Abstract:
BACKGROUND:We analyzed inflamed mucosal/submucosal layers of ulcerative colitis (UC = 63) and Crohn's colitis (CC = 50), and unexpectedly, we unveiled a pool of free hemoglobin alpha (Hb-α) chain. Patients with colitides have increased reactive oxidative stress (ROS), DNA oxidation products, free iron in mucosa, in preneoplastic, and in colitis-cancers and increased risks of developing colorectal cancer. All inflammatory bowel disease-related colorectal cancer lesions are found in segments with colitis. Linking this information, we investigated whether free Hb-α is key transformational stepping that increases colitis-related colorectal cancer vulnerability. METHODS:UC/CC samples were profiled using matrix-assisted laser desorption/ionization mass spectrometry; protein identification was made by liquid chromatography. Diverticulitis was used as control (Ctrl). The presence of Hb(n) (n = α, β, or hemin)/Hb was validated by Western blotting and immunohistochemistry. We tested for DNA damage (DNAD) by exposing normal colonic epithelial cell line, NCM460, to 10 μM and 100 μM of Hb(n)/Hb, individually for 2, 6, and 12 hours. Quantification of Hb-α staining was done by Nikon Elements Advance Research Analysis software. ROS was measured by the production of 8-OHdG. DNAD was assessed by Comet assay. Colonic tissue homogenate antioxidants Nrf2-, CAT-, SOD-, and GPx-expressions were analyzed densitometrically/normalized by β-actin. RESULTS:Immunohistochemistry of CC/UC mucosal/submucosal compartments stained strongly positive for Hb-α and significantly higher versus Ctrl. NCM460 exposed to Hb(n)/Hb exhibited steadily increasing ROS and subsequent DNAD. DNAD was higher in 10 μM than 100 μM in Hb-β/hemin the first 2 hours then plateaued followed by DNAD repair. This may be likely due to apoptosis in the later concentration. Nrf2 enzyme activities among UC, CC, and ulcerative colitis-associated colon cancer (UCAC) were observed impaired in all inflammatory bowel disease subjects. Decreased levels of Nrf2 among patients with UC versus patients with CC with active disease were insignificant as well as versus Ctrls but significantly lower in UCAC versus Ctrl. SOD was decreased in UC and UCAC and GPx in CC but statistically not significant. Comparing CC versus UC, SOD was significantly lower in CC (P < 0.05). CAT was observed increased among patients with CC/UC/UCAC and GPx in UC and UCAC versus Ctrl, respectively, and significantly increased in CC versus Ctrl (P < 0.01). CONCLUSIONS:In the colitides, mucosal/submucosal tissue microenvironments demonstrated pool of free Hb-α chain. In vitro exposure of NCM460 cells to Hb(n)/Hb induced ROS and DNAD. Toxic effect of free Hb-α, in colonic epithelial cells, is therefore through production of ROS formation modulated by impairment of antioxidant effects. Targeting reduction-oxidation-sensitive pathways and transcription factors may offer options for inflammatory bowel disease-management and colitis-related cancer prevention.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Myers JN,Schäffer MW,Korolkova OY,Williams AD,Gangula PR,MʼKoma AEdoi
10.1097/MIB.0000000000000144subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1530-47issue
9eissn
1078-0998issn
1536-4844journal_volume
20pub_type
杂志文章abstract:BACKGROUND:We sought to investigate whether variants in genes involved in bacterial sensing and autophagy (NOD2, TLR5, IRGM, ATG16L1) and the interleukin-23 signaling pathway (IL12B, IL23R, STAT3) were associated with development of antimicrobial antibodies in patients with Crohn's disease (CD). METHODS:A cohort of 61...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.22884
更新日期:2012-09-01 00:00:00
abstract::There is no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic acid. In this review the current practice in 2,4,6-trinitrobenzene sulfonic acid colitis is studied using 20 recently published articles. We compare the different protocols, discuss the mechanism of disease and give recommendat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/01.mib.0000227817.54969.5e
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND:Interleukin (IL)-6/signal transducers and activators of transcription 3 (STAT3) signaling plays an important role in the development of colitis-associated colorectal cancer (CAC). The mechanism of CAC formation remains unclear, and the relationship between miRNAs and the IL-6/STAT3 signaling pathway in the d...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz281
更新日期:2020-03-04 00:00:00
abstract:BACKGROUND:The goal of this study was to determine the rate of work disability, unemployment, and sick leave in an unselected inflammatory bowel disease (IBD) cohort and to measure the effect of working status and disability on the patient's health-related quality of life (HRQOL). MATERIALS AND METHODS:All eligible pa...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000218762.61217.4a
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Acute pancreatitis has occasionally been associated with Crohn's disease (CD), but whether a causal association exists remains unclear. We sought to determine the frequency of etiologies in a consecutive series of patients with CD with acute pancreatitis. METHODS:A centralized diagnostic index was used to i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.mib.0000186485.30623.ad
更新日期:2005-12-01 00:00:00
abstract::The complex and yet unknown etiology of Crohn's disease (CD) might consist of various disease endophenotypes, each of which represent their own pathogenesis. This review focuses on the disease endophenotype linked to polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) protein and on the ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21656
更新日期:2011-11-01 00:00:00
abstract::Tolerance, the regulated inability to respond to a specific immunologic stimulant, is a physiological event important to normal immune function. Just as loss of tolerance to self-proteins results in autoimmune diseases, we assert that loss of tolerance to commensal flora in the intestinal lumen leads to inflammatory b...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200407000-00023
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:The early molecular changes preceding the onset of mucosal inflammation in colitis and their temporal relationship with gut permeability remain poorly defined. This study investigated functional and transcriptomic changes in mdr1a(-/-) mice lacking the intestinal transporter P-glycoprotein, which develop col...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20375
更新日期:2008-05-01 00:00:00
abstract::The conventional treatment of inflammatory bowel disease (IBD) has focused on nonspecifically targeting mucosal inflammation. In the last decade, with the advent of novel biological agents that directly inhibit proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), rapid progress has been made in clin...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21336
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:A common feature of preclinical models of colitis is that the time-course, magnitude, and persistence of inflammation vary considerably within the experimental animal group. Accordingly, noninvasive, serial quantification of colonic inflammation could advantageously guide dosing regimens and assess drug effi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20800
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:The accuracy and utility of electronic health record (EHR)-derived phenotypes in replicating genotype-phenotype relationships have been infrequently examined. Low circulating vitamin D levels are associated with severe outcomes in inflammatory bowel disease (IBD); however, the genetic basis for vitamin D ins...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000524
更新日期:2015-11-01 00:00:00
abstract:Background:Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods:We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izy014
更新日期:2018-03-19 00:00:00
abstract:BACKGROUND:Fistulas are a common complication of Crohn's disease (CD) and are difficult to treat effectively. This study aimed to assess the effects of fistula on annual costs of healthcare and resource utilization for patients with CD. METHODS:A retrospective analysis, using the PharMetrics database, of patients with...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20530
更新日期:2008-12-01 00:00:00
abstract::The role of endoscopy in inflammatory bowel disease (IBD) has grown over the last decade in both diagnostic and therapeutic realms. It aids in the initial diagnosis of the disease and also in the assessment of the extent and severity of disease. IBD is associated with development of multiple complications such as stri...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000626
更新日期:2016-05-01 00:00:00
abstract::Inflammatory bowel diseases are chronic intestinal inflammatory diseases thought to reflect a dysregulated immune response. Although antibody-based inhibition of tumor necrosis factor-α (TNF-α) has provided relief to many inflammatory bowel diseases patients, these therapies are either ineffective in a patient subset ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000442839.28664.75
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND AND AIMS:There is evidence that several inflammatory diseases are associated with increased cardiovascular risk. Whether this is true for inflammatory bowel diseases remains controversial. We aimed to assess this risk, corrected for the effects of conventional vascular risk factors and IBD disease activity. ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa156
更新日期:2020-07-03 00:00:00
abstract:BACKGROUND:Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that significantly impacts the health-related quality of life (HR-QOL). A decreased HR-QOL has been demonstrated in patients with active disease compared with patients in remission. In this cross-sectional study, we e...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e318281f395
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Although infliximab is widely accepted as a therapeutic option for inflammatory bowel disease, its therapeutic efficacy for the treatment of intestinal Behçet's disease (BD) is unknown. We investigated the short-term and long-term response rates to infliximab in intestinal BD and predictive factors of sustai...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0b013e31828f19c9
更新日期:2013-08-01 00:00:00
abstract:Background:Cancer and death are the most severe outcomes that affect patients with inflammatory bowel disease (IBD). These outcomes are even more severe if they occur at a young age but are rare, even in the general population. We conducted a systematic review to provide an overview of all reported pediatric (PIBD) pat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izx104
更新日期:2018-03-19 00:00:00
abstract::Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are poorly understood disorders affecting the intestinal tract. The current model for disease suggests that genetically susceptible patients develop intolerance to gut microflora, and chronic inflammation develops as a result of environmental i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000344
更新日期:2015-06-01 00:00:00
abstract::Inflammatory bowel diseases (IBDs) are highly heterogeneous in disease phenotype, behavior, and response to therapy. Diagnostic and therapeutic decisions in IBD are based primarily on clinical and endoscopic severity and histopathologic analysis of intestinal biopsies. With this approach, however, only a minority of p...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa217
更新日期:2020-09-18 00:00:00
abstract:BACKGROUND:Mesalazine preparations are widely used to treat mild to moderately severe ulcerative colitis (UC). We compared once-daily administration of oral mesalazine in patients with quiescent UC with the established 3-times-daily prescription, assessing the efficacy and safety of each method in maintaining remission...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/MIB.0b013e318286fa3d
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Patients with inflammatory bowel disease (IBD) have identified a need for more information about their disease. PURPOSE:To assess the effect of an educational intervention on health-related quality of life (HRQOL) in patients with IBD. METHODS:Consecutive ambulatory IBD patients were randomized to receive ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00054725-200207000-00005
更新日期:2002-07-01 00:00:00
abstract:BACKGROUND:Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21537
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel disease (IBD) patients are at increased risk of venous thromboembolism (VTE), which is most pronounced during a disease flare. We explored the cost-effectiveness of pharmacological VTE prophylaxis in an outpatient setting. METHODS:Markov decision analysis was conducted from a societal per...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0b013e31829c01ef
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Differentiating ulcerative colitis (UC) from Crohn's colitis (CC) can be difficult and may lead to inaccurate diagnoses in up to 30% of inflammatory bowel disease (IBD) patients. Much of the diagnostic uncertainty arises from the overlap of clinical and histologic features. Matrix-assisted laser desorption/i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21442
更新日期:2011-04-01 00:00:00
abstract::Inflammatory bowel disease (IBD) is a chronic remitting disorder with increasing incidence worldwide. The intestinal epithelial barrier plays a major role in IBD, contributing to its pathogenesis, evolution, and perpetuation over time. Until recently, studies focused on exploring the role of the intestinal epithelium ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1093/ibd/izy275
更新日期:2018-11-29 00:00:00
abstract:BACKGROUND:Mucosal dye spraying (chromoendoscopy [CE]) has been shown in controlled studies to enhance lesion detection in colitis surveillance. Narrow band imaging (NBI) potentially offers a more convenient mode of highlighting mucosal lesions. The primary objectives of this study were to compare CE and NBI in colitis...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e31829637b9
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Toll-like receptor 5 (TLR5) is implicated in the innate and adaptive immune responses that are associated with inflammatory bowel disease (IBD). In humans TLR5 is expressed on CD4(+) T cells and costimulation with flagellin potentiates effector and regulatory T cell responses. The aim of this study was to de...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21738
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The women's health aspect of inflammatory bowel disease (IBD) is a newer area of study; childbearing issues have received little attention despite the fact that IBD affects women predominantly during their childbearing years. The aim of this study was to better understand patients' considerations about pregn...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20082
更新日期:2007-05-01 00:00:00