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HUANG J, LUO Q, DONG G, PENG W, HE J, DAI W. Xiahuo Pingwei San attenuated intestinal inflammation in dextran sulfate sodium-induced ulcerative colitis mice through inhibiting the receptor for advanced glycation end-products signaling pathway. J TRADIT CHIN MED 2025; 45:311-325. [PMID: 40151118 PMCID: PMC11955771 DOI: 10.19852/j.cnki.jtcm.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 11/11/2024] [Indexed: 03/29/2025]
Abstract
OBJECTIVE To evaluate the therapeutic effects of Xiahuo Pingwei San (, XHPWS) on ulcerative colitis (UC) in mice and to explore the underlying mechanisms through a network pharmacology approach. METHODS Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was utilized to identify the chemical composition and authenticate the active constituents of XHPWS, ensuring rigorous quality control across batches. A dextran sulfate sodium (DSS)-induced UC model was established in C57BL/6 mice, which were treated with XHPWS in vivo. The efficacy against UC was assessed by measuring parameters such as body weight, disease activity index (DAI) scores, and colon length. Levels of inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α), in colonic tissue were evaluated using enzyme-linked immunosorbent assay (ELISA). Histological analysis of colon sections was conducted using hematoxylin and eosin staining. A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment. Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry (IHC) and Western blotting techniques. RESULTS XHPWS effectively alle viated DSS-induced UC symptoms in mice, as evidenced by restored body weight, reduced colon shortening, and decreased DAI scores. Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration, restored intestinal epithelial permeability, and increased goblet cell count. Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment. Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway. Notably, quercetin, kaempferol, wogonin, and nobiletin, the main components of XHPWS, showed strong correlations with the core targets. Additionally, experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6 (IL-6), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in UC mice, while downregulating the expression of proteins related to the AGE-RAGE pathway. CONCLUSION Our study demonstrated that XHPWS effectively alle viates colitis symptoms and inflammation in UC mice, potentially through the regulation of the AGE-RAGE pathway. These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment, thereby broadening its clinical applications.
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Affiliation(s)
- Jiaen HUANG
- 1 Department of Pharmacy, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan 528400, China
| | - Qing LUO
- 2 State Key Laboratory of Quality Research in Chinese Medicine & Faculty of Chinese Medicine, Macau University of Science and Technology, Macau SAR 999078, China
| | - Gengting DONG
- 3 Pharmacology Laboratory, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan 528400, China
| | - Weiwen PENG
- 1 Department of Pharmacy, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan 528400, China
| | - Jianhong HE
- 1 Department of Pharmacy, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan 528400, China
| | - Weibo DAI
- 3 Pharmacology Laboratory, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan 528400, China
- 4 National Bngineering Research Center for Modernization of Traditional Chinese Medicine, Hospital Prepration Transformation Branch, Zhongshan 528400, China
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Mansouri P, Mansouri P, Behmard E, Najafipour S, Kouhpayeh A, Farjadfar A. Novel targets for mucosal healing in inflammatory bowel disease therapy. Int Immunopharmacol 2025; 144:113544. [PMID: 39571265 DOI: 10.1016/j.intimp.2024.113544] [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: 06/01/2024] [Revised: 10/13/2024] [Accepted: 10/28/2024] [Indexed: 12/15/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.
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Affiliation(s)
- Pardis Mansouri
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran; Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran
| | - Pegah Mansouri
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran; Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran
| | - Esmaeil Behmard
- School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran; Zarrin Avaye Kowsar Salamat (ZAX Company), Fasa, Iran
| | - Sohrab Najafipour
- School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran; Zarrin Avaye Kowsar Salamat (ZAX Company), Fasa, Iran
| | - Amin Kouhpayeh
- Department of Pharmacology, Faculty of Medicine, Fasa University of Medical Sciences, Fasa, Iran; Zarrin Avaye Kowsar Salamat (ZAX Company), Fasa, Iran.
| | - Akbar Farjadfar
- Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran; Zarrin Avaye Kowsar Salamat (ZAX Company), Fasa, Iran.
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Gomollón F. New treatments in inflammatory bowel disease - A thrilling time ahead. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:657-660. [PMID: 39364707 DOI: 10.17235/reed.2024.10764/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Except for some surgical techniques, up to 1940 the clinical course of inflammatory bowel disease was determined by its own natural history: most medical interventions even worsened prognosis. The empyrical introduction of salazopyrine early in the 1940s, pioneered by Nanna Svartz in Sweden, was followed relatively soon by the incorporation of corticosteroids during the 1950s. However, it took both a long time to reach patients, and quality scientific evidence to better establish their indications built up very slowly.
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Affiliation(s)
- Fernando Gomollón
- Medicina, Psiquiatría y Dermatología, Facultad de Medicina. Universidad de Zaragoza, Spain
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4
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Delen S, Jaghult S, Blumenstein I, Pouillon L, Bossuyt P. Framework of IBD Care Delivery Across Ages. J Crohns Colitis 2024; 18:ii55-ii66. [PMID: 39475083 PMCID: PMC11523023 DOI: 10.1093/ecco-jcc/jjae093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 05/23/2024] [Accepted: 06/14/2024] [Indexed: 11/02/2024]
Abstract
IBD care has gone through a real transformation over the last century, moving from the mere unidirectional interaction between the physician and the patient to a stronger framework with multiple stakeholders who interconnect and strengthen each other. The patient has evolved from a passive subject to the central pole in the care pathway. Key elements of the future framework include patient self-care and empowerment, and remote monitoring [eHealth]. This care will be delivered by a multidisciplinary team acknowledging the pivotal role of the IBD nurse, and emphasising and measuring the quality of its work. The big challenge for the future is to establish a financially viable model to make this evolution durable in the long term, and this by using the principles of value-based health care.
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Affiliation(s)
- Stefan Delen
- Department of Gastroenterology, Ziekenhuis Oost Limburg [ZOL] Maas en Kempen, Maaseik, Belgium
| | - Susanna Jaghult
- Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden
| | - Irina Blumenstein
- Department of Gastroenterology, University Hospital, Goethe University, Frankfurt, Germany
| | - Lieven Pouillon
- Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium
| | - Peter Bossuyt
- Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium
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Hassan SA, Kapur N, Sheikh F, Fahad A, Jamal S. Disease clearance in ulcerative colitis: A new therapeutic target for the future. World J Gastroenterol 2024; 30:1801-1809. [PMID: 38659483 PMCID: PMC11036494 DOI: 10.3748/wjg.v30.i13.1801] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 02/16/2024] [Accepted: 03/19/2024] [Indexed: 04/03/2024] Open
Abstract
Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression. This has fueled the identification of molecular targets, resulting in a rapidly expanding therapeutic armamentarium. Subsequently, management strategies have evolved from symptomatic resolution to well-defined objective endpoints, including clinical remission, endoscopic remission and mucosal healing. While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications, studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures. Current recommendations lack consideration of histological healing. The simultaneous achievement of clinical, endoscopic, and histologic remission has not been fully investigated. This has laid the groundwork for a novel therapeutic outcome termed disease clearance (DC). This article summarizes the concept of DC and its current evidence.
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Affiliation(s)
- Syed Adeel Hassan
- Division of Digestive Disease and Nutrition, University of Kentucky, Lexington, KY 40536, United States
| | - Neeraj Kapur
- Division of Digestive Disease and Nutrition, University of Kentucky, Lexington, KY 40536, United States
| | - Fahad Sheikh
- Department of Pathology and Laboratory Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY 10461, United States
| | - Anam Fahad
- Division of Primary Care, Essen Healthcare, New York, NY 10457, United States
| | - Somia Jamal
- Department of Internal Medicine, Karachi Medical and Dental College, Karachi 74700, Sindh, Pakistan
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Xiong D, Chen Y, Zhu S, Liu L, Zhao L, Zeng C, Li Y, Wang H, Tu L, Zou K, Hou X, Yang L, Zhu L, Bai T. Exploring the relationship between urinary phthalate metabolites and Crohn's disease via oxidative stress, and the potential moderating role of gut microbiota: A conditional mediation model. Free Radic Biol Med 2023; 208:468-477. [PMID: 37690673 DOI: 10.1016/j.freeradbiomed.2023.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 08/31/2023] [Accepted: 09/07/2023] [Indexed: 09/12/2023]
Abstract
OBJECTIVE Interactions between phthalic acid esters (PAEs) exposure and Crohn's disease (CD) were unknown. This study aims to examine the association between exposure to PAEs and CD activity and to explore the roles of oxidative stress and microbiota. METHODS A cross-sectional study with 127 CD patients was conducted. The disease activity was evaluated based on symptoms (Harvey-Bradshaw index, HBI), endoscopy findings (Simple Endoscopic Score for CD, SES-CD), and computed tomography enterography (CTE-scores). Ten urinary PAEs metabolites (mPAEs), two urinary oxidative stress biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α), as well as 16S rRNA sequencing of stool samples were determined. Multiple linear regression models and Hayes's PROCESS macro for SPSS were used to evaluate the interplays between urinary PAEs metabolites, CD activities, oxidative stress, and microbiota diversity. RESULTS There were positive associations between most mPAEs and HBI. Oxidative stress mediated 20.69-89.29% of the indirect associations between low molecular weight (LMW) mPAEs and HBI, while the majority of the high molecular weight (HMW) mPAEs were directly associated with HBI. In addition, microbiota diversity moderated the indirect associations of LMW mPAEs on HBI. CONCLUSIONS PAEs exposure was related to CD activity, and the association could be mediated by oxidative stress and reversed or alleviated by rich gut microbiota.
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Affiliation(s)
- Danping Xiong
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Youli Chen
- State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Siran Zhu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Linlin Liu
- State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Occupational and Environmental Health, Key Laboratory of Environment & Health, Ministry of Education of the People's Republic of China, Wuhan, China
| | - Lei Zhao
- State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Occupational and Environmental Health, Key Laboratory of Environment & Health, Ministry of Education of the People's Republic of China, Wuhan, China
| | - Cui Zeng
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanling Li
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huan Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Tu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kaifang Zou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liangle Yang
- State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Occupational and Environmental Health, Key Laboratory of Environment & Health, Ministry of Education of the People's Republic of China, Wuhan, China.
| | - Liangru Zhu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Tao Bai
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Alsarhan A, Aljasmi R, Ajaka N, Krishnamurthy B, Kader A, Aljasmi M, Nahdi N, Malik E, Murbati B, Aljabri E, Tzivinikos C. Challenges in Managing Paediatric Crohn's Disease With Crohn's Disease Exclusion Diet (CDED): The First Single-Center Study in the United Arab Emirates. Cureus 2023; 15:e43970. [PMID: 37746457 PMCID: PMC10515460 DOI: 10.7759/cureus.43970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2023] [Indexed: 09/26/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease has been increasing significantly. For that, many modalities of treatment have shown promising results including a special diet. In our study, we looked at Crohn's disease dietary management for induction and subsequently maintenance of treatment. The research question was how feasible was applying this approach and what difficulties the patients and their parents faced. METHODOLOGY We reviewed the electronic medical system. We had 32 paediatric patients who were diagnosed with Crohn's disease and used the special diet plan (Crohn's disease exclusion diet or exclusion enteral nutrition) to induce remission or maintenance. Then, we used a questionnaire to identify the difficulties they faced while using the special diet. RESULTS AND DISCUSSION We have found that the cohort had used the special diet for a variable duration. The majority of patients opted to start with Crohn's disease exclusion diet. The clinical response was inconsistent due to poor compliance. Only 57 % of the patients were able to bear with the dietary plan beyond 12 weeks. Patients reported the following factors which caused non-compliance: intolerance/difficulty to follow (40%), cost (19%), poor clinical response (19%), and others. CONCLUSIONS In managing Crohn's disease, a multidisciplinary approach, including dietary interventions, is crucial. However, adherence to specialized diets poses several challenges identified in this study based on patient feedback. Addressing barriers and prioritizing dietitians' role is essential for improved patient outcomes in inflammatory bowel disease management.
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Affiliation(s)
- Ali Alsarhan
- Pediatric Gastroenterology, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Rehab Aljasmi
- Medical Affairs, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Natacha Ajaka
- Nutrition, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Balaji Krishnamurthy
- Pediatric Gastroenterology, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Ajmal Kader
- Pediatric Gastronetrology, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Masooma Aljasmi
- Nutrition, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Noor Nahdi
- Nutrition, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Ehsan Malik
- Pediatric Gastroenterology, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Buthaina Murbati
- Pediatric Gastroenterology, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Eiman Aljabri
- Pediatric Gastroenterology, Al Jalila Children's Speciality Hospital, Dubai, ARE
| | - Christos Tzivinikos
- Pediatric Gastroenterology, Al Jalila Children's Speciality Hospital, Dubai, ARE
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Jamieson PE, Carbonero F, Stevens JF. Dietary (poly)phenols mitigate inflammatory bowel disease: Therapeutic targets, mechanisms of action, and clinical observations. Curr Res Food Sci 2023; 6:100521. [PMID: 37266414 PMCID: PMC10230173 DOI: 10.1016/j.crfs.2023.100521] [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] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/14/2023] [Accepted: 05/16/2023] [Indexed: 06/03/2023] Open
Abstract
Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are a rapidly growing public health concern worldwide. These diseases are heterogeneous at the clinical, immunological, molecular, genetic, and microbial level, but characteristically involve a disrupted immune-microbiome axis. Shortcomings in conventional treatment options warrant the need for novel therapeutic strategies to mitigate these life-long and relapsing disorders of the gastrointestinal tract. Polyphenols, a diverse group of phytochemicals, have gained attention as candidate treatments due to their array of biological effects. Polyphenols exert broad anti-inflammatory and antioxidant effects through the modulation of cellular signaling pathways and transcription factors important in IBD progression. Polyphenols also bidirectionally modulate the gut microbiome, supporting commensals and inhibiting pathogens. One of the primary means by which gut microbiota interface with the host is through the production of metabolites, which are small molecules produced as intermediate or end products of metabolism. There is growing evidence to support that modulation of the gut microbiome by polyphenols restores microbially derived metabolites critical to the maintenance of intestinal homeostasis that are adversely disrupted in IBD. This review aims to define the therapeutic targets of polyphenols that may be important for mitigation of IBD symptoms, as well as to collate evidence for their clinical use from randomized clinical trials.
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Affiliation(s)
- Paige E. Jamieson
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA
| | - Franck Carbonero
- Department of Nutrition and Exercise Physiology, Washington State University, Spokane, WA, 99202, USA
| | - Jan F. Stevens
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331, USA
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Development of novel oridonin analogs as specifically targeted NLRP3 inflammasome inhibitors for the treatment of dextran sulfate sodium-induced colitis. Eur J Med Chem 2022; 245:114919. [DOI: 10.1016/j.ejmech.2022.114919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/07/2022] [Accepted: 11/07/2022] [Indexed: 11/13/2022]
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Pravda J. Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide. World J Gastroenterol 2022; 28:4263-4298. [PMID: 36159014 PMCID: PMC9453768 DOI: 10.3748/wjg.v28.i31.4263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 04/19/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
In this comprehensive evidence-based analysis of ulcerative colitis (UC), a causal role is identified for colonic epithelial hydrogen peroxide (H2O2) in both the pathogenesis and relapse of this debilitating inflammatory bowel disease. Studies have shown that H2O2 production is significantly increased in the non-inflamed colonic epithelium of individuals with UC. H2O2 is a powerful neutrophilic chemotactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular “trail” that attracts adjacent intravascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC. A novel therapy aimed at removing the inappropriate H2O2 mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one (biopsy-proven) histologic remission lasting 14 years to date. The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H2O2 mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease. Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects. It is the aim of this paper to present experimental and clinical evidence that identifies H2O2 produced by the colonic epithelium as the causal agent in the pathogenesis of UC. A detailed explanation of a novel therapeutic intervention to normalize colonic H2O2, its rationale, components, and formulation is also provided.
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Affiliation(s)
- Jay Pravda
- Disease Pathogenesis, Inflammatory Disease Research Centre, Palm Beach Gardens, FL 33410, United States
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11
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Chemistry of Hydrogen Peroxide Formation and Elimination in Mammalian Cells, and Its Role in Various Pathologies. STRESSES 2022. [DOI: 10.3390/stresses2030019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Hydrogen peroxide (H2O2) is a compound involved in some mammalian reactions and processes. It modulates and signals the redox metabolism of cells by acting as a messenger together with hydrogen sulfide (H2S) and the nitric oxide radical (•NO), activating specific oxidations that determine the metabolic response. The reaction triggered determines cell survival or apoptosis, depending on which downstream metabolic pathways are activated. There are several ways to produce H2O2 in cells, and cellular systems tightly control its concentration. At the cellular level, the accumulation of hydrogen peroxide can trigger inflammation and even apoptosis, and when its concentration in the blood reaches toxic levels, it can lead to bioenergetic failure. This review summarizes existing research from a chemical perspective on the role of H2O2 in various enzymatic pathways and how this biochemistry leads to physiological or pathological responses.
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Odeyinka O, Alhashimi R, Thoota S, Ashok T, Palyam V, Azam AT, Sange I. The Role of Capsule Endoscopy in Crohn's Disease: A Review. Cureus 2022; 14:e27242. [PMID: 36039259 PMCID: PMC9401636 DOI: 10.7759/cureus.27242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2022] [Indexed: 12/09/2022] Open
Abstract
Crohn’s disease (CD) is a chronic inflammatory disorder with a predilection for the small bowel. Although awareness of this disorder has increased over the years, it remains a diagnostic challenge for many physicians. This is exacerbated by the rising incidence and high recurrence rate following therapy in certain individuals. It is currently agreed that a multimodality approach is the best one, but with the advent of new modalities, that could be changing. Furthermore, given its impact on the mental health of patients and the cost of treatment, it is pertinent that we arrive at not only convenient but accurate modalities in its diagnosis and management. Among these investigative modalities is the relatively novel capsule endoscopy (CE) that not only provides a more patient-friendly alternative but avoids the need for invasiveness. Asides from its diagnostic capability, its influence on therapy and monitoring of known CD patients following treatment has been shown. This article has reviewed the current literature comparing the relevance of CE with other available modalities in diagnosing CD patients. We explored its therapeutic impact and how it influences monitoring post-treatment in CD. This article also discusses the complications of CE and the possible solutions to these complications in the future.
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Li K, Feng C, Chen H, Feng Y, Li J. Trends in Worldwide Research in Inflammatory Bowel Disease Over the Period 2012–2021: A Bibliometric Study. Front Med (Lausanne) 2022; 9:880553. [PMID: 35665364 PMCID: PMC9160461 DOI: 10.3389/fmed.2022.880553] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 04/22/2022] [Indexed: 01/19/2023] Open
Abstract
Background Inflammatory bowel disease (IBD) is a continuously increasing and worldwide disease, and the number of publications of IBD has been expanding in the past 10 years. The purpose of this study is to analyze the published articles of IBD in the past decade via machine learning and text analysis and get a more comprehensive understanding of the research trends and changes in IBD in the past 10 years. Method In November 2021, we downloaded the published articles related to IBD in PubMed for the past 10 years (2012–2021). We utilized Python to extract the title, publication date, MeSH terms, and abstract from the metadata of each publication for bibliometric assessment. Latent Dirichlet allocation (LDA) was used to the abstracts to identify publications' research topics with greater specificity. Result We finally identified and analyzed 34,458 publications in total. We found that publications in the last 10 years were mainly focused on treatment and mechanism. Among them, publications on biological agents and Gastrointestinal Microbiome have a significant advantage in terms of volume and rate of publications. In addition, publications related to IBD and coronavirus disease 2019 (COVID-19) have increased sharply since the outbreak of the worldwide pandemic caused by novel β-coronavirus in 2019. However, researchers seem to pay less attention to the nutritional and psychological status of patients with IBD. Conclusion IBD is still a worldwide disease of concern with the publication of IBD-related research has expanded continuously over the past decade. More research related nutritional and psychological status of patients with IBD is needed in the future. Besides, it is worth noting that the management of chronic diseases such as IBD required additional attention during an infectious disease epidemic.
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Affiliation(s)
- Kemin Li
- Department of Gastroenterology, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Chenzhe Feng
- Department of Oncology, Second Xiangya Hospital of Central South University, Changsha, China
- Department of Surgery, Xiangya Hospital of Central South University, Changsha, China
| | - Haolin Chen
- Department of Mathematics, University of California, Davis, Davis, CA, United States
| | - Yeqian Feng
- Department of Oncology, Second Xiangya Hospital of Central South University, Changsha, China
- *Correspondence: Jingnan Li
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Yeqian Feng
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14
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De Sousa JFM, Paghdar S, Khan TM, Patel NP, Chandrasekaran S, Tsouklidis N. Stress and Inflammatory Bowel Disease: Clear Mind, Happy Colon. Cureus 2022; 14:e25006. [PMID: 35582022 PMCID: PMC9107617 DOI: 10.7759/cureus.25006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 05/14/2022] [Indexed: 12/22/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a condition whose prevalence in the general population worldwide is increasing at an exponential pace. Many risk factors affect the incidence, progression, and overall outcome of IBD, one of them being psychological stress. This study examined the relationship between psychological stress and inflammatory bowel disease. A search for relevant studies was conducted using PubMed, Google Scholar, ResearchGate, and SCOPUS. A systematic review was conducted on the relevant articles after critical appraisal. This article mainly focused on studies that evaluated the presence of inflammatory markers observed in individuals who have been diagnosed with IBD and have high levels of psychological stress. It also assessed if lowering an individual’s psychological stress could help improve the outcomes of IBD. Psychological stress can have a detrimental effect on individuals diagnosed with IBD. There is a need to conduct studies that can further confirm the association between psychological stressors, mental health conditions, and IBD. We should also encourage medical practitioners to educate patients who have been diagnosed with IBD regarding the benefits of stress reduction.
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15
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Knyazev OV, Kagramanova AV, Parfenov AI. Ulcerative colitis. To the 180th anniversary of the description by Karl Rokytansky. TERAPEVT ARKH 2022; 93:1564-1568. [DOI: 10.26442/00403660.2021.12.201219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 01/16/2022] [Indexed: 11/22/2022]
Abstract
The article describes the main historical milestones in the description and study of ulcerative colitis from the time of Hippocrates to the present day. The first description of the morphological picture of non-specific ulcerative colitis (NUC) was presented by the Viennese pathologist Karl Rokitansky in 1842. The term "ulcerative colitis" was coined by S. Wilks in 1859. A detailed description of the disease was presented in 1875 by S. Wilks and W. Maxon. In an independent nosological form, NUC was isolated in 1888 by the English doctor White. Boas in 1903. For the first time, he presented the differential diagnosis of NUC and chronic dysentery. The term "non-specific ulcerative colitis" in Russia was first introduced by A.S. Kazachenko in a report at the XIII Congress of Russian Surgeons in 1913.
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16
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Sauceda C, Bayne C, Sudqi K, Gonzalez A, Dulai PS, Knight R, Gonzalez DJ, Gonzalez CG. Stool multi-omics for the study of host-microbe interactions in inflammatory bowel disease. Gut Microbes 2022; 14:2154092. [PMID: 36503356 PMCID: PMC9746627 DOI: 10.1080/19490976.2022.2154092] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 11/04/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is a chronic immune-mediated inflammatory disease of the gastrointestinal tract that is a growing public burden. Gut microbes and their interactions with hosts play a crucial role in disease pathogenesis and progression. These interactions are complex, spanning multiple physiological systems and data types, making comprehensive disease assessment difficult, and often overwhelming single-omic capabilities. Stool-based multi-omics is a promising approach for characterizing host-gut microbiome interactions using deep integration of technologies such as 16S rRNA sequencing, shotgun metagenomics, meta-transcriptomics, metabolomics, and metaproteomics. The wealth of information generated through multi-omic studies is poised to usher in advancements in IBD research and precision medicine. This review highlights historical and recent findings from stool-based muti-omic studies that have contributed to unraveling IBD's complexity. Finally, we discuss common pitfalls, issues, and limitations, and how future pipelines should address them to standardize multi-omics in IBD research and beyond.
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Affiliation(s)
- Consuelo Sauceda
- Department of Pharmacology, University of California San Diego, La Jolla, CA, USA
- Skaggs School of Pharmacy, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Charlie Bayne
- Department of Pharmacology, University of California San Diego, La Jolla, CA, USA
- Skaggs School of Pharmacy, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Khadijeh Sudqi
- Department of Pharmacology, University of California San Diego, La Jolla, CA, USA
- Skaggs School of Pharmacy, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
| | - Antonio Gonzalez
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Parambir S. Dulai
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL, USA
| | - Rob Knight
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
| | - David J. Gonzalez
- Department of Pharmacology, University of California San Diego, La Jolla, CA, USA
- Skaggs School of Pharmacy, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Carlos G. Gonzalez
- Department of Pharmacology, University of California San Diego, La Jolla, CA, USA
- Skaggs School of Pharmacy, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
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Abstract
Current practice in IBD is to classify patients based on clinical signs and symptoms and provide treatments accordingly. However, the response of IBD patients to available treatments is highly variable, highlighting clinically significant heterogeneity among patients. Thus, more accurate patient stratification is urgently needed to more effectively target therapeutic interventions to specific patients. Here we review the degree of heterogeneity in IBD, discussing how the microbiota, genetics, and immune system may contribute to the variation among patients. We highlight how molecular heterogeneity may relate to clinical phenotype, but in other situations may be independent of clinical phenotype, encouraging future studies to fill the gaps. Finally, we discuss novel stratification methodologies as a foundation for precision medicine, in particular a novel stratification strategy based on conserved genes across species. All of these dimensions of heterogeneity have potential to provide strategies for patient stratification and move IBD practice towards personalised medicine.
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Affiliation(s)
- Katja A Selin
- Division of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden
- Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Gastroenterology Unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine, Solna, Division of Clinical Medicine, Karolinska Institutet, Solna, Sweden
| | - Charlotte R H Hedin
- Gastroenterology Unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine, Solna, Division of Clinical Medicine, Karolinska Institutet, Solna, Sweden
| | - Eduardo J Villablanca
- Division of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden
- Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Medicine, Solna, Division of Clinical Medicine, Karolinska Institutet, Solna, Sweden
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18
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Reelin levels in inflammatory bowel disease: A case-control study. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.855197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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19
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Khatri V, Kalyanasundaram R. Therapeutic implications of inflammasome in inflammatory bowel disease. FASEB J 2021; 35:e21439. [PMID: 33774860 PMCID: PMC8010917 DOI: 10.1096/fj.202002622r] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 12/14/2022]
Abstract
Inflammatory bowel disease (IBD) remains a persistent health problem with a global burden surging over 6.8 million cases currently. Clinical pathology of IBD is complicated; however, hyperactive inflammatory and immune responses in the gut is shown to be one of the persistent causes of the disease. Human gut inflammasome, the activator of innate immune system is believed to be a primary underlying cause for the pathology and is largely associated with the progression of IBD. To manage IBD, there is a need to fully understand the role of inflammasome activation in IBD. Since inflammasome potentially play a significant role in IBD, systemic modulation of inflammasome may provide an effective therapeutic and clinical approach to control IBD symptoms. In this review, we have focused on this association between IBD and gut inflammasome, and recent advances in the research and therapeutic strategies for IBD. We have discussed inflammasomes and their components, outcomes from the experimental animals and human studies, inflammasome inhibitors, and developments in the inflammasome-targeted therapies for IBD.
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Affiliation(s)
- Vishal Khatri
- Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, USA
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20
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Dong N, Xue C, Zhang L, Zhang T, Wang C, Bi C, Shan A. Oleanolic acid enhances tight junctions and ameliorates inflammation in Salmonella typhimurium-induced diarrhea in mice via the TLR4/NF-κB and MAPK pathway. Food Funct 2020; 11:1122-1132. [PMID: 31825448 DOI: 10.1039/c9fo01718f] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Salmonella typhimurium (S.T) is a common cause of acute, self-limiting food-borne diarrhea with severe intestinal inflammation and intestinal barrier damage. Oleanolic acid (OA), isolated from almost 2000 plant species, has been shown to have anti-inflammatory roles. The purpose of this study was to investigate the potential protective effects of OA on S.T-induced diarrhea and enteritis and to elucidate its anti-inflammatory mechanisms. A total of eighty BALB/c mice (4-week-old) were randomly divided into the control group (no S.T, no OA), the S.T group (S.T only), the S.T + OA group (S.T plus 100 mg kg-1 OA) and the OA group (100 mg kg-1 OA only). Compared with the S.T group, OA administration significantly reduced clinical symptoms and weight loss, and the severity of diarrhea and intestinal structural damage was significantly alleviated, which was confirmed by a decrease in the diarrhea index (DI) and jejunal histological damage. In addition, in the infected jejunum, OA maintained the expression and localization of occludin, claudin-1 and ZO-1 to protect the jejunal barrier, thereby maintaining the integrity of the gut barrier. Finally, OA treatment not only reduced the levels of COX-2 and iNOS but also inhibited the secretion of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. Furthermore, western blotting results showed that OA treatment significantly inhibited IκB phosphorylation and degradation in intestinal tissues and the nuclear translocation of p65, and OA also decreased the level of TLR4 and the activation of the MAPK pathway. To summarise, OA can maintain the intestinal tight junction barrier and prevent diarrhea caused by S.T. as well as reduce intestinal inflammation through the NF-κB and MAPK signaling pathways.
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Affiliation(s)
- Na Dong
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
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21
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Van Kruiningen HJ. What the early pathologists got wrong, and right, about the pathology of Crohn's disease: a historical perspective. APMIS 2020; 128:621-625. [PMID: 32956512 DOI: 10.1111/apm.13081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 09/11/2020] [Indexed: 11/30/2022]
Abstract
Surgeons, who documented what they had seen and felt in the abdomen of the patient, made the earliest descriptions of Crohn's disease (CD). Dalziel wrote the first pathology description in 1913. Crohn and his coworkers reinvented what Dalziel had written about and called it by a different name, 'regional enteritis'. Later others elaborated on the histologic features, at first the lymphoid follicles, later the granulomas. Some thought the latter were comprised of lymphatic endothelial cells and that endothelial plugs obstructed the lymphatics. Tonelli and others recognized that lymphedema was important and caused by obstructions to lymphatic vasculature. Some lymphatics they described contained lymphocyte plugs and others granulomas. Immunohistochemistry (IHC) has now shown that endothelial cells are not the cause of lymphatic obstruction, but rather CD68-positive macrophages, concluding that the 'lymphocyte thrombi' are passive, caught upstream of granuloma-obstructed lymphatics. Numerous authors recognized that transmural edema was the most significant change in Crohn's disease and that this was later followed by fibrosis and contracture of the diseased segment. Key descriptive papers spoke of the segmental lymphedema. Most recently, attention has been given to attachments of the intralymphatic CD68+ granulomas to a focal point where endothelial damage occurred, damage suggesting infectious penetration of the mucosa, necrosis of lymphatic endothelium and then granulomatous response, both inside and outside the lymphatics, of submucosa, muscularis, and subserosa. D2-40 IHC outlines the endothelium, and anti-CD68 shows the granulomas. IHC adds a valuable perspective when reviewing CD resections.
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22
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Moura FA, Goulart MOF, Campos SBG, da Paz Martins AS. The Close Interplay of Nitro-Oxidative Stress, Advanced Glycation end Products and Inflammation in Inflammatory Bowel Diseases. Curr Med Chem 2020; 27:2059-2076. [PMID: 30182837 DOI: 10.2174/0929867325666180904115633] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 07/29/2018] [Accepted: 08/11/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Inflammatory Bowel Disease (IBD) exhibits no defined aetiology. However, factors such as genetic and nitro-oxidative stress are associated with chronic inflammation and IBD progression to Colorectal Cancer (CRC). The present review discusses the association of nitro-oxidative stress, inflammation and Advanced Glycation End products (AGE) and their corresponding receptor (RAGE) in IBD and examines the connection between these factors and nuclear factors, such as Nuclear Factor Kappa B (NF-κB), factorerythroid 2-related factor-2 (Nrf2), and p53 Mutant (p53M). METHODS We searched the PubMed, ScienceDirect and Web of Science databases using a combination of the following terms: IBD, CRC, oxidative stress, inflammation, NF-κB, Nrf2, p53M, AGE and RAGE. RESULTS Oxidative stress and inflammation activated two cellular pathways, the nuclear expression of pro-inflammatory, pro-oxidant and pro-oncogenic genes based on NF-κB and p53M, which is associated with NF-κB activation, Deoxyribonucleic acid (DNA) damage and the expression of pro-oncogenic genes. Nrf2 stimulates the nuclear expression of enzymatic and non-enzymatic antioxidant systems and anti-inflammatory genes, and is inhibited by chronic oxidative stress, NF-κB and p53M. AGE/RAGE are involved in inflammation progression because RAGE polymorphisms and increased RAGE levels are found in IBD patients. Alterations of these pathways in combination with oxidative damage are responsible for IBD symptoms and the progression to CRC. CONCLUSION IBD is an inflammatory and nitro-oxidative stress-based bowel disease. Achieving a molecular understanding of the biochemical events and their complicated interactions will impact basic and applied research, animal models, and clinical trials.
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Affiliation(s)
- Fabiana Andréa Moura
- Faculdade de Nutrição/Universidade Federal de Alagoas (FANUT/UFAL), Campus A. C. Simões, Avenida Lourival Melo Mota, s/n, Tabuleiro dos Martins, 57072-970 Maceió, Alagoas, Brazil
| | | | - Samara Bonfim Gomes Campos
- Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Universidade Federal de Alagoas (UFAL), 57072-970 Maceió, Alagoas, Brazil
| | - Amylly Sanuelly da Paz Martins
- Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Universidade Federal de Alagoas (UFAL), 57072-970 Maceió, Alagoas, Brazil
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23
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Jakubczyk D, Leszczyńska K, Górska S. The Effectiveness of Probiotics in the Treatment of Inflammatory Bowel Disease (IBD)-A Critical Review. Nutrients 2020; 12:nu12071973. [PMID: 32630805 PMCID: PMC7400428 DOI: 10.3390/nu12071973] [Citation(s) in RCA: 184] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/19/2020] [Accepted: 06/30/2020] [Indexed: 12/17/2022] Open
Abstract
Inflammatory bowel disease (IBD), which affects millions of people worldwide, includes two separate diseases: Crohn's disease (CD) and ulcerative colitis (UC). Although the background (chronic inflammatory state) and some of the symptoms of CD and UC are similar, both diseases differ from each other. It is becoming clear that a combination of many factors, in particular genetic background, host immune response and microbial reduced diversity status are associated with IBD. One potential strategy to prevent/treat IBD is gut modulation by probiotics. Over the last twenty years, many publications have focused on the role of probiotics in the course of IBD. The review discusses the utility of different strains of probiotics, especially Bifidobacterium spp., in all factors potentially involved in the etiology of IBD. The probiotic modulatory properties among different study models (cell lines, animal models of colitis, clinical study) are discussed and probiotic usefulness is assessed in relation to the treatment, prevention, and remission of diseases.
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24
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Pravda J. Hydrogen peroxide and disease: towards a unified system of pathogenesis and therapeutics. Mol Med 2020; 26:41. [PMID: 32380940 PMCID: PMC7204068 DOI: 10.1186/s10020-020-00165-3] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 04/07/2020] [Indexed: 02/07/2023] Open
Abstract
Although the immune response has a prominent role in the pathophysiology of ulcerative colitis, sepsis, and systemic lupus erythematosus, a primary immune causation has not been established to explain the pathogenesis of these diseases. However, studies have reported significantly elevated levels of colonic epithelial hydrogen peroxide (a known colitic agent) in ulcerative colitis prior to the appearance of colitis. And patients with sepsis are reported to have toxic levels of blood hydrogen peroxide, whose pathologic effects mirror the laboratory and clinical abnormalities observed in sepsis. More recently, evidence supports a causal role for cellular hydrogen peroxide (a potent apoptotic agent) in the enhanced apoptosis believed to be the driving force behind auto-antigenic exposure and chronic immune activation in systemic lupus erythematosus. The different biological properties of hydrogen peroxide exert distinct pathologic effects depending on the site of accumulation within the body resulting in a unique disease patho-phenotype. On a cellular level, the build-up of hydrogen peroxide triggers apoptosis resulting in systemic lupus erythematosus, on a tissue level (colonic epithelium) excess hydrogen peroxide leads to inflammation and ulcerative colitis, and on a systemic level the pathologic effects of toxic concentrations of blood hydrogen peroxide result in bioenergetic failure and microangiopathic dysfunction leading to multiple organ failure and circulatory shock, characteristic of advanced sepsis. The aim of this paper is to provide a unified evidence-based common causal role for hydrogen peroxide in the pathogenesis of ulcerative colitis, sepsis, and systemic lupus erythematosus. Based on this new theory of pathogenesis, a novel evidence-based treatment of sepsis is also discussed.
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25
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Hobbs MM, Ortega-Loayza AG. Pyoderma gangrenosum: From historical perspectives to emerging investigations. Int Wound J 2020; 17:1255-1265. [PMID: 32378319 DOI: 10.1111/iwj.13389] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/20/2020] [Accepted: 04/21/2020] [Indexed: 01/01/2023] Open
Abstract
Pyoderma gangrenosum (PG) is a rare disease of unknown aetiology, first described over a century ago. Initially thought to have an infectious cause, and now primarily considered an autoinflammatory condition, PG continues to be poorly understood, commonly misdiagnosed, and difficult to treat. In this review, we discuss the journey of our understanding of PG to date, including first descriptions, challenges with diagnosis, presumed pathogenesis, and treatments used. We highlight major historical landmarks and their importance, explain the rationale behind current investigations, note outstanding gaps in knowledge, and explore the future directions of PG research. We summarise what we have known, what we are working on knowing, and what we have yet to explore about PG, illustrating overall trends to invigorate future research.
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Affiliation(s)
| | - Alex G Ortega-Loayza
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA
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26
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History of Inflammatory Bowel Diseases. J Clin Med 2019; 8:jcm8111970. [PMID: 31739460 PMCID: PMC6912289 DOI: 10.3390/jcm8111970] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 11/02/2019] [Accepted: 11/12/2019] [Indexed: 12/19/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal mucosa and unknown etiology. In this review, we identified three main eras in the IBD history. Between the 19th and the 20th century, the primary task had been the definition of the diagnostic criteria in order to differentiate the new entity from intestinal tuberculosis. In the 20th century, an intense and prolific therapeutic research prevailed, culminating in the introduction of biological drugs in the clinical setting. Since the beginning of the 21st century, traditional definition criteria have been challenged by holistic criteria in an effort to seek a still unattained cure. Centuries of worldwide efforts on IBD etiology and therapy search have culminated in this novel strategy.
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27
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Li TH, Liu L, Hou YY, Shen SN, Wang TT. C-type lectin receptor-mediated immune recognition and response of the microbiota in the gut. Gastroenterol Rep (Oxf) 2019; 7:312-321. [PMID: 31687150 PMCID: PMC6821170 DOI: 10.1093/gastro/goz028] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Revised: 06/05/2019] [Accepted: 06/12/2019] [Indexed: 02/07/2023] Open
Abstract
C-type lectin receptors (CLRs) are powerful pattern-recognition receptors that discern ‘self’ and ‘non-self’ in our body and protect us from invasive pathogens by mediating immune recognition and response. The gastrointestinal tract is very important for the maintenance of homeostasis; it is the largest shelter for the billions of microorganisms in the body and CLRs play a crucial regulatory role in this system. This study focuses on several CLRs, including Dectin-1, Dectin-2, Dectin-3 and Mincle. We summarize the roles of CLRs in maintaining gastrointestinal immune-system homeostasis, especially their functions in mediating immune recognition and responses in the gut, discuss their relationships to some diseases, highlight the significance of CLR-mediated sensing of microbial and non-microbial compounds in the gut immune system and identify new therapeutic targets.
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Affiliation(s)
- Tian-Hang Li
- Immunology and Reproduction Biology Lab, Medical School of Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, P. R. China
| | - Ling Liu
- Immunology and Reproduction Biology Lab, Medical School of Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, P. R. China
| | - Ya-Yi Hou
- Immunology and Reproduction Biology Lab, Medical School of Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, P. R. China.,Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, P. R. China
| | - Su-Nan Shen
- Immunology and Reproduction Biology Lab, Medical School of Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, P. R. China.,Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, P. R. China
| | - Ting-Ting Wang
- Immunology and Reproduction Biology Lab, Medical School of Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, P. R. China.,Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, P. R. China
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M'Koma AE. The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview. GASTROINTESTINAL DISORDERS 2019; 1:75-105. [PMID: 37577036 PMCID: PMC10416806 DOI: 10.3390/gidisord1010007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The gastrointestinal system where inflammatory bowel disease occurs is central to the immune system where the innate and the adaptive/acquired immune systems are balanced in interactions with gut microbes under homeostasis conditions. This article overviews the high-throughput research screening on multifactorial interplay between genetic risk factors, the intestinal microbiota, urbanization, modernization, Westernization, the environmental influences and immune responses in the etiopathogenesis of inflammatory bowel disease in humans. Inflammatory bowel disease is an expensive multifactorial debilitating disease that affects thousands new people annually worldwide with no known etiology or cure. The conservative therapeutics focus on the established pathology where the immune dysfunction and gut injury have already happened but do not preclude or delay the progression. Inflammatory bowel disease is evolving globally and has become a global emergence disease. It is largely known to be a disease in industrial-urbanized societies attributed to modernization and Westernized lifestyle associated with environmental factors to genetically susceptible individuals with determined failure to process certain commensal antigens. In the developing nations, increasing incidence and prevalence of inflammatory bowel disease (IBD) has been associated with rapid urbanization, modernization and Westernization of the population. In summary, there are identified multiple associations to host exposures potentiating the landscape risk hazards of inflammatory bowel disease trigger, that include: Western life-style and diet, host genetics, altered innate and/or acquired/adaptive host immune responses, early-life microbiota exposure, change in microbiome symbiotic relationship (dysbiosis/dysbacteriosis), pollution, changing hygiene status, socioeconomic status and several other environmental factors have long-standing effects/influence tolerance. The ongoing multipronged robotic studies on gut microbiota composition disparate patterns between the rural vs. urban locations may help elucidate and better understand the contribution of microbiome disciplines/ecology and evolutionary biology in potentially protecting against the development of inflammatory bowel disease.
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Affiliation(s)
- Amosy E M'Koma
- Meharry Medical College School of Medicine, Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Nashville, TN 37208, USA
- Vanderbilt University School of Medicine, Department of Surgery, Colon and Rectal Surgery, Nashville, TN 37232, USA
- The American Society of Colon and Rectal Surgeons (ASCRS), Arlington Heights, IL 60005, USA
- The American Gastroenterological Association (AGA), Bethesda, MD 20814, USA
- Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN 37232, USA
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Bhattacharya S, Chattu VK, Singh A. Health promotion and prevention of bowel disorders through toilet designs: A myth or reality? JOURNAL OF EDUCATION AND HEALTH PROMOTION 2019; 8:40. [PMID: 30993133 PMCID: PMC6432810 DOI: 10.4103/jehp.jehp_198_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Accepted: 11/14/2018] [Indexed: 06/09/2023]
Abstract
Now, lifestyle diseases are quite common globally. The risk factors of lifestyle diseases such as sedentary habits, lack of physical exercise, and lack of fiber result in the development of noncommunicable diseases. However, when the point of discussion slightly shifted toward toilet habits, it is always seems to be a secret affair. In fact, the discussion of defecation-related matter openly is considered a taboo. This is not uncommon even in medical fraternity. In fact, during the early 1980s, some researches on the association between the diarrhea prevalence, open-air defecation, and latrine use rate were documented. However, nobody acknowledges it socially desirable, now, to discuss defecation-related issues. The public health experts completely ignored the discussion of ill-effects of the use of pedestal latrine on human health. It is evident from scientific studies over a period, that many of the abdominal disorders of the human due change in his toilet habits from a squatting-to-sitting posture using a pedestal latrine. That disease correlation was ignored at that time. The increase in disease burden is due to nonmaintaining the ergonomic design during the construction of this kind of toilets. Squatting posture for the defecation is the most appropriate way, as in this case, abdominal muscles work actively and complete evacuation takes place. To conclude, the time has come to reacquaint people with their natural habits and put this unfortunate experiment to an end.
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Affiliation(s)
- Sudip Bhattacharya
- Department of Community Medicine, Himalayan Institute of Medical Sciences, Dehradun, India
| | - Vijay Kumar Chattu
- Public Health Unit, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago
| | - Amarjeet Singh
- Professor, Department of Community Medicine, School of Public Health, PGIMER, Chandigarh, India
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Balseiro A, Perez V, Juste RA. Chronic regional intestinal inflammatory disease: A trans-species slow infection? Comp Immunol Microbiol Infect Dis 2018; 62:88-100. [PMID: 30711052 DOI: 10.1016/j.cimid.2018.12.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 11/27/2018] [Accepted: 12/07/2018] [Indexed: 01/08/2023]
Abstract
Crohn's disease and ulcerative colitis in humans and paratuberculosis in domestic and wild ruminants can be defined as chronic regional intestinal inflammatory diseases (CRIID). This review is a literature overview on these diseases in humans, non-human primates, dogs, cats, rabbits, equids and ruminants with a focus on pathological and microbiological features aimed identifying common characteristics that could lead to a unified pathological classification for a better understanding of their mechanisms and causes. The result is a framework of inflammatory forms throughout the different species indicative of common mechanisms of the slow infection type characterized by a time course varying from weeks to months or even years, and where the inflammatory component would be more prominent in the intestinal interphase between host and environment and be morphologically characterized by an infiltrate ranging from lymphoplasmacytic to histiocytic. This should provide new insights for causation demonstration and therapeutic approaches in human IBD.
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Affiliation(s)
- Ana Balseiro
- Centro de Biotecnología Animal, Servicio Regional de Investigación y Desarrollo Agroalimentario (SERIDA), 33394 Gijón, Asturias, Spain
| | - Valentin Perez
- Departamento de Sanidad Animal, Instituto de Ganadería de Montaña (CSIC-ULE), Facultad de Veterinaria, Universidad de León, 24071 León, Spain
| | - Ramon A Juste
- Direccion. Servicio Regional de Investigación y Desarrollo Agroalimentario (SERIDA), 33300 Villaviciosa, Asturias, Spain.
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31
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Mijan MA, Lim BO. Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends. World J Gastroenterol 2018; 24:2673-2685. [PMID: 29991873 PMCID: PMC6034142 DOI: 10.3748/wjg.v24.i25.2673] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 05/19/2018] [Accepted: 06/09/2018] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a serious health concern among western societies. The disease is also on the rise in some East Asian countries and in Australia. Health professionals and dietitians around the world are facing an unprecedented challenge to prevent and control the increasing prevalence of IBD. The current therapeutic strategy that includes drugs and biological treatments is inefficient and are associated with adverse health consequences. In this context, the use of natural products is gaining worldwide attention. In vivo studies and clinical evidence suggest that well-planned dietary regimens with specific nutrients can alleviate gastrointestinal inflammation by modulating inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), IL-6, IL-1β, and IL-10. Alternatively, the avoidance of high-fat and high-carbohydrate diets is regarded as an effective tool to eliminate the causes of IBD. Many functional foods and bioactive components have received attention for showing strong therapeutic effects against IBD. Both animal and human studies suggest that bioactive functional foods can ameliorate IBD by downregulating the pro-inflammatory signaling pathways, such as nuclear factor κB, STAT1, STAT6, and pro-inflammatory cytokines, including IL-1β, IL-4, IL-6, COX-2, TNF-α, and interferon γ. Therefore, functional foods and diets have the potential to alleviate IBD by modulating the underlying pathogenic mechanisms. Future comprehensive studies are needed to corroborate the potential roles of functional foods and diets in the prevention and control of IBD.
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Affiliation(s)
- Mohammad Al Mijan
- Department of Integrated Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, South Korea
| | - Beong Ou Lim
- Department of Integrated Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, South Korea
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Abstract
In the 21st century, urbanization represents a major demographic shift in developed and developing countries. Rapid urbanization in the developing world has been associated with an increasing incidence of several autoimmune diseases, including IBD. Patients with IBD exhibit a decrease in the diversity and richness of the gut microbiota, while urbanization attenuates the gut microbial diversity and might have a role in the pathogenesis of IBD. Environmental exposures during urbanization, including Westernization of diet, increased antibiotic use, pollution, improved hygiene status and early-life microbial exposure, have been shown to affect the gut microbiota. The disparate patterns of the gut microbiota composition in rural and urban areas offer an opportunity to understand the contribution of a 'rural microbiome' in potentially protecting against the development of IBD. This Perspective discusses the effect of urbanization and its surrogates on the gut microbiome (bacteriome, virome, mycobiome and helminths) in both human health and IBD and how such changes might be associated with the development of IBD.
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Mahadevan U, Silverberg MS. Inflammatory Bowel Disease-Gastroenterology Diamond Jubilee Review. Gastroenterology 2018; 154:1555-1558. [PMID: 29550591 DOI: 10.1053/j.gastro.2017.12.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 12/08/2017] [Indexed: 12/16/2022]
Affiliation(s)
- Uma Mahadevan
- University of California, San Francisco, California, and Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Canada.
| | - Mark S Silverberg
- University of California, San Francisco, California, and Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Canada
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Abstract
Fungi and mammals share a co-evolutionary history and are involved in a complex web of interactions. Studies focused on commensal bacteria suggest that pathological changes in the microbiota, historically known as dysbiosis, are at the root of many inflammatory diseases of non-infectious origin. However, the importance of dysbiosis in the fungal community - the mycobiota - was only recently acknowledged to have a pathological role, as novel findings have suggested that mycobiota disruption can have detrimental effects on host immunity. Fungal dysbiosis and homeostasis are dynamic processes that are probably more common than actual fungal infections, and therefore constantly shape the immune response. In this Review, we summarize specific mycobiota patterns that are associated with fungal dysbiosis, and discuss how mucosal immunity has evolved to distinguish fungal infections from dysbiosis and how it responds to these different conditions. We propose that gut microbiota dysbiosis is a collective feature of complex interactions between prokaryotic and eukaryotic microbial communities that can affect immunity and that can influence health and disease.
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Affiliation(s)
- Iliyan D Iliev
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA
| | - Irina Leonardi
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA
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35
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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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Abstract
Over 1 million residents in the USA and 2.5 million in Europe are estimated to have IBD, with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients. The majority of patients are diagnosed early in life and the incidence continues to rise; therefore, the effect of IBD on health-care systems will rise exponentially. Moreover, IBD has emerged in newly industrialized countries in Asia, South America and Middle East and has evolved into a global disease with rising prevalence in every continent. Understanding the worldwide epidemiological patterns of IBD will prepare us to manage the burden of IBD over time. The goal of this article is to establish the current epidemiology of IBD in the Western world, contrast it with the increase in IBD in newly industrialized countries and forecast the global effects of IBD in 2025.
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Sherlock ME, MacDonald JK, Griffiths AM, Steinhart AH, Seow CH. Oral budesonide for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2015; 2015:CD007698. [PMID: 26497719 PMCID: PMC9239584 DOI: 10.1002/14651858.cd007698.pub3] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Corticosteroids are first-line therapy for induction of remission in ulcerative colitis. Although corticosteroids may improve symptoms, they have significant adverse effects. Steroids which act topically, with less systemic side-effects may be more desirable. Budesonide is a topically acting corticosteroid with extensive first pass hepatic metabolism. There are currently three formulations of budesonide: two standard formulations including a controlled-ileal release capsule and a pH-dependent capsule both designed to release the drug in the distal small intestine and right colon; and the newer Budesonide-MMX® capsule designed to release the drug throughout the entire colon. OBJECTIVES The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in ulcerative colitis. SEARCH METHODS We searched MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Group Specialised Register from inception to April 2015. We also searched reference lists of articles, conference proceedings and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials comparing oral budesonide to placebo or another active therapy for induction of remission in ulcerative colitis were considered eligible. There were no exclusions based on patient age or the type, dose, duration or formulation of budesonide therapy. DATA COLLECTION AND ANALYSIS Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was induction of remission (as defined by the primary studies) at week eight. Secondary outcomes included clinical, endoscopic and histologic improvement, adverse events and early withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome and the mean difference (MD) and corresponding 95% CI for each continuous outcome. Data were analysed on an intention-to-treat basis. MAIN RESULTS Six studies (1808 participants) were included. Four studies compared budesonide-MMX® with placebo, one small pilot study looked at clinical remission at week four, and was subsequently followed by three large, studies that assessed combined clinical and endoscopic remission at week eight. Although two placebo-controlled studies had mesalamine and Entocort (standard budesonide) treatment arms, these studies were not sufficiently powered to compare Budesonide-MMX® with these active comparators. One small study compared standard budesonide with prednisolone and one study compared standard budesonide to mesalamine. Four studies were rated as low risk of bias and two studies had an unclear risk of bias. A pooled analysis of three studies (900 participants) showed that budesonide-MMX® 9 mg was significantly superior to placebo for inducing remission (combined clinical and endoscopic remission) at 8 weeks. Fifteen per cent (71/462) of budesonide-MMX® 9 mg patients achieved remission compared to 7% (30/438) of placebo patients (RR 2.25, 95% CI 1.50 to 3.39). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (101 events). A subgroup analysis by concurrent mesalamine use suggests higher efficacy in the 442 patients who were not considered to be mesalamine-refractory (RR 2.89, 95% CI 1.59 to 5.25). A subgroup analysis by disease location suggests budesonide is most effective in patients with left-sided disease (RR 2.98, 95% CI 1.56 to 5.67; 289 patients). A small pilot study reported no statistically significant difference in endoscopic remission between budesonide and prednisolone (RR 0.75, 95% CI 0.23 to 2.42; 72 patients). GRADE indicated that the overall quality of the evidence supporting this outcome was very low due to unclear risk of bias and very sparse data (10 events). Standard oral budesonide was significantly less likely to induce clinical remission than oral mesalamine after 8 weeks of therapy (RR 0.72, 95% CI 0.57 to 0.91; 1 study, 343 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (161 events). Another study found no difference in remission rates between budesonide-MMX® 9 mg and mesalamine (RR 1.48, 95% CI 0.81 to 2.71; 247 patients). GRADE indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (37 events). One study found no difference in remission rates between budesonide-MMX® 9 mg and standard budesonide 9 mg (RR 1.38, 95% CI 0.72 to 2.65; 212 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (32 events). Suppression of plasma cortisol was more common in prednisolone-treated patients (RR 0.02, 95% CI 0.0 to 0.33). While budesonide does appear to suppress morning cortisol to some extent, mean morning cortisol values remained within the normal range in 2 large studies (n = 899) and there was no difference in glucocorticoid-related side-effects across different treatment groups. Further, study withdrawal due to adverse events was not more common in budesonide compared with placebo treated patients (RR 0.85, 95% CI 0.53 to 1.38). Common adverse events included worsening ulcerative colitis, headache, pyrexia, insomnia, back pain, nausea, abdominal pain, diarrhoea, flatulence and nasopharyngitis. AUTHORS' CONCLUSIONS Moderate quality evidence to supports the use of oral budesonide-MMX® at a 9 mg daily dose for induction of remission in active ulcerative colitis, particularly in patients with left-sided colitis. Budesonide-MMX® 9 mg daily is effective for induction of remission in the presence or absence of concurrent 5-ASA therapy. Further, budesonide-MMX® appears to be safe, and does not lead to significant impairment of adrenocorticoid function compared to placebo. Moderate quality evidence from a single study suggests that mesalamine may be superior to standard budesonide for the treatment of active ulcerative colitis. Low quality evidence from one study found no difference in remission rates between budesonide MMX® and mesalamine. Very low quality evidence from one small study showed no difference in endoscopic remission rates between standard budesonide and prednisolone. Low quality evidence from one study showed no difference in remission rates between budesonide-MMX® and standard budesonide. Adequately powered studies are needed to allow conclusions regarding the comparative efficacy and safety of budesonide versus prednisolone, budesonide-MMX® versus standard budesonide and budesonide versus mesalamine.
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Affiliation(s)
- Mary E Sherlock
- McMaster Children's HospitalDivision of Gastroenterology & NutritionHamilton Health Sciences1280 Main Street WestHamiltonONCanada
| | - John K MacDonald
- Robarts Research InstituteRobarts Clinical TrialsP.O. Box 5015100 Perth DriveLondonONCanadaN6A 5K8
| | - Anne Marie Griffiths
- The Hospital for Sick ChildrenDivision of Gastroenterology, Hepatology & Nutrition555 University Ave.TorontoONCanadaM5G 1X8
| | - A Hillary Steinhart
- Mount Sinai HospitalDepartment of Medicine, Division of GastroenterologyRoom 445, 600 University AvenueTorontoONCanadaM5G 1X5
| | - Cynthia H Seow
- University of CalgaryDepartment of MedicineTRW Building Rm 6D183280 Hospital Drive NWCalgaryABCanadaT2N 4Z6
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Malik TA. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors. Surg Clin North Am 2015; 95:1105-22, v. [PMID: 26596917 DOI: 10.1016/j.suc.2015.07.006] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD) describes a group of closely related yet heterogeneous predominantly intestinal disease processes that are a result of an uncontrolled immune mediated inflammatory response. It is estimated that approximately one and a half million persons in North America have IBD. Pathogenesis of IBD involves an uncontrolled immune mediated inflammatory response in genetically predisposed individuals to a still unknown environmental trigger that interacts with the intestinal flora. There continues to be an enormous amount of information emanating from epidemiological studies providing expanded insight into the occurrence, distribution, determinants, and mechanisms of inflammatory bowel disease.
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Affiliation(s)
- Talha A Malik
- Department of Medicine-Gastroenterology, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 391, Birmingham, AL 35294, USA; Department of Epidemiology, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 391, Birmingham, AL 35294, USA.
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Abstract
Crohn disease involves the perineum and rectum in approximately one-third of patients. Symptoms can range from mild, including skin tags and hemorrhoids, to unremitting and severe, requiring a proctectomy in a small, but significant, portion. Fistula-in-ano and perineal sepsis are the most frequent manifestation seen on presentation. Careful diagnosis, including magnetic resonance imaging or endorectal ultrasound with examination under anesthesia and aggressive medical management, usually with a tumor necrosis factor-alpha, is critical to success. Several options for definitive surgical repair are discussed, including fistulotomy, fibrin glue, anal fistula plug, endorectal advancement flap, and ligation of intersphincteric fistula tract procedure. All suffer from decreased efficacy in patients with Crohn disease. In the presence of active proctitis or perineal disease, no surgical therapy other than drainage of abscesses and loose seton placement is recommended, as iatrogenic injury and poor wound healing are common in that scenario.
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Affiliation(s)
- Robert T. Lewis
- Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Joshua I. S. Bleier
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania
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40
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Yuan H, Zhao XM, Yuan ZY, Wang HM, Zhao WH. Treatment with Carthamus Tinctorius Injection up-regulates IL-4 expression and down-regulates IL-1β expression in ulcerative colitis in rats. Shijie Huaren Xiaohua Zazhi 2012; 20:3678-3682. [DOI: 10.11569/wcjd.v20.i36.3678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the therapeutic effects of Carthamus Tinctorius Injection (CTI) against ulcerative colitis (UC) induced with 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats and to explore the possible mechanisms involved.
METHODS: Thirty male Wistar rats were randomly divided into a treatment group, a model group, and a normal control group (n = 10 for each group). UC was induced with TNBS in rats in both the treatment group and model group. The treatment group was additionally treated with CTI. At the end of the treatment, colonic mucosal samples were taken to calculate disease activity index (DAI) and observe gross morphology of the colon and tissue injury. Colonic mucosal pathological changes were observed by HE staining. The expression of interleukin-4 (IL-4) and IL-1β mRNAs and proteins in colon tissue was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC).
RESULTS: Compared to the model group, the DAI and gross morphology and pathological changes in colon tissue were significantly improved in the treatment group (all P < 0.05). The level of IL-4 in the treatment group was significantly higher than that in the model group (P < 0.05), but no differences was detected between the treatment group and control group. The level of IL-1β in treatment group and model group was significantly higher than that in control group (P < 0.05), but the level in treatment group was significantly lower than that in model group (P < 0.05).
CONCLUSION: CTI treatment relieved TNBS-induced colitis in rats possibly via mechanism associated with increasing IL-4 expression and decreasing IL-1β expression.
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Parray FQ, Wani ML, Malik AA, Wani SN, Bijli AH, Irshad I, Nayeem-Ul-Hassan. Ulcerative colitis: a challenge to surgeons. Int J Prev Med 2012; 3. [PMID: 23189226 PMCID: PMC3506086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
Ulcerative colitis is a chronic disease that specifically affects the mucosa of the rectum and colon. Although the etiology of this recurring inflammatory disorder remains essentially unknown, there have been significant advances in identifying the likely genetic and environmental factors that contribute to its pathogenesis. The clinical course of the disease typically manifests with remissions and exacerbations characterized by rectal bleeding and diarrhea. Since ulcerative colitis most commonly affects patients in their youth or early middle age, the disease can have serious long-term local and systemic consequences. There is no specific medical therapy that is curative. Although medical therapy can ameliorate the inflammatory process and control most symptomatic flares, it provides no definitive treatment for the disease. Proctocolectomy or total removal of the colon and rectum provides the only complete cure; however, innovative surgical alternatives have eliminated the need for a permanent ileostomy. The aim of this review is to provide a detailed account of the surgical management of ulcerative colitis.
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Affiliation(s)
- Fazl Q Parray
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, India
| | - Mohd L Wani
- Department of Cardiac Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, India,Correspondence to: Dr. Mohd Lateef Wani, Cardiac Surgery, SKIMS Srinagar, India. E-mail:
| | - Ajaz A Malik
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, India
| | - Shadab N Wani
- Department of Cardiac Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, India
| | - Akram H Bijli
- Department of Plastic Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, India
| | - Ifat Irshad
- Department of Radiology, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, India
| | - Nayeem-Ul-Hassan
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Soura, Srinagar, India
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Qin X. Etiology of inflammatory bowel disease: a unified hypothesis. World J Gastroenterol 2012; 18:1708-22. [PMID: 22553395 PMCID: PMC3332284 DOI: 10.3748/wjg.v18.i15.1708] [Citation(s) in RCA: 97] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2011] [Revised: 02/20/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), including both ulcerative colitis (UC) and Crohn's disease (CD), emerged and dramatically increased for about a century. Despite extensive research, its cause remains regarded as unknown. About a decade ago, a series of findings made me suspect that saccharin may be a key causative factor for IBD, through its inhibition on gut bacteria and the resultant impaired inactivation of digestive proteases and over digestion of the mucus layer and gut barrier (the Bacteria-Protease-Mucus-Barrier hypothesis). It explained many puzzles in IBD such as its emergence and temporal changes in last century. Recently I further found evidence suggesting sucralose may be also linked to IBD through a similar mechanism as saccharin and have contributed to the recent worldwide increase of IBD. This new hypothesis suggests that UC and CD are just two symptoms of the same morbidity, rather than two different diseases. They are both caused by a weakening in gut barrier and only differ in that UC is mainly due to increased infiltration of gut bacteria and the resultant recruitment of neutrophils and formation of crypt abscess, while CD is mainly due to increased infiltration of antigens and particles from gut lumen and the resultant recruitment of macrophages and formation of granulomas. It explained the delayed appearance but accelerated increase of CD over UC and many other phenomena. This paper aims to provide a detailed description of a unified hypothesis regarding the etiology of IBD, including the cause and mechanism of IBD, as well as the relationship between UC and CD.
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Lakatos G, Sipos F, Miheller P, Hritz I, Varga MZ, Juhász M, Molnár B, Tulassay Z, Herszényi L. The behavior of matrix metalloproteinase-9 in lymphocytic colitis, collagenous colitis and ulcerative colitis. Pathol Oncol Res 2012; 18:85-91. [PMID: 21678108 DOI: 10.1007/s12253-011-9420-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2010] [Accepted: 05/26/2011] [Indexed: 02/05/2023]
Abstract
Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been proposed that matrix metalloproteinase-9 (MMP-9) is involved in epithelial damage in ulcerative colitis (UC). However, to our knowledge, no data are available in terms of MMP-9 expression in microscopic colitis. Determination of mucosal protein expression levels of MMP-9 in lymphocytic colitis (LC), collagenous colitis (CC) and UC. MMP-9 immunohistochemical expressions were analyzed in paraffin-embedded tissue samples by immunohistochemistry including patients with LC, CC, UC, active diverticulitis, inactive diverticular disease and healthy control subjects. UC was also subgrouped according to the severity of inflammation. Immunostaining was determined semiquantitatively. Independent colonic biopsies from healthy and severe UC cases were used for gene expression analyses. For further comparison MMP-9 serum antigen levels were also determined in patients with UC and control patients without macroscopic or microscopic changes during colonoscopy. MMP-9 mucosal expression was significantly higher in UC (26.7 ± 19.5%) compared to LC (6.6 ± 9.3%), CC (6.4 ± 7.6%), active diverticulitis (5.33 ± 2.4%), inactive diverticular disease (5.0 ± 2.2%) and controls (6.3 ± 2.6%) (P < 0.001). The immunohistochemical expression of MMP-9 in LC and CC was similar as compared to controls. MMP-9 expression was significantly higher in each inflammatory group of UC compared to controls (mild: 11.0 ± 2.8%, moderate: 23.9 ± 3.7%, severe UC: 52.6 ± 3.9% and 6.3 ± 2.6%, respectively, P < 0.005). The gene expression microarray data and RT-PCR results demonstrated a significantly higher expression of MMP-9 in severely active UC compared to healthy controls (P < 0.001). Significantly higher MMP-9 serum antigen concentrations were observed in UC patients compared with the control group (P < 0.05). MMP-9 seems to play no role in the inflammatory process of LC and CC. In contrast, the mucosal up-regulation of MMP-9 correlated with the severity of inflammation in UC. The increased MMP-9 expression could contribute to the severity of mucosal damage in active UC.
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Affiliation(s)
- Gábor Lakatos
- 2nd Department of Medicine, Semmelweis University, Budapest, Hungary
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Lakatos G, Sipos F, Miheller P, Hritz I, Varga MZ, Juhász M, Molnár B, Tulassay Z, Herszényi L. The behavior of matrix metalloproteinase-9 in lymphocytic colitis, collagenous colitis and ulcerative colitis. Pathol Oncol Res 2011. [PMID: 21678108 DOI: 10.1007/s12253-011-9420-9.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been proposed that matrix metalloproteinase-9 (MMP-9) is involved in epithelial damage in ulcerative colitis (UC). However, to our knowledge, no data are available in terms of MMP-9 expression in microscopic colitis. Determination of mucosal protein expression levels of MMP-9 in lymphocytic colitis (LC), collagenous colitis (CC) and UC. MMP-9 immunohistochemical expressions were analyzed in paraffin-embedded tissue samples by immunohistochemistry including patients with LC, CC, UC, active diverticulitis, inactive diverticular disease and healthy control subjects. UC was also subgrouped according to the severity of inflammation. Immunostaining was determined semiquantitatively. Independent colonic biopsies from healthy and severe UC cases were used for gene expression analyses. For further comparison MMP-9 serum antigen levels were also determined in patients with UC and control patients without macroscopic or microscopic changes during colonoscopy. MMP-9 mucosal expression was significantly higher in UC (26.7 ± 19.5%) compared to LC (6.6 ± 9.3%), CC (6.4 ± 7.6%), active diverticulitis (5.33 ± 2.4%), inactive diverticular disease (5.0 ± 2.2%) and controls (6.3 ± 2.6%) (P < 0.001). The immunohistochemical expression of MMP-9 in LC and CC was similar as compared to controls. MMP-9 expression was significantly higher in each inflammatory group of UC compared to controls (mild: 11.0 ± 2.8%, moderate: 23.9 ± 3.7%, severe UC: 52.6 ± 3.9% and 6.3 ± 2.6%, respectively, P < 0.005). The gene expression microarray data and RT-PCR results demonstrated a significantly higher expression of MMP-9 in severely active UC compared to healthy controls (P < 0.001). Significantly higher MMP-9 serum antigen concentrations were observed in UC patients compared with the control group (P < 0.05). MMP-9 seems to play no role in the inflammatory process of LC and CC. In contrast, the mucosal up-regulation of MMP-9 correlated with the severity of inflammation in UC. The increased MMP-9 expression could contribute to the severity of mucosal damage in active UC.
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Affiliation(s)
- Gábor Lakatos
- 2nd Department of Medicine, Semmelweis University, Budapest, Hungary
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Kaplan GG, Hubbard J, Korzenik J, Sands BE, Panaccione R, Ghosh S, Wheeler AJ, Villeneuve PJ. The inflammatory bowel diseases and ambient air pollution: a novel association. Am J Gastroenterol 2010; 105:2412-9. [PMID: 20588264 PMCID: PMC3180712 DOI: 10.1038/ajg.2010.252] [Citation(s) in RCA: 189] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The inflammatory bowel diseases (IBDs) emerged after industrialization. We studied whether ambient air pollution levels were associated with the incidence of IBD. METHODS The health improvement network (THIN) database in the United Kingdom was used to identify incident cases of Crohn's disease (n=367) or ulcerative colitis (n=591), and age- and sex-matched controls. Conditional logistic regression analyses assessed whether IBD patients were more likely to live in areas of higher ambient concentrations of nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), and particulate matter <10 μm (PM(10)), as determined by using quintiles of concentrations, after adjusting for smoking, socioeconomic status, non-steroidal anti-inflammatory drugs (NSAIDs), and appendectomy. Stratified analyses investigated effects by age. RESULTS Overall, NO(2), SO(2), and PM(10) were not associated with the risk of IBD. However, individuals ≤23 years were more likely to be diagnosed with Crohn's disease if they lived in regions with NO(2) concentrations within the upper three quintiles (odds ratio (OR)=2.31; 95% confidence interval (CI)=1.25-4.28), after adjusting for confounders. Among these Crohn's disease patients, the adjusted OR increased linearly across quintile levels for NO(2) (P=0.02). Crohn's disease patients aged 44-57 years were less likely to live in regions of higher NO(2) (OR=0.56; 95% CI=0.33-0.95) and PM(10) (OR=0.48; 95% CI=0.29-0.80). Ulcerative colitis patients ≤25 years (OR=2.00; 95% CI=1.08-3.72) were more likely to live in regions of higher SO(2); however, a dose-response effect was not observed. CONCLUSIONS On the whole, air pollution exposure was not associated with the incidence of IBD. However, residential exposures to SO(2) and NO(2) may increase the risk of early-onset ulcerative colitis and Crohn's disease, respectively. Future studies are needed to explore the age-specific effects of air pollution exposure on IBD risk.
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Affiliation(s)
- Gilaad G Kaplan
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada,Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada,Division of Gastroenterology, Departments of Medicine and Community Health Sciences, University of Calgary, Teaching Research and Wellness Center, 3280 Hospital Drive NW, 6th Floor, Room 6D17, Calgary, AB, Canada, T2N 4N1. E-mail:
| | - James Hubbard
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Joshua Korzenik
- MGH Crohn's and Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Bruce E Sands
- MGH Crohn's and Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Remo Panaccione
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Subrata Ghosh
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | - Paul J Villeneuve
- Population Studies Division, Health Canada, Ottawa, Ontario, Canada,Dalla Lana School of Public Health, University of Toronto, Ontario, Canada
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Sherlock ME, Seow CH, Steinhart AH, Griffiths AM. Oral budesonide for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2010:CD007698. [PMID: 20927762 DOI: 10.1002/14651858.cd007698.pub2] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Corticosteroids remain one of the most popular medication choices for the induction of remission in ulcerative colitis and Crohn's disease. While corticosteroids may improve symptoms, they do not always result in mucosal healing and have significant adverse effects. Steroids which act topically, with less systemic side-effects may be more desirable. Oral budesonide, a topically acting corticosteroid with extensive first pass hepatic metabolism, is effective in Crohn's disease and in enema formulation for left-sided ulcerative colitis. Data are limited regarding the role of oral budesonide in ulcerative colitis. OBJECTIVES To systematically review the safety and efficacy of oral budesonide for induction of remission in ulcerative colitis. SEARCH STRATEGY Electronic searching of the MEDLINE and EMBASE databases was performed. Two authors independently reviewed all identified titles and abstracts. Full text articles of all potentially relevant studies were retrieved. Reference lists of review articles were searched in an attempt to identify additional studies. Abstracts of the major gastroenterology scientific meetings, held over the past 3 years, were hand searched. The ClinicalTrials.gov website as well as the Cochrane Registry of Controlled Trials was searched to identify any ongoing trials. Direct communication with pharmaceutical manufacturers was established to identify any ongoing or unpublished studies. SELECTION CRITERIA Randomized controlled trials of oral budesonide for the induction of remission in ulcerative colitis, with either a parallel arm or cross-over design, were considered eligible for inclusion. There were no exclusions based on patient age or the type, dose or duration of budesonide therapy. The primary outcome was the induction of clinical remission in ulcerative colitis. Secondary outcomes included clinical, histologic and endoscopic improvement, endoscopic mucosal healing, change in disease activity index scores, adverse events and study withdrawals. DATA COLLECTION AND ANALYSIS Studies were reviewed for eligibility, data were extracted and quality assessed by 2 independent investigators. It was not possible to perform a meta-analysis of the included studies due to significant heterogeneity, with each study comparing budesonide to a different control medication. MAIN RESULTS Three studies met the inclusion criteria. Oral budesonide was significantly less likely to induce clinical remission than oral mesalamine after 8 weeks of therapy (RR 0.72, 95% CI 0.57 to 0.91). There was no significant benefit of oral budesonide in comparison to placebo for inducing clinical remission after 4 weeks of treatment (RR 1.41, 95% CI 0.59 to 3.39). A small pilot study reported no statistically significant difference in endoscopic remission between budesonide and prednisolone (RR 0.75, 95% CI 0.23 to 2.42). The study was small and not powered to evaluate the impact of budesonide on clinical remission. Suppression of plasma cortisol was significantly more common in prednisolone treated patients (RR 0.02, 95% CI 0.0 to 0.33). Two multicenter studies are ongoing. AUTHORS' CONCLUSIONS At present, there is no evidence to recommend the clinical use of oral budesonide for the induction of remission in active ulcerative colitis. Mesalamine is superior to budesonide for the treatment of active ulcerative colitis.
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Affiliation(s)
- Mary E Sherlock
- Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8
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Extreme evolutionary disparities seen in positive selection across seven complex diseases. PLoS One 2010; 5:e12236. [PMID: 20808933 PMCID: PMC2923198 DOI: 10.1371/journal.pone.0012236] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2010] [Accepted: 07/12/2010] [Indexed: 12/22/2022] Open
Abstract
Positive selection is known to occur when the environment that an organism inhabits is suddenly altered, as is the case across recent human history. Genome-wide association studies (GWASs) have successfully illuminated disease-associated variation. However, whether human evolution is heading towards or away from disease susceptibility in general remains an open question. The genetic-basis of common complex disease may partially be caused by positive selection events, which simultaneously increased fitness and susceptibility to disease. We analyze seven diseases studied by the Wellcome Trust Case Control Consortium to compare evidence for selection at every locus associated with disease. We take a large set of the most strongly associated SNPs in each GWA study in order to capture more hidden associations at the cost of introducing false positives into our analysis. We then search for signs of positive selection in this inclusive set of SNPs. There are striking differences between the seven studied diseases. We find alleles increasing susceptibility to Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), and Crohn's Disease (CD) underwent recent positive selection. There is more selection in alleles increasing, rather than decreasing, susceptibility to T1D. In the 80 SNPs most associated with T1D (p-value <7.01 x 10(-5)) showing strong signs of positive selection, 58 alleles associated with disease susceptibility show signs of positive selection, while only 22 associated with disease protection show signs of positive selection. Alleles increasing susceptibility to RA are under selection as well. In contrast, selection in SNPs associated with CD favors protective alleles. These results inform the current understanding of disease etiology, shed light on potential benefits associated with the genetic-basis of disease, and aid in the efforts to identify causal genetic factors underlying complex disease.
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Kim MH, Ki HS, Cho DK, Yoon KW, Park SY, Kim HS, Choi SG, Rew JS. Clinical Features in Patients with Ulcerative Colitis. Chonnam Med J 2010. [DOI: 10.4068/cmj.2010.46.3.177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Min-Hyung Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Ho-Seok Ki
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Dong-Keun Cho
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Kyung-Won Yoon
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Sung-Gyu Choi
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Jong-Sun Rew
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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