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Qin S, Yang Z, Lei J, Xie Q, Jiang L, Fan Y, Luo Y, Wei K, Luo W, Yu B. Comparative efficacy of preventive vs. therapeutic resveratrol in modulating gut microbiota and alleviating inflammation in DSS-induced colitis. BMC Immunol 2025; 26:42. [PMID: 40437375 PMCID: PMC12121039 DOI: 10.1186/s12865-025-00718-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Accepted: 05/06/2025] [Indexed: 06/01/2025] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) management remains challenging due to limited preventive strategies and the low bioavailability of therapeutic agents like resveratrol (RSV). While RSV exhibits anti-inflammatory properties, its preventive potential via gut microbiome modulation remains unexplored. METHODS A murine colitis model was established using 2.5% DSS, with mice randomized into control (CON), DSS, therapeutic RSV treatment (RSV), and preventive RSV treatment (PRE) groups. Clinical outcomes, intestinal barrier integrity, inflammatory cytokines, macrophage polarization, TLR4/NF-κB signaling, and gut microbiota (16S rRNA sequencing) were systematically evaluated. RESULTS Preventive RSV (PRE) outperformed therapeutic RSV across all metrics. PRE attenuated colitis severity by 51.4% (weight loss, P < 0.001 vs. RSV) and restored mucosal architecture (P = 0.048 vs. DSS). Mechanistically, PRE normalized barrier function via transcriptional (ZO-1: 56.7% of CON; Occludin: 14-fold induction vs. DSS) and protein-level recovery (ZO-1: 96.5% of CON, P = 0.02), suppressed pro-inflammatory cytokines (TNF-α: 80.8%; IL-6: 69.9%; IL-18: >96%, P < 0.001 vs. DSS), and promoted M2 macrophage polarization (CD206: 1.7-fold vs. CON, P = 0.02) through TLR4/NF-κB inhibition (53% TLR4 reduction vs. 15% with RSV, P < 0.001). Despite comparable α-diversity between RSV and PRE, PRE uniquely enriched barrier-protective taxa (Lactococcus, Muribaculum) and restored microbial amino acid biosynthesis. Crucially, PRE's efficacy despite low systemic bioavailability implicated microbiome-mediated "luminal priming" as its primary mechanism. CONCLUSIONS This study redefines preventive RSV as a microbial ecosystem engineer that preemptively fortifies the gut against inflammation via microbiome-immune-metabolic crosstalk. By prioritizing ecological prevention over symptom suppression, our findings offer a transformative "food as medicine" strategy for IBD, highlighting RSV's potential as a chronotherapeutic agent to reshape clinical paradigms.
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Affiliation(s)
- Senmei Qin
- Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Zongjing Yang
- Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Jinqing Lei
- Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Qingli Xie
- Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Linsui Jiang
- Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Yuanyuan Fan
- Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Yonggu Luo
- Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Kecong Wei
- Department of Neurosurgery, Wuming Hospital of Guangxi Medical University, Wuming, 530199, Guangxi, China
| | - Wei Luo
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
| | - Bing Yu
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi, China.
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Alotaibi AD, Al-Abdulwahab AA, Ismail MH, AlElyani JM, Alamri TA, Alsulaiman RM, Alhafid IA, Alzahrani IM, AlSulaiman RS, Althubaity A, Buhulaigah SH, AlQurain AA, Alrezuk AM. Prevalence of H. Pylori in inflammatory bowel disease patients and its association with severity. BMC Gastroenterol 2025; 25:317. [PMID: 40301738 PMCID: PMC12042615 DOI: 10.1186/s12876-025-03892-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Accepted: 04/14/2025] [Indexed: 05/01/2025] Open
Abstract
INTRODUCTION One key area of interest in gastroenterology research is the relationship between Helicobacter pylori (H. pylori) and Inflammatory bowel disease (IBD). Several studies have shown varying results regarding the prevalence of H. pylori in IBD patients and its impact on disease progression, severity, and overall outcome. METHOD This is a prospective cohort study conducted at King Fahad University Hospital in Al Khobar, Saudi Arabia from November 2023 to May 2024 to determine the prevalence of H. pylori in IBD patients and its association with severity. The study included 2 arms for comparison which are IBD patients and control group, IBD will be further classified to CD and UC. Prevalence of H. pylori infection and severity of the disease was compared between these groups. RESULTS A total of 360 patients were included in the study which were divided equally into IBD group and control group. The IBD was subdivided into CD with 91 cases and UC with 89 cases. H. Pylori was significantly higher in control group (23.3%) compared with UC cases (13.2%) p value: 0.048. H. pylori infection was significantly high in smokers p value = < 0.0001. The presence of autoimmune disease was significantly associated with H. Pylori infection (16.4%) p value: 0.023. CONCLUSION H. pylori infection was significantly higher in the control group in comparison to IBD group. In addition, smoking and autoimmune disease were significantly associated with H. pylori infection. Finally, the overall association between severity of CD, UC and medication use with H. Pylori were insignificant.
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Affiliation(s)
- Abdullah D Alotaibi
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia.
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia.
| | - Abdullah A Al-Abdulwahab
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Mona H Ismail
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Jaber M AlElyani
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Turki A Alamri
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Raed M Alsulaiman
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Ibrahim A Alhafid
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Ibrahim M Alzahrani
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Reem S AlSulaiman
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia.
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia.
| | - Arwa Althubaity
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Sarah H Buhulaigah
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Abdulaziz A AlQurain
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Abdulaziz M Alrezuk
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
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Chen G, Li X, Xu W, Wang H, Jiang Y, Shi R, Zhu C, Xiao Z. Inflammation Targeting-Triggered Healing Hydrogel for In Situ Reconstruction of Colonic Mucosa. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2411010. [PMID: 39815450 PMCID: PMC11904975 DOI: 10.1002/advs.202411010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 11/13/2024] [Indexed: 01/18/2025]
Abstract
Inflammatory bowel disease (IBD) is characterized by intestinal mucosal damage that exacerbates inflammation and promotes disease recurrence. Although hydrogel-based therapies have shown potential for mucosal repair, challenges remain due to inadequate targeting and low hydrogel density, leading to ongoing infiltration of harmful substances and delayed mucosal healing. In this study, an inflammation-targeting-triggered healing hydrogel (ITTH hydrogel) is developed, composed of polyvinyl alcohol-alginate microgels (PALMs) and a cyclodextrin polymer crosslinker (CPC). This hydrogel specifically targets inflamed colonic sites and crosslinks in situ to form a dense network. The results demonstrate that the ITTH hydrogel adheres effectively to inflamed colonic tissue in both IBD mouse models and human samples. The dense crosslinked network acts like the mucosal barrier, preventing the penetration of detrimental substances such as bacteria and small molecules, thereby protecting the underlying mucosal tissue. Furthermore, the ITTH hydrogel significantly improved therapeutic outcomes in mice with dextran sulfate sodium (DSS)-induced colitis. These findings suggest that the ITTH hydrogel is a promising candidate for in situ reconstruction of colonic mucosa and the treatment of IBD.
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Affiliation(s)
- Gaoxian Chen
- Collaborative Innovation Center for Clinical and Translational ScienceDepartment of Pharmacology and Chemical Biology, & Institute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Xinyi Li
- Collaborative Innovation Center for Clinical and Translational ScienceDepartment of Pharmacology and Chemical Biology, & Institute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Wei Xu
- School of Life SciencesShanghai UniversityShanghai200444China
| | - Haoze Wang
- Collaborative Innovation Center for Clinical and Translational ScienceDepartment of Pharmacology and Chemical Biology, & Institute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Yichao Jiang
- Collaborative Innovation Center for Clinical and Translational ScienceDepartment of Pharmacology and Chemical Biology, & Institute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Ruofan Shi
- Collaborative Innovation Center for Clinical and Translational ScienceDepartment of Pharmacology and Chemical Biology, & Institute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Chengying Zhu
- Collaborative Innovation Center for Clinical and Translational ScienceDepartment of Pharmacology and Chemical Biology, & Institute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Zeyu Xiao
- Collaborative Innovation Center for Clinical and Translational ScienceDepartment of Pharmacology and Chemical Biology, & Institute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
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Gibson G, Rioux JD, Cho JH, Haritunians T, Thoutam A, Abreu MT, Brant SR, Kugathasan S, McCauley JL, Silverberg M, McGovern D. Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics. Inflamm Bowel Dis 2025; 31:272-284. [PMID: 39700476 PMCID: PMC11700891 DOI: 10.1093/ibd/izae269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Indexed: 12/21/2024]
Abstract
The past 2 decades have witnessed extraordinary advances in our understanding of the genetic factors influencing inflammatory bowel disease (IBD), providing a foundation for the approaching era of genomic medicine. On behalf of the NIDDK IBD Genetics Consortium, we herein survey 11 grand challenges for the field as it embarks on the next 2 decades of research utilizing integrative genomic and systems biology approaches. These involve elucidation of the genetic architecture of IBD (how it compares across populations, the role of rare variants, and prospects of polygenic risk scores), in-depth cellular and molecular characterization (fine-mapping causal variants, cellular contributions to pathology, molecular pathways, interactions with environmental exposures, and advanced organoid models), and applications in personalized medicine (unmet medical needs, working toward molecular nosology, and precision therapeutics). We review recent advances in each of the 11 areas and pose challenges for the genetics and genomics communities of IBD researchers.
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Affiliation(s)
- Greg Gibson
- School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - John D Rioux
- Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada
| | - Judy H Cho
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Talin Haritunians
- Widjaja Foundation IBD Research Institute, Cedars Sinai Health Center, Los Angeles, CA, USA
| | - Akshaya Thoutam
- School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - Maria T Abreu
- Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA
| | - Steven R Brant
- Robert Wood Johnson School of Medicine, Rutgers University, Piscataway, NJ, USA
| | - Subra Kugathasan
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Jacob L McCauley
- Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA
| | - Mark Silverberg
- Lunenfeld-Tanenbaum Research Institute IBD, University of Toronto, Toronto, ON, Canada
| | - Dermot McGovern
- Widjaja Foundation IBD Research Institute, Cedars Sinai Health Center, Los Angeles, CA, USA
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Dou Z, Zheng H, Shi Y, Li Y, Jia J. Analysis of global prevalence, DALY and trends of inflammatory bowel disease and their correlations with sociodemographic index: Data from 1990 to 2019. Autoimmun Rev 2024; 23:103655. [PMID: 39366514 DOI: 10.1016/j.autrev.2024.103655] [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: 04/17/2024] [Revised: 09/11/2024] [Accepted: 09/29/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a kind of chronic inflammatory disorders of the gastrointestinal tract with diverse prevalence rates and patterns globally. Accurate comprehension of the disease's epidemiological characteristics is imperative for disease control and prevention all over the world. OBJECTIVE To provide the most updated estimates on the global burden of IBD using the 2019 Global Burden of Disease (GBD) study data, to systematically analyze the IBD epidemiological characteristics at the global, regional, and national levels including the prevalence, incidence, and disability-adjusted life years (DALY) rates, and to analyze the correlations of the socioeconomic development level with IBD epidemiological characteristics. METHODS We conducted an overall analysis of the global, regional, and national burden of IBD from 1990 to 2019, data from the 2019 GBD study. The GBD's classification of the world into 21 regions and 204 countries and territories facilitated a thorough examination. Age-standardized estimated annual percentage changes (EAPCs) were computed to assess the temporal trends in IBD age-standardized rates (ASRs), with age standardization employed to mitigate potential confounding effects from age structure. The sociodemographic Index (SDI) was used to correlate the socioeconomic development level with the epidemiological characteristics of IBD. RESULTS From 1990 to 2019, the global age-standardized prevalence, incidence, and DALY rates of IBD remained high. There was a slight downward trend in the global age-standardized incidence and DALY rates of IBD and men exhibited higher DALY rates than women. In 2019, high-income North America recorded the highest age-standardized prevalence, incidence, and DALY rates, while Oceania had the lowest age-standardized prevalence and incidence rates. South Asia had the lowest age-standardized DALY rates. The age-standardized mortality and DALY rates decreased as SDI values increased and remained higher than the expected levels over the past three decades. A negative correlation was observed between age-standardized DALY rates and SDI at the national level. CONCLUSIONS This analysis of the GBD 2019 database demonstrates that the overall global burden of IBD is still high. Meanwhile, an increasing disease burden is observed in the middle and low SDI locations.
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Affiliation(s)
- Zhili Dou
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, PR China; Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, PR China
| | - Huiling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, PR China
| | - Yanyan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, PR China.
| | - Yuan Li
- Department of Gastroenterology, Peking University International Hospital, Beijing 102206, PR China.
| | - Jinzhu Jia
- Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, PR China; Center for Statistical Science, Peking University, Beijing 100191, PR China.
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Choi WG, Ko SJ, Jung D, Kim SC, Choi NR, Park JW, Kim BJ. Therapeutic Effects of Zanthoxyli Pericarpium on Intestinal Inflammation and Network Pharmacological Mechanism Analysis in a Dextran Sodium Sulfate-Induced Colitis Mouse Model. Nutrients 2024; 16:3521. [PMID: 39458516 PMCID: PMC11510417 DOI: 10.3390/nu16203521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/04/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
(1) Background: IBD (inflammatory bowel disease) is characterized by chronic intestinal inflammation leading to persistent symptoms and a lack of effective treatments. ZP (Zanthoxyli Pericarpium) has been used in traditional Chinese medicine for its anti-inflammatory and antioxidant properties for the management of intestinal disorders. (2) Methods: This study aimed to investigate the components of ZP, their specific targets, and associated diseases using the TCMSP (Traditional Chinese Medicine Systems Pharmacology) analysis platform, TCMBank database, and ETCM2.0 (Encyclopedia of Traditional Chinese Medicine 2.0) database. Additionally, we explored the protective effects of ZP on the colon and the underlying molecular mechanisms in the treatment of IBD. (3) Results: We identified 59 compounds in ZP that target 38 genes related to IBD, including PTGS2, PPARG, and GPBAR1. In a mice model of DSS (dextran sodium sulfate)-induced colitis, ZP significantly reduced colonic epithelial damage and oxidative stress markers, such as iNOS and nitrotyrosine, demonstrating its antioxidant properties. (4) Conclusions: These findings suggest that ZP has protective effects against DSS-induced colonic damage owing to its anti-inflammatory and antioxidant properties, making it a potential candidate for IBD treatment. However, further research and clinical trials are required to confirm its therapeutic potential and safety in humans.
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Affiliation(s)
- Woo-Gyun Choi
- Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea; (W.-G.C.); (N.-R.C.)
| | - Seok-Jae Ko
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea;
- Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Daehwa Jung
- Department of Pharmaceutical Engineering, Daegu Hanny University, Gyeongsan 38610, Republic of Korea;
| | - Sang Chan Kim
- College of Oriental Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea;
| | - Na-Ri Choi
- Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea; (W.-G.C.); (N.-R.C.)
- Department of Korean Medical Science, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea
| | - Jae-Woo Park
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea;
- Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Byung Joo Kim
- Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea; (W.-G.C.); (N.-R.C.)
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Li D, Liu Z, Fan X, Zhao T, Wen D, Huang X, Li B. Lactic Acid Bacteria-Gut-Microbiota-Mediated Intervention towards Inflammatory Bowel Disease. Microorganisms 2024; 12:1864. [PMID: 39338538 PMCID: PMC11433943 DOI: 10.3390/microorganisms12091864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 09/01/2024] [Accepted: 09/02/2024] [Indexed: 09/30/2024] Open
Abstract
Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), arises from intricate interactions involving genetics, environment, and pharmaceuticals with an ambiguous pathogenic mechanism. Recently, there has been an increasing utilization of lactic acid bacteria (LAB) in managing IBD, attributed to their ability to enhance intestinal barrier function, mitigate inflammatory responses, and modulate gut microbiota. This review initiates by elucidating the pathogenesis of IBD and its determinants, followed by an exploration of the mechanisms underlying LAB therapy in UC and CD. Special attention is directed towards their influence on intestinal barrier function and homeostasis regulated by gut microbiota. Furthermore, the review investigates the complex interplay among pivotal gut microbiota, metabolites, and pathways associated with inflammation. Moreover, it underscores the limitations of LAB in treating IBD, particularly in light of their varying roles in UC and CD. This comprehensive analysis endeavors to offer insights for the optimized application of LAB in IBD therapy.
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Affiliation(s)
- Diantong Li
- Institute of Animal Husbandry and Veterinary, Xizang Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa 850000, China; (D.L.); (Z.L.); (X.F.); (T.Z.); (D.W.)
- School of Public Health, Lanzhou University, Lanzhou 730000, China
| | - Zhenjiang Liu
- Institute of Animal Husbandry and Veterinary, Xizang Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa 850000, China; (D.L.); (Z.L.); (X.F.); (T.Z.); (D.W.)
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China
| | - Xueni Fan
- Institute of Animal Husbandry and Veterinary, Xizang Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa 850000, China; (D.L.); (Z.L.); (X.F.); (T.Z.); (D.W.)
- School of Public Health, Lanzhou University, Lanzhou 730000, China
| | - Tingting Zhao
- Institute of Animal Husbandry and Veterinary, Xizang Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa 850000, China; (D.L.); (Z.L.); (X.F.); (T.Z.); (D.W.)
- School of Public Health, Lanzhou University, Lanzhou 730000, China
| | - Dongxu Wen
- Institute of Animal Husbandry and Veterinary, Xizang Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa 850000, China; (D.L.); (Z.L.); (X.F.); (T.Z.); (D.W.)
| | - Xiaodan Huang
- Institute of Animal Husbandry and Veterinary, Xizang Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa 850000, China; (D.L.); (Z.L.); (X.F.); (T.Z.); (D.W.)
- School of Public Health, Lanzhou University, Lanzhou 730000, China
| | - Bin Li
- Institute of Animal Husbandry and Veterinary, Xizang Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa 850000, China; (D.L.); (Z.L.); (X.F.); (T.Z.); (D.W.)
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Madhvapathy SR, Bury MI, Wang LW, Ciatti JL, Avila R, Huang Y, Sharma AK, Rogers JA. Miniaturized implantable temperature sensors for the long-term monitoring of chronic intestinal inflammation. Nat Biomed Eng 2024; 8:1040-1052. [PMID: 38499643 DOI: 10.1038/s41551-024-01183-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 02/09/2024] [Indexed: 03/20/2024]
Abstract
Diagnosing and monitoring inflammatory bowel diseases, such as Crohn's disease, involves the use of endoscopic imaging, biopsies and serology. These infrequent tests cannot, however, identify sudden onsets and severe flare-ups to facilitate early intervention. Hence, about 70% of patients with Crohn's disease require surgical intestinal resections in their lifetime. Here we report wireless, miniaturized and implantable temperature sensors for the real-time chronic monitoring of disease progression, which we tested for nearly 4 months in a mouse model of Crohn's-disease-like ileitis. Local measurements of intestinal temperature via intraperitoneally implanted sensors held in place against abdominal muscular tissue via two sutures showed the development of ultradian rhythms at approximately 5 weeks before the visual emergence of inflammatory skip lesions. The ultradian rhythms showed correlations with variations in the concentrations of stress hormones and inflammatory cytokines in blood. Decreasing average temperatures over the span of approximately 23 weeks were accompanied by an increasing percentage of inflammatory species in ileal lesions. These miniaturized temperature sensors may aid the early treatment of inflammatory bowel diseases upon the detection of episodic flare-ups.
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Affiliation(s)
- Surabhi R Madhvapathy
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA
| | - Matthew I Bury
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
- Stanley Manne Children's Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL, USA
| | - Larry W Wang
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Joanna L Ciatti
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA
| | - Raudel Avila
- Department of Mechanical Engineering, Rice University, Houston, TX, USA
| | - Yonggang Huang
- Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA
- Department of Civil Engineering, Northwestern University, Evanston, IL, USA
| | - Arun K Sharma
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
- Stanley Manne Children's Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL, USA.
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
- Simpson Querrey Institute, Northwestern University, Chicago, IL, USA.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
| | - John A Rogers
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
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Deas J, Shah ND, Konijeti GG, Lundin A, Lanser O, Magavi P, Ali S. Dietary therapies for adult and pediatric inflammatory bowel disease. Nutr Clin Pract 2024; 39:530-545. [PMID: 38505875 DOI: 10.1002/ncp.11146] [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: 12/25/2023] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/21/2024] Open
Abstract
Diet is an environmental exposure implicated in the development of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Dietary therapy is also a tool for management of these conditions. Nutrition therapy for IBD has been shown to reduce intestinal inflammation, promote healing, and alleviate symptoms, as well as improve patients' nutrition status. Although the mechanisms of action of most nutrition therapies for IBD are not well understood, the diets are theorized to eliminate triggers for gut dysbiosis and mucosal immune dysfunction associated with the typical Western diet. Exclusive enteral nutrition and the Crohn's disease exclusion diet are increasingly being used as the primary treatment modality for the induction of remission and/or maintenance therapy in children, and in some adults, with CD. Several other diets, such as the Mediterranean diet, anti-inflammatory diet for IBD, and diets excluding gluten, FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), lactose, or other compounds, may be helpful in symptom management in both CD and UC, though evidence for biochemical efficacy is limited. In this review, we discuss the role of diet components in IBD pathogenesis and examine diets currently used in the management of children and adults with IBD. We also address practical, psychosocial, and cultural considerations for dietary therapy across diverse populations.
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Affiliation(s)
- Jessica Deas
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Los Angeles, California, USA
| | - Neha D Shah
- Colitis and Crohn's Disease Center, University of California San Francisco, San Francisco, California, USA
| | - Gauree G Konijeti
- Division of Gastroenterology & Hepatology, Scripps Clinic, La Jolla, California, USA
| | - Abigail Lundin
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Benioff Children Hospitals, University of California San Francisco, San Francisco, California, USA
| | - Olivia Lanser
- Division of Gastroenterology & Hepatology, Scripps Clinic, La Jolla, California, USA
| | - Pooja Magavi
- Division of Gastroenterology & Hepatology, Scripps Clinic, La Jolla, California, USA
| | - Sabina Ali
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Benioff Children Hospitals, University of California San Francisco, San Francisco, California, USA
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10
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Tian J, Yang C, Wang Y, Zhou C. Evaluation of the Mechanism of Sinomenii Caulis in Treating Ulcerative Colitis based on Network Pharmacology and Molecular Docking. Curr Comput Aided Drug Des 2024; 20:195-207. [PMID: 37078344 PMCID: PMC10641851 DOI: 10.2174/1573409919666230420083102] [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: 08/31/2022] [Revised: 02/22/2023] [Accepted: 02/23/2023] [Indexed: 04/21/2023]
Abstract
BACKGROUND Studies have indicated that Sinomenii Caulis (SC) has several physiological activities, such as anti-inflammatory, anti-cancer, immunosuppression, and so on. SC is currently widely used in the treatment of rheumatoid arthritis, skin disease, and other diseases. However, the mechanism of SC in the treatment of ulcerative colitis (UC) remains unclear. AIMS To predict the active components of SC and determine the mechanism of SC on UC. METHODS Active components and targets of SC were screened and obtained by TCMSP, PharmMapper, and CTD databases. The target genes of UC were searched from GEO (GSE9452), and DisGeNET databases. Based on the String database, Cytoscape 3.7.2 software, and David 6.7 database, we analyzed the relationship between SC active components and UC potential targets or pathways. Finally, identification of SC targets in anti-UC by molecular docking. GROMACS software was used to perform molecular dynamics simulations of protein and compound complexes and to perform free energy calculations. RESULTS Six main active components, 61 potential anti-UC gene targets, and the top 5 targets with degree value are IL6, TNF, IL1β, CASP3, and SRC. According to GO enrichment analysis, the vascular endothelial growth factor receptor and vascular endothelial growth factor stimulus may be relevant biological processes implicated in the treatment of UC by SC. The KEGG pathway analysis result was mainly associated with the IL-17, AGE-RAGE, and TNF signaling pathways. Based on molecular docking results, beta-sitosterol, 16-epi-Isositsirikine, Sinomenine, and Stepholidine are strongly bound to the main targets. Molecular dynamics simulation results showed that IL1B/beta-sitosterol and TNF/16-epi-Isositsirikine binding was more stable. CONCLUSION SC can play a therapeutic role in UC through multiple components, targets, and pathways. The specific mechanism of action needs to be further explored.
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Affiliation(s)
- Juan Tian
- Life Science and Technology School, Lingnan Normal University, Zhanjiang, Guangdong, 524048, China
| | - Changgeng Yang
- Life Science and Technology School, Lingnan Normal University, Zhanjiang, Guangdong, 524048, China
| | - Yun Wang
- Life Science and Technology School, Lingnan Normal University, Zhanjiang, Guangdong, 524048, China
| | - Canlin Zhou
- Life Science and Technology School, Lingnan Normal University, Zhanjiang, Guangdong, 524048, China
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11
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Tong JKC, Mascuilli T, Wirtalla C, Aarons CB, Saur NM, Mahmoud NN, Karakousis GC, Kelz RR. Evaluating Changes in Surgical Outcomes for Patients With Inflammatory Bowel Disease Following Medicaid Expansion. Inflamm Bowel Dis 2023; 29:1579-1585. [PMID: 36573827 DOI: 10.1093/ibd/izac255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Indexed: 10/05/2023]
Abstract
BACKGROUND Little is known about the impact of Medicaid expansion on the surgical care of inflammatory bowel disease. We sought to determine whether Medicaid expansion is associated with improved postsurgical outcomes for patients with inflammatory bowel disease undergoing a colorectal resection. METHODS We performed a risk-adjusted difference-in-difference study examining postsurgical outcomes for patients ages 26 to 64 with Crohn's disease or ulcerative colitis undergoing a colorectal resection across 15 states that did and did not expand Medicaid before (2012-2013) and after (2016-2018) policy reform. Primary study outcomes included 30-day readmission and postoperative complication. RESULTS Study population included 11 394 patients with inflammatory bowel disease that underwent a colorectal resection. States that underwent Medicaid expansion were associated with a rise in Medicaid enrollment following policy reform (11.8% pre-Medicaid expansion vs 19.7% post-Medicaid expansion). Difference-in-difference analysis revealed a statistically significant lower odds of 30-day readmission in patients undergoing a colorectal resection in expansion states following policy reform relative to patients in nonexpansion states prior to reform (odds ratio, 0.56; 95% confidence interval, 0.36-0.86). No changes in odds of postoperative complication were noted across expansion and nonexpansion states. CONCLUSIONS Medicaid expansion is associated with a rise in Medicaid enrollment in expansion states following policy reform. There were greater improvements in postoperative outcomes associated with patients in expansion states following policy reform relative to patients in nonexpansion states prior to reform, which may have been related to improved perioperative care and medical management.
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Affiliation(s)
- Jason K C Tong
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
- National Clinicians Scholars Veterans Affairs Scholar, Philadelphia, PA, USA
| | - Tory Mascuilli
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
| | - Christopher Wirtalla
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
| | - Cary B Aarons
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
- University of Pennsylvania, Department of Surgery, Division of Colon and Rectal Surgery, Philadelphia, PA, USA
| | - Nicole M Saur
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
- University of Pennsylvania, Department of Surgery, Division of Colon and Rectal Surgery, Philadelphia, PA, USA
| | - Najjia N Mahmoud
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
- University of Pennsylvania, Department of Surgery, Division of Colon and Rectal Surgery, Philadelphia, PA, USA
| | - Giorgos C Karakousis
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Rachel R Kelz
- University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA, USA
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
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12
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Zhou HF, Yang C, Li JY, He YY, Huang Y, Qin RJ, Zhou QL, Sun F, Hu DS, Yang J. Quercetin serves as the major component of Xiang-lian Pill to ameliorate ulcerative colitis via tipping the balance of STAT1/PPARγ and dictating the alternative activation of macrophage. JOURNAL OF ETHNOPHARMACOLOGY 2023; 313:116557. [PMID: 37142141 DOI: 10.1016/j.jep.2023.116557] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 04/21/2023] [Accepted: 04/24/2023] [Indexed: 05/06/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The traditional Chinese herbal formula, Xiang-lian Pill (XLP), is commonly prescribed for ulcerative colitis (UC) patients to relieve their clinical symptom. Nonetheless, the underlying cellular and molecular mechanisms of XLP's anti-UC effect remain incompletely understood. AIM OF THE STUDY To evaluate the therapeutic effect and elucidate the possible working mechanisms of XLP in UC treatment. The major active component of XLP was also characterized. MATERIALS AND METHODS Colitis was induced in C57BL/6 mice with 3% dextran sulfate sodium (DSS) dissolved in drinking water for 7 consecutive days. The UC mice were grouped and treated with XLP (3640 mg/kg) or vehicle orally during the procedure of DSS induction. Mouse body weight, disease activity index (DAI) score and colon length were recorded. Histopathological changes and inflammatory cell infiltration were evaluated by pathological staining and flow cytometric analysis (FACS). Network pharmacology, bioinformatic analysis, widely targeted and targeted metabolomics analysis were performed to screen the potential effective ingredients and key targets. Bone marrow derived macrophages (BMDMs), peripheral blood mononuclear cells (PBMCs), RAW264.7 and THP-1 cells were used to dissect the anti-inflammatory effect of XLP. RESULTS Oral administration of XLP ameliorated DSS induced mouse colitis, as evidenced by reduced DAI and colonic inflammatory destruction. FACS results demonstrated that XLP treatment effectively restored immune tolerance in colon, inhibited the generation of monocyte derived macrophages and skewed macrophage polarization into M2 phenotype. Network pharmacology analysis suggested that innate effector modules related to macrophage activation comprise the major targets of XLP, and the counter-regulatory STAT1/PPARγ signaling possibly serves as the critical downstream pathway. Subsequent experiments unveiled an imbalance of STAT1/PPARγ signaling in monocytes derived from UC patients, and validated that XLP suppressed LPS/IFN-γ induced macrophage activation (STAT1 mediated) but facilitated IL-4 induced macrophage M2 polarization (PPARγ dependent). Meanwhile, our data showed that quercetin served as the major component of XLP to recapitulate the regulatory effect on macrophages. CONCLUSION Our findings revealed that quercetin serves as the major component of XLP that regulates macrophage alternative activation via tipping the balance of STAT1/PPARγ, which provides a mechanistic explanation for the therapeutic effect of XLP in UC treatment.
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Affiliation(s)
- Hai-Feng Zhou
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Chao Yang
- Department of Geratology, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan, 430015, China.
| | - Jun-Yi Li
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Yu-Yao He
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Yun Huang
- Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
| | - Ren-Jie Qin
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Qiao-Li Zhou
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Fei Sun
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, 430030, China.
| | - De-Sheng Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Jia Yang
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Yan Y, Li K, Jiang J, Jiang L, Ma X, Ai F, Qiu S, Si W. Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota. Stem Cell Res Ther 2023; 14:43. [PMID: 36941715 PMCID: PMC10029206 DOI: 10.1186/s13287-023-03263-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 03/06/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder the therapeutic application. Exosomes derived from MSCs have shown promising therapeutic potential in many diseases. However, the heterogeneity of MSCs may lead to differences in the function of secreting exosomes. In this study, the therapeutic effects of hUC-Exos and hFP-Exos on the DSS-induced colitis mouse model were investigated. METHODS The colitis mouse models were randomly divided into four groups: (1) DSS administered for 7 days and euthanasia (DSS7D), (2) DSS administered for 7 days and kept for another 7 days without any treatment (DSS14D), (3) DSS administered for 7 days and followed with hUC-EVs infusion for 7 days (hUC-EVs) and (4) DSS administered for 7 days and followed with hFP-EVs infusion for 7 days (hFP-EVs). We analyzed colon length, histopathology, Treg cells, cytokines and gut microbiota composition in each group. RESULTS A large amount of IL-6, IL-17 and IFN-γ were produced along with the decrease in the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells in DSS7D group, which indicated that Th17 cells were activated and Treg cells were suppressed. We found that the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells increased in order to suppress inflammation, but the length of colon did not recover and the symotoms were worsened of the colonic tissue in DSS14D group. The subsequent infusion of either hUC-Exos or hFP-Exos mediated the transformation of Treg and Th17 cells in colitis mice to maintain immune balance. The infusion of hUC-Exos and hFP-Exos also both reduced the abundance of pro-inflammatory intestinal bacterial such as Verrucomicrobia and Akkermansia muciniphila to improve colitis. CONCLUSIONS We found that Foxp3 + Treg cells can inhibit the inflammatory response, and the over-activated Treg cells can still further damage the intestinal mucosa. hUC-Exos and hFP-Exos can control inflammation by regulating the balance between Th17 cells and Treg cells. Decreased inflammatory response improved the structure of colon wall in mice and reduced the abundance of pro-inflammatory bacteria in the intestine. The improvement of intestinal wall structure provides conditions for the reproduction of beneficial bacteria, which further contributes to the reduction of colitis.
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Affiliation(s)
- Yaping Yan
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China
| | - Kaixiu Li
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China
| | - Jiang Jiang
- Department of Obstetrics, The First People's Hospital of Yunnan Province, Kunming, 650032, Yunnan, China
- Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China
| | - Lihong Jiang
- Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China
- Yunnan Key Laboratory of Innovative Application of Traditional Chinese Medicine, The First People's Hospital of Yunnan Province, Kunming, 650032, Yunnan, China
| | - Xiang Ma
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China
| | - Fang Ai
- Department of Obstetrics, The First People's Hospital of Yunnan Province, Kunming, 650032, Yunnan, China
- Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China
| | - Shuai Qiu
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China
| | - Wei Si
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
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Inhibition of Canonical Transient Receptor Potential Channels 4/5 with Highly Selective and Potent Small-Molecule HC-070 Alleviates Mechanical Hypersensitivity in Rat Models of Visceral and Neuropathic Pain. Int J Mol Sci 2023; 24:ijms24043350. [PMID: 36834762 PMCID: PMC9964505 DOI: 10.3390/ijms24043350] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/01/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Transient receptor potential channels C4/C5 are widely expressed in the pain pathway. Here, we studied the putative analgesic efficacy of the highly selective and potent TRPC4/C5 antagonist HC-070 in rats. Inhibitory potency on human TRPC4 was assessed by using the whole-cell manual patch-clamp technique. Visceral pain sensitivity was assessed by the colonic distension test after intra-colonic trinitrobenzene sulfonic acid injection and partial restraint stress. Mechanical pain sensitivity was assessed by the paw pressure test in the chronic constriction injury (CCI) neuropathic pain model. We confirm that HC-070 is a low nanomolar antagonist. Following single oral doses (3-30 mg/kg in male or female rats), colonic hypersensitivity was significantly and dose-dependently attenuated, even fully reversed to baseline. HC-070 also had a significant anti-hypersensitivity effect in the established phase of the CCI model. HC-070 did not have an effect on the mechanical withdrawal threshold of the non-injured paw, whereas the reference compound morphine significantly increased it. Analgesic effects are observed at unbound brain concentrations near the 50% inhibitory concentration (IC50) recorded in vitro. This suggests that analgesic effects reported here are brought about by TRPC4/C5 blocking in vivo. The results strengthen the idea that TRPC4/C5 antagonism is a novel, safe non-opioid treatment for chronic pain.
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15
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Sanmarco LM, Chao CC, Wang YC, Kenison JE, Li Z, Rone JM, Rejano-Gordillo CM, Polonio CM, Gutierrez-Vazquez C, Piester G, Plasencia A, Li L, Giovannoni F, Lee HG, Faust Akl C, Wheeler MA, Mascanfroni I, Jaronen M, Alsuwailm M, Hewson P, Yeste A, Andersen BM, Franks DG, Huang CJ, Ekwudo M, Tjon EC, Rothhammer V, Takenaka M, de Lima KA, Linnerbauer M, Guo L, Covacu R, Queva H, Fonseca-Castro PH, Bladi MA, Cox LM, Hodgetts KJ, Hahn ME, Mildner A, Korzenik J, Hauser R, Snapper SB, Quintana FJ. Identification of environmental factors that promote intestinal inflammation. Nature 2022; 611:801-809. [PMID: 36266581 PMCID: PMC9898826 DOI: 10.1038/s41586-022-05308-6] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/01/2022] [Indexed: 02/06/2023]
Abstract
Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)1-a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity2. However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPβ signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases.
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Affiliation(s)
- Liliana M Sanmarco
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Chun-Cheih Chao
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Yu-Chao Wang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jessica E Kenison
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Zhaorong Li
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Joseph M Rone
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Claudia M Rejano-Gordillo
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Carolina M Polonio
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Cristina Gutierrez-Vazquez
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Gavin Piester
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Agustin Plasencia
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lucinda Li
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Federico Giovannoni
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Hong-Gyun Lee
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Camilo Faust Akl
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Michael A Wheeler
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- The Broad Institute of Harvard and MIT, Cambridge, MA, USA
| | - Ivan Mascanfroni
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Merja Jaronen
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Moneera Alsuwailm
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Patrick Hewson
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ada Yeste
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Brian M Andersen
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Diana G Franks
- Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA, USA
| | - Chien-Jung Huang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Millicent Ekwudo
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Emily C Tjon
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Veit Rothhammer
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Maisa Takenaka
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Kalil Alves de Lima
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mathias Linnerbauer
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lydia Guo
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ruxandra Covacu
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Hugo Queva
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Maha Al Bladi
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Laura M Cox
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Kevin J Hodgetts
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mark E Hahn
- Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA, USA
| | | | - Joshua Korzenik
- Department of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Russ Hauser
- Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Scott B Snapper
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Francisco J Quintana
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
- The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
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Xu S, Chen S, Zhang M, An W, Li J, Sun Z, Xu Y. Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on Competitive Endogenous RNAs in Ulcerative Colitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:4572181. [PMID: 36310619 PMCID: PMC9616663 DOI: 10.1155/2022/4572181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 10/08/2022] [Indexed: 11/24/2022]
Abstract
Ulcerative colitis (UC) is a common autoimmune disease worldwide. Circular RNA (circRNA) is a type of noncoding ribonucleic acids (ncRNAs). In addition to their roles in numerous biological processes, circRNAs are also linked to a vast range of diseases including UC. Although previous studies have examined many circRNAs, the physiological and pathological roles of the circRNA-associated competing endogenous RNA (ceRNA) network in UC remain unclear. Thus, we constructed a circRNA-miRNA-mRNA network based on the ceRNA hypothesis by analyzing data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) database. Genes with higher degree values than others in the ceRNA network were selected as central nodes when constructing the corresponding core subnetworks. To fully understand the biological function of the ceRNA network, we entered all differentially expressed mRNAs (DEmRNAs) from the ceRNA network into the Database for Annotation and Integrated Discovery (DAVID), which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We further entered DEmRNAs into the STRING database for protein-protein interaction (PPI) network analysis. The results elucidated that the ceRNA network comprised 403 circRNA nodes, 5 miRNA nodes, 138 mRNA nodes, and 559 edges. Three core ceRNA subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p, and hsa-miR-142-3p were reconstructed in this study. GO and KEGG enrichment analyses identified 167 enriched GO categories and 14 enriched KEGG pathway terms. The core PPI network was composed of 15 core targets, of which CD44, HIF1A, and MMP2 were the most significant. In summary, 3 hub miRNAs (hsa-miR-342-3p, hsa-miR-199a-5p, hsa-miR-142-3p) and 3 hub genes (CD44, HIF1A, and MMP2) might play an important role in the development of UC. These hub nodes, first proposed here, might also be used as potential diagnostic markers and therapeutic targets.
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Affiliation(s)
- Sai Xu
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Shouqiang Chen
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Menghe Zhang
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Wenrong An
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Jie Li
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Zhenhai Sun
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Yunsheng Xu
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
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17
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Fei Y, Ma Y, Zhang H, Li H, Feng G, Fang J. Nanotechnology for research and treatment of the intestine. J Nanobiotechnology 2022; 20:430. [PMID: 36175955 PMCID: PMC9523975 DOI: 10.1186/s12951-022-01517-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022] Open
Abstract
The establishment of intestinal in vitro models is crucial for elucidating intestinal cell-microbe intrinsic connections and interaction mechanisms to advance normalized intestinal diagnosis and precision therapy. This review discusses the application of nanomaterials in mucosal therapy and mechanism research in combination with the study of nanoscaffold in vitro models of the gut. By reviewing the original properties of nanomaterials synthesized by different physicochemical principles and modifying the original properties, the contribution of nanomaterials to solving the problems of short survival period, low cell differentiation rate, and poor reduction ability in traditional intestinal models is explored. According to nanomaterials’ different diagnostic mediators and therapeutic targets, the current diagnostic principles in inflammatory bowel disease, intestinal cancer, and other diseases are summarized inductively. In addition, the mechanism of action of nanomedicines in repairing mucosa, inhibiting inflammation, and alleviating the disease process is also discussed. Through such systematic elaboration, it offers a basis for nanomaterials to help advance in vitro research on the intestine and provide precision treatments in the clinic.
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Affiliation(s)
- Yanquan Fei
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, 410128, Hunan, China
| | - Yong Ma
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, 410128, Hunan, China
| | - Huaizu Zhang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, 410128, Hunan, China
| | - Hao Li
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China
| | - Guangfu Feng
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, 410128, Hunan, China.
| | - Jun Fang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, 410128, Hunan, China.
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18
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Yang Z, Lin S, Feng W, Liu Y, Song Z, Pan G, Zhang Y, Dai X, Ding X, Chen L, Wang Y. A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization. Front Pharmacol 2022; 13:999179. [PMID: 36147340 PMCID: PMC9486102 DOI: 10.3389/fphar.2022.999179] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 08/12/2022] [Indexed: 11/13/2022] Open
Abstract
Intestinal macrophages are the main participants of intestinal immune homeostasis and intestinal inflammation. Under different environmental stimuli, intestinal macrophages can be polarized into classical activated pro-inflammatory phenotype (M1) and alternative activated anti-inflammatory phenotype (M2). Its different polarization state is the “guide” to promoting the development and regression of inflammation. Under normal circumstances, intestinal macrophages can protect the intestine from inflammatory damage. However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages will lead to the imbalance in the regulation of intestinal inflammation and transform the physiological inflammatory response into pathological intestinal injury. In UC patients, the disorder of intestinal inflammation is closely related to the imbalance of intestinal M1/M2 macrophage polarization. Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for UC. Evidence has shown that traditional Chinese medicine (TCM) has positive therapeutic effects on UC by restoring the balance of M1/M2 macrophage polarization. This review summarizes the clinical evidence of TCM for UC, the vital role of macrophage polarization in the pathophysiology of UC, and the potential mechanism of TCM regulating macrophage polarization in the treatment of UC. We hope this review may provide some new enlightenment for the clinical treatment, fundamental research, and research and development of new Chinese medicine of UC.
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Affiliation(s)
- Zhihua Yang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shanshan Lin
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wanying Feng
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yangxi Liu
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhihui Song
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Guiyun Pan
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuhang Zhang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiangdong Dai
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xinya Ding
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lu Chen
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Lu Chen, ; Yi Wang,
| | - Yi Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Lu Chen, ; Yi Wang,
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19
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Wu J, Wu Y, Feng W, Chen Q, Wang D, Liu M, Yu H, Zhang Y, Wang T. Role of Microbial Metabolites of Histidine in the Development of Colitis. Mol Nutr Food Res 2022; 66:e2101175. [PMID: 35585003 DOI: 10.1002/mnfr.202101175] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 04/17/2022] [Indexed: 12/31/2022]
Abstract
SCOPE Colitis is a chronic relapsing inflammatory disease of colon. Clinical studies show that meat-rich diet plays a critical role in the relapse of colitis. However, it is unclear whether the microbial metabolites of histidine, which is an amino acid widely found in meat, have an impact on the health of the intestine. METHODS AND RESULTS Six metabolites of histidine are given to IEC-6 cells. The cell activity measurement shows that imidazole propionate (IMP) is the most detrimental metabolite. Then, IMP is injected to mice by rectal administration, with blood and colon tissues collected for the measurement of colitis related parameters. The results show that treatment with IMP significantly increased NF-κB, iNOS, and IL-6, decreased number of goblet cell, and inhibited expressions of miR-146b. However, overexpression of miR-146b in mice rescues the decline of the physical condition. Additionally, Notch receptor 1 (Notch1) is identified as a target gene of miR-146b. Further analysis shows that miR-146b restored the abundance of goblet cells by regulating Notch1 signaling pathway. CONCLUSION IMP is able to induce intestinal inflammation, impairs the intestinal barrier, and affects the proliferation of goblet cells. The underlined mechanism may partially contribute to the dysregulation of miR-146b/Notch1 axis.
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Affiliation(s)
- Jiaqi Wu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China
| | - Yuzheng Wu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.,Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China
| | - Wen Feng
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China
| | - Qian Chen
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.,Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China
| | - Dan Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.,Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China
| | - Mengyang Liu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.,Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China
| | - Haiyang Yu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China
| | - Yi Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China
| | - Tao Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin, 300193, China
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20
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Abstract
PURPOSE OF REVIEW Diet remains an important topic for patients with inflammatory bowel disease (IBD), yet few guidelines for dietary recommendations exist. There is a growing interest in the use of diet as treatment or adjuvant therapy for both ulcerative colitis and Crohn's disease. Here, we highlight the latest evidence on the use of diet for treatment of symptoms, active disease and maintenance of remission in ulcerative colitis and Crohn's disease. RECENT FINDINGS The Crohn's Disease Exclusion Diet (CDED) and the Specific Carbohydrate Diet (SCD) are studied diets that have gained popularity, but there is growing interest in the use and efficacy of less restrictive diets such as the Mediterranean diet. Recent data suggest healthful dietary patterns alone, with an emphasis on whole foods that are high in vegetable fibre and that promote less consumption of ultra-processed foods may also help achieve remission in patients with ulcerative colitis and Crohn's disease. SUMMARY In this review, we summarize the literature on diet as treatment for IBD. We highlight the latest clinical dietary studies, randomized clinical trials, as well as new and emerging diets for the treatment of IBD.
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Affiliation(s)
- Frank A Cusimano
- Department of Medicine, Jackson Memorial Health System/University of Miami
| | - Oriana M Damas
- Division of Gastroenterology, Department of Medicine, University of Miami-Leonard Miller School of Medicine, Miami, Florida, USA
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21
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Chen K, Gao C, Tang M, Dong Q, Wang N, Man S, Lu F, Wang H. Dietary soybeans worsen dextran sodium sulfate-induced colitis by disrupting intestinal ecology. Food Funct 2022; 13:6205-6216. [PMID: 35583076 DOI: 10.1039/d2fo00446a] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Food mediates susceptibility to inflammatory bowel diseases (IBDs) associated with the microbiome. Existing studies suggest that a high-sugar and high-fat diet promotes IBDs, but whether a plant-based diet is fully harmless to IBD improvement remains unknown. In this study, for the first time, we assessed the effect of soybean and its carbohydrates on dextran sodium sulfate (DSS)-induced colitis. In a DSS-induced colitis mouse model (BALB/C WT), the oral administration of soybeans worsened colitis, which was associated with higher disease activity index, histology score and expression of pro-inflammatory cytokines, and lower expression of anti-inflammatory cytokines. Here, 16S rRNA sequencing and elimination of gut bacteria by antibiotics showed that the exacerbating colitis caused by soybeans depends on the changes in the intestinal flora. Furthermore, the gavage of soybean carbohydrates such as sucrose and raffinose-family oligosaccharides altered the intestinal microbiota and worsened inflammation. When co-cultured with macrophages (RAW 264.7), the metabolites of the disordered intestinal flora, isolated Escherichia coli and purified LPS showed high macrophage toxicity to inhibit pathogen clearance. These results indicate that the intake of soybeans and soybean carbohydrates is not conducive to recovery from IBDs based on changes in gut microbiota and metabolites affecting the activities of macrophages.
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Affiliation(s)
- Kaiyang Chen
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Congcong Gao
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Ming Tang
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Qinchen Dong
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Ningyu Wang
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Shuli Man
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Fuping Lu
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Haikuan Wang
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
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22
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Abd El-Wahab EW, Youssef EI, Hassouna E. Helicobacter pylori infection in patients with inflammatory bowel diseases: a single-centre, prospective, observational study in Egypt. BMJ Open 2022; 12:e057214. [PMID: 35504642 PMCID: PMC9066476 DOI: 10.1136/bmjopen-2021-057214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 04/13/2022] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE Conflicting results have been reported by numerous epidemiological studies investigating the association between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD). We aimed in this study to assess the possible association between H. pylori infection and IBD and its effects on disease progression. DESIGN Prospective observational study. SETTING Specialised IBD care clinics at Alexandria University Student Hospital in northern Egypt, between March and June 2019. PARTICIPANTS 182 patients with IBD. ANALYSIS AND OUTCOME MEASURES Participants with IBD were screened for H. pylori infection and clinically evaluated at the initial visit and bimonthly for 3 months to record any potential improvement/flare of the IBD condition. RESULTS Overall, 90 (49.5%) patients with IBD had evidence of H. pylori infection. The course of IBD did not significantly differ in association with H. pylori infection or IBD treatment strategy. Cox regression analysis revealed that patients aged 20-35 years (HR=6.20 (95% CI: 1.74 to 22.12)) and 35-55 years (557.9 (17.4-17 922.8)), high socioeconomic status (2.9 (1.11-7.8)), daily consumption of fibre-rich food (5.1 (1.32-19.5)), occasional consumption of snacks between meals (2.8 (2.5-70.5)) and eating four meals per day (13.3 (1.0-7.7)) were predictive of IBD flare. By contrast, eating fruits and vegetables showed a strongly protective association (HR=0.001 (95% CI: 0.0002 to 0.02)). The probabilities of improvement of IBD symptoms after 12 weeks of follow-up were comparable in assessments based on H. pylori infection status (0.793 for H. pylori negative vs 0.778 for H. pylori positive) and IBD treatment option (0.811 for conventional therapy vs 0.750 for biological therapy). CONCLUSION The association between IBD and H. pylori infection is unresolved and should be further investigated in the context of specific environmental exposures that can influence the development or relapse of IBD.
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Affiliation(s)
- Ekram W Abd El-Wahab
- Tropical Health Department, High Institute of Public Health, Alexandria University, 21561 Alexandria, Egypt
| | - Ebtessam I Youssef
- Tropical Health Department, High Institute of Public Health, Alexandria University, 21561 Alexandria, Egypt
| | - Ehab Hassouna
- Internal Medicine Department, Faculty of Medicine, Alexandria University, 21568 Alexandria, Egypt
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23
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Qian K, Chen S, Wang J, Sheng K, Wang Y, Zhang M. A β- N-acetylhexosaminidase Amuc_2109 from Akkermansia muciniphila protects against dextran sulfate sodium-induced colitis in mice by enhancing intestinal barrier and modulating gut microbiota. Food Funct 2022; 13:2216-2227. [PMID: 35133390 DOI: 10.1039/d1fo04094d] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is associated with the microbial composition of the gut and its metabolites. Akkermansia muciniphila is a probiotic that exerts a significant alleviative or therapeutic effect on host enteritis. This study was designed to determine the protective effect and potential mechanism underlying the secretion of β-acetylaminohexosidase (Amuc_2109) by A. muciniphila against dextran sulfate sodium (DSS)-induced colitis in mice. C57BL/6 mice were gavaged with Amuc_2109 for 21 days, and during the last seven days of treatment, they drank DSS dissolved in their drinking water to induce colitis. Our results showed that supplementation with Amuc_2109 improved DSS-induced colitis as evidenced by lowered disease activity index (DAI) scores, reduced weight loss, increased colon length, and inhibited oxidative stress. In addition, Amuc_2109 inhibited the overexpression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome in DSS-induced colitis. Furthermore, supplementation with Amuc_2109 also restored the mRNA expression of tight junction proteins (ZO-1, occludin, claudin-1). Further analysis of fecal microbial 16S rRNA sequences showed that Amuc_2109 reshaped the intestinal microbiota. While the anti-inflammatory effects of Amuc_2109 were only manifested with the wild-type protein, the anti-inflammatory effects were completely lost after the mutation of its key catalytic amino acids rendered Amuc_2109 inactive. In summary, these findings demonstrate the potential of Amuc_2109, as a therapeutic agent for ulcerative colitis. We posit that it will provide additional assistance in the prevention and treatment of mucus layer-related diseases such as ulcerative colitis.
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Affiliation(s)
- Kaiyue Qian
- School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China
| | - Shoujun Chen
- School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China
| | - Junchao Wang
- School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China.,Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, Anhui, China
| | - Kangliang Sheng
- School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China
| | - Yongzhong Wang
- School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China
| | - Min Zhang
- School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China
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24
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Baker KA, Miller TD, Marino FE, Hartmann TE. The exercise-induced inflammatory response in inflammatory bowel disease: A systematic review and meta-analysis. PLoS One 2022; 17:e0262534. [PMID: 35120159 PMCID: PMC8815877 DOI: 10.1371/journal.pone.0262534] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 12/28/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND This study investigated selected inflammatory responses to acute and chronic exercise in individuals with inflammatory bowel disease (IBD). METHODS A systematic review and meta-analysis was conducted on all relevant exercise-based intervention publications with IBD participants. The study included articles that utilised a broad range of acute and chronic exercise interventions, with inflammatory biomarkers measured and symptoms documented, both pre- and post-exercise for those with IBD. The search was limited to studies published in English, the use of human participants, and primary studies, with no restrictions on date of publication or participant's age. Articles were retrieved through the electronic databases: PubMed, SPORTDiscus, and Scopus. This study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS Six inflammatory markers were included in the meta-analysis which consisted of five studies. Exercise interventions resulted in no significant difference in IL-6 (SMD = -0.09; 95% CI = -0.49, 0.30; P = 0.64), TNF-α (SMD = 0.08; 95% CI = -0.31, 0.48; P = 0.68), CRP (SMD = -0.04; 95% CI = -0.58, 0.50; P = 0.89), IL-17 (SMD = 0.15; 95% CI = -0.45, 0.76; P = 0.62), leukocytes (SMD = 0.40; 95% CI = -0.53, 1.33; P = 0.40) or lymphocytes (SMD = 0.32; 95% CI = -0.33, 0.97; P = 0.33), thus, indicating exercise may have no effect on inflammatory markers in IBD. Bowel symptoms improved following regular moderate exercise that incorporated stress management. CONCLUSION Heterogeneity among the identified literature may have led to exercise interventions being ineffective in reducing inflammation. Although the limited number of eligible studies may reduce the reliability of results, it emphasises the need for additional research in this domain. Importantly, no adverse symptomatic responses to exercise indicate that exercise is safe for IBD patients.
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Affiliation(s)
- Kelly A. Baker
- School of Allied Health, Exercise and Sport Sciences, Charles Sturt University, Bathurst, New South Wales, Australia
| | - Timothy D. Miller
- School of Allied Health, Exercise and Sport Sciences, Charles Sturt University, Bathurst, New South Wales, Australia
| | - Frank E. Marino
- School of Allied Health, Exercise and Sport Sciences, Charles Sturt University, Bathurst, New South Wales, Australia
| | - Tegan E. Hartmann
- School of Allied Health, Exercise and Sport Sciences, Charles Sturt University, Bathurst, New South Wales, Australia
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Qi Y, Wu HM, Yang Z, Zhou YF, Jin L, Yang MF, Wang FY. New Insights into the Role of Oral Microbiota Dysbiosis in the Pathogenesis of Inflammatory Bowel Disease. Dig Dis Sci 2022; 67:42-55. [PMID: 33527328 DOI: 10.1007/s10620-021-06837-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 01/09/2021] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory disorders with a prolonged duration characterized by recurrent relapse and remission. The exact etiology of IBD remains poorly understood despite the identification of relevant risk factors, including individual genetic susceptibility, environmental triggers, and disruption of immune homeostasis. Dysbiosis of the gut microbiota is believed to exacerbate the progression of IBD. Recently, increasing evidence has also linked oral microbiota dysbiosis with the development of IBD. On the one hand, IBD patients show significantly unbalanced composition and function of the oral microbiota known as dysbiosis. On the other, overabundances of oral commensal bacteria with opportunistic pathogenicity have been found in the gut microbiota of IBD patients. Herein, we review the current information on the causative factors of IBD, especially recent evidence of IBD-associated oral microbiota dysbiosis, which has seldom been covered in the previous literature review, highlighting the pathogenic mechanisms of specific oral bacteria in the development of IBD. Ectopic colonization of several oral bacteria, including a subset of Porphyromonas gingivalis, Streptococcus mutans, Fusobacterium nucleatum, Campylobacter concisus, and Klebsiella pneumoniae, may lead to destruction of the intestinal epithelial barrier, excessive secretion of inflammatory cytokines, disruption of the host immune system, and dysbiosis of gut microbiota, consequently aggravating chronic intestinal inflammation. Studying oral microbiota dysbiosis may open future horizons for understanding IBD pathogenesis and provide novel biomarkers for IBD. This review also presents the current treatment and new perspectives for IBD treatment.
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Affiliation(s)
- Ying Qi
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Hui-Min Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Zhao Yang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Yi-Fei Zhou
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Lei Jin
- Department of Stomatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Miao-Fang Yang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Fang-Yu Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China.
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26
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Liu R, Wan Q, Zhao R, Xiao H, Cen Y, Xu X. Risk of non-melanoma skin cancer with biological therapy in common inflammatory diseases: a systemic review and meta-analysis. Cancer Cell Int 2021; 21:614. [PMID: 34809619 PMCID: PMC8607648 DOI: 10.1186/s12935-021-02325-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 11/10/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown. METHODS We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model. RESULTS The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years. CONCLUSIONS Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.
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Affiliation(s)
- Ruolin Liu
- Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, No 37 Wainan Guoxue Road, Chengdu, 610041, China
| | - Qianyi Wan
- Department of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Rui Zhao
- Department of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Haitao Xiao
- Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, No 37 Wainan Guoxue Road, Chengdu, 610041, China
| | - Ying Cen
- Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, No 37 Wainan Guoxue Road, Chengdu, 610041, China.
| | - Xuewen Xu
- Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, No 37 Wainan Guoxue Road, Chengdu, 610041, China.
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Tian L, Zhao JL, Kang JQ, Guo SB, Zhang N, Shang L, Zhang YL, Zhang J, Jiang X, Lin Y. Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling. Front Immunol 2021; 12:740565. [PMID: 34589089 PMCID: PMC8473681 DOI: 10.3389/fimmu.2021.740565] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 08/26/2021] [Indexed: 12/24/2022] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.
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Affiliation(s)
- Lianlian Tian
- Department of Pediatrics, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Jun-Long Zhao
- State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Air Force Medical University, Xi'an, China
| | - Jian-Qin Kang
- Department of Pediatrics, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Shi-Bo Guo
- Department of Pediatrics, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Nini Zhang
- Department of Pediatrics, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Lei Shang
- Department of Health Statistics and Ministry of Education, Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Xi'an, China
| | - Ya-Long Zhang
- Department of Pediatrics, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Jian Zhang
- State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China
| | - Xun Jiang
- Department of Pediatrics, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Yan Lin
- Department of Pediatrics, Tangdu Hospital, Air Force Medical University, Xi'an, China
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Chen S, Wu X, Yu Z. Juglone Suppresses Inflammation and Oxidative Stress in Colitis Mice. Front Immunol 2021; 12:674341. [PMID: 34421890 PMCID: PMC8375437 DOI: 10.3389/fimmu.2021.674341] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 07/12/2021] [Indexed: 12/22/2022] Open
Abstract
Juglone (JUG), a natural product found in walnut trees and other plants, shows potent antioxidant, antimicrobial, and immunoregulatory activities. However, it remains unknown whether JUG can alleviate ulcerative colitis. This study aims to explore the effect of JUG on dextran sulfate sodium (DSS)-induced colitis in mice. The mice were randomly assigned into three groups: the vehicle group, the DSS group, and the JUG group. The experiments lasted for 17 days; during the experiment, all mice received dimethyl sulfoxide (DMSO, 0.03% v/v)-containing water, while the mice in the JUG group received DMSO-containing water supplemented with JUG (0.04 w/v). Colitis was induced by administering DSS (3% w/v) orally for 10 consecutive days. The results showed that the JUG treatment significantly ameliorated body weight loss and disease activity index and improved the survival probability, colon length, and tissue damage. JUG reversed the DSS-induced up-regulation of proinflammatory cytokines, including interleukin (IL)-6, 12, 21, and 23, and tumor necrosis factor-alpha, and anti-inflammatory cytokines, such as IL-10 and transforming growth factor-beta, in the serum of the colitis mice. Additionally, the activation of mitochondrial uncoupling protein 2 and phospho-Nuclear Factor-kappa B p65 and the inhibition of the kelch-like ECH-associated protein 1 and NF-E2-related factor 2 induced by DSS were also reversed under JUG administration. Although the JUG group possessed a similar microbial community structure as the DSS group, JUG enriched potential beneficial microbes such as Lachnospiraceae_NK4A136_group but not pathogens such as Escherichia Shigella, which was dominative in DSS group, at the genus level. In conclusion, our results demonstrated that JUG could be a promising agent for UC prevention to regulate inflammatory cytokines and oxidative stress.
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Affiliation(s)
- Shuai Chen
- School of Public Health, Xinxiang Medical University, Xinxiang, China.,Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Xin Wu
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Zengli Yu
- School of Public Health, Xinxiang Medical University, Xinxiang, China.,School of Public Health, Zhengzhou University, Zhengzhou, China
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29
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Wang C, Li S, Hong K, Yu L, Tian F, Zhao J, Zhang H, Chen W, Zhai Q. The roles of different Bacteroides fragilis strains in protecting against DSS-induced ulcerative colitis and related functional genes. Food Funct 2021; 12:8300-8313. [PMID: 34308455 DOI: 10.1039/d1fo00875g] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
The role of supplementation with different Bacteroides fragilis (B. fragilis) strains in alleviating ulcerative colitis (UC) is unclear due to the controversial results from animal experiments. In this study, three B. fragilis strains were evaluated for their ability to alleviate dextran sulfate sodium (DSS)-induced UC in C57BL/6J mice. We analyzed the anti-inflammatory effects of different B. fragilis strains and the changes they caused in the intestinal microbiota composition, intestinal epithelial permeability, cytokine concentrations, protein expression of nuclear factor kappa-B (NF-κB) and the underlying specific genes. The results showed that when orally administered, the different B. fragilis strains exerted different effects on the assessed parameters of the mice. The results of real-time quantitative polymerase chain reaction and immunofluorescence staining showed that the supplementation of B. fragilis FSHCM14E1, but not FJSWX11BF, enhanced the expression of the tight-junction proteins ZO-1, occludin and claudin-1. Western blot analysis showed that the anti-inflammatory effects of B. fragilis FSHCM14E1 were related to the NF-κB pathway. Genomic analysis suggested that the anti-inflammatory effects of FSHCM14E1 may be mediated through specific genes associated with defense mechanisms and the secretion of SCFAs. Overall, this study indicates the therapeutic potential of B. fragilis FSHCM14E1 for the prevention of UC.
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Affiliation(s)
- Chen Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Sijia Li
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Kan Hong
- Wuxi People's Hospital Afliated to Nanjing Medical University, Wuxi 214023, Jiangsu, People's Republic of China
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China and Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch 214122, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
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30
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Zhang H, Wang X. Risk Factors of Venous Thromboembolism in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:693927. [PMID: 34262920 PMCID: PMC8273255 DOI: 10.3389/fmed.2021.693927] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 05/31/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Patients suffering from chronic inflammatory disorders, such as inflammatory bowel disorder, are at higher risk of developing thromboembolism. The chronic inflammatory nature of inflammatory bowel disease has been identified as a predominant reason for a state of Virchow's triad (i.e., endothelial dysfunction, stasis, and general hypercoagulability), eventually leading to the onset of venous thromboembolism. Recent studies show that certain factors, such as demographics, medication history, and history of surgical intervention may increase thromboembolism risk in patients with inflammatory bowel disease. However, to date, no study has attempted to evaluate the effect of different risk factors associated with the development of venous thromboembolism in inflammatory bowel disease patients. Objective: To evaluate the risk factors that can influence the incidence of venous thromboembolism in patients with inflammatory bowel disease. Methods: Academic literature was systematically searched based on the PRISMA guidelines across five databases: Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE. A random-effect meta-analysis was conducted to evaluate the hazard ratio for the risk factors (i.e., aging, gender, steroid therapy, surgery, and ulcerative colitis) that can influence the incidence of venous thromboembolism in patients with inflammatory bowel disease. Results: From a total of 963 studies, 18 eligible studies with 1,062,985 (44.59 ± 10.18 years) patients suffering from inflammatory bowel disease were included in the review. A meta-analysis revealed a higher risk of aging (Hazard's ratio: 2.19), steroids (1.87), surgery (1.48), and ulcerative colitis (2.06) on venous thromboembolism in patients with inflammatory bowel disease. We also found that the female gender (0.92) did not increase the incidence of venous thromboembolism in inflammatory bowel disease patients. Conclusion: The study provides preliminary evidence regarding high risks associated with ulcerative colitis, steroid consumption, and aging for the development of venous thromboembolism in patients with inflammatory bowel disease. The findings from this study may contribute to developing awareness among clinicians, better risk stratification and prevention of venous thromboembolic complications in patients with inflammatory bowel disease.
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Affiliation(s)
- Hua Zhang
- Department of Nursing, Xiangya Second Hospital of Central South University, Changsha, China
| | - Xuehong Wang
- Department of Gastroenterology, Xiangya Second Hospital of Central South University, Changsha, China
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31
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Mahmoud TN, El-Maadawy WH, Kandil ZA, Khalil H, El-Fiky NM, El Alfy TSMA. Canna x generalis L.H. Bailey rhizome extract ameliorates dextran sulfate sodium-induced colitis via modulating intestinal mucosal dysfunction, oxidative stress, inflammation, and TLR4/ NF-ҡB and NLRP3 inflammasome pathways. JOURNAL OF ETHNOPHARMACOLOGY 2021; 269:113670. [PMID: 33301917 DOI: 10.1016/j.jep.2020.113670] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 11/15/2020] [Accepted: 12/01/2020] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Genus Canna is used in folk medicine as demulcent, diaphoretic, antipyretic, mild laxative and in gastrointestinal upsets therapy. Canna x generalis (CG) L.H. Bailey is traditionally used as anti-inflammatory, analgesic and antipyretic. Besides, CG is used in Ayurvedic medicines' preparations and in the treatment of boils, wounds, and abscess. Nevertheless, its anti-inflammatory effects against ulcerative colitis (UC) are not yet investigated. AIM This study aimed to investigate the phytoconstituents of CG rhizome ethanol extract (CGE). Additionally, we aimed to comparatively evaluate its therapeutic effects and underlying mechanisms against the reference drug "sulphasalazine (SAS)" in dextran sodium sulfate (DSS)-induced UC in mice. MATERIAL AND METHODS Metabolic profiling of CG rhizomes was performed via UHPLC/qTOF-HRMS; the total phenolic, flavonoid and steroid contents were determined, and the main phytoconstituents were isolated and identified. Next, DSS-induced (4%) acute UC was established in C57BL/6 mice. DSS-induced mice were administered either CGE (100 and 200 mg/kg) or SAS (200 mg/kg) for 7 days. Body weight, colon length, disease activity index (DAI) and histopathological alterations in colon tissues were examined. Colon levels of oxidative stress (GSH, MDA, SOD and catalase) and pro-inflammatory [Myeloperoxidase (MPO), nitric oxide (NO), IL-1β, IL-12, TNF-α, and INF-γ] markers were colourimetrically determined. Serum levels of lipopolysaccharide (LPS) and relative mRNA expressions of occludin, TLR4 and ASC (Apoptosis-Associated Speck-Like Protein Containing CARD) using RT-PCR were measured. Protein levels of NLRP3 inflammasome and cleaved caspase-1 were determined by Western blot. Furthermore, immunohistochemical examinations of caspase-3, NF-ҡB and claudin-1 were performed. RESULTS Major identified constituents of CGE were flavonoids, phenolic acids, phytosterols, beside five isolated phytoconstituents (β-sitosterol, triacontanol fatty alcohol, β-sitosterol-3-O-β-glucoside, rosmarinic acid, 6-O-p-coumaroyl-β-D-fructofuranosyl α-D-glucopyranoside). The percentage of the phenolic, flavonoid and steroid contents in CGE were 20.55, 6.74 and 98.09 μg of gallic acid, quercetin and β-sitosterol equivalents/mg extract, respectively. In DSS-induced mice, CGE treatment ameliorated DAI, body weight loss and colon shortening. CGE attenuated the DSS-induced colonic histopathological alternations, inflammatory cell infiltration and histological scores. CGE elevated GSH, SOD and catalase levels, and suppressed MDA, pro-inflammatory mediators (MPO and NO) as well as cytokines levels in colonic tissues. Moreover, CGE downregulated LPS/TLR4 signaling, caspase-3 and NF-ҡB expressions. CGE treatment inhibited NLRP3 signaling pathway as indicated by the suppression of the protein expression of NLRP3 and cleaved caspase-1, and the ASC mRNA expression in colonic tissues. Additionally, CGE restored tight junction proteins' (occludin and claudin-1) expressions. CONCLUSION Our findings provided evidence for the therapeutic potential of CGE against UC. CGE restored intestinal mucosal barrier's integrity, mitigated oxidative stress, inflammatory cascade, as well as NF-ҡB/TLR4 and NLRP3 pathways activation in colonic tissues. Notably, CGE in a dose of 200 mg/kg was more effective in ameliorating DSS-induced UC as compared to SAS at the same dose.
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Affiliation(s)
- Toka N Mahmoud
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr Al Aini Street, Cairo, P.O. Box 11562, Egypt.
| | - Walaa H El-Maadawy
- Department of Pharmacology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt.
| | - Zeinab A Kandil
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr Al Aini Street, Cairo, P.O. Box 11562, Egypt
| | - Heba Khalil
- Department of Pathology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt
| | - Nabaweya M El-Fiky
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr Al Aini Street, Cairo, P.O. Box 11562, Egypt
| | - Taha Shahat M A El Alfy
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr Al Aini Street, Cairo, P.O. Box 11562, Egypt
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Du Y, Rong L, Cong Y, Shen L, Zhang N, Wang B. Macrophage polarization: an effective approach to targeted therapy of inflammatory bowel disease. Expert Opin Ther Targets 2021; 25:191-209. [PMID: 33682588 DOI: 10.1080/14728222.2021.1901079] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Inflammatory bowel disease (IBD) is a systemic disease with immune abnormalities that can affect the entire digestive tract. A high percentage of patients with IBD are unresponsive to current pharmacological agents, hence the need exists for novel therapeutic approaches. There is compelling evidence that macrophage polarization plays a key role in the remission of IBD patients and that it could open up future treatment options for patients.Areas covered: This paper highlights the crucial role of macrophage polarization in IBD. The authors shed light on the phenotype and function of macrophages and potential drug targets for polarization regulation. Existing approaches for regulating macrophage polarization are discussed and potential solutions for safety concerns are considered. We performed a literature search on the IBD and macrophage polarization mainly published in PubMed January 2010-July 2020.Expert opinion: Evidence indicates that there are fewer M2 macrophages and a high proportion of M1 macrophages in the intestinal tissues of individuals who are non- responsive to treatment. Regulating macrophage polarization is a potential novel targeted option for IBD treatment. Improved mechanistic insights are required to uncover more precise and effective targets for skewing macrophages into a proper phenotype.
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Affiliation(s)
- Yaoyao Du
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lan Rong
- Department of Digestive Diseases, Huashan Hospital Affiliated to Fudan University, Shanghai, China
| | - Yuanhua Cong
- Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, China
| | - Lan Shen
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ning Zhang
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Bing Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, China
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Farsi F, Ebrahimi-Daryani N, Barati M, Janani L, Karimi MY, Akbari A, Irandoost P, Mesri Alamdari N, Agah S, Vafa M. Effects of coenzyme Q10 on health-related quality of life, clinical disease activity and blood pressure in patients with mild to moderate ulcerative colitis: a randomized clinical trial. Med J Islam Repub Iran 2021; 35:3. [PMID: 33996654 PMCID: PMC8111632 DOI: 10.47176/mjiri.35.3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Indexed: 12/14/2022] Open
Abstract
Background: Ulcerative colitis (UC) is specified by a chronic mucosal inflammation that has a deleterious impact on the quality of life (QoL). Coenzyme Q10 (CoQ10) appears to influence disease activity by its obvious properties. Therefore, the current research intends to assess the impacts of CoQ10 on QoL, disease activity, and blood pressure in UC patients. Methods: This clinical trial performed on men and women with UC in 2017 who were attended the gastrointestinal center of Hazrat Rasool Akram Hospital and private clinic. Eighty-eight UC patients were randomly allocated to receive either CoQ10 (200 mg/day) or placebo for 8 weeks. The anthropometric parameters, blood pressure, inflammatory bowel disease questionnaire-32 (IBDQ-32) score, and the Simple Clinical Colitis Activity Index (SCCAI) score were measured pre and post-intervention. P-value <0.05 was considered to be statistically significant. All statistical analysis was done using SPSS software version 24. Results: Eighty-six UC patients (44 males) with a mean age of 39.29 (10.19) years completed the trial. The results of between- and within-group analysis revealed that the SCCAI score (p<0.001 and p<0.001, respectively), diastolic blood pressure (p=0.025 and p=0.001, respectively), and systolic blood pressure (p=0.001 and p<0.001, respectively) decremented significantly; while, the mean IBDQ-32 (p<0.001 and p=0.001, respectively) increased substantially in the CoQ10 group; whereas there was no significant difference in anthropometric indices in both groups. Conclusion: Findings suggest that CoQ10 can be used as a potential intervention for diminishing the disease severity and blood pressure and may improve QoL and UC patients. IRCT number: IRCT20090822002365N17.
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Affiliation(s)
- Farnaz Farsi
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi-Daryani
- Division of Gastroenterology, Imam Khomeini Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmood Barati
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.,Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran
| | - Leila Janani
- Preventive Medicine and Public Health Research Center, Psychosocial Health Research Institute (PHRI), Iran University of Medical sciences, Tehran, Iran
| | | | - Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Pardis Irandoost
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical sciences, Tehran, Iran
| | - Naimeh Mesri Alamdari
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical sciences, Tehran, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Vafa
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
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Effect of 2′-fucosyllactose supplementation on intestinal flora in mice with intestinal inflammatory diseases. Int Dairy J 2020. [DOI: 10.1016/j.idairyj.2020.104797] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Ismailov RM, Pouillon L, Selinger CP, Khasanova ZD. Knowledge and awareness of biosimilars and shared decision-making among gastroenterology team members in Colorado, USA. Expert Opin Biol Ther 2020; 21:111-119. [PMID: 33107355 DOI: 10.1080/14712598.2020.1842355] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Background: There are gaps in gastroenterologist team members' understanding of various topics related to biosimilars. We aimed to examine perspectives, views, and attitudes toward biosimilar and shared decision-making (SDM) among gastroenterology team members in Colorado, USA. The ultimate goal was to increase knowledge and awareness of biosimilars and SDM. Research design and methods: We developed educational materials focused on biosimilars and SDM and distributed them to each participating gastroenterology office. Subsequently, we conducted a survey of all team members from participating offices. Results: Responses were obtained from 54 gastroenterology team members. Most respondents identified the correct answer regarding biosimilars, the nocebo effect, and SDM. Almost half (47.2%) of respondents scored their level of awareness regarding biosimilars prior to reading our educational materials as poor, and nearly one quarter (26.4%) indicated so for SDM. Improvement in scores after reading our materials was significant for both biosimilars and SDM (i.e. biosimilar: z = 6.276, p-value <0.001 and SDM z = 6.328, p-value <0.001). Conclusions: Educational efforts effectively increased the low baseline knowledge and awareness of biosimilars and SDM among gastroenterology team members. More educational projects focused on biosimilars and SDM are needed to reduce the nocebo effect and prevent hampering of the cost-savings of biosimilars.
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Affiliation(s)
- Rovshan M Ismailov
- Complex Mechanisms of Disease, Aging and Trauma (CMDAT) Research Foundation , Denver, CO, USA
| | - Lieven Pouillon
- Imelda GI Clinical Research Centre, Imeldaziekenhuis Bonheiden , Bonheiden, Belgium
| | - Christian P Selinger
- Gastroenterology, Leeds Teaching Hospitals NHS Trust , Leeds, UK.,University of Leeds , Leeds, UK
| | - Zaytuna D Khasanova
- Complex Mechanisms of Disease, Aging and Trauma (CMDAT) Research Foundation , Denver, CO, USA
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Liu Y, Sheng Y, Pan Q, Xue Y, Yu L, Tian F, Zhao J, Zhang H, Zhai Q, Chen W. Identification of the key physiological characteristics of Lactobacillus plantarum strains for ulcerative colitis alleviation. Food Funct 2020; 11:1279-1291. [PMID: 31984399 DOI: 10.1039/c9fo02935d] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Lactobacillus plantarum is a probiotic that is widely used to prevent ulcerative colitis (UC). However, the effects of this species are strain-specific. We believe that the physiological characteristics of L. plantarum strains may affect their UC-alleviating function. Therefore, this study investigated the relationship between the alleviating effect of L. plantarum strains on UC and their physiological characteristics in vitro. The physiological characteristics of 14 L. plantarum strains were assayed in vitro, including gastrointestinal transit tolerance, oligosaccharide fermentation, HT-29 cell adhesion, generation time, exopolysaccharide production, acetic acid production, and conjugated linoleic acid (CLA) synthesis. To create animal models, colitis was established in C57BL/6 mice by adding 3.5% dextran sulfate sodium to drinking water for 7 days. L. plantarum strains with significantly different physiological characteristics were orally administered to the mice at a dose of 3 × 109 CFU. The results indicated that among the tested L. plantarum strains, L. plantarum N13 and L. plantarum CCFM8610 significantly alleviated colitis in the mice, as observed from the restoration of the body weight and disease activity index (DAI) score, recovery of the gut microbiota composition, reduced expression of pro-inflammatory cytokines, and significantly inhibited expression of p65. Correlation analysis indicated that four of the measured physiological characteristics (gastrointestinal transit tolerance, HT-29 cell adhesion, generation time, and CLA synthesis) were related to the UC-alleviating effects to different degrees. The strongest correlation was observed between the CLA synthesis ability and UC-alleviating effects (with Pearson correlation coefficients for IL-1β, IL-6, IL-17F, TNF-α, myeloperoxidase, and the DAI all below -0.95). The ability to synthesize CLA may be the key physiological characteristic of L. plantarum in UC alleviation. Our findings may contribute to the rapid screening of lactic acid bacterial strains with UC-alleviating effects.
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Affiliation(s)
- Yang Liu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Yingyue Sheng
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
| | - Qiqi Pan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Yuzheng Xue
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China and Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, China and (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China and Beijing Innovation Center of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China
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Qi Y, Zang SQ, Wei J, Yu HC, Yang Z, Wu HM, Kang Y, Tao H, Yang MF, Jin L, Zen K, Wang FY. High-throughput sequencing provides insights into oral microbiota dysbiosis in association with inflammatory bowel disease. Genomics 2020; 113:664-676. [PMID: 33010388 DOI: 10.1016/j.ygeno.2020.09.063] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 09/16/2020] [Accepted: 09/29/2020] [Indexed: 12/12/2022]
Abstract
Although the prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, the etiology remains elusive. Investigating oral microbiota dysbiosis is essential to understanding IBD pathogenesis. Our study evaluated variations in salivary microbiota and identified potential associations with IBD. The saliva microbiota of 22 IBD patients and 8 healthy controls (HCs) was determined using 16S ribosomal RNA (rRNA) gene sequencing and analyzed using QIIME2. A distinct saliva microbiota dysbiosis in IBD, characterized by alterations in microbiota biodiversity and composition, was identified. Saccharibacteria (TM7), Absconditabacteria (SR1), Leptotrichia, Prevotella, Bulleidia, and Atopobium, some of which are oral biofilm-forming bacteria, were significantly increased. Moreover, levels of inflammatory cytokines associated with IBD were elevated and positively correlated with TM7 and SR1. Functional variations include down-regulation of genetic information processing, while up-regulation of carbohydrate metabolism and protein processing in the endoplasmic reticulum in IBD. Our data implicate salivary microbiota dysbiosis involving in IBD pathogenesis.
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Affiliation(s)
- Ying Qi
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Sheng-Qi Zang
- Department of Stomatology, Jinling Hospital, Nanjing, Jiangsu, China
| | - Juan Wei
- Department of Gastroenterology and Hepatology, Jinling Hospital, Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Hong-Chuan Yu
- Department of Stomatology, Jinling Hospital, Nanjing, Jiangsu, China
| | - Zhao Yang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Hui-Min Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Ying Kang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Hui Tao
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Miao-Fang Yang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Lei Jin
- Department of Stomatology, Jinling Hospital, Nanjing, Jiangsu, China
| | - Ke Zen
- School of life sciences, Nanjing University, Nanjing, Jiangsu, China
| | - Fang-Yu Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China..
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Walter L, Canup B, Pujada A, Bui TA, Arbasi B, Laroui H, Merlin D, Garg P. Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer. Cell Death Dis 2020; 11:767. [PMID: 32943603 PMCID: PMC7498454 DOI: 10.1038/s41419-020-02959-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 07/15/2020] [Accepted: 07/16/2020] [Indexed: 12/13/2022]
Abstract
Colitis-associated cancer (CAC) is a subtype of colon cancer that is driven by chronic inflammation and is prevalent in chronic ulcerative colitis patients. The development of CAC is associated with the inflammation-dysplasia-carcinoma pathway which is significantly different than adenoma-carcinoma pathway of sporadic colon cancer (CRC). Matrix Metalloproteinase 9 (MMP9) is a zinc-dependent endopeptidase against extracellular matrix (ECM) proteins expressed in the gastrointestinal tract during inflammation. We have previously shown that MMP9 plays a tumor suppressor role in CAC via “MMP9-Notch1-ARF-p53 axis” pathway. The aim of this study is to determine the role of MMP9 in maintaining genomic stability in CAC. Homozygous transgenic mice with constitutive-expression of MMP9 in the colonic epithelium (TgM9) with their wild-type littermates (WT) and stably transfected HCT116 cells with/without MMP9 were used for in vivo and in vitro experiments, respectively. As ‘proof of concept’ model, nanoparticles (NPs) loaded with MMP9 siRNA were used to examine the effect of MMP9 silencing in the colonic epithelium. In CAC, colonic epithelium of TgM9 mice exhibited lower amounts of reactive oxygen species (ROS), less DNA damage, and increased expression of mismatch repair genes compared to WTs. Our study showed that MMP9 expression correlates with the reduced ROS levels, decreased DNA damage, and upregulated mismatch repair pathway. This suggests that MMP9 expression is a natural biological way to suppress CAC by limiting ROS accumulation and DNA damage in the colon. Therefore, MMP9 inhibition could be deleterious for CAC patient.
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Affiliation(s)
- Lewins Walter
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States
| | - Brandon Canup
- Department of Chemistry, Georgia State University, Atlanta, GA, United States
| | - Adani Pujada
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States
| | - Tien Anh Bui
- Department of Biology, Georgia State University, Atlanta, GA, United States
| | - Behafarin Arbasi
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States
| | - Hamed Laroui
- Department of Chemistry, Georgia State University, Atlanta, GA, United States
| | - Didier Merlin
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States
| | - Pallavi Garg
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States.
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Shin MY, Yong CC, Oh S. Regulatory Effect of Lactobacillus brevis Bmb6 on Gut Barrier Functions in Experimental Colitis. Foods 2020; 9:foods9070864. [PMID: 32630643 PMCID: PMC7404641 DOI: 10.3390/foods9070864] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 06/26/2020] [Accepted: 06/29/2020] [Indexed: 02/06/2023] Open
Abstract
The integrity of gut barrier functions is closely associated with the pathogenesis of colitis. It is speculated that Lactobacillus brevis Bmb6 alleviates colitis by improving the tight junction (TJ) of the inflamed intestinal epithelial layer. In the present study, the regulatory effects of L. brevis Bmb6 on the TJ barrier to ameliorate colitis-symptoms were investigated. Preliminary screening showed that L. brevis Bmb6 exhibited strong acid and bile acid tolerance, along with antioxidants and β-galactosidase activities. In a 14-day dextran sulfate sodium (DSS)-induced colitis mouse model, treatment with L. brevis Bmb6 significantly decreased in the disease activity index score. In addition, histological analyses showed that treatment with L. brevis Bmb6 protected the structural integrity of the intestinal epithelial layer and mucin-secreting goblet cells from DSS-induced damage, with only slight infiltration of immune cells. Interestingly, western blotting analyses showed that the expression of the TJ protein, zona occluden-1, was restored in Bmb6-treated mice, but not in DSS-induced mice. Consistently, the gene expression of inflammatory cytokines (tumor necrosis factor-α and interferon-γ) was also suppressed in the Bmb6-treated mice. Hence, our findings suggest that suppression of inflammatory conditions enhanced expression of TJ protein, ZO-1, or vice versa, contributing to a colitis-ameliorating effect in L. brevis Bmb6.
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Affiliation(s)
- Mi-Young Shin
- Microbiology and Functionality Research Group, World Institute of Kimchi, Gwangju 61755, Korea;
- Division of Animal Science, Chonnam National University, Gwangju 61186, Korea;
| | - Cheng-Chung Yong
- Division of Animal Science, Chonnam National University, Gwangju 61186, Korea;
| | - Sejong Oh
- Division of Animal Science, Chonnam National University, Gwangju 61186, Korea;
- Correspondence: ; Tel.: +82-62-530-2116
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Inflammatory bowel disease in Mexico: Epidemiology, burden of disease, and treatment trends. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2020. [DOI: 10.1016/j.rgmxen.2019.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
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Yamamoto-Furusho JK, Bosques-Padilla FJ, Charúa-Guindic L, Cortés-Espinosa T, Miranda-Cordero RM, Saez A, Ledesma-Osorio Y. Inflammatory bowel disease in Mexico: Epidemiology, burden of disease, and treatment trends. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2020; 85:246-256. [PMID: 32143974 DOI: 10.1016/j.rgmx.2019.07.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 05/16/2019] [Accepted: 07/15/2019] [Indexed: 06/10/2023]
Abstract
INTRODUCTION AND AIMS There is no systematized information for determining/monitoring the burden of inflammatory bowel disease in Mexico. The aim of the present study was to estimate the annual burden of inflammatory bowel disease on the Mexican National Healthcare System, by number of patients seen, hospitalizations, and specific deaths, stratified into age groups. MATERIALS AND METHODS Utilizing specific databases of the Mexican National Healthcare System registries coded as ICD-10: K50 and K51, we retrieved and analyzed the data corresponding to the patients seen and hospitalized in 2015, stratified by age group, as well as the specific deaths. Treatment trends among physicians were also examined. RESULTS In 2015, 5,009 women (8.1) and 4,944 men (8.4) with Crohn's disease received medical attention (prevalence of cases seen) and 35.1% of those patients were ≥50years of age. In that same period, 17,177 women (27.7) and 15,883 men (26.9) with ulcerative colitis were seen and 31.6% of those patients were ≥50years of age. The hospitalized cases (prevalence of hospitalized cases) were 1,097 patients (0.91) with Crohn's disease and 43.7% of those patients were ≥50years of age; and 5,345 patients (4.42) with ulcerative colitis and 47.6% of those patients were ≥50years of age. Deaths (specific mortality rate) were: 32 women (0.52) and 36 men (0.50) due to Crohn's disease, and 267 women (4.31) and 186 men (3.15) due to ulcerative colitis. CONCLUSIONS Inflammatory bowel disease is a burden on the health of Mexican adults and the Mexican National Healthcare System, and it is expected to increase over the next 15years.
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Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
| | - F J Bosques-Padilla
- Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
| | - L Charúa-Guindic
- Departamento de Coloproctología, Hospital Ángeles Lomas, Ciudad de México, México
| | - T Cortés-Espinosa
- Centro de Enfermedad Inflamatoria Intestinal. Centro Médico Nacional 20 de Noviembre ISSSTE, Ciudad de México, México
| | - R M Miranda-Cordero
- Clínica de Enfermedad Inflamatoria Intestinal, Centro Médico ISSEMyM, Estado de México, Ciudad de México, México
| | - A Saez
- Dirección Médica, Takeda Ecuador & Peru, Quito, Ecuador; Fundación Mano Amiga, Sistema Universitario Anáhuac, Ciudad de México, México
| | - Y Ledesma-Osorio
- Dirección Médica, Takeda México SA de CV, Estado de México, Ciudad de México, México
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Tian M, Ma P, Zhang Y, Mi Y, Fan D. Ginsenoside Rk3 alleviated DSS-induced ulcerative colitis by protecting colon barrier and inhibiting NLRP3 inflammasome pathway. Int Immunopharmacol 2020; 85:106645. [PMID: 32521491 DOI: 10.1016/j.intimp.2020.106645] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/28/2020] [Accepted: 05/23/2020] [Indexed: 12/19/2022]
Abstract
Ginsenosides have a variety of pharmacological activities, including immunomodulatory, antitumor and anti-inflammatory activities. However, the effect of Rk3 on ulcerative colitis has rarely been reported. This study evaluated the effect of Rk3 on DSS-induced ulcerative colitis and preliminarily explored the anti-inflammatory mechanisms. Rk3 administration significantly attenuated the weight loss, increased DAI scores, colonic shortening, and increased MPO and iNOS activities caused by DSS in mice. Histological improvement was apparent, tight junctions in the colon were restored, and the levels of short-chain fatty acids (acetic acid, butyric acid and isovaleric acid) were increased. In addition, Rk3 reduced the expression of proinflammatory factors (TNF-α, IL-1β and IL-6), NLRP3, ASC, and Caspase-1, indicating blockade of the NLRP3 inflammasome pathway. These results show that Rk3 can improve DSS-induced ulcerative colitis by protecting intestinal barrier function and inhibiting NLRP3 inflammasome expression, indicating that Rk3 could be used as a potential drug for treating ulcerative colitis.
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Affiliation(s)
- Mi Tian
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Pei Ma
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Yan Zhang
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Yu Mi
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China.
| | - Daidi Fan
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China.
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Regional Incidence of Inflammatory Bowel Disease in a Czech Pediatric Population: 16 Years of Experience (2002-2017). J Pediatr Gastroenterol Nutr 2020; 70:586-592. [PMID: 32058417 PMCID: PMC7170436 DOI: 10.1097/mpg.0000000000002660] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Inflammatory bowel disease (IBD) is today a global disease, the incidence of which is growing in the pediatric population. This prospective study aims to decipher IBD incidence and its trend in a pediatric population through 16 years in the South Moravian Region of the Czech Republic. METHODS We evaluated data concerning 358 pediatric patients with newly diagnosed IBD at University Hospital Brno, which is a gastroenterology center for the entire pediatric population (0-18 years) and cares for all pediatric IBD patients in the South Moravian Region (1,187,667 inhabitants). RESULTS The study encompassed 3,488,907 children during 16 years. We diagnosed 192 children (53.6%) with Crohn disease (CD), 123 (34.4%) with ulcerative colitis (UC), and 43 (12.0%) with IBD-unclassified (IBD-U). The incidence of IBD increased from 3.8 (CD 2.9, UC 0.9, and IBD-U 0.0) per 100 000/year in 2002 to 14.7 (CD 9.8, UC 4.0, and IBD-U 0.9) per 100,000/year in 2017 (P < 0.001). The overall IBD incidence per 100,000/year was 9.8 (95% confidence interval [CI]: 8.8--10.9). Constituent incidences per 100,000/year were CD 5.2 (95% CI: 4.5--6.0), UC 3.4 (95% CI: 2.8--4.0), and IBD-U 1.2 (95% CI: 0.9--1.6). IBD incidence was projected to reach 18.9 per 100,000/year in 2022. CONCLUSIONS The overall incidence of pediatric IBD in the Czech Republic is increasing, and especially that of CD, whereas trends in UC and IBD-U appear to be constant. These data highlight the need to identify risk factors involved in the rising incidence of IBD.
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Wang W, Zhang F, Li X, Luo J, Sun Y, Wu J, Li M, Wen Y, Liang H, Wang K, Niu J, Miao Y. Heat shock transcription factor 2 inhibits intestinal epithelial cell apoptosis through the mitochondrial pathway in ulcerative colitis. Biochem Biophys Res Commun 2020; 527:173-179. [PMID: 32446363 DOI: 10.1016/j.bbrc.2020.04.103] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 04/20/2020] [Indexed: 12/29/2022]
Abstract
UC is a chronic inflammatory disease of the colonic mucosa and lacks effective treatments because of unclear pathogenesis. Excessive apoptosis of IECs damages the intestinal epithelial barrier and is involved in the progression of UC, but the mechanism is unknown. HSPs are important in maintaining homeostasis and regulate apoptosis through the mitochondrial pathway. In our previous studies, HSF2, an important regulator of HSPs, was highly expressed in UC patients and negatively correlated with inflammation in mice and IECs. Therefore, we hypothesized that HSF2 may protect against intestinal mucositis by regulating the apoptosis of IECs. In this study, a DSS-induced colitis model of hsf2-/- mice was used to explore the relationship between HSF2 and apoptosis in IECs for the first time. The expression of HSF2 increased in the WT + DSS group compared with that in the WT + H2O group. Moreover, the extent of apoptosis was more severe in the KO + DSS group than in the WT + DSS group. The results showed that HSF2 was negatively correlated with apoptosis in vivo. The expression of HSF2 in Caco-2 cells was changed by lentiviral transfection, and the expression of Bax, cytoplasmic Cyto-C, Cleaved Caspase-9 and Cleaved Caspase-3 were negatively correlated with the different levels of HSF2. These results suggest that HSF2 negatively regulates apoptosis of IECs through the mitochondrial pathway. This may be one of the potential mechanisms to explain the protective role of HSF2 in UC.
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Affiliation(s)
- Wen Wang
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Fengrui Zhang
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Xiaoyu Li
- Department of Respiration, The First Hospital of Changsha, Changsha, Hunan, 410005, China
| | - Juan Luo
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Yang Sun
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Jing Wu
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Maojuan Li
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Yunling Wen
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Hao Liang
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Kunhua Wang
- Department of General Surgery, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China
| | - Junkun Niu
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China.
| | - Yinglei Miao
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan, 650032, China.
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Choi YI, Kim YJ, Chung JW, Kim KO, Kim H, Park RW, Park DK. Effect of Age on the Initiation of Biologic Agent Therapy in Patients With Inflammatory Bowel Disease: Korean Common Data Model Cohort Study. JMIR Med Inform 2020; 8:e15124. [PMID: 32293578 PMCID: PMC7191339 DOI: 10.2196/15124] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/23/2019] [Accepted: 01/27/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The Observational Health Data Sciences and Informatics (OHDSI) network is an international collaboration established to apply open-source data analytics to a large network of health databases, including the Korean common data model (K-CDM) network. OBJECTIVE The aim of this study is to analyze the effect that age at diagnosis has on the prognosis of inflammatory bowel disease (IBD) in Korea using a CDM network database. METHODS We retrospectively analyzed the K-CDM network database from 2005 to 2015. We transformed the electronic medical record into the CDM version 5.0 used in OHDSI. A worsened IBD prognosis was defined as the initiation of therapy with biologic agents, including infliximab and adalimumab. To evaluate the effect that age at diagnosis had on the prognosis of IBD, we divided the patients into an early-onset (EO) IBD group (age at diagnosis <40 years) and a late-onset (LO) IBD group (age at diagnosis ≥40 years) with the cutoff value of age at diagnosis as 40 years, which was calculated using the Youden index method. We then used the logrank test and Cox proportional hazards model to analyze the effect that age at diagnosis (EO group vs LO group) had on the prognosis in patients with IBD. RESULTS A total of 3480 patients were enrolled. There was 2017 patients with ulcerative colitis (UC) and 1463 with Crohn's disease (CD). The median follow up period was 109.5 weeks. The EO UC group was statistically significant and showed less event-free survival (ie, experiences of biologic agents) than the LO UC group (P<.001). In CD, the EO CD group showed less event-free survival (ie, experiences of biologic agents) than the LO CD group. In the Cox proportional hazard analysis, the odds ratio (OR) of the EO UC group on experiences of biologic agents compared with the LO UC group was 2.3 (95% CI 1.3-3.8, P=.002). The OR of the EO CD group on experiences of biologic agents compared with the LO CD group was 5.4 (95% CI 1.9-14.9, P=.001). CONCLUSIONS The EO IBD group showed a worse prognosis than the LO IBD group in Korean patients with IBD. In addition, this study successfully verified the CDM model in gastrointestinal research.
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Affiliation(s)
- Youn I Choi
- Department of Gastroenterology, Gil Medical Center, Gachon University College of Internal Medicine, Incheon, Republic of Korea
| | - Yoon Jae Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University College of Internal Medicine, Incheon, Republic of Korea
| | - Jun-Won Chung
- Department of Gastroenterology, Gil Medical Center, Gachon University College of Internal Medicine, Incheon, Republic of Korea
| | - Kyoung Oh Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University College of Internal Medicine, Incheon, Republic of Korea
| | - Hakki Kim
- Health IT Research Center, Gil Medical Center, Gachon University, Incheon, Republic of Korea
| | | | - Dong Kyun Park
- Department of Gastroenterology, Gil Medical Center, Gachon University College of Internal Medicine, Incheon, Republic of Korea
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Experiences With Traditional Chinese Medicine Among Patients With Inflammatory Bowel Disease: A Qualitative Study. Gastroenterol Nurs 2020; 43:135-145. [PMID: 32251215 DOI: 10.1097/sga.0000000000000418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Despite the increasing number of inflammatory bowel disease (IBD) patients using traditional Chinese medicine (TCM), relatively few studies have examined their experiences with TCM in the Chinese healthcare context. The aim of this study was to explore these experiences from the perspective of IBD patients. Adopting a qualitative descriptive method, IBD patients from several comprehensive hospitals in Hangzhou, Zhejiang were recruited through purposive sampling. Data were collected using semistructured interviews and analyzed by a conventional content analysis method. The results are presented thematically. Fourteen IBD patients participated in the study. They often used TCM, such as Chinese herbal medicine, retention enemas of Chinese medicine, and acupuncture, as a complementary therapy instead of as an alternative to conventional therapies. Three themes emerged from the analysis: triggers for initiating TCM, the experienced efficacies of TCM, and disturbances caused by TCM use. The IBD patients initiate TCM treatment due to the unsatisfactory effects of conventional therapies and TCM culture. However, the efficacies of TCM are subjective and slow acting and vary across individuals. There are communication gaps between physicians and patients concerning TCM. Thus, healthcare professionals are encouraged to gain more knowledge on these therapies and employ a participatory decision-making style based on this understanding.
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Du G, Xiong L, Li X, Zhuo Z, Zhuang X, Yu Z, Wu L, Xiao D, Liu Z, Jie M, Liu X, Luo G, Guo Z, Chen H. Peroxisome Elevation Induces Stem Cell Differentiation and Intestinal Epithelial Repair. Dev Cell 2020; 53:169-184.e11. [PMID: 32243783 DOI: 10.1016/j.devcel.2020.03.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/20/2020] [Accepted: 03/03/2020] [Indexed: 02/08/2023]
Abstract
Epithelial-repair-dependent mucosal healing (MH) is associated with a more favorable prognosis for patients with inflammatory bowel disease (IBD). MH is accomplished via repair and regeneration of the intestinal epithelium. However, the mechanism underlying MH is ill defined. We found a striking upregulation of peroxisomes in the injured crypts of IBD patients. By increasing peroxisome levels in Drosophila midguts, we found that peroxisome elevation enhanced RAB7-dependent late endosome maturation, which then promoted stem and/or progenitor-cell differentiation via modulation of Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-SOX21A signaling. This in turn enhanced ISC-mediated regeneration. Importantly, RAB7 and SOX21 were upregulated in the crypts of IBD patients. Moreover, administration of drugs that increased peroxisome levels reversed the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients.
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Affiliation(s)
- Gang Du
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China; Laboratory for Stem Cell and anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Lishou Xiong
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Xiaorong Li
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Zhangpeng Zhuo
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Xiaojun Zhuang
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Zihua Yu
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Lijian Wu
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Danqing Xiao
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Zhiming Liu
- Laboratory for Stem Cell and anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Minwen Jie
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Xuehong Liu
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Guanzheng Luo
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China
| | - Zheng Guo
- Department of Medical Genetics, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Haiyang Chen
- Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China; Laboratory for Stem Cell and anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
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Zhang J, Zhao Y, Hou T, Zeng H, Kalambhe D, Wang B, Shen X, Huang Y. Macrophage-based nanotherapeutic strategies in ulcerative colitis. J Control Release 2020; 320:363-380. [DOI: 10.1016/j.jconrel.2020.01.047] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 01/11/2020] [Accepted: 01/26/2020] [Indexed: 12/21/2022]
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Dietary practices and beliefs of British South Asians with inflammatory bowel disease: A prospective study from the United Kingdom. Proc Nutr Soc 2020. [DOI: 10.1017/s0029665119001368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Affiliation(s)
- Michael A Kamm
- St Vincent's Hospital, Melbourne, Victoria, Australia.,University of Melbourne, Melbourne, Victoria, Australia
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