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Liang B, Bai R, Wang J, Shi S, Guo Y, Wang Q, Peng H, Tang J, Liu S, Zhu J, Yi C, Hou M, Li H. Innovative applications of acellular adipose matrix derived film in skin soft tissue expansion. BIOMATERIALS ADVANCES 2025; 173:214291. [PMID: 40154149 DOI: 10.1016/j.bioadv.2025.214291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 03/04/2025] [Accepted: 03/22/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Skin dilation generates "extra" skin tissue through mechanical traction, but its effectiveness is limited by the proliferation capacity of keratinocytes, fibroblasts and the level of angiogenesis. Cutaneous application of drug and subcutaneous injection are common interventions to promote skin dilation, but they have defects such as uneven drug distribution, high risk of infection and single targeting. Although Acellular adipose matrix (AAM) has the potential to promote cell proliferation and angiogenesis, its hydrogel/powder dosage forms still need frequent injection, which limits clinical application. RESULTS In this study, Acellular adipose matrix derived film (AAF) was successfully developed, and a flexible film was formed by acellular - lyophilized - enzymolysis - self-assembly process. In vitro experiments confirmed that AAF significantly promoted the activity of Human Immortalized Epidermal Cells (HaCaTs), Normal Skin Fibroblasts (NFbs) and Human Umbilical Endothelial Cells (HUVECs); It was also found that AAF can induce adipose mesenchymal stem cells (ASCs) to differentiate into adipocytes and promote subcutaneous fat regeneration. In vivo, the rat model showed that AAF wrapping expander could effectively improve the skin expansion efficiency, promote the skin thickness increase in the expanded area, and the density of new blood vessels was significantly increased compared with the comparative group, and there was no complication such as infection or skin collapse. It was found for the first time that AAF successfully formed new adipose tissue in the subcutaneous area. CONCLUSION AAF innovatively integrates the bionic structure of extracellular matrix and slow-release function, and solves the uneven drug distribution and associated infection risk of traditional intervention methods by regulating the synergistic regeneration of epidermodermis and vascular units. Its mechanical adaptability (dry toughness/wet plasticity) and the ability of inducing adipose regeneration provide a new strategy of both structural strengthening and metabolic support for skin dilation, also laying a mechanism and empirical foundation for clinical transformation of tissue engineering materials.
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Affiliation(s)
- Baoyan Liang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Ruoxue Bai
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Jiayang Wang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Shuyang Shi
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Yajie Guo
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Qi Wang
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Han Peng
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Innovation Research Institute, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Jiezhang Tang
- Department of Plastic and Burn Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Shuai Liu
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Jun Zhu
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Chenggang Yi
- Department of Plastic Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Mengmeng Hou
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Innovation Research Institute, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Huichen Li
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Innovation Research Institute, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
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Eerdekens H, Pirlet E, Willems S, Bronckaers A, Pincela Lins PM. Extracellular vesicles: innovative cell-free solutions for wound repair. Front Bioeng Biotechnol 2025; 13:1571461. [PMID: 40248643 PMCID: PMC12003306 DOI: 10.3389/fbioe.2025.1571461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 03/17/2025] [Indexed: 04/19/2025] Open
Abstract
Chronic non-healing wounds are often associated with conditions such as diabetes and peripheral vascular disease, pose significant medical and socioeconomic challenges. Cell-based therapies have shown promise in promoting wound healing but have major drawbacks such as immunogenicity and tumor formation. As a result, recent research has shifted to the potential of extracellular vesicles (EVs) derived from these cells. EVs are nanosized lipid bilayer vesicles, naturally produced by all cell types, which facilitate intercellular communication and carry bioactive molecules, offering advantages such as low immunogenicity, negligible toxicity and the potential to be re-engineered. Recent evidence recognizes that during wound healing EVs are released from a wide range of cells including immune cells, skin cells, epithelial cells and platelets and they actively participate in wound repair. This review comprehensively summarizes the latest research on the function of EVs from endogenous cell types during the different phases of wound healing, thereby presenting interesting therapeutic targets. Additionally, it gives a critical overview of the current status of mesenchymal stem cell-derived EVs in wound treatment highlighting their tremendous therapeutic potential as a non-cellular of-the-shelf alternative in wound care.
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Affiliation(s)
- Hanne Eerdekens
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Elke Pirlet
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Sarah Willems
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Annelies Bronckaers
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Paula M. Pincela Lins
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
- Flemish Institute for Technological Research (VITO), Environmental Intelligence Unit, Mol, Belgium
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Saadh MJ, Jasim NY, Ahmed MH, Ballal S, Kumar A, Atteri S, Vashishth R, Rizaev J, Alhili A, Jawad MJ, Yazdi F, Salajegheh A, Akhavan-Sigari R. Critical roles of miR-21 in promotions angiogenesis: friend or foe? Clin Exp Med 2025; 25:66. [PMID: 39998742 PMCID: PMC11861128 DOI: 10.1007/s10238-025-01600-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 02/11/2025] [Indexed: 02/27/2025]
Abstract
MiRNAs are small RNA strands that are managed following transcription and are of substantial importance in blood vessel formation. It is essential to oversee the growth, differentiation, death, movement and construction of tubes by angiogenesis-affiliated cells. If miRNAs are not correctly regulated in regard to angiogenesis, it can deteriorate the health and lead to various illnesses, which include cancer, cardiovascular disorder, critical limb ischemia, Crohn's disease, ocular diseases, diabetic microvascular complications, and more. Consequently, it is vital to understand the crucial part that miRNAs play in the development of blood vessels, so we can develop reliable treatment plans for vascular diseases. This write-up will assess the critical role of miR-21/exosomal miR-21 in managing angiogenesis associated with bone growth, wound recovery, and other pathological conditions like tumor growth, ocular illnesses, diabetes, and other diseases connected to formation of blood vessels. Previous investigations have demonstrated that miR-21 is present at higher amounts in certain cancerous cells, and it influences a multitude of genes that moderate the increased creation of blood vessels. Furthermore, studies demonstrated that exosomal miR-21 has the capacity to interact with endothelial cells to foster tumor angiogenesis. For that reason, this review explains the critical importance of miR-21/exosomal miR-21 in managing both healthy and diseased states of angiogenesis.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | - Nisreen Yasir Jasim
- College of Nursing, National University of Science and Technology, Nasiriyah, Dhi Qar, Iraq
| | | | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Abhishek Kumar
- School of Pharmacy-Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Gangoh, Uttar Pradesh, 247341, India
- Department of Pharmacy, Arka Jain University, Jamshedpur, Jharkhand, 831001, India
| | - Shikha Atteri
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjheri, Mohali, Punjab, 140307, India
| | - Raghav Vashishth
- Department of Surgery, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, India
| | - Jasur Rizaev
- Department of Public Health and Healthcare Management, Rector, Samarkand State Medical University, 18, Amir Temur Street, Samarkand, Uzbekistan
| | - Ahmed Alhili
- Medical Technical College, Al-Farahidi University, Baghdad, Iraq
| | | | - Farzaneh Yazdi
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
| | | | - Reza Akhavan-Sigari
- Dr. Schneiderhan GmbH and ISAR Klinikum, Munich, Germany
- Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw, Management University Warsaw, Warsaw, Poland
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Mansour RM, Mageed SSA, Awad FA, Sadek MM, Adel SA, Ashraf A, Alam-Eldein KM, Ahmed NE, Abdelaziz RY, Tolba EF, Mohamed HH, Rizk NI, Mohamed MO, Mohammed OA, Doghish AS. miRNAs and their multifaceted role in cutaneous wound healing. Funct Integr Genomics 2025; 25:33. [PMID: 39903291 DOI: 10.1007/s10142-025-01535-y] [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: 12/05/2024] [Revised: 01/13/2025] [Accepted: 01/13/2025] [Indexed: 02/06/2025]
Abstract
The dynamic, complex process of cutaneous wound healing is required to restore skin integrity following an injury. This intricate process consists of four sequential and overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Hemostasis immediately begins to function in response to vascular injury, forming a clot that stops the bleeding. To fight infection and remove debris, immune cells are enlisted during the inflammatory phase. Angiogenesis, re-epithelialization, and the creation of new tissue are all components of proliferation, whereas tissue maturation and scarring are the outcomes of remodeling. Chronic wounds, like those found in diabetic ulcers, frequently stay in a state of chronic inflammation because they are unable to go through these stages in a coordinated manner. The important regulatory roles that microRNAs (miRNAs) play in both normal and pathological wound healing have been highlighted by recent investigations. The miRNAs, small non-coding RNAs, modulate gene expression post-transcriptionally, profoundly impacting cellular functions. During the inflammatory phase, miRNAs control pro- and anti-inflammatory cytokines, as well as the activity of immune cells such as neutrophils and macrophages. Additionally, miRNAs are essential components of signaling networks related to inflammation, such as the toll-like receptor (TLR), nuclear factor kappa B (NF-kB), and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Some miRNAs have been discovered to either increase or alleviate inflammatory reactions, indicating their potential as therapeutic targets. Other miRNAs aid in angiogenesis by promoting the development of new blood vessels, which are essential for providing oxygen and nutrients to the healing tissue. They also affect keratinocyte migration and proliferation during the re-epithelialization phase, which involves growing new epithelial cells over the lesion. Another function of miRNAs is that they control the deposition of extracellular matrix (ECM) and the creation of scars during the remodeling phase. The abnormal expression of miRNAs in chronic wounds has led to the exploration of miRNA-based treatments. With a focus on resistant instances such as diabetic wounds, these therapeutic techniques seek to improve wound healing results by correcting the dysregulated miRNA expression.
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Affiliation(s)
- Reda M Mansour
- Zoology and Entomology Department, Faculty of Science, Helwan University, Cairo, Egypt
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Farah A Awad
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Mohamed M Sadek
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Shehab Ahmed Adel
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Alaa Ashraf
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Khaled M Alam-Eldein
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Nada E Ahmed
- Medical Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Rana Y Abdelaziz
- Medical Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Esraa Farid Tolba
- Medical Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
- Research and Development Specialist at Misr Technology for Biological Industries (MTBI), Cairo, Egypt
| | - Hend H Mohamed
- School of Biotechnology and Science Academy, Badr University in Cairo, Badr City, Cairo, 11829, Egypt
| | - Nehal I Rizk
- Department of Biochemistry, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, 11786, Egypt
| | - Mohamed O Mohamed
- Department of Biotechnology, Faculty of Agriculture, Ain Shams University, Cairo, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt.
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Klein B, Nguyen NTK, Moallemian R, Kahlenberg JM. Keratinocytes - Amplifiers of Immune Responses in Systemic Lupus Erythematosus. Curr Rheumatol Rep 2024; 27:1. [PMID: 39570551 DOI: 10.1007/s11926-024-01168-3] [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] [Accepted: 10/22/2024] [Indexed: 11/22/2024]
Abstract
PURPOSE OF REVIEW Epithelial cells have been acknowledged as important players in autoimmune diseases by directing and enhancing inflammatory responses. Here, we summarize recent publications that examine keratinocyte (KC) dysfunction and its contribution to cutaneous and systemic disease in systemic lupus erythematosus patients. RECENT FINDINGS Chronic upregulation of type I interferon (IFN) in KCs is a feature of both lesional and nonlesional lupus skin. This IFN rich environment modulates epidermal cell death responses and promotes inflammatory responses to UV light exposure. In addition, newer technologies such as single cell RNA-seq are informing our understanding of lupus-specific intercellular crosstalk and how this contributes to disease. Recent discoveries in KC dysfunction in lupus skin include aberrant IFN responses to environmental stress, enhanced cytokine and chemokine secretion and epigenetic changes leading to increased cell death. Further research will enable precision therapies for lupus treatment.
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Affiliation(s)
- Benjamin Klein
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - Nguyen Thi Kim Nguyen
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - Rezvan Moallemian
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - J Michelle Kahlenberg
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
- Department of Dermatology, University of Michigan, Ann Arbor, USA.
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Kim G, Lee SY, Oh S, Jang JW, Lee J, Kim HS, Son KH, Byun K. Anti-Inflammatory Effects of Extracellular Vesicles from Ecklonia cava on 12-O-Tetradecanoylphorbol-13-Acetate-Induced Skin Inflammation in Mice. Int J Mol Sci 2024; 25:12522. [PMID: 39684233 DOI: 10.3390/ijms252312522] [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: 09/05/2024] [Revised: 11/15/2024] [Accepted: 11/18/2024] [Indexed: 12/18/2024] Open
Abstract
Steroids, which are often used to treat the inflammation associated with various skin diseases, have several negative side effects. As Ecklonia cava extract has anti-inflammatory effects in various diseases, we evaluated the efficacy of Ecklonia cava-derived extracellular vesicles (EVEs) in decreasing 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. We determined the effect of the EVEs on the TLR4/NF-κB/NLRP3 inflammasome in human keratinocytes and mouse ear skin. TPA-treated human keratinocytes showed an increased expression of TLR4 and its ligands HMGB1 and S100A8. TPA also increased the expression of (1) NF-κB; (2) the NLRP3 inflammasome components NLRP3, ASC, and caspase 1; and (3) the pyroptosis-related factors GSDMD-NT, IL-18, and IL-1β. However, the expression of these molecules decreased in the TPA-treated human keratinocytes after EVE treatment. Similar to the in vitro results, TPA increased the expression of these molecules in mouse ear skin, and EVE treatment decreased their expression. The TPA treatment of skin increased edema, redness, neutrophil infiltration, and epidermal thickness, and EVE reduced these symptoms of inflammation. In conclusion, the EVEs decreased TPA-induced skin inflammation, which was associated with a decrease in the TLR4/NF-κB/NLRP3 inflammasome.
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Affiliation(s)
- Geebum Kim
- Misogain Dermatology Clinic, Gimpo 10108, Republic of Korea
| | - So Young Lee
- Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea
| | - Seyeon Oh
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - Jong-Won Jang
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
| | - Jehyuk Lee
- Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea
- Doctorbom Clinic, Seoul 06614, Republic of Korea
| | - Hyun-Seok Kim
- Kim Hyun Seok Plastic Surgery Clinic, Seoul 06030, Republic of Korea
| | - Kuk Hui Son
- Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea
| | - Kyunghee Byun
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
- Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea
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Hussein WH, Ramadan H, Labib S, Hegazy GA, Shaker OG, Yusuf SM, Hassanien MA, Haroon MM. Expression Levels of lncRNA NEAT1, miRNA-21, and IL-17 in a Group of Egyptian Patients with Behçet's Disease: Relation to Disease Manifestations and Activity. Biologics 2024; 18:327-337. [PMID: 39555123 PMCID: PMC11568774 DOI: 10.2147/btt.s493191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/06/2024] [Indexed: 11/19/2024]
Abstract
Background Long noncoding ribonucleic acids (lncRNAs), small noncoding RNAs known as microRNAs (miRNAs) as well as some cytokines are recently thought to have a role in many inflammatory and autoimmune disorders including Behçet's disease (BD). This chronic multisystem disease lacks the particular histological or laboratory findings that might aid in its diagnosis. Therefore, any association with such molecules may have an impact on understanding the disease pathogenesis and/or management. The current study compared the levels of NEAT1, miR-21 and IL17 levels in sera of Egyptian BD patients and healthy individuals. The expression levels of these molecules were further investigated for their association with BD manifestations and activity aiming to explore their potential application in disease management. Results NEAT1 & miR-21 showed down-regulation while IL-17 showed up-regulation among BD patients as compared to controls. IL-17 had significant correlation with major vessels involvement and cyclophosphamide intake. NEAT1 showed a significant negative correlation with colchicine intake. Disease activity did not correlate significantly with any of NEAT1, miR-21 or IL-17. Conclusion NEAT1, miR-21 and IL17 might have a role in Behçet's disease pathogenesis, so more research is needed to unveil that role and their potential usage as biomarkers for the diagnosis or therapeutic targets.
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Affiliation(s)
- Wafaa H Hussein
- Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hala Ramadan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Safa Labib
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Gehan A Hegazy
- Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
- Medical Division Department, National Research Centre, Giza, Egypt
| | - Olfat G Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sherif M Yusuf
- Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Mohammed A Hassanien
- Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - Maysa M Haroon
- Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Li K, Wu L, Jiang J. Apigenin accelerates wound healing in diabetic mice by promoting macrophage M2-type polarization via increasing miR-21 expression. Mol Cell Biochem 2024; 479:3119-3127. [PMID: 38261238 DOI: 10.1007/s11010-023-04885-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 10/19/2023] [Indexed: 01/24/2024]
Abstract
The alteration of inflammatory phenotype by macrophage polarization plays an important role in diabetic wound repair. Apigenin has been reported to be anti-inflammatory and promote tissue repair; however, whether it regulates macrophage polarization to participate in diabetic wound repair remains to be investigated. We found that apigenin promoted miR-21 expression in LPS-stimulated RAW264.7 cells, inhibited cellular M1-type factor TNF-α and IL-1β secretion and increased M2-type factor IL-10 and TGF-β secretion, and accelerated macrophage conversion from M1 type to M2 type, whereas this protective effect of apigenin was counteracted by a miR-21 inhibitor. Moreover, we established a macrophage-HUVECs cell in vitro co-culture system and found that apigenin accelerated the migration, proliferation, and VEGF secretion of HUVECs by promoting macrophage miR-21 expression. Further, mechanistic studies revealed that this was mediated by the TLR4/Myd88/NF-κB axis. In in vivo study, diabetic mice had significantly delayed wound healing compared to non-diabetic mice, accelerated wound healing in apigenin-treated diabetic mice, and decreased M1-type macrophages and increased M2-type macrophages in wound tissues.
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Affiliation(s)
- Ke Li
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China
- Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China
| | - Lijun Wu
- Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China
| | - Jingting Jiang
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
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Dong Y, Wang M, Wang Q, Cao X, Chen P, Gong Z. Single-cell RNA-seq in diabetic foot ulcer wound healing. Wound Repair Regen 2024; 32:880-889. [PMID: 39264020 PMCID: PMC11584366 DOI: 10.1111/wrr.13218] [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: 02/06/2024] [Revised: 08/20/2024] [Accepted: 08/25/2024] [Indexed: 09/13/2024]
Abstract
Diabetic foot ulcer (DFU) is a chronic and serious complication of diabetes mellitus. It is mainly caused by hyperglycaemia, diabetic peripheral vasculopathy and diabetic peripheral neuropathy. These conditions result in ulceration of foot tissues and chronic wounds. If left untreated, DFU can lead to amputation or even endanger the patient's life. Single-cell RNA sequencing (scRNA-seq) is a technique used to identify and characterise transcriptional subpopulations at the single-cell level. It provides insight into cellular function and the molecular drivers of disease. The objective of this paper is to examine the subpopulations, genes and molecules of cells associated with chronic wounds of diabetic foot by using scRNA-seq. The paper aims to explore the wound-healing mechanism of DFU from three aspects: inflammation, angiogenesis and extracellular matrix remodelling. The goal is to gain a better understanding of the mechanism of DFU wound healing and identify possible DFU therapeutic targets, providing new insights for the application of DFU personalised therapy.
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Affiliation(s)
- Yan Dong
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Mengting Wang
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Qianqian Wang
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Xiaoliang Cao
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Peng Chen
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Zhenhua Gong
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
- Nantong Clinical Medical CollegeKangda College of Nanjing Medical UniversityNantongChina
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Manzoor T, Farooq N, Sharma A, Shiekh PA, Hassan A, Dar LA, Nazir J, Godha M, Sheikh FA, Gugjoo MB, Saleem S, Ahmad SM. Exosomes in nanomedicine: a promising cell-free therapeutic intervention in burn wounds. Stem Cell Res Ther 2024; 15:355. [PMID: 39385310 PMCID: PMC11462792 DOI: 10.1186/s13287-024-03970-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 10/01/2024] [Indexed: 10/12/2024] Open
Abstract
Burn injuries are serious injuries that have a big impact on a person's health and can even cause death. Incurring severe burns can incite an immune response and inflammation within the body, alongside metabolic changes. It is of utmost importance to grasp the fact that the effects of the burn injury extend beyond the body, affecting the mind and overall well-being. Burn injuries cause long-lasting changes that need to be taken care of in order to improve their quality of life. The intricate process of skin regeneration at the site of a burn wound involves a complex and dynamic interplay among diverse cells, growth factors, nerves, and blood vessels. Exciting opportunities have arisen in the field of stem cells and regenerative medicine, allowing us to explore the development of cell-free-based alternatives that can aid in the treatment of burn injuries. These cell-free-based therapies have emerged as a promising facet within regenerative medicine. Exosomes, also referred to as naturally occurring nanoparticles, are small endosome-derived vesicles that facilitate the delivery of molecular cargo between the cells, thus allowing intercellular communication. The knowledge gained in this field has continued to support their therapeutic potential, particularly in the domains of wound healing and tissue regeneration. Notably, exosomes derived from mesenchymal stem cells (MSCs) can be safely administered in the system, which is then adeptly uptaken and internalized by fibroblasts/epithelial cells, subsequently accelerating essential processes such as migration, proliferation, and collagen synthesis. Furthermore, exosomes released by immune cells, specifically macrophages, possess the capability to modulate inflammation and effectively diminish it in adjacent cells. Exosomes also act as carriers when integrated with a scaffold, leading to scarless healing of cutaneous wounds. This comprehensive review examines the role of exosomes in burn wound healing and their potential utility in regeneration and repair.
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Affiliation(s)
- Tasaduq Manzoor
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
- School of Life and Basic Sciences, Jaipur National University, Jagatpura, Jaipur, India
| | - Nida Farooq
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Arushi Sharma
- Centre for Biomedical Engineering, Indian Institute of Technology-Delhi, New Delhi, India
| | - Parvaiz A Shiekh
- Centre for Biomedical Engineering, Indian Institute of Technology-Delhi, New Delhi, India
| | - Amreena Hassan
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Lateef Ahmad Dar
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Junaid Nazir
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Meena Godha
- School of Life and Basic Sciences, Jaipur National University, Jagatpura, Jaipur, India
| | - Faheem A Sheikh
- Department of Nanotechnology, University of Kashmir, Srinagar, Kashmir, India
| | - Mudasir Bashir Gugjoo
- Veterinary Clinical Services Complex, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST- Srinagar, Kashmir, India
| | - Sahar Saleem
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Syed Mudasir Ahmad
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India.
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11
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Soheilifar MH, Masoudi-Khoram N, Hassani M, Hajialiasgary Najafabadi A, Khojasteh M, Keshmiri Neghab H, Jalili Z. Angio-microRNAs in diabetic foot ulcer-: Mechanistic insights and clinical perspectives. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2024; 192:1-10. [PMID: 39069213 DOI: 10.1016/j.pbiomolbio.2024.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 07/13/2024] [Accepted: 07/26/2024] [Indexed: 07/30/2024]
Abstract
Diabetic foot ulcers, as one of the chronic wounds, are a serious challenge in the global healthcare system which have shown notable growth in recent years. DFU is associated with impairment in various stages of wound healing, including angiogenesis. Aberrant expression of microRNAs (miRNAs) involved in the disruption of the balance between angiogenic and anti-angiogenic factors, plays a crucial role in angiogenesis dysfunction. Alteration in the expression of angiomiRNAs (angiomiRs) have the potential to function as biomarkers in chronic wounds. Additionally, considering the rising importance of therapeutic RNAs, there is potential for utilizing angiomiRs in wound healing to induce angiogenesis. This review aims to explore angiogenesis in chronic wounds and investigate the mechanisms mediated by pro- and anti-angiomiRs in the context of diabetic foot ulcers.
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Affiliation(s)
| | - Nastaran Masoudi-Khoram
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Hassani
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhossein Hajialiasgary Najafabadi
- Department of Quantitative and Computational Biology, Max Planck Institute for Multidisciplinary Sciences, Goettingen, 37077, Germany; Research Group Translational Epigenetics, Department of Pathology, University of Goettingen, Goettingen, 37075, Germany
| | - Mahdieh Khojasteh
- Heart Center of Goettingen, University Medicine Goettingen, Goettingen, Germany
| | - Hoda Keshmiri Neghab
- Department of Medical Laser, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
| | - Zahra Jalili
- Department of Medical Laser, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
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12
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Chen WT, Luo Y, Chen XM, Xiao JH. Role of exosome-derived miRNAs in diabetic wound angiogenesis. Mol Cell Biochem 2024; 479:2565-2580. [PMID: 37891446 DOI: 10.1007/s11010-023-04874-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 10/05/2023] [Indexed: 10/29/2023]
Abstract
Chronic wounds with high disability are among the most common and serious complications of diabetes. Angiogenesis dysfunction impair wound healing in patients with diabetes. Compared with traditional therapies that can only provide symptomatic treatment, stem cells-owing to their powerful paracrine properties, can alleviate the pathogenesis of chronic diabetic wounds and even cure them. Exosome-derived microRNAs (miRNAs), important components of stem cell paracrine signaling, have been reported for therapeutic use in various disease models, including diabetic wounds. Exosome-derived miRNAs have been widely reported to be involved in regulating vascular function and have promising applications in the repair and regeneration of skin wounds. Therefore, this article aims to review the current status of the pathophysiology of exosome-derived miRNAs in the diabetes-induced impairment of wound healing, along with current knowledge of the underlying mechanisms, emphasizing the regulatory mechanism of angiogenesis, we hope to document the emerging theoretical basis for improving wound repair by restoring angiogenesis in diabetes.
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Affiliation(s)
- Wen-Ting Chen
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China
| | - Yi Luo
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China
- Guizhou Provincial Universities Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China
| | - Xue-Mei Chen
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China
| | - Jian-Hui Xiao
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China.
- Guizhou Provincial Universities Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China.
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China.
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13
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Li Q, Pang B, Dang E, Wang G. Endothelial Dysfunction in Psoriasis: An Integrative Review. J Invest Dermatol 2024; 144:1935-1942. [PMID: 38493385 DOI: 10.1016/j.jid.2024.02.013] [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: 10/30/2023] [Revised: 02/07/2024] [Accepted: 02/20/2024] [Indexed: 03/18/2024]
Abstract
Vascular endothelial cells (ECs), the inner layer of blood vessels, were previously considered to be a passive lining that facilitates cellular and molecular exchange. However, recent studies have revealed that ECs can respond to various stimuli and actively regulate vascular function and skin inflammation. Specific subtypes of ECs are known to have significant roles in a diverse range of physiological and pathological processes in the skin. This review suggests that EC dysfunction is both causal and consequential in the pathogenesis of psoriasis. Further investigations into dysregulated pathways in EC dysfunction may provide new insights for the treatment of psoriasis.
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Affiliation(s)
- Qingyang Li
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People Republic of China
| | - Bingyu Pang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People Republic of China
| | - Erle Dang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People Republic of China
| | - Gang Wang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People Republic of China.
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14
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Peng H, Du F, Wang J, Wu Y, Wei Q, Chen A, Duan Y, Shi S, Zhang J, Yu S. Adipose-Derived Stem-Cell-Membrane-Coated PLGA-PEI Nanoparticles Promote Wound Healing via Efficient Delivery of miR-21. Pharmaceutics 2024; 16:1113. [PMID: 39339150 PMCID: PMC11434648 DOI: 10.3390/pharmaceutics16091113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 07/31/2024] [Accepted: 08/21/2024] [Indexed: 09/30/2024] Open
Abstract
miRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles.
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Affiliation(s)
- Huiyu Peng
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Fangzhou Du
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Jingwen Wang
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Yue Wu
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Qian Wei
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Aoying Chen
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Yuhan Duan
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Shuaiguang Shi
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Jingzhong Zhang
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
- School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China
| | - Shuang Yu
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
- School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China
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15
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Hou Y, Tang Y, Cai S. Advances in the study of microparticles in diabetic retinopathy. Postgrad Med J 2024; 100:626-634. [PMID: 38572927 DOI: 10.1093/postmj/qgae046] [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: 12/29/2023] [Revised: 03/07/2024] [Accepted: 03/16/2024] [Indexed: 04/05/2024]
Abstract
Diabetic retinopathy (DR) is one of the common diabetic microangiopathies, which severely impairs vision in diabetic population. The underlying mechanisms regarding the development of DR are not fully understood, and there is a lack of biomarkers to guide clinical, assessment of disease progression. Recently researchers have found that microparticles (MP) and its bioactive molecules are involved in the development of DR. MP is widely distributed in the circulation and can exert autocrine and paracrine benefits in intercellular signalling, provide a catalytic platform for the thrombospondin complex to promote coagulation, and promote the accumulation of reactive oxygen species to cause endothelial damage. MP interacts with advanced glycosylation end products (AGE) and AGE receptor (RAGE) to activate inflammatory pathways. MP carries a variety of miRNAs that regulate the vascular endothelial growth factor generation pathway. MP has also been applied to the exploration of mesenchymal stromal cell replacement therapy to treat DR. In a word, MP provides new ideas for the study of DR. MP has emerged as a marker to assess the progression of DR. As a potential therapeutic target, MP also has considerable research value.
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Affiliation(s)
- Yifeng Hou
- Department of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
- Guizhou Eye Hospital, Zunyi 563003, Guizhou Province, China
- Special Key Laboratory of Ocular Diseases of Guizhou Province, Zunyi 563003, Guizhou Province, China
- Special Key Laboratory of Ocular Diseases of Guizhou Province, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Yun Tang
- Department of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
- Guizhou Eye Hospital, Zunyi 563003, Guizhou Province, China
- Special Key Laboratory of Ocular Diseases of Guizhou Province, Zunyi 563003, Guizhou Province, China
- Special Key Laboratory of Ocular Diseases of Guizhou Province, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Shanjun Cai
- Department of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
- Guizhou Eye Hospital, Zunyi 563003, Guizhou Province, China
- Special Key Laboratory of Ocular Diseases of Guizhou Province, Zunyi 563003, Guizhou Province, China
- Special Key Laboratory of Ocular Diseases of Guizhou Province, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
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16
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Xing X, Rodeo SA. Emerging roles of non-coding RNAs in fibroblast to myofibroblast transition and fibrotic diseases. Front Pharmacol 2024; 15:1423045. [PMID: 39114349 PMCID: PMC11303237 DOI: 10.3389/fphar.2024.1423045] [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: 04/25/2024] [Accepted: 07/01/2024] [Indexed: 08/10/2024] Open
Abstract
The transition of fibroblasts to myofibroblasts (FMT) represents a pivotal process in wound healing, tissue repair, and fibrotic diseases. This intricate transformation involves dynamic changes in cellular morphology, gene expression, and extracellular matrix remodeling. While extensively studied at the molecular level, recent research has illuminated the regulatory roles of non-coding RNAs (ncRNAs) in orchestrating FMT. This review explores the emerging roles of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating this intricate process. NcRNAs interface with key signaling pathways, transcription factors, and epigenetic mechanisms to fine-tune gene expression during FMT. Their functions are critical in maintaining tissue homeostasis, and disruptions in these regulatory networks have been linked to pathological fibrosis across various tissues. Understanding the dynamic roles of ncRNAs in FMT bears therapeutic promise. Targeting specific ncRNAs holds potential to mitigate exaggerated myofibroblast activation and tissue fibrosis. However, challenges in delivery and specificity of ncRNA-based therapies remain. In summary, ncRNAs emerge as integral regulators in the symphony of FMT, orchestrating the balance between quiescent fibroblasts and activated myofibroblasts. As research advances, these ncRNAs appear to be prospects for innovative therapeutic strategies, offering hope in taming the complexities of fibrosis and restoring tissue equilibrium.
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Affiliation(s)
- Xuewu Xing
- Department of Orthopaedics, Tianjin First Central Hospital, Tianjin, China
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, United States
| | - Scott A. Rodeo
- Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, United States
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17
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Kamal R, Awasthi A, Pundir M, Thakur S. Healing the diabetic wound: Unlocking the secrets of genes and pathways. Eur J Pharmacol 2024; 975:176645. [PMID: 38759707 DOI: 10.1016/j.ejphar.2024.176645] [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: 03/04/2024] [Revised: 05/03/2024] [Accepted: 05/13/2024] [Indexed: 05/19/2024]
Abstract
Diabetic wounds (DWs) are open sores that can occur anywhere on a diabetic patient's body. They are often complicated by infections, hypoxia, oxidative stress, hyperglycemia, and reduced growth factors and nucleic acids. The healing process involves four phases: homeostasis, inflammation, proliferation, and remodeling, regulated by various cellular and molecular events. Numerous genes and signaling pathways such as VEGF, TGF-β, NF-κB, PPAR-γ, MMPs, IGF, FGF, PDGF, EGF, NOX, TLR, JAK-STAT, PI3K-Akt, MAPK, ERK, JNK, p38, Wnt/β-catenin, Hedgehog, Notch, Hippo, FAK, Integrin, and Src pathways are involved in these events. These pathways and genes are often dysregulated in DWs leading to impaired healing. The present review sheds light on the pathogenesis, healing process, signaling pathways, and genes involved in DW. Further, various therapeutic strategies that target these pathways and genes via nanotechnology are also discussed. Additionally, clinical trials on DW related to gene therapy are also covered in the present review.
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Affiliation(s)
- Raj Kamal
- Department of Quality Assurance, ISF College of Pharmacy, Moga, Punjab, 142001, India
| | - Ankit Awasthi
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001, India.
| | - Mandeep Pundir
- School of Pharmaceutical Sciences, RIMT University, Punjab, 142001, India; Chitkara College of Pharmacy, Chitkara University, Punjab, 142001, India
| | - Shubham Thakur
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001, India
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18
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Li Y, Wang S, Dong Y, Jin X, Wang J, Zhang H. Tetrahedral DNA-Based Functional MicroRNA-21 Delivery System: Application to Corneal Epithelial Wound Healing. Adv Healthc Mater 2024; 13:e2304381. [PMID: 38549217 DOI: 10.1002/adhm.202304381] [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: 12/10/2023] [Revised: 03/26/2024] [Indexed: 05/12/2024]
Abstract
Corneal injury occurs frequently which may lead to serious visual impairment. Rapid and efficient re-epithelialization after corneal epithelial injury is the key issue for maintaining corneal homeostasis. Among various treatment strategies, microRNA (miR)-based therapy shows great potential. However, structural limitations of miRNAs hinder its biomedical functionality. Nucleic acid nanotechnology is an appealing candidate for gene delivery because of its flexible modification and excellent biocompatibility. Herein, modified 3D tetrahedral framework nucleic acids (tFNAs) utilized as gene carriers for miR-21 delivery are constructed. TFNAs-miR-21 (T-21) shows great enzymatic resistance in extracellular environment and payload delivery into human corneal epithelial cells (HCECs) via clathrin-mediated endocytosis. T-21 facilitates proliferation and migration in HCECs via activating PI3K/AKT and ERK1/2 signaling pathways in vitro. In vivo studies, T-21 can be internalized by corneal epithelium in mice. In the mice corneal scratch model, T-21 ophthalmic solutions used as eye drops show no apparent side effects on the ocular surface histologically and exert great potential in accelerating corneal wound healing. These findings demonstrate that modified tFNAs are promising candidates for miRNA delivery for corneal wound healing. The convenient administration and great biocompatibility of tetrahedral DNA nanoparticles highlight its potential as gene transporter in solving ocular problems.
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Affiliation(s)
- Yulin Li
- Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China
| | - Shu Wang
- Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China
| | - Yueyan Dong
- Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China
| | - Xin Jin
- Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China
| | - Jingrao Wang
- Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China
| | - Hong Zhang
- Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China
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19
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Song X, Liu F, Chen M, Zhu M, Zheng H, Wang W, Chen D, Li M, Chen S. MiR-21 regulates skeletal muscle atrophy and fibrosis by targeting TGF-beta/SMAD7-SMAD2/3 signaling pathway. Heliyon 2024; 10:e33062. [PMID: 39027432 PMCID: PMC11254527 DOI: 10.1016/j.heliyon.2024.e33062] [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: 12/11/2023] [Revised: 06/12/2024] [Accepted: 06/13/2024] [Indexed: 07/20/2024] Open
Abstract
Long-term denervation-induced atrophy and fibrosis of skeletal muscle due to denervation leads to poor recovery of muscle function. Studies have shown that the transforming growth factor-β1 (TGF-β1)-Smad signaling pathway plays a central role in muscle atrophy and fibrosis. Recent studies demonstrate the role of microRNAs (miRs) in various pathological conditions, including muscle regeneration. miR-21 has been shown to play a dynamic role in inflammatory responses and in accelerating injury responses to fibrosis. We used both RNA sequencing and quantitative RT-PCR strategies to examine the alternations of miRNAs during denervation-induced gastrocnemius muscle atrophy and fibrosis. Our data showed that MiR-21 was upregulated in denervated gastrocnemius muscle tissue, and TGF-β1treatment increased miR-21 expression. Inhibition of miR-21 reduced gastrocnemius muscle fibrosis and significantly downregulated the expression of p-SMAD2/3 and the fibrosis-associated markers TGF-β1, connective tissue growth factor, alpha smooth muscle actin. Masson's trichrome staining revealed that atrophy and fibrosis in gastrocnemius muscle tissue were reduced in the miR-21 inhibition group compared to the control group. We confirmed that SMAD7 is a direct target of miR-21 using a dual luciferase assay. Furthermore, Immunofluorescence and Western blot analyses revealed that miR-21 inhibition reduced SMAD2/3 phosphorylation and nuclear translocation. While SMAD7-siRNA abolished the effect. Consequently, the discovery that miR-21 regulates the atrophy and fibrosis of the gastrocnemius muscle offers a possible therapeutic approach for their management.
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Affiliation(s)
- Xianmin Song
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
| | - Fei Liu
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
| | - Mengjie Chen
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
| | - Minhui Zhu
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
| | - Hongliang Zheng
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
| | - Wei Wang
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
| | - Donghui Chen
- Department of Otorhinolaryngology, The First Affiliate Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Meng Li
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
| | - Shicai Chen
- From the Department of Otorhinolaryngology & Head and Neck Surgery, Changhai Hospital, Naval Military Medical University (The Second Military Medical University), Shanghai, 200433, China
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20
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Liu C, Zhang Q, Liu Z, Zhuang D, Wang S, Deng H, Shi Y, Sun J, Guo J, Wei F, Wu X. miR-21 Expressed by Dermal Fibroblasts Enhances Skin Wound Healing Through the Regulation of Inflammatory Cytokine Expression. Inflammation 2024; 47:572-590. [PMID: 38041730 DOI: 10.1007/s10753-023-01930-2] [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: 05/30/2023] [Revised: 10/20/2023] [Accepted: 11/06/2023] [Indexed: 12/03/2023]
Abstract
The management of skin wound healing is still a challenge. MicroRNA-21 (miR-21) has been reported to play important roles in wound repair; however, the underlying mechanism needs to be further clarified. The present study aimed to study the direct role of miR-21 in skin wound healing in miR-21 KO mice and to investigate the role of miR-21 in controlling the migration and proliferation of primary human skin cells and its underlying mechanism(s). miR-21 KO and wild-type (WT) mice were used for in vivo wound healing assays, while mouse and human primary skin cells were used for in vitro assays. miR-21 inhibitors or mimics or negative control small RNAs were transfected to either inhibit or enhance miR-21 expression in the human primary dermal fibroblasts or epidermal cells. RNA sequencing analysis was performed to identify the potential molecular pathways involved. We found that the loss of miR-21 resulted in slower wound healing in miR-21 KO mouse skin and especially delayed the healing of dermal tissue. In vitro assays demonstrated that the reduced expression of miR-21 caused by its inhibitor inhibited the migration of human primary dermal fibroblasts, which could be enhanced by increased miR-21 expression caused by miR-21 mimics. RNA-sequence analysis revealed that the inhibition of miR-21 expression downregulated the inflammatory response pathways associated with the decreased expression of inflammatory cytokines, and the addition of IL-1β into the culture medium enhanced the migration and proliferation of dermal fibroblasts in vitro. In conclusion, miR-21 in dermal fibroblasts can promote the migration and growth of epidermal and dermal cells to enhance skin wound healing through controlling the expression of inflammatory cytokines.
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Affiliation(s)
- Chang Liu
- Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Qun Zhang
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Zhenan Liu
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Dexuan Zhuang
- Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Shuangshuang Wang
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Huiting Deng
- Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China
| | - Yuxin Shi
- Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China
| | - Jianfeng Sun
- Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China
| | - Jing Guo
- Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, China
| | - Fulan Wei
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, China.
| | - Xunwei Wu
- Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, China.
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China.
- Suzhou Research Institute, Shandong University, No. 388 Ruoshui Road, Suzhou, Jiangsu, China.
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21
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Gu F, Huang X, Huang W, Zhao M, Zheng H, Wang Y, Chen R. The role of miRNAs in Behçet's disease. Front Immunol 2023; 14:1249826. [PMID: 37860009 PMCID: PMC10584330 DOI: 10.3389/fimmu.2023.1249826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/12/2023] [Indexed: 10/21/2023] Open
Abstract
The symptoms of Behçet's disease (BD), a multisystemic condition with autoimmune and inflammation as hallmarks, include arthritis, recurring oral and vaginal ulcers, skin rashes and lesions, and involvement of the nervous, gastrointestinal, and vascular systems. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), may be important regulators of inflammation and autoimmune disease. These ncRNAs are essential to the physiological and pathophysiological disease course, and miRNA in particular has received significant attention for its role and function in BD and its potential use as a diagnostic biomarker in recent years. Although promising as therapeutic targets, miRNAs must be studied further to fully comprehend how miRNAs in BD act biologically.
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Affiliation(s)
| | | | | | | | | | - Yuanyin Wang
- College and Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China
| | - Ran Chen
- College and Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China
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22
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Das K, Paul S, Mukherjee T, Ghosh A, Sharma A, Shankar P, Gupta S, Keshava S, Parashar D. Beyond Macromolecules: Extracellular Vesicles as Regulators of Inflammatory Diseases. Cells 2023; 12:1963. [PMID: 37566042 PMCID: PMC10417494 DOI: 10.3390/cells12151963] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/12/2023] Open
Abstract
Inflammation is the defense mechanism of the immune system against harmful stimuli such as pathogens, toxic compounds, damaged cells, radiation, etc., and is characterized by tissue redness, swelling, heat generation, pain, and loss of tissue functions. Inflammation is essential in the recruitment of immune cells at the site of infection, which not only aids in the elimination of the cause, but also initiates the healing process. However, prolonged inflammation often brings about several chronic inflammatory disorders; hence, a balance between the pro- and anti-inflammatory responses is essential in order to eliminate the cause while producing the least damage to the host. A growing body of evidence indicates that extracellular vesicles (EVs) play a major role in cell-cell communication via the transfer of bioactive molecules in the form of proteins, lipids, DNA, RNAs, miRNAs, etc., between the cells. The present review provides a brief classification of the EVs followed by a detailed description of how EVs contribute to the pathogenesis of various inflammation-associated diseases and their implications as a therapeutic measure. The latter part of the review also highlights how EVs act as a bridging entity in blood coagulation disorders and associated inflammation. The findings illustrated in the present review may open a new therapeutic window to target EV-associated inflammatory responses, thereby minimizing the negative outcomes.
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Affiliation(s)
- Kaushik Das
- Department of Cellular and Molecular Biology, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA
| | - Subhojit Paul
- School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India; (S.P.); (A.G.)
| | - Tanmoy Mukherjee
- School of Medicine, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA;
| | - Arnab Ghosh
- School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India; (S.P.); (A.G.)
| | - Anshul Sharma
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA;
| | - Prem Shankar
- Department of Neurobiology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA;
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura 281406, India;
| | - Shiva Keshava
- Department of Cellular and Molecular Biology, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA
| | - Deepak Parashar
- Department of Medicine, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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23
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Kalhori MR, Soleimani M, Alibakhshi R, Kalhori AA, Mohamadi P, Azreh R, Farzaei MH. The Potential of miR-21 in Stem Cell Differentiation and its Application in Tissue Engineering and Regenerative Medicine. Stem Cell Rev Rep 2023; 19:1232-1251. [PMID: 36899116 DOI: 10.1007/s12015-023-10510-8] [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] [Accepted: 01/18/2023] [Indexed: 03/12/2023]
Abstract
MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two important types of non-coding RNAs that are not translated into protein. These molecules can regulate various biological processes, including stem cell differentiation and self-renewal. One of the first known miRNAs in mammals is miR-21. Cancer-related studies have shown that this miRNA has proto-oncogene activity and is elevated in cancers. However, it is confirmed that miR-21 inhibits stem cell pluripotency and self-renewal and induces differentiation by targeting various genes. Regenerative medicine is a field of medical science that tries to regenerate and repair damaged tissues. Various studies have shown that miR-21 plays an essential role in regenerative medicine by affecting stem cell proliferation and differentiation. In this review, we will discuss the function of miR-21 in regenerative medicine of the liver, nerve, spinal cord, wound, bone, and dental tissues. In addition, the function of natural compounds and lncRNAs will be analyzed as potential regulators of miR-21 expression in regenerative medicine.
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Affiliation(s)
- Mohammad Reza Kalhori
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Masoud Soleimani
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Reza Alibakhshi
- Department of Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amir Ali Kalhori
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Parisa Mohamadi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical, Sciences, Tehran, Iran
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Rasoul Azreh
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Hosien Farzaei
- Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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24
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Amini A, Ghasemi Moravej F, Mostafavinia A, Ahmadi H, Chien S, Bayat M. Photobiomodulation Therapy Improves Inflammatory Responses by Modifying Stereological Parameters, microRNA-21 and FGF2 Expression. J Lasers Med Sci 2023; 14:e16. [PMID: 37583493 PMCID: PMC10423949 DOI: 10.34172/jlms.2023.16] [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: 01/09/2023] [Accepted: 03/13/2023] [Indexed: 08/17/2023]
Abstract
Introduction: Photobiomodulation treatment (PBMT) is a relatively invasive method for treating wounds. An appropriate type of PBMT can produce desired and directed cellular and molecular processes. The aim of this study was to investigate the impacts of PBMT on stereological factors, bacterial count, and the expression of microRNA-21 and FGF2 in an infected, ischemic, and delayed wound healing model in rats with type one diabetes mellitus. Methods: A delayed, ischemic, and infected wound was produced on the back skin of all 24 DM1 rats. Then, they were put into 4 groups at random (n=6 per group): 1=Control group day4 (CGday4); 2=Control group day 8 (CGday8); 3=PBMT group day4 (PGday4), in which the rats were exposed to PBMT and killed on day 4; 4=PBMT group day8 (PGday8), in which the rats received PBMT and they were killed on day 8. The size of the wound, the number of microbial colonies, stereological parameters, and the expression of microRNA-21 and FGF2 were all assessed in this study throughout the inflammation (day 4) and proliferation (day 8) stages of wound healing. Results: On days 4 and 8, we discovered that the PGday4 and PGday8 groups significantly improved stereological parameters in comparison with the same CG groups. In terms of ulcer area size and microbiological counts, the PGday4 and PGday8 groups performed much better than the same CG groups. Simultaneously, the biomechanical findings in the PGday4 and PGday8 groups were much more extensive than those in the same CG groups. On days 4 and 8, the expression of FGF2 and microRNA-21 was more in all PG groups than in the CG groups (P<0.01). Conclusion: PBMT significantly speeds up the repair of ischemic and MARS-infected wounds in DM1 rats by lowering microbial counts and modifying stereological parameters, microRNA-21, and FGF2 expression.
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Affiliation(s)
- Abdollah Amini
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Ghasemi Moravej
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atarodalsadat Mostafavinia
- Department of Anatomy, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Hossein Ahmadi
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sufan Chien
- Price Institute of Surgical Research, University of Louisville, and Noveratech LLC, Louisville, Kentucky, USA
| | - Mohammad Bayat
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Price Institute of Surgical Research, University of Louisville, and Noveratech LLC, Louisville, Kentucky, USA
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25
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Spiers HVM, Stadler LKJ, Smith H, Kosmoliaptsis V. Extracellular Vesicles as Drug Delivery Systems in Organ Transplantation: The Next Frontier. Pharmaceutics 2023; 15:891. [PMID: 36986753 PMCID: PMC10052210 DOI: 10.3390/pharmaceutics15030891] [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: 11/23/2022] [Revised: 02/22/2023] [Accepted: 02/24/2023] [Indexed: 03/12/2023] Open
Abstract
Extracellular vesicles are lipid bilayer-delimited nanoparticles excreted into the extracellular space by all cells. They carry a cargo rich in proteins, lipids and DNA, as well as a full complement of RNA species, which they deliver to recipient cells to induce downstream signalling, and they play a key role in many physiological and pathological processes. There is evidence that native and hybrid EVs may be used as effective drug delivery systems, with their intrinsic ability to protect and deliver a functional cargo by utilising endogenous cellular mechanisms making them attractive as therapeutics. Organ transplantation is the gold standard for treatment for suitable patients with end-stage organ failure. However, significant challenges still remain in organ transplantation; prevention of graft rejection requires heavy immunosuppression and the lack of donor organs results in a failure to meet demand, as manifested by growing waiting lists. Pre-clinical studies have demonstrated the ability of EVs to prevent rejection in transplantation and mitigate ischemia reperfusion injury in several disease models. The findings of this work have made clinical translation of EVs possible, with several clinical trials actively recruiting patients. However, there is much to be uncovered, and it is essential to understand the mechanisms behind the therapeutic benefits of EVs. Machine perfusion of isolated organs provides an unparalleled platform for the investigation of EV biology and the testing of the pharmacokinetic and pharmacodynamic properties of EVs. This review classifies EVs and their biogenesis routes, and discusses the isolation and characterisation methods adopted by the international EV research community, before delving into what is known about EVs as drug delivery systems and why organ transplantation represents an ideal platform for their development as drug delivery systems.
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Affiliation(s)
- Harry V M Spiers
- Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Cambridge CB2 0QQ, UK
| | - Lukas K J Stadler
- Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Cambridge CB2 0QQ, UK
| | - Hugo Smith
- Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
| | - Vasilis Kosmoliaptsis
- Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Cambridge CB2 0QQ, UK
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26
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Chen J, Qin S, Liu S, Zhong K, Jing Y, Wu X, Peng F, Li D, Peng C. Targeting matrix metalloproteases in diabetic wound healing. Front Immunol 2023; 14:1089001. [PMID: 36875064 PMCID: PMC9981633 DOI: 10.3389/fimmu.2023.1089001] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 02/06/2023] [Indexed: 02/19/2023] Open
Abstract
Chronic inflammation participates in the progression of multiple chronic diseases, including obesity, diabetes mellitus (DM), and DM related complications. Diabetic ulcer, characterized by chronic wounds that are recalcitrant to healing, is a serious complication of DM tremendously affecting the quality of life of patients and imposing a costly medical burden on society. Matrix metalloproteases (MMPs) are a family of zinc endopeptidases with the capacity of degrading all the components of the extracellular matrix, which play a pivotal part in healing process under various conditions including DM. During diabetic wound healing, the dynamic changes of MMPs in the serum, skin tissues, and wound fluid of patients are in connection with the degree of wound recovery, suggesting that MMPs can function as essential biomarkers for the diagnosis of diabetic ulcer. MMPs participate in various biological processes relevant to diabetic ulcer, such as ECM secretion, granulation tissue configuration, angiogenesis, collagen growth, re-epithelization, inflammatory response, as well as oxidative stress, thus, seeking and developing agents targeting MMPs has emerged as a potential way to treat diabetic ulcer. Natural products especially flavonoids, polysaccharides, alkaloids, polypeptides, and estrogens extracted from herbs, vegetables, as well as animals that have been extensively illustrated to treat diabetic ulcer through targeting MMPs-mediated signaling pathways, are discussed in this review and may contribute to the development of functional foods or drug candidates for diabetic ulcer therapy. This review highlights the regulation of MMPs in diabetic wound healing, and the potential therapeutic ability of natural products for diabetic wound healing by targeting MMPs.
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Affiliation(s)
- Junren Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Siqi Qin
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shengmeng Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Kexin Zhong
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yiqi Jing
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xuan Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China
| | - Fu Peng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Pharmacology, Sichuan University, Chengdu, China
- Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Dan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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27
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Dolivo DM, Sun LS, Rodrigues AE, Galiano RD, Mustoe TA, Hong SJ. Epidermal Potentiation of Dermal Fibrosis: Lessons from Occlusion and Mucosal Healing. THE AMERICAN JOURNAL OF PATHOLOGY 2023; 193:510-519. [PMID: 36740181 DOI: 10.1016/j.ajpath.2023.01.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/05/2023]
Abstract
Fibrotic skin conditions, such as hypertrophic and keloid scars, frequently result from injury to the skin and as sequelae to surgical procedures. The development of skin fibrosis may lead to patient discomfort, limitation in range of motion, and cosmetic disfigurement. Despite the frequency of skin fibrosis, treatments that seek to address the root causes of fibrosis are lacking. Much research into fibrotic pathophysiology has focused on dermal pathology, but less research has been performed to understand aberrations in fibrotic epidermis, leading to an incomplete understanding of dermal fibrosis. The literature on occlusion, a treatment modality known to reduce dermal fibrosis, in part through accelerating wound healing and regulating aberrant epidermal inflammation that otherwise drives fibrosis in the dermis, is reviewed. There is a focus on epidermal-dermal crosstalk, which contributes to the development and maintenance of dermal fibrosis, an underemphasized interplay that may yield novel strategies for treatment if understood in more detail.
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Affiliation(s)
- David M Dolivo
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Lauren S Sun
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Adrian E Rodrigues
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Robert D Galiano
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Thomas A Mustoe
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Seok Jong Hong
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
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28
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Deka Dey A, Yousefiasl S, Kumar A, Dabbagh Moghaddam F, Rahimmanesh I, Samandari M, Jamwal S, Maleki A, Mohammadi A, Rabiee N, Cláudia Paiva‐Santos A, Tamayol A, Sharifi E, Makvandi P. miRNA-encapsulated abiotic materials and biovectors for cutaneous and oral wound healing: Biogenesis, mechanisms, and delivery nanocarriers. Bioeng Transl Med 2023; 8:e10343. [PMID: 36684081 PMCID: PMC9842058 DOI: 10.1002/btm2.10343] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/21/2022] [Accepted: 04/23/2022] [Indexed: 01/25/2023] Open
Abstract
MicroRNAs (miRNAs) as therapeutic agents have attracted increasing interest in the past decade owing to their significant effectiveness in treating a wide array of ailments. These polymerases II-derived noncoding RNAs act through post-transcriptional controlling of different proteins and their allied pathways. Like other areas of medicine, researchers have utilized miRNAs for managing acute and chronic wounds. The increase in the number of patients suffering from either under-healing or over-healing wound demonstrates the limited efficacy of the current wound healing strategies and dictates the demands for simpler approaches with greater efficacy. Various miRNA can be designed to induce pathway beneficial for wound healing. However, the proper design of miRNA and its delivery system for wound healing applications are still challenging due to their limited stability and intracellular delivery. Therefore, new miRNAs are required to be identified and their delivery strategy needs to be optimized. In this review, we discuss the diverse roles of miRNAs in various stages of wound healing and provide an insight on the most recent findings in the nanotechnology and biomaterials field, which might offer opportunities for the development of new strategies for this chronic condition. We also highlight the advances in biomaterials and delivery systems, emphasizing their challenges and resolutions for miRNA-based wound healing. We further review various biovectors (e.g., adenovirus and lentivirus) and abiotic materials such as organic and inorganic nanomaterials, along with dendrimers and scaffolds, as the delivery systems for miRNA-based wound healing. Finally, challenges and opportunities for translation of miRNA-based strategies into clinical applications are discussed.
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Affiliation(s)
| | - Satar Yousefiasl
- School of DentistryHamadan University of Medical SciencesHamadanIran
| | - Arun Kumar
- Chitkara College of PharmacyChitkara UniversityPunjabIndia
| | - Farnaz Dabbagh Moghaddam
- Department of Biology, Science and Research BranchIslamic Azad UniversityTehranIran
- Institute for Photonics and Nanotechnologies, National Research Council, Via Fosso del Cavaliere, 100RomeItaly
| | - Ilnaz Rahimmanesh
- Applied Physiology Research CenterCardiovascular Research Institute, Isfahan University of Medical SciencesIsfahanIran
| | | | - Sumit Jamwal
- Department of Psychiatry, Yale School of MedicineYale UniversityNew HavenConnecticutUSA
| | - Aziz Maleki
- Department of Pharmaceutical Nanotechnology, School of PharmacyZanjan University of Medical SciencesZanjanIran
- Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC)Zanjan University of Medical SciencesZanjanIran
- Cancer Research CentreShahid Beheshti University of Medical SciencesTehranIran
| | | | - Navid Rabiee
- Department of PhysicsSharif University of TechnologyTehranIran
- School of EngineeringMacquarie UniversitySydneyNew South WalesAustralia
| | - Ana Cláudia Paiva‐Santos
- Department of Pharmaceutical TechnologyFaculty of Pharmacy of the University of Coimbra, University of CoimbraCoimbraPortugal
- LAQV, REQUIMTE, Department of Pharmaceutical TechnologyFaculty of Pharmacy of the University of Coimbra, University of CoimbraCoimbraPortugal
| | - Ali Tamayol
- Department of Biomedical EngineeringUniversity of ConnecticutFarmingtonConnecticutUSA
| | - Esmaeel Sharifi
- Department of Tissue Engineering and Biomaterials, School of Advanced Medical Sciences and TechnologiesHamadan University of Medical SciencesHamadanIran
| | - Pooyan Makvandi
- Istituto Italiano di Tecnologia, Centre for Materials InterfacesPontederaItaly
- School of Chemistry, Damghan UniversityDamghanIran
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29
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Lyttle BD, Vaughn AE, Bardill JR, Apte A, Gallagher LT, Zgheib C, Liechty KW. Effects of microRNAs on angiogenesis in diabetic wounds. Front Med (Lausanne) 2023; 10:1140979. [PMID: 37020673 PMCID: PMC10067680 DOI: 10.3389/fmed.2023.1140979] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 02/27/2023] [Indexed: 04/07/2023] Open
Abstract
Diabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds. Over recent years, microRNAs (miRNAs) have been implicated in the dysregulation of angiogenesis in multiple pathologies including diabetes. This review explores the pathways of angiogenesis that become dysregulated in diabetes, focusing on miRNAs that have been identified and the mechanisms by which they affect angiogenesis.
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Affiliation(s)
- Bailey D. Lyttle
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, School of Medicine, University of Colorado Denver—Anschutz Medical Campus, Aurora, CO, United States
- *Correspondence: Bailey D. Lyttle,
| | - Alyssa E. Vaughn
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, School of Medicine, University of Colorado Denver—Anschutz Medical Campus, Aurora, CO, United States
| | - James R. Bardill
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, School of Medicine, University of Colorado Denver—Anschutz Medical Campus, Aurora, CO, United States
| | - Anisha Apte
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, College of Medicine, University of Arizona Health Sciences College of Medicine—Tucson, Tucson, AZ, United States
| | - Lauren T. Gallagher
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, School of Medicine, University of Colorado Denver—Anschutz Medical Campus, Aurora, CO, United States
| | - Carlos Zgheib
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, College of Medicine, University of Arizona Health Sciences College of Medicine—Tucson, Tucson, AZ, United States
| | - Kenneth W. Liechty
- Laboratory for Fetal and Regenerative Biology, Department of Surgery, College of Medicine, University of Arizona Health Sciences College of Medicine—Tucson, Tucson, AZ, United States
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Song B, Chen Q, Li Y, Zhan S, Zhao R, Shen X, Liu M, Tong C. Functional Roles of Exosomes in Allergic Contact Dermatitis. J Microbiol Biotechnol 2022; 32:1506-1514. [PMID: 36377198 PMCID: PMC9843815 DOI: 10.4014/jmb.2206.06024] [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: 06/16/2022] [Revised: 08/29/2022] [Accepted: 09/06/2022] [Indexed: 11/17/2022]
Abstract
Allergic contact dermatitis (ACD) is an allergen-specific T-cell-mediated inflammatory response, albeit with unclear pathogenesis. Exosomes are nanoscale extracellular vesicles secreted by several cell types and widely distributed in various biological fluids. Exosomes affect the occurrence and development of ACD through immunoregulation among other ways. Nevertheless, the role of exosomes in ACD warrants further clarification. This review examines the progress of research into exosomes and their involvement in the pathogenesis, diagnosis, and treatment of ACD and provides ideas for exploring new diagnostic and treatment methods for this disease.
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Affiliation(s)
- Bocui Song
- Department of Pharmaceutical Engineering, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, P.R. China,
B. Song Phone/ Fax: +86-6819296 E-mail:
| | - Qian Chen
- Molecular Mechanism of Disease and Research and Development of Bioactive Substances, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, P.R. China
| | - Yuqi Li
- Molecular Mechanism of Disease and Research and Development of Bioactive Substances, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, P.R. China
| | - Shuang Zhan
- Animal Husbandry and Veterinary Station of Yongji Economic Development Zone, Jilin 132200, Jilin Province, P.R. China
| | - Rui Zhao
- Department of Pharmaceutical Engineering, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, P.R. China
| | - Xue Shen
- Molecular Mechanism of Disease and Research and Development of Bioactive Substances, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, P.R. China
| | - Min Liu
- Department of Pharmaceutical Engineering, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, P.R. China
| | - Chunyu Tong
- Department of Biological Science, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, P.R. China,Corresponding authors C. Tong Phone/ Fax: +86-6819296 E-mail:
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Tang YB, Uwimana MMP, Zhu SQ, Zhang LX, Wu Q, Liang ZX. Non-coding RNAs: Role in diabetic foot and wound healing. World J Diabetes 2022; 13:1001-1013. [PMID: 36578864 PMCID: PMC9791568 DOI: 10.4239/wjd.v13.i12.1001] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/26/2022] [Accepted: 11/18/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetic foot ulcer (DFU) and poor wound healing are chronic complications in patients with diabetes. The increasing incidence of DFU has resulted in huge pressure worldwide. Diagnosing and treating this condition are therefore of great importance to control morbidity and improve prognosis. Finding new markers with potential diagnostic and therapeutic utility in DFU has gathered increasing interest. Wound healing is a process divided into three stages: Inflammation, proliferation, and regeneration. Non-coding RNAs (ncRNAs), which are small protected molecules transcribed from the genome without protein translation function, have emerged as important regulators of diabetes complications. The deregulation of ncRNAs may be linked to accelerated DFU development and delayed wound healing. Moreover, ncRNAs can be used for therapeutic purposes in diabetic wound healing. Herein, we summarize the role of microRNAs, long ncRNAs, and circular RNAs in diverse stages of DFU wound healing and their potential use as novel therapeutic targets.
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Affiliation(s)
- Yi-Bo Tang
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Muhuza Marie Parfaite Uwimana
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Shu-Qi Zhu
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Li-Xia Zhang
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Qi Wu
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Zhao-Xia Liang
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
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Lu S, Lu L, Liu Y, Li Z, Fang Y, Chen Z, Zhou J. Native and engineered extracellular vesicles for wound healing. Front Bioeng Biotechnol 2022; 10:1053217. [PMID: 36568307 PMCID: PMC9780283 DOI: 10.3389/fbioe.2022.1053217] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022] Open
Abstract
Extracellular vesicles (EVs) that act as messengers mediate communication between parent and recipient cells through their contents, including nucleic acids, proteins, and lipids. These endogenous vesicles have emerged as a novel cell-free strategy for the treatment of diseases. EVs can be released by various types of cells with unique biological properties. Recent studies have shown that native EVs are used as therapeutic agents to promote tissue repair by delivering various growth factors and trophic factors including VEGF, EGF, TFN-α, IL-1β, and TGF-β to participate in all physiological processes of wound healing. Furthermore, to improve their specificity, safety, and efficiency for wound healing, the content and surface of EVs can be designed, modified, and engineered. The engineering strategies of EVs are divided into parent cell modification and indirect modification of EVs. The therapeutic potential of current EVs and engineered EVs for wound healing still requires the exploration of their large-scale clinical applications through innovative approaches. Herein, we provide an overview of the current biological knowledge about wound healing and EVs, as well as the application of native EVs in promoting wound healing. We also outline recent advances in engineering EV methodologies to achieve ideal therapeutic potential. Finally, the therapeutic applications of engineered EVs in wound healing are reviewed, and the challenges and prospects for the translation of engineered EVs to clinical applications are discussed.
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Affiliation(s)
- Shengli Lu
- Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Liping Lu
- Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yang Liu
- Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Leiden University Medical Center, Leiden, Netherland
| | - Zenan Li
- Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yuan Fang
- Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Zhizhao Chen
- Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Jianda Zhou
- Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
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Shen J, Zhao X, Zhong Y, Yang P, Gao P, Wu X, Wang X, An W. Exosomal ncRNAs: The pivotal players in diabetic wound healing. Front Immunol 2022; 13:1005307. [PMID: 36420273 PMCID: PMC9677725 DOI: 10.3389/fimmu.2022.1005307] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 10/06/2022] [Indexed: 11/09/2022] Open
Abstract
Diabetes is the most prevalent metabolic disease in the world today. In addition to elevated blood glucose, it also causes serious complications, which has a significant effect on the quality of life of patients. Diabetic trauma is one of complications as a result of the interaction of diabetic neuropathy, peripheral vascular disease, infection, trauma, and other factors. Diabetic trauma usually leads to poor healing of the trauma and even to severe foot ulcers, wound gangrene, and even amputation, causing serious psychological, physical, and financial burdens to diabetic patients. Non-coding RNAs (ncRNAs) carried by exosomes have been demonstrated to be relevant to the development and treatment of diabetes and its complications. Exosomes act as vehicle, which contain nucleic acids such as mRNA and microRNA (miRNA), and play a role in the intercellular communication and the exchange of substances between cells. Because exosomes are derived from cells, there are several advantages over synthetic nanoparticle including good biocompatibility and low immunogenicity. Exosomal ncRNAs could serve as markers for the clinical diagnosis of diabetes and could also be employed to accelerate diabetic wound healing via the regulation of the immune response and modulation of cell function. ncRNAs in exosomes can be employed to promote diabetic wound healing by regulating inflammation and accelerating re-vascularization, re-epithelialization, and extracellular matrix remodeling. Herein, exosomes in terms of ncRNA (miRNA, lncRNA, and circRNA) to accelerate diabetic wounds healing were summarized, and we discussed the challenge of the loading strategy of ncRNA into exosomes.
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Affiliation(s)
| | | | | | | | | | | | | | - Wenlin An
- *Correspondence: Xudong Wang, ; Wenlin An,
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Nallakumarasamy A, Jeyaraman M, Maffulli N, Jeyaraman N, Suresh V, Ravichandran S, Gupta M, Potty AG, El-Amin SF, Khanna M, Gupta A. Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Wound Healing. Life (Basel) 2022; 12:1733. [PMID: 36362890 PMCID: PMC9699035 DOI: 10.3390/life12111733] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 10/24/2022] [Indexed: 07/26/2023] Open
Abstract
The well-orchestrated process of wound healing may be negatively impacted from interrupted or incomplete tissue regenerative processes. The healing potential is further compromised in patients with diabetes mellitus, chronic venous insufficiency, critical limb ischemia, and immunocompromised conditions, with a high health care burden and expenditure. Stem cell-based therapy has shown promising results in clinical studies. Mesenchymal stem cell-derived exosomes (MSC Exos) may favorably impact intercellular signaling and immunomodulation, promoting neoangiogenesis, collagen synthesis, and neoepithelization. This article gives an outline of the biogenesis and mechanism of extracellular vesicles (EVs), particularly exosomes, in the process of tissue regeneration and discusses the use of preconditioned exosomes, platelet-rich plasma-derived exosomes, and engineered exosomes in three-dimensional bioscaffolds such as hydrogels (collagen and chitosan) to prolong the contact time of exosomes at the recipient site within the target tissue. An appropriate antibiotic therapy based on culture-specific guidance coupled with the knowledge of biopolymers helps to fabricate nanotherapeutic materials loaded with MSC Exos to effectively deliver drugs locally and promote novel approaches for the management of chronic wounds.
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Affiliation(s)
- Arulkumar Nallakumarasamy
- Department of Orthopaedics, All India Institute of Medical Sciences, Bhubaneswar 751019, Odissa, India
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226010, Uttar Pradesh, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India
| | - Madhan Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- Department of Medical Research and Translational Medicine, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India
- South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045, USA
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders, School of Medicine and Surgery, University of Salerno, 84084 Fisciano, Italy
- San Giovanni di Dio e Ruggi D’Aragona Hospital “Clinica Ortopedica” Department, Hospital of Salerno, 84124 Salerno, Italy
- Barts and the London School of Medicine and Dentistry, Centre for Sports and Exercise Medicine, Queen Mary University of London, London E1 4DG, UK
- School of Pharmacy and Bioengineering, Keele University School of Medicine, Stoke on Trent ST5 5BG, UK
| | - Naveen Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India
- Fellow in Joint Replacement, Department of Orthopaedics, Atlas Hospitals, Tiruchirappalli 620002, Tamil Nadu, India
| | - Veerasivabalan Suresh
- Department of Obstetrics-Gynecology, Madras Medical College and Hospital, Chennai 600003, Tamil Nadu, India
| | - Srinath Ravichandran
- Department of General and GI Surgery, Stepping Hill Hospital, Stockport NHS Foundation Trust, Stockport SK27JE, UK
| | - Manu Gupta
- Polar Aesthetics Dental & Cosmetic Centre, Noida 201301, Uttar Pradesh, India
| | - Anish G. Potty
- South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045, USA
| | - Saadiq F. El-Amin
- El-Amin Orthopaedic & Sports Medicine Institute, Lawrenceville, GA 30043, USA
- Regenerative Sports Medicine, Lawrenceville, GA 30043, USA
- BioIntegrate, Lawrenceville, GA 30043, USA
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India
- Department of Orthopaedics, Autonomous State Medical College, Ayodhya 224135, Uttar Pradesh, India
| | - Ashim Gupta
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India
- South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045, USA
- BioIntegrate, Lawrenceville, GA 30043, USA
- Regenerative Orthopaedics, Noida 201301, Uttar Pradesh, India
- Future Biologics, Lawrenceville, GA 30043, USA
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35
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Zhang M, Wang L, Chen Z. Research progress of extracellular vesicles in type 2 diabetes and its complications. Diabet Med 2022; 39:e14865. [PMID: 35509124 PMCID: PMC9543097 DOI: 10.1111/dme.14865] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 04/14/2022] [Accepted: 04/30/2022] [Indexed: 11/29/2022]
Abstract
Type 2 diabetes is one of the most common chronic diseases in modern society. However, there is still insufficient research on the pathogenesis, diagnosis and treatment of type 2 diabetes and its complications. Extracellular vesicles are small bilayer vesicles secreted by cells. In recent years, the effect of extracellular vesicles in type 2 diabetes and its complications has aroused extensive attention. The research on the influence of protein and nucleic acids carried by extracellular vesicles secreted by stem cells and inflammatory cells on the pathogenesis of type 2 diabetes and its complications provides new ideas for its diagnosis and treatment. This review focuses on the influence of extracellular vesicles on insulin resistance by regulating inflammation and glucose transporter 4 expression. The second part mainly discusses the research progress and limitations of extracellular vesicles use in treating and diagnosing type 2 diabetes and its complications. This review introduces the current research status of type 2 diabetes and its complications, illustrates the biogenesis of extracellular vesicles, their effect on type 2 diabetes pathogenesis and its complications and their potential as therapeutic tools and diagnostic markers in type 2 diabetes and its complications.
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Affiliation(s)
- Mengting Zhang
- First Clinical Medical CollegeGannan Medical UniversityGanzhouJiangxi ProvinceChina
- Department of Laboratory MedicineFirst Affiliated Hospital of Gannan Medical UniversityGanzhouJiangxi ProvinceChina
| | - Lanfeng Wang
- Department of NephrologyFirst Affiliated Hospital of Gannan Medical UniversityGanzhouJiangxi ProvinceChina
| | - Zhiping Chen
- First Clinical Medical CollegeGannan Medical UniversityGanzhouJiangxi ProvinceChina
- Department of Laboratory MedicineFirst Affiliated Hospital of Gannan Medical UniversityGanzhouJiangxi ProvinceChina
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36
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Sothivelr V, Hasan MY, Mohd Saffian S, Zainalabidin S, Ugusman A, Mahadi MK. Revisiting miRNA-21 as a Therapeutic Strategy for Myocardial Infarction: A Systematic Review. J Cardiovasc Pharmacol 2022; 80:393-406. [PMID: 35767710 DOI: 10.1097/fjc.0000000000001305] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/11/2022] [Indexed: 01/31/2023]
Abstract
Several types of cardiovascular cells use microRNA-21 ( miR-21 ), which has been linked to cardioprotection. In this study, we systematically reviewed the results of published papers on the therapeutic effect of miR-21 for myocardial infarction. Studies described the cardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic, and anti-inflammatory mechanisms. Results suggest that cardioprotective effects of miR-21 may work synergistically to prevent the deterioration of cardiac function during postischemia. However, there are other results that indicate that miR-21 positively regulates tissue fibrosis, potentially worsening a postischemic injury. The dual functionalities of miR-21 occur through the targeting of genes and signaling pathways, such as PTEN , PDCD4 , KBTBD7 , NOS3 , STRN , and Spry-1 . This review provides insights into the future advancement of safe miR-21 -based genetic therapy in the treatment of myocardial infarction.
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Affiliation(s)
- Vivisana Sothivelr
- Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan, Malaysia
| | - Mohammad Y Hasan
- Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan, Malaysia
| | - Shamin Mohd Saffian
- Centre for Quality Management of Medicine, Faculty of Pharmacy, Universiti Kebangsaan, Malaysia
| | - Satirah Zainalabidin
- Centre of Toxicology and Health Risk Study, Faculty of Health Sciences, Universiti Kebangsaan, Malaysia; and
| | - Azizah Ugusman
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan, Malaysia
| | - Mohd K Mahadi
- Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan, Malaysia
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Mechanical Stretch Induced Skin Regeneration: Molecular and Cellular Mechanism in Skin Soft Tissue Expansion. Int J Mol Sci 2022; 23:ijms23179622. [PMID: 36077018 PMCID: PMC9455829 DOI: 10.3390/ijms23179622] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/16/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
Skin soft tissue expansion is one of the most basic and commonly used techniques in plastic surgery to obtain excess skin for a variety of medical uses. However, skin soft tissue expansion is faced with many problems, such as long treatment process, poor skin quality, high retraction rate, and complications. Therefore, a deeper understanding of the mechanisms of skin soft tissue expansion is needed. The key to skin soft tissue expansion lies in the mechanical stretch applied to the skin by an inflatable expander. Mechanical stimulation activates multiple signaling pathways through cellular adhesion molecules and regulates gene expression profiles in cells. Meanwhile, various types of cells contribute to skin expansion, including keratinocytes, dermal fibroblasts, and mesenchymal stem cells, which are also regulated by mechanical stretch. This article reviews the molecular and cellular mechanisms of skin regeneration induced by mechanical stretch during skin soft tissue expansion.
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Yu H, Wang Y, Wang D, Yi Y, Liu Z, Wu M, Wu Y, Zhang Q. Landscape of the epigenetic regulation in wound healing. Front Physiol 2022; 13:949498. [PMID: 36035490 PMCID: PMC9403478 DOI: 10.3389/fphys.2022.949498] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 07/19/2022] [Indexed: 12/13/2022] Open
Abstract
Wound healing after skin injury is a dynamic and highly coordinated process involving a well-orchestrated series of phases, including hemostasis, inflammation, proliferation, and tissue remodeling. Epigenetic regulation refers to genome-wide molecular events, including DNA methylation, histone modification, and non-coding RNA regulation, represented by microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Epigenetic regulation is pervasively occurred in the genome and emerges as a new role in gene expression at the post-transcriptional level. Currently, it is well-recognized that epigenetic factors are determinants in regulating gene expression patterns, and may provide evolutionary mechanisms that influence the wound microenvironments and the entire healing course. Therefore, this review aims to comprehensively summarize the emerging roles and mechanisms of epigenetic remodeling in wound healing. Moreover, we also pose the challenges and future perspectives related to epigenetic modifications in wound healing, which would bring novel insights to accelerated wound healing.
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Affiliation(s)
| | | | | | | | | | - Min Wu
- *Correspondence: Min Wu, ; Yiping Wu, ; Qi Zhang,
| | - Yiping Wu
- *Correspondence: Min Wu, ; Yiping Wu, ; Qi Zhang,
| | - Qi Zhang
- *Correspondence: Min Wu, ; Yiping Wu, ; Qi Zhang,
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Evaluation of Platelet-Derived Extracellular Vesicles in Gingival Fibroblasts and Keratinocytes for Periodontal Applications. Int J Mol Sci 2022; 23:ijms23147668. [PMID: 35887008 PMCID: PMC9321144 DOI: 10.3390/ijms23147668] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/06/2022] [Accepted: 07/08/2022] [Indexed: 02/01/2023] Open
Abstract
Gingival regeneration aims at restoring the architecture and functionality of oral damaged tissue. Different biomaterials or biological materials have been tested for tissue repair, such as platelet concentrates such as PL. In this article, the use of extracellular vesicles (EVs) derived from platelet lysate (PL) and their combination with hyaluronic acid biomaterials (HA) in an in vitro wound healing assay is investigated. EVs were isolated by size exclusion chromatography from PL. In addition, HA gels were formulated with PL or EVs. EVs or HA combined with EVs (HA-EVs) were tested in vitro in gingival fibroblasts and keratinocytes for biocompatibility (LDH activity and metabolic activity) and by an in vitro wound-healing assay and gene expression analysis. EVs and EVs-HA treatments were biocompatible in gingival fibroblasts and keratinocytes and showed an increase in wound healing in vitro compared to control. Moreover, changes in gene expression related to extracellular matrix remodeling were observed after the treatment with EVs. EVs can be combined with HA biomaterials, showing good biocompatibility and preserving their activity and functionality. Therefore, platelet-derived EVs could emerge as a new application for periodontal regeneration in combination with biomaterials in order to enhance their clinical use.
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40
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Kose O, Botsali A, Caliskan E. Role of exosomes in skin diseases. J Cosmet Dermatol 2022; 21:3219-3225. [PMID: 35686395 DOI: 10.1111/jocd.15152] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 05/30/2022] [Accepted: 06/07/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Exosomes, as a family member of extracellular vesicles, are cell-secreted nanoscale structures that play pivotal roles in regulating physiological and pathophysiological processes of the skin. Exosomes induce communication between cells and are responsible for transporting cellular components such as microRNAs, mRNAs, DNA, lipids, metabolites, and cell-surface proteins. Numerous preclinical and clinical trials searched the contribution of exosomes to skin functions and disorders. Thus, exosomes are gaining increasing attention within investigational dermatology. In advance, stem-cell-derived exosomes were integrated into the functional cosmetics industry nominated as cell-free regenerative medicine. OBJECTIVE This review aims to demonstrate the roles of exosomes in inflammatory skin disorders, stem cell, and tumor biology through a comprehensive evaluation of the diagnostic, prognostic, and therapeutic perspectives. METHODS A comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar" using key words ''exosomes'', ''skin'', ''wound healing''. CONCLUSION Exosomes are regarded as promising diagnostic and prognostic biomarkers for various skin diseases. Future prospects are repurposing exosomes to treat skin disorders, either as drug carriers or drugs themselves.
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Affiliation(s)
- Osman Kose
- Dermatologist, Private Practice, Ankara, Turkey
| | - Aysenur Botsali
- Department of Dermatology, Gülhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Ercan Caliskan
- Department of Dermatology, Gülhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey
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A time to heal: microRNA and circadian dynamics in cutaneous wound repair. Clin Sci (Lond) 2022; 136:579-597. [PMID: 35445708 PMCID: PMC9069467 DOI: 10.1042/cs20220011] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 12/11/2022]
Abstract
Many biological systems have evolved circadian rhythms based on the daily cycles of daylight and darkness on Earth. Such rhythms are synchronised or entrained to 24-h cycles, predominantly by light, and disruption of the normal circadian rhythms has been linked to elevation of multiple health risks. The skin serves as a protective barrier to prevent microbial infection and maintain homoeostasis of the underlying tissue and the whole organism. However, in chronic non-healing wounds such as diabetic foot ulcers (DFUs), pressure sores, venous and arterial ulcers, a variety of factors conspire to prevent wound repair. On the other hand, keloids and hypertrophic scars arise from overactive repair mechanisms that fail to cease in a timely fashion, leading to excessive production of extracellular matrix (ECM) components such as such as collagen. Recent years have seen huge increases in our understanding of the functions of microRNAs (miRNAs) in wound repair. Concomitantly, there has been growing recognition of miRNA roles in circadian processes, either as regulators or targets of clock activity or direct responders to external circadian stimuli. In addition, miRNAs are now known to function as intercellular signalling mediators through extracellular vesicles (EVs). In this review, we explore the intersection of mechanisms by which circadian and miRNA responses interact with each other in relation to wound repair in the skin, using keratinocytes, macrophages and fibroblasts as exemplars. We highlight areas for further investigation to support the development of translational insights to support circadian medicine in the context of these cells.
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The anti-angiogenesis mechanism of Geniposide on rheumatoid arthritis is related to the regulation of PTEN. Inflammopharmacology 2022; 30:1047-1062. [PMID: 35389123 DOI: 10.1007/s10787-022-00975-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 03/10/2022] [Indexed: 12/14/2022]
Abstract
Rheumatoid arthritis (RA) is a systemic immune disease characterized by joint inflammation and pannus. The nascent pannus contributes to synovial hyperplasia, cartilage, and tissue damage in RA. This study aims to explore the therapeutic effect and potential mechanism of Geniposide (GE) on RA angiogenesis, involving the participation of phosphate and tension homology deleted on chromosome ten (PTEN) and downstream pathways. Clinical manifestations, synovial pathomorphology, microvessel density, and the level of angiogenesis-related factors were used to evaluate the therapeutic effect of GE on adjuvant-induced arthritis (AA) rats. The proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) indicate the degree of angiogenesis in vitro. Lentivirus over-expression of PTEN was employed to elucidate the potential mechanism. The results showed that GE improved the degree of arthritis and angiogenesis in AA rats. The expression of PTEN was decreased significantly in vivo and in vitro, and over-expression of PTEN improved the biological function of HUVECs to inhibit angiogenesis. GE inhibited the proliferation, migration, and tubule formation of HUVECs and plays an anti-angiogenesis role in vitro. Mechanism study showed that PTEN expression was increased and p-PI3K and p-Akt expression was decreased with GE treatment. It suggests that GE up-regulated the expression of PTEN and inhibited the activation of PI3K-Akt signal, which plays a role in inhibiting angiogenesis in RA in vivo and in vitro.
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Xie J, Wu W, Zheng L, Lin X, Tai Y, Wang Y, Wang L. Roles of MicroRNA-21 in Skin Wound Healing: A Comprehensive Review. Front Pharmacol 2022; 13:828627. [PMID: 35295323 PMCID: PMC8919367 DOI: 10.3389/fphar.2022.828627] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 02/10/2022] [Indexed: 12/12/2022] Open
Abstract
MicroRNA-21 (miR-21), one of the early mammalian miRNAs identified, has been detected to be upregulated in multiple biological processes. Increasing evidence has demonstrated the potential values of miR-21 in cutaneous damage and skin wound healing, but lack of a review article to summarize the current evidence on this issue. Based on this review, relevant studies demonstrated that miR-21 played an essential role in wound healing by constituting a complex network with its targeted genes (i.e., PTEN, RECK. SPRY1/2, NF-κB, and TIMP3) and the cascaded signaling pathways (i.e., MAPK/ERK, PI3K/Akt, Wnt/β-catenin/MMP-7, and TGF-β/Smad7-Smad2/3). The treatment effectiveness developed by miR-21 might be associated with the promotion of the fibroblast differentiation, the improvement of angiogenesis, anti-inflammatory, enhancement of the collagen synthesis, and the re-epithelialization of the wound. Currently, miRNA nanocarrier systems have been developed, supporting the feasibility clinical feasibility of such miR-21-based therapy. After further investigations, miR-21 may serve as a potential therapeutic target for wound healing.
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Affiliation(s)
- Jie Xie
- Department of Emergency Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Weizhou Wu
- Department of Urology, Maoming People's Hospital, Guangdong, China
| | - Liying Zheng
- Postgraduate Pepartment, First Affiliated Hospital of Gannan Medical College, Ganzhou, China
| | - Xuesong Lin
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yuncheng Tai
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yajie Wang
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Le Wang
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
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Yang M, Jin Y, Yang J, Wang C, Wang X, Wang Y. Preparation of Codonopsis pilosula polysaccharide microcapsules and its effect and mechanism on skin wound healing in rats. J Biomater Appl 2022; 36:1723-1736. [PMID: 35235468 DOI: 10.1177/08853282211054333] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In this study, after optimizing the extraction process of CPP (Codonopsis pilosula polysaccharides), CPPM (CPP microcapsules) were prepared. Subsequently, the structural characteristics and physicochemical properties were studied. The results showed that CPPM is a hollow sac-like structure with rough folds and protuberances and comes in spherical or ellipsoidal shapes with uniform particle size. CPPM has certain swelling degree, low hardness, good adhesion, and stability. Then, the effect of CPPM on wounds repair was investigated by a rat model. The results showed that CPPM could improve the wound healing rate. Histological evaluation showed CPPM could promote neovascularization and fibroblast proliferation. By investigating the healing mechanism, it was found that CPPM increased the hydroxyproline content in granulation tissue and had an excellent antioxidant ability, and then inhibited lipid peroxidation, in addition, it significantly increased the transcript levels of VEGF and miRNA-21 genes, indicating that CPPM play an influential role in vascular remodeling during wound healing by up-regulating the expression of VEGF and miRNA-21 genes.
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Affiliation(s)
- Mingjun Yang
- School of Life Science and Engineering, 56677Lanzhou University of Technology, Lanzhou, China
| | - Yongming Jin
- School of Life Science and Engineering, 56677Lanzhou University of Technology, Lanzhou, China
| | - Jumei Yang
- 74713Lanzhou University Second Hospital, Lanzhou, China
| | - Chenliang Wang
- School of Life Science and Engineering, 56677Lanzhou University of Technology, Lanzhou, China
| | - Xinjian Wang
- School of Life Science and Engineering, 56677Lanzhou University of Technology, Lanzhou, China
| | - Yonggang Wang
- School of Life Science and Engineering, 56677Lanzhou University of Technology, Lanzhou, China
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Li D, Niu G, Landén NX. Beyond the Code: Noncoding RNAs in Skin Wound Healing. Cold Spring Harb Perspect Biol 2022; 14:a041230. [PMID: 35197246 PMCID: PMC9438779 DOI: 10.1101/cshperspect.a041230] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
An increasing number of noncoding RNAs (ncRNAs) have been found to regulate gene expression and protein functions, playing important roles in diverse biological processes and diseases. Their crucial functions have been reported in almost every cell type and all stages of skin wound healing. Evidence of their pathogenetic roles in common wound complications, such as chronic nonhealing wounds and excessive scarring, is also accumulating. Given their unique expression and functional properties, ncRNAs are promising therapeutic and diagnostic entities. In this review, we discuss current knowledge about the functional roles of noncoding elements, such as microRNAs, long ncRNAs, and circular RNAs, in skin wound healing, focusing on in vivo evidence from studies of human wound samples and animal wound models. Finally, we provide a perspective on the outlook of ncRNA-based therapeutics in wound care.
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Affiliation(s)
- Dongqing Li
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Guanglin Niu
- Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
| | - Ning Xu Landén
- Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
- Ming Wai Lau Centre for Reparative Medicine, Stockholm Node, Karolinska Institute, 17177 Stockholm, Sweden
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Exosomes and Other Extracellular Vesicles with High Therapeutic Potential: Their Applications in Oncology, Neurology, and Dermatology. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27041303. [PMID: 35209095 PMCID: PMC8879284 DOI: 10.3390/molecules27041303] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 01/28/2022] [Accepted: 02/08/2022] [Indexed: 02/06/2023]
Abstract
Until thirty years ago, it was believed that extracellular vesicles (EVs) were used to remove unnecessary compounds from the cell. Today, we know about their enormous potential in diagnosing and treating various diseases. EVs are essential mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Compared to laboratory-created drug nanocarriers, they are stable in physiological conditions. Furthermore, they are less immunogenic and cytotoxic compared to polymerized vectors. Finally, EVs can transfer cargo to particular cells due to their membrane proteins and lipids, which can implement them to specific receptors in the target cells. Recently, new strategies to produce ad hoc exosomes have been devised. Cells delivering exosomes have been genetically engineered to overexpress particular macromolecules, or transformed to release exosomes with appropriate targeting molecules. In this way, we can say tailor-made therapeutic EVs are created. Nevertheless, there are significant difficulties to solve during the application of EVs as drug-delivery agents in the clinic. This review explores the diversity of EVs and the potential therapeutic options for exosomes as natural drug-delivery vehicles in oncology, neurology, and dermatology. It also reflects future challenges in clinical translation.
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Pandit A, Begum Y, Saha P, Srivastava AK, Swarnakar S. Approaches Toward Targeting Matrix Metalloproteases for Prognosis and Therapies in Gynecological Cancer: MicroRNAs as a Molecular Driver. Front Oncol 2022; 11:720622. [PMID: 35145899 PMCID: PMC8821656 DOI: 10.3389/fonc.2021.720622] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 12/30/2021] [Indexed: 12/24/2022] Open
Abstract
Gene expression can be regulated by small non-coding RNA molecules like microRNAs (miRNAs) which act as cellular mediators necessary for growth, differentiation, proliferation, apoptosis, and metabolism. miRNA deregulation is often observed in many human malignancies, acting both as tumor-promoting and suppressing, and their abnormal expression is linked to unrestrained cellular proliferation, metastasis, and perturbation in DNA damage as well as cell cycle. Matrix Metalloproteases (MMPs) have crucial roles in both growth, and tissue remodeling in normal conditions, as well as in promoting cancer development and metastasis. Herein, we outline an integrated interactive study involving various MMPs and miRNAs and also feature a way in which these communications impact malignant growth, movement, and metastasis. The present review emphasizes on important miRNAs that might impact gynecological cancer progression directly or indirectly via regulating MMPs. Additionally, we address the likely use of miRNA-mediated MMP regulation and their downstream signaling pathways towards the development of a potential treatment of gynecological cancers.
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Affiliation(s)
- Anuradha Pandit
- Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Yasmin Begum
- Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Priyanka Saha
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Amit Kumar Srivastava
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Snehasikta Swarnakar
- Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
- *Correspondence: Snehasikta Swarnakar,
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Wang J, Pothana K, Chen S, Sawant H, Travers JB, Bihl J, Chen Y. Ultraviolet B Irradiation Alters the Level and miR Contents of Exosomes Released by Keratinocytes in Diabetic Condition. Photochem Photobiol 2021; 98:1122-1130. [PMID: 34931322 PMCID: PMC9511213 DOI: 10.1111/php.13583] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 12/14/2021] [Indexed: 12/17/2022]
Abstract
Ultraviolet B (UVB) stimulates the generation of extracellular vesicles, which elicit systemic effects. Here, we studied whether UVB affects the release and microRNA (miR) content of keratinocyte exosomes (EXs) in diabetic conditions. In vitro, we examined the UVB effects on affecting EX release from keratinocyte HaCaT cells (HaCaT‐EX) pretreated with high glucose. HaCaT‐EX functions were evaluated on Schwann cells (SCs). In vivo, UVB‐induced miR change in skin EXs of diabetic db/db mice was analyzed. The miRs of interest were validated in HaCaT‐EXs. We found that: (1) UVB promoted HaCaT‐EX generation in dose‐ and time‐dependent manners; 100 and 1800 J m−2 of UVB had the most prominent effect and were selected as effective low‐ and high‐fluence UVB in vitro. (2) A total of 13 miRs were differentially expressed >3‐fold in skin EXs in UVB‐treated db/db mice; miR‐126 was the most up‐regulated by low‐fluence UVB. (3) Functional studies revealed that the SC viability was improved by low‐fluence UVB HaCaT‐EXs, while worsened by high‐fluence UVB HaCaT‐EXs. (4) MiR‐126 inhibitor attenuated the effects induced by low‐fluence UVB HaCaT‐EXs. Our data have demonstrated that low‐ and high‐fluence UVBs promote HaCaT‐EX generation but differentially affect exosomal miR levels and functions under diabetic conditions.
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Affiliation(s)
- Jinju Wang
- Department of Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Kartheek Pothana
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA
| | - Shuzhen Chen
- Department of Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Harshal Sawant
- Department of Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Jeffrey B Travers
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.,The Dayton V.A. Medical Center, Dayton, OH, USA
| | - Ji Bihl
- Department of Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Yanfang Chen
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA
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Dow R, Ridger V. Neutrophil microvesicles and their role in disease. Int J Biochem Cell Biol 2021; 141:106097. [PMID: 34655813 DOI: 10.1016/j.biocel.2021.106097] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 10/08/2021] [Accepted: 10/11/2021] [Indexed: 12/19/2022]
Abstract
Microvesicles are formed through shedding from the plasma membrane, a process shared by almost all human cells. Microvesicles are highly abundant and have been detected in blood, urine, cerebrospinal fluid, and saliva. They contain a library of cargo derived from their parental cell during formation, including proteases, micro-RNAs and lipids and delivery of this parental cell-derived cargo to other cells can alter target cell function and drive disease. Cell specific molecules on the surface of microvesicles, obtained during microvesicle formation, allows their parental cell to be identified and populations of microvesicles to be investigated for roles in the pathogenesis of various diseases. For instance, recent work by our group has identified a role for neutrophil microvesicles in atherosclerosis. Microvesicle profiles could in future be associated with certain diseases and act as a biomarker to allow for earlier diagnosis. This short review will discuss some of the processes central to all microvesicles before focusing on neutrophil microvesicles, their potential role in cardiovascular disease and the mechanisms that may underpin this.
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Affiliation(s)
- Reece Dow
- Department of Infection Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Victoria Ridger
- Department of Infection Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
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Li X, Li N, Li B, Feng Y, Zhou D, Chen G. Noncoding RNAs and RNA-binding proteins in diabetic wound healing. Bioorg Med Chem Lett 2021; 50:128311. [PMID: 34438011 DOI: 10.1016/j.bmcl.2021.128311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/15/2022]
Abstract
Poor wound healing is a common complication in diabetic patients. It often leads to intractable infections and lower limb amputations and is associated with cardiovascular morbidity and mortality. NcRNAs, which can regulate gene expression, have emerged as important regulators of various physiological processes. Herein, we summarize the diverse roles of ncRNAs in the key stages of diabetic wound healing, including inflammation, angiogenesis, re-epithelialization, and extracellular matrix remodeling. Meanwhile, the potential use of ncRNAs as novel therapeutic targets for wound healing in diabetic patients is also discussed. In addition, we summarize the role of RNA-binding proteins (RBPs) in the regulation of gene expression and signaling pathways during skin repair, which may provide opportunities for therapeutic intervention for this potentially devastating disease. However, so far, research on the modulated drug based on ncRNAs that lead to significantly altered gene expression in diabetic patients is scarce. We have compiled some drugs that may be able to modulate ncRNAs, which significantly regulate the gene expression in diabetic patients.
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Affiliation(s)
- Xue Li
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China
| | - Ning Li
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China
| | - Bingxin Li
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China
| | - Yuan Feng
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China
| | - Di Zhou
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
| | - Gang Chen
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, People's Republic of China; Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, People's Republic of China.
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