scholarly journals Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3401
Author(s):  
David Meléndez-Martínez ◽  
Luis Fernando Plenge-Tellechea ◽  
Ana Gatica-Colima ◽  
Martha Sandra Cruz-Pérez ◽  
José Manuel Aguilar-Yáñez ◽  
...  

Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4610
Author(s):  
Hye-Jin Lee ◽  
Moses Jeong ◽  
Young-Guk Na ◽  
Sung-Jin Kim ◽  
Hong-Ki Lee ◽  
...  

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.


Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 700
Author(s):  
Kamila Raziyeva ◽  
Yevgeniy Kim ◽  
Zharylkasyn Zharkinbekov ◽  
Kuat Kassymbek ◽  
Shiro Jimi ◽  
...  

Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.


2019 ◽  
Vol 7 (6) ◽  
pp. 940-952 ◽  
Author(s):  
Weihan Xie ◽  
Xiaoling Fu ◽  
Fengling Tang ◽  
Yunfei Mo ◽  
Jun Cheng ◽  
...  

Many pathophysiologic conditions can interrupt the normal wound healing process and lead to chronic wounds due to the arrest of macrophages in their inflammatory phenotype.


2020 ◽  
Vol 10 (21) ◽  
pp. 7613
Author(s):  
Domagoj Marijanović ◽  
Damir Filko

Chronic wounds or wounds that are not healing properly are a worldwide health problem that affect the global economy and population. Alongside with aging of the population, increasing obesity and diabetes patients, we can assume that costs of chronic wound healing will be even higher. Wound assessment should be fast and accurate in order to reduce the possible complications, and therefore shorten the wound healing process. Contact methods often used by medical experts have drawbacks that are easily overcome by non-contact methods like image analysis, where wound analysis is fully or partially automated. Two major tasks in wound analysis on images are segmentation of the wound from the healthy skin and background, and classification of the most important wound tissues like granulation, fibrin, and necrosis. These tasks are necessary for further assessment like wound measurement or healing evaluation based on tissue representation. Researchers use various methods and algorithms for image wound analysis with the aim to outperform accuracy rates and show the robustness of the proposed methods. Recently, neural networks and deep learning algorithms have driven considerable performance improvement across various fields, which has a led to a significant rise of research papers in the field of wound analysis as well. The aim of this paper is to provide an overview of recent methods for non-contact wound analysis which could be used for developing an end-to-end solution for a fully automated wound analysis system which would incorporate all stages from data acquisition, to segmentation and classification, ending with measurement and healing evaluation.


2019 ◽  
Vol 25 (41) ◽  
pp. 5772-5781 ◽  
Author(s):  
Marieke Haalboom

Background: A major global health issue is the existence of chronic wounds. Appropriate diagnosis and treatment is essential to promote wound healing and prevent further complications. Traditional methods for treatment and diagnosis of chronic wounds have shown to be of limited effectiveness. Therefore, there is a need for the development of diagnostic and therapeutic innovations in chronic wound care. Objective: This mini-review aims to provide insight in the current knowledge of the wound healing process and the deficiencies encountered in chronic wounds, which provides a basis for the development of innovations in chronic wound care. Furthermore, promising diagnostic and therapeutic innovations will be highlighted. Methods: Literature was searched for recent articles (=<10 years) describing the current knowledge about the wound healing process and chronic wounds. The most promising diagnostic and therapeutic innovations were gathered from articles published in the past 5 years. Results/Conclusion: Wound healing is a well-organized process consisting of four phases: coagulation, inflammation, proliferation and wound remodelling. Chronic wounds often stagnate in the inflammatory phase and/or experience an impaired proliferative phase. This mini-review has demonstrated that increased knowledge about the processes involved in wound healing has paved the way for the development of new diagnostic tools and treatments for chronic wounds. Increased knowledge about bacterial invasion and infection in has encouraged researchers to develop diagnostic tools to help clinicians detect these phenomena appropriately and in time. Other researchers have shown that they are able to design/extract biochemical compounds that intervene in the disrupted healing processes in chronic wounds.


Author(s):  
Jeon Il Kang ◽  
Kyung Min Park

Skin wounds can be classified into two categories, namely acute and chronic. While acute wounds are healed by the normal wound healing process, chronic wounds are not normally healed, causing...


Author(s):  
Davide Vincenzo Verdolino ◽  
Helen A. Thomason ◽  
Andrea Fotticchia ◽  
Sarah Cartmell

Chronic wounds represent an economic burden to healthcare systems worldwide and a societal burden to patients, deeply impacting their quality of life. The incidence of recalcitrant wounds has been steadily increasing since the population more susceptible, the elderly and diabetic, are rapidly growing. Chronic wounds are characterised by a delayed wound healing process that takes longer to heal under standard of care than acute (i.e. healthy) wounds. Two of the most common problems associated with chronic wounds are inflammation and infection, with the latter usually exacerbating the former. With this in mind, researchers and wound care companies have developed and marketed a wide variety of wound dressings presenting different compositions but all aimed at promoting healing. This makes it harder for physicians to choose the correct therapy, especially given a lack of public quantitative data to support the manufacturers’ claims. This review aims at giving a brief introduction to the clinical need for chronic wound dressings, focusing on inflammation and evaluating how bio-derived and synthetic dressings may control excess inflammation and promote healing.


2021 ◽  
Vol 506 (1-2) ◽  
Author(s):  
Nguyen Ngoc Tuan ◽  
Nguyen Tran Ngoc Tu ◽  
Nguyen Tien Dung

Objective: Our aim was to evaluate topical EGF, VEGF, MMP12 concentrations of ​​chronic wounds which after Autologous Platelet - Rich Plasma(PRP) therapy. Methods: The study conducted a descriptive longitudinal study at the Wound Healing Center of the Vietnam National Burn Hospital from 11/2018 to 2/2020. 24 patients with chronic wounds and aged 18 years old or older were enrolled in this study. These patients were injected autologous PRP at wound bed. We biopsied chronic wound bed tissue for evaluating EGF, VEGF and MMP12 by the Elisa technique at the first, second and third week of follow-up. Results: After PRP therapy, topical EGF and VEGF concentration increased after 1 week of treatment. MMP12 concentraiton significantly reduced compaired to before PRP therapy. Conclusion: In addition to PRP therapy had a beneficial effect on cutaneous regeneration and wound healing of the chronic wound. The autologous PRP promoted the wound healing process byincreating topical EGF and VEGF, reducing MMP12 which known as a pro-inflammatiory mediator.


2018 ◽  
Vol 16 (1) ◽  
pp. 26-41 ◽  
Author(s):  
Srijita Chakrabarti ◽  
Pronobesh Chattopadhyay ◽  
Johirul Islam ◽  
Subhabrata Ray ◽  
Pakalapati Srinivas Raju ◽  
...  

Wound infections impose a remarkable clinical challenge that has a considerable influence on morbidity and mortality of patients, influencing the cost of treatment. The unprecedented advancements in molecular biology have come up with new molecular and cellular targets that can be successfully applied to develop smarter therapeutics against diversified categories of wounds such as acute and chronic wounds. However, nanotechnology-based diagnostics and treatments have achieved a new horizon in the arena of wound care due to its ability to deliver a plethora of therapeutics into the target site, and to target the complexity of the normal wound-healing process, cell type specificity, and plethora of regulating molecules as well as pathophysiology of chronic wounds. The emerging concepts of nanobiomaterials such as nanoparticles, nanoemulsion, nanofibrous scaffolds, graphene-based nanocomposites, etc., and nano-sized biomaterials like peptides/proteins, DNA/RNA, oligosaccharides have a vast application in the arena of wound care. Multi-functional, unique nano-wound care formulations have acquired major attention by facilitating the wound healing process. In this review, emphasis has been given to different types of nanomaterials used in external wound healing (chronic cutaneous wound healing); the concepts of basic mechanisms of wound healing process and the promising strategies that can help in the field of wound management.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 961
Author(s):  
Sibusiso Alven ◽  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe

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.


Sign in / Sign up

Export Citation Format

Share Document