Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Oral Mucosal In Vitro Cell Culture Model to Study the Effect of Fructilactobacillus Phage on the Interplay between Food Components and Oral Microbiota

Author(s): Darab Ghadimi*, Michael Ebsen, Christoph Röcken, Regina Fölster-Holst, Birte Groessner-Schreiber, Christof Dörfer and Wilhelm Bockelmann

Volume 23, Issue 3, 2023

Published on: 23 August, 2022

Page: [356 - 374] Pages: 19

DOI: 10.2174/1871530322666220408215101

Price: $65

Abstract

Background and Aims: Dietary habits, food, and nutrition-associated oral dysbiosis lead to the formation of microbial biofilm, which affects the overall health of an individual by promoting systemic diseases like cardiovascular disease, immunological disorders, and diabetes. Today's diets contain a variety of fermentable carbohydrates, including highly processed starch and novel synthetic carbohydrates such as oligofructose, sucralose, and glucose polymers. These constitute risk factors in the initiation and progression of oral dysbiosis. Oral, lung and gut microbiomes are interlinked with each other via direct and indirect ways. It is unknown whether or not lactobacilli and Lactobacillus phages are able to rescue dysbiotic effects by decreasing the uptake into the cells of excess simple sugars and their derivatives present within the digestive tract.

Materials and Methods: Using transwell cell culture plate inserts, six groups of in vitro co-cultured TR146 and HepG2 cells, grown in DMEM medium either with or without sucrose (10 % v/v), were treated with 1) PBS, 2) Fructilactobacillus sanfranciscensis (F.s) H2A, 3) F.s H2A and sucrose, 4) F.s H2A plus sucrose plus phage EV3 lysate, 5) F.s H2A plus sucrose plus phage EV3 supernatant, and 6) F.s H2A plus sucrose plus phage EV3 particles. The pH of the culture medium (indicating lactic acid production) and key oral biomarkers, including cytokines (IL-1β and IL-6), inflammatory chemokines (e.g., CXCL8 and CCL2), and homeostatic chemokines (e.g., CXCL4 and CCL18) were measured.

Results: Excess sucrose significantly enhanced inflammatory signal molecules (e.g., IL-1β, IL-6, and CCL2) secretion, concomitant with the enhancement of intracellular triglycerides in co-cultured HepG2 cells. Co-culture with F.s H2A decreased the sucrose-induced release of inflammatory signal molecules from co-cultured cells, these effects being abolished by F.s phage EV3.

Conclusion: This study shows that Lactobacillus phages apparently influence the interplay between food components, oral microbiota, and the oral cellular milieu, at least in part by affecting the microbial uptake of excess free simple sugars from the oral milieu. To confirm the biological consequences of these effects on human oral microbiota and health, further studies are warranted, incorporating ex vivo studies of human dental plaque biofilms and host biomarkers, such as cytohistological, molecular, or biochemical measurements.

Keywords: Lactobacillus phages, high-sugar diets, oral dysbiosis, inflammation, metabolism, cytokine.

Graphical Abstract
[1]
Luong, T.; Salabarria, A.C.; Edwards, R.A.; Roach, D.R. Standardized bacteriophage purification for personalized phage therapy. Nat. Protoc., 2020, 15(9), 2867-2890.
[http://dx.doi.org/10.1038/s41596-020-0346-0] [PMID: 32709990]
[2]
Xiao, J.; Fiscella, K.A.; Gill, S.R. Oral microbiome: Possible harbinger for children’s health. Int. J. Oral Sci., 2020, 12(1), 12.
[http://dx.doi.org/10.1038/s41368-020-0082-x] [PMID: 32350240]
[3]
Groeger, S.; Meyle, J. Oral mucosal epithelial cells. Front. Immunol., 2019, 10, 208.
[http://dx.doi.org/10.3389/fimmu.2019.00208] [PMID: 30837987]
[4]
Molero-Abraham, M.; Sanchez-Trincado, J.L.; Gomez-Perosanz, M.; Torres-Gomez, A.; Subiza, J.L.; Lafuente, E.M.; Reche, P.A. Human oral epithelial cells impair bacteria-mediated maturation of dendritic cells and render T cells unresponsive to stimulation. Front. Immunol., 2019, 10, 1434.
[http://dx.doi.org/10.3389/fimmu.2019.01434] [PMID: 31316504]
[5]
Olsen, I.; Yamazaki, K. Can oral bacteria affect the microbiome of the gut? J. Oral Microbiol., 2019, 11(1), 1586422.
[http://dx.doi.org/10.1080/20002297.2019.1586422] [PMID: 30911359]
[6]
Liu, N.N.; Ma, Q.; Ge, Y.; Yi, C.X.; Wei, L.Q.; Tan, J.C.; Chu, Q.; Li, J.Q.; Zhang, P.; Wang, H. Microbiome dysbiosis in lung cancer: From composition to therapy. NPJ Precis. Oncol., 2020, 4(1), 33.
[http://dx.doi.org/10.1038/s41698-020-00138-z] [PMID: 33303906]
[7]
Esberg, A.; Haworth, S.; Hasslöf, P.; Lif Holgerson, P.; Johansson, I. Oral microbiota profile associates with sugar intake and taste preference genes. Nutrients, 2020, 12(3), 681.
[http://dx.doi.org/10.3390/nu12030681] [PMID: 32138214]
[8]
Lu, M.; Xuan, S.; Wang, Z. Oral microbiota: A new view of body health. Food Sci. Hum. Wellness, 2019, 8(1), 8-15.
[http://dx.doi.org/10.1016/j.fshw.2018.12.001]
[9]
Moynihan, P.; Petersen, P.E. Diet, nutrition and the prevention of dental diseases. Public Health Nutr., 2004, 7(1A), 201-226.
[http://dx.doi.org/10.1079/PHN2003589] [PMID: 14972061]
[10]
D’Alessandro, M.E.; Selenscig, D.; Illesca, P.; Chicco, A.; Lombardo, Y.B. Time course of adipose tissue dysfunction associated with antioxidant defense, inflammatory cytokines and oxidative stress in dyslipemic insulin resistant rats. Food Funct., 2015, 6(4), 1299-1309.
[http://dx.doi.org/10.1039/C4FO00903G] [PMID: 25765549]
[11]
Rosales-Gómez, C.A.; Martínez-Carrillo, B.E.; Reséndiz-Albor, A.A.; Ramírez-Durán, N.; Valdés-Ramos, R.; Mondragón-Velásquez, T.; Escoto-Herrera, J.A. Chronic consumption of sweeteners and its effect on glycaemia, cytokines, hormones, and lymphocytes of GALT in CD1 mice. BioMed Res. Int., 2018, 2018, 1345282.
[http://dx.doi.org/10.1155/2018/1345282] [PMID: 29854725]
[12]
Tappy, L. Q&A: ‘toxic’ effects of sugar: Should we be afraid of fructose? BMC Biol., 2012, 10(1), 42.
[http://dx.doi.org/10.1186/1741-7007-10-42] [PMID: 22613805]
[13]
Malik, V.S.; Hu, F.B. Fructose and cardiometabolic health: What the evidence from sugar-sweetened beverages tells us. J. Am. Coll. Cardiol., 2015, 66(14), 1615-1624.
[http://dx.doi.org/10.1016/j.jacc.2015.08.025] [PMID: 26429086]
[14]
Perazza, L.R.; Mitchell, P.L.; Jensen, B.A.H.; Daniel, N.; Boyer, M.; Varin, T.V.; Bouchareb, R.; Nachbar, R.T.; Bouchard, M.; Blais, M.; Gagné, A.; Joubert, P.; Sweeney, G.; Roy, D.; Arsenault, B.J.; Mathieu, P.; Marette, A. Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in LDLr-/-ApoB100/100 mice. Atherosclerosis, 2020, 304, 9-21.
[http://dx.doi.org/10.1016/j.atherosclerosis.2020.05.002] [PMID: 32563005]
[15]
Bonestroo, M.H.; Kusters, B.J.; de Wit, J.C.; Rombouts, F.M. Glucose and sucrose fermenting capacity of homofermentative lactic acid bacteria used as starters in fermented salads. Int. J. Food Microbiol., 1992, 15(3-4), 365-376.
[http://dx.doi.org/10.1016/0168-1605(92)90070-J] [PMID: 1419542]
[16]
Korakli, M.; Schwarz, E.; Wolf, G.; Hammes, W.P. Production of mannitol by Lactobacillus sanfranciscensis. Adv. Food Sci., 2000, 22, 1-4.
[17]
Ghadimi, D.; Vrese, M.; Heller, K.J.; Schrezenmeir, J. Effect of natural commensal-origin DNA on toll-like receptor 9 (TLR9) signaling cascade, chemokine IL-8 expression, and barrier integritiy of polarized intestinal epithelial cells. Inflamm. Bowel Dis., 2010, 16(3), 410-427.
[http://dx.doi.org/10.1002/ibd.21057] [PMID: 19714766]
[18]
Van Belleghem, J.D. Dąbrowska, K.; Vaneechoutte, M.; Barr, J.J.; Bollyky, P.L. Interactions between bacteriophage, bacteria, and the mammalian immune system. Viruses, 2018, 11(1), 10.
[http://dx.doi.org/10.3390/v11010010] [PMID: 30585199]
[19]
Ashraf, R.; Vasiljevic, T.; Smith, S.C.; Donkor, O.N. Effect of cell-surface components and metabolites of lactic acid bacteria and probiotic organisms on cytokine production and induction of CD25 expression in human peripheral mononuclear cells. J. Dairy Sci., 2014, 97(5), 2542-2558.
[http://dx.doi.org/10.3168/jds.2013-7459] [PMID: 24582449]
[20]
Boratyński, J.; Syper, D.; Weber-Dabrowska, B.; Łusiak-Szelachowska, M.; Poźniak, G.; Górski, A. Preparation of endotoxin-free bacteriophages. Cell. Mol. Biol. Lett., 2004, 9(2), 253-259.
[PMID: 15213806]
[21]
Zheng, J.; Wittouck, S.; Salvetti, E.; Franz, C.M.A.P.; Harris, H.M.B.; Mattarelli, P.; O’Toole, P.W.; Pot, B.; Vandamme, P.; Walter, J.; Watanabe, K.; Wuyts, S.; Felis, G.E.; Gänzle, M.G.; Lebeer, S. A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int. J. Syst. Evol. Microbiol., 2020, 70(4), 2782-2858.
[http://dx.doi.org/10.1099/ijsem.0.004107] [PMID: 32293557]
[22]
Picozzi, C.; Gallina, S.; Della Fera, T.; Foschino, R. Comparison of cultural media for the enumeration of sourdough lactic acid bacteria. Ann. Microbiol., 2005, 55(4), 317-320.
[23]
Picozzi, C.; Bonacina, G.; Vigentini, I.; Foschino, R. Genetic diversity in Italian Lactobacillus sanfranciscensis strains assessed by multilocus sequence typing and pulsed-field gel electrophoresis analyses. Microbiology, 2010, 156(Pt 7), 2035-2045.
[http://dx.doi.org/10.1099/mic.0.037341-0] [PMID: 20360177]
[24]
Scientific Committee. Introduction of a Qualified Presumption of Safety (QPS) approach for assessment of selected microorganisms referred to EFSA. EFSA J., 2007, 587, 1-16.
[25]
Zotta, T.; Parente, E.; Ricciardi, A. Aerobic metabolism in the genus Lactobacillus: Impact on stress response and potential applications in the food industry. J. Appl. Microbiol., 2017, 122(4), 857-869.
[http://dx.doi.org/10.1111/jam.13399] [PMID: 28063197]
[26]
Weber-Dąbrowska, B.; Jończyk-Matysiak, E.; Żaczek, M.; Łobocka, M.; Łusiak-Szelachowska, M.; Górski, A. Bacteriophage procurement for therapeutic purposes. Front. Microbiol., 2016, 7, 1177.
[PMID: 27570518]
[27]
Bonilla, N.; Rojas, M.I.; Netto Flores Cruz, G.; Hung, S.H.; Rohwer, F.; Barr, J.J. Phage on tap-a quick and efficient protocol for the preparation of bacteriophage laboratory stocks. PeerJ, 2016, 4, e2261.
[http://dx.doi.org/10.7717/peerj.2261] [PMID: 27547567]
[28]
Foschino, R.; Venturelli, E.; Picozzi, C. Isolation and characterization of a virulent Lactobacillus sanfranciscensis bacteriophage and its impact on microbial population in sourdough. Curr. Microbiol., 2005, 51(6), 413-418.
[http://dx.doi.org/10.1007/s00284-005-0122-y] [PMID: 16235023]
[29]
Bachrach, U.; Friedmann, A. Practical procedures for the purification of bacterial viruses. Appl. Microbiol., 1971, 22(4), 706-715.
[http://dx.doi.org/10.1128/am.22.4.706-715.1971] [PMID: 4108648]
[30]
Bourdin, G.; Schmitt, B.; Marvin Guy, L.; Germond, J.E.; Zuber, S.; Michot, L.; Reuteler, G.; Brüssow, H. Amplification and purification of T4-like escherichia coli phages for phage therapy: From laboratory to pilot scale. Appl. Environ. Microbiol., 2014, 80(4), 1469-1476.
[http://dx.doi.org/10.1128/AEM.03357-13] [PMID: 24362424]
[31]
Khan Mirzaei, M.; Khan, M.A.A.; Ghosh, P.; Taranu, Z.E.; Taguer, M.; Ru, J.; Chowdhury, R.; Kabir, M.M.; Deng, L.; Mondal, D.; Maurice, C.F. Bacteriophages isolated from stunted children can regulate gut bacterial communities in an age-specific manner. Cell Host Microbe, 2020, 27(2), 199-212.e5.
[http://dx.doi.org/10.1016/j.chom.2020.01.004] [PMID: 32053789]
[32]
Sabelnikov, A.G. Spectrophotometric determination of phage concentration in lysates. Anal. Biochem., 1972, 48(2), 629-632.
[http://dx.doi.org/10.1016/0003-2697(72)90120-0] [PMID: 5070053]
[33]
Hershey, A.D.; Dixon, J.; Chase, M. Nucleic acid economy in bacteria infected with bacteriophage T2. I. Purine and pyrimidine composition. J. Gen. Physiol., 1953, 36(6), 777-789.
[http://dx.doi.org/10.1085/jgp.36.6.777] [PMID: 13069681]
[34]
Vanhercke, T.; Ampe, C.; Tirry, L.; Denolf, P. Rescue and in situ selection and evaluation (RISE): A method for high-throughput panning of phage display libraries. J. Biomol. Screen., 2005, 10(2), 108-117.
[http://dx.doi.org/10.1177/1087057104271956] [PMID: 15799954]
[35]
Jacobsen, J.; Van Deurs, B.; Pedersen, M.; Rassing, M.R. TR146 cells grown on filters as a model for human buccal epithelium: I. Morphology, growth, barrier properties, and permeability. Int. J. Pharm., 1995, 125(2), 165-184.
[http://dx.doi.org/10.1016/0378-5173(95)00109-V]
[36]
Ghadimi, D.; Nielsen, A.; Yoness Hassan, M.F.; Fölster-Holst, R.; de Vrese, M.; Heller, K.J. Modulation of GSK - 3β/β - catenin cascade by commensal bifidobacteria plays an important role for the inhibition of metaflammation-related biomarkers in response to LPS or non-physiological concentrations of fructose: An in vitro study. PharmaNutrition, 2019, 8, 100145.
[http://dx.doi.org/10.1016/j.phanu.2019.100145]
[37]
Mørck Nielsen, H.; Rømer Rassing, M. TR146 cells grown on filters as a model of human buccal epithelium: V. Enzyme activity of the TR146 cell culture model, human buccal epithelium and porcine buccal epithelium, and permeability of leu-enkephalin. Int. J. Pharm., 2000, 200(2), 261-270.
[http://dx.doi.org/10.1016/S0378-5173(00)00394-X] [PMID: 10867256]
[38]
Nguyen, S.; Baker, K.; Padman, B.S.; Patwa, R.; Dunstan, R.A.; Weston, T.A.; Schlosser, K.; Bailey, B.; Lithgow, T.; Lazarou, M.; Luque, A.; Rohwer, F.; Blumberg, R.S.; Barr, J.J. bacteriophage transcytosis provides a mechanism to cross epithelial cell layers. MBio, 2017, 8(6), e01874-e17.
[http://dx.doi.org/10.1128/mBio.01874-17] [PMID: 29162715]
[39]
Garza, A.Z.; Park, S.B.; Kocz, R. Drug elimination; StatPearls Publishing: Treasure Island, FL, 2019.
[40]
Belstrøm, D. The salivary microbiota in health and disease. J. Oral Microbiol., 2020, 12(1), 1723975.
[http://dx.doi.org/10.1080/20002297.2020.1723975] [PMID: 32128039]
[41]
Maciejewska, B.; Olszak, T.; Drulis-Kawa, Z. Applications of bacteriophages versus phage enzymes to combat and cure bacterial infections: An ambitious and also a realistic application? Appl. Microbiol. Biotechnol., 2018, 102(6), 2563-2581.
[http://dx.doi.org/10.1007/s00253-018-8811-1] [PMID: 29442169]
[42]
Fréour, T.; Jarry, A.; Bach-Ngohou, K.; Dejoie, T.; Bou-Hanna, C.; Denis, M.G.; Mosnier, J.F.; Laboisse, C.L.; Masson, D. TACE inhibition amplifies TNF-alpha-mediated colonic epithelial barrier disruption. Int. J. Mol. Med., 2009, 23(1), 41-48.
[PMID: 19082505]
[43]
Faralli, A.; Shekarforoush, E.; Mendes, A.C.; Chronakis, I.S. Enhanced transepithelial permeation of gallic acid and (-)-epigallocatechin gallate across human intestinal caco-2 cells using electrospun xanthan nanofibers. Pharmaceutics, 2019, 11(4), 155.
[http://dx.doi.org/10.3390/pharmaceutics11040155] [PMID: 30939805]
[44]
Wu, Y.R.; Choi, H.J.; Kang, Y.G.; Kim, J.K.; Shin, J.W. In vitro study on anti-inflammatory effects of epigallocatechin-3-gallate-loaded nano- and microscale particles. Int. J. Nanomedicine, 2017, 12, 7007-7013.
[http://dx.doi.org/10.2147/IJN.S146296] [PMID: 29026297]
[45]
Zhao, L.; Liu, S.; Xu, J.; Li, W.; Duan, G.; Wang, H.; Yang, H.; Yang, Z.; Zhou, R. A new molecular mechanism underlying the EGCG-mediated autophagic modulation of AFP in HepG2 cells. Cell Death Dis., 2017, 8(11), e3160.
[http://dx.doi.org/10.1038/cddis.2017.563] [PMID: 29095434]
[46]
Yamamoto, T.; Uemura, K.; Moriyama, K.; Mitamura, K.; Taga, A. Inhibitory effect of maple syrup on the cell growth and invasion of human colorectal cancer cells. Oncol. Rep., 2015, 33(4), 1579-1584.
[http://dx.doi.org/10.3892/or.2015.3777] [PMID: 25647359]
[47]
Liu, X.; Yin, S.; Chen, Y.; Wu, Y.; Zheng, W.; Dong, H.; Bai, Y.; Qin, Y.; Li, J.; Feng, S.; Zhao, P. LPS induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF κB, STAT3 or AP 1 activation. Mol. Med. Rep., 2018, 17(4), 5484-5491.
[http://dx.doi.org/10.3892/mmr.2018.8542] [PMID: 29393460]
[48]
Sieuwerts, S.; Bron, P.A.; Smid, E.J. Mutually stimulating interactions between lactic acid bacteria and Saccharomyces cerevisiae in sourdough fermentation. Lebensm. Wiss. Technol., 2018, 90, 201-206.
[http://dx.doi.org/10.1016/j.lwt.2017.12.022]
[49]
Kimmelshue, C.; Goggi, A.S.; Cademartiri, R. The use of biological seed coatings based on bacteriophages and polymers against Clavibacter michiganensis subsp. nebraskensis in maize seeds. Sci. Rep., 2019, 9(1), 17950.
[http://dx.doi.org/10.1038/s41598-019-54068-3] [PMID: 31784552]
[50]
Zhang, Y.; Zhang, H.; Ghosh, D. The stabilizing excipients in dry state therapeutic phage formulations. AAPS PharmSciTech, 2020, 21(4), 133.
[http://dx.doi.org/10.1208/s12249-020-01673-5] [PMID: 32415395]
[51]
Della Corte, K.W.; Perrar, I.; Penczynski, K.J.; Schwingshackl, L.; Herder, C.; Buyken, A.E. Effect of dietary sugar intake on biomarkers of subclinical inflammation: A systematic review and meta-analysis of intervention studies. Nutrients, 2018, 10(5), 606.
[http://dx.doi.org/10.3390/nu10050606] [PMID: 29757229]
[52]
Calder, P.C. Biomarkers of immunity and inflammation for use in nutrition interventions: International Life Sciences Institute European Branch work on selection criteria and interpretation. Endocr. Metab. Immune Disord. Drug Targets, 2014, 14(4), 236-244.
[http://dx.doi.org/10.2174/1871530314666140709091650] [PMID: 25008763]
[53]
ISO, 10993-5:2009. Biological evaluation of medical devices. Part 5: Tests for in vitro cytotoxicity; Geneva, Switzerland, , 2009.
[54]
Melo, L.D.R.; Ferreira, R.; Costa, A.R.; Oliveira, H.; Azeredo, J. Efficacy and safety assessment of two enterococci phages in an in vitro biofilm wound model. Sci. Rep., 2019, 9(1), 6643.
[http://dx.doi.org/10.1038/s41598-019-43115-8] [PMID: 31040333]
[55]
Marbouty, M.; Thierry, A.; Millot, G.A.; Koszul, R. MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut. eLife, 2021, 10, e60608.
[http://dx.doi.org/10.7554/eLife.60608] [PMID: 33634788]
[56]
Lerner, A.; Matthias, T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun. Rev., 2015, 14(6), 479-489.
[http://dx.doi.org/10.1016/j.autrev.2015.01.009] [PMID: 25676324]
[57]
Schoultz, I.; Keita, Å.V. The intestinal barrier and current techniques for the assessment of gut permeability. Cells, 2020, 9(8), 1909.
[http://dx.doi.org/10.3390/cells9081909] [PMID: 32824536]
[58]
Satokari, R. High intake of sugar and the balance between pro- and anti-inflammatory gut bacteria. Nutrients, 2020, 12(5), 1348.
[http://dx.doi.org/10.3390/nu12051348] [PMID: 32397233]
[59]
De Angelis, M.; Di Cagno, R.; Gallo, G.; Curci, M.; Siragusa, S.; Crecchio, C.; Parente, E.; Gobbetti, M. Molecular and functional characterization of Lactobacillus sanfranciscensis strains isolated from sourdoughs. Int. J. Food Microbiol., 2007, 114(1), 69-82.
[http://dx.doi.org/10.1016/j.ijfoodmicro.2006.10.036] [PMID: 17223214]
[60]
Michl, J.; Park, K.C.; Swietach, P. Evidence-based guidelines for controlling pH in mammalian live-cell culture systems. Commun. Biol., 2019, 2(1), 144.
[http://dx.doi.org/10.1038/s42003-019-0393-7] [PMID: 31044169]
[61]
Międzybrodzki, R.; Borysowski, J.; Kłak, M.; Jończyk-Matysiak, E.; Obmińska-Mrukowicz, B.; Suszko-Pawłowska, A.; Bubak, B.; Weber-Dąbrowska, B.; Górski, A. In Vivo studies on the influence of bacteriophage preparations on the autoimmune inflammatory process. BioMed Res. Int., 2017, 2017, 3612015.
[http://dx.doi.org/10.1155/2017/3612015] [PMID: 29201902]
[62]
Marra, F.; Tacke, F. Roles for chemokines in liver disease. Gastroenterology, 2014, 147(3), 577-594.e1.
[http://dx.doi.org/10.1053/j.gastro.2014.06.043] [PMID: 25066692]
[63]
Pavlovic, N.; Rani, B.; Gerwins, P.; Heindryckx, F. Platelets as key factors in hepatocellular carcinoma. Cancers (Basel), 2019, 11(7), 1022.
[http://dx.doi.org/10.3390/cancers11071022] [PMID: 31330817]
[64]
Ripoche, J. Blood platelets and inflammation: Their relationship with liver and digestive diseases. Clin. Res. Hepatol. Gastroenterol., 2011, 35(5), 353-357.
[http://dx.doi.org/10.1016/j.clinre.2011.02.012] [PMID: 21482218]
[65]
Montero, R.M.; Bhangal, G.; Pusey, C.D.; Frankel, A.H.; Tam, F.W. CCL18 synergises with high concentrations of glucose in stimulating fibronectin production in human renal tubuloepithelial cells. BMC Nephrol., 2016, 17(1), 139.
[http://dx.doi.org/10.1186/s12882-016-0352-1] [PMID: 27686838]
[66]
Linke, H.A.; Birchmeier, R.I. Effect of increasing sucrose concentrations on oral lactic acid production. Ann. Nutr. Metab., 2000, 44(3), 121-124.
[http://dx.doi.org/10.1159/000012833] [PMID: 11053898]
[67]
Trebinska-Stryjewska, A.; Swiech, O.; Opuchlik, L.J.; Grzybowska, E.A.; Bilewicz, R. Impact of Medium pH on DOX Toxicity toward HeLa and A498 Cell Lines. ACS Omega, 2020, 5(14), 7979-7986.
[http://dx.doi.org/10.1021/acsomega.9b04479] [PMID: 32309708]
[68]
Łusiak-Szelachowska, M.; Weber-Dąbrowska, B.; Żaczek, M.; Borysowski, J.; Górski, A. The presence of bacteriophages in the human body: Good, bad or neutral? Microorganisms, 2020, 8(12), 2012.
[http://dx.doi.org/10.3390/microorganisms8122012] [PMID: 33339331]
[69]
Townsend, E.M.; Kelly, L.; Muscatt, G.; Box, J.D.; Hargraves, N.; Lilley, D.; Jameson, E. The human gut phageome: Origins and roles in the human gut microbiome. Front. Cell. Infect. Microbiol., 2021, 11, 643214.
[http://dx.doi.org/10.3389/fcimb.2021.643214] [PMID: 34150671]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy