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Golan-Gerstl R, Ben Ya’acov A, Musseri M, Goldenberg R, Chammah Y, Cherki T, Reif S, Bar Gil Shitrit A. Expression Profile of MicroRNAs in Breast Milk of Women With Inflammatory Bowel Disease: Correlation With Disease Activity and Medical Treatments. Inflamm Bowel Dis 2025; 31:912-922. [PMID: 39820274 PMCID: PMC11985391 DOI: 10.1093/ibd/izae290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Indexed: 01/19/2025]
Abstract
BACKGROUND Although most inflammatory bowel disease (IBD) medications are considered safe during pregnancy, their impact on microRNAs (miRNAs) in breast milk is largely unknown. MiRNAs in milk, carried by milk-derived extracellular vesicles (MDEs), are transmitted to the newborn's gut to regulate genes. Aberrant miRNA expression profiles have been found in IBD within tissue, blood, and feces, but data on mother's milk are scarce. METHODS We collected breast milk samples from 32 mothers with Crohn's disease (CD), 14 mothers with ulcerative colitis (UC), and 44 healthy controls. We analyzed miRNA expression through qualitative real-time polymerase chain reaction and Affymetrix miRNA chips. Target genes of differentially expressed miRNAs were predicted using miRATBase. Statistical analyses were conducted using GraphPad Prism software with Mann-Whitney tests. RESULTS Milk-derived extracellular vesicles from mothers with IBD showed altered miRNA profiles compared to controls. Specifically, miR-21 and miR-320 were downregulated, while Let-7a was upregulated in IBD mothers. The expression patterns varied between CD and UC, with significantly lower MiR-21 in UC and higher Let-7a in CD. Additionally, anti-tumor necrosis factor treatment during pregnancy was associated with reduced miR-21 and miR-148a levels in MDEs. Pathway analysis revealed that these miRNAs are involved in immune regulation, particularly interleukin signaling pathways. CONCLUSIONS This study highlights that miRNAs in breast milk are differentially expressed in mothers with IBD, influenced by the disease and its treatments. These findings emphasize the impact of maternal health on milk composition and potential implications for infant immune development. Understanding these findings may guide personalized treatment strategies for mothers and promote breastfeeding among mothers with IBD.
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Affiliation(s)
- Regina Golan-Gerstl
- Department of Pediatrics, Hebrew University Hadassah Medical Center, Jerusalem, Israel
| | - Ami Ben Ya’acov
- Digestive Diseases Institute, Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Mirit Musseri
- Department of Pediatrics, Hebrew University Hadassah Medical Center, Jerusalem, Israel
| | - Rosi Goldenberg
- Digestive Diseases Institute, Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Yehudit Chammah
- Digestive Diseases Institute, Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Tal Cherki
- Digestive Diseases Institute, Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Shimon Reif
- Department of Pediatrics, Hebrew University Hadassah Medical Center, Jerusalem, Israel
| | - Ariella Bar Gil Shitrit
- Digestive Diseases Institute, Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
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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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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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Alshahrani SH, Yuliastanti T, Al-Dolaimy F, Korotkova NL, Rasulova I, Almuala AF, Alsaalamy A, Ali SHJ, Alasheqi MQ, Mustafa YF. A glimpse into let-7e roles in human disorders; friend or foe? Pathol Res Pract 2024; 253:154992. [PMID: 38103367 DOI: 10.1016/j.prp.2023.154992] [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: 10/15/2023] [Revised: 11/17/2023] [Accepted: 11/27/2023] [Indexed: 12/19/2023]
Abstract
MicroRNAs (miRNAs) have been linked to abnormal expression and regulation in a number of diseases, including cancer. Recent studies have concentrated on miRNA Let-7e's significance in precision medicine for cancer screening and diagnosis as well as its prognostic and therapeutic potential. Differential let-7e levels in bodily fluids have the possibility to enable early detection of cancer utilizing less-invasive techniques, reducing biopsy-related risks. Although Let-7e miRNAs have been described as tumor suppressors, it is crucial to note that there exists proof to support their oncogenic activity in vitro and in in vivo. Let-7e's significance in chemo- and radiation treatment decisions has also been demonstrated. Let-7e can also prevent the synthesis of proinflammatory cytokines in a number of degenerative disorders, including musculoskeletal and neurological conditions. For the first time, an overview of the significance of let-7e in the prevention, detection, and therapy of cancer and other conditions has been given in the current review. Additionally, we focused on the specific molecular processes that underlie the actions of let-7e, more particularly, on malignant cells.
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Affiliation(s)
| | | | | | - Nadezhda L Korotkova
- I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation; Federal State Budgetary Educational Institution of Higher Education "Privolzhsky Research Medical University" of the Ministry of Health of the Russian Federation, Nizhny Novgorod, Russian Federation
| | - Irodakhon Rasulova
- School of Humanities, Natural & Social Sciences, New Uzbekistan University, 54 Mustaqillik Ave., Tashkent 100007, Uzbekistan; Department of Public Health, Samarkand State Medical University, Amir Temur Street 18, Samarkand, Uzbekistan
| | - Abbas Firras Almuala
- College of Technical Engineering, the Islamic University, Najaf, Iraq; College of Technical Engineering, the Islamic University of Al Diwaniyah, Iraq; College of Technical Engineering, the Islamic University of Babylon, Iraq
| | - Ali Alsaalamy
- College of Technical Engineering, Imam Ja'afar Al-Sadiq University, Al-Muthanna 66002, Iraq
| | - Saad Hayif Jasim Ali
- Department of Medical Laboratory, College of Health and Medical Technololgy, Al-Ayen University, Thi-Qar, Iraq
| | | | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq
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