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Preclinical, Journal: Metagonimus miyatai ameliorates dextran sodium sulfate-induced colitis in mice. (Pubmed Central) - Mar 15, 2020
Mice were infected with M. miyatai, and colitis was then induced through oral administration of dextran sulfate sodium (DSS)...The expression levels of tumor necrosis factor-α, interleukin-1b, and cyclooxygenase-2 in mice infected with helminth were lower than those in DSS-treated mice without helminthic infection (p < .05). The results of the research showed that pre-infection with M. miyatai ameliorated DSS-induced colitis in mice and may be a novel therapeutic strategy for the treatment of immunological diseases.
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Preclinical, Journal: Emu Oil reduces disease severity in a mouse model of chronic ulcerative colitis. (Pubmed Central) - Mar 14, 2020
Emu Oil attenuated clinically- and histologically-assessed disease severity in a mouse model of chronic UC. Emu Oil demonstrates promise as an adjunct to conventional treatment options for UC management.
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Journal: Cinobufacini ameliorates experimental colitis via modulating the composition of gut microbiota. (Pubmed Central) - Mar 13, 2020
Cinobufacini prevents colitis in mice by modifying the composition and function of gut microbiota. The current study provides additional mechanistic insight in the therapeutic effect of cinobufacini treatment and may pave the way for clinical application of cinobufacini in colitis therapy.
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Preclinical, Journal: Polysaccharides isolated from Nostoc commune Vaucher inhibit colitis-associated colon tumorigenesis in mice and modulate gut microbiota. (Pubmed Central) - Mar 10, 2020
In this study, we examined the protective effects of the polysaccharides isolated from N. commune (NVPS) against colitis-associated colon tumorigenesis in mice treated with azoxymethane (AOM) and dextran sulfate sodium salt (DSS) and the impact of these polysaccharides on the intestinal microbiota...These compositional alterations induced by the NVPS were associated with the suppressed colonic inflammation and carcinogenesis. In conclusion, our results demonstrated an appreciable capability of NVPS to restore the gut microbiota profile altered by AOM/DSS, indicating the potential of NVPS as a promising prebiotic candidate for the prevention and treatment of colorectal cancer.
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THE LACK OF CHROMOGRANIN-A MODIFIES THE GUT MICROBIOTA COMPOSITION AND REGULATES EXPERIMENTAL COLONIC INFLAMMATION () - Mar 8, 2020 - Abstract #CDDW2020CDDW_137;
However, the interplay between CHGA, as a pro-hormone, and the gut microbiome remains elusive.Aims in homoeostatic and pathophysiologic conditions, we investigated the functional consequences of the lack of Chgaon the distal colonic microbiota.Methods Acute colitis (5 % dextran sulfate sodium [DSS], 5 days) was induced in Chga-C57BL/6-deficient (Chga-/-) and wild-type (Chga+/+)mice...Therefore, targeting CHGA could provide a novel therapeutic strategy by regulating the gut microbiome in physiological and pathophysiological conditions. Funding Agencies CIHR
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INTESTINAL EPITHELIAL NCOR1 TARGETS TRYPTOPHAN METABOLISM AND PROTECTS AGAINST EXPERIMENTAL COLITIS () - Mar 8, 2020 - Abstract #CDDW2020CDDW_136;
NCOR1ΔIEC and control littermate mice were treated with dextran sulfate sodium (DSS) in drinking water...Conclusions Our Results highlight the critical role of NCOR1 to maintain intestinal inflammatory homeostasis during experimental colitis and uncover a novel function for NCOR1 in the regulation of Ido1 expression and potentially tryptophan metabolism. Funding Agencies CIHR
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THE INFLUENCE OF IL10 ON COLITIS DEVELOPMENT IN NOD2 DEFICIENT MICE () - Mar 8, 2020 - Abstract #CDDW2020CDDW_104;
A subset of mice from each genotype received 3.5% dextran sulfate sodium (DSS) supplemented water for 5 days starting at eight weeks of age...The role of IL10 in modulating the gut microbiome using this model remains to be assessed. Funding Agencies CAG
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HELMINTH ANTIGENS OR REGULATORY MACROPHAGES REDUCE THE SEVERITY OF COLORECTAL CANCER () - Mar 8, 2020 - Abstract #CDDW2020CDDW_95;
Given the relationship between inflammation and cancer – patients with inflammatory bowel disease (IBD) have a higher risk of colorectal cancer (CRC).Aims To test the hypothesis that intraperitoneal administration of excretory/secretory products from the tapeworm Taenia crassiceps (TcES) or IL-4-treated macrophages (M(IL-4)) (characteristic of the immune response to helminths) would affect the outcome of CRC.Methods CRC was induced in female BALB/c and male C57Bl/6 mice using azoxymethane (AOM) (10 mg, ip) and three cycles of Dextran sulfate sodium (DSS: 7 days, 1–2% wt./vol.) separated by 2 weeks of normal tap water...Contrary to this, the data herein show that the TcES reduced CRC; and, that murine macrophages (M(IL4)) also actually limit the severity of inflammation-driven CRC by directly targeting the cancer cells or reducing the inflammatory stimulus. These findings add emphasis to the consideration of autologous regulatory macrophage transfer to treat IBD and CRC Funding Agencies CCCCONACYT (Mexico)
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CHROMOFUNGIN PROTECTS AGAINST DSS-INDUCED COLITIS BY REGULATING P-53 APOPTITIC PATHWAY () - Mar 8, 2020 - Abstract #CDDW2020CDDW_38;
Chromofungin (CHR), a chromogranin-A derived peptide expressing a cell penetrating peptide motif, decreased the severity of colitis via the suppression of mucosal and pro-inflammatory macrophages-related p53-dependent apoptosis.Aims We aimed to investigate a) whether the gene profile expression of apoptosis could be extended to other p53-associated genes; b) whether the gene expression of some of the p53-apoptosis marker could be confirmed by protein analysis; and c) whether due to the cell penetrating peptide motif, CHR could enter into peritoneal macrophages.Methods UC-related colitis was induced in C57BL/6 mice (7 weeks) by administering dextran sulfate sodium (DSS) (5%, 5 days)...Targeting functional analysis of CHR may lead in the future to novel therapeutics for UC. Funding Agencies CCCNSERC
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Journal: NUDT7 Loss Promotes Kras CRC Development. (Pubmed Central) - Mar 7, 2020
Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into Nudt7 knockout (Nudt7) mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of Nudt7-overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes...We observed an increased level of palmitic acid in the colon of Nudt7 mice and attachment of palmitic acid-conjugated chitosan patch into the colon of mice induced the expression levels of b-catenin and CRC-related genes. Overall, our data reveal a novel role for peroxisomal NUDT7 in Kras-driven CRC development.
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Journal: Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression. (Pubmed Central) - Mar 7, 2020
Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium...Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.
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Journal: DICAM Attenuates Experimental Colitis via Stabilizing Junctional Complex in Mucosal Barrier. (Pubmed Central) - Mar 4, 2020
Colitis was induced with oral administration of 2.5% dextran sulfate sodium (DSS) in 8-week-old male mice for 5 days...Furthermore, Caco-2 cells with DICAM overexpression maintained intestinal barrier function under IFN-γ treatment as estimated by transepithelial electrical resistance. Our study demonstrates that DICAM which is increased in an inflammatory condition has a protective role in experimental colitis by stabilizing the integrity of junctional complex in the intestinal mucosal barrier.
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Journal: Commensal viruses maintain intestinal intraepithelial lymphocytes via noncanonical RIG-I signaling. (Pubmed Central) - Mar 2, 2020
The recovery of IELs by interleukin-15 administration reverses the susceptibility of commensal virus-depleted mice to dextran sulfate sodium-induced colitis. Collectively, our results indicate that commensal viruses maintain the IELs and consequently sustain intestinal homeostasis via noncanonical RIG-I signaling.
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Preclinical, Journal: Profiling of histone 3 lysine 27 acetylation reveals its role in a chronic DSS-induced colitis mouse model. (Pubmed Central) - Feb 28, 2020
Here, we established a dextran sulfate sodium (DSS)-induced chronic colitis model and performed RNA-sequencing (RNA-seq) and Chromatin Immunoprecipitation followed by NGS sequencing (ChIP-seq) for H3K27ac in the mice colon tissues to investigate whether H3K27ac is involved in the development of intestinal inflammation...We further predicted transcription factors (TFs) involved in DSS-induced colitis according to the enhancers with increased H3K27ac. H3K27ac increase in special typical-enhancers in the DSS group is possibly related to the development of intestinal inflammation by up-regulating adjacent gene expression and shifting TF networks, which will provide new insight into the pathogenesis and therapy of IBD.
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Preclinical, Journal: The Possible Anti-Inflammatory Effect of Dehydrocostus Lactone on DSS-Induced Colitis in Mice. (Pubmed Central) - Feb 23, 2020
The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice...DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.
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Journal: Alpha7 Nicotinic Acetylcholine Receptor Alleviates Inflammatory Bowel Disease Through Induction of AMPK-mTOR-p70S6K-Mediated Autophagy. (Pubmed Central) - Feb 22, 2020
Three percent dextran sulfate sodium (DSS) was used for the creation of IBD mice model and lipopolysaccharides (LPS)/DSS as an inflammatory stressor in murine bone marrow-derived macrophages (BMDMs)...The alleviative effect of activating α7nAChR was attenuated through inhibiting adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mediated signaling. In conclusion, α7nAChR contributes to alleviate IBD through the induction of AMPK-mammalian target of rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K)-mediated autophagy, thus providing a novel target for the treatment of IBD.
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Preclinical, Journal: Strain-Specific Anti-inflammatory Properties of Two Akkermansia muciniphila Strains on Chronic Colitis in Mice. (Pubmed Central) - Feb 21, 2020
The specific capacity of strain ATCC to modulate the differentiation of Tregs as well as increase production of short chain fatty acids, demonstrated strain-specific characteristics for these two A. muciniphila strains. This study suggests the potential beneficial effect of A. muciniphila on IBD and the importance of the future study of the function of A. muciniphila at the strain-level.
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Preclinical, Journal: Regenerating islet-derived protein (Reg)3β plays a crucial role in attenuation of ileitis and colitis in mice. (Pubmed Central) - Feb 21, 2020
Moreover, the expression of Interleukin 6, an inflammatory cytokine and Chitinase-like 3, a marker for tissue repair macrophages was elevated in the colon of Reg3b mice compared to wild-type mice after DSS treatment. Together, these results suggest that attenuation of colitis and ileitis is a result of Reg3β's real function.
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Clinical, Journal: Microbial Colonization in Adulthood Shapes the Intestinal Macrophage Compartment. (Pubmed Central) - Feb 14, 2020
Our results indicate that oats retain their biological properties even after the germination process. This study provides the first data indicating that after colonization of adult mice, the numeric, phenotypic, and functional restoration of the macrophage compartment requires the presence of intestinal microbiota and is time dependent.
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Alginate/Chitosan Microparticles for Oral Delivery of Therapeutic Protein Nanoparticles (109B, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_14624;
We have previously shown that a Salmonella effector enzyme, AvrA, delivered by NPs is capable of modulating inflammatory signals in a murine dextran sulfate sodium (DSS) colitis model...Oral administration of AvrA NPs encapsulated in alginate/chitosan MPs delivered protein to intestinal epithelia and reduced clinical and histological scores of inflammation in a murine DSS-induced colitis model. Altogether, NPs in alginate/chitosan MPs are a potential oral delivery vehicle for protein therapeutics.
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Preclinical, Journal: Physalis angulata Calyces Modulate Macrophage Polarization and Alleviate Chemically Induced Intestinal Inflammation in Mice. (Pubmed Central) - Feb 10, 2020
In this work, we investigated the immunomodulatory effect of PADF in activated macrophages and during dextran sulfate sodium (DSS)-induced colitis...In vivo, the administration of PADF to mice with chronic DSS-colitis reduced disease signs (i.e., body weight loss and colon shortening), and improved the histology score by diminishing the levels of pro-inflammatory cytokines and increasing the production of IL-10. Overall, results suggest that the regulatory effect on PADF towards macrophages might contribute to the therapeutic activity observed in the murine model of inflammatory bowel disease.
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Preclinical, Journal: TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis. (Pubmed Central) - Feb 10, 2020
Extracellular vesicles, which elicit similar biological activity to the stem cell themselves, have been used experimentally to treat dextran sulfate sodium (DSS)-induced colitis in murine models though immunosuppressive potential...Importantly, EVs obtained from primed stem cells effectively induced macrophage polarization toward an anti-inflammatory M2 phenotype and suppressed activated immunity by enhancing regulatory T cells in inflamed colon in mice. Our results provide a new and effective therapy for the EVs obtained from ASC stimulated with TNF-α and IFN-γ against not only IBD, but also immune-mediated disease.
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Journal: VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer. (Pubmed Central) - Feb 9, 2020
We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) -induced CRC mice models and nicotine-treated CRC cells via the PI3K/AKT/c-Jun pathway...VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and the downstream cell cycle or EMT-related factors...Suppression of NESG1 increased cell growth, migration, and invasion via the reversion of the VPS33B-modulating signal in VPS33B-overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and thus suppress the malignant phenotype of CRC.
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Preclinical, Journal: Oral Supplementation of Tocotrienol-Rich Fraction Alleviates Severity of Ulcerative Colitis in Mice. (Pubmed Central) - Feb 8, 2020
Dextran sulfate sodium (DSS)-induced UC mice were treated with vehicle control, TRF, alpha-tocopherol (αTP) and 5-aminosalicylic acid (5-ASA)...TRF alleviated the signs and symptoms of acute UC in murine model via the reduction of local inflammatory reactions and oxidative stress. These effects suggested that TRF could serve as a gut health supplement for preventive measures for UC condition in patients.
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Journal: High-Fat Diet Propelled AOM/DSS-Induced Colitis-Associated Colon Cancer Alleviated by Administration of Aster glehni via STAT3 Signaling Pathway. (Pubmed Central) - Feb 8, 2020
Previously, we found that Aster glehni (AG) exerts chemopreventive effects on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC in a mice model, and has anti-adipogenic effects in a HFD-induced obesity mice model...Furthermore, AG significantly inhibited the signal transducer and activator of transcription 3 (STAT3) signaling pathway and attenuated the protein expression of the STAT3 target gene, which mediates transcription factor-dependent tumor cell proliferation. These results indicate that AG abrogates inflammation-induced tumor progression in HFD-propelled CAC mice by inhibiting STAT3 activation.
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Journal: The role of the miR-21-5p-mediated inflammatory pathway in ulcerative colitis. (Pubmed Central) - Feb 6, 2020
A UC rat model was established using dextran sulfate sodium...Furthermore, STAT3 was confirmed to be a target of miR-21-5p in RAW264.7 cells. Collectively, these data demonstrated that miR-21-5p inhibition mediated the IL-6/STAT3 pathway in UC rats to decrease the levels of inflammation and apoptosis in RAW264.7 cells, and suggested that miR-21-5p may be an important therapy target in human UC.
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Preclinical, Journal: LC-MS-based metabolomics analysis of Berberine treatment in ulcerative colitis rats. (Pubmed Central) - Feb 1, 2020
To explore the relationship between IBD, metabolism and Berberine, dextran sulfate sodium-induced ulcerative colitis (UC) model was built and urine and feces samples were analyzed with ultra-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry, followed by multivariate statistical analyses...Furthermore, microbiome metabolism may be regulated by Berberine in UC. In general, this study provides a useful approach for exploring the mechanism of Berberine in the treatment of UC from the perspective of metabolomics.
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Journal: Lipidomics Provides Novel Insights into Understanding the Bee Pollen Lipids Transepithelial Transport and Metabolism in Human Intestinal Cells. (Pubmed Central) - Jan 31, 2020
The results showed that BPL-Cs protected Caco-2 cells against dextran sulfate sodium (DSS)-induced intestinal barrier dysfunction by improving cell viability, maintaining membrane integrity, increasing tight junctions (ZO-1 and Claudin-1), and eliciting the expressions of antioxidative-related genes (NQO1, Nrf2, Txnrd1, and GSTA1)...Finally, eight classes of lipids were identified as the potential biomarkers for evaluating DSS-induced Caco-2 cell dysfunctions and BPL-intervened modulation. These findings shed a light on the development of BPL as gastrointestinal protective food supplements in the future.
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Preclinical, Journal: pVAX1-A20 alleviates colitis in mice by promoting regulatory T cells. (Pubmed Central) - Jan 30, 2020
These findings shed a light on the development of BPL as gastrointestinal protective food supplements in the future. A20 plays a key role in the regulation of intestinal inflammation and that the overexpression of A20 in the intestine protects mice from dextran sulfate sodium induced chronic colitis.
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Preclinical, Journal: Anti-inflammatory effects of apocynin on dextran sulfate sodium-induced mouse colitis model. (Pubmed Central) - Jan 30, 2020
This study also revealed the unique action of apocynin compared to the currently prescribed drug, sulfasalazine. Given its excellent safety profile and potent efficacy with novel action mechanism, apocynin can be a new therapeutic molecule for the IBD treatment, which can be added to the currently available drugs.
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Journal: Hepatic and intestinal biotransformation gene expression and drug disposition in a dextran sulfate sodium-induced colitis mouse model. (Pubmed Central) - Jan 30, 2020
The impact of the colitis on in vivo clearance of oral drugs varied for four different drugs tested: a small decrease for nifedipine, a relatively large decrease for lovastatin, but no change for pravastatin, and a large decrease in the absorption of cyclosporine A. To further assess the scope of influence of gut inflammation on gene expression, we performed genome-wide expression analysis using RNA-seq, which showed down-regulation of many CYPs, non-CYP phase-I enzymes, phase-II enzymes and transporters, and up-regulation of many other members of these gene families, in both liver and intestine of adult C57BL/6 mice, by DSS-induced colitis. Overall, our results indicate that gut inflammation suppresses the expression of many P450s and other biotransformation genes in the intestine and liver, and alters the pharmacokinetics for some but not all drugs, potentially affecting therapeutic efficacy or causing adverse effects in a drug-specific fashion.
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Journal: L-Fucose ameliorates DSS-induced acute colitis via inhibiting macrophage M1 polarization and inhibiting NLRP3 inflammasome and NF-kB activation. (Pubmed Central) - Jan 29, 2020
We studied the anti-inflammatory effects of L-fucose on Dextran sulfate sodium (DSS)-induced acute colitis in vivo and on LPS/ATP-induced bone marrow derived macrophages (BMDMs) damage in vitro...Finally, L-fucose can inhibit the expression of p-NF-kB in vivo and in vitro. Overall, our results show that L-fucose can attenuate colitis by inhibiting macrophage M1 polarization, inhibiting NLRP3 inflammasome and NF-kB activation, and down-regulation of pro-inflammatory cytokines.
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