scholarly journals Wei Chang an Pill Alleviates TNBS-induced Ulcerative Colitis Through Inhibition of EMTProcess

2021 ◽  
Author(s):  
Yaxin Qi ◽  
Lijuan Chai ◽  
Min Zhang ◽  
Sitong Jia ◽  
Lin Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Body Weight ◽  
Epithelial Mesenchymal Transition ◽  
Activity Index ◽  
Pharmaceutical Preparation ◽  
Damage Index ◽  
The Body ◽  
Active Ingredients ◽  
Mesenchymal Transition ◽  
Anti Inflammatory

Abstract Background: Wei Chang An pill (WCA) is a traditional Chinese pharmaceutical preparation which has been widely used to treat various gastrointestinal diseases including Ulcerative colitis (UC). The aim of our study was investigate the inhibitory effect and mechanism of WCA in the treatment of 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC in rats.Methods: We established the TNBS-induced UC model and then WCA was administrated orally for one week. Body weight, colon lengths, Disease Activity Index (DAI) score and Colon Mucosa Damage Index (CMDI) score were recorded. The expression of cytokines factors in LPS-stimulated THP-1 cells was recorded to evaluate the anti-inflammatory effects of WCA and its herb active ingredients. Immunohistochemistry and immunofluorescence were used to evaluate the Epithelial-Mesenchymal Transition (EMT) process in UC rats and Caco-2 cells which were induced by LPS-stimulated THP-1 cells uponWCA treatment.Results: WCA significantly decreased the body weight loss, higher DAI and CMDI score, colon length shortening and histological damage in UC rats. Furthermore, both of the activities of myeloperoxidase dismutase (MPO) and the mRNA expressions of cytokine in UC tissues were significantly inhibited. In THP-1 cells, the mRNA expressions of IP-10, TNF-α, IL-6 and IkBα were significantly suppressed by WCA or its active ingredients. In UC rats and Caco-2 cells, both of their EMT process were strongly suppressed by WCA.Conclusion: These results show that through improving inflammatory microenvironment to inhibit the EMT process, WCA retarded the development of UC in rats to play its anti-inflammatory effect.

scholarly journals ROLE OF ANTIOXIDANT AND MYELOPEROXIDASE LEVELS IN 7, 12-DIMETHYLBENZ [A] ANTHRACENE INDUCED EXPERIMENTAL RAT MODEL: EVIDENCE FOR OXIDATIVE DAMAGE IN ACTIVE ULCERATIVE COLITIS.

2017 ◽  
Vol 9 (3) ◽  
pp. 282
Author(s):  
P. Geetha ◽  
B. Lakshman Kumar ◽  
U. Indra ◽  
B. Pavithra Sheetal
Keyword(s):  
Ulcerative Colitis ◽  
Body Weight ◽  
Antioxidant Status ◽  
Activity Index ◽  
Disease Activity Index ◽  
The Body ◽  
Unknown Etiology ◽  
Steady Increase ◽  
Tissue Samples ◽  
Significant Change

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.

scholarly journals Galectin-1 reduces the severity of ulcerative colitis induced by dextran sulfate sodium via suppressing inflammatory and oxidative mediators

2020 ◽  
Author(s):  
Pelin Arda-Pirincci ◽  
Guliz Aykol-Celik
Keyword(s):  
Ulcerative Colitis ◽  
Cell Proliferation ◽  
Body Weight ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Proliferation Index ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory

Ulcerative colitis is an inflammatory bowel disease and many people suffers from this disease across the word. Dextran sulfate sodium (DSS) is a synthetic sulfated polysaccharide that is used to produce ulcerative colitis in rodents. Galectin-1 is a β-galactoside binding animal lectin which plays key roles in many biological events. In this study, we investigated the role of galectin-1 on colon morphology, cell proliferation, oxidative stress, anti-oxidant system, inflammatory and anti-inflammatory mediators in the model of experimental ulcerative colitis induced by DSS in mice. C57BL/6  mice were fed orally 3% DSS in their drinking water for 5 days for acute colitis induction. Animals were injected with 1 mg/kg recombinant human galectin-1 for 7 consecutive days. Oral DSS application resulted in colitis injury by causing histopathological changes; an increase in disease activity index (DAI), lipid peroxidation (MDA), myeloperoxidase (MPO) and TNF-α levels; a decrease in body weight, colon length, cell proliferation index, catalase (CAT), glutahione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, gluathione (GSH) and IL-10 levels. However, treatment with galectin-1 prevented DSS-induced colitis injury through the reduction of DAI, MDA, MPO and TNF-α levels, and the increase of body weight, colon length, cell proliferation, antioxidant enzymes activities, GSH and IL-10 levels. As a result, this study showed that galectin-1 has proliferative, anti-oxidant, anti-inflammatory, and cytoprotective effects against DSS-induced colitis in mice. In addition, galectin-1 reduces the severity of ulcerative colitis via suppressing inflammatory and oxidative mediators.

scholarly journals Interference With the AMPKα/mTOR/NLRP3 Signaling and the IL-23/IL-17 Axis Effectively Protects Against the Dextran Sulfate Sodium Intoxication in Rats: A New Paradigm in Empagliflozin and Metformin Reprofiling for the Management of Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmoud Youssef ◽  
Eslam Abd El-Fattah ◽  
Amir Abdelhamid ◽  
Hanan Eissa ◽  
Eman El-Ahwany ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cell ◽  
Activity Index ◽  
Damage Index ◽  
Cell Polarization ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Ampk Phosphorylation ◽  
T Cell Polarization ◽  
Anti Inflammatory

Empagliflozin and metformin are widely used for the treatment of type 2 diabetes. These drugs showed marked anti-inflammatory effects in different animal models via enhancing AMPK activity. Yet, the protective anti-inflammatory effects of their combination against ulcerative colitis have not been previously investigated. The current study aimed to explore the potential of empagliflozin/metformin combination to mitigate the DSS-induced rat colitis model. The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated. In this study, distal colons were examined for macroscopic and microscopic pathological alterations. ELISA, qRT-PCR, and immunohistochemistry techniques were applied to detect proteins and cytokines involved in AMPK/mTOR/NLRP3 axis and T Cell polarization. Oral administration of empagliflozin (10 mg/kg/day) and metformin (200 mg/kg/day) combination alleviated colitis as revealed by the reduced disease activity index, macroscopic damage index, colon weight/length ratio, and histopathologic scoring values. Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Reduced mTOR expression and reduced IL-6 levels led to a reduction in Th17 cell polarization and maintenance. Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated via enhancing AMPK phosphorylation. Since adult humans with diabetes mellitus are at greater risk for developing inflammatory bowel diseases, clinical application of empagliflozin/metformin combination represents a novel therapeutic approach for treating diabetic patients with ulcerative colitis.

scholarly journals Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β

2018 ◽  
Vol 19 (11) ◽  
pp. 3672 ◽  
Author(s):  
Yutaro Tsubakihara ◽  
Aristidis Moustakas
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Basement Membranes ◽  
The Body ◽  
Common Denominator ◽  
Adhesion Forces ◽  
Mesenchymal Transition

Metastasis of tumor cells from primary sites of malignancy to neighboring stromal tissue or distant localities entails in several instances, but not in every case, the epithelial-mesenchymal transition (EMT). EMT weakens the strong adhesion forces between differentiated epithelial cells so that carcinoma cells can achieve solitary or collective motility, which makes the EMT an intuitive mechanism for the initiation of tumor metastasis. EMT initiates after primary oncogenic events lead to secondary secretion of cytokines. The interaction between tumor-secreted cytokines and oncogenic stimuli facilitates EMT progression. A classic case of this mechanism is the cooperation between oncogenic Ras and the transforming growth factor β (TGFβ). The power of TGFβ to mediate EMT during metastasis depends on versatile signaling crosstalk and on the regulation of successive waves of expression of many other cytokines and the progressive remodeling of the extracellular matrix that facilitates motility through basement membranes. Since metastasis involves many organs in the body, whereas EMT affects carcinoma cell differentiation locally, it has frequently been debated whether EMT truly contributes to metastasis. Despite controversies, studies of circulating tumor cells, studies of acquired chemoresistance by metastatic cells, and several (but not all) metastatic animal models, support a link between EMT and metastasis, with TGFβ, often being a common denominator in this link. This article aims at discussing mechanistic cases where TGFβ signaling and EMT facilitate tumor cell dissemination.

scholarly journals A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

2018 ◽  
Vol 19 (12) ◽  
pp. 3968 ◽  
Author(s):  
Enrico Spugnini ◽  
Mariantonia Logozzi ◽  
Rossella Di Raimo ◽  
Davide Mizzoni ◽  
Stefano Fais
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
The Body ◽  
Mesenchymal Transition ◽  
Metastatic Cascade ◽  
Target Organs

Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial–mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches” in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors.

scholarly journals Dietary Fiber's Effect on High Sensitivity C-reactive Protein Serum in Sedentary Workers

2021 ◽  
Vol 5 (1) ◽  
pp. 40
Author(s):  
Livia Kurniati Saputra ◽  
Dian Novita Chandra ◽  
Ninik Mudjihartini
Keyword(s):  
Body Weight ◽  
High Sensitivity ◽  
The Body ◽  
Low Grade ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Dietary Fiber Intake ◽  
Anti Inflammatory ◽  
Low Grade Inflammation ◽  
Inflammatory Effect

Low grade inflammation has been recognized of being involved in the pathogenesis of chronic disease pandemic. Individual lifestyle plays a major role in the development of low grade inflammation. Sedentary workers are at risk of low grade inflammation due to the nature of their work. Dietary habit also contributes to inflammatory status in the body. Dietary fiber intake indirectly affects the immune system. It has been hypothesized that fiber has anti-inflammatory effects, both body weight-related and body weight-unrelated This review will focus more on body weight-unrelated anti-inflammatory effect of fiber, especially through fiber’s fermentation metabolites, the short chain fatty acid (SCFA). Its anti-inflammatory effect can be seen by monitoring a biomarker of inflammation in the body, the high sensitivity C-reactive protein (hsCRP). This review’s objective is to cover the mechanisms and role of dietary fiber intake on serum hsCRP level as a marker of low grade inflammation on sedentary workers. 

scholarly journals Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

2018 ◽  
Vol 27 (9) ◽  
pp. 1352-1367 ◽  
Author(s):  
Fu Yuan Yang ◽  
Rui Chen ◽  
Xiaohu Zhang ◽  
Biao Huang ◽  
Lai Ling Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Therapeutic Effect ◽  
T Cell Activation ◽  
Activity Index ◽  
Intraperitoneal Administration ◽  
The Body ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

scholarly journals Jiaweishaoyao Decoction Alleviates DSS-Induced Ulcerative Colitis via Inhibiting Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Huixia Qiao ◽  
Yahui Huang ◽  
Xiaoyan Chen ◽  
Long Yang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Body Weight ◽  
Nlrp3 Inflammasome ◽  
Activity Index ◽  
Raw264.7 Cells ◽  
Spleen Weight ◽  
Associated Proteins ◽  
Histopathological Score

Purpose. Jiaweishaoyao decoction (JWSYD) is a traditional prescription of Chinese medicine that is initially used for the treatment of diarrhea. This study is aimed at investigating the effects of JWSYD on DSS-induced ulcerative colitis (UC). Methods. DSS-induced UC mice and LPS-induced RAW264.7 cells were used as the UC model in vivo and in vitro. UC was assessed by body weight, disease activity index (DAI), colon length, spleen weight, and histopathological score (HE staining). The levels of TNF-α, IL-1β, and IL-6 were analyzed by ELISA and qRT-PCR. The levels of NLRP3 inflammasome- and NF-κB pathway-associated proteins were measured by western blot. Results. JWSYD alleviated DSS-induced UC in respect to body weight, DAI, colon length, spleen weight, and histopathological score. JWSYD reduced the levels of TNF-α, IL-1β, and IL-6 in DSS-induced UC mice and the supernatants of LPS-induced RAW264.7 cells. JWSYD suppressed the protein levels of inflammasome-associated proteins, including NLRP3, ASC1, Procaspase-1, Cleaved caspase-1, and Cleaved IL-1β in DSS-induced UC mice and LPS-induced RAW264.7 cells. In addition, JWSYD suppressed the NF-κB pathway in vitro and in vivo. Conclusion. JWSYD alleviated DSS-induced UC via inhibiting the NLRP3 inflammasome and NF-κB pathway.

scholarly journals The association between inflammatory potential of diet and disease activity: results from a cross-sectional study in patients with inflammatory bowel disease

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Carlijn R. Lamers ◽  
Nicole M. de Roos ◽  
Ben J. M. Witteman
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Statistical Significance ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Abstract Background Diet may play a role in disease status in patients with inflammatory bowel disease. We tested whether the inflammatory potential of diet, based on a summation of pro- and anti-inflammatory nutrients, is associated with disease activity in patients with Crohn’s disease and ulcerative colitis. Methods Participants completed a disease activity questionnaire (short Crohn’s Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI)) and a Food Frequency Questionnaire (FFQ). FFQ data were used to calculate the Dietary Inflammatory Index (DII) which enables categorization of individuals’ diets according to their inflammatory potential on a continuum from pro- to anti-inflammatory. Associations with disease activity were investigated by multiple linear regression. Results The analysis included 329 participants; 168 with Crohn’s disease (median sCDAI score 93 [IQR 47–156]), and 161 with ulcerative colitis (median P-SCCAI score 1 [IQR 1–3]). Mean DII was 0.71 ± 1.33, suggesting a slightly pro-inflammatory diet. In Crohn’s disease, the DII was positively associated with disease activity, even after adjustment for confounders (p = 0.008). The mean DII was significantly different between participants in remission and with mild and moderately active disease (0.64, 0.97 and 1.52 respectively, p = 0.027). In ulcerative colitis, the association was not significant. Conclusions Disease activity was higher in IBD participants with a more pro-inflammatory diet with statistical significance in Crohn’s disease. Although the direction of causality is not clear, this association strengthens the role for diet in medical treatment, which should be tested in an intervention study.

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