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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Mechanistic Investigation of Glycyrrhiza uralensis Effects against Respiratory Ailments: Application of Network Pharmacology and Molecular Docking Approaches

Author(s): Munazza Ijaz, Xianju Huang, Manal Buabeid, Tahir Ali Chohan, Ghulam Murtaza* and Saba Shamim*

Volume 19, Issue 5, 2022

Published on: 08 December, 2021

Page: [397 - 412] Pages: 16

DOI: 10.2174/1570180818666211119113853

Price: $65

Abstract

Background: Glycyrrhiza uralensis, also known as liquorice, is a herbal remedy that is traditionally used worldwide for treating respiratory ailments and ameliorating breathing.

Objective: The objective of this systematic study was to investigate active ingredients of Glycyrrhiza uralensis and determine its mode of action in silico against severe and acute respiratory complications of respiratory ailments through network pharmacology and molecular docking studies.

Methods: TCMSP database search helped retrieve the compounds of Glycyrrhiza uralensis and their protein targets, especially related to respiratory ailments. Subsequently, the protein-protein association was attained as a network by using the STITCH database. Cytoscape and its ClueGO plugin were used to study gene ontology (GO) enrichment. In addition, seven natural compounds were docked in the active site of four different molecular targets; JUN-FOS, COX2, MAPK14 and IL-6, to identify the binding mechanism of ligands under study.

Results: TCMSP database search resulted in the retrieval of 280 compounds of Glycyrrhiza uralensis (including formononetin, naringenin, sitosterol, isorhamnetin, kaempferol, quercetin and Glycyrrhizin) and 135 protein targets. A careful study of targets showed that 26 prospective targets (including JUN, FOS, IL6, MAPK14 and PTGS2) related to respiratory ailments were identified. Gene ontology (GO) enrichment analysis resulted in the retrieval of 176 GO terms, which were associated with respiratory ailments. This study proposed that Glycyrrhiza uralensis acts against respiratory ailments through various proteins, such as JUN, FOS, IL6, MAPK14 and PTGS2. Docking results revealed that among all studied ligands, the flavonoid-based compounds isorhamnetin and kaempferol form stronger complexes with JUN-FOS-DNA, MAPK-14, and IL-6 proteins (Cscore=6.81, 4.27, and 4.77, respectively) and the saponin based compound glycyrrhizin (Cscore=13.07) demonstrated stronger binding affinity towards COX2 enzyme.

Conclusion: Conclusively, isorhamnetin, kaempferol and glycyrrhizin in Glycyrrhiza uralensis may regulate several signaling pathways through JUN-FOS-DNA, MAPK-14, and IL-6, which might play a therapeutic role against respiratory ailments.

Keywords: Biological effects, cytoscape, respiratory ailments, mechanism of action, molecular targets, interleukin-6, Glycyrrhiza uralensis, STITCH.

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[1]
Zhang, D.H.; Zhang, X.; Peng, B.; Deng, S.Q.; Wang, Y.F.; Yang, L.; Zhang, K.Z.; Ling, C.Q.; Wu, K.L. Network pharmacology suggests biochemical rationale for treating COVID-19 symptoms with a Traditional Chinese Medicine. Commun. Biol., 2020, 3(1), 466.
[http://dx.doi.org/10.1038/s42003-020-01190-y] [PMID: 32811894]
[2]
Shamim, S.; Khan, M.; Kharaba, Z.J.; Ijaz, M.; Murtaza, G. Potential strategies for combating COVID-19. Arch. Virol., 2020, 165(11), 2419-2438.
[http://dx.doi.org/10.1007/s00705-020-04768-3] [PMID: 32778950]
[3]
Li, G.; Fan, Y.; Lai, Y.; Han, T.; Li, Z.; Zhou, P.; Pan, P.; Wang, W.; Hu, D.; Liu, X.; Zhang, Q.; Wu, J. Coronavirus infections and immune responses. J. Med. Virol., 2020, 92(4), 424-432.
[http://dx.doi.org/10.1002/jmv.25685] [PMID: 31981224]
[4]
Lin, L.; Lu, L.; Cao, W.; Li, T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg. Microbes Infect., 2020, 9(1), 727-732.
[http://dx.doi.org/10.1080/22221751.2020.1746199] [PMID: 32196410]
[5]
Filippou, P.S.; Karagiannis, G.S. Cytokine storm during chemotherapy: a new companion diagnostic emerges? Oncotarget, 2020, 11(3), 213-215.
[http://dx.doi.org/10.18632/oncotarget.27442] [PMID: 32076483]
[6]
Mehta, P.; McAuley, D.F.; Brown, M.; Sanchez, E.; Tattersall, R.S.; Manson, J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 2020, 395(10229), 1033-1034.
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578]
[7]
Pedersen, S.F.; Ho, Y.C. SARS-CoV-2: a storm is raging. J. Clin. Invest., 2020, 130(5), 2202-2205.
[http://dx.doi.org/10.1172/JCI137647] [PMID: 32217834]
[8]
Yang, S.J.; Wang, Z.Y.; Zhao, H.H.; Ren, X.Q. Modern research of tibetan medicine. World J. Tradit. Chin. Med., 2019, 5, 131-138.
[http://dx.doi.org/10.4103/wjtcm.wjtcm_10_19]
[9]
Tong, H.Y.; Zhang, S.Q.; Murtaza, G.; Zhao, H.H.; Huang, X.J. Hu-Rilebagen, The present scenario, challenges, and future anticipation of traditional Mongolian medicine in China. World J. Tradit. Chin. Med., 2019, 4, 187-192.
[10]
Yang, N.; Patil, S.; Zhuge, J.; Wen, M.C.; Bolleddula, J.; Doddaga, S.; Goldfarb, J.; Sampson, H.A.; Li, X.M. Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI™, inhibit memory Th2 responses in vitro and in vivo. Phytother. Res., 2013, 27(9), 1381-1391.
[http://dx.doi.org/10.1002/ptr.4862] [PMID: 23165939]
[11]
Luo, H.; Gao, Y.; Zou, J.; Zhang, S.; Chen, H.; Liu, Q.; Tan, D.; Han, Y.; Zhao, Y.; Wang, S. Reflections on treatment of COVID-19 with traditional Chinese medicine. Chin. Med., 2020, 15, 94.
[http://dx.doi.org/10.1186/s13020-020-00375-1] [PMID: 32905189]
[12]
Chen, K.X. Academician kai-xian chen talks about the development of traditional Chinese medicine and global medicine. World J. Tradit. Chin. Med., 2020, 6, 1-11.
[http://dx.doi.org/10.4103/wjtcm.wjtcm_30_19]
[13]
Gao, L.; Jia, C.H.; Wang, W. Recent advances in the study of ancient books on traditional Chinese medicine. World J. Tradit. Chin. Med., 2020, 6, 61-66.
[http://dx.doi.org/10.4103/wjtcm.wjtcm_3_20]
[14]
Bailly, C.; Vergoten, G. Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome? Pharmacol. Ther., 2020, 214107618
[http://dx.doi.org/10.1016/j.pharmthera.2020.107618] [PMID: 32592716]
[15]
Cui, Y.; Ao, M.; Li, W.; Hu, J.; Yu, L. Anti-inflammatory activity of licochalcone A isolated from Glycyrrhiza inflata. Z. Naturforsch. C J. Biosci., 2008, 63(5-6), 361-365.
[http://dx.doi.org/10.1515/znc-2008-5-609] [PMID: 18669021]
[16]
Ram, A.; Mabalirajan, U.; Das, M.; Bhattacharya, I.; Dinda, A.K.; Gangal, S.V.; Ghosh, B. Glycyrrhizin alleviates experimental allergic asthma in mice. Int. Immunopharmacol., 2006, 6(9), 1468-1477.
[http://dx.doi.org/10.1016/j.intimp.2006.04.020] [PMID: 16846841]
[17]
Pilcher, H. Liquorice may tackle SARS. Nature, 2003.
[http://dx.doi.org/10.1038/news030609-16]
[18]
Yin, X.; Miao, X.; Aldossary, S.A.; Murtaza, G.; Zhang, X. A network pharmacology paradigm to decipher the mode of action of tangshen formula in diabetic cardiomyopathy. Lat. Am. J. Pharm., 2020, 39(7), 1446-1454.
[19]
Gao, K.; Yang, R.; Zhang, J.; Wang, Z.; Jia, C.; Zhang, F.; Li, S.; Wang, J.; Murtaza, G.; Xie, H.; Zhao, H.; Wang, W.; Chen, J. Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology. Pharmacol. Res., 2018, 130, 93-109.
[http://dx.doi.org/10.1016/j.phrs.2018.01.011] [PMID: 29391233]
[20]
Cheng, D.; Murtaza, G.; Ma, S.; Li, L.; Li, X.; Tian, F.; Zheng, J.; Lu, Y. In silico prediction of the anti-depression mechanism of a herbal formula (Tiansi Liquid) containing Morinda officinalis and Cuscuta chinensis. Molecules, 2017, 22(10), 1614-1630.
[http://dx.doi.org/10.3390/molecules22101614] [PMID: 28954415]
[21]
Buabeid, M.A.; Arafa, E.S.A.; Hassan, W.; Murtaza, G. In silico prediction of the mode of action of viola odorata in diabetes. Bio- Med. Res. Int. 2020, 2020.
[http://dx.doi.org/10.1155/2020/2768403]
[22]
Zhao, W.; Lin, K.; Zu, Z.; Anam, H.; Asad, M.H.H.B.; Murtaza, G. In silico decipherment of Corydalis yanhusuo mode of action in the femoral head osteonecrosis. Lat. Am. J. Pharm., 2020, 39(6), 1200-1209.
[23]
Jianxian, C.; Dastgeer, S.; Saad, A.A.; Asad, M.H.H.B.; Murtaza, G. In silico assessment of mode of action of radix salvia miltiorrhiza in cardiovascular diseases. Lat. Am. J. Pharm., 2020, 39(6), 1192-1199.
[24]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6, 13-19.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[25]
Zhao, K.; Shi, N.; Sa, Z.; Wang, H.X.; Lu, C.H.; Xu, X.Y. Text mining and analysis of treatise on febrile diseases based on natural language processing. World J. Tradit. Chin. Med., 2020, 6, 67-73.
[http://dx.doi.org/10.4103/wjtcm.wjtcm_28_19]
[26]
O’Donovan, C.; Martin, M.J.; Gattiker, A.; Gasteiger, E.; Bairoch, A.; Apweiler, R. High-quality protein knowledge resource: SWISS-PROT and TrEMBL. Brief. Bioinform., 2002, 3(3), 275-284.
[http://dx.doi.org/10.1093/bib/3.3.275] [PMID: 12230036]
[27]
Kuhn, M.; Szklarczyk, D.; Pletscher-Frankild, S.; Blicher, T.H.; von Mering, C.; Jensen, L.J.; Bork, P. STITCH 4: integration of protein-chemical interactions with user data. Nucleic Acids Res., 2014, 42(Database issue), D401-D407.
[http://dx.doi.org/10.1093/nar/gkt1207] [PMID: 24293645]
[28]
Wu, Y.; Zhang, F.; Yang, K.; Fang, S.; Bu, D.; Li, H.; Sun, L.; Hu, H.; Gao, K.; Wang, W.; Zhou, X.; Zhao, Y.; Chen, J. SymMap: an integrative database of traditional Chinese medicine enhanced by symptom mapping. Nucleic Acids Res., 2019, 47(D1), D1110-D1117.
[http://dx.doi.org/10.1093/nar/gky1021] [PMID: 30380087]
[29]
Bindea, G.; Mlecnik, B.; Hackl, H.; Charoentong, P.; Tosolini, M.; Kirilovsky, A.; Fridman, W.H.; Pagès, F.; Trajanoski, Z.; Galon, J. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics, 2009, 25(8), 1091-1093.
[http://dx.doi.org/10.1093/bioinformatics/btp101] [PMID: 19237447]
[30]
Glover, J.N.; Harrison, S.C. Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature, 1995, 373(6511), 257-261.
[http://dx.doi.org/10.1038/373257a0] [PMID: 7816143]
[31]
Limongelli, V.; Bonomi, M.; Marinelli, L.; Gervasio, F.L.; Cavalli, A.; Novellino, E.; Parrinello, M. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition. Proc. Natl. Acad. Sci. USA, 2010, 107(12), 5411-5416.
[http://dx.doi.org/10.1073/pnas.0913377107] [PMID: 20215464]
[32]
Xu, G-Y.; Yu, H-A.; Hong, J.; Stahl, M.; McDonagh, T.; Kay, L.E.; Cumming, D.A. Solution structure of recombinant human interleukin-6. J. Mol. Biol., 1997, 268(2), 468-481.
[http://dx.doi.org/10.1006/jmbi.1997.0933] [PMID: 9159484]
[33]
Watterson, D.M.; Grum-Tokars, V.L.; Roy, S.M.; Schavocky, J.P.; Bradaric, B.D.; Bachstetter, A.D.; Xing, B.; Dimayuga, E.; Saeed, F.; Zhang, H.; Staniszewski, A.; Pelletier, J.C.; Minasov, G.; Anderson, W.F.; Arancio, O.; Van Eldik, L.J. Development of novel in vivo chemical probes to address CNS protein kinase involvement in synaptic dysfunction. PLoS One, 2013, 8(6)e66226
[http://dx.doi.org/10.1371/journal.pone.0066226] [PMID: 23840427]
[34]
Jain, A.N. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J. Med. Chem., 2003, 46(4), 499-511.
[http://dx.doi.org/10.1021/jm020406h] [PMID: 12570372]
[35]
Case, D.A.; Darden, T.; Cheatham, T.E., III; Simmerling, C.; Wang, J.; Duke, R.E. AMBER 9; University of California, San Francisco, , 2006.
[36]
Powell, M.J. A fast algorithm for nonlinearly constrained optimization calculations.Numerical analysis; Springer, 1978, pp. 144-157.
[37]
SYBYL-X 1.3. Molecular Modeling Software; Tripose Inc: South Hanley Road, St. Louis, MO 631444, USA, 1699.
[38]
Jain, A.N. Scoring noncovalent protein-ligand interactions: a continuous differentiable function tuned to compute binding affinities. J. Comput. Aided Mol. Des., 1996, 10(5), 427-440.
[http://dx.doi.org/10.1007/BF00124474] [PMID: 8951652]
[39]
Chohan, T.A.; Qian, H-Y.; Pan, Y-L.; Chen, J-Z. Molecular simulation studies on the binding selectivity of 2-anilino-4-(thiazol-5-yl)-pyrimidines in complexes with CDK2 and CDK7. Mol. Biosyst., 2016, 12(1), 145-161.
[http://dx.doi.org/10.1039/C5MB00630A] [PMID: 26565382]
[40]
Yi, L.; Cui, J.; Wang, W.; Tang, W.; Teng, F.; Zhu, X.; Qin, J.; Wuniqiemu, T.; Sun, J.; Wei, Y.; Dong, J. Formononetin attenuates airway inflammation and oxidative stress in murine allergic asthma. Front. Pharmacol., 2020, 11533841
[http://dx.doi.org/10.3389/fphar.2020.533841] [PMID: 33013383]
[41]
Lin, Y.; Tan, D.; Kan, Q.; Xiao, Z.; Jiang, Z. The protective effect of naringenin on airway remodeling after Mycoplasma pneumoniae Infection by Inhibiting Autophagy-Mediated Lung Inflammation and Fibrosis. Mediators Inflamm., 2018, 20188753894
[http://dx.doi.org/10.1155/2018/8753894] [PMID: 29849498]
[42]
Zhou, B.X.; Li, J.; Liang, X.L.; Pan, X.P.; Hao, Y.B.; Xie, P.F.; Jiang, H.M.; Yang, Z.F.; Zhong, N.S. β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling. Acta Pharmacol. Sin., 2020, 41(9), 1178-1196.
[http://dx.doi.org/10.1038/s41401-020-0403-9] [PMID: 32504068]
[43]
Ruan, Y.; Hu, K.; Chen, H. Autophagy inhibition enhances isorhamnetin induced mitochondria dependent apoptosis in non small cell lung cancer cells. Mol. Med. Rep., 2015, 12(4), 5796-5806.
[http://dx.doi.org/10.3892/mmr.2015.4148] [PMID: 26238746]
[44]
Gong, J.H.; Shin, D.; Han, S.Y.; Kim, J.L.; Kang, Y.H. Kaempferol suppresses eosionphil infiltration and airway inflammation in airway epithelial cells and in mice with allergic asthma. J. Nutr., 2012, 142(1), 47-56.
[http://dx.doi.org/10.3945/jn.111.150748] [PMID: 22157542]
[45]
Heinz, S.A.; Henson, D.A.; Austin, M.D.; Jin, F.; Nieman, D.C. Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial. Pharmacol. Res., 2010, 62(3), 237-242.
[http://dx.doi.org/10.1016/j.phrs.2010.05.001] [PMID: 20478383]
[46]
Luo, P.; Liu, D. Li, J. Pharmacological perspective: glycyrrhizin may be an efficacious therapeutic agent for COVID-19. Int. J. Antimicrob. Agents, 2020, 55(6)105995
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105995] [PMID: 32335281]
[47]
Murck, H. Symptomatic protective action of glycyrrhizin (Licorice) in COVID-19 infection? Front. Immunol., 2020, 11, 1239.
[http://dx.doi.org/10.3389/fimmu.2020.01239] [PMID: 32574273]
[48]
Rahman, I.; MacNee, W. Role of transcription factors in inflammatory lung diseases. Thorax, 1998, 53(7), 601-612.
[http://dx.doi.org/10.1136/thx.53.7.601] [PMID: 9797762]
[49]
Mudd, P.A.; Crawford, J.C.; Turner, J.S.; Souquette, A.; Reynolds, D.; Bender, D. Targeted immunosuppression distinguishes COVID-19 from influenza in moderate and severe disease. medRxiv, 2020.
[50]
Sinha, P.; Mostaghim, A.; Bielick, C.G.; McLaughlin, A.; Hamer, D.H.; Wetzler, L.M.; Bhadelia, N.; Fagan, M.A.; Linas, B.P.; Assoumou, S.A.; Ieong, M.H.; Lin, N.H.; Cooper, E.R.; Brade, K.D.; White, L.F.; Barlam, T.F.; Sagar, M. Early administration of interleukin-6 inhibitors for patients with severe COVID-19 disease is associated with decreased intubation, reduced mortality, and increased discharge. Int. J. Infect. Dis., 2020, 99, 28-33.
[http://dx.doi.org/10.1016/j.ijid.2020.07.023] [PMID: 32721528]
[51]
Ruan, Q.; Yang, K.; Wang, W.; Jiang, L.; Song, J. Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med., 2020, 46(6), 1294-1297.
[http://dx.doi.org/10.1007/s00134-020-06028-z] [PMID: 32253449]
[52]
Keeler, S.P.; Gerovac, B.J.; Wu, K.; Wang, X.; Chartock, J.R.; Byers, D.E.; Romero, A.G.; Holtzman, M.J. Epithelial-immune cell interactions for drug discovery in chronic obstructive pulmonary disease. Ann. Am. Thorac. Soc., 2018, 15(Suppl. 4), S260-S265.
[http://dx.doi.org/10.1513/AnnalsATS.201808-531MG] [PMID: 30759005]
[53]
Yu, G.; Kovkarova-Naumovski, E.; Jara, P.; Parwani, A.; Kass, D.; Ruiz, V.; Lopez-Otín, C.; Rosas, I.O.; Gibson, K.F.; Cabrera, S.; Ramírez, R.; Yousem, S.A.; Richards, T.J.; Chensny, L.J.; Selman, M.; Kaminski, N.; Pardo, A. Matrix metalloproteinase-19 is a key regulator of lung fibrosis in mice and humans. Am. J. Respir. Crit. Care Med., 2012, 186(8), 752-762.
[http://dx.doi.org/10.1164/rccm.201202-0302OC] [PMID: 22859522]
[54]
Finigan, J.H.; Faress, J.A.; Wilkinson, E.; Mishra, R.S.; Nethery, D.E.; Wyler, D.; Shatat, M.; Ware, L.B.; Matthay, M.A.; Mason, R.; Silver, R.F.; Kern, J.A. Neuregulin-1-human epidermal receptor-2 signaling is a central regulator of pulmonary epithelial permeability and acute lung injury. J. Biol. Chem., 2011, 286(12), 10660-10670.
[http://dx.doi.org/10.1074/jbc.M110.208041] [PMID: 21247898]
[55]
Shimizu, S.; Takezawa-Yasuoka, K.; Ogawa, T.; Tojima, I.; Kouzaki, H.; Shimizu, T. The epidermal growth factor receptor inhibitor AG1478 inhibits eosinophilic inflammation in upper airways. Clin. Immunol., 2018, 188, 1-6.
[http://dx.doi.org/10.1016/j.clim.2017.11.010] [PMID: 29183867]
[56]
Rahman, A.; Henry, K.M.; Herman, K.D.; Thompson, A.A.; Isles, H.M.; Tulotta, C.; Sammut, D.; Rougeot, J.J.; Khoshaein, N.; Reese, A.E.; Higgins, K.; Tabor, C.; Sabroe, I.; Zuercher, W.J.; Savage, C.O.; Meijer, A.H.; Whyte, M.K.; Dockrell, D.H.; Renshaw, S.A.; Prince, L.R. Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation. eLife, 2019, 8e50990
[http://dx.doi.org/10.7554/eLife.50990] [PMID: 31613219]
[57]
Lee, H.S.; Kim, H.J.; Moon, C.S.; Chong, Y.H.; Kang, J.L. Inhibition of c-Jun NH2-terminal kinase or extracellular signal-regulated kinase improves lung injury. Respir. Res., 2004, 5, 23.
[http://dx.doi.org/10.1186/1465-9921-5-23] [PMID: 15566575]
[58]
Tkacova, R.; Ukropec, J.; Skyba, P.; Ukropcova, B.; Pobeha, P.; Kurdiova, T.; Joppa, P.; Klimes, I.; Tkac, I.; Gasperikova, D. Increased adipose tissue expression of proinflammatory CD40, MKK4 and JNK in patients with very severe chronic obstructive pulmonary disease. Respiration, 2011, 81(5), 386-393.
[http://dx.doi.org/10.1159/000319957] [PMID: 20699612]
[59]
Chen, K.; Kolls, J.K. T cell-mediated host immune defenses in the lung. Annu. Rev. Immunol., 2013, 31, 605-633.
[http://dx.doi.org/10.1146/annurev-immunol-032712-100019] [PMID: 23516986]
[60]
Prigge, A.D.; Ma, R.; Coates, B.M.; Singer, B.D.; Ridge, K.M. Age-dependent differences in T-cell responses to influenza a virus. Am. J. Respir. Cell Mol. Biol., 2020, 63(4), 415-423.
[http://dx.doi.org/10.1165/rcmb.2020-0169TR] [PMID: 32609537]
[61]
Boleto, G.; Guignabert, C.; Pezet, S.; Cauvet, A.; Sadoine, J.; Tu, L.; Nicco, C.; Gobeaux, C.; Batteux, F.; Allanore, Y.; Avouac, J. T-cell costimulation blockade is effective in experimental digestive and lung tissue fibrosis. Arthritis Res. Ther., 2018, 20(1), 197.
[http://dx.doi.org/10.1186/s13075-018-1694-9] [PMID: 30157927]

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