, J.; Bley, T. Hairy Root Culture: Copying Nature in New Bioprocesses.Medicinal Plant Biotechnology; Arora, R., Ed.; CAB International: Oxon, 2010, pp. 156-175.
[http://dx.doi.org/10.1079/9781845936785.0156]
[103]
Gómez-Galera, S.; Pelacho, A.M.; Gené, A.; Capell, T.; Christou, P. The genetic manipulation of medicinal and aromatic plants. Plant Cell Rep., 2007, 26(10), 1689-1715.
[http://dx.doi.org/10.1007/s00299-007-0384-x] [PMID: 17609957]
[104]
Jouhikainen, K.; Lindgren, L.; Jokelainen, T.; Hiltunen, R.; Teeri, T.H.; Oksman-Caldentey, K.M. Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering. Planta, 1999, 208(4), 545-551.
[http://dx.doi.org/10.1007/s004250050592]
[105]
Zhang, L.; Ding, R.; Chai, Y.; Bonfill, M.; Moyano, E.; Oksman-Caldentey, K.M.; Xu, T.; Pi, Y.; Wang, Z.; Zhang, H.; Kai, G.; Liao, Z.; Sun, X.; Tang, K. Engineering tropane biosynthetic pathway in Hyoscyamus niger hairy root cultures. Proc. Natl. Acad. Sci. USA, 2004, 101(17), 6786-6791.
[http://dx.doi.org/10.1073/pnas.0401391101] [PMID: 15084741]
[106]
Scalcinati, G.; Partow, S.; Siewers, V.; Schalk, M.; Daviet, L.; Nielsen, J. Combined metabolic engineering of precursor and co-factor supply to increase α-santalene production by Saccharomyces cerevisiae. Microb. Cell Fact., 2012, 11(1), 117.
[http://dx.doi.org/10.1186/1475-2859-11-117] [PMID: 22938570]
[107]
Liang, Y.; Zhao, S.; Zhang, X. Antisense suppression of cycloartenol synthase results in elevated ginsenoside levels in Panax ginseng hairy roots. Plant Mol. Biol. Report., 2009, 27, 298-304.
[http://dx.doi.org/10.1007/s11105-008-0087-7]
[108]
Kim, O.T.; Kim, S.H.; Ohyama, K.; Muranaka, T.; Choi, Y.E.; Lee, H.Y.; Kim, M.Y.; Hwang, B. Upregulation of phytosterol and triterpene biosynthesis in Centella asiatica hairy roots overexpressed ginseng farnesyl diphosphate synthase. Plant Cell Rep., 2010, 29(4), 403-411.
[http://dx.doi.org/10.1007/s00299-010-0831-y] [PMID: 20195611]
[109]
White, N.J. Qinghaosu (artemisinin): the price of success. Science, 2008, 320(5874), 330-334.
[http://dx.doi.org/10.1126/science.1155165] [PMID: 18420924]
[110]
Qinghaosu Antimalaria Coordinating Research Group. Antimalaria studies on Qinghaosu. Chin. Med. J. (Engl.), 1979, 92(12), 811-816.
[PMID: 117984]
[111]
Ferreira, J.F.; Simon, J.E.; Janick, J. Developmental studies of Artemisia annua: flowering and artemisinin production under greenhouse and field conditions. Planta Med., 1995, 61(2), 167-170.
[http://dx.doi.org/10.1055/s-2006-958040] [PMID: 17238070]
[112]
Martinez, B.C.; Staba, J. The production of artemisininin Artemisia annua L. tissue cultures. Adv. Cell Cult., 1988, 6, 69-87.
[http://dx.doi.org/10.1016/B978-0-12-007906-3.50009-7]
[113]
Fulzele, D.P.; Sipahimalani, A.T.; Heble, M.R. Tissue cultures of Artemisia annua: organogenesis and artemisinin production. Phytother. Res., 1991, 5, 149-153.
[http://dx.doi.org/10.1002/ptr.2650050402]
[114]
Whipkey, A.; Simon, J.E.; Charles, D.J.; Janick, J. In vitro productiun of artemisinin from Artemisia annua L. J. Herbs Spices Med. Plants, 1992, 1, 15-25.
[http://dx.doi.org/10.1300/J044v01n01_03]
[115]
Jha, S.; Jha, T.B.; Mahato, S.B. Tissue culture of Artemisia annua L.: A potential source of an antimalarial drug. Curt. Sci., 1988, 57, 344-346.
[116]
Woerdenbag, H.J.; Lüers, J.F.; van Uden, W.; Pras, N.; Malingré, T.M.; Alfermann, A.W. Production of the new antimalarial drug artemisinin in shoot cultures of Artemisia annua L. Plant Cell Tissue Organ Cult., 1993, 32(2), 247-257.
[http://dx.doi.org/10.1007/BF00029850]
[117]
Paniego, N.B.; Giulietti, A.M. Artemisia annua L.: dedifferentiated and differentiated cultures. Plant Cell Tissue Organ Cult., 1994, 36, 163-168.
[http://dx.doi.org/10.1007/BF00037715]
[118]
Nair, M.S.R.; Acton, N.; Klayman, D.L.; Kendrick, K.; Basile, D.V.; Mante, S. Production of artemisinin in tissue cultures of Artemisia annua. J. Nat. Prod., 1986, 49(3), 504-507.
[http://dx.doi.org/10.1021/np50045a021] [PMID: 3760887]
[119]
Tawfiq, N.K.; Anderson, L.A.; Roberts, M.F.; Phillipson, J.D.; Bray, D.H.; Warhurst, D.C. Antiplasmodial activity of Artemisia annua plant cell cultures. Plant Cell Rep., 1989, 8(7), 425-428.
[http://dx.doi.org/10.1007/BF00270085] [PMID: 24233369]
[120]
Kim, N.C.; Kim, J.G.; Lira, H.J.; Hahn, T.R.; Kim, S.U. Production of secondary metabolites by tissue culture of Artemisia annua L. Appl. Biol. Chem., 1992, 35, 99-105.
[121]
Ferreira, J.F.; Janick, J. Roots as an enhancing factor for the production of artemisinin in shoot cultures of Artemisia annua. Plant Cell Tissue Organ Cult., 1996, 44(3), 211-217.
[http://dx.doi.org/10.1007/BF00048526]
[122]
Brown, G.D. Production of anti-malarial and anti-migraine drugs in tissue culture of Artemisia annua and Tanacetum parthenium. Acta Hortic., 1993, (330), 269-276.
[http://dx.doi.org/10.17660/ActaHortic.1993.330.35]
[123]
Woerdenbag, H.J.; Pras, N.; Uden, W.V.; Boer, A.D.; Batterman, S.; Visser, J.F.; Malingré, T.M. High peroxidase activity in cell cultures of Artemisia annua with minute artemisinin contents. Nat. Prod. Lett., 1992, 1(2), 121-128.
[http://dx.doi.org/10.1080/10575639208048899]
[124]
He, X.C.; Zeng, M.Y.; Li, G.F.; Liang, Z. Callus induction and regeneration of plantlets from Artemisia annua and changes of qinghaosu contents. Acta Bot. Sin., 1983, 25, 87-90.
[125]
De Jesus-Gonzalez, L.; Weathers, P.J. Tetraploid Artemisia annua hairy roots produce more artemisinin than diploids. Plant Cell Rep., 2003, 21(8), 809-813.
[http://dx.doi.org/10.1007/s00299-003-0587-8] [PMID: 12789527]
[126]
Patra, N.; Sharma, S.; Srivastava, A.K. Statistical Media Optimization for Enhanced Biomass and Artemisinin Production in Artemisia annua Hairy Roots.Chemistry of Phytopotentials: Health, Energy and Environmental Perspectives; Khemani, L.D.; Srivastava, M.M; Srivastava, S., Ed.; Springer: Berlin, Heidelberg, 2012, pp. 173-176.
[http://dx.doi.org/10.1007/978-3-642-23394-4_37]
[127]
Liu, C.; Wang, Y.; Ouyang, F.; Ye, H.; Li, G. Technical factors of artemisin biosynthesis in Artemisia annua hairy root culture. Acta Bot. Sin., 1998, 40(9), 831-835.
[128]
Weathers, P.J.; Hemmavanh, D.D.; Walcerz, D.B.; Cheetham, R.D.; Smith, T.C. Interactive effects of nitrate and phosphate salts, sucrose, and inoculum culture age on growth and sesquiterpene production in Artemisia annua hairy root cultures. In Vitro Cell. Dev. Biol. Plant, 1997, 33(4), 306-312.
[http://dx.doi.org/10.1007/s11627-997-0056-0]
[129]
Weathers, P.J.; DeJesus-Gonzalez, L.; Kim, Y.J.; Souret, F.F.; Towler, M.J. Alteration of biomass and artemisinin production in Artemisia annua hairy roots by media sterilization method and sugars. Plant Cell Rep., 2004, 23(6), 414-418.
[http://dx.doi.org/10.1007/s00299-004-0837-4] [PMID: 15551137]
[130]
Wang, J.W.; Tan, R.X. Artemisinin production in Artemisia annua hairy root cultures with improved growth by altering the nitrogen source in the medium. Biotechnol. Lett., 2002, 24(14), 1153-1156.
[http://dx.doi.org/10.1023/A:1016126917795]
[131]
Weathers, P.; Smith, T. Hemmavanh, D.; Follansbee, E.; Ryan, J.; Cheetham, R. Production of the antimalarial, artemisinin, by transformed roots of Artemisia annua. Acta Hortic., 1996, (426), 157-164.
[http://dx.doi.org/10.17660/ActaHortic.1996.426.17]
[132]
Cai, G.; Li, G.; Ye, H.; Li, G. Hairy root culture of Artemisia annua L. by Ri plasmid transformation and biosynthesis of artemisinin. Chin. J. Biotechnol., 1995, 11(4), 227-235.
[PMID: 8739100]
[133]
Paniego, N.B.; Giulietti, A.M. Artemisinin production by Artemisia annua L.-transformed organ cultures. Enzyme Microb. Technol., 1996, 18(7), 526-530.
[http://dx.doi.org/10.1016/0141-0229(95)00216-2]
[134]
Wang, J.W.; Kong, F.X.; Tan, R.X. Improved artemisinin accumulation in hairy root cultures of Artemisia annua by (22S, 23S)-homobrassinolide. Biotechnol. Lett., 2002, 24(19), 1573-1577.
[http://dx.doi.org/10.1023/A:1020377130657]
[135]
Weathers, P.J.; Bunk, G.; McCoy, M.C. The effect of phytohormones on growth and artemisinin production in Artemisia annua hairy roots. In Vitro Cell. Dev. Biol. Plant, 2005, 41(1), 47-53.
[http://dx.doi.org/10.1079/IVP2004604]
[136]
Arora, M.; Saxena, P.; Choudhary, D.K.; Abdin, M.Z.; Varma, A. Dual symbiosis between Piriformospora indica and Azotobacter chroococcum enhances the artemisinin content in Artemisia annua L. World J. Microbiol. Biotechnol., 2016, 32(2), 19.
[http://dx.doi.org/10.1007/s11274-015-1972-5] [PMID: 26745979]
[137]
Wang, J.W.; Zhang, Z.; Tan, R.X. Stimulation of artemisinin production in Artemisia annua hairy roots by the elicitor from the endophytic Colletotrichum sp. Biotechnol. Lett., 2001, 23(11), 857-860.
[http://dx.doi.org/10.1023/A:1010535001943]
[138]
Putalun, W.; Luealon, W.; De-Eknamkul, W.; Tanaka, H.; Shoyama, Y. Improvement of artemisinin production by chitosan in hairy root cultures of Artemisia annua L. Biotechnol. Lett., 2007, 29(7), 1143-1146.
[http://dx.doi.org/10.1007/s10529-007-9368-8] [PMID: 17426924]
[139]
Wang, H. Effects of fungal elicitors on cell growth and artemisinin accumulation in hairy root cultures of Artemisia annua. J. Integr. Plant Biol., 2000, 42(9), 905-909.
[140]
Wang, J.W.; Zheng, L.P.; Tan, R.X. The preparation of an elicitor from a fungal endophyte to enhance artemisinin production in hairy root cultures of Artemisia annua L. Sheng Wu Gong Cheng Xue Bao, 2006, 22(5), 829-834.
[PMID: 17037210]
[141]
Zhang, B.; Zou, T.; Lu, Y.H.; Wang, J.W. Stimulation of artemisinin biosynthesis in Artemisia annua hairy roots by oligogalacturonides. Afr. J. Biotechnol., 2010, 9(23), 3437-3442.
[142]
Zheng, L.P.; Guo, Y.T.; Wang, J.W.; Tan, R.X. Nitric oxide potentiates oligosaccharide-induced artemisinin production in Artemisia annua hairy roots. J. Integr. Plant Biol., 2008, 50(1), 49-55.
[http://dx.doi.org/10.1111/j.1744-7909.2007.00589.x] [PMID: 18666951]
[143]
Zheng, L.P.; Zhang, B.; Zou, T.; Chen, Z.H.; Wang, J.W. Nitric oxide interacts with reactive oxygen species to regulate oligosaccharide-induced artemisinin biosynthesis in Artemisia annua hairy roots. J. Med. Plants Res., 2010, 4(9), 758-766.
[144]
Guo, C.; Liu, C.; Ye, H.; Li, G. Effect of temperature on growth and artemisinin biosynthesis in hairy root cultures of Artemisia annua. Acta Bot. Boreali-Occident. Sin., 2004, 24(10), 1828-1831.
[145]
Liu, C.Z.; Guo, C.; Wang, Y.C.; Ouyang, F. Effect of light irradiation on hairy root growth and artemisinin biosynthesis of Artemisia annua L. Process Biochem., 2002, 38(4), 581-585.
[http://dx.doi.org/10.1016/S0032-9592(02)00165-6]
[146]
Patra, N.; Srivastava, A.K.; Sharma, S. Study of various factors for enhancement of artemisinin in Artemisia annua hairy roots. Int. J. Chem. Eng. Appl., 2013, 4(3), 157.
[http://dx.doi.org/10.7763/IJCEA.2013.V4.284]
[147]
Ahlawat, S.; Saxena, P.; Alam, P.; Wajid, S.; Abdin, M.Z. Modulation of artemisinin biosynthesis by elicitors, inhibitor, and precursor in hairy root cultures of Artemisia annua L. J. Plant Interact., 2014, 9(1), 811-824.
[http://dx.doi.org/10.1080/17429145.2014.949885]
[148]
Liu, C.Z.; Wang, Y.C.; Zhao, B.; Guo, C.; Ouyang, F.; Ye, H.C.; Li, G.F. Development of a nutrient mist bioreactor for growth of hairy roots. In Vitro Cell. Dev. Bio. Plant, 1999, 5(3), 271-274.
[http://dx.doi.org/10.1007/s11627-999-0091-0]
[149]
Liu, C.Z.; Wang, Y.C.; Guo, C.; Ouyang, F.; Ye, H.C.; Li, G.F. Production of artemisinin by shoot cultures of Artemisia annua L. in a modified inner-loop mist bioreactor. Plant Sci., 1998, 135(2), 211-217.
[http://dx.doi.org/10.1016/S0168-9452(98)00086-7]
[150]
Liu, C.Z.; Wang, Y.C.; Ouyang, F.; Ye, H.C.; Li, G.F. Production of artemisinin by hairy root cultures of Artemisia annua L in bioreactor. Biotechnol. Lett., 1998, 20(3), 265-268.
[http://dx.doi.org/10.1023/A:1005382020039]
[151]
Liu, C.; Wang, Y.; Guo, C.; Ouyang, F.; Ye, H.; Li, G. Enhanced production of artemisinin by Art emisia annua L hairy root cultures in a modified inner-loop airlift bioreactor. Bioprocess Eng., 1998, 19(5), 389-392.
[152]
Towler, M.J.; Weathers, P.J. Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways. Plant Cell Rep., 2007, 26(12), 2129-2136.
[http://dx.doi.org/10.1007/s00299-007-0420-x] [PMID: 17710406]
[153]
Ram, M.; Khan, M.A.; Jha, P.; Khan, S.; Kiran, U.; Ahmad, M.M.; Javed, S.; Abdin, M.Z. HMG-CoA reductase limits artemisinin biosynthesis and accumulation in Artemisia annua L. plants. Acta Physiol. Plant., 2010, 32(5), 859-866.
[http://dx.doi.org/10.1007/s11738-010-0470-5]
[154]
Liu, B.; Wang, H.; Du, Z.; Li, G.; Ye, H. Metabolic engineering of artemisinin biosynthesis in Artemisia annua L. Plant Cell Rep., 2011, 30(5), 689-694.
[http://dx.doi.org/10.1007/s00299-010-0967-9] [PMID: 21184232]
[155]
Abdin, M.Z.; Alam, P. Genetic engineering of artemisinin biosynthesis: prospects to improve its production. Acta Physiol. Plant., 2015, 37(2), 33.
[http://dx.doi.org/10.1007/s11738-015-1771-5]
[156]
Chen, D.H.; Liu, C.J.; Ye, H.C.; Li, G.F.; Liu, B.Y.; Meng, Y.L.; Chen, X.Y. Ri-mediated transformation of Artemisia annua with a recombinant farnesyl diphosphate synthase gene for artemisinin production. Plant Cell Tissue Organ Cult., 1999, 57(3), 157-162.
[http://dx.doi.org/10.1023/A:1006326818509]
[157]
Lu, S. Salvia miltiorrhiza: An Economically and Academically Important Medicinal Plant.The Salvia miltiorrhiza Genome; Lu, S., Ed.; Springer: Cham, 2019, pp. 1-15.
[http://dx.doi.org/10.1007/978-3-030-24716-4_1]
[158]
Shao, F.; Qiu, D. Tissue Culture and Hairy Root Induction of Salvia miltiorrhiza.The Salvia miltiorrhiza Genome; Lu, S., Ed.; Springer: Cham, 2019, pp. 163-171.
[http://dx.doi.org/10.1007/978-3-030-24716-4_12]
[159]
Zhi, B.H.; Alfermann, A.W. Diterpenoid production in hairy root cultures of Salvia miltiorrhiza. Phytochemistry, 1993, 32(3), 699-703.
[http://dx.doi.org/10.1016/S0031-9422(00)95156-2]
[160]
Yan, Q.; Hu, Z.; Tan, R.X.; Wu, J. Efficient production and recovery of diterpenoid tanshinones in Salvia miltiorrhiza hairy root cultures with in situ adsorption, elicitation and semi-continuous operation. J. Biotechnol., 2005, 119(4), 416-424.
[http://dx.doi.org/10.1016/j.jbiotec.2005.04.020] [PMID: 15963590]
[161]
Yan, Q.; Shi, M.; Ng, J.; Wu, J.Y. Elicitor-induced rosmarinic acid accumulation and secondary metabolism enzyme activities in Salvia miltiorrhiza hairy roots. Plant Sci., 2006, 170(4), 853-858.
[http://dx.doi.org/10.1016/j.plantsci.2005.12.004]
[162]
Ming, Q.; Su, C.; Zheng, C.; Jia, M.; Zhang, Q.; Zhang, H.; Rahman, K.; Han, T.; Qin, L. Elicitors from the endophytic fungus Trichoderma atroviride promote Salvia miltiorrhiza hairy root growth and tanshinone biosynthesis. J. Exp. Bot., 2013, 64(18), 5687-5694.
[http://dx.doi.org/10.1093/jxb/ert342] [PMID: 24127517]
[163]
Yan, Y.; Zhang, S.; Yang, D.; Zhang, J.; Liang, Z. Effects of Streptomyces pactum Act12 on Salvia miltiorrhiza hairy root growth and tanshinone synthesis and its mechanisms. Appl. Biochem. Biotechnol., 2014, 173(4), 883-893.
[http://dx.doi.org/10.1007/s12010-014-0876-4] [PMID: 24733528]
[164]
Yan, Y.; Zhang, S.; Zhang, J.; Ma, P.; Duan, J.; Liang, Z. Effect and mechanism of endophytic bacteria on growth and secondary metabolite synthesis in Salvia miltiorrhiza hairy roots. Acta Physiol. Plant., 2014, 36(5), 1095-1105.
[http://dx.doi.org/10.1007/s11738-014-1484-1]
[165]
Wang, X.Y.; Cui, G.H.; Huang, L.Q.; Qiu, D.Y. Effects of methyl jasmonat on accumulation and release of tanshinones in suspension cultures of Salvia miltiorrhiza hairy root. Zhongguo Zhongyao Zazhi, 2007, 32(4), 300-302.
[PMID: 17455461]
[166]
Chen, Z.W.; Zhang, J.J.; Zhao, S.J.; Wang, Z.T.; Hu, Z.B. Effect of methyl jasmonate on the accumulation of phenolic acids in Salvia miltiorrhiza hairy root. Chung Kuo Yao Hsueh Tsa Chih, 2010, 45, 970-974.
[167]
Xing, B.; Yang, D.; Liu, L.; Han, R.; Sun, Y.; Liang, Z. Phenolic acid production is more effectively enhanced than tanshinone production by methyl jasmonate in Salvia miltiorrhiza hairy roots. Plant Cell Tissue Organ Cult., 2018, 134(1), 119-129.
[http://dx.doi.org/10.1007/s11240-018-1405-x]
[168]
Liang, Z.; Ma, Y.; Xu, T.; Cui, B.; Liu, Y.; Guo, Z.; Yang, D. Effects of abscisic acid, gibberellin, ethylene and their interactions on production of phenolic acids in salvia miltiorrhiza bunge hairy roots. PLoS One, 2013, 8(9)e72806
[http://dx.doi.org/10.1371/journal.pone.0072806] [PMID: 24023778]
[169]
Sheng, D.F.; Zhang, Y.L. Effects of ABA on tanshinones accumulation of Salvia miltiorrhiza hairy root. Zhong Yao Cai, 2013, 36(3), 354-358.
[PMID: 24010312]
[170]
Yang, D.; Ma, P.; Liang, X.; Wei, Z.; Liang, Z.; Liu, Y.; Liu, F. PEG and ABA trigger methyl jasmonate accumulation to induce the MEP pathway and increase tanshinone production in Salvia miltiorrhiza hairy roots. Physiol. Plant., 2012, 146(2), 173-183.
[http://dx.doi.org/10.1111/j.1399-3054.2012.01603.x] [PMID: 22356467]
[171]
Ge, X.; Wu, J. Induction and potentiation of diterpenoid tanshinone accumulation in Salvia miltiorrhiza hairy roots by β-aminobutyric acid. Appl. Microbiol. Biotechnol., 2005, 68(2), 183-188.
[http://dx.doi.org/10.1007/s00253-004-1873-2] [PMID: 15672269]
[172]
Xiao, Y.; Gao, S.; Di, P.; Chen, J.; Chen, W.; Zhang, L. Lithospermic acid B is more responsive to silver ions (Ag+) than rosmarinic acid in Salvia miltiorrhiza hairy root cultures. Biosci. Rep., 2009, 30(1), 33-40.
[http://dx.doi.org/10.1042/BSR20080124] [PMID: 19210264]
[173]
Xing, B.; Yang, D.; Guo, W.; Liang, Z.; Yan, X.; Zhu, Y.; Liu, Y. Ag+ as a more effective elicitor for production of tanshinones than phenolic acids in Salvia miltiorrhiza hairy roots. Molecules, 2014, 20(1), 309-324.
[http://dx.doi.org/10.3390/molecules20010309] [PMID: 25547728]
[174]
Yan, Q. Influence of biotic and abiotic elicitors on production of tanshinones in Salvia miltiorrhiza hairy root culture. Chin. Tradit. Herbal Drugs, 1994, 2, 107-110.
[175]
Zhao, J.L.; Zhou, L.G.; Wu, J.Y. Effects of biotic and abiotic elicitors on cell growth and tanshinone accumulation in Salvia miltiorrhiza cell cultures. Appl. Microbiol. Biotechnol., 2010, 87(1), 137-144.
[http://dx.doi.org/10.1007/s00253-010-2443-4] [PMID: 20195862]
[176]
Zhou, J.; Fang, L.; Wang, X.; Guo, L.P.; Huang, L.Q. La dramaticaly enhances the accumulation of tanshinones in Salvia miltiorrhiza hairy root cultures; Earth Sci. Res, 2012, p. 2.
[177]
Han, M.; Guo, W.; Liang, Z.; Yang, D.; Yan, X.; Zhu, Y.; Liu, Y. Effects of cerous nitrate on growth and tanshinone production in Salvia miltiorrhiza hairy roots. J. Rare Earths, 2015, 33(11), 1228-1235.
[http://dx.doi.org/10.1016/S1002-0721(14)60549-4]
[178]
Liu, L.; Yang, D.; Liang, T.; Zhang, H.; He, Z.; Liang, Z. Phosphate starvation promoted the accumulation of phenolic acids by inducing the key enzyme genes in Salvia miltiorrhiza hairy roots. Plant Cell Rep., 2016, 35(9), 1933-1942.
[http://dx.doi.org/10.1007/s00299-016-2007-x] [PMID: 27271760]
[179]
Wu, J.Y.; Shi, M. Ultrahigh diterpenoid tanshinone production through repeated osmotic stress and elicitor stimulation in fed-batch culture of Salvia miltiorrhiza hairy roots. Appl. Microbiol. Biotechnol., 2008, 78(3), 441-448.
[http://dx.doi.org/10.1007/s00253-007-1332-y] [PMID: 18189134]
[180]
Wang, C.H.; Zheng, L.P.; Tian, H.; Wang, J.W. Synergistic effects of ultraviolet-B and methyl jasmonate on tanshinone biosynthesis in Salvia miltiorrhiza hairy roots. J. Photochem. Photobiol. B, 2016, 159, 93-100.
[http://dx.doi.org/10.1016/j.jphotobiol.2016.01.012] [PMID: 27043259]
[181]
Hao, G.; Ji, H.; Li, Y.; Shi, R.; Wang, J.; Feng, L.; Huang, L. Exogenous ABA and polyamines enhanced salvianolic acids contents in hairy root cultures of Salvia miltiorrhiza Bge. f. alba. Plant Omics, 2012, 5(5), 446.
[182]
Wang, Y.; Shen, Y.; Shen, Z.; Zhao, L.; Ning, D.; Jiang, C.; Zhao, R.; Huang, L. Comparative proteomic analysis of the response to silver ions and yeast extract in Salvia miltiorrhiza hairy root cultures. Plant Physiol. Biochem., 2016, 107, 364-373.
[http://dx.doi.org/10.1016/j.plaphy.2016.06.028] [PMID: 27372730]
[183]
Cheng, Q.; He, Y.; Li, G.; Liu, Y.; Gao, W.; Huang, L. Effects of combined elicitors on tanshinone metabolic profiling and SmCPS expression in Salvia miltiorrhiza hairy root cultures. Molecules, 2013, 18(7), 7473-7485.
[http://dx.doi.org/10.3390/molecules18077473] [PMID: 23807574]
[184]
Zhang, S.; Liu, Y.; Shen, S.; Liang, Z.; Yang, D. Effects of elicitors on accumulation of phenolic acids and tanshinones in Salvia miltiorrhiza hairy root; China J. Chin. Mater. Med, 2011, p. 10.
[185]
Siu, K.C.; Wu, J.Y. Enhanced release of tanshinones and phenolics by nonionic surfactants from Salvia miltiorrhiza hairy roots. Eng. Life Sci., 2014, 14(6), 685-690.
[http://dx.doi.org/10.1002/elsc.201400159]
[186]
Wang, M.; Lu, S. Genetic Transformation of Salvia miltiorrhiza.The Salvia miltiorrhiza Genome; Lu, S., Ed.; Springer: Cham, 2019, pp. 173-192.
[http://dx.doi.org/10.1007/978-3-030-24716-4_13]
[187]
Eibl, R.; Eibl, D. Design of bioreactors suitable for plant cell and tissue cultures. Phytochem. Rev., 2008, 7, 593-598.
[http://dx.doi.org/10.1007/s11101-007-9083-z]
[188]
Srivastava, S.; Srivastava, A.K. Hairy root culture for mass-production of high-value secondary metabolites. Crit. Rev. Biotechnol., 2007, 27(1), 29-43.
[http://dx.doi.org/10.1080/07388550601173918] [PMID: 17364688]
[189]
Flores, H.E.; Curtis, W.R. Approaches to understanding and manipulating the biosynthetic potential of plant roots. Ann. N. Y. Acad. Sci., 1992, 665, 188-209.
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb42584.x] [PMID: 1416603]
[190]
Ramakrishnan, D.; Curtis, W.R. Fluid dynamic studies on plant root cultures for application to bioreactor design.Studies in Plant Science. Advances in Plant Biotechnology: Production of Secondary Metabolites; Ryu, D.D.Y; Furusaki, S., Ed.; Elsevier: Amsterdam, 1994, pp. 281-305.
[http://dx.doi.org/10.1016/B978-0-444-89939-2.50019-X]
[191]
Patra, N.; Srivastava, A.K. Use of model-based nutrient feeding for improved production of artemisinin by hairy roots of Artemisia annua in a modified stirred tank bioreactor. Appl. Biochem. Biotechnol., 2015, 177(2), 373-388.
[http://dx.doi.org/10.1007/s12010-015-1750-8] [PMID: 26206459]
[192]
Patra, N.; Srivastava, A.K. Enhanced production of artemisinin by hairy root cultivation of Artemisia annua in a modified stirred tank reactor. Appl. Biochem. Biotechnol., 2014, 174(6), 2209-2222.
[http://dx.doi.org/10.1007/s12010-014-1176-8] [PMID: 25172060]
[193]
Palazón, J.; Mallol, A.; Eibl, R.; Lettenbauer, C.; Cusidó, R.M.; Piñol, M.T. Growth and ginsenoside production in hairy root cultures of Panax ginseng using a novel bioreactor. Planta Med., 2003, 69(4), 344-349.
[http://dx.doi.org/10.1055/s-2003-38873] [PMID: 12709902]
[194]
Kochan, E.; Szymczyk, P.; Kuźma, Ł.; Lipert, A.; Szymańska, G. Yeast extract stimulates ginsenoside production in hairy root cultures of American ginseng cultivated in shake flasks and nutrient sprinkle bioreactors. Molecules, 2017, 22(6), 880.
[http://dx.doi.org/10.3390/molecules22060880] [PMID: 28587128]
[195]
Kochan, E.; Królicka, A.; Chmiel, A. Growth and ginsenoside production in Panax quinquefolium hairy roots cultivated in flasks and nutrient sprinkle bioreactor. Acta Physiol. Plant., 2012, 34(4), 1513-1518.
[http://dx.doi.org/10.1007/s11738-012-0949-3]
[196]
Thakore, D.; Srivastava, A.K.; Sinha, A.K. Mass production of Ajmalicine by bioreactor cultivation of hairy roots of Catharanthus roseus. Biochem. Eng. J., 2017, 119, 84-91.
[http://dx.doi.org/10.1016/j.bej.2016.12.010]
[197]
Du, M.; Wu, X.J.; Ding, J.; Hu, Z.B.; White, K.N.; Branford-White, C.J. Astragaloside IV and polysaccharide production by hairy roots of Astragalus membranaceus in bioreactors. Biotechnol. Lett., 2003, 25(21), 1853-1856.
[http://dx.doi.org/10.1023/A:1026233728375] [PMID: 14677711]
[198]
Kuźma, Ł.; Bruchajzer, E.; Wysokińska, H. Methyl jasmonate effect on diterpenoid accumulation in Salvia sclarea hairy root culture in shake flasks and sprinkle bioreactor. Enzyme Microb. Technol., 2009, 44(6-7), 406-410.
[http://dx.doi.org/10.1016/j.enzmictec.2009.01.005]
[199]
Grzegorczyk, I.; Wysokinska, H. Antioxidant compounds in Salvia officinalis L. shoot and hairy root cultures in the nutrient sprinkle bioreactor. Acta Soc. Bot. Pol., 2010, 79(1), 7-10.
[http://dx.doi.org/10.5586/asbp.2010.001]
[200]
Kintzios, S.; Makri, O.; Pistola, E.; Matakiadis, T.; Shi, H.P.; Economou, A. Scale-up production of puerarin from hairy roots of Pueraria phaseoloides in an airlift bioreactor. Biotechnol. Lett., 2004, 26(13), 1057-1059.
[http://dx.doi.org/10.1023/B:BILE.0000032963.41208.e8] [PMID: 15218379]
[201]
Sudo, H.; Yamakawa, T.; Yamazaki, M.; Aimi, N.; Saito, K. Bioreactor production of camptothecin by hairy root cultures of Ophiorrhiza pumila. Biotechnol. Lett., 2002, 24(5), 359-363.
[http://dx.doi.org/10.1023/A:1014568904957]
[202]
Shimomura, K.; Sudo, H.; Saga, H.; Kamada, H. Shikonin production and secretion by hairy root cultures of Lithospermum erythrorhizon. Plant Cell Rep., 1991, 10(6-7), 282-285.
[http://dx.doi.org/10.1007/BF00193142] [PMID: 24221657]
[203]
Facchini, P.J. Alkaloid biosynthesis in plants: biochemistry, cell biology, molecular regulation, and metabolic engineering applications. Annu. Rev. Plant Physiol. Plant Mol. Biol., 2001, 52, 29-66.
[http://dx.doi.org/10.1146/annurev.arplant.52.1.29] [PMID: 11337391]
[204]
Moyano, E.; Fornalé, S.; Palazón, J.; Cusidó, R.M.; Bonfill, M.; Morales, C.; Piñol, M.T. Effect of Agrobacterium rhizogenes T-DNA on alkaloid production in Solanaceae plants. Phytochemistry, 1999, 52, 1287-1292.
[http://dx.doi.org/10.1016/S0031-9422(99)00421-5]
[205]
Jung, G.; Tepfer, D. Use of genetic transformation by the Ri T-DNA of Agrobacterium rhizogenes to stimulate biomass and tropane alkaloid production in Atropa belladona and Calystegia sepium roots grown in vitro. Plant Sci., 1987, 50, 145-151.
[http://dx.doi.org/10.1016/0168-9452(87)90151-8]
[206]
Jaziri, M.; Yoshimatsu, K.; Homes, J.; Vanhaelen, M. Tropane alkaloid production by hairy root cultures of Datura stramonium and Hyocyamus niger. Phytochemistry, 1988, 27, 419-420.
[http://dx.doi.org/10.1016/0031-9422(88)83111-X]
[207]
Yokota, S.; Onohara, Y.; Shoyama, Y. Immunofluorescence and immunoelectron microscopic localization of medicinal substance, Rb1, in several plant parts of Panax ginseng. Curr. Drug Discov. Technol., 2011, 8(1), 51-59.
[http://dx.doi.org/10.2174/157016311794519938] [PMID: 21143133]
[208]
Sangwan, R.S.; Das Chaurasiya, N.; Lal, P.; Misra, L.; Tuli, R.; Sangwan, N.S. Withanolide A is inherently de novo biosynthesized in roots of the medicinal plant Ashwagandha (Withania somnifera). Physiol. Plant., 2008, 133(2), 278-287.
[http://dx.doi.org/10.1111/j.1399-3054.2008.01076.x] [PMID: 18312497]
[209]
Dräger, B. Tropinone reductases, enzymes at the branch point of tropane alkaloid metabolism. Phytochemistry, 2006, 67(4), 327-337.
[http://dx.doi.org/10.1016/j.phytochem.2005.12.001] [PMID: 16426652]
[210]
Murthy, H.N.; Dijkstra, C.; Anthony, P.; White, D.A.; Davey, M.R.; Power, J.B.; Hahn, E.J.; Paek, K.Y. Establishment of Withania somnifera hairy root cultures for the production of withanolide A. J. Integr. Plant Biol., 2008, 50(8), 975-981.
[http://dx.doi.org/10.1111/j.1744-7909.2008.00680.x] [PMID: 18713347]
[211]
Lorence, A.; Medina-Bolivar, F.; Nessler, C.L. Camptothecin and 10-hydroxycamptothecin from Camptotheca acuminata hairy roots. Plant Cell Rep., 2004, 22(6), 437-441.
[http://dx.doi.org/10.1007/s00299-003-0708-4] [PMID: 13680137]
[212]
Shanks, J.V.; Bhadra, R.; Morgan, J.; Rijhwani, S.; Vani, S. Quantification of metabolites in the indole alkaloid pathways of Catharanthus roseus: Implications for metabolic engineering. Biotechnol. Bioeng., 1998, 58(2-3), 333-338.
[http://dx.doi.org/10.1002/(SICI)1097-0290(19980420)58:2/3333::AID-BIT35>3.0.CO;2-A] [PMID: 10191413]
[213]
Parr, A.J.; Peerless, A.C.J.; Hamill, J.D.; Walton, N.J.; Robins, R.J.; Rhodes, M.J.C. Alkaloid production by transformed root cultures of Catharanthus roseus. Plant Cell Rep., 1988, 7(5), 309-312.
[http://dx.doi.org/10.1007/BF00269925] [PMID: 24241871]
[214]
Murata, J.; Roepke, J.; Gordon, H.; De Luca, V. The leaf epidermome of Catharanthus roseus reveals its biochemical specialization. Plant Cell, 2008, 20(3), 524-542.
[http://dx.doi.org/10.1105/tpc.107.056630] [PMID: 18326827]
[215]
Park, S.U.; Facchini, P.J. Agrobacterium rhizogenes-mediated transformation of opium poppy, Papaver somniferum l., and California poppy, Eschscholzia californica cham., root cultures. J. Exp. Bot., 2000, 51(347), 1005-1016.
[http://dx.doi.org/10.1093/jexbot/51.347.1005] [PMID: 10948228]

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      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=106673
      900μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 30 limit 1
      920μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 30
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and sj.journal_id!=30 group by `j`.`nid`) as `aggregate_table`
      1.57msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and sj.journal_id!=30 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.26msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.82msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.67msalphaeurekaselec_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` = '106673'
      1.74msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 106673
      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` = '106673'
      4.51msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 106673
      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` = '106673' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.37msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 106673
      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
      340μsalphaeurekaselec_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
      730μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 30 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      35.4msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      15.5msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      13.35msalphaeurekaselec_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` = 106673 limit 1
      260μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 106673
      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 = 106673 and content_type = 'article' order by status desc limit 1
      340μsalphaeurekaselec_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` = 182005 limit 1
      240μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 182005
      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
      240μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CPB' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      310μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPB
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '106673' 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 = '10559' 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) )
      350μsalphaeurekaselec_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 = '2947' 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) )
      300μsalphaeurekaselec_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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2947) 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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2947) 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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2947)
      11.94msalphaeurekaselec_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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10559) 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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10559) 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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10559)
      620μsalphaeurekaselec_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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 106673) 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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 106673) 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 <= 58768607 and j.to_ip >=58768607 )) and ((j.from_date <= 1740675393 and j.to_date >= 1740675393 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 106673)
      540μsalphaeurekaselec_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` < '592' and is_uploaded = 1 and issue_id = 10559 order by cast(first_page as SIGNED) desc limit 1
      510μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 592
      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` > '608' and is_uploaded = 1 and issue_id = 10559 order by cast(first_page as SIGNED) asc limit 1
      450μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 608
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      210μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      180μsalphaeurekaselec_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` = 106673 limit 1
      2.39msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 106673
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 30 and `b`.`banner_from_date` <= 1740675393 and `b`.`banner_to_date` >= 1740675393 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.15msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740675393
      • 4: 1740675393
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 30 and `b`.`banner_from_date` <= 1740675393 and `b`.`banner_to_date` >= 1740675393 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.08msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740675393
      • 4: 1740675393
      • 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='b05878e39ec7f17da214dfdc276cb3e5'
      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
        o6DGPSZTQs4L8SwQUnIs800ymidBoKldxlbdhkLU
        uc_cart_id
        b05878e39ec7f17da214dfdc276cb3e5
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/106673" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/106673
        status_code
        200
        
        status_text
        OK
        format
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        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        []
        
        response_headers
        0 of 0
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        0 of 0
        array:5 [ "_token" => "o6DGPSZTQs4L8SwQUnIs800ymidBoKldxlbdhkLU" "uc_cart_id" => "b05878e39ec7f17da214dfdc276cb3e5" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/106673" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-27 16:56:33GET/article/106673414361