Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent Advances

Author(s): Saeed Aslani, Seyed Mohamad Javad Mirarefin, Habib Zarredar, Milad Asadi, Mohammad Reza Javan, Arezou Khosrojerdi*, Thomas P. Johnston and Amirhossein Sahebkar*

Volume 31, Issue 29, 2024

Published on: 03 July, 2023

Page: [4621 - 4639] Pages: 19

DOI: 10.2174/0929867330666230503143824

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Psoriasis is defined as a chronic autoimmune disorder of the skin in which abnormal proliferation and differentiation of keratinocytes are blamed as the central culprit of disease etiopathogenesis. A complex interplay between environmental factors and genetic risk factors has been suggested to trigger the disease. However, epigenetic regulation appears to connect external stimuli and genetic abnormalities in the development of psoriasis. The discordance in the prevalence of psoriasis between monozygotic twins and environmental factors that contribute to its onset have caused a paradigm shift regarding the mechanisms underlying the pathogenesis of this disease. Epigenetic dysregulation may be involved in aberrancies of keratinocyte differentiation, T-cell activation, and other plausible cells, leading to the initiation and perpetuation of psoriasis. Epigenetics is characterized by heritable alterations in the transcription of genes without nucleotide change and is commonly considered at three levels, i.e., DNA methylation, histone modifications, and microRNAs. To date, scientific evidence has indicated abnormal DNA methylation, histone modifications, and non-coding RNA transcription in psoriatic patients. In order to reverse aberrant epigenetic changes in psoriasis patients, several compounds and drugs (epi-drugs) have been developed to affect the major enzymes involved in the methylation of DNA, or the acetylation of histones, which aim to correct the aberrant methylation and acetylation patterns. A number of clinical trials have suggested the therapeutic potential of such drugs in the treatment of psoriasis. In the present review, we attempt to clarify recent findings with respect to epigenetic irregularities in psoriasis and discuss future challenges.

Keywords: Psoriasis, autoimmunity, epigenetics, DNA methylation, histone modifications, non-coding RNA.

« Previous Next »
[1]
Frischknecht, L.; Vecellio, M.; Selmi, C. The role of epigenetics and immunological imbalance in the etiopathogenesis of psoriasis and psoriatic arthritis. Ther. Adv. Musculoskeletal D., 2019, 11, 1759720X19886505.
[2]
Iskandar, I.Y.K.; Parisi, R.; Griffiths, C.E.M.; Ashcroft, D.M.; Atlas, G.P. Systematic review examining changes over time and variation in the incidence and prevalence of psoriasis by age and gender. Br. J. Dermatol., 2021, 184(2), 243-258.
[http://dx.doi.org/10.1111/bjd.19169] [PMID: 32358790]
[3]
Chandran, V.; Raychaudhuri, S.P. Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J. Autoimmun., 2010, 34(3), J314-J321.
[http://dx.doi.org/10.1016/j.jaut.2009.12.001] [PMID: 20034760]
[4]
Gervin, K.; Vigeland, M.D.; Mattingsdal, M.; Hammerø, M.; Nygård, H.; Olsen, A.O.; Brandt, I.; Harris, J.R.; Undlien, D.E.; Lyle, R. DNA methylation and gene expression changes in monozygotic twins discordant for psoriasis: Identification of epigenetically dysregulated genes. PLoS Genet., 2012, 8(1), e1002454.
[http://dx.doi.org/10.1371/journal.pgen.1002454] [PMID: 22291603]
[5]
Vecellio, M.; Paraboschi, E.M.; Ceribelli, A.; Isailovic, N.; Motta, F.; Cardamone, G.; Robusto, M.; Asselta, R.; Brescianini, S.; Sacrini, F.; Costanzo, A.; De Santis, M.; Stazi, M.A.; Duga, S.; Selmi, C. DNA methylation signature in monozygotic twins discordant for psoriatic disease. Front. Cell Dev. Biol., 2021, 9, 778677.
[http://dx.doi.org/10.3389/fcell.2021.778677] [PMID: 34901024]
[6]
Zhao, M.; Wang, Z.; Yung, S.; Lu, Q. Epigenetic dynamics in immunity and autoimmunity. Int. J. Biochem. Cell Biol., 2015, 67, 65-74.
[http://dx.doi.org/10.1016/j.biocel.2015.05.022] [PMID: 26026281]
[7]
Zhao, S.; Long, H.; Lu, Q. Epigenetic perspectives in systemic lupus erythematosus: pathogenesis, biomarkers, and therapeutic potentials. Clin. Rev. Allergy Immunol., 2010, 39(1), 3-9.
[http://dx.doi.org/10.1007/s12016-009-8165-7] [PMID: 19639427]
[8]
Hedrich, C.M.; Tsokos, G.C. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases. Trends Mol. Med., 2011, 17(12), 714-724.
[http://dx.doi.org/10.1016/j.molmed.2011.07.005] [PMID: 21885342]
[9]
Jeffries, M.A.; Sawalha, A.H. Autoimmune disease in the epigenetic era: How has epigenetics changed our understanding of disease and how can we expect the field to evolve? Expert Rev. Clin. Immunol., 2015, 11(1), 45-58.
[http://dx.doi.org/10.1586/1744666X.2015.994507] [PMID: 25534978]
[10]
Long, H.; Yin, H.; Wang, L.; Gershwin, M.E.; Lu, Q. The critical role of epigenetics in systemic lupus erythematosus and autoimmunity. J. Autoimmun., 2016, 74, 118-138.
[http://dx.doi.org/10.1016/j.jaut.2016.06.020] [PMID: 27396525]
[11]
Okada, S.; Weatherhead, E.; Targoff, I.N.; Wesley, R.; Miller, F.W. Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease. Arthritis Rheum., 2003, 48(8), 2285-2293.
[http://dx.doi.org/10.1002/art.11090] [PMID: 12905483]
[12]
Tan, G.; Niu, J.; Shi, Y.; Ouyang, H.; Wu, Z.H. NF-κB-dependent microRNA-125b up-regulation promotes cell survival by targeting p38α upon ultraviolet radiation. J. Biol. Chem., 2012, 287(39), 33036-33047.
[http://dx.doi.org/10.1074/jbc.M112.383273] [PMID: 22854965]
[13]
Chen, I.P.; Henning, S.; Faust, A.; Boukamp, P.; Volkmer, B.; Greinert, R. UVA-induced epigenetic regulation of P16INK4a in human epidermal keratinocytes and skin tumor derived cells. Photochem. Photobiol. Sci., 2012, 11(1), 180-190.
[http://dx.doi.org/10.1039/c1pp05197k] [PMID: 21986889]
[14]
Shahrad M, B.; Shahdad E, B.; John Y, K. Smoking and Psoriasis. Skinmed, 2005, 4(3), 174-176.
[http://dx.doi.org/10.1111/j.1540-9740.2005.03716.x] [PMID: 15891254]
[15]
Harlid, S.; Xu, Z.; Panduri, V.; Sandler, D.P.; Taylor, J.A. CpG sites associated with cigarette smoking: Analysis of epigenome-wide data from the Sister Study. Environ. Health Perspect., 2014, 122(7), 673-678.
[http://dx.doi.org/10.1289/ehp.1307480] [PMID: 24704585]
[16]
Aslani, S.; Jafari, N.; Javan, M.R.; Karami, J.; Ahmadi, M.; Jafarnejad, M. Epigenetic modifications and therapy in multiple sclerosis. Neuromole. Med., 2017, 19(1), 11-23.
[http://dx.doi.org/10.1007/s12017-016-8422-x] [PMID: 27382982]
[17]
Aslani, S.; Mahmoudi, M.; Garshasbi, M.; Jamshidi, A.R.; Karami, J.; Nicknam, M.H. Evaluation of DNMT1 gene expression profile and methylation of its promoter region in patients with ankylosing spondylitis. Clin. Rheumatol., 2016, 35(11), 2723-2731.
[http://dx.doi.org/10.1007/s10067-016-3403-x] [PMID: 27637577]
[18]
Mousavi, M.J.; Jamshidi, A.; Chopra, A.; Aslani, S.; Akhlaghi, M.; Mahmoudi, M. Implications of the noncoding RNAs in rheumatoid arthritis pathogenesis. J. Cell. Physiol., 2019, 234(1), 335-347.
[http://dx.doi.org/10.1002/jcp.26911] [PMID: 30069877]
[19]
Karami, J.; Mahmoudi, M.; Amirzargar, A.; Gharshasbi, M.; Jamshidi, A.; Aslani, S.; Nicknam, M.H. Promoter hypermethylation of BCL11B gene correlates with downregulation of gene transcription in ankylosing spondylitis patients. Genes Immun., 2017, 18(3), 170-175.
[http://dx.doi.org/10.1038/gene.2017.17] [PMID: 28794504]
[20]
Soltanzadeh-Yamchi, M.; Shahbazi, M.; Aslani, S.; Mohammadnia-Afrouzi, M. MicroRNA signature of regulatory T cells in health and autoimmunity. Biomed. Pharmacother., 2018, 100, 316-323.
[http://dx.doi.org/10.1016/j.biopha.2018.02.030] [PMID: 29453041]
[21]
Aslani, S.; Sobhani, S.; Gharibdoost, F.; Jamshidi, A.; Mahmoudi, M. Epigenetics and pathogenesis of systemic sclerosis; the ins and outs. Hum. Immunol., 2018, 79(3), 178-187.
[http://dx.doi.org/10.1016/j.humimm.2018.01.003] [PMID: 29330110]
[22]
Ahmadi, M.; Gharibi, T.; Dolati, S.; Rostamzadeh, D.; Aslani, S.; Baradaran, B.; Younesi, V.; Yousefi, M. Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases. Biomed. Pharmacother., 2017, 87, 596-608.
[http://dx.doi.org/10.1016/j.biopha.2016.12.072] [PMID: 28086135]
[23]
Fathollahi, A.; Aslani, S.; Jamshidi, A.; Mahmoudi, M. Epigenetics in osteoarthritis: Novel spotlight. J. Cell. Physiol., 2019, 234(8), 12309-12324.
[http://dx.doi.org/10.1002/jcp.28020] [PMID: 30659623]
[24]
Foma, A.M.; Aslani, S.; Karami, J.; Jamshidi, A.; Mahmoudi, M. Epigenetic involvement in etiopathogenesis and implications in treatment of systemic lupus erythematous. Inflamm. Res., 2017, 66(12), 1057-1073.
[http://dx.doi.org/10.1007/s00011-017-1082-y] [PMID: 28741130]
[25]
Karami, J.; Aslani, S.; Tahmasebi, M.N.; Mousavi, M.J.; Sharafat Vaziri, A.; Jamshidi, A.; Farhadi, E.; Mahmoudi, M. Epigenetics in rheumatoid arthritis; fibroblast-like synoviocytes as an emerging paradigm in the pathogenesis of the disease. Immunol. Cell Biol., 2020, 98(3), 171-186.
[http://dx.doi.org/10.1111/imcb.12311] [PMID: 31856314]
[26]
Feinberg, A.P. The key role of epigenetics in human disease prevention and mitigation. N. Engl. J. Med., 2018, 378(14), 1323-1334.
[http://dx.doi.org/10.1056/NEJMra1402513] [PMID: 29617578]
[27]
Pacini, G.; Paolino, S.; Andreoli, L.; Tincani, A.; Gerosa, M.; Caporali, R.; Iagnocco, A.; Ospelt, C.; Smith, V.; Cutolo, M. Epigenetics, pregnancy and autoimmune rheumatic diseases. Autoimmun. Rev., 2020, 19(12), 102685.
[http://dx.doi.org/10.1016/j.autrev.2020.102685] [PMID: 33115633]
[28]
Zouali, M. B lymphocytes, the gastrointestinal tract and autoimmunity. Autoimmun. Rev., 2021, 20(4), 102777.
[http://dx.doi.org/10.1016/j.autrev.2021.102777] [PMID: 33609796]
[29]
Farhat, S.C.L.; Yariwake, V.Y.; Veras, M.M.; Braga, A.L.F.; Maluf, A.E.; Silva, C.A. Inhaled ultrafine particles, epigenetics and systemic autoimmune rheumatic diseases. Autoimmun. Rev., 2020, 19(10), 102640.
[http://dx.doi.org/10.1016/j.autrev.2020.102640] [PMID: 32801038]
[30]
O’Connell, R.M.; Rao, D.S.; Baltimore, D. microRNA regulation of inflammatory responses. Annu. Rev. Immunol., 2012, 30(1), 295-312.
[http://dx.doi.org/10.1146/annurev-immunol-020711-075013] [PMID: 22224773]
[31]
Qureshi, I.A.; Mehler, M.F. Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nat. Rev. Neurosci., 2012, 13(8), 528-541.
[http://dx.doi.org/10.1038/nrn3234] [PMID: 22814587]
[32]
Pivarcsi, A.; Ståhle, M.; Sonkoly, E. Genetic polymorphisms altering microRNA activity in psoriasis - a key to solve the puzzle of missing heritability? Exp. Dermatol., 2014, 23(9), 620-624.
[http://dx.doi.org/10.1111/exd.12469] [PMID: 24917490]
[33]
Kulkarni, S.; Qi, Y.; O’hUigin, C.; Pereyra, F.; Ramsuran, V.; McLaren, P.; Fellay, J.; Nelson, G.; Chen, H.; Liao, W.; Bass, S.; Apps, R.; Gao, X.; Yuki, Y.; Lied, A.; Ganesan, A.; Hunt, P.W.; Deeks, S.G.; Wolinsky, S.; Walker, B.D.; Carrington, M. Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease. Proc. Natl. Acad. Sci. USA, 2013, 110(51), 20705-20710.
[http://dx.doi.org/10.1073/pnas.1312237110] [PMID: 24248364]
[34]
Aslani, S.; Mahmoudi, M.; Karami, J.; Jamshidi, A.R.; Malekshahi, Z.; Nicknam, M.H. Epigenetic alterations underlying autoimmune diseases. Autoimmunity, 2016, 49(2), 69-83.
[http://dx.doi.org/10.3109/08916934.2015.1134511] [PMID: 26761426]
[35]
Mahmoudi, M.; Aslani, S.; Nicknam, M.H.; Karami, J.; Jamshidi, A.R. New insights toward the pathogenesis of ankylosing spondylitis; genetic variations and epigenetic modifications. Mod. Rheumatol., 2017, 27(2), 198-209.
[http://dx.doi.org/10.1080/14397595.2016.1206174] [PMID: 27425039]
[36]
Krueger, G.G.; Duvic, M. Epidemiology of psoriasis: Clinical issues. J. Invest. Dermatol., 1994, 102(6), 14S-18S.
[http://dx.doi.org/10.1111/1523-1747.ep12386079] [PMID: 8006427]
[37]
Zeng, J.; Luo, S.; Huang, Y.; Lu, Q. Critical role of environmental factors in the pathogenesis of psoriasis. J. Dermatol., 2017, 44(8), 863-872.
[http://dx.doi.org/10.1111/1346-8138.13806] [PMID: 28349593]
[38]
Um, J.Y.; Chung, B.Y.; Kim, H.B.; Kim, J.C.; Park, C.W.; Kim, H.O. Aryl hydrocarbon receptor repressor is hypomethylated in psoriasis and promotes psoriasis-like inflammation in HaCaT cells. Int. J. Mol. Sci., 2021, 22(23), 12715.
[http://dx.doi.org/10.3390/ijms222312715] [PMID: 34884515]
[39]
Chandra, A.; Senapati, S.; Roy, S.; Chatterjee, G.; Chatterjee, R. Epigenome-wide DNA methylation regulates cardinal pathological features of psoriasis. Clin. Epigenetics, 2018, 10(1), 108.
[http://dx.doi.org/10.1186/s13148-018-0541-9] [PMID: 30092825]
[40]
Verma, D.; Ekman, A.K.; Bivik Eding, C.; Enerbäck, C. Genome-wide DNA methylation profiling identifies differential methylation in uninvolved psoriatic epidermis. J. Invest. Dermatol., 2018, 138(5), 1088-1093.
[http://dx.doi.org/10.1016/j.jid.2017.11.036] [PMID: 29247660]
[41]
Deng, M.; Su, Y.; Wu, R.; Li, S.; Zhu, Y.; Tang, G.; Shi, X.; Zhou, T.; Zhao, M.; Lu, Q. DNA methylation markers in peripheral blood for psoriatic arthritis. J. Dermatol. Sci., 2022, 108(1), 39-47.
[http://dx.doi.org/10.1016/j.jdermsci.2022.11.001] [PMID: 36404219]
[42]
Charras, A.; Garau, J.; Hofmann, S.R.; Carlsson, E.; Cereda, C.; Russ, S.; Abraham, S.; Hedrich, C.M. DNA methylation patterns in CD8+ T cells discern psoriasis From psoriatic arthritis and correlate with cutaneous disease activity. Front. Cell Dev. Biol., 2021, 9, 746145.
[http://dx.doi.org/10.3389/fcell.2021.746145] [PMID: 34746142]
[43]
Zhou, F.; Shen, C.; Hsu, Y.H.; Gao, J.; Dou, J.; Ko, R.; Zheng, X.; Sun, L.; Cui, Y.; Zhang, X. DNA methylation-based subclassification of psoriasis in the Chinese Han population. Front. Med., 2018, 12(6), 717-725.
[http://dx.doi.org/10.1007/s11684-017-0588-6] [PMID: 29623515]
[44]
Pollock, R.A.; Zaman, L.; Chandran, V.; Gladman, D.D. Epigenome-wide analysis of sperm cells identifies IL22 as a possible germ line risk locus for psoriatic arthritis. PLoS One, 2019, 14(2), e0212043.
[http://dx.doi.org/10.1371/journal.pone.0212043] [PMID: 30779748]
[45]
Wu, M.; Li, X.; Zhang, C.; Zhang, C.; Qian, D.; Ma, J.; Cai, M.; Tang, L.; Cheng, H.; Shen, C.; Chen, G.; Zheng, X.; Zhang, X.; Zhou, F. DNA methylation profile of psoriatic skins from different body locations. Epigenomics, 2019, 11(14), 1613-1625.
[http://dx.doi.org/10.2217/epi-2018-0225] [PMID: 31701765]
[46]
Deb, S.; Bandiera, S.M. Characterization and expression of extrahepatic CYP2S1. Expert Opin. Drug Metab. Toxicol., 2009, 5(4), 367-380.
[http://dx.doi.org/10.1517/17425250902865586] [PMID: 19368491]
[47]
Smith, G.; Wolf, C.R.; Deeni, Y.Y.; Dawe, R.S.; Evans, A.T.; Comrie, M.M.; Ferguson, J.; Ibbotson, S.H. Cutaneous expression of cytochrome P450 CYP2S1: Individuality in regulation by therapeutic agents for psoriasis and other skin diseases. Lancet, 2003, 361(9366), 1336-1343.
[http://dx.doi.org/10.1016/S0140-6736(03)13081-4] [PMID: 12711469]
[48]
Zhou, F.; Wang, W.; Shen, C.; Li, H.; Zuo, X.; Zheng, X.; Yue, M.; Zhang, C.; Yu, L.; Chen, M.; Zhu, C.; Yin, X.; Tang, M.; Li, Y.; Chen, G.; Wang, Z.; Liu, S.; Zhou, Y.; Zhang, F.; Zhang, W.; Li, C.; Yang, S.; Sun, L.; Zhang, X. Epigenome-wide association analysis identified nine skin DNA methylation loci for psoriasis. J. Invest. Dermatol., 2016, 136(4), 779-787.
[http://dx.doi.org/10.1016/j.jid.2015.12.029] [PMID: 26743604]
[49]
Sheng, Y.; Wen, L.; Zheng, X.; Li, M.; Wang, D.; Chen, S.; Li, R.; Tang, L.; Zhou, F. CYP2S1 might regulate proliferation and immune response of keratinocyte in psoriasis. Epigenetics, 2021, 16(6), 618-628.
[http://dx.doi.org/10.1080/15592294.2020.1814486] [PMID: 32924783]
[50]
Krueger, G.G.; Hill, H.R.; Jederberg, W.W. Inflammatory and immune cell function in psoriasis-a subtle disorder I. in vivo and in vitro survey. J. Invest. Dermatol., 1978, 71(3), 189-194.
[http://dx.doi.org/10.1111/1523-1747.ep12547129] [PMID: 690482]
[51]
Zarrabeitia, M.T.; Fariñas, M.C.; Rodríguez-Valverde, V.; Riancho, J.A.; Llaca, H.F. T and B cell function in psoriasis and psoriatic arthropathy. Allergol. Immunopathol. (Madr.), 1989, 17(3), 155-159.
[PMID: 2816658]
[52]
Schön, M.; Kubitza, R.C.; Ruzicka, T.; Schön, M.P.; Denzer, D. Critical role of neutrophils for the generation of psoriasiform skin lesions in flaky skin mice. J. Invest. Dermatol., 2000, 114(5), 976-983.
[http://dx.doi.org/10.1046/j.1523-1747.2000.00953.x] [PMID: 10771480]
[53]
Rocha-Pereira, P.; Santos-Silva, A.; Rebelo, I.; FigneiRedo, A.; Quintanilha, A.; Teixeira, F. Erythrocyte damage in mild and severe psoriasis. Br. J. Dermatol., 2004, 150(2), 232-244.
[http://dx.doi.org/10.1111/j.1365-2133.2004.05801.x] [PMID: 14996093]
[54]
Zhang, K.; Zhang, R.; Li, X.; Yin, G.; Niu, X. Promoter methylation status of p15 and p21 genes in HPP-CFCs of bone marrow of patients with psoriasis. Eur. J. Dermatol., 2009, 19(2), 141-146.
[http://dx.doi.org/10.1684/ejd.2008.0618] [PMID: 19153068]
[55]
Zhang, R.L.; Niu, X.P.; Li, X.H.; Zhang, K.M.; Yin, G.H. CFU-HPP colony formation of bone marrow hematopoietic proginitor cells in psoriatic patients and methylation of p16 gene promotor in CFU-HPP colony cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2007, 15(4), 780-784.
[PMID: 17708803]
[56]
Griffiths, C.E.M.; Barker, J.N.W.N. Pathogenesis and clinical features of psoriasis. Lancet, 2007, 370(9583), 263-271.
[http://dx.doi.org/10.1016/S0140-6736(07)61128-3] [PMID: 17658397]
[57]
Wrone-Smith, T.; Mitra, R.S.; Thompson, C.B.; Jasty, R.; Castle, V.P.; Nickoloff, B.J. Keratinocytes derived from psoriatic plaques are resistant to apoptosis compared with normal skin. Am. J. Pathol., 1997, 151(5), 1321-1329.
[PMID: 9358758]
[58]
Chen, M.; Chen, Z-Q.; Cui, P-G.; Yao, X.; Li, Y-M.; Li, A-S.; Gong, J-Q.; Cao, Y-H. The methylation pattern of p16 INK4a gene promoter in psoriatic epidermis and its clinical significance. Br. J. Dermatol., 2008, 158(5), 987-993.
[http://dx.doi.org/10.1111/j.1365-2133.2008.08505.x] [PMID: 18373711]
[59]
Ruchusatsawat, K.; Wongpiyabovorn, J.; Shuangshoti, S.; Hirankarn, N.; Mutirangura, A. SHP-1 promoter 2 methylation in normal epithelial tissues and demethylation in psoriasis. J. Mol. Med. (Berl.), 2006, 84(2), 175-182.
[http://dx.doi.org/10.1007/s00109-005-0020-6] [PMID: 16389548]
[60]
Chen, M.; Wang, Y.; Yao, X.; Li, C.; Jiang, M.; Cui, P.; Wang, B. Hypermethylation of HLA-C may be an epigenetic marker in psoriasis. J. Dermatol. Sci., 2016, 83(1), 10-16.
[http://dx.doi.org/10.1016/j.jdermsci.2016.04.003] [PMID: 27132688]
[61]
Zong, W.; Ge, Y.; Han, Y.; Yang, X.; Li, Q.; Chen, M. Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis. Oncotarget, 2017, 8(7), 12323-12332.
[http://dx.doi.org/10.18632/oncotarget.12468] [PMID: 27713139]
[62]
Tang, L.; Yao, T.; Fang, M.; Zheng, X.; Chen, G.; Li, M.; Wang, D.; Li, X.; Ma, H.; Wang, X.; Qian, Y.; Zhou, F. Genomic DNA methylation in HLA-Cw*0602 carriers and non-carriers of psoriasis. J. Dermatol. Sci., 2020, 99(1), 23-29.
[http://dx.doi.org/10.1016/j.jdermsci.2020.05.006] [PMID: 32522384]
[63]
Zhou, F.; Shen, C.; Xu, J.; Gao, J.; Zheng, X.; Ko, R.; Dou, J.; Cheng, Y.; Zhu, C.; Xu, S.; Tang, X.; Zuo, X.; Yin, X.; Cui, Y.; Sun, L.; Tsoi, L.C.; Hsu, Y.H.; Yang, S.; Zhang, X. Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis. Clin. Epigenetics, 2016, 8(1), 131.
[http://dx.doi.org/10.1186/s13148-016-0297-z] [PMID: 27980695]
[64]
Ruchusatsawat, K.; Thiemsing, L.; Mutirangura, A.; Wongpiyabovorn, J. BCAP 31 expression and promoter demethylation in psoriasis. Asian Pac. J. Allergy Immunol., 2016.
[PMID: 27996285]
[65]
Black, J.C.; Van Rechem, C.; Whetstine, J.R. Histone lysine methylation dynamics: Establishment, regulation, and biological impact. Mol. Cell, 2012, 48(4), 491-507.
[http://dx.doi.org/10.1016/j.molcel.2012.11.006] [PMID: 23200123]
[66]
Peserico, A.; Simone, C. Physical and functional HAT/HDAC interplay regulates protein acetylation balance. J. Biomed. Biotechnol., 2011, 2011, 1-10.
[http://dx.doi.org/10.1155/2011/371832] [PMID: 21151613]
[67]
Masalha, M.; Ben-Dov, I.Z.; Ram, O.; Meningher, T.; Jacob-Hirsch, J.; Kassem, R.; Sidi, Y.; Avni, D. H3K27Ac modification and gene expression in psoriasis. J. Dermatol. Sci., 2021, 103(2), 93-100.
[http://dx.doi.org/10.1016/j.jdermsci.2021.07.003] [PMID: 34281744]
[68]
Liao, Y.; Su, Y.; Wu, R.; Zhang, P.; Feng, C. Overexpression of Wilms tumor 1 promotes IL-1β expression by upregulating histone acetylation in keratinocytes. Int. Immunopharmacol., 2021, 96, 107793.
[http://dx.doi.org/10.1016/j.intimp.2021.107793] [PMID: 34162155]
[69]
Zeng, J.; Zhang, Y.; Zhang, H.; Zhang, Y.; Gao, L.; Tong, X.; Xie, Y.; Hu, Q.; Chen, C.; Ding, S.; Lu, J. RPL22 overexpression promotes psoriasis-like lesion by inducing keratinocytes abnormal biological behavior. Front. Immunol., 2021, 12, 699900.
[http://dx.doi.org/10.3389/fimmu.2021.699900] [PMID: 34220863]
[70]
Zhang, T.; Yang, L.; Ke, Y.; Lei, J.; Shen, S.; Shao, S.; Zhang, C.; Zhu, Z.; Dang, E.; Wang, G. EZH2-dependent epigenetic modulation of histone H3 lysine-27 contributes to psoriasis by promoting keratinocyte proliferation. Cell Death Dis., 2020, 11(10), 826.
[http://dx.doi.org/10.1038/s41419-020-03028-1] [PMID: 33011750]
[71]
Li, H.; Yao, Q.; Mariscal, A.G.; Wu, X.; Hülse, J.; Pedersen, E.; Helin, K.; Waisman, A.; Vinkel, C.; Thomsen, S.F.; Avgustinova, A.; Benitah, S.A.; Lovato, P.; Norsgaard, H.; Mortensen, M.S.; Veng, L.; Rozell, B.; Brakebusch, C. Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation. Nat. Commun., 2018, 9(1), 1420.
[http://dx.doi.org/10.1038/s41467-018-03704-z] [PMID: 29650963]
[72]
Xia, X.; Cao, G.; Sun, G.; Zhu, L.; Tian, Y.; Song, Y.; Guo, C.; Wang, X.; Zhong, J.; Zhou, W.; Li, P.; Zhang, H.; Hao, J.; Li, Z.; Deng, L.; Yin, Z.; Gao, Y. GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis. J. Clin. Invest., 2020, 130(10), 5180-5196.
[http://dx.doi.org/10.1172/JCI129269] [PMID: 32831293]
[73]
Zhang, P.; Su, Y.; Zhao, M.; Huang, W.; Lu, Q. Abnormal histone modifications in PBMCs from patients with psoriasis vulgaris. Eur. J. Dermatol., 2011, 21(4), 552-557.
[http://dx.doi.org/10.1684/ejd.2011.1383] [PMID: 21715244]
[74]
Trowbridge, R.M.; Pittelkow, M.R. Epigenetics in the pathogenesis and pathophysiology of psoriasis vulgaris. J. Drugs Dermatol., 2014, 13(2), 111-118.
[PMID: 24509958]
[75]
Ovejero-Benito, M.C.; Reolid, A.; Sánchez-Jiménez, P.; Saiz-Rodríguez, M.; Muñoz-Aceituno, E.; Llamas-Velasco, M.; Martín-Vilchez, S.; Cabaleiro, T.; Román, M.; Ochoa, D.; Daudén, E.; Abad-Santos, F. Histone modifications associated with biological drug response in moderate-to-severe psoriasis. Exp. Dermatol., 2018, 27(12), 1361-1371.
[http://dx.doi.org/10.1111/exd.13790] [PMID: 30260532]
[76]
Blander, G.; Bhimavarapu, A.; Mammone, T.; Maes, D.; Elliston, K.; Reich, C.; Matsui, M.S.; Guarente, L.; Loureiro, J.J. SIRT1 promotes differentiation of normal human keratinocytes. J. Invest. Dermatol., 2009, 129(1), 41-49.
[http://dx.doi.org/10.1038/jid.2008.179] [PMID: 18563176]
[77]
Hwang, Y.J.; Na, J.I.; Byun, S.Y.; Kwon, S.H.; Yang, S.H.; Lee, H.S.; Choi, H.R.; Cho, S.; Youn, S.W.; Park, K.C. Histone deacetylase 1 and sirtuin 1 expression in psoriatic skin: A comparison between guttate and plaque psoriasis. Life (Basel), 2020, 10(9), 157.
[http://dx.doi.org/10.3390/life10090157] [PMID: 32825671]
[78]
Shukla, G.C.; Singh, J.; Barik, S. MicroRNAs: Processing, maturation, target recognition and regulatory functions. Mol. Cell. Pharmacol., 2011, 3(3), 83-92.
[PMID: 22468167]
[79]
Baltimore, D.; Boldin, M.P.; O’Connell, R.M.; Rao, D.S.; Taganov, K.D. MicroRNAs: new regulators of immune cell development and function. Nat. Immunol., 2008, 9(8), 839-845.
[http://dx.doi.org/10.1038/ni.f.209] [PMID: 18645592]
[80]
Qiao, M.; Ding, J.; Yan, J.; Li, R.; Jiao, J.; Sun, Q. Circular RNA expression profile and analysis of their potential function in psoriasis. Cell. Physiol. Biochem., 2018, 50(1), 15-27.
[http://dx.doi.org/10.1159/000493952] [PMID: 30278433]
[81]
Liu, R.; Wang, Q.; Chang, W.; Zhou, L.; Li, J.; Zhang, K. Characterisation of the circular RNA landscape in mesenchymal stem cells from psoriatic skin lesions. Eur. J. Dermatol., 2019, 29(1), 29-38.
[PMID: 30827946]
[82]
Haschka, J.; Simon, D.; Bayat, S.; Messner, Z.; Kampylafka, E.; Fagni, F.; Skalicky, S.; Hackl, M.; Resch, H.; Zwerina, J.; Kleyer, A.; Cavallaro, A.; Sticherling, M.; Schett, G.; Kocijan, R.; Rech, J. Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis. Rheumatology, 2023.
[83]
Soonthornchai, W.; Tangtanatakul, P.; Meesilpavikkai, K.; Dalm, V.; Kueanjinda, P.; Wongpiyabovorn, J. MicroRNA-378a-3p is overexpressed in psoriasis and modulates cell cycle arrest in keratinocytes via targeting BMP2 gene. Sci. Rep., 2021, 11(1), 14186.
[http://dx.doi.org/10.1038/s41598-021-93616-8] [PMID: 34244572]
[84]
Sonkoly, E.; Wei, T.; Janson, P.C.J.; Sääf, A.; Lundeberg, L.; Tengvall-Linder, M.; Norstedt, G.; Alenius, H.; Homey, B.; Scheynius, A.; Ståhle, M.; Pivarcsi, A. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One, 2007, 2(7), e610.
[http://dx.doi.org/10.1371/journal.pone.0000610] [PMID: 17622355]
[85]
Primo, M.N.; Bak, R.O.; Schibler, B.; Mikkelsen, J.G. Regulation of pro-inflammatory cytokines TNFα and IL24 by microRNA-203 in primary keratinocytes. Cytokine, 2012, 60(3), 741-748.
[http://dx.doi.org/10.1016/j.cyto.2012.07.031] [PMID: 22917968]
[86]
Mostafa, S.A.; Mohammad, M.H.S.; Negm, W.A.; Batiha, G.E.S.; Alotaibi, S.S.; Albogami, S.M.; Waard, M.D.; Tawfik, N.Z.; Abdallah, H.Y. Circulating microRNA203 and its target genes’ role in psoriasis pathogenesis. Front. Med. (Lausanne), 2022, 9, 988962.
[http://dx.doi.org/10.3389/fmed.2022.988962] [PMID: 36341243]
[87]
Leal, B.; Carvalho, C.; Ferreira, A.M.; Nogueira, M.; Brás, S.; Silva, B.M.; Selores, M.; Costa, P.P.; Torres, T. Serum levels of miR-146a in patients with psoriasis. Mol. Diagn. Ther., 2021, 25(4), 475-485.
[http://dx.doi.org/10.1007/s40291-021-00531-9] [PMID: 33937970]
[88]
Shen, H.; Wang, D.; Zhan, M.; Ding, H.; Zhao, H. MicroRNA-146a and microRNA-146b deficiency correlates with exacerbated disease activity, and their longitude increment relates to etanercept response in psoriasis patients. J. Clin. Lab. Anal., 2022, 36(2), e24198.
[http://dx.doi.org/10.1002/jcla.24198] [PMID: 34952998]
[89]
Lena, A.M.; Shalom-Feuerstein, R.; di Val Cervo, P.R.; Aberdam, D.; Knight, R.A.; Melino, G.; Candi, E. miR-203 represses ‘stemness’ by repressing ΔNp63. Cell Death Differ., 2008, 15(7), 1187-1195.
[http://dx.doi.org/10.1038/cdd.2008.69] [PMID: 18483491]
[90]
Zibert, J.R.; Løvendorf, M.B.; Litman, T.; Olsen, J.; Kaczkowski, B.; Skov, L. MicroRNAs and potential target interactions in psoriasis. J. Dermatol. Sci., 2010, 58(3), 177-185.
[http://dx.doi.org/10.1016/j.jdermsci.2010.03.004] [PMID: 20417062]
[91]
Meng, Z.; Qiu, J.; Zhang, H. MiR-221-3p as a potential bfor Patients with psoriasis and its role in inflammatory responses in keratinocytes. Skin Pharmacol. Physiol., 2021, 34(5), 300-306.
[http://dx.doi.org/10.1159/000515114] [PMID: 34091460]
[92]
Xu, N.; Brodin, P.; Wei, T.; Meisgen, F.; Eidsmo, L.; Nagy, N.; Kemeny, L.; Ståhle, M.; Sonkoly, E.; Pivarcsi, A. MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. J. Invest. Dermatol., 2011, 131(7), 1521-1529.
[http://dx.doi.org/10.1038/jid.2011.55] [PMID: 21412257]
[93]
Su, F.; Jin, L.; Liu, W. MicroRNA-125acorrelates with decreased psoriasis severity and inflammation and represses keratinocyte proliferation. Dermatology, 2021, 237(4), 568-578.
[http://dx.doi.org/10.1159/000510681] [PMID: 33735868]
[94]
Joyce, C.E.; Zhou, X.; Xia, J.; Ryan, C.; Thrash, B.; Menter, A.; Zhang, W.; Bowcock, A.M. Deep sequencing of small RNAs from human skin reveals major alterations in the psoriasis miRNAome. Hum. Mol. Genet., 2011, 20(20), 4025-4040.
[http://dx.doi.org/10.1093/hmg/ddr331] [PMID: 21807764]
[95]
Meisgen, F.; Xu, N.; Wei, T.; Janson, P.C.; Obad, S.; Broom, O.; Nagy, N.; Kauppinen, S.; Kemény, L.; Ståhle, M.; Pivarcsi, A.; Sonkoly, E. MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis. Exp. Dermatol., 2012, 21(4), 312-314.
[http://dx.doi.org/10.1111/j.1600-0625.2012.01462.x] [PMID: 22417311]
[96]
Xu, N.; Meisgen, F.; Butler, L.M.; Han, G.; Wang, X.J.; Söderberg-Nauclér, C.; Ståhle, M.; Pivarcsi, A.; Sonkoly, E. MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40. J. Immunol., 2013, 190(2), 678-688.
[http://dx.doi.org/10.4049/jimmunol.1202695] [PMID: 23233723]
[97]
Ye, Y.; Wang, P.; Zhou, F. miR-489-3p inhibits TLR4/NF-κB signaling to prevent inflammation in psoriasis. Exp. Ther. Med., 2021, 22(1), 744.
[http://dx.doi.org/10.3892/etm.2021.10176] [PMID: 34055060]
[98]
Lerman, G.; Avivi, C.; Mardoukh, C.; Barzilai, A.; Tessone, A.; Gradus, B.; Pavlotsky, F.; Barshack, I.; Polak-Charcon, S.; Orenstein, A.; Hornstein, E.; Sidi, Y.; Avni, D. MiRNA expression in psoriatic skin: reciprocal regulation of hsa-miR-99a and IGF-1R. PLoS One, 2011, 6(6), e20916.
[http://dx.doi.org/10.1371/journal.pone.0020916] [PMID: 21687694]
[99]
Choi, H.R.; Nam, K.M.; Park, S.J.; Kim, D.S.; Huh, C.H.; Park, W.Y.; Park, K.C. Suppression of miR135b increases the proliferative potential of normal human keratinocytes. J. Invest. Dermatol., 2014, 134(4), 1161-1164.
[http://dx.doi.org/10.1038/jid.2013.427] [PMID: 24129066]
[100]
Ichihara, A.; Jinnin, M.; Yamane, K.; Fujisawa, A.; Sakai, K.; Masuguchi, S.; Fukushima, S.; Maruo, K.; Ihn, H. microRNA-mediated keratinocyte hyperproliferation in psoriasis vulgaris. Br. J. Dermatol., 2011, 165(5), 1003-1010.
[http://dx.doi.org/10.1111/j.1365-2133.2011.10497.x] [PMID: 21711342]
[101]
Ichihara, A.; Jinnin, M.; Oyama, R.; Yamane, K.; Fujisawa, A.; Sakai, K.; Masuguchi, S.; Fukushima, S.; Maruo, K.; Ihn, H. Increased serum levels of miR-1266 in patients with psoriasis vulgaris. Eur. J. Dermatol., 2012, 22(1), 68-71.
[http://dx.doi.org/10.1684/ejd.2011.1600] [PMID: 22133505]
[102]
Bian, J.; Liu, R.; Fan, T.; Liao, L.; Wang, S.; Geng, W.; Wang, T.; Shi, W.; Ruan, Q. miR-340 alleviates psoriasis in mice through direct targeting of IL-17A. J. Immunology, 2018, 201(5), 1412-1420.
[103]
Zhao, M.; Wang, L.; Liang, G.; Zhang, P.; Deng, X.; Tang, Q.; Zhai, H.; Chang, C.C.; Su, Y.; Lu, Q. Up-regulation of microRNA-210 induces immune dysfunction via targeting FOXP3 in CD4+ T cells of psoriasis vulgaris. Clin. Immunol., 2014, 150(1), 22-30.
[http://dx.doi.org/10.1016/j.clim.2013.10.009] [PMID: 24316592]
[104]
Wu, R.; Zeng, J.; Yuan, J.; Deng, X.; Huang, Y.; Chen, L.; Zhang, P.; Feng, H.; Liu, Z.; Wang, Z.; Gao, X.; Wu, H.; Wang, H.; Su, Y.; Zhao, M.; Lu, Q. MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation. J. Clin. Invest., 2018, 128(6), 2551-2568.
[http://dx.doi.org/10.1172/JCI97426] [PMID: 29757188]
[105]
Jiang, M.; Sun, Z.; Dang, E.; Li, B.; Fang, H.; Li, J.; Gao, L.; Zhang, K.; Wang, G. TGFβ/SMAD/microRNA-486-3p signaling axis mediates keratin 17 expression and keratinocyte hyperproliferation in psoriasis. J. Invest. Dermatol., 2017, 137(10), 2177-2186.
[http://dx.doi.org/10.1016/j.jid.2017.06.005]
[106]
Zhang, W.; Yi, X.; An, Y.; Guo, S.; Li, S.; Song, P.; Chang, Y.; Zhang, S.; Gao, T.; Wang, G.; Li, C. MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes: Implication for the pathogenesis of psoriasis. Cell Death Dis., 2018, 9(5), 567.
[http://dx.doi.org/10.1038/s41419-018-0621-y] [PMID: 29752469]
[107]
Li, Q.; Zhang, J.; Liu, S.; Zhang, F.; Zhuang, J.; Chen, Y. MicroRNA-17-3p is upregulated in psoriasis and regulates keratinocyte hyperproliferation and pro-inflammatory cytokine secretion by targeting CTR9. Eur. J. Histochem., 2022, 66(1), 66.
[http://dx.doi.org/10.4081/ejh.2022.3275] [PMID: 35016493]
[108]
Liu, S.; Gong, J. miR-124-3p delivered using exosomes attenuates the keratinocyte response to IL-17A stimulation in psoriasis. Oxid. Med. Cell. Longev., 2022, 2022, 1-11.
[http://dx.doi.org/10.1155/2022/6264474] [PMID: 36275890]
[109]
Yan, J.J.; Qiao, M.; Li, R.H.; Zhao, X.T.; Wang, X.Y.; Sun, Q. Downregulation of miR-145-5p contributes to hyperproliferation of keratinocytes and skin inflammation in psoriasis. Br. J. Dermatol., 2019, 180(2), 365-372.
[http://dx.doi.org/10.1111/bjd.17256] [PMID: 30269330]
[110]
Shen, H.; Zeng, B.; Wang, C.; Tang, X.; Wang, H.; Liu, W.; Yang, Z. MiR-330 inhibits IL-22-induced keratinocyte proliferation through targeting CTNNB1. Biomed. Pharmacother., 2017, 91, 803-811.
[http://dx.doi.org/10.1016/j.biopha.2017.05.005] [PMID: 28501007]
[111]
Zheng, Y.Z.; Chen, C.F.; Jia, L.Y.; Yu, T.G.; Sun, J.; Wang, X.Y. Correlation between microRNA-143 in peripheral blood mononuclear cells and disease severity in patients with psoriasis vulgaris. Oncotarget, 2017, 8(31), 51288-51295.
[http://dx.doi.org/10.18632/oncotarget.17260] [PMID: 28881648]
[112]
Xu, L.; Leng, H.; Shi, X.; Ji, J.; Fu, J.; Leng, H. MiR-155 promotes cell proliferation and inhibits apoptosis by PTEN signaling pathway in the psoriasis. Biomed. Pharmacother., 2017, 90, 524-530.
[http://dx.doi.org/10.1016/j.biopha.2017.03.105] [PMID: 28402921]
[113]
Koga, Y.; Jinnin, M.; Ichihara, A.; Fujisawa, A.; Moriya, C.; Sakai, K.; Fukushima, S.; Inoue, Y.; Ihn, H. Analysis of expression pattern of serum microRNA levels in patients with psoriasis. J. Dermatol. Sci., 2014, 74(2), 170-171.
[http://dx.doi.org/10.1016/j.jdermsci.2014.01.005] [PMID: 24517871]
[114]
Jorn Bovenschen, H.; van de Kerkhof, P.C.; van Erp, P.E.; Woestenenk, R.; Joosten, I.; Koenen, H.J.P.M. Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin. J. Invest. Dermatol., 2011, 131(9), 1853-1860.
[http://dx.doi.org/10.1038/jid.2011.139] [PMID: 21654831]
[115]
Hammitzsch, A.; Tallant, C.; Fedorov, O.; O’Mahony, A.; Brennan, P.E.; Hay, D.A.; Martinez, F.O.; Al-Mossawi, M.H.; de Wit, J.; Vecellio, M.; Wells, C.; Wordsworth, P.; Müller, S.; Knapp, S.; Bowness, P. CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. Proc. Natl. Acad. Sci. USA, 2015, 112(34), 10768-10773.
[http://dx.doi.org/10.1073/pnas.1501956112] [PMID: 26261308]
[116]
Samuelov, L.; Bochner, R.; Magal, L.; Malovitski, K.; Sagiv, N.; Nousbeck, J.; Keren, A.; Fuchs-Telem, D.; Sarig, O.; Gilhar, A.; Sprecher, E. Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis. Exp. Dermatol., 2022, 31(4), 567-576.
[http://dx.doi.org/10.1111/exd.14502] [PMID: 34787924]
[117]
Orecchia, A.; Scarponi, C.; Di Felice, F.; Cesarini, E.; Avitabile, S.; Mai, A.; Mauro, M.L.; Sirri, V.; Zambruno, G.; Albanesi, C.; Camilloni, G.; Failla, C.M. Sirtinol treatment reduces inflammation in human dermal microvascular endothelial cells. PLoS One, 2011, 6(9), e24307.
[http://dx.doi.org/10.1371/journal.pone.0024307] [PMID: 21931678]
[118]
Thatikonda, S.; Pooladanda, V.; Sigalapalli, D.K.; Godugu, C. Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation. Cell Death Dis., 2020, 11(1), 21.
[http://dx.doi.org/10.1038/s41419-019-2212-y] [PMID: 31924750]
[119]
Feng, H.; Wu, R.; Zhang, S.; Kong, Y.; Liu, Z.; Wu, H.; Wang, H.; Su, Y.; Zhao, M.; Lu, Q. Topical administration of nanocarrier miRNA-210 antisense ameliorates imiquimod-induced psoriasis-like dermatitis in mice. J. Dermatol., 2020, 47(2), 147-154.
[http://dx.doi.org/10.1111/1346-8138.15149] [PMID: 31773789]
[120]
Rajitha, P.; Biswas, R.; Sabitha, M.; Jayakumar, R. Methotrexate in the treatment of psoriasis and rheumatoid arthritis: mechanistic insights, current issues and novel delivery approaches. Curr. Pharm. Des., 2017, 23(24), 3550-3566.
[PMID: 28571554]

Rights & Permissions Print Cite
Article Metrics
44
1
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy