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Yang H, Zheng Y, Yu T, Wu B, Liu Z, Liu S, Sun X, Zhou L. A functional role for myostatin in muscle hyperplasia and hypertrophy revealed by comparative transcriptomics in Yesso scallop Patinopecten yessoensis. Int J Biol Macromol 2025; 307:142308. [PMID: 40118415 DOI: 10.1016/j.ijbiomac.2025.142308] [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: 12/12/2024] [Revised: 03/03/2025] [Accepted: 03/18/2025] [Indexed: 03/23/2025]
Abstract
Elucidating the molecular regulatory mechanisms underlying muscle growth and development is of profound significance in aquaculture. Yesso scallop is a cold-water bivalve of considerable economic importance, having its primary edible component of adductor muscle. In this study, comparative transcriptomics and histological analysis at different sampling times after Myostatin (MSTN) interference were performed to identify the potential candidate genes potentially involved in muscle growth and development. The comparative transcriptomics revealed that growth factors and cytokines, extracellular matrix proteins and ubiquitin-proteasome system are potentially involved in muscle hypertrophy and hyperplasia. After MSTN interference, striated adductor muscle displays significant muscle hypertrophy (51.77 % increase on day 7 and 59.83 % increase on day 21) and muscle hyperplasia (59.36 % increase on day 7 and 61.83 % increase on day 21). WGCNA identifies the key darkolivegreen module, which may play crucial roles in muscle hyperplasia and hypertrophy within the striated muscle of the scallop. Five key transcription factors (zf-CCCH, zf-C2H2, PPP1R10, LRRFIP2, and Gon4) are identified by analyzing the co-expression patterns of core genes within the module. These findings will aid in understanding the regulatory mechanisms of muscle growth in scallops and provide a basis for genetic improvement in shellfish aquaculture.
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Affiliation(s)
- Hongsu Yang
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Laoshan Laboratory, Qingdao, Shandong 266237, China; Fisheries College, Zhejiang Ocean University, Zhoushan 316022, China
| | - Yanxin Zheng
- Changdao Enhancement and Experiment Station, Chinese Academy of Fishery Sciences, Changdao, China
| | - Tao Yu
- Changdao Enhancement and Experiment Station, Chinese Academy of Fishery Sciences, Changdao, China
| | - Biao Wu
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Laoshan Laboratory, Qingdao, Shandong 266237, China
| | - Zhihong Liu
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Laoshan Laboratory, Qingdao, Shandong 266237, China
| | - Shufang Liu
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Laoshan Laboratory, Qingdao, Shandong 266237, China
| | - Xiujun Sun
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Laoshan Laboratory, Qingdao, Shandong 266237, China.
| | - Liqing Zhou
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Laoshan Laboratory, Qingdao, Shandong 266237, China
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Li Y, Dai Y, Jin T, Liu X, Xie L. Study on the changes of extracellular matrix morphology and components in COPD animal model by using lung decellularized scaffold. FASEB J 2025; 39:e70463. [PMID: 40150895 PMCID: PMC11950666 DOI: 10.1096/fj.202401522rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 02/10/2025] [Accepted: 03/05/2025] [Indexed: 03/29/2025]
Abstract
Airway remodeling is a critical pathological process that influences the progression of chronic obstructive pulmonary disease(COPD). To better study small airway remodeling in COPD, we employed advanced techniques such as decellularized scaffolds, immunofluorescence, scanning electron microscopy, and proteomics to analyze morphological and compositional changes in the extracellular matrix (ECM). Our study revealed significant ultrastructural abnormalities in the decellularized scaffolds from the COPD group, including thinning of alveolar septa, enlargement of alveolar spaces, and fusion of multiple alveoli. Additionally, the ECM composition in the COPD group exhibited notable changes characterized by an increase in collagen fibers, type I and IV collagens, fibronectin, and laminin (p < .05), along with a decrease in elastin and glycosaminoglycans (p < .05). Proteomic analysis identified 70 differentially expressed proteins between the COPD group and the control group. These included 34 upregulated proteins such as Smarca2, Skt, Acvrl1, Myl2 (all with ratios >10.64), and 36 downregulated proteins such as Col6a6, Col6a5, and AnK3 (all with ratios <0.27). Pathway analysis indicated that activation of apoptosis (Enrichment Score, ES = 0.23) and epithelial-mesenchymal transition (ES = 0.38) genes and inhibition of collagen synthesis (ES = -0.43) and degradation (ES = -0.63) genes were observed in the COPD group. These findings enhance our understanding of the mechanisms underlying airway remodeling and provide a scientific basis for developing novel therapeutic strategies for COPD.
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Affiliation(s)
- Yuan Li
- Department of Pulmonary and Critical Care MedicineThe Third Xiangya Hospital of Central South UniversityChangshaChina
| | - Yingbing Dai
- Department of Internal MedicineHunan Provincial Chest HospitalChangshaChina
| | - Ting Jin
- Department of Pulmonary and Critical Care MedicineThe Third Xiangya Hospital of Central South UniversityChangshaChina
| | - Xianyang Liu
- Department of Pulmonary and Critical Care MedicineThe Third Xiangya Hospital of Central South UniversityChangshaChina
| | - Lihua Xie
- Department of Pulmonary and Critical Care MedicineThe Third Xiangya Hospital of Central South UniversityChangshaChina
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Bernier LP, Hefendehl JK, Scott RW, Tung LW, Lewis CA, Soliman H, Simm S, Dissing-Olesen L, Hofmann J, Guo D, DeMeglio M, Rossi FM, Underhill TM, MacVicar BA. Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke. Nat Neurosci 2025; 28:517-535. [PMID: 39962273 DOI: 10.1038/s41593-025-01872-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 12/18/2024] [Indexed: 03/12/2025]
Abstract
Functional revascularization is key to stroke recovery and requires remodeling and regeneration of blood vessels around which is located the brain's only stromal compartment. Stromal progenitor cells (SPCs) are critical for tissue regeneration following injury in many organs, yet their identity in the brain remains elusive. Here we show that the perivascular niche of brain SPCs includes pericytes, venular smooth muscle cells and perivascular fibroblasts that together help cerebral microvasculature regenerate following experimental stroke. Ischemic injury triggers amplification of pericytes and perivascular fibroblasts in the infarct region where they associate with endothelial cells inside a reactive astrocyte border. Fate-tracking of Hic1+ SPCs uncovered a transient functional and transcriptional phenotype of stroke-activated pericytes and perivascular fibroblasts. Both populations of these cells remained segregated, displaying distinct angiogenic and fibrogenic profiles. Therefore, pericytes and perivascular fibroblasts are distinct subpopulations of SPCs in the adult brain that coordinate revascularization and scar formation after injury.
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Affiliation(s)
- Louis-Philippe Bernier
- University of British Columbia, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Colombia, Canada.
| | - Jasmin K Hefendehl
- University of British Columbia, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Colombia, Canada
- Goethe University Frankfurt, Institute for Cell biology and Neuroscience, Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany
| | - R Wilder Scott
- University of British Columbia, Biomedical Research Centre, Vancouver, British Colombia, Canada
- Dept. of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Colombia, Canada
| | - Lin Wei Tung
- University of British Columbia, Biomedical Research Centre, Vancouver, British Colombia, Canada
| | - Coral-Ann Lewis
- University of British Columbia, Biomedical Research Centre, Vancouver, British Colombia, Canada
| | - Hesham Soliman
- University of British Columbia, Biomedical Research Centre, Vancouver, British Colombia, Canada
| | - Stefan Simm
- University Medicine Greifswald, Institute for Bioinformatics, Greifswald, Germany
| | - Lasse Dissing-Olesen
- University of British Columbia, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Colombia, Canada
| | - Jan Hofmann
- Goethe University Frankfurt, Institute for Cell biology and Neuroscience, Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany
| | - David Guo
- University of British Columbia, Biomedical Research Centre, Vancouver, British Colombia, Canada
| | - Murphy DeMeglio
- Goethe University Frankfurt, Institute for Cell biology and Neuroscience, Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany
| | - Fabio M Rossi
- University of British Columbia, Biomedical Research Centre, Vancouver, British Colombia, Canada
| | - T Michael Underhill
- University of British Columbia, Biomedical Research Centre, Vancouver, British Colombia, Canada
- Dept. of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Colombia, Canada
| | - Brian A MacVicar
- University of British Columbia, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Colombia, Canada.
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Li P, Cao L, Liu T, Lu X, Ma Y, Wang H. The Effect of Adipose-Derived Stem Cell (ADSC)-Exos on the Healing of Autologous Skin Grafts in Miniature Pigs. Int J Mol Sci 2025; 26:479. [PMID: 39859193 PMCID: PMC11764972 DOI: 10.3390/ijms26020479] [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: 10/16/2024] [Revised: 12/06/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
The skin functions as the body's primary defense barrier; when compromised, it can lead to dehydration, infection, shock, or potentially life-threatening conditions. Miniature pigs exhibit skin characteristics and healing processes highly analogous to humans. Mesenchymal stem cells contribute to skin injury repair through a paracrine mechanism involving exosomes. This research examines whether adipose-derived MSC exosomes effectively enhance healing following autologous skin grafting in miniature pigs. It also compares the roles and distinctions of ADSCs and ADSC-Exos in inflammatory responses and tissue regeneration. This study found significantly reduced levels of oxidative stress products and pro-inflammatory factors, while antioxidant factors, anti-inflammatory factors, and pro-regenerative factors were elevated, and anti-regenerative factor levels decreased. Moreover, the expression levels of key markers-namely, PI3K, Akt, and mTOR-in the regeneration-associated signaling pathway were increased. The alterations in these indicators indicate that ADSC-Exos can regulate inflammatory responses and promote regeneration. This study provides a novel theoretical foundation for the implementation of acellular therapy in clinical settings.
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Affiliation(s)
- Pujun Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150300, China; (P.L.); (L.C.); (T.L.); (X.L.); (Y.M.)
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150300, China
| | - Lei Cao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150300, China; (P.L.); (L.C.); (T.L.); (X.L.); (Y.M.)
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150300, China
| | - Tao Liu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150300, China; (P.L.); (L.C.); (T.L.); (X.L.); (Y.M.)
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150300, China
| | - Xiangyu Lu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150300, China; (P.L.); (L.C.); (T.L.); (X.L.); (Y.M.)
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150300, China
| | - Yajun Ma
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150300, China; (P.L.); (L.C.); (T.L.); (X.L.); (Y.M.)
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150300, China
| | - Hongbin Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150300, China; (P.L.); (L.C.); (T.L.); (X.L.); (Y.M.)
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150300, China
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Chen YS, Chien AS, Li CC, Lin CC, Wu RJ. Effects of Commonly Used Vegetable Oils on Skin Barrier Function and Staphylococcus aureus Biofilm. J Oleo Sci 2025; 74:97-106. [PMID: 39756997 DOI: 10.5650/jos.ess24032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025] Open
Abstract
Adding of vegetable oils to skincare products or the use of plant oils for oil care is a current trend. Therefore, the safety and functionality of vegetable oils are of great concern to consumers and cosmetics manufacturers. This study focused on three types of vegetable oils: sunflower oil (SO), andiroba oil (AO) and hydrogenated olive oil (HOO). We conducted a comprehensive evaluation of the oils, which encompassed their ability to protect mouse skin keratinocytes (XB-2) and mouse fibroblasts (NIH 3T3) from damage caused by the surfactant sodium lauryl sulfate (SLS), their influence on the levels of filaggrin and collagen, their potential to aid in wound healing, and their effectiveness in anti-Staphylococcus aureus biofilm formation. The results showed that SO, AO and HOO at a concentration of 1.5 × 10-4 % (v/v) have the ability to defend against SLS-induced cell damage, increase wound healing ability and the filaggrin and collagen content to XB-2 or NIH 3T3 cells. SO, AO and HOO at a concentration of 3.75 × 10-3 % also have the anti-biofilm ability. Among the oils, AO can inhibit S. aureus biofilm composed of either polysaccharides or proteins. Therefore, the tested vegetable oils and can be applied to the cosmetics field as ingredients to repair damaged skin and preserve skin barrier stability.
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Affiliation(s)
- Yi-Shyan Chen
- Department of Cosmetic Science, Providence University
| | - An-Sin Chien
- Department of Cosmetic Science, Providence University
| | - Chih-Ching Li
- Department of Applied Chemistry, Providence University
- Department of Pediatrics, Chang Bing Show Chwan Memorial Hospital
| | | | - Ren-Jang Wu
- Department of Applied Chemistry, Providence University
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Henderson J, O'Callaghan J, Campbell M. Gene therapy for glaucoma: Targeting key mechanisms. Vision Res 2024; 225:108502. [PMID: 39423611 PMCID: PMC11579448 DOI: 10.1016/j.visres.2024.108502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 10/04/2024] [Accepted: 10/04/2024] [Indexed: 10/21/2024]
Abstract
Glaucoma is a group of optic neuropathies characterised by progressive retinal ganglion cell (RGC) degeneration and is the leading cause of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP) with topical medications. However, many patients do not achieve sufficient IOP reductions with such treatments. Patient compliance to dosing schedules also poses a significant challenge, further limiting their effectiveness. While surgical options exist for resistant cases, these are invasive and carry risks of complications. Thus, there is a critical need for better strategies to prevent irreversible vision loss in glaucoma. Gene therapy holds significant promise in this regard, offering potential long-term solutions by targeting the disease's underlying causes at a molecular level. Gene therapy strategies for glaucoma primarily target the two key hallmarks of the disease: elevated IOP and RGC death. This review explores key mechanisms underlying these hallmarks and discusses the current state of gene therapies targeting them. In terms of IOP reduction, this review covers strategies aimed at enhancing extracellular matrix turnover in the conventional outflow pathway, targeting fibrosis, regulating aqueous humor production, and targeting myocilin for gene-specific therapy. Neuroprotective strategies explored include targeting neurotrophic factors and their receptors, reducing oxidative stress and mitochondrial dysfunction, and preventing Wallerian degeneration. This review also briefly highlights key research priorities for advancing gene therapies for glaucoma through the clinical pipeline, such as refining delivery vectors and improving transgene regulation. Addressing these priorities will be essential for translating advancements from preclinical models into effective clinical therapies for glaucoma.
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Affiliation(s)
- Jeff Henderson
- Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland
| | | | - Matthew Campbell
- Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
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Phanish MK, Heidebrecht F, Jackson M, Rigo F, Dockrell MEC. Targeting alternative splicing of fibronectin in human renal proximal tubule epithelial cells with antisense oligonucleotides to reduce EDA+ fibronectin production and block an autocrine loop that drives renal fibrosis. Exp Cell Res 2024; 442:114186. [PMID: 39098465 DOI: 10.1016/j.yexcr.2024.114186] [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: 05/19/2024] [Revised: 07/14/2024] [Accepted: 07/25/2024] [Indexed: 08/06/2024]
Abstract
TGFβ1 is a powerful regulator of fibrosis; secreted in a latent form, it becomes active after release from the latent complex. During tissue fibrosis, the EDA + isoform of cellular fibronectin is overexpressed. In pulmonary fibrosis it has been proposed that the fibronectin splice variant including an EDA domain (FN EDA+) activates latent TGFβ. Our work investigates the potential of blocking the 'splicing in' of EDA with antisense oligonucleotides to inhibit TGFβ1-induced EDA + fibronectin and to prevent the cascade of events initiated by TGFβ1 in human renal proximal tubule cells (PTEC). Human primary PTEC were treated with TGFβ1 for 48 h, medium removed and the cells transfected with RNase H-independent antisense oligonucleotides (ASO) designed to block EDA exon inclusion (ASO5). The efficacy of ASO to block EDA exon inclusion was assessed by EDA + fibronectin RNA and protein expression; the expression of TGFβ, αSMA (α smooth muscle actin), MMP2 (matrix metalloproteinse-2), MMP9 (matrix metalloproteinse-9), Collagen I, K Cadherin and connexin 43 was analysed. Targeting antisense oligonucleotides designed to block EDA exon inclusion in fibronectin pre mRNA were effective in reducing the amount of TGFβ1 -induced cellular EDA + fibronectin RNA and secreted EDA + fibronectin protein (assessed by western immunoblotting and immunocytochemistry) in human proximal tubule cells in an in vitro cell culture model. The effect was selective for EDA + exon with no effect on EDB + fibronectin RNA and total fibronectin mRNA. Exogenous TGFβ1 induced endogenous TGFβ, αSMA, MMP2, MMP9 and Col I mRNA. TGFβ1 treatment for 48h reduced the expression of K-Cadherin and increased the expression of connexin-43. These TGFβ1-induced pro-fibrotic changes were attenuated by ASO5 treatment. 48 h after the removal of exogenous TGFβ, further increases in αSMA, MMP2, MMP9 was observed; ASO5 significantly inhibited this subsequent increase. ASO5 treatment also significantly inhibited ability of the cell culture medium harvested at the end of the experiment (96h) to stimulate SMAD3 reporter cells. The role of endogenous TGFβ1 was confirmed by the use of a TGFβ receptor inhibitor. Our results demonstrate a critical role of FN EDA+ in a cycle of TGFβ driven pro-fibrotic responses in human PTEC and blocking its production with ASO technology offers a potential therapy to interrupt this vicious circle and hence limit the progression of renal fibrosis.
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Affiliation(s)
- Mysore Keshavmurthy Phanish
- SWT Institute for Renal Research, Renal Unit, St Helier Hospital, Epsom and St Helier University Hospitals NHS Trust, London, UK; St Georges' University of London, London, UK.
| | - Felicia Heidebrecht
- SWT Institute for Renal Research, Renal Unit, St Helier Hospital, Epsom and St Helier University Hospitals NHS Trust, London, UK
| | - Michaela Jackson
- IONIS Pharmaceuticals, 2855, Gazelle Ct, Carlsbad, CA 92010, USA
| | - Frank Rigo
- IONIS Pharmaceuticals, 2855, Gazelle Ct, Carlsbad, CA 92010, USA
| | - Mark Edward Carl Dockrell
- SWT Institute for Renal Research, Renal Unit, St Helier Hospital, Epsom and St Helier University Hospitals NHS Trust, London, UK; St Georges' University of London, London, UK.
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Hassan N, Krieg T, Kopp A, Bach AD, Kröger N. Challenges and Pitfalls of Research Designs Involving Magnesium-Based Biomaterials: An Overview. Int J Mol Sci 2024; 25:6242. [PMID: 38892430 PMCID: PMC11172609 DOI: 10.3390/ijms25116242] [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: 04/17/2024] [Revised: 05/31/2024] [Accepted: 06/01/2024] [Indexed: 06/21/2024] Open
Abstract
Magnesium-based biomaterials hold remarkable promise for various clinical applications, offering advantages such as reduced stress-shielding and enhanced bone strengthening and vascular remodeling compared to traditional materials. However, ensuring the quality of preclinical research is crucial for the development of these implants. To achieve implant success, an understanding of the cellular responses post-implantation, proper model selection, and good study design are crucial. There are several challenges to reaching a safe and effective translation of laboratory findings into clinical practice. The utilization of Mg-based biomedical devices eliminates the need for biomaterial removal surgery post-healing and mitigates adverse effects associated with permanent biomaterial implantation. However, the high corrosion rate of Mg-based implants poses challenges such as unexpected degradation, structural failure, hydrogen evolution, alkalization, and cytotoxicity. The biocompatibility and degradability of materials based on magnesium have been studied by many researchers in vitro; however, evaluations addressing the impact of the material in vivo still need to be improved. Several animal models, including rats, rabbits, dogs, and pigs, have been explored to assess the potential of magnesium-based materials. Moreover, strategies such as alloying and coating have been identified to enhance the degradation rate of magnesium-based materials in vivo to transform these challenges into opportunities. This review aims to explore the utilization of Mg implants across various biomedical applications within cellular (in vitro) and animal (in vivo) models.
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Affiliation(s)
- Nourhan Hassan
- Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital Cologne, 50937 Cologne, Germany
- Institute for Laboratory Animal Science and Experimental Surgery, University of Aachen Medical Center, Faculty of Medicine, RWTH-Aachen University, 52074 Aachen, Germany
- Biotechnology Department, Faculty of Science, Cairo University, Giza 12613, Egypt
| | - Thomas Krieg
- Translational Matrix Biology, Medical Faculty, University of Cologne, 50937 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50937 Cologne, Germany
- Center for Molecular Medicine (CMMC), University of Cologne, 50937 Cologne, Germany
| | | | - Alexander D. Bach
- Department of Plastic, Aesthetic and Hand Surgery, St. Antonius Hospital Eschweiler, 52249 Eschweiler, Germany
| | - Nadja Kröger
- Institute for Laboratory Animal Science and Experimental Surgery, University of Aachen Medical Center, Faculty of Medicine, RWTH-Aachen University, 52074 Aachen, Germany
- Department of Plastic, Aesthetic and Hand Surgery, St. Antonius Hospital Eschweiler, 52249 Eschweiler, Germany
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Bicer M. Revolutionizing dermatology: harnessing mesenchymal stem/stromal cells and exosomes in 3D platform for skin regeneration. Arch Dermatol Res 2024; 316:242. [PMID: 38795200 PMCID: PMC11127839 DOI: 10.1007/s00403-024-03055-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/09/2024] [Accepted: 04/26/2024] [Indexed: 05/27/2024]
Abstract
Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.
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Affiliation(s)
- Mesude Bicer
- Department of Bioengineering, Faculty of Life and Natural Sciences, Abdullah Gul University, Kayseri, 38080, Turkey.
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Noh CH, Park S, Seong HR, Lee AY, Tsolmon KE, Geum D, Hong SC, Kim TM, Choi EK, Kim YB. An Exosome-Rich Conditioned Medium from Human Amniotic Membrane Stem Cells Facilitates Wound Healing via Increased Reepithelization, Collagen Synthesis, and Angiogenesis. Cells 2023; 12:2698. [PMID: 38067126 PMCID: PMC10705799 DOI: 10.3390/cells12232698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 11/17/2023] [Accepted: 11/23/2023] [Indexed: 12/18/2023] Open
Abstract
Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.
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Affiliation(s)
- Chan Ho Noh
- College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea; (C.H.N.)
- Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea (T.M.K.); (E.-K.C.)
| | - Sangryong Park
- Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea (T.M.K.); (E.-K.C.)
| | - Hye-Rim Seong
- Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea (T.M.K.); (E.-K.C.)
| | - Ah-young Lee
- Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea (T.M.K.); (E.-K.C.)
| | - Khan-Erdene Tsolmon
- College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea; (C.H.N.)
| | - Dongho Geum
- Department of Biomedical Science, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Soon-Cheol Hong
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Tae Myoung Kim
- Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea (T.M.K.); (E.-K.C.)
| | - Ehn-Kyoung Choi
- Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea (T.M.K.); (E.-K.C.)
| | - Yun-Bae Kim
- College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea; (C.H.N.)
- Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea (T.M.K.); (E.-K.C.)
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11
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Avila-Martinez N, Gansevoort M, Verbakel J, Jayaprakash H, Araujo IM, Vitorino M, Tiscornia G, van Kuppevelt TH, Daamen WF. Matrisomal components involved in regenerative wound healing in axolotl and Acomys: implications for biomaterial development. Biomater Sci 2023; 11:6060-6081. [PMID: 37525590 DOI: 10.1039/d3bm00835e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl (Ambystoma mexicanum) are capable of regenerating whole organs and even limbs, most mammals heal their wounds via fibrotic scarring. Recently, the African spiny mouse (Acomys sp.) has been shown to be injury resistant and capable of regenerating several tissue types. A major focal point of research with Acomys has been the identification of drivers of regeneration. In this search, the matrisome components related to the extracellular matrix (ECM) are often overlooked. In this review, we compare Acomys and axolotl skin wound healing and blastema-mediated regeneration by examining their wound healing responses and comparing the expression pattern of matrisome genes, including glycosaminoglycan (GAG) related genes. The goal of this review is to identify matrisome genes that are upregulated during regeneration and could be potential candidates for inclusion in pro-regenerative biomaterials. Research papers describing transcriptomic or proteomic coverage of either skin regeneration or blastema formation in Acomys and axolotl were selected. Matrisome and GAG related genes were extracted from each dataset and the resulting lists of genes were compared. In our analysis, we found several genes that were consistently upregulated, suggesting possible involvement in regenerative processes. Most of the components have been implicated in regulation of cell behavior, extracellular matrix remodeling and wound healing. Incorporation of such pro-regenerative factors into biomaterials may help to shift pro-fibrotic processes to regenerative responses in treated wounds.
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Affiliation(s)
- Nancy Avila-Martinez
- Department of Medical BioSciences, Radboud Research Institute, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
| | - Merel Gansevoort
- Department of Medical BioSciences, Radboud Research Institute, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
| | - Juul Verbakel
- Department of Medical BioSciences, Radboud Research Institute, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
| | - Haarshaadri Jayaprakash
- Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139, Faro, Portugal
- Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139, Faro, Portugal
| | - Ines Maria Araujo
- Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139, Faro, Portugal
- Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, 8005-139, Faro, Portugal
| | - Marta Vitorino
- Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139, Faro, Portugal
- Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139, Faro, Portugal
- Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, 8005-139, Faro, Portugal
| | - Gustavo Tiscornia
- Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139, Faro, Portugal
- Eugin Barcelona, Balmes, 236, 08006 Barcelona, Spain
| | - Toin H van Kuppevelt
- Department of Medical BioSciences, Radboud Research Institute, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
| | - Willeke F Daamen
- Department of Medical BioSciences, Radboud Research Institute, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
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12
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Shi X, Wang Y, Liu H, Han R. Targeting Hub Genes Involved in Muscle Injury Induced by Jumping Load Based on Transcriptomics. DNA Cell Biol 2023; 42:498-506. [PMID: 37339448 DOI: 10.1089/dna.2022.0285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/22/2023] Open
Abstract
The purpose of this study was to find hub genes that may play key roles in skeletal muscle injury induced by jumping load. Twelve female Sprague Dawley rats were divided into the normal control (NC) group and the jumping-induced muscle injury (JI) group. After 6 weeks of jumping, transmission electron microscopy, hematoxylin-eosin staining, transcriptomics sequencing and genes analysis, interaction network prediction of multiple proteins, real-time PCR detection, and Western blotting were performed on gastrocnemius muscles from NC and JI groups. As compared with NC rats, excessive jumping can result in notable structural damage and inflammatory infiltration in JI rats. A total of 112 differentially expressed genes were confirmed in NC rats versus JI rats, with 59 genes upregulated and 53 genes downregulated. Using the online String database, four hub genes in the transcriptional regulatory network were targeted, including FOS, EGR1, ATF3, and NR4A3. All expression levels of FOS, EGR1, ATF3, and NR4A3 mRNAs were decreased in JI rats compared with NC rats (p < 0.05 or p < 0.01). All expression levels of c-Fos, EGR1, ATF3, and NOR1 proteins were upregulated in JI rats (p < 0.01, p < 0.05, p > 0.05, and p < 0.01, respectively). Collectively, these findings indicate that FOS, EGR1, ATF3, and NR4A3 genes may be functionally important in jumping-induced muscle injury.
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Affiliation(s)
- Xiaolan Shi
- Wushu College, Henan University, Kaifeng, China
| | - Yijie Wang
- School of Physical Education and Sport, Henan University, Kaifeng, China
| | - Haitao Liu
- School of Physical Education and Sport, Henan University, Kaifeng, China
- Sports Reform and Development Research Center, Henan University, Kaifeng, China
| | - Rui Han
- School of Physical Education and Sport, Henan University, Kaifeng, China
- Sports Reform and Development Research Center, Henan University, Kaifeng, China
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13
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Kidzeru EB, Lebeko M, Sharma JR, Nkengazong L, Adeola HA, Ndlovu H, P Khumalo N, Bayat A. Immune cells and associated molecular markers in dermal fibrosis with focus on raised cutaneous scars. Exp Dermatol 2023; 32:570-587. [PMID: 36562321 PMCID: PMC10947010 DOI: 10.1111/exd.14734] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 08/04/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022]
Abstract
Raised dermal scars including hypertrophic, and keloid scars as well as scalp-associated fibrosing Folliculitis Keloidalis Nuchae (FKN) are a group of fibrotic raised dermal lesions that mostly occur following cutaneous injury. They are characterized by increased extracellular matrix (ECM) deposition, primarily excessive collagen type 1 production by hyperproliferative fibroblasts. The extent of ECM deposition is thought to be proportional to the severity of local skin inflammation leading to excessive fibrosis of the dermis. Due to a lack of suitable study models, therapy for raised dermal scars remains ill-defined. Immune cells and their associated markers have been strongly associated with dermal fibrosis. Therefore, modulation of the immune system and use of anti-inflammatory cytokines are of potential interest in the management of dermal fibrosis. In this review, we will discuss the importance of immune factors in the pathogenesis of raised dermal scarring. The aim here is to provide an up-to-date comprehensive review of the literature, from PubMed, Scopus, and other relevant search engines in order to describe the known immunological factors associated with raised dermal scarring. The importance of immune cells including mast cells, macrophages, lymphocytes, and relevant molecules such as cytokines, chemokines, and growth factors, antibodies, transcription factors, and other immune-associated molecules as well as tissue lymphoid aggregates identified within raised dermal scars will be presented. A growing body of evidence points to a shift from proinflammatory Th1 response to regulatory/anti-inflammatory Th2 response being associated with the development of fibrogenesis in raised dermal scarring. In summary, a better understanding of immune cells and associated molecular markers in dermal fibrosis will likely enable future development of potential immune-modulated therapeutic, diagnostic, and theranostic targets in raised dermal scarring.
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Affiliation(s)
- Elvis Banboye Kidzeru
- Wound Healing And Keloid Scar Unit, Medical Research Council (South Africa), Hair and Skin Research Laboratory, Division of Dermatology, Department of MedicineUniversity of Cape TownCape TownSouth Africa
- Microbiology, Infectious Diseases, and Immunology Laboratory (LAMMII)Centre for Research on Health and Priority Pathologies (CRSPP)Institute of Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific Research and InnovationYaoundéCameroon
| | - Maribanyana Lebeko
- Wound Healing And Keloid Scar Unit, Medical Research Council (South Africa), Hair and Skin Research Laboratory, Division of Dermatology, Department of MedicineUniversity of Cape TownCape TownSouth Africa
- Present address:
Cape Biologix Technologies (PTY, LTD)Cape TownSouth Africa
| | - Jyoti Rajan Sharma
- Wound Healing And Keloid Scar Unit, Medical Research Council (South Africa), Hair and Skin Research Laboratory, Division of Dermatology, Department of MedicineUniversity of Cape TownCape TownSouth Africa
- Biomedical Research and Innovation Platform, South African Medical Research Council, Francie van Zijl Drive, Parow ValleyCape TownSouth Africa
- Present address:
Biomedical Research and Innovation Platform, South African Medical Research Council, Francie van Zijl Drive, Parow ValleyCape TownSouth Africa
| | - Lucia Nkengazong
- Microbiology, Infectious Diseases, and Immunology Laboratory (LAMMII)Centre for Research on Health and Priority Pathologies (CRSPP)Institute of Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific Research and InnovationYaoundéCameroon
| | - Henry Ademola Adeola
- Wound Healing And Keloid Scar Unit, Medical Research Council (South Africa), Hair and Skin Research Laboratory, Division of Dermatology, Department of MedicineUniversity of Cape TownCape TownSouth Africa
| | - Hlumani Ndlovu
- Department of Integrative Biomedical SciencesUniversity of Cape TownCape TownSouth Africa
| | - Nonhlanhla P Khumalo
- Wound Healing And Keloid Scar Unit, Medical Research Council (South Africa), Hair and Skin Research Laboratory, Division of Dermatology, Department of MedicineUniversity of Cape TownCape TownSouth Africa
| | - Ardeshir Bayat
- Wound Healing And Keloid Scar Unit, Medical Research Council (South Africa), Hair and Skin Research Laboratory, Division of Dermatology, Department of MedicineUniversity of Cape TownCape TownSouth Africa
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14
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Bates JHT, Herrmann J, Casey DT, Suki B. An agent-based model of tissue maintenance and self-repair. Am J Physiol Cell Physiol 2023; 324:C941-C950. [PMID: 36878841 PMCID: PMC10089306 DOI: 10.1152/ajpcell.00531.2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/10/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023]
Abstract
We hypothesized that a system that possesses the capacity for ongoing maintenance of its tissues will necessarily also have the capacity to self-heal following a perturbation. We used an agent-based model of tissue maintenance to investigate this idea, and in particular to determine the extent to which the current state of the tissue must influence cell behavior in order for tissue maintenance and self-healing to be stable. We show that a mean level of tissue density is robustly maintained when catabolic agents digest tissue at a rate proportional to local tissue density, but that the spatial heterogeneity of the tissue at homeostasis increases with the rate at which tissue is digested. The rate of self-healing is also increased by increasing either the amount of tissue removed or deposited at each time step by catabolic or anabolic agents, respectively, and by increasing the density of both agent types on the tissue. We also found that tissue maintenance and self-healing are stable with an alternate rule in which cells move preferentially to tissue regions of low density. The most basic form of self-healing can thus be achieved with cells that follow very simple rules of behavior, provided these rules are based in some way on the current state of the local tissue. Straightforward mechanisms can accelerate the rate of self-healing, as might be beneficial to the organism.
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Affiliation(s)
- Jason H T Bates
- Department of Medicine, University of Vermont, Burlington, Vermont, United States
| | - Jacob Herrmann
- Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States
| | - Dylan T Casey
- Department of Medicine, University of Vermont, Burlington, Vermont, United States
- Complex Systems Center, University of Vermont, Burlington, Vermont, United States
| | - Béla Suki
- Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States
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15
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CD73-Positive Cell Spheroid Transplantation Attenuates Colonic Atrophy. Pharmaceutics 2023; 15:pharmaceutics15030845. [PMID: 36986706 PMCID: PMC10051511 DOI: 10.3390/pharmaceutics15030845] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/27/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
The incidence of inflammatory bowel diseases (IBD) is increasing worldwide. Mesenchymal stem/stromal cells (MSCs) have immunomodulatory functions and are a promising source for cell transplantation therapy for IBD. However, owing to their heterogeneous nature, their therapeutic efficacy in colitis is controversial and depends on the delivery route and form of transplanted cells. Cluster of differentiation (CD) 73 is widely expressed in MSCs and used to obtain a homogeneous MSC population. Herein, we determined the optimal method for MSC transplantation using CD73+ cells in a colitis model. mRNA sequencing analysis showed that CD73+ cells exhibited a downregulation of inflammatory gene expression and an upregulation of extracellular matrix-related gene expression. Furthermore, three-dimensional CD73+ cell spheroids showed enhanced engraftment at the injured site through the enteral route, facilitated extracellular matrix remodeling, and downregulated inflammatory gene expression in fibroblasts, leading to the attenuation of colonic atrophy. Therefore, the interaction between intestinal fibroblasts and exogenous MSCs via tissue remodeling is one mechanism that can be exploited for colitis prevention. Our results highlight that the transplantation of homogeneous cell populations with well-characterized properties is beneficial for IBD treatment.
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16
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Interdonato L, Marino Y, Franco GA, Arangia A, D’Amico R, Siracusa R, Cordaro M, Impellizzeri D, Fusco R, Cuzzocrea S, Paola RD. Açai Berry Administration Promotes Wound Healing through Wnt/β-Catenin Pathway. Int J Mol Sci 2023; 24:ijms24010834. [PMID: 36614291 PMCID: PMC9821151 DOI: 10.3390/ijms24010834] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 12/22/2022] [Accepted: 12/26/2022] [Indexed: 01/05/2023] Open
Abstract
Recently, wound healing has received increased attention from both a scientific and clinical point of view. It is characterized by an organized series of processes: angiogenesis, cell migration and proliferation, extracellular matrix production, and remodeling. Many of these processes are controlled by the Wnt pathway, which activates them. The aim of the study was to evaluate the molecular mechanism of açai berry administration in a mouse model of wound healing. CD1 male mice were used in this research. Two full-thickness excisional wounds (5 mm) were performed with a sterile biopsy punch on the dorsum to create two circular, full-thickness skin wounds on either side of the median line on the dorsum. Açai berry was administered by oral administration (500 mg/kg dissolved in saline) for 6 days after induction of the wound. Our study demonstrated that açai berry can modulate the Wnt pathway, reducing the expression of Wnt3a, the cysteine-rich domain of frizzled (FZ)8, and the accumulation of cytosolic and nuclear β-catenin. Moreover, açai berry reduced the levels of TNF-α and IL-18, which are target genes strictly downstream of the Wnt/β-catenin pathway. It also showed important anti-inflammatory activities by reducing the activation of the NF-κB pathway. Furthermore, Wnt can modulate the activity of growth factors, such as TGF-β, and VEGF, which are the basis of the wound-healing process. In conclusion, we can confirm that açai berry can modulate the activity of the Wnt/β-catenin pathway, as it is involved in the inflammatory process and in the activity of the growth factor implicated in wound healing.
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Affiliation(s)
- Livia Interdonato
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Ylenia Marino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Gianluca Antonio Franco
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Alessia Arangia
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Ramona D’Amico
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Rosalba Siracusa
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Marika Cordaro
- Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Daniela Impellizzeri
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Roberta Fusco
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
- Correspondence:
| | - Salvatore Cuzzocrea
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
| | - Rosanna Di Paola
- Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
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17
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Quilling GM, Lee KS, Ebben B. Shear wave elastography imaging in a porcine tendinopathy model. Skeletal Radiol 2022; 51:2167-2173. [PMID: 35639127 DOI: 10.1007/s00256-022-04073-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 05/10/2022] [Accepted: 05/11/2022] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To quantify the effect of structural damage in an ex vivo animal tendinopathy model using shear wave elastography (SWE). MATERIALS AND METHODS Sixteen porcine flexor tendons were injected with a 0.05 mL bolus of 1.5% collagenase solution to induce focal structural damage without surfacing tears. Control tendons were injected with saline (n = 16). Eight tendons from each group were incubated at 37 °C for 3.5 h while the remaining 8 from each group were incubated for 7 h. Tendons were mechanically stretched to 0% and 1% strain. Simultaneously, SWE was acquired proximal to, at, and distal to the injection site using a clinical ultrasound scanner. RESULTS There were significant differences in SWS (saline > collagenase) at 1% strain and 7-h incubation for all three locations (PROX p = 0.0031, ROI p = 0.001, DIST p = 0.0043). There were also significant differences at 0% strain and 7 h, but only at (p = 0.0005), and distal to (p = 0.0035), the injection site. No statistically significant differences were observed for 3.5-h incubation, at 0% or 1% strain. CONCLUSIONS Collagenase-mediated structural damage does appear to convey decreased tissue elasticity on SWE when ex vivo tendons are incubated for 7 h. These findings suggest that SWE may be a useful tool for predicting ultimate tissue strength in tendinopathic tissues. Pull-to-failure testing should be performed in the future and are expected to show that tendons with decreased SWS, and, therefore, decreased elasticity, rupture at lower pulls forces.
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Affiliation(s)
- Grant M Quilling
- School of Medicine and Public Health, University of Wisconsin, 750 Highland Ave, Madison, WI, 53726, USA
| | - Kenneth S Lee
- Department of Radiology, University of Wisconsin Hospitals and Clinics, 621 Science Drive, Madison, WI, 53711, USA.
| | - Beau Ebben
- Department of Radiology, University of Wisconsin Hospitals and Clinics, 621 Science Drive, Madison, WI, 53711, USA
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18
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Barbosa A, Zazula MF, Oliveira MCD, Teleken JL, Costa RM, Bonfleur ML, Torrejais MM. Maternal exposure to glyphosate-based herbicide promotes changes in the muscle structure of C57BL/6 mice offspring. Anat Rec (Hoboken) 2022; 305:3307-3316. [PMID: 35338770 DOI: 10.1002/ar.24922] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 03/09/2022] [Accepted: 03/14/2022] [Indexed: 11/06/2022]
Abstract
Glyphosate (GBH) is a worldwide consumption pesticide and is used in the formulation of Roundup®, one of the most commercialized herbicides in the world. Maternal exposure to this herbicide can promote changes and adaptations in the offspring; however, the effects on skeletal muscle are poorly understood. In this sense, the present study sought to evaluate the effect of exposure to GBH on the characteristics of the soleus (SOL) and extensor digitorum longus (EDL) muscles. C57BL/6 pregnant female mice were divided into two groups: control (CTL) receiving water and glyphosate (GBH; n = 6) receiving 0.5% glyphosate. Male puppies were designated according to the group to which the mothers belonged, such as CTL-F1 and GBH-F1 and then euthanized at 150 days of age. There was a reduction in body weight and nasoanal length of animals exposed to GBH, while there was an increase in EDL weight, reduction in the proportion of fibers and number of nuclei, and an increase in the connective tissue of the SOL. The animals exposed to GBH presented higher values of body characteristics, mainly adiposity gain, while they presented a reduction in neuromuscular junctions (NMJ), and an increase in fibrosis in the SOL muscle, while there was a reduction in the number of nuclei, and an increase in the weight of the EDL muscle. These findings indicate that glyphosate can promote changes in the offspring's body growth, the deposition of adipose panicles and its effects on muscle can lead to changes in the structure and functioning of this tissue.
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Affiliation(s)
- Ariadne Barbosa
- Laboratório Experimental de Morfologia - Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil
| | - Matheus Felipe Zazula
- Laboratório de Plasticidade Morfofuncional - Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
| | - Mylena Campos de Oliveira
- Laboratório Experimental de Morfologia - Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil
| | - Jakeline Liara Teleken
- Laboratório de Fisiologia Endócrina e Metabolismo - Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil
| | - Rose Meire Costa
- Laboratório de Biologia Estrutural e Funcional - Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil
| | - Maria Lucia Bonfleur
- Laboratório de Fisiologia Endócrina e Metabolismo - Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil
| | - Marcia Miranda Torrejais
- Laboratório Experimental de Morfologia - Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil
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19
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Sabarees G, Tamilarasi G, Velmurugan V, Alagarsamy V, Sibuh BZ, Sikarwar M, Taneja P, Kumar A, Gupta PK. Emerging trends in silk fibroin based nanofibers for impaired wound healing. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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20
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Abstract
Despite the evolutionary loss of tissue regenerative potential, robust skeletal muscle repair processes are largely retained even in higher vertebrates. In mammals, the skeletal muscle regeneration program is driven by resident stem cells termed satellite cells, guided by the coordinated activity of multiple intrinsic and extrinsic factors and other cell types. A thorough understanding of muscle repair mechanisms is crucial not only for combating skeletal myopathies, but for its prospective aid in devising therapeutic strategies to endow regenerative potential on otherwise regeneration-deficient organs. In this review, we discuss skeletal muscle regeneration from an evolutionary perspective, summarize the current knowledge of cellular and molecular mechanisms, and highlight novel paradigms of muscle repair revealed by explorations of the recent decade.
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Affiliation(s)
- Sajedah M Hindi
- Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
| | - Douglas P Millay
- Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
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21
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Tschaikowsky M, Brander S, Barth V, Thomann R, Rolauffs B, Balzer BN, Hugel T. The articular cartilage surface is impaired by a loss of thick collagen fibers and formation of type I collagen in early osteoarthritis. Acta Biomater 2022; 146:274-283. [PMID: 35487427 DOI: 10.1016/j.actbio.2022.04.036] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 04/03/2022] [Accepted: 04/21/2022] [Indexed: 12/14/2022]
Abstract
Osteoarthritis (OA) is a joint disease affecting millions of patients worldwide. During OA onset and progression, the articular cartilage is destroyed, but the underlying complex mechanisms remain unclear. Here, we uncover changes in the thickness of collagen fibers and their composition at the onset of OA. For articular cartilage explants from knee joints of OA patients, we find that type I collagen-rich fibrocartilage-like tissue was formed in macroscopically intact cartilage, distant from OA lesions. Importantly, the number of thick fibers (>100 nm) has decreased early in the disease, followed by complete absence of thick fibers in advanced OA. We have obtained these results by a combination of high-resolution atomic force microscopy imaging under near-native conditions, immunofluorescence, scanning electron microscopy and a fluorescence-based classification of the superficial chondrocyte spatial organization. Taken together, our data suggests that the loss of tissue functionality in early OA cartilage is caused by a reduction of thick type II collagen fibers, likely due to the formation of type I collagen-rich fibrocartilage, followed by the development of focal defects in later OA stages. We anticipate that such an integrative characterization will be very beneficial for an in-depth understanding of other native biological tissues and the development of sustainable biomaterials. STATEMENT OF SIGNIFICANCE: In early osteoarthritis (OA) the cartilage appears macroscopically intact. However, this study demonstrates that the collagen network already changes in early OA by collagen fiber thinning and the formation of fibrocartilage-like tissue. Both nanoscopic deficiencies already occur in macroscopically intact regions of the human knee joint and are likely connected to processes that result in a weakened extracellular matrix. This study enhances the understanding of earliest progressive cartilage degeneration in the absence of external damage. The results suggest a determination of the mean collagen fiber thickness as a new target for the detection of early OA and a regulation of type I collagen synthesis as a new path for OA treatment.
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22
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Al-Akayleh F, Jaber N, Al-Remawi M, Al Odwan G, Qinna N. Chitosan-biotin topical film: Preparation and evaluation of burn wound healing activity. Pharm Dev Technol 2022; 27:479-489. [DOI: 10.1080/10837450.2022.2079132] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Faisal Al-Akayleh
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan.
| | - Nisrein Jaber
- Faculty of Pharmacy, Al-Zaytoonah University, Amman, Jordan
| | - Mayyas Al-Remawi
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan.
| | - Ghazi Al Odwan
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan.
| | - Nidal Qinna
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan.
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23
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Lai PT, Wu SL, Huang CY, Yang SF. A retrospective cohort study on outcome and interactions among prognostic factors of endodontic microsurgery. J Formos Med Assoc 2022; 121:2220-2226. [PMID: 35450740 DOI: 10.1016/j.jfma.2022.04.005] [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: 03/23/2022] [Accepted: 04/07/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND/PURPOSE Endodontic microsurgery (EMS) is a reliable treatment for teeth with non-healing apical periodontitis. This study evaluated the outcome of EMS with mineral trioxide aggregate as the retrograde filling material and identified potential prognostic factors associated with the EMS outcome. METHODS Consecutive clinical and radiographic records of EMS performed in a teaching hospital from 2013 to 2017 were reviewed. Cases of root fracture, cemental tear, re-surgery, and incomplete records were excluded. After selection, 268 EMS-treated teeth with the follow-up period more than one year were included. Surgical outcome as success or failure was evaluated according to Molven's criteria. For analysis of potential prognostic factors, multivariate logistic regression was performed followed by bivariate chi-square tests. Stratified analysis was performed to understand the interactions between two prognostic factors. RESULTS The overall EMS success rate was 89.9% in this study. Tooth type (anteriors vs. molars, odds ratio (OR) = 6.83, P = 0.001, anteriors vs. premolars, OR = 4.27, P = 0.010) and endodontic-periodontal (endo-perio) communicating defects (with vs. without, OR = 4.92, P = 0.005) both had a significant influence on the EMS outcome. The negative impact of endo-perio communicating defects was closely associated with tooth type. Premolars with endo-perio communicating defects had significantly higher rates of failure. CONCLUSION The EMS outcome is significantly affected by the tooth type and endo-perio communicating defect. The presence of endo-perio communicating defects has a greater negative influence on the success rate for premolars than for anteriors and molars.
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Affiliation(s)
- Po-Tang Lai
- Division of Endodontics and Periodontology, Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Dentistry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Shang-Liang Wu
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chih-Yang Huang
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Biological Science and Technology, China Medical University, Taichung, Taiwan; Cardiovascular and Mitochondria Related Diseases Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; Holistic Education Center, Tzu Chi University of Science and Technology, Hualien, Taiwan
| | - Shue-Fen Yang
- Division of Endodontics and Periodontology, Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
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24
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Optimization of Titanium Dental Mesh Surfaces for Biological Sealing and Prevention of Bacterial Colonization. MATERIALS 2022; 15:ma15072651. [PMID: 35407983 PMCID: PMC9000448 DOI: 10.3390/ma15072651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/21/2022] [Accepted: 03/31/2022] [Indexed: 02/04/2023]
Abstract
Titanium dental meshes have a wide application in order to ensure the retention of calcium phosphate-based biomaterials to regenerate bone tissue. These meshes are temporary and must grow a soft tissue to prevent bacterial colonization and provide stability. In this work, we aimed to optimize the roughness of the meshes to obtain a good biological seal while maintaining a behavior that did not favor bacterial colonization. To this end, six types of surfaces were studied: machined as a control, polished, sandblasted with three different alumina sizes and sintered. The roughness, contact angles and biological behavior of the samples using fibroblast cultures at 7, 24 and 72 h were determined as well as cytotoxicity studies. Cultures of two very common bacterial strains in the oral cavity were also carried out: Streptococcus sanguinis and Lactobacillus salivarius. The results showed that the samples treated with alumina particles by sandblasting at 200 micrometers were the ones that performed best with fibroblasts and also with the number of bacterial colonies in both strains. According to the results, we see in this treatment a candidate for the surface treatment of dental meshes with an excellent performance.
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25
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Robinson S, Parigoris E, Chang J, Hecker L, Takayama S. Contracting scars from fibrin drops. Integr Biol (Camb) 2022; 14:1-12. [PMID: 35184163 PMCID: PMC8934703 DOI: 10.1093/intbio/zyac001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Indexed: 11/13/2022]
Abstract
This paper describes a microscale fibroplasia and contraction model that is based on fibrin-embedded lung fibroblasts and provides a convenient visual readout of fibrosis. Cell-laden fibrin microgel drops are formed by aqueous two-phase microprinting. The cells deposit extracellular matrix (ECM) molecules such as collagen while fibrin is gradually degraded. Ultimately, the cells contract the collagen-rich matrix to form a compact cell-ECM spheroid. The size of the spheroid provides the visual readout of the extent of fibroplasia. Stimulation of this wound-healing model with the profibrotic cytokine TGF-β1 leads to an excessive scar formation response that manifests as increased collagen production and larger cell-ECM spheroids. Addition of drugs also shifted the scarring profile: the FDA-approved fibrosis drugs (nintedanib and pirfenidone) and a PAI-1 inhibitor (TM5275) significantly reduced cell-ECM spheroid size. Not only is the assay useful for evaluation of antifibrotic drug effects, it is relatively sensitive; one of the few in vitro fibroplasia assays that can detect pirfenidone effects at submillimolar concentrations. Although this paper focuses on lung fibrosis, the approach opens opportunities for studying a broad range of fibrotic diseases and for evaluating antifibrotic therapeutics.
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Affiliation(s)
| | - Eric Parigoris
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine, Atlanta, GA, USA,The Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
| | - Jonathan Chang
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine, Atlanta, GA, USA,The Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
| | - Louise Hecker
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Shuichi Takayama
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine, Atlanta, GA, USA,The Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
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26
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Hassan SU, Chua EG, Paz EA, Kaur P, Tay CY, Greeff JC, Liu S, Martin GB. Investigating the development of diarrhoea through gene expression analysis in sheep genetically resistant to gastrointestinal helminth infection. Sci Rep 2022; 12:2207. [PMID: 35140270 PMCID: PMC8828848 DOI: 10.1038/s41598-022-06001-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 01/13/2022] [Indexed: 12/13/2022] Open
Abstract
Gastrointestinal helminths infect livestock causing health problems including severe diarrhoea. To explore the underlying biological mechanisms relating to development and control of diarrhoea, we compared 4 sheep that were susceptible to development of diarrhoea with 4 sheep that were diarrhoea-resistant. Transcriptomes in the tissues where the parasites were located were analyzed using RNASeq. By considering low-diarrhoea sheep as control, we identified 114 genes that were down-regulated and 552 genes that were up-regulated genes in the high-diarrhoea phenotype. Functional analysis of DEGs and PPI sub-network analysis showed that down-regulated genes in the high-diarrhoea phenotype were linked to biological processes and pathways that include suppression of ‘antigen processing and presentation’, ‘immune response’, and a list of biological functional terms related to ‘suppression in immune tolerance’. On the other hand, up-regulated genes in the high-diarrhoea phenotype probably contribute to repair processes associated with tissue damage, including ‘extracellular matrix organization’, ‘collagen fibril organization’, ‘tissue morphogenesis’, ‘circulatory system development’, ‘morphogenesis of an epithelium’, and ‘focal adhesion’. The genes with important roles in the responses to helminth infection could be targeted in breeding programs to prevent diarrhoea.
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Affiliation(s)
- Shamshad Ul Hassan
- UWA School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia.,Helicobacter Research Laboratory, The Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| | - Eng Guan Chua
- Helicobacter Research Laboratory, The Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| | - Erwin A Paz
- UWA School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia.,Helicobacter Research Laboratory, The Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| | - Parwinder Kaur
- UWA School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia
| | - Chin Yen Tay
- Helicobacter Research Laboratory, The Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| | - Johan C Greeff
- UWA School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia.,Department of Primary Industries and Regional Development, Western Australia, 3 Baron Hay Court, South Perth, WA, 6151, Australia
| | - Shimin Liu
- UWA School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia
| | - Graeme B Martin
- UWA School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia.
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27
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Mu Z, Guo J, Zhang D, Xu Y, Zhou M, Guo Y, Hou Y, Gao X, Han X, Geng L. Therapeutic Effects of Shikonin on Skin Diseases: A Review. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 49:1871-1895. [PMID: 34961421 DOI: 10.1142/s0192415x21500889] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Shikonin is one of the primary active components extracted from the dried root ofZicao (Lithospermum erythrorhizon, Onosma paniculata, or Arnebia euchroma), a traditional Chinese herbal medicine. Shikonin is known to not only exert anti-proliferative, anti-inflammatory, and anti-angiogenic activities, but also play a crucial role in triggering the production of reactive oxygen species, suppressing the release of exosomes, and inducing apoptosis. Increasing evidence suggests that shikonin has a protective effect against skin diseases, including psoriasis, melanoma, and hypertrophic scars. In order to evaluate the application potential of shikonin in the treatment of skin diseases, this review is the first of its kind to provide comprehensive and up-to-date information regarding the uses of shikonin and its derivatives on skin diseases and its underlying mechanisms. In this review, we have focused on the signaling pathways and cellular targets involved in the anti-dermatosis effects of shikonin to bridge the gaps in the literature, thereby providing scientific support for the research and development of new drugs from a traditional medicinal plant.
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Affiliation(s)
- Zhenzhen Mu
- China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110000, P. R. China.,Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China.,Department of Dermatology, Shengjing Hospital of China Medical University, 36N, Sanhao Street, Heping District, Shenyang, Liaoning 110000, P. R. China
| | - Jinrong Guo
- China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110000, P. R. China.,Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China.,Department of Dermatology, Jincheng People's Hospital, 456N, Wenchang East Street, Jincheng, Shanxi 048000, P. R. China
| | - Dongxia Zhang
- Department of Dermatology, Zhongshan Torch Development Zone Hospital, 123N, Yixian Road, Torch Zone, Zhongshan 528400, Guangdong, P. R. China
| | - Yuanyuan Xu
- Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China
| | - Mingming Zhou
- China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110000, P. R. China.,Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China
| | - Yimeng Guo
- China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110000, P. R. China.,Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China
| | - Yuzhu Hou
- China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110000, P. R. China.,Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China
| | - Xinghua Gao
- Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China
| | - Xiuping Han
- Department of Dermatology, Shengjing Hospital of China Medical University, 36N, Sanhao Street, Heping District, Shenyang, Liaoning 110000, P. R. China
| | - Long Geng
- Department of Dermatology, No. 1 Hospital of China Medical University, 155N, Nanjing Street, Heping District, Shenyang, Liaoning 110000, P. R. China
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28
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Marofi F, Alexandrovna KI, Margiana R, Bahramali M, Suksatan W, Abdelbasset WK, Chupradit S, Nasimi M, Maashi MS. MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy. Stem Cell Res Ther 2021; 12:597. [PMID: 34863308 PMCID: PMC8642895 DOI: 10.1186/s13287-021-02662-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/14/2021] [Indexed: 12/18/2022] Open
Abstract
Currently, mesenchymal stem/stromal stem cell (MSC) therapy has become a promising option for accelerating cutaneous wound healing. In vivo reports have outlined the robust competences of MSCs to offer a solid milieu by inhibition of inflammatory reactions, which in turn, enables skin regeneration. Further, due to their great potential to stimulate angiogenesis and also facilitate matrix remodeling, MSCs hold substantial potential as future therapeutic strategies in this context. The MSCs-induced wound healing is thought to mainly rely on the secretion of a myriad of paracrine factors in addition to their direct differentiation to skin-resident cells. Besides, MSCs-derived exosomes as nanoscale and closed membrane vesicles have recently been suggested as an effective and cell-free approach to support skin regeneration, circumventing the concerns respecting direct application of MSCs. The MSCs-derived exosomes comprise molecular components including lipid, proteins, DNA, microRNA, and also mRNA, which target molecular pathways and also biological activities in recipient cells (e.g., endothelial cell, keratinocyte, and fibroblast). The secreted exosome modifies macrophage activation, stimulates angiogenesis, and instigates keratinocytes and dermal fibroblast proliferations as well as migrations concurrently regulate inherent potential of myofibroblast for adjustment of turnover of the ECM. In the present review, we will focus on the recent findings concerning the application of MSCs and their derivative exosome to support wound healing and skin regeneration, with special focus on last decade in vivo reports.
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Affiliation(s)
- Faroogh Marofi
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Ria Margiana
- Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Master’s Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Mahta Bahramali
- Biotechnology Department, University of Tehran, Tehran, Iran
| | - Wanich Suksatan
- Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, 10210 Thailand
| | - Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Supat Chupradit
- Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200 Thailand
| | | | - Marwah Suliman Maashi
- Stem Cells and Regenerative Medicine Unit at King Fahad Medical Research Centre, Jeddah, Saudi Arabia
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29
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Singh B, Nathawat S, Sharma RA. Ethnopharmacological and phytochemical attributes of Indian Tinospora species: A comprehensive review. ARAB J CHEM 2021. [DOI: 10.1016/j.arabjc.2021.103381] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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30
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De Lisle SP, Bolnick DI. Male and female reproductive fitness costs of an immune response in natural populations . Evolution 2021;75:2509-2523. [PMID: 33991339 PMCID: PMC8488946 DOI: 10.1111/evo.14266] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 04/20/2021] [Accepted: 04/23/2021] [Indexed: 12/29/2022]
Abstract
Parasites can mediate host fitness both directly, via effects on survival and reproduction, or indirectly by inducing host immune defense with costly side-effects. The evolution of immune defense is determined by a complex interplay of costs and benefits of parasite infection and immune response, all of which may differ for male and female hosts in sexual lineages. Here, we examine fitness costs associated with an inducible immune defense in a fish-cestode host-parasite system. Cestode infection induces peritoneal fibrosis in threespine stickleback (Gasterosteus aculeatus), constraining cestode growth and sometimes encasing and killing the parasite. Surveying two wild populations of stickleback, we confirm that the presence of fibrosis scar tissue is associated with reduced parasite burden in both male and female fish. However, fibrotic fish had lower foraging success and reproductive fitness (reduced female egg production and male nesting success), indicating strong costs of the lingering immunopathology. Consistent with substantial sexually concordant fitness effects of immune response, we find alignment of multivariate selection across the sexes despite sexual antagonism over morphological shape. Although both sexes experienced costs of fibrosis, the net impacts are unequal because in the two study populations females had higher cestode exposure. To evaluate whether this difference in risk should drive sex-specific immune strategies, we analyze a quantitative genetic model of host immune response to a trophically transmitted parasite. The model and empirical data illustrate how shared costs and benefits of immune response lead to shared evolutionary interests of male and female hosts, despite unequal infection risks across the sexes.
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Affiliation(s)
- Stephen P. De Lisle
- Department of Ecology & Evolutionary Biology University of Connecticut Storrs, CT 06269
- Department of Biology, Evolutionary Ecology Unit, Lund University, Lund, Sweden
| | - Daniel I. Bolnick
- Department of Ecology & Evolutionary Biology University of Connecticut Storrs, CT 06269
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31
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Yang Z, Yang Y, Qi X, Liu N, Wang P, Zhang L, Han M, Han S. Thickening of the walls of deep brain abscesses is associated with macrophage infiltration. Exp Ther Med 2021; 22:1080. [PMID: 34447473 PMCID: PMC8355639 DOI: 10.3892/etm.2021.10514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 11/11/2020] [Indexed: 12/22/2022] Open
Abstract
The present study aimed to compare the thickness of brain abscesses in the deep and the superficial brain and to investigate the factors that influence the capsule of brain abscesses. The thickness of the brain abscess wall was evaluated on imaging. Bacteriological examination was performed on the abscess pus and wall, and immunohistochemical staining was used to count the number of macrophages. Kaplan-Meier curves were used to analyze overall survival. The results indicated that the wall of deep-brain abscesses was thicker than that of superficial abscesses. There was a difference in the extent of macrophage infiltration of deep- and superficial-brain abscess walls, and differences in the extent of macrophage infiltration in the wall of brain abscesses caused by various microorganisms were statistically significant. Of note, among the brain abscesses caused by Staphylococcus, the extent of macrophage/microglia infiltration and the thickness of the wall of the deep-brain abscesses were greater than those of superficial-brain abscesses and there was a positive correlation between the number of macrophages and the thickness of the abscess wall. The overall survival (OS) of patients with deep-brain abscess was not significantly shorter than that of patients with superficial-brain abscess. Furthermore, OS was not significantly different among groups of patients receiving different types of treatment. In conclusion, the wall of deep-brain abscesses is thicker than that of superficial abscesses and the infiltration of macrophages is abundant. The thick wall of abscesses in the deep brain may be associated with macrophage infiltration.
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Affiliation(s)
- Zuocheng Yang
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
| | - Yakun Yang
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
| | - Xueling Qi
- Department of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
| | - Ning Liu
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
| | - Pengfei Wang
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
| | - Linpeng Zhang
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
| | - Mingyang Han
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
| | - Song Han
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
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Abstract
From the clinical standpoint, systemic sclerosis (SSc) is characterized by skin and internal organ fibrosis, diffuse fibroproliferative vascular modifications, and autoimmunity. Clinical presentation and course are highly heterogenous and life expectancy variably affected mostly dependent on lung and heart involvement. SSc touches more women than men with differences in disease severity and environmental exposure. Pathogenetic events originate from altered homeostasis favored by genetic predisposition, environmental cues and a variety of endogenous and exogenous triggers. Epigenetic modifications modulate SSc pathogenesis which strikingly associate profound immune-inflammatory dysregulation, abnormal endothelial cell behavior, and cell trans-differentiation into myofibroblasts. SSc myofibroblasts show enhanced survival and enhanced extracellular matrix deposition presenting altered structure and altered physicochemical properties. Additional cell types of likely pathogenic importance are pericytes, platelets, and keratinocytes in conjunction with their relationship with vessel wall cells and fibroblasts. In SSc, the profibrotic milieu is favored by cell signaling initiated in the one hand by transforming growth factor-beta and related cytokines and in the other hand by innate and adaptive type 2 immune responses. Radical oxygen species and invariant receptors sensing danger participate to altered cell behavior. Conventional and SSc-specific T cell subsets modulate both fibroblasts as well as endothelial cell dysfunction. Beside autoantibodies directed against ubiquitous antigens important for enhanced clinical classification, antigen-specific agonistic autoantibodies may have a pathogenic role. Recent studies based on single-cell RNAseq and multi-omics approaches are revealing unforeseen heterogeneity in SSc cell differentiation and functional states. Advances in system biology applied to the wealth of data generated by unbiased screening are allowing to subgroup patients based on distinct pathogenic mechanisms. Deciphering heterogeneity in pathogenic mechanisms will pave the way to highly needed personalized therapeutic approaches.
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O'Regan A, O'Brien CJ, Eivers SB. The lysophosphatidic acid axis in fibrosis: Implications for glaucoma. Wound Repair Regen 2021; 29:613-626. [PMID: 34009724 DOI: 10.1111/wrr.12929] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/13/2021] [Accepted: 04/28/2021] [Indexed: 12/27/2022]
Abstract
Glaucoma is a common progressive optic neuropathy that results in visual field defects and can lead to irreversible blindness. The pathophysiology of glaucoma involves dysregulated extracellular matrix remodelling in both the trabecular meshwork in the anterior chamber and in the lamina cribrosa of the optic nerve head. Fibrosis in these regions leads to raised intraocular pressure and retinal ganglion cell degeneration, respectively. Lysophosphatidic acid (LPA) is a bioactive lipid mediator which acts via six G-protein coupled receptors on the cell surface to activate intracellular pathways that promote cell proliferation, transcription and survival. LPA signalling has been implicated in both normal wound healing and pathological fibrosis. LPA enhances fibroblast proliferation, migration and contraction, and induces expression of pro-fibrotic mediators such as connective tissue growth factor. The LPA axis plays a major role in diseases such as idiopathic pulmonary fibrosis, where it has been identified as an important pharmacological target. In glaucoma, LPA is present in high levels in the aqueous humour, and its signalling has been found to increase resistance to aqueous humour outflow through altered trabecular meshwork cellular contraction and extracellular matrix deposition. LPA signalling may, therefore, also represent an attractive target for treatment of glaucoma. In this review we wish to describe the role of LPA and its related proteins in tissue fibrosis and glaucoma.
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Affiliation(s)
- Amy O'Regan
- UCD Clinical Research Centre, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Colm J O'Brien
- UCD Clinical Research Centre, Mater Misericordiae University Hospital, Dublin, Ireland.,Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Sarah B Eivers
- UCD Clinical Research Centre, Mater Misericordiae University Hospital, Dublin, Ireland
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Avoiding tensional equilibrium in cells migrating on a matrix with cell-scale stiffness-heterogeneity. Biomaterials 2021; 274:120860. [PMID: 34004486 DOI: 10.1016/j.biomaterials.2021.120860] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 03/24/2021] [Accepted: 04/23/2021] [Indexed: 12/25/2022]
Abstract
Intracellular stresses affect various cell functions, including proliferation, differentiation and movement, which are dynamically modulated in migrating cells through continuous cell-shaping and remodeling of the cytoskeletal architecture induced by spatiotemporal interactions with extracellular matrix stiffness. When cells migrate on a matrix with cell-scale stiffness-heterogeneity, which is a common situation in living tissues, what intracellular stress dynamics (ISD) emerge? In this study, to explore this issue, finite element method-based traction force microscopy was applied to cells migrating on microelastically patterned gels. Two model systems of microelastically patterned gels (stiff/soft stripe and stiff triangular patterns) were designed to characterize the effects of a spatial constraint on cell-shaping and of the presence of different types of cues to induce competing cellular taxis (usual and reverse durotaxis) on the ISD, respectively. As the main result, the prolonged fluctuation of traction stress on a whole-cell scale was markedly enhanced on single cell-size triangular stiff patterns compared with homogeneous gels. Such ISD enhancement was found to be derived from the interplay between the nomadic migration of cells to regions with different degrees of stiffness and domain shape-dependent traction force dynamics, which should be an essential factor for keeping cells far from tensional equilibrium.
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35
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Krátká M, Čermák J, Vachelová J, Davídková M, Romanyuk N, Kromka A, Rezek B. Gamma radiation effects on diamond field-effect biosensors with fibroblasts and extracellular matrix. Colloids Surf B Biointerfaces 2021; 204:111689. [PMID: 33932892 DOI: 10.1016/j.colsurfb.2021.111689] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 08/17/2020] [Accepted: 03/06/2021] [Indexed: 01/05/2023]
Abstract
Due to high biocompatibility, miniaturization, optical transparency and low production cost together with high radiation hardness the diamond-based sensors are considered promising for radiation medicine and biomedicine in general. Here we present detection of fibroblast cell culture properties by nanocrystalline diamond solution-gated field-effect transistors (SG-FET), including effects of gamma irradiation. We show that blank nanocrystalline diamond field-effect biosensors are stable at least up to 300 Gy of γ irradiation. On the other hand, gate current of the diamond SG-FET biosensors with fibroblastic cells increases exponentially over an order of magnitude with increasing radiation dose. Extracellular matrix (ECM) formation is also detected and analyzed by correlation of electronic sensor data with optical, atomic force, fluorescence, and scanning electron microscopies.
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Affiliation(s)
- Marie Krátká
- Institute of Physics CAS, Cukrovarnická 10, 16200, Prague 6, Czech Republic.
| | - Jan Čermák
- Institute of Physics CAS, Cukrovarnická 10, 16200, Prague 6, Czech Republic
| | - Jana Vachelová
- Nuclear Physics Institute CAS, Řež 130, 25068, Řež, Czech Republic
| | - Marie Davídková
- Nuclear Physics Institute CAS, Řež 130, 25068, Řež, Czech Republic
| | - Nataliya Romanyuk
- Deparment of Neuroregeneration, Institute of Experimental Medicine CAS, Vídeňská 1083, 14220, Prague, Czech Republic
| | - Alexander Kromka
- Institute of Physics CAS, Cukrovarnická 10, 16200, Prague 6, Czech Republic
| | - Bohuslav Rezek
- Faculty of Electrical Engineering, Czech Technical University, Technická 2, 16627, Prague, Czech Republic
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36
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Liu Y, Holmes C. Tissue Regeneration Capacity of Extracellular Vesicles Isolated From Bone Marrow-Derived and Adipose-Derived Mesenchymal Stromal/Stem Cells. Front Cell Dev Biol 2021; 9:648098. [PMID: 33718390 PMCID: PMC7952527 DOI: 10.3389/fcell.2021.648098] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 02/02/2021] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cell (MSC)-based therapies have demonstrated tissue repair and regeneration capacity in various preclinical models. These therapeutic effects have recently been largely attributed to the paracrine effects of the MSC secretome, including proteins and extracellular vesicles (EVs). EVs are cell-secreted nano-sized vesicles with lipid bilayer membranes that facilitate cell–cell signaling. Treatments based on MSC-derived EVs are beginning to be explored as an alternative to MSC transplantation-based therapies. However, it remains to be determined which MSC source produces EVs with the greatest therapeutic potential. This review compares the tissue regeneration capacity of EVs isolated from the two most common clinical sources of adult MSCs, bone marrow and adipose tissue, with a particular focus on their angiogenic, osteogenic, and immunomodulatory potentials. Other important issues in the development of MSC-derived EV based therapies are also discussed.
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Affiliation(s)
- Yuan Liu
- Department of Chemical and Biomedical Engineering, Florida A&M University-Florida State University College of Engineering, Tallhassee, FL, United States
| | - Christina Holmes
- Department of Chemical and Biomedical Engineering, Florida A&M University-Florida State University College of Engineering, Tallhassee, FL, United States
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İbiloglu İ, Alabalik U, Keles AN, Aydogdu G, Basuguy E, Buyukbayram H. Ecballium elaterium extract reduces fibrosis during wound healing in rats. BIOTECHNOL BIOTEC EQ 2021. [DOI: 10.1080/13102818.2021.1920847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- İbrahim İbiloglu
- Department of Pathology, School of Medicine, Dicle University, Diyarbakir, Turkey
| | - Ulas Alabalik
- Department of Pathology, School of Medicine, Dicle University, Diyarbakir, Turkey
| | - Ayse Nur Keles
- Department of Pathology, School of Medicine, Dicle University, Diyarbakir, Turkey
| | - Gulay Aydogdu
- Department of Pathology, School of Medicine, Dicle University, Diyarbakir, Turkey
| | - Erol Basuguy
- Department of Pediatric Surgery, School of Medicine, Dicle University, Diyarbakir, Turkey
| | - Huseyin Buyukbayram
- Department of Pathology, School of Medicine, Dicle University, Diyarbakir, Turkey
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Suki B, Herrmann J, Bates JHT. An Analytic Model of Tissue Self-Healing and Its Network Implementation: Application to Fibrosis and Aging. Front Physiol 2020; 11:583024. [PMID: 33250776 PMCID: PMC7673435 DOI: 10.3389/fphys.2020.583024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 09/28/2020] [Indexed: 11/16/2022] Open
Abstract
Here we present a model capable of self-healing and explore its ability to resolve pathological alterations in biological tissue. We derive a simple analytic model consisting of an agent representing a cell that exhibits anabolic or catabolic activity, and which interacts with its tissue substrate according to tissue stiffness. When perturbed, this system returns toward a stable fixed point, a process corresponding to self-healing. We implemented this agent-substrate mechanism numerically on a hexagonal elastic network representing biological tissue. Agents, representing fibroblasts, were placed on the network and allowed to migrate around while they remodeled the network elements according to their activity which was determined by the stiffnesses of network elements that each agent encountered during its random walk. Initial injury to the network was simulated by increasing the stiffness of a single central network element above baseline. This system also exhibits a fixed point represented by the uniform baseline state. During the approach to the fixed point, interactions between the agents and the network create a transient spatially extended halo of stiffer network elements around the site of initial injury, which aids in overall injury repair. Non-equilibrium constraints generated by persistent injury prohibit the network to return to baseline and results in progressive stiffening, mimicking the development of fibrosis. Additionally, reducing anabolic or catabolic rates delay self-healing, reminiscent of aging. Our model thus embodies what may be the simplest set of attributes required of a spatiotemporal self-healing system, and so may help understand altered self-healing in chronic fibrotic diseases and aging.
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Affiliation(s)
- Béla Suki
- Department of Biomedical Engineering, Boston University, Boston, MA, United States
| | - Jacob Herrmann
- Department of Biomedical Engineering, Boston University, Boston, MA, United States
| | - Jason H T Bates
- Department of Medicine, The University of Vermont, Burlington, VT, United States
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Karakaya S, Süntar I, Yakinci OF, Sytar O, Ceribasi S, Dursunoglu B, Ozbek H, Guvenalp Z. In vivo bioactivity assessment on Epilobium species: A particular focus on Epilobium angustifolium and its components on enzymes connected with the healing process. JOURNAL OF ETHNOPHARMACOLOGY 2020; 262:113207. [PMID: 32730870 DOI: 10.1016/j.jep.2020.113207] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/15/2020] [Accepted: 07/19/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Epilobium species are generally known as "Yakı Otu" in Turkey, which mens "plaster herb" in English. Young shoots of Epilobium angustifolium L., Epilobium stevenii Boiss., and Epilobium hirsutum L. are consumed as salad or meal. These species have been used as a poultice for the treatment of mouth wounds in traditional medicine. An ointment prepared from leaves is used for skin disorders in children. AIM OF THE STUDY We aimed to evaluate the ethnopharmacological use of Epilobium angustifolium, E. stevenii, and E. hirsutum by using in vivo and in vitro experimental models, and to identify the active wound-healer compound(s) and to explain the probable mechanism of the wound-healing activity. MATERIALS AND METHODS Evaluation of wound healing effects of plant extracts was performed in rats and mice by linear incision and circular excision wound models. Determination of total phenolic constituents and antioxidant capacities, which are known to promote the wound healing process, were carried out through Folin-Ciocalteau method and 2,2 Diphenyl 1 picrylhydrazyl (DPPH) scavenging assay as well as determination of total antioxidant status (TAS) and total oxidant status (TOS) on the treated tissues. The active ethyl acetate (EtOAc) sub-extract of E. angustifolium was fractionated by different chromatographic separation techniques. The structures of isolated compounds were elucidated via detailed analyzes (NMR and LC/MS). In addition, in vitro collagenase, hyaluronidase, and elastase enzymes inhibitory activity tests were performed on the isolated compounds to discover the activation pathways of the samples. RESULTS Among the methanol (MeOH) extracts, E. angustifolium had the highest wound healing activity. Among the sub-extracts, EtOAc showed the highest wound healing activity. Thus, EtOAc sub-extract was subjected to chromatography to isolate the active compounds. Five known flavonoids namely hyperoside (quercetin-3-O-β-D-galactoside) (1), kaempferol (2), kaempferol-3-O-α-L-rhamno pyranoside (3), quercetin-3-O-α-L-rhamno pyranoside (4), and quercetin-3-O-α-L-arabino pyranoside (5) were isolated from the EtOAc sub-extract of E. angustifolium. In vitro tests showed that hyperoside could be the compound responsible for the wound-healing activity by its significant anti-hyaluronidase, anti-collagenase, and antioxidant activities. CONCLUSION The EtOAc sub-extract of the aerial part of Epilobium angustifolium displayed remarkable wound-healing activity with anti-hyaluronidase, anti-collagenase, and antioxidant activities. Hyperoside was detected as the primary active compound of the aerial parts. According to the results, we suggest that EtOAc sub-extract of E. angustifolium and hyperoside may be a potent nominee to be used for the improvement of a wound-healing agent.
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Affiliation(s)
- Songul Karakaya
- Department of Pharmacognosy, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
| | - Ipek Süntar
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
| | - Omer Faruk Yakinci
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey; National Poison Information Service, Ministry of Health, Ankara, Turkey
| | - Oksana Sytar
- Department of Plant Biology, Institute of Biology, Kiev National University of Taras Shevchenko, Kyiv, Ukraine; Department of Plant Physiology, Slovak University of Agriculture in Nitra, Slovakia
| | - Songul Ceribasi
- Department of Pathology, Faculty of Veterinary Medicine, Firat University, Elazıg, Turkey
| | - Benan Dursunoglu
- Department of Pharmacognosy, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
| | - Hilal Ozbek
- Department of Pharmacognosy, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
| | - Zuhal Guvenalp
- Department of Pharmacognosy, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
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Prasad YS, Miryala S, Lalitha K, Saritha B, Maheswari CU, Sridharan V, Srinandan CS, Nagarajan S. An injectable self-healing anesthetic glycolipid-based oleogel with antibiofilm and diabetic wound skin repair properties. Sci Rep 2020; 10:18017. [PMID: 33093507 PMCID: PMC7582191 DOI: 10.1038/s41598-020-73708-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 09/22/2020] [Indexed: 12/26/2022] Open
Abstract
Globally, wound infections are considered as one of the major healthcare problems owing to the delayed healing process in diabetic patients and microbial contamination. Thus, the development of advanced materials for wound skin repair is of great research interest. Even though several biomaterials were identified as wound healing agents, gel-based scaffolds derived from either polymer or small molecules have displayed promising wound closure mechanism. Herein, for the first time, we report an injectable and self-healing self-assembled anesthetic oleogel derived from glycolipid, which exhibits antibiofilm and wound closure performance in diabetic rat. Glycolipid derived by the reaction of hydrophobic vinyl ester with α-chloralose in the presence of novozyme 435 undergoes spontaneous self-assembly in paraffin oil furnished an oleogel displaying self-healing behavior. In addition, we have prepared composite gel by encapsulating curcumin in the 3D fibrous network of oleogel. More interestingly, glycolipid in its native form demoed potential in disassembling methicillin-resistant Staphylococcus aureus, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa biofilms. Both oleogel and composite gel enhanced the wound skin repair in diabetic induced Wistar rats by promoting collagen synthesis, controlling free radical generation and further regulating tissue remodeling phases. Altogether, the reported supramolecular self-assembled anesthetic glycolipid could be potentially used for diabetic skin wound repair and to treat bacterial biofilm related infections.
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Affiliation(s)
- Yadavali Siva Prasad
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India
| | - Sandeep Miryala
- Biofilm Biology Lab, Centre for Research in Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India
| | - Krishnamoorthy Lalitha
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India
| | - Balasubramani Saritha
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India
| | - C Uma Maheswari
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India
| | - Vellaisamy Sridharan
- Department of Chemistry and Chemical Sciences, Central University of Jammu, Rahya-Suchani (Bagla), District-Samba, Jammu, J&K, 181143, India
| | - C S Srinandan
- Biofilm Biology Lab, Centre for Research in Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.
| | - Subbiah Nagarajan
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.
- Department of Chemistry, National Institute of Technology Warangal, Warangal, Telangana, 506004, India.
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Deng Z, Fear MW, Suk Choi Y, Wood FM, Allahham A, Mutsaers SE, Prêle CM. The extracellular matrix and mechanotransduction in pulmonary fibrosis. Int J Biochem Cell Biol 2020; 126:105802. [PMID: 32668329 DOI: 10.1016/j.biocel.2020.105802] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/06/2020] [Accepted: 07/10/2020] [Indexed: 12/11/2022]
Abstract
Pulmonary fibrosis is characterised by excessive scarring in the lung which leads to compromised lung function, serious breathing problems and in some diseases, death. It includes several lung disorders with idiopathic pulmonary fibrosis (IPF) the most common and most severe. Pulmonary fibrosis is considered to be perpetuated by aberrant wound healing which leads to fibroblast accumulation, differentiation and activation, and deposition of excessive amounts of extracellular matrix (ECM) components, in particular, collagen. Recent studies have identified the importance of changes in the composition and structure of lung ECM during the development of pulmonary fibrosis and the interaction between ECM and lung cells. There is strong evidence that increased matrix stiffness induces changes in cell function including proliferation, migration, differentiation and activation. Understanding how changes in the ECM microenvironment influence cell behaviour during fibrogenesis, and the mechanisms regulating these changes, will provide insight for developing new treatments.
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Affiliation(s)
- Zhenjun Deng
- Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Nedlands, 6009, WA, Australia
| | - Mark W Fear
- Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Nedlands, 6009, WA, Australia; Institute for Respiratory Health, Nedlands, WA, Australia
| | - Yu Suk Choi
- School of Human Sciences, The University of Western Australia, Crawley, WA, Australia
| | - Fiona M Wood
- Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Nedlands, 6009, WA, Australia; Burns Service of Western Australia, Perth Children's Hospital, Nedlands, WA, Australia; Fiona Stanley Hospital, Murdoch, WA, Australia
| | - Amira Allahham
- Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Nedlands, 6009, WA, Australia
| | - Steven E Mutsaers
- Institute for Respiratory Health, Nedlands, WA, Australia; Centre for Respiratory Health, School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia
| | - Cecilia M Prêle
- Institute for Respiratory Health, Nedlands, WA, Australia; Centre for Respiratory Health, School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia.
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Forcina L, Cosentino M, Musarò A. Mechanisms Regulating Muscle Regeneration: Insights into the Interrelated and Time-Dependent Phases of Tissue Healing. Cells 2020; 9:E1297. [PMID: 32456017 PMCID: PMC7290814 DOI: 10.3390/cells9051297] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 05/18/2020] [Accepted: 05/20/2020] [Indexed: 12/12/2022] Open
Abstract
Despite a massive body of knowledge which has been produced related to the mechanisms guiding muscle regeneration, great interest still moves the scientific community toward the study of different aspects of skeletal muscle homeostasis, plasticity, and regeneration. Indeed, the lack of effective therapies for several physiopathologic conditions suggests that a comprehensive knowledge of the different aspects of cellular behavior and molecular pathways, regulating each regenerative stage, has to be still devised. Hence, it is important to perform even more focused studies, taking the advantage of robust markers, reliable techniques, and reproducible protocols. Here, we provide an overview about the general aspects of muscle regeneration and discuss the different approaches to study the interrelated and time-dependent phases of muscle healing.
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Affiliation(s)
| | | | - Antonio Musarò
- Laboratory affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via Antonio Scarpa, 14, 00161 Rome, Italy; (L.F.); (M.C.)
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Op 't Veld RC, Walboomers XF, Jansen JA, Wagener FADTG. Design Considerations for Hydrogel Wound Dressings: Strategic and Molecular Advances. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:230-248. [PMID: 31928151 DOI: 10.1089/ten.teb.2019.0281] [Citation(s) in RCA: 154] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Wound dressings are traditionally used to protect a wound and to facilitate healing. Currently, their function is expanding. There is an urgent need for new smart products that not only act as a protective barrier but also actively support the wound healing process. Hydrogel dressings are an example of such innovative products and typically facilitate wound healing by providing a hospitable and moist environment in which cells can thrive, while the wound can still breathe and exudate can be drained. These dressings also tend to be less painful or have a soothing effect and allow for additional drug delivery. In this review, various strategic and molecular design considerations are discussed that are relevant for developing a hydrogel into a wound dressing product. These considerations vary from material choice to ease of use and determine the dressing's final properties, application potential, and benefits for the patient. The focus of this review lies on identifying and explaining key aspects of hydrogel wound dressings and their relevance in the different phases of wound repair. Molecular targets of wound healing are discussed that are relevant when tailoring hydrogels toward specific wound healing scenarios. In addition, the potential of hydrogels is reviewed as medicine advances from a repair-based wound healing approach toward a regenerative-based one. Hydrogels can play a key role in the transition toward personal wound care and facilitating regenerative medicine strategies by acting as a scaffold for (stem) cells and carrier/source of bioactive molecules and/or drugs. Impact statement Improved wound healing will lead to a better quality of life around the globe. It can be expected that this coincides with a reduction in health care spending, as the duration of treatment decreases. To achieve this, new and modern wound care products are desired that both facilitate healing and improve comfort and outcome for the patient. It is proposed that hydrogel wound dressings can play a pivotal role in improving wound care, and to that end, this review aims to summarize the various design considerations that can be made to optimize hydrogels for the purpose of a wound dressing.
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Affiliation(s)
- Roel C Op 't Veld
- Department of Dentistry-Biomaterials, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.,Department of Dentistry-Orthodontics and Craniofacial Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands
| | - X Frank Walboomers
- Department of Dentistry-Biomaterials, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands
| | - John A Jansen
- Department of Dentistry-Biomaterials, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands
| | - Frank A D T G Wagener
- Department of Dentistry-Orthodontics and Craniofacial Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands
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Wu SY, Chen YT, Tsai GY, Hsu FY, Hwang PA. Protective Effect of Low-Molecular-Weight Fucoidan on Radiation-Induced Fibrosis Through TGF-β1/Smad Pathway-Mediated Inhibition of Collagen I Accumulation. Mar Drugs 2020; 18:E136. [PMID: 32120789 PMCID: PMC7142431 DOI: 10.3390/md18030136] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 02/20/2020] [Accepted: 02/25/2020] [Indexed: 12/22/2022] Open
Abstract
Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we quantified cellular metabolic activity, fibrosis-related mRNA expression, transforming growth factor beta-1 (TGF-β1), and collagen-1 protein expression, and fibroblast contractility in response to LMF. LMF pre + post-treatment could more effectively increase cellular metabolic activity compared with LMF post-treatment. LMF pre + post-treatment inhibited TGF-β1 expression, which mediates negative activation of phosphorylated Smad3 (pSmad3) and Smad4 complex formation and suppresses downstream collagen I accumulation. In addition, LMF pre + post-treatment significantly reduced actin-stress fibers in irradiated NIH3T3 cells. LMF, a natural substance obtained from brown seaweed, may be a candidate agent for preventing or inhibiting RIF.
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Affiliation(s)
- Szu-Yuan Wu
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan;
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
- Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung 413, Taiwan
| | - Yu-Ting Chen
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; (Y.-T.C.); (G.-Y.T.); (F.-Y.H.)
| | - Guo-Yu Tsai
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; (Y.-T.C.); (G.-Y.T.); (F.-Y.H.)
| | - Fu-Yin Hsu
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; (Y.-T.C.); (G.-Y.T.); (F.-Y.H.)
| | - Pai-An Hwang
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; (Y.-T.C.); (G.-Y.T.); (F.-Y.H.)
- Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan
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45
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Margetts PJ, Bonniaud P. Basic Mechanisms and Clinical Implications of Peritoneal Fibrosis. Perit Dial Int 2020. [DOI: 10.1177/089686080302300604] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Peter J. Margetts
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Philippe Bonniaud
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
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46
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Adler M, Mayo A, Zhou X, Franklin RA, Meizlish ML, Medzhitov R, Kallenberger SM, Alon U. Principles of Cell Circuits for Tissue Repair and Fibrosis. iScience 2020; 23:100841. [PMID: 32058955 PMCID: PMC7005469 DOI: 10.1016/j.isci.2020.100841] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 12/31/2019] [Accepted: 01/10/2020] [Indexed: 12/27/2022] Open
Abstract
Tissue repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, a pathological state of excessive scarring. To pinpoint the dynamic mechanisms underlying fibrosis, it is important to understand the principles of the cell circuits that carry out tissue repair. In this study, we establish a cell-circuit framework for the myofibroblast-macrophage circuit in wound healing, including the accumulation of scar-forming extracellular matrix. We find that fibrosis results from multistability between three outcomes, which we term "hot fibrosis" characterized by many macrophages, "cold fibrosis" lacking macrophages, and normal wound healing. This framework clarifies several unexplained phenomena including the paradoxical effect of macrophage depletion, the limited time-window in which removing inflammation leads to healing, and why scar maturation takes months. We define key parameters that control the transition from healing to fibrosis, which may serve as potential targets for therapeutic reduction of fibrosis.
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Affiliation(s)
- Miri Adler
- Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA
| | - Avi Mayo
- Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Xu Zhou
- Howard Hughes Medical Institute Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Ruth A Franklin
- Howard Hughes Medical Institute Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Matthew L Meizlish
- Howard Hughes Medical Institute Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Ruslan Medzhitov
- Howard Hughes Medical Institute Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Stefan M Kallenberger
- Digital Health Center, Berlin Institute of Health (BIH) and Charité, Berlin 10178, Germany; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
| | - Uri Alon
- Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
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Jiang N, Zhang Q, Chau MK, Yip MS, Lui SL, Liu S, Chu KM, Ngan HY, Chan TM, Yung S. Anti-fibrotic effect of decorin in peritoneal dialysis and PD-associated peritonitis. EBioMedicine 2020; 52:102661. [PMID: 32062358 PMCID: PMC7016379 DOI: 10.1016/j.ebiom.2020.102661] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 01/11/2020] [Accepted: 01/22/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Progressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We investigated the anti-fibrotic properties of decorin secreted by peritoneal mesothelial cells. METHODS Dialysate decorin level in stable PD patients and those with peritonitis was measured. In vitro experiments were conducted to investigate the effect of decorin in fibrotic response in human peritoneal mesothelial cells (HPMC). FINDINGS Increasing PD duration was associated with a progressive decrease of dialysate decorin and CA125 levels. Dialysate decorin level correlated with CA125 level. Peritonitis episodes were associated with a massive drop of dialysate decorin, which persisted for over three months despite clinical recovery. Dialysate decorin level correlated with that of TGF-β1, but was inversely related to IL-1β and IL-8. TGF-β1, IL-1β, IL-6, IL-8, or TNF-α reduced decorin secretion in HPMC, but induced fibronectin expression. The effects were mediated in part through increased p38 MAPK and AKT/PI3K phosphorylation. Decorin abrogated the induction of fibronectin expression in mesothelial cells by PD fluids or pro-fibrotic cytokines, through decreased TGF-βRI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3β phosphorylation. Decorin gene-silencing resulted in increased fibronectin expression under these conditions. INTERPRETATION Our data demonstrate anti-fibrotic actions of decorin in HPMC, when these cells are subjected to the pro-fibrotic effect of peritoneal dialysate and pro-fibrotic cytokines in PD, especially during peritonitis.
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Affiliation(s)
- Na Jiang
- Department of Medicine, The University of Hong Kong, Hong Kong; Department of Nephrology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Qing Zhang
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Mel Km Chau
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Ming S Yip
- Department of Medicine, The University of Hong Kong, Hong Kong
| | | | | | - Kent Man Chu
- Department of Surgery, The University of Hong Kong, Hong Kong
| | | | - Tak Mao Chan
- Department of Medicine, The University of Hong Kong, Hong Kong.
| | - Susan Yung
- Department of Medicine, The University of Hong Kong, Hong Kong.
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Čolić J, Matucci Cerinic M, Guiducci S, Damjanov N. Microparticles in systemic sclerosis, targets or tools to control fibrosis: This is the question! JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2020; 5:6-20. [PMID: 35382401 PMCID: PMC8922594 DOI: 10.1177/2397198319857356] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 05/20/2019] [Indexed: 07/25/2023]
Abstract
Systemic sclerosis is the main systemic fibrotic disease with unknown etiology characterized by peripheral microvascular injury, activation of immune system, and wide-spread progressive fibrosis. Microparticles can be derived from any cell type during normal cellular differentiation, senescence, and apoptosis, and also upon cellular activation. Carrying along a broad range of surface cytoplasmic and nuclear molecules of originating cells, microparticles are closely implicated in inflammation, thrombosis, angiogenesis, and immunopathogenesis. Recently, microparticles have been proposed as biomarkers of endothelial injury, which is the primary event in the genesis of tissue fibrosis. Microparticles may have a role in fostering endothelial to mesenchymal transition, thus giving a significant contribution to the development of myofibroblasts, the most important final effectors responsible for tissue fibrosis and fibroproliferative vasculopathy. Thanks to potent profibrotic mediators, such as transforming growth factor beta, platelet-derived growth factor, high mobility group box 1 protein, nicotinamide adenine dinucleotide phosphate oxidase 4, and antifibrotic agents, such as matrix metalloproteinases, microparticles may play an opposite role in fibrosis.
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Affiliation(s)
- Jelena Čolić
- Department of Rheumatology, Institute of
Rheumatology, Belgrade, Serbia
| | - Marco Matucci Cerinic
- Division of Rheumatology, Department of
Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi (AOUC)
and Denothe Centre, University of Florence, Florence, Italy
| | - Serena Guiducci
- Division of Rheumatology, Department of
Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi (AOUC)
and Denothe Centre, University of Florence, Florence, Italy
| | - Nemanja Damjanov
- Department of Rheumatology, Institute of
Rheumatology, Belgrade, Serbia
- School of Medicine, University of
Belgrade, Belgrade, Serbia
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49
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Moeini A, Pedram P, Makvandi P, Malinconico M, Gomez d'Ayala G. Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: A review. Carbohydr Polym 2020; 233:115839. [PMID: 32059889 DOI: 10.1016/j.carbpol.2020.115839] [Citation(s) in RCA: 388] [Impact Index Per Article: 77.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 01/06/2020] [Accepted: 01/06/2020] [Indexed: 02/06/2023]
Abstract
Wound healing can lead to complex clinical problems, hence finding an efficient approach to enhance the healing process is necessary. An ideal wound dressing should treat wounds at reasonable costs, with minimal inconveniences for the patient. Chitosan is one of the most investigated biopolymers for wound healing applications due to its biocompatibility, biodegradability, non-toxicity, and antimicrobial activity. Moreover, chitosan and its derivative have attracted numerous attentions because of the accelerating wound healing, and easy processability into different forms (gels, foams, membranes, and beads). All these properties make chitosan-based materials particularly versatile and promising for wound dressings. Besides, secondary natural metabolites could potentially act like the antimicrobial and anti-inflammatory agents and accelerate the healing process. This review collected almost all studies regarding natural compounds applications in wound healing by focusing on the chitosan-based bioactive wound dressing systems. An accurate analysis of different chitosan formulations and the influence of bioactive compounds on their wound healing properties are reported.
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Affiliation(s)
- Arash Moeini
- Department of Chemical Sciences, Universityof Naples "Federico II", Italy.
| | - Parisa Pedram
- Department of Chemical, Materialsand Industrial Production Engineering, University of Naples Federico II, Italy; Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia (IIT@CRIB), Italy
| | - Pooyan Makvandi
- Institute for Polymers, Composites and Biomaterials, National Research Council, Italy; Department of Medical Nanotechnology, Faculty of Advanced Technology in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mario Malinconico
- Institute for Polymers, Composites and Biomaterials, National Research Council, Italy
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50
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Silva T, Silva JC, Colaco B, Gama A, Duarte-Araújo M, Fernandes MH, Bettencourt A, Gomes P. In vivo tissue response and antibacterial efficacy of minocycline delivery system based on polymethylmethacrylate bone cement. J Biomater Appl 2019; 33:380-391. [PMID: 30223730 DOI: 10.1177/0885328218795290] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This study aims the in vivo biological characterization of an innovative minocycline delivery system, based on polymethylmethacrylate bone cement. Bone cements containing 1% or 2.5% (w/w) minocycline were formulated and evaluated through solid-state characterization. Biological evaluation was conducted in vivo, within a rat model, following the subcutaneous and bone tissue implantation, and tissue implantation associated with Staphylococcus aureus is challenging. The assessment of the tissue/biomaterial interaction was conducted by histologic, histomorphometric and microtomographic techniques. Minocycline addition to the composition of the polymethylmethacrylate bone cement did not modify significantly the cement properties. Drug release profile was marked by an initial burst release followed by a low-dosage sustained release. Following the subcutaneous tissue implantation, a reduced immune-inflammatory reaction was verified, with diminished cell recruitment and a thinner fibro-connective capsule formation. Minocycline-releasing cements were found to enhance the bone-to-implant contact and bone tissue formation, following the tibial implantation. Lastly, an effective antibacterial activity was mediated by the implanted cement following the tissue challenging with S. aureus. Kinetic minocycline release profile, attained with the developed polymethylmethacrylate system, modulated adequately the in vivo biological response, lessening the immune-inflammatory activation and enhancing bone tissue formation. Also, an effective in vivo antibacterial activity was established. These findings highlight the adequacy and putative application of the developed system for orthopedic applications.
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Affiliation(s)
- Tiago Silva
- 1 Faculty of Dental Medicine, University of Porto, Porto, Portugal
| | - Jose C Silva
- 1 Faculty of Dental Medicine, University of Porto, Porto, Portugal
| | - Bruno Colaco
- 2 University of Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Adelina Gama
- 2 University of Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | | | - Maria H Fernandes
- 1 Faculty of Dental Medicine, University of Porto, Porto, Portugal.,4 REQUIMTE/LAQV - University of Porto, Porto, Portugal
| | - Ana Bettencourt
- 5 Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Pedro Gomes
- 1 Faculty of Dental Medicine, University of Porto, Porto, Portugal.,4 REQUIMTE/LAQV - University of Porto, Porto, Portugal
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