scholarly journals Immunologic Roles of Hyaluronan in Dermal Wound Healing

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1234
Author(s):  
Aditya Kaul ◽  
Walker D. Short ◽  
Sundeep G. Keswani ◽  
Xinyi Wang
Keyword(s):  
Molecular Weight ◽  
Wound Healing ◽  
Tissue Repair ◽  
Wound Repair ◽  
Low Molecular Weight ◽  
Immune Systems ◽  
Dermal Wound Healing ◽  
Adaptive Immune ◽  
Adaptive Immune Systems ◽  
Dermal Wound

Hyaluronic acid (HA), a glycosaminoglycan ubiquitous in the skin, has come into the limelight in recent years for its role in facilitating dermal wound healing. Specifically, HA’s length of linearly repeating disaccharides—in other words, its molecular weight (MW)—determines its effects. High molecular weight (HMW)-HA serves an immunosuppressive and anti-inflammatory role, whereas low molecular weight (LMW)-HA contributes to immunostimulation and thus inflammation. During the inflammatory stage of tissue repair, direct and indirect interactions between HA and the innate and adaptive immune systems are of particular interest for their long-lasting impact on wound repair. This review seeks to synthesize the literature on wound healing with a focus on HA’s involvement in the immune subsystems.

scholarly journals Hypoxia Preconditioned Serum (HPS)-Hydrogel Can Accelerate Dermal Wound Healing in Mice—An In Vivo Pilot Study

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 176
Author(s):  
Jun Jiang ◽  
Ursula Kraneburg ◽  
Ulf Dornseifer ◽  
Arndt F. Schilling ◽  
Ektoras Hadjipanayi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Lymphatic Vessels ◽  
Scar Tissue ◽  
Tissue Samples ◽  
Medicine Research ◽  
Dermal Wound Healing ◽  
Wound Model ◽  
Dermal Wound

The ability to use the body’s resources to promote wound repair is increasingly becoming an interesting area of regenerative medicine research. Here, we tested the effect of topical application of blood-derived hypoxia preconditioned serum (HPS) on wound healing in a murine wound model. Alginate hydrogels loaded with two different HPS concentrations (10 and 40%) were applied topically on full-thickness wounds created on the back of immunocompromised mice. We achieved a significant dose-dependent wound area reduction after 5 days in HPS-treated groups compared with no treatment (NT). On average, both HPS-10% and HPS-40% -treated wounds healed 1.4 days faster than NT. Healed tissue samples were investigated on post-operative day 15 (POD 15) by immunohistology and showed an increase in lymphatic vessels (LYVE-1) up to 45% with HPS-40% application, while at this stage, vascularization (CD31) was comparable in the HPS-treated and NT groups. Furthermore, the expression of proliferation marker Ki67 was greater on POD 15 in the NT-group compared to HPS-treated groups, in accordance with the earlier completion of wound healing observed in the latter. Collagen deposition was similar in all groups, indicating lack of scar tissue hypertrophy as a result of HPS-hydrogel treatment. These findings show that topical HPS application is safe and can accelerate dermal wound healing in mice.

scholarly journals Effect of Pulsed 810 nm Laser Photobiomodulation on Dermal Wound Healing and Oxidative Stress in Immunosuppressed Rats

2021 ◽  
Vol 6 (2) ◽  
pp. 122-127
Author(s):  
Gaurav K. Keshri ◽  
Saurabh Verma ◽  
Asheesh Gupta
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Illumination Time ◽  
Dermal Wound Healing ◽  
Pulsed Mode ◽  
Penetration Ability ◽  
And Oxidative Stress ◽  
Dermal Wound

Under immunosuppression, the sequential overlapping wound repair phases get hampered due to dysregulated or persistent inflammation leading to non-healing chronic wounds formation. The present study investigates the effect of low-power 810 nm diode laser (70 mW mean output power; 40 mW/cm2 average irradiance; 24 J/cm2 total fluence; 10 Hz pulse frequency; duty cycle 50 per cent; 10 min. illumination time once daily for seven days) photobiomodulation (PBM) on dermal penetration ability, wound healing and oxidative stress in hydrocortisone-induced immunosuppressed rats. The results of the penetration ability of 810 nm laser irradiation to the depth of the sub-dermal region revealed that the transmitted power of laser at 10 Hz pulsed-mode was better and easier than continuous-mode. The present findings clearly delineated that PBM with 810 nm laser at 10 Hz significantly augmented healing and reduced oxidative stress as evidenced by decreased free radicals, nitric oxide (NO) levels, enhanced superoxide dismutase (SOD) enzyme activity and wound area contraction facilitating the cellular redox homeostasis and promoting the tissue repair process. In conclusion, PBM with NIR 810 nm laser at pulsed-mode 10 Hz frequency showed better penetration and accelerated dermal wound healing in immunosuppressed rats.

scholarly journals Protective effect of FGF-2 and low-molecular-weight heparin/protamine nanoparticles on radiation-induced healing-impaired wound repair in rats

2017 ◽  
Vol 59 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Jun Kinoda ◽  
Masayuki Ishihara ◽  
Shingo Nakamura ◽  
Masanori Fujita ◽  
Koichi Fukuda ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Wound Healing ◽  
Low Molecular Weight Heparin ◽  
Wound Repair ◽  
Dermal Fibroblasts ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Low Molecular Weight ◽  
X Irradiation ◽  
Radiation Induced

Abstract We examined the effectiveness of localized administration of fibroblast growth factor-2 containing low-molecular-weight heparin/protamine nanoparticles (FGF-2&LMWH/P NPs) on apoptosis in vivo and on healing of radiation-induced skin injury in a rat model. FGF-2 binds onto LMWH/P NPs, which can significantly enhance and stabilize FGF-2 as a local carrier. X-irradiation at a dose of 25 Gy was administered to the lower part of the back (using a lead sheet with two holes) 1 h before the administration of FGF-2&LMWH/P NPs. Cutaneous full-thickness defect wounds were then formed in X-irradiated areas to examine the time-course of wound healing, and the wound tissues were microscopically and histologically compared and examined. Wound healing was significantly delayed by X-irradiation, but FGF-2&LMWH/P NPs administration prior to irradiation led to a significantly shorter delay compared with FGF-2 alone, LMWH/P NPs alone, and controls. Furthermore, terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) staining showed that the proportions of apoptotic dermal fibroblasts in X-irradiated skin were significantly lower in rats administered FGF-2&LMWH/P NPs than in controls. However, 8-hydroxy-2’-deoxyguanosine (8-OHdG) staining showed no differences. Thus, localized administration of FGF-2&LMWH/P NPs prior to irradiation may alleviate X-irradiation-induced healing-impaired wound repair in normal tissue.

scholarly journals IL-10 Promotes Endothelial Progenitor Cell Driven Wound Neovascularization and Enhances Healing via STAT3

2019 ◽  
Author(s):  
Swathi Balaji ◽  
Emily Steen ◽  
Xinyi Wang ◽  
Hima V. Vangapandu ◽  
Natalie Templeman ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Network Formation ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Dermal Wound Healing ◽  
Anti Inflammatory ◽  
The Impact ◽  
Dermal Wound

AbstractEvidence from prior studies of cutaneous trauma, burns, and chronic diabetic wound repair demonstrates that endothelial progenitor cells (EPCs) contribute tode novoangiogenesis, anti-inflammatory reactions, tissue regeneration, and remodeling. We have shown that IL-10, a potent anti-inflammatory cytokine, promotes regenerative tissue repair in an adult model of dermal scar formation via the regulation of fibroblast-specific hyaluronan synthesis in a STAT3 dependent manner. While it is known that IL-10 drives EPC recruitment and neovascularization after myocardial infarction, its specific mode of action, particularly in dermal wound healing and neovascularization in both control and diabetic wounds remains to be defined. Here we show that IL-10 promotes EPC recruitment into the dermal wound microenvironment to facilitate neovascularization and wound healing of control and diabetic (db/db) wounds via vascular endothelial growth factor (VEGF) and stromal-cell derived factor 1 (SDF-1α) signaling. Inducible skin-specific STAT3 knockout (KO) mice were studied to determine whether the impact of IL-10 on the neovascularization and wound healing is STAT3 dependent. We found that IL-10 treatment significantly promotes dermal wound healing with enhanced wound closure, robust granulation tissue formation and neovascularization. This was associated with elevated wound EPC counts as well as increased VEGF and high SDF-1α levels in control mice, an effect that was abrogated in STAT3 KO transgenic mice. These findings were supportedin vitro, wherein IL-10-enhanced VEGF and SDF-1α synthesis in primary murine dermal fibroblasts. IL-10-conditioned fibroblast media was shown to promote sprouting and network formation in aortic ring assays. We conclude that overexpression of IL-10 in the wound-specific milieu recruits EPCs and promote neovascularization, which occurs in a STAT3-dependent manner via regulation of VEGF and SDF-1α levels. Collectively, our studies demonstrate that IL-10 increases EPC recruitment leading to enhanced neovascularization and healing of dermal wounds.

scholarly journals An Evolutionary Link between Natural Transformation and CRISPR Adaptive Immunity

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Peter Jorth ◽  
Marvin Whiteley
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Bacterial Diversity ◽  
Natural Transformation ◽  
Bacterial Species ◽  
Comparative Genomic ◽  
Content Type ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

ABSTRACTNatural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history ofAggregatibacter actinomycetemcomitans, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway.IMPORTANCEThe human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogenAggregatibacter actinomycetemcomitans, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competentA. actinomycetemcomitansstrains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.

scholarly journals Emerging evidence of an effect of salt on innate and adaptive immunity

2018 ◽  
Vol 34 (12) ◽  
pp. 2007-2014 ◽  
Author(s):  
Rhys D R Evans ◽  
Marilina Antonelou ◽  
Scott Henderson ◽  
Stephen B Walsh ◽  
Alan D Salama
Keyword(s):  
Laboratory Animal ◽  
Salt Intake ◽  
Natural Diet ◽  
Innate And Adaptive Immunity ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Multiple Components ◽  
Excess Salt Intake ◽  
Adaptive Immune Systems ◽  
Recent Laboratory

AbstractSalt intake as part of a western diet currently exceeds recommended limits, and the small amount found in the natural diet enjoyed by our Paleolithic ancestors. Excess salt is associated with the development of hypertension and cardiovascular disease, but other adverse effects of excess salt intake are beginning to be recognized, including the development of autoimmune and inflammatory disease. Over the last decade there has been an increasing body of evidence demonstrating that salt affects multiple components of both the innate and adaptive immune systems. In this review we outline the recent laboratory, animal and human data, highlighting the effect of salt on immunity, with a particular focus on the relevance to inflammatory kidney disease.

scholarly journals Ex vivoexpanded haematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms

2009 ◽  
Vol 18 (5) ◽  
pp. 445-453 ◽  
Author(s):  
Christian Templin ◽  
Karsten Grote ◽  
Kai Schledzewski ◽  
Jelena-Rima Ghadri ◽  
Sabine Schnabel ◽  
...  
Keyword(s):  
Wound Healing ◽  
Progenitor Cells ◽  
Dermal Wound Healing ◽  
Dermal Wound

scholarly journals Augmentation of Dermal Wound Healing by Adipose Tissue-Derived Stromal Cells (ASC)

2018 ◽  
Vol 5 (4) ◽  
pp. 91 ◽  
Author(s):  
Joris van Dongen ◽  
Martin Harmsen ◽  
Berend van der Lei ◽  
Hieronymus Stevens
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Adipose Tissue ◽  
Stromal Cells ◽  
Randomized Clinical Trials ◽  
Cell Types ◽  
Matrix Remodeling ◽  
Skin Wound Healing ◽  
Dermal Wound Healing ◽  
Dermal Wound

The skin is the largest organ of the human body and is the first line of defense against physical and biological damage. Thus, the skin is equipped to self-repair and regenerates after trauma. Skin regeneration after damage comprises a tightly spatial-temporally regulated process of wound healing that involves virtually all cell types in the skin. Wound healing features five partially overlapping stages: homeostasis, inflammation, proliferation, re-epithelization, and finally resolution or fibrosis. Dysreguled wound healing may resolve in dermal scarring. Adipose tissue is long known for its suppressive influence on dermal scarring. Cultured adipose tissue-derived stromal cells (ASCs) secrete a plethora of regenerative growth factors and immune mediators that influence processes during wound healing e.g., angiogenesis, modulation of inflammation and extracellular matrix remodeling. In clinical practice, ASCs are usually administered as part of fractionated adipose tissue i.e., as part of enzymatically isolated SVF (cellular SVF), mechanically isolated SVF (tissue SVF), or as lipograft. Enzymatic isolation of SVF obtained adipose tissue results in suspension of adipocyte-free cells (cSVF) that lack intact intercellular adhesions or connections to extracellular matrix (ECM). Mechanical isolation of SVF from adipose tissue destructs the parenchyma (adipocytes), which results in a tissue SVF (tSVF) with intact connections between cells, as well as matrix. To date, due to a lack of well-designed prospective randomized clinical trials, neither cSVF, tSVF, whole adipose tissue, or cultured ASCs can be indicated as the preferred preparation procedure prior to therapeutic administration. In this review, we present and discuss current literature regarding the different administration options to apply ASCs (i.e., cultured ASCs, cSVF, tSVF, and lipografting) to augment dermal wound healing, as well as the available indications for clinical efficacy.

scholarly journals CRISPR-Cas immunity repressed by a biofilm-activating pathway inPseudomonas aeruginosa

2019 ◽  
Author(s):  
Adair L. Borges ◽  
Bardo Castro ◽  
Sutharsan Govindarajan ◽  
Tina Solvik ◽  
Veronica Escalante ◽  
...  
Keyword(s):  
Genetic Screen ◽  
Type I ◽  
Two Component System ◽  
Component System ◽  
Forward Genetic Screen ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Biofilm Production ◽  
Two Component ◽  
Adaptive Immune Systems

CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases. While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB/AlgB), previously characterized in regulatingPseudomonas aeruginosavirulence and biofilm establishment, as a regulator of the biogenesis and activity of the Type I-F CRISPR-Cas system. Downstream of the KinB/AlgB system, activators of biofilm production AlgU (a σEorthologue) and AlgR, act as repressors of CRISPR-Cas activity during planktonic and surface-associated growth. AmrZ, another biofilm activator, functions as a surface-specific repressor of CRISPR-Cas immunity.Pseudomonasphages and plasmids have taken advantage of this regulatory scheme, and carry hijacked homologs of AmrZ, which are functional CRISPR-Cas repressors. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.

scholarly journals Epidemiological and evolutionary consequences of CRISPR-Cas reactivity

2021 ◽  
Author(s):  
Hélène Chabas ◽  
Viktor Müller ◽  
Sebastian Bonhoeffer ◽  
Roland R. Regoes
Keyword(s):  
Critical Threshold ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Phage Evolution ◽  
Evolutionary Consequences ◽  
Adaptive Immune Systems ◽  
Control Challenge

AbstractAdaptive immune systems face a control challenge: they should react with enough strength to clear an infection while avoiding to harm their organism. CRISPR-Cas systems are adaptive immune systems of prokaryotes that defend against fast evolving viruses. Here, we explore the CRISPR-Cas control challenge and look how its reactivity, i.e. its probability to acquire a new resistance, impacts the epidemiological outcome of a phage outbreak and the prokaryote’s fitness. We show that in the absence of phage evolution, phage extinction is driven by the probability to acquire at least one resistance. However, when phage evolution is fast, phage extinction is driven by an epidemiological critical threshold: any reactivity below this critical threshold leads to phage survival whereas any reactivity above it leads to phage extinction. We also show that in the absence of autoimmunity, high levels of reactivity evolve. However, when CRISPR-Cas systems are prone to autoimmune reactions, intermediate levels of reactivity are evolutionarily optimal. These results help explaining why natural CRISPR-Cas systems do not show high levels of reactivity.

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