scholarly journals Administration of Nrf-2-Modified Hair-Follicle MSCs Ameliorates DSS-Induced Ulcerative Colitis in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Lin Zhou ◽  
Fengjuan Yan ◽  
Rui Jiang ◽  
Jing Liu ◽  
Limin Cai ◽  
...  

Ulcerative colitis (UC) is a common chronic nonspecific intestinal inflammation of unknown etiology associated with a low cure rate and a high relapse rate. Hair follicle mesenchymal stem cells (HF-MSCs) are a class of pluripotent stem cells that have differentiation potential and strong proliferation ability. Nuclear factor red system related factor (Nrf-2) is a key factor in the oxidative stress response. Dextran sulfate sodium- (DSS-) induced rat UC models closely mimic human UC in terms of symptoms and histological changes. Animals were divided into five groups, including a healthy group and UC model rats treated with normal saline, Nrf-2, HF-MSCs, or Nrf-2-expressing HF-MSC group. Based on the expression of intestinal stem cells, inflammatory factors, anti-inflammatory factors, and disease activity index scores, Nrf-2-expressing HF-MSCs had the most obvious therapeutic effect under the same treatment regimen. This study provided a new potential clinical treatment option for ulcerative colitis.

2021 ◽  
Vol 12 ◽  
Author(s):  
Linghang Qu ◽  
Xiong Lin ◽  
Chunlian Liu ◽  
Chang Ke ◽  
Zhongshi Zhou ◽  
...  

In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.


Author(s):  
P. Geetha ◽  
B. Lakshman Kumar ◽  
U. Indra ◽  
B. Pavithra Sheetal

Objective: Ulcerative colitis known as inflammatory bowel disease (IBD) of unknown etiology. We examined the antioxidant and myeloperoxidase status in a murine model of 7,12-dimethylbenz[a]anthracene induced colitis to elucidate the exact mechanism behind the inflammation.Methods: Male Wistar rats were exposed to ulcerative colitis using various concentration of DMBA (7,12-Dimethylbenz[A]anthracene) were periodically analysed on 4th, 8th, 12th, 24th and 32nd week from the date of induction. To determine the disease activity index changes in body weight, food consumption, the presence of gross blood in stool and consistency of feces and diarrhea were observed. Macroscopic characters were elucidated based on clinical features of the colon and rectum using scoring pattern. Tissue inflammation status was noted through myeloperoxidase (MPO) assay. The antioxidant status in tissue samples was analysed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total reduced glutathione (GSH).Results: Gavage intubation of DMBA induced colitis showed significant changes from 4th week and severity on 32nd week. The body weight was gradually reduced. Macroscopic scoring showed severe scoring pattern the inflammation was significantly heavier by week 4; and by the end of 32 w, inflammation in rats was double that of the controls, tissue myeloperoxidase (MPO) activity showed the steady increase of neutrophil infiltration and inflammation rate every week. A significant change was noted in tissue antioxidant status and it showed the oxidation level. Statistically, significant change was recorded from 4th week till 32nd week.Conclusion: The conventional biochemical changes in colitis induced animal model revealed the association between the oxidative stress and ulcerative colitis.


2020 ◽  
Author(s):  
Qi-yue Yang ◽  
Ya-nan He ◽  
Le-le Ma ◽  
Run-chun Xu ◽  
Nan Li ◽  
...  

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB,TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.


2018 ◽  
Vol 26 (3) ◽  
pp. 335-343 ◽  
Author(s):  
Danusia Onişor ◽  
Alina Boeriu ◽  
Ofelia Pascarenco ◽  
Olga Brusnic ◽  
Daniela Dobru

Abstract Background: The clinical utility of non-invasive markers in the diagnosis and monitoring of ulcerative colitis (UC) has been intensively studied. The aim of our study was to evaluate the value of fecal calprotectin (FC) in differentiating between UC and irritable bowel syndrome (IBS), and in estimating inflammatory activity in UC. Method: A total number of 140 patients were included in the study. All patients underwent ileocolonoscopy with biopsies, quantitative determination of FC, and blood tests (white blood cell count, CRP, ESR). The severity of UC was assessed by using the Ulcerative Colitis Disease Activity Index (UCDAI) and Mayo endoscopic score. Results: In patients with active UC the mean values of FC were 373.8 +/- 146.3 μg/g, significantly higher than those in the inactive UC (mean values 36.04 +/- 13.25 μg/g), and in IBS (42.9 +/- 16.00 μg/g). In univariate regression analysis, elevated FC levels strongly correlated with pancolitis (p=0.0001), UCDAI and Mayo scores (p=0.0001), and elevated CRP levels. In multivariate regression model, FC was positively associated with severe pancolitis, and elevated CRP. The optimal cutoff value of FC for the prediction of severe pancolitis (Mayo score˃ 3) was 540 μg/g. We obtained 71.4% sensitivity (CI95%: 41.95-91.6) and 96.1% specificity (CI95%: 89.2 -99.2) of FC in assessing the severity of inflammation in UC patients. Conclusion: FC is a promising marker that can be used in clinical practice to select patients with organic intestinal disorders, compared with those with functional disorders. It also correlates very well with the extent of lesions and the severity of clinical symptoms in UC, with increased sensitivity and specificity.


2020 ◽  
Vol 52 (6) ◽  
pp. 675-682
Author(s):  
Guangmeng Xu ◽  
Yajuan Sun ◽  
Huaiqiang He ◽  
Qiuli Xue ◽  
Yajie Liu ◽  
...  

Abstract In this study, we aimed to explore the effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis. The mouse model of ulcerative colitis was established by medication, and 40 SPF C57BL/6J mice (8 weeks old) were randomly divided into normal group (healthy mice, n = 10), control group (sham-operated mice, n = 10), model group (model mice without any treatment, n = 10), and K252a group (model mice treated with 100 μmol/kg TrkB-PLC/IP3 pathway inhibitor for 5 days before clysis, n = 10). The results showed that mice in the model and K252a groups, as compared with normal and control groups, had no significant changes in the levels and protein expressions of serum tumor necrosis factor-α (TNF-α) and TNF-γ in the colon tissues (P>0.05), and had a significant increase in disease activity index, colon mucosa damage index, tissue damage index scores, and levels and protein expressions of serum interleukin-4 (IL-4) and IL-8, but had a significant decrease in the level and protein expression of serum IL-10 (P<0.05). Mice in the model and K252a groups showed blocked enterocyte cycle progression, elevated apoptosis ratio, and significantly increased mRNA and protein expressions of Caspase3, Bax, FasL, and Fas, but significantly reduced mRNA and protein expressions of p-TrkB, PLC-γ1, IP3, and Bcl-2 (P<0.05). Moreover, intestinal inflammation and apoptosis induced by colitis in the K252a group became more aggravated by inhibiting the activity of TrkB-PLC/IP3 pathway. In conclusion, inhibition of TrkB-PLC/IP3 pathway can increase the expression of intestinal inflammatory factors and promote enterocyte apoptosis in mice with colitis.


2021 ◽  
Vol 11 (8) ◽  
pp. 1339-1346
Author(s):  
Wenjing Yang ◽  
Zhe Wang ◽  
Yao Wang ◽  
Fei Mao ◽  
Chen Chen ◽  
...  

The experiments in this paper was to investigate the effect of ectomesenchymal stem cells-conditional medium (EMSCs-CM) in DSS-induced ulcerative colitis (UC) which is expected to provide a therapeutic treatment for DSS-induced UC. Herein, EMSCs were isolated from the nasal cavity of mice and its supernatants without FBS were collected as conditioned medium for EMSCs (EMCSs-CM). The concentrated EMCSs-CM was further prepared by dissolving freeze-dried CM with PBS. Depending on different treatments, C57 mice was classified into normal group, DSS model group and EMSCs-C group. To build model mice, DSS at 3% concentration was accepted. The effects of intervention were assessed on the basis of body weight changes, disease activity index (DAI) score, colon length, pathological variations and colitis biomarkers. Results revealed that EMSCs-CM could express TGF-β, SHH and Laminin in vitro, respectively and significantly reduce the disease activity index and alleviate the severity of mice in vivo. a low level of inflammatory cytokine expression was also monitored in the EMSCs-CM group. In conclusion, EMSCs-CM is conducive to improve the DSS-induced UC, owing to multiple factors secreted by EMSCs.


1990 ◽  
Vol 4 (7) ◽  
pp. 468-471 ◽  
Author(s):  
MG Robinson ◽  
DL Decktor

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1684 ◽  
Author(s):  
Larissa Celiberto ◽  
Roseli Pinto ◽  
Elizeu Rossi ◽  
Bruce Vallance ◽  
Daniela Cavallini

Modulation of the gut microbiota through the use of probiotics has been widely used to treat or prevent several intestinal diseases. However, inconsistent results have compromised the efficacy of this approach, especially in severe conditions such as inflammatory bowel disease (IBD). The purpose of our study was to develop a personalized probiotic strategy and assess its efficacy in a murine model of intestinal inflammation. Commensal bacterial strains were isolated from the feces of healthy mice and then administered back to the host as a personalized treatment in dextran sodium sulfate (DSS)-induced colitis. Colonic tissues were collected for histological analysis and to investigate inflammatory markers such as Il-1β, Il-6, TGF-β, and Il-10, and the enzyme myeloperoxidase as a neutrophil marker. The group that received the personalized probiotic showed reduced susceptibility to DSS-colitis as compared to a commercial probiotic. This protection was characterized by a lower disease activity index and reduced histopathological damage in the colon. Moreover, the personalized probiotic was more effective in modulating the host immune response, leading to decreased Il-1β and Il-6 and increased TGF-β and Il-10 expression. In conclusion, our study suggests that personalized probiotics may possess an advantage over commercial probiotics in treating dysbiotic-related conditions, possibly because they are derived directly from the host’s own microbiota.


2018 ◽  
Vol 154 (6) ◽  
pp. S-587-S-588
Author(s):  
Steven Bots ◽  
Kim Nylund ◽  
Mark Löwenberg ◽  
Krisztina Gecse ◽  
Odd Helge Gilja ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mansoor Karimifar ◽  
Khosro Akbari ◽  
Reza ArefNezhad ◽  
Farshid Fathi ◽  
Mohammad Moosaeepour ◽  
...  

Abstract Objective Systemic lupus erythematous (SLE) disease is a chronic autoimmune disease with unknown etiology that can involve different organs. Polymorphisms in Fcγ receptors have been identified as genetic factors in susceptibility to SLE. This study was aimed to investigate effects of two single nucleotide polymorphisms (SNPs) within FcγRIIB and FcγRIIIA genes on systemic lupus erythematous disease activity index (SLEDAI) in an Iranian population. Results Our findings indicated TT and GG genotypes were the common genotypes of FcγRIIB and FcγRIIIA SNPs in SLE patients, respectively. There were no significant differences in genotype and allele frequencies of FcγRIIB and FcγRIIIA SNPs in SLE and healthy subjects. However, the frequencies of genotypes and alleles of FcγRIIB and FcγRIIIA SNPs were significantly associated with some clinical manifestations used to determine SLEDAI (P < 0.001–0.5).


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