scholarly journals Nitric Oxide Release from Antimicrobial Peptide Hydrogels for Wound Healing

Biomolecules ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 4 ◽  
Author(s):  
Joana Durão ◽  
Nuno Vale ◽  
Salomé Gomes ◽  
Paula Gomes ◽  
Cristina C. Barrias ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Antimicrobial Peptide ◽  
Chronic Wounds ◽  
Dermal Fibroblasts ◽  
Initial Increase ◽  
No Donor ◽  
Collagen Production ◽  
Nitric Oxide Release ◽  
Lysine Residues

Nitric oxide (NO) is an endogenously produced molecule that has been implicated in several wound healing mechanisms. Its topical delivery may improve healing in acute or chronic wounds. In this study an antimicrobial peptide was synthesized which self-assembled upon a pH shift, forming a hydrogel. The peptide was chemically functionalized to incorporate a NO-donor moiety on lysine residues. The extent of the reaction was measured by ninhydrin assay and the NO release rate was quantified via the Griess reaction method. The resulting compound was evaluated for its antimicrobial activity against Escherichia coli, and its effect on collagen production by fibroblasts was assessed. Time-kill curves point to an initial increase in bactericidal activity of the functionalized peptide, and collagen production by human dermal fibroblasts when incubated with the NO-functionalized peptide showed a dose-dependent increase in the presence of the NO donor within a range of 0–20 μM.

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 Redox for Repair: Cold Physical Plasmas and Nrf2 Signaling Promoting Wound Healing

Antioxidants ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 146 ◽  
Author(s):  
Anke Schmidt ◽  
Sander Bekeschus
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Chronic Wounds ◽  
Health Care Systems ◽  
Molecular Switches ◽  
Dermal Fibroblasts ◽  
Tissue Response ◽  
Related Factor ◽  
Plasma Effects ◽  
Care Systems

Chronic wounds and ulcers are major public health threats. Being a substantial burden for patients and health care systems alike, better understanding of wound pathophysiology and new avenues in the therapy of chronic wounds are urgently needed. Cold physical plasmas are particularly effective in promoting wound closure, irrespective of its etiology. These partially ionized gases deliver a therapeutic cocktail of reactive oxygen and nitrogen species safely at body temperature and without genotoxic side effects. This field of plasma medicine reanimates the idea of redox repair in physiological healing. This review compiles previous findings of plasma effects in wound healing. It discusses new links between plasma treatment of cells and tissues, and the perception and intracellular translation of plasma-derived reactive species via redox signaling pathways. Specifically, (i) molecular switches governing redox-mediated tissue response; (ii) the activation of the nuclear E2-related factor (Nrf2) signaling, together with antioxidative and immunomodulatory responses; and (iii) the stabilization of the scaffolding function and actin network in dermal fibroblasts are emphasized in the light of wound healing.

Role of Nitric Oxide in Wound Healing

2002 ◽  
Vol 4 (1) ◽  
pp. 5-15 ◽  
Author(s):  
Beverly B. Childress ◽  
Joyce K. Stechmiller
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Growth Factors ◽  
Animal Studies ◽  
Chronic Wounds ◽  
Current Knowledge ◽  
Wound Care ◽  
Impaired Wound Healing ◽  
Normal Wound Healing ◽  
Age Related

Chronic wounds mainly affect elderly individuals and persons with comorbid diseases due to a compromised immune status. An age-related decline in immune function deters proper healing of wounds in an orderly and timely manner. Thus, older adults with 1 or more concomitant illnesses are more likely to experience and suffer from a nonhealing wound, which may drastically decrease their quality of life and financial resources. Novel therapies in wound care management rely heavily on our current knowledge of wound healing physiology. It is well established that normal wound healing occurs sequentially and is strictly regulated by pro-inflammatory cytokines and growth factors. A multitude of commercial products such as growth factors are available; however, their effectiveness in healing chronic wounds has yet to be proven. Recently, investigators have implicated nitric oxide (NO) in the exertion of regulatory forces on various cellular activities of the inflammatory and proliferative phases of wound healing. Gene therapy in animal studies has shown promising results and is furthering our understanding of impaired wound healing. The purpose of this article is to review the literature on NO and its role in wound healing. A discussion of the physiology of normal healing and the pathophysiology of chronic wounds is provided.

Nitric oxide release from a cucurbituril encapsulated NO-donor

2018 ◽  
Vol 16 (23) ◽  
pp. 4272-4278 ◽  
Author(s):  
A. Acuña ◽  
N. Basílio ◽  
M. Parajó ◽  
J. C. Mejuto ◽  
J. Pérez-Juste ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chemical Stimulus ◽  
No Donor ◽  
Nitric Oxide Release

The denitrosation of a S-nitrosothiol derivative, nitrosomercaptopyridine (SNO+), can be inhibited by incorporation into the cucurbit[7]uril cavity. Owing to the reversible character of host : guest complexation, SNO+ can be expelled from the host cavity through the application of a chemical stimulus allowing controlled nitric oxide release.

scholarly journals Effect of nitric oxide release from NOR-3 on urea synthesis, viability and oxygen consumption of rat hepatocyte cultures

2007 ◽  
pp. 427-432
Author(s):  
R Chimenti ◽  
G Martino ◽  
S Mazzulla ◽  
S Sesti
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Cell Viability ◽  
Urea Synthesis ◽  
Rat Hepatocyte ◽  
Trypan Blue Exclusion ◽  
No Donor ◽  
Nitric Oxide Release ◽  
Hepatocyte Cultures ◽  
Trypan Blue Exclusion Test

As nitric oxide is considered a mediator of liver oxidative metabolism during sepsis, we studied the effects of exogenous nitric oxide, produced by NO-donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3), on cell viability, urea biosynthesis and oxygen consumption in rat hepatocyte cultures. Nitric oxide release from NOR-3 was studied using 4,5-diaminofluorescein diacetate. Urea levels were measured by the spectrophotometric method. Cell viability was determined by the MTT test and trypan blue exclusion test, whereas oxygen consumption was measured by a polarographic technique. After 2 h treatment, NOR-3 induced an increase in the levels of nitric oxide. After 2 h of treatment and 24 h after the end of the treatment with NOR-3, both cell viability and urea synthesis were significantly reduced in comparison to the controls for NOR-3 concentrations equal to or greater than 50 microM. A reduction in oxygen consumption was observed in hepatocytes after 40 min treatment with 100 microM NOR-3, even if the cell viability was unchanged. Reduction of oxygen consumption is an early indicator of the metabolic alterations in hepatocytes exposed to nitric oxide. These findings suggest that nitric oxide accumulation acts on hepatocyte cultures inducing cell death and reduction of urea synthesis after 2 hours.

scholarly journals Dermal fibroblasts cultured from donors with type 2 diabetes mellitus retain an epigenetic memory associated with poor wound healing responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aaiad H. A. Al-Rikabi ◽  
Desmond J. Tobin ◽  
Kirsten Riches-Suman ◽  
M. Julie Thornton
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Wound Healing ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Wounds ◽  
Dermal Fibroblasts ◽  
Necrosis Factor Alpha ◽  
Tnf Α

AbstractThe prevalence of Type 2 diabetes mellitus (T2DM) is escalating globally. Patients suffer from multiple complications including the development of chronic wounds that can lead to amputation. These wounds are characterised by an inflammatory environment including elevated tumour necrosis factor alpha (TNF-α). Dermal fibroblasts (DF) are critical for effective wound healing, so we sought to establish whether there were any differences in DF cultured from T2DM donors or those without diabetes (ND-DF). ND- and T2DM-DF when cultured similarly in vitro secreted comparable concentrations of TNF-α. Functionally, pre-treatment with TNF-α reduced the proliferation of ND-DF and transiently altered ND-DF morphology; however, T2DM-DF were resistant to these TNF-α induced changes. In contrast, TNF-α inhibited ND- and T2DM-DF migration and matrix metalloprotease expression to the same degree, although T2DM-DF expressed significantly higher levels of tissue inhibitor of metalloproteases (TIMP)-2. Finally, TNF-α significantly increased the secretion of pro-inflammatory cytokines (including CCL2, CXCL1 and SERPINE1) in ND-DF, whilst this effect in T2DM-DF was blunted, presumably due to the tendency to higher baseline pro-inflammatory cytokine expression observed in this cell type. Collectively, these data demonstrate that T2DM-DF exhibit a selective loss of responsiveness to TNF-α, particularly regarding proliferative and secretory functions. This highlights important phenotypic changes in T2DM-DF that may explain the susceptibility to chronic wounds in these patients.

Recent Advances in the Development of Nitric Oxide-Releasing Biomaterials and Their Application Potentials in Chronic Wound Healing

2021 ◽  
Author(s):  
Min Wu ◽  
Zhihui Lu ◽  
Keke Wu ◽  
Changwoo Nam ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Persistent Infection ◽  
Diabetic Foot ◽  
Chronic Wounds ◽  
Pressure Ulcers ◽  
Chronic Wound ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Nitric Oxide Releasing

Chronic wounds, such as pressure ulcers, vascular ulcers and diabetic foot ulcers (DFUs), often stays in a state of pathological inflammation and suffers from persistent infection, excess inflammation, and hypoxia,...

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