Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.

Wound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employe...

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Main Authors: Eman Maher Zahran, Reham H Mohyeldin, Fatma Mohamed Abd El-Mordy, Sherif A Maher, Nehad M Reda Abdel-Maqsoud, Faisal H Altemani, Naseh A Algehainy, Mohammed A Alanazi, Mohammed M Jalal, Mahmoud A Elrehany, Gerhard Bringmann, Usama Ramadan Abdelmohsen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0300543&type=printable
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author Eman Maher Zahran
Reham H Mohyeldin
Fatma Mohamed Abd El-Mordy
Sherif A Maher
Nehad M Reda Abdel-Maqsoud
Faisal H Altemani
Naseh A Algehainy
Mohammed A Alanazi
Mohammed M Jalal
Mahmoud A Elrehany
Gerhard Bringmann
Usama Ramadan Abdelmohsen
author_facet Eman Maher Zahran
Reham H Mohyeldin
Fatma Mohamed Abd El-Mordy
Sherif A Maher
Nehad M Reda Abdel-Maqsoud
Faisal H Altemani
Naseh A Algehainy
Mohammed A Alanazi
Mohammed M Jalal
Mahmoud A Elrehany
Gerhard Bringmann
Usama Ramadan Abdelmohsen
author_sort Eman Maher Zahran
collection DOAJ
description Wound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employed in wound-repairing activities. This work investigates the mesenchymal stem cells in the combined capacity of the bone marrow (BMMSC) for wound healing and Cystoseira sp. Algae extract in immunosuppressed rats. High-resolution liquid chromatography / MS investigation of Cystoseira extract revealed the prevalence of fatty acids that have wound-soothing potential. From constructed PPI network for wound healing and further analysis through molecular docking and molecular dynamics (MD) simulation experiments suggested that cystalgerone metabolite may be responsible for the wound healing-promoting effect of Cystoseira extract. According to the CD marker characterization of the BMMSC, 98.21% of them expressed CD90, and 97.1% expressed CD105. Sixteen d after immunity suppression (by 40 mg/kg hydrocortisone daily), an incision was made in the dorsal skin of the rat. The treatments were applied for 16 d and samples were taken from the tested groups on the 8th, 14th, and 16th days. The BMMSCs / Cystoseira group showed significantly improved wound closure, thickness, density of new layers, and skin elasticity than the control group (p < 0.001). The BMMSCs / Cystoseira combination significantly reduced the oxidative indicators, pro-inflammatory cytokines, and immune markers, according to the RT-PCR gene expression study. In order to delve deeper into the complex interconnections among wound healing-related biological targets and pinpoint key factors in this complex process, we engaged in network pharmacology and computational research. Subsequently, we conducted a comprehensive computational analysis, including reverse docking, free energy (ΔG) computation, and molecular dynamics simulations, on the molecular structures of the annotated compounds. The purpose of this investigation was to identify potential new targets for these chemicals as well as any potential interactions they may have with different signaling pathways related to the wound healing process. Our research indicates that the primary compounds of Cystoseira holds potential wound healing therapeutic activity. Although more safety testing and clinical studies are required, the combination has great potential for regenerative medicine and could be a revolutionary advance in the healing of the wounds of immunosuppressed patients.
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spelling doaj.art-241a86b7d6894cfe988174336fac2a612024-04-11T05:32:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01194e030054310.1371/journal.pone.0300543Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.Eman Maher ZahranReham H MohyeldinFatma Mohamed Abd El-MordySherif A MaherNehad M Reda Abdel-MaqsoudFaisal H AltemaniNaseh A AlgehainyMohammed A AlanaziMohammed M JalalMahmoud A ElrehanyGerhard BringmannUsama Ramadan AbdelmohsenWound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employed in wound-repairing activities. This work investigates the mesenchymal stem cells in the combined capacity of the bone marrow (BMMSC) for wound healing and Cystoseira sp. Algae extract in immunosuppressed rats. High-resolution liquid chromatography / MS investigation of Cystoseira extract revealed the prevalence of fatty acids that have wound-soothing potential. From constructed PPI network for wound healing and further analysis through molecular docking and molecular dynamics (MD) simulation experiments suggested that cystalgerone metabolite may be responsible for the wound healing-promoting effect of Cystoseira extract. According to the CD marker characterization of the BMMSC, 98.21% of them expressed CD90, and 97.1% expressed CD105. Sixteen d after immunity suppression (by 40 mg/kg hydrocortisone daily), an incision was made in the dorsal skin of the rat. The treatments were applied for 16 d and samples were taken from the tested groups on the 8th, 14th, and 16th days. The BMMSCs / Cystoseira group showed significantly improved wound closure, thickness, density of new layers, and skin elasticity than the control group (p < 0.001). The BMMSCs / Cystoseira combination significantly reduced the oxidative indicators, pro-inflammatory cytokines, and immune markers, according to the RT-PCR gene expression study. In order to delve deeper into the complex interconnections among wound healing-related biological targets and pinpoint key factors in this complex process, we engaged in network pharmacology and computational research. Subsequently, we conducted a comprehensive computational analysis, including reverse docking, free energy (ΔG) computation, and molecular dynamics simulations, on the molecular structures of the annotated compounds. The purpose of this investigation was to identify potential new targets for these chemicals as well as any potential interactions they may have with different signaling pathways related to the wound healing process. Our research indicates that the primary compounds of Cystoseira holds potential wound healing therapeutic activity. Although more safety testing and clinical studies are required, the combination has great potential for regenerative medicine and could be a revolutionary advance in the healing of the wounds of immunosuppressed patients.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0300543&type=printable
spellingShingle Eman Maher Zahran
Reham H Mohyeldin
Fatma Mohamed Abd El-Mordy
Sherif A Maher
Nehad M Reda Abdel-Maqsoud
Faisal H Altemani
Naseh A Algehainy
Mohammed A Alanazi
Mohammed M Jalal
Mahmoud A Elrehany
Gerhard Bringmann
Usama Ramadan Abdelmohsen
Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.
PLoS ONE
title Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.
title_full Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.
title_fullStr Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.
title_full_unstemmed Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.
title_short Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.
title_sort wound healing potential of cystoseira mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno inflammatory crosstalk
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0300543&type=printable
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