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Preclinical, Journal: Preventive Effects of Pyungwi-san against Dextran Sulfate Sodium- and Clostridium difficile-Induced Inflammatory Bowel Disease in Mice. (Pubmed Central) - May 6, 2020
We observed that exposure of DSS + CD-treated animals to PWS significantly decreased the disease activity index; prevented the shortening of colonic length and increases in spleen size and weight; restored colonic histological parameters by significantly increasing mucus thickness, crypt depth, and goblet cell numbers; protected the tight junction proteins; improved the profiles of pro-inflammatory and anti-inflammatory cytokines; and normalized the abundance ratio of the Firmicutes/Bacteroidetes in the gut. Thus, PWS exerted a number of protective effects on DSS + CD-induced colitis, which might be mediated via restoration of a balance in gut microbial communities.
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PK/PD data, Preclinical, Journal: Preclinical pharmacokinetics of M10 after intragastrical administration of M10-H and M10-Na in Wistar rats. (Pubmed Central) - May 6, 2020
It has better activity than myricetin in preventing azoxymethane/dextran sulfate sodium - induced ulcerative colitis...This method was applied to a pharmacokinetic study of intragastrical administration of M10-H and M10-Na in Wistar rats. In addition, the relative bioavailability of M10-H to M10-Na in Wistar rats was 60 ± 19%, calculated by the ratio of area under concentration (AUC) of M10-H to M10-Na after intragastrical administration of a single dose (100 mg·kg for M10-H and M10-Na, respectively) in Wistar rats.
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Preclinical, Journal: Effect of medicated thread moxibustion of Chinese Zhuang Minority medicine on colonic inflammatory impairment and Th17/IL-17F signaling in rats with ulcerative colitis (Pubmed Central) - May 6, 2020
In addition, the relative bioavailability of M10-H to M10-Na in Wistar rats was 60 ± 19%, calculated by the ratio of area under concentration (AUC) of M10-H to M10-Na after intragastrical administration of a single dose (100 mg·kg for M10-H and M10-Na, respectively) in Wistar rats. Medicated thread moxibustion of Zhuang Minority medicine can reduce the inflammatory damage of colon tissue in UC rats, which is associated with its effects in suppressing the expression of RORγt, production of Th17 cells, and secretion of pro-inflammatory factor IL-17F in colon tissue.
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Journal: Lactobacillus fermentum V3 ameliorates colitis-associated tumorigenesis by modulating the gut microbiome. (Pubmed Central) - May 6, 2020
In this study, we aim to examine the effect of Lactobacillus fermentum, Lactobacillus acidophilus and Lactobacillus rhamnosus on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer...Moreover, linear discriminant analysis scores revealed that Lactobacillus fermentum within phylum Firmicutes was the prominent species existing in the Lac.ferm-treated group. Overall, the above findings suggest that dietary Lac.ferm could modulate the gut microbial community, which might be beneficial to alleviating colon cancer progression.
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CELL TYPE CONTRIBUTIONS OF THE INTERLEUKIN 4 RECEPTOR TO COLONIC TUMORIGENESIS () - May 4, 2020 - Abstract #DDW2020DDW_6751;
In contrast, epithelial IL4Ra contributes to the outgrowth of colonic tumors. These data support our overarching idea that the type II receptor IL4 receptor, expressed by tumor epithelium, is a potential tumor target.
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LRIG1-BASED LINEAGE TRACING HAS DISTINCT PATTERNS WITHIN THE CONTEXT OF DSS COLITIS RECOVERY () - May 4, 2020 - Abstract #DDW2020DDW_6735;
Lrig1 persists as a marker of colonic stem cells during recovery from Dextran Sulfate Sodium (DSS)-induced colitis and can be used to understand how the colon is able to recover...Methods Utilizing Lrig1-Cre ERT2/+;R26R-YFP/+ mice, 3% DSS was administered for seven days and then a single intraperitoneal injection of tamoxifen (2mg/mL) was given at the end of treatment to induce Lrig1-based lineage contribution within the colonic crypt...In addition, there was an increase in isolated lineage traced cells throughout the crypts of recovering colons that are negative for Lrig1 protein and differentiation markers. These cells appear to be undergoing a change to their genetic program which we are addressing via single-cell RNA sequencing
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PROBIOTIC-DERIVED POLYPHOSPHATE IMPROVES DAMAGED INTESTINAL EPITHELIA THROUGH INDUCING PLATELET-DERIVED CELL GROWTH MOLECULES () - May 4, 2020 - Abstract #DDW2020DDW_6691;
In this study, we assessed the interaction of poly P and platelets in the models of dextran sulfate sodium (DSS)-induced colitis and epithelial wound healing...[Conclusion] Poly P induced the accumulation of platelets in inflammatory mucosa and the release of platelet-derived epithelial cell growth molecules, leading to improvement in epithelial injury in an in vivo intestinal inflammation model and an in vitro wound healing assay. This is a novel mechanism for the poly P-mediated upregulation of the intestinal barrier function in experimental models and possibly UC patients as well
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PARD6B REGULATES INTESTINAL BARRIER FUNCTION IN INFLAMMATORY BOWEL DISEASE () - May 4, 2020 - Abstract #DDW2020DDW_5993;
The small molecule inhibitor ameliorates DSS-induced colitis by reducing intestinal permeability. Targeting the intestinal barrier function for treatment of IBD has not yet been achieved.
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EPITHELIAL TLR4-SHAPED MICROBIOTA INCREASES SUSCEPTIBILITY TO TUMORIGENESIS () - May 4, 2020 - Abstract #DDW2020DDW_4121;
Furthermore, they suggest that increased epithelial redox activity does not play a direct pro-tumorigenic role, but instead might participate in modifying the microbial community. Our results suggest that overexpression of TLR4 during CRC contributes to dysbiosis and therefore facilitates tumor initiation and progression.
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PROTECTIVE EFFECT OF ALISMATIS RHIZOMA ON DEXTRAN SULFATE SODIUM-INDUCED COLITIS MICE MODEL () - May 4, 2020 - Abstract #DDW2020DDW_4070;
The current results suggest that AOE has protective effects against colitis in mice through inhibiting contraction of colon which is closely related to the symptom of diarrhea in colitis patients. Further investigation, including the exact mechanisms is needed.
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TUMOR NECROSIS FACTOR RECEPTOR 2 REGULATES COLON EPITHELIAL PATTERNING IN HOMEOSTASIS AND REPAIR () - May 4, 2020 - Abstract #DDW2020DDW_3989;
TNFR2 expression is induced in the colonic epithelium during injury and represents an adaptive change in response to an injury-specific microenvironment. The regulation of crypt structure by TNFR2 suggests a critical role for TNFR2 in colonic crypt patterning in homeostasis and repair
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CLONAL ARCHITECTURE OF EPITHELIAL STEM CELL REPROGRAMMING DURING COLONIC INJURY AND INFLAMMATION () - May 4, 2020 - Abstract #DDW2020DDW_3895;
Methods Mice were exposed to dextran sulfate sodium (DSS)-induced injury...To resolve structural changes to individual crypts during injury, we induced DSS injury 8 wks after tamoxifen initiation of clonal lineage tracing in Vil1::CreERT2;Rosa26::Confetti (Vil1-Confetti) mice...Conclusions Colonic epithelial cell dynamics in repair differ dramatically from homeostatic regeneration. Repair is associated with the rapid selection and expansion of a distinct stem cell population coupled to 3d remodeling of crypts
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Journal: Intestinal epithelial PKM2 serves as a safeguard against experimental colitis via activating β-catenin signaling. (Pubmed Central) - Apr 29, 2020
Similar reduction of intestinal epithelial PKM2 was observed in mice with dextran sulfate sodium-induced colitis...Increasing mouse intestinal epithelial PKM2 expression via delivery of a PKM2-expressing plasmid attenuated experimental colitis. In conclusion, our studies demonstrate that intestinal epithelial PKM2 increases cell survival and wound healing under the colitic condition via activating the Wnt/β-catenin signaling.
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Journal: Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction. (Pubmed Central) - Apr 29, 2020
In this study, we used a proteomics approach to explore the molecular intestinal response in two rhesus macaque (RM) animal models of experimentally induced colitis using dextran sulfate sodium (DSS) and simian immunodeficiency virus (SIV) infection...Proteomic signatures of barrier damage were apparent in both DSS treatment or SIV infection. These results demonstrate that DSS treatment in a non-human primate model resembles features of human ulcerative colitis, making this a promising tool to study important immunological mechanisms in inflammatory bowel disease.
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Journal: Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity. (Pubmed Central) - Apr 29, 2020
Cell permeable recombined fusion protein TAT-CRYAB was injected intraperitoneally into dextran sulfate sodium (DSS)- or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice to assess its anti-inflammatory effects...Consistently, administration of TAT-CRYAB fusion protein significantly alleviated DSS- or TNBS-induced colitis in mice and protected intestinal barrier integrity. CRYAB regulates inflammatory response in intestinal mucosa by inhibiting IKKβ-mediated signaling and may serve as a novel therapeutic approach in the treatment of IBD.
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Journal: Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2. (Pubmed Central) - Apr 28, 2020
The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS)...Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.
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Journal: TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis. (Pubmed Central) - Apr 28, 2020
Adipose tissue derived mesenchymal stem/stromal cell (ASC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice...Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) and polarizing macrophage from M1 to M2 in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs and macrophage polarization from M1 to M2 in the colon.
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Journal: Cav3.2 calcium channel inhibition: a new target for colonic hypersensitivity associated with low-grade inflammation. (Pubmed Central) - Apr 27, 2020
In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs and macrophage polarization from M1 to M2 in the colon. These results suggest that ethosuximide represents a promising drug reposition strategy and that Cav3.2 inhibition is an attractive therapeutic approach for relieving CHS in IBS or IBD.
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HY209 alleviates inflammation in colitis mice through NLRP3 inflammasome inhibition (Board Number: P1046) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_2456;
In here, we evaluated the therapy efficacy of HY209 in an acute colitis mice model which induced by using dextran sulfate sodium (DSS)...In vitro, HY209 showed a strong inhibition to LPS and ATP/BzATP activated NLRP3 inflammasome formation in the bone marrow derived macrophages (BMDMs). In summary, our findings demonstrated that HY209 alleviates inflammation in colitis mice through NLRP3 inflammasome inhibition, discovery the potential of HY209 as a therapeutic option for colitis.
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IL-17 promotes protective antibody during gut infection through IκB-ζ -dependent LN stromal cell activation (Board Number: P159) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1909;
We employed Dextran Sulfate Sodium (DSS) induced-colitis followed by Citrobacter rodentium infection model...RNAseq data suggest GC survival factors such as IL-6 and BAFF were increased by IL-17 signaling in FRCs. In conclusion, IL-17 indirectly promotes GC formation and antibody responses by inducing IκB-ζ expression in activated LN stromal cells during gut infection.
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Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal epithelial barrier (Board Number: P798) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1400;
The results showed that HS administration significantly inhibit weight loss and reduce inflammatory damage in dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC) mice model...Our results also indicated that HS administration reduce intestinal epithelial barrier permeability by decreasing the dextran concentrations in serum, inhibit dysbiotic Enterobacteriaceae expansion, increasing mucus secretion in the colonic lumen, and promoting the expression of intestinal interepithelial tight junction protein. Taken together, we identified the mechanism by which exogenous H2-improved “microbial hydrogen economy” regulates metabolic reprogramming of colonocyte through microbiota-activated PPAR-γ signaling pathway to provide colonic anaerobic environment, and reinforces intestinal epithelial barrier function, thereby promoting the recovery of intestinal homeostasis.
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B cells produce anti-inflammatory cytokine IL-27 in the gut upon induction by cyclic dinucleotides and to prevent murine colitis (Board Number: P810) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1389;
In mouse gut-associated lymphoid tissues and mesenteric lymph nodes, B cells were the primary source of IL-27 in homeostasis and upon induction by dextran sulfate sodium (DSS)-elicited intestinal injury...Furthermore, B cell-specific deficiency in IL-27 (but not IL-35) or STING in DSS-treated mice resulted in specific impairment in generating plasma cells and T-bet+NCR+ Group 3 innate lymphoid cells (ILC3s), reduced IgA secretion into the gut lumen and expression of anti-inflammatory IL-22 (and concomitant increase in pro-inflammatory IL-17, as produced by T-bet–NCR– ILC3s) and severe colitis-like symptoms. These, together with the ability of IL-27-producing B cells generated in vitro by cGAMP priming and CD154 stimulation to prevent lethality caused by sustained DSS treatment, show that B cells in the gut respond to immunoactive CDNs to induce IL-27 for the maintenance of intestinal homeostasis.
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Lymphotoxin-beta receptor expression by neutrophils prevents metabolic activation and colitis pathogenesis (Board Number: P790) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1387;
We have previously reported that a member of the TNF superfamily, TNFSF14 (LIGHT), and its interaction with the lymphotoxin beta receptor (LTβR), is required for preventing severe disease in a mouse model of dextran sulfate sodium (DSS) induced colitis...Interestingly, these increased levels of mitochondrial mass, ROS production and glycolytic activity persist in LtbrΔneut colonic neutrophils during DSS-induced colitis. In sum, our results demonstrate that neutrophil LTβR signaling plays a critical role in the immune activation associated with DSS-induced colitis.
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Toll-like receptor 7 protects against intestinal inflammation and restricts the development of tissue-resident memory CD8+ T cells (Board Number: P805) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1383;
Furthermore, Tlr7-/- mice were more susceptible to dextran sulfate sodium (DSS) colitis with more severe inflammation (Histoscore: WT: 7.6, Tlr7-/-: 12.7, p < 0.005), increased disease activity index (WT: 5.5, Tlr7-/-: 7.4, p < 0.05), and increased secretion of IFNg (WT: 5.2, Tlr7-/-: 24.2 ng/ml, p < 0.005) and TNFα (WT: 108.6, Tlr7-/-: 191.8 pg/ml, p < 0.05)...Our data shows that TLR7-deficiency promotes the development of LP Trm CD8+ T cells and increases susceptibility to DSS colitis. In conclusion, TLR7 plays an important role in maintaining immune response to intestinal viruses and protects against development of colitis.
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Schisandrin B and Alantolactone ameliorates experimental autoimmune encephalomyelitis in mice (Board Number: P1042) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_593;
Previous studies have revealed that both molecules impact STAT3, Nrf2 and Smad-mediated signaling pathways, and that Sch-B has protective effects in dextran sulfate sodium (DSS)-induced colitis models...Protection from disease correlated with elevated Treg and IL-10 levels. To our knowledge this is the first report demonstrating a prophylactic benefit for Sch B and ALT in a Multiple Sclerosis model and our results warrant further studies as to the use of both molecules after disease onset and mechanism of action.
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The role of JAML-CAR costimulation in gamma delta T cell-mediated repair of the intestinal epithelium (Board Number: P855) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_530;
Here we evaluated the role of JAML-CAR costimulation in the activation and function of γδ IELs using the dextran sulfate sodium (DSS) model of intestinal injury and repair...In addition, we found evidence of impaired γδ IEL production of IL-17, a cytokine known to protect against DSS-induced epithelial injury. Taken together our results suggest that JAML-CAR costimulation may be needed for the activation of tissue repair functions in γδ T cells across barrier tissues and supports targeting this pathway for therapeutic approaches for the acceleration of healing.
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Journal: Inhibition of LEF1-mediated DCLK1 by Niclosamide Attenuates Colorectal Cancer Stemness. (Pubmed Central) - Apr 22, 2020
Disruption of the LEF1/DCLK1-B axis by niclosamide eradicates cancer stemness and elicits therapeutic effects on CRC initiation, progression, and resistance. These findings provide a preclinical rationale to broaden the clinical evaluation of niclosamide for the treatment of CRC.
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Journal: JunB plays a crucial role in development of regulatory T cells by promoting IL-2 signaling. (Pubmed Central) - Apr 22, 2020
Here we show that mice lacking JunB in CD4 T cells (JunbCd4-Cre mice) were more susceptible to dextran sulfate sodium (DSS)-induced colitis because of impaired development of regulatory T (Treg) cells...Injection of IL-2-anti-IL-2 antibody complexes induced expansion of Treg cells and alleviated DSS-induced colitis in JunbCd4-Cre mice. Thus JunB plays a crucial role in the development of Treg cells by facilitating IL-2 signaling.
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