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1
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Dey S, Ghosh M, Dev A. Signalling and molecular pathways, overexpressed receptors of colorectal cancer and effective therapeutic targeting using biogenic silver nanoparticles. Gene 2025; 936:149099. [PMID: 39557372 DOI: 10.1016/j.gene.2024.149099] [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: 08/15/2024] [Revised: 10/18/2024] [Accepted: 11/13/2024] [Indexed: 11/20/2024]
Abstract
Increasing morbidity and mortality in CRC is a potential threat to human health. The major challenges for better treatment outcomes are the heterogeneity of CRC cases, complicated molecular pathway cross-talks, the influence of gut dysbiosis in CRC, and the lack of multimodal target-specific drug delivery. The overexpression of many receptors in CRC cells may pave the path for targeting them with multiple ligands. The design of a more target-specific drug-delivery device with multiple ligand-functionalized, green-synthesized silver nanoparticles is highly promising and may also deliver other approved chemotherapeutic agents. This review presents the various aspects of colorectal cancer and over-expressed receptors that can be targeted with appropriate ligands to enhance the specific drug delivery potency of green synthesised silver nanoparticles. This review aims to broaden further research into this multi-ligand functionalised, safer and effective silver nano drug delivery system.
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Affiliation(s)
- Sandip Dey
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Jharkhand, India
| | - Manik Ghosh
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Jharkhand, India
| | - Abhimanyu Dev
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Jharkhand, India.
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2
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Dalis C, Mesfin FM, Manohar K, Liu J, Shelley WC, Brokaw JP, Markel TA. Volatile Organic Compound Assessment as a Screening Tool for Early Detection of Gastrointestinal Diseases. Microorganisms 2023; 11:1822. [PMID: 37512994 PMCID: PMC10385474 DOI: 10.3390/microorganisms11071822] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/13/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Gastrointestinal (GI) diseases have a high prevalence throughout the United States. Screening and diagnostic modalities are often expensive and invasive, and therefore, people do not utilize them effectively. Lack of proper screening and diagnostic assessment may lead to delays in diagnosis, more advanced disease at the time of diagnosis, and higher morbidity and mortality rates. Research on the intestinal microbiome has demonstrated that dysbiosis, or unfavorable alteration of organismal composition, precedes the onset of clinical symptoms for various GI diseases. GI disease diagnostic research has led to a shift towards non-invasive methods for GI screening, including chemical-detection tests that measure changes in volatile organic compounds (VOCs), which are the byproducts of bacterial metabolism that result in the distinct smell of stool. Many of these tools are expensive, immobile benchtop instruments that require highly trained individuals to interpret the results. These attributes make them difficult to implement in clinical settings. Alternatively, electronic noses (E-noses) are relatively cheaper, handheld devices that utilize multi-sensor arrays and pattern recognition technology to analyze VOCs. The purpose of this review is to (1) highlight how dysbiosis impacts intestinal diseases and how VOC metabolites can be utilized to detect alterations in the microbiome, (2) summarize the available VOC analytical platforms that can be used to detect aberrancies in intestinal health, (3) define the current technological advancements and limitations of E-nose technology, and finally, (4) review the literature surrounding several intestinal diseases in which headspace VOCs can be used to detect or predict disease.
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Affiliation(s)
- Costa Dalis
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Fikir M Mesfin
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Krishna Manohar
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Jianyun Liu
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - W Christopher Shelley
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - John P Brokaw
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Troy A Markel
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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3
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Yang L, Li A, Wang Y, Zhang Y. Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy. Signal Transduct Target Ther 2023; 8:35. [PMID: 36646684 PMCID: PMC9842669 DOI: 10.1038/s41392-022-01304-4] [Citation(s) in RCA: 174] [Impact Index Per Article: 87.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 10/31/2022] [Accepted: 12/26/2022] [Indexed: 01/18/2023] Open
Abstract
Microorganisms, including bacteria, viruses, fungi, and other eukaryotes, play critical roles in human health. An altered microbiome can be associated with complex diseases. Intratumoral microbial components are found in multiple tumor tissues and are closely correlated with cancer initiation and development and therapy efficacy. The intratumoral microbiota may contribute to promotion of the initiation and progression of cancers by DNA mutations, activating carcinogenic pathways, promoting chronic inflammation, complement system, and initiating metastasis. Moreover, the intratumoral microbiota may not only enhance antitumor immunity via mechanisms including STING signaling activation, T and NK cell activation, TLS production, and intratumoral microbiota-derived antigen presenting, but also decrease antitumor immune responses and promote cancer progression through pathways including upregulation of ROS, promoting an anti-inflammatory environment, T cell inactivation, and immunosuppression. The effect of intratumoral microbiota on antitumor immunity is dependent on microbiota composition, crosstalk between microbiota and the cancer, and status of cancers. The intratumoral microbiota may regulate cancer cell physiology and the immune response by different signaling pathways, including ROS, β-catenin, TLR, ERK, NF-κB, and STING, among others. These viewpoints may help identify the microbiota as diagnosis or prognosis evaluation of cancers, and as new therapeutic strategy and potential therapeutic targets for cancer therapy.
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Affiliation(s)
- Li Yang
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, P.R. China.
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, 450052, China.
| | - Aitian Li
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Ying Wang
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Yi Zhang
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, P.R. China.
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, 450052, China.
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4
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Yinhang W, Wei W, Jing Z, Qing Z, Yani Z, Yangyanqiu W, Shuwen H. Biological roles of toll-like receptors and gut microbiota in colorectal cancer. Future Microbiol 2022; 17:1071-1089. [PMID: 35916158 DOI: 10.2217/fmb-2021-0072] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most considerably common malignancies of the alimentary system, with high mortality and incidence rates. The present study suggested that the occurrence of CRC is closely related to bacteria, as the large intestine is a gathering place for human micro-organisms. However, the nosogenesis of bacteria leading to tumorigenesis is still obscure. Recently, many studies have reported that toll-like receptors and their related molecular pathways are involved in the process of gut micro-organisms generating CRC. Gut micro-organisms can promote or inhibit the development of CRC via binding to special toll-like receptors. In this paper, the authors review the relationship among toll-like receptors, gut micro-organisms and CRC in order to provide a reference for future tumor immunotherapy and targeted therapy.
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Affiliation(s)
- Wu Yinhang
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,The Second School of Clinical Medicine, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, 310053, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Wu Wei
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhuang Jing
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhou Qing
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhou Yani
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Graduate School of Medicine Faculty, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang Province, 310058, China
| | - Wang Yangyanqiu
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Graduate School of Medicine Faculty, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang Province, 310058, China
| | - Han Shuwen
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
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5
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Saccon TD, Dhahbi JM, Schneider A, Nunez Lopez YO, Qasem A, Cavalcante MB, Sing LK, Naser SA, Masternak MM. Plasma miRNA Profile of Crohn's Disease and Rheumatoid Arthritis Patients. BIOLOGY 2022; 11:508. [PMID: 35453708 PMCID: PMC9033111 DOI: 10.3390/biology11040508] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/21/2022] [Accepted: 03/22/2022] [Indexed: 06/14/2023]
Abstract
Crohn's disease (CD) and rheumatoid arthritis (RA) are immune mediated inflammatory diseases. Several studies indicate a role for microRNAs (miRNAs) in the pathogenesis of a variety of autoimmune diseases, including CD and RA. Our study's goal was to investigate circulating miRNAs in CD and RA patients to identify potential new biomarkers for early detection and personalized therapeutic approaches for autoimmune diseases. For this study, subjects with CD (n = 7), RA (n = 8) and healthy controls (n = 7) were recruited, and plasma was collected for miRNA sequencing. Comparison of the expression patterns of miRNAs between CD and healthy patients identified 99 differentially expressed miRNAs. Out of these miRNAs, 4 were down regulated, while 95 were up regulated. Comparison of miRNAs between RA and healthy patients identified 57 differentially expressed miRNAs. Out of those, 12 were down regulated, while 45 were up regulated. For all the miRNAs down regulated in CD and RA patients, 420 GO terms for biological processes were similarly regulated between both groups. Therefore, the identification of new plasma miRNAs allows the emergence of new biomarkers that can assist in the diagnosis and treatment of CD and RA.
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Affiliation(s)
- Tatiana D. Saccon
- Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas 96010-610, Brazil;
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
| | - Joseph M. Dhahbi
- Department of Medical Education, School of Medicine, California University of Science & Medicine, San Bernardino, CA 92324, USA; (J.M.D.); (L.K.S.)
| | - Augusto Schneider
- Faculdade de Nutrição, Universidade Federal de Pelotas, Pelotas 96010-610, Brazil;
| | | | - Ahmad Qasem
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
| | - Marcelo B. Cavalcante
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
- Department of Obstetrics and Gynecology, Fortaleza University, Fortaleza 60811-905, Brazil
| | - Lauren K. Sing
- Department of Medical Education, School of Medicine, California University of Science & Medicine, San Bernardino, CA 92324, USA; (J.M.D.); (L.K.S.)
| | - Saleh A. Naser
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
| | - Michal M. Masternak
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
- Department of Head and Neck Surgery, Poznan University of Medical Sciences, 61-701 Poznan, Poland
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6
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Bruland T, Østvik AE, Sandvik AK, Hansen MD. Host-Viral Interactions in the Pathogenesis of Ulcerative Colitis. Int J Mol Sci 2021; 22:ijms221910851. [PMID: 34639191 PMCID: PMC8509287 DOI: 10.3390/ijms221910851] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/04/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
Ulcerative colitis is characterized by relapsing and remitting colonic mucosal inflammation. During the early stages of viral infection, innate immune defenses are activated, leading to the rapid release of cytokines and the subsequent initiation of downstream responses including inflammation. Previously, intestinal viruses were thought to be either detrimental or neutral to the host. However, persisting viruses may have a role as resident commensals and confer protective immunity during inflammation. On the other hand, the dysregulation of gut mucosal immune responses to viruses can trigger excessive, pathogenic inflammation. The purpose of this review is to discuss virus-induced innate immune responses that are at play in ulcerative colitis.
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Affiliation(s)
- Torunn Bruland
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway; (T.B.); (A.E.Ø.); (A.K.S.)
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, 7030 Trondheim, Norway
| | - Ann Elisabet Østvik
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway; (T.B.); (A.E.Ø.); (A.K.S.)
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, 7030 Trondheim, Norway
| | - Arne Kristian Sandvik
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway; (T.B.); (A.E.Ø.); (A.K.S.)
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, 7030 Trondheim, Norway
- Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, 7491 Trondheim, Norway
| | - Marianne Doré Hansen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway; (T.B.); (A.E.Ø.); (A.K.S.)
- Department of Medical Microbiology, Clinic of Laboratory Medicine, St. Olav’s University Hospital, 7030 Trondheim, Norway
- Correspondence:
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7
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Toll-Like Receptors (TLRs): Structure, Functions, Signaling, and Role of Their Polymorphisms in Colorectal Cancer Susceptibility. BIOMED RESEARCH INTERNATIONAL 2021; 2021:1157023. [PMID: 34552981 PMCID: PMC8452412 DOI: 10.1155/2021/1157023] [Citation(s) in RCA: 174] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/04/2021] [Accepted: 08/19/2021] [Indexed: 12/14/2022]
Abstract
Toll-like receptors (TLRs) are the important mediators of inflammatory pathways in the gut which play a major role in mediating the immune responses towards a wide variety of pathogen-derived ligands and link adaptive immunity with the innate immunity. Numerous studies in different populations across the continents have reported on the significant roles of TLR gene polymorphisms in modulating the risk of colorectal cancer (CRC). CRC is one of the major malignancies affecting the worldwide population and is currently ranking the third most common cancer in the world. In this review, we have attempted to discuss the structure, functions, and signaling of TLRs in comprehensive detail together with the role played by various TLR gene SNPs in CRC susceptibility.
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8
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Wei L, Wen XS, Xian CJ. Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways. Int J Mol Sci 2021; 22:ijms22179474. [PMID: 34502383 PMCID: PMC8431669 DOI: 10.3390/ijms22179474] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/26/2021] [Accepted: 08/28/2021] [Indexed: 02/06/2023] Open
Abstract
Chemotherapy-induced intestinal mucositis, a painful debilitating condition affecting up to 40–100% of patients undergoing chemotherapy, can reduce the patients’ quality of life, add health care costs and even postpone cancer treatment. In recent years, the relationships between intestinal microbiota dysbiosis and mucositis have drawn much attention in mucositis research. Chemotherapy can shape intestinal microbiota, which, in turn, can aggravate the mucositis through toll-like receptor (TLR) signaling pathways, leading to an increased expression of inflammatory mediators and elevated epithelial cell apoptosis but decreased epithelial cell differentiation and mucosal regeneration. This review summarizes relevant studies related to the relationships of mucositis with chemotherapy regimens, microbiota, TLRs, inflammatory mediators, and intestinal homeostasis, aiming to explore how gut microbiota affects the pathogenesis of mucositis and provides potential new strategies for mucositis alleviation and treatment and development of new therapies.
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Affiliation(s)
- Ling Wei
- School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China;
| | - Xue-Sen Wen
- School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China;
- Correspondence: (X.-S.W.); (C.J.X.); Tel.: +86-531-88382028 (X.-S.W.); +61-88302-1944 (C.J.X.)
| | - Cory J. Xian
- UniSA Clinical & Health Science, City West Campus, University of South Australia, Adelaide, SA 5001, Australia
- Correspondence: (X.-S.W.); (C.J.X.); Tel.: +86-531-88382028 (X.-S.W.); +61-88302-1944 (C.J.X.)
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9
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The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms 2020; 8:microorganisms8111715. [PMID: 33139627 PMCID: PMC7692443 DOI: 10.3390/microorganisms8111715] [Citation(s) in RCA: 1018] [Impact Index Per Article: 203.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/13/2020] [Accepted: 10/31/2020] [Indexed: 02/07/2023] Open
Abstract
The two most important bacterial phyla in the gastrointestinal tract, Firmicutes and Bacteroidetes, have gained much attention in recent years. The Firmicutes/Bacteroidetes (F/B) ratio is widely accepted to have an important influence in maintaining normal intestinal homeostasis. Increased or decreased F/B ratio is regarded as dysbiosis, whereby the former is usually observed with obesity, and the latter with inflammatory bowel disease (IBD). Probiotics as live microorganisms can confer health benefits to the host when administered in adequate amounts. There is considerable evidence of their nutritional and immunosuppressive properties including reports that elucidate the association of probiotics with the F/B ratio, obesity, and IBD. Orally administered probiotics can contribute to the restoration of dysbiotic microbiota and to the prevention of obesity or IBD. However, as the effects of different probiotics on the F/B ratio differ, selecting the appropriate species or mixture is crucial. The most commonly tested probiotics for modifying the F/B ratio and treating obesity and IBD are from the genus Lactobacillus. In this paper, we review the effects of probiotics on the F/B ratio that lead to weight loss or immunosuppression.
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10
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Ravnik Z, Muthiah I, Dhanaraj P. Computational studies on bacterial secondary metabolites against breast cancer. J Biomol Struct Dyn 2020; 39:7056-7064. [PMID: 32779523 DOI: 10.1080/07391102.2020.1805361] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Microbes exist in the human body provide more benefits by modulating metabolic processes, immunity, and signal transduction. However, microbial dysbiosis with harmful bacterial species can cause chronic inflammation and cancers. Hence human probiotics were recently paid more attention to immune responses, therapy, and diagnosis. Breast cancer is the second leading cancer worldwide and causes more death in women. The role of breast microbiome secondary metabolites in breast cancer is poorly studied. Research shows that breast has a specific microbiome inhabited with particular bacterial species. More significantly probiotics produced from breast microbiomes may act as a potential biomarker for breast cancer diagnosis. Hence this computational research aimed at the effect of chosen metabolites on breast cancer cell receptor G-protein-coupled bile acid receptor, Gpbar1 (TGR5). The current research suggested that cadaverine, succinate, p-cresol, and its derivatives could be used as a molecular marker in the diagnosis of breast cancer.
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Affiliation(s)
- Zina Ravnik
- Department of Biotechnology, Karunya Institute of Technology and Sciences (Deemed to be University), Coimbatore, Tamil Nadu, India
| | - Indiraleka Muthiah
- Department of Biotechnology, Mepco Schlenk Engineering College, Sivakasi, Tamil Nadu, India
| | - Premnath Dhanaraj
- Department of Biotechnology, Karunya Institute of Technology and Sciences (Deemed to be University), Coimbatore, Tamil Nadu, India
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11
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Eslami-S Z, Majidzadeh-A K, Halvaei S, Babapirali F, Esmaeili R. Microbiome and Breast Cancer: New Role for an Ancient Population. Front Oncol 2020; 10:120. [PMID: 32117767 PMCID: PMC7028701 DOI: 10.3389/fonc.2020.00120] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 01/22/2020] [Indexed: 12/11/2022] Open
Abstract
There are many risk factors associated with breast cancer (BC) such as the familial history of BC, using hormone replacement therapy, obesity, personal habits, and other clinical factors; however, not all BC cases are attributed to these risk factors. Recent researches show a correlation between patient microbiome and BC suggested as a new risk factor. The present review article aimed at evaluating the role of the microbiome as a risk factor in the occurrence of BC, investigating the proposed mechanisms of interaction between the microbiome and human genes involved in BC, and assessing the impact of the altered composition of breast, gut, and milk microbiome in the physiological status of normal breast as well as cancerous or non-cancerous breast lesions. The study also evaluated the growing evidence that these altered populations may hinder chemotherapeutic treatment. The role of microbiome in the development and maintenance of inflammation, estrogen metabolism, and epigenetic alterations was properly investigated. Finally, clinical and therapeutic applications of the microbiome- e.g., probiotics, microbiome genome modulation, and engineered microbiome enzymes in the management of BC were reviewed.
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Affiliation(s)
- Zahra Eslami-S
- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.,Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, Montpellier, France
| | - Keivan Majidzadeh-A
- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Sina Halvaei
- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Fatemeh Babapirali
- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.,University of Science and Culture, Basic Science and Advanced Technologies in Biology, Tehran, Iran
| | - Rezvan Esmaeili
- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
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12
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Aono K, Azuma YT, Nabetani T, Hatoya S, Furuya M, Miki M, Hirota K, Fujimoto Y, Nishiyama K, Ogata Y, Mochizuki T, Tani H. Correlation between toll-like receptor 4 and nucleotide-binding oligomerization domain 2 (NOD2) and pathological severity in dogs with chronic gastrointestinal diseases. Vet Immunol Immunopathol 2019; 210:15-22. [PMID: 30947975 DOI: 10.1016/j.vetimm.2019.03.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 02/27/2019] [Accepted: 03/09/2019] [Indexed: 12/12/2022]
Abstract
Toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain 2 (NOD2), and TNF-α play important roles in human inflammatory bowel diseases. The aim of this study was to elucidate the relationship between Toll-like receptor 4, NOD2, and TNF-α and the severity of chronic gastrointestinal diseases in dogs. We examined the expression levels of TLR4, NOD2, and TNF-α in the stomach, duodenum, ileum, colon, and rectum obtained from 21 dogs with chronic gastrointestinal disease, including inflammatory bowel disease, high-grade lymphoma, food responsive enteropathy, chronic pancreatitis, low-grade lymphoma, inflammatory colorectal polyp, and chronic colitis. Next, we demonstrated whether there is good correlation between the expression levels of TLR4, NOD2, and TNF-α and the histopathological analysis of each sample. We found that the level of TLR4 expression in the ileum of dogs with chronic gastrointestinal disease was positively associated with the histopathological severity. We also found that the level of NOD2 expression in the duodenum, stomach, and rectum was positively associated with the histopathological severity. However, there was no correlation between TNF-α expression in the 5 regions tested in this study and the histopathological severity. These findings indicate that TLR4 and NOD2 are remarkably associated with the severity of chronic gastrointestinal disease in dogs.
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Affiliation(s)
- Kimiya Aono
- Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan
| | - Yasu-Taka Azuma
- Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan.
| | - Tomoyo Nabetani
- Veterinary Medical Center, Osaka Prefecture University College of Life, Environmental, and Advanced Sciences, Izumisano, Osaka, Japan
| | - Shingo Hatoya
- Laboratory of Cell Pathobiology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan
| | - Masaru Furuya
- Laboratory of Veterinary Internal Medicine, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan
| | - Mariko Miki
- Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan
| | - Kana Hirota
- Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan
| | - Yasuyuki Fujimoto
- Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan
| | - Kazuhiro Nishiyama
- Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan
| | - Yoshiyuki Ogata
- Laboratory of Functional Genomics, Course of Integrated Bioscience, Division of Applied Life Sciences, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Sakai, Osaka, Japan
| | - Tomofumi Mochizuki
- Laboratory of Plant Pathology, Course of Plant Production Science, Division of Applied Life Sciences, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Sakai, Osaka, Japan
| | - Hiroyuki Tani
- Laboratory of Veterinary Internal Medicine, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka, Japan.
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13
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Sharifi L, Moshiri M, Dallal MM, Asgardoon MH, Nourizadeh M, Bokaie S, Mirshafiey A. The Inhibitory Role of M2000 (β-D-Mannuronic Acid) on Expression of Toll-like Receptor 2 and 4 in HT29 Cell Line. RECENT PATENTS ON INFLAMMATION & ALLERGY DRUG DISCOVERY 2019; 13:57-65. [PMID: 30539708 PMCID: PMC6778985 DOI: 10.2174/1872213x13666181211160238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 12/01/2018] [Accepted: 12/04/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND/OBJECTIVES Anti-inflammatory agents play a crucial role in controlling inflammatory diseases such as Inflammatory Bowel Disease (IBD) but their use is restricted due to their vast side effects. M2000 (β-D-mannuronic acid) is a new immunomodulatory drug. According to the capacity of M2000 in suppressing some molecules involved in Toll Like Receptors (TLRs) signaling and reducing oxidative stress we hypothesize that, this molecule may have a potential role in decreasing inflammatory responses in IBD. The aim of this study was to evaluate the cytotoxicity of M2000 and its effect on the gene expression of TLR2 and TLR4. METHODS HEK293 cell line was grown and divided into 96-well cell plate and MTT assay was performed. HT29 cells were cultured and treated with low and high doses of M2000. Total RNA was extracted and cDNA synthesized and quantitative real-time PCR was done to quantify the TLR2 and TLR4 mRNA expression. RESULTS We found that M2000 at the concentration of ≤ 1000µg/ml had no obvious cytotoxicity effect on the HEK293 cells. Also, low and high doses of M2000 could significantly down-regulate both TLR2 and TLR4 mRNA expression. Moreover, a significant reduction in gene expression of TLR2 and TLR4 in an inflammatory condition resulted in high doses of M2000 in the presence of LPS. CONCLUSION Our study which was conducted in colonic epithelial cell model, shows that M2000 can be considered as a new anti-inflammatory agent in IBD. However, more comprehensive experimental and clinical studies are required to recognize the molecular mechanism of M2000 and also its safety and efficacy.
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Affiliation(s)
| | | | | | | | | | | | - Abbas Mirshafiey
- Address correspondence to this author at the Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Tel/Fax: +98 (21) 88954913; E-mail:
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14
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Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS PROTEOMICS & BIOINFORMATICS 2018. [PMID: 29474889 DOI: 10.1016/j.gpb.2017.06.002.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
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15
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Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS, PROTEOMICS & BIOINFORMATICS 2018; 16:33-49. [PMID: 29474889 PMCID: PMC6000254 DOI: 10.1016/j.gpb.2017.06.002] [Citation(s) in RCA: 275] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 06/08/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
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16
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Lu Y, Li X, Liu S, Zhang Y, Zhang D. Toll-like Receptors and Inflammatory Bowel Disease. Front Immunol 2018; 9:72. [PMID: 29441063 PMCID: PMC5797585 DOI: 10.3389/fimmu.2018.00072] [Citation(s) in RCA: 237] [Impact Index Per Article: 33.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 01/11/2018] [Indexed: 12/20/2022] Open
Abstract
Inflammatory bowel disease (IBD) is one relapsing and lifelong disease that affects millions of patients worldwide. Increasing evidence has recently highlighted immune-system dysfunction, especially toll-like receptors (TLRs)-mediated innate immune dysfunction, as central players in the pathogenesis of IBD. TLRs and TLR-activated signaling pathways are involved not only in the pathogenesis but also in the efficacy of treatment of IBD. By understanding these molecular mechanisms, we might develop a strategy for relieving the experience of long-lasting suffering of those patients and improving their quality of life. The purpose of this review article is to summarize the potential mechanisms of TLR signaling pathways in IBD and the novel potential therapeutic strategies against IBD.
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Affiliation(s)
- Yue Lu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xinrui Li
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Shanshan Liu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yifan Zhang
- Center for Infectious and Inflammation Diseases, Texas A&M University, Houston, TX, United States
| | - Dekai Zhang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.,Center for Infectious and Inflammation Diseases, Texas A&M University, Houston, TX, United States
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17
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Paarnio K, Väyrynen S, Klintrup K, Ohtonen P, Mäkinen MJ, Mäkelä J, Karttunen TJ. Divergent expression of bacterial wall sensing Toll-like receptors 2 and 4 in colorectal cancer. World J Gastroenterol 2017; 23:4831-4838. [PMID: 28765705 PMCID: PMC5514649 DOI: 10.3748/wjg.v23.i26.4831] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Revised: 03/14/2017] [Accepted: 05/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa.
METHODS We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed.
RESULTS Normal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancer-specific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression (P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours.
CONCLUSION Tumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease.
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18
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Chen D, Liu L, Luo X, Mu A, Yan L, Chen X, Wang L, Wang N, He H, Zhou H, Zhang T. Effect of SMYD3 on the microRNA expression profile of MCF-7 breast cancer cells. Oncol Lett 2017; 14:1831-1840. [PMID: 28789418 DOI: 10.3892/ol.2017.6320] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 03/28/2017] [Indexed: 01/02/2023] Open
Abstract
SET and MYND domain containing 3 (SMYD3) is a histone methyltransferase (HMT) and transcription factor, which serves important roles in carcinogenesis. Numerous downstream target genes of SMYD3 have been identified in previous studies. However, the downstream microRNA (miRNA) s regulated by SMYD3 are yet to be elucidated. In the present study, the results of miRNA microarray demonstrated that 30 miRNA expression profiles were upregulated, whilst 24 miRNAs were downregulated by >2.0-fold in the SMYD3-overexpressed MCF-7 breast cancer cells. The HMT activity was demonstrated to be essential for SMYD3-mediated transactivation of miR-200c-3p and the overexpression of miR-200c-3p inhibited the transactivation effects of SMYD3 on myocardin-related transcription factor-A-dependent migration-associated genes. To our best knowledge, the current study is the first to report on the transcriptional regulation of SMYD3 on miRNAs, and miR-200c may be a downstream negative regulator of the SMYD3-mediated pathway in the migration of breast cancer cells. These results may provide a novel theoretical basis to understand the mechanisms underlying the initiation, progression, diagnosis, prevention and therapy of breast cancer.
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Affiliation(s)
- Dongju Chen
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Lei Liu
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Xuegang Luo
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Ai Mu
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Lihua Yan
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Xiaoying Chen
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Lei Wang
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Nan Wang
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Hongpeng He
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Hao Zhou
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
| | - Tongcun Zhang
- Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.,Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China
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19
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Demeyer D, Mertens B, De Smet S, Ulens M. Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat: A Review. Crit Rev Food Sci Nutr 2017; 56:2747-66. [PMID: 25975275 DOI: 10.1080/10408398.2013.873886] [Citation(s) in RCA: 132] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The vast majority of CRC cases have been linked to environmental causes rather than to heritable genetic changes. Over the last decades, epidemiological evidence linking the consumption of red and, more convincingly, of processed red meat to CRC has accumulated. In parallel, hypotheses on carcinogenic mechanisms underlying an association between CRC and the intake of red and processed red meat have been proposed and investigated in biological studies. The hypotheses that have received most attention until now include (1) the presence of polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, two groups of compounds recognized as carcinogenic, (2) the enhancing effect of (nitrosyl)heme on the formation of carcinogenic N-nitroso compounds and lipid peroxidation. However, none of these hypotheses completely explains the link between red and processed red meat intake and the CRC risk. Consequently, scientists have proposed additional mechanisms or refined their hypotheses. This review first briefly summarizes the development of CRC followed by an in-depth overview and critical discussion of the different potential carcinogenic mechanisms underlying the increased CRC risk associated with the consumption of red and processed red meat.
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Affiliation(s)
- Daniel Demeyer
- a Superior Health Council , Brussels , Belgium.,b Laboratory for Animal Nutrition and Animal Product Quality , Faculty of Bioscience Engineering, Ghent University , Melle , Belgium
| | - Birgit Mertens
- a Superior Health Council , Brussels , Belgium.,c Program Toxicology, Department of Food , Medicines and Consumer Safety, Scientific Institute of Public Health (Site Elsene) , Brussels , Belgium
| | - Stefaan De Smet
- a Superior Health Council , Brussels , Belgium.,b Laboratory for Animal Nutrition and Animal Product Quality , Faculty of Bioscience Engineering, Ghent University , Melle , Belgium
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Abstract
INTRODUCTION The potential roles of toll-like receptors (TLRs) in immunopathogenesis of Ebola virus disease should be unraveled to provoke possible prophylactic or therapeutic implications of TLRs for EVD. Areas covered: The Ebola virus (EBOV) infection virtually paralyses all the main mechanisms responsible for induction of type I interferon (IFN-I) response. To summarize, EBOV infection interferes with: a) the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway that is mediated by TLR3 and TLR4 signaling; b) the interferon regulatory factor 7 (IRF7) pathway that is stimulated by TLR7 and TLR9; c) the intracellular signaling that is induced by retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs); and d) the autocrine/paracrine feedback loop that is mediated by the IFN-stimulated gene factor 3 (ISGF3) complex. Upon infection with EBOV infection, TLR4 plays a key role in production of proinflammatory mediators. Expert opinion: It is theoretically possible that use of TLRs 3, 4, 7, and 9 agonists would be beneficial to improve the IFN-I response, despite their systemic side effects. Also, antagonist of TLR4 can be utilized to prevent production of proinflammatory cytokines. Additionally, it is highly recommended to design future investigations aimed at determining if the utilization of IFN-I would be beneficial for prophylactic/therapeutic programs of Ebola.
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Affiliation(s)
- Amene Saghazadeh
- a Research Center for Immunodeficiencies, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,b Systematic Review and Meta-Analysis Expert Group (SRMEG) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Nima Rezaei
- a Research Center for Immunodeficiencies, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,b Systematic Review and Meta-Analysis Expert Group (SRMEG) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran.,c Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.,d Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA) , Universal Scientific Education and Research Network (USERN) , Sheffield , UK
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Abstract
Deregulated inflammatory response plays a pivotal role in the initiation, development and progression of tumours. Potential molecular mechanism(s) that drive the establishment of an inflammatory-tumour microenvironment is not entirely understood owing to the complex cross-talk between pro-inflammatory and tumorigenic mediators such as cytokines, chemokines, oncogenes, enzymes, transcription factors and immune cells. These molecular mediators are critical linchpins between inflammation and cancer, and their activation and/or deactivation are influenced by both extrinsic (i.e. environmental and lifestyle) and intrinsic (i.e. hereditary) factors. At present, the research pertaining to inflammation-associated cancers is accumulating at an exponential rate. Interest stems from hope that new therapeutic strategies against molecular mediators can be identified to assist in cancer treatment and patient management. The present review outlines the various molecular and cellular inflammatory mediators responsible for tumour initiation, progression and development, and discusses the critical role of chronic inflammation in tumorigenesis.
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Dheer R, Davies JM, Abreu MT. Inflammation and Colorectal Cancer. INTESTINAL TUMORIGENESIS 2015:211-256. [DOI: 10.1007/978-3-319-19986-3_8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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23
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Fadakar K, Dadkhahfar S, Esmaeili A, Rezaei N. The role of Toll-like receptors (TLRs) in stroke. Rev Neurosci 2014; 25:699-712. [PMID: 24807166 DOI: 10.1515/revneuro-2013-0069] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Accepted: 04/06/2014] [Indexed: 02/05/2023]
Abstract
Toll-like receptors (TLRs) recognizing the exogenous pathogen-associated molecular patterns (PAMPs) are part of the innate immune system that plays a role in various challenging interactions between the neurons and the immune system. Stroke as a major injury to the central nervous system (CNS) is one of the hot points of such cross-talk. The various roles of the different types of TLRs in stroke can be classified into three major categories: (1) the hazardous effect of TLRs with a focus on the part in poststroke neurodegeneration, (2) the beneficial effect of those types of TLRs that exert a neuroprotective effect following an ischemic insult, and (3) the role of TLRs in immunomodulation on one hand and the possible autoimmunity as a consequence of neuronal injury due to an ischemic attack on the other hand. However, the mentioned functions of TLRs, similar to many other parts of the immune system, might overlap in many aspects. The current review article, including both experimental and clinical studies, is an attempt to bring together the studies that have investigated the roles of TLRs in stroke while referring to the apparent controversies in this field, with pointing out the new ideas for further considerations.
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24
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Shahanavaj K, Gil-Bazo I, Castiglia M, Bronte G, Passiglia F, Carreca AP, del Pozo JL, Russo A, Peeters M, Rolfo C. Cancer and the microbiome: potential applications as new tumor biomarker. Expert Rev Anticancer Ther 2014; 15:317-30. [PMID: 25495037 DOI: 10.1586/14737140.2015.992785] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Microbial communities that colonize in humans are collectively described as microbiome. According to conservative estimates, about 15% of all types of neoplasms are related to different infective agents. However, current knowledge is not sufficient to explain how the microbiome contributes to the growth and development of cancers. Large and thorough studies involving colonized, diverse and complex microbiome entities are required to identify microbiome as a potential cancer marker and to understand how the immune system is involved in response to pathogens. This article reviews the existing evidence supporting the enigmatic association of transformed microbiome with the development of cancer through the immunological modification. Ascertaining the connection between microbiome and immunological responses with risk of cancer may direct to explaining significant advances in the etiology of cancer, potentially disclosing a novel paradigm of research for the management and prevention of cancer.
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Affiliation(s)
- Khan Shahanavaj
- Department of Bioscience, Shri Ram Group of College (SRGC), Muzaffarnagar, UP, India
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25
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Chang LC, Fan CW, Tseng WK, Chein HP, Hsieh TY, Chen JR, Hwang CC, Hua CC. IFNAR1 is a predictor for overall survival in colorectal cancer and its mRNA expression correlated with IRF7 but not TLR9. Medicine (Baltimore) 2014; 93:e349. [PMID: 25546690 PMCID: PMC4602595 DOI: 10.1097/md.0000000000000349] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Toll-like receptor (TLR) 9 plays a role in intestinal inflammation that, in turn, is related to the tumorigenesis of colorectal cancer. Nuclear factor κB (NFκB), and interferon regulatory factor (IRF) 5 and IRF7 can be activated by TLR9 and induce the production of proinflammatory cytokines and type I interferon, respectively. This study investigated the mRNA expressions of TLR9 and its downstream signaling molecules in both the tumor and the normal tissues of colorectal cancer. Eighty-four subjects with colorectal cancer were consecutively recruited at a community-based hospital, and the mRNA expression of TLR9, NFκB, IRF5, IRF7, interleukin 6 (IL6), and interferon α/β/ω receptor 1 (IFNAR1) in the tumor and normal tissue were determined by real-time reverse transcription polymerase chain reaction using TaqMan FAM-labeled MGB probes (Life Technologies, Carlsbad, CA). The tumor had higher percentages of detection of TLR9, IFNAR1, and IL6 mRNA expressions than normal tissue. The absence of detectable TLR9 mRNA expression was associated with an absence of significance in the correlation between IL6 and NFκB or IRF5, but not that between IRF7 and IFNAR1 in both the tumor and the normal tissues. An absence of detectable IFNAR1 mRNA expression in the tumor (hazard ratio: 3.77; 95% confidence interval: 1.22-11.60) and advanced stage (stages III and IV, 7.86; 1.76-35.40) were significant predictors for overall survival. IFNAR1 is a predictor for overall survival and mRNA expression is correlated to IRF7, but not TLR9 in colorectal cancer. The results cast doubt on the usefulness of TLR9 agonist in treating colorectal cancer.
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Affiliation(s)
- Liang-Che Chang
- From the Department of Pathology (L-CC, T-YH, H-PC, J-RC, C-CH); Division of Colon and Rectal Surgery (C-WF, W-KT); and Department of Internal Medicine (C-CH), Chang Gung Memorial Hospital, Keelung, and Chang Gung University, Taoyuan, Taiwan
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26
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Yesudhas D, Gosu V, Anwar MA, Choi S. Multiple roles of toll-like receptor 4 in colorectal cancer. Front Immunol 2014; 5:334. [PMID: 25076949 PMCID: PMC4097957 DOI: 10.3389/fimmu.2014.00334] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 07/01/2014] [Indexed: 12/14/2022] Open
Abstract
Toll-like receptor (TLR) signaling has been implicated in the inflammatory responses in intestinal epithelial cells (IECs). Such inflammatory signals mediate complex interactions between commensal bacteria and TLRs and are required for IEC proliferation, immune response, repair, and homeostasis. The upregulation of certain TLRs in colorectal cancer (CRC) tissues suggests that TLRs may play an essential role in the prognosis of chronic and inflammatory diseases that ultimately culminate in CRC. Here, we provide a comprehensive review of the literature on the involvement of the TLR pathway in the initiation, progression, and metastasis of CRC, as well as inherited genetic variation and epigenetic regulation. The differential expression of TLRs in epithelial cells has also been discussed. In particular, we emphasize the physiological role of TLR4 in CRC development and pathogenesis, and propose novel and promising approaches for CRC therapeutics with the aid of TLR ligands.
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Affiliation(s)
- Dhanusha Yesudhas
- Department of Molecular Science and Technology, Ajou University , Suwon , South Korea
| | - Vijayakumar Gosu
- Department of Molecular Science and Technology, Ajou University , Suwon , South Korea
| | - Muhammad Ayaz Anwar
- Department of Molecular Science and Technology, Ajou University , Suwon , South Korea
| | - Sangdun Choi
- Department of Molecular Science and Technology, Ajou University , Suwon , South Korea
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Abreu MT, Peek RM. Gastrointestinal malignancy and the microbiome. Gastroenterology 2014; 146:1534-1546.e3. [PMID: 24406471 PMCID: PMC3995897 DOI: 10.1053/j.gastro.2014.01.001] [Citation(s) in RCA: 234] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 12/18/2013] [Accepted: 01/03/2014] [Indexed: 12/13/2022]
Abstract
Microbial species participate in the genesis of a substantial number of malignancies-in conservative estimates, at least 15% of all cancer cases are attributable to infectious agents. Little is known about the contribution of the gastrointestinal microbiome to the development of malignancies. Resident microbes can promote carcinogenesis by inducing inflammation, increasing cell proliferation, altering stem cell dynamics, and producing metabolites such as butyrate, which affect DNA integrity and immune regulation. Studies in human beings and rodent models of cancer have identified effector species and relationships among members of the microbial community in the stomach and colon that increase the risk for malignancy. Strategies to manipulate the microbiome, or the immune response to such bacteria, could be developed to prevent or treat certain gastrointestinal cancers.
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Affiliation(s)
- Maria T Abreu
- Division of Gastroenterology, Departments of Medicine and Microbiology and Immunology, University of Miami, Miami, Florida
| | - Richard M Peek
- Division of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University, Nashville, Tennessee.
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Role of toll-like receptor 4 in colorectal carcinogenesis: a meta-analysis. PLoS One 2014; 9:e93904. [PMID: 24705379 PMCID: PMC3976338 DOI: 10.1371/journal.pone.0093904] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 03/09/2014] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE This meta-analysis was performed to evaluate the role of toll-like receptor 4 (TLR-4) in colorectal carcinogenesis. METHODS The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through November 1st, 2013 without language restrictions. Odds ratios (ORs) or standardized mean differences (SMD) with their 95% confidence intervals (CI) were calculated. RESULTS Fourteen case-control studies met the inclusion criteria for this meta-analysis. A total of 1,209 colorectal cancer (CRC) cases and 1,218 healthy controls were involved in this meta-analysis. Two common polymorphisms (299 A>G and 399 C>T) in the TLR-4 gene, TLR-4 mRNA and protein expression were assessed. Our meta-analysis results revealed that the TLR-4 399 C>T polymorphism might increase the risk of CRC (allele model: OR = 1.77, 95%CI = 1.32 ∼ 2.36, P<0.001; dominant model: OR = 1.83, 95%CI = 1.32 ∼ 2.52, P<0.001; respectively). However, we found no correlation between the TLR-4 299 A>G polymorphism and CRC risk (all P>0.05). A subgroup analysis by ethnicity suggested that TLR-4 genetic polymorphisms were associated with an increased risk of CRC among Asians (allele model: OR = 1.50, 95%CI = 1.19 ∼ 1.88, P = 0.001; dominant model: OR = 1.49, 95%CI = 1.16 ∼ 1.92, P = 0.002; respectively), but not among Caucasians and Africans (all P>0.05). Furthermore, our results showed that TLR-4 mRNA and protein levels in CRC patients were higher than those in healthy controls (TLR-4 mRNA: SMD = 2.51, 95%CI = 0.98 ∼ 4.05, P = 0.001; TLR-4 protein: OR = 4.75, 95%CI = 1.16 ∼ 19.36, P = 0.030; respectively). CONCLUSION Our findings provide empirical evidence that TLR-4 may play an important role in colorectal carcinogenesis. Thus, TLR-4 is a promising potential biomarker for the early diagnosis of CRC.
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