Therapeutic Effect of Ribbon-Type Nuclear Factor-&amp;kappa;B Decoy Oligonucleotides in a Rat Model of Inflammatory Bowel Disease

Ozaki, Kohei; Makino, Hírofumi; Aoki, Motokuni; Miyake, Takashi; Yasumasa, Natsuki; Osako, Mariana Kiomy; Nakagami, Hironori; Rakugi, Hiromi; Morishita, Ryuichi

doi:10.2174/156652312803519814

Cited by 17 publications

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“…On the other hand, those belonging to the groups that received water with DSS addition (4%) exhibited weight loss and / or altered stool consistency (loose stool and diarrhea), and / or presence of occult blood in the stool and apparent blood from the third day of induction. These results are consistent with other authors who had used the same method of induction [16,18,54,55]. …”

Section: Resultssupporting

confidence: 93%

Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis

et al. 2017

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BackgroundSome probiotic strains have the potential to assist in relieving the symptoms of inflammatory bowel disease. The impact of daily ingestion of a soy-based product fermented by Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 with the addition of Bifidobacterium longum ATCC 15707 on chemically induced colitis has been investigated thereof within a period of 30 days.MethodsColitis was induced by dextran sulfate sodium. The animals were randomly assigned into five groups: Group C: negative control; Group CL: positive control; Group CLF: DSS with the fermented product; Group CLP: DSS with the non-fermented product (placebo); Group CLS: DSS with sulfasalazine. The following parameters were monitored: disease activity index, fecal microbial analyses, gastrointestinal survival of probiotic microorganisms and short-chain fatty acids concentration in the feces. At the end of the protocol the animals’ colons were removed so as to conduct a macroscopical and histopathological analysis, cytokines and nitrite quantification.ResultsAnimals belonging to the CLF group showed fewer symptoms of colitis during the induction period and a lower degree of inflammation and ulceration in their colon compared to the CL, CLS and CLP groups (p<0.05). The colon of the animals in groups CL and CLS presented severe crypt damage, which was absent in CLF and CLP groups. A significant increase in the population of Lactobacillus spp. and Bifidobacterium spp. at the end of the protocol was verified only in the CLF animals (p<0.05). This group also showed an increase in short-chain fatty acids (propionate and acetate). Furthermore, the intestinal survival of E. faecium CRL 183 and B. longum ATCC 15707 in the CLF group has been confirmed by biochemical and molecular analyzes.ConclusionsThe obtained results suggest that a regular intake of the probiotic product, and placebo to a lesser extent, can reduce the severity of DSS-induced colitis on rats.

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Section: Resultssupporting

confidence: 93%

Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis

et al. 2017

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“…Becaue synthesized decoy ODNs for HIF‐1 contain the consensus core sequence of the HRE, transfected decoy ODNs bind to free HIF‐1, resulting in blockade of the binding of HIF‐1 to the promoter regions and suppression of transcriptional activity. Moreover, in the present study, we employed ribbon‐type decoy ODNs (Figure ), which we developed to increase stability in vivo and resistance to nuclease compared to conventional double‐stranded decoy ODNs . Although double‐stranded decoy ODNs were reported to have therapeutic potential for various diseases, we chose ribbon‐type decoy ODNs as a tool for the suppression of transcriptional activity of HIF‐1 because of their potency and improved stability in vivo , aiming to demonstrate precisely the effect of suppressing HIF‐1 activation and to confirm our hypothesis.…”

Section: Introductionmentioning

confidence: 79%

Therapeutic effect of intra‐articular injection of ribbon‐type decoy oligonucleotides for hypoxia inducible factor‐1 on joint contracture in an immobilized knee animal model

Sotobayashi

Kawahata

Anada

et al. 2016

The Journal of Gene Medicine

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“…However, recent developments have increased their stability and made them more nuclease-resistant. Administration of an NFKB decoy oligonucleotide in rats limited the expression of proinflammatory pathways and showed increased survival rate on inducing DSS-induced colitis 131. Another NFKB inhibitor, dehydroxymethylepoxyquinomicin, blocks the nuclear translocation of NFKB and ameliorated experimental TNBS-induced and DSS-induced colitis in mice 132.…”

Section: Dres As Therapeutic Targetsmentioning

confidence: 99%

Non-coding DNA in IBD: from sequence variation in DNA regulatory elements to novel therapeutic potential

Meddens

List

Nieuwenhuis

et al. 2019

Gut

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Genome-wide association studies have identified over 200 loci associated with IBD. We and others have recently shown that, in addition to variants in protein-coding genes, the majority of the associated loci are related to DNA regulatory elements (DREs). These findings add a dimension to the already complex genetic background of IBD. In this review we summarise the existing evidence on the role of DREs in IBD. We discuss how epigenetic research can be used in candidate gene approaches that take non-coding variants into account and can help to pinpoint the essential pathways and cell types in the pathogenesis of IBD. Despite the increased level of genetic complexity, these findings can contribute to novel therapeutic options that target transcription factor binding and enhancer activity. Finally, we summarise the future directions and challenges of this emerging field.

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Therapeutic Effect of Ribbon-Type Nuclear Factor-κB Decoy Oligonucleotides in a Rat Model of Inflammatory Bowel Disease

Abstract: These data suggest that intracolonic administration of R-ODN may be effective to treat DSS-induced colitis.

Cited by 17 publications

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Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis

Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis

Therapeutic effect of intra‐articular injection of ribbon‐type decoy oligonucleotides for hypoxia inducible factor‐1 on joint contracture in an immobilized knee animal model

Non-coding DNA in IBD: from sequence variation in DNA regulatory elements to novel therapeutic potential

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