scholarly journals Thrombin Cleaves Prolactin Into a Potent 5.6-kDa Vasoinhibin: Implication for Tissue Repair

Endocrinology ◽  
2021 ◽  
Vol 162 (12) ◽  
Author(s):  
Magdalena Zamora ◽  
Juan Pablo Robles ◽  
Manuel B Aguilar ◽  
Sergio de Jesús Romero-Gómez ◽  
Thomas Bertsch ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Tissue Repair ◽  
High Performance ◽  
Tissue Injury ◽  
Healing Process ◽  
Fibrin Clot ◽  
Wound Healing Process ◽  
Thrombin Cleavage ◽  
Recombinant Production ◽  
Intramolecular Disulfide Bond

Abstract Vasoinhibin is an endogenous prolactin (PRL) fragment with profibrinolytic, antivasopermeability, and antiangiogenic effects. The fact that blood clotting, vascular permeability, and angiogenesis are functionally linked during the wound-healing process led us to investigate whether thrombin, a major protease in tissue repair, generates vasoinhibin. Here, we have incubated human PRL with thrombin and analyzed the resulting proteolytic products by Western blot, mass spectrometry, high-performance liquid chromatography purification, recombinant production, and bioactivity. We unveil a main thrombin cleavage site at R48-G49 that rapidly (< 10 minutes) generates a 5.6-kDa fragment (residues 1-48) with full vasoinhibin activity, that is, it inhibited the proliferation, invasion, and permeability of cultured endothelial cells and promoted the lysis of a fibrin clot in plasma with a similar potency to that of a conventional 14-kDa vasoinhibin (residues 1-123). The R48-G49 cleavage site is highly conserved throughout evolution and precedes the intramolecular disulfide bond (C58-C174), thereby allowing the 5.6-kDa vasoinhibin to be released without a reduction step. Furthermore, the 5.6-kDa vasoinhibin is produced by endogenous thrombin during the clotting process. These findings uncover the smallest vasoinhibin known, add thrombin to the list of PRL-cleaving proteases generating vasoinhibin, and introduce vasoinhibin as a thrombin-activated mechanism for the regulation of hemostasis, vasopermeability, and angiogenesis in response to tissue injury.

scholarly journals Aqueous Extract of Brazilian Green Propolis: Primary Components, Evaluation of Inflammation and Wound Healing by Using Subcutaneous Implanted Sponges

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Sandra Aparecida Lima de Moura ◽  
Giuseppina Negri ◽  
Antônio Salatino ◽  
Luiza Dias da Cunha Lima ◽  
Luana Pereira Antunes Dourado ◽  
...  
Keyword(s):  
Wound Healing ◽  
Aqueous Extract ◽  
Mass Spectroscopy ◽  
High Performance ◽  
Healing Process ◽  
Treated Group ◽  
Progressive Increase ◽  
Health Condition ◽  
Wound Healing Process ◽  
Morphometric Analyses

Propolis is a chemically complex resinous bee product which has gained worldwide popularity as a means to improve health condition and prevent diseases. The main constituents of an aqueous extract of a sample of green propolis from Southeast Brazil were shown by high performance liquid chromatography/mass spectroscopy/mass spectroscopy to be mono- and di-O-caffeoylquinic acids; phenylpropanoids known as important constituents of alcohol extracts of green propolis, such as artepillin C and drupanin were also detected in low amounts in the aqueous extract. The anti-inflammatory activity of this extract was evaluated by determination of wound healing parameters. Female Swiss mice were implanted subcutaneously with polyesther-polyurethane sponge discs to induce wound healing responses, and administered orally with green propolis (500 mg kg−1). At 4, 7 and 14 days post-implantation, the fibrovascular stroma and deposition of extracellular matrix were evaluated by histopathologic and morphometric analyses. In the propolis-treated group at Days 4 and 7 the inflammatory process in the sponge was reduced in comparison with control. A progressive increase in cell influx and collagen deposition was observed in control and propolis-treated groups during the whole period. However, these effects were attenuated in the propolis-treated group at Days 4 and 7, indicating that key factors of the wound healing process are modulated by propolis constituents.

scholarly journals Effect of low-dose electron radiation on rat skin wound healing

2007 ◽  
Vol 18 (3) ◽  
pp. 208-214 ◽  
Author(s):  
Solange Maria de Almeida ◽  
Adriana Dibo da Cruz ◽  
Rívea Inês Ferreira ◽  
Mário Roberto Vizioli ◽  
Frab Norberto Bóscolo
Keyword(s):  
Wound Healing ◽  
Electron Irradiation ◽  
Tissue Repair ◽  
Low Dose ◽  
Healing Process ◽  
Male Rats ◽  
Wound Healing Process ◽  
Electron Radiation ◽  
Rat Skin ◽  
Beam Radiation

The aim of this study was to assess the effect of low-dose electron irradiation on morphological features of the wound healing process in rat skin. Surgical wounds were inflicted with a 2.3 x 1.4 cm template on 84 male rats that were assigned to 4 groups: IG1, immediately irradiated; IG2, irradiated 3 days after inflicting the wound; CG1 and CG2, control groups. Rats in IG1 and IG2 groups had their wounds exposed to 1 Gy of 6 MeV electron beam radiation, immediately after surgery and on the third postoperative day, respectively. Qualitative and histophotometric evaluations of tissue repair structures were carried out. Data were analyzed by ANOVA and Tukey's test (alpha = 0.05) and regression analysis. The repair process was delayed since the first sacrifice time in both irradiated groups, but in IG1, wound healing was closer to that of CG1; whereas in IG2, the delay was more pronounced. Based on the histological findings, it is possible to conclude that a low-dose of electron radiation delayed tissue repair in rat skin. The delay was longer in the skin irradiated 3 days after the beginning of tissue repair. However, the low-energy electron irradiation did not prevent wound healing.

scholarly journals New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Miriam D. Neher ◽  
Sebastian Weckbach ◽  
Markus S. Huber-Lang ◽  
Philip F. Stahel
Keyword(s):  
Inflammatory Response ◽  
Major Trauma ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Healing Process ◽  
Wound Healing Process ◽  
Peroxisome Proliferator ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Major trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been identified as potent modulators of inflammation in various acute and chronic inflammatory conditions. The main mechanism of action mediated by ligand binding to PPARs is the inhibition of the nuclear transcription factor NF-κB, leading to downregulation of downstream gene transcription, such as for genes encoding proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti-inflammatory properties in various animal models of tissue injury, including central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In addition, PPAR agonists have been shown to induce wound healing process after tissue trauma. The present review was designed to provide an up-to-date overview on the current understanding of the role of PPARs in the pathophysiology of the inflammatory response after major trauma. Therapeutic options for using recombinant PPAR agonists as pharmacological agents in the management of posttraumatic inflammation will be discussed.

scholarly journals Application of ADSCs and their Exosomes in Scar Prevention

2021 ◽  
Author(s):  
Cong Li ◽  
Shuqiang Wei ◽  
Quanchen Xu ◽  
Yu Sun ◽  
Xuchao Ning ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Adipose Tissue ◽  
Tissue Injury ◽  
Healing Process ◽  
Treatment Method ◽  
Scar Tissue ◽  
Wound Healing Process ◽  
Target Cells ◽  
Cellular Components

AbstractScar is a common way of healing after tissue injury. The poor scar healing will not only cause dysfunction of tissues and organs but also affect the appearance of the patients’ body surface, which causes the pressure of life and spirit to the patients. However, the formation of scar tissue is an extremely complex process and its mechanism is not fully understood. At present, there is no treatment method to eliminate scars completely. Fibroblasts are the most abundant cells in the dermis, which have the ability to synthesize and remodel extracellular matrix (ECM). Myofibroblasts actively participate in the wound healing process and influence the outcome. Therefore, both of them play important roles in wound healing and scar formation. Adipose tissue-derived stem cells (ADSCs) are pluripotent stem cells that can act on target cells by paracrine. Adipose tissue stem cell-derived exosomes (ADSC-Exos) are important secretory substances of ADSCs. They are nanomembrane vesicles that can transport a variety of cellular components and fuse with target cells. In this review, we will discuss the effects of ADSCs and ADSC-Exos on the behavior of fibroblasts and myofibroblasts during wound healing and scarring stage in combination with recent studies. Graphical Abstract

scholarly journals The portrait of neem leaves-based high performance wound healing activity on zebrafish

2021 ◽  
Vol 27 (1) ◽  
pp. 23-27
Author(s):  
Nour Athiroh ◽  
Ari Hayati ◽  
Istirochah Pudjiwati ◽  
Ahmad Taufiq ◽  
Nurul Jadid Mubarakati
Keyword(s):  
Wound Healing ◽  
High Performance ◽  
Healing Process ◽  
Vital Role ◽  
Control Group ◽  
Wound Healing Process ◽  
Physiological Factors ◽  
Neem Leaves ◽  
Significant Difference ◽  
Speed Up

This study was designed to evaluate the role of sliced and dropping models of neem leaves (Azadirachta indica) and environmental factors on zebrafish wound shrinkage. This study employed two treatment models: neem leaf slices and drops model. The treatment in the neem leaf slice model was the control group (fish was injured without neem leaf slices treatment, and G1-G3 of each fish was injured at 0.3 cm + 0.5, 1, and 2 g. Treatment in the neem leaf drop model was control group (fish was injured without neem leaves drops, and G1-G3 of each fish was injured at 0.3 cm + 1, 2, 4 drops. Findings suggest that there is a significant difference between the control group by treating G1, G2, and G3 on the shrinkage of zebrafish wound area both in the neem leaf slice and drop models, but G1 was not significantly different from G2 and G3, as well as G2 and G3 both in the neem leaf slice and drop model. Neem leaves contain nutrients that play a vital role in the formation of collagen and the formation of new capillaries to help speed up the wound healing process. The healing process involves the dynamic interaction of physiological factors.

scholarly journals Collagen in Wound Healing

2021 ◽  
Vol 8 (5) ◽  
pp. 63
Author(s):  
Shomita S. Mathew-Steiner ◽  
Sashwati Roy ◽  
Chandan K. Sen
Keyword(s):  
Wound Healing ◽  
Tissue Injury ◽  
Wound Care ◽  
Healing Process ◽  
Wound Healing Process ◽  
Key Factors ◽  
Wound Therapy ◽  
Normal Wound Healing ◽  
Persistent Inflammation ◽  
Soluble Components

Normal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Impairments in any of these phases stall the wound in a chronic, non-healing state that typically requires some form of intervention to guide the process back to completion. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components caused by elevated metalloproteinases and other enzymes and improper activation of soluble mediators of the wound healing process. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. In this work the significance of collagen in different biological processes relevant to wound healing are reviewed and a summary of the current literature on the use of collagen-based products in wound care is provided.

scholarly journals Toll-Like Receptors, Tissue Injury, and Tumourigenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Savvas Ioannou ◽  
Michael Voulgarelis
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Tissue Injury ◽  
Healing Process ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Innate Immune ◽  
Wound Healing Process ◽  
Toll Like Receptors ◽  
And Function

Toll-like receptors (TLRs) belong to a class of molecules known as pattern recognition receptors, and they are part of the innate immune system, although they modulate mechanisms that impact the development of adaptive immune responses. Several studies have shown that TLRs, and their intracellular signalling components, constitute an important cellular pathway mediating the inflammatory process. Moreover, their critical role in the regulation of tissue injury and wound healing process as well as in the regulation of apoptosis is well established. However, interest in the role of these receptors in cancer development and progression has been increasing over the last years. TLRs are likely candidates to mediate effects of the innate immune system within the tumour microenvironment. A rapidly expanding area of research regarding the expression and function of TLRs in cancer cells and its association with chemoresistance and tumourigenesis, and TLR-based therapy as potential immunotherapy in cancer treatment is taking place over the last years.

scholarly journals The earthworm Dendrobaena veneta (Annelida): A new experimental-organism for photobiomodulation and wound healing

2018 ◽  
Author(s):  
Andrea Amaroli ◽  
Sara Ferrando ◽  
Marina Pozzolini ◽  
Lorenzo Gallus ◽  
Steven Parker ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Injury ◽  
Healing Process ◽  
Experimental Models ◽  
Metabolic Effects ◽  
Wound Healing Process ◽  
Light Sources ◽  
Tissue Degeneration ◽  
Experimental Organism ◽  
Set Up

Photobiomodulation (PBM) is a manipulation of cellular behavior using non-ablative low intensity light sources. This manipulation triggers a cascade of metabolic effects and physiological changes resulting in improved tissue repair, of benefit in the treatment of tissue injury, degenerative or autoimmune diseases. PBM has witnessed an exponential increase in both clinical instrument technology and applications. It is therefore of benefit to find reliable experimental models to test the burgeoning laser technology for medical applications. In our work, we proposed the earthworm Dendrobaena veneta for the study of non-ablative laser-light effects on wound healing. In our preliminary work, D. veneta has been shown to be positively affected by PBM. New tests using D. veneta were set up to evaluate the effectiveness of a chosen 808 nm-64 J/cm2–1W-CW laser therapy using the AB2799 hand-piece with flat-top bean profile, on the wound healing process of the earthworm. Effective outcome was assimilated through examining the macroscopic, histological, and molecular changes on the irradiated posterior-segment of excised-earthworms with respect to controls. Three successive treatments, one every 24 hours, were concluded as sufficient to promote the wound healing, by effects on muscular and blood vessel contraction, decrement of bacteria load, reduction of inflammatory processes and tissue degeneration. D. veneta was demonstrated to be a reliable experimental organism that meets well the 3Rs principles and the National Science Foundation statement. Through their genetic and evolutionary peculiarity, comparable to those of scientifically accredited models, D. veneta allows the effect of laser therapies by multidisciplinary methods, at various degree of complexity and costs to be investigated.

The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 988-995 ◽  
Author(s):  
Robert A. S. Ariëns ◽  
Helen Philippou ◽  
Chandrasekaran Nagaswami ◽  
John W. Weisel ◽  
David A. Lane ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Factor Xiii ◽  
High Performance ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Catalytic Efficiency ◽  
Similar Rate ◽  
Cross Linking ◽  
Fibrinopeptide A ◽  
Thrombin Cleavage

Factor XIII on activation by thrombin cross-links fibrin. A common polymorphism Val to Leu at position 34 in the FXIII A subunit is under investigation as a risk determinant of thrombosis. Because Val34Leu is close to the thrombin cleavage site, the hypothesis that it would alter the function of FXIII was tested. Analysis of FXIII subunit proteolysis by thrombin using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance liquid chromatography showed that FXIII 34Leu was cleaved by thrombin more rapidly and by lower doses than 34Val. Mass spectrometry of isolated activation peptides confirmed the predicted single methyl group difference and demonstrated that the thrombin cleavage site is unaltered by Val34Leu. Kinetic analysis of activation peptide release demonstrated that the catalytic efficiency (kcat/Km) of thrombin was 0.5 for FXIII 34Leu and 0.2 (μmol/L)−1× sec−1 for 34Val. Presence of fibrin increased the catalytic efficiency to 4.8 and 2.2 (μmol/L)−1 × sec−1, respectively. Although the 34Leu peptide was released at a similar rate as fibrinopeptide A, the 34Val peptide was released more slowly than fibrinopeptide A but more quickly than fibrinopeptide B generation. Cross-linking of γ- and -chains appeared earlier when fibrin was incubated with FXIII 34Leu than with 34Val. Fully activated 34Leu and 34Val FXIII showed similar cross-linking activity. Analysis of fibrin clots prepared using plasma from FXIII 34Leu subjects by turbidity and permeability measurements showed reduced fiber mass/length ratio and porosity compared to 34Val. The structural differences were confirmed by electron microscopy. These results demonstrate that Val34Leu accelerates activation of FXIII by thrombin and consequently affects the structure of the cross-linked fibrin clot.

Ozonated Oils and Cutaneous Wound Healing

2019 ◽  
Vol 25 (20) ◽  
pp. 2264-2278 ◽  
Author(s):  
Yunsook Lim ◽  
Heaji Lee ◽  
Brittany Woodby ◽  
Giuseppe Valacchi
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Wound Closure ◽  
State Of The Art ◽  
Healing Process ◽  
Actual State ◽  
Wound Healing Process ◽  
Cutaneous Wounds ◽  
Positive Effects ◽  
Wound Tissue

Wound tissue repair is a complex and dynamic process of restoring cellular structures and tissue layers. Improvement in this process is necessary to effectively treat several pathologies characterized by a chronic delayed wound closure, such as in diabetes, and the investigation of new approaches aimed to ameliorate the wound healing process is under continuous evolution. Recently, the usage of vegetable matrices in the form of ozonated oils has been proposed, and several researchers have shown positive effects on wound healing, due to the bactericidal, antiviral, and antifungal properties of these ozonated oils. <p></p> In the present review, we intend to summarize the actual state of the art of the topical usage of ozonated oil in cutaneous wounds with special emphasis to the importance of the ozonated degree of the oil.

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