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Preclinical, Journal: 17β-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice. (Pubmed Central) - Dec 23, 2020
Previously, we reported that 17β-estradiol (E2) inhibits azoxymethane/dextran sulfate sodium (AOM/DSS)-induced tumorigenesis in male mice...Our findings suggest that estrogen alters the gut microbiota in ICR (CrljOri:CD1) mice, particularly AOM/DSS-treated males, by decreasing the F/B ratio and changing Shannon and Simpson index by supply of estrogen. This highlights another possibility that estrogen could cause changes in the gut microbiota, thereby reducing the risk of developing CRC.
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Journal: Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer. (Pubmed Central) - Dec 22, 2020
Our results showed that PL could inhibit the inflammation of DSS-induced mouse colitis and reduce the number of large neoplasms (diameter >2 mm) of AOM/DSS-induced mouse colorectal cancer by downregulation of proinflammatory cytokines cyclooxygenase-2 and interleukin-6 and epithelial-mesenchymal transition-related factors, β-catenin, and snail expressions, but fail to improve the colitis symptoms and to decrease the incidence of colonic neoplasms and the number of small neoplasms (diameter <2 mm). These data suggested that PL might be an effective agent in treating colitis and colorectal cancer.
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Preclinical, Journal: Protective Effect of Cicer arietinum L. (Chickpea) Ethanol Extract in the Dextran Sulfate Sodium-Induced Mouse Model of Ulcerative Colitis. (Pubmed Central) - Dec 20, 2020
Although DSS upregulated pro-inflammatory mediators and activated transcription factors, CEE downregulated the mRNA expression of cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, protein expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as activation of nuclear factor-kappa B (NF-кB) and signal transducer and activator of transcription 3 (STAT3). Hence, our findings reveal that the anti-inflammatory properties of CEE, involving the downregulation of the expression of pro-inflammatory mediators by inactivating NF-кB and STAT3 in DSS-induced colitis mice.
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Journal: Enhanced O-linked Glcnacylation in Crohn's disease promotes intestinal inflammation. (Pubmed Central) - Dec 20, 2020
Intestinal inflammation in CD is associated with increased O-GlcNAc modification, which is required for NF-κB activation and suppression of autophagy. Targeting O-GlcNAc could be an effective therapy for inflammatory bowel disease.
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Journal, PD(L)-1 Biomarker, IO Biomarker: Dextran Sulfate Protects Pancreatic β-Cells, Reduces Autoimmunity and Ameliorates Type 1 Diabetes. (Pubmed Central) - Dec 20, 2020
Low-molecular-weight dextran sulfate (DS) is a sulfated semisynthetic polysaccharide with demonstrated cytoprotective and immunomodulatory properties in vitro...DS administration also increases the expression of the inhibitory co-stimulatory molecule programmed death-1 (PD-1) in T-cells, reduces interferon-γ+ CD4+ and CD8+ T-cells and enhances the number of FoxP3+ cells. Collectively, these studies demonstrate that the action of one single molecule, DS, on β-cell protection, extracellular matrix preservation and immunomodulation can reverse diabetes in NOD mice highlighting its therapeutic potential for the treatment of T1D.
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Preclinical, Journal: The α-D-glucan from marine fungus Phoma herbarum YS4108 ameliorated mice colitis by repairing mucosal barrier and maintaining intestinal homeostasis. (Pubmed Central) - Dec 18, 2020
In the study, the therapeutic effect and intestinal regulatory activity of YCP (40 mg/kg, intraperitoneal injection) on UC were investigated in dextran sulfate sodium (DSS)-induced colitis mice...In addition, YCP resulted in prominent alterations on specific microbiota including Firmicutes, Bacteroidetes, Proteobacteria, Clostridiales, and Lachnospiraceae which are closely related to immune regulation and mucus repair. Therefore, YCP may be a candidate for curing UC because of its conspicuous effects comparable to 5-aminosalicylic acid (5-ASA).
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Journal: Polysaccharide from flammuliana velutipes improves colitis via regulation of colonic microbial dysbiosis and inflammatory responses. (Pubmed Central) - Dec 18, 2020
Effect of FVP on colitis was evaluated using dextran sulfate sodium (DSS)-induced colitis in rats...Our results showed that FVP treatment could regulate the colonic microbial dysbiosis and promote the levels of caecal short fatty chain acids, leading to down-regulation of TLR4NF-κB signal pathway, which finally ameliorate the colitis. Thus, the present study is the first attempt to elucidate the effect of FVP on colitis and support the potential application of FVP as a functional food ingredient or preventive drugs for colitis.
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Preclinical, Journal: Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis. (Pubmed Central) - Dec 18, 2020
Here, we investigated the effect of the monosaccharide fucose on inflammation, metabolism, intestinal microbiota, and social behavior in the Dextran Sulfate Sodium (DSS)-induced chronic colitis mouse model...Our results suggest a possible mechanism by which intestinal inflammation affects social behavior in male mice. We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test.
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Journal: Garcinone C suppresses colon tumorigenesis through the Gli1-dependent hedgehog signaling pathway. (Pubmed Central) - Dec 18, 2020
We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test. Garcinone C can suppress colon tumorigenesis in vitro and in vivo through Gli1-dependent non-canonical Hedgehog signaling, suggesting that it may serve as a potent chemopreventive agent against colon tumorigenesis.
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Preclinical, Journal: Short-term tissue permeability actions of dextran sulfate sodium studied in a colon organ culture system. (Pubmed Central) - Dec 17, 2020
Nuclei of various cell types in the lamina propria, including both cells of the innate and adaptive immune system, are novel targets for a rapid action of DSS, and from previous in vitro studies, polyanions like DSS are known to disrupt nucleosomes by binding to the histones. We therefore propose that nuclear targeting is one way whereby DSS exerts its inflammatory action as a colitogen in animal models of inflammatory bowel diseases.
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Journal: Peroxisome Elevation Induces Stem Cell Differentiation and Intestinal Epithelial Repair. (Pubmed Central) - Dec 17, 2020
Moreover, administration of drugs that increased peroxisome levels reversed the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients.
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Preclinical, Journal: TL1A primed dendritic cells activation exacerbated chronic murine colitis. (Pubmed Central) - Dec 16, 2020
This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients. TL1A exacerbated DSS-induced chronic experimental colitis, probably through activation and migration of dendritic cells, and therefore increasing the secretion of pro-inflammatory cytokines.
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Journal: Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease. (Pubmed Central) - Dec 15, 2020
Bowel localization and systemic biodistribution of the nanoconjugate were analyzed upon injection in a murine model of chronic IBD obtained through repeated administration of dextran sulfate sodium salt...P@QD-MdC NPs efficiently detected bowel inflammation foci, accurately following the expression pattern of MAdCAM-1. Fine-tuning of this nanoconjugate with appropriate imaging agents offers a promising non-invasive tool for specific IBD diagnosis.
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Journal: Dietary intake of fermented kimchi prevented colitis-associated cancer. (Pubmed Central) - Dec 10, 2020
Using azoxymethane-initiated and dextran sulfate sodium-promoted colitic cancer models, we have administrated fermented or non-fermented kimchi to modulate colitic cancer preemptively...Repression of NF-kB p65, induction of tumor suppressive 15-PGDH, and inactivation of ERK1/2 by cpkimchi contributed to colitic cancer prevention. Dietary intake of cpkimchi ameliorated colitis and prevented colitic cancer via concerted anti-inflammatory, antioxidative, and anti-mutagenic actions.
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Journal: Transient receptor potential ankyrin 1 contributes to somatic pain hypersensitivity in experimental colitis. (Pubmed Central) - Dec 2, 2020
Transient receptor potential ankyrin 1 (TRPA1) has been reported to contribute to visceral pain-like behavior in dextran sulfate sodium (DSS)-evoked colitis...DSS treatment increased expression of TRPA1 mRNA in cultured dorsal root ganglion (DRG) neurons, but not trigeminal ganglion neurons, and selectively enhanced currents evoked by the TRPA1 agonist, allyl isothiocyanate, in cultured DRG neurons. Our findings indicate that the TRPA1 channel contributes to colitis-associated mechanical hypersensitivity in somatic tissues, an effect associated with upregulation of TRPA1 expression and responsiveness in DRG nociceptors.
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Journal: CD47 is a negative regulator of intestinal epithelial cell self-renewal following DSS-induced experimental colitis. (Pubmed Central) - Dec 1, 2020
CD47 deficient mice are resistant to dextran sulfate sodium (DSS)-induced experimental colitis...Mechanistically, western blot and functional assays indicated that CD47 deficiency promoting mouse intestinal epithelial cell proliferation and migration follow cell injury is likely through upregulating expression of four Yamanaka transcriptional factors Oct4, Sox2, Klf4 and c-Myc (OSKM in abbreviation). Our studies thus reveal CD47 as a negative regulator in intestinal epithelial cell renewal during colitis through downregulating OSKM transcriptional factors.
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Journal: Evodiamine Attenuates Experimental Colitis Injury Via Activating Autophagy and Inhibiting NLRP3 Inflammasome Assembly. (Pubmed Central) - Nov 28, 2020
Herein, we examine the effect of evodiamine, extracted from the fruit of Evodiae Fructus, on experimental colitis induced by dextran sulfate sodium and exposit whether evodiamine effects on autophagy and NLRP3 inflammasome...Our results demonstrated evodiamine inhibit NLRP3 inflammasome activation via the induction of autophagosome-mediated degradation of inflammasome and the inhibition of NFκB pathway, which synergistically contribute to the effect of evodiamine in colitis. It indicates the potential use of evodiamine in inflammatory bowel diseases treatment.
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Preclinical, Journal: Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis. (Pubmed Central) - Nov 28, 2020
Moreover, colonic tissues of CHL1 mice showed a marked increase in neutrophil and macrophage infiltration, be accompanied by more severe damage to intestinal epithelial cells and higher fluorescein isothiocyanate (FITC) leakage. Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice.
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Biomarker, Preclinical, Journal: Comprehensive analysis of key biomarkers, immune infiltration and potential therapeutic agents for ulcerative colitis. (Pubmed Central) - Nov 28, 2020
Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice. The current study comprehensively analyzed the DEGs and immune infiltration in UC, as well as screened for potential agents for UC treatment.
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Journal, IO Biomarker: New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD. (Pubmed Central) - Nov 27, 2020
A better understanding of the role of autophagy in IBD pathogenesis may provide better sub-classification of IBD phenotypes and novel approaches for disease management. Abbreviations: AIEC: adherent-invasive Escherichia coli; AMPK: AMP-activated protein kinase; ATF6: activating transcription factor 6; ATG: autophagy related; Atg16l1[ΔIEC] mice: mice with Atg16l1 depletion specifically in intestinal epithelial cells; Atg16l1[HM] mice: mice hypomorphic for Atg16l1 expression; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related; CALCOCO2: calcium binding and coiled-coil domain 2; CASP: caspase; CD: Crohn disease; CGAS: cyclic GMP-AMP synthase; CHUK/IKKA: conserved helix-loop-helix ubiquitous kinase; CLDN2: claudin 2; DAPK1: death associated protein kinase 1; DCs: dendritic cells; DSS: dextran sulfate sodium; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK: eukaryotic translation initiation factor 2 alpha kinase; ER: endoplasmic reticulum; ERBIN: Erbb2 interacting protein; ERN1/IRE1A: ER to nucleus signaling 1; FNBP1L: formin binding protein 1-like; FOXP3: forkhead box P3; GPR65: G-protein coupled receptor 65; GSK3B: glycogen synthase kinase 3 beta; IBD: inflammatory bowel disease; IECs: intestinal epithelial cells; IFN: interferon; IL: interleukin; IL10R: interleukin 10 receptor; IRGM: immunity related GTPase M; ISC: intestinal stem cell; LAMP1: lysosomal-associated membrane protein 1; LAP: LC3-associated phagocytosis; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; LPS: lipopolysaccharide; LRRK2: leucine-rich repeat kinase 2; MAPK: mitogen-activated protein kinase; MHC: major histocompatibility complex; MIF: macrophage migration inhibitory factor; MIR/miRNA: microRNA; MTMR3: myotubularin related protein 3; MTOR: mechanistic target of rapamycin kinase; MYD88: myeloid differentiation primary response gene 88; NLRP3: NLR family, pyrin domain containing 3; NOD2: nucleotide-binding oligomerization domain containing 2; NPC: Niemann-Pick disease type C; NPC1: NPC intracellular cholesterol transporter 1; OMVs: outer membrane vesicles; OPTN: optineurin; PI3K: phosphoinositide 3-kinase; PRR: pattern-recognition receptor; PTPN2: protein tyrosine phosphatase, non-receptor type 2; PTPN22: protein tyrosine phosphatase, non-receptor type 22 (lymphoid); PYCARD/ASC: PYD and CARD domain containing; RAB2A: RAB2A, member RAS oncogene family; RELA: v-rel reticuloendotheliosis viral oncogene homolog A (avian); RIPK2: receptor (TNFRSF)-interacting serine-threonine kinase 2; ROS: reactive oxygen species; SNPs: single nucleotide polymorphisms; SQSTM1: sequestosome 1; TAX1BP1: Tax1 binding protein 1; Th: T helper 1; TIRAP/TRIF: toll-interleukin 1 receptor (TIR) domain-containing adaptor protein; TLR: toll-like receptor; TMEM173/STING: transmembrane protein 173; TMEM59: transmembrane protein 59; TNF/TNFA: tumor necrosis factor; Treg: regulatory T; TREM1: triggering receptor expressed on myeloid cells 1; UC: ulcerative colitis; ULK1: unc-51 like autophagy activating kinase 1; WT: wild-type; XBP1: X-box binding protein 1; XIAP: X-linked inhibitor of apoptosis.
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Journal: PAM3 protects against DSS-induced colitis by altering the M2:M1 ratio. (Pubmed Central) - Nov 26, 2020
Human IBD is modeled by administering dextran sulfate sodium (DSS) to mice...The critical role of M2 macrophages in this process was established by transferring purified M2 macrophages from PAM3 treated control donors into DSS recipients and reducing colitis. These findings suggest that PAM3 may represent a novel approach to the treatment of human IBD.
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Journal: Effects of emodin on inflammatory bowel diseases related osteoporosis. (Pubmed Central) - Nov 25, 2020
An IBD model in Sprague Dawley male rats was established by administering 2.5% dextran sulfate sodium (DSS) in the drinking water...Emodin significantly abolished IBD-enhanced Traf6, NFATC1 and c-fos expression. Our data demonstrated that emodin suppresses IBD-induced osteoporosis by inhibiting osteoclast formation.
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Journal: Near infrared readouts offer sensitive and rapid assessments of intestinal permeability and disease severity in inflammatory bowel disease models. (Pubmed Central) - Nov 25, 2020
The increased sensitivity of NIR readouts for colon permeability is shown using dextran sulfate sodium (DSS) and anti-CD40 murine colitis models in response to interleukin-22 immunoglobulin Fc (IL22Fc) fusion protein and anti-p40 monoclonal antibody treatments, respectively...Confocal laser endomicroscopy (CLE) and tissue imaging allow visualization of spatial NE activity throughout diseased colon as well as changes in disease severity from IL22Fc treatment. Our findings with the 800CW dye and the NE probe highlight the ease of their implementation in preclinical IBD research.
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Preclinical, Journal: In Vitro Antioxidant, Anti-inflammatory, and In Vivo Anticolitis Effects of Combretin A and Combretin B on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice. (Pubmed Central) - Nov 21, 2020
For in vivo analysis, we used the model of ulcerative colitis induced by Dextran Sulfate Sodium (DSS)...These compounds significantly reduced the signs of DSS-induced colitis in the treated animals by preventing the weight loss of the animals, by significantly reducing the disease activity index, improving the condition of the stool, preventing the reduction of the length of the colon, and preventing the degradation of the colon. This study revealed that Combretin A and Combretin B have anti-inflammatory, antioxidant, and curative properties against colitis experimentally induced by DSS in rats.
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Journal: Interleukin-37 Inhibits Colon Carcinogensis During Chronic Colitis. (Pubmed Central) - Nov 21, 2020
Colon carcinogenesis was triggered by intragastric administration of celecoxib...In conclusion, IL-37 transgene expression protects IL-10KO mice from colon carcinogenesis. It remains unclear whether IL-37 has direct tumor suppressing properties.
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Journal: Electroacupuncture preserves intestinal barrier integrity through modulating the gut microbiota in DSS-induced chronic colitis. (Pubmed Central) - Nov 21, 2020
Collectively, our data suggest a novel regulatory function of TRAF5 in supporting the proinflammatory function of TRAF2 in nonhematopoietic cells, which may be important for acute inflammatory responses in the intestine. EA can relieve chronic experimental colitis, and this effect may depend on activation of the MAPK signaling pathway through modulation of the gut microbiota to preserve the intestinal barrier.
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Preclinical, Journal, IO Biomarker: Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model. (Pubmed Central) - Nov 19, 2020
acidophilus) cell lysates combined with an anti-CTL antigen-4 blocking antibody (CTLA-4 mAb) in syngeneic BALB/c mice CRC models induce by a single intraperitoneal injection of 10 mg/kg azoxymethane (AOM), followed by three cycles of 2% dextran sulfate sodium (DSS) in drinking water...Finally, the 16S rRNA gene sequencing of fecal microbiota demonstrated that the combined administration significantly inhibited the abnormal increase in the relative abundance of proteobacteria and partly counterbalance CRC-induced dysbiosis in model mice. Overall, these data support promising clinical possibilities of L. acidophilus lysates with CTLA-4 mAb in cancer patients and the hypothesis that probiotics help shape the anticancer immune response.
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