scholarly journals Insulin Promotes Wound Healing by Inactivating NFkβP50/P65 and Activating Protein and Lipid Biosynthesis and alternating Pro/Anti-inflammatory Cytokines Dynamics

2019 ◽  
Vol 10 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Pawandeep Kaur ◽  
Diptiman Choudhury
Keyword(s):  
Wound Healing ◽  
Inflammatory Cytokines ◽  
Chronic Wounds ◽  
Lipid Biosynthesis ◽  
Wound Recovery ◽  
Anti Inflammatory ◽  
Free Body ◽  
Treatment Of Wounds ◽  
Potential Use ◽  
Wound Tissue

AbstractFour hundred and twenty-two million people have diabetes due to excess free body glucose in their body fluids. Diabetes leads to various problems including retinopathy, neuropathy, arthritis, damage blood vessels etc; it also causes a delay in wound healing. Insufficiency of insulin is the main reason for diabetes-I and systemic insulin treatment is a remedy. The perspective of the potential use of insulin/insulin based drugs to treat chronic wounds in diabetic conditions is focused on in this review. At the site of the wound, TNF-ɑ, IFN-ϒ, IL-1β and IL-6 pro-inflammatory cytokines cause the generation of free radicals, leading to inflammation which becomes persistent in diabetes. Insulin induces expression of IL-4/IL-13, IL-10 anti-inflammatory cytokines etc which further down-regulates NFkβP50/P65 assembly. Insulin shifts the equilibrium towards NFkβP50/P50 which leads to down-regulation of inflammatory cytokines such as IL-6, IL-10 etc through STAT6, STAT3 and c-Maf activation causing nullification of an inflammatory condition. Insulin also promotes protein and lipid biosynthesis which indeed promotes wound recovery. Here, in this article, the contributions of insulin in controlling wound tissue microenvironments and remodulation of tissue have been summarised, which may be helpful to develop novel insulin-based formulation(s) for effective treatment of wounds in diabetic conditions.

scholarly journals Inflammatory M1-like macrophages polarized by NK-4 undergo enhanced phenotypic switching to an anti-inflammatory M2-like phenotype upon co-culture with apoptotic cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
Apoptotic Cells ◽  
Phenotypic Switch ◽  
Inflammatory Phase ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background NK-4 has been used to promote wound healing since the early-1950s; however, the mechanism of action of NK-4 is unknown. In this study, we examined whether NK-4 exerts a regulatory effect on macrophages, which play multiple roles during wound healing from the initial inflammatory phase until the tissue regeneration phase. Results NK-4 treatment of THP-1 macrophages induced morphological features characteristic of classically-activated M1 macrophages, an inflammatory cytokine profile, and increased expression of the M1 macrophage-associated molecules CD38 and CD86. Interestingly, NK-4 augmented TNF-α production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis of latex beads. These results indicate that NK-4 drives macrophage polarization toward an inflammatory M1-like phenotype with increased phagocytic activity. Efferocytosis is a crucial event for resolution of the inflammatory phase in wound healing. NK-4-treated THP-1 macrophages co-cultured with apoptotic Jurkat E6.1 (Apo-J) cells switched from an M1-like phenotype to an M2-like phenotype, as seen in the inverted ratio of TNF-α to IL-10 produced in response to LPS. We identified two separate mechanisms that are involved in this phenotypic switch. First, recognition of phosphatidylserine molecules on Apo-J cells by THP-1 macrophages downregulates TNF-α production. Second, phagocytosis of Apo-J cells by THP-1 macrophages and activation of PI3K/Akt signaling pathway upregulates IL-10 production. Conclusion It is postulated that the phenotypic switch from a proinflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype is dysregulated due to impaired efferocytosis of apoptotic neutrophils at the wound site. Our results demonstrate that NK-4 improves phagocytosis of apoptotic cells, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

scholarly journals Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 961
Author(s):  
Sibusiso Alven ◽  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Mechanical Performance ◽  
Healing Process ◽  
Aloe Vera ◽  
Antimicrobial Properties ◽  
Biological Properties ◽  
Wound Management ◽  
Wound Healing Process ◽  
Treatment Of Wounds

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.

scholarly journals Squalene Stimulates a Key Innate Immune Cell to Foster Wound Healing and Tissue Repair

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Cristina Sánchez-Quesada ◽  
Alicia López-Biedma ◽  
Estefania Toledo ◽  
José J. Gaforio
Keyword(s):  
Wound Healing ◽  
Inflammatory Cytokines ◽  
Tissue Repair ◽  
Immune Cell ◽  
Critical Role ◽  
Virgin Olive Oil ◽  
Skin Damage ◽  
Macrophage Response ◽  
Anti Inflammatory ◽  
Minor Compounds

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-α and NF-κB in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.

TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP

2001 ◽  
Vol 114 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Y.P. Han ◽  
T.L. Tuan ◽  
H. Wu ◽  
M. Hughes ◽  
W.L. Garner
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Human Skin ◽  
Inflammatory Cytokines ◽  
Intracellular Signaling ◽  
Chronic Wounds ◽  
Dermal Fibroblasts ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Pro Inflammatory Cytokines

Tumor necrosis factor-alpha (TNF-(alpha)) is an important mediator during the inflammatory phase of wound healing. Excessive amounts of pro-inflammatory cytokines such as TNF-(alpha) are associated with inflammatory diseases including chronic wounds. Matrix metalloproteinases (MMPs) are involved in matrix re-modeling during wound healing, angiogenesis and tumor metastasis. As with pro-inflammatory cytokines, high levels of MMPs have been found in inflammatory states such as chronic wounds. In this report we relate these two phenomena. TNF-(alpha) stimulates secretion of active MMP-2, a type IV collagenase, in organ-cultured full-thickness human skin. This suggests a mechanism whereby excess inflammation affects normal wound healing. To investigate this observation at the cellular and molecular levels, we examined TNF-(alpha) mediated activation of pro-MMP-2, induction of MT1-MMP, and the intracellular signaling pathways that regulate the proteinase in isolated human dermal fibroblasts. We found that TNF-(alpha) substantially promoted activation of pro-MMP-2 in dermal fibroblasts embedded in type-I collagen. In marked contrast, collagen or TNF-(alpha) individually had little influence on the fibroblast-mediated pro-MMP-2 activation. One well-characterized mechanism for pro-MMP-2 activation is through a membrane type matrix metalloproteinase, such as MT1-MMP. We report that TNF-(alpha) significantly induced MT1-MMP at the mRNA and protein levels when the dermal fibroblasts were grown in collagen. Although the intracellular signaling pathway regulating mt1-mmp gene expression is still obscure, both TNF-(alpha) and collagen activate the NF-(kappa)B pathway. In this report we provide three sets of evidence to support a hypothesis that activation of NF-(kappa)B is essential to induce MT1-MMP expression in fibroblasts after TNF-(alpha) exposure. First, SN50, a peptide inhibitor for NF-(kappa)B nuclear translocation, simultaneously blocked the TNF-(alpha) and collagen mediated MT1-MMP induction and pro-MMP-2 activation. Secondly, TNF-(alpha) induced I(kappa)B to breakdown in fibroblasts within the collagen lattice, a critical step leading to NF-(kappa)B activation. Lastly, a consensus binding site for p65 NF-(kappa)B (TGGAGCTTCC) was found in the 5′-flanking region of human mt1-mmp gene. Based on these results and previous reports, we propose a model to explain TNF-(alpha) activation of MMP-2 in human skin. Activation of NF(kappa)B signaling in fibroblasts embedded in collagen induces mt1-mmp gene expression, which subsequently activates the pro-MMP-2. The findings provide a specific mechanism whereby TNF-(alpha) may affect matrix remodeling during wound healing and other physiological and pathological processes.

scholarly journals Inflammatory M1-like macrophages polarized by NK-4 undergo enhanced phenotypic switching to an anti-inflammatory M2-like phenotype upon co-culture with apoptotic cells

2020 ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Poly I:C ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Inflammatory Phase ◽  
Macrophage Phagocytosis ◽  
M1 Macrophage ◽  
Anti Inflammatory

Abstract Background: NK-4 has been used to promote wound healing since the early-1950s; however, the mechanism of action of NK-4 is unknown. In this study, we examined whether NK-4 exerts a regulatory effect on macrophages, which play multiple roles during wound healing from the initial inflammatory phase until the tissue regeneration phase. Results: NK-4 treatment of THP-1 macrophages induced morphological features characteristic of classically-activated M1 macrophages, an inflammatory cytokine profile, and increased expression of the M1 macrophage-associated molecules CD38 and CD86. Interestingly, NK-4 augmented TNF-a production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis. These results indicate that NK-4 drives macrophage polarization toward an inflammatory M1-like phenotype with increased phagocytic activity. Efferocytosis is a crucial event for resolution of the inflammatory phase in wound healing. NK-4-treated THP-1 macrophages co-cultured with apoptotic Jurkat E6.1 (Apo-J) cells switched from an M1-like phenotype to an M2-like phenotype, as seen in the inverted ratio of TNF-a to IL-10 produced in response to LPS. We identified two separate mechanisms that are involved in this phenotypic switch. First, recognition of phosphatidylserine molecules on Apo-J cells by THP-1 macrophages downregulates TNF-a production. Second, phagocytosis of Apo-J cells by THP-1 macrophages and activation of PI3K/Akt signaling pathway upregulates IL-10 production. Conclusion: It is postulated that the phenotypic switch from a proinflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype is dysregulated due to impaired efferocytosis of apoptotic neutrophils at the wound site. Our results demonstrate that NK-4 improves efferocytosis, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

scholarly journals Wound Healing Activities and Potential of Selected African Medicinal Plants and Their Synthesized Biogenic Nanoparticles

Plants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2635
Author(s):  
Caroline Tyavambiza ◽  
Phumuzile Dube ◽  
Mediline Goboza ◽  
Samantha Meyer ◽  
Abram Madimabe Madiehe ◽  
...  
Keyword(s):  
Wound Healing ◽  
Medicinal Plants ◽  
Wound Repair ◽  
Chronic Wounds ◽  
In Vivo Models ◽  
Repair Mechanisms ◽  
Treatment Of Wounds ◽  
Biogenic Nanoparticles

In Africa, medicinal plants have been traditionally used as a source of medicine for centuries. To date, African medicinal plants continue to play a significant role in the treatment of wounds. Chronic wounds are associated with severe healthcare and socio-economic burdens despite the use of conventional therapies. Emergence of novel wound healing strategies using medicinal plants in conjunction with nanotechnology has the potential to develop efficacious wound healing therapeutics with enhanced wound repair mechanisms. This review identified African medicinal plants and biogenic nanoparticles used to promote wound healing through various mechanisms including improved wound contraction and epithelialization as well as antibacterial, antioxidant and anti-inflammatory activities. To achieve this, electronic databases such as PubMed, Scifinder® and Google Scholar were used to search for medicinal plants used by the African populace that were scientifically evaluated for their wound healing activities in both in vitro and in vivo models from 2004 to 2021. Additionally, data on the wound healing mechanisms of biogenic nanoparticles synthesized using African medicinal plants is included herein. The continued scientific evaluation of wound healing African medicinal plants and the development of novel nanomaterials using these plants is imperative in a bid to alleviate the detrimental effects of chronic wounds.

scholarly journals PREPARATION AND EVALUATION OF COPPER NANOPARTICLES LOADED HYDROGEL FOR BURNS

2021 ◽  
pp. 180-189
Author(s):  
ASHISH KUMAR ◽  
VINAY PANDIT ◽  
UPENDRA NAGAICH
Keyword(s):  
Wound Healing ◽  
Inflammatory Cytokines ◽  
Copper Nanoparticles ◽  
Wound Closure ◽  
Hydroxypropyl Methylcellulose ◽  
Influential Factors ◽  
Factor Screening ◽  
Closure Rate ◽  
Screening Study ◽  
Anti Inflammatory

Objective: The present study focuses on the development and optimization of copper nanoparticles (CNPs) loaded hydrogel for the treatment of dermal burn injuries. Methods: CNPs gel was prepared by dispersing the variable concentration of polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC) in distilled water, PEG 400, and copper nanoparticles. factor screening study was performed for identification of influential factors, followed by optimization study using three-factor Box-Behnken design. Results: Optimized nanogel formulation, when compared to normal control (NC), shows a significant reduction of pro-inflammatory cytokines (IL-6 = 39.74 % and TNF-α =49.37%) and increased level of anti-inflammatory cytokines (IL-10 = 30.90%), indicating reduced inflammation. Further, the wound closure rate of CNPs gel shows significant (12.27 %) wound closure as compared to the NC group and complete wound closure (100 %) on the 14th day, indicating accelerated wound healing. Conclusion: the present investigation endorses accelerated scar-free, accelerated wound healing potential of copper nanoparticles gel with anti-inflammatory potential.

scholarly journals In Vitro Evaluation of Antioxidant, Anti-Inflammatory, Antimicrobial and Wound Healing Potential of Thymus Sipyleus Boiss. Subsp. Rosulans (Borbas) Jalas

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3353 ◽  
Author(s):  
Oya Ustuner ◽  
Ceren Anlas ◽  
Tulay Bakirel ◽  
Fulya Ustun-Alkan ◽  
Belgi Diren Sigirci ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Folk Medicine ◽  
Traditional Use ◽  
Necrosis Factor Alpha ◽  
Treatment Protocols ◽  
Fibroblast Migration ◽  
Anti Inflammatory ◽  
Treatment Of Wounds

Thymus sipyleus Boiss. subsp. rosulans (Borbas) Jalas (TS) is a commonly used plant in the treatment of various complaints, including skin wounds in Turkish folk medicine. Despite the widespread traditional use of TS, there is not any scientific report confirming the effectiveness of this plant on the healing process. This research aimed to investigate the effects of different extracts obtained from TS on biological events during wound healing, on a cellular basis. In this context, proliferative activities of the extracts, as well as the effects on wound closure and hydroxyproline synthesis, were determined. In addition to wound healing properties, the antioxidant, antibacterial and anti-inflammatory activities of the extracts were evaluated. Decoction (D) and infusion (I) extracts contained the highest amount of phenolic content and showed the most potent activity against DPPH radical. All extracts exhibited complete protection against the damage induced by hydrogen peroxide (H2O2) by increasing cell viability compared to only H2O2-treated groups, both in co-treatment and pre-treatment protocols. None of the extracts exhibited cytotoxic activity, and most of the extracts from the TS stimulated fibroblast proliferation and migration. All TS extracts exert anti-inflammatory activity by suppressing the overproduction of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO). The most pronounced activity on hydroxyproline synthesis was observed in D extract. In summary, it was observed that TS extracts can promote the healing process by enhancing fibroblast migration, proliferation and collagen synthesis as well as suppressing pro-inflammatory cytokines. The obtained data in this work support the traditional use of TS as a valuable plant-based compound for the treatment of wounds.

Natural Inorganic Ingredients in Wound Healing

2020 ◽  
Vol 26 (6) ◽  
pp. 621-641 ◽  
Author(s):  
Fátima García-Villén ◽  
Iane M.S. Souza ◽  
Raquel de Melo Barbosa ◽  
Ana Borrego-Sánchez ◽  
Rita Sánchez-Espejo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clay Minerals ◽  
Chronic Wounds ◽  
Inorganic Materials ◽  
Wound Dressings ◽  
Mechanical Resistance ◽  
Efficient Treatment ◽  
Antimicrobial Effects ◽  
Chemical Release ◽  
Treatment Of Wounds

Background: One of the major clinical challenges is to achieve a rapid and efficient treatment of complex chronic wounds. Nowadays, most wound dressings currently available are unable to find a solution the challenges of resistance to bacterial infection, protein adsorption and increased levels of exudates. Natural inorganic ingredients (clay minerals, metal cations, zeolites, etc) could be the key to solve the problem satisfactorily. Some of these materials have shown biocompatibility and ability to enhance cell adhesion, proliferation and cellular differentiation and uptake. Besides, some natural inorganic ingredients effectively retain drugs, allowing the design of drug delivery matrices. Objective: possibilities of natural inorganic ingredients in wound healing treatments have been reviewed, the following sections have been included: 1. Introduction 2. Functions of Inorganic Ingredients in wound healing 2.1. Antimicrobial effects 2.2. Hemostatic effects 3. Clay minerals for wound healing 3.1. Clay minerals 3.2. Clay mineral semisolid formulations 3.3. Clay/polymer composites and nanocomposites 3.4. Clay minerals in wound dressings 4. Other inorganic materials for wound healing 4.1. Zeolites 4.2. Silica and other silicates 4.3. Other minerals 4.4. Transition metals 5. Conclusion Conclusion: inorganic ingredients possess useful features in the development of chronic wounds advanced treatments. They improve physical (mechanical resistance and water vapor transmission), chemical (release of drugs, hemostasis and/or adsorption of exudates and moisture) and biological (antimicrobial effects and improvement of healing) properties of wound dressings. In summary, inorganic ingredients have proved to be a promising and easily accessible products in the treatment of wounds and, more importantly, chronic wounds.

scholarly journals Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Monika Styrczewska ◽  
Anna Kostyn ◽  
Anna Kulma ◽  
Grazyna Majkowska-Skrobek ◽  
Daria Augustyniak ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Wound Closure ◽  
Chronic Wounds ◽  
Flax Fiber ◽  
Great Promise ◽  
Dependent Manner ◽  
Skin Cells ◽  
Anti Inflammatory

Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. Inin vitroproliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, butβ-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- andβ-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification.

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