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Journal: Quercetin Alleviates Intestinal Oxidative Damage Induced by HO via Modulation of GSH: In Vitro Screening and In Vivo Evaluation in a Colitis Model of Mice. (Pubmed Central) - Apr 21, 2020
Furthermore, quercetin ameliorated dextran sulfate sodium salt (DSS)-induced colitis and further increased the serum GSH...Increased extracellular HO concentration induced by quercetin under oxidative stress was related to the inhibition of AQP3 and upregulation of NOX1/2, which may contribute to the observed protective effects of quercetin. Moreover, the novel HO-induced oxidative stress cell model based on the real-time cellular analysis system was an effective model to screen natural products to deal with intestinal oxidative damage and help accelerate the discovery of new drugs for inflammatory bowel disease (IBD).
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Biomarker, Journal, IO Biomarker: Estrogen receptor β activation ameliorates DSS-induced chronic colitis by inhibiting inflammation and promoting Treg differentiation. (Pubmed Central) - Apr 19, 2020
This study aimed to assess the clinical value of ERβCD4 T cells in IBD patients and examine the anti-inflammatory role of ERβ activation in dextran sulfate sodium (DSS)-induced chronic colitis in mice...In vitro, we found that ERβ activation enhanced Treg differentiation, immunosuppression, and TGF-β1/Smad signaling in CD4 T cells. Our data suggest that ERβCD4 T cells represent a potential biomarker for evaluating IBD disease severity, and ERβ activation may be valuable for the treatment of IBD by enhancing the Treg response.
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Preclinical, Journal, IO Biomarker: Obacunone Protects Against Ulcerative Colitis in Mice by Modulating Gut Microbiota, Attenuating TLR4/NF-κB Signaling Cascades, and Improving Disrupted Epithelial Barriers. (Pubmed Central) - Apr 17, 2020
We found that obacunone efficiently alleviated the severity of dextran sulfate sodium (DSS)-induced mouse UC by modulating the abnormal composition of the gut microbiota and attenuating the excessive activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling...However, obacunone promoted the expression of tight junction proteins (TJP1 and occludin) and repressed the activation of inflammatory signaling cascades. In summary, our findings demonstrated that obacunone attenuated the symptoms of experimental UC in mice through modulation of the gut microbiota, attenuation of TLR4/NF-κB signaling cascades, and restoration of intestinal epithelial barrier integrity.
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Journal: Orally Delivered Antisense Oligodeoxyribonucleotides of TNF-α via Polysaccharide-Based Nanocomposites Targeting Intestinal Inflammation. (Pubmed Central) - Apr 16, 2020
The nanocomposites carried by the CA hydrogel with the loading amount of 83.5% are then orally administered and specifically released to the inflamed intestine, followed by internalization into intestinal cells such as macrophages, to reduce TNF-α production by 36.4% and dextran sulfate sodium-induced inflammation by decreasing myeloperoxidase and malondialdehyde. This study defines a new strategy for the oral delivery of antisense oligonucleotides to attenuate inflammatory response, demonstrating a notable potential for clinical applications in intestine-inflammation-targeted therapy.
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Journal: Protein tyrosine phosphatase non-receptor type 22 modulates colitis in a microbiota-dependent manner. (Pubmed Central) - Apr 14, 2020
Here, we demonstrate that mice carrying the PTPN22 variant (619W mice) were protected from acute dextran sulfate sodium (DSS) colitis, but suffered from pronounced inflammation upon chronic DSS treatment...Transfer of microbiota from 619W mice after the first DSS cycle into treatment-naive 619W mice promoted colitis, indicating that changes in microbial composition enhanced chronic colitis in those animals. This indicates that presence of the PTPN22 variant affects intestinal inflammation by modulating the host's response to the intestinal microbiota.
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Journal: IRW and IQW Reduce Colitis-Associated Cancer Risk by Alleviating DSS-Induced Colonic Inflammation. (Pubmed Central) - Apr 14, 2020
The colitis model of mice was induced by dextran sulfate sodium (DSS)...No other significant effects were observed. The present study demonstrated that intracolic administration of IRW and IQW might be a novel option for preventing inflammatory bowel disease via regulating the level of serum amino acid and enhancing the intestinal immune defense.
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Journal: Deficiency in intestinal epithelial Reg4 ameliorates intestinal inflammation and alters the colonic bacterial composition. (Pubmed Central) - Apr 12, 2020
In the current study, the functional roles and involved mechanisms of intestinal epithelial Reg4 in intestinal inflammation were studied in healthy and inflamed states using human intestinal specimens, an intestinal conditional Reg4 knockout mouse (Reg4) model and dextran sulfate sodium (DSS)-induced colitis model...In vitro, Reg4 was showed to promote the growth of colonic organoids, and that this occurs through a mechanism involving activation of signal transducer and activator of transcription 3 (STAT3). In conclusion, our findings demonstrated intestinal-epithelial Reg4 deficiency protects against experimental colitis and mucosal injury via a mechanism involving alteration of bacterial homeostasis and STAT3 activation.
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Preclinical, Journal: OGG1 deficiency alters the intestinal microbiome and increases intestinal inflammation in a mouse model. (Pubmed Central) - Apr 12, 2020
Taken together, these data indicate that in addition to their proclivity to obesity and metabolic disease, Ogg1-/- mice are prone to colonic inflammation. Further, these data point to alterations in the intestinal microbiome as potential mediators of the metabolic and intestinal inflammatory response in Ogg1-/- mice.
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Journal: VSIG4 mediates transcriptional inhibition of Nlrp3 and Il-1β in macrophages. (Pubmed Central) - Apr 10, 2020
The agonistic VSIG4 antibodies (VG11), acting through NLRP3 and IL-1β suppression, show significant therapeutic efficacy in mouse EAE. These findings highlight VSIG4 as a prospective target for treating NLRP3-associated inflammatory disorders.
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Clinical, Journal: Promising Anti-diabetic Effect of Dextran Sulfate Sodium: Is It its Clinical Come Back? (Pubmed Central) - Apr 10, 2020
Clinical studies showed that dextran sulfate sodium (DSS) alleviates stroke, diabetic retinopathy and hypercholesterolemia, yet its mechanism of action was unrevealed. This study show that DSS reduces hyperglycemia, plasma insulin and enhances glucose utilization by attenuating ROS production, suggesting a novel therapeutic use of DSS in diabetes and its complication.
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Journal: Acetylcholine-producing T-cells augment innate immune driven colitis but are redundant in T-cell driven colitis. (Pubmed Central) - Apr 10, 2020
Together, our results indicate that ChATT-cells aggravate the acute innate immune response upon mucosal barrier disruption in an acute DSS-induced colitis model, while they are supporting the later resolution process of this innate immune driven colitis. Surprisingly, ChAT expression in T-cells seems redundant in the context of T-cell driven colitis.
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Preclinical, Journal: Chitosan Ameliorates DSS-Induced Ulcerative Colitis Mice by Enhancing Intestinal Barrier Function and Improving Microflora. (Pubmed Central) - Apr 10, 2020
The present work aimed to investigate the effect of chitosan (CS) on intestinal microflora and intestinal barrier function in dextran sulfate sodium (DSS)-induced UC mice and to explore the underlying mechanisms...This is the first time that the effect of original CS against UC in mice has been reported and it is through promoting dominant intestinal microflora such as Blautia, mitigating intestinal microflora dysbiosis, and regulating the expressions of TNF-α, claudin-1, occludin, and ZO-1. CS can be developed as an effective food and health care product for the prevention and treatment of UC.
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Journal: Hypothalamic paraventricular nucleus neurons activated by estrogen GPER1 receptors promote anti-inflammation effects in the early stage of colitis. (Pubmed Central) - Apr 10, 2020
In this study, we used the dextran sulfate sodium (DSS)-induced mice colitis model, gene editing, and RNA interference to determine the effects of PVN neurons on intestinal inflammation...The colitis noticeably worsened in GPER1-knockout mice and local PVN GPER1-knockdown mice. These results indicated that PVN GPER1 positive neurons potentially have a protective function during the early stages of DSS-induced colitis, and this may be a mechanism by which the central nervous system attempts to suppress intestinal inflammation to achieve self-protection.
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Preclinical, Journal: Effect of dehydroepiandrosterone on the immune response and gut microbiota in dextran sulfate sodium-induced colitis mice. (Pubmed Central) - Apr 10, 2020
The 16S rDNA gene sequencing demonstrated that DHEA decreased the Pseudomonas abundance in DSS-induced colitis mice. In conclusion, our data demonstrated that DHEA reduces oxidative damage through regulating antioxidant enzyme activity; inhibits pro-inflammatory cytokines production by blocking the activation of p38 MAPK and NF-κB signal pathway; protects colon barrier integrity via increasing tight junction protein expression and modulating gut microbiota taxa; all that finally alleviates DSS-induced experimental colitis in mice.
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Preclinical, Journal: The Ventrolateral Periaqueductal Gray Contributes to Depressive-Like Behaviors in Recovery of Inflammatory Bowel Disease Rat Model. (Pubmed Central) - Apr 9, 2020
We used dextran sulfate sodium (DSS)-induced visceral pain model to evoke depression-like behaviors, assessed by tail suspension test (TST) and sucrose preference test (SPT), and electrophysiological recordings from vlPAG...Furthermore, intra-vlPAG application of AMPA and AMPA receptor-mediated antidepressant (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] reversed the DSS-induced depression-like behaviors in the remission phase of visceral abnormalities. Our results suggest that vlPAG glutamatergic transmission mediates depression-like behaviors during remission of DSS-induced visceral pain, suggesting that vlPAG mapping to the gut-brain axis contributes to depression during remission of IBD.
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Journal: Effects of Genetic and Pharmacologic Inhibition of COX-2 on Colitis-associated Carcinogenesis in Mice. (Pubmed Central) - Apr 9, 2020
In the COX-2 null (COX-2 ) mice, there was about 30% reduction in the incidence of colon tumors, and the tumor multiplicity was also markedly reduced (7.7 ± 2.5 vs. 2.43 ± 1.4, P < 0.01). As both pharmacologic inhibition and genetic ablation of COX-2 gene could not completely suppress colon tumor formation following treatment with AOM and DSS, it is speculated that other pro-inflammatory mediators, including COX-1 and iNOS, should be additionally targeted to prevent inflammation-associated colon carcinogenesis.
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Trial completion date, Trial primary completion date: A Safety and Tolerability Study of ILB in Patients With Amyothrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - Apr 8, 2020
P2, N=15, Recruiting,
As both pharmacologic inhibition and genetic ablation of COX-2 gene could not completely suppress colon tumor formation following treatment with AOM and DSS, it is speculated that other pro-inflammatory mediators, including COX-1 and iNOS, should be additionally targeted to prevent inflammation-associated colon carcinogenesis. Trial completion date: Mar 2020 --> Apr 2021 | Trial primary completion date: Mar 2020 --> Apr 2021
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Review, Journal: ROLE OF BIOACTIVE LIPOFISHINS IN PREVENTION OF INFLAMMATION AND COLON CANCER. (Pubmed Central) - Apr 5, 2020
Preliminary data in a limited number of cases indicate that about 50% of the patients showed a reduction in the levels of tumor markers (TM), and this response was much more evident in patients with cancer, when TM values are over normal range. Finally all the above mentioned results suggest that diet has a major role in controlling inflammation and thereby plays an important role in the development or prevention of various chronic diseases, hence public health steps should be taken to modify individual's whole diet and promote the intake of specific natural compounds.
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Journal: Indigo Naturalis Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating the Intestinal Microbiota Community. (Pubmed Central) - Apr 4, 2020
The therapeutic effect of IN may be closely related to the anaerobic gram-positive bacteria of Turicibacter and Peptococcus. The inferred metagenomes from 16S data using PICRUSt demonstrated that decreased metabolic genes, such as through biosynthesis of siderophore group nonribosomal peptides, non-homologous end-joining, and glycosphingolipid biosynthesis of lacto and neolacto series, may maintain microbiota homeostasis during inflammation from IN treatment in DSS-induced colitis.
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Preclinical, Journal: Elevated ER stress exacerbates dextran sulfate sodium-induced colitis in PRDX4-knockout mice. (Pubmed Central) - Mar 29, 2020
Because PRDX4 functions as an ER thiol oxidase as well as an antioxidant, DSS induced oxidative damage and ER stress to a greater degree in PRDX4 than WT mice. These findings suggest that PRDX4 may represent a novel therapeutic molecule in intestinal inflammation.
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Journal: Heterozygous knockout insulin-like growth factor-1 receptor (IGF-1R) regulates mitochondrial functions and prevents colitis and colorectal cancer. (Pubmed Central) - Mar 29, 2020
Heterozygous knockout IGF-1R attenuated azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and colitis associated cancer (CAC) in Igf1r mice...Further analysis suggests the protection mechanisms of Igf1r cells from oxidative stress through the activation of the mitochondrial respiratory chain and LKB1/AMPK pathways. These results highlight the biological roles of IGF-1R at the nexus between oxidative damage and mitochondrial function and a connection between colitis and colorectal cancer.
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Journal: RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis. (Pubmed Central) - Mar 29, 2020
RORα mice exhibit excessive intestinal inflammation and highly activated inflammatory responses in the dextran sulfate sodium (DSS) mouse colitis model...Chromatin immunoprecipitation analysis reveals corecruitment of RORα and histone deacetylase 3 (HDAC3) on NF-κB target promoters and subsequent dismissal of CREB binding protein (CBP) and bromodomain-containing protein 4 (BRD4) for transcriptional repression. Together, we demonstrate that RORα/HDAC3-mediated attenuation of NF-κB signaling controls the balance of inflammatory responses, and therapeutic strategies targeting this epigenetic regulation could be beneficial to the treatment of chronic inflammatory diseases, including inflammatory bowel disease (IBD).
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Preclinical, Journal: The efficacy of conditioned medium released by tonsil-derived mesenchymal stem cells in a chronic murine colitis model. (Pubmed Central) - Mar 26, 2020
The aim of this study was to verify the therapeutic effect of conditioned medium (CM) released by TMSC (TMSC-CM) in a mouse model of dextran sulfate sodium (DSS)-induced chronic colitis...TMSC-CM showed an equivalent effect to TMSC related to the improvement of inflammation in the chronic colitis mouse model. The data obtained support the use of TMSC-CM to treat inflammatory bowel disease without any cell transplantation.
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Journal: Krill Oil-Incorporated Liposomes As An Effective Nanovehicle To Ameliorate The Inflammatory Responses Of DSS-Induced Colitis. (Pubmed Central) - Mar 24, 2020
In mice subjected to dextran sulfate sodium-induced colitis, oral administration of BDS-entrapped KO liposomes suppressed tumor necrosis factor-α production (by 84.1%), interleukin-6 production (by 35.3%), and the systemic level of endotoxin (by 96.8%), and slightly reduced the macroscopic signs of the disease. Taken together, KO liposomes may have great potential as a nanovehicle for oral delivery of IBD drugs.
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Journal: Sesamin Enhances Nrf2-Mediated Protective Defense against Oxidative Stress and Inflammation in Colitis via AKT and ERK Activation. (Pubmed Central) - Mar 22, 2020
Furthermore, SSM displayed a better protective effect against dextran sulfate sodium- (DSS-) induced UC compared with 5-aminosalicylic acid (5-ASA) in C57BL/6 mice...These results first demonstrate the protective effect of SSM against UC and indicate that the effect is associated with AKT/ERK activation and subsequent Nrf2 signaling enhancement. This study provides a new insight into the medicinal value of SSM and proposes it as a new natural nutrition for better managing the symptoms of UC.
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Journal, IO Biomarker: Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis. (Pubmed Central) - Mar 18, 2020
DSS + MC-LR also resulted in greater increases in pro-inflammatory transcripts within colonic tissue (TNF-α, IL-1β, CD40, MCP-1) and the pro-fibrotic marker, PAI-1, as compared to DSS-only ingestion. These findings demonstrate that MC-LR exposure not only prolongs, but also worsens the severity of pre-existing colitis, strengthening evidence of MC-LR as an under-recognized environmental toxin in vulnerable populations, such as those with IBD.
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Preclinical, Journal: Dietary Tricin Suppresses Inflammation-Related Colon Carcinogenesis in Mice. (Pubmed Central) - Mar 17, 2020
This study was designed to determine whether dietary tricin exerts inflammation-associated colon carcinogenesis induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in mice...Tricin feeding significantly suppressed the TNF-α expression in the normal appearing crypts. Our findings may suggest a potential use of tricin for clinical trials of colorectal cancer chemoprevention in the inflamed colon.
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Preclinical, Journal: Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo. (Pubmed Central) - Mar 17, 2020
Furthermore, intestinal epithelial cell (IEC)-specific loss of CD47 does not induce spontaneous immune-mediated intestinal barrier disruption but results in defective mucosal repair after biopsy-induced colonic wounding or Dextran Sulfate Sodium (DSS)-induced mucosal damage...Defective wound repair after CD47 loss is linked to decreased epithelial β1 integrin and focal adhesion signaling, as well as reduced thrombospondin-1 and TGF-β1. These results demonstrate a critical role for IEC-expressed CD47 in regulating mucosal repair and raise important considerations for possible alterations in wound healing secondary to therapeutic targeting of CD47.
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Scavenger Receptor-Mediated Uptake of DNAZyme-Gold Nanoparticle Conjugates in Alveolar Macrophages Using Two Photon Microscopy Analysis (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area C) - Mar 15, 2020 - Abstract #ATS2020ATS_6044;
DzNP uptake in alveolar macrophages is dose dependent with a Poisson distribution and is mediated by scavenger receptors. With spectral resolution around 170 nm, spacial localization of DzNP within the cell is possible with relative precision without the need for fluorescent labeling, thus offering greater optical versatility when fluorescent labeling is necessary to visualize other proteins or organelles of interest.
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