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Therapeutic candidates for keloid scars identified by qualitative review of scratch assay research for wound healing.
Alishahedani, ME, Yadav, M, McCann, KJ, Gough, P, Castillo, CR, Matriz, J, Myles, IA
PloS one. 2021;(6):e0253669
Abstract
The scratch assay is an in vitro technique used to analyze cell migration, proliferation, and cell-to-cell interaction. In the assay, cells are grown to confluence and then 'scratched' with a sterile instrument. For the cells in the leading edge, the resulting polarity induces migration and proliferation in attempt to 'heal' the modeled wound. Keloid scars are known to have an accelerated wound closure phenotype in the scratch assay, representing an overactivation of wound healing. We performed a qualitative review of the recent literature searching for inhibitors of scratch assay activity that were already available in topical formulations under the hypothesis that such compounds may offer therapeutic potential in keloid treatment. Although several shortcomings in the scratch assay literature were identified, caffeine and allicin successfully inhibited the scratch assay closure and inflammatory abnormalities in the commercially available keloid fibroblast cell line. Caffeine and allicin also impacted ATP production in keloid cells, most notably with inhibition of non-mitochondrial oxygen consumption. The traditional Chinese medicine, shikonin, was also successful in inhibiting scratch closure but displayed less dramatic impacts on metabolism. Together, our results partially summarize the strengths and limitations of current scratch assay literature and suggest clinical assessment of the therapeutic potential for these identified compounds against keloid scars may be warranted.
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Nanoceutical Adjuvants as Wound Healing Material: Precepts and Prospects.
Banerjee, K, Madhyastha, R, Nakajima, Y, Maruyama, M, Madhyastha, H
International journal of molecular sciences. 2021;(9)
Abstract
Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers.
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The Modulatory Influence of Plant-Derived Compounds on Human Keratinocyte Function.
Merecz-Sadowska, A, Sitarek, P, Zajdel, K, Kucharska, E, Kowalczyk, T, Zajdel, R
International journal of molecular sciences. 2021;(22)
Abstract
The plant kingdom is a rich source of secondary metabolites with numerous properties, including the potential to modify keratinocyte biology. Keratinocytes are important epithelial cells that play a protective role against various chemical, physical and biological stimuli, and participate in reactive oxygen scavenging and inflammation and wound healing processes. The epidermal cell response may be modulated by phytochemicals via changes in signal transduction pathways. Plant extracts and single secondary compounds can possess a high antioxidant capacity and may suppress reactive oxygen species release, inhibit pro-apoptotic proteins and apoptosis and activate antioxidant enzymes in keratinocytes. Moreover, selected plant extracts and single compounds also exhibit anti-inflammatory properties and exposure may result in limited production of adhesion molecules, pro-inflammatory cytokines and chemokines in keratinocytes. In addition, plant extracts and single compounds may promote keratinocyte motility and proliferation via the regulation of growth factor production and enhance wound healing. While such plant compounds may modulate keratinocyte functions, further in vitro and in vivo studies are needed on their mechanisms of action, and more specific toxicity and clinical studies are needed to ensure their effectiveness and safety for use on human skin.
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Maytenus macrocarpa (Ruiz & Pav.) Briq.: Phytochemistry and Pharmacological Activity.
Malaník, M, Treml, J, Rjašková, V, Tížková, K, Kaucká, P, Kokoška, L, Kubatka, P, Šmejkal, K
Molecules (Basel, Switzerland). 2019;(12)
Abstract
Maytenus macrocarpa (Celastraceae) is a tree native to Amazonia. Its roots, leaves, bark, and combinations of these are used in traditional medicine mainly to treat rheumatism and, to a lesser extent, to heal wounds and to combat bronchitis and diarrhea. To date, mainly triterpenes and dihydro-β-agarofuran sesquiterpenes were isolated from M. macrocarpa. Extracts and selected pure compounds isolated from the leaves, roots, and stem bark showed antibacterial, antiviral, antiparasitic, anti-inflammatory, and cytotoxic activities in vitro. The aim of this review is to summarize the available ethnobotanical, phytochemical, and pharmacological information about this traditional Amazonian medicinal tree, as well as to attract the attention of phytochemists and pharmacognosists to this potentially interesting source of ethnopharmaceuticals.
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The Wound Healing Properties of Betulin from Birch Bark from Bench to Bedside.
Scheffler, A
Planta medica. 2019;(7):524-527
Abstract
With central European approval in January 2016 for a betulin-oleogel (Episalvan), used to accelerate wound closure in partial thickness wounds, the herbal active ingredient triterpene dry extract (betulin), from birch bark, was introduced into therapy for the first time. Clinical evidence of accelerated wound healing was provided in a new study design by means of intraindividual comparison of split-thickness skin graft donor wounds and burn wounds. Clinical results of a phase II study evidencing accelerated wound healing in the rare disease epidermolysis bullosa are also available, and a pivotal multi-centre phase III study is currently being conducted. The mode of action affects all three phases of wound healing (inflammation, migration, and differentiation), and it has been possible, in some cases, to shed light on this down to the molecular level. After temporary stimulation of the inflammatory phase, the keratinocytes migrate more rapidly to the wound closure and, finally, epidermal differentiation is stimulated. With this project, we have shown that scientifically founded new developments in phytotherapy are possible in Europe. The active ingredient is new and its indication is for the first time clearly proven in studies. Betulin-oleogel is the first drug of its indication and is patented until 2030. In addition, it is the first phytotherapeutic agent in surgery, and thus opens up a new therapeutic area for phytotherapy. The birch bark contains about 22% betulin in its cork tissue, meaning that the active ingredient is sustainably available from Northern Europe's wood-processing industry on a scale of several 100,000 t/a.
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Skin Burns: Review of Molecular Mechanisms and Therapeutic Approaches.
Roshangar, L, Soleimani Rad, J, Kheirjou, R, Reza Ranjkesh, M, Ferdowsi Khosroshahi, A
Wounds : a compendium of clinical research and practice. 2019;(12):308-315
Abstract
Burn wounds are one of the main causes of skin damage. Based on World Health Organization statistics, almost 300 000 people worldwide die of burns each year. In severe burns, the cells and blood vessels are often injured and the blood supply to the wound is disturbed. Many factors such as oxygenation, infection, aging, hormones, and nutrition potentially can influence burn progression and disrupt repair with unbalanced release of various growth factors and cytokines. Different treatment approaches such as dressings and skin substitutes have been applied to aid wound healing. A thorough understanding of the effective factors on burns can improve wound healing outcomes. This review evaluates articles published on the Scopus, EMBASE, and PubMed databases that attempt to explain the pathophysiology, molecular components, and therapeutic approaches involved in the burn wound healing process.
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7.
Role of gut microbiota in intestinal wound healing and barrier function.
Alam, A, Neish, A
Tissue barriers. 2018;(3):1539595
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Abstract
The mammalian intestine harbors a highly complex and abundant ensemble of bacteria that flourish in a nutrient-rich environment while profoundly influencing many aspects of host biology. The intestine coevolved with its resident microbes in a manner where the mucosa developed a barrier function to segregate the resident microbes from the rest of the body, and yet paradoxically, allowing integration of microbial signals for the host benefit. In this review, we provided a comprehensive overview of why the gut microbiota is key to the efficient development and maintenance of the intestinal barrier. We also highlighted how a destabilized equilibrium between gut microbiota and the host may eventuate in a wide range of intestinal diseases characterized by the disrupted intestinal barrier. Finally, the review delineated how microenvironmental changes in the injured mucosa result in an enrichment of a pro-regenerating consortium of bacteria, which augments mucosal wound repair and restoration of barrier functions.
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Povidone iodine in wound healing: A review of current concepts and practices.
Bigliardi, PL, Alsagoff, SAL, El-Kafrawi, HY, Pyon, JK, Wa, CTC, Villa, MA
International journal of surgery (London, England). 2017;:260-268
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Abstract
BACKGROUND Of the many antimicrobial agents available, iodophore-based formulations such as povidone iodine have remained popular after decades of use for antisepsis and wound healing applications due to their favorable efficacy and tolerability. Povidone iodine's broad spectrum of activity, ability to penetrate biofilms, lack of associated resistance, anti-inflammatory properties, low cytotoxicity and good tolerability have been cited as important factors, and no negative effect on wound healing has been observed in clinical practice. Over the past few decades, numerous reports on the use of povidone iodine have been published, however, many of these studies are of differing design, endpoints, and quality. More recent data clearly supports its use in wound healing. METHODS Based on data collected through PubMed using specified search criteria based on above topics and clinical experience of the authors, this article will review preclinical and clinical safety and efficacy data on the use of povidone iodine in wound healing and its implications for the control of infection and inflammation, together with the authors' advice for the successful treatment of acute and chronic wounds. RESULTS AND CONCLUSION Povidone iodine has many characteristics that position it extraordinarily well for wound healing, including its broad antimicrobial spectrum, lack of resistance, efficacy against biofilms, good tolerability and its effect on excessive inflammation. Due to its rapid, potent, broad-spectrum antimicrobial properties, and favorable risk/benefit profile, povidone iodine is expected to remain a highly effective treatment for acute and chronic wounds in the foreseeable future.
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Efficacy of a Disease-Specific Nutritional Support for Pressure Ulcer Healing: A Systematic Review and Meta-Analysis.
Cereda, E, Neyens, JCL, Caccialanza, R, Rondanelli, M, Schols, JMGA
The journal of nutrition, health & aging. 2017;(6):655-661
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Abstract
OBJECTIVES The aim of this systematic review was to summarize the evidence on the efficacy of high-calorie, high-protein nutritional formula enriched with arginine, zinc, and antioxidants (disease-specific support) in patients with pressure ulcers (PUs). METHODS Randomized controlled trials in English published from January 1997 until October 2015 were searched for in electronic databases (EMBASE, Medline, PubMed, and CINAHL). Studies comparing a disease-specific nutritional support (oral supplements or tube feeding) to a control nutritional intervention enabling the satisfaction of energy requirements regardless of the use of high-calorie formula or placebo or no support for at least 4 weeks were considered eligible. Study outcomes were the percentage of change in PU area, complete healing and reduction in the PU area ≥40% at 8 weeks, and the percentage of change in area at 4 weeks. RESULTS A total of 3 studies could be included in the meta-analysis. Compared with control interventions, formulas enriched with arginine, zinc and antioxidants resulted in significantly higher reduction in ulcer area (-15.7% [95%CI, -29.9, -1.5]; P=0.030; I2=58.6%) and a higher proportion of participants having a 40% or greater reduction in PU size (OR=1.72 [95%CI, 1.04, 2.84]; P=0.033; I2=0.0%) at 8 weeks. A nearly significant difference in complete healing at 8 weeks (OR=1.72 [95%CI, 0.86, 3.45]; P=0.127; I2=0.0%) and the percentage of change in the area at 4 weeks (-7.1% [95%CI, -17.4, 3.3]; P=0.180; I2=0.0%) was also observed. CONCLUSIONS This systematic review shows that the use of formulas enriched with arginine, zinc and antioxidants as oral supplements and tube feeds for at least 8 weeks are associated with improved PU healing compared with standard formulas.
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Factors affecting the periapical healing process of endodontically treated teeth.
Holland, R, Gomes, JE, Cintra, LTA, Queiroz, ÍOA, Estrela, C
Journal of applied oral science : revista FOB. 2017;(5):465-476
Abstract
Tissue repair is an essential process that reestablishes tissue integrity and regular function. Nevertheless, different therapeutic factors and clinical conditions may interfere in this process of periapical healing. This review aims to discuss the important therapeutic factors associated with the clinical protocol used during root canal treatment and to highlight the systemic conditions associated with the periapical healing process of endodontically treated teeth. The antibacterial strategies indicated in the conventional treatment of an inflamed and infected pulp and the modulation of the host's immune response may assist in tissue repair, if wound healing has been hindered by infection. Systemic conditions, such as diabetes mellitus and hypertension, can also inhibit wound healing. The success of root canal treatment is affected by the correct choice of clinical protocol. These factors are dependent on the sanitization process (instrumentation, irrigant solution, irrigating strategies, and intracanal dressing), the apical limit of the root canal preparation and obturation, and the quality of the sealer. The challenges affecting the healing process of endodontically treated teeth include control of the inflammation of pulp or infectious processes and simultaneous neutralization of unpredictable provocations to the periapical tissue. Along with these factors, one must understand the local and general clinical conditions (systemic health of the patient) that affect the outcome of root canal treatment prediction.