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Zhao M, Lei Y, Wang M, Chen Y, Hou S, Dai X, Gao D, Liu Y, Mazet B, Sha L. Carbon monoxide produced by HO-1 upregulation is the main factor behind the abnormal motility seen in experimental ulcerative colitis in mice. Am J Physiol Gastrointest Liver Physiol 2025; 328:G311-G322. [PMID: 39925143 DOI: 10.1152/ajpgi.00179.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/11/2023] [Accepted: 01/15/2025] [Indexed: 02/11/2025]
Abstract
The colonic motility is altered in patients with ulcerative colitis (UC), but the mechanism is not clear. Carbon monoxide (CO) is the molecule regulating the resting membrane potential (RMP) gradient across colonic smooth muscle wall. Changes in RMP will affect the contractility of smooth muscle. In this study, we investigated the altered colonic motility in dextran sodium sulfate-induced UC mice and the role of CO. The results showed that in the UC group, the frequency of spontaneous colonic contractions was increased while the AUC was decreased compared with the control group. HO-1-, but not HO-2-, positive cells were increased in the colonic smooth muscle wall of the UC group. These HO-1-positive cells were mainly in the myenteric plexus and PGP9.5 positive, suggesting neuronal overproduction of CO. The RMP of circular smooth muscle cells (SMCs) in the colon of UC group was hyperpolarized compared with that of control group. In control group, application of CORM-3, a CO donor, altered colonic spontaneous contractions by increasing their frequency and decreasing amplitude. In the UC group, ZnPPIX, a HO-1 inhibitor, reduced the frequency and increased the amplitude. CORM-3 hyperpolarized the RMP of colonic SMCs and abolished its gradient in the control group, while ZnPPIX depolarized the RMP of colonic SMCs and restored its gradient in the UC group. CO produced by HO-1 upregulation is the main factor behind the altered colonic motility seen in UC mice. CO is a potential candidate as a therapeutic target for patients with UC who suffer from abnormal colonic motility.NEW & NOTEWORTHY Carbon monoxide (CO) produced by HO-1 upregulation in myenteric plexus is the main factor that abolishes the RMP gradient across colonic muscle wall causing the altered colonic motility seen in experimental ulcerative colitis (UC) mice. CO is a potential candidate as a therapeutic target for patients with UC who suffer from abnormal colonic motility.
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MESH Headings
- Animals
- Colitis, Ulcerative/physiopathology
- Colitis, Ulcerative/chemically induced
- Colitis, Ulcerative/metabolism
- Colitis, Ulcerative/enzymology
- Carbon Monoxide/metabolism
- Gastrointestinal Motility/drug effects
- Gastrointestinal Motility/physiology
- Up-Regulation
- Colon/physiopathology
- Colon/drug effects
- Colon/metabolism
- Colon/innervation
- Mice
- Male
- Heme Oxygenase-1/metabolism
- Muscle, Smooth/metabolism
- Muscle, Smooth/physiopathology
- Muscle, Smooth/drug effects
- Dextran Sulfate
- Disease Models, Animal
- Myocytes, Smooth Muscle/metabolism
- Myocytes, Smooth Muscle/drug effects
- Mice, Inbred C57BL
- Muscle Contraction/drug effects
- Myenteric Plexus/metabolism
- Organometallic Compounds/pharmacology
- Membrane Proteins
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Affiliation(s)
- Mengchao Zhao
- Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan, China
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Yaru Lei
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Mengyuan Wang
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Yixin Chen
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Shaozhang Hou
- Department of Pathology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Xinyuan Dai
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Di Gao
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Yudan Liu
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Bruno Mazet
- Institute of NeuroPhysiopathology (INP)-UMR CNRS 7051, Aix-Marseille University, Marseilles, France
| | - Lei Sha
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
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Dong XQ, Zhang YH, Luo J, Li MJ, Ma LQ, Qi YT, Miao YL. Keratin 1 modulates intestinal barrier and immune response via kallikrein kinin system in ulcerative colitis. World J Gastroenterol 2025; 31:102070. [PMID: 39958441 PMCID: PMC11752705 DOI: 10.3748/wjg.v31.i6.102070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 12/19/2024] [Indexed: 01/10/2025] Open
Abstract
BACKGROUND External factors in ulcerative colitis (UC) exacerbate colonic epithelial permeability and inflammatory responses. Keratin 1 (KRT1) is crucial in regulating these alterations, but its specific role in the progression of UC remains to be fully elucidated. AIM To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC. METHODS A KRT1 antibody concentration gradient test, along with a dextran sulfate sodium (DSS)-induced animal model, was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system (KKS) and the cleavage of bradykinin (BK)/high molecular weight kininogen (HK) in UC. RESULTS Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation, induced apoptosis, reduced HK expression, and increased BK expression. It further downregulated intestinal barrier proteins, including occludin, zonula occludens-1, and claudin, and negatively impacted the coagulation factor XII. These changes led to enhanced activation of BK and HK cleavage, thereby intensifying KKS-mediated inflammation in UC. In the DSS-induced mouse model, administration of KRT1 antibody mitigated colonic injury, increased colon length, alleviated weight loss, and suppressed inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-α. It also facilitated repair of the intestinal barrier, reducing DSS-induced injury. CONCLUSION KRT1 inhibits BK expression, suppresses inflammatory cytokines, and enhances markers of intestinal barrier function, thus ameliorating colonic damage and maintaining barrier integrity. KRT1 is a viable therapeutic target for UC.
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Affiliation(s)
- Xiang-Qian Dong
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Ying-Hui Zhang
- Department of Gastroenterology, Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan Province, China
| | - Juan Luo
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Mao-Juan Li
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Lan-Qing Ma
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Ya-Ting Qi
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Ying-Lei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
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Zhang M, Jin Y, Wu T, Zhao Q, Li H, Zhang H, Lu Y, Chen S, Liu T, Gong Z, Wang D, Liu W. Metabolomics combined with network pharmacology revealed a paradigm for determining the mechanism underlying the metabolic action of Gegen Qinlian Decoction amelioration of ulcerative colitis in mice. J Chromatogr B Analyt Technol Biomed Life Sci 2025; 1250:124352. [PMID: 39571215 DOI: 10.1016/j.jchromb.2024.124352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 09/10/2024] [Accepted: 10/26/2024] [Indexed: 12/09/2024]
Abstract
Ulcerative colitis (UC) is a common disease of the digestive system that is challenging to treat. Gegen Qinlian Decoction (GQD), which is an ancient classic formula in Chinese medicine, is effective at alleviating the symptoms of UC, but comprehensive research on its mechanism of action has not been performed. Here, we explored the material basis and potential molecular mechanism underlying GQD-mediated protection against UC by integrated metabolomics and network pharmacology. First, differentially expressed metabolites were screened and identified via a metabolomics approach, and the metabolic pathway was analyzed via MetaboAnalyst. Second, a protein-protein interaction (PPI) network was constructed to identify hub genes that encode metabolic enzymes. Third, the differentially expressed metabolites were used to construct a compound-reaction-enzyme-gene network. Finally, the metabolites were compared with relevant active components for molecular docking, molecular dynamics (MD) simulation, and verification experiment. GQD intervention alleviated UC in mice and significantly inhibited metabolic dysfunction in mice with UC; specifically, GQD reversed the abnormal changes in metabolites in the colon and serum, and regulated the arachidonic acid metabolism, tryptophan metabolism, glycerophospholipid metabolism, and purine metabolism pathways. Further literature review and molecular docking analysis with targeted MD simulation and Poisson-Boltzmann surface area (MM-PBSA) analysis were performed, revealing that GQD may inhibit the disruption of arachidonic acid metabolism and tryptophan metabolism by suppressing PTGS2 and CYP450 protein expression; these results were verified by qRT-PCR, WB, and surface plasmon resonance (SPR) assays. Our experiments indicated that GQD alleviated UC in mice by systematically regulating arachidonic acid metabolism and tryptophan metabolism, supporting further research and the development of GQD as a novel drug for ameliorating UC.
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Affiliation(s)
- Ming Zhang
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, China; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; Natural Products Research Center of Guizhou Province, Guiyang 550014, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China
| | - Yang Jin
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China
| | - Tiantai Wu
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, China; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China
| | - Qing Zhao
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China
| | - Herong Li
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China
| | - Huan Zhang
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China
| | - Yuan Lu
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China
| | - Shuaishuai Chen
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China
| | - Ting Liu
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China
| | - Zipeng Gong
- Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China
| | - Daoping Wang
- Natural Products Research Center of Guizhou Province, Guiyang 550014, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China
| | - Wen Liu
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, China; Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China.
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Chew DCH, Khoo XH, Lee TS, Chin KY, Raja Ali RA, Muhammad Nawawi KN, Wan Ibrahim NR, Hilmi I. A Systematic Review on the Increasing Incidence of Inflammatory Bowel Disease in Southeast Asia: Looking Beyond the Urbanization Phenomenon. Inflamm Bowel Dis 2024; 30:1566-1578. [PMID: 37935628 DOI: 10.1093/ibd/izad189] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Indexed: 11/09/2023]
Abstract
The incidence of inflammatory bowel disease (IBD) has been increasing in Southeast Asia (SEA) in tandem with its economic growth and urbanization over the past 2 decades. Specific characteristics of IBD in SEA are similar to East Asia and the West, such as the declining ratio of ulcerative colitis to Crohn's disease. However, exceptionally low familial aggregation is seen. Smoking is also not a common risk factor in patients with Crohn's disease. The incidence of perianal disease is higher in SEA than in Australia and is comparable to the West. In a multiracial population, such as Singapore and Malaysia, Indians have the highest incidence and prevalence rates, which are likely to be due to important putative mutations. For instance, a higher frequency of the NOD2 predisposing mutation SNP5 and IBD risk allele IGR2198a and IGR2092a were found in Indians. Although differences in the genetic constitution play an important role in the epidemiology and prognosis of IBD in SEA, the emergence of this disease offers a unique opportunity to identify potential exposomes that contribute to its pathogenesis.
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Affiliation(s)
- Deborah Chia Hsin Chew
- Gastroenterology and hepatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Xin-Hui Khoo
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Tiong See Lee
- Department of Gastroenterology and Hepatology, Selayang Hospital, Kuala Lumpur, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Raja Affendi Raja Ali
- Gastroenterology and hepatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Khairul Najmi Muhammad Nawawi
- Gastroenterology and hepatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | | | - Ida Hilmi
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Dong S, Xiang X, Zhang Y, Liu R, Ye L, Cao Q. Differences of clinical phenotype between familial and sporadic Crohn's disease in East China. Int J Colorectal Dis 2024; 39:107. [PMID: 39001900 PMCID: PMC11246305 DOI: 10.1007/s00384-024-04688-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/09/2024] [Indexed: 07/15/2024]
Abstract
PURPOSE Family history is one of the strongest risk factors for inflammatory bowel diseases (IBD) while studies about the clinical phenotype of familial IBD are limited. This study aimed to compare the phenotypic features of familial Crohn's disease (CD) with sporadic CD. METHODS Familial CD was defined as CD patients having one or more first, second, third, fourth degree, or above relatives with CD. Sporadic CD patients hospitalized during the same period were matched 1:3 by age and gender. Differences in clinical characteristics, phenotype distribution, extraintestinal manifestations, and complications at diagnosis, as well as treatment regimen and surgery, were compared between familial and sporadic CD. RESULTS The familial CD was associated with a higher rate of past appendectomy history (P = 0.009), more intestinal perforation at onset (P = 0.012), more MRI results of anal lesion (P = 0.023), and gastrointestinal perforation (P = 0.040) at diagnosis, higher rate of past intestinal surgery history (P = 0.007), more number of intestinal surgeries (P = 0.037), longer duration of follow-up (P = 0.017), lower rate of taking biologicals for current maintenance (P = 0.043), lower tendency to upgrade to biologicals during follow-up (P = 0.013), higher possibility to experience gastrointestinal obstruction (P = 0.047), and abdominal abscess during follow-up (P = 0.045). CONCLUSION Familial CD is associated with a more aggressive clinical phenotype.
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Affiliation(s)
- Siyuan Dong
- Department of Gastroenterology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Inflammatory Bowel Disease Center, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Institute of Gastroenterology, Zhejiang University, Zhejiang Province, Hangzhou, 310016, China
| | - Xiaoxia Xiang
- Department of Gastroenterology, Haiyan People's Hospital, Jiaxing, 314300, China
| | - Yu Zhang
- Department of Gastroenterology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Inflammatory Bowel Disease Center, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Institute of Gastroenterology, Zhejiang University, Zhejiang Province, Hangzhou, 310016, China
| | - Rongbei Liu
- Department of Gastroenterology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Inflammatory Bowel Disease Center, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Institute of Gastroenterology, Zhejiang University, Zhejiang Province, Hangzhou, 310016, China
| | - Lingna Ye
- Department of Gastroenterology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Inflammatory Bowel Disease Center, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
- Institute of Gastroenterology, Zhejiang University, Zhejiang Province, Hangzhou, 310016, China
| | - Qian Cao
- Department of Gastroenterology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
- Inflammatory Bowel Disease Center, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
- Institute of Gastroenterology, Zhejiang University, Zhejiang Province, Hangzhou, 310016, China.
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Li Q, Zheng S, Niu K, Qiao Y, Liu Y, Zhang Y, Li B, Zheng C, Yu B. Paeoniflorin improves ulcerative colitis via regulation of PI3K‑AKT based on network pharmacology analysis. Exp Ther Med 2024; 27:125. [PMID: 38414786 PMCID: PMC10895587 DOI: 10.3892/etm.2024.12414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/24/2023] [Indexed: 02/29/2024] Open
Abstract
Paeoniflorin (PF) is the primary component derived from Paeonia lactiflora and white peony root and has been used widely for the treatment of ulcerative colitis (UC) in China. UC primarily manifests as a chronic inflammatory response in the intestine. In the present study, a network pharmacology approach was used to explore the specific effects and underlying mechanisms of action of PF in the treatment of UC. A research strategy based on network pharmacology, combining target prediction, network construction, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking simulation was used to predict the targets of PF. A total of 288 potential targets of PF and 599 UC-related targets were identified. A total of 60 therapeutic targets of PF against UC were identified. Of these, 20 core targets were obtained by protein-protein interaction network construction. GO and KEGG pathway analyses showed that PF alleviated UC through EGFR tyrosine kinase inhibitor resistance, the IL-17 signaling pathway, and the PI3K/AKT signaling pathway. Molecular docking simulation showed that AKT1 and EGFR had good binding energy with PF. Animal-based experiments revealed that the administration of PF ameliorated the colonic pathological damage in a dextran sulfate sodium-induced mouse model, resulting in lower levels of proinflammatory cytokines including IL-1β, IL-6, and TNF-α, and higher levels of IL-10 and TGF-β. PF decreased the mRNA and protein expression levels of AKT1, EGFR, mTOR, and PI3K. These findings suggested that PF plays a therapeutic protective role in the treatment of UC by regulating the PI3K/AKT signaling pathway.
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Affiliation(s)
- Qifang Li
- Department of Traditional Chinese Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong 272069, P.R. China
| | - Shuyue Zheng
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Kai Niu
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Yi Qiao
- School of Public Health, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Yuan Liu
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Ying Zhang
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Bingbing Li
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Canlei Zheng
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Bin Yu
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
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He S, Jiang H, Tian Y, Zhang W, Teng G, Wang H. Ulcerative colitis overall disease severity index predicts colectomy: a prospective cohort study. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:77-82. [PMID: 37706493 DOI: 10.17235/reed.2023.9754/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/15/2023]
Abstract
BACKGROUND ulcerative colitis (UC) overall disease severity index (DSI) has been established. A prospective cohort study was performed to find the value of DSI to predict colectomy within one and four years and explored the association between DSI and other indexes. METHODS the hospitalized UC patients were enrolled from March 2018 to January 2019 in this single center study. DSI, Truelove and Witts criteria, Mayo index and Seo index were assessed by medical records. Outcome was whether to undergo colectomy within one and four years and was obtained by telephone survey or medical records. Index values of predicting colectomy within one and four years were evaluated using receiver operating characteristics (ROC) curves. RESULTS one hundred and thirty-eight of 233 hospitalized UC patients were enrolled. Within one year, the follow-up period was less than one year for six patients and two patients had died. A further nine patients underwent colectomy. The Spearman correlation coefficient between DSI and Truelove and Witts criteria, Mayo index and Seo index were 0.730, 0.839 and 0.843, respectively. Using these indices to predict colectomy within one and four years, the area under the curve of DSI was more than those of other indices and the cut-off value of DSI was 79. CONCLUSIONS a good correlation of DSI with other indexes was demonstrated. DSI can be used to predict the need for colectomy within one or four years.
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Affiliation(s)
- Shengduo He
- Gastroenterology, Peking University First Hospital, China
| | - Hong Jiang
- Gastroenterology, Peking University First Hospital, China
| | - Yu Tian
- Gastroenterology, Peking University First Hospital
| | - Wei Zhang
- Gastroenterology, Peking University First Hospital
| | - Guigen Teng
- Gastroenterology, Peking University First Hospital, China
| | - Huahong Wang
- Gastroenterology, Peking University First Hospital, China
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Wan J, Shen J, Wu X, Zhong J, Chen Y, Zhu L, Miao Y, Hu N, Chen J, Liang J, Wu K. Geographical heterogeneity in the disease characteristics and management of patients with inflammatory bowel disease, the preliminary results of a Chinese database for IBD (CHASE-IBD). Therap Adv Gastroenterol 2023; 16:17562848231210367. [PMID: 38106983 PMCID: PMC10725104 DOI: 10.1177/17562848231210367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 10/11/2023] [Indexed: 12/19/2023] Open
Abstract
Background The incidence of inflammatory bowel disease (IBD) is rapidly increasing in China, a vast country with significant geographical differences. The socioeconomic status of Eastern China is significantly higher than that of Western China. Objectives This study aimed to describe the geographical heterogeneity in the characteristics and management of patients with IBD in both Eastern and Western China. Design This was a multicenter, cross-sectional study. Methods Patients with IBD with ages ⩾18 years up to 18 January 2023 were included in the analysis from the Chinese database for IBD. Logistic regression was used to identify risk factors associated with surgeries among patients with IBD. Results Among 8305 patients with IBD, the ratio of ulcerative colitis (UC) to Crohn's disease (CD) was 4.13 and 0.33 in Western and Eastern China, respectively. The median age at diagnosis of UC and CD was 40.69 and 28.58 years, respectively. There was a male predominance among patients with UC (54.3%) and CD (68.0%). The two regions exhibited a similar distribution of disease locations in UC. However, Western China had a higher proportion of L2 involvement (30.0% versus 19.1%) and more advanced disease behavior (B2 and B3) (48.8% versus 39.8%) than Eastern China. Patients with IBD in Western China received more 5-aminosalicylic acid and corticosteroids and fewer immunomodulators and biologicals. In terms of surgical risk, Eastern China [versus Western China, odds ratios (OR): 5.36, 95% confidence intervals (CI): 2.96-9.68] was associated with a higher risk of surgery in UC, while Western China (versus Eastern China, OR: 3.39, 95% CI: 2.37-4.86) was associated with a higher risk of surgery in CD. Conclusion Geographical heterogeneity exists in the disease characteristics and management of IBD in Eastern and Western China. These findings have the potential to guide the formulation of location-specific strategies aimed at enhancing the long-term outcomes of patients with IBD.
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Affiliation(s)
- Jian Wan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Jun Shen
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiaoping Wu
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Jie Zhong
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Chen
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lanxiang Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yinglei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Naizhong Hu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jie Chen
- Department of Gastroenterology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, China
| | - Jie Liang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Kaichun Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 Changle West Road, Xi’an, Shaanxi 710032, China
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Dou W, Xu H, Feng S, Liu T, Xiao L, Wu Y, Chen S, Pan Y, Wang X. The Alleviating Effects and Mechanisms of Betaine on Dextran Sulfate Sodium-Induced Colitis in Mice. Mol Nutr Food Res 2023; 67:e2300376. [PMID: 37815169 DOI: 10.1002/mnfr.202300376] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/17/2023] [Indexed: 10/11/2023]
Abstract
SCOPE Ulcerative colitis (UC) is an intestinal disease that is becoming increasingly prevalent and is often overlooked in early stages, and its pathogenesis is often closely related to inflammatory processes. Betaine is a natural product with anti-inflammatory effects that exists in a wide range of plants and animals. METHODS AND RESULTS In this study, the protective effects of betaine are investigated on intestinal barrier function in a mouse model, a dextran sulfate sodium-induced ulcerative colitis and its mechanism of action in the inflammatory context. FITC-dextran 4000 Da (FD-4) flux, disease activity index, histopathological scores, and inflammatory factor levels in sera are determined across different groups. In addition, Caco-2 cell monolayer barrier function is evaluated by transepithelial resistance and FD-4 flux. The expression levels and distribution of tight junction proteins are determined using Western blot and immunofluorescence, respectively. Activation of the NF-κBp65/MLCK/p-MLC signaling pathway is detected by Western blot. Chromatin immunoprecipitation is performed to examine the binding of NF-κB to the MLCK gene promoter. The results indicated that betaine inhibits NF-κB-mediated activation of the MLCK/p-MLC signaling pathway to protect the intestinal barrier function of mice with UC. CONCLUSION Betaine can be used as a potential candidate drug to improve intestinal barrier dysfunction in patients with UC.
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Affiliation(s)
- Weidong Dou
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Hao Xu
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Shuo Feng
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Tao Liu
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Lin Xiao
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Yingchao Wu
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Shanwen Chen
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Yisheng Pan
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Xin Wang
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
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Kubota K, Imai Y, Okuyama T, Ishiyama Y, Ueno S, Kario K. Dramatically Improved Severe Pulmonary Arterial Hypertension Caused by Qing-Dai (Chinese Herbal Drug) for Ulcerative Colitis. Int Heart J 2023; 64:316-320. [PMID: 37005323 DOI: 10.1536/ihj.22-563] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/04/2023]
Abstract
Pulmonary arterial hypertension (PAH) is a rare and fatal disease for which some causative drugs have been developed. Qing-Dai is a Chinese herbal drug that is sometimes used as a specific treatment for ulcerative colitis in Asia, including Japan. Here, we report a case of severe Qing-Dai-induced PAH. A 19-year-old woman who has been taking Qing-Dai for 8 months was admitted for exertional dyspnea. Her mean pulmonary artery pressure dramatically improved from 72 to 18 mmHg with Qing-Dai discontinuation and PAH-specific therapy. After 6 years of onset, she had not relapsed with PAH with PAH-specific therapy.
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Affiliation(s)
- Kana Kubota
- Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University
| | - Yasushi Imai
- Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University
- Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University
| | - Takafumi Okuyama
- Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University
| | - Yusuke Ishiyama
- Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University
| | | | - Kazuomi Kario
- Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University
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11
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Li Y, Tang M, Zhang FJ, Huang Y, Zhang J, Li J, Wang Y, Yang J, Zhu S. Screening of ulcerative colitis biomarkers and potential pathways based on weighted gene co-expression network, machine learning and ceRNA hypothesis. Hereditas 2022; 159:42. [PMID: 36419192 PMCID: PMC9685902 DOI: 10.1186/s41065-022-00259-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 11/12/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) refers to an intractable intestinal inflammatory disease. Its increasing incidence rate imposes a huge burden on patients and society. The UC etiology has not been determined, so screening potential biomarkers is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. METHODS The microarray datasets of intestinal mucosal biopsy of UC patients were selected from the GEO database, and integrated with R language to screen differentially expressed genes and draw proteins interaction network diagrams. GO, KEGG, DO and GSEA enrichment analyses were performed to explore their biological functions. Through machine learning and WGCNA analysis, targets that can be used as UC potential biomarkers are screened out. ROC curves were drawn to verify the reliability of the results and predicted the mechanism of marker genes from the aspects of immune cell infiltration, co-expression analysis, and competitive endogenous network (ceRNA). RESULTS Two datasets GSE75214 and GSE87466 were integrated for screening, and a total of 107 differentially expressed genes were obtained. They were mainly related to biological functions such as humoral immune response and inflammatory response. Further screened out five marker genes, and found that they were associated with M0 macrophages, quiescent mast cells, M2 macrophages, and activated NK cells in terms of immune cell infiltration. The co-expression network found significant co-expression relationships between 54 miRNAs and 5 marker genes. According to the ceRNA hypothesis, NEAT1-miR-342-3p/miR-650-SLC6A14, NEAT1-miR-650-IRAK3, and XIST-miR-342-3p-IRAK3 axes were found as potential regulatory pathways in UC. CONCLUSION This study screened out five biomarkers that can be used for the diagnosis and treatment of UC, namely SLC6A14, TIMP1, IRAK3, HMGCS2, and APOBEC3B. Confirmed that they play a role in the occurrence and development of UC at the level of immune infiltration, and proposed a potential RNA regulatory pathway that controls the progression of UC.
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Affiliation(s)
- Ying Li
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Jinan, China ,grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, The First College for Clinical Medicine, Jinan, China
| | - Mengyao Tang
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, College of Innovation and Research of Traditional Chinese Medicine, Jinan, 250000 China
| | - Feng Jun Zhang
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Jinan, China ,grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, The First College for Clinical Medicine, Jinan, China
| | - Yihan Huang
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Jinan, China
| | - Jing Zhang
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Jinan, China
| | - Junqi Li
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Jinan, China
| | - Yunpeng Wang
- grid.479672.9Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Gastroenterology, Jinan, China
| | - Jinguang Yang
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, The First College for Clinical Medicine, Jinan, China
| | - Shu Zhu
- grid.464402.00000 0000 9459 9325Shandong University of Traditional Chinese Medicine, College of Innovation and Research of Traditional Chinese Medicine, Jinan, 250000 China
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12
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Shao B, Yang W, Cao Q. Landscape and predictions of inflammatory bowel disease in China: China will enter the Compounding Prevalence stage around 2030. Front Public Health 2022; 10:1032679. [PMID: 36388296 PMCID: PMC9641090 DOI: 10.3389/fpubh.2022.1032679] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 10/10/2022] [Indexed: 01/29/2023] Open
Abstract
Background This study aims to explore the epidemiological trends of inflammatory bowel disease (IBD) over the past three decades in China and further predict the trends of IBD in the next 25 years. Methods The prevalence, incidence, mortality, years of life lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and annual percentage changes of the above metrics of IBD in China from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019. The corresponding trends in the next 25 years were predicted. Results From 1990 to 2019, the cases of IBD in China raised to 484 thousand [95% uncertainty interval (UI) 411-571] and 427 thousand (366-498) among males and females, respectively. The age-standardized incidence rate of IBD increased from 1.72 per 100,000 population (1.44-2.05) to 3.35 per 100,000 population (2.88-3.88) among males and from 1.20 per 100,000 population (1.02-1.42) to 2.65 per 100,000 population (2.29-3.08) among females. The highest incidence rate occurred in people aged 35-39 years. The total YLDs attributed to IBD significantly increased, but the YLLs showed a decreasing trend, resulting in minor alterations of the DALYs. In the next 25 years, the incidence of IBD would continue to increase until a plateau by 2030, and IBD-related deaths would also increase to about 7.57 thousand by 2044 despite the decreasing age-standardized mortality rate. Similar trends were observed for both sexes, with a slight male predominance. Conclusions Although China is still a low-endemic area of IBD, the prevalence and incidence of IBD dramatically increased in the past three decades. The burden of IBD in China is expected to grow continuously in the next 25 years due to the large population base and severe aging problem. China is estimated to enter the Compounding Prevalence stage around 2030.
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Affiliation(s)
- Bule Shao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China,*Correspondence: Bule Shao
| | - Wenjing Yang
- Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou, China
| | - Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China,Qian Cao
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UGAR M, KAMIŞ F, BEYAZIT Y. İnflamatuvar barsak hastalığı olan hastalarda klinik özellikler, tedavi seçenekleri ve komplikasyonların değerlendirilmesi. FAMILY PRACTICE AND PALLIATIVE CARE 2022. [DOI: 10.22391/fppc.1088562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Introduction: Inflammatory bowel diseases (IBD) form a group of inflammatory diseases occurring in genetically-susceptible people, which are characterized by chronic progression and whose cause is not fully known. The aim of this study is to determine the incidence of IBD in our region and examine the clinical characteristics, sociodemographic features, and treatment results of IBD patients.Methods: Our study retrospectively investigates 211 patients over 18 years of age who were monitored for an IBD diagnosis between January 2, 2013, and December 31, 2019, by the gastroenterology department of Canakkale Onsekiz Mart University’s Faculty of Medicine. The mean age, female-male ratio, smoking habits, disease severity, and localization sites were identified for included patients. Local and systemic complications of administered treatment types and reasons for surgical treatment were also assessed in patients.Results: Of the 211 patients with IBD diagnoses, 158 (74.9%) had Ulcerative Colitis (UC) and 53 (25.1%) had a diagnosis of Crohn’s disease (CD). The mean age at the time of diagnosis was 43.97±16.22 years for UC patients and 42.30±14.73 years for CD cases. The involvement sites for UC were distal colitis for 58.4% of patients, left colon for 24.1% of patients, pancolitis for 16.5% of patients, and backwash ileitis for 7% of patients. According to the treatment results, 152 (72.0%) patients took 5-aminosalicylate (5-ASA) alone, 48 (22.8%) took thiopurine, and 20 (9.5%) took anti-TNF.Conclusion: Knowing the demographic, clinical, and laboratory features of these diseases, which are frequently seen in our region, can support the early identification of probable complications that may occur and the selection of appropriate approaches during diagnosis, treatment, and follow-up monitoring of these diseases.Keywords: Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn’s Disease, Severity of Illness Index, Abdominal Pain, Diarrhea
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Affiliation(s)
- Mücahit UGAR
- Department of Internal Medicine, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale
| | - Fatih KAMIŞ
- Department of Internal Medicine, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale
| | - Yavuz BEYAZIT
- Department of Gastroenterology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale
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14
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Yang H, Zhou R, Bai X, Guo M, Ruan G, Wang L, Qian J. Trend and Geographic Variation in Incidence and Prevalence of Inflammatory Bowel Disease in Regions Across China: A Nationwide Employee Study Between 2013 and 2016. Front Med (Lausanne) 2022; 9:900251. [PMID: 35957856 PMCID: PMC9357923 DOI: 10.3389/fmed.2022.900251] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 05/31/2022] [Indexed: 11/13/2022] Open
Abstract
Background Incidence and prevalence rates and trends of inflammatory bowel disease (IBD) in China remain largely unknown. Objective This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in China between 2013 and 2016. Methods We conducted a population-based analysis using data from the National Urban Employee Basic Medical Insurance database. Patients with at least three claims of IBD diagnosis were identified. A Joinpoint regression model was used to analyze the annual percent change (APC) of the age-standardized incidence and prevalence. Results The age-standardized prevalence of Crohn's disease (CD) increased from 1.59/100,000 in 2013 to 3.39/100,000 (p < 0.05) in 2016, and that of ulcerative colitis (UC) increased from 8.72/100,000 to 17.24/100,000 (p < 0.05) during the period, with a UC/CD ratio of 5.09 in 2016. The age-standardized incidence of CD varied between 0.82/100,000 and 0.97/100,000 (p = 0.9), whereas that of UC slightly increased from 4.54/100,000 to 4.85/100,000 (p = 0.7). The eastern region of China had the highest incidence and prevalence, and the western region had the lowest rates, in both UC and CD, showing an east-to-west gradient. Conclusion The incidence and prevalence of IBD in most urban regions in China had an emerging trend over the study period, and an east-to-west gradient was observed, which indicated a greater burden in eastern China. Efforts to improve prevention strategies and promote awareness of IBD are needed, particularly in young men who are at higher risk for CD.
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Affiliation(s)
- Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Runing Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingyue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
- Li Wang
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Jiaming Qian
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15
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Asari T, Kikuchi H, Kawaguchi S, Sakuraba H, Yoshida S, Akemoto Y, Maeda T, Shinji O, Murai Y, Higuchi N, Hoshi K, Fukutoku Y, Hiraga H, Sasaki K, Fukuda S. Polygonum tinctorium leaves suppress sodium dextran sulfate-induced colitis through interleukin-10-related pathway. Biochem Biophys Rep 2022; 30:101272. [PMID: 35535330 PMCID: PMC9077533 DOI: 10.1016/j.bbrep.2022.101272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 04/03/2022] [Accepted: 04/28/2022] [Indexed: 02/07/2023] Open
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16
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Yoshimatsu Y, Sujino T, Miyamoto K, Harada Y, Tanemoto S, Ono K, Umeda S, Yoshida K, Teratani T, Suzuki T, Mikami Y, Nakamoto N, Sasaki N, Takabayashi K, Hosoe N, Ogata H, Sawada K, Imamura T, Yoshimura A, Kanai T. Aryl hydrocarbon receptor signals in epithelial cells govern the recruitment and location of Helios + Tregs in the gut. Cell Rep 2022; 39:110773. [PMID: 35545035 DOI: 10.1016/j.celrep.2022.110773] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 12/30/2021] [Accepted: 04/12/2022] [Indexed: 01/21/2023] Open
Abstract
CD4+Foxp3+ regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios+ Tregs and MHC class II+ epithelial cells (ECs) in the colon. Interactions between Tregs and MHC class II+ ECs occur mainly near the crypt bottom in the steady state, whereas Tregs dramatically increase and shift toward the crypt top following IN treatment. Moreover, the number of CD25+ T cells is increased near the surface of ECs in IN-treated UC patients compared with that in patients treated with other therapies. We also highlight additional AhR-signaling mechanisms in intestinal ECs that determine the accumulation and localization of Helios+ Tregs in the colon.
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Affiliation(s)
- Yusuke Yoshimatsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tomohisa Sujino
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan.
| | - Kentaro Miyamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; Miyarisan Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Yosuke Harada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shun Tanemoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Keiko Ono
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Satoko Umeda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kosuke Yoshida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Toshiaki Teratani
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takahiro Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; Miyarisan Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Yohei Mikami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Nobuhiro Nakamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Nobuo Sasaki
- Institute of Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
| | - Kaoru Takabayashi
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Kazuaki Sawada
- Department of Molecular Medicine for Pathogenesis, Ehime University, Toon, Japan
| | - Takeshi Imamura
- Department of Molecular Medicine for Pathogenesis, Ehime University, Toon, Japan
| | - Akihiko Yoshimura
- Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
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Park SB, Yoon JY, Cha JM. What Are the Different Phenotypes of Inflammatory Bowel Disease in Asia? Gut Liver 2022; 16:676-685. [PMID: 35145045 PMCID: PMC9474490 DOI: 10.5009/gnl210385] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 11/16/2021] [Accepted: 11/23/2021] [Indexed: 12/04/2022] Open
Abstract
The burden of inflammatory bowel disease (IBD) in Asia has been increasing over the past decades. Although patients with IBD show heterogenous phenotypes depending on the individual characteristics, no significant differences have been established in the IBD phenotypes of Western and Asian populations. However, despite the much lower incidence of IBD in Asia than in Western countries, the incidence has been rapidly increasing in Asia while remaining stable in Western countries. The incidence of ulcerative colitis (UC) showed an earlier and a more marked increase than the incidence of Crohn disease (CD), but the UC-to-CD ratio has recently decreased because of a relative increase in the incidence of CD in Asia. While CD shows a significant male predominance, UC only shows a slight male predominance. A recent study reported that the incidence of IBD in Asia showed a bimodal age distribution with increasing IBD prevalence, similar to the findings of Western studies. CD in Asian patients, especially those in East Asia, is characterized by ileocolonic involvement and perianal fistula. The frequency of extraintestinal manifestations, including primary sclerosing cholangitis, appears to be lower in Asia, but this finding should be interpreted with caution due to the transient and nonspecific nature of these manifestations. Although familial aggregation is lower in East Asia, it may also be explained by the low prevalence of IBD in Asia. Thus, more studies should focus on the differences in phenotypes in Asian IBD patients versus Western patients.
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Affiliation(s)
- Su Bee Park
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Jin Young Yoon
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
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18
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Sun YX, Yang GY, Karamacoska D, Wang X, Li YX, Hou WB, Zheng YY, Liu JP, Liu ZL. Chinese Patent Medicine as Adjuvant for Mild-to-Moderate Active Ulcerative Colitis: A Network Meta-Analysis of Randomized Controlled Trials. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:1075886. [PMID: 34484384 PMCID: PMC8413025 DOI: 10.1155/2021/1075886] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 08/17/2021] [Indexed: 01/30/2023]
Abstract
OBJECTIVE To evaluate the effectiveness and safety of Chinese patent medicine for mild-to-moderate active ulcerative colitis (UC) using network meta-analysis (NMA). METHODS We systematically searched PubMed, Cochrane library, Embase, Sino-Med, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journal Database (VIP) databases to October, 2020. We included randomized controlled trials (RCTs) on Chinese patent medicine for mild-to-moderate active UC. The main analysis was complemented by network subanalyses and standard pairwise comparisons. Statistical heterogeneity, inconsistencies, and ranking probability were also evaluated. RESULTS The databases search identified 3222 citations, of which 33 RCTs involving 2971 patients met the inclusion criteria. A total of 15 Chinese patent medicines were analyzed. The overall quality of the included studies was low. Pairwise meta-analysis showed that Chinese patent medicine was superior to Mesalazine in improving disappearances of clinical symptoms, recurrence rate, and Mayo score. Based on decreases in adverse events, results from NMA showed that Xilei powder plus Mesalazine was more effective than other drugs. Other NMA results indicated that Danshen freeze-dried powder plus Mesalazine (RR: 0.13; 95% CI, 0.02-0.78) and Kangfuxin lotion plus Mesalazine (RR: 0.24; 95% CI, 0.07-0.57) were superior to Mesalazine in decreasing recurrence rate. Another NMA result indicated that Kangfuxin lotion plus Mesalazine (RR: 0.00; 95% CI, 0.00-0.02) and Zhi Kang capsule plus Mesalazine (RR: 0.00; 95% CI, 0.00-0.02) were superior to Mesalazine in increasing the disappearance of tenesmus. CONCLUSION In the probability sorting, Xilei powder combined with Mesalazine ranked first for having the fewest adverse events, Maintaining Intestines Antidiarrheal Pills combined with Mesalazine ranked first for having the lowest recurrence rate, Xilei powder combined with Mesalazine ranked first for improving disappearance rate of mucopurulent bloody stool/abdominal pain, and Kangfuxin lotion combined with Mesalazine ranked first for improving the disappearance rate of diarrhea/tenesmus. However, there is a lack of direct comparisons among Chinese patent medicines for UC. More multiarm RCTs are needed in the future to provide direct comparative evidence.
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Affiliation(s)
- Yu-Xin Sun
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Guo-Yan Yang
- NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia
| | - Diana Karamacoska
- NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia
| | - Xiao Wang
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yuan-Xi Li
- College of Statistics and Data Science, Faculty of Science, Beijing University of Technology, Beijing 100124, China
| | - Wen-Bin Hou
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - You-You Zheng
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jian-Ping Liu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Zhao-Lan Liu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
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19
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Differences in inflammatory bowel diseases between East and West: a Chinese perspective. J Public Health (Oxf) 2021. [DOI: 10.1007/s10389-019-01102-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021; 18:56-66. [PMID: 33033392 PMCID: PMC7542092 DOI: 10.1038/s41575-020-00360-x] [Citation(s) in RCA: 704] [Impact Index Per Article: 176.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/18/2020] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD) is a global disease; its evolution can be stratified into four epidemiological stages: Emergence, Acceleration in Incidence, Compounding Prevalence and Prevalence Equilibrium. In 2020, developing countries are in the Emergence stage, newly industrialized countries are in the Acceleration in Incidence stage, and Western regions are in the Compounding Prevalence stage. Western regions will eventually transition to the Prevalence Equilibrium stage, in which the accelerating prevalence levels off as the IBD population ages and possibly as a result of an unexpected rise in mortality during the COVID-19 pandemic. Mitigating the global burden of IBD will require concerted efforts in disease prevention and health-care delivery innovations that respond to changing demographics of the global IBD population. In this Perspective, we summarize the global epidemiology of IBD and use these data to stratify disease evolution into four epidemiological stages.
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Affiliation(s)
- Gilaad G. Kaplan
- grid.22072.350000 0004 1936 7697Department of Medicine, University of Calgary, Calgary, Alberta Canada ,grid.22072.350000 0004 1936 7697Department of Community Health Sciences, University of Calgary, Calgary, Alberta Canada
| | - Joseph W. Windsor
- grid.22072.350000 0004 1936 7697Department of Medicine, University of Calgary, Calgary, Alberta Canada ,grid.22072.350000 0004 1936 7697Department of Community Health Sciences, University of Calgary, Calgary, Alberta Canada
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21
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Bodiwala V, Marshall T, Das KM, Brant SR, Seril DN. Comparison of Disease Phenotypes and Clinical Characteristics Among South Asian and White Patients with Inflammatory Bowel Disease at a Tertiary Referral Center. Inflamm Bowel Dis 2020; 26:1869-1877. [PMID: 32144933 DOI: 10.1093/ibd/izaa019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The prevalence and clinical features of inflammatory bowel disease (IBD) vary among different racial and ethnic groups. The aim of this study was to compare the clinical and phenotypic features of Crohn's disease (CD) and ulcerative colitis (UC) in South Asian patients living in the United States with those of a white cohort. METHODS The demographic, clinical, and phenotypic characteristics of 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive white patients (245 CD and 163 UC). RESULTS South Asian IBD patients were significantly more likely to have UC (58.0% vs 40.0%; P = 0.005) than white patients. South Asians with CD were less likely to have a family history of IBD (9.7% vs 26.9%; P = 0.037) and required fewer CD-related surgeries (22.5% vs 46.1; P = 0.012). South Asians were also less likely to be active or former smokers in both the CD (P = 0.004) and UC (P = 0.020) groups. South Asians with UC had a higher incidence of Clostridium difficile infection compared with white patients (19.0% vs 8.6%; P = 0.050). CONCLUSIONS A cohort of South Asian patients with IBD were more likely to have UC and had differing family and tobacco risk factors, requirements for surgery, and Clostridium difficile infection rates as compared with white patients.
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Affiliation(s)
- Vimal Bodiwala
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
| | | | - Kiron M Das
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.,Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Steven R Brant
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.,Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Darren N Seril
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.,Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
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22
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Orihara Y, Asakura M, Hida N, Kawai M, Sato T, Nishimura K, Masai K, Matsumoto Y, Okuhara Y, Goda A, Masuyama T, Nakamura S, Ishihara M. Effect of Oral Qing-Dai Medication on Pulmonary Arterial Pressure Levels in Patients With Ulcerative Colitis. Circ J 2020; 84:1339-1345. [PMID: 32595175 DOI: 10.1253/circj.cj-19-1112] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
BACKGROUND Qing-Dai (QD) treatment of patients with ulcerative colitis (UC) sometimes causes pulmonary arterial hypertension (PAH). However, the relationship of QD treatment to pulmonary arterial systolic pressure (PASP) in patients with UC has not been clarified. METHODS AND RESULTS The 27 patients with UC who were screened for PAH by transthoracic echocardiography (TTE) and underwent repeat TTE at 1 year were analyzed in this prospective observational study. Mean age was 44.0 years old, and median follow-up duration was 392. During the follow-up, 21 patients continued QD treatment (continuous group) and 6 patients discontinued the treatment (discontinuous group). In all patients, no significant difference in PASP levels between baseline and at follow-up was observed (21.4 vs. 21.3 mmHg, P=0.802). Furthermore, the mean PASP of patients in the continuous group did not differ from baseline to follow-up (21.4 mmHg to 22.6 mmHg, P=0.212); however, in the discontinuous group mean PASP was significantly decreased (21.5 mmHg to 16.8 mmHg, P=0.005). Moreover, changes in PASP from baseline to follow-up differed between the continuous and discontinuous groups (+1.1 mmHg vs. -4.7 mmHg, P=0.004). In addition, multivariable analyses revealed that only the duration of oral QD at baseline affected the increase of PASP. CONCLUSIONS In patients with UC, QD treatment may have an undesirable association with an increase in PASP.
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Affiliation(s)
- Yoshiyuki Orihara
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Masanori Asakura
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Nobuyuki Hida
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine
| | - Mikio Kawai
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine
| | - Toshiyuki Sato
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine
| | - Koichi Nishimura
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Kumiko Masai
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Yuki Matsumoto
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Yoshitaka Okuhara
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Akiko Goda
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Tohru Masuyama
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Shiro Nakamura
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine
| | - Masaharu Ishihara
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
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Matsuno Y, Hirano A, Torisu T, Okamoto Y, Fuyuno Y, Fujioka S, Umeno J, Moriyama T, Nagai S, Hori Y, Fujiwara M, Kitazono T, Esaki M. Short-term and long-term outcomes of indigo naturalis treatment for inflammatory bowel disease. J Gastroenterol Hepatol 2020; 35:412-417. [PMID: 31389626 DOI: 10.1111/jgh.14823] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/24/2019] [Accepted: 08/03/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective in inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with inflammatory bowel disease. METHODS Data were collected from the electric medical records of patients with inflammatory bowel disease who had started IN treatment between March 2015 and April 2017 at Kyushu University Hospital. Clinical response and remission rates were assessed based on the clinical activity index determined by Rachmilewitz index or Crohn's disease (CD) activity index. Cumulative IN continuation rates were estimated using the Kaplan-Meier method. Overall adverse events (AEs) during follow-up were also analyzed. RESULTS Seventeen UC patients and eight CD patients were enrolled. Clinical response and remission rates at week 8 were 94.1% and 88.2% in UC patients and 37.5% and 25.0% in CD patients, respectively. Clinical remission rates, as assessed through non-responders imputation analyses at weeks 52 and 104, were 76.4% and 70.4% in UC patients and 25.0% and 25.0% in CD patients, respectively. Ten patients (40%) experienced AEs during follow-up. Three patients (12%) experienced severe AEs, including acute colitis requiring hospitalization in two patients and acute colitis with intussusception requiring surgery in one patient. CONCLUSIONS Indigo naturalis showed favorable therapeutic efficacy in UC, whereas its therapeutic efficacy in CD appeared to be modest. The risk of severe AEs should be recognized for IN treatment.
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Affiliation(s)
- Yuichi Matsuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Atsushi Hirano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takehiro Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuharu Okamoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuta Fuyuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shin Fujioka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomohiko Moriyama
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shuntaro Nagai
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshifumi Hori
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Minako Fujiwara
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Motohiro Esaki
- Department of Endoscopic Diagnostics and Therapeutics, Saga University Hospital, Saga, Japan
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24
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Lu PD, Zhao YH. Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines. Chin Med 2020; 15:15. [PMID: 32063999 PMCID: PMC7011253 DOI: 10.1186/s13020-020-0296-z] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 01/30/2020] [Indexed: 12/15/2022] Open
Abstract
Nuclear factor-kappa B (NF-κB) is a kind of multi-functional nuclear transcription factor involved in regulating gene transcription to influence pathological evolution of inflammatory and immune diseases. Numerous literature evidence that NF-κB pathway plays an essential role in pathogenic development of ulcerative colitis (UC). UC is a chronic non-specific inflammatory bowel disease, and until now, therapeutic agents for UC including aminosalicylates, corticosteroids and immune inhibitors still cannot exert satisfied effects on patients. In recent years, Chinese medicines suggest the advantages of alleviating symptoms and signs, decreasing side-effects and recurrence, whose one of mechanisms is related to regulation of NF-κB pathway. In this review, we categorize Chinese medicines according to their traditional therapeutic functions, and summarize the characteristics of Chinese medicines targeting NF-κB pathway in UC treatment. It indicates that 85 kinds of Chinese medicines’ compounds and formulae can directly act on NF-κBp65; while 58 Chinese medicines’ ingredients and formulae indirectly suppress NF-κBp65 by regulation of its upstream or other related pathways. Moreover, by the analysis of Chinese medicines’ category based on their traditional functions, we conclude the category of dampness-drying and detoxificating medicine targeting NF-κB pathway accounts for primary status for amelioration of UC. Simultaneously, this review also contributes to the choices of Chinese medicine category and provides curative potential of Chinese medicines for clinical UC treatment.
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Affiliation(s)
- Peng-De Lu
- 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yong-Hua Zhao
- 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao, Special Administrative Region of China
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Zeng A, Peng M, Liu H, Guo Z, Xu J, Wang S, He L, Tan Z. Effects of Debaryomyces hansenii treatment on intestinal mucosa microecology in mice with antibiotic-associated diarrhea. PLoS One 2019; 14:e0224730. [PMID: 31725747 PMCID: PMC6855419 DOI: 10.1371/journal.pone.0224730] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 10/15/2019] [Indexed: 12/12/2022] Open
Abstract
AIM To confirm the effects of Debaryomyces hansenii on intestinal microecology in mice with antibiotic-associated diarrhea (AAD). METHODS This study took the mucosal microecology as the entry point and an antibiotic mixture was used to induce diarrhea in mice. D. hansenii suspension was used to treat the mice and the bacterial communities of mucosa was analyzed using high-throughput sequencing. RESULTS The Shannon-Wiener index indicated that the sequencing depth is reasonable and reflected the majority of microbial information. The principal coordinate analysis results showed that mice in the treatment group and the normal group had a similar microbial community structure, while differences in microbial community structure were observed between the model group and the treatment group. The inter-group bacterial structures were analyzed at the phylum level and genus level. The results revealed that antibiotic treatment increased the proportion of Proteobacteria and decreased the proportion of Bacteroides, while D. hansenii treatment inhibited the increase in Proteobacteria. Linear discriminant analysis coupled with effect size measurements (LEfSe) suggested d that the beneficial bacteria Candidatus Arthromitus were the only common bacteria in the normal group (P<0.05). CONCLUSION The treatment with D.hansenii could contribute to the maintenance of the structure of the mucosal microbiota in comparison with the normal group and inhibit the proliferation of opportunistic bacteria. However, high-dose antibiotic treatment causes mucosal dysbiosis and the proliferation of opportunistic bacteria during the self-recovery period, such as Pseudoalteromonas, Alteromonas, Vibrio.
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Affiliation(s)
- Ao Zeng
- Hunan Institute of Microbiology, Changsha, Hunan Province, China
- Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Maijiao Peng
- Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Huizhi Liu
- Hunan Institute of Microbiology, Changsha, Hunan Province, China
| | - Zhaohui Guo
- Hunan Institute of Microbiology, Changsha, Hunan Province, China
| | - Jun Xu
- Hunan Institute of Microbiology, Changsha, Hunan Province, China
| | - Shengping Wang
- Hunan Institute of Microbiology, Changsha, Hunan Province, China
| | - Lu He
- Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Zhoujin Tan
- Hunan University of Chinese Medicine, Changsha, Hunan Province, China
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26
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Urushikubo J, Yanai S, Nakamura S, Kawasaki K, Akasaka R, Sato K, Toya Y, Asakura K, Gonai T, Matsumoto T. Efficacy of Indigo Naturalis Therapy for Ulcerative Colitis: A Case Series. Intern Med 2019; 58:2299-2304. [PMID: 31118381 PMCID: PMC6746630 DOI: 10.2169/internalmedicine.2446-18] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Objective Indigo naturalis (IN) is a traditional Chinese medicine that has recently been reported to be effective for ulcerative colitis (UC). The aim of this study was to evaluate the efficacy and safety of IN. Methods We performed a retrospective observational study for 14 patients with UC treated with IN from October 2015 to December 2016. Results After 8 weeks of oral administration of IN, the partial Mayo score decreased from 4 (2-5) to 1.5 (0-4) [median, interquartile range (IQR), p=0.015]. Among 10 active UC patients, 5 (50%) showed a clinical response, and 4 (40%) achieved clinical remission. Serial changes of endoscopic activity were evaluated in nine patients using the Mayo endoscopic subscore (MES), Rachmilewitz endoscopic index (REI), and UC endoscopy index of severity (UCEIS). The MES decreased from 2 (2-3) to 1 (1-2) [median (IQR), p=0.005], the REI decreased from 7 (5.5-11) to 3 (1-7) [median (IQR), p=0.008], and the UCEIS decreased from 3 (3-4.5) to 1 (0.5-3.5) [median (IQR), p=0.039]. One patient developed acute right-sided colitis with wall thickening and edematous change, and the remaining 13 showed no adverse events. Conclusion We conclude that IN is effective for patients with UC as a therapy for inducing remission.
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Affiliation(s)
- Jun Urushikubo
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Shunichi Yanai
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Shotaro Nakamura
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Keisuke Kawasaki
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Risaburo Akasaka
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Kunihiko Sato
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Yosuke Toya
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Kensuke Asakura
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Takahiro Gonai
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
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Banerjee R, Pal P, Hutfless S, Ganesh BG, Reddy DN. Familial aggregation of inflammatory bowel disease in India: prevalence, risks and impact on disease behavior. Intest Res 2019; 17:486-495. [PMID: 31370386 PMCID: PMC6821951 DOI: 10.5217/ir.2018.00174] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 06/14/2019] [Indexed: 01/06/2023] Open
Abstract
Background/Aims Information about familial aggregation of inflammatory bowel disease (IBD) in Asia is limited. We aimed to analyze the prevalence and risk of familial IBD in an Indian cohort and compare familial and sporadic cases. Methods Familial IBD cases were identified from a large prospectively maintained IBD registry. The prevalence of IBD in first- and seconddegree relatives of index cases was evaluated. The disease behavior was compared to that of sporadic cases. Results Total 3,553 patients (ulcerative colitis [UC], 2,053; Crohn’s disease [CD], 1,500) were included. Familial IBD was noted in 4.13% of CD and 4.34% of UC patients. Family history was commoner in pediatric group (< 18 years) (P= 0.0002; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6–4.8). Majority had paternal transmission (UC, 67.42%; CD, 70.97%). Concordance of disease type was higher in UC (79.7%) compared to CD (37.1%). Familial IBD was associated with higher cumulative relapse rate (CD, P< 0.001; UC, P< 0.001), higher cumulative rate of surgery (CD, P< 0.001; UC, P< 0.001) and higher rate of biologic use (CD, P= 0.010; UC, P= 0.015). Pan-colitis was higher in familial UC (P= 0.003; OR, 1.935; 95% CI, 1.248–3.000). Fistulizing disease was commoner in familial CD (P= 0.041; OR, 2.044; 95% CI, 1.030–4.056). Conclusions The prevalence of familial IBD in India appears comparable to rest of Asia but lower than the West. It is associated with a younger age of onset, higher incidence of pan-colitis in UC and fistulizing complications in CD. Familial IBD has higher cumulative relapse, surgery and biologic use rates. Hence, family history of IBD could have important prognostic implications.
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Affiliation(s)
- Rupa Banerjee
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Partha Pal
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Susan Hutfless
- Division of Gastroenterology and Hepatology, Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
| | - B Girish Ganesh
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - D Nageshwar Reddy
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
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He Z, Zhou Q, Wen K, Wu B, Sun X, Wang X, Chen Y. Huangkui Lianchang Decoction Ameliorates DSS-Induced Ulcerative Colitis in Mice by Inhibiting the NF-kappaB Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2019; 2019:1040847. [PMID: 31093294 PMCID: PMC6481129 DOI: 10.1155/2019/1040847] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 03/20/2019] [Accepted: 03/26/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND The nuclear factor kappa beta (NF-κB) signaling pathway plays an important role in ulcerative colitis (UC). Huangkui Lianchang decoction (HLD) is an effective traditional Chinese medicinal compound used in the treatment of UC. HLD has good effects in the clinic, but the mechanism by which HLD acts is unclear. This study aims to reveal the exact molecular mechanism of HLD in the treatment of UC. METHODS Mouse ulcerative colitis was induced by dextran sulfate sodium (DSS) and treated with HLD. Intestinal damage was assessed by disease activity index (DAI), colon macroscopic lesion scores, and histological scores. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β were detected in colon tissue using ELISA. Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities in the colonic mucosa were measured. The levels of IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). The expression of NF-κB, IκBα, and p-IκBα in the colon was measured by Western blot. RESULTS After treatment with HLD, the DAI scores, macroscopic lesion scores, and histological scores decreased, and the levels of inflammatory cytokines related to the NF-κB signaling pathway, such as IL-6, TNF-α, and IL-1β, as well as those of iNOS and COX-2, were reduced; at the same time, colonic pathological damage was alleviated, and the MPO and SOD activities decreased. Western blot confirmed that HLD can inhibit the NF-κB signaling pathway in DSS-induced ulcerative colitis. CONCLUSION HLD can alleviate the inflammation caused by ulcerative colitis. In particular, high doses of HLD can significantly alleviate intestinal inflammation and have comparable efficacy to Mesalazine. We propose that the anti-inflammatory activity of HLD on DSS-induced colitis in mice may involve the inhibition of the NF-κB pathway.
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Affiliation(s)
- Zongqi He
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210046, China
- Department of Colorectal Surgery, Suzhou Hospital Affiliated with Nanjing University of Chinese Medicine, Suzhou 215009, China
| | - Qing Zhou
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210046, China
| | - Ke Wen
- Department of Colorectal Surgery, Suzhou Hospital Affiliated with Nanjing University of Chinese Medicine, Suzhou 215009, China
| | - Bensheng Wu
- Department of Colorectal Surgery, Suzhou Hospital Affiliated with Nanjing University of Chinese Medicine, Suzhou 215009, China
| | - Xueliang Sun
- Department of Colorectal Surgery, Suzhou Hospital Affiliated with Nanjing University of Chinese Medicine, Suzhou 215009, China
| | - Xiaopeng Wang
- Department of Colorectal Surgery, Suzhou Hospital Affiliated with Nanjing University of Chinese Medicine, Suzhou 215009, China
| | - Yugen Chen
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210046, China
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Minacapelli CD, Bajpai M, Geng X, Van Gurp J, Poplin E, Amenta PS, Brant SR, Das KM. miR-206 as a Biomarker for Response to Mesalamine Treatment in Ulcerative Colitis. Inflamm Bowel Dis 2019; 25:78-84. [PMID: 30204869 DOI: 10.1093/ibd/izy279] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND MicroRNAs (miRNAs) are important post-translational regulators. Elevated levels of miR-206 in ulcerative colitis (UC) were associated with suppression of anti-inflammatory A3 adenosine receptor (A3AR) expression. However, the relationship of miR-206 to histologic remission in UC patients remains unknown. This study correlates expression levels of miR-206 with histologic remission in patients treated via long-term mesalamine treatment to identify a possible mode of action for this mainstay drug for UC. METHODS Expression of miR-206 and its target A3AR were analyzed in HT29 cell line before and after mesalamine treatment (2 mM) at different time points (0, 4, 12, and 24 hours) by qRT-PCR and western blot analysis. Expression of miR-206 and pathological scores of colonoscopic biopsy specimens were studied in 10 UC patients treated with mesalamine treatment for 2 to 6 years. RESULTS miR-206 transcripts decreased 2.23-fold (P = 0.0001) 4 hours after 2 mM mesalamine treatment in HT29 colon cells compared with untreated controls. However, the mRNA/protein levels of A3AR increased by 4-fold (P = 0.04) and 2-fold, respectively, in same cells. miR-206 relative expression decreased significantly in patients treated with 4.8 g of mesalamine (P = 0.002) but not with 2.4 g (P = 0.35). Tissue assessment of sequential mesalamine-treated colonoscopic biopsies indicate a strong correlation between downregulation of miR-206 and histologic improvement (R = 0.9111). CONCLUSION Mesalamine treatment has an effect on epithelial miRNAs. Downregulation of miR-206 by long-term mesalamine treatment may confer a protective effect in inducing and maintaining histologic remission. Thus, miR-206 expression levels can be utilized as a possible biomarker for therapeutic response to mesalamine treatment.
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Affiliation(s)
- Carlos D Minacapelli
- Division of Gastroenterology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Manisha Bajpai
- Division of Gastroenterology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Xin Geng
- Division of Gastroenterology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - James Van Gurp
- Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | | | - Peter S Amenta
- Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Steven R Brant
- Division of Gastroenterology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Kiron M Das
- Division of Gastroenterology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.,Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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30
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Zhu L, Gu P, Shen H. Gallic acid improved inflammation via NF-κB pathway in TNBS-induced ulcerative colitis. Int Immunopharmacol 2018; 67:129-137. [PMID: 30544066 DOI: 10.1016/j.intimp.2018.11.049] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 11/23/2018] [Accepted: 11/28/2018] [Indexed: 12/20/2022]
Abstract
Gallic acid (GA), as an active component, has been found in many fruits and plants, and it exhibits potential protective effects, such as anti-inflammatory, antioxidant, antiviral and anticancer. However, the effects of GA on ulcerative colitis (UC) remain unknown. The purpose of this study was to investigate the effects of GA on IL-1β-induced HIEC-6 cells and TNBS-induced UC in mice. Various biochemical analyses including proliferation and apoptosis were assessed in HIEC-6 cells. In addition, body weight of mice, the level of cytokines and histological changes were utilized to analyze the GA protecting mice with UC. Our results showed that administration of GA significantly increased the expressions of IL-4, and IL-10, while down-regulated IL-1, IL-6, IL-12, IL-17, IL-23, TGF-β and TNF-α expressions compared with a model control group in vitro and in vivo. Moreover, flow cytometry and TUNEL analysis revealed that administration of GA significantly inhibited the apoptosis of HIEC-6 cells and mics in UC. Furthermore, pretreatment with GA obviously reversed the decrease in body weight, increase in colon weight, and attenuated the histological changes derived from UC. In addition, western blot analysis demonstrated that GA efficiently suppressed NF-κB signaling pathway in TNBS-induced UC. In conclusion, the findings of this study demonstrated that GA plays an anti-inflammatory role in UC via inhibiting NF-κB pathway.
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Affiliation(s)
- Lei Zhu
- Department of Gastroenterology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine (Jiang Su Province Hospital of Traditional Chinese Medicine), Nanjing 210029, China
| | - PeiQing Gu
- Department of Gastroenterology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine (Jiang Su Province Hospital of Traditional Chinese Medicine), Nanjing 210029, China
| | - Hong Shen
- Department of Gastroenterology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine (Jiang Su Province Hospital of Traditional Chinese Medicine), Nanjing 210029, China.
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31
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Sohail G, Xu X, Christman MC, Tompkins TA. Probiotic Medilac-S ® for the induction of clinical remission in a Chinese population with ulcerative colitis: A systematic review and meta-analysis. World J Clin Cases 2018; 6:961-984. [PMID: 30568952 PMCID: PMC6288505 DOI: 10.12998/wjcc.v6.i15.961] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 10/16/2018] [Accepted: 11/14/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To assess the effects of probiotic Medilac-S® as adjunctive therapy for the induction of remission of ulcerative colitis (UC) in a Chinese population through a systematic review and meta-analysis. METHODS A systematic literature search was conducted to find randomized, controlled trials in a Chinese population with at least two study arms - a control arm which receives a conventional, oral aminosalicylate drug, and a treatment arm, which administers the same conventional drug in conjunction with the probiotic Medilac-S® per os. Both English and Chinese databases were searched, including PubMed, EMBASE, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Search, and study data was extracted onto standardized abstraction sheets. Meta-analyses were conducted for primary and secondary outcomes of interest using a fixed or random effects model. The primary outcome was the induction of clinical remission and the secondary outcomes included changes in Sutherland index, endoscopic and histological scores, proportion of reported clinical symptoms and adverse events (AEs). For outcomes with sufficient data, the type of conventional drug therapy was also assessed to determine if the effects of combination therapy with Medilac-S® was influenced by drug type. All tests were conducted using a type I error rate of 0.05 and all confidence intervals (CI) were based on a 95% confidence level. Review protocol was uploaded to PROSPERO (CRD42018085658 upon completion). RESULTS Fifty-three clinical trials with a total of 3984 participants were identified and included in the review. Medilac-S® adjunctive therapy significantly improved induction of clinical remission (RR = 1.21; 95%CI: 1.18-1.24; P < 0.0001) with the estimated likelihood of effective treatment, on average, 21% higher for those consuming the probiotic. Sutherland index scores showed the control mean was on average 3.10 (CI: 2.41-3.78; P = 0.0428) units greater than the treatment mean, thereby demonstrating significant improvement in participants taking the probiotic. Similarly, a significant difference was seen between the overall reduction of endoscopic and histological scores of control and treatment arm participants, with score decreases in the control groups 0.71 (CI: 0.3537-1.0742) and 1.1 (CI: 0.9189-1.2300) units smaller than treatment group score decreases. The proportion of participants reporting clinical symptoms, (abdominal pain, tenesmus, blood and mucous in stool, and diarrhea) was significantly reduced after combination therapy with Medilac-S® (P < 0.0001) and estimated to be on average 44% (RR = 0.44, CI: 0.32-0.59), 53% (RR = 0.53, CI: 0.38-74), 40% (RR = 0.40, CI: 0.28-0.58) and 47% (RR = 0.47 CI: 0.36-0.42) respectively, of the proportion of individuals reporting the aforementioned symptoms after conventional therapy alone. The risk of AEs was also significantly reduced with adjunctive Medilac-S® therapy. The proportion of individuals in the treatment groups reporting AEs was an estimated 72% of the proportion of individuals in the control groups reporting AEs (RR = 0.72, CI: 0.55-0.94, P = 0.0175). Upon comparing effect means for different drug types in conjunction with Medilac-S®, evidence of significant variability (P < 0.0001) was observed, and sulfasalazine was found to be the most effective drug in both primary and secondary outcomes. CONCLUSION Evidence suggests Medilac-S® adjunctive therapy should be considered standard care for UC in a Chinese population because it aids in the induction of clinical remission, improves symptoms of the gastrointestinal tract and reduces risk of AEs.
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Affiliation(s)
- Ghania Sohail
- Lallemand Health Solutions Inc., Montreal, QC H4P 2R2, Canada
| | - Xiaoyu Xu
- Lallemand Health Solutions Inc., Montreal, QC H4P 2R2, Canada
| | - Mary C Christman
- MCC Statistical Consulting, Gainesville, FL 32605, United States
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Qiao C, Yang L, Wan J, Liu X, Pang C, You W, Zhao G. Long noncoding RNA ANRIL contributes to the development of ulcerative colitis by miR-323b-5p/TLR4/MyD88/NF-κB pathway. Biochem Biophys Res Commun 2018; 508:217-224. [PMID: 30477744 DOI: 10.1016/j.bbrc.2018.11.100] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 11/15/2018] [Indexed: 12/20/2022]
Abstract
The aim of this study was to investigate the role and possible mechanism of long noncoding RNA ANRIL in the development of ulcerative colitis (UC). The expression of ANRIL in colonic mucosa tissues collected from the sigmoid colon of UC patients and healthy control was determined. Subsequently, fetal human cells (FHCs) were treated with lipopolysaccharide (LPS) to stimulate UC-caused inflammatory injury, followed by detection of the effects of suppression of ANRIL on cell viability, apoptosis and cytokines production in LPS-stimulated FHCs. Moreover, the regulatory relationship between ANRIL and miR-323b-5p as well as the target relationship between miR-323b-5p and TLR4 were investigated. Furthermore, the effects of ANRIL/miR-323b-5p axis on the activation of TLR4/MyD88/NF-κB pathway in LPS-stimulated FHCs were investigated. LncRNA ANRIL was highly expressed in colonic mucosa tissues of UC patients. In addition, LPS markedly induced cell injury in FHC cells (inhibited cell viability and promoted cell apoptosis and cytokine production). Suppression of ANRIL alleviated LPS-induced injury in FHC cells, which was achieved by negatively regulating miR-323b-5p. Moreover, miR-323b-5p negatively regulated TLR4 expression and TLR4 was a target of miR-323b-5p. Knockdown of TLR4 reversed the effects of miR-323b-5p suppression on LPS-induced injury in LPS-stimulated FHCs. Furthermore, the effects of ANRIL on LPS-induced cell injury were achieved by TLR4/MyD88/NF-κB pathway. Our data indicate that suppression of ANRIL may inhibit the development of UC by regulating miR-323b-5p/TLR4/MyD88/NF-κB pathway. ANRIL/miR-323b-5p/TLR4/MyD88/NF-κB pathway may provide a new strategy for UC therapy.
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Affiliation(s)
- Cuixia Qiao
- Department of Anorectal, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China; School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China
| | - Lili Yang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China; Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jine Wan
- Department of High Pressure Oxygen, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Xiaoling Liu
- Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, Shandong, 266000, China
| | - Chengjian Pang
- Department of Anorectal, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Wenli You
- Department of Anorectal, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Gang Zhao
- Department of Anorectal, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China.
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Feng W, Ao H, Yue S, Peng C. Systems pharmacology reveals the unique mechanism features of Shenzhu Capsule for treatment of ulcerative colitis in comparison with synthetic drugs. Sci Rep 2018; 8:16160. [PMID: 30385774 PMCID: PMC6212405 DOI: 10.1038/s41598-018-34509-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 10/16/2018] [Indexed: 12/17/2022] Open
Abstract
In clinic, both synthetic drugs and Shenzhu Capsule (SZC), one kind of traditional Chinese medicines (TCMs), are used to treat ulcerative colitis (UC). In our study, a systems pharmacology approach was employed to elucidate the chemical and mechanism differences between SZC and synthetic drugs in treating UC. First, the compound databases were constructed for SZC and synthetic drugs. Then, the targets of SZC were predicted with on-line tools and validated using molecular docking method. Finally, chemical space, targets, and pathways of SZC and synthetic drugs were compared. Results showed that atractylenolide I, atractylone, kaempferol, etc., were bioactive compounds of SZC. Comparison of SZC and synthetic drugs showed that (1) in chemical space, the area of SZC encompasses the area of synthetic drugs; (2) SZC can act on more targets and pathways than synthetic drugs; (3) SZC can not only regulate immune and inflammatory reactions but also act on ulcerative colitis complications (bloody diarrhea) and prevent UC to develop into colorectal cancer whereas synthetic drugs mainly regulate immune and inflammatory reactions. Our study could help us to understand the compound and mechanism differences between TCM and synthetic drugs.
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Affiliation(s)
- Wuwen Feng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hui Ao
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shijun Yue
- College of Pharmacy and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Cheng Peng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
- State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Wang Y, Tang Q, Duan P, Yang L. Curcumin as a therapeutic agent for blocking NF-κB activation in ulcerative colitis. Immunopharmacol Immunotoxicol 2018; 40:476-482. [PMID: 30111198 DOI: 10.1080/08923973.2018.1469145] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is a chronic, relapsing, remitting, and inflammatory disorder that afflicts millions of people around the world. It carries a substantial economic burden, reducing the quality of life, ability to work, and increasing disability. Conventional medical treatment of UC includes the use of aminosalicylates, corticosteroids, and immunosuppressive drugs. However, these medicines are not always effective due to some serious side effects. Nuclear factor-kappa B (NF-κB) is a key factor in the inflammatory setting and strongly affects the course of mucosal inflammation in UC. This review aims to describe the complex role of NF-κB in UC and discuss existing pharmacological attempts by curcumin for blocking NF-κB activation to develop new therapeutic strategies in UC. Several studies have shown intriguing pharmacologic effects associated with curcumin, which inhibits NF-κB expression by regulating NF-κB/IkB pathway and down-regulation expression of pro-inflammatory cytokines, such as Interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α. The efficacy of curcumin has been confirmed in several experimental models of UC. Furthermore, curcumin significantly induced clinical remission in active mild-to-moderate UC patients and reduced clinical relapse in quiescent UC patients. The inhibitory effects of curcumin on NF-κB and its unrivaled safety profile indicate that it remains effective for the treatment of UC. In addition, curcumin is a nontoxic, inexpensive, and easily available natural polyphenol. In conclusion, curcumin can be used as a potential and safe drug in the management of patients with remission and mild-to-moderate UC.
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Affiliation(s)
- Yiqing Wang
- a Department of Gastroenterology , Yancheng First Peoples' Hospital , Yancheng , Jiangsu , China
| | - Qichun Tang
- b Department of Nursing , Yancheng First Peoples' Hospital , Yancheng , Jiangsu , China
| | - Peibei Duan
- c Department of Nursing , Jiangsu Province Hospital of Traditional Chinese Medicine , Nanjing , Jiangsu , China
| | - Lihua Yang
- d Department of Oncology , Jiangsu Province Hospital of Traditional Chinese Medicine , Nanjing , Jiangsu , China
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Cui G, Yuan A. A Systematic Review of Epidemiology and Risk Factors Associated With Chinese Inflammatory Bowel Disease. Front Med (Lausanne) 2018; 5:183. [PMID: 29971235 PMCID: PMC6018203 DOI: 10.3389/fmed.2018.00183] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 05/31/2018] [Indexed: 01/30/2023] Open
Abstract
Background: Recent epidemiological data have revealed a dramatically rising prevalence and incidence of inflammatory bowel diseases (IBDs) in Mainland China, a rapidly growing industrialized region, over the last two decades. Objectives: We performed a systematic review to investigate the changing trends in the incidence of IBD in Mainland China and summarized the recent findings in risk factors associated with Chinese IBD. Methods: Relevant references were obtained from an electronic database search via MEDLINE and EMBASE (for English literatures), the China Academic Journals Full-text Database (CJFD) and the China Science Periodical Database (CSPD) in Wanfang Data (for Chinese literatures). Results: Total 1,584 abstracts in Chinese and 171 abstracts in English were collected. Eight full-text with epidemiological data, 25 with risk factor data in Chinese and 7 full-text with epidemiological data, 12 with risk factor data in English were finally identified and included for analysis. Data from included epidemiological studies has showed a striking increase in the incidence rate of IBD in Mainland China over time, and current incidence rates for IBD, UC, and CD were 1.80 (IBD), 1.33 (UC), and 0.46/1,000,000 (CD), though it varies among regions and ethnic minority populations. In addition, several risk factors including environmental factors, diet, intestinal infectious agents, hygiene, stress, and lifestyle have been reported to be associated with the increased incidence of Chinese IBD. Conclusion: This systematic review revealed an increased incidence of IBD in Mainland China. Although it is still lower than that in the Western world, however, China has a huge population; therefore, the total number of IBD patients might not be so little as previously thought and the disease burden of IBD in China is likely underestimated. HIGHLIGHTS Recent epidemiological data have revealed a dramatically rising prevalence and incidence of inflammatory bowel diseases (IBD) in Mainland China, a rapidly growing industrialized region, over the last two decades.This systematic review based on recent epidemiological data has revealed a striking increase in the incidence rate of IBD in Mainland China, though it varies among regions and ethnic minority populations.Several potential risk factors of IBD including environmental factors, diet, intestinal infectious agents, hygiene, stress, and lifestyle have been reported to be associated with the increased incidence of Chinese IBD.This systematic review on epidemiologic and risk factor studies has expanded understanding of the occurrence, distribution, geographic variance and risk factors of Chinese IBD and will provide clinicians important information in understanding current status of IBD in Mainland China.
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Affiliation(s)
- Guanglin Cui
- Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Faculty of Health Science, Nord University, Bodø, Norway
| | - Aping Yuan
- Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Luo CX, Wen ZH, Zhen Y, Wang ZJ, Mu JX, Zhu M, Ouyang Q, Zhang H. Chinese research into severe ulcerative colitis has increased in quantity and complexity. World J Clin Cases 2018; 6:35-43. [PMID: 29564356 PMCID: PMC5852397 DOI: 10.12998/wjcc.v6.i3.35] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 02/06/2018] [Accepted: 02/28/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the current state of research output from Chinese studies into severe ulcerative colitis (SUC) using a bibliometric analysis of publications. METHODS The contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015). The number of publications in each year was recorded to assess the temporal trends of research output. All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously. The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers. RESULTS There were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC. The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period. There was a significant increase in analytical studies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating. Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management. About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38. The number of patients reported in each 5-year period significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis. CONCLUSION The output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.
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Affiliation(s)
- Cheng-Xin Luo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhong-Hui Wen
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu Zhen
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhu-Jun Wang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jing-Xi Mu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Min Zhu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Qin Ouyang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hu Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Naganuma M, Sugimoto S, Mitsuyama K, Kobayashi T, Yoshimura N, Ohi H, Tanaka S, Andoh A, Ohmiya N, Saigusa K, Yamamoto T, Morohoshi Y, Ichikawa H, Matsuoka K, Hisamatsu T, Watanabe K, Mizuno S, Suda W, Hattori M, Fukuda S, Hirayama A, Abe T, Watanabe M, Hibi T, Suzuki Y, Kanai T. Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis. Gastroenterology 2018; 154:935-947. [PMID: 29174928 DOI: 10.1053/j.gastro.2017.11.024] [Citation(s) in RCA: 137] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 10/27/2017] [Accepted: 11/17/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. METHODS We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0-1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. RESULTS The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P < .0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P = .0004) and the 2.0 g IN group (38.1%, (P = .0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P = .0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. CONCLUSIONS In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5-2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).
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Affiliation(s)
- Makoto Naganuma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shinya Sugimoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan
| | - Naoki Yoshimura
- Department of Internal Medicine, Division of IBD, Tokyo Yamate Medical Center, Tokyo, Japan
| | - Hidehisa Ohi
- Department of Gastroenterology, Imamura Hospital, Kagoshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Akira Andoh
- Department of Medicine, Shiga University of Medical Science, Otsu, Japan
| | - Naoki Ohmiya
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Keiichiro Saigusa
- Department of Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan
| | | | - Yuichi Morohoshi
- Department of Medicine, Yokohama Municipal Citizen's Hospital, Yokohama, Japan
| | - Hitoshi Ichikawa
- Department of Gastroenterology, Tokai University Hachioji Hospital, Hachioji, Japan
| | - Katsuyoshi Matsuoka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan
| | - Kenji Watanabe
- Division of Gastroenterology, Osaka City General Hospital, Osaka, Japan; Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Japan
| | - Shinta Mizuno
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Wataru Suda
- Department of Immunology, Keio University School of Medicine, Tokyo, Japan; Laboratory of Metagenomics, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan
| | - Masahira Hattori
- Laboratory of Metagenomics, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan
| | - Shinji Fukuda
- Institute for Advanced Biosciences, Keio University, Yamagata, Japan
| | - Akiyoshi Hirayama
- Institute for Advanced Biosciences, Keio University, Yamagata, Japan
| | - Takayuki Abe
- Department of Preventive Medicine and Public Health, Biostatistics Unit at Clinical and Translational Research Center, Keio University School of Medicine, Tokyo, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan
| | - Yasuo Suzuki
- Department of Gastroenterology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
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Current smoking improves ulcerative colitis patients' disease behaviour in the northwest of China. GASTROENTEROLOGY REVIEW 2017; 12:286-290. [PMID: 29358998 PMCID: PMC5771453 DOI: 10.5114/pg.2017.72104] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Accepted: 10/29/2016] [Indexed: 12/21/2022]
Abstract
Introduction The incidence of ulcerative colitis has increased tremendously over the past few decades, and caused much more attention in China. Several studies have revealed that both environmental and genetic factors play crucial roles in the formation and development of this disease. Among the environmental factors, the smoking condition is highly significant. Although current smoking has been associated with a protective effect on both the development and progression of ulcerative colitis (UC), the clinical characteristics of UC patients with current smoking in China is still unclear. Aim To clarify the relationship between current smoking and the UC in the northwest of China, patients diagnosed with ulcerative colitis in the General Hospital of Ningxia Medical University from 2003.03 to 2012.09 were assessed. Material and methods Data were collected about clinical features, cigarette smoking conditions, disease location, and therapeutic requirements. A total of 421 patients were included in this study, at diagnosis, 341 (81%) patients were non-smokers, and the current smokers amounted to 80 (19%). Results As for disease location, there were no differences between the current smokers and non-smokers regarding proctitis and extensive colitis, but the current smokers had less left-sided colitis than non-smokers (p = 0.049). Based on the Modified Mayo score, heavier smokers had lower scores than other smokers and non-smokers. For the therapeutic requirements, current smokers needed fewer corticosteroids than non-smokers (p = 0.048). Conclusions We found that current smoking is closely associated with a protective factor for UC.
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A New Chinese Medicine Intestine Formula Greatly Improves the Effect of Aminosalicylate on Ulcerative Colitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:7323129. [PMID: 29358969 PMCID: PMC5735632 DOI: 10.1155/2017/7323129] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 08/13/2017] [Accepted: 08/29/2017] [Indexed: 12/21/2022]
Abstract
Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon. Current medical treatment of UC relies predominantly on the use of traditional drugs, including aminosalicylates, corticosteroids, and immunosuppressants, which failed to effectively control this disease's progression and produced various side effects. Here, we report a new Chinese medicine intestine formula (CIF) which greatly improved the effect of mesalazine, an aminosalicylate, on UC. In the present study, 60 patients with chronic UC were treated with oral mesalazine alone or in combination with CIF enema. The combination of mesalazine and CIF greatly and significantly improved the clinical symptoms and colon mucosal condition and improved the Mayo Clinic Disease Activity Index and health-related quality of life, when compared to mesalazine alone. In particular, the addition of CIF further decreased serum levels of tumor necrosis factor-alpha and hypersensitivity C-reactive protein but in contrast increased interleukin-4. Thus, the results demonstrate the beneficial role of CIF in UC treatment, which may be mediated by the regulation of inflammation.
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Abstract
BACKGROUND Inflammatory bowel disease (IBD), once considered to be a Western disease, is increasingly being reported from India and other Asian countries. The present review summarizes epidemiology and disease characteristics of IBD in India with reference to other Asian countries and the West. SUMMARY India is projected to have one of the highest disease burden of IBD across the globe. The overall genetic risk and microbial signature in Indian IBD patients are similar to those of patients in the West as demonstrated by the similar incidence of IBD in second-generation Indian immigrants and matching perturbations in the structural and functional component of gut microbiota in Indian studies. The concept of the hygiene hypothesis continues to remain controversial with Indian studies demonstrating contradictory findings. The disease characteristics, long-term outcomes including the risk of colorectal cancer, and the effect of pregnancy on IBD and vice versa in Indian patients with IBD are in general similar with few differences. Unlike patients in the West, very few Indian patients have a positive family history. KEY MESSAGE The Indian disease pattern is going through a phase of epidemiological transition with a surge in the incidence of IBD. The epidemiology and disease characteristics of IBD mirror the patterns observed in the West.
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Affiliation(s)
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Hou J, Hu X, Chen B, Chen X, Zhao L, Chen Z, Liu F, Liu Z. miR-155 targets Est-1 and induces ulcerative colitis via the IL-23/17/6-mediated Th17 pathway. Pathol Res Pract 2017; 213:1289-1295. [PMID: 28888763 DOI: 10.1016/j.prp.2017.08.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 07/12/2017] [Accepted: 08/15/2017] [Indexed: 01/19/2023]
Abstract
BACKGROUND Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) affecting millions of people worldwide. miR-155 has been reported to be upregulated in various inflammatory diseases and is a positive regulator of the T-cell response. IL-17 secreting helper T (Th17) cells have been heavily implicated in tissue-specific immune pathology, including UC. METHODS AND RESULTS Therefore, we targeted miR-155 and investigated its expression levels in a DSS-induced UC mouse model, revealing increased expression. Est-1 expression was found to have decreased, but the levels of IL-23/17/6 were raised significantly and Th17 had experienced an obvious increase. We overexpressed miR-155 using a lentiviral treatment. Increased miR-155 expression induced a more severe damage to colon tissues. In this case, the level of Est-1 decreased even further, thereby enhancing IL-23/17/6-mediated Th17 differentiation. CONCLUSION miR-155 seems to target Est-1 and induces UC via the IL-23/17/6-mediated Th17 pathway.
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Affiliation(s)
- Jiangtao Hou
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Xueying Hu
- The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Bin Chen
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Xu Chen
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Lina Zhao
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Zhuoqun Chen
- Clinical Skills Center, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Fengbin Liu
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Zhihui Liu
- Department of Laboratory, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
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Jung YS, Han M, Kim WH, Park S, Cheon JH. Incidence and Clinical Outcomes of Inflammatory Bowel Disease in South Korea, 2011-2014: A Nationwide Population-Based Study. Dig Dis Sci 2017; 62:2102-2112. [PMID: 28593437 DOI: 10.1007/s10620-017-4640-9] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 05/29/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The incidence of inflammatory bowel disease (IBD) is increasing in East Asia; however, population-based data from this region are lacking. AIM We conducted a nationwide, population-based study to examine the incidence and disease course of IBD in South Korea. METHODS Using the National Health Insurance claims data, we collected data on patients diagnosed with IBD [10,049 with ulcerative colitis (UC) and 5595 with Crohn's disease (CD)] from 2011 to 2014. RESULTS During the study period, the average annual incidence of UC was 5.0 per 105, while that of CD was 2.8 per 105. Among patients with UC, the cumulative rates of surgery 1 and 4 years after diagnosis were 1.0 and 2.0%; those among patients with CD were 9.0 and 13.9%, respectively. The 1- and 4-year cumulative rates of moderate- to high-dose corticosteroid use were, respectively, 26.6 and 45.2% among patients with UC, and 29.9 and 50.8% among those with CD. Similarly, the 1- and 4-year cumulative rates of immunomodulator use were 14.1 and 26.4% among patients with UC, and 58.3 and 76.1% among those with CD, respectively. With regard to biologic use, the 1- and 4-year cumulative rates were 3.0 and 9.0% among patients with UC, and 11.1 and 31.7% among those with CD, respectively. CONCLUSIONS The recent incidence of IBD in South Korea has been the highest in East Asia. Patients who had been diagnosed recently with IBD showed lower rates of surgery and higher rates of immunomodulator and biologic use compared to those reported ever in South Korea.
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Affiliation(s)
- Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Minkyung Han
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea
| | - Won Ho Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Sohee Park
- Department of Biostatistics, Graduate School of Public Health, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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Gupta A, Bopanna S, Kedia S, Yadav DP, Goyal S, Jain S, Makharia G, Ahuja V. Familial aggregation of inflammatory bowel disease in patients with ulcerative colitis. Intest Res 2017; 15:388-394. [PMID: 28670236 PMCID: PMC5478764 DOI: 10.5217/ir.2017.15.3.388] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 10/07/2016] [Accepted: 10/12/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS Familial occurrence of inflammatory bowel disease (IBD) is well documented. Reports from Western countries have shown a higher familial occurrence of ulcerative colitis (UC) in first- and second-degree relatives than that in the Asian UC population. No data are currently available from the Indian subcontinent in this regard. We present our data on the familial aggregation of UC. METHODS Records of patients with UC followed at the Inflammatory Bowel Disease Clinic at the All India Institute of Medical Sciences, New Delhi from August 2004 to January 2016 were reviewed. Details regarding the prevalence of family history and characteristics of these patients were recorded. Affected family members were contacted and disease characteristics were noted for assessment of familial aggregation. RESULTS Of the 2,058 UC patients included in the analysis, a positive family history of IBD was confirmed in 31 patients (1.5%), 24 (77.4%) of whom had only first-degree relatives affected. All the affected relatives had UC and none had Crohn's disease. Among first-degree relatives, siblings were found to have the highest prevalence of IBD (53.3%), followed by parents (26.7%). CONCLUSIONS The probability of occurrence of IBD in family members of affected North Indian UC patients is lower than that reported in Western populations.
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Affiliation(s)
- Akshita Gupta
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sawan Bopanna
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Dawesh Prakash Yadav
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Goyal
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Saransh Jain
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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Zobeiri M, Bashiri H, Askari L, Keshavars AA, Tavvafzadeh R, Fatahi K, Najafi F. Epidemiologic Characteristics of Patients with Inflammatory Bowel Disease in Kermanshah, Iran. Middle East J Dig Dis 2017; 9:164-169. [PMID: 28894519 PMCID: PMC5585909 DOI: 10.15171/mejdd.2017.68] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND
This study was done to define some epidemiological aspects of inflammatory bowel disease
(IBD), and to describe its characteristics in west of Iran.
METHODS
In this descriptive study all patient with the diagnosis of IBD who were visited in universityaffiliated
medical centers, between 2014 and 2015 were recruited. Their demographic characteristics,
disease-related manifestations, complications, disease course and their chief complaints were analyzed.
RESULTS
Of 156 referred individuals, 153 patients had ulcerative colitis (UC) and 3 patients had Crohn’s
diseases (CD). The mean age of the patients at diagnosis was 35.69±12.35 (range: 17-80) years with the
most common age group of 25-35 years and slight female predominance (51.9%). More urban patients
were registered (90.4%) and 57% had high school or upper education. Positive family history of the
disease was in 25.6% and 66.6% had four or more family members. Furthermore, 51.9% had left sided
colitis and 40.4% had pancolitis with bloody diarrhea (79.5%) and abdominal pain (68.6%) as the most
common manifestations.
36.5% had other autoimmune diseases. Multiple flare was seen in 47.4%, most commonly due to
drug discontinuation (26.28%). Hospital admission was reported in 34.6%. History of contraceptive
pill use was in 38.8% of the female patients.
CONCLUSION
The demographic and clinical manifestations of IBD are usually the same as other developing
countries; however, the rarity of CD is eminent. Although the accurate epidemiological characteristic
of IBD in Iran is still obscure, it is not a rare disease as previously thought and it seems that gradual
reception of a western lifestyle may be linked to the ongoing rise in IBD.
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Affiliation(s)
- Mehdi Zobeiri
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Homayoon Bashiri
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Lotfollah Askari
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ali Asghar Keshavars
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ramin Tavvafzadeh
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Kiomars Fatahi
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farid Najafi
- Kermanshah Health Research Center (KHRC), Kermanshah University of Medical Sciences, Kermanshah, Iran
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Prevalence of Adherent-Invasive Escherichia coli with fimH Gene Isolated from Iranian Patients with Ulcerative Colitis. Jundishapur J Microbiol 2017. [DOI: 10.5812/jjm.13858] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Kaplan GG, Ng SC. Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology 2017; 152:313-321.e2. [PMID: 27793607 DOI: 10.1053/j.gastro.2016.10.020] [Citation(s) in RCA: 787] [Impact Index Per Article: 98.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 10/19/2016] [Accepted: 10/20/2016] [Indexed: 02/06/2023]
Abstract
The inflammatory bowel diseases (IBDs) are contemporary conditions of industrialized societies. The prevalence of IBD continues to increase steadily in Western countries, and newly industrialized countries have a rapidly increasing incidence. The global spread of IBD appears to associate with Westernization of diets and environments, which affects the intestinal microbiome and increases the risk of IBD in genetically susceptible individuals. It is important to increase our understanding of these events to slow progression of IBD. We present a long-term plan to develop interventions that slow or stop the global increase in the incidence of IBD.
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Affiliation(s)
- Gilaad G Kaplan
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China.
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Mendoza Ladd A, Jia Y, Yu C, Elhanafi S, Dwivedi A, Liu J, Song G, Hall M, Zuckerman MJ. Demographic and Clinical Characteristics of a Predominantly Hispanic Population with Inflammatory Bowel Disease on the US-Mexico Border. South Med J 2016; 109:792-797. [PMID: 27911976 DOI: 10.14423/smj.0000000000000571] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Information regarding Hispanics with inflammatory bowel disease (IBD) is scarce. In this study we aimed to describe a predominantly Hispanic population with IBD in a city located along the US-Mexico border and to identify clinical or demographic differences between Hispanics and non-Hispanics. METHODS Retrospective cohort analysis of patients with IBD between 2003 and 2013 at a tertiary care center. Information collected included age, sex, ethnicity, diagnosis, diagnosis status (new vs old), endoscopic extent of disease (EOD), extraintestinal manifestations, medical treatment, and surgeries performed. Continuous and categorical variables were compared using a two-sided unpaired t test/Wilcoxon rank sum test and the Fisher exact test, respectively. Results with P ≤ 5% were considered statistically significant. RESULTS Hispanics accounted for 71% of the population sample. A total of 141 patients (68%) were diagnosed as having ulcerative colitis (UC) and 67 (32%) as having Crohn disease (CD). The only statistically significant differences between Hispanics and non-Hispanics were older age at diagnosis and a higher proportion of new diagnoses in Hispanics with CD (P = 0.008 and 0.009, respectively) The most common EOD in patients with UC was extensive colitis, whereas isolated colonic disease predominated in CD, regardless of ethnicity. Immunomodulators and biologics were used in 3% and 1% of cases, respectively. Treatment regimens were similar in both ethnic groups. Patients with CD were more likely than those with UC to have undergone surgery (27% vs 11%, P = 0.004). Surgery rates did not differ between Hispanics and non-Hispanics. CONCLUSIONS In our population, UC was more common than CD, and the EOD of both conditions differed from the one previously described in other Hispanic populations in the United States. The use of immunomodulators and biologics is the lowest reported to date in the country. No clinically relevant differences were seen between Hispanics and non-Hispanics.
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Affiliation(s)
- Antonio Mendoza Ladd
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Yi Jia
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Christine Yu
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Sherif Elhanafi
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Alok Dwivedi
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Jiayang Liu
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Giangqing Song
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Mark Hall
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
| | - Marc J Zuckerman
- From the Department of Medicine, Division of Gastroenterology, the Division of Biostatistics & Epidemiology, and the Division of Biostatistics, Texas Tech University Health Sciences Center at El Paso, and the Paul L. Foster School of Medicine, Texas Tech University, El Paso
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Kaplan GG, Ng SC. Globalisation of inflammatory bowel disease: perspectives from the evolution of inflammatory bowel disease in the UK and China. Lancet Gastroenterol Hepatol 2016; 1:307-316. [PMID: 28404201 DOI: 10.1016/s2468-1253(16)30077-2] [Citation(s) in RCA: 154] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 07/20/2016] [Accepted: 07/28/2016] [Indexed: 02/07/2023]
Abstract
The UK and China provide unique historical perspectives on the evolution of the incidence of inflammatory bowel disease, which might provide insight into its pathogenesis. Historical records from the UK document the emergence of ulcerative colitis during the mid-1800s, which was later followed by the recognition of Crohn's disease in 1932. During the second half of the 20th century, the incidence of inflammatory bowel disease rose dramatically in high-income countries. Globalisation at the turn of the 21st century led to rapid economic development of newly industrialised countries such as China. In China, the modernisation of society was accompanied by the recognition of a sharp rise in the incidence of inflammatory bowel disease. The prevalence of inflammatory bowel disease is expected to continue to rise in high-income countries and is also likely to accelerate in the developing world. An understanding of the shared and different environmental determinants underpinning the pathogenesis of inflammatory bowel disease in western and eastern countries is essential to implement interventions that will blunt the rising global burden of inflammatory bowel disease.
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Affiliation(s)
- Gilaad G Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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Fujii T, Sato M, Hosoi K, Ohbayashi N, Ikuse T, Jimbo K, Aoyagi Y, Kudo T, Ohtsuka Y, Shimizu T. Assessment of the Family History of Patients With Ulcerative Colitis at a Single Center in Japan. J Pediatr Gastroenterol Nutr 2016; 63:512-515. [PMID: 27352080 DOI: 10.1097/mpg.0000000000001275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES The prevalence of ulcerative colitis (UC) differs by country, which is likely due to differences in genetic factors among ethnicities. Moreover, the prevalence of pediatric UC with a family history (FH) is 4.1% in Japanese patients; its clinical course begins at an early age and is more severe. Recently, a genome-wide association study identified 3 new susceptibility loci for adult Japanese patients with UC. METHODS To assess the effects of FH in patients with UC, 60 children were enrolled. Age at diagnosis, clinical features of the initial symptoms, and family structure were assessed in patients with and without an FH. The 3 new loci were examined in patients who provided informed consent. RESULTS Of the patients with UC, 10 (16.7%) had an FH involving first-degree relatives, including 7 mothers, 1 father, and 2 sisters. There was a trend toward a younger age at onset in the positive FH group. There were, however, no significant differences in the clinical characteristics of the patients regardless of FH. From the genomic analyses, there were significant differences in the polymorphisms of the solute carrier family 26, member 3 (SLC26A3) between those with and without an FH. CONCLUSIONS Although the etiology of UC remains unknown, there were no observed relation between clinical symptoms and FH. SLC26A3 may, however, contribute to the pathogenesis of UC in Japanese individuals with an FH.
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Affiliation(s)
- Tohru Fujii
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
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Ghanadi K, Valizadeh J, Hasanvand A. Epidemiological and clinical aspects of ulcerative colitis in west of Iran: a cross sectional study. SPRINGERPLUS 2016; 5:1588. [PMID: 27652161 PMCID: PMC5025405 DOI: 10.1186/s40064-016-3248-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 09/07/2016] [Indexed: 12/22/2022]
Abstract
Introduction One of the forms of inflammatory bowel disease (IBD) that causes inflammation and ulcers in colon is ulcerative colitis (UC). This study was aimed to determine the epidemiological and clinical aspects of patients with ulcerative colitis in the west of Iran. Methods In this cross sectional study, we evaluated 150 patients with definite diagnosis of UC who referred to a subspecialty gastroenterology clinic in Khorramabad, Iran. The study was performed from May 2014 to August 2015 by using census method. Demographic characteristics as well as patients’ clinical profiles were extracted using a checklist. Disease severity was determined by the Truelove and Witt’s classification of ulcerative colitis (UC). Data were analyzed using SPSS software, version 17 for windows (IBM Inc., NY, US). Results A total of 150 patients with definite diagnosis of UC were analyzed, including 84 (56 %) women and 66 (44 %) men (male/female ratio = 1.27). The mean age of patients was 33.7 ± 12.5 years with an age range of 17–98 years. The age of the majority of patients was 20–29 and most of them (56 %) were women and living in urban areas (70.7 %). The most common site of the involvement in colon was rectosigmoid (66 patients, 44 %). Severity of the disease was mild in 36 patients (24.1 %), moderate and severe in 74 and 40 patients (49.3 and 26.6 %), respectively. The most common clinical manifestation of the patients was dysentery (68 %) and then rectorrhagia (60 %). Only 12 of all patients (7.8 %) mentioned a positive family history of IBD in their first degree kinfolks. Ten patients (6.7 %) had a history of regular smoking and four of them (2.6 %) mentioned a history of appendectomy. Four patients (5.3 %) had a positive history of smoking by their mothers during their pregnancy. Conclusion The results of this study demonstrate differences and similarities in demographic and clinical characteristics of UC in this part of Iran in comparison to other parts of the country.
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Affiliation(s)
- Koroush Ghanadi
- Gastroenterology and Hepatology, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Javad Valizadeh
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Afshin Hasanvand
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
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