Huang Zongxu’s Experience in Treating Chronic Colitis with Warm-Benefiting Spleen and Kidney

Abstract Diet is believed to be an important factor in the pathogenesis of Inflammatory Bowel Disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high fructose diet (HFrD) in experimental colitis. First, we determined whether the pro-colitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared to pectin, inulin or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.

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B. adolescentis ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling

Gut Microbes ◽

10.1080/19490976.2020.1826746 ◽

2021 ◽

Vol 13 (1) ◽

pp. 1-17

Author(s):

Lina Fan ◽

Yadong Qi ◽

Siwen Qu ◽

Xueqin Chen ◽

Aiqing Li ◽

...

Keyword(s):

Gut Microbiota ◽

Chronic Colitis ◽

Th2 Response

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CADHERIN-11, AN ESSENTIAL REGULATOR OF CELL-CELL ADHESION UPREGULATED IN IBD PATIENTS, PLAYS ESSENTIAL ROLES IN PROMOTING FIBROBLAST ACTIVATION AND DEVELOPMENT OF INTESTINAL INFLAMMATION AND FIBROSIS

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.084 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S34-S35

Author(s):

Jiannan Li ◽

Ilyssa Gordon ◽

Dina Dejanovic ◽

Sinan Lin ◽

Jie Wang ◽

...

Keyword(s):

Weight Loss ◽

Smooth Muscle ◽

Knockout Mice ◽

Clinical Severity ◽

Intestinal Cells ◽

Full Thickness ◽

Chronic Colitis ◽

Expression Levels ◽

Clinical Scores ◽

Human Intestinal Cells

Abstract Background Intestinal fibrosis is a severe complication of inflammatory bowel diseases (IBD) leading to intestinal strictures and need for surgery. No effective anti-fibrotic therapy is available. Cadherin-11 (Cad-11) is an adherens junction protein, which is upregulated in rheumatoid arthritis (RA), idiopathic pulmonary fibrosis (IPF) and skin fibrosis. Inhibition of cadherin-11 has shown beneficial effects in RA and IPF animal models. A phase II clinical trial of cadherin-11 inhibition in RA has shown a good safety profile. Our aim was to evaluate the expression levels and function of Cad-11 in IBD patients using intestinal tissues, primary human intestinal cells, and the murine dextran sulfate sodium (DSS)-induced chronic colitis model. Methods IBD (Crohn’s disease (CD) n=20; Ulcerative colitis (UC) (n=10) and control (n=10) full thickness resected intestinal tissues were procured from adults in accordance with IRB approval. Protein and mRNA were extracted for western blot (WB) and quantitative polymerase chain reaction (qPCR). Distribution of Cad-11 was evaluated by immunofluorescence (IF) and RNA hybridization in frozen and formalin-fixed paraffin-embedded (FFPE) tissue sections, respectively. Primary human intestinal myofibroblasts (HIMF) were used in functional experiments. Recombinant human Fc and Cad-11 extracellular domain (hCAD-11-Fc) was used as activator and siRNA as inhibitor of Cad-11 in HIMF. Murine chronic colitis was induced in wildtype BALB/c mice and cadherin-11 knockout mice by DSS. Anti-Cad-11 monoclonal antibody (H1M1) was used for the treatment of BALB/c mouse colitis. Results Increased gene and protein expression levels of Cad-11 were found in intestinal full thickness IBD tissue compared to controls (45-fold, p<0.01). Cad-11 colocalized with alpha smooth muscle actin (α-SMA) (Figure 1), indicating that Cad-11 is selectively expressed in intestinal myofibroblasts and smooth muscle cells. Among all the primary human intestinal cells, Cad-11 was expressed exclusively in HIMF and HIMC cells. Level of Cad-11 was increased in IBD HIMFs compared to non-IBD controls, and increased upon stimulation with TNF-α, IL-1β, b-FGF and TGF-β (all p<0.01). Knocking down Cad-11 with siRNA decreased FN expression, while hCAD-11-Fc increased the expression FN in a dose- and time-dependent manner as well as the proliferation of HIMF. Upon treatment with H1M1 antibody, DSS-treated mice showed lower clinical scores and weight loss compared to control mice (p<0.001. Figure 2), as well as less FN expression (p<0.001). Cadherin-11 knockout mice also showed lower clinical scores and weight loss compared to wild type mice (p<0.001). Conclusions Cad-11 expression is increased in CD stricture tissues and its blockade reduces profibrotic effects in HIMF in vitro. Inhibition of Cad-11 in vivo reduces clinical severity and fibrosis of experimental colitis.

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Si-Ni-San ameliorates chronic colitis by modulating type I interferons-mediated inflammation

Phytomedicine ◽

10.1016/j.phymed.2021.153495 ◽

2021 ◽

Vol 84 ◽

pp. 153495

Author(s):

Yajie Cai ◽

Bing Xu ◽

Fei Zhou ◽

Jianzhi Wu ◽

Shuo Li ◽

...

Keyword(s):

Type I Interferons ◽

Type I ◽

Chronic Colitis

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Interleukin 7 Transgenic Mice Develop Chronic Colitis with Decreased Interleukin 7 Protein Accumulation in the Colonic Mucosa

Journal of Experimental Medicine ◽

10.1084/jem.187.3.389 ◽

1998 ◽

Vol 187 (3) ◽

pp. 389-402 ◽

Cited By ~ 152

Author(s):

Mamoru Watanabe ◽

Yoshitaka Ueno ◽

Tomoharu Yajima ◽

Susumu Okamoto ◽

Tatsuhiko Hayashi ◽

...

Keyword(s):

T Cells ◽

Epithelial Cells ◽

Transgenic Mice ◽

Chronic Inflammation ◽

Colonic Mucosa ◽

Flow Cytometric Analysis ◽

Receptor Expression ◽

Protein Accumulation ◽

Chronic Colitis ◽

Interleukin 7

We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SRα promoter developed chronic colitis in concert with the expression of SRα/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4–12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell–depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell type 1 CD4+ T cells. Flow cytometric analysis demonstrated that CD4+ intraepithelial T cells were increased, but T cell receptor γ/δ T cells and CD8α/α cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell–derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.

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An Analysis of the Association of Gastroenteric Lesions with Chronic Wasting Syndrome of Marmosets

Veterinary Pathology ◽

10.1177/030098588201907s11 ◽

1982 ◽

Vol 19 (7_suppl) ◽

pp. 141-162 ◽

Cited By ~ 33

Author(s):

L. V. Chalifoux ◽

R. T. Bronson ◽

A. Escajadillo ◽

S. McKenna

Keyword(s):

Lymphoid Hyperplasia ◽

Chronic Colitis ◽

Saguinus Oedipus ◽

Chi Square ◽

Wasting Syndrome ◽

Distinct Disease ◽

Disease Entities ◽

Pathology Data ◽

Increased Susceptibility ◽

Cell Atypia

Retrospective pathology data from necropsies of 162 marmosets, Saguinus oedipus, were studied to determine the nature of chronic wasting syndrome, a poorly defined entity associated with a high mortality rate in many marmoset colonies. Paraffin sections of the gastroenteric organs of 116 of these marmosets were re-examined in detail; lesions were identified, quantitated, and analyzed with a method of multiple chi-square testing for possible associations between findings. Five distinct disease entities were identified: prosthenorchosis, amebiasis, paramyxovirus disease, sepsis, and chronic colitis. Lesions of several of these often occurred in the same monkey, and all but the first were associated with cachexia. Lesions of chronic colitis were crypt abscesses, mononuclear and polymorphonuclear infiltration of the lamina propria, epithelial cell atypia, karyorrhexis, and lymphoid hyperplasia. The cause of chronic colitis was not identified, nor was any explanation found for weight loss and increased susceptibility to disease.

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