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1
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Riggers DS, Xenoulis PG, Karra DA, Enderle LL, Köller G, Böttcher D, Steiner JM, Heilmann RM. Fecal Calprotectin Concentrations in Cats with Chronic Enteropathies. Vet Sci 2023; 10:419. [PMID: 37505825 PMCID: PMC10385529 DOI: 10.3390/vetsci10070419] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/18/2023] [Accepted: 06/27/2023] [Indexed: 07/29/2023] Open
Abstract
Diagnosis of feline chronic inflammatory enteropathies (CIE) and the differentiation from small cell intestinal lymphoma (SCL) can be challenging. Intestinally expressed calprotectin (S100A8/A9 protein complex) appears to be part of the complex pathogenesis of feline chronic enteropathies (FCE). Fecal calprotectin is a non-invasive biomarker for intestinal inflammation in humans and dogs but has not yet been evaluated in cats. We hypothesized that fecal calprotectin (fCal) concentrations are increased in FCE, correlate with clinical and/or histologic disease severity, and distinguish cases of CIE from SCL. This case-control study included fecal samples and patient data from cats with CIE (n = 34), SCL (n = 17), other gastrointestinal (GI) diseases (n = 16), and cats with no clinical signs of GI disease (n = 32). fCal concentrations were measured using the immunoturbidimetric fCal turbo assay (Bühlmann Laboratories). Compared to healthy cats, fCal concentrations were significantly increased in CIE, SCL, and other diseases (all p < 0.0001), but were not different between these three groups (all p > 0.05), or between cats with extra-GI diseases and healthy controls. These findings suggest that fCal may have utility as a clinical biomarker for FCE but not for intestinal disease differentiation. It further supports the role of calprotectin in the pathogenesis of the spectrum of FCE, which includes CIE and SCL.
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Affiliation(s)
- Denise S Riggers
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Panagiotis G Xenoulis
- Clinic of Medicine, Faculty of Veterinary Science, University of Thessaly, Trikalon 224, 43100 Karditsa, Greece
| | - Dimitra A Karra
- Clinic of Medicine, Faculty of Veterinary Science, University of Thessaly, Trikalon 224, 43100 Karditsa, Greece
| | - Lena L Enderle
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Gabor Köller
- Department for Large Animals, College of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Denny Böttcher
- Institute of Veterinary Pathology, College of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Joerg M Steiner
- Gastrointestinal Laboratory, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4474, USA
| | - Romy M Heilmann
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany
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2
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Rokos T, Pribulova T, Kozubik E, Biringer K, Holubekova V, Kudela E. Exploring the Bioactive Mycocompounds (Fungal Compounds) of Selected Medicinal Mushrooms and Their Potentials against HPV Infection and Associated Cancer in Humans. Life (Basel) 2023; 13:244. [PMID: 36676192 PMCID: PMC9861011 DOI: 10.3390/life13010244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/11/2022] [Accepted: 12/30/2022] [Indexed: 01/19/2023] Open
Abstract
Medicinal mushrooms have been used as a medicinal tool for many centuries and, nowadays, are used in the prevention and therapy of various diseases, including as an adjunct to cancer treatment. It is estimated that 14-16% of global cancer cases are caused by infectious events; one well-known infectious agent that leads to cancer is the human papillomavirus (HPV). HPV is responsible for more than 99.7% of cervical cancer cases and also may play a role in vaginal, vulvar, penile, anal, rectal, and oropharyngeal carcinogenesis. Coriolus versicolor, a basidiomycetes class mushroom, consists of glycoproteins called polysaccharide-K (PSK) and polysaccharopeptide (PSP), which are mainly responsible for its effectiveness in the fight against a variety of cancers. Its beneficial effect lies in its ability to arrest different phases of the cell cycle, immunomodulation or induction of apoptosis. Coriolus versicolor extractcan reduces BCL-2 expression or increases the expression of p53 tumour suppressor genes in breast tumour cell lines. Inhibition of proliferation was also demonstrated with HeLa cells, while cervical cytology abnormalities improved in patients who locally applied Coriolus versicolor-based vaginal gel. Coriolus versicolor extract itself, and also its combination with another medicinal mushroom, Ganoderma lucidum, leads to improved HPV clearance in HPV cervical or oral-positive patients. Medicinal mushrooms can also increase the effectiveness of vaccination. This review considers the use of medicinal mushrooms as a suitable adjunct to the treatment of many cancers or precanceroses, including those caused by the HPV virus.
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Affiliation(s)
- Tomas Rokos
- Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4A, 036 01 Martin, Slovakia
| | - Terezia Pribulova
- Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4A, 036 01 Martin, Slovakia
| | - Erik Kozubik
- Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4A, 036 01 Martin, Slovakia
| | - Kamil Biringer
- Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4A, 036 01 Martin, Slovakia
| | - Veronika Holubekova
- Department of Molecular Oncology and Diagnostics, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4C, 036 01 Martin, Slovakia
| | - Erik Kudela
- Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4A, 036 01 Martin, Slovakia
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Aleman RS, Moncada M, Aryana KJ. Leaky Gut and the Ingredients That Help Treat It: A Review. Molecules 2023; 28:619. [PMID: 36677677 PMCID: PMC9862683 DOI: 10.3390/molecules28020619] [Citation(s) in RCA: 72] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/31/2022] [Accepted: 01/01/2023] [Indexed: 01/11/2023] Open
Abstract
The human body is in daily contact with potentially toxic and infectious substances in the gastrointestinal tract (GIT). The GIT has the most significant load of antigens. The GIT can protect the intestinal integrity by allowing the passage of beneficial agents and blocking the path of harmful substances. Under normal conditions, a healthy intestinal barrier prevents toxic elements from entering the blood stream. However, factors such as stress, an unhealthy diet, excessive alcohol, antibiotics, and drug consumption can compromise the composition of the intestinal microbiota and the homeostasis of the intestinal barrier function of the intestine, leading to increased intestinal permeability. Intestinal hyperpermeability can allow the entry of harmful agents through the junctions of the intestinal epithelium, which pass into the bloodstream and affect various organs and systems. Thus, leaky gut syndrome and intestinal barrier dysfunction are associated with intestinal diseases, such as inflammatory bowel disease and irritable bowel syndrome, as well as extra-intestinal diseases, including heart diseases, obesity, type 1 diabetes mellitus, and celiac disease. Given the relationship between intestinal permeability and numerous conditions, it is convenient to seek an excellent strategy to avoid or reduce the increase in intestinal permeability. The impact of dietary nutrients on barrier function can be crucial for designing new strategies for patients with the pathogenesis of leaky gut-related diseases associated with epithelial barrier dysfunctions. In this review article, the role of functional ingredients is suggested as mediators of leaky gut-related disorders.
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Affiliation(s)
- Ricardo Santos Aleman
- School of Nutrition and Food Sciences, Louisiana State University Agricultural Center, Baton Rouge, LA 28081, USA
| | - Marvin Moncada
- Department of Food, Bioprocessing & Nutrition Sciences and the Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus, Kannapolis, NC 27599, USA
| | - Kayanush J. Aryana
- School of Nutrition and Food Sciences, Louisiana State University Agricultural Center, Baton Rouge, LA 28081, USA
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Wang J, Gao H, Xie Y, Wang P, Li Y, Zhao J, Wang C, Ma X, Wang Y, Mao Q, Xia H. Lycium barbarum polysaccharide alleviates dextran sodium sulfate-induced inflammatory bowel disease by regulating M1/M2 macrophage polarization via the STAT1 and STAT6 pathways. Front Pharmacol 2023; 14:1044576. [PMID: 37144216 PMCID: PMC10151498 DOI: 10.3389/fphar.2023.1044576] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 04/05/2023] [Indexed: 05/06/2023] Open
Abstract
Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways.
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Affiliation(s)
- Juan Wang
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
- Department of Pathology, School of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Huiying Gao
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Yuan Xie
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Peng Wang
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Yu Li
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Junli Zhao
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Chunlin Wang
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Xin Ma
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Yuwen Wang
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
| | - Qinwen Mao
- Department of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States
| | - Haibin Xia
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China
- *Correspondence: Haibin Xia, ,
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Zhang Y, Feng X, Lin H, Chen X, He P, Wang Y, Chu Q. Tieguanyin extracts ameliorated DSS-induced mouse colitis by suppressing inflammation and regulating intestinal microbiota. Food Funct 2022; 13:13040-13051. [PMID: 36453715 DOI: 10.1039/d2fo02781j] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Previous studies have shown that a typical kind of oolong tea, Tieguanyin, has multiple health benefits, while there is no research investigating its effects on inflammatory bowel disease (IBD). In this study, we aimed to explore the alleviation effects of Tieguanyin water (TWE) and ethanol (TES) extracts on IBD. Physiological activity status, colitis severity (disease activity index (DAI), colon and spleen weight), inflammatory cytokines (interleukin (IL)-4, interferon-γ (IFN-γ), IL-17, transforming growth factor-β (TGF-β), and IL-10) and microbiota composition were measured in experimental colitis mice induced by dextran sulfate sodium (DSS). TWE and TES exerted remarkable protective effects against experimental colitis, showing decreased colitis severity and improved colon morphology. TES also suppressed colonic inflammation via downregulation of pro-inflammatory cytokines (IL-4, IFN-γ, IL-17, and TGF-β) and upregulation of the anti-inflammatory cytokine IL-10. In addition, TWE and TES treatment caused significant alterations in the gut microbiota. Oolong tea extract treatment reduced the community abundance of pernicious bacteria Escherichia-Shigella from 21.6% (DSS) to 0.9% (TES) and 1.2% (TWE), and elevated that of probiotics Lachnospiraceae_NK4A136_group from 2.2% to 15.2% (TES) and 11.9% (TWE). Therefore, TWE and TES both remarkably ameliorated DSS-induced colitis, which suggested oolong extracts could be a candidate for IBD treatment.
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Affiliation(s)
- Yuxi Zhang
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China. .,Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
| | - Xinyu Feng
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China. .,Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China.,Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China
| | - Haiyu Lin
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China. .,Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
| | - Xue Chen
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China. .,Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
| | - Puming He
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China. .,Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
| | - Yuefei Wang
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China. .,Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
| | - Qiang Chu
- Institute of Tea Science, Zhejiang University, Hangzhou 310058, China. .,Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, China
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6
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Wang S, Zhang YR, Yu YB. The important role of fungi in inflammatory bowel diseases. Scand J Gastroenterol 2021; 56:1312-1322. [PMID: 34392745 DOI: 10.1080/00365521.2021.1963838] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 06/23/2021] [Accepted: 07/28/2021] [Indexed: 02/04/2023]
Abstract
Inflammatory bowel disease (IBD) is a life-threatening and chronic inflammatory disease of gastrointestinal tissue, with complex pathogenesis. Current research on IBD has mainly focused on bacteria; however, the role of fungi in IBD is largely unknown due to the incomplete annotation of fungi in current genomic databases. With the development of molecular techniques, the gut mycobiome has been found to have great diversity. In addition, increasing evidence has shown intestinal mycobiome plays an important role in the physiological and pathological processes of IBD. In this review, we will systemically introduce the recent knowledge about multi-dimensional fungal dysbiosis associated with IBD, the interactions between fungus and bacteria, the role of fungi in inflammation in IBD, and highlight recent advances in the potential therapeutic role of fungus in IBD, which may hold the keys to develop new predictive, therapeutic or prognostic approaches in IBD.
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Affiliation(s)
- Sui Wang
- Laboratory of Translational Gastroenterology, Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yu-Rong Zhang
- Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- Key Laboratory of Assisted Reproduction, Ministry of Education (Peking University), Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Yan-Bo Yu
- Department of Gastroenterology, Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
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7
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Chen G, Li Y, Li X, Zhou D, Wang Y, Wen X, Wang C, Liu X, Feng Y, Li B, Li N. Functional foods and intestinal homeostasis: The perspective of in vivo evidence. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.02.075] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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8
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Habtemariam S. Trametes versicolor (Synn. Coriolus versicolor) Polysaccharides in Cancer Therapy: Targets and Efficacy. Biomedicines 2020; 8:biomedicines8050135. [PMID: 32466253 PMCID: PMC7277906 DOI: 10.3390/biomedicines8050135] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/20/2020] [Accepted: 05/21/2020] [Indexed: 12/12/2022] Open
Abstract
Coriolus versicolor (L.) Quél. is a higher fungi or mushroom which is now known by its accepted scientific name as Trametes versicolor (L.) Lloyd (family Polyporaceae). The polysaccharides, primarily two commercial products from China and Japan as PSP and PSK, respectively, have been claimed to serve as adjuvant therapy for cancer. In this paper, research advances in this field, including direct cytotoxicity in cancer cells and immunostimulatory effects, are scrutinised at three levels: in vitro, in vivo and clinical outcomes. The level of activity in the various cancers, key targets (both in cancer and immune cells) and pharmacological efficacies are discussed.
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Affiliation(s)
- Solomon Habtemariam
- Pharmacognosy Research Laboratories & Herbal Analysis Services UK, University of Greenwich, Chatham-Maritime, Kent ME4 4TB, UK
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9
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Mijan MA, Lim BO. Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends. World J Gastroenterol 2018; 24:2673-2685. [PMID: 29991873 PMCID: PMC6034142 DOI: 10.3748/wjg.v24.i25.2673] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 05/19/2018] [Accepted: 06/09/2018] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a serious health concern among western societies. The disease is also on the rise in some East Asian countries and in Australia. Health professionals and dietitians around the world are facing an unprecedented challenge to prevent and control the increasing prevalence of IBD. The current therapeutic strategy that includes drugs and biological treatments is inefficient and are associated with adverse health consequences. In this context, the use of natural products is gaining worldwide attention. In vivo studies and clinical evidence suggest that well-planned dietary regimens with specific nutrients can alleviate gastrointestinal inflammation by modulating inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), IL-6, IL-1β, and IL-10. Alternatively, the avoidance of high-fat and high-carbohydrate diets is regarded as an effective tool to eliminate the causes of IBD. Many functional foods and bioactive components have received attention for showing strong therapeutic effects against IBD. Both animal and human studies suggest that bioactive functional foods can ameliorate IBD by downregulating the pro-inflammatory signaling pathways, such as nuclear factor κB, STAT1, STAT6, and pro-inflammatory cytokines, including IL-1β, IL-4, IL-6, COX-2, TNF-α, and interferon γ. Therefore, functional foods and diets have the potential to alleviate IBD by modulating the underlying pathogenic mechanisms. Future comprehensive studies are needed to corroborate the potential roles of functional foods and diets in the prevention and control of IBD.
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Affiliation(s)
- Mohammad Al Mijan
- Department of Integrated Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, South Korea
| | - Beong Ou Lim
- Department of Integrated Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, South Korea
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10
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Qiu X, Ma J, Jiao C, Mao X, Zhao X, Lu M, Wang K, Zhang H. Alterations in the mucosa-associated fungal microbiota in patients with ulcerative colitis. Oncotarget 2017; 8:107577-107588. [PMID: 29296188 PMCID: PMC5746090 DOI: 10.18632/oncotarget.22534] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 10/28/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Fungi colonize the human gut and might play a key role in the pathogenesis of ulcerative colitis (UC). However, studies on the fungal composition in the gut (especially adhering to the intestinal mucosa) of UC patients is limited. RESULTS The number of fungi decreased significantly in inflamed mucosa compared with that in HS mucosa. Fifteen major genera were examined, among which Wickerhamomyces, unidentified genus of Saccharomycetales, Aspergillus, Sterigmatomyces, and Candida showed increasing trends, whereas Exophiala, Alternaria, Emericella, Epicoccum, Acremonium, Trametes, and Penicillium showed decreasing trends in UC patients compared to the HS. The pro-inflammatory cytokines (IL-Iβ, TNF-α, INF-γ, IL-6, IL-17A, and IL-23) were up-regulated in the UC group. The genera Wickerhamomyces, Nigrospora, and Penicillium were positively correlated, while Sporobolomyces and Trametes were negatively correlated with the expression of several colonic pro-inflammatory cytokines and the Baron and/or Mayo score. CONCLUSIONS Our study confirms the alteration of the colonic fungal microbiota in the UC patients, which might be associated with mucosal inflammation and pathogenesis of UC. Further studies need to identify the roles of different intestinal fungi in detail, and to determine the mechanism of the host-fungal interaction underlying the development of UC. METHODS Mucosal samples of inflamed descending colon from 14 active UC patients and 15 healthy subjects (HS) were analyzed by high-throughput sequencing to compare the fungal microbiota. The expressions of pro-inflammatory cytokines (IL-Iβ, TNF-α, INF-γ, IL-6, IL-17A, and IL-23) in intestinal mucosal tissues were examined. The Baron and Mayo scores of UC patients were evaluated, and the correlation between intestinal fungal composition and intestinal inflammatory status was analyzed.
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Affiliation(s)
- Xinyun Qiu
- Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Jingjing Ma
- Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Chunhua Jiao
- Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Xiaqiong Mao
- Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Xiaojing Zhao
- Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Meijiao Lu
- Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Kai Wang
- Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
| | - Hongjie Zhang
- Department of Gastroenterology, First Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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11
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Awadasseid A, Hou J, Gamallat Y, Xueqi S, Eugene KD, Musa Hago A, Bamba D, Meyiah A, Gift C, Xin Y. Purification, characterization, and antitumor activity of a novel glucan from the fruiting bodies of Coriolus Versicolor. PLoS One 2017; 12:e0171270. [PMID: 28178285 PMCID: PMC5298263 DOI: 10.1371/journal.pone.0171270] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Accepted: 01/17/2017] [Indexed: 02/01/2023] Open
Abstract
Cancer is one of the most common causes of deaths worldwide. Herein, we report an efficient natural anticancer glucan (CVG) extracted from Coriolus Versicolar (CV). CVG was extracted by the hot water extraction method followed by ethanol precipitation and purified using gas exclusion chromatography. Structural analysis revealed that CVG has a linear α-glucan chain composed of only (1→ 6)-α-D-Glcp. The antitumor activity of CVG on Sarcoma-180 cells was investigated in vitro and in vivo. Mice were treated with three doses of CVG (40, 100, 200 mg/kg body weight) for 9 days. Tumor weight, relative spleen, thymus weight, and lymphocyte proliferation were studied. A significant increase (P< 0.01) in relative spleen and thymus weight and a decrease (P< 0.01) in tumor weight at the doses of 100 and 200 mg/kg were observed. The results obtained demonstrate CVG has antitumor activity towards Sarcoma-180 cells by its immunomodulation activity.
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Affiliation(s)
- Annoor Awadasseid
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
- Department of Biochemistry and Molecular Biology, Northeast Normal University, Changchun, P.R. China
- Department of Biochemistry & Food Sciences, University of Kordofan, El-Obeid, The Republic of Sudan
| | - Jie Hou
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
| | - Yaser Gamallat
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
| | - Shang Xueqi
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
| | - Kuugbee D. Eugene
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
| | - Ahmed Musa Hago
- Department of pathology and pathophysiology, Dalian Medical University, Dalian, P.R. China
| | - Djibril Bamba
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
| | - Abdo Meyiah
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
| | - Chiwala Gift
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
| | - Yi Xin
- Department of Biotechnology, Dalian Medical University, Dalian, P.R. China
- * E-mail:
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12
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13
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Joo YE. Natural product-derived drugs for the treatment of inflammatory bowel diseases. Intest Res 2014; 12:103-9. [PMID: 25349576 PMCID: PMC4204705 DOI: 10.5217/ir.2014.12.2.103] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 01/28/2014] [Accepted: 01/29/2014] [Indexed: 12/21/2022] Open
Abstract
Natural products have been used as drugs for millennia, and the therapeutic potential of natural products has been studied for more than a century. Since the mid-1880s, approximately 60% of drugs have originated from natural products. Recently, the importance of using natural products has increased, as has interest in discovering efficient new drugs. Natural drugs are desirable for the treatment of inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. This review discusses the discovery and development of drugs derived from natural products for the treatment of inflammatory bowel diseases.
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Affiliation(s)
- Young-Eun Joo
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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14
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Singh UP, Singh NP, Guan H, Busbee B, Price RL, Taub DD, Mishra MK, Fayad R, Nagarkatti M, Nagarkatti PS. Leptin antagonist ameliorates chronic colitis in IL-10⁻/⁻ mice. Immunobiology 2013; 218:1439-51. [PMID: 23726523 PMCID: PMC3778116 DOI: 10.1016/j.imbio.2013.04.020] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Revised: 04/27/2013] [Accepted: 04/27/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although the etiology of two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are unknown and evidence suggests that chronic intestinal inflammation is caused by an excessive immune response to mucosal antigens. Previous studies support the role for TGF-β1 through 3 in the initiation and maintenance of tolerance via the induction of regulatory T cells (Tregs) to control intestinal inflammation. Leptin, a satiety hormone produced primarily by adipose tissue, has been shown to increase during colitis progression and is believed to contribute to disease genesis and/or progression. AIM We investigated the ability of a pegylated leptin antagonist (PG-MLA) to ameliorate the development of chronic experimental colitis. RESULTS Compared to vehicle control animals, PG-MLA treatment of mice resulted in an (1) attenuated clinical score; (2) reversed colitis-associated pathogenesis including a decrease in body weight; (3) reduced systemic and mucosal inflammatory cytokine expression; (4) increased insulin levels and (5) enhanced systemic and mucosal Tregs and CD39⁺ Tregs in mice with chronic colitis. The percentage of systemic and mucosal TGF-β1, -β2 and -β3 expressing CD4⁺ T cells were augmented after PG-MLA treatment. The activation of STAT1 and STAT3 and the expression of Smad7 were also reduced after PG-MLA treatment in the colitic mice. These findings clearly suggest that PG-MLA treatment reduces intestinal Smad7 expression, restores TGF-β1-3 signaling and reduces STAT1/STAT3 activation that may increase the number of Tregs to ameliorate chronic colitis. CONCLUSION This study clearly links inflammation with the metabolic hormone leptin suggesting that nutritional status influences immune tolerance through the induction of functional Tregs. Inhibiting leptin activity through PG-MLA might provide a new and novel therapeutic strategy for the treatment of IBD.
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Affiliation(s)
- Udai P Singh
- Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
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15
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Kuan YC, Wu YJ, Hung CL, Sheu F. Trametes versicolor protein YZP activates regulatory B lymphocytes - gene identification through de novo assembly and function analysis in a murine acute colitis model. PLoS One 2013; 8:e72422. [PMID: 24019869 PMCID: PMC3760908 DOI: 10.1371/journal.pone.0072422] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2013] [Accepted: 07/10/2013] [Indexed: 12/31/2022] Open
Abstract
Background Trametes versicolor (Yun-Zhi) is a medicinal fungus used as a chemotherapy co-treatment to enhance anti-tumor immunity. Although the efficacies of T. versicolor extracts have been documented, the active ingredients and mechanisms underlying the actions of these extracts remain uncharacterized. Results We purified a new protein, YZP, from the fruiting bodies of T. versicolor and identified the gene encoding YZP using RNA-seq and de novo assembly technologies. YZP is a 12-kDa non-glycosylated protein comprising 139 amino acids, including an 18-amino acids signal peptide. YZP induced a greater than 60-fold increase in IL-10 secretion in mice B lymphocytes; moreover, YZP specifically triggered the differentiation of CD1d+ B cells into IL-10-producing regulatory B cells (Bregs) and enhanced the expression of CD1d. YZP-induced B cells suppressed approximately 40% of the LPS-activated macrophage production of inflammatory cytokines in a mixed leukocyte reaction and significantly alleviated the disease activity and colonic inflammation in a DSS-induced acute colitis murine model. Furthermore, YZP activated Breg function via interaction with TLR2 and TLR4 and up-regulation of the TLR-mediated signaling pathway. Conclusions We purified a novel Breg-stimulating protein, YZP, from T. versicolor and developed an advanced approach combining RNA-seq and de novo assembly technologies.to clone its gene. We demonstrated that YZP activated CD1d+ Breg differentiation through TLR2/4-mediated signaling pathway, and the YZP-stimulated B cells exhibited anti-inflammatory efficacies in vitro and in murine acute colitis models.
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Affiliation(s)
- Yen-Chou Kuan
- Center for Biotechnology, National Taiwan University, Taipei, Taiwan
- Department of Horticulture, National Taiwan University, Taipei, Taiwan
| | - Ying-Jou Wu
- Department of Horticulture, National Taiwan University, Taipei, Taiwan
| | - Chih-Liang Hung
- Department of Horticulture, National Taiwan University, Taipei, Taiwan
| | - Fuu Sheu
- Center for Biotechnology, National Taiwan University, Taipei, Taiwan
- Department of Horticulture, National Taiwan University, Taipei, Taiwan
- * E-mail:
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16
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Natural products as a source of anti-inflammatory agents associated with inflammatory bowel disease. Molecules 2013; 18:7253-70. [PMID: 23783459 PMCID: PMC6270544 DOI: 10.3390/molecules18067253] [Citation(s) in RCA: 106] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Revised: 06/05/2013] [Accepted: 06/14/2013] [Indexed: 02/07/2023] Open
Abstract
Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors.
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17
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Li Y, Deuring J, Peppelenbosch MP, Kuipers EJ, de Haar C, van der Woude CJ. STAT1, STAT6 and adenosine 3',5'-cyclic monophosphate (cAMP) signaling drive SOCS3 expression in inactive ulcerative colitis. Mol Med 2012; 18:1412-9. [PMID: 23154639 DOI: 10.2119/molmed.2012.00277] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Accepted: 11/01/2012] [Indexed: 01/04/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic disease associated with long periods of quiescent disease followed by fulminant exacerbation. Imminent relapse in UC is associated with high mucosal expression of suppressor of cytokine signaling 3 (SOCS3); hence, knowledge of the mechanisms driving mucosal SOCS3 expression may provide important clues as to rational therapy. Thus, here we aim to characterize the molecular forces driving SOCS3 expression in the mucosal compartment, focusing on druggable pathways. The colon epithelial cell line Caco-2 was stimulated with interferon (IFN)-γ, interleukin (IL)-4 or prostaglandin E(2) (PGE(2)) to allow correlations between SOCS3 expression with signal transducer and activator of transcription 1 (STAT1), STAT6 and adenosine 3',5'-cyclic monophosphate (cAMP) signaling, respectively. The physiological relevance of the findings obtained was assessed by immunohistochemical staining for the activated forms of STAT1, STAT6, protein kinase A (PKA)-Cγ and cAMP response element-binding protein (CREB) in biopsies from inactive UC patients and controls. Stimulation with IFN-γ, IL-4 or PGE(2) induced activation of STAT1, STAT6 and cAMP, respectively, in colonic cells, without any signs of concomitant STAT3 activation. Forced activation of all these signaling pathways was sufficient for SOCS3 expression. Biopsies from patients with inactive UC showed significant increase of phosphorylated STAT1 (p-STAT1) (p < 0.0001), p-STAT6 (p = 0.0001), p-PKA-Cγ (p = 0.0003) and p-CREB (p = 0.0025) expression compared with controls. STAT3-independent SOCS3 induction in inactive UC involves multiple proinflammatory signaling pathways and contradicts the usefulness of pathway-specific antiinflammatory drugs for preventing relapse. Our findings suggest that broad-spectrum antiinflammatory drugs are essential to counteract increases in SOCS3 expression and exacerbation of disease. Our results highlight the multifactorial nature of the factors that cause exacerbation in UC.
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Affiliation(s)
- Yi Li
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands.
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18
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Icardi L, De Bosscher K, Tavernier J. The HAT/HDAC interplay: multilevel control of STAT signaling. Cytokine Growth Factor Rev 2012; 23:283-91. [PMID: 22989617 DOI: 10.1016/j.cytogfr.2012.08.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2012] [Accepted: 08/20/2012] [Indexed: 12/13/2022]
Abstract
Besides the transcription-promoting role of histone acetyltransferases (HATs) and the transcription-delimiting function of histone deacetylases (HDACs) through histone acetylation and deacetylation respectively, HATs and HDACs also regulate the activity of several non-histone proteins. This includes signal transducers and activators of transcription (STATs), key proteins in cytokine signaling. Unlike Tyr phosphorylation/dephosphorylation, which mainly acts as an on/off switch of STAT activity, the control exerted by HATs and HDACs appears multifaceted and far more complex than initially imagined. Our review focuses on the latest trends and novel hypotheses to explain differential context-dependent STAT regulation by complex posttranslational modification patterns. We chart the knowledge on how STATs interact with HATs and HDACs, and additionally bring a transcriptional regulatory and gene-set specific role for HDACs in the picture. Indeed, a growing amount of evidence demonstrates, paradoxically, that not only HAT but also HDAC activity can be required for STAT-dependent transcription, in a STAT subtype- and cell type-dependent manner. Referring to recent reports, we review and discuss the various molecular mechanisms that have recently been proposed to account for this peculiar regulation, in an attempt to shed more light on the difficult yet important question on how STAT specificity is being generated.
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Affiliation(s)
- Laura Icardi
- Department of Medical Protein Research, VIB, Ghent, Belgium
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