{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:32:24Z","timestamp":1767904344352,"version":"3.49.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["F22YY8109033"],"award-info":[{"award-number":["F22YY8109033"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2020R1l1A1A01052277"],"award-info":[{"award-number":["2020R1l1A1A01052277"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>CRISPR-Cas9-mediated leptin (<jats:italic>Lep<\/jats:italic>) knockout (KO) mice exhibited prominent phenotypes for constipation, even though they were not compared with other model animals. This study compared the stool excretion, gastrointestinal motility, histological structure, mucin secretion, and enteric nerve function in <jats:italic>Lep<\/jats:italic> KO and high fat diet (HFD)-treated mice to determine if there were differences in their phenotypes for constipation. Most obesity phenotypes, including fat weight, adipocyte size, expression of lipolytic proteins (HSL, perilipin, and ATGL), and glucose concentrations, were detected similarly in the <jats:italic>Lep<\/jats:italic> KO and HFD-treated mice. They showed a similar decrease in the excretion parameters, including the stool number, weight, and water content, while the same pattern was detected in the gastrointestinal motility and intestinal length. A similar decrease in the mucosal layer thickness, muscle thickness, ability for mucin secretion, and expression of water channel (aquaporin 3 and 8) genes was detected in the mid-colon of the <jats:italic>Lep<\/jats:italic> KO and HFD-treated mice, but the alteration rate in some levels was greater in the HFD-treated group than the <jats:italic>Lep<\/jats:italic> KO mice. On the other hand, the levels of c-kit, nNOS, NSE, and PGP9.5 expression for the enteric neurons and intestitial cells of Cajal (ICC) were remarkably lower in the mid-colon of the HFD-treated mice than in the <jats:italic>Lep<\/jats:italic> KO mice, but the level of most proteins in both groups remained lower than those in the control group. A similar alteration pattern in the expression of muscarinic acetylcholine receptors (mAChRs) and serotonin receptors was detected in the <jats:italic>Lep<\/jats:italic> KO and HFD-treated mice. These results suggest that most phenotypes for obesity-induced constipation were similarly detected in the <jats:italic>Lep<\/jats:italic> KO and HFD-treated mice, but there was a difference in the regulatory function of the enteric nervous system (ENS).<\/jats:p>","DOI":"10.1371\/journal.pone.0276445","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T18:49:47Z","timestamp":1671734987000},"page":"e0276445","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Similarities and differences in constipation phenotypes between Lep knockout mice and high fat diet-induced obesity mice"],"prefix":"10.1371","volume":"17","author":[{"given":"Ji Eun","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayun","family":"Seol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun Ju","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You Jeong","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Jeong","family":"Roh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Jin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-1725","authenticated-orcid":true,"given":"Dae Youn","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"pone.0276445.ref001","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1542\/peds.101.S2.518","article-title":"Health consequences of obesity in youth: childhood predictors of adult disease","volume":"101","author":"WH Dietz","year":"1998","journal-title":"Pediatrics"},{"key":"pone.0276445.ref002","doi-asserted-by":"crossref","first-page":"e377","DOI":"10.1542\/peds.2005-0490","article-title":"Increased prevalence of obesity in children with functional constipation evaluated in an academic medical center","volume":"116","author":"DS Pashankar","year":"2005","journal-title":"Pediatrics"},{"key":"pone.0276445.ref003","first-page":"151","article-title":"Obesity and functional constipation; a community-based study in Iran.","volume":"18","author":"MA Pourhoseingholi","year":"2009","journal-title":"J Gastrointestin Liver Dis"},{"key":"pone.0276445.ref004","first-page":"2384","article-title":"Constipation and obesity: a statistical analysis","volume":"57","author":"P Pecora","year":"1981","journal-title":"Boll Soc Ital Biol Sper"},{"key":"pone.0276445.ref005","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jpeds.2004.04.022","article-title":"Increased prevalence of constipation and fecal soiling in a population of obese children","volume":"145","author":"L Fishman","year":"2004","journal-title":"J Pediatr"},{"key":"pone.0276445.ref006","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1177\/014860710603000281","article-title":"Chronic constipation in overweight children.","volume":"30","author":"S Misra","year":"2006","journal-title":"JPEN J Parenter Enteral Nutr"},{"key":"pone.0276445.ref007","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1113\/JP273269","article-title":"Western diet induces colonic nitrergic myenteric neuropathy and dysmotility in mice via saturated fatty acid- and lipopolysaccharide-induced TLR4 signalling","volume":"595","author":"F Reichardt","year":"2017","journal-title":"J Physiol"},{"key":"pone.0276445.ref008","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1007\/s10620-019-05954-3","article-title":"High-fat diet causes constipation in mice via decreasing colonic mucus","volume":"65","author":"R Mukai","year":"2020","journal-title":"Dig Dis Sci"},{"key":"pone.0276445.ref009","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.1038\/s41598-021-92459-7","article-title":"Rhamnan sulphate from green algae Monostroma nitidum improves constipation with gut microbiome alteration in double-blind placebo-controlled trial","volume":"11","author":"Y Shimada","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0276445.ref010","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.3945\/jn.111.144246","article-title":"Consumption of a resistant protein, sericin, elevates fecal immunoglobulin A, mucins, and cecal organic acids in rats fed a high-fat diet","volume":"141","author":"Y Okazaki","year":"2011","journal-title":"J Nutr"},{"key":"pone.0276445.ref011","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1038\/oby.2004.213","article-title":"Alterations of gastrointestinal motility in obesity","volume":"12","author":"J Xing","year":"2004","journal-title":"Obes Res"},{"key":"pone.0276445.ref012","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1136\/gut.34.1.129","article-title":"Contractile activity of the human colon: lessons from 24-hour studies","volume":"34","author":"G Bassotti","year":"1993","journal-title":"Gut"},{"key":"pone.0276445.ref013","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/S0016-5085(85)80067-6","article-title":"Diurnal changes in myoelectric spiking activity of the human colon","volume":"88","author":"J Frexinos","year":"1985","journal-title":"Gastroenterology"},{"key":"pone.0276445.ref014","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1136\/gut.46.2.205","article-title":"Effects of fat and carbohydrate meals on colonic motor response","volume":"46","author":"SS Rao","year":"2000","journal-title":"Gut"},{"key":"pone.0276445.ref015","doi-asserted-by":"crossref","first-page":"G382","DOI":"10.1152\/ajpgi.90286.2008","article-title":"High body mass alters colonic sensory-motor function and transit in humans","volume":"295","author":"S Delgado-Aros","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"pone.0276445.ref016","doi-asserted-by":"crossref","first-page":"G424","DOI":"10.1152\/ajpgi.00048.2012","article-title":"Serotonin availability in rat colon is reduced during a Western diet model of obesity","volume":"303","author":"RL Bertrand","year":"2012","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"pone.0276445.ref017","doi-asserted-by":"crossref","first-page":"9464","DOI":"10.3390\/ijms21249464","article-title":"Molecular characterization of constipation disease as novel phenotypes in CRISPR-Cas9-Generated leptin knockout mice with obesity.","volume":"21","author":"JE Kim","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0276445.ref018","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1538\/expanim.17-0123","article-title":"CRISPR-Cas9-mediated generation of obese and diabetic mouse models","volume":"67","author":"JI Roh","year":"2018","journal-title":"Exp Anim"},{"key":"pone.0276445.ref019","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.3390\/ijms22115845","article-title":"Novel characterization of constipation phenotypes in ICR mice orally administrated with polystyrene microplastics.","volume":"22","author":"YJ Choi","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pone.0276445.ref020","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"key":"pone.0276445.ref021","doi-asserted-by":"crossref","first-page":"e10631","DOI":"10.1097\/MD.0000000000010631","article-title":"Chronic constipation. A review of literature.","volume":"97","author":"M Forootan","year":"2018","journal-title":"Medicine"},{"key":"pone.0276445.ref022","doi-asserted-by":"crossref","first-page":"16B","DOI":"10.1155\/2011\/169319","article-title":"The pathophysiology of chronic constipation","volume":"25","author":"CN Andrews","year":"2011","journal-title":"Can J Gastroenterol"},{"key":"pone.0276445.ref023","doi-asserted-by":"crossref","first-page":"197636","DOI":"10.1155\/2011\/197636","article-title":"Biology of obesity: lessons from animal models of obesity","volume":"2011","author":"K Kanasaki","year":"2011","journal-title":"J Biomed Biotechnol"},{"key":"pone.0276445.ref024","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/oxfordjournals.jhered.a106073","article-title":"Obese, a new mutation in the house mouse","volume":"41","author":"AM Ingalls","year":"1950","journal-title":"J Hered"},{"key":"pone.0276445.ref025","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/372425a0","article-title":"Positional cloning of the mouse obese gene and its human homologue","volume":"372","author":"Y Zhang","year":"1994","journal-title":"Nature"},{"key":"pone.0276445.ref026","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0092-8674(00)81294-5","article-title":"Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db\/db mice","volume":"84","author":"H Chen","year":"1996","journal-title":"Cell"},{"key":"pone.0276445.ref027","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/379632a0","article-title":"Abnormal splicing of the leptin receptor in diabetic mice","volume":"379","author":"GH Lee","year":"1996","journal-title":"Nature"},{"key":"pone.0276445.ref028","first-page":"R1025","article-title":"Dietary obesity in nine inbred mouse strains","volume":"262","author":"DB West","year":"1992","journal-title":"Am J Physiol Cell Physiol"},{"key":"pone.0276445.ref029","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.physbeh.2004.02.006","article-title":"Genetic vulnerability to diet-induced obesity in the C57BL\/6J mouse: physiological and molecular characteristics","volume":"81","author":"S Collins","year":"2004","journal-title":"Physiol Behav"},{"key":"pone.0276445.ref030","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1538\/expanim.17-0123","article-title":"CRISPR-Cas9-mediated generation of obese and diabetic mouse models","volume":"67","author":"JI Roh","year":"2018","journal-title":"Exp Anim"},{"key":"pone.0276445.ref031","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1007\/s00125-015-3656-y","article-title":"Metabolite profiling in plasma and tissues of ob\/ob and db\/db mice identifies novel markers of obesity and type 2 diabetes","volume":"58","author":"P Giesbertz","year":"2015","journal-title":"Diabetologia"},{"key":"pone.0276445.ref032","first-page":"5587848","article-title":"Antiobesity and Antidiabetic Effects of Portulaca oleracea Powder Intake in High-Fat Diet-Induced Obese C57BL\/6 Mice","volume":"2021","author":"JH Jung","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"pone.0276445.ref033","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejphar.2015.11.045","article-title":"Emodin improves lipid and glucose metabolism in high fat diet-induced obese mice through regulating SREBP pathway","volume":"770","author":"J Li","year":"2016","journal-title":"Eur J Pharmacol"},{"key":"pone.0276445.ref034","doi-asserted-by":"crossref","first-page":"19556","DOI":"10.1038\/s41598-019-55987-x","article-title":"Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL\/6 mice.","volume":"9","author":"P Lang","year":"2019","journal-title":"Scientific Reports"},{"key":"pone.0276445.ref035","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jdiacomp.2015.09.018","article-title":"Gender-specific differences in diabetic neuropathy in BTBR ob\/ob mice","volume":"30","author":"PD O\u2019Brien","year":"2016","journal-title":"J Diabetes Complications"},{"key":"pone.0276445.ref036","doi-asserted-by":"crossref","first-page":"e75998","DOI":"10.1371\/journal.pone.0075998","article-title":"Gender-specific metabolomic profiling of obesity in leptin-deficient ob\/ob mice by 1H NMR spectroscopy","volume":"8","author":"EY Won","year":"2013","journal-title":"PLoS One"},{"key":"pone.0276445.ref037","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/oby.2009.273","article-title":"Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice.","volume":"18","author":"LL Hwang","year":"2010","journal-title":"Obesity"},{"key":"pone.0276445.ref038","doi-asserted-by":"crossref","first-page":"dmm048909","DOI":"10.1242\/dmm.048909","article-title":"Sex differences in insulin resistance, but not peripheral neuropathy, in a diet-induced prediabetes mouse model.","volume":"14","author":"SE Elzinga","year":"2021","journal-title":"Dis Model Mech."},{"key":"pone.0276445.ref039","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1113\/EP085427","article-title":"Sex-related differences in small intestinal transit and serotonin dynamics in high-fat-diet-induced obesity in mice","volume":"101","author":"M France","year":"2016","journal-title":"Exp Physiol"},{"key":"pone.0276445.ref040","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/1472-6882-13-333","article-title":"Aqueous extracts of Liriope platyphylla induced significant laxative effects on loperamide-induced constipation of SD rats","volume":"13","author":"JE Kim","year":"2013","journal-title":"BMC Complement Altern Med"},{"key":"pone.0276445.ref041","doi-asserted-by":"crossref","first-page":"e0161144","DOI":"10.1371\/journal.pone.0161144","article-title":"Gallotannin-enriched extract isolated from Galla Rhois may be a functional candidate with laxative effects for treatment of loperamide-induced constipation of SD rats","volume":"11","author":"JE Kim","year":"2016","journal-title":"PLoS ONE"},{"key":"pone.0276445.ref042","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12876-017-0576-y","article-title":"Uridine stimulate laxative effect in the loperamide-induced constipation of SD rats through regulation of the mAChRs signaling pathway and mucin secretion","volume":"17","author":"JE Kim","year":"2017","journal-title":"BMC Gastroenterol"},{"key":"pone.0276445.ref043","doi-asserted-by":"crossref","first-page":"223","DOI":"10.5625\/lar.2018.34.4.223","article-title":"Regulation of gastrointestinal hormones during laxative activity of gallotannin-enriched extract isolated from Galla Rhois in loperamide-induced constipation of SD rats","volume":"34","author":"JE Kim","year":"2018","journal-title":"Lab Anim Res"},{"key":"pone.0276445.ref044","doi-asserted-by":"crossref","first-page":"896","DOI":"10.3390\/molecules24050896","article-title":"Laxative effect of spicatoside A by cholinergic regulation of enteric nerve in loperamide-induced constipation: ICR mice model","volume":"24","author":"JE Kim","year":"2019a","journal-title":"Molecules"},{"key":"pone.0276445.ref045","doi-asserted-by":"crossref","first-page":"e0215205","DOI":"10.1371\/journal.pone.0215205","article-title":"Constipation in Tg2576 mice model for Alzheimer\u2019s disease associated with dysregulation of mechanism involving the mAChR signaling pathway and ER stress response.","volume":"14","author":"JE Kim","year":"2019b","journal-title":"PLoS One"},{"key":"pone.0276445.ref046","doi-asserted-by":"crossref","first-page":"e0246363","DOI":"10.1371\/journal.pone.0246363","article-title":"Antioxidant activity and laxative effects of tannin-enriched extract of Ecklonia cava in loperamide-induced constipation of SD rats","volume":"16","author":"JE Kim","year":"2021","journal-title":"PLoS ONE"},{"key":"pone.0276445.ref047","first-page":"e21221","article-title":"Deficiency of complement component 3 may be linked to the development of constipation in FVB\/N-C3(em1Hlee) \/Korl mice","volume":"35","author":"JW Park","year":"2021","journal-title":"FASEB J"},{"key":"pone.0276445.ref048","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1471-230X-13-52","article-title":"Laxative effects of Salecan on normal and two models of experimental constipated mice","volume":"13","author":"M Zhou","year":"2013","journal-title":"BMC Gastroenterol"},{"key":"pone.0276445.ref049","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1111\/nmo.12387","article-title":"Circular muscle contraction in the mice rectum plays a key role in morphine-induced constipation","volume":"26","author":"H Ono","year":"2014","journal-title":"Neurogastroenterol Motil"},{"key":"pone.0276445.ref050","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1124\/jpet.113.204313","article-title":"Mechanisms that underlie \u03bc-opioid receptor agonist-induced constipation: differential involvement of \u03bc-opioid receptor sites and responsible regions","volume":"347","author":"T Mori","year":"2013","journal-title":"J Pharmacol Exp Ther"},{"key":"pone.0276445.ref051","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1097\/YIC.0b013e32835b08d2","article-title":"In a randomized placebo-controlled add-on study orlistat significantly reduced clozapine-induced constipation","volume":"28","author":"E Chukhin","year":"2013","journal-title":"Int Clin Psychopharmacol"},{"key":"pone.0276445.ref052","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.3892\/mmr.2015.3737","article-title":"Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon-induced constipated mice","volume":"12","author":"X Zhao","year":"2015","journal-title":"Mol Med Rep"},{"key":"pone.0276445.ref053","doi-asserted-by":"crossref","first-page":"i67","DOI":"10.1136\/gut.51.suppl_1.i67","article-title":"Role of visceral sensitivity in the pathophsiololgy of irritable bowel syndrome","volume":"51","author":"M. Delvaux","year":"2002","journal-title":"Gut"},{"key":"pone.0276445.ref054","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1111\/nmo.12365","article-title":"Markers for visceral hypersensitivity in patients with irritable bowel syndrome.","volume":"26","author":"S Ludidi","year":"2014","journal-title":"Neurogastroenterol Motil."},{"key":"pone.0276445.ref055","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/1319-3767.105909","article-title":"The importance of interstitial cells of cajal in the gastrointestinal tract","volume":"19","author":"OA Al-Shboul","year":"2013","journal-title":"Saudi J Gastroenterol"},{"key":"pone.0276445.ref056","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/modpathol.3800748","article-title":"Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation.","volume":"20","author":"G Bassotti","year":"2007","journal-title":"Mod Pathol"},{"key":"pone.0276445.ref057","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1111\/j.1440-1746.2005.03809.x","article-title":"Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon","volume":"20","author":"JI Lee","year":"2005","journal-title":"J Gastroenterol Hepatol"},{"key":"pone.0276445.ref058","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1006\/clin.1995.1047","article-title":"Decreased levels of complement receptor 1 (CD35) on B lymphocytes in persons with HIV infection.","volume":"75","author":"LG Munson","year":"1995","journal-title":"Clin Immunol Immunopathol"},{"key":"pone.0276445.ref059","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1046\/j.1365-2249.1996.17721.x","article-title":"Distribution of activated complement, C3b, and its degraded fragments, iC3b\/C3dg, in the colonic mucosa of ulcerative colitis (UC).","volume":"104","author":"T Ueki","year":"1996","journal-title":"Clin Exp Immunol"},{"key":"pone.0276445.ref060","first-page":"567","article-title":"Primary gastrointestinal motility disorders in childhood.","volume":"64","author":"AK Yeung","year":"2012","journal-title":"Minerva Pediatr"},{"key":"pone.0276445.ref061","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1053\/j.gastro.2020.12.062","article-title":"miR-10b-5p Rescues Diabetes and Gastrointestinal Dysmotility","volume":"160","author":"R Singh","year":"2021","journal-title":"Gastroenterology"},{"key":"pone.0276445.ref062","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.3892\/mmr.2014.2009","article-title":"Component analysis of Pu-erh and its anti-constipation effects","volume":"9","author":"G Li","year":"2014","journal-title":"Mol Med Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276445","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T18:50:16Z","timestamp":1671735016000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276445"}},"subtitle":[],"editor":[{"given":"Seungil","family":"Ro","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,22]]},"references-count":62,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0276445","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,22]]}}}