Abstract
Galectin 1(Gal-1), a β-galactoside binding mammalian lectin of 14KDa, is implicated in many signalling pathways, immune responses associated with cancer progression and immune disorders. Inhibition of human Gal-1 has been regarded as one of the potential therapeutic approaches for the treatment of cancer, as it plays a major role in tumour development and metastasis by modulating various biological functions viz. apoptosis, angiogenesis, migration, cell immune escape. Gal-1 is considered as a biomarker in diagnosis, prognosis and treatment condition. The overexpression of Gal-1 is well established and seen in many types of cancer progression like osteosarcoma, breast, lung, prostate, melanoma, etc. Gal-1 greatly accelerates the binding kinetics of HIV-1 to susceptible cells, leading to faster viral entry and a more robust viral replication by specific binding of CD4 cells. Hence, the Gal-1 is considered a promising molecular target for the development of new therapeutic drugs for cancer and HIV. The present review laid emphasis on structural insights and functional role of Gal-1 in the disease, current Gal-1 inhibitors and future prospects in the design of specific Gal-1 inhibitors.
Keywords: Galectin 1, cancer, HIV, Gal-1 inhibitors, apoptosis, glycoprotein.
Graphical Abstract
[1]
(a)Barondes, S.H.; Cooper, D.N.; Gitt, M.A.; Leffler, H. Galectins. Structure and Function of a Large Family of Animal Lectins. J. Biol. Chem., 1994, 269(1), 20807-20810.
(b)Wu, M-H.; Chen, Y-L.; Lee, K-H.; Chang, C-C.; Cheng, T-M.; Wu, S-Y.; Tu, C-C.; Tsui, W-L. Glycosylation-Dependent Galectin-1/Neuropilin-1 Interactions Promote Liver Fibrosis through Activation of TGF-β- and PDGF-like Signals in Hepatic Stellate Cells. Sci. Rep., 2017, 7(1), 20807-20810.
(b)Wu, M-H.; Chen, Y-L.; Lee, K-H.; Chang, C-C.; Cheng, T-M.; Wu, S-Y.; Tu, C-C.; Tsui, W-L. Glycosylation-Dependent Galectin-1/Neuropilin-1 Interactions Promote Liver Fibrosis through Activation of TGF-β- and PDGF-like Signals in Hepatic Stellate Cells. Sci. Rep., 2017, 7(1), 20807-20810.
[2]
Dings, R.; Miller, M.; Griffin, R.; Mayo, K. Galectins as molecular targets for therapeutic intervention. Intl. J. Mol. Sci., 2018, 19(1), 905.
[3]
David, M.; Piero, C. New druggable targets in the RAS pathway. Curr. Opin. Mol. Ther., 2010, 12(1), 6-, 674-683.
[4]
Cousin, J.; Cloninger, M. The role of Galectin-1 in cancer progression, and synthetic multivalent systems for the study of Galectin-1. Intl. J. Mol. Sci., 2016, 17(1), 1566.
[5]
Al-Obaidi, N.; Mohan, S.; Liang, S.; Zhao, Z.; Nayak, B.K.; Li, B.; Sriramarao, P.; Habib, S.L. Galectin-1 Is a new fibrosis protein in Type 1 and Type 2 diabetes. FASEB J., 2018, 33(1), 1-2.
[6]
Astorgues-Xerri, L.; Riveiro, M.E.; Tijeras-Raballand, A.; Serova, M.; Neuzillet, C.; Albert, S.; Raymond, E.; Faivre, S. Unraveling galectin-1 as a novel therapeutic target for cancer. Cancer Treat. Rev., 2014, 40(1), 307-319.
[7]
St-Pierre, C.; Manya, H.; Ouellet, M.; Clark, G.F.; Endo, T.; Tremblay, M.J.; Sato, S. Host-Soluble Galectin-1 promotes HIV-1 Replication through a direct interaction with Glycans of viral Gp120 and Host CD4. J. Virol., 2011, 85(1), 11742-11751.
[8]
Croci, D.O.; Salatino, M.; Rubinstein, N.; Cerliani, J.P.; Cavallin, L.E.; Leung, H.J.; Ouyang, J.; Ilarregui, J.M.; Toscano, M.A.; Domaica, C.I.; Croci, M.C.; Shipp, M.A.; Mesri, E.A.; Albini, A.; Rabinovich, G.A. Disrupting Galectin-1 interactions with N-Glycans suppresses Hypoxia-Driven angiogenesis and tumorigenesis in Kaposi’s sarcoma. J. Exp. Med., 2012, 209(11), 1985-2000.
[9]
Hosseini, Y.; Mollica, A.; Mirzaie, S. Structure-Based virtual screening efforts against HIV-1 reverse transcriptase to introduce the new potent non-nucleoside reverse transcriptase inhibitor. J. Mol. Struct., 2016, 1125(1), 592-600.
[10]
Miao, J-H.; Wang, S-Q.; Zhang, M-H.; Yu, F-B.; Zhang, L.; Yu, Z-X.; Kuang, Y. Knockdown of Galectin-1 suppresses the growth and invasion of osteosarcoma cells through inhibition of the MAPK/ERK Pathway. Oncol. Rep., 2014, 32(1), 1497-1504.
[11]
Dalotto-Moreno, T.; Croci, D.O.; Cerliani, J.P.; Martinez-Allo, V.C.; Dergan-Dylon, S.; Mendez-Huergo, S.P.; Stupirski, J.C.; Mazal, D.; Osinaga, E.; Toscano, M.A.; Sundblad, V.; Rabinovich, G.A.; Salatino, M. Targeting Galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Res., 2013, 73(1), 1107-1117.
[12]
Kuo, P-L.; Huang, M-S.; Cheng, D-E.; Hung, J-Y.; Yang, C-J.; Chou, S-H. Lung Cancer-Derived Galectin-1 enhances tumorigenic potentiation of tumor-associated dendritic cells by expressing heparin-binding EGF-like growth factor. J. Biol. Chem., 2012, 287(1), 9753-9764.
[13]
Compagno, D.; Gentilini, L.D.; Jaworski, F.M.; Perez, I.G.; Contrufo, G.; Laderach, D.J. Glycans and galectins in prostate cancer biology, angiogenesis and metastasis. Glycobiology, 2014, 24(10), 899-906.
[14]
Huang, C-S.; Tang, S-J.; Chung, L-Y.; Yu, C-P.; Ho, J-Y.; Cha, T-L.; Hsieh, C-C.; Wang, H-H.; Sun, G-H.; Sun, K-H. Galectin-1 Upregulates CXCR4 to promote tumor progression and poor outcome in kidney cancer. J. Am. Soc. Nephrol., 2014, 25(7), 1486-1495.
[15]
Kim, H-J.; Do, I-G.; Jeon, H-K.; Cho, Y.J.; Park, Y.A.; Choi, J-J.; Sung, C.O.; Lee, Y-Y.; Choi, C.H.; Kim, T-J.; Kim, B-G.; Lee, J-W.; Bae, D-S. Galectin 1 expression is associated with tumor invasion and metastasis in stage IB to IIA cervical cancer. Hum. Pathol., 2013, 44(1), 62-68.
[16]
Mathieu, V.; de Lassalle, E.M.; Toelen, J.; Mohr, T.; Bellahcène, A.; Van Goietsenoven, G.; Verschuere, T.; Bouzin, C.; Debyser, Z.; De Vleeschouwer, S.; Van Gool, S.; Poirier, F.; Castronovo, V.; Kiss, R.; Feron, O. Galectin-1 in melanoma biology and related Neo-Angiogenesis processes. J. Invest. Dermatol., 2012, 132(9), 2245-2254.
[17]
Martinez-Bosch, N.; Barranco, L.E.; Orozco, C.A.; Moreno, M.; Visa, L.; Iglesias, M.; Oldfield, L.; Neoptolemos, J.P.; Greenhalf, W.; Earl, J.; Carrato, A.; Costello, E.; Navarro, P. Increased plasma levels of Galectin-1 in pancreatic cancer: Potential use as biomarker. Oncotarget, 2018, 9(68), 32984-32996.
[18]
Thijssen, V.L.; Heusschen, R.; Caers, J.; Griffioen, A.W. Galectin expression in cancer diagnosis and prognosis: A systematic review. Biochim. Biophys. Acta, 2015, 1855(2), 235-247.
[19]
Elola, M.T.; Chiesa, M.E.; Alberti, A.F.; Mordoh, J.; Fink, N.E. Galectin-1 receptors in different cell types. J. Biomed. Sci., 2005, 12(1), 13-29.
[20]
Sörme, P.; Kahl-Knutsson, B.; Huflejt, M.; Nilsson, U.J.; Leffler, H. Fluorescence polarization as an analytical tool to evaluate Galectin-Ligand interactions. Analyt. Biochem., 2004, 334(1), 36-47.
[21]
Wu, R.; Wu, T.; Wang, K.; Luo, S.; Chen, Z.; Fan, M.; Xue, D.; Lu, H.; Zhuang, Q.; Xu, X. Prognostic significance of Galectin-1 expression in patients with cancer: A meta-Analysis. Cancer Cell Intl., 2018, 18(1), 108.
[22]
Blanchard, H.; Bum-Erdene, K.; Bohari, M.H.; Yu, X. Galectin-1 inhibitors and their potential therapeutic applications: A patent review. Expert Opin. Ther. Pat., 2016, 26(5), 537-554.
[23]
López-Lucendo, M.F.; Solís, D.; André, S.; Hirabayashi, J.; Kasai, K.; Kaltner, H.; Gabius, H-J.; Romero, A. Growth-Regulatory Human Galectin-1: Crystallographic characterisation of the structural changes induced by Single-Site mutations and their impact on the thermodynamics of ligand binding. J. Mol. Biol., 2004, 343(4), 957-970.
[24]
Salomonsson, E.; Larumbe, A.; Tejler, J.; Tullberg, E.; Rydberg, H.; Sundin, A.; Khabut, A.; Frejd, T.; Lobsanov, Y.D.; Rini, J.M.; Nilsson, U.J.; Leffler, H. Monovalent interactions of Galectin-1. Biochemistry, 2010, 49(44), 9518-9532.
[25]
Leppänen, A.; Stowell, S.; Blixt, O.; Cummings, R.D. Dimeric Galectin-1 binds with high affinity to Alpha2,3-Sialylated and Non-Sialylated terminal N-Acetyllactosamine units on surface-bound extended glycans. J. Biol. Chem., 2005, 280(1), 5549-5562.
[26]
Cho, M.; Cummings, R.D. Characterization of monomeric forms of Galectin-1 Generated by Site-Directed mutagenesis. Biochemistry, 1996, 35(1), 13081-13088.
[27]
Kadoya, T.; Horie, H. Structural and functional studies of galectin-1: A novel axonal regeneration-promoting activity for Oxidized Galectin-1. Curr. Drug Targets, 2005, 6(1), 375-383.
[28]
Guardia, C.M.; Caramelo, J.J.; Trujillo, M.; Méndez-Huergo, S.P.; Radi, R.; Estrin, D.A.; Rabinovich, G.A. Structural basis of redox-dependent modulation of Galectin-1 dynamics and function. Glycobiology, 2014, 24(5), 428-441.
[29]
Echeverria, I.; Amzel, L.M. Disaccharide binding to Galectin-1: Free energy calculations and molecular recognition mechanism. Biophys. J., 2011, 100(9), 2283-2292.
[30]
Horlacher, T.; Oberli, M.A.; Werz, D.B.; Kröck, L.; Bufali, S.; Mishra, R.; Sobek, J.; Simons, K.; Hirashima, M.; Niki, T.; Seeberger, P.H. Determination of carbohydrate-binding preferences of human galectins with carbohydrate microarrays. Chem. Bio. Chem., 2010, 11(1), 1563-1573.
[31]
Fischer, C.; Sanchez-Ruderisch, H.; Welzel, M.; Wiedenmann, B.; Sakai, T.; André, S.; Gabius, H-J.; Khachigian, L.; Detjen, K.M.; Rosewicz, S. Galectin-1 Interacts with the A5β1 fibronectin receptor to restrict carcinoma cell growth via Induction of P21 and P27. J. Bio. Chem.., 2005, 280(1), 37266-37277.
[32]
Le, Q-T.; Shi, G.; Cao, H.; Nelson, D.W.; Wang, Y.; Chen, E.Y.; Zhao, S.; Kong, C.; Richardson, D.; O’Byrne, K.J.; Giaccia, A.J.; Koong, A.C. Galectin-1: A link between tumor hypoxia and tumor immune privilege. J. Clin. Oncol., 2005, 23(35), 8932-8941.
[33]
Ito, K.; Scott, S.A.; Cutler, S.; Dong, L-F.; Neuzil, J.; Blanchard, H.; Ralph, S.J. Thiodigalactoside inhibits murine cancers by concurrently blocking effects of Galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress. Angiogenesis, 2011, 14, 293-307.
[34]
Ito, K.; Ralph, S.J. Inhibiting Galectin-1 Reduces murine lung metastasis with increased CD4+ and CD8+ T cells and reduced cancer cell adherence. Clin. Exp. Metastasis, 2012, 29(6), 561-572.
[35]
Dings, R.P.M.; Miller, M.C.; Nesmelova, I.; Astorgues-Xerri, L.; Kumar, N.; Serova, M.; Chen, X.; Raymond, E.; Hoye, T.R.; Mayo, K.H. Antitumor agent calixarene 0118 targets human Galectin-1 as an allosteric inhibitor of carbohydrate binding. J. Med. Chem., 2012, 55(11), 5121-5129.
[36]
Sirois, S.; Giguère, D.; Roy, R. A First QSAR model for galectin-3 glycomimetic inhibitors based on 3D docked structures. Med. Chem., 2006, 2(5), 481-489.
[37]
Salameh, B.A.; Leffler, H.; Nilsson, U.J. 3-(1,2,3-Triazol-1-Yl)-1-Thio-Galactosides as small, Efficient, and hydrolytically stable inhibitors of Galectin-3. Bioorg. Med. Chem. Lett., 2005, 15(14), 3344-3346.
[38]
Tejler, J.; Leffler, H.; Nilsson, U.J. Synthesis of O-Galactosyl Aldoximes as potent LacNAc-Mimetic Galectin-3 inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(9), 2343-2345.
[39]
Cumpstey, I.; Carlsson, S.; Leffler, H.; Nilsson, U.J. Synthesis of a Phenyl Thio-β-d-Galactopyranoside library from 1,5-Difluoro-2,4-Dinitrobenzene: Discovery of efficient and selective monosaccharide inhibitors of Galectin-7. Org. Biomol. Chem., 2005, 3(10), 1922.
[40]
Salameh, B.A.; Sundin, A.; Leffler, H.; Nilsson, U.J. Thioureido N-Acetyllactosamine derivatives as potent Galectin-7 and 9N Inhibitors. Bioorg. Med. Chem., 2006, 14(4), 1215-1220.
[41]
Cumpstey, I.; Sundin, A.; Leffler, H.; Nilsson, U.J. C2-Symmetrical Thiodigalactoside Bis-Benzamido Derivatives as High-Affinity inhibitors of Galectin-3: Efficient lectin inhibition through double Arginine-Arene interactions. Angew. Chem. Int. Ed. Engl., 2005, 44(32), 5110-5112.
[42]
Tejler, J.; Tullberg, E.; Frejd, T.; Leffler, H.; Nilsson, U.J. Synthesis of multivalent lactose derivatives by 1,3-Dipolar cycloadditions: Selective Galectin-1 inhibition. Carbohydr. Res., 2006, 341(10), 1353-1362.
[43]
Rabinovich, G.A.; Cumashi, A.; Bianco, G.A.; Ciavardelli, D.; Iurisci, I.; D’Egidio, M.; Piccolo, E.; Tinari, N.; Nifantiev, N.; Iacobelli, S. Synthetic Lactulose Amines: Novel class of anticancer agents that induce tumor-cell apoptosis and inhibit Galectin-Mediated homotypic cell aggregation and endothelial cell morphogenesis. Glycobiology, 2006, 16(3), 210-220.
[44]
Giguère, D.; Bonin, M-A.; Cloutier, P.; Patnam, R.; St-Pierre, C.; Sato, S.; Roy, R. Synthesis of stable and selective inhibitors of human Galectins-1 and -3. Bioorg. Med. Chem., 2008, 16, 7811-7823.
[45]
Giguère, D.; Sato, S.; St-Pierre, C.; Sirois, S.; Roy, R. Aryl O- and S-Galactosides and lactosides as specific inhibitors of human galectins-1 and -3: Role of electrostatic potential at O-3. Bioorg. Med. Chem. Lett., 2006, 16(16), 1668-1672.
[46]
Peterson, K.; Kumar, R.; Stenström, O.; Verma, P.; Verma, P.R.; Håkansson, M.; Kahl-Knutsson, B.; Zetterberg, F.; Leffler, H.; Akke, M.; Logan, D.T.; Nilsson, U.J. Systematic tuning of fluoro-galectin-3 interactions provides thiodigalactoside derivatives with single-digit Nm affinity and high Selectivity. J. Med. Chem., 2018, 61(3), 1164-1175.
[47]
Rajput, V.K.; Leffler, H.; Nilsson, U.J.; Mukhopadhyay, B. Synthesis and evaluation of iminocoumaryl and coumaryl derivatized glycosides as galectin Antagonists. Bioorg. Med. Chem. Lett., 2014, 24(15), 3516-3520.
[48]
Tejler, J.; Salameh, B.; Leffler, H.; Nilsson, U.J. Fragment-Based development of Triazole-Substituted O-Galactosyl Aldoximes with Fragment-Induced affinity and selectivity for Galectin-3. Org. Biomol. Chem., 2009, 7(19), 3982.
[49]
van Hattum, H.; Branderhorst, H.M.; Moret, E.E.; Nilsson, U.J.; Leffler, H.; Pieters, R.J. Tuning the preference of thiodigalactoside- and Lactosamine-Based ligands to Galectin-3 over Galectin-1. J. Med. Chem., 2013, 56(3), 1350-1354.
[50]
Giguère, D.; Patnam, R.; Bellefleur, M-A.; St-Pierre, C.; Sato, S.; Roy, R. Carbohydrate triazoles and isoxazoles as inhibitors of Galectins-1 and -3. Chem. Commun., 2006, 22(1), 2379-2381.
[51]
Pandey, R.K.; Dougherty, T.J. Galectin recognized photosensitizers for photodynamic therapy, U. S. Patent, US6849607B2 2005.
[52]
André, S.; Giguère, D.; Dam, T.K.; Brewer, F.; Gabius, H-J.; Roy, R. Synthesis and screening of a small glycomimetic library for inhibitory activity on medically relevant Galactoside-Specific lectins in assays of increasing Biorelevance. New J. Chem., 2010, 34(10), 2229.
[53]
Cumpstey, I.; Salomonsson, E.; Sundin, A.; Leffler, H.; Nilsson, U.J. Double Affinity Amplification of Galectin-Ligand Interactions through Arginine-Arene Interactions: Synthetic, thermodynamic, and computational studies with aromatic diamido Thiodigalactosides. Chemistry, 2008, 14(14), 4233-4245.
[54]
Cumpstey, I.; Salomonsson, E.; Sundin, A.; Leffler, H.; Nilsson, U.J. Studies of Arginine-Arene interactions through synthesis and evaluation of a series of Galectin-Binding aromatic lactose esters. ChemBioChem, 2007, 8(12), 1389-1398.
[55]
Juers, D.H.; Matthews, B.W.; Huber, R.E. LacZ β-Galactosidase: Structure and function of an enzyme of historical and molecular biological importance. Protein Sci., 2012, 21(1), 1792-1807.
[56]
Huflejt, M.; Mossine, V.; Croft, M. Galectins -1 and -4 in tumor development. US20030109464A1 2003.
[57]
Vrasidas, I.; André, S.; Valentini, P.; Böck, C.; Lensch, M.; Kaltner, H.; Liskamp, R.M.J.; Gabius, H-J.; Pieters, R.J. Rigidified multivalent lactose molecules and their interactions with mammalian Galectins: A route to selective inhibitors. Org. Biomol. Chem., 2003, 1(5), 803-810.
[58]
Tejler, J.; Tullberg, E.; Frejd, T.; Leffler, H.; Nilsson, U.J. Synthesis of Multivalent Lactose Derivatives by 1,3-Dipolar Cycloadditions: Selective Galectin-1 inhibition. Carbohydr. Res., 2006, 341(10), 1353-1362.
[59]
Klyosov, A.; Zomer, E.; Platt, D. DAVANAT ® (GM-CT-01) and Colon Cancer: Preclinical and clinical (Phase I and II) Studies. In: Glycobiology and Drug Design; Klyosov, A.A., Ed.; American Chemical Society: Washington, DC, 2012; Vol. 1102, pp. 89-130.
[60]
Liu, Q.; Sacco, P.; Marsich, E.; Furlani, F.; Arib, C.; Djaker, N.; Lamy de la Chapelle, M.; Donati, I.; Spadavecchia, J. Lactose-modified chitosan Gold(III)-PEGylated Complex-Bioconjugates: From synthesis to interaction with targeted Galectin-1 protein. Bioconjug. Chem., 2018, 29(10), 3352-3361.
[61]
Dings, R.P.M.; Arroyo, M.M.; Lockwood, N.A.; van Eijk, L.I.; Haseman, J.R.; Griffioen, A.W.; Mayo, K.H. Beta-Sheet is the bioactive conformation of the anti-angiogenic anginex peptide. Biochem. J., 2003, 373(1), 281-288.
[62]
Mayo, K.H.; Dings, R.P.M.; Flader, C.; Nesmelova, I.; Hargittai, B.; van der Schaft, D.W.J.; van Eijk, L.I.; Walek, D.; Haseman, J.; Hoye, T.R.; Griffioen, A.W. Design of a partial peptide mimetic of anginex with antiangiogenic and anticancer activity. J. Biol. Chem., 2003, 278(1), 45746-45752.
[63]
Dings, R.P.M.; Kumar, N.; Miller, M.C.; Loren, M.; Rangwala, H.; Hoye, T.R.; Mayo, K.H. Structure-Based optimization of angiostatic agent 6DBF7, an allosteric antagonist of Galectin-1. J. Pharmacol. Exp. Ther., 2013, 344(3), 589-599.
[64]
Dings, R.P.M.; Van Laar, E.S.; Webber, J.; Zhang, Y.; Griffin, R.J.; Waters, S.J.; MacDonald, J.R.; Mayo, K.H. Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic Irofulven. Cancer Lett., 2008, 265(2), 270-280.
[65]
Zucchetti, M.; Bonezzi, K.; Frapolli, R.; Sala, F.; Borsotti, P.; Zangarini, M.; Cvitkovic, E.; Noel, K.; Ubezio, P.; Giavazzi, R.; D’Incalci, M.; Taraboletti, G. Pharmacokinetics and antineoplastic activity of Galectin-1-Targeting OTX008 in combination with sunitinib. Cancer Chemother. Pharmacol., 2013, 72(4), 879-887.
[66]
Rabinovich, G.; Castagna, L.; Landa, C.; Riera, C.M.; Sotomayor, C. Regulated expression of a 16-Kd Galectin-like protein in Activated rat macrophages. J. Leukoc. Biol., 1996, 59(3), 363-370.
[67]
St-Pierre, C.; Ouellet, M.; Tremblay, M.J.; Sato, S. Galectin-1 and HIV-1 infection. Methods Enzymol., 2010, 480(1), 267-294.
[68]
St-Pierre, C.; Ouellet, M.; Giguère, D.; Ohtake, R.; Roy, R.; Sato, S.; Tremblay, M.J. Galectin-1-Specific inhibitors as a new class of compounds to treat HIV-1 infection. Antimicrob. Agents Chemother., 2012, 56(1), 154-162.
[69]
Aalinkeel, R.; Mangum, C.S.; Abou-Jaoude, E.; Reynolds, J.L.; Liu, M.; Sundquist, K.; Parikh, N.U.; Chaves, L.D.; Mammen, M.J.; Schwartz, S.A.; Mahajan, S.D. Galectin-1 reduces neuroinflammation via modulation of nitric Oxide-Arginase signaling in hiv-1 transfected microglia: A gold Nanoparticle-Galectin-1 “Nanoplex” a possible neurotherapeutic? J. Neuroimmune Pharmacol., 2017, 12(1), 133-151.
[70]
Chatterjee, A.; Ratner, D.M.; Ryan, C.M.; Johnson, P.J.; O’Keefe, B.R.; Secor, W.E.; Anderson, D.J.; Robbins, P.W.; Samuelson, J. Anti-Retroviral lectins have modest effects on adherence of trichomonas vaginalis to epithelial cells in vitro and on recovery of tritrichomonas foetus in a mouse vaginal model. PLOS One, 2015, 10(2)e0135340
Related Books
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Natural Product Chemistry
Therapeutic Use of Plant Secondary Metabolites
Therapeutic Implications of Natural Bioactive Compounds
Frontiers in Bioactive Compounds
Frontiers in Natural Product Chemistry
Frontiers in Natural Product Chemistry
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Natural Product Chemistry
Frontiers in Natural Product Chemistry
Article Metrics
88
8
1