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Li T, Hu G, Fu S, Qin D, Song Z. Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway. Microbiol Spectr 2025; 13:e0200624. [PMID: 39699220 PMCID: PMC11792488 DOI: 10.1128/spectrum.02006-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 10/29/2024] [Indexed: 12/20/2024] Open
Abstract
Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.
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Affiliation(s)
- Tong Li
- College of Veterinary Medicine, Jilin University, changchun, China
| | - Guiqiu Hu
- College of Veterinary Medicine, Jilin University, changchun, China
| | - Shoupeng Fu
- College of Veterinary Medicine, Jilin University, changchun, China
| | - Di Qin
- College of Animal Science and Technology, Jilin University, changchun, China
| | - Zheyu Song
- Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, changchun, China
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Bianchi R, Mamadou-Pathé B, von Känel R, Roth R, Schreiner P, Rossel JB, Burk S, Dora B, Kloth P, Rickenbacher A, Turina M, Greuter T, Misselwitz B, Scharl M, Rogler G, Biedermann L, on behalf of the or the Swiss IBD cohort study. Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD cohort study patients. PLoS One 2022; 17:e0274665. [PMID: 36112586 PMCID: PMC9481029 DOI: 10.1371/journal.pone.0274665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 09/01/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity. METHODS We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design. RESULTS Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients. CONCLUSION As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.
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Affiliation(s)
- Rahel Bianchi
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Barry Mamadou-Pathé
- Department of Epidemiology and Health System, Unisanté, Lausanne, Switzerland
| | - Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, Zurich, Switzerland
| | - René Roth
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Internal Medicine, Limmattalspital, Schlieren, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Jean-Benoit Rossel
- Department of Epidemiology and Health System, Unisanté, Lausanne, Switzerland
| | - Sabine Burk
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Babara Dora
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Patrizia Kloth
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Andreas Rickenbacher
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Matthias Turina
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Gastroenterology and Hepatology, CHUV, Lausanne, Switzerland
| | - Benjamin Misselwitz
- Department of Visceral Medicine, University Hospital Bern, Bern, Switzerland
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Ito A, Murasugi S, Omori T, Nakamura S, Tokushige K. Relationship between mucosal healing by tacrolimus and relapse of refractory ulcerative colitis: a retrospective study. BMC Gastroenterol 2020; 20:203. [PMID: 32590945 PMCID: PMC7320561 DOI: 10.1186/s12876-020-01317-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 05/22/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Tacrolimus (TAC) is a powerful remission-inducing drug for refractory ulcerative colitis (UC). However, it is unclear whether mucosal healing (MH) influences relapse after completion of TAC.We investigated whether MH is related to relapse after TAC. PATIENTS Among 109 patients treated with TAC, 86 patients achieved clinical remission and 55 of them underwent colonoscopy at the end of TAC. These 55 patients were investigated. METHODS Patients with MH at the end of TAC were classified into the MH group (n = 41), while patients without MH were classified into the non-MH group (n = 14). These groups were compared with respect to 1) clinical characteristics before treatment, 2) clinical characteristics on completion of treatment, and 3) the relapse rate and adverse events rates. This is a retrospective study conducted at a single institution. RESULTS 1) There was a significant difference in baseline age between the two groups before TAC therapy, but there were no significant differences in other clinical characteristics. The NMH group was younger (MH group: 48.1 (23-79) years, NMH group: 36.3 (18-58) years, P = 0.007). Endoscopic scores showed significant differences between the 2 groups at the end of TAC. There were also significant differences in the steroid-free rate after 24 weeks (MH group: 85.3%, NMH group 50%, P = 0.012). There was no significant difference in the relapse rate between the 2 groups at 100 days after remission, but a significant difference was noted at 300 days (17% vs. 43%), 500 days (17% vs. 75%), and 1000 days (17% vs. 81%) (all P < 0.05). CONCLUSIONS TAC is effective for refractory ulcerative colitis. However, even if clinical remission is achieved, relapse is frequent when colonoscopy shows that MH has not been achieved. It is important to evaluate the mucosal response by colonoscopy on completion of TAC.
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Affiliation(s)
- Ayumi Ito
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Syun Murasugi
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Teppei Omori
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Shinichi Nakamura
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Katsutoshi Tokushige
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
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Khan N, Patel D, Shah Y, Lichtenstein G, Yang YX. A Novel User-Friendly Model to Predict Corticosteroid Utilization in Newly Diagnosed Patients with Ulcerative Colitis. Inflamm Bowel Dis 2017; 23:991-997. [PMID: 28328623 DOI: 10.1097/mib.0000000000001080] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Corticosteroid (CS) use is an important marker of poor prognosis in ulcerative colitis (UC). Our aim was to develop and validate a model to predict the risk of CS utilization over the course of disease in newly diagnosed patients with UC. METHODS Newly diagnosed patients with UC from a nationwide VA cohort were followed over time to evaluate factors predictive of CS use. Multivariate logistic regression was performed. Model development was performed in a random 2/3 of the total cohort and then validated in the remaining 1/3. The primary outcome was the use of CS for the management of UC. Candidate predictors included routinely available data at the time of UC diagnosis, including demographics, laboratory results, and index colonoscopy findings. RESULTS Six hundred ninety-nine eligible patients with UC were followed for a median duration of 8 years. Two hundred eighty-eight patients (41.2%) required CS use for the management of UC. Key predictors for CS utilization selected for the model were as follows: age, non-African American ethnicity, presence of hypoalbuminemia, and iron-deficiency anemia at the time of UC diagnosis, endoscopic extent, or severity of disease at index colonoscopy. Model discrimination was good (area under the receiver operator curve 0.71 [95% confidence interval, 0.66-0.76] for the model including baseline UC extent and 0.71 [95% confidence interval, 0.67-0.76]) for the model including baseline UC severity. Model calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit P > 0.05). The models performed similarly in the internal validation cohort. CONCLUSIONS We developed and internally validated a novel prognostic model to predict CS use among patients with newly diagnosed UC.
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Affiliation(s)
- Nabeel Khan
- *Section of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; †Section of Gastroenterology, VA Medical Center, Philadelphia, Pennsylvania; and ‡Department of Internal Medicine, Mercy Catholic Medical Center, Darby, Pennsylvania
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Mei WQ, Hu HZ, Liu Y, Li ZC, Wang WG. Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis. World J Gastroenterol 2015; 21:6044-6051. [PMID: 26019471 PMCID: PMC4438041 DOI: 10.3748/wjg.v21.i19.6044] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 11/25/2014] [Accepted: 12/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC).
METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators.
RESULTS: The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety.
CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.
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Khan NH, Almukhtar RM, Cole EB, Abbas AM. Early corticosteroids requirement after the diagnosis of ulcerative colitis diagnosis can predict a more severe long-term course of the disease - a nationwide study of 1035 patients. Aliment Pharmacol Ther 2014; 40:374-81. [PMID: 24961751 DOI: 10.1111/apt.12834] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Revised: 07/15/2013] [Accepted: 05/22/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND There are limited data regarding clinical outcomes in ulcerative colitis (UC) patients who require early corticosteroids (CS) use. AIM To evaluate the rate of early CS utilisation (within 30 days of diagnosis) as a predictive marker for long-term outcomes, colectomy and CS dependency, in a population-based cohort of incident UC cases. METHODS Nationwide data were obtained from the Veterans Affairs (VA) health care system for the period 2001-2011. Incident UC cases were identified. A retrospective cohort design and time-to-event survival analysis were used to track outcomes of interest. Cox regression multivariate analysis was employed. RESULTS One thousand and thirty-five newly diagnosed patients with UC were identified and included in the analysis; 236 (23%) of those patients required early CS therapy. Patients were followed-up over a median time of 4.7 years (IQR 2.8-6.8) after UC diagnosis. The 5-year cumulative probability of requiring colectomy varied significantly by early CS use status (13% among early CS users compared to 4% among those who did not require early CS treatment, P < 0.001). Similar variation in the 5-year cumulative probability of CS dependency by early CS status was observed. Early CS users were more likely to require colectomy 2.9 (CI 1.7-5.0, P < 0.001) and to become CS dependent 4.5 (95% CI 3.6-5.7, P < 0.001) than non-users. CONCLUSIONS Early CS use can help identify those patients who have a more active disease course of UC. Recognising this can be among the indicators that can help physicians identify patients who may require early initiation of more aggressive therapy.
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Affiliation(s)
- N H Khan
- Department of Internal Medicine, Section of Gastroenterology, Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA; Department of Internal Medicine, Section of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA, USA
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