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Journal, IO Biomarker: Interleukin-33 delays recovery of mucosal inflammation via downregulation of homeostatic ABCG5/8 in the colon. (Pubmed Central) - Sep 27, 2020
Il33 mice were more tolerant to dextran sulfate sodium-induced acute colitis than the wild type and also showed delayed recovery from colitis with recombinant IL-33 (rIL-33) administration...Together, these results indicated that colonic ABCG5/8 play a regulatory role in TLR-induced inflammation, while histological inflammation in human UC was correlated positively with the level of mucosal IL-33 and inversely with that of colonic ABCG5/8. This is the first report of IL-33-mediated downregulation of colonic ABCG5/8 in a colitis recovery phase, indicating their involvement in UC pathogenesis and potential as a therapeutic target.
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Journal: Modulation of lymphocyte-mediated tissue repair by rational design of heterocyclic aryl hydrocarbon receptor agonists. (Pubmed Central) - Sep 27, 2020
In a murine model of dextran sulfate sodium-induced colitis, orally administered compounds increase interleukin-22 (IL-22) production and accelerate mucosal healing by modulating mucosal adaptive and innate lymphoid cells...Significant induction of IL-22 was also observed using human T cells from patients with IBD. Our findings support rationally designed AHR agonists for IBD therapy.
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Preclinical, Journal: Glutamine relieves oxidative stress through PI3K/Akt signaling pathway in DSS-induced ulcerative colitis mice. (Pubmed Central) - Sep 25, 2020
The mice in the experimental group drank 4% dextran sulfate sodium salt (DSS) for 7 consecutive days...Administration of Gln to the DSS-induced colitis mice led to a clearly reduction in oxidative stress-induced injury. The Gln is confirmed as inhibiting the PI3K/Akt signaling pathway activity.
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Preclinical, Journal: Enterotoxigenic Bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model. (Pubmed Central) - Sep 21, 2020
The azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model is commonly used to study colitis-associated cancer...In conclusion, WT-ETBF promoted polyp development in AOM/DSS murine model with increased colitis in BALB/c mice. The model described herein provides an experimental platform for understanding ETBF-induced colonic tumorigenesis and studying colorectal cancer in wild-type mice.
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Preclinical, Journal: Therapeutic effect of cinnamaldehyde on ulcerative colitis in mice induced by dextran sulfate sodium with Candida albicans colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway (Pubmed Central) - Sep 20, 2020
The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and β-1,3-glucan in serum, reduce the contents of TNF-α, IL-1β, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.
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Preclinical, Journal: Exercise Preconditioning Attenuates the Response to Experimental Colitis and Modifies Composition of Gut Microbiota in Wild-Type Mice. (Pubmed Central) - Sep 20, 2020
This study investigated the suppressive effect of exercise preconditioning against colitis induced by high-fat diet (HF) plus dextran sulfate sodium (DSS) in wild-type mice...Exercise preconditioning alleviated HF+DSS-induced colitis and caused significant modifications in gut microbiota: decreased Bacteroides vulgatus (p = 0.050) and increased Akkermansia muciniphila (p = 0.050). The current findings suggest that exercise preconditioning attenuates the severity of HF+DSS-induced colitis in C57BL/6 mice.
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Journal: Cadmium exacerbates dextran sulfate sodium-induced chronic colitis and impairs intestinal barrier. (Pubmed Central) - Sep 18, 2020
In conclusion, long-term exposure of environmental dose of cadmium aggravated DSS-induced chronic colitis and disrupted intestinal barrier and impaired the adherent and tight junction proteins. These findings provide a better understanding about the health risk of cadmium in the environment.
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Preclinical, Journal: Oleoylethanolamide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats. (Pubmed Central) - Sep 16, 2020
Administration of OEA produced significant improvement in a colitis model, possibly by inhibiting the nuclear factor kappa B signaling pathway through PPAR-α receptors. OEA could be a potential new treatment for IBD.
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Journal, IO Biomarker: IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils. (Pubmed Central) - Sep 16, 2020
Our findings also emphasize the potential use of IL-33 as an adjuvants in CRC immunotherapy. AOM: azoxymethane; bmRPMI: bone marrow RPMI; CRC: colorectal cancer; CFSE: carboxyfluorescein succinimidyl ester; DSS: dextran sulfate sodium; EPX: eosinophil peroxidase; INF-γ: interferon gamma; ILC: innate lymphoid cell; IL-33: interleukin-33; IL-5: interleukin-5; MDSC: myeloid derived suppressor cells; NK cells: natural killer cells; P/S: penicillin/streptomycin; rm: recombinant mouse; T regs: regulatory T cells; TATE: tumor associated tissue eosinophilia; TNF-α: tumor necrosis factor alpha.
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Journal: Dietary Ziziphus jujuba Fruit Attenuates Colitis-Associated Tumorigenesis: A Pivotal Role of the NF-κB/IL-6/JAK1/STAT3 Pathway. (Pubmed Central) - Sep 13, 2020
Mice (n = 42, two sets) were injected with azoxymethane (AOM) followed by three cycles of 2% (w/v) dextran sulfate sodium (DSS) in drinking water to induce CAC...In addition, dietary ZJ increased colon length (P < 0.001) and suppressed the activation of NF-кB/IL-6/JAK1/STAT3 signaling pathway. In conclusion, we suggest that dietary ZJ attenuates inflammation by interfering NF-κB/IL-6/JAK1/STAT3 signaling pathway, thereby inhibits AOM/DSS-induced colon tumorigenesis in mice.
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Journal, IO Biomarker: Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation. (Pubmed Central) - Sep 13, 2020
Last, we show that treatment with dexamethasone potently inhibits CCM formation in mice because of the combined effect of action at both brain endothelial cells and gut epithelial cells. These studies define a gut-brain disease axis in an experimental model of CCM in which a single gene is required for two critical components: gut epithelial function and brain endothelial signaling.
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Preclinical, Journal: Synbiotic Combination of Djulis (Chenopodium formosanum) and Lactobacillus acidophilus Inhibits Colon Carcinogenesis in Rats. (Pubmed Central) - Sep 10, 2020
This study examined the preventive effect of djulis alone or in combination with Lactobacillus acidophilus on colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS)...D, DLA, and DHA significantly reduced the numbers of total ACF, sialomucin-producing ACF (SIM-ACF), and mucin-depleted foci (MDF) in the distal colon compared to C. Additionally, DLA and DHA further downregulated the expressions of proliferating cell nuclear antigen (PCNA) and cyclooxygenase-2 (COX-2) and regulated apoptosis-related proteins. These results suggest that synbiotic combination of djulis and L. acidophilus shows the best inhibitory effect on colon carcinogenesis via regulation of proliferative, inflammatory, and apoptotic pathways.
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Preclinical, Journal, IO Biomarker: Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice. (Pubmed Central) - Sep 10, 2020
The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract...Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.
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Journal: TRPA1-expressing lamina propria mesenchymal cells regulate colonic motility. (Pubmed Central) - Sep 9, 2020
Abnormal colorectal contractions were significantly prevented by pharmacological and genetic inhibition of TRPA1. In conclusion, in the lower gastrointestinal tract, mesenchymal TRPA1 activation results in PGE2 release and consequently promotes colorectal contraction, representing what we believe is a novel physiological and inflammatory bowel disease-associated mechanism of gastrointestinal motility.
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Preclinical, Journal: Attenuation of NF-κB in intestinal epithelial cells is sufficient to mitigate the bone loss co-morbidity of experimental mouse colitis. (Pubmed Central) - Sep 5, 2020
We first demonstrate that serum as well as IECs collected from the intestine of dextran sulfate sodium (DSS)-induced colitis mice contain high levels of inflammatory and osteoclastogenic cytokines...Finally, using the DSS-induced colitis model, pharmacologic inhibition of IKK2 was effective in reducing frequency of ILC1 and ILC3 cells, attenuated circulating levels of inflammatory cytokines and halted colitis-associated bone loss. Our findings identify IKK2 in IECs as viable therapeutic target for colitis-associated osteopenia.
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Biomarker, Clinical, Journal: The diagnostic efficacy of circulating miRNAs in monitoring the early development of colitis-induced colorectal cancer: The accuracy of circulating microRNAs as noninvasive biomarkers using a stepwise carcinogenesis mouse model. (Pubmed Central) - Sep 5, 2020
This was accomplished through assessing the expression levels of five miRNAs (miR-141, miR-15b, miR-17-3p, miR-21, and miR-29a) in serum and their corresponding tissue samples through the different cycles of colorectal carcinogenesis cascade using the azoxymethane/dextran sulfate sodium murine model...Our data also revealed that serum miR-15b, miR-21, and miR-29a showed the best performance in terms of diagnostic power. Our findings highlight the efficiency of these circulating miRNAs not only for early diagnostics purposes, but also for monitoring progress in the colorectal carcinogenesis process, and therefore encouraging integrating these noninvasive biomarkers into the clinical diagnostic settings beside the traditional diagnostic markers for accurate screening of the early progress of colon carcinogenesis.
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Journal: Protective Effects of Polysaccharide Extracted from Portulacae oleracea L. on Colitis Induced by Dextran Sulfate Sodium. (Pubmed Central) - Sep 2, 2020
The results showed that these two protein levels were all increased in colitis and decreased after POLP treatment, indicating that these two proteins were closely related with the protective effect of POLP. Because the synthesis of PGE is catalyzed by COX-2 and phosphorylation of STAT3 can induce the expression of COX-2, it was concluded that STAT3 was a key protein related to the POLP exerting its activity in colitis.
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Preclinical, Journal: Phosphodiesterase-4 inhibition attenuates murine ulcerative colitis via interfering with mucosal immunity. (Pubmed Central) - Sep 2, 2020
Because the synthesis of PGE is catalyzed by COX-2 and phosphorylation of STAT3 can induce the expression of COX-2, it was concluded that STAT3 was a key protein related to the POLP exerting its activity in colitis. PDE4 inhibition by apremilast exerted protective effects in UC via interfering with mucosal immunity, which represented a promising strategy for regulating intestinal inflammation.
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Journal: ABIN1 alleviates inflammatory responses and colitis via facilitating A20 activity. (Pubmed Central) - Aug 28, 2020
Dextran sulfate sodium (DSS)-induced colitis was established to determine the effects of ABIN1 on the survival time, body weight, colon length, and colon histopathological changes...The underlying mechanisms revealed that ABIN1 impaired macrophages-mediated inflammatory responses, in part by regulating the NF-κB signal pathway, and its ameliorated effects on the symptoms of DSS-induced colitis were associated with A20/tumor necrosis factor α-induced protein 3 (TNFAIP3). ABIN1 attenuated inflammatory responses and colitis by regulating A20/TNFAIP3 activities.
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Preclinical, Journal, IO Biomarker: Anti-Inflammatory and Chemopreventive Effects of Bryophyllum pinnatum (Lamarck) Leaf Extract in Experimental Colitis Models in Rodents. (Pubmed Central) - Aug 28, 2020
We hypothesized that hydroethanolic B. pinnatum leaf extract has intestinal anti-inflammatory effects on two experimental colitis models: 2.4-dinitrobenzene sulfonic acid (DNBS) in rats, and dextran sulfate sodium (DSS) in mice...Moreover, the extract improved the cytoarchitecture of the colonic tissue and the integrity of the intestinal epithelial barrier by restoring the expression of the proteins associated with mucosa protection. In view of the beneficial effects showed by the B. pinnatum leaf extract in preclinical rodent models of colitis there is the potential to conduct some future clinical studies to ensure safe and effective development of a phytotherapeutic treatment for human inflammatory bowel diseases.
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Journal, IO Biomarker: Kuijieyuan Decoction Improved Intestinal Barrier Injury of Ulcerative Colitis by Affecting TLR4-Dependent PI3K/AKT/NF-κB Oxidative and Inflammatory Signaling and Gut Microbiota. (Pubmed Central) - Aug 28, 2020
Forty-eight rats were divided into 6 groups, health control (CG), UC model (UG), sulfasalazine (SG), low-dose KD (LG), middle-dose KD (MG), and high-dose KD (HG) groups...The main components of KD consist of gallic acid, paeoniflorin, emodin, berberine, coptisine, palmatine, jatrorrhizine, baicalein and baicalin...KD treatment increased the proportion of Alloprevotella, Treponema, Prevotellaceae, and Prevotella, and reduced the proportion of Escherichia_Shigella and Desulfovibrio in gut microbiota. KD improved intestinal barrier injury of ulcerative colitis, antioxidant and anti-inflammatory properties by affecting TLR4-dependent PI3K/AKT/NF-κB signaling possibly through the combination of its main compounds, and improving gut microbiota.
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Preclinical, Journal: Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. (Pubmed Central) - Aug 27, 2020
Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.
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Journal: Pristimerin suppresses colorectal cancer through inhibiting inflammatory responses and Wnt/β-catenin signaling. (Pubmed Central) - Aug 27, 2020
Here, we found that pristimerin protected mice from dextran sulfate sodium (DSS)-induced colitis, restoring epithelial damage and reducing tissue inflammation and inflammatory cell infiltration...In HCT116 colon cancer xenografts and APC mice, which undergo spontaneous intestinal tumorigenesis, administration of pristimerin reduced the tumor progression and decreased the expression of phosphorylated GSK3β Ser 9, β-catenin, cyclin D1 and c-Myc. These results suggest that pristimerin is a potent agent for preventing colon inflammation and carcinogenesis.
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Preclinical, Journal: Intestinal fungi are causally implicated in microbiome assembly and immune development in mice. (Pubmed Central) - Aug 27, 2020
Ovalbumin-induced airway inflammation reveals that bacterial, but not fungal colonization is necessary to decrease airway inflammation, yet fungi selectively promotes macrophage infiltration in the airway. Together, our findings demonstrate a causal role for fungi in microbial ecology and host immune functionality, and therefore prompt the inclusion of fungi in therapeutic approaches aimed at modulating early life microbiomes.
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Preclinical, Journal: Hydroalcoholic extract of Tagetes erecta L. flowers, rich in the carotenoid lutein, attenuates inflammatory cytokine secretion and improves the oxidative stress in an animal model of ulcerative colitis. (Pubmed Central) - Aug 23, 2020
Experimental UC was established by adding 5% dextran sulfate sodium (DSS) to drinking water, with the effects of DHETE (30-300 mg/kg, once a day for 7 days) on the morphological (colon length and weight), clinical (disease activity index and body weight loss), microscopic (histological score and mucin levels), and biochemical parameters analyzed...The extract also increased reduced glutathione levels and catalase activity and normalized superoxide dismutase and glutathione-S-transferase activities. In conclusion, DHETE reduced colitis severity by attenuating inflammatory cytokine secretion and improved the endogenous antioxidant defense in DSS-induced UC in mice.
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Preclinical, Journal: Yarrow oil ameliorates ulcerative colitis in mice model via regulating the NF-κB and PPAR-γ pathways. (Pubmed Central) - Aug 22, 2020
Groups 2 and 3 received 5% dextran sulfate sodium (DSS) in drinking water for 9 days, and concomitantly, only group 3 was given 100 mg/kg yarrow oil...The oil normalized the tumor necrosis factor-α expression, restored the normal serum level of interleukin-10 (IL-10) and reduced the serum level of IL-6. Yarrow oil mitigated UC symptoms and regulated the inflammatory cytokines secretion via regulation of NF-κB and PPAR-γ pathways in the mice model, however, this recommendation requires further investigations using clinical studies to confirm the use of the oil on humans.
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Journal: Calcium/calmodulin-dependent protein kinase IV signaling pathway is upregulated in experimental necrotizing enterocolitis. (Pubmed Central) - Aug 18, 2020
These findings establish a critical role for the microbiota and their products, specifically butyrate, in the regulated expression of SYNPO for intestinal homeostasis and reveal a direct mechanistic link between microbiota-derived butyrate and barrier restoration. CaMKIV expression and activation are upregulated in experimental NEC suggesting a potential contributing factor in the pathogenesis of NEC.
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Preclinical, Journal: The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice. (Pubmed Central) - Aug 12, 2020
All of the four fecal components showed certain degree of efficacy in DSS-induced colitis, while transplantation of fecal suspension showed the most potent effect as demonstrated by less body weight loss, lower disease activity scores, more expression of tight junction proteins and TRAF6 and IκBα, less expression of TNF-α, IL-1β, IL-10, TLR-4, and MyD88 in gut tissue, as well as restoration of fecal β-glucuronidase and decreases in fecal digestive proteases. These results provide a novel insight into the possible mechanism of FMT and may help to improve and optimize clinical use of FMT.
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Preclinical, Journal: Comparison of the anti-colitis activities of Qing Dai/Indigo Naturalis constituents in mice. (Pubmed Central) - Aug 11, 2020
This study investigates the effects of QD on murine dextran sulfate sodium salt-induced colitis...Combining these two fractions resulted in full anti-colitis activity. Further clarification of the active constituents will help in the discovery of a safe and potent prescription for UC.
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Preclinical, Journal: Cyclic nigerosylnigerose ameliorates DSS-induced colitis with restoration of goblet cell number and increase in IgA reactivity against gut microbiota in mice. (Pubmed Central) - Aug 11, 2020
To investigate the effect of administration of CNN to promote IgA secretion on gut inflammation, experimental colitis was induced with dextran sulfate sodium (DSS) in Balb/c mice after 6 weeks of CNN pre-feeding...Although there was no difference in the IgA concentration among groups, a higher proportion of cecal microbiota were coated with IgA in the CNN-DSS group compared with that in the DSS group. These results suggest that CNN might preserve goblet cells in the colon and promote IgA coating of gut microbiota, which synergistically ameliorate gut inflammation in mice with DSS-induced colitis.
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Journal: Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis. (Pubmed Central) - Aug 9, 2020
NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS)...Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.
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Clinical, Journal: Mechanism underlying the significant role of the miR-4262/SIRT1 axis in children with inflammatory bowel disease. (Pubmed Central) - Aug 9, 2020
Firstly, reverse transcription-quantitative PCR (RT-qPCR) was used to detect the expression of miR-4262 in 30 IBD colonic mucosa tissues, 30 normal tissues, 2% dextran sulfate sodium (DSS)-treated Caco-2 cells and normal cells...All the effects of miR-4262 inhibitor on Caco-2 cells were eliminated following transfection with SIRT1-siRNA. It was thus concluded that miR-4262 may serve a role in the progression of IBD via targeting SIRT1, and miR-4262/SIRT1 may represent a potential target for the diagnosis and treatment of IBD.
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Preclinical, Journal, IO Biomarker: The inhibitory effects of Qingchang Wenzhong granule on the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium-induced colitis. (Pubmed Central) - Aug 6, 2020
It was thus concluded that miR-4262 may serve a role in the progression of IBD via targeting SIRT1, and miR-4262/SIRT1 may represent a potential target for the diagnosis and treatment of IBD. QCWZG could relieve rats with DSS-induced colitis from UC symptoms by improving the intestinal physical barrier, which resists the interactive network of inflammation, oxidative stress, apoptosis, and their overactivated interactions.
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Journal: Sphk1 promotes ulcerative colitis via activating JAK2/STAT3 signaling pathway. (Pubmed Central) - Aug 5, 2020
A dextran sulfate sodium (DSS)-induced mouse model was established to investigate the effect of SphK1 on the progression of UC in vivo...Additionally, overexpression of Sphk1 increased the secretion of pro-inflammatory cytokines and activated the JAK2/STAT3 signaling pathway in RAW264.7 cells, and JSI-124 partially suppressed these effects...The SphK1 inhibitor (PF-543) had an inhibitory effect on DSS-induced UC mice. Sphk1 had significant pro-inflammatory effects on the progression of UC, and may thus be a potential novel therapeutic target for the treatment of UC.
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[VIRTUAL] Cell free DNA as potential marker of inflammatory diseases (Interactive e-Poster Area) - Aug 4, 2020 - Abstract #ESHG2020ESHG_743;
Our results suggest the utility of cfDNA as a potential screening marker for IBD and even its specific stages and pathophysiological processes behind them. Funded by: Slovak Research and Development Agency, grant APVV-17-0526.
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Preclinical, Journal, IO Biomarker: CD73 promotes colitis-associated tumorigenesis in mice. (Pubmed Central) - Jul 30, 2020
A mouse model of colitis-associated tumorigenesis (CAT) induced by azoxymethane and dextran sulfate sodium was successfully constructed...Therefore, inhibition of CD73 attenuated IBD-associated tumorigenesis, while activation of adenosine receptors exacerbated tumorigenesis in a C57BL/6J mouse model. This effect may be associated with the expression of pro-inflammatory cytokines and the regulation of ALOX15, Bcl2l15 and Nat8l.
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