1
|
Vukovic J, Jukic I, Tonkic A. The Challenges in Treating Inflammatory Bowel Diseases During the COVID-19 Pandemic: An Opinion. J Clin Med 2024; 13:7128. [PMID: 39685586 DOI: 10.3390/jcm13237128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 11/18/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
The COVID-19 pandemic posed significant challenges in the treatment of chronic diseases, particularly inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis. These challenges are multifaceted, encompassing difficulties in maintaining routine care, concerns about the safety of immunosuppressive therapies, disruptions in healthcare delivery, and the complexities of managing IBD in patients who contract COVID-19. This article explores the various obstacles faced in the treatment of IBD during the pandemic and discusses potential strategies to overcome these challenges.
Collapse
Affiliation(s)
- Jonatan Vukovic
- Department of Gastroenterology and Hepatology, Internal Clinic, Clinical Hospital Centre Split, Spinciceva 1, 21000 Split, Croatia
- Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, Croatia
| | - Ivana Jukic
- Department of Gastroenterology and Hepatology, Internal Clinic, Clinical Hospital Centre Split, Spinciceva 1, 21000 Split, Croatia
- University Department of Health Studies, University of Split, 21000 Split, Croatia
| | - Ante Tonkic
- Department of Gastroenterology and Hepatology, Internal Clinic, Clinical Hospital Centre Split, Spinciceva 1, 21000 Split, Croatia
- Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, Croatia
| |
Collapse
|
2
|
Lu X, Fan M, Ma Y, Feng Y, Pan L. Redox-sensitive hydrogel based on hyaluronic acid with selenocystamine cross-linking for the delivery of Limosilactobacillus reuteri in a DSS-induced colitis mouse model. Int J Biol Macromol 2024; 276:133855. [PMID: 39032895 DOI: 10.1016/j.ijbiomac.2024.133855] [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: 01/03/2024] [Revised: 06/30/2024] [Accepted: 07/11/2024] [Indexed: 07/23/2024]
Abstract
Disrupted gut microbiota homeostasis is an important cause of inflammatory colitis. Studies have shown that effective supplementation with probiotics can maintain microbial homeostasis and alleviate colitis. Here, to increase the viability of probiotics in the harsh gastrointestinal environments and enable targeted delivery, a redox-sensitive selenium hyaluronic acid (HA-Se) hydrogel encapsulating probiotics was developed. HA was modified with selenocystamine dihydrochloride and crosslinked by an amide reaction to generate a redox-sensitive hydrogel with stable mechanical properties, a low hemolysis rate and satisfactory biocompatibility. The HA-Se hydrogel exhibited suitable sensitivity to 10 mM GSH or 100 μM H2O2. The encapsulation of Limosilactobacillus reuteri (LR) in the HA-Se hydrogel (HA-Se-LR) significantly increased the survival rate of the probiotics in simulated gastric and intestinal fluid. HA-Se-LR administration increased the survival rate of mice with dextran sulfate sodium (DSS)-induced colitis, significantly alleviated oxidative stress and inflammation, and increased the effect of LR on microbiota α diversity. These results indicate that the HA-Se hydrogel constructed in this study can be used as a delivery platform to treat colitis, expanding the targeted applications of the natural polymer HA in disease treatment and the administration of probiotics as drugs to alleviate disease symptoms.
Collapse
Affiliation(s)
- Xi Lu
- College of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710000, China.
| | - Mingming Fan
- College of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710000, China
| | - Yuzhe Ma
- College of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710000, China
| | - Yimeng Feng
- Mathematics Teaching and Research Group, Dajindian Town Junior High School, Zhengzhou 450000, China
| | - Lei Pan
- Tangdu Hospital, Air Force Military Medical University, Xi'an 710000, China
| |
Collapse
|
3
|
Weibel N, Curcio M, Schreiber A, Arriaga G, Mausy M, Mehdy J, Brüllmann L, Meyer A, Roth L, Flury T, Pecina V, Starlinger K, Dernič J, Jungfer K, Ackle F, Earp J, Hausmann M, Jinek M, Rogler G, Antunes Westmann C. Engineering a Novel Probiotic Toolkit in Escherichia coli Nissle 1917 for Sensing and Mitigating Gut Inflammatory Diseases. ACS Synth Biol 2024; 13:2376-2390. [PMID: 39115381 PMCID: PMC11334186 DOI: 10.1021/acssynbio.4c00036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 06/13/2024] [Accepted: 07/25/2024] [Indexed: 08/17/2024]
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation with no cure and limited treatment options that often have systemic side effects. In this study, we developed a target-specific system to potentially treat IBD by engineering the probiotic bacterium Escherichia coli Nissle 1917 (EcN). Our modular system comprises three components: a transcription factor-based sensor (NorR) capable of detecting the inflammation biomarker nitric oxide (NO), a type 1 hemolysin secretion system, and a therapeutic cargo consisting of a library of humanized anti-TNFα nanobodies. Despite a reduction in sensitivity, our system demonstrated a concentration-dependent response to NO, successfully secreting functional nanobodies with binding affinities comparable to the commonly used drug Adalimumab, as confirmed by enzyme-linked immunosorbent assay and in vitro assays. This newly validated nanobody library expands EcN therapeutic capabilities. The adopted secretion system, also characterized for the first time in EcN, can be further adapted as a platform for screening and purifying proteins of interest. Additionally, we provided a mathematical framework to assess critical parameters in engineering probiotic systems, including the production and diffusion of relevant molecules, bacterial colonization rates, and particle interactions. This integrated approach expands the synthetic biology toolbox for EcN-based therapies, providing novel parts, circuits, and a model for tunable responses at inflammatory hotspots.
Collapse
Affiliation(s)
- Nathalie Weibel
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Martina Curcio
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Atilla Schreiber
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Gabriel Arriaga
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Marine Mausy
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Jana Mehdy
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Lea Brüllmann
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Andreas Meyer
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Len Roth
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Tamara Flury
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Valerie Pecina
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Kim Starlinger
- University
of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland
| | - Jan Dernič
- Institute
of Pharmacology and Toxicology, University
of Zürich, Winterthurerstrasse
190, CH-8057 Zürich, Switzerland
| | - Kenny Jungfer
- Department
of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
| | - Fabian Ackle
- Institute
of Medical Microbiology, University of Zürich, Gloriastrasse 28/30, CH-8006 Zürich, Switzerland
| | - Jennifer Earp
- Institute
of Medical Microbiology, University of Zürich, Gloriastrasse 28/30, CH-8006 Zürich, Switzerland
| | - Martin Hausmann
- Department
of Gastroenterology and Hepatology, University
Hospital Zürich and Zürich University, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Martin Jinek
- Department
of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
| | - Gerhard Rogler
- Department
of Gastroenterology and Hepatology, University
Hospital Zürich and Zürich University, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Cauã Antunes Westmann
- Department
of Evolutionary Biology and Environmental Studies, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
- Swiss
Institute of Bioinformatics, Quartier Sorge-Batiment Genopode, 1015 Lausanne, Switzerland
| |
Collapse
|
4
|
Salvador-Martín S, Rubbini G, Vellosillo P, Zapata-Cobo P, Velasco M, Palomino LM, Clemente S, Segarra O, Moreno-Álvarez A, Fernández-Lorenzo A, Pérez-Moneo B, Montraveta M, Sánchez C, Tolín M, Loverdos I, Fobelo MJ, Navas-López VM, Magallares L, García-Romero R, Torres-Peral R, Rodríguez A, Bossacoma F, Merino-Bohórquez V, Salcedo E, Álvarez R, Dopazo A, Sanjurjo-Sáez M, López-Fernández LA. Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment. Biomed Pharmacother 2024; 173:116299. [PMID: 38401525 DOI: 10.1016/j.biopha.2024.116299] [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: 11/11/2023] [Revised: 02/06/2024] [Accepted: 02/17/2024] [Indexed: 02/26/2024] Open
Abstract
BACKGROUND/AIMS Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. METHODS We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. RESULTS Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10-7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). CONCLUSIONS We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.
Collapse
Affiliation(s)
- Sara Salvador-Martín
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - Gianluca Rubbini
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - Perceval Vellosillo
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Unidad de Investigación Materno Infantil Fundación Familia Alonso (UDIMIFFA), Spain.
| | - Paula Zapata-Cobo
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - Marta Velasco
- Hospital Universitario Infantil Niño Jesús, Madrid, Spain.
| | | | | | | | | | | | | | | | - Cesar Sánchez
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - Mar Tolín
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | | | - María José Fobelo
- Hospital Universitario Virgen de Valme, Universidad de Sevilla, Sevilla, Spain.
| | | | | | | | | | | | - Ferrán Bossacoma
- Servicio de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Sant Joan de Dèu, Barcelona, Spain.
| | | | | | - Rebeca Álvarez
- Genomics Unit, Spanish National Center for Cardiovascular Disease (CNIC), Madrid 28029, Spain.
| | - Ana Dopazo
- Genomics Unit, Spanish National Center for Cardiovascular Disease (CNIC), Madrid 28029, Spain.
| | - María Sanjurjo-Sáez
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - Luis A López-Fernández
- Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| |
Collapse
|
5
|
Lan L, Huang C, Liu D, Cheng Y, Tang R, Gu J, Geng L, Cheng Y, Gong S. WNT2B activates macrophages via NF-κB signaling pathway in inflammatory bowel disease. FASEB J 2024; 38:e23551. [PMID: 38489235 DOI: 10.1096/fj.202302213r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 01/31/2024] [Accepted: 02/27/2024] [Indexed: 03/17/2024]
Abstract
Inflammation is a significant pathological manifestation of inflammatory bowel disease (IBD), yet its mechanism has remained unclear. Although WNT2B is enriched in the intestinal inflammatory tissue of IBD patients, the specific mechanism of WNT2B in the formation of intestinal inflammation remains unclear. This study was aimed to investigate whether macrophages expressing WNT2B can aggravate intestinal tissue inflammation. Samples were collected from both normal individuals and patients with IBD at multiple colon sites. Macrophages were identified using tissue immunofluorescence. IκB kinase (IKK)-interacting protein (IKIP), which interacts with WNT2B, was found by protein cross-linking and protein mass spectrometry. The expression of WNT2B, IKIP, the NF-κB pathway, and downstream molecules were analyzed. An acute colitis model of C57BL/6J mice was established using an adeno-associated virus (AAV)-mediated WNT2B knockdown system and 3% dextran sulfate sodium (DSS). The degree of intestinal inflammation in mice was assessed upon WNT2B knockdown in macrophages. Macrophages expressing WNT2B were found to be enriched in the colitis tissues of IBD patients. WNT2B in macrophages activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines. By competitively binding IKIP, WNT2B reduced the binding of IKIP to IKKβ and promoted the activation of the NF-κB pathway. Using an AAV-mediated WNT2B knockdown system, WNT2B expression in intestinal macrophages was suppressed, leading to a reduction in intestinal inflammation. WNT2B activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines by competitively binding to IKIP, potentially contributing to colon inflammatory injury in IBD.
Collapse
Affiliation(s)
- Lin Lan
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Digestive Diseases, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| | - Chuxiang Huang
- Department of Digestive Diseases, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| | - Danqiong Liu
- Department of Digestive Diseases, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| | - Yanling Cheng
- Department of Pediatrics, Shantou Central Hospital, Shantou, China
| | - Rui Tang
- Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| | - Jianbiao Gu
- Department of Digestive Diseases, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| | - Lanlan Geng
- Department of Digestive Diseases, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| | - Yang Cheng
- Department of Digestive Diseases, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| | - Sitang Gong
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Digestive Diseases, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China
| |
Collapse
|
6
|
Behnoush AH, Maroufi SP, Reshadmanesh T, Mohtasham Kia Y, Norouzi M, Mohammadi SM, Klisic A, Khalaji A. Circulatory resistin levels in inflammatory bowel disease: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:107. [PMID: 38486190 PMCID: PMC10941394 DOI: 10.1186/s12876-024-03199-7] [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: 11/14/2023] [Accepted: 03/11/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing-remitting systemic disease of the gastrointestinal tract with rising incidence. Studies have shown that adipocytes play a crucial role in patients with IBD by actively participating in systemic immune responses. The present study was designed to investigate the correlation between the circulatory levels of resistin, as an adipokine, and active and remission phases of IBD in comparison with healthy controls. METHODS Relevant articles were retrieved from PubMed, Embase, the Web of Science, and Scopus from inception until June 2023. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of plasma/serum resistin levels between IBD patients, patients in remission, and healthy controls were conducted through random-effect meta-analysis. RESULTS A total of 19 studies were included, assessing 1836 cases. Meta-analysis indicated that generally, serum/plasma resistin levels were higher in IBD patients in comparison with healthy controls (SMD 1.33, 95% CI 0.58 to 2.08, p-value < 0.01). This was true for each of the UC and CD separate analyses, as well. Moreover, it was shown that higher serum/plasma resistin levels were detected in the active phase of IBD than in the remission phase (SMD 1.04, 95% CI 0.65 to 1.42, p-value = 0.01). Finally, higher serum/plasma resistin levels were found in the remission phase compared to healthy controls (SMD 0.60, 95% CI 0.15 to 1.06, p-value < 0.01). CONCLUSION The results of this systematic review and meta-analysis support the conclusion that circulating resistin levels are increased in IBD (both UC and CD). Also, higher resistin levels were recorded in the remission phase of IBD in comparison with healthy controls. This indicates that further studies may provide valuable insights into the role of resistin in the pathogenesis of IBD.
Collapse
Affiliation(s)
- Amir Hossein Behnoush
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, 1417613151, Tehran, Iran.
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Seyede Parmis Maroufi
- Neurosurgical Research Network, Universal Scientific Education and Research Network, Tehran University of Medical Sciences, Tehran, Iran
| | - Tara Reshadmanesh
- Student Research Center, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
| | | | - Mitra Norouzi
- Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | | | - Aleksandra Klisic
- Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
- Center for Laboratory Diagnostics, Primary Health Care Center, Podgorica, Montenegro
| | - Amirmohammad Khalaji
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, 1417613151, Tehran, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
7
|
Kather S, Kacza J, Pfannkuche H, Böttcher D, Sung CH, Steiner JM, Gäbel G, Dengler F, Heilmann RM. Expression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy. PLoS One 2024; 19:e0296024. [PMID: 38206981 PMCID: PMC10783779 DOI: 10.1371/journal.pone.0296024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 12/04/2023] [Indexed: 01/13/2024] Open
Abstract
Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients.
Collapse
Affiliation(s)
- Stefanie Kather
- Small Animal Clinic, Veterinary Teaching Hospital, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
- Institute of Veterinary Physiology, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Johannes Kacza
- BioImaging Core Facility, College of Veterinary Medicine, Saxon Incubator for Clinical Translation, University of Leipzig, Leipzig, SN, Germany
| | - Helga Pfannkuche
- Institute of Veterinary Physiology, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Denny Böttcher
- Institute of Veterinary Pathology, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Chi-Hsuan Sung
- Gastrointestinal Laboratory, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States of America
| | - Joerg M. Steiner
- Gastrointestinal Laboratory, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States of America
| | - Gotthold Gäbel
- Institute of Veterinary Physiology, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Franziska Dengler
- Institute of Veterinary Physiology, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
- Institute for Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria
| | - Romy M. Heilmann
- Small Animal Clinic, Veterinary Teaching Hospital, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| |
Collapse
|
8
|
Geng Z, Wu L, Wang Q, Ma J, Shi Z. Non B Cell-Derived Immunoglobulins in Intestinal Tract. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1445:137-149. [PMID: 38967756 DOI: 10.1007/978-981-97-0511-5_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
Intestinal epithelium constitutes a barrier to the unrestricted movement of pathogens, and other detrimental substances from the external world (gut lumen) into the interstitial environment. Intestinal epithelial cells obstruct harmful substances passing through the epithelium as a physical and chemical barrier; Moreover, the epithelial cells can express Toll-like receptors (TLRs) and cytokines to exert innate immune function. In addition, high levels of immunoglobulin A (IgA) and other antibodies exist in the intestinal mucosa, maintaining intestinal immune homeostasis in conjunction with intestinal probiotics. Traditionally, these antibodies have been deemed to be secreted by submucosal plasma cells. Nonetheless, in recent years, it has been demonstrated that intestinal epithelial cells produce a substantial amount of Igs, especially IgA or free Ig light chains, which are involved in intestinal immune homeostasis and the survival of normal epithelial cells. Furthermore, mounting evidence affirms that many human carcinoma cells, including colorectal cancer (CRC), can overexpress Igs, particularly IgG. Cancer-derived Igs exhibit a unique V(D)J rearrangement pattern distinct from B cell-derived Ig; moreover, this cancer cell-derived IgG also has a unique sialic acid modification on the 162 site of CH1 domain (SIA-IgG). The SIA-IgG plays a crucial role in promoting cancer initiation, progression, metastasis, and tumour immune escape. Simultaneously, CRC cells can also express free Ig light chains, which promote colitis, colitis-associated colon carcinogenesis, and CRC progression. Therefore, Igs expressed by CRC cells could be a potential target for diagnosing and preventing the transformation of inflammation into cancer, as well as treating CRC.
Collapse
Affiliation(s)
- Zihan Geng
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Lina Wu
- Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Qianqian Wang
- School of Food and Drug, Shenzhen Polytechnic University, Shenzhen, China
| | - Junfan Ma
- Department of Clinical Research, Sinocelltech Group Limited, Beijing, China
| | - Zhan Shi
- Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
9
|
Ren Q, Liu Z, Wu L, Yin G, Xie X, Kong W, Zhou J, Liu S. C/EBPβ: The structure, regulation, and its roles in inflammation-related diseases. Biomed Pharmacother 2023; 169:115938. [PMID: 38000353 DOI: 10.1016/j.biopha.2023.115938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 11/08/2023] [Accepted: 11/21/2023] [Indexed: 11/26/2023] Open
Abstract
Inflammation, a mechanism of the human body, has been implicated in many diseases. Inflammatory responses include the release of inflammatory mediators by activating various signaling pathways. CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor in the C/EBP family, contains the leucine zipper (bZIP) domain. The expression of C/EBPβ is mediated at the transcriptional and post-translational levels, such as phosphorylation, acetylation, methylation, and SUMOylation. C/EBPβ has been involved in inflammatory responses by mediating several signaling pathways, such as MAPK/NF-κB and IL-6/JAK/STAT3 pathways. C/EBPβ plays an important role in the pathological development of inflammation-related diseases, such as osteoarthritis, pneumonia, hepatitis, inflammatory bowel diseases, and rheumatoid arthritis. Here, we comprehensively discuss the structure and biological effects of C/EBPβ and its role in inflammatory diseases.
Collapse
Affiliation(s)
- Qun Ren
- Department of Pharmacy, Gannan Medical University, Ganzhou 341000, China
| | - Zhaowen Liu
- Department of Pharmacy, Gannan Medical University, Ganzhou 341000, China
| | - Longhuo Wu
- Department of Pharmacy, Gannan Medical University, Ganzhou 341000, China
| | - Guoqiang Yin
- Ganzhou People's Hospital Affiliated to Nanchang University, Ganzhou 341000, China
| | - Xunlu Xie
- Department of Joint Surgery, Ganzhou People's Hospital, Ganzhou 341000, China
| | - Weihao Kong
- Department of Joint Surgery, Ganzhou People's Hospital, Ganzhou 341000, China
| | - Jianguo Zhou
- Department of Joint Surgery, Ganzhou People's Hospital, Ganzhou 341000, China
| | - Shiwei Liu
- Department of Joint Surgery, Ganzhou People's Hospital, Ganzhou 341000, China.
| |
Collapse
|
10
|
Fan L, Shi J, Yang X. Prunetin alleviates dextran sulfate sodium-induced colitis via the regulation of inflammatory response based on network pharmacology and experimental evidence. ALL LIFE 2023. [DOI: 10.1080/26895293.2022.2164359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Affiliation(s)
- Ludi Fan
- Department of Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Jinglong Shi
- Department of General Surgery, Guangzhou Twelfth People’s Hospital, Guangzhou, People’s Republic of China
| | - Xiaobo Yang
- Department of Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| |
Collapse
|
11
|
Sun C, Zhang L, Zhang M, Wang J, Rong S, Lu W, Dong H. Zinc pyrithione induces endothelium-dependent hyperpolarization-mediated mesenteric vasorelaxation in healthy and colitic mice. Biochem Pharmacol 2023; 217:115828. [PMID: 37774954 DOI: 10.1016/j.bcp.2023.115828] [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: 07/30/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND Although Zinc pyrithione (ZPT) could lower blood pressure by inducing vasorelaxation, it is unclear if it is able to induce vasorelaxation of mesenteric arterioles in health and ulcerative colitis (UC) to exert anti-colitic action. METHODS The vasorelaxation of the second-order branch of the mesenteric artery from wide type (WT) mice, TRPV1-/-(KO) mice, and TRPV4-/-(KO) mice was determined using a Mulvany-style wire myograph. Calcium imaging and patch clamp were applied to analyze the actions of ZPT in human vascular endothelial cells. Mouse model of UC was used to evaluate the anti-colitic action of ZPT. RESULTS ZPT dose-dependently induced mesenteric vasorelaxation predominately through endothelium-dependent hyperpolarization (EDH), which could be attenuated by intracellular Zn2+ and Ca2+ chelators TPEN and BAPTA-AM. The ZPT/EDH-mediated vasorelaxation via TRPV1, TRPV4 and TRPA1 channels was verified by a combination of selective pharmacological inhibitors and TRPV1-KO and TRPV4-KO mice. Moreover. ZPT induced Ca2+ entry via vascular endothelial TRPV1/4 and TRPA1 channels and enhanced membrane non-selective currents through these channels. Notably, ZPT exerted anti-colitic effects by rescuing the impaired acetylcholine (ACh)-induced mesenteric vasorelaxation in colitic mice. CONCLUSIONS ZPT/Zn2+ induces EDH-mediated mesenteric vasorelaxation through activating endothelial multiple TRPV1/4 and TPPA1 channels in health, and rescues the impaired ACh-induced vasorelaxation to exert anti-colitic action. Our study may open a new avenue of potential vessel-specific targeted therapy for UC.
Collapse
Affiliation(s)
- Chensijin Sun
- Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China
| | - Luyun Zhang
- Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China; Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Mengting Zhang
- Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China
| | - Jianxin Wang
- Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China
| | - Shaoya Rong
- Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China
| | - Wei Lu
- Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China.
| | - Hui Dong
- Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China.
| |
Collapse
|
12
|
Choi SH, Eom JY, Kim HJ, Seo W, Kwun HJ, Kim DK, Kim J, Cho YE. Aloe-derived nanovesicles attenuate inflammation and enhance tight junction proteins for acute colitis treatment. Biomater Sci 2023; 11:5490-5501. [PMID: 37367827 DOI: 10.1039/d3bm00591g] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the digestive tract that causes pain and weight loss and also increases the risk of colon cancer. Inspired by the benefits of plant-derived nanovesicles and aloe, we herein report aloe-derived nanovesicles, including aloe vera-derived nanovesicles (VNVs), aloe arborescens-derived nanovesicles (ANVs), and aloe saponaria-derived nanovesicles (SNVs) and evaluate their therapeutic potential and molecular mechanisms in a dextran sulfate sodium (DSS)-induced acute experimental colitis mouse model. Aloe-derived nanovesicles not only facilitate markedly reduced DSS-induced acute colonic inflammation, but also enable the restoration of tight junction (TJ) and adherent junction (AJ) proteins to prevent gut permeability in DSS-induced acute colonic injury. These therapeutic effects are ascribed to the anti-inflammatory and anti-oxidant effects of aloe-derived nanovesicles. Therefore, aloe-derived nanovesicles are a safe treatment option for IBD.
Collapse
Affiliation(s)
- Sang-Hun Choi
- Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea.
| | - Jung-Young Eom
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea
| | - Hyun-Jin Kim
- Department of Food and Nutrition, Andong National University, Andong 36729, Republic of Korea.
| | - Wonhyo Seo
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Hyo-Jung Kwun
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Do-Kyun Kim
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea
| | - Jihoon Kim
- Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea.
| | - Young-Eun Cho
- Department of Food and Nutrition, Andong National University, Andong 36729, Republic of Korea.
| |
Collapse
|
13
|
Parihar N, Bhatt LK. Topotecan alleviates acetic acid-induced ulcerative colitis in rats via attenuation of the RORγT transcription factor. Life Sci 2023; 328:121915. [PMID: 37414139 DOI: 10.1016/j.lfs.2023.121915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 06/23/2023] [Accepted: 07/03/2023] [Indexed: 07/08/2023]
Abstract
AIMS Ulcerative colitis is characterized as a chronic immune-mediated inflammatory condition, affecting the intestinal gastroenteric tissue. Previous studies revealed that Th-17 cells are key players in the pathogenesis of ulcerative colitis. RORγT (Retinoic-acid-receptor-related orphan receptor-gamma T) is a lineage-specific transcription factor of Th-17 cells and thus has a role in their differentiation. Transient inhibition of RORγT has been reported to attenuate the differentiation of Th-17 cells and secretion of interleukin-17 (IL-17). Here, we investigated the efficacy of topotecan in ameliorating ulcerative colitis in rodents, via inhibition of the RORγT transcription factor. MAIN METHODS AND KEY FINDINGS Experimental ulcerative colitis was induced in rats by intrarectal acetic acid administration. Topotecan attenuated the severity of ulcerative colitis in rats by revoking neutrophils and macrophage infiltration to the colon. It also alleviated diarrhea and rectal bleeding and improved body weight. Further, attenuation of RORγT and IL-17 expression was observed in topotecan treated animals. Levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the colon tissue were reduced by topotecan treatment. Significant reduction in malondialdehyde level, elevation of superoxide dismutase (SOD) and catalase activity was observed in the colon tissue of rats treated with topotecan compared to the diseased group. SIGNIFICANCE This study shows the therapeutic potential of topotecan in attenuating ulcerative colitis in rats probably via inhibition of the RORγT transcription factor and downstream mediators of Th-17 cells.
Collapse
Affiliation(s)
- Niraj Parihar
- Department of Pharmacology, SVKM's Dr Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India
| | - Lokesh Kumar Bhatt
- Department of Pharmacology, SVKM's Dr Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.
| |
Collapse
|
14
|
Tang HJ, Bie CQ, Guo LL, Zhong LX, Tang SH. Efficacy and safety of vedolizumab in the treatment of patients with inflammatory bowel disease: A systematic review and meta‑analysis of randomized controlled trials. Exp Ther Med 2023; 25:298. [PMID: 37229320 PMCID: PMC10203751 DOI: 10.3892/etm.2023.11997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 04/05/2023] [Indexed: 05/27/2023] Open
Abstract
Few studies have thoroughly assessed the efficacy and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD). Therefore, this systematic review and meta-analysis was performed to further evaluate this association. PubMed, Embase, and the Cochrane databases were searched until April 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of VDZ in the treatment of IBD were included. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome using a random effects model. A total of 12 RCTs, including 4,865 patients, met the inclusion criteria. In the induction phase, VDZ was more effective than placebo for patients with ulcerative colitis and Crohn's disease (CD) in clinical remission (RR=2.09; 95% CI=1.66-2.62) and clinical response (RR=1.54; 95% CI=1.34-1.78). In the maintenance therapy group, VDZ reached higher clinical remission (RR=1.98; 95% CI=1.58-2.49) and clinical response (RR=1.78; 95% CI=1.40-2.26) rates compared with the placebo group. VDZ particularly improved clinical remission (RR=2.07; 95% CI=1.48-2.89) and clinical response (RR=1.84; 95% CI=1.54-2.21) in patients with TNF antagonist failure. In terms of corticosteroid-free remission, VDZ was also more effective than placebo in patients with IBD (RR=1.98; 95% CI=1.51-2.59). In Crohn's patients, VDZ was more effective than placebo in terms of mucosal healing (RR=1.78; 95% CI=1.27-2.51). With respect to adverse events, VDZ significantly reduced the risk of IBD exacerbation compared with the placebo (RR=0.60; 95% CI=0.39-0.93; P=0.023). However, when compared with the placebo, VDZ increased the risk of nasopharyngitis in patients with CD (RR=1.77; 95% CI=1.01-3.10; P=0.045). No significant differences in other adverse events were observed. Although there might be underlying risk, such as selection bias, in the present study it can be safely concluded that VDZ is a safe and effective biological agent for IBD, particularly for patients with TNF antagonist failure.
Collapse
Affiliation(s)
- Hui-Jun Tang
- Department of Gastroenterology, Shenzhen Integrated Traditional Chinese and Western Medicine Hospital, Shenzhen, Guangdong 518104, P.R. China
| | - Cai-Qun Bie
- Department of Gastroenterology, Shenzhen Integrated Traditional Chinese and Western Medicine Hospital, Shenzhen, Guangdong 518104, P.R. China
| | - Li-Liangzi Guo
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Li-Xian Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Shao-Hui Tang
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| |
Collapse
|
15
|
Elahimanesh M, Najafi M. Cross talk between bacterial and human gene networks enriched using ncRNAs in IBD disease. Sci Rep 2023; 13:7704. [PMID: 37169818 PMCID: PMC10175251 DOI: 10.1038/s41598-023-34780-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 05/08/2023] [Indexed: 05/13/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a long-term inflammatory immune-mediated gut illness with several extra-intestinal complications. The aims of this study were to identify a novel network-based meta-analysis approach on the basis of the combinations of the differentially expressed genes (DEGs) from microarray data, to enrich the functional modules from human protein-protein interaction (PPI) and gene ontology (GO) data, and to profile the ncRNAs on the genes involved in IBD. The gene expression profiles of GSE126124, GSE87473, GSE75214, and GSE95095 are obtained from the Gene Expression Omnibus (GEO) database based on the study criteria between 2017 and 2022. The DEGs were screened by the R software. DEGs were then used to examine gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The ncRNAs including the miRNAs and ceRNAs were predicted on the PPIs visualized using Cytoscape. Enrichment analysis of genes with differential expression (n = 342) using KEGG and GO showed that the signaling pathways related with staphylococcus aureus and pertussis bacterial infections may stimulate the immune system and exacerbate IBD via the interaction with human proteins including Fibrinogen gamma chain (FGG), Keratin 10 (KRT10), and Toll like receptor 4 (TLR4). By building a ceRNA network, lncRNA XIST and NEAT1 were determined by affecting common miRNAs, hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-6763-5p, hsa-miR-4436a, and hsa-miR-520a-5p. Additionally, the chromosome regions including NM_001039703 and NM_006267, which produce the most potent circRNAs play a significant role in the ceRNA network of IBD. Also, we predicted the siRNAs that would be most effective against the bacterial genes in staphylococcus aureus and pertussis infections. These findings suggested that three genes (FGG, KRT10, and TLR4), six miRNAs (hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-4436a, hsa-miR-520a-5p, and hsa-miR-6763-5p), two lncRNAs (XIST and NEAT1), and chromosomal regions including NM_001039703 and NM_006267 with the production of the most effective circRNAs are involved in the ncRNA-associated ceRNA network of IBD. These ncRNA profiles are related to the described gene functions and may play therapeutic targets in controlling inflammatory bowel disease.
Collapse
Affiliation(s)
- Mohammad Elahimanesh
- Clinical Biochemistry Department, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Najafi
- Clinical Biochemistry Department, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
- Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
16
|
Giordani AS, Candelora A, Fiacca M, Cheng C, Barberio B, Baritussio A, Marcolongo R, Iliceto S, Carturan E, De Gaspari M, Rizzo S, Basso C, Tarantini G, Savarino EV, Alp C. Myocarditis and inflammatory bowel diseases: A single-center experience and a systematic literature review. Int J Cardiol 2023; 376:165-171. [PMID: 36738845 DOI: 10.1016/j.ijcard.2023.01.071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 01/06/2023] [Accepted: 01/24/2023] [Indexed: 02/05/2023]
Abstract
BACKGROUND Myocarditis and inflammatory bowel diseases (IBD) are rare conditions, but may coexist. Myocarditis in IBD may be infective, immune-mediated, or due to mesalamine toxicity. A gap of knowledge exists on the clinical features of patients that present myocarditis in association with IBD, especially for endomyocardial biopsy-proven cases. Our aims are: 1) to describe the clinical characteristics of patients with an associated diagnosis of myocarditis and IBD in a single-center hospital, 2) to perform a systematic review of the literature of analogous cases. METHODS We retrospectively analyzed data of patients followed up at the outpatient Cardio-immunology and Gastroenterology Clinic of Padua University Hospital, to identify those with an associated diagnosis of myocarditis and IBD. In addition, a systematic review of the literature was conducted. We performed a qualitative analysis of the overall study population. RESULTS The study included 104 patients (21 from our single center cohort, 83 from the literature review). Myocarditis in IBD more frequently affects young (median age 31 years) males (72%), predominantly with infarct-like presentation (58%), within an acute phase of the IBD (67%) and with an overall benign clinical course (87%). Nevertheless, a not negligible quote of patients may present giant cell myocarditis, deserve immunosuppression and have a chronic, or even fatal course. Histological evidence of mesalamine hypersensitivity is scarce and its incidence may be overestimated. CONCLUSIONS Our study shows that myocarditis in association with IBD, if correctly managed, may have a spontaneous benign course, but predictors of worse prognosis must be promptly recognized.
Collapse
Affiliation(s)
- A S Giordani
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - A Candelora
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - M Fiacca
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - C Cheng
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - B Barberio
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - A Baritussio
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - R Marcolongo
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - S Iliceto
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - E Carturan
- Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - M De Gaspari
- Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - S Rizzo
- Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - C Basso
- Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - G Tarantini
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - E V Savarino
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy
| | - Caforio Alp
- Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua and Azienda Ospedale Università di Padova, Padua, Italy.
| |
Collapse
|
17
|
Yu H, Liu Z. GNA12 regulates C5a-induced migration by downregulating C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling. BIOPHYSICS REPORTS 2023; 9:33-44. [PMID: 37426201 PMCID: PMC10323775 DOI: 10.52601/bpr.2023.230001] [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] [Received: 01/12/2023] [Accepted: 02/21/2023] [Indexed: 07/11/2023] Open
Abstract
Gna12 has been identified as one of the reported inflammatory bowel disease (IBD) susceptibility genes in genome-wide association studies (GWAS). However, the function of GNA12 in intestinal homeostasis remains unknown. Here we report that GNA12, a G-protein α subunit, regulates C5a-induced migration in macrophages. Deficiency of GNA12 results in enhanced migration induced by C5a in macrophages. Mechanistically, GNA12 suppresses C5a-induced migration by downregulating the C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling. Therefore, our study reveals that GNA12 is an anti-inflammatory factor, which might alleviate the development of inflammation by inhibiting the excessive chemotactic migration of macrophages.
Collapse
Affiliation(s)
- Haonan Yu
- Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zhihua Liu
- Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
- Institute for Immunology, Tsinghua University, Beijing 100084, China
- Tsinghua-Peking Center for Life Sciences, Beijing 100084, China
| |
Collapse
|
18
|
Proietti E, Pauwels RW, de Vries AC, Orecchini E, Volpi C, Orabona C, Peppelenbosch MP, Fuhler GM, Mondanelli G. Modulation of Indoleamine 2,3-Dioxygenase 1 During Inflammatory Bowel Disease Activity in Humans and Mice. Int J Tryptophan Res 2023; 16:11786469231153109. [PMID: 36798536 PMCID: PMC9926376 DOI: 10.1177/11786469231153109] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 01/08/2023] [Indexed: 02/11/2023] Open
Abstract
Background and Aims Indoleamine 2,3 dioxygenase-1 (IDO1), a key enzyme in tryptophan metabolism, is strongly up-regulated both in human inflammatory bowel disease (IBD) and animal models of colitis, however its role in the pathogenesis is still controversial. In this study, we investigated IDO1 expression and activity in a mouse model of DSS-induced chronic colitis as well as in colon biopsies and sera from IBD patients. Methods Chronic colitis was induced in mice through the oral administration of dextran sodium sulfate (DSS), and IDO1 activity was induced by i.p. treatment with N-acetyl serotonin (NAS). IDO1 expression and catalytic activity (measured as Kyn/Trp ratio) was evaluated in sera and tissue samples collected from mice and 93 IBD patients under immunotherapy with Vedolizumab (VDZ) or Ustekinumab (UST). Results Strong up-regulation of IDO1 was found in colons of mice with acute colitis, which follows disease activity. Enhanced IDO1 activity by NAS treatment protects the intestinal mucosa during the recovery phase of chronic colitis. In IBD patients, IDO1 expression and activity correlate with the severity of mucosal inflammation with inflamed regions showing higher IDO1 expression compared to non-inflamed regions within the same patient. Endoscopic response to VDZ/UST treatment is associated with decreased expression of IDO1. Conclusions This is the first study demonstrating immunomodulatory activity of IDO1 in a chronic mouse model of DSS-induced colitis. As its expression and catalytic activity correlate with the grade of mucosal inflammation and treatment response, IDO1 could represent a promising biomarker for disease severity and treatment monitoring in IBD.
Collapse
Affiliation(s)
- Elisa Proietti
- Department of Experimental Medicine, University of Perugia, Italy,Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | - Renske W.M. Pauwels
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | - Elena Orecchini
- Department of Experimental Medicine, University of Perugia, Italy
| | - Claudia Volpi
- Department of Experimental Medicine, University of Perugia, Italy
| | - Ciriana Orabona
- Department of Experimental Medicine, University of Perugia, Italy
| | | | - Gwenny M. Fuhler
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | - Giada Mondanelli
- Department of Experimental Medicine, University of Perugia, Italy,Giada Mondanelli, Department of Medicine and Surgery, University of Perugia, Piazza Severi, 1, Perugia, Umbria 06132, Italy.
| |
Collapse
|
19
|
Synthesis, Characterization of Low Molecular Weight Chitosan Selenium Nanoparticles and Its Effect on DSS-Induced Ulcerative Colitis in Mice. Int J Mol Sci 2022; 23:ijms232415527. [PMID: 36555167 PMCID: PMC9779469 DOI: 10.3390/ijms232415527] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/04/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Selenium nanoparticles have attracted extensive attention due to their good bioavailability and activity. In the present study, a new form of selenium nanoparticle (Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs)) were synthesized in a system of sodium selenite and acetic acid. The size, element state, morphology and elementary composition of LCS-SeNPs were characterized by using various spectroscopic and microscopic measurements. The protection of LCS-SeNPs against dextran sulfate sodium (DSS)-induced intestinal barrier dysfunction and the inherent mechanisms of this process were investigated. The results showed that LCS-SeNPs, with an average diameter of 198 nm, zero-valent and orange-red relatively uniform spherical particles were prepared. LCS-SeNPs were mainly composed of C, N, O and Se elements, of which Se accounted for 39.03% of the four elements C, N, O and Se. LCS-SeNPs reduced colon injury and inflammation symptoms and improved intestinal barrier dysfunction. LCS-SeNPs significantly reduced serum and colonic inflammatory cytokines TNF-α and IL-6 levels. Moreover, LCS-SeNPs remarkably increased antioxidant enzyme GSH-Px levels in serum and colonic tissue. Further studies on inflammatory pathways showed that LCS-SeNPs alleviated DSS-induced colitis through the NF-κB signaling pathway, and relieved inflammatory associated oxidative stress through the Nrf2 signaling pathway. Our findings suggested that LCS-SeNPs are a promising selenium species with potential applications in the treatment of oxidative stress related inflammatory intestinal diseases.
Collapse
|
20
|
Yasmin F, Sahito AM, Mir SL, Khatri G, Shaikh S, Gul A, Hassan SA, Koritala T, Surani S. Electrical neuromodulation therapy for inflammatory bowel disease. World J Gastrointest Pathophysiol 2022; 13:128-142. [PMID: 36187600 PMCID: PMC9516456 DOI: 10.4291/wjgp.v13.i5.128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 02/19/2022] [Accepted: 07/18/2022] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal (GI) tract. It has financial and quality of life impact on patients. Although there has been a significant advancement in treatments, a considerable number of patients do not respond to it or have severe side effects. Therapeutic approaches such as electrical neuromodulation are being investigated to provide alternate options. Although bioelectric neuromodulation technology has evolved significantly in the last decade, sacral nerve stimulation (SNS) for fecal incontinence remains the only neuromodulation protocol commonly utilized use for GI disease. For IBD treatment, several electrical neuromodulation techniques have been studied, such as vagus NS, SNS, and tibial NS. Several animal and clinical experiments were conducted to study the effectiveness, with encouraging results. The precise underlying mechanisms of action for electrical neuromodulation are unclear, but this modality appears to be promising. Randomized control trials are required to investigate the efficacy of intrinsic processes. In this review, we will discuss the electrical modulation therapy for the IBD and the data pertaining to it.
Collapse
Affiliation(s)
- Farah Yasmin
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Abdul Moiz Sahito
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Syeda Lamiya Mir
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Govinda Khatri
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Somina Shaikh
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Ambresha Gul
- Department of Medicine, People’s University of Medical and Health Sciences, Nawabshah 67480, Pakistan
| | - Syed Adeel Hassan
- Department of Medicine, University of Louisville, Louiseville, KY 40292, United States
| | - Thoyaja Koritala
- Department of Medicine, Mayo Clinic, Rochester, NY 55902, United States
| | - Salim Surani
- Department of Medicine, Texas A&M University, College Station, TX 77843, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55902, United States
| |
Collapse
|
21
|
Resveratrol and resveratrol nano-delivery systems in the treatment of inflammatory bowel disease. J Nutr Biochem 2022; 109:109101. [PMID: 35777588 DOI: 10.1016/j.jnutbio.2022.109101] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 04/04/2022] [Accepted: 06/08/2022] [Indexed: 12/22/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic disorder associated with the inflammation in the digestive tract. The exact cause of IBD is unknown; nevertheless, in IBD, the homeostasis of key regulatory factors involved in intestinal immunity has been documented to be disrupted. Despite the lack of a viable treatment for IBD, synthetic drugs and monoclonal antibodies are currently used to treat it. However, these treatments have side effects, and the high relapse rate limits their usage. Dietary polyphenols constitute a great variety of compounds and have shown an array of biological properties. Resveratrol is a natural polyphenol found in grapevines and berries. The therapeutic ability of resveratrol against IBD is amply demonstrated in many in vivo studies. Resveratrol can interact with several molecular targets (Nf-kB, SIRT1, mTOR, HIF-1α, miRNAs, and TNF-α) and effectively prevent/ alleviate IBD symptoms with promising results. Although resveratrol has profound anti-inflammatory properties against IBD, its therapeutic employment is limited due to its low water solubility, less chemical stability, less bioavailability, and rapid metabolism in vivo. Hence, resveratrol encapsulation using different carries and its controlled release has become a promising strategy to overcome limitations. Herein, we meticulously review, talk-over the anti-inflammatory effect and mechanisms of resveratrol in IBD. We further provide the latest information on resveratrol formulations and nano-delivery systems used in oral delivery of resveratrol for the treatment of IBD and offer our view on future research on resveratrol in IBD treatment.
Collapse
|
22
|
Noh JY, Wu CS, DeLuca JAA, Devaraj S, Jayaraman A, Alaniz RC, Tan XD, Allred CD, Sun Y. Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging. Int J Mol Sci 2022; 23:2219. [PMID: 35216335 PMCID: PMC8875592 DOI: 10.3390/ijms23042219] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/13/2022] [Accepted: 02/14/2022] [Indexed: 01/25/2023] Open
Abstract
Chronic low-grade inflammation is a hallmark of aging, which is now coined as inflamm-aging. Inflamm-aging contributes to many age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, and inflammatory bowel disease (IBD). We have shown that gut hormone ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), regulates energy metabolism and inflammation in aging. Emerging evidence suggests that gut microbiome has a critical role in intestinal immunity of the host. To determine whether microbiome is an integral driving force of GHS-R mediated immune-metabolic homeostasis in aging, we assessed the gut microbiome profiles of young and old GHS-R global knockout (KO) mice. While young GHS-R KO mice showed marginal changes in Bacteroidetes and Firmicutes, aged GHS-R KO mice exhibited reduced Bacteroidetes and increased Firmicutes, featuring a disease-susceptible microbiome profile. To further study the role of GHS-R in intestinal inflammation in aging, we induced acute colitis in young and aged GHS-R KO mice using dextran sulfate sodium (DSS). The GHS-R KO mice showed more severe disease activity scores, higher proinflammatory cytokine expression, and decreased expression of tight junction markers. These results suggest that GHS-R plays an important role in microbiome homeostasis and gut inflammation during aging; GHS-R suppression exacerbates intestinal inflammation in aging and increases vulnerability to colitis. Collectively, our finding reveals for the first time that GHS-R is an important regulator of intestinal health in aging; targeting GHS-R may present a novel therapeutic strategy for prevention/treatment of aging leaky gut and inflammatory bowel disease.
Collapse
Affiliation(s)
- Ji Yeon Noh
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (J.Y.N.); (C.-S.W.); (J.A.A.D.); (C.D.A.)
| | - Chia-Shan Wu
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (J.Y.N.); (C.-S.W.); (J.A.A.D.); (C.D.A.)
| | - Jennifer A. A. DeLuca
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (J.Y.N.); (C.-S.W.); (J.A.A.D.); (C.D.A.)
| | - Sridevi Devaraj
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA;
| | - Arul Jayaraman
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA;
| | - Robert C. Alaniz
- Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, TX 77843, USA;
| | - Xiao-Di Tan
- Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA;
| | - Clinton D. Allred
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (J.Y.N.); (C.-S.W.); (J.A.A.D.); (C.D.A.)
- Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27412, USA
| | - Yuxiang Sun
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (J.Y.N.); (C.-S.W.); (J.A.A.D.); (C.D.A.)
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
| |
Collapse
|
23
|
Medgyesy K, Horrigan J, Tadros M. Bilateral Pulmonary Embolism in a Hospitalized Ulcerative Colitis Patient. Cureus 2022; 14:e21861. [PMID: 3527384 PMCID: PMC8901111 DOI: 10.7759/cureus.21861] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2022] [Indexed: 01/13/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism (VTE), though physicians may be unaware of this risk or hesitant to start pharmacologic VTE prophylaxis in the presence of active gastrointestinal bleeding. We report a case of a 38-year-old patient hospitalized with acute severe ulcerative colitis (UC) who was not placed on pharmacologic VTE prophylaxis and developed bilateral pulmonary embolism (PE). The patient's UC did not respond to medical therapy. Due to his PE, the patient’s total proctocolectomy was delayed six months. He also developed a large pelvic hematoma after colectomy requiring further surgical intervention. Hospitalized inflammatory bowel disease (IBD) patients require pharmacologic VTE prophylaxis unless they have life-threatening bleeding.
Collapse
|
24
|
Morsy Y, Brillant N, Franc Y, Scharl M, Wawrzyniak M. Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease. Cells 2021; 10:cells10123589. [PMID: 34944097 PMCID: PMC8700574 DOI: 10.3390/cells10123589] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/08/2021] [Accepted: 12/16/2021] [Indexed: 12/17/2022] Open
Abstract
Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn’s disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD.
Collapse
Affiliation(s)
- Yasser Morsy
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (Y.M.); (N.B.); (M.W.)
| | - Nathalie Brillant
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (Y.M.); (N.B.); (M.W.)
| | - Yannick Franc
- Center for Primary Care and Public Health (Unisanté), University of Lausanne, 1101 Lausanne, Switzerland;
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (Y.M.); (N.B.); (M.W.)
- Correspondence: ; Tel.: +41-44-255-3419
| | - Marcin Wawrzyniak
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (Y.M.); (N.B.); (M.W.)
| | | |
Collapse
|
25
|
Fung KY, Louis C, Metcalfe RD, Kosasih CC, Wicks IP, Griffin MDW, Putoczki TL. Emerging roles for IL-11 in inflammatory diseases. Cytokine 2021; 149:155750. [PMID: 34689057 DOI: 10.1016/j.cyto.2021.155750] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 10/08/2021] [Accepted: 10/11/2021] [Indexed: 12/16/2022]
Abstract
Interleukin-11 (IL-11) is a cytokine that has been strongly implicated in the pathogenesis of fibrotic diseases and solid malignancies. Elevated IL-11 expression is also associated with several non-malignant inflammatory diseases where its function remains less well-characterized. Here, we summarize current literature surrounding the contribution of IL-11 to the pathogenesis of autoimmune inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, diabetes and systemic sclerosis, as well as other chronic inflammatory conditions such as periodontitis, asthma, chronic obstructive pulmonary disease, psoriasis and colitis.
Collapse
Affiliation(s)
- Ka Yee Fung
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Victoria 3053, Australia.
| | - Cynthia Louis
- Department of Medical Biology, University of Melbourne, Victoria 3053, Australia; Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia
| | - Riley D Metcalfe
- Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Technology Institute, University of Melbourne, Victoria 3010, Australia
| | - Clara C Kosasih
- Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Technology Institute, University of Melbourne, Victoria 3010, Australia
| | - Ian P Wicks
- Department of Medical Biology, University of Melbourne, Victoria 3053, Australia; Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia; Rheumatology Unit, The Royal Melbourne Hospital, Victoria 3050, Australia
| | - Michael D W Griffin
- Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Technology Institute, University of Melbourne, Victoria 3010, Australia
| | - Tracy L Putoczki
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Victoria 3053, Australia.
| |
Collapse
|
26
|
Potential Roles of Exosomal lncRNAs in the Intestinal Mucosal Immune Barrier. J Immunol Res 2021; 2021:7183136. [PMID: 34485536 PMCID: PMC8413039 DOI: 10.1155/2021/7183136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/15/2021] [Accepted: 08/17/2021] [Indexed: 12/31/2022] Open
Abstract
The intestinal mucosal immune barrier protects the host from the invasion of foreign pathogenic microorganisms. Immune cells and cytokines in the intestinal mucosa maintain local and systemic homeostasis by participating in natural and adaptive immunity. Deficiency of the intestinal mucosal immune barrier is associated with a variety of intestinal illnesses. Exosomes are phospholipid bilayer nanovesicles that allow cell-cell communication by secreting physiologically active substances including proteins, lipids, transcription factors, mRNAs, micro-RNAs (miRNAs), and long noncoding RNAs (lncRNAs). Exosomal lncRNAs are involved in immune cell differentiation and the modulation of the immune response. This review briefly introduces the potential role of exosomal lncRNAs in the intestinal mucosal immune barrier and discusses their relevance to intestinal illnesses.
Collapse
|
27
|
Child and Family Perspectives on Adjustment to and Coping With Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2020; 71:e16-e27. [PMID: 32142001 DOI: 10.1097/mpg.0000000000002693] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Children with inflammatory bowel disease (IBD) are at increased risk for poor mental health. The etiology of this risk is not clear, though may be related to the disease, its treatment, and/or the experience of these. We sought to describe the challenges that children with IBD and their families face in living with a chronic condition and undergoing repeated intravenous infusions; and identify coping mechanisms to understand how medical systems may support resilience. METHODS Semistructured qualitative interviews with 18 patient-guardian dyads at a tertiary outpatient infusion center, explored feelings related to IBD, the infusion process, and coping. Interviews were recorded, transcribed, and analyzed in ATLAS.ti. Two coders identified themes; developed a codebook and coded transcripts using the constant comparative method; and described themes/patterns. RESULTS Participants identified challenges related to IBD (unpredictable nature, disrupted normalcy, treatment decisions, managing relationships, life transitions) and a subset of challenges related to the infusion procedure (anxiety of unknown, managing pain/anxiety during IV placement, logistics). Participants coped through social support, cognitive strategies (positive attitude) and/or behavioral strategies for managing emotions (preparation for intravenous [IV] placement), and confidence in the medical care. By employing these coping strategies, participants came to accept IBD, adapt to the "new norm," and learned life lessons and resilience. CONCLUSIONS To support coping, clinical teams might provide anticipatory guidance to decrease anxiety of the unknown and identify cognitive-behavioral strategies for managing emotions. Delivery systems that build relationships, maintain normalcy, and consider needs of the family may further facilitate coping.
Collapse
|
28
|
Baudino MN, Gamwell KL, Roberts CM, Grunow JE, Jacobs NJ, Gillaspy SR, Edwards CS, Mullins LL, Chaney JM. Disease Severity and Depressive Symptoms in Adolescents With Inflammatory Bowel Disease: The Mediating Role of Parent and Youth Illness Uncertainty. J Pediatr Psychol 2020; 44:490-498. [PMID: 30551150 DOI: 10.1093/jpepsy/jsy091] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 10/27/2018] [Accepted: 10/29/2018] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE The objective of this study is to examine parent and youth appraisals of illness uncertainty as potential serial mediators in the relation between disease severity and youth depressive symptoms in adolescents with inflammatory bowel disease (IBD). METHODS Participants were 85 adolescents 13-18 years of age (Mage = 15.75, SD =1.51) with a confirmed diagnosis of IBD (Crohn's disease, 59%; ulcerative colitis, 41%) and a primary caregiver. At a scheduled outpatient visit, caregivers completed a measure of illness uncertainty, while adolescents completed measures of illness uncertainty and depressive symptoms. Pediatric gastroenterologists provided global estimates of disease severity. RESULTS Path analysis revealed several significant direct and indirect associations among the modeled variables. Importantly, results provided support for the hypothesized disease severity→parent illness uncertainty→youth illness uncertainty→youth depressive symptoms serial mediation path (95% confidence interval = 0.04 to 1.10). CONCLUSIONS Results indicate that increased disease activity may serve to magnify the unpredictable nature of IBD for parents, reflected in heightened perceptions of illness uncertainty. Our findings also suggest that increased parent illness uncertainty has a significant influence on youth illness uncertainty appraisals, which in turn translates into elevated depressive symptoms in adolescents with IBD. The clinical implications of our findings and suggestions for future studies are discussed.
Collapse
|
29
|
A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J Immunol Res 2019; 2019:7247238. [PMID: 31886308 PMCID: PMC6914932 DOI: 10.1155/2019/7247238] [Citation(s) in RCA: 544] [Impact Index Per Article: 90.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 11/15/2019] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The pathogenesis of IBD is complex. Recent studies have greatly improved our knowledge of the pathophysiology of IBD, leading to great advances in the treatment as well as diagnosis of IBD. In this review, we have systemically reviewed the pathogenesis of IBD and highlighted recent advances in host genetic factors, gut microbiota, and environmental factors and, especially, in abnormal innate and adaptive immune responses and their interactions, which may hold the keys to identify novel predictive or prognostic biomarkers and develop new therapies.
Collapse
|
30
|
Bourdier P, Saidi O, Rochette E, Ratel S, Merlin E, Pereira B, Duché P. Physical activity and sedentary levels in children with juvenile idiopathic arthritis and inflammatory bowel disease. A systematic review and meta-analysis. Pediatr Res 2019; 86:149-156. [PMID: 31029060 DOI: 10.1038/s41390-019-0409-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 03/28/2019] [Accepted: 04/16/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Physical activity (PA) is essential for children throughout their growth and maturation. It improves physiological and psychological health and limits the risk of developing metabolic disorders. However, some chronic physiological and metabolic diseases may lead to decreased PA. The diversity of outcomes in the literature offers no consensus for physical activity and sedentary levels in children with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). METHODS A literature review and a meta-analysis were carried out with original studies from a Medline database search. Only high-quality studies (STROBE checklist) written in English comparing PA level or sedentary behavior (SB) between children with the disorders and their healthy peers were considered. The aim was to examine PA and SB in children with JIA or IBD compared to their healthy peers. RESULTS The literature review and meta-analysis identified decreased PA and increased time spent in SB in these populations, which may exacerbate both their lower physical fitness and the symptoms of their health disorders. CONCLUSION Results nevertheless show discrepancies due to the different materials and methods used and the variables measured. Further studies are needed to establish a gold standard method for assessing PA level in these populations.
Collapse
Affiliation(s)
- Pierre Bourdier
- Laboratoire des Adaptations Métaboliques en conditions Physiologiques et Physiopathologiques (AME2P), Université Clermont Auvergne, 3533, Clermont-Ferrand, France.,CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - Oussama Saidi
- Laboratoire des Adaptations Métaboliques en conditions Physiologiques et Physiopathologiques (AME2P), Université Clermont Auvergne, 3533, Clermont-Ferrand, France.,CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - Emmanuelle Rochette
- CRNH-Auvergne, 63000, Clermont-Ferrand, France.,CHU Clermont-Ferrand, Pédiatrie, Hôpital Estaing, 63000, Clermont-Ferrand, France.,Université Clermont Auvergne, INSERM, CIC 1405, Unité CRECHE, 63000, Clermont-Ferrand, France.,Université de Toulon, Laboratoire IAPS, 83041, Toulon, France
| | - Sébastien Ratel
- Laboratoire des Adaptations Métaboliques en conditions Physiologiques et Physiopathologiques (AME2P), Université Clermont Auvergne, 3533, Clermont-Ferrand, France.,CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - Etienne Merlin
- CHU Clermont-Ferrand, Pédiatrie, Hôpital Estaing, 63000, Clermont-Ferrand, France.,Université Clermont Auvergne, INSERM, CIC 1405, Unité CRECHE, 63000, Clermont-Ferrand, France.,Université Clermont Auvergne, INRA, UMR 1019 UNH, ECREIN, 63000, Clermont-Ferrand, France
| | - Bruno Pereira
- CHU Clermont-Ferrand, Délégation de la Recherche Clinique et Innovations, 63000, Clermont-Ferrand, France
| | - Pascale Duché
- Université de Toulon, Laboratoire IAPS, 83041, Toulon, France.
| |
Collapse
|
31
|
Candan G, Kahraman R, Ergen A. Irak-4 rs4251481 gene variant: as a risk factor on inflammatory bowel disease. Turk J Med Sci 2019; 49:478-482. [PMID: 30997787 PMCID: PMC7018251 DOI: 10.3906/sag-1807-279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background/aim Abnormal immune response occurs in individuals who have alleles associated with innate and adaptive immune mechanisms that predispose to inflammatory bowel disease (IBD). Interleukin-1 receptor-associated kinase 4 (IRAK-4) involved in the pathway produces cytokines that initiate and maintain inflammation through Toll-like receptors and interleukin-1 receptors on the membranes of innate immune cells are stimulated with antigens. It was aimed to investigate whether IRAK-4 rs3794262 and rs4251481 polymorphisms predispose to IBD and the possible effects of these polymorphisms by examining these gene polymorphisms with the clinic and prognostic parameters of IBD. Material and methods Real-time PCR technique was used to detect IRAK-4 polymorphisms in 107 patients with IBD and 103 healthy controls. Results As a result of experimental studies, the frequency of occurrence of rs4251481 polymorphism related AG genotype (P = 0.029) and G allele (P = 0.005) was found to increase statistically in patients compared to controls. In the control group, the rs4251481 AA genotype rate of incidence increased compared with the patient group (P = 0.005). Conclusion Consequently, this is the first study in terms of both polymorphisms on IBD. These results suggest that rs4251481 AG genotype and G allele are associated with increased IBD risk in patients.
Collapse
|
32
|
Mayangsari Y, Suzuki T. Resveratrol Ameliorates Intestinal Barrier Defects and Inflammation in Colitic Mice and Intestinal Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:12666-12674. [PMID: 30426751 DOI: 10.1021/acs.jafc.8b04138] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
This study is aimed to investigate the ameliorative effect of resveratrol in a dextran sodium sulfate (DSS)-induced colitis mouse model and intestinal Caco-2 cells, focusing on neutrophil infiltration and tight junction (TJ) barriers. DSS administration caused body weight loss (day8, control 104 ± 1, DSS 72 ± 2%, p < 0.05), shortening of colon length (control 5.1 ± 0.1, DSS 3.8 ± 0.1 cm, p < 0.05), pro-inflammatory cytokines increase-including interleukin (IL)-1β (control 1.0 ± 0.2, DSS 58.5 ± 29.6 arbitrary unit (AU), p < 0.05), IL-6 (control 1.0 ± 0.3, DSS 312 ± 82 AU, p < 0.05), and chemokine motif ligand 2 (CXCL-2, a murine IL-8 homologue, control 1.0 ± 0.4, DSS 696 ± 262 AU, p < 0.05), decreased TJ proteins (e.g., occludin, control 1.0 ± 0.05, DSS 0.11 ± 0.03 AU, p < 0.05), and neutrophil infiltration (control 1.2 ± 0.2, DSS 25.9 ± 1.1 cells, p < 0.05). Supplemental resveratrol (0.1% (w/w) in the diet) partially or totally reversed these symptoms (body weight change 100 ± 1, colon length 4.6 ± 0.1; IL-1β 5.9 ± 1.8, IL-6 10 ± 3, CXCL-2 14 ± 7, occludin 0.76 ± 0.06, neutrophil infiltration 9.3 ± 0.7, p < 0.05). Pretreatment of intestinal Caco-2 cells with resveratrol suppressed the TNF-α-induced production of IL-8 (control 1.00 ± 0.04, TNFα 3.40 ± 0.16, TNFα+Res 1.81 ± 0.28 AU, p < 0.05) and phosphorylation of the inflammatory signaling molecules including NF-κB, extracellular signal-regulated kinase and stress c-Jun N-terminal protein kinase. Collectively, the reduction of TJ barrier defect and IL-8 in intestinal cells, leading to reduced neutrophil infiltration into colonic tissues, appears to be one of the central mechanisms for the resveratrol-mediated effect.
Collapse
Affiliation(s)
- Yunika Mayangsari
- Department of Biofunctional Science and Technology, Graduate School of Biosphere Science , Hiroshima University , Kagamiyama, Higashi Hiroshima City 739-8528 , Japan
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology , Universitas Gadjah Mada , Sleman, Yogyakarta 55281 , Indonesia
| | - Takuya Suzuki
- Department of Biofunctional Science and Technology, Graduate School of Biosphere Science , Hiroshima University , Kagamiyama, Higashi Hiroshima City 739-8528 , Japan
| |
Collapse
|
33
|
The Complex Interplay between Chronic Inflammation, the Microbiome, and Cancer: Understanding Disease Progression and What We Can Do to Prevent It. Cancers (Basel) 2018; 10:cancers10030083. [PMID: 29558443 PMCID: PMC5876658 DOI: 10.3390/cancers10030083] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 03/15/2018] [Accepted: 03/15/2018] [Indexed: 12/12/2022] Open
Abstract
Cancer is a multifaceted condition, in which a senescent cell begins dividing in an irregular manner due to various factors such as DNA damage, growth factors and inflammation. Inflammation is not typically discussed as carcinogenic; however, a significant percentage of cancers arise from chronic microbial infections and damage brought on by chronic inflammation. A hallmark cancer-inducing microbe is Helicobacter pylori and its causation of peptic ulcers and potentially gastric cancer. This review discusses the recent developments in understanding microbes in health and disease and their potential role in the progression of cancer. To date, microbes can be linked to almost every cancer, including colon, pancreatic, gastric, and even prostate. We discuss the known mechanisms by which these microbes can induce cancer growth and development and how inflammatory cells may contribute to cancer progression. We also discuss new treatments that target the chronic inflammatory conditions and their associated cancers, and the impact microbes have on treatment success. Finally, we examine common dietary misconceptions in relation to microbes and cancer and how to avoid getting caught up in the misinterpretation and over inflation of the results.
Collapse
|
34
|
Nakamura H, Lim T, Puri P. Inflammatory bowel disease in patients with Hirschsprung's disease: a systematic review and meta-analysis. Pediatr Surg Int 2018; 34:149-154. [PMID: 28983688 DOI: 10.1007/s00383-017-4182-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/21/2017] [Indexed: 12/21/2022]
Abstract
AIM AND OBJECTIVES Hirschsprung-associated enterocolitis (HAEC) continues to be an important cause of morbidity in patients with Hirschsprung's disease (HSCR). HAEC can occur at any time during the course of the disease. The reported incidence of HAEC before surgery ranges from 6 to 50%, and after surgery, it ranges from 2 to 35%. HAEC and inflammatory bowel disease (IBD) have similar clinical presentation including diarrhea, hematochezia, and abdominal pain. In recent years, isolated cases of IBD have been reported in patients who had surgical treatment for HSCR. The exact pathogenesis of HAEC or IBD is not known. However, both conditions are characterized by an abnormal intestinal mucosal barrier function, which may be a common pathway. The purpose of this meta-analysis was to determine the clinical presentation and outcome in patients with HSCR who developed IBD after pull-through operation. MATERIALS AND METHODS A systematic literature search for relevant articles was performed in four databases using the combinations of the following terms "inflammatory bowel disease", "Crohn/Crohn's disease", "ulcerative colitis", and "Hirschsprung disease/Hirschsprung's disease" for studies published between 1990 and 2017. The relevant cohorts of HSCR associated with IBD were systematically searched for clinical presentation and outcomes. RESULTS 14 studies met defined inclusion criteria, reporting a total of 66 patients who had HSCR associated with IBD. Mean age at first operation for HSCR was 5.8 months, mean age at diagnosis of IBD was 7.7 years, and the majority of patients were male (73%). The extent of aganglionosis was total colonic aganglionosis in 41% of patients, long segment in 45%, and rectosigmoid in 14%. The majority of patients underwent a Duhamel procedure (84%) for HSCR. The distribution of IBD was Crohn's disease in 72.3% of patients, ulcerative colitis in 16.9%, and others in 10.8%. Eight articles (47 patients) reported about HAEC, and 22 patients (47%) had experienced HAEC after surgery for HSCR. CONCLUSION Male patients with extensive colonic aganglionosis who continue to suffer from postoperative HAEC after a Duhamel procedure are more susceptible to develop IBD. Recognition of IBD may be important in the long-term follow-up of HSCR patients who have had postoperative HAEC.
Collapse
Affiliation(s)
- H Nakamura
- National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland
| | - T Lim
- Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA
| | - P Puri
- National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland. .,School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research University College Dublin, Dublin, Ireland.
| |
Collapse
|
35
|
Xiong H, Tian L, Zhao Z, Chen S, Zhao Q, Hong J, Xie Y, Zhou N, Fu Y. The sinomenine enteric-coated microspheres suppressed the TLR/NF-κB signaling in DSS-induced experimental colitis. Int Immunopharmacol 2017; 50:251-262. [PMID: 28711031 DOI: 10.1016/j.intimp.2017.06.033] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Revised: 06/27/2017] [Accepted: 06/29/2017] [Indexed: 10/19/2022]
Abstract
Sinomenine is a pure alkaloid with immunosuppressive effects that is extracted from the Chinese medicinal plant Sinomenium acutum. We studied the therapeutic effects of sinomenine on inflammatory bowel disease. In this study, we randomly divided mice into the following ten groups: Control group; DSS-induced colitis group; Salicylazosulfapyridine (SASP)-treated group; Chitosan-treated group; low-, medium-, and high-dose sinomenine-treated and sinomenine enteric-coated microspheres-treated groups. We recorded changes in colon length, disease activity index (DAI), and colon pathology, measured TLR4, MyD88, SIGIRR, NF-κB p65 protein levels and inflammatory serum cytokine levels. Except for the Control group, the weight of mice in each group decreased, the DAI of the DSS-induced colitis group was significantly higher than the other groups, and the DAIs of the sinomenine- and sinomenine enteric-coated microspheres-treated groups were significantly lower than that of the SASP-treated group. TLR4, MyD88, NF-κB p65 and proinflammatory cytokine expressions decreased dose dependently in the sinomenine and sinomenine enteric-coated microspheres-treated groups and were generally lower in the sinomenine enteric-coated microspheres groups. However, SIGIRR and anti-inflammatory IL-10 expressions exhibited the opposite pattern. Based on the superior therapeutic effect, sinomenine enteric-coated microspheres might regulate TLR/NF-κB signaling and would be beneficial for an effective and safe therapy of inflammatory bowel disease.
Collapse
Affiliation(s)
- Huifang Xiong
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Liang Tian
- Department of Pharmacy, Shanghai Neuromedical Center, Shanghai, China
| | - Zihan Zhao
- First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu Province, China
| | - Shuping Chen
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Qiaoyun Zhao
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Junbo Hong
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Yong Xie
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China.
| | - Nanjin Zhou
- Jiangxi Provincial Academy of Medical Science, Nanchang University, Nanchang, Jiangxi Province, China.
| | - Yingjun Fu
- School of Pharmacy, Nanchang University, Nanchang, Jiangxi Province, China
| |
Collapse
|
36
|
Abstract
Inflammatory bowel disease (IBD), including Crohn disease, ulcerative colitis, and IBD-unspecified, is a chronic immune-mediated condition of the gastrointestinal tract in which the goal of treatment is to induce and maintain durable remission. In pediatrics, there is a wide spectrum of presenting symptoms, but esophagogastroduodenoscopy and colonoscopy are imperative to confirming the diagnosis. Treatment goals include achieving mucosal healing of the gastrointestinal tract, reaching growth potential, limiting medication toxicities, and optimizing quality of life for all patients.
Collapse
Affiliation(s)
- Máire A Conrad
- Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Joel R Rosh
- Pediatric Gastroenterology, Clinical Development and Research Affairs, Goryeb Children's Hospital/Atlantic Health, Icahn School of Medicine at Mount Sinai, 100 Madison Avenue, Morristown, NJ 07962, USA.
| |
Collapse
|
37
|
Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease. Mediators Inflamm 2017; 2017:4810258. [PMID: 28420941 PMCID: PMC5379128 DOI: 10.1155/2017/4810258] [Citation(s) in RCA: 108] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 02/22/2017] [Indexed: 12/17/2022] Open
Abstract
Cytokines play an important role in the immunopathogenesis of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, where they drive and regulate multiple aspects of intestinal inflammation. The imbalance between proinflammatory and anti-inflammatory cytokines that occurs in IBD results in disease progression and tissue damage and limits the resolution of inflammation. Targeting cytokines have been novel strategies in the treatment of IBD. Recent studies show the beneficial effects of anticytokine treatments to IBD patients, and multiple novel cytokines are found to be involved in the pathogenesis of IBD. In this review, we will discuss the recent advances of novel biologics in clinics and clinical trials, and novel proinflammatory and anti-inflammatory cytokines found in IBD with focusing on IL-12 family and IL-1 family members as well as their relevance to the potential therapy of IBD.
Collapse
|
38
|
Chouliaras G, Margoni D, Dimakou K, Fessatou S, Panayiotou I, Roma-Giannikou E. Disease impact on the quality of life of children with inflammatory bowel disease. World J Gastroenterol 2017; 23:1067-1075. [PMID: 28246481 PMCID: PMC5311096 DOI: 10.3748/wjg.v23.i6.1067] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 11/16/2016] [Accepted: 01/11/2017] [Indexed: 02/06/2023] Open
Abstract
AIM
To assess the impact of disease characteristics on the quality of life (QOL) in children with inflammatory bowel diseases (IBD).
METHODS
This was a cross-sectional study conducted at the First Department of Pediatrics of the University of Athens at the “Aghia Sophia” Children’s Hospital. Children diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC), who were followed as outpatients or during a hospitalization, participated, after informed consent was obtained from their legal representative. QOL was assessed by the IMPACT-III questionnaire. Demographic data and disease characteristics were also collected. Statistical analyses included parametric (Student’s t-test and Pearson’s r) and non-parametric (Mann-Whitney test, Fisher’s test and Spearman’s rho) procedures.
RESULTS
Ninety-nine patients (UC: 37, 73.0% females, CD: 62, 51.6% females), aged 12.8 ± 2.6 years were included. Overall, as well as, sub-domain scores did not differ between UC and CD (overall score: 73.9 ± 13.3 vs 77.5 ± 11.2, respectively, P = 0.16). In the entire sample, total score was related to physician’s global assessment (PGA, patients classified as “mild/moderate” active disease had, on average, 14.8 ± 2.7 points lower total scores compared to those “in remission”, P < 0.001) and age at IMPACT completion (Pearson’s r = 0.29, P = 0.05). Disease activity assessed by the indices Pediatric Ulcerative Colitis activity index, Pediatric Crohn’s disease activity index or PGA was significantly associated with all subdomains scores. Presence of extraintestinal manifestations had a negative impact on emotional and social functioning domains.
CONCLUSION
Disease activity is the main correlate of QOL in children with IBD, underlining the importance of achieving and sustaining clinical remission
Collapse
|
39
|
DeFilippis EM, Sockolow R, Barfield E. Health Care Maintenance for the Pediatric Patient With Inflammatory Bowel Disease. Pediatrics 2016; 138:peds.2015-1971. [PMID: 27489295 DOI: 10.1542/peds.2015-1971] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2016] [Indexed: 11/24/2022] Open
Abstract
Nearly one-quarter of patients with inflammatory bowel disease (IBD) are younger than 20 years of age at diagnosis. Furthermore, the incidence of IBD in children continues to increase. Nevertheless, variation in management exists within the care of patients with IBD with regards to disease screening and preventive care. A multidisciplinary approach that involves the general practitioner and pediatric gastroenterologist is needed to routinely monitor growth, bone health, vitamin and mineral deficiencies, vaccination status, and endoscopic surveillance. It is also important to monitor for extraintestinal manifestations of IBD that may affect the liver, joints, skin, and eyes. The purpose of this article is to provide an updated overview of comprehensive care for pediatric patients with IBD.
Collapse
|
40
|
Levy RL, van Tilburg MA, Langer SL, Romano JM, Walker LS, Mancl LA, Murphy TB, Claar RL, Feld SI, Christie DL, Abdullah B, DuPen MM, Swanson KS, Baker MD, Stoner SA, Whitehead WE. Effects of a Cognitive Behavioral Therapy Intervention Trial to Improve Disease Outcomes in Children with Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:2134-48. [PMID: 27542131 PMCID: PMC4995069 DOI: 10.1097/mib.0000000000000881] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Studies testing the efficacy of behavioral interventions to modify psychosocial sequelae of inflammatory bowel disease in children are limited. This report presents outcomes through a 6-month follow-up from a large randomized controlled trial testing the efficacy of a cognitive behavioral intervention for children with inflammatory bowel disease and their parents. METHODS One hundred eighty-five children aged 8 to 17 years with a diagnosis of Crohn's disease or ulcerative colitis and their parents were randomized to one of two 3-session conditions: (1) a social learning and cognitive behavioral therapy condition or (2) an education support condition designed to control for time and attention. RESULTS There was a significant overall treatment effect for school absences due to Crohn's disease or ulcerative colitis (P < 0.05) at 6 months after treatment. There was also a significant overall effect after treatment for child-reported quality of life (P < 0.05), parent-reported increases in adaptive child coping (P < 0.001), and reductions in parents' maladaptive responses to children's symptoms (P < 0.05). Finally, exploratory analyses indicated that for children with a higher level of flares (2 or more) prebaseline, those in social learning and cognitive behavioral therapy condition experienced a greater reduction in flares after treatment. CONCLUSIONS This trial suggests that a brief cognitive behavioral intervention for children with inflammatory bowel disease and their parents can result in improved child functioning and quality of life, and for some children may decrease disease activity.
Collapse
Affiliation(s)
| | | | | | - Joan M. Romano
- University of Washington, Psychiatry & Behavioral Sciences
| | | | | | | | - Robyn L. Claar
- University of North Carolina, Division of Gastroenterology and Hepatology
| | - Shara I. Feld
- University of Wisconsin, School of Medicine and Public Health
| | | | | | | | | | | | | | | |
Collapse
|
41
|
Tavares M, de Lima C, Fernandes W, Martinelli V, de Lucena M, Lima F, Telles A, Brandão L, de Melo Júnior M. Tumour necrosis factor-alpha (-308G/A) promoter polymorphism is associated with ulcerative colitis in Brazilian patients. Int J Immunogenet 2016; 43:376-382. [DOI: 10.1111/iji.12289] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 06/13/2016] [Accepted: 07/28/2016] [Indexed: 01/26/2023]
Affiliation(s)
- M. Tavares
- Laboratory of Immunopathology Keizo Asami; Federal University of Pernambuco; Recife Brazil
| | - C. de Lima
- Laboratory of Immunopathology Keizo Asami and Department of Genetics; Federal University of Pernambuco; Recife Brazil
| | - W. Fernandes
- Master in Pathology; Federal University of Pernambuco; Recife Brazil
| | - V. Martinelli
- Department of Gastroenterology; University Hospital; Federal University of Pernambuco; Recife Brazil
| | - M. de Lucena
- Maurílio Toscano de Lucena; Department of Proctology; Barão de Lucena Hospital; Recife Brazil
| | - F. Lima
- Department of Surgery; University Hospital; Federal University of Pernambuco; Recife Brazil
| | - A. Telles
- Department of Pathology; Federal University of Pernambuco; Recife Brazil
| | - L. Brandão
- Department of Pathology; Federal University of Pernambuco; Recife Brazil
| | - M. de Melo Júnior
- Department of Pathology; Federal University of Pernambuco; Recife Brazil
| |
Collapse
|
42
|
Arvanitis M, DeWalt DA, Martin CF, Long MD, Chen W, Jaeger B, Sandler RS, Kappelman MD. Patient-Reported Outcomes Measurement Information System in Children with Crohn's Disease. J Pediatr 2016; 174:153-159.e2. [PMID: 27157449 PMCID: PMC5157125 DOI: 10.1016/j.jpeds.2016.03.069] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 02/23/2016] [Accepted: 03/25/2016] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To assess the criterion validity and responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) in a web-based cohort of children with Crohn's disease. STUDY DESIGN We recruited children with Crohn's disease (ages 9-17 years) and their parents from the web-based Crohn's and Colitis Foundation of America Kids and Teens Study cohort. Upon entry into the cohort and 6 months later, children self-reported Crohn's disease activity, health-related quality of life, and PROMIS domains of pain interference, anxiety, depression, fatigue, and peer relationships. RESULTS Mean PROMIS scores for the 276 participating patients were worse among those with worse self-reported Crohn's disease activity (per Short Crohn's Disease Activity Index, P < .005 for all), Crohn's disease activity in the prior 6 months (per Manitoba Index, P < .01 for all), and health-related quality of life (per IMPACT-35, P < .001 for all). One hundred forty-three patients and their parents completed follow-up questionnaires, 75% of whom reported stable disease activity. Those with improved Crohn's disease activity reported improved PROMIS scores, and those with worsened Crohn's disease activity reported worse PROMIS scores for all domains except anxiety. All participants reported improved anxiety from baseline, but those with stable or worsened Crohn's disease activity reported less improvement (P = .07). CONCLUSIONS PROMIS scores were significantly associated with Crohn's disease activity in a linear and clinically meaningful manner, and responded to change in Crohn's disease activity over a 6-month period. This supports the criterion validity and responsiveness of pediatric PROMIS.
Collapse
Affiliation(s)
| | | | | | | | - Wenli Chen
- University of North Carolina at Chapel Hill
| | | | | | | |
Collapse
|
43
|
Nyuyki KD, Pittman QJ. Toward a better understanding of the central consequences of intestinal inflammation. Ann N Y Acad Sci 2016; 1351:149-54. [PMID: 26378439 DOI: 10.1111/nyas.12935] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 08/14/2015] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel diseases (IBDs), which include Crohn's disease and ulcerative colitis, are inflammatory diseases of the gastrointestinal tract. Quality of life for IBD patients is negatively affected by associated pain and gastrointestinal dysfunction, but also by serious behavioral symptoms that include depression, anxiety, fatigue, and cognitive dysfunction. Because these behavioral comorbidities are poorly understood, we have investigated them in a rat model of IBD caused by infusion of a hapten (trinitrobenzene sulfonic acid (TNBS)) into the lower colon. TNBS colitis has many similarities to Crohn's disease, and we have found that it is associated with changes in central nervous system function. TNBS-treated animals have lowered seizure thresholds, which resolve following remission, and hippocampal slices from such animals display increased excitability. There are significant changes in excitatory, AMPA receptor-mediated transmission, in part due to increased numbers of AMPA receptors lacking the GluR2 subunit. Long-term potentiation and depression are reduced in colitic animals, and the synaptic alterations are reversed if microglial activation and tumor necrosis factor α synthesis within the brain are blocked.
Collapse
Affiliation(s)
- Kewir D Nyuyki
- Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Quentin J Pittman
- Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| |
Collapse
|
44
|
Engelmann G, Erhard D, Petersen M, Parzer P, Schlarb AA, Resch F, Brunner R, Hoffmann GF, Lenhartz H, Richterich A. Health-related quality of life in adolescents with inflammatory bowel disease depends on disease activity and psychiatric comorbidity. Child Psychiatry Hum Dev 2015; 46:300-7. [PMID: 24838299 DOI: 10.1007/s10578-014-0471-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Adolescent patients with inflammatory bowel disease (IBD) show an increased risk for behavioral and emotional dysfunction. Health-related quality of life (HRQoL) is influenced by medical illnesses, as well as by psychiatric disorders, but for adolescents with IBD, the extent to which HRQoL is influenced by these two factors is unclear. For 47 adolescent IBD patients, we analyzed disease activity, HRQoL and whether or not a psychiatric disorder was present. Disease activity was estimated using pediatric Ulcerative Colitis Activity Index and pediatric Crohn's Disease Activity Index. The IMPACT-III and the EQ-5D were used to measure HRQoL and QoL, respectively. In addition, patient and parent diagnostic interviews were performed. 55.3 % patients fulfilled DSM-IV criteria for one or more psychiatric disorders. In all patients, psychiatric comorbidity together with disease activity contributed to a reduction in quality of life. Adolescents with IBD are at a high risk for clinically relevant emotional or behavioral problems resulting in significantly lower HRQoL. We conclude that accessible, optimally structured psychotherapeutic and/or psychiatric help is needed in adolescent patients with IBD.
Collapse
Affiliation(s)
- G Engelmann
- Department of Pediatrics, Lukas Hospital, 41464, Neuss, Germany,
| | | | | | | | | | | | | | | | | | | |
Collapse
|
45
|
Werner H, Braegger CP, Buehr P, Koller R, Nydegger A, Spalinger J, Heyland K, Schibli S, Landolt MA. Shorter time since inflammatory bowel disease diagnosis in children is associated with lower mental health in parents. Acta Paediatr 2015; 104:e32-8. [PMID: 25164428 DOI: 10.1111/apa.12781] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 06/18/2014] [Accepted: 08/18/2014] [Indexed: 11/28/2022]
Abstract
AIM This study assessed the mental health of parents of children with inflammatory bowel disease (IBD), compared their mental health with age-matched and gender-matched references and examined parental and child predictors for mental health problems. METHODS A total of 125 mothers and 106 fathers of 125 children with active and inactive IBD from the Swiss IBD multicentre cohort study were included. Parental mental health was assessed by the Symptom Checklist 27 and child behaviour problems by the Strengths and Difficulties Questionnaire. Child medical data were extracted from hospital records. RESULTS While the mothers reported lower mental health, the fathers' mental health was similar, or even better, than in age-matched and gender-matched community controls. In both parents, shorter time since the child's diagnosis was associated with poorer mental health. In addition, the presence of their own IBD diagnosis and child behaviour problems predicted maternal mental health problems. CONCLUSIONS Parents of children with IBD may need professional support when their child is diagnosed, to mitigate distress. This, in turn, may help the child to adjust better to IBD. Particular attention should be paid to mothers who have their own IBD diagnosis and whose children display behaviour problems.
Collapse
Affiliation(s)
- H Werner
- Department of Psychosomatics and Psychiatry; University Children's Hospital Zurich; Zurich Switzerland
| | - CP Braegger
- Divison of Gastroenterology and Nutrition; University Children's Hospital Zurich; Zurich Switzerland
- Children's Research Center; University Children's Hospital Zurich; Zurich Switzerland
| | - P Buehr
- Divison of Gastroenterology and Nutrition; University Children's Hospital Zurich; Zurich Switzerland
| | - R Koller
- Divison of Gastroenterology and Nutrition; University Children's Hospital Zurich; Zurich Switzerland
| | - A Nydegger
- Division of Gastroenterology; University Children's Hospital Lausanne; Lausanne Switzerland
| | - J Spalinger
- Division of Gastroenterology; Children's Hospital Lucerne; Lucerne Switzerland
| | - K Heyland
- Division of Gastroenterology; Children's Hospital Winterthur; Winterthur Switzerland
| | - S Schibli
- Division of Gastroenterology; University Children's Hospital Berne; Berne Switzerland
| | - MA Landolt
- Department of Psychosomatics and Psychiatry; University Children's Hospital Zurich; Zurich Switzerland
- Children's Research Center; University Children's Hospital Zurich; Zurich Switzerland
- Department of Child and Adolescent Health Psychology; Institute of Psychology; University of Zurich; Zurich Switzerland
| | | |
Collapse
|
46
|
Loreaux KL, Gray WN, Denson LA, Hommel KA. Health-Related Quality of Life in Adolescents With Inflammatory Bowel Disease: The Relation of Parent and Adolescent Depressive Symptoms. CHILDRENS HEALTH CARE 2014. [DOI: 10.1080/02739615.2014.912943] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
47
|
Quick V, McWilliams R, Byrd-Bredbenner C. A case-control study of current psychological well-being and weight-teasing history in young adults with and without bowel conditions. J Hum Nutr Diet 2014; 28:28-36. [DOI: 10.1111/jhn.12202] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- V. Quick
- Division of Intramural Population Health Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS; Bethesda MD USA
| | - R. McWilliams
- Department of Human Ecology; Rutgers University; New Brunswick NJ USA
| | - C. Byrd-Bredbenner
- Department of Nutritional Sciences; Rutgers University; New Brunswick NJ USA
| |
Collapse
|
48
|
Characterization of relations among sleep, inflammation, and psychiatric dysfunction in depressed youth with Crohn disease. J Pediatr Gastroenterol Nutr 2013; 57:335-42. [PMID: 23591911 PMCID: PMC3758389 DOI: 10.1097/mpg.0b013e31829641df] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Recent reports demonstrate a link between inflammatory bowel disease (IBD) and sleep disturbance. Increased psychiatric dysfunction is consistently reported in patients with IBD. Our objective is to examine relations among sleep disturbance, inflammation, and psychiatric dysfunction in a pediatric population with Crohn disease (CD) and depression. METHODS Pediatric patients with CD with depression (n = 96) and healthy controls (n = 19) completed measures of sleep (Pittsburgh Sleep Quality Index [PSQI]), depression, anxiety, and abdominal pain, and provided blood for inflammatory markers. CD activity was determined by the Pediatric Crohn's Disease Activity Index. Factor analysis was performed on subscales of the PSQI to derive measures of sleep disturbance. Univariate and multivariate regression analyses assessed relations between sleep disturbance, psychosocial, and biological measures of CD and psychiatric dysfunction. RESULTS Sleep disturbance in depressed youth with CD was significantly greater than healthy controls, and was significantly related to measures of abdominal pain, depression, and anxiety, but not biomarkers of inflammation. Factor analysis of the PSQI demonstrated a 2-factor solution. The first factor, termed "Qualitative," included Subjective Sleep Quality, Daytime Dysfunction, Sleep Disturbance, and Sleep Latency, whereas the second factor, "Quantitative," consisted of Habitual Sleep Efficiency and Sleep Duration. This factor showed a significant relation to inflammatory markers. Multivariate modeling suggested that qualitative sleep disturbance was predicted by disease activity, pain, and anxiety, whereas quantitative sleep disturbance was predicted by disease activity. CONCLUSIONS These results indicate that sleep disturbance in depressed youth with CD differs depending upon illness activity. Patients may require different interventions depending upon the sleep disturbance exhibited.
Collapse
|
49
|
Mackner LM, Greenley RN, Szigethy E, Herzer M, Deer K, Hommel KA. Psychosocial issues in pediatric inflammatory bowel disease: report of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2013; 56:449-58. [PMID: 23287808 PMCID: PMC3609923 DOI: 10.1097/mpg.0b013e3182841263] [Citation(s) in RCA: 129] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pediatric inflammatory bowel disease (IBD) can affect many areas of psychosocial functioning, and comprehensive medical care includes consideration of psychosocial issues as well as disease factors. The purpose of this clinical report is to review research on psychosocial functioning in pediatric IBD and to provide recommendations for care providers in the areas of psychopathology, health-related quality of life, and social, family, and school functioning. Youth with IBD are at increased risk for difficulty in all areas reviewed, and many psychosocial factors are associated with disease activity, which highlights the importance of monitoring psychosocial functioning as part of clinical care. Several interventions have empirical support or show promise for addressing psychosocial difficulty, and recommendations for monitoring and treating these issues are provided.
Collapse
Affiliation(s)
- Laura M Mackner
- Center for Biobehavioral Health, Nationwide Children's Hospital, Columbus, OH, USA.
| | | | | | | | | | | |
Collapse
|
50
|
Besharat S, Amiriani T, Roshandel G, Besharat M, Semnani S, Kamkar M. Depressive mood and disease activity in inflammatory bowel disease. Arab J Gastroenterol 2012; 13:136-8. [DOI: 10.1016/j.ajg.2012.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Revised: 11/04/2011] [Accepted: 03/11/2012] [Indexed: 02/05/2023]
|