{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:32:23Z","timestamp":1771050743607,"version":"3.50.1"},"reference-count":111,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Autophagy is an intracellular process whereby cytoplasmic constituents are degraded within lysosomes. Autophagy functions to eliminate unwanted or damaged materials such as proteins and organelles as their accumulation would be harmful to the cellular system. Autophagy also acts as a defense mechanism against invading pathogens and plays an important role in innate and adaptive immunity. In physiological processes, autophagy is involved in the regulation of tissue development, differentiation and remodeling, which are essential for maintaining cellular homeostasis. Recent studies have demonstrated that autophagy is linked to various diseases and involved in pathophysiological roles, such as adaptation during starvation, anti-aging, antigen presentation, tumor suppression and cell death. The modulation of autophagy has shown greatest promise in Crohn\u2019s disease as most of autophagy drugs involved in these diseases are currently under clinical trials and some has been approved by Food and Drug Administration. This review article discusses autophagy and potential drugs that are currently available for its modulation in Crohn\u2019s disease.<\/jats:p>","DOI":"10.3390\/medicina55060224","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T11:31:28Z","timestamp":1559129488000},"page":"224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Crohn\u2019s Disease: Potential Drugs for Modulation of Autophagy"],"prefix":"10.3390","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6525-6603","authenticated-orcid":false,"given":"Nursyuhada","family":"Azzman","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Universiti Teknologi MARA, Cawangan Pulau Pinang Kampus Bertam, 13200 Kepala Batas, Pulau Pinang, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1053\/j.gastro.2010.06.070","article-title":"Risk factors associated with progression to intestinal complications of Crohn\u2019s disease in a population-based cohort","volume":"139","author":"Thia","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1053\/j.gastro.2011.10.001","article-title":"Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review","volume":"142","author":"Molodecky","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1053\/j.gastro.2013.04.007","article-title":"Incidence and Phenotype of Inflammatory Bowel Disease Based on Results From the Asia-Pacific Crohn\u2019s and Colitis Epidemiology Study","volume":"145","author":"Ng","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1111\/j.1572-0241.2008.02158.x","article-title":"An update on the epidemiology of inflammatory bowel disease in Asia","volume":"103","author":"Thia","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.5217\/ir.2016.14.2.111","article-title":"Changing epidemiological trends of inflammatory bowel disease in Asia","volume":"14","author":"Ng","year":"2016","journal-title":"Intest. Res."},{"key":"ref_7","first-page":"3204","article-title":"Current treatment of ulcerative colitis","volume":"17","author":"Meier","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1097\/MIB.0b013e31828134b3","article-title":"Challenges in IBD research: Update on progress and prioritization of the CCFA\u2019s research agenda","volume":"19","author":"Denson","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1242\/jcs.01620","article-title":"The molecular machinery of autophagy: Unanswered questions","volume":"118","author":"Klionsky","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_10","unstructured":"Hayat, M.A. (2014). Chapter 1\u2014Introduction to Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Volumes 1\u20144. Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Academic Press."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3410\/B3-25","article-title":"The puzzling origin of the autophagosomal membrane","volume":"3","author":"Mari","year":"2011","journal-title":"F1000 Biol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bbadis.2008.10.016","article-title":"Autophagy: Principles and significance in health and disease","volume":"1792","author":"Todde","year":"2009","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1242\/jcs.064576","article-title":"The regulation of autophagy\u2014Unanswered questions","volume":"124","author":"Chen","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1172\/JCI26390","article-title":"Autophagy in cell death: An innocent convict?","volume":"115","author":"Levine","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/ncb3062","article-title":"Foxk proteins repress the initiation of starvation-induced atrophy and autophagy programs","volume":"16","author":"Bowman","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cell.2004.11.046","article-title":"Growth Factor Regulation of Autophagy and Cell Survival in the Absence of Apoptosis","volume":"120","author":"Lum","year":"2005","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1128\/EC.01.1.11-21.2002","article-title":"Autophagy in the eukaryotic cell","volume":"1","author":"Reggiori","year":"2002","journal-title":"Eukaryot. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1091\/mbc.e08-12-1249","article-title":"ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery","volume":"20","author":"Jung","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1105\/tpc.104.025395","article-title":"Processing of ATG8s, ubiquitin-like proteins, and their deconjugation by ATG4s are essential for plant autophagy","volume":"16","author":"Yoshimoto","year":"2004","journal-title":"Plant Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8531","DOI":"10.1074\/jbc.H116.762948","article-title":"Zinc deficiency: An unexpected trigger for autophagy","volume":"292","author":"Ding","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5360","DOI":"10.1091\/mbc.e08-01-0080","article-title":"Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG","volume":"19","author":"Itakura","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cell.2007.05.021","article-title":"Atg8, a Ubiquitin-like Protein Required for Autophagosome Formation, Mediates Membrane Tethering and Hemifusion","volume":"130","author":"Nakatogawa","year":"2007","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrm2239","article-title":"Self-eating and self-killing: Crosstalk between autophagy and apoptosis","volume":"8","author":"Maiuri","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"883","DOI":"10.4161\/auto.19652","article-title":"Dual roles of Atg8-PE deconjugation by Atg4 in autophagy","volume":"8","author":"Yu","year":"2012","journal-title":"Autophagy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/auto.1.1.1270","article-title":"Maturation of autophagic vacuoles in Mammalian cells","volume":"1","author":"Eskelinen","year":"2005","journal-title":"Autophagy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a008813","DOI":"10.1101\/cshperspect.a008813","article-title":"Regulation and function of autophagy during cell survival and cell death","volume":"4","author":"Das","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1056\/NEJMra020831","article-title":"Inflammatory bowel disease","volume":"347","author":"Podolsky","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1177\/1756283X15592585","article-title":"Crohn\u2019s disease: A clinical update","volume":"8","author":"Ha","year":"2015","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1586\/egh.09.47","article-title":"Role of gut microbiota in Crohn\u2019s disease","volume":"3","author":"Baker","year":"2009","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8787","DOI":"10.3748\/wjg.v21.i29.8787","article-title":"Role of the normal gut microbiota","volume":"21","author":"Jandhyala","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.immuni.2007.04.014","article-title":"Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL","volume":"26","author":"He","year":"2007","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.immuni.2010.07.003","article-title":"The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut","volume":"33","author":"Suzuki","year":"2010","journal-title":"Immunity"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1128\/iai.58.9.3073-3077.1990","article-title":"Secretory immunoglobulin A carries oligosaccharide receptors for Escherichia coli type 1 fimbrial lectin","volume":"58","author":"Wold","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/mi.2009.16","article-title":"Cholera toxin B suppresses allergic inflammation through induction of secretory IgA","volume":"2","author":"Smits","year":"2009","journal-title":"Mucosal Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1097\/MIB.0000000000000085","article-title":"Role of genetics in pediatric inflammatory bowel disease","volume":"20","author":"Okou","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5813","DOI":"10.1128\/AEM.02614-10","article-title":"Adherent-Invasive Phenotype Displayed by Intestinal Pathogenic E. coli Strains from Cats, Dogs, and Swine","volume":"77","author":"Barnich","year":"2011","journal-title":"J. Appl. Environ. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1462-5822.2009.01381.x","article-title":"Crohn\u2019s disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly","volume":"12","author":"Lapaquette","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1159\/000345129","article-title":"Autophagy and Crohn\u2019s disease","volume":"5","author":"Nguyen","year":"2013","journal-title":"J. Innate Immun."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Al Nabhani, Z., Dietrich, G., Hugot, J.-P., and Barreau, F. (2017). Nod2: The intestinal gate keeper. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006177"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1080\/14728222.2017.1397627","article-title":"NOD2 and bacterial recognition as therapeutic targets for Crohn\u2019s disease AU\u2014De Bruyn, Magali","volume":"21","author":"Vermeire","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1136\/gutjnl-2011-301775","article-title":"The intermediate filament protein, vimentin, is a regulator of NOD2 activity","volume":"62","author":"Stevens","year":"2013","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nm.2069","article-title":"NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation","volume":"16","author":"Cooney","year":"2010","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: Process and function","volume":"21","author":"Mizushima","year":"2007","journal-title":"Genes Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1091\/mbc.e07-12-1257","article-title":"The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy","volume":"19","author":"Fujita","year":"2008","journal-title":"Mol. Biol. Cell."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.4049\/jimmunol.172.2.1163","article-title":"Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia","volume":"172","author":"Feng","year":"2004","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/j.1462-5822.2012.01768.x","article-title":"Defects in autophagy favour adherent-invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response","volume":"14","author":"Lapaquette","year":"2012","journal-title":"Cell Microbiol."},{"key":"ref_47","first-page":"393","article-title":"Antibiotic use and the risk of Crohn\u2019s disease","volume":"9","author":"Bernstein","year":"2013","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/ng1954","article-title":"A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1","volume":"39","author":"Hampe","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/ng2032","article-title":"Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis","volume":"39","author":"Rioux","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"Xavier","year":"2007","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1172\/JCI30587","article-title":"The fundamental basis of inflammatory bowel disease","volume":"117","author":"Strober","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1086\/510385","article-title":"The role of microbes in Crohn\u2019s disease","volume":"44","author":"Eckburg","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1136\/gutjnl-2017-314903","article-title":"Adherent-invasive Escherichia coli in inflammatory bowel disease","volume":"67","author":"Palmela","year":"2018","journal-title":"Gut"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1099\/jmm.0.000331","article-title":"An overview of the bacterial contribution to Crohn disease pathogenesis","volume":"65","author":"Alhagamhmad","year":"2016","journal-title":"J. Med. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1172\/JCI44632","article-title":"Crohn disease\u2014Associated adherent-invasive E. coli bacteria target mouse and human Peyer\u2019s patches via long polar fimbriae","volume":"121","author":"Chassaing","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dreux, N., Denizot, J., Martinez-Medina, M., Mellmann, A., Billig, M., Kisiela, D., Chattopadhyay, S., Sokurenko, E., Neut, C., and Gower-Rousseau, C. (2013). Point Mutations in FimH Adhesin of Crohn\u2019s Disease-Associated Adherent-Invasive Escherichia coli Enhance Intestinal Inflammatory Response. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003141"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/labinvest.2011.156","article-title":"Replication of Crohn\u2019s disease-associated AIEC within macrophages is dependent on TNF-alpha secretion","volume":"92","author":"Bringer","year":"2012","journal-title":"Lab. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1084\/jem.20090741","article-title":"Crohn\u2019s disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM","volume":"206","author":"Carvalho","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5529","DOI":"10.1128\/IAI.69.9.5529-5537.2001","article-title":"Adherent invasive Escherichia coli strains from patients with Crohn\u2019s disease survive and replicate within macrophages without inducing host cell death","volume":"69","author":"Glasser","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1111\/j.1365-2958.2007.05638.x","article-title":"OmpC and the sigma(E) regulatory pathway are involved in adhesion and invasion of the Crohn\u2019s disease-associated Escherichia coli strain LF82","volume":"63","author":"Rolhion","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1172\/JCI30504","article-title":"CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease","volume":"117","author":"Barnich","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/j.1462-5822.2006.00868.x","article-title":"Adherent-invasive Escherichia coli isolated from Crohn\u2019s disease patients induce granulomas in vitro","volume":"9","author":"Meconi","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.4049\/jimmunol.168.3.1328","article-title":"Induction of TNF in human alveolar macrophages as a potential evasion mechanism of virulent mycobacterium tuberculosis","volume":"168","author":"Engele","year":"2002","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e01023-15","DOI":"10.1128\/mBio.01023-15","article-title":"Targeting Mycobacterium tuberculosis Tumor Necrosis Factor Alpha-Downregulating Genes for the Development of Antituberculous Vaccines","volume":"7","author":"Olsen","year":"2016","journal-title":"J. mBio."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/S0006-2952(03)00490-8","article-title":"Regulation of proliferation, survival and apoptosis by members of the TNF superfamily","volume":"66","author":"Gaur","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cmet.2011.02.018","article-title":"The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon","volume":"13","author":"Donohoe","year":"2011","journal-title":"Cell Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1042\/BCJ20160510","article-title":"Introduction to the human gut microbiota","volume":"474","author":"Thursby","year":"2017","journal-title":"Biochem. J."},{"key":"ref_68","first-page":"185","article-title":"Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health","volume":"7","author":"Margolles","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1365-2036.2007.03562.x","article-title":"Review article: The role of butyrate on colonic function","volume":"27","author":"Hamer","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3390\/nu7010017","article-title":"The impact of diet and lifestyle on gut microbiota and human health","volume":"7","author":"Conlon","year":"2014","journal-title":"Nutrients"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jubelin, G., Desvaux, M., Sch\u00fcller, S., Etienne-Mesmin, L., Muniesa, M., and Blanquet-Diot, S. (2018). Modulation of Enterohaemorrhagic Escherichia coli Survival and Virulence in the Human Gastrointestinal Tract. Microorganisms, 6.","DOI":"10.3390\/microorganisms6040115"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1038\/cti.2016.17","article-title":"Regulation of immune cell function by short-chain fatty acids","volume":"5","author":"Fachi","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1099\/mic.0.023499-0","article-title":"Regulation of virulence by butyrate sensing in enterohaemorrhagic Escherichia coli","volume":"155","author":"Nakanishi","year":"2009","journal-title":"Microbiology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6115","DOI":"10.1128\/IAI.68.11.6115-6126.2000","article-title":"The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli","volume":"68","author":"Elliott","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/ajg.2008.168","article-title":"Management of Crohn\u2019s disease in adults","volume":"104","author":"Lichtenstein","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1056\/NEJMra1100030","article-title":"Genomics and the multifactorial nature of human autoimmune disease","volume":"365","author":"Cho","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"208073","DOI":"10.1155\/2013\/208073","article-title":"Practical medical management of Crohn\u2019s disease","volume":"2013","author":"Baran","year":"2013","journal-title":"ISRN Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11938-005-0014-z","article-title":"The role of antibiotics in inflammatory bowel disease","volume":"8","author":"Thukral","year":"2005","journal-title":"Curr. Treat. Options Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1053\/j.gastro.2006.01.048","article-title":"American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease","volume":"130","author":"Lichtenstein","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1177\/1756283X11413315","article-title":"Certolizumab pegol for the treatment of Crohn\u2019s disease","volume":"4","author":"Schreiber","year":"2011","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/ajg.2018.27","article-title":"ACG Clinical Guideline: Management of Crohn\u2019s Disease in Adults","volume":"113","author":"Lichtenstein","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1136\/gut.2008.157297","article-title":"Use of sirolimus (rapamycin) to treat refractory Crohn\u2019s disease","volume":"57","author":"Massey","year":"2008","journal-title":"Gut"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.crohns.2014.08.014","article-title":"The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children","volume":"8","author":"Kiparissi","year":"2014","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1111\/j.1572-0241.2008.02024.x","article-title":"A multicenter, randomized, double-blind trial of everolimus versus azathioprine and placebo to maintain steroid-induced remission in patients with moderate-to-severe active Crohn\u2019s disease","volume":"103","author":"Reinisch","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nrgastro.2013.66","article-title":"Autophagy: A new target or an old strategy for the treatment of Crohn\u2019s disease?","volume":"10","author":"Nys","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Wu, Y.C., Wang, X.J., Yu, L., Chan, F.K., Cheng, A.S., Yu, J., Sung, J.J., Wu, W.K., and Cho, C.H. (2012). Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037572"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/sj.bjp.0707193","article-title":"Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis","volume":"150","author":"Fiorucci","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/s41598-017-01174-9","article-title":"Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"20511","DOI":"10.1074\/jbc.M114.632257","article-title":"Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus","volume":"290","author":"Tsuboi","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1038\/leusup.2012.25","article-title":"Inhibition of autophagy with clarithromycin: A new strategy to enhance sensitivity of CML stem cells to tyrosine kinase inhibitors","volume":"1","author":"Carella","year":"2012","journal-title":"Leuk. Suppl."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2147\/CEG.S110546","article-title":"Next generation of biologics for the treatment of Crohn\u2019s disease: an evidence-based review on ustekinumab","volume":"10","author":"Somers","year":"2017","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.3748\/wjg.v24.i17.1868","article-title":"Anti-integrin therapy for inflammatory bowel disease","volume":"24","author":"Park","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.2174\/138920012803341366","article-title":"Is the autophagy induced by thiopurines beneficial or deleterious?","volume":"13","author":"Guijarro","year":"2012","journal-title":"Curr. Drug Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1055\/s-2007-991026","article-title":"Medical management of Crohn\u2019s disease","volume":"20","author":"Feldman","year":"2007","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1111\/febs.13771","article-title":"Death in the intestinal epithelium-basic biology and implications for inflammatory bowel disease","volume":"283","author":"Blander","year":"2016","journal-title":"FEBS J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1007\/s10620-012-2133-4","article-title":"Intestinal epithelial cells with impaired autophagy lose their adhesive capacity in the presence of TNF-alpha","volume":"57","author":"Saito","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_97","first-page":"Cd008870","article-title":"Aminosalicylates for induction of remission or response in Crohn\u2019s disease","volume":"7","author":"Lim","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1177\/1756283X11405250","article-title":"Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease","volume":"4","author":"Williams","year":"2011","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/ecco-jcc\/jjw127","article-title":"Inflammatory Bowel Disease Drugs: A Focus on Autophagy","volume":"11","author":"Hooper","year":"2016","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1136\/gut.38.1.115","article-title":"5-Aminosalicylic acid inhibits the impaired epithelial barrier function induced by gamma interferon","volume":"38","author":"Merrett","year":"1996","journal-title":"Gut"},{"key":"ref_101","first-page":"9","article-title":"Five-Aminosalicylic Acid: An Update for the Reappraisal of an Old Drug","volume":"2015","author":"Perrotta","year":"2015","journal-title":"J. Gastroenterol. Res. Pract."},{"key":"ref_102","first-page":"399","article-title":"5-ASA abrogates T-cell proliferation by blocking interleukin-2 production in peripheral blood mononuclear cells","volume":"272","author":"Stevens","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1053\/j.gastro.2006.08.035","article-title":"Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon","volume":"131","author":"Schicho","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/978-3-319-18144-8_11","article-title":"H2S and Pain: A Novel Aspect for Processing of Somatic, Visceral and Neuropathic Pain Signals","volume":"230","author":"Terada","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/sj.bjp.0704858","article-title":"The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a physiological role to control intestinal contractility","volume":"137","author":"Teague","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.tips.2007.09.003","article-title":"Hydrogen sulfide-releasing anti-inflammatory drugs","volume":"28","author":"Wallace","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.freeradbiomed.2006.12.011","article-title":"Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative","volume":"42","author":"Li","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1093\/ibd\/izy116","article-title":"Iron Sequestration in Microbiota Biofilms As A Novel Strategy for Treating Inflammatory Bowel Disease","volume":"24","author":"Motta","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4291\/wjgp.v2.i6.114","article-title":"Gene and cell therapy based treatment strategies for inflammatory bowel diseases","volume":"2","author":"Majowicz","year":"2011","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1023\/A:1005537411244","article-title":"Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: Randomized, double-blind, placebo-controlled pilot study","volume":"45","author":"Vernia","year":"2000","journal-title":"Dig. Dis. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/j.1365-2036.2005.02639.x","article-title":"Oral butyrate for mildly to moderately active Crohn\u2019s disease","volume":"22","author":"Morera","year":"2005","journal-title":"Aliment. Pharmacol. Ther."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/6\/224\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:28Z","timestamp":1760187268000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/6\/224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,29]]},"references-count":111,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["medicina55060224"],"URL":"https:\/\/doi.org\/10.3390\/medicina55060224","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,29]]}}}