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Jalali P, Rezaee M, Yaghoobi A, Piroozkhah M, Zabihi MR, Aliyari S, Salehi Z. Bioinformatics analysis reveals shared molecular pathways for relationship between ulcerative colitis and primary sclerosing cholangitis. Genomics Inform 2025; 23:12. [PMID: 40375266 DOI: 10.1186/s44342-025-00045-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 04/09/2025] [Indexed: 05/18/2025] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders, including ulcerative colitis (UC) and Crohn's disease, affecting the gastrointestinal tract and is associated with high morbidity and mortality. Accumulating evidence indicates that IBD not only impacts the gastrointestinal tract but also affects multiple extraintestinal organs, which may manifest prior to the diagnosis of IBD. Among these extraintestinal manifestations associated with IBD, primary sclerosing cholangitis (PSC) stands out as a prominent example. PSC is recognized as a progressive cholestatic disorder, characterized by the narrowing of bile ducts, eventual development of liver cirrhosis, end-stage liver disease, and the potential emergence of cholangiocarcinoma. This study aimed to identify the molecular contributors in UC-induced PSC by detecting the essential regulatory genes that are differentially expressed in both diseases. MATERIALS AND METHODS The common single-nucleotide polymorphisms (SNPs) and differentially expressed genes (DEGs) were detected using DisGeNET and GEO databases, respectively. Then, the top module and hub genes within the protein-protein interaction network were identified. Furthermore, the co-expression network of the top module was constructed using the HIPPIE database. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Finally, we searched the DGIdb database for possible interacting drugs with UC-PSC top module genes. RESULTS A total of 132 SNPs and their associated genes were found to be shared between UC and PSC. Gene expression analysis identified 56 common DEGs between the two diseases. Following functional enrichment analysis, 207 significant biological processes (BP), 48 molecular functions (MF), and 8 KEGG pathways, with notable enrichment in mRNA-related processes such as mRNA splicing and RNA binding, were defined. Particularly, the PTPN2 gene was the only gene common between UC and PSC at both the SNP level and the expression level. Additionally, the top cluster of PPI network analysis was consisted of PABPC1, SNRPA1, NOP56, NHP2L1, and HNRNPA2B1 genes. Finally, ceRNA network involving 4 mRNAs, 94 miRNAs, and 200 selected circRNAs was constructed. CONCLUSION The present study provides novel potential candidate genes that may be involved in the molecular association between ulcerative colitis and primary sclerosing cholangitis, resulting in the development of diagnostic tools and therapeutic targets to prevent the progression of PSC from UC.
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Affiliation(s)
- Pooya Jalali
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Malihe Rezaee
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Yaghoobi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Moein Piroozkhah
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zabihi
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahram Aliyari
- Division of Applied Bioinformatics, German Cancer Research Center DKFZ Heidelberg, Heidelberg, Germany
| | - Zahra Salehi
- Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.
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Suri K, Hosur V, Panchakshari R, Amiji MM. A Multimodal Therapeutic Strategy for Inflammatory Bowel Disease Using MicroRNA-146a Mimic Encapsulated in Lipid Nanoparticles. Mol Pharm 2025. [PMID: 40324972 DOI: 10.1021/acs.molpharmaceut.5c00014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Dysregulated microRNAs (miRNAs) have significant potential as diagnostic tools for various chronic diseases; however, their therapeutic applications remain largely unexplored. Given their capacity to regulate multiple pathways, miRNAs are promising candidates for treating pleiotropic diseases, such as inflammatory bowel disease (IBD). In our study, we conducted a comprehensive review of the literature of miRNA-146 levels in the inflamed tissues of IBD patients and murine colitis models. Initially, we quantified the expression of miRNA-146a and miRNA-146b in the colons of mice using the dextran sodium sulfate (DSS)-inducedacute model of IBD. We selected miRNA-146a for further study due to its anti-inflammatory properties and potential relevance in IBD treatment. We hypothesized that a macrophage model of inflammation would be well-suited to studying the effects of this miRNA. Subsequently, we investigated the use of lipid nanoparticles (LNPs) for the targeted delivery of miRNA-146a to macrophages, which play a key role in IBD. Our results indicated that miRNA-146a levels increased in the DSS model and LNP-mediated delivery effectively downregulated genes associated with inflammation. These findings highlight the critical role of miRNA-146a in modulating IBD and suggest that LNP-based delivery could be a promising therapeutic strategy for managing inflammatory responses.
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Affiliation(s)
- Kanika Suri
- Takeda Development Center Americas, Cambridge, Massachusetts 02142, United States
- Department of Bioengineering, College of Engineering, Northeastern University, Boston, Massachusetts 02120, United States
| | - Vishnu Hosur
- The Jackson Laboratory, Bar Harbor, Maine 04609, United States
| | - Rohit Panchakshari
- Takeda Development Center Americas, Cambridge, Massachusetts 02142, United States
| | - Mansoor M Amiji
- Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, Boston, Massachusetts 02115, United States
- Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, Massachusetts 02115, United States
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Rai RP, Syed A, Elgorban AM, Abid I, Wong LS, Khan MS, Khatoon J, Prasad KN, Ghoshal UC. Expressions of selected microRNAs in gastric cancer patients and their association with Helicobacter pylori and its cag pathogenicity island. Microb Pathog 2025; 202:107442. [PMID: 40049249 DOI: 10.1016/j.micpath.2025.107442] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 02/24/2025] [Accepted: 02/28/2025] [Indexed: 03/12/2025]
Abstract
BACKGROUND Helicobacter pylori infection and the resulting inflammation of the stomach are widely recognized as the primary risk factors for the development of gastric cancer (human health). Despite numerous attempts, the correlation between various virulence factors of H. pylori and stomach cancer remains mainly unexplained. The cag pathogenicity island (cagPAI) is a widely recognized indicator of virulence in H. pylori. MicroRNAs play crucial roles in a wide range of biological and pathological processes and dysregulated expressions of miRNAs have been detected in numerous cancer types. However, research on the correlation between H. pylori infection and its cagPAI, as well as the differential expression of microRNAs in gastric cancer, is lacking. AIM The aim of this study was to examine the differential expression of miRNAs in 80 patients with gastric cancer, specifically in connection to the presence of H. pylori and its cag pathogenicity island (cagPAI). METHODS Biopsies of 80 gastric cancer patients were collected and used for H. pylori DNA isolation and tissue miRNA isolation, and further analyzed for cagPAI and miRNA expression and their association. RESULTS Elevated levels of miR-21, miR-155, and miR-223 were detected in malignant tissues. The expression of miR-21 and miR-223 was considerably elevated in biopsies that tested positive for H. pylori, whereas the expression of miR-34a was reduced. H. pylori cagPAI samples that are functionally intact exhibit greater expression of miR-21 and miR-223 compared to cagPAI samples that are partially deleted, in both normal and malignant tissues. CONCLUSION Thus, the novelty of our study lies in its focus on the differential expression of specific miRNAs in relation to the functional integrity of the cagPAI in H. pylori-infected gastric cancer patients, offering a more detailed understanding of the interplay between H. pylori virulence factors and miRNA regulation than previous studies.
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Affiliation(s)
- Ravi Prakash Rai
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Asad Syed
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
| | - Abdallah M Elgorban
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Islem Abid
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Putra Nilai, 71800, Nilai, Negeri Sembilan, Malaysia.
| | - Mohd Sajid Khan
- Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Jahanarah Khatoon
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Kashi N Prasad
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, Lucknow, India.
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Holland AM, Jehoul R, Vranken J, Wohl SG, Boesmans W. MicroRNA regulation of enteric nervous system development and disease. Trends Neurosci 2025; 48:268-282. [PMID: 40089421 PMCID: PMC11981837 DOI: 10.1016/j.tins.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/04/2025] [Accepted: 02/18/2025] [Indexed: 03/17/2025]
Abstract
The enteric nervous system (ENS), an elaborate network of neurons and glia woven through the gastrointestinal tract, is integral for digestive physiology and broader human health. Commensurate with its importance, ENS dysfunction is linked to a range of debilitating gastrointestinal disorders. MicroRNAs (miRNAs), with their pleiotropic roles in post-transcriptional gene regulation, serve as key developmental effectors within the ENS. Herein, we review the regulatory dynamics of miRNAs in ENS ontogeny, showcasing specific miRNAs implicated in both congenital and acquired enteric neuropathies, such as Hirschsprung's disease (HSCR), achalasia, intestinal neuronal dysplasia (IND), chronic intestinal pseudo-obstruction (CIPO), and slow transit constipation (STC). By delineating miRNA-mediated mechanisms in these diseases, we underscore their importance for ENS homeostasis and highlight their potential as therapeutic targets.
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Affiliation(s)
- Amy Marie Holland
- Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium; Department of Pathology, GROW - Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Reindert Jehoul
- Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium
| | - Jorunn Vranken
- Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium
| | - Stefanie Gabriele Wohl
- Department of Biological and Vision Sciences, College of Optometry, The State University of New York, New York, NY, USA
| | - Werend Boesmans
- Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium; Department of Pathology, GROW - Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands.
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Popa ML, Ichim C, Anderco P, Todor SB, Pop-Lodromanean D. MicroRNAs in the Diagnosis of Digestive Diseases: A Comprehensive Review. J Clin Med 2025; 14:2054. [PMID: 40142862 PMCID: PMC11943142 DOI: 10.3390/jcm14062054] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/14/2025] [Accepted: 03/15/2025] [Indexed: 03/28/2025] Open
Abstract
MicroRNAs (miRNAs) have emerged as crucial regulators in digestive pathologies, including inflammatory bowel disease (miR-31, miR-155, and miR-21), colorectal cancer (miR-21, miR-598, and miR-494), and non-alcoholic fatty liver disease (miR-21, miR-192, and miR-122). Their capacity to modulate gene expression at the post-transcriptional level makes them highly promising candidates for biomarkers and therapeutic interventions. However, despite considerable progress, their clinical application remains challenging. Research has shown that miRNA expression is highly dynamic, varying across patients, disease stages, and different intestinal regions. Their dual function as both oncogenes and tumor suppressors further complicates their therapeutic use, as targeting miRNAs may yield unpredictable effects. Additionally, while miRNA-based therapies hold great potential, significant hurdles persist, including off-target effects, immune activation, and inefficiencies in delivery methods. The intricate interplay between miRNAs and gut microbiota adds another layer of complexity, influencing disease mechanisms and treatment responses. This review examined the role of miRNAs in digestive pathologies, emphasizing their diagnostic and therapeutic potential. While they offer new avenues for disease management, unresolved challenges underscore the need for further research to refine their clinical application.
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Affiliation(s)
| | - Cristian Ichim
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (M.L.P.); (S.B.T.); (D.P.-L.)
| | - Paula Anderco
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (M.L.P.); (S.B.T.); (D.P.-L.)
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Doghish AS, Elazazy O, Mohamed HH, Mansour RM, Ghanem A, Faraag AHI, Elballal MS, Elrebehy MA, Elesawy AE, Abdel Mageed SS, Saber S, Nassar YA, Abulsoud AI, Abdel-Reheim MA, Elawady AS, Ali MA, Basiouny MS, Hemdan M, Lutfy RH, Awad FA, El-Sayed SA, Ashour MM, El-Sayyad GS, Mohammed OA. A Review on miRNAs in Enteric Bacteria-mediated Host Pathophysiology: Mechanisms and Implications. J Biochem Mol Toxicol 2025; 39:e70160. [PMID: 39907181 DOI: 10.1002/jbt.70160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 12/22/2024] [Accepted: 01/16/2025] [Indexed: 02/06/2025]
Abstract
Recently, many studies focused on the billions of native bacteria found inside and all over the human body, commonly known as the microbiota, and its interactions with the eukaryotic host. One of the niches for such microbiota is the gastrointestinal tract (GIT), which harbors hundreds to thousands of bacterial species commonly known as enteric bacteria. Changes in the enteric bacterial populations were linked to various pathologies such as irritable bowel syndrome and obesity. The gut microbiome could affect the health status of individuals. MicroRNAs (miRNAs) are one of the extensively studied small-sized noncoding RNAs (ncRNAs) over the past decade to explore their multiple roles in health and disease. It was proven that miRNAs circulate in almost all body fluids and tissues, showing signature patterns of dysregulation associated with pathologies. Both cellular and circulating miRNAs participate in the posttranscriptional regulation of genes and are considered the potential key regulators of genes and participate in cellular communication. This manuscript explores the unique interplay between miRNAs and enteric bacteria in the gastrointestinal tract, emphasizing their dual role in shaping host-microbiota dynamics. It delves into the molecular mechanisms by which miRNAs influence bacterial colonization and host immune responses, linking these findings to gut-related diseases. The review highlights innovative therapeutic and diagnostic opportunities, offering insights for targeted treatments of dysbiosis-associated pathologies.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Egypt
| | - Ola Elazazy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
| | - Hend H Mohamed
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Reda M Mansour
- Zoology and Entomology Department, Faculty of Science, Helwan University, Helwan, Egypt
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Aml Ghanem
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Ahmed H I Faraag
- Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, Egypt
- Medical Department, School of Biotechnology, Badr University in Cairo, Badr City, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Galala University, New Galala City, Egypt
| | - Ahmed E Elesawy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
| | - Sameh Saber
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
| | - Yara A Nassar
- Department of Botany, Faculty of Science, Biotechnology and Its Application Program, Mansoura University, Mansoura, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
- Department of Biochemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Egypt
| | | | - Alaa S Elawady
- Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Mohamed A Ali
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | | | - Mohamed Hemdan
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Radwa H Lutfy
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Farah A Awad
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Salma A El-Sayed
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Mohamed M Ashour
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Gharieb S El-Sayyad
- Medical Laboratory Technology Department, Faculty of Applied Health Sciences Technology, Badr University in Cairo (BUC), Cairo, Egypt
- Microbiology and Immunology Department, Faculty of Pharmacy, Galala University, New Galala city, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi Arabia
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Arumugam P, Saha K, Nighot P. Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways. Inflamm Bowel Dis 2025; 31:259-271. [PMID: 39321109 DOI: 10.1093/ibd/izae232] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Indexed: 09/27/2024]
Abstract
Intestinal epithelial tight junctions (TJs), a dynamically regulated barrier structure composed of occludin and claudin family of proteins, mediate the interaction between the host and the external environment by allowing selective paracellular permeability between the luminal and serosal compartments of the intestine. TJs are highly dynamic structures and can undergo constant architectural remodeling in response to various external stimuli. This is mediated by an array of intracellular signaling pathways that alters TJ protein expression and localization. Dysfunctional regulation of TJ components compromising the barrier homeostasis is an important pathogenic factor for pathological conditions including inflammatory bowel disease (IBD). Previous studies have elucidated the significance of TJ barrier integrity and key regulatory mechanisms through various in vitro and in vivo models. In recent years, considerable efforts have been made to understand the crosstalk between various signaling pathways that regulate formation and disassembly of TJs. This review provides a comprehensive view on the novel mechanisms that regulate the TJ barrier and permeability. We discuss the latest evidence on how ion transport, cytoskeleton and extracellular matrix proteins, signaling pathways, and cell survival mechanism of autophagy regulate intestinal TJ barrier function. We also provide a perspective on the context-specific outcomes of the TJ barrier modulation. The knowledge on the diverse TJ barrier regulatory mechanisms will provide further insights on the relevance of the TJ barrier defects and potential target molecules/pathways for IBD.
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Affiliation(s)
- Priya Arumugam
- Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA, USA
| | - Kushal Saha
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Prashant Nighot
- Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA, USA
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Jafari N, Abediankenari S. Role of microRNAs in immunoregulatory functions of epithelial cells. BMC Immunol 2024; 25:84. [PMID: 39707170 PMCID: PMC11662810 DOI: 10.1186/s12865-024-00675-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/27/2024] [Indexed: 12/23/2024] Open
Abstract
Epithelial cells (ECs) provide the first line of defense against microbial threats and environmental challenges. They participate in the host's immune responses via the expression and secretion of various immune-related molecules such as cytokines and chemokines, as well as interaction with immune cells. A growing body of evidence suggests that the dysregulated function of ECs can be involved in the pathophysiology of a broad range of infectious, autoimmune, and inflammatory diseases, including inflammatory bowel disease (IBD), asthma, multiple sclerosis, and rheumatoid arthritis. To maintain a substantial immunoregulatory function of ECs, precise expression of different molecules and their regulatory effects are indispensable. MicroRNAs (miRNAs, miRs) are small non-coding RNAs that regulate gene expression commonly at post-transcriptional level through degradation of target messenger RNAs (mRNAs) or suppression of protein translation. MiRNAs implicate as critical regulators in many cellular processes, including apoptosis, growth, differentiation, and immune response. Due to the crucial roles of miRNAs in such a vast range of biological processes, they have become the spotlight of biological research for more than two decades, but we are still at the beginning stages of the use of miRNA-based therapies in the improvement of human health. Hence, in the present paper, attempts are made to provide a comprehensive overview with regard to the roles of miRNAs in the immunoregulatory functions of ECs. A better understanding of the molecular mechanisms through which immunoregulatory properties of ECs are manifested, could aid the development of efficient strategies to prevent and treat multiple human diseases.
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Affiliation(s)
- Narjes Jafari
- Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Saeid Abediankenari
- Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
- Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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Apte A, Dutta Dey P, Julakanti SR, Midura-Kiela M, Skopp SM, Canchis J, Fauser T, Bardill J, Seal S, Jackson DM, Ghishan FK, Kiela PR, Zgheib C, Liechty KW. Oral Delivery of miR146a Conjugated to Cerium Oxide Nanoparticles Improves an Established T Cell-Mediated Experimental Colitis in Mice. Pharmaceutics 2024; 16:1573. [PMID: 39771552 PMCID: PMC11679827 DOI: 10.3390/pharmaceutics16121573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/02/2024] [Accepted: 12/04/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Dysregulated inflammation and oxidative stress are strongly implicated in the pathogenesis of inflammatory bowel disease. We have developed a novel therapeutic that targets inflammation and oxidative stress. It is comprised of microRNA-146a (miR146a)-loaded cerium oxide nanoparticles (CNPs) (CNP-miR146a). We hypothesized that oral delivery of CNP-miR146a would reduce colonic inflammation in a mouse model of established, chronic, T cell-mediated colitis. Methods: The stability of CNP-miR146a and mucosal delivery was assessed in vitro with simulated gastrointestinal fluid and in vivo after oral gavage by quantitative real-time RT-PCR. The efficacy of orally administered CNP-miR146a was tested in mice with established colitis using the model of adoptive naïve T-cell transfer in recombinant activating gene 2 knockout (Rag2-/-) mice. Measured outcomes included histopathology; CD45+ immune cell infiltration; oxidative DNA damage (tissue 8-hydroxy-2'-deoxyguanosine; 8-OHdG); expression of IL-6 and TNF mRNA and protein, and flow cytometry analysis of lamina propria Th1 and Th17 cell populations. Results: miR146a expression remained stable in simulated gastric and intestinal conditions. miR146a expression increased in the intestines of mice six hours following oral gavage of CNP-miR146a. Oral delivery of CNP-miR146a in mice with colitis was associated with reduced inflammation and oxidative stress in the proximal and distal colons as evidenced by histopathology scoring, reduced immune cell infiltration, reduced IL-6 and TNF expression, and decreased populations of CD4+Tbet+IFNg+ Th1, CD4+RorgT+IL17+ Th17, as well as pathogenic double positive IFNg+IL17+ T cells. Conclusions: CNP-miR146a represents a novel orally available therapeutic with high potential to advance into clinical trials.
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Affiliation(s)
- Anisha Apte
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA
| | - Pujarini Dutta Dey
- Department of Pediatrics, Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, University of Arizona Health Sciences Center, Tucson, AZ 85621, USA
| | - Srisaianirudh Reddy Julakanti
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA
| | - Monica Midura-Kiela
- Department of Pediatrics, Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, University of Arizona Health Sciences Center, Tucson, AZ 85621, USA
| | - Stacy M. Skopp
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA
| | - Jimena Canchis
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA
| | - Tobias Fauser
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA
| | - James Bardill
- Laboratory for Fetal and Regenerative Biology, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO 80045, USA
| | - Sudipta Seal
- Advanced Materials Processing and Analysis Center, Nanoscience Technology Center, University of Central Florida, Orlando, FL 32826, USA
| | | | - Fayez K. Ghishan
- Department of Pediatrics, Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, University of Arizona Health Sciences Center, Tucson, AZ 85621, USA
| | - Pawel R. Kiela
- Department of Pediatrics, Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, University of Arizona Health Sciences Center, Tucson, AZ 85621, USA
- Department of Immunobiology, University of Arizona Health Sciences Center, Tucson, AZ 85621, USA
| | - Carlos Zgheib
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA
- Ceria Therapeutics, Inc., Tucson, AZ 85721, USA
| | - Kenneth W. Liechty
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA
- Ceria Therapeutics, Inc., Tucson, AZ 85721, USA
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Joudaki N, Khodadadi A, Shamshiri M, Dehnavi S, Asadirad A. Alterations in the expression of serum-derived exosome-enclosed inflammatory microRNAs in Covid-19 patients. Heliyon 2024; 10:e39303. [PMID: 39640730 PMCID: PMC11620257 DOI: 10.1016/j.heliyon.2024.e39303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 10/05/2024] [Accepted: 10/11/2024] [Indexed: 12/07/2024] Open
Abstract
Introduction MicroRNAs in exosomes play a role in biological processes such as inflammation and Epithelial-mesenchymal transition (EMT). In EMT, epithelial cells undergo phenotypic changes and become similar to mesenchymal cells. EMT increases the invasion and metastasis of cancer cells. We aimed to evaluate the expression levels of miRNA-21, miRNA-218, miRNA-155, and miRNA-10b, which are effective in the pathway of inflammation and EMT in serum-derived exosome of COVID-19 patients. Method Blood samples were taken from 30 patients with COVID-19 and five healthy individuals as a control group. After separating the serum from the collected blood, the exosomes were purified from the serum. Relative expression of microRNAs was measured by real-time PCR method. Results The relative expression of miRNA-21, miRNA-218, and miRNA-155 in serum-derived exosomes of patients with COVID-19 had a significant increase (p < 0.0001). Also, the relative expression of miRNA-10b was significantly increased in the patient group (p < 0.01), but the changes in the expression level of miRNA-10b were not as significant as the changes in the expression level of other microRNAs. Conclusion miRNA-21, miRNA-218, miRNA-155, and miRNA-10b are involved in the pathogenesis of COVID-19 disease, and their transmission by exosomes leads to pathogenic lesions and problems in other parts of the body.
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Affiliation(s)
- Nazanin Joudaki
- Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Ali Khodadadi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Marziye Shamshiri
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sajad Dehnavi
- Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Asadirad
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Moustafa HAM, Elsakka EGE, Abulsoud AI, Elshaer SS, Rashad AA, El-Dakroury WA, Sallam AAM, Rizk NI, Zaki MB, Gomaa RM, Elesawy AE, Mohammed OA, Abdel Mageed SS, Eleragi AMS, ElBoghdady JA, El-Fayoumi SH, Abdel-Reheim MA, Doghish AS. The miRNA Landscape in Crohn's disease: Implications for novel therapeutic approaches and interactions with Existing therapies. Exp Cell Res 2024; 442:114234. [PMID: 39233267 DOI: 10.1016/j.yexcr.2024.114234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/25/2024] [Accepted: 09/01/2024] [Indexed: 09/06/2024]
Abstract
MicroRNAs (miRNAs), which are non-coding RNAs consisting of 18-24 nucleotides, play a crucial role in the regulatory pathways of inflammatory diseases. Several recent investigations have examined the potential role of miRNAs in forming Crohn's disease (CD). It has been suggested that miRNAs serve as diagnostics for both fibrosis and inflammation in CD due to their involvement in the mechanisms of CD aggravation and fibrogenesis. More information on CD pathophysiology could be obtained by identifying the miRNAs concerned with CD and their target genes. These findings have prompted several in vitro and in vivo investigations into the putative function of miRNAs in CD treatment. Although there are still many unanswered questions, the growing body of evidence has brought miRNA-based therapy one step closer to clinical practice. This extensive narrative study offers a concise summary of the most current advancements in CD. We go over what is known about the diagnostic and therapeutic benefits of miRNA mimicry and inhibition so far, and we see what additional miRNA family targets could be useful for treating CD-related inflammation and fibrosis.
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Affiliation(s)
- Hebatallah Ahmed Mohamed Moustafa
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Shereen Saeid Elshaer
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Department of Biochemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo 11823, Egypt
| | - Ahmed A Rashad
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Al-Aliaa M Sallam
- epartment of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Nehal I Rizk
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mohamed Bakr Zaki
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt
| | - Rania M Gomaa
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr City, Cairo P.O. Box 11829, Egypt
| | - Ahmed E Elesawy
- epartment of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Ali M S Eleragi
- Department of Microorganisms and Clinical Parasitology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia
| | - Jasmine A ElBoghdady
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Shaimaa H El-Fayoumi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | | | - Ahmed S Doghish
- epartment of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt; Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
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12
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Kumar P, Kedia S, Ahuja V. Target potential of miRNAs in ulcerative colitis: what do we know? Expert Opin Ther Targets 2024; 28:829-841. [PMID: 39307951 DOI: 10.1080/14728222.2024.2408423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 09/27/2024]
Abstract
INTRODUCTION The global rise in ulcerative colitis (UC) incidence highlights the urgent need for enhanced diagnostic and therapeutic strategies. Recent advances in genome-wide association studies (GWAS) have identified genetic loci associated with UC, providing insights into the disease's molecular mechanisms, including immune modulation, mucosal defense, and epithelial barrier function. Despite these findings, many GWAS signals are located in non-coding regions and are linked to low risk, suggesting that protein-coding genes alone do not fully explain UC's pathophysiology. Emerging research emphasizes the potential of microRNAs (miRNAs) as biomarkers and therapeutic targets due to their crucial role in UC. This review explores the current understanding of miRNAs in UC, including their mechanisms of action and their potential as both biomarkers and therapeutic targets. The present review provides the latest update on their potential as a biomarker and therapeutic target. AREAS COVERED This review synthesizes an extensive literature search on miRNAs in UC, focusing on their roles in the mucosal barrier, innate and adaptive immunity, and their potential applications as biomarkers and therapeutic modalities. EXPERT OPINION While miRNAs present promising opportunities as biomarkers and novel therapeutic agents in UC, challenges in validation, specificity, delivery, and clinical application need to be addressed through rigorous, large-scale studies.
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Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
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13
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Ramadan YN, Kamel AM, Medhat MA, Hetta HF. MicroRNA signatures in the pathogenesis and therapy of inflammatory bowel disease. Clin Exp Med 2024; 24:217. [PMID: 39259390 PMCID: PMC11390904 DOI: 10.1007/s10238-024-01476-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 08/20/2024] [Indexed: 09/13/2024]
Abstract
Inflammatory bowel disease (IBD) is a persistent inflammatory illness of the gastrointestinal tract (GIT) triggered by an inappropriate immune response to environmental stimuli in genetically predisposed persons. Unfortunately, IBD patients' quality of life is negatively impacted by the symptoms associated with the disease. The exact etiology of IBD pathogenesis is not fully understood, but the emerging research indicated that the microRNA (miRNA) plays an important role. miRNAs have been documented to possess a significant role in regulating pro- and anti-inflammatory pathways, in addition to their roles in several physiological processes, including cell growth, proliferation, and apoptosis. Variations in the miRNA profiles might be a helpful prognostic indicator and a valuable tool in the differential diagnosis of IBD. Most interestingly, these miRNAs have a promising therapeutic target in several pre-clinical animal studies and phase 2 clinical studies to alleviate inflammation and improve patient's quality of life. This comprehensive review discusses the current knowledge about the significant physiological role of different miRNAs in the health of the intestinal immune system and addresses the role of the most relevant differentially expressed miRNAs in IBD, identify their potential targets, and emphasize their diagnostic and therapeutic potential for future research.
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Affiliation(s)
- Yasmin N Ramadan
- Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut, 71515, Egypt.
| | - Ayat M Kamel
- Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut, 71515, Egypt
| | - Mohammed A Medhat
- Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt
| | - Helal F Hetta
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, 71491, Tabuk, Saudi Arabia
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14
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Marini S, Huber A, Cash MN, Salemi M, Cook RL, Borsa P, Mavian CN. Oral Cannabidiol Treatment Is Associated with an Anti-Inflammatory Gene Expression Signature in Myeloid Cells of People Living with HIV. Cannabis Cannabinoid Res 2024; 9:1028-1037. [PMID: 38252549 DOI: 10.1089/can.2023.0139] [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] [Indexed: 01/24/2024] Open
Abstract
Introduction: HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning of this effect are not well investigated. Our main objective is to detect gene expression alterations in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least 1 month of CBD treatment. Materials and Methods: We analyzed ∼41,000 PBMCs from three PLWH at baseline and after CBD treatment (27-60 days) through single-cell RNA sequencing. Results: We obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells. Conclusions: Our study shows how CBD is associated with alterations of gene expression in myeloid cells after CBD treatment. Clinical Trial Registration: NCT05209867.
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Affiliation(s)
- Simone Marini
- Department of Epidemiology, University of Florida, Gainesville, Florida, USA
- Department of Pathology, University of Florida, Gainesville, Florida, USA
| | - Amanda Huber
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA
| | - Melanie N Cash
- Department of Pathology, University of Florida, Gainesville, Florida, USA
- Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA
| | - Marco Salemi
- Department of Pathology, University of Florida, Gainesville, Florida, USA
- Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA
| | - Robert L Cook
- Department of Epidemiology, University of Florida, Gainesville, Florida, USA
- Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA
| | - Paul Borsa
- Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA
| | - Carla N Mavian
- Department of Pathology, University of Florida, Gainesville, Florida, USA
- Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA
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Israni DK, Patel ML, Dodiya RK. Exploring the versatility of miRNA-128: a comprehensive review on its role as a biomarker and therapeutic target in clinical pathways. Mol Biol Rep 2024; 51:860. [PMID: 39068606 DOI: 10.1007/s11033-024-09822-w] [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: 05/14/2024] [Accepted: 07/23/2024] [Indexed: 07/30/2024]
Abstract
MicroRNAs (miRNAs/ miRs) are short, noncoding RNAs, usually consisting of 18 to 24 nucleotides, that control gene expression after the process of transcription and have crucial roles in several clinical processes. This article seeks to provide an in-depth review and evaluation of the many activities of miR-128, accentuating its potential as a versatile biomarker and target for therapy; The circulating miR-128 has garnered interest because of its substantial influence on gene regulation and its simplicity in extraction. Several miRNAs, such as miR-128, have been extracted from circulating blood cells, cerebrospinal fluid, and plasma/serum. The miR-128 molecule can specifically target a diverse range of genes, enabling it to have intricate physiological impacts by concurrently regulating many interrelated pathways. It has a vital function in several biological processes, such as modulating the immune system, regulating brain plasticity, organizing the cytoskeleton, and inducing neuronal death. In addition, miR-128 modulates genes associated with cell proliferation, the cell cycle, apoptosis, plasma LDL levels, and gene expression regulation in cardiac development. The dysregulation of miR-128 expression and activity is associated with the development of immunological responses, changes in neural plasticity, programmed cell death, cholesterol metabolism, and heightened vulnerability to autoimmune illnesses, neuroimmune disorders, cancer, and cardiac problems; The paper highlights the importance of studying the consequences of miR-128 dysregulation in these specific locations. By examining the implications of miRNA-128 dysregulation in these areas, the article underscores its significance in diagnosis and treatment, providing a foundation for research and clinical applications.
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Affiliation(s)
- Dipa K Israni
- Department of Pharmacology, L.J. Institute of Pharmacy, LJ University, SG Highway, Sanand Cross-Road, Ahmedabad, Gujarat, 382210, India.
| | - Manish L Patel
- LJ Institute of Pharmacy, LJ University, Ahmedabad, Gujarat, India
| | - Rohinee K Dodiya
- Department of Pharmacology, L.J. Institute of Pharmacy, LJ University, SG Highway, Sanand Cross-Road, Ahmedabad, Gujarat, 382210, India
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16
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Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers. Biomedicines 2024; 12:1520. [PMID: 39062093 PMCID: PMC11274502 DOI: 10.3390/biomedicines12071520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/30/2024] [Accepted: 07/06/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.
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Affiliation(s)
- Antonio Mestrovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Nikola Perkovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Dorotea Bozic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
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Hong SM, Baek DH. Diagnostic Procedures for Inflammatory Bowel Disease: Laboratory, Endoscopy, Pathology, Imaging, and Beyond. Diagnostics (Basel) 2024; 14:1384. [PMID: 39001273 PMCID: PMC11241288 DOI: 10.3390/diagnostics14131384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 06/26/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024] Open
Abstract
Diagnosing inflammatory bowel disease (IBD) can often be challenging, and differentiating between Crohn's disease and ulcerative colitis can be particularly difficult. Diagnostic procedures for IBD include laboratory tests, endoscopy, pathological tests, and imaging tests. Serological and stool tests can be easily performed in an outpatient setting and provide critical diagnostic clues. Although endoscopy is an invasive procedure, it offers essential diagnostic information and allows for tissue biopsy and therapeutic procedures. Video capsule endoscopy and device-assisted enteroscopy are endoscopic procedures used to evaluate the small bowel. In addition to endoscopy, magnetic resonance imaging, computed tomography, and ultrasound (US) are valuable tools for small bowel assessment. Among these, US is noninvasive and easily utilized, making its use highly practical in daily clinical practice. Endoscopic biopsy aids in the diagnosis of IBD and is crucial for assessing the histological activity of the disease, facilitating a thorough evaluation of disease remission, and aiding in the development of treatment strategies. Recent advances in artificial intelligence hold promise for enhancing various aspects of IBD management, including diagnosis, monitoring, and precision medicine. This review compiles current procedures and promising future tools for the diagnosis of IBD, providing comprehensive insights.
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Affiliation(s)
- Seung Min Hong
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Dong Hoon Baek
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
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Oliveira ECSD, Quaglio AEV, Grillo TG, Di Stasi LC, Sassaki LY. MicroRNAs in inflammatory bowel disease: What do we know and what can we expect? World J Gastroenterol 2024; 30:2184-2190. [PMID: 38690020 PMCID: PMC11056918 DOI: 10.3748/wjg.v30.i16.2184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 02/09/2024] [Accepted: 03/19/2024] [Indexed: 04/26/2024] Open
Abstract
MicroRNAs (miRNAs), small non-coding RNAs composed of 18-24 nucleotides, are potent regulators of gene expression, contributing to the regulation of more than 30% of protein-coding genes. Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells, there is an interest in exploring their importance in inflammatory bowel disease (IBD). IBD is a chronic and multifactorial disease of the gastrointestinal tract; the main forms are Crohn's disease and ulcerative colitis. Several studies have investigated the dysregulated expression of miRNAs in IBD, demonstrating their important roles as regulators and potential biomarkers of this disease. This editorial presents what is known and what is expected regarding miRNAs in IBD. Although the important regulatory roles of miRNAs in IBD are clearly established, biomarkers for IBD that can be applied in clinical practice are lacking, emphasizing the importance of further studies. Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.
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Affiliation(s)
| | | | - Thais Gagno Grillo
- Department of Internal Medicine, Medical School, São Paulo State University (Unesp), Botucatu 18618-686, São Paulo, Brazil
| | - Luiz Claudio Di Stasi
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, São Paulo State University (Unesp), Botucatu 18618-686, São Paulo, Brazil
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de Síbia CDF, Quaglio AEV, de Oliveira ECS, Pereira JN, Ariede JR, Lapa RML, Severino FE, Reis PP, Sassaki LY, Saad-Hossne R. microRNA-mRNA Networks Linked to Inflammation and Immune System Regulation in Inflammatory Bowel Disease. Biomedicines 2024; 12:422. [PMID: 38398024 PMCID: PMC10886709 DOI: 10.3390/biomedicines12020422] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/29/2023] [Accepted: 12/02/2023] [Indexed: 02/25/2024] Open
Abstract
UNLABELLED The molecular processes linked to the development and progression of Crohn's disease (CD) and ulcerative colitis (UC) are not completely understood. MicroRNAs (miRNAs) regulate gene expression and are indicated as diagnostic, prognostic, and predictive biomarkers in chronic degenerative diseases. Our objectives included the identification of global miRNA expression in CD and UC, as well as miRNA target genes, miRNA-mRNA interaction networks, and biological functions associated with these different forms of inflammatory bowel disease (IBD). METHODS By performing a comprehensive meta-analysis, we integrated miRNA expression data from nine studies in IBD. We obtained detailed information on significantly deregulated miRNAs (fold change, FC ≥ 2 and p < 0.05), sample type and number, and platform applied for analysis in the training and validation sets. Further bioinformatic analyses were performed to identify miRNA target genes, by using the microRNA Data Integration Portal tool. We also sought to identify statistically enriched pathways of genes regulated by miRNAs using ToppGene Suite. Additional analyses were performed to filter for genes expressed in intestinal tissue using the European Bioinformatics Institute (EBI) database. RESULTS Our findings showed the upregulation of 15 miRNAs in CD and 33 in UC. Conversely, six miRNAs were downregulated in CD, while seven were downregulated in UC. These results indicate a greater deregulation of miRNAs in UC compared to CD. Of note, miRNA target genes were enriched for immune system regulation pathways. Among significantly deregulated miRNAs with a higher number of miRNA-target gene interactions, we identified miR-199a-5p and miR-362-3p altered in CD, while among UC case patients, miRNA-target gene interactions were higher for miR-155-5p. CONCLUSIONS The identified miRNAs play roles in regulating genes associated with immune system regulation and inflammation in IBD. Such miRNAs and their target genes have the potential to serve as clinically relevant biomarkers. These findings hold promise for enhancing the accuracy of diagnoses and facilitating the development of personalized treatment strategies for individuals with various forms of IBD.
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Affiliation(s)
- Carina de F. de Síbia
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
| | - Ana E. V. Quaglio
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18607-440, SP, Brazil;
| | - Ellen C. S. de Oliveira
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (J.N.P.); (L.Y.S.)
| | - Jéssica N. Pereira
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (J.N.P.); (L.Y.S.)
| | - Jovita R. Ariede
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
- Experimental Research Unity (UNIPEX), Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
| | - Rainer M. L. Lapa
- Facultad de Ingeniería Zootecnista, Agronegocios y Biotecnología, Instituto de Investigación en Ganadería y Biotecnología, Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas, Chachapoyas 01001, Peru;
- Facultad de Ciencias de la Salud, Instituto de Investigación de Salud Integral Intercultural, Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas, Chachapoyas 01001, Peru
| | - Fábio E. Severino
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
- Experimental Research Unity (UNIPEX), Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
| | - Patricia P. Reis
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
- Experimental Research Unity (UNIPEX), Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
| | - Lígia Y. Sassaki
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (J.N.P.); (L.Y.S.)
| | - Rogerio Saad-Hossne
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (C.d.F.d.S.); (J.R.A.); (F.E.S.); (P.P.R.)
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20
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Pratscher B, Kuropka B, Csukovich G, Doulidis PG, Spirk K, Kramer N, Freund P, Rodríguez-Rojas A, Burgener IA. Traces of Canine Inflammatory Bowel Disease Reflected by Intestinal Organoids. Int J Mol Sci 2024; 25:576. [PMID: 38203746 PMCID: PMC10778911 DOI: 10.3390/ijms25010576] [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: 10/11/2023] [Revised: 12/12/2023] [Accepted: 12/14/2023] [Indexed: 01/12/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects humans and several domestic animal species, including cats and dogs. In this study, we have analyzed duodenal organoids derived from canine IBD patients using quantitative proteomics. Our objective was to investigate whether these organoids show phenotypic traits of the disease compared with control organoids obtained from healthy donors. To this aim, IBD and control organoids were subjected to quantitative proteomics analysis via liquid chromatography-mass spectrometry. The obtained data revealed notable differences between the two groups. The IBD organoids exhibited several alterations at the levels of multiple proteins that are consistent with some known IBD alterations. The observed phenotype in the IBD organoids to some degree mirrors the corresponding intestinal condition, rendering them a compelling approach for investigating the disease and advancing drug exploration. Additionally, our study revealed similarities to some human IBD biomarkers, further emphasizing the translational and comparative value of dogs for future investigations related to the causes and treatment of IBD. Relevant proteins such as CALU, FLNA, MSN and HMGA2, which are related to intestinal diseases, were all upregulated in the IBD duodenal organoids. At the same time, other proteins such as intestinal keratins and the mucosal immunity PIGR were depleted in these IBD organoids. Based on these findings, we propose that these organoids could serve as a valuable tool for evaluating the efficacy of therapeutic interventions against canine IBD.
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Affiliation(s)
- Barbara Pratscher
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
| | - Benno Kuropka
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany;
| | - Georg Csukovich
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
| | - Pavlos G. Doulidis
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
| | - Katrin Spirk
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
| | - Nina Kramer
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
| | - Patricia Freund
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
| | - Alexandro Rodríguez-Rojas
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
| | - Iwan A. Burgener
- Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria; (B.P.); (G.C.); (P.G.D.); (K.S.); (P.F.)
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21
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Yan L, Gu C, Gao S, Wei B. Epigenetic regulation and therapeutic strategies in ulcerative colitis. Front Genet 2023; 14:1302886. [PMID: 38169708 PMCID: PMC10758477 DOI: 10.3389/fgene.2023.1302886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/07/2023] [Indexed: 01/05/2024] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease, and is characterized by the diffuse inflammation and ulceration in the colon and rectum mucosa, even extending to the caecum. Epigenetic modifications, including DNA methylations, histone modifications and non-coding RNAs, are implicated in the differentiation, maturation, and functional modulation of multiple immune and non-immune cell types, and are influenced and altered in various chronic inflammatory diseases, including UC. Here we review the relevant studies revealing the differential epigenetic features in UC, and summarize the current knowledge about the immunopathogenesis of UC through epigenetic regulation and inflammatory signaling networks, regarding DNA methylation, histone modification, miRNAs and lncRNAs. We also discuss the epigenetic-associated therapeutic strategies for the alleviation and treatment of UC, which will provide insights to intervene in the immunopathological process of UC in view of epigenetic regulation.
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Affiliation(s)
- Liwei Yan
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China
- Departments of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Chao Gu
- Departments of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shanyu Gao
- Departments of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Benzheng Wei
- Center for Medical Artificial Intelligence, Shandong University of Traditional Chinese Medicine, Jinan, China
- Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
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22
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Yan R, Liang X, Hu J. miR-141-3p alleviates ulcerative colitis by targeting SUGT1 to inhibit colonic epithelial cell pyroptosis. Autoimmunity 2023; 56:2220988. [PMID: 37317573 DOI: 10.1080/08916934.2023.2220988] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 05/11/2023] [Accepted: 05/28/2023] [Indexed: 06/16/2023]
Abstract
Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the colon that result in the destruction and inflammation of the colonic mucosa. Current research has established a strong correlation between pyroptosis of colonic epithelial cells and the onset and progression of UC. In addition, miRNAs have been implicated in the development and progression of UC and pyroptosis. This aimed of this study was to identify specific miRNAs that could inhibit pyroptosis in colon epithelial cells and alleviate UC. Lipopolysaccharide (LPS) was used to induce inflammation in FHC normal colonic epithelial cells to construct an enteritis cell model and downregulated expression levels of miRNAs were detected in inflammatory bowel disease mucosal tissue model. Pyroptosis indicators were detected using Cell Counting Kit-8, flow cytometry, ELISA, qPCR, western blot, and immunofluorescence, and miRNA target genes were predicted by miRDB, TargetScan, pyroptosis pathway from KEGG, and double luciferase assay was used for verification. The effect of miR-141-3p on colitis was observed in the mouse DSS colitis model. The results showed that miR-141-3p was the most significantly downregulated miRNA in LPS-induced FHC cells, and promoted the proliferation of LPS-induced FHC cells and suppressed their apoptosis. In addition, miR-141-3p decreased the expression of pyroptosis-related proteins such as NLRP3, caspase-1, N-GSDMD, and the other proteins, as well as the release of IL-18 and IL-1β inflammatory factors. Conversely, the miR-141-3p inhibitor promoted LPS-induced FHC pyroptosis. Dual luciferase experiments confirmed that miR-141-3p could target the HSP90 molecular chaperone SUGT1. Further experiments demonstrated that SUGT1 overexpression could restore the inhibitory effect of miR-141-3p on pyroptosis, while SUGT1 knockdown could alleviate the promotion of pyroptosis induced by miR-141-3p inhibitor. Furthermore, miR-141-3p alleviated the inflammatory phenotype of mouse colonic mucosa in the mouse DSS colitis model. Therefore, miR-141-3p inhibits LPS-induced pyroptosis of colonic epithelial cells by targeting SUGT1. miR-141-3p could also alleviate DSS-induced colitis in mice, suggesting that miR-141-3p may become a nucleic acid drug for the treatment of UC.
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Affiliation(s)
- Rong Yan
- The Fourth Affiliated Hospital of Guangzhou Medical University (Zengcheng District people's Hospital of Guangzhou)
| | - Xinghua Liang
- The Fourth Affiliated Hospital of Guangzhou Medical University (Zengcheng District people's Hospital of Guangzhou)
| | - Juan Hu
- The Fourth Affiliated Hospital of Guangzhou Medical University (Zengcheng District people's Hospital of Guangzhou)
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23
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Steigleder KM, Pascoal LB, Siqueira NSN, Simino LADP, Ayrizono MDLS, Ferreira MM, Fagundes JJ, Azevedo ATD, Torsoni AS, Leal RF. Mathematical Models Including microRNA Levels of Mesenteric Adipose Tissue May Predict Postoperative Relapse in Crohn's Disease Patients. GASTRO HEP ADVANCES 2023; 3:17-30. [PMID: 39132178 PMCID: PMC11307883 DOI: 10.1016/j.gastha.2023.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 08/21/2023] [Indexed: 08/13/2024]
Abstract
Background and Aims Recent evidence suggests that the mesenteric adipose tissue (MAT) near the affected intestine may play a role in Crohn's disease (CD) pathophysiology. Modulation of several transcripts has already been identified in the MAT of CD in the literature. Therefore, our aim was to validate the microRNA (miRNA) transcript levels and their target genes in the MAT of active CD patients and correlate them with clinical and epidemiological data. Methods Samples from the MAT of surgical specimens from 25 active CD patients were obtained. The control group comprised fifteen patients who underwent surgery for other diseases, except inflammatory bowel diseases. Transcriptional levels of miRNA and their target genes were assessed by quantitative real-time polymerase chain reaction. The correlation between transcripts and clinical characteristics was obtained using multiple linear regression. The mathematical models (M) underwent a statistical filter to ensure robustness and reliability (P value < .05; adjusted R-squared (Rˆ2)> .99; correct predictions of more than 60%). Results miRNA-650 and miRNA-29c were upregulated in the MAT of CD compared to the control group (P < .0001 and P = .0032, respectively), besides presenting decreased levels of their target genes. Two were target genes of the miRNA-650: glutamine-fructose-6-phosphate transaminase 2 (P = .012) and aldehyde dehydrogenase 4 family (P = .0035); and 4 were targets of the miRNA-29c: cell death-inducing DFFA-like effector c (P = .001), E2F transcription factor-1 (P = .007), hypoxia-inducible factor 3 subunit alpha (P = .0029), and pyruvate dehydrogenase kinase 4 (P = .0054). We found 2 M with statistical strength and robustness. The performance test identified one model with 100% accuracy for predicting the month of recurrence and determining patients with less risk of early relapse after surgery. Conclusion We demonstrate that miRNA-650 and miRNA-29c and some of their target genes, besides clinical and epidemiological variables, may be useful in a model to predict when disease relapse may occur in CD patients who underwent surgery. These findings constitute a potential tool to guide postoperative clinical management.
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Affiliation(s)
- Karine Mariane Steigleder
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Lívia Bitencourt Pascoal
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Natália Souza Nunes Siqueira
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Laís Angélica de Paula Simino
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Marciane Milanski Ferreira
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
| | - João José Fagundes
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Aníbal Tavares de Azevedo
- Simulation Laboratory, School of Applied Sciences, University of Campinas (Unicamp), Limeira, Brazil
| | - Adriana Souza Torsoni
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
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24
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Caliendo G, D'Elia G, Makker J, Passariello L, Albanese L, Molinari AM, Vietri MT. Biological, genetic and epigenetic markers in ulcerative colitis. Adv Med Sci 2023; 68:386-395. [PMID: 37813048 DOI: 10.1016/j.advms.2023.09.010] [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: 11/17/2022] [Revised: 04/15/2023] [Accepted: 09/18/2023] [Indexed: 10/11/2023]
Abstract
In this review, we have summarized the existing knowledge of ulcerative colitis (UC) markers based on current literature, specifically, the roles of potential new biomarkers, such as circulating, fecal, genetic, and epigenetic alterations, in UC onset, disease activity, and in therapy response. UC is a complex multifactorial inflammatory disease. There are many invasive and non-invasive diagnostic methods in UC, including several laboratory markers which are employed in diagnosis and disease assessment; however, colonoscopy remains the most widely used method. Common laboratory abnormalities currently used in the clinical practice include inflammation-induced alterations, serum autoantibodies, and antibodies against bacterial antigens. Other new serum and fecal biomarkers are supportive in diagnosis and monitoring disease activity and therapy response; and potential salivary markers are currently being evaluated as well. Several UC-related genetic and epigenetic alterations are implied in its pathogenesis and therapeutic response. Moreover, the use of artificial intelligence in the integration of laboratory biomarkers and big data could potentially be useful in clinical translation and precision medicine in UC management.
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Affiliation(s)
- Gemma Caliendo
- Unity of Clinical and Molecular Pathology, AOU University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giovanna D'Elia
- Unity of Clinical and Molecular Pathology, AOU University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Jasmine Makker
- Department of GKT School of Medical Education, King's College London, London, UK
| | - Luana Passariello
- Unity of Clinical and Molecular Pathology, AOU University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Luisa Albanese
- Unity of Clinical and Molecular Pathology, AOU University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Anna Maria Molinari
- Unity of Clinical and Molecular Pathology, AOU University of Campania "Luigi Vanvitelli", Naples, Italy; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Teresa Vietri
- Unity of Clinical and Molecular Pathology, AOU University of Campania "Luigi Vanvitelli", Naples, Italy; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
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25
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Liu H, Shen L, Zhao H, Yang J, Huang D. Parkinson's disease patients combined with constipation tend to have higher serum expression of microRNA 29c, prominent neuropsychiatric disorders, possible RBD conversion, and a substandard quality of life. Neurol Sci 2023; 44:3141-3150. [PMID: 37067722 DOI: 10.1007/s10072-023-06793-x] [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: 02/23/2023] [Accepted: 04/02/2023] [Indexed: 04/18/2023]
Abstract
INTRODUCTION The symptom of constipation has been confirmed as an early diagnose criteria for Parkinson's disease (PD). Furthermore, evidences suggest that pathogenesis of PD initiates in gut, rather than brain. If so, identifying biomarkers for constipation in PD might have potentials to assist early diagnosis and initial treatment. METHOD We first identified that microRNA 29c (miR-29c) was dysregulated both in PD and constipation patients through bioinformatics analysis. Then, serological analysis of the expression of miR-29c in 67 PD patients with constipation (PD-C), 51 PD patients without constipation (PD-NC), and 50 healthy controls (HC) was carried out by qPCR. Demographic and clinical features were also compared. Patients in PD-C group were further classified into two groups: those with prodromal stage constipation (PD-C-Pro) (n = 36) and those with clinical stage constipation (PD-C-Clinic) (n = 31), to explore their different characteristics. RESULTS The levels of miR-29c in PD-C group were higher than that in PD-NC group, both higher than HC group. PD-C-Pro group's miR-29c levels were statistically higher compared with PD-C-Clinic group's. What is more, PD-C group had higher scores of MDS-UPDRS-I, NMSS, NMSS3, NMSS4, NMSS6, NMSS9, SCOPA-AUT, HAMD, HAMA, RBDSQ, CSS, and PACQOL compared with PD-NC party. Relative to the PD-C-Clinic, patients in PD-C-Pro group had higher MDS-UPDRS-I, NMSS, NMSS3, HAMD, and HAMA scores, and were more likely to have RBD. CONCLUSION Our results indicated that miR-29c seems to be an underlying cause for developing constipation in patients with PD and PD-C identifies a group of patients with more severe non-motor impairment, prominent neuropsychiatric disorders, and possible RBD conversion as well as a substandard quality of life. We further confirmed that there is a close relationship between symptoms representing the same pathological origin, especially constipation and RBD.
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Affiliation(s)
- Hong Liu
- Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
| | - Lei Shen
- Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Haonan Zhao
- Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Jie Yang
- Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Dongya Huang
- Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
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26
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Margiana R, Kzar HH, Hussam F, Hameed NM, Al-Qaim ZH, Al-Gazally ME, Kandee M, Saleh MM, Toshbekov BBU, Tursunbaev F, Karampoor S, Mirzaei R. Exploring the impact of miR-128 in inflammatory diseases: A comprehensive study on autoimmune diseases. Pathol Res Pract 2023; 248:154705. [PMID: 37499519 DOI: 10.1016/j.prp.2023.154705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 07/19/2023] [Accepted: 07/19/2023] [Indexed: 07/29/2023]
Abstract
microRNAs (miRNAs) play a crucial role in various biological processes, including immune system regulation, such as cell proliferation, tolerance (central and peripheral), and T helper cell development. Dysregulation of miRNA expression and activity can disrupt immune responses and increase susceptibility to neuroimmune disorders. Conversely, miRNAs have been shown to have a protective role in modulating immune responses and preventing autoimmunity. Specifically, reducing the expression of miRNA-128 (miR-128) in an Alzheimer's disease (AD) mouse model has been found to improve cognitive deficits and reduce neuropathology. This comprehensive review focuses on the significance of miR-128 in the pathogenesis of neuroautoimmune disorders, including multiple sclerosis (MS), AD, Parkinson's disease (PD), Huntington's disease (HD), epilepsy, as well as other immune-mediated diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Additionally, we present compelling evidence supporting the potential use of miR-128 as a diagnostic or therapeutic biomarker for neuroimmune disorders. Collectively, the available literature suggests that targeting miR-128 could be a promising strategy to alleviate the behavioral symptoms associated with neuroimmune diseases. Furthermore, further research in this area may uncover new insights into the molecular mechanisms underlying these disorders and potentially lead to the development of novel therapeutic approaches.
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Affiliation(s)
- Ria Margiana
- Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Master's Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Hamzah H Kzar
- Veterinary Medicine College, Al-Qasim Green University, Al-Qasim, Iraq
| | - Fadhil Hussam
- College of Medical Technology, Medical Lab Techniques, Al-farahidi University, Iraq
| | - Noora M Hameed
- Anesthesia Techniques, Al-Nisour University College, Iraq
| | | | | | - Mahmoud Kandee
- Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Hofuf 31982, Al-Ahsa, Saudi Arabia; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University, Kafrelshikh 33516, Egypt
| | - Marwan Mahmood Saleh
- Department of Biophysics, College of Applied Sciences, University Of Anbar, Anbar, Iraq
| | | | - Farkhod Tursunbaev
- MD, Independent Researcher, "Medcloud" educational centre, Tashkent, Uzbekistan
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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27
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Datta N, Johnson C, Kao D, Gurnani P, Alexander C, Polytarchou C, Monaghan TM. MicroRNA-based therapeutics for inflammatory disorders of the microbiota-gut-brain axis. Pharmacol Res 2023; 194:106870. [PMID: 37499702 DOI: 10.1016/j.phrs.2023.106870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 07/22/2023] [Accepted: 07/24/2023] [Indexed: 07/29/2023]
Abstract
An emerging but less explored shared pathophysiology across microbiota-gut-brain axis disorders is aberrant miRNA expression, which may represent novel therapeutic targets. miRNAs are small, endogenous non-coding RNAs that are important transcriptional repressors of gene expression. Most importantly, they regulate the integrity of the intestinal epithelial and blood-brain barriers and serve as an important communication channel between the gut microbiome and the host. A well-defined understanding of the mode of action, therapeutic strategies and delivery mechanisms of miRNAs is pivotal in translating the clinical applications of miRNA-based therapeutics. Accumulating evidence links disorders of the microbiota-gut-brain axis with a compromised gut-blood-brain-barrier, causing gut contents such as immune cells and microbiota to enter the bloodstream leading to low-grade systemic inflammation. This has the potential to affect all organs, including the brain, causing central inflammation and the development of neurodegenerative and neuropsychiatric diseases. In this review, we have examined in detail miRNA biogenesis, strategies for therapeutic application, delivery mechanisms, as well as their pathophysiology and clinical applications in inflammatory gut-brain disorders. The research data in this review was drawn from the following databases: PubMed, Google Scholar, and Clinicaltrials.gov. With increasing evidence of the pathophysiological importance for miRNAs in microbiota-gut-brain axis disorders, therapeutic targeting of cross-regulated miRNAs in these disorders displays potentially transformative and translational potential. Further preclinical research and human clinical trials are required to further advance this area of research.
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Affiliation(s)
- Neha Datta
- School of Medicine, University of Nottingham, Nottingham, UK
| | - Charlotte Johnson
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Dina Kao
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Pratik Gurnani
- Division of Molecular Therapeutics & Formulation, School of Pharmacy, University of Nottingham, Nottingham, UK
| | - Cameron Alexander
- Division of Molecular Therapeutics & Formulation, School of Pharmacy, University of Nottingham, Nottingham, UK
| | - Christos Polytarchou
- Department of Biosciences, John van Geest Cancer Research Centre, School of Science & Technology, Nottingham Trent University, Nottingham, UK.
| | - Tanya M Monaghan
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.
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Alfaifi J, Germain A, Heba AC, Arnone D, Gailly L, Ndiaye NC, Viennois E, Caron B, Peyrin-Biroulet L, Dreumont N. Deep Dive Into MicroRNAs in Inflammatory Bowel Disease. Inflamm Bowel Dis 2023; 29:986-999. [PMID: 36545755 DOI: 10.1093/ibd/izac250] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Indexed: 06/02/2023]
Abstract
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is thought to develop in genetically predisposed individuals as a consequence of complex interactions between dysregulated inflammatory stimuli, immunological responses, and environmental factors. The pathogenesis of IBD has yet to be fully understood. The global increase in the incidence of IBD suggests a gap in the current understanding of the disease. The development of a new diagnostic tool for inflammatory bowel disease that is both less invasive and more cost-effective would allow for better management of this condition. MicroRNAs (miRNAs) are a class of noncoding RNAs with important roles as posttranscriptional regulators of gene expression, which has led to new insights into understanding IBD. Using techniques such as microarrays and real-time polymerase chain reactions, researchers have investigated the patterns in which patients with Crohn's disease and ulcerative colitis show alterations in the expression of miRNA in tissue, blood, and feces. These miRNAs are found to be differentially expressed in IBD and implicated in its pathogenesis through alterations in autophagy, intestinal barrier, and immune homeostasis. In this review, we discuss the miRNA expression profiles associated with IBD in tissue, peripheral blood, and feces and provide an overview of the miRNA mechanisms involved in IBD.
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Affiliation(s)
- Jaber Alfaifi
- Department of Hepatobiliary, Colorectal, and Digestive Surgery, Nancy University Hospital, University of Lorraine, Nancy, France
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Adeline Germain
- Department of Hepatobiliary, Colorectal, and Digestive Surgery, Nancy University Hospital, University of Lorraine, Nancy, France
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Anne-Charlotte Heba
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Djésia Arnone
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Laura Gailly
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Ndeye Coumba Ndiaye
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Emilie Viennois
- INSERM U1149, Center of Research on Inflammation, Université de Paris, Paris, France
| | - Bénédicte Caron
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
- Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Nancy, France
| | - Laurent Peyrin-Biroulet
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
- Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Nancy, France
| | - Natacha Dreumont
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
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Oliveira ECSD, Quaglio AEV, Magro DO, Di Stasi LC, Sassaki LY. Intestinal Microbiota and miRNA in IBD: A Narrative Review about Discoveries and Perspectives for the Future. Int J Mol Sci 2023; 24:ijms24087176. [PMID: 37108339 PMCID: PMC10138604 DOI: 10.3390/ijms24087176] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/04/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC) and comprises a chronic gastrointestinal tract disorder characterized by hyperactive and dysregulated immune responses to environmental factors, including gut microbiota and dietary components. An imbalance of the intestinal microbiota may contribute to the development and/or worsening of the inflammatory process. MicroRNAs (miRNAs) have been associated with various physiological processes, such as cell development and proliferation, apoptosis, and cancer. In addition, they play an important role in inflammatory processes, acting in the regulation of pro- and anti-inflammatory pathways. Differences in the profiles of miRNAs may represent a useful tool in the diagnosis of UC and CD and as a prognostic marker in both diseases. The relationship between miRNAs and the intestinal microbiota is not completely elucidated, but recently this topic has gained prominence and has become the target of several studies that demonstrate the role of miRNAs in the modulation of the intestinal microbiota and induction of dysbiosis; the microbiota, in turn, can regulate the expression of miRNAs and, consequently, alter the intestinal homeostasis. Therefore, this review aims to describe the interaction between the intestinal microbiota and miRNAs in IBD, recent discoveries, and perspectives for the future.
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Affiliation(s)
- Ellen Cristina Souza de Oliveira
- Department of Internal Medicine, Medical School, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-970, Brazil
| | - Ana Elisa Valencise Quaglio
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-689, Brazil
| | - Daniéla Oliveira Magro
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Sao Paulo CEP 13083-970, Brazil
| | - Luiz Claudio Di Stasi
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-689, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-970, Brazil
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30
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Innocenti T, Bigagli E, Lynch EN, Galli A, Dragoni G. MiRNA-Based Therapies for the Treatment of Inflammatory Bowel Disease: What Are We Still Missing? Inflamm Bowel Dis 2023; 29:308-323. [PMID: 35749310 DOI: 10.1093/ibd/izac122] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Indexed: 02/05/2023]
Abstract
Micro-RNAs (miRNAs) are noncoding RNAs usually 24-30 nucleotides long that play a central role in epigenetic mechanisms of inflammatory diseases and cancers. Recently, several studies have assessed the involvement of miRNAs in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated neoplasia. Particularly, it has been shown that many members of miRNAs family are involved in the pathways of inflammation and fibrogenesis of IBD; therefore, their use as inflammatory and fibrosis biomarkers has been postulated. In light of these results, the role of miRNAs in IBD therapy has been proposed and is currently under investigation with many in vitro and in vivo studies, murine models, and a phase 2a trial. The accumulating data have pushed miRNA-based therapy closer to clinical practice, although many open questions remain. With this systematic review, we discuss the current knowledge about the therapeutic effects of miRNAs mimicking and inhibition, and we explore the new potential targets of miRNA family for the treatment of inflammation and fibrosis in IBD.
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Affiliation(s)
- Tommaso Innocenti
- IBD Referral Center, Gastroenterology Department, Careggi University Hospital, Florence, Italy.,Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Elisabetta Bigagli
- Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
| | - Erica Nicola Lynch
- IBD Referral Center, Gastroenterology Department, Careggi University Hospital, Florence, Italy.,Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Gabriele Dragoni
- IBD Referral Center, Gastroenterology Department, Careggi University Hospital, Florence, Italy.,Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences "Mario Serio", University of Florence, Florence, Italy
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31
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Aggeletopoulou I, Mouzaki A, Thomopoulos K, Triantos C. miRNA Molecules-Late Breaking Treatment for Inflammatory Bowel Diseases? Int J Mol Sci 2023; 24:2233. [PMID: 36768556 PMCID: PMC9916785 DOI: 10.3390/ijms24032233] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/19/2023] [Accepted: 01/20/2023] [Indexed: 01/24/2023] Open
Abstract
MicroRNAs (miRNAs) are a group of non-coding RNAs that play a critical role in regulating epigenetic mechanisms in inflammation-related diseases. Inflammatory bowel diseases (IBDs), which primarily include ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic recurrent inflammation of intestinal tissues. Due to the multifactorial etiology of these diseases, the development of innovative treatment strategies that can effectively maintain remission and alleviate disease symptoms is a major challenge. In recent years, evidence for the regulatory role of miRNAs in the pathogenetic mechanisms of various diseases, including IBD, has been accumulating. In light of these findings, miRNAs represent potential innovative candidates for therapeutic application in IBD. In this review, we discuss recent findings on the role of miRNAs in regulating inflammatory responses, maintaining intestinal barrier integrity, and developing fibrosis in clinical and experimental IBD. The focus is on the existing literature, indicating potential therapeutic application of miRNAs in both preclinical experimental IBD models and translational data in the context of clinical IBD. To date, a large and diverse data set, which is growing rapidly, supports the potential use of miRNA-based therapies in clinical practice, although many questions remain unanswered.
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Affiliation(s)
- Ioanna Aggeletopoulou
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
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32
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Li X, Zhang M, Zhou G, Xie Z, Wang Y, Han J, Li L, Wu Q, Zhang S. Role of Rho GTPases in inflammatory bowel disease. Cell Death Dis 2023; 9:24. [PMID: 36690621 PMCID: PMC9871048 DOI: 10.1038/s41420-023-01329-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 01/08/2023] [Accepted: 01/11/2023] [Indexed: 01/24/2023]
Abstract
Rat sarcoma virus homolog (Rho) guanosine triphosphatases (GTPases) function as "molecular switch" in cellular signaling regulation processes and are associated with the pathogenesis of inflammatory bowel disease (IBD). This chronic intestinal tract inflammation primarily encompasses two diseases: Crohn's disease and ulcerative colitis. The pathogenesis of IBD is complex and considered to include four main factors and their interactions: genetics, intestinal microbiota, immune system, and environment. Recently, several novel pathogenic components have been identified. In addition, potential therapies for IBD targeting Rho GTPases have emerged and proven to be clinically effective. This review mainly focuses on Rho GTPases and their possible mechanisms in IBD pathogenesis. The therapeutic possibility of Rho GTPases is also discussed.
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Affiliation(s)
- Xiaoling Li
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Mudan Zhang
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Gaoshi Zhou
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Zhuo Xie
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Ying Wang
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Jing Han
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Li Li
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Qirui Wu
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Shenghong Zhang
- grid.12981.330000 0001 2360 039XDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
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33
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Bai L, Dermadi D, Kalesinskas L, Dvorak M, Chang SE, Ganesan A, Rubin SJS, Kuo A, Cheung P, Donato M, Utz PJ, Habtezion A, Khatri P. Mass-cytometry-based quantitation of global histone post-translational modifications at single-cell resolution across peripheral immune cells in IBD. J Crohns Colitis 2022; 17:804-815. [PMID: 36571819 PMCID: PMC10155749 DOI: 10.1093/ecco-jcc/jjac194] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND AIMS Current understanding of histone post-translational modifications (histone modifications) across immune cell types in patients with inflammatory bowel disease (IBD) during remission and flare is limited. The study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls. METHODS We performed a case-control study of 94 subjects (83 IBD patients and 11 healthy controls). IBD patients had either UC (n=38) or CD (n=45) in clinical remission or flare. We used epigenetic profiling by time-of-flight (EpiTOF) to investigate changes in histone modifications within peripheral blood mononuclear cells from IBD patients. RESULTS We discovered substantial heterogeneity in histone modifications across multiple immune cell types in IBD patients. They had a higher proportion of less differentiated CD34 + hematopoietic progenitors, and a subset of CD56 bright NK cells and γδ T cells characterized by distinct histone modifications associated with the gene transcription. The subset of CD56 bright NK cells had increased several histone acetylations. An epigenetically defined subset of NK was associated with higher levels of CRP in peripheral blood. CD14+ monocytes from IBD patients had significantly decreased cleaved H3T22, suggesting they were epigenetically primed for macrophage differentiation. CONCLUSION We describe the first systems-level quantification of histone modifications across immune cells from IBD patients at a single-cell resolution revealing the increased epigenetic heterogeneity that is not possible with traditional ChIP-seq profiling. Our data open new directions in investigating the association between histone modifications and IBD pathology using other epigenomic tools.
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Affiliation(s)
- Lawrence Bai
- Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305 USA
| | - Denis Dermadi
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Laurynas Kalesinskas
- Biomedical Informatics Training Program, Stanford University School of Medicine, 1265 Welch Road, MSOB X-343, Stanford, CA 94305 USA
| | - Mai Dvorak
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Sarah E Chang
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Ananthakrishnan Ganesan
- Computational and Mathematical Engineering, Stanford University, 475 Via Ortega, Suite B060, Stanford, CA 94305 USA
| | - Samuel J S Rubin
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States
| | - Alex Kuo
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Peggie Cheung
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Michele Donato
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Paul J Utz
- Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305 USA.,Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Aida Habtezion
- Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305 USA.,Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States
| | - Purvesh Khatri
- Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305 USA.,Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.,Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA
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34
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Qu J, Shao C, Ying Y, Wu Y, Liu W, Tian Y, Yin Z, Li X, Yu Z, Shuai J. The spring-like effect of microRNA-31 in balancing inflammatory and regenerative responses in colitis. Front Microbiol 2022; 13:1089729. [PMID: 36590397 PMCID: PMC9800619 DOI: 10.3389/fmicb.2022.1089729] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders caused by the disruption of immune tolerance to the gut microbiota. MicroRNA-31 (MIR31) has been proven to be up-regulated in intestinal tissues from patients with IBDs and colitis-associated neoplasias. While the functional role of MIR31 in colitis and related diseases remain elusive. Combining mathematical modeling and experimental analysis, we systematically explored the regulatory mechanism of MIR31 in inflammatory and epithelial regeneration responses in colitis. Level of MIR31 presents an "adaptation" behavior in dextran sulfate sodium (DSS)-induced colitis, and the similar behavior is also observed for the key cytokines of p65 and STAT3. Simulation analysis predicts MIR31 suppresses the activation of p65 and STAT3 but accelerates the recovery of epithelia in colitis, which are validated by our experimental observations. Further analysis reveals that the number of proliferative epithelial cells, which characterizes the inflammatory process and the recovery of epithelia in colitis, is mainly determined by the inhibition of MIR31 on IL17RA. MIR31 promotes epithelial regeneration in low levels of DSS-induced colitis but inhibits inflammation with high DSS levels, which is dominated by the competition for MIR31 to either inhibit inflammation or promote epithelial regeneration by binding to different targets. The binding probability determines the functional transformation of MIR31, but the functional strength is determined by MIR31 levels. Thus, the role of MIR31 in the inflammatory response can be described as the "spring-like effect," where DSS, MIR31 action strength, and proliferative epithelial cell number are regarded as external force, intrinsic spring force, and spring length, respectively. Overall, our study uncovers the vital roles of MIR31 in balancing inflammation and the recovery of epithelia in colitis, providing potential clues for the development of therapeutic targets in drug design.
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Affiliation(s)
- Jing Qu
- Department of Physics, and Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Chunlei Shao
- State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Yongfa Ying
- Department of Physics, and Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Yuning Wu
- Department of Mathematics and Physics, Fujian Jiangxia University, Fuzhou, China
| | - Wen Liu
- Department of Physics, and Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Yuhua Tian
- State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Zhiyong Yin
- Department of Physics, and Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Xiang Li
- Department of Physics, and Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
- National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, China
- State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China
| | - Zhengquan Yu
- State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Jianwei Shuai
- Department of Physics, and Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
- National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, China
- State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), University of Chinese Academy of Sciences, Wenzhou, China
- Wenzhou Institute, Wenzhou Key Laboratory of Biophysics, University of Chinese Academy of Sciences, Wenzhou, China
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35
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Giuffrè M, Gazzin S, Zoratti C, Llido JP, Lanza G, Tiribelli C, Moretti R. Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation. Int J Mol Sci 2022; 23:15564. [PMID: 36555205 PMCID: PMC9779232 DOI: 10.3390/ijms232415564] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/04/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Celiac disease (CD) is a complex multi-organ disease with a high prevalence of extra-intestinal involvement, including neurological and psychiatric manifestations, such as cerebellar ataxia, peripheral neuropathy, epilepsy, headache, cognitive impairment, and depression. However, the mechanisms behind the neurological involvement in CD remain controversial. Recent evidence shows these can be related to gluten-mediated pathogenesis, including antibody cross-reaction, deposition of immune-complex, direct neurotoxicity, and in severe cases, vitamins or nutrients deficiency. Here, we have summarized new evidence related to gut microbiota and the so-called "gut-liver-brain axis" involved in CD-related neurological manifestations. Additionally, there has yet to be an agreement on whether serological or neurophysiological findings can effectively early diagnose and properly monitor CD-associated neurological involvement; notably, most of them can revert to normal with a rigorous gluten-free diet. Moving from a molecular level to a symptom-based approach, clinical, serological, and neurophysiology data might help to disentangle the many-faceted interactions between the gut and brain in CD. Eventually, the identification of multimodal biomarkers might help diagnose, monitor, and improve the quality of life of patients with "neuroCD".
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Affiliation(s)
- Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
| | - Silvia Gazzin
- The Liver-Brain Unit “Rita Moretti”, Italian Liver Foundation, 34149 Trieste, Italy
| | - Caterina Zoratti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
| | - John Paul Llido
- The Liver-Brain Unit “Rita Moretti”, Italian Liver Foundation, 34149 Trieste, Italy
- Department of Life Sciences, University of Trieste, 34128 Trieste, Italy
- Philippine Council for Healthcare Research and Development, Department of Science and Technology, Bicutan Taguig City 1631, Philippines
| | - Giuseppe Lanza
- Department of Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy
- Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, 94018 Troina, Italy
| | - Claudio Tiribelli
- The Liver-Brain Unit “Rita Moretti”, Italian Liver Foundation, 34149 Trieste, Italy
| | - Rita Moretti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
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Jergens AE, Heilmann RM. Canine chronic enteropathy—Current state-of-the-art and emerging concepts. Front Vet Sci 2022; 9:923013. [PMID: 36213409 PMCID: PMC9534534 DOI: 10.3389/fvets.2022.923013] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Over the last decade, chronic inflammatory enteropathies (CIE) in dogs have received great attention in the basic and clinical research arena. The 2010 ACVIM Consensus Statement, including guidelines for the diagnostic criteria for canine and feline CIE, was an important milestone to a more standardized approach to patients suspected of a CIE diagnosis. Great strides have been made since understanding the pathogenesis and classification of CIE in dogs, and novel diagnostic and treatment options have evolved. New concepts in the microbiome-host-interaction, metabolic pathways, crosstalk within the mucosal immune system, and extension to the gut-brain axis have emerged. Novel diagnostics have been developed, the clinical utility of which remains to be critically evaluated in the next coming years. New directions are also expected to lead to a larger spectrum of treatment options tailored to the individual patient. This review offers insights into emerging concepts and future directions proposed for further CIE research in dogs for the next decade to come.
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Affiliation(s)
- Albert E. Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
- *Correspondence: Albert E. Jergens
| | - Romy M. Heilmann
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
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Wu X, Xu X, Xiang Y, Fan D, An Q, Yue G, Jin Z, Ding J, Hu Y, Du Q, Xu J, Xie R. Exosome-mediated effects and applications in inflammatory diseases of the digestive system. Eur J Med Res 2022; 27:163. [PMID: 36045437 PMCID: PMC9429695 DOI: 10.1186/s40001-022-00792-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 08/17/2022] [Indexed: 11/24/2022] Open
Abstract
Exosomes are membranous vesicles containing RNA and proteins that are specifically secreted in vivo. Exosomes have many functions, such as material transport and signal transduction between cells. Many studies have proven that exosomes can not only be used as biomarkers for disease diagnosis but also as carriers to transmit information between cells. Exosomes participate in a variety of physiological and pathological processes, including the immune response, antigen presentation, cell migration, cell differentiation, and tumour development. Differences in exosome functions depend on cell type. In recent years, exosome origin, cargo composition, and precise regulatory mechanisms have been the focus of research. Although exosomes have been extensively reported in digestive tumours, few articles have reviewed their roles in inflammatory diseases of the digestive system, especially inflammatory-related diseases (such as reflux oesophagitis, gastritis, inflammatory bowel disease, hepatitis, and pancreatitis). This paper briefly summarizes the roles of exosomes in inflammatory diseases of the digestive system to provide a basis for research on the mechanism of inflammatory diseases of the digestive system targeted by exosomes.
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Affiliation(s)
- Xianli Wu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Xiaolin Xu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Yiwei Xiang
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Dongdong Fan
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Qiming An
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Gengyu Yue
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Zhe Jin
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Jianhong Ding
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Yanxia Hu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Qian Du
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Jingyu Xu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China. .,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China.
| | - Rui Xie
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China. .,The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China.
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38
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MicroRNAs in Inflammatory Bowel Disease and Its Complications. Int J Mol Sci 2022; 23:ijms23158751. [PMID: 35955886 PMCID: PMC9369281 DOI: 10.3390/ijms23158751] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/03/2022] [Accepted: 08/04/2022] [Indexed: 11/17/2022] Open
Abstract
Inflammatory bowel disease (IBD), classified primarily between Crohn's disease and ulcerative colitis, is a collection of chronic gastrointestinal inflammatory conditions that cause multiple complications because of systemic alterations in the immune response. One major player is microRNA (miRNA), which is found to be associated with multiple pathways in mediating inflammation, especially those of a chronic nature in IBD, as well as irritable bowel syndrome. Although there have been studies linking miRNA alterations in IBD, even differentiating Crohn's disease and ulcerative colitis, this review focuses mainly on how miRNAs cause and mechanistically influence the pathologic complications of IBD. In addition to its role in the well-known progression towards colorectal cancer, we also emphasize how miRNA manifests the many extraintestinal complications in IBD such as cardiovascular diseases; neuropsychiatric conditions such as depression and anxiety disorders; and others, including various musculoskeletal, dermatologic, ocular, and hepatobiliary complications. We conclude through a description of its potential use in bettering diagnostics and the future treatment of IBD and its systemic symptoms.
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MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23147991. [PMID: 35887337 PMCID: PMC9318064 DOI: 10.3390/ijms23147991] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/13/2022] [Accepted: 07/18/2022] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD). These are autoimmune diseases of the gastrointestinal tract with a chronic relapsing and remitting course. Due to complex interactions between multiple factors in the etiology of IBD, the discovery of new predictors of disease course and response to therapy, and the development of effective therapies is a significant challenge. The dysregulation of microRNAs (miRNAs), a class of conserved endogenous, small non-coding RNA molecules with a length of 18–25 nucleotides, that regulate gene expression by an RNA interference process, is implicated in the complex pathogenetic context of IBD. Both tissue-derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of disease severity of IBD. In this review, we summarize the expressed miRNA profile in blood, mucosal tissue, and stool and highlight the role of miRNAs as biomarkers with potential diagnostic and therapeutic applications in ulcerative colitis and Crohn’s disease. Moreover, we discuss the new perspectives in developing a new screening model for the detection of colorectal cancer (CRC) based on fecal miRNAs.
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The Current Status of Molecular Biomarkers for Inflammatory Bowel Disease. Biomedicines 2022; 10:biomedicines10071492. [PMID: 35884797 PMCID: PMC9312796 DOI: 10.3390/biomedicines10071492] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/20/2022] [Accepted: 06/21/2022] [Indexed: 12/12/2022] Open
Abstract
Diagnosis and prognosis of inflammatory bowel disease (IBD)-a chronic inflammation that affects the gastrointestinal tract of patients-are challenging, as most clinical symptoms are not specific to IBD, and are often seen in other inflammatory diseases, such as intestinal infections, drug-induced colitis, and monogenic diseases. To date, there is no gold-standard test for monitoring IBD. Endoscopy and imaging are essential diagnostic tools that provide information about the disease's state, location, and severity. However, the invasive nature and high cost of endoscopy make it unsuitable for frequent monitoring of disease activity in IBD patients, and even when it is possible to replace endoscopy with imaging, high cost remains a concern. Laboratory testing of blood or feces has the advantage of being non-invasive, rapid, cost-effective, and standardizable. Although the specificity and accuracy of laboratory testing alone need to be improved, it is increasingly used to monitor disease activity or to diagnose suspected IBD cases in combination with endoscopy and/or imaging. The literature survey indicates a dearth of summarization of biomarkers for IBD testing. This review introduces currently available non-invasive biomarkers of clinical importance in laboratory testing for IBD, and discusses the trends and challenges in the IBD biomarker studies.
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Yarani R, Shojaeian A, Palasca O, Doncheva NT, Jensen LJ, Gorodkin J, Pociot F. Differentially Expressed miRNAs in Ulcerative Colitis and Crohn’s Disease. Front Immunol 2022; 13:865777. [PMID: 35734163 PMCID: PMC9208551 DOI: 10.3389/fimmu.2022.865777] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 04/13/2022] [Indexed: 12/14/2022] Open
Abstract
Differential microRNA (miRNA or miR) regulation is linked to the development and progress of many diseases, including inflammatory bowel disease (IBD). It is well-established that miRNAs are involved in the differentiation, maturation, and functional control of immune cells. miRNAs modulate inflammatory cascades and affect the extracellular matrix, tight junctions, cellular hemostasis, and microbiota. This review summarizes current knowledge of differentially expressed miRNAs in mucosal tissues and peripheral blood of patients with ulcerative colitis and Crohn’s disease. We combined comprehensive literature curation with computational meta-analysis of publicly available high-throughput datasets to obtain a consensus set of miRNAs consistently differentially expressed in mucosal tissues. We further describe the role of the most relevant differentially expressed miRNAs in IBD, extract their potential targets involved in IBD, and highlight their diagnostic and therapeutic potential for future investigations.
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Affiliation(s)
- Reza Yarani
- Translational Type 1 Diabetes Research, Department of Clinical Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States
- *Correspondence: Reza Yarani, ; Flemming Pociot,
| | - Ali Shojaeian
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Oana Palasca
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nadezhda T. Doncheva
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Lars Juhl Jensen
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
| | - Jan Gorodkin
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Pociot
- Translational Type 1 Diabetes Research, Department of Clinical Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Copenhagen Diabetes Research Center, Department of Pediatrics, Herlev University Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- *Correspondence: Reza Yarani, ; Flemming Pociot,
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Xiao X, Mao X, Chen D, Yu B, He J, Yan H, Wang J. miRNAs Can Affect Intestinal Epithelial Barrier in Inflammatory Bowel Disease. Front Immunol 2022; 13:868229. [PMID: 35493445 PMCID: PMC9043318 DOI: 10.3389/fimmu.2022.868229] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/18/2022] [Indexed: 11/17/2022] Open
Abstract
The most obvious pathological characterization of inflammatory bowel disease (IBD) is intestinal epithelium erosion and severe inflammation invasion. Micro-ribonucleic acids (miRNA or microRNA), single-stranded noncoding RNAs of ~22 nucleotides, have been considered as the potential therapeutic targets in the pathogenesis of IBD. Many previous studies have focused on the mechanisms that miRNAs use to regulate inflammation, immunity, and microorganisms in IBD. The review highlights in detail the findings of miRNAs in the intestinal epithelial barrier of IBD, and focuses on their gene targets, signaling pathways associated with IBD, and some potential therapies. It will be beneficial for the elucidation of the interaction between miRNAs and the intestinal epithelial barrier in IBD and provide a theoretical reference for preventing and treating IBD in the future.
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Affiliation(s)
- Xiangjun Xiao
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Daiwen Chen
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Jianping Wang
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
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P-Cadherin Regulates Intestinal Epithelial Cell Migration and Mucosal Repair, but Is Dispensable for Colitis Associated Colon Cancer. Cells 2022; 11:cells11091467. [PMID: 35563773 PMCID: PMC9100778 DOI: 10.3390/cells11091467] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/20/2022] [Accepted: 04/23/2022] [Indexed: 12/16/2022] Open
Abstract
Recurrent chronic mucosal inflammation, a characteristic of inflammatory bowel diseases (IBD), perturbs the intestinal epithelial homeostasis resulting in formation of mucosal wounds and, in most severe cases, leads to colitis-associated colon cancer (CAC). The altered structure of epithelial cell-cell adhesions is a hallmark of intestinal inflammation contributing to epithelial injury, repair, and tumorigenesis. P-cadherin is an important adhesion protein, poorly expressed in normal intestinal epithelial cells (IEC) but upregulated in inflamed and injured mucosa. The goal of this study was to investigate the roles of P-cadherin in regulating intestinal inflammation and CAC. P-cadherin expression was markedly induced in the colonic epithelium of human IBD patients and CAC tissues. The roles of P-cadherin were investigated in P-cadherin null mice using dextran sulfate sodium (DSS)-induced colitis and an azoxymethane (AOM)/DSS induced CAC. Although P-cadherin knockout did not affect the severity of acute DSS colitis, P-cadherin null mice exhibited faster recovery after colitis. No significant differences in the number of colonic tumors were observed in P-cadherin null and control mice. Consistently, the CRISPR/Cas9-mediated knockout of P-cadherin in human IEC accelerated epithelial wound healing without affecting cell proliferation. The accelerated migration of P-cadherin depleted IEC was driven by activation of Src kinases, Rac1 GTPase and myosin II motors and was accompanied by transcriptional reprogramming of the cells. Our findings highlight P-cadherin as a negative regulator of IEC motility in vitro and mucosal repair in vivo. In contrast, this protein is dispensable for IEC proliferation and CAC development.
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Mohammad Rahimi H, Yadegar A, Asadzadeh Aghdaei H, Mirjalali H, Zali MR. Modulation of microRNAs and claudin-7 in Caco-2 cell line treated with Blastocystis sp., subtype 3 soluble total antigen. BMC Microbiol 2022; 22:111. [PMID: 35459091 PMCID: PMC9027909 DOI: 10.1186/s12866-022-02528-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 04/13/2022] [Indexed: 12/15/2022] Open
Abstract
Background Blastocystis sp., is a eukaryote of the large intestine, which is reported from almost all countries. The pathogenesis of this protist is not clear. The current study aimed to analyze the effects of Blastocystis sp., ST3 soluble total antigen (B3STA) on the microRNAs (miRNAs) involved in the gut permeability and also pro-inflammatory cytokines, occludin, and claudin-7. Methods Blastocystis sp., ST3 isolated from stool sample was purified, and its soluble total antigen was extracted using freeze and thawing. The Caco-2 cell line was treated with B3STA for 24 h and the expression levels of mir-16, mir-21, mir-29a, mir-223, and mir-874 were analyzed. In addition, the expression levels of il-8, il-15, occludin, and claudin-7 genes were assessed. Results B3STA significantly upregulated the expression of mir-223, and mir-874, and downregulated mir-29a. The expression of mir-16 and mir-21 was not significant. In addition, the expression of il-8 and il-15 was not significant. B3STA significantly decreased the expression level of claudin-7 (P-value < 0.0001), but the expression of occludin was not significant. Our results showed significant correlation between all studied miRNAs, except mir-29a, with downregulation of claudin-7. Conclusions This is the first study investigating the effects of Blastocystis sp., ST3 isolated from symptomatic subjects on the expression levels of miRNAs involved in the gut permeability. Our results demonstrated that B3STA may change miRNA expression, which are involved in the gut barrier integrity, and downregulates claudin-7, which is known as sealing factor.
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Affiliation(s)
- Hanieh Mohammad Rahimi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wu S, Yuan W, Luo W, Nie K, Wu X, Meng X, Shen Z, Wang X. MiR-126 downregulates CXCL12 expression in intestinal epithelial cells to suppress the recruitment and function of macrophages and tumorigenesis in a murine model of colitis-associated colorectal cancer. Mol Oncol 2022; 16:3465-3489. [PMID: 35363937 PMCID: PMC9533691 DOI: 10.1002/1878-0261.13218] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 02/23/2022] [Accepted: 03/30/2022] [Indexed: 12/02/2022] Open
Abstract
Inflammatory bowel disease, characterised by chronic relapsing‐remitting colitis, is a significant risk factor for colorectal cancer (CRC). Previously, we showed that miR‐126 functions as a tumour suppressor in CRC and is inversely correlated with tumour proliferation, metastasis and patient prognosis. In the current study, we documented a protective role for miR‐126 in colitis‐associated CRC (CAC) and its underlying mechanism. We detected downregulated miR‐126 expression during colorectal tumorigenesis in the mouse CAC model and in specimens from patients with CRC. The deficiency of miR‐126 in intestinal epithelial cells (IECs) exacerbated tumorigenesis in mice. We identified CXCL12 as a direct target of miR‐126 in inhibiting the development of colitis and CAC. Moreover, miR‐126 regulated the recruitment of macrophages via CXCL12 and decreased the levels of proinflammatory cytokines (IL‐6, IL‐12 and IL‐23). In addition, IL‐6 secreted by macrophages, which were regulated by cocultured transfected CRC cells, altered the proliferation and migration of colon cells. Our data suggest that miR‐126 exerts an antitumour effect on CAC by regulating the crosstalk between IECs and macrophages via CXCL12‐IL‐6 signalling. Our study contributes to the understanding of cancer progression and suggests miR‐126 as a potential therapy for CRC.
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Affiliation(s)
- Shuai Wu
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China
| | - Wei Yuan
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China.,Department of Hepatology, The First Affiliated Hospital, The Hunan University of Chinese Medicine, Changsha, Hunan, P.R. China
| | - Weiwei Luo
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China
| | - Kai Nie
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China
| | - Xing Wu
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China
| | - Xiangrui Meng
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China
| | - Zhaohua Shen
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China
| | - Xiaoyan Wang
- Department of Gastroenterology, The Central South University, Changsha, Hunan, China.,Key Laboratory of Non-resolving Inflammation and Cancer of the Hunan Province, The Third Xiangya Hospital, The Central South University, Changsha, Hunan, China
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Kociszewska D, Vlajkovic SM. The Association of Inflammatory Gut Diseases with Neuroinflammatory and Auditory Disorders. Front Biosci (Elite Ed) 2022; 14:8. [PMID: 35730449 DOI: 10.31083/j.fbe1402008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/11/2022] [Accepted: 02/24/2022] [Indexed: 11/06/2022]
Abstract
Disorders such as inflammatory bowel disease (IBD) and celiac disease (CeD) result in intestinal hyperpermeability or 'leaky' gut. The increased permeability of the intestinal barrier allows microbial metabolites, toxins, and pathogens to infiltrate the bloodstream and extraintestinal tissues, causing systemic inflammation. Despite differences in aetiology and pathophysiology, IBD and CeD share several extraintestinal manifestations such as neuroinflammation, neurological and psychiatric manifestations, and sensorineural hearing loss (SNHL). This narrative review focuses on the association between intestinal hyperpermeability with the brain and inner ear diseases. We postulate that the microbial metabolites and pathogens released from the gut increase the permeability of natural barriers, such as the blood-brain barrier (BBB) and blood-labyrinth barrier (BLB). The barrier breakdown allows the spreading of inflammatory processes to the brain and inner ear, leading to disease.
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Affiliation(s)
- Dagmara Kociszewska
- Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 1142 Auckland, New Zealand
| | - Srdjan M Vlajkovic
- Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 1142 Auckland, New Zealand
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Li T, Liu W, Hui W, Shi T, Liu H, Feng Y, Gao F. Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration. DISEASE MARKERS 2022; 2022:4983471. [PMID: 35308140 PMCID: PMC8931176 DOI: 10.1155/2022/4983471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/08/2022] [Accepted: 02/17/2022] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is a progressive intestine inflammatory disease that is prone to recur. Herein, we utilize microarray technology and bioinformatics to reveal the underlying pathogenesis of UC and provide novel markers. Colonic biopsies were taken from eight UC patients and eight healthy controls. Three differentially expressed miRNAs (DEMIs) and 264 differentially expressed genes (DEGs) were screened using mRNA and miRNA microarray. Most DEGs were significantly associated with immune response and were markedly enriched in the IL-17 signaling pathway. Among the target genes of DEMIs, PHLPP2 overlapped with DEGs and the downregulation of PHLPP2 group was mainly involved in the epithelial-mesenchymal transition. PHLPP2 was downregulated in UC patients, which was validated in 5 GEO datasets and qRT-PCR. The ROC curve demonstrated that PHLPP2 has a perfect ability to distinguish UC patients from healthy controls. Moreover, PHLPP2 was low expression in patients with active UC. CIBERSORT algorithm indicated that the abundance of gamma delta T cells (P = 0.04), M0 macrophages (P = 0.01), and activated mast cells (P < 0.01) was significantly greater than that of the control group. The Spearman correlation analysis showed that PHLPP2 was positively correlated with the proportion of activated NK cells (rho = 0.62, P = 0.013) and Tregs (rho = 0.55, P = 0.03), but negatively correlated with those of activated mast cells (rho = -0.8, P < 0.01) and macrophages (rho = -0.73, P < 0.01). These results indicate that PHLPP2 is associated with immune cells in the pathogenesis of UC, as well as provide new prospects and future directions of investigation.
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Affiliation(s)
- Ting Li
- Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Weidong Liu
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Wenjia Hui
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Tian Shi
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Huan Liu
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Yan Feng
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Feng Gao
- Xinjiang Medical University, Urumqi, Xinjiang, China
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
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Pinacchio C, Scordio M, Santinelli L, Frasca F, Sorrentino L, Bitossi C, Oliveto G, Viscido A, Ceci FM, Celani L, Ceccarelli G, Antonelli G, Mastroianni CM, d’Ettorre G, Scagnolari C. Analysis of serum microRNAs and rs2910164 GC single-nucleotide polymorphism of miRNA-146a in COVID-19 patients. J Immunoassay Immunochem 2022; 43:347-364. [DOI: 10.1080/15321819.2022.2035394] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Claudia Pinacchio
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Mirko Scordio
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
| | - Letizia Santinelli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Federica Frasca
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
| | - Leonardo Sorrentino
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
| | - Camilla Bitossi
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
| | - Giuseppe Oliveto
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
| | - Agnese Viscido
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
| | - Flavio Maria Ceci
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Luigi Celani
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Guido Antonelli
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
- Microbiology and Virology Unit, Sapienza University, Hospital Policlinico Umberto I, Rome, Italy
- Department of Molecular Medicine, Pasteur Institute Italy, Cenci Bolognetti Foundation, Rome, Italy
| | | | - Gabriella d’Ettorre
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Carolina Scagnolari
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University, Rome, Italy
- Department of Molecular Medicine, Pasteur Institute Italy, Cenci Bolognetti Foundation, Rome, Italy
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Pareek S, Sanchenkova X, Sakaguchi T, Murakami M, Okumura R, Kayama H, Kawauchi S, Motooka D, Nakamura S, Okuzaki D, Kishimoto T, Takeda K. Epithelial miR‐215 negatively modulates Th17‐dominant inflammation by inhibiting CXCL12 production in the small intestine. Genes Cells 2022; 27:243-253. [DOI: 10.1111/gtc.12922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/17/2022] [Accepted: 01/20/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Siddhika Pareek
- Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles CA 90048 USA
| | - Xenia Sanchenkova
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
| | - Taiki Sakaguchi
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Mari Murakami
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Ryu Okumura
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Hisako Kayama
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
- Institute for Advanced Co‐Creation Studies Osaka University Osaka 5650871 Japan
| | - Saya Kawauchi
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
| | - Daisuke Motooka
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Genome Information Research Center Research Institute for Microbial Diseases Osaka University Osaka 5650871 Japan
| | - Shota Nakamura
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Genome Information Research Center Research Institute for Microbial Diseases Osaka University Osaka 5650871 Japan
| | - Daisuke Okuzaki
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Genome Information Research Center Research Institute for Microbial Diseases Osaka University Osaka 5650871 Japan
| | - Tadamitsu Kishimoto
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
| | - Kiyoshi Takeda
- WPI Immunology Frontier Research Center Osaka University Osaka 5650871 Japan
- Laboratory of Immune Regulation Department of Microbiology and Immunology Graduate School of Medicine Osaka University Osaka 5650871 Japan
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Abstract
Growing evidence supports a potential link between dietary gluten intake and neurodegenerative disease in susceptible populations. Observational data supporting this link are described along with interventional study data evaluating the effects of restricting gluten from the diet in patients with neurologic disorders. Suggested underlying mechanisms between gluten intake and neurodegeneration are discussed.
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Affiliation(s)
- Ashok Philip
- Ashok Philip, Director of Assessment and Professor of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, College of Pharmacy 4301 W. Markham
- Little Rock, AR 72205, USA. e-mail:
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