Baicalin modulates immuno-inflammatory response in patients with ulcerative colitis

Abstract Nigella A, also named Sieboldianoside A, has been extracted from many kinds of Traditional Chinese Medicine (TCM), such as Nigella glandulifera, Stauntonia chinensis DC., and the leaves of Acanthopanax sieboldianus. Nigella A exhibited potential analgesic, anti-inflammatory, anti-tumor, and antioxidant activities. However, whether Nigella A could treat ulcerative colitis (UC) is still unknown. As saponins always be regarded as the kinds of ingredients that could regulate immunity and intestinal flora. This research aimed to investigate the therapeutic effect of Nigella A on UC and explore its effect on intestinal flora. We noted that Nigella A and Sulfasalazine (SASP) could significantly improve the signs and symptoms, alleviate colonic pathological injury in DSS-induced mice. The changing of many specific bacterial genus such as Lactobacillus, Porphyromonadaceae, Bacteroides and Escherichia might closely related to the recovery of intestinal inflammatory response. This study initially confirmed the therapeutic effect of Nigella A and SASP on DSS-induced colitis by improving the diversity of intestinal microbial composition. Nigella A has the potential to be developed for the treatment of UC and other disorders related to the imbalance of intestinal flora.

Download Full-text

P013 The JAK-3 and TYK-2 / STAT pathways are activated in moderate to severe ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.142 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S136-S137

Author(s):

M Loza ◽

J M Brea ◽

C Calviño-Suarez ◽

I Baston-Rey ◽

R Ferreiro-Iglesias ◽

...

Keyword(s):

Ulcerative Colitis ◽

Animal Models ◽

Inflammatory Response ◽

Western Blot ◽

Signalling Pathways ◽

Target Engagement ◽

Inclusion Criteria ◽

Phosphorylated Proteins ◽

Single Centre Study ◽

Stat Pathway

Abstract Background Ulcerative colitis (UC) is a chronic, progressive and disabling disease with a complex pathology of unknown aetiology influenced by genetic, environmental and microbiota factors that lead to an immunological and inflammatory response in the colon. Janus Activated Kinase (JAK) family plays a key role in modulating the adaptive and innate inflammatory response. The JAK/STAT pathway involvement in UC has been demonstrated in both animal models and human studies. Thus, overexpressed JAK-3 has been detected in the intestine of patients with UC, suggesting a key role in their pathophysiology and the inhibition of TYK-2 in animal models resulted in an improvement of the disease, which would explain its implication in the inflammatory process. We hypothesise here that there could be an activation of JAK-3 and TYK-2 signalling pathways in UC patients. Thus, we aimed to detect the activation of both signalling pathways by means of western-blot studies in UC patient samples Methods A prospective, observational single-centre study was designed. Inclusion criteria were adult patients with endoscopic active UC (more than Mayo-0) confirmed in a programmed colonoscopy. All patients signed informed consent. Samples were obtained from overstock of routine biopsies in the more severe segment affected of the large bowel. Tissues were homogenised and processed in order to obtain cell lysates by employing RIPA buffer and ultrasounds. The degree of activation of the JAK-3 and TYK-2 pathways was measured by detecting the phosphorylation of both targets as well as of STAT1, STAT3, STAT4, STAT5 and STAT6 through western blot by employing specific antibodies for total and phosphorylated proteins. Results 19 UC patients were consecutively included. Mean age was 46 years old. 53% were female, 47% were extensive colitis (E3) and 53% left-side colitis (E2). Regarding endoscopic activity, 26% had Mayo-1, 53% Mayo-2, and 21% Mayo-3. Immunoreactive bands for both phosphorylated JAK-3 and TYK-2 were detected in the biopsies from UC patients, evidencing that colonic inflammation leads to an activation of both targets. The study of STATs phosphorylation showed immunoreactive bands for phosphorylated forms of STAT1, STAT3, STAT4, STAT5 and STAT6 confirming the activation of both signalling-pathways in these patients (Figure 1). Conclusion The developed translational workflows involving basic/clinical research confirm the activation of both JAK-3 and TYK-2-dependent signalling pathways in UC patients, validating both kinases as targets for treating UC. The developed methodology allows studying the target engagement for future JAK-3/ TYK-2 inhibitors employed in clinical trials.

Download Full-text

IL-8 and LYPD8 expression levels are associated with the inflammatory response in the colon of patients with ulcerative colitis

Biomedical Reports ◽

10.3892/br.2020.1280 ◽

2020 ◽

Author(s):

Tomoyuki Okada ◽

Tsutomu Kanda ◽

Naoki Ueda ◽

Yuichiro Ikebuchi ◽

Keiichi Hashiguchi ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Response ◽

Expression Levels

Download Full-text

Investigation of Potential Genetic Biomarkers and Molecular Mechanism of Ulcerative Colitis Utilizing Bioinformatics Analysis

10.21203/rs.2.13329/v1 ◽

2019 ◽

Author(s):

Jiaqi Zhang ◽

Xue Wang ◽

Lin Xu ◽

Zedan Zhang ◽

Fengyun Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gene Therapy ◽

Inflammatory Response ◽

Signaling Pathway ◽

Functional Enrichment ◽

Hub Genes ◽

Amyloid A ◽

Chemokine Signaling ◽

Chemokine Signaling Pathway ◽

Potential Biomarkers

Abstract Objectives: To reveal the molecular mechanisms of ulcerative colitis (UC) and provide potential biomarkers for UC gene therapy. Methods: We downloaded the GSE87473 microarray dataset from the Gene Expression Omnibus (GEO) and identified the differentially expressed genes (DEGs) between UC samples and normal samples. Then ,a module partition analysis was performed based on a weighted gene co-expression network analysis (WGCNA),followed by pathway and functional enrichment analyses. Furthermore, we investigated the hub genes . At last, data validation was performed to ensure the reliability of the hub genes. Results: Between UC group and normal group, 988 DEGs were investigated . The DEGs were clustered into 5 modules using WGCNA. These DEGs were mainly enriched in functions such as the immune response, the inflammatory response and chemotaxis, and they were mainly enriched in KEGG pathways such as the cytokine-cytokine receptor interaction , chemokine signaling pathway, and complement and coagulation cascades. The hub genes, including dual oxidase maturation factor 2(DUOXA2), serum amyloid A (SAA) 1 and SAA2, TNFAIP3-interacting protein 3(TNIP3), C-X-C motif chemokine (CXCL1), solute carrier family 6 member 14(SLC6A14) and complement decay-accelerating factor (CD antigen CD55),were revealed as potential tissue biomarkers for UC diagnosis or treatment. Conclusions: This study provides supportive evidence that DUOXA2, A-SAA, TNIP3, CXCL1, SLC6A14 and CD55 might be used as potential biomarkers for tissue biopsy of UC, especially SLC6A14 and CD55, which may be new targets for UC gene therapy. Moreover, the DUOX2/DUOXA2, NF-κB /TNIP3 and CXCL1/CXCR2 pathways might play an important role in the progression of UC through the chemokine signaling pathway and inflammatory response.

Download Full-text