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Zhao L, Jiang T, Zhang Y, Shen Z. Epimedium polysaccharides ameliorate ulcerative colitis by inhibiting oxidative stress and regulating autophagy. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:2655-2670. [PMID: 39540346 DOI: 10.1002/jsfa.14037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 10/09/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Epimedium polysaccharide (EPS) is a bioactive compound derived from the traditional Chinese herb Epimedium brevicornum. The objective of this study was to investigate the protective effects of EPS on ulcerative colitis (UC) and to elucidate the underlying mechanisms involved. RESULTS The findings showed that EPS treatment mitigated UC symptoms, including weight loss, anal bleeding, elevated disease activity index (DAI), and colon shortening. Hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining demonstrated that EPS alleviated histopathological damage and improved the integrity of the colonic mucosa. Mechanistically, EPS was found to substantially decrease inflammation by inhibiting the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and to alleviate oxidative stress through modulation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (Keap1/Nrf2) pathway. Notably, EPS failed to exert protective effects against dextran sulfate sodium (DSS)-induced UC in Nrf2-knockout (Nrf2-/-) mice. Additionally, Western blotting and immunohistochemical analysis demonstrated that EPS facilitated autophagy via the adenosine monophosphate-dependent protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway. In vitro experiments revealed that EPS effectively suppressed lipopolysaccharide (LPS)-mediated cellular damage and oxidative stress by regulating Keap1/Nrf2 pathway. Transcriptomic analysis of LPS-treated Caco-2 cells following EPS treatment revealed a significant up-regulation of Nrf2 expression. CONCLUSION In conclusion, the findings of this study suggest that EPS exerts protective effects against DSS-induced UC through the inhibition of the TLR4/NF-κB signaling pathway, regulation of the Keap1/Nrf2 pathway, and promotion of autophagy via the AMPK/mTOR pathway. Consequently, EPS may represent a potential therapeutic target for the treatment of UC. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Linxian Zhao
- Department of Gastrointestinal, Colorectal, and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Tao Jiang
- Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yuxin Zhang
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Zhen Shen
- Department of Gastrointestinal, Colorectal, and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
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2
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Li T, Li Q, Liu S, Cao J, Mei J, Gong J, Chen J, Wang X, Zhang R, Li X, Wang Q, Zhang H, Wang B, Cao H, Yang H, Fung SY. Targeted V-type peptide-decorated nanoparticles prevent colitis by inhibiting endosomal TLR signaling and modulating intestinal macrophage polarization. Biomaterials 2025; 314:122843. [PMID: 39321686 DOI: 10.1016/j.biomaterials.2024.122843] [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: 04/06/2024] [Revised: 08/26/2024] [Accepted: 09/14/2024] [Indexed: 09/27/2024]
Abstract
Inflammatory bowel disease (IBD) has become a serious and challenging health problem globally without curative medical treatments. Mounting evidence suggests that intestinal macrophages and their phenotypes are key players in the pathogenesis of IBD. Modulating the phenotypes and functions of intestinal macrophages through targeted interventions could be a promising approach to manage detrimental gut inflammation in IBD. In this study, we rationally design and fabricate a novel class of V-type peptide-decorated nanoparticles, VP-NP, with potent anti-inflammatory activity. Such a design allows two functional motifs FFD in a single peptide molecule to enhance the bioactivity of the nanoparticles. As expected, VP-NP exhibits a strong inhibitory activity on endosomal Toll-like receptor (TLR) signaling. Surprisingly, VP-NP can inhibit M1 polarization while facilitating M2 polarization in mouse bone marrow-derived macrophages through regulating the key transcription factors NF-κB, STAT1 and PPAR-γ. Mechanistically, VP-NP is internalized by macrophages in the endosomes, where it blocks endosomal acidification to inhibit endosomal TLR signaling; the transcriptomic analysis reveals that VP-NP potently down-regulates many genes in TLR, NF-κB, JAK-STAT, and cytokine/chemokine signaling pathways associated with inflammatory responses. In a colitis mouse model, the intraperitoneally administered VP-NP effectively alleviates the disease activities by decreasing colon inflammation and injuries, pro-inflammatory cytokine production, and myeloid cell infiltration in the gut. Furthermore, VP-NP primarily targets intestinal macrophages and alters their phenotypes from inflammatory M1-type toward the anti-inflammatory M2-type. This study provides a new nanotherapeutic strategy to specifically regulate macrophage activation and phenotypes through a dual mechanism to control gut inflammation, which may augment current clinical treatments for IBD.
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Affiliation(s)
- Tongxuan Li
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Qianqian Li
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Sixia Liu
- The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology and Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Intensive Care Unit of the Second Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Jiazhu Cao
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Jian Mei
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Jiameng Gong
- The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology and Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Intensive Care Unit of the Second Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Jiugeng Chen
- Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoyu Wang
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Rui Zhang
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Xiaomeng Li
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Qian Wang
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Hefan Zhang
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Hong Yang
- The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology and Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Intensive Care Unit of the Second Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China.
| | - Shan-Yu Fung
- State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Science, Department of Gastroenterology and Hepatology, General Hospital, International Joint Laboratory of Ocular Diseases, Ministry of Education, Tianjin Medical University, Tianjin, China.
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3
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Bosáková V, Papatheodorou I, Kafka F, Tomášiková Z, Kolovos P, Hortová Kohoutková M, Frič J. Serotonin attenuates tumor necrosis factor-induced intestinal inflammation by interacting with human mucosal tissue. Exp Mol Med 2025; 57:364-378. [PMID: 39894823 PMCID: PMC11873120 DOI: 10.1038/s12276-025-01397-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 10/13/2024] [Accepted: 11/19/2024] [Indexed: 02/04/2025] Open
Abstract
The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.
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Affiliation(s)
- Veronika Bosáková
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
- Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Ioanna Papatheodorou
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
- Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Filip Kafka
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
- Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Zuzana Tomášiková
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
- Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Petros Kolovos
- Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
| | - Marcela Hortová Kohoutková
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
- International Clinical Research Center, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
| | - Jan Frič
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
- International Clinical Research Center, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
- Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
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4
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Ghosh A, Gorain B. Mechanistic insight of neurodegeneration due to micro/nano-plastic-induced gut dysbiosis. Arch Toxicol 2025; 99:83-101. [PMID: 39370473 DOI: 10.1007/s00204-024-03875-3] [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: 08/10/2024] [Accepted: 09/19/2024] [Indexed: 10/08/2024]
Abstract
Despite offering significant conveniences, plastic materials contribute substantially in developing environmental hazards and pollutants. Plastic trash that has not been adequately managed may eventually break down into fragments caused by human or ecological factors. Arguably, the crucial element for determining the biological toxicities of plastics are micro/nano-forms of plastics (MPs/NPs), which infiltrate the mammalian tissue through different media and routes. Infiltration of MPs/NPs across the intestinal barrier leads to microbial architectural dysfunction, which further modulates the population of gastrointestinal microbes. Thereby, it triggers inflammatory mediators (e.g., IL-1α/β, TNF-α, and IFN-γ) by activating specific receptors located in the gut barrier. Mounting evidence indicates that MPs/NPs disrupt host pathophysiological function through modification of junctional proteins and effector cells. Moreover, the alteration of microbial diversity by MPs/NPs causes the breakdown of the blood-brain barrier and translocation of metabolites (e.g., SCFAs, LPS) through the vagus nerve. Potent penetration affects the neuronal networks, neuronal protein accumulation, acceleration of oxidative stress, and alteration of neurofibrillary tangles, and hinders distinctive communicating pathways. Conclusively, alterations of these neurotoxic factors are possibly responsible for the associated neurodegenerative disorders due to the exposure of MPs/NPs. In this review, the hypothesis on MPs/NPs associated with gut microbial dysbiosis has been interlinked to the distinct neurological impairment through the gut-brain axis.
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Affiliation(s)
- Arya Ghosh
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India
| | - Bapi Gorain
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India.
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De Salvo C, Osme A, Ghannoum M, Cominelli F, Di Martino L. A New Probiotic Formulation Promotes Resolution of Inflammation in a Crohn's Disease Mouse Model by Inducing Apoptosis in Mucosal Innate Immune Cells. Int J Mol Sci 2024; 25:12066. [PMID: 39596135 PMCID: PMC11593709 DOI: 10.3390/ijms252212066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 11/02/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024] Open
Abstract
The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn's disease (CD), where microbiome dysregulation can alter immune responses, leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of a recently developed probiotic + amylase blend in the SAMP1/YitFc (SAMP) mouse model of CD-like ileitis. Four groups of SAMP mice were gavaged for 56 days with the following treatments: 1) probiotic strains + amylase (0.25 mg/100 µL PBS); 2) only probiotics; 3) only amylase; PBS-treated controls. Ilea were collected for GeoMx Digital Spatial Profiler (DSP) analysis and histological evaluation. Histology assessment for inflammation indicated a significantly reduced level of ileitis in mice administered the probiotics + amylase blend. DSP analysis showed decreased abundance of neutrophils and increased abundance of dendritic cells, regulatory T cells, and macrophages, with a significant enrichment of five intracellular pathways related to apoptosis, in probiotics + amylase-treated mice. Increased apoptosis occurrence was confirmed by (TdT)- deoxyuridine triphosphate (dUTP)-biotin nick end labeling assay. Our data demonstrate a beneficial role of the probiotic and amylase blend, highlighting an increased apoptosis of innate immunity-associated cell subsets, thus promoting the resolution of inflammation. Hence, we suggest that the developed probiotic enzyme blend may be a therapeutic tool to manage CD and therefore is a candidate formulation to be tested in clinical trials.
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Affiliation(s)
- Carlo De Salvo
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; (C.D.S.); (F.C.)
| | - Abdullah Osme
- Department of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Mahmoud Ghannoum
- Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA;
| | - Fabio Cominelli
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; (C.D.S.); (F.C.)
- Case Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
- Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Luca Di Martino
- Case Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
- Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
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Kou RW, Li ZQ, Wang JL, Jiang SQ, Zhang RJ, He YQ, Xia B, Gao JM. Ganoderic Acid A Mitigates Inflammatory Bowel Disease through Modulation of AhR Activity by Microbial Tryptophan Metabolism. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:17912-17923. [PMID: 39078661 DOI: 10.1021/acs.jafc.4c01166] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/31/2024]
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex gastrointestinal condition influenced by genetic, microbial, and environmental factors, among which the gut microbiota plays a crucial role and has emerged as a potential therapeutic target. Ganoderic acid A (GAA), which is a lanostane triterpenoid compound derived from edible mushroom Ganoderma lucidum, has demonstrated the ability to modulate gut dysbiosis. Thus, we investigated the impact of GAA on IBD using a dextran sodium sulfate (DSS)-induced colitis mouse model. GAA effectively prevented colitis, preserved epithelial and mucus layer integrity, and modulated the gut microbiota. In addition, GAA promoted tryptophan metabolism, especially 3-IAld generation, activated the aryl hydrocarbon receptor (AhR), and induced IL-22 production. Fecal microbiota transplantation validated the mediating role of the gut microbiota in the IBD protection conferred by GAA. Our study suggests that GAA holds potential as a nutritional intervention for ameliorating IBD by influencing the gut microbiota, thereby regulating tryptophan metabolism, enhancing AhR activity, and ultimately improving gut barrier function.
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Affiliation(s)
- Rong-Wei Kou
- School of Science, Xi'an University of Technology, Xi'an 710048, Shaanxi, People's Republic of China
| | - Zhi-Qing Li
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China
| | - Jia-Lin Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China
| | - Shi-Qi Jiang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China
| | - Rui-Jing Zhang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China
| | - Yang-Qing He
- School of Science, Xi'an University of Technology, Xi'an 710048, Shaanxi, People's Republic of China
| | - Bing Xia
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China
| | - Jin-Ming Gao
- Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China
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Hu Y, Jiang S, Zhang Q, Zhou W, Liang J, Xu Y, Su W. Protective effect of Cordycepin on blood-testis barrier against pre-puberty polystyrene nanoplastics exposure in male rats. Part Fibre Toxicol 2024; 21:30. [PMID: 39118174 PMCID: PMC11312894 DOI: 10.1186/s12989-024-00590-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 07/25/2024] [Indexed: 08/10/2024] Open
Abstract
Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.
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Affiliation(s)
- Ying Hu
- Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, China
- National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, Units of Medical Laboratory, The First Hospital of China Medical University, Chinese Academy of Medical Sciences, Shenyang, 110001, China
| | - Shuyi Jiang
- Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, China
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qiang Zhang
- Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, China
| | - Wenjie Zhou
- Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, China
| | - Jinhong Liang
- Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, China
| | - Ying Xu
- Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, China.
| | - Wenhui Su
- Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, China.
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Alajoleen RM, Oakland DN, Estaleen R, Shakeri A, Lu R, Appiah M, Sun S, Neumann J, Kawauchi S, Cecere TE, McMillan RP, Reilly CM, Luo XM. Tlr5 deficiency exacerbates lupus-like disease in the MRL/ lpr mouse model. Front Immunol 2024; 15:1359534. [PMID: 38352866 PMCID: PMC10862078 DOI: 10.3389/fimmu.2024.1359534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 01/15/2024] [Indexed: 02/16/2024] Open
Abstract
Introduction Leaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives lupus through bacterial flagellin-mediated activation of toll-like receptor 5 (TLR5). Methods We created MRL/lpr mice with global Tlr5 deletion through CRISPR/Cas9 and investigated lupus-like disease in these mice. Result Contrary to our hypothesis that the deletion of Tlr5 would attenuate lupus, our results showed exacerbation of lupus with Tlr5 deficiency in female MRL/lpr mice. Remarkably higher levels of proteinuria were observed in Tlr5 -/- MRL/lpr mice suggesting aggravated glomerulonephritis. Histopathological analysis confirmed this result, and Tlr5 deletion significantly increased the deposition of IgG and complement C3 in the glomeruli. In addition, Tlr5 deficiency significantly increased renal infiltration of Th17 and activated cDC1 cells. Splenomegaly and lymphadenopathy were also aggravated in Tlr5-/- MRL/lpr mice suggesting impact on lymphoproliferation. In the spleen, significant decreased frequencies of regulatory lymphocytes and increased germinal centers were observed with Tlr5 deletion. Notably, Tlr5 deficiency did not change host metabolism or the existing leaky gut; however, it significantly reshaped the fecal microbiota. Conclusion Global deletion of Tlr5 exacerbates lupus-like disease in MRL/lpr mice. Future studies will elucidate the underlying mechanisms by which Tlr5 deficiency modulates host-microbiota interactions to exacerbate lupus.
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Affiliation(s)
- Razan M. Alajoleen
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - David N. Oakland
- Graduate Program of Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
| | - Rana Estaleen
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Aida Shakeri
- Department of Biological Sciences, College of Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Ran Lu
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Michael Appiah
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Sha Sun
- Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States
| | - Jonathan Neumann
- Transgenic Mouse Facility, University of California, Irvine, Irvine, CA, United States
| | - Shimako Kawauchi
- Transgenic Mouse Facility, University of California, Irvine, Irvine, CA, United States
| | - Thomas E. Cecere
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Ryan P. McMillan
- Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Christopher M. Reilly
- Department of Biomedical Sciences, Edward Via College of Osteopathic Medicine, Blacksburg, VA, United States
| | - Xin M. Luo
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
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Hassan HA, Mohamed Abdelhamid A, Samy W, Osama Mohammed H, Mortada Mahmoud S, Fawzy Abdel Mageed A, Abbas NAT. Ameliorative effects of androstenediol against acetic acid-induced colitis in male wistar rats via inhibiting TLR4-mediated PI3K/Akt and NF-κB pathways through estrogen receptor β activation. Int Immunopharmacol 2024; 127:111414. [PMID: 38141404 DOI: 10.1016/j.intimp.2023.111414] [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: 09/27/2023] [Revised: 12/13/2023] [Accepted: 12/16/2023] [Indexed: 12/25/2023]
Abstract
5-androstenediol (ADIOL) functions as a selective estrogen receptor β (ERβ) ligand with a protective effect against many diseases. So, we conducted a novel insight into its role in acetic acid (AA)-induced colitis and investigated its effect on TLR4-Mediated PI3K/Akt and NF-κB Pathways and the potential role of ERβ as contributing mechanisms. METHODS Rats were randomized into 5 Groups; Control, Colitis, Colitis + mesalazine (MLZ), Colitis + ADIOL, and Colitis + ADIOL + PHTPP (ER-β antagonist). The colitis was induced through a rectal enema of acetic acid (AA) on the 8th day. At the end of treatment, colons were collected for macroscopic assessment. Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor kappa b (NF-κB), toll-like receptor (TLR4), and phosphorylated Protein kinase B (pAKT) were measured. Besides, Gene expression of interleukin-1beta (IL-1β), metalloproteases 9 (Mmp9), inositol 3 phosphate kinase (PI3K), Neutrophil gelatinase-associated lipocalin (NGAL), ERβ and NLRP6 were assessed. Histopathological and immunohistochemical studies were also investigated. RESULTS Compared to the untreated AA group, the disease activity index (DAI) and macroscopic assessment indicators significantly decreased with ADIOL injections. Indeed, ADIOL significantly decreased colonic tissue levels of MDA, TLR4, pAKT, and NF-κB immunostainig while increased SOD activity and β catenin immunostainig. ADIOL mitigated the high genetic expressions of IL1β, NGAL, MMP9, and PI3K while increased ERβ and NLRP6 gene expression. Also, the pathological changes detected in AA groups were markedly ameliorated with ADIOL. The specific ERβ antagonist, PHTPP, largely diminished these protective effects of ADIOL. CONCLUSION ADIOL could be beneficial against AA-induced colitis mostly through activating ERβ.
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Affiliation(s)
- Heba A Hassan
- Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt; Pharmacology Department, Faculty of Medicine, Mutah University, Mutah, Al-karak 61710, Jordan.
| | - Amira Mohamed Abdelhamid
- Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
| | - Walaa Samy
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine -Zagazig University, Zagazig 45519, Egypt.
| | - Heba Osama Mohammed
- Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
| | - Samar Mortada Mahmoud
- Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
| | - Amal Fawzy Abdel Mageed
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine -Zagazig University, Zagazig 45519, Egypt.
| | - Noha A T Abbas
- Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
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Ye X, Zhang M, Zhang N, Wei H, Wang B. Gut-brain axis interacts with immunomodulation in inflammatory bowel disease. Biochem Pharmacol 2024; 219:115949. [PMID: 38036192 DOI: 10.1016/j.bcp.2023.115949] [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: 07/27/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 12/02/2023]
Abstract
The brain and the gastrointestinal (GI) tract are important sensory organs in the body and the two-way interaction that exists between them regulates key physiological and homeostatic functions. A growing body of research suggests that this bidirectional communication influences the development and progression of functional GI disorders and plays an important role in the treatment of central nervous system (CNS) disorders. Inflammatory bowel disease (IBD) is a classic intestinal disorder with a high prevalence but still unclear pathogenesis that has been widely discussed in recent years. However, in the studies available to date, we find that many authors have chosen to discuss the influence of the brain on intestinal disorders from the top down, starting with physical and psychological disorders. Coming very naturally, based on these substantial research evidence, we focus on exploring the links between bidirectional communication in the gut-brain axis and IBD, and highlight the role of the gut microbiota, vagus nerve (VN), receptors and immune cells involved in regulating IBD through the gut-brain axis in this review.
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Affiliation(s)
- Xianglu Ye
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Miao Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ning Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Hai Wei
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Bing Wang
- Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
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11
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Markovich Z, Abreu A, Sheng Y, Han SM, Xiao R. Deciphering internal and external factors influencing intestinal junctional complexes. Gut Microbes 2024; 16:2389320. [PMID: 39150987 PMCID: PMC11332634 DOI: 10.1080/19490976.2024.2389320] [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: 06/13/2024] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 08/18/2024] Open
Abstract
The intestinal barrier, an indispensable guardian of gastrointestinal health, mediates the intricate exchange between internal and external environments. Anchored by evolutionarily conserved junctional complexes, this barrier meticulously regulates paracellular permeability in essentially all living organisms. Disruptions in intestinal junctional complexes, prevalent in inflammatory bowel diseases and irritable bowel syndrome, compromise barrier integrity and often lead to the notorious "leaky gut" syndrome. Critical to the maintenance of the intestinal barrier is a finely orchestrated network of intrinsic and extrinsic factors that modulate the expression, composition, and functionality of junctional complexes. This review navigates through the composition of key junctional complex components and the common methods used to assess intestinal permeability. It also explores the critical intracellular signaling pathways that modulate these junctional components. Lastly, we delve into the complex dynamics between the junctional complexes, microbial communities, and environmental chemicals in shaping the intestinal barrier function. Comprehending this intricate interplay holds paramount importance in unraveling the pathophysiology of gastrointestinal disorders. Furthermore, it lays the foundation for the development of precise therapeutic interventions targeting barrier dysfunction.
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Affiliation(s)
- Zachary Markovich
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, USA
- Graduate Program in Biomedical Sciences, College of Medicine, University of Florida, Gainesville, FL, USA
- Center for Smell and Taste, University of Florida, Gainesville, FL, USA
| | - Adriana Abreu
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Yi Sheng
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Sung Min Han
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Rui Xiao
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, USA
- Center for Smell and Taste, University of Florida, Gainesville, FL, USA
- Institute on Aging, University of Florida, Gainesville, FL, USA
- Genetics Institute, University of Florida, Gainesville, FL, USA
- UF Health Cancer Center, University of Florida, Gainesville, FL, USA
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12
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Roco-Videla Á, Villota-Arcos C, Pino-Astorga C, Mendoza-Puga D, Bittner-Ortega M, Corbeaux-Ascui T. Intermittent Fasting and Reduction of Inflammatory Response in a Patient with Ulcerative Colitis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1453. [PMID: 37629743 PMCID: PMC10456230 DOI: 10.3390/medicina59081453] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 08/03/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023]
Abstract
Ulcerative colitis is an inflammatory disease that affects the colon, generating a crisis period associated with diarrhea and ulcerations. Stress plays a pivotal role in modulating the inflammatory response and aggravating progression. Different studies have shown that fasting reduces inflammation markers, and intermittent fasting decreases inflammatory markers such as IL-2, IL-6, and RCP. Goal: To evaluate the impact of intermittent fasting on a patient diagnosed with ulcerative colitis. A female patient underwent intermittent fasting (10/14) for eight weeks. Clinical tests were performed for blood count, RCP, biochemical profile, glycemia, and T4/TSH levels. Fecal calprotectin was determined. Clinical exams were assessed before and after intermittent fasting. Inflammation markers, such as CRP and calprotectin, were significantly reduced after eight weeks of intermittent fasting. The patient reported feeling better and was seizure-free during the following months when she continued fasting intermittently. Intermittent fasting allowed for a reduction in inflammation markers.
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Affiliation(s)
- Ángel Roco-Videla
- Facultad de Salud y Ciencias Sociales, Universidad de las Américas, Providencias, Santiago 7500975, Chile
| | - Claudio Villota-Arcos
- Escuela de Nutrición y Dietética, Facultad de Ciencias de la Salud, Universidad Bernardo O’Higgins, Santiago 8370993, Chile;
- Laboratorio de Microbiologia y Biotecnologia Oral, Facultad de Ciencias de la Vida, Universidad Andres Bello, Echaurren 237, Piso 6, Santiago 8370133, Chile;
| | - Carolina Pino-Astorga
- Escuela de Nutrición y Dietética, Facultad de Ciencias de la Salud, Universidad Bernardo O’Higgins, Santiago 8370993, Chile;
| | - Daniela Mendoza-Puga
- Integramédica, Parte de BUPA, Director Médico ITR-IBB-ITA, Cerro Colorado 5240, Las Condes, Santiago 7560995, Chile;
| | - Mauricio Bittner-Ortega
- Laboratorio de Microbiologia y Biotecnologia Oral, Facultad de Ciencias de la Vida, Universidad Andres Bello, Echaurren 237, Piso 6, Santiago 8370133, Chile;
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Han Y, Jia R, Zhang J, Zhu Q, Wang X, Ji Q, Zhang W. Hypoxia Attenuates Colonic Innate Immune Response and Inhibits TLR4/NF-κB Signaling Pathway in Lipopolysaccharide-Induced Colonic Epithelial Injury Mice. J Interferon Cytokine Res 2023; 43:43-52. [PMID: 36603105 DOI: 10.1089/jir.2022.0194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
High altitude hypoxia can lead to a spectrum of gastrointestinal problems. As the first line of host immune defense, innate immune response in the intestinal mucosa plays a pivotal role in maintaining intestinal homeostasis and protecting against intestinal injury at high altitude. This study aimed to investigate the effect of hypoxia on the colonic mucosal barrier and toll-like receptor 4 (TLR4)-mediated innate immune responses in the colon. The mice were exposed to a hypobaric chamber to simulate a 5,000 m plateau environment for 7 days, and the colonic mucosa changes were recorded. At the same time, the inflammation model was established by lipopolysaccharide (LPS) to explore the effects of hypoxia on the TLR4/nuclear factor kappa B (NF-κB) signaling pathway and its downstream inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ] in the colon. We found that hypoxic exposure caused weight loss and structural disturbance of the colonic mucosa in mice. Compared with the control group, the protein levels of TLR4 [fold change (FC) = 0.75 versus FC = 0.23], MyD88 (FC = 0.80 versus FC = 0.30), TIR-domain-containing adaptor protein inducing interferon-β (TRIF: FC = 0.89 versus FC = 0.38), and NF-κB p65 (FC = 0.75 versus FC = 0.24) in the colon of mice in the hypobaric hypoxia group were significantly decreased. LPS-induced upregulation of the TLR4/NF-κB signaling and its downstream inflammatory factors was inhibited by hypoxia. Specifically, compared with the LPS group, the protein levels of TLR4 (FC = 1.18, FC = 0.86), MyD88 (FC = 1.20, FC = 0.80), TRIF (FC = 1.20, FC = 0.86), and NF-κB p65 (FC = 1.29, FC = 0.62) and the mRNA levels of IL-1β (FC = 7.38, FC = 5.06), IL-6 (FC = 16.06, FC = 9.22), and IFN-γ (FC = 2.01, FC = 1.16) were reduced in the hypobaric hypoxia plus LPS group. Our findings imply that hypoxia could lead to marked damage of the colonic mucosa and a reduction of TLR4-mediated colonic innate immune responses, potentially reducing host defense responses to colonic pathogens.
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Affiliation(s)
- Ying Han
- Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China
| | - Ruhan Jia
- Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China
| | - Jingxuan Zhang
- Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China
| | - Qinfang Zhu
- Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China
| | - Xiaozhou Wang
- Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China
| | - Qiaorong Ji
- Department of Pathophysiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, China
| | - Wei Zhang
- Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China
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Ephraim R, Feehan J, Fraser S, Nurgali K, Apostolopoulos V. Cancer Immunotherapy: The Checkpoint between Chronic Colitis and Colorectal Cancer. Cancers (Basel) 2022; 14:cancers14246131. [PMID: 36551617 PMCID: PMC9776998 DOI: 10.3390/cancers14246131] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 12/07/2022] [Indexed: 12/15/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is a group of diseases that cause intestinal inflammation and lesions because of an abnormal immune response to host gut microflora. Corticosteroids, anti-inflammatories, and antibiotics are often used to reduce non-specific inflammation and relapse rates; however, such treatments are ineffective over time. Patients with chronic colitis are more susceptible to developing colorectal cancer, especially those with a longer duration of colitis. There is often a limit in using chemotherapy due to side effects, leading to reduced efficacy, leaving an urgent need to improve treatments and identify new therapeutic targets. Cancer immunotherapy has made significant advances in recent years and is mainly categorized as cancer vaccines, adoptive cellular immunotherapy, or immune checkpoint blockade therapies. Checkpoint markers are expressed on cancer cells to evade the immune system, and as a result checkpoint inhibitors have transformed cancer treatment in the last 5-10 years. Immune checkpoint inhibitors have produced long-lasting clinical responses in both single and combination therapies. Winnie mice are a viable model of spontaneous chronic colitis with immune responses like human IBD. Determining the expression levels of checkpoint markers in tissues from these mice will provide insights into disease initiation, progression, and cancer. Such information will lead to identification of novel checkpoint markers and the development of treatments with or without immune checkpoint inhibitors or vaccines to slow or stop disease progression.
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Affiliation(s)
- Ramya Ephraim
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
| | - Jack Feehan
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
- Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia
| | - Sarah Fraser
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
| | - Kulmira Nurgali
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
- Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia
| | - Vasso Apostolopoulos
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
- Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia
- Correspondence:
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Jatrorrhizine Alleviates DSS-Induced Ulcerative Colitis by Regulating the Intestinal Barrier Function and Inhibiting TLR4/MyD88/NF-κB Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3498310. [PMID: 36193153 PMCID: PMC9526656 DOI: 10.1155/2022/3498310] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 07/28/2022] [Accepted: 08/10/2022] [Indexed: 11/18/2022]
Abstract
Background Ulcerative colitis (UC), a kind of autoimmune disease with unknown etiology, has been troubling human physical and mental health. Jatrorrhizine (Jat) is a natural isoquinoline alkaloid isolated from Coptis Chinensis, which has been proved to have antibacterial, anti-inflammatory, and antitumor effects. Purpose The purpose is to explore the therapeutic effect of Jat on DSS-induced UC and the mechanism of action. Study Design. The UC mice model was induced by 3% DSS in drinking water. The mice were orally administered with Jat (40, 80, 160 mg/kg) for 10 days. Methods The changes in body weight, colon length, spleen wet weight index, disease activity index (DAI), colonic histopathology, and inflammatory factors of serum and colon tissue were analyzed to evaluate the severity of colitis mice. The colon mucus secretion capacity was analyzed by Alcian blue periodic acid Schiff (AB-PAS) staining. Furthermore, protein expressions such as TLR4, MyD88, p–NF–κB-p65, NF-κB-p65, COX-2, ZO-1, and Occludin were detected to elucidate the molecular mechanism of Jat on DSS-induced colitis model. Results The results showed that Jat could significantly alleviate the symptoms, colon shortening, spleen index, and histological damage and restore the body weight in DSS-induced colitis mice. Jat also suppressed the levels of inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines. In addition, Jat repaired the intestinal barrier function by upregulating the level of colonic tight junction (TJ) proteins and enhancing the secretion of mucin produced by goblet cells. Furthermore, Jat could significantly suppress the expression of TLR4, MyD88, p–NF–κB-p65/NF-κB-p65, and COX-2 in colon tissue. Conclusion The results suggested that Jat plays a protective role in DSS-induced colitis by regulating the intestinal barrier function and inhibiting the TLR4/MyD88/NF-κB signaling pathway. This study, for the first time, demonstrates the therapeutic and protective effects of Jat on UC.
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16
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Liu Y, Yang M, Tang L, Wang F, Huang S, Liu S, Lei Y, Wang S, Xie Z, Wang W, Zhao X, Tang B, Yang S. TLR4 regulates RORγt + regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila. MICROBIOME 2022; 10:98. [PMID: 35761415 PMCID: PMC9235089 DOI: 10.1186/s40168-022-01296-x] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/25/2022] [Indexed: 05/05/2023]
Abstract
BACKGROUND Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). Toll-like receptor 4 (TLR4) functions as a sensor mediating the crosstalk between the intestinal commensal microbiome and host immunity, but the influence of TLR4 on the shaping of intestinal microbiota and immune responses during colon inflammation remains poorly characterized. We investigated whether the different susceptibilities to colitis between wild-type (WT) and TLR4-/- mice were gut microbiota-dependent and aimed to identify the potential immunity modulation mechanism. METHODS We performed antibiotic depletion of the microbiota, cohousing experiments, and faecal microbiota transplantation (FMT) in WT and TLR4-/- mice to assess the influence of TLR4 on intestinal microbial ecology. 16S rRNA sequencing was performed to dissect microbial discrepancies, and dysbiosis-associated immune perturbation was investigated by flow cytometry. Akkermansia muciniphila (A. muciniphila)-mediated immune modulation was confirmed through the T-cell transfer colitis model and bone marrow chimaera construction. RESULTS TLR4-/- mice experienced enhanced susceptibility to DSS-induced colitis. 16S rRNA sequencing showed notable discrepancy in the gut microbiota between WT and TLR4-/- mice. In particular, A. muciniphila contributed most to distinguishing the two groups. The T-cell transfer colitis model and bone marrow transplantation (BMT) consistently demonstrated that A. muciniphila ameliorated colitis by upregulating RORγt+ Treg cell-mediated immune responses. Mucosal biopsies from human manifested parallel outcomes with colon tissue from WT mice, as evidenced by the positive correlation between TLR4 expression and intestinal A. muciniphila colonization during homeostasis. CONCLUSIONS Our results demonstrate a novel protective role of TLR4 against intestinal inflammation, wherein it can modulate A. muciniphila-associated immune responses. These findings provide a new perspective on host-commensal symbiosis, which may be beneficial for developing potential therapeutic strategies. Video abstract.
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Affiliation(s)
- Yaojiang Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Min Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
| | - Li Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
| | - Fengchao Wang
- State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing, 400037, China
| | - Shengjie Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Shuang Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
| | - Yuanyuan Lei
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
| | - Sumin Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
| | - Zhuo Xie
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
| | - Wei Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China
| | - Xiaoyan Zhao
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China.
| | - Bo Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China.
| | - Shiming Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Third Military Medical University, 400037, Chongqing, China.
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Selvakumar D, Evans D, Coyte KZ, McLaughlin J, Brass A, Hancock L, Cruickshank S. Understanding the development and function of the gut microbiota in health and inflammation. Frontline Gastroenterol 2022; 13:e13-e21. [PMID: 35812026 PMCID: PMC9234741 DOI: 10.1136/flgastro-2022-102119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 04/29/2022] [Indexed: 02/04/2023] Open
Abstract
The gut microbiota is known to play an important role in maintaining gut health through a symbiotic relationship with the host. Altered gut microbiota is a common feature of several diseases of the gastrointestinal tract; however, the causal relationship between microbiota and disease pathogenesis is poorly understood. Necrotising enterocolitis (NEC) and inflammatory bowel disease (IBD) are both severe inflammatory diseases affecting the gastrointestinal tract. Although they affect very different patient populations, with NEC primarily being a disease of prematurity and IBD predominantly affecting adults although children can be affected, they both demonstrate common features of gut microbial dysbiosis and a dysregulated host immune response. By comparing and contrasting the changes in gut microbiota, host immune response and function, we aim to highlight common features in diseases that may seem clinically unrelated. Key areas of interest are the role of pattern recognition receptors in altered recognition and responses to the gut microbiota by the host immune system and the associated dysfunctional gut epithelial barrier. The challenge of identifying causal relationships between microbiota and disease is ever-present; however, considering a disease-agnostic approach may help to identify mechanistic pathways shared across several clinical diseases.
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Affiliation(s)
- Deepak Selvakumar
- Department of Colorectal Surgery, Manchester University NHS Foundation Trust, Manchester, UK,Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK
| | - Dolan Evans
- Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK
| | - Katharine Z Coyte
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - John McLaughlin
- Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK,Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Andy Brass
- Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Laura Hancock
- Department of Colorectal Surgery, Manchester University NHS Foundation Trust, Manchester, UK,Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Sheena Cruickshank
- Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
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Wu H, Wang Y, Li H, Meng L, Zheng N, Wang J. Protective Effect of Alkaline Phosphatase Supplementation on Infant Health. Foods 2022; 11:foods11091212. [PMID: 35563935 PMCID: PMC9101100 DOI: 10.3390/foods11091212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/13/2022] [Accepted: 04/13/2022] [Indexed: 12/03/2022] Open
Abstract
Alkaline phosphatase (ALP) is abundant in raw milk. Because of its high heat resistance, ALP negative is used as an indicator of successful sterilization. However, pasteurized milk loses its immune protection against allergy. Clinically, ALP is also used as an indicator of organ diseases. When the activity of ALP in blood increases, it is considered that diseases occur in viscera and organs. Oral administration or injecting ALP will not cause harm to the body and has a variety of probiotic effects. For infants with low immunity, ALP intake is a good prebiotic for protecting the infant’s intestine from potential pathogenic bacteria. In addition, ALP has a variety of probiotic effects for any age group, including prevention and treatment intestinal diseases, allergies, hepatitis, acute kidney injury (AKI), diabetes, and even the prevention of aging. The prebiotic effects of alkaline phosphatase on the health of infants and consumers and the content of ALP in different mammalian raw milk are summarized. The review calls on consumers and manufacturers to pay more attention to ALP, especially for infants with incomplete immune development. ALP supplementation is conducive to the healthy growth of infants.
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Affiliation(s)
- Haoming Wu
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (H.W.); (H.L.); (L.M.); (J.W.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yang Wang
- State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
| | - Huiying Li
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (H.W.); (H.L.); (L.M.); (J.W.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Lu Meng
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (H.W.); (H.L.); (L.M.); (J.W.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Nan Zheng
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (H.W.); (H.L.); (L.M.); (J.W.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Correspondence: ; Tel.: +86-10-62816069
| | - Jiaqi Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (H.W.); (H.L.); (L.M.); (J.W.)
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
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Chen H, Du G, Yan X, Ye H, Guo Q, Wang Z, Yuan Y, Yue T. Selenium-Enriched Pediococcus acidilactici MRS-7 Alleviates Patulin-Induced Jejunum Injuries in Mice and Its Possible Mechanisms. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:4755-4764. [PMID: 35394776 DOI: 10.1021/acs.jafc.2c00949] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Patulin (PAT) is a common mycotoxin. Oral ingestion of PAT could damage the intestinal mucosa. Both selenium and probiotics can alleviate intestinal damage, but there are few reports on selenium-enriched probiotics. Here, we studied the protective effects of a new selenium-enriched Pediococcus acidilactici MRS-7 (SeP) on PAT-induced jejunum injuries in mice. Results show that PAT induced jejunum injuries such as loss of crypts, ulceration of the mucosa, and intestinal epithelial barrier function impairment. However, SeP could protect against PAT-induced jejunum injuries and significantly inhibit the reduction of goblet cell numbers. SeP could not only alleviate PAT-induced oxidative stress by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the jejunum tissues but also alleviate the inflammatory response caused by PAT by reducing the levels of inflammatory factors (interleukin (IL)-6 snd IL-1β and tumor necrosis factor-α (TNF-α)) in the serum and jejunum tissues. In addition, SeP also inhibited the expression of nuclear factor-κB (NF-κB) and Toll-like receptor 4 (TLR-4), increased the expression of tight junction proteins (occludin, ZO-1, and claudin-1), and increased the selenium content in the jejunum, thereby antagonizing the jejunum injuries caused by PAT exposure. Finally, SeP rebalanced the intestinal microbiota and improved probiotic abundance such as Turicibacter, Bifidobacterium, Ileibacterium, and Pediococcus in PAT-treated mice. These results support the possibility of SeP as a novel protective agent to mitigate the toxicity of PAT.
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Affiliation(s)
- Hong Chen
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
| | - Gengan Du
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
| | - Xiaohai Yan
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
| | - Huanfeng Ye
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
| | - Qi Guo
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
| | - Zhouli Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
| | - Yahong Yuan
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
| | - Tianli Yue
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China
- College of Food Science and Technology, Northwest University, Xi'an 710000, China
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20
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Roselli M, Maruszak A, Grimaldi R, Harthoorn L, Finamore A. Galactooligosaccharide Treatment Alleviates DSS-Induced Colonic Inflammation in Caco-2 Cell Model. Front Nutr 2022; 9:862974. [PMID: 35495925 PMCID: PMC9047546 DOI: 10.3389/fnut.2022.862974] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 03/04/2022] [Indexed: 12/19/2022] Open
Abstract
The biological activities of dietary bioactive polysaccharides have been largely explored. Studies on the immunomodulating effects of oligosaccharides and polysaccharides have shown that they are able to modulate innate immunity. Prebiotics are a class of poorly digested carbohydrates that are mainly produced from dietary fibers, which are carbohydrate polymers with ten or more monomeric units as defined by the Codex Alimentarius Commission in 2009. Considering the capacity of prebiotics in reducing gut inflammation, the aim of this study was to investigate the anti-inflammatory activity of galactooligosaccharide (Bimuno® GOS) in an in vitro model of ulcerative colitis (UC)-like inflamed intestinal cells. Differentiated Caco-2 cells were exposed to 2 % dextran-sulfate-sodium salt (DSS) to induce inflammation, and then with different concentrations of Bimuno GOS (1-1,000 μg/ml). Cell monolayer permeability, tight- and adherent junction protein distribution, pro-inflammatory cytokine secretion, and NF-kB cascade were assessed. Bimuno GOS at different concentrations, while not affecting cell monolayer permeability, was shown to counteract UC-like intestinal inflammatory responses and damages induced by DSS. Indeed, Bimuno GOS was able to counteract the detrimental effects of DSS on cell permeability, determined by transepithelial electrical resistance, phenol red apparent permeability, and tight- and adherent junction protein distribution. Furthermore, Bimuno GOS inhibited the DSS-induced NF-kB nuclear translocation and pro-inflammatory cytokine secretion. Further analyses showed that Bimuno GOS was able to revert the expression levels of most of the proteins involved in the NF-kB cascade to control levels. Thus, the prebiotic Bimuno GOS can be a safe and effective way to modulate the gut inflammatory state through NF-kB pathway modulation, and could possibly further improve efficacy in inducing remission of UC.
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Affiliation(s)
- Marianna Roselli
- Research Centre for Food and Nutrition, CREA (Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria), Rome, Italy
| | | | | | | | - Alberto Finamore
- Research Centre for Food and Nutrition, CREA (Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria), Rome, Italy
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21
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The Anti-Inflammatory Effect of Bovine Bone-Gelatin-Derived Peptides in LPS-Induced RAW264.7 Macrophages Cells and Dextran Sulfate Sodium-Induced C57BL/6 Mice. Nutrients 2022; 14:nu14071479. [PMID: 35406093 PMCID: PMC9003490 DOI: 10.3390/nu14071479] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 01/14/2023] Open
Abstract
The bioactive peptides hydrolyzed from bone collagen have been found to possess health-promoting effects by regulating chronic diseases such as arthritis and hypertension. In the current study, the anti-inflammatory effect of bovine bone gelatin peptides (GP) was evaluated in 264.7 macrophages cells and followed by animal trials to investigate their interference on inflammatory cytokines and gut microbiota compositions in dextran sodium sulfate (DSS)-induced C57BL/6 mice. The GP was demonstrated to alleviate the extra secretion of interleukin-6 (IL-6), nitric oxide (NO) and tumor necrosis factor-α(TNF-α) in lipopolysaccharide (LPS)-induced RAW264.7 cells. In DSS-induced colitis mice, the gavage of GP was demonstrated to ameliorate the IBD symptoms of weight loss, hematochezia and inflammatory infiltration in intestinal tissues. In serum, the proinflammatory cytokines (TNF-α,IL-6, MCP-1, IL-1β) were suppressed along with the decreasing effect on toll-like receptor 4 and cyclooxygenase-2 by GP treatment. In the analysis of gut microbiota, the GP was checked to modulate the abundance of Akkermansia, Parasutterella, Peptococcus, Bifidobacterium and Saccharibacteria. The above results imply that GP could attenuate DSS-induced colitis by suppressing the inflammatory cytokines and regulating the gut microbiota.
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22
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de Souza-Silva TG, Oliveira IA, da Silva GG, Giusti FCV, Novaes RD, de Almeida Paula HA. Impact of microplastics on the intestinal microbiota: A systematic review of preclinical evidence. Life Sci 2022; 294:120366. [DOI: 10.1016/j.lfs.2022.120366] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 12/14/2022]
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23
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The Multifaceted Effects of Gut Microbiota on the Immune System of the Intestinal Mucosa. IMMUNO 2021. [DOI: 10.3390/immuno1040041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The gut microbiota has diverse microbial components, including bacteria, viruses, and fungi. The interaction between gut microbiome components and immune responses has been studied extensively over the last decade. Several studies have reported the potential role of the gut microbiome in maintaining gut homeostasis and the development of disease. The commensal microbiome can preserve the integrity of the mucosal barrier by acting on the host immune system. Contrastingly, dysbiosis-induced inflammation can lead to the initiation and progression of several diseases through inflammatory processes and oxidative stress. In this review, we describe the multifaceted effects of the gut microbiota on several diseases from the perspective of mucosal immunological responses.
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24
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MicroRNA as a Potential Biomarker and Treatment Strategy for Ischemia-Reperfusion Injury. Int J Genomics 2021; 2021:9098145. [PMID: 34845433 PMCID: PMC8627352 DOI: 10.1155/2021/9098145] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 11/02/2021] [Indexed: 12/14/2022] Open
Abstract
Ischemia-reperfusion (I/R) injury is a progressive injury that aggravates the pathological state when the organ tissue restores blood supply after a certain period of ischemia, including the myocardial, brain, liver, kidney, and intestinal. With growing evidence that microRNAs (miRNAs) play an important role as posttranscription gene silencing mediators in many I/R injury, in this review, we highlight the microRNAs that are related to I/R injury and their regulatory molecular pathways. In addition, we discussed the potential role of miRNA as a biomarker and its role as a target in I/R injury treatment. Developing miRNAs are not without its challenges, but prudent design combined with existing clinical treatments will result in more effective therapies for I/R injury. This review is aimed at providing new research results obtained in this research field. It is hoped that new research on this topic will not only generate new insights into the pathophysiology of miRNA in I/R injury but also can provide a basis for the clinical application of miRNA in I/R.
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25
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Chen Z, Lv Y, Xu H, Deng L. Herbal Medicine, Gut Microbiota, and COVID-19. Front Pharmacol 2021; 12:646560. [PMID: 34305582 PMCID: PMC8293616 DOI: 10.3389/fphar.2021.646560] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 06/25/2021] [Indexed: 01/08/2023] Open
Abstract
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. The symptoms of COVID-19 range from mild flu-like symptoms, including cough and fever, to life threatening complications. There are still quite a number of patients with COVID-19 showed enteric symptoms including nausea, vomiting, and diarrhea. The gastrointestinal tract may be one of the target organs of SARS-CoV-2. Angiotensin converting enzyme 2 (ACE2) is the main receptor of SARS-CoV-2 virus, which is significantly expressed in intestinal cells. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Intestinal flora imbalance and endotoxemia may accelerate the progression of COVID-19. Many herbs have demonstrated properties relevant to the treatment of COVID-19, by supporting organs and systems of the body affected by the virus. Herbs can restore the structure of the intestinal flora, which may further modulate the immune function after SARS-CoV-2 infection. Regulation of intestinal flora by herbal medicine may be helpful for the treatment and recovery of the disease. Understanding the role of herbs that regulate intestinal flora in fighting respiratory virus infections and maintaining intestinal flora balance can provide new ideas for preventing and treating COVID-19.
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Affiliation(s)
- Ziqi Chen
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
- Medical College, Sun Yat-sen University, Guangzhou, China
| | - Yiwen Lv
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Huachong Xu
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Li Deng
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
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26
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Jalanka J, Lam C, Bennett A, Hartikainen A, Crispie F, Finnegan LA, Cotter PD, Spiller R. Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome: Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine. J Neurogastroenterol Motil 2021; 27:279-291. [PMID: 33795545 PMCID: PMC8026366 DOI: 10.5056/jnm20205] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/23/2020] [Accepted: 11/09/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. Methods We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient’s stool microbiota composition was analysed through 16S ribosomal RNA sequencing. Results We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4’s downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. Conclusions Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.
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Affiliation(s)
- Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK
| | - Ching Lam
- Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK
| | - Andrew Bennett
- Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK.,FRAME Alternatives Laboratory, School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham, Notts, UK
| | - Anna Hartikainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Fiona Crispie
- Teagasc Food Research Center, Moorepark, Fermoy, Co. Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Laura A Finnegan
- Teagasc Food Research Center, Moorepark, Fermoy, Co. Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Paul D Cotter
- Teagasc Food Research Center, Moorepark, Fermoy, Co. Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Robin Spiller
- Nottingham Digestive Diseases Center and NIHR Nottingham Biomedical Research Center at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, Notts, UK
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Momtaz S, Navabakhsh M, Bakouee N, Dehnamaki M, Rahimifard M, Baeeri M, Abdollahi A, Abdollahi M, Farzaei MH, Abdolghaffari AH. Cinnamaldehyde targets TLR-4 and inflammatory mediators in acetic-acid induced ulcerative colitis model. Biologia (Bratisl) 2021. [DOI: 10.1007/s11756-021-00725-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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28
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Intestinal Alkaline Phosphatase Combined with Voluntary Physical Activity Alleviates Experimental Colitis in Obese Mice. Involvement of Oxidative Stress, Myokines, Adipokines and Proinflammatory Biomarkers. Antioxidants (Basel) 2021; 10:antiox10020240. [PMID: 33557311 PMCID: PMC7914798 DOI: 10.3390/antiox10020240] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/20/2021] [Accepted: 01/29/2021] [Indexed: 01/01/2023] Open
Abstract
Intestinal alkaline phosphatase (IAP) is an essential mucosal defense factor involved in the process of maintenance of gut homeostasis. We determined the effect of moderate exercise (voluntary wheel running) with or without treatment with IAP on the course of experimental murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis by assessing disease activity index (DAI), colonic blood flow (CBF), plasma myokine irisin levels and the colonic and adipose tissue expression of proinflammatory cytokines, markers of oxidative stress (SOD2, GPx) and adipokines in mice fed a standard diet (SD) or high-fat diet (HFD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant decrease in CBF, and a significant increase in the colonic expression of tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β and leptin mRNAs and decrease in the mRNA expression of adiponectin. These effects were aggravated in sedentary HFD mice but reduced in exercising animals, potentiated by concomitant treatment with IAP, especially in obese mice. Exercising HFD mice demonstrated a substantial increase in the mRNA for adiponectin and a decrease in mRNA leptin expression in intestinal mucosa and mesenteric fat as compared to sedentary animals. The expression of SOD2 and GPx mRNAs was significantly decreased in adipose tissue in HFD mice, but these effects were reversed in exercising mice with IAP administration. Our study shows for the first time that the combination of voluntary exercise and oral IAP treatment synergistically favored healing of intestinal inflammation, strengthened the antioxidant defense and ameliorated the course of experimental colitis; thus, IAP may represent a novel adjuvant therapy to alleviate inflammatory bowel disease (IBD) in humans.
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29
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Zhu Q, Wang J, Ma J, Sheng X, Li F. Changes in inflammatory factors in the Brown Norway rat model of food allergy. BMC Immunol 2021; 22:8. [PMID: 33499808 PMCID: PMC7839196 DOI: 10.1186/s12865-021-00398-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 01/05/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The role of serum S100A8/A9 in intestinal inflammation has been confirmed, and its role in food allergy is currently being investigated. OBJECTIVE To explore the levels of S100A8/A9 and inflammatory factors, including Toll-like receptors 4 (TLR4), Nuclear transcription factors (NF-κB) and Tumor necrosis factor α (TNF-α), in mild food allergies. METHODS Eighty 3-week-old male Brown Norway rats were used. Forty rats were randomly assigned to the ovalbumin-sensitized experimental group, while 40 rats were assigned to the normal saline sham-sensitized control group. Body weight and length and the levels of serum ovalbumin-specific IgE (OVA-IgE), histamine, Th1-associated and Th2-associated factors, S100A8/A9 and inflammation-associated cytokines were compared. RESULTS Through the evaluation of OVA-IgE level and Th1/Th2 balance in the experimental group, a successful IgE-mediated food allergy model was constructed. Compared with the control group, the experimental group had higher serum S100A8/A9 levels on days 21, 28, 35 and 42 (all P < 0.05); higher TLR4 levels on days 28, 35 and 42 (all P < 0.05); higher TNF-α levels on days 28, 35 and 42 (all P < 0.05); higher NF-κB levels on days 35 and 42 (all P < 0.05); and higher IL-1β and IL-6 levels on days 7 to 42 (all P < 0.05). Moreover, positive correlations were found between the serum levels of S100A8/A9 and inflammation-associated cytokines [TNF-α: r = 0.378, P = 0.039; IL-1β: r = 0.679, P = 0.000; IL-6: r = 0.590, P = 0.001]. CONCLUSION S100A8/A9 and inflammatory-related factors, including TLR4, NF-κB, TNF-α, IL-6 and IL-1β, is closely related to food allergies. Moreover, immune and inflammatory factors interact with each other in food allergies, which may provide insight into food allergy causes and treatments.
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Affiliation(s)
- Qingling Zhu
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China.,Department of Children Healthcare, Quanzhou Women's and Children's Hospital, Quanzhou, 362000, Fujian, China
| | - Junli Wang
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China
| | - Jingqiu Ma
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China
| | - Xiaoyang Sheng
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China.
| | - Feng Li
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China.
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30
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Zhao B, Xia B, Li X, Zhang L, Liu X, Shi R, Kou R, Liu Z, Liu X. Sesamol Supplementation Attenuates DSS-Induced Colitis via Mediating Gut Barrier Integrity, Inflammatory Responses, and Reshaping Gut Microbiome. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:10697-10708. [PMID: 32893621 DOI: 10.1021/acs.jafc.0c04370] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Sesamol, a liposoluble lignan extract, has already been proved to possess potent anti-inflammatory properties, and it could also regulate gut dysfunction. The purpose of the present research is to explore the protective effect of sesamol on colitis mice. In the current research, sesamol treatment (100 mg/kg bodyweight/day) for 6 weeks inhibited the dextran sulphate sodium (DSS)-induced bodyweight loss of mice. Transmission electron microscopy and hematoxylin and eosin staining results showed that the DSS-induced histopathological changes of mice were also recovered by sesamol supplementation. In addition, DSS-induced inflammatory responses were inhibited by sesamol supplementation via the NF-κB signaling pathway in mice colon. Moreover, sesamol treatment prevented gut barrier damages by enhancing the expression of tight junction proteins (occludin, claudin-1, and ZO-1) and recovering the loss of gut mucus layer. Furthermore, sesamol supplementation also increased the short-chain fatty acid (SCFAs) contents of acetate, propionate, and butyrate. Furthermore, sesamol supplementation changed the gut microbiome structure by enhancing the relative abundance of Coprococcuscus, Butyricicoccus, Odoribacter, and AF12 in colitis mice. In conclusion, sesamol could effectively ameliorate DSS-induced colitis by promoting gut microecology.
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Affiliation(s)
- Beita Zhao
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Bing Xia
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Xiaohan Li
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Li Zhang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Xiaoning Liu
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Renjie Shi
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Rongwei Kou
- College of Chemistry and Pharmacy, Northwest A&F University, Yangling 712100, China
| | - Zhigang Liu
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Department of Food Science, Cornell University, Ithaca, New York 14850, United States
| | - Xuebo Liu
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
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Kalkanli Tas S, Kirkik D, Tanoglu A, Kahraman R, Ozturk K, Esen MF, Coskunpinar ME, Cagiltay E. Polymorphisms in Toll-like receptors 1, 2, 5, and 10 are associated with predisposition to Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2020; 32:1141-1146. [PMID: 32541244 DOI: 10.1097/meg.0000000000001797] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Toll-like receptors (TLRs) are significant receptors to the innate immune system which symbolizes a family of pattern recognition receptors. We aimed to investigate associations between rs4833095 polymorphism of TLR1, rs3804099 polymorphism of TLR2, rs5744174 polymorphism of TLR5, and rs10004195 polymorphism of TLR10 in dyspeptic individuals with Helicobacter pylori infection. METHODS Genomic DNA was isolated and genotyping of rs4833095 polymorphism in TLR1, rs3804099 polymorphism in TLR2, rs5744174 polymorphism in TLR5, and rs10004195 polymorphism in TLR10 were investigated in 400 individuals (205 in dyspeptic individuals with H. pylori-positive subjects and 195 dyspeptic individuals with H. pylori-negative subjects) by real-time PCR. Statistical analysis was performed by Pearson's Chi-square test. RESULTS According to our study; rs4833095 polymorphism in TLR1 C allele, rs3804099 polymorphism in TLR2 C allele, rs5744174 polymorphism in TLR5 C allele, and rs10004195 polymorphism in TLR10 A allele increased the risk of H. pylori infection [odds ratio (OR), 2.01; 95% confidence interval (CI), 1.39-3.16; OR, 1.78; 95% CI, 1.19-2.6; OR, 1.87; 95% CI, 1.25-2.78; OR, 2.66; 95% CI, 1.72-4.099, respectively]. CONCLUSION This is the first study that investigates TLRs in H. pylori infection in Turkey. Our findings may support the hypothesis that polymorphisms in certain TLRs may cause a genetic predisposition to H. pylori-related gastric problems.
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Affiliation(s)
| | - Duygu Kirkik
- Medical Biology, Hamidiye Medicine Faculty, University of Health Sciences
| | - Alpaslan Tanoglu
- Department of Gastroenterology, Sultan Abdulhamid Han Training and Research Hospital
| | - Resul Kahraman
- Department of Gastroenterology, Umraniye Training and Research Hospital
| | - Kubra Ozturk
- Medical Biology, Hamidiye Medicine Faculty, University of Health Sciences
| | - Muhammed Fevzi Esen
- Department of Health Information Systems, Hamidiye Medicine Faculty, University of Health Sciences
| | | | - Eylem Cagiltay
- Department of Endocrinology, Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey
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32
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Ghavami SB, Yadegar A, Aghdaei HA, Sorrentino D, Farmani M, Mir AS, Azimirad M, Balaii H, Shahrokh S, Zali MR. Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease. Int J Mol Sci 2020; 21:6266. [PMID: 32872480 PMCID: PMC7503552 DOI: 10.3390/ijms21176266] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 08/27/2020] [Accepted: 08/27/2020] [Indexed: 12/15/2022] Open
Abstract
In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs). Herein, we assessed the immunomodulatory effects of four probiotic strains including Lactobacillus salivarius, Bifidobacterium bifidum, Bacillus coagulans and Bacillus subtilis natto on the expression of co-stimulatory molecules, cytokine production and gene expression of signal-transducing receptors in DCs from IBD patients. Human monocyte-derived DCs from IBD patients and healthy controls were exposed to four probiotic strains. The expression of co-stimulatory molecules was assessed and supernatants were analyzed for anti-inflammatory cytokines. The gene expression of toll-like receptors (TLRs), IL-12p40 and integrin αvβ8 were also analyzed. CD80 and CD86 were induced by most probiotic strains in ulcerative colitis (UC) patients whereas only B. bifidum induced CD80 and CD86 expression in Crohn's disease (CD) patients. IL-10 and TGF-β production was increased in a dose-independent manner while TLR expression was decreased by all probiotic bacteria except B. bifidum in DCs from UC patients. TLR-4 and TLR-9 expression was significantly downregulated while integrin ß8 was significantly increased in the DCs from CD patients. IL-12p40 expression was only significantly downregulated in DCs from CD patients. Our findings point to the general beneficial effects of probiotics in DC immunomodulation and indicate that probiotic bacteria favorably modulate the expression of co-stimulatory molecules, proinflammatory cytokines and TLRs in DCs from IBD patients.
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Affiliation(s)
- Shaghayegh Baradaran Ghavami
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (S.B.G.); (H.A.A.); (M.F.)
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (A.Y.); (M.A.)
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (S.B.G.); (H.A.A.); (M.F.)
| | - Dario Sorrentino
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA
- Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, 33100 Udine, Italy
| | - Maryam Farmani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (S.B.G.); (H.A.A.); (M.F.)
| | - Adil Shamim Mir
- Department of Internal Medicine, Roanoke Memorial Hospital, Carilion Clinic, VA 24014, USA;
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (A.Y.); (M.A.)
| | - Hedieh Balaii
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (H.B.); (S.S.); (M.R.Z.)
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (H.B.); (S.S.); (M.R.Z.)
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (H.B.); (S.S.); (M.R.Z.)
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Yousefi-Manesh H, Dejban P, Mumtaz F, Abdollahi A, Chamanara M, Dehpour A, Hasanvand A, Rashidian A. Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway. Immunopharmacol Immunotoxicol 2020; 42:464-472. [PMID: 32787472 DOI: 10.1080/08923973.2020.1808987] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIM The purpose of the present study is to explore the anti-inflammatory potential of risperidone in acetic acid-induced rat colitis through inhibition of TLR4/NF-kB pathway. METHODS Acute colitis induction was done by intra-rectal administration of 2 mL of 4% diluted acetic acid solution. Two h after colitis induction, dexamethasone (2 mg/kg) as standard drugorrisperidone (2, 4 and 6 mg/kg) were administered orally to wistar rats for five consecutive days. 24 h after the last treatment, animals were sacrificed by cervical dislocation. Macroscopic and microscopic damage evaluation was done. Biochemical and ELISA methods were used to assess myeloid peroxidase (MPO) enzyme activity and tumor necrosis factor-α (TNF-α) level respectively. Moreover, immunohistochemistry (IHC) was performed to detect the expression of TLR4 and pNF-kBproteins. RESULTS Dexamethasone (2 mg/kg) or risperidone (2, 4 and 6 mg/kg) improved acetic acid-induced macroscopic (p < .001) and microscopic lesions. Additionally, risperidone (2, 4 and 6 mg/kg) inhibited the activity of MPO and TNF-α (p < .01, p < .001) in the colon tissue compared to acetic acid group. Furthermore, bothdexamethasone and risperidone (2, 4 and 6 mg/kg) significantly reduced acetic acid-induced expression of TLR4and pNF-kB proteins (p < .05, p < .01, p < .001). CONCLUSION The anti-inflammatory effect of risperidone on acetic acid-induced colitis in rats may involve inhibition of TLR4 and NF-kB signaling pathway.
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Affiliation(s)
- Hasan Yousefi-Manesh
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Pegah Dejban
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Faiza Mumtaz
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Abdollahi
- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Chamanara
- Department of Pharmacology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Dehpour
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amin Hasanvand
- Department of Pharmacology, School of Medicine, Lorestan University of Medical Sciences, Lorestan, Iran
| | - Amir Rashidian
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Sharma U, Olson RK, Erhart FN, Zhang L, Meng J, Segura B, Banerjee S, Sharma M, Saluja AK, Ramakrishnan S, Abreu MT, Roy S. Prescription Opioids induce Gut Dysbiosis and Exacerbate Colitis in a Murine Model of Inflammatory Bowel Disease. J Crohns Colitis 2020; 14:801-817. [PMID: 31773170 PMCID: PMC7346895 DOI: 10.1093/ecco-jcc/jjz188] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Opioids are the most prescribed analgesics for pain in inflammatory bowel diseases [IBD]; however, the consequences of opioid use on IBD severity are not well defined. This is the first study investigating consequences of hydromorphone in both dextran sodium sulphate [DSS]-induced colitis and spontaneous colitis (IL-10 knockout [IL-10-/-]) mouse models of IBD. METHODS To determine the consequences of opioids on IBD pathogenesis, wild-type [WT] mice were treated with clinically relevant doses of hydromorphone and colitis was induced via 3% DSS in drinking water for 5 days. In parallel we also determined the consequences of opioids in a spontaneous colitis model. RESULTS Hydromorphone and DSS independently induced barrier dysfunction, bacterial translocation, disruption of tight junction organisation and increased intestinal and systemic inflammation, which were exacerbated in mice receiving hydromorphone in combination with DSS. Hydromorphone + DSS-treated mice exhibited significant microbial dysbiosis. Predictive metagenomic analysis of the gut microbiota revealed high abundance in the bacterial communities associated with virulence, antibiotic resistance, toxin production, and inflammatory properties. Hydromorphone modulates tight junction organisation in a myosin light chain kinase [MLCK]-dependent manner. Treatment with MLCK inhibitor ML-7 ameliorates the detrimental effects of hydromorphone on DSS-induced colitis and thus decreases severity of IBD. Similarly, we demonstrated that hydromorphone treatment in IL-10-/- mice resulted in accelerated clinical manifestations of colitis compared with control mice. CONCLUSIONS Opioids used for pain management in IBD accelerate IBD progression by dysregulation of the gut microbiota, leading to expansion of pathogenic bacteria, translocation of bacteria, immune deregulation and sustained inflammation.
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Affiliation(s)
- Umakant Sharma
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | | | | | - Li Zhang
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Jingjing Meng
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Bradley Segura
- Department of Surgery, University of Minnesota, Minneapolis, MN, USA
| | - Santanu Banerjee
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Madhulika Sharma
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Ashok Kumar Saluja
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Sundaram Ramakrishnan
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Maria T Abreu
- Division of Gastroenterology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Sabita Roy
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
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35
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Xie Y, Zhou L, Yao X, Li Y. Protective Effects of Clostridium Butyricum in a Murine Model of Dextran Sodium Sulfate-Induced Colitis That Involve Inhibition of the TLR2 Signaling Pathway and T Helper 17 Cells. Am J Med Sci 2020; 360:176-191. [PMID: 32553747 DOI: 10.1016/j.amjms.2020.05.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 03/08/2020] [Accepted: 05/14/2020] [Indexed: 01/01/2023]
Abstract
BACKGROUND This study aimed to investigate the role of Clostridium butyricum (C. butyricum) in conjunction with the Toll-like receptor2 (TLR2) signaling pathway and T helper 17 (Th17) cells in dextran sodium sulfate (DSS)-induced colitis in mice. METHODS Forty 8-week-old BALB/c mice were randomly divided into 5 groups of 8 mice for 7 days: control, DSS (5% DSS), DSS+C. butyricum (1 × 109 CFU), DSS+C. butyricum (1 × 108 CFU) and DSS+C. butyricum (1 × 107 CFU) groups. We assessed the disease activity index (DAI) and histological damage scores. The expression levels of TLR2, myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B p65 (NF-κBp65), interleukin (IL) 17 (IL17), IL23 and retineic acid receptor related orphan nuclear receptor gamma t (RORγt) were determined through immunohistochemical staining, western blot and quantitative real-time PCR (qRT-PCR). The expression levels of CD3+CD4+IL17+ cells in peripheral blood were measured by flow cytometry. RESULTS C. butyricum dose-dependently decreased DAI and histological damage scores in DSS mice and down-regulated the mRNA and protein levels of TLR2, MyD88 and NF-κBp65 in mouse colon tissue (all P < 0.05). In addition, C. butyricum dose-dependently decreased the levels of CD3+CD4+IL17+ cells in peripheral blood and down-regulated the mRNA and protein levels of IL17, IL23 and RORγt in mouse colon tissue (all P < 0.05). Moreover, the effect of C. butyricum on TLR2 was positively correlated with IL17, IL23 and RORγt. CONCLUSIONS C. butyricum exerts a dose-dependently protective effect on acute intestinal inflammation induced by DSS in mice, by inhibiting the TLR2 signaling pathway, down-regulating the expression of IL23 and RORγt, and inhibiting the secretion of IL17.
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Affiliation(s)
- Ying Xie
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China
| | - Linyan Zhou
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China
| | - Xinjie Yao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China
| | - Yan Li
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
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36
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Lei L, Li X, Yuan YJ, Chen ZL, He JH, Wu JH, Cai XS. Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates 2,4,6-trinitrobenzenesulfonic acid-induced colitis via repressing toll-like receptor 4/nuclear factor-kappa B. Kaohsiung J Med Sci 2020; 36:705-711. [PMID: 32396274 DOI: 10.1002/kjm2.12225] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 04/13/2020] [Accepted: 04/16/2020] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by recurring inflammatory disorders in digestive system, and devoid of effective treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9), stimulated via inflammation whose inhibition could decrease secretion of inflammatory factors. We then determined whether inhibition of PCSK9 could improve the inflammation. First, rats model of colitis was first established via administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS), and then verified via determination of body weight loss, myeloperoxidase (MPO) activity, and histopathological analysis of colonic damage. Results showed that treatment with TNBS induced a great body weight loss, MPO activity increase, and serious colonic damage, showing an obviously character of IBD. PCSK9 was elevated in TNBS-induced rats, and PCSK9 inhibition delivered by adenovirus vector increased the body weight, decreased MPO activity, and ameliorated histological change of colon. Second, the protective effect of PCSK9 inhibition against TNBS-induced colitis was accompanied by decrease of proinflammatory factors secretion, including tumor necrosis factor-α, interleukin-1β, interleukin-6, intercellular adhesion molecule 1, and monocyte chemoattractant protein-1. TNBS could activate toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway, while PCSK9 inhibition suppressed activation of TLR4/NF-κB in TNBS-induced rats. In conclusion, PCSK9 inhibition attenuated TNBS-induced rat colitis through anti-inflammatory effect under inactivation of TLR4/NF-κB, suggesting potential therapeutic strategy in IBD.
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Affiliation(s)
- Lei Lei
- GI Medicine, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Xu Li
- Cardiothoracic Surgery, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - You-Jun Yuan
- Department of Emergency, WenZhou Central Hospital, Wenzhou City, China
| | - Zhi-Li Chen
- Department of Emergency, WenZhou Central Hospital, Wenzhou City, China
| | - Jian-Hua He
- GI Medicine, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Jian-Hua Wu
- Department of Emergency, WenZhou Central Hospital, Wenzhou City, China
| | - Xiao-Sheng Cai
- Department of Emergency, WenZhou Central Hospital, Wenzhou City, China
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37
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Zhang X, Zou Q, Zhao B, Zhang J, Zhao W, Li Y, Liu R, Liu X, Liu Z. Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders. Redox Biol 2020; 32:101535. [PMID: 32305005 PMCID: PMC7162980 DOI: 10.1016/j.redox.2020.101535] [Citation(s) in RCA: 101] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 03/27/2020] [Accepted: 04/04/2020] [Indexed: 12/18/2022] Open
Abstract
Intermittent fasting (IF) has been reported to have beneficial effects on improving gut function via lowering gut inflammation and altering the gut microbiome diversity. In this study, we aimed to investigate the differential effects of three different common IF treatments, alternate day fasting (ADF), time-restricted fasting (TRF), and intermittent energy restriction (IER), on a dextran sodium sulfate (DSS)-induced colitis mouse model. The results indicated that TRF and IER, but not ADF improved the survival rates of the colitis mice. TRF and IER, but not ADF, reversed the colitis pathological development by improving the gut barrier integrity and colon length. Importantly, TRF and IER suppressed the inflammatory responses and oxidative stress in colon tissues. Interestingly, TRF and IER also attenuated colitis-related anxiety-like and obsessive-compulsive disorder behavior and alleviated the neuroinflammation and oxidative stress. TRF and IER also altered the gut microbiota composition, including the decrease of the enrichments of colitis-related microbes such as Shigella and Escherichia Coli, and increase of the enrichments of anti-inflammatory-related microbes. TRF and IER also improved the short chain fatty acid formation in colitis mice. In conclusion, the TRF and IER but not ADF exhibited the protective effects against colitis and related behavioral disorders, which could be partly explained by improving the gut microbiome compositions and preventing gut leak, and consequently suppressing the inflammation and oxidative damages in both colon and brain. The current research indicates that proper IF regimens could be effective strategies for nutritional intervention for the prevention and treatment of colitis.
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Affiliation(s)
- Xin Zhang
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaan Xi, China
| | - Qianhui Zou
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaan Xi, China
| | - Beita Zhao
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaan Xi, China
| | - Jingwen Zhang
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaan Xi, China
| | - Weiyang Zhao
- Department of Food Science, Cornell University, Ithaca, NY, 14853, United States
| | - Yitong Li
- Department of Food Science, Cornell University, Ithaca, NY, 14853, United States
| | - Ruihai Liu
- Department of Food Science, Cornell University, Ithaca, NY, 14853, United States
| | - Xuebo Liu
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaan Xi, China
| | - Zhigang Liu
- Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaan Xi, China; Department of Food Science, Cornell University, Ithaca, NY, 14853, United States.
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Gorczynski RM, Hoffmann G. Combined IMIG and immune Ig attenuates inflammatory colitis in mice. Int Immunopharmacol 2020; 83:106464. [PMID: 32278130 DOI: 10.1016/j.intimp.2020.106464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/13/2020] [Accepted: 03/29/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND Using a combination of homologous and heterologous (mouse/human) polyclonal anti-idiotypic Igs and immune Igs in BALB/c mice we have previously reported attenuation of allergic type responses following OVA immunization. We have now investigated attenuation of an inflammatory colitis in C57BL/6 mice receiving dextran sodium sulfate (DSS) in their drinking water, using additional treatment of DSS-exposed mice with combined human Igs, commercial IVIG (given IM, hence hereafter IMIG) as a source of pooled anti-idiotype Ig, and human anti-Tet as immune Ig. METHODS Acute or chronic colitis was induced by DSS in groups of C57BL/6 mice. Mice also received weekly immunotherapy with im injections of polyclonal immune Ig, polyclonal anti-idiotype Ig, or the combined Igs, for a total of 5 injections, beginning with DSS treatment or after 2 cycles of DSS. Weight loss and mortality were monitored daily, and the extent of colitis was determined further using colonic length measurement, and by ELISA measurement of inflammatory cytokines in supernatants from colonic explant cultures. RESULTS Mice developed colitis in both the acute and chronic models with loss of body weight, shortened colon lengths, and increased expression of inflammatory cytokines in colonic tissue. Loss of body weight, and inflammatory cytokine production, was attenuated only in chronic colitis, and only after combined IMIG and immune Ig treatment, and not in groups receiving only IMIG or immune Ig alone. CONCLUSION Heterologous combinations of polyclonal IMIG and immune Ig can attenuate inflammatory colitis in mice. Given the described efficacy of this treatment for allergic desensitization, we hypothesize this methodology may have widespread clinic utility.
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Affiliation(s)
- R M Gorczynski
- Universityof Toronto, ON, Canada; Network Immunology, Vancouver, BC, Canada.
| | - G Hoffmann
- Network Immunology, Vancouver, BC, Canada
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Li B, Ding Y, Cheng X, Sheng D, Xu Z, Rong Q, Wu Y, Zhao H, Ji X, Zhang Y. Polyethylene microplastics affect the distribution of gut microbiota and inflammation development in mice. CHEMOSPHERE 2020; 244:125492. [PMID: 31809927 DOI: 10.1016/j.chemosphere.2019.125492] [Citation(s) in RCA: 359] [Impact Index Per Article: 71.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 10/28/2019] [Accepted: 11/26/2019] [Indexed: 05/23/2023]
Abstract
Environmental pollution caused by plastics has become a public health problem. However, the effect of microplastics on gut microbiota, inflammation development and their underlying mechanisms are not well characterized. In the present study, we assessed the effect of exposure to different amounts of polyethylene microplastics (6, 60, and 600 μg/day for 5 consecutive weeks) in a C57BL/6 mice model. Treatment with a high concentration of microplastics increased the numbers of gut microbial species, bacterial abundance, and flora diversity. Feeding groups showed a significant increase in Staphylococcus abundance alongside a significant decrease in Parabacteroides abundance, as compared to the blank (untreated) group. In addition, serum levels of interleukin-1α in all feeding groups were significantly greater than that in the blank group. Of note, treatment with microplastics decreased the percentage of Th17 and Treg cells among CD4+ cells, while no significant difference was observed between the blank and treatment groups with respect to the Th17/Treg cell ratio. The intestine (colon and duodenum) of mice fed high-concentration microplastics showed obvious inflammation and higher TLR4, AP-1, and IRF5 expression. Thus, polyethylene microplastics can induce intestinal dysbacteriosis and inflammation, which provides a theoretical basis for the prevention and treatment of microplastics-related diseases.
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Affiliation(s)
- Boqing Li
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Yunfei Ding
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Xue Cheng
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Dandan Sheng
- Yantai City Hospital for Infectious Diseases, No.62, Huanshan Road, Yantai, 264003, China
| | - Zheng Xu
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Qianyu Rong
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Yulong Wu
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Huilin Zhao
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Xiaofei Ji
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China
| | - Ying Zhang
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China.
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40
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Luzardo-Ocampo I, Campos-Vega R, Gonzalez de Mejia E, Loarca-Piña G. Consumption of a baked corn and bean snack reduced chronic colitis inflammation in CD-1 mice via downregulation of IL-1 receptor, TLR, and TNF-α associated pathways. Food Res Int 2020; 132:109097. [PMID: 32331643 DOI: 10.1016/j.foodres.2020.109097] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 12/06/2019] [Accepted: 02/10/2020] [Indexed: 12/12/2022]
Abstract
Ulcerative colitis (UC) is a condition that has been rising in the number of cases around the world. Food products made from natural ingredients such as corn and common bean might serve as alternatives for the treatment of UC. This study aimed to assess the anti-inflammatory effect of the consumption of a baked corn and bean snack (CBS) in an in vivo model of UC using 2% dextran sodium sulfate (DSS) as inductor of colitis. CD-1 mice (45, n = 9/group) were randomly separated into 5 groups, treated for 6-weeks as follows: G1 (basal diet, BD), G2 (2% DSS), G3 (20 g CBS/body weight BW/day + BD), G4 (40 g CBS/BW/day + BD) and G5 (60 g CBS/BW/day + BD). BW, Disease Activity Index (DAI), and feces were collected throughout the treatment. After euthanasia, organs (spleen, liver, and colon) were excised and weighed. Feces were analyzed for β-glucuronidase (β-GLUC) activity and gas-chromatography. The colons were analyzed for histopathology, myeloperoxidase (MPO) activity, and gene analysis. At the end of treatments, among the DSS-induced groups, G3 exhibited the lowest BW losses (11.5%), MPO activity (10.4%) and β-GLUC (8.6%). G4 presented the lowest DAI (0.88), relative spleen weight, and histological inflammation score (p < 0.05). Compared to G2, CBS consumption significantly (p < 0.05) reduced serum TNF-α, IL-10, and MCP-1 levels. The fecal metabolome analysis ranked 9-decenoic acid, decane, and butyric acid as the main contributors of pathways associated with the β-oxidation of fatty acids. G4 showed the highest fecal/cecal contents of short-chain fatty acids among all the DSS-induced groups. For the gene expression, G4 was clustered with G1, showing a differential inhibition of the pro-inflammatory genes Il1r1, Il1a, Tlr4, Tlr2, and Tnfrsf1b. In conclusion, CBS consumption decreased the inflammatory state and reduced the expression of the IL-1 receptor, TLR, and TNF-α-associated pathways in DSS-induced UC in CD-1 mice.
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Affiliation(s)
- Ivan Luzardo-Ocampo
- Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Program in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, 76010 Queretaro, Mexico; Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 228-230 ERML, 1201 W. Gregory Dr., Urbana, IL 61801, United States.
| | - Rocio Campos-Vega
- Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Program in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, 76010 Queretaro, Mexico.
| | - Elvira Gonzalez de Mejia
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 228-230 ERML, 1201 W. Gregory Dr., Urbana, IL 61801, United States.
| | - Guadalupe Loarca-Piña
- Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Program in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, 76010 Queretaro, Mexico.
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Dworsky-Fried Z, Kerr BJ, Taylor AMW. Microbes, microglia, and pain. NEUROBIOLOGY OF PAIN 2020; 7:100045. [PMID: 32072077 PMCID: PMC7016021 DOI: 10.1016/j.ynpai.2020.100045] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 01/23/2020] [Accepted: 01/24/2020] [Indexed: 02/08/2023]
Abstract
Explore the connection between the gut microbiome and microglia in chronic pain. Discuss mechanisms by which gut bacteria might influence microglia to contribute to chronic pain. Highlight gaps in knowledge and discuss future directions for the field. Globally, it is estimated that one in five people suffer from chronic pain, with prevalence increasing with age. The pathophysiology of chronic pain encompasses complex sensory, immune, and inflammatory interactions within both the central and peripheral nervous systems. Microglia, the resident macrophages of the central nervous system (CNS), are critically involved in the initiation and persistence of chronic pain. Microglia respond to local signals from the CNS but are also modulated by signals from the gastrointestinal tract. Emerging data from preclinical and clinical studies suggest that communication between the gut microbiome, the community of bacteria residing within the gut, and microglia is involved in producing chronic pain. Targeted strategies that manipulate or restore the gut microbiome have been shown to reduce microglial activation and alleviate symptoms associated with inflammation. These data indicate that manipulations of the gut microbiome in chronic pain patients might be a viable strategy in improving pain outcomes. Herein, we discuss the evidence for a connection between microglia and the gut microbiome and explore the mechanisms by which commensal bacteria might influence microglial reactivity to drive chronic pain.
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Affiliation(s)
- Zoë Dworsky-Fried
- Department of Pharmacology, University of Alberta, Edmonton T6G2H7, Canada
| | - Bradley J Kerr
- Department of Pharmacology, University of Alberta, Edmonton T6G2H7, Canada.,Neuroscience and Mental Health Institute, University of Alberta, Edmonton T6G2H7, Canada.,Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton T6G2H7, Canada
| | - Anna M W Taylor
- Department of Pharmacology, University of Alberta, Edmonton T6G2H7, Canada.,Neuroscience and Mental Health Institute, University of Alberta, Edmonton T6G2H7, Canada.,Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton T6G2H7, Canada
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Sireswar S, Biswas S, Dey G. Adhesion and anti-inflammatory potential of Lactobacillus rhamnosus GG in a sea buckthorn based beverage matrix. Food Funct 2020; 11:2555-2572. [DOI: 10.1039/c9fo02249j] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
A seabuckthorn based beverage matrix retains the functionality of L. rhamnosus GG and exhibits enhanced anti-inflammatory effects against LPS-induced inflammation in zebrafish.
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Affiliation(s)
- Srijita Sireswar
- School of Biotechnology
- Kalinga Institute of Industrial Technology
- Deemed to be University
- Bhubaneswar
- India
| | | | - Gargi Dey
- School of Biotechnology
- Kalinga Institute of Industrial Technology
- Deemed to be University
- Bhubaneswar
- India
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Yoo JH, Donowitz M. Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases. World J Gastroenterol 2019; 25:4125-4147. [PMID: 31435168 PMCID: PMC6700704 DOI: 10.3748/wjg.v25.i30.4125] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 06/14/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
The introduction of biologics such as anti-tumor necrosis factor (TNF) monoclonal antibodies followed by anti-integrins has dramatically changed the therapeutic paradigm of inflammatory bowel diseases (IBD). Furthermore, a newly developed anti-p40 subunit of interleukin (IL)-12 and IL-23 (ustekinumab) has been recently approved in the United States for patients with moderate to severe Crohn’s disease who have failed treatment with anti-TNFs. However, these immunosuppressive therapeutics which focus on anti-inflammatory mechanisms or immune cells still fail to achieve long-term remission in a significant percentage of patients. This strongly underlines the need to identify novel treatment targets beyond immune suppression to treat IBD. Recent studies have revealed the critical role of intestinal epithelial cells (IECs) in the pathogenesis of IBD. Physical, biochemical and immunologic driven barrier dysfunctions of epithelial cells contribute to the development of IBD. In addition, the recent establishment of adult stem cell-derived intestinal enteroid/organoid culture technology has allowed an exciting opportunity to study human IECs comprising all normal epithelial cells. This long-term epithelial culture model can be generated from endoscopic biopsies or surgical resections and recapitulates the tissue of origin, representing a promising platform for novel drug discovery in IBD. This review describes the advantages of intestinal enteroids/organoids as a research tool for intestinal diseases, introduces studies with these models in IBD, and gives a description of the current status of therapeutic approaches in IBD. Finally, we provide an overview of the current endeavors to identify a novel drug target for IBD therapy based on studies with human enteroids/organoids and describe the challenges in using enteroids/organoids as an IBD model.
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Affiliation(s)
- Jun-Hwan Yoo
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
- Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam 13496, South Korea
| | - Mark Donowitz
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
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Zheng JD, He Y, Yu HY, Liu YL, Ge YX, Li XT, Li X, Wang Y, Guo MR, Qu YL, Qin XF, Jiang MS, Wang XH. Unconjugated bilirubin alleviates experimental ulcerative colitis by regulating intestinal barrier function and immune inflammation. World J Gastroenterol 2019; 25:1865-1878. [PMID: 31057300 PMCID: PMC6478610 DOI: 10.3748/wjg.v25.i15.1865] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 03/05/2019] [Accepted: 03/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Unconjugated bilirubin (UCB) is generally considered toxic but has gained recent prominence for its anti-inflammatory properties. However, the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved. AIM To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis. METHODS Acute colitis was induced by 3% (w/v) dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d. Concurrently, mice with colitis were administered 0.2 mL UCB (400 μmol/L) by intra-gastric gavage for 7 d. Disease activity index (DAI) was monitored daily. Mice were sacrificed at the end of the experiment. The length of the colon and weight of the spleen were recorded. Serum level of D-lactate, intestinal digestive proteases activity, and changes to the gut flora were analyzed. In addition, colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins. RESULTS Mice treated with UCB had significantly relieved severity of colitis, including lower DAI, longer colon length, and lower spleen weight (colon length: 4.92 ± 0.09 cm vs 3.9 ± 0.15 cm; spleen weight: 0.33 ± 0.04 vs 0.74 ± 0.04, P < 0.001). UCB administration inactivated digestive proteases (chymotrypsin: 18.70 ± 0.69 U/g vs 44.81 ± 8.60 U/g; trypsin: 1.52 ± 0.23 U/g vs 9.05 ± 1.77 U/g, P < 0.01), increased expression of tight junction (0.99 ± 0.05 vs 0.57 ± 0.03, P < 0.001), decreased serum level of D-lactate (31.76 ± 3.37 μmol/L vs 54.25 ± 1.45 μmol/L, P < 0.001), and lowered histopathological score (4 ± 0.57 vs 7 ± 0.57, P < 0.001) and activity of myeloperoxidase (46.79 ± 2.57 U/g vs 110.32 ± 19.19 U/g, P < 0.001). UCB also regulated the intestinal microbiota, inhibited expression of tumor necrosis factor (TNF) α and interleukin 1β (TNF-α: 52.61 ± 7.81 pg/mg vs 105.04 ± 11.92 pg/mg, interleukin 1β: 13.43 ± 1.68 vs 32.41 ± 4.62 pg/mg, P < 0.001), decreased expression of Toll-like receptor 4 (0.61 ± 0.09 vs 1.07 ± 0.03, P < 0.001) and myeloid differentiation primary response gene 88 (0.73 ± 0.08 vs 1.01 ± 0.07, P < 0.05), and increased expression of TNF-receptor-associated factor 6 (0.79 ± 0.02 vs 0.43 ± 0.09 P < 0.05) and inhibitor of kappa B α (0.93 ± 0.07 vs 0.72 ± 0.07, P < 0.05) in the colon. CONCLUSION UCB can protect intestinal barrier function, regulate normal intestinal homeostasis, and suppress inflammation via the Toll-like receptor 4/ nuclear factor-κB signaling pathway.
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Affiliation(s)
- Jia-Dong Zheng
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Yan He
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Heng-Yuan Yu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Yuan-Li Liu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Yi-Xuan Ge
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Xue-Ting Li
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Xue Li
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Yan Wang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Meng-Ru Guo
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Yi-Lin Qu
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Xiao-Fa Qin
- Founder, GI Biopharma Inc., Westfield, NJ 07090, United States
| | - Ming-Shan Jiang
- Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Xiu-Hong Wang
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150086, Heilongjiang Province, China
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Stephens M, Liao S, von der Weid PY. Mesenteric Lymphatic Alterations Observed During DSS Induced Intestinal Inflammation Are Driven in a TLR4-PAMP/DAMP Discriminative Manner. Front Immunol 2019; 10:557. [PMID: 30972059 PMCID: PMC6443629 DOI: 10.3389/fimmu.2019.00557] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 03/01/2019] [Indexed: 12/11/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD) is characterized by both acute and chronic phase inflammation of the gastro-intestinal (GI) tract that affect a large and growing number of people worldwide with little to no effective treatments. This is in part due to the lack of understanding of the disease pathogenesis and also the currently poorly described involvement of other systems such as the lymphatics. During DSS induced colitis, mice also develop a severe inflammation of terminal ileum with many features similar to IBD. As well as inflammation within the ileum we have previously demonstrated lymphatic remodeling within the mesentery and mesenteric lymph nodes of DSS-treated mice. The lymphatic remodeling includes lymphangiogenesis, lymphatic vessel dilation and leakiness, as well as cellular infiltration into the surrounding tissue and peripheral draining lymph nodes. Methods: Intestinal inflammation was induced in C57BL/6 mice by administration of 2.5% DSS in drinking water for 7 days. Mice were treated with TLR4 blocker C34 or Polymyxin-B (PMXB) daily from days 3 to 7 of DSS treatment via I.P. injection, and their therapeutic effects on disease activity and lymphatic function were examined. TLR activity and subsequent effect on lymphangiogenesis, lymphadenopathy, and mesenteric lymph node cellular composition were assessed. Results: DSS Mice treated with TLR4 inhibitor, C34, had a significantly improved disease phenotype characterized by reduced ileal and colonic insult. The change correlated with significant reduction in colonic and mesenteric inflammation, resolved mesenteric lymphangiectasia, and CD103+ DC migration similar to that of healthy control. PMXB treatment however did not resolve inflammation within the colon or associated mesenteric lymphatic dysfunction but did however prevent lymphadenopathy within the MLN through alteration of CCL21 gradients and CD103+ DC migration. Conclusions: TLR4 appears to mediate several changes within the mesenteric lymphatics, more specifically it is shown to have different outcomes whether stimulation occurs through pathogen derived factors such as LPS or tissue derived DAMPs, a novel phenomenon.
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Affiliation(s)
- Matthew Stephens
- Department of Physiology and Pharmacology, Inflammation Research Network, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Shan Liao
- Department of Microbiology, Immunology and Infectious Diseases, Inflammation Research Network, Cumming School of Medicine, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Pierre-Yves von der Weid
- Department of Physiology and Pharmacology, Inflammation Research Network, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
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Nier A, Brandt A, Rajcic D, Bruns T, Bergheim I. Short-Term Isocaloric Intake of a Fructose- but not Glucose-Rich Diet Affects Bacterial Endotoxin Concentrations and Markers of Metabolic Health in Normal Weight Healthy Subjects. Mol Nutr Food Res 2019; 63:e1800868. [PMID: 30570214 PMCID: PMC6590154 DOI: 10.1002/mnfr.201800868] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 12/06/2018] [Indexed: 12/18/2022]
Abstract
SCOPE Dietary pattern and impairments of intestinal barrier function are discussed to be critical in the development of metabolic impairments. Here, it is determined if an isocaloric exchange of complex carbohydrates with monosaccharides affects markers of intestinal permeability and metabolic health in healthy subjects. METHODS AND RESULTS After a dietary standardization for 4 days, all 12 subjects aged 21-33 years receive an isocaloric fructose- and glucose-enriched diet for 3 days separated by a wash-out phase. Anthropometry, blood pressure, markers of intestinal permeability and metabolic as well as inflammatory parameters are determined in blood samples or isolated peripheral blood mononuclear cells collected at baseline, after standardizations and the monosaccharide interventions, respectively. While anthropometric and inflammatory parameters are not changed, the intake of an isocaloric fructose- but not glucose-enriched diet is associated with a significant increase of bacterial endotoxin plasma levels and alanine aminotransferase activity in serum, while total plasma nitrate/nitrite concentrations are significantly decreased. In peripheral blood mononuclear cells, Toll like receptors 4, 2, and MYD88 mRNA expressions are significantly induced after the fructose-rich but not the glucose-rich diet. CONCLUSION In metabolically healthy subjects, even a short-term intake of a fructose-rich diet can elevate bacterial endotoxin levels and change markers of liver health and vascular endothelial function.
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Affiliation(s)
- Anika Nier
- Department of Nutritional SciencesMolecular Nutritional ScienceUniversity of Vienna1090ViennaAustria
- SD Model Systems of Molecular NutritionInstitute of NutritionFriedrich–Schiller University Jena07743JenaGermany
| | - Annette Brandt
- Department of Nutritional SciencesMolecular Nutritional ScienceUniversity of Vienna1090ViennaAustria
- SD Model Systems of Molecular NutritionInstitute of NutritionFriedrich–Schiller University Jena07743JenaGermany
| | - Dragana Rajcic
- Department of Nutritional SciencesMolecular Nutritional ScienceUniversity of Vienna1090ViennaAustria
| | - Tony Bruns
- Department of Internal Medicine IVUniversity Hospital Jena07743JenaGermany
| | - Ina Bergheim
- Department of Nutritional SciencesMolecular Nutritional ScienceUniversity of Vienna1090ViennaAustria
- SD Model Systems of Molecular NutritionInstitute of NutritionFriedrich–Schiller University Jena07743JenaGermany
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Du G, Xiao M, Zhu Q, Zhou C, Wang A, Cai W. Intestinal transcriptional profiling reveals fava bean-induced immune response in DBA/1 mice. Biol Res 2019; 52:9. [PMID: 30823938 PMCID: PMC6396536 DOI: 10.1186/s40659-019-0216-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 02/14/2019] [Indexed: 12/14/2022] Open
Abstract
Background Fava beans (FBs) have long been used as food, and their principal disadvantage is derived from their haemotoxicity. We hypothesized that FB ingestion alters the intestinal gene expression pattern, thereby inducing an immune response. Results In-depth sequence analysis identified 769 differentially expressed genes (DEGs) associated with the intestine in FB-treated DBA/1 mouse intestines. The identified genes were shown to be associated with biological processes (such as response to stimulus and immune system processes), human disease pathways (such as infectious diseases, endocrine and metabolic diseases, and immune diseases), and organismal system pathways (such as the digestive system, endocrine system, environmental adaptation, and immune system). Moreover, plasma total immunoglobulin E (IgE), histamine, interleukin (IL)-4 and IL-13 levels were significantly increased when the mice were treated with FBs. Conclusions These results demonstrated that FBs affect the intestinal immune response and IgE and cytokine secretion in DBA/1 mice. Electronic supplementary material The online version of this article (10.1186/s40659-019-0216-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Guankui Du
- Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, 571199, China.
| | - Man Xiao
- Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, 571199, China
| | - Qiwei Zhu
- Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, 571199, China
| | - Chen Zhou
- Biotechnology Major, Hainan Medical College, Haikou, 571199, China
| | - Ao Wang
- Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, 571199, China
| | - Wangwei Cai
- Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, 571199, China.
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Abstract
PURPOSE OF REVIEW To summarize the current understanding and recent advances on the genetic aetiology in the pathogenesis of very early onset inflammatory bowel disease (VEO-IBD). RECENT FINDINGS IBD is a chronic disorder of the gastrointestinal tract whose manifestation is a result of complex interactions between genetics, environment, immune system and microbial flora. Over 230 IBD risk loci have been reported in genome wide association studies but the genetic contribution of the majority of these loci in the manifestation of IBD is very low. Patients with VEO-IBD present with a more severe disease than older patients, characterized by poor prognosis and failure of conventional therapy. Recent studies have reported several monogenic diseases with high penetrance that present with IBD and IBD-like intestinal manifestations and overlap with primary immunodeficiencies. Increasing body of evidence supports a prominent role of genetics in the onset of VEO-IBD. New genetic variants and diagnoses in VEO-IBD are reviewed and current challenges in therapy with potential strategy to manage the disease are discussed. SUMMARY Functional analysis of the genes implicated in monogenic IBD has increased the understanding of the underlying pathobiological mechanism of the disease. This knowledge can be used to personalize medicine for specific patients, improving the standard of care and quality of life.
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Affiliation(s)
- Vritika Batura
- SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Institute for Medical Science and Biochemistry, University of Toronto, Hospital for Sick Children,Toronto, Ontario, Canada
| | - Aleixo M Muise
- SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Institute for Medical Science and Biochemistry, University of Toronto, Hospital for Sick Children,Toronto, Ontario, Canada
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Kesharwani SS, Ahmad R, Bakkari MA, Rajput MK, Dachineni R, Valiveti CK, Kapur S, Jayarama Bhat G, Singh AB, Tummala H. Site-directed non-covalent polymer-drug complexes for inflammatory bowel disease (IBD): Formulation development, characterization and pharmacological evaluation. J Control Release 2018; 290:165-179. [DOI: 10.1016/j.jconrel.2018.08.004] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Revised: 07/20/2018] [Accepted: 08/02/2018] [Indexed: 12/29/2022]
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Bahrami A, Parsamanesh N, Atkin SL, Banach M, Sahebkar A. Effect of statins on toll-like receptors: a new insight to pleiotropic effects. Pharmacol Res 2018; 135:230-238. [PMID: 30120976 DOI: 10.1016/j.phrs.2018.08.014] [Citation(s) in RCA: 134] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/13/2018] [Indexed: 12/27/2022]
Abstract
The toll-like receptors (TLRs) are a class of transmembrane-spanning receptors that are sentinels of both innate and adaptive immunity. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the most commonly prescribed therapeutic agents for treating hypercholesterolemia globally. However, statin therapy appears to have pleiotropic effects including attenuation of chronic low-grade inflammation and modulation of TLR activity. Statins through abolition of TLR4 expression and regulation of the TLR4/Myd88/NF-κB signaling pathway may slow the progression of atherosclerosis and other inflammatory diseases. In this review, we have focused on the impact and mechanism of action of statins on cardiovascular and non-cardiovascular diseases.
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Affiliation(s)
- Afsane Bahrami
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Negin Parsamanesh
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | | | - Maciej Banach
- Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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