SciCombinator

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Concept: Scar

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Every element or cell in the human body produces substances that communicate and respond in an autocrine or paracrine mode, consequently affecting organs and structures that are seemingly far from each other. The same also applies to the skin. In fact, when the integrity of the skin has been altered, or when its healing process is disturbed, it becomes a source of symptoms that are not merely cutaneous. The skin is an organ, and similar to any other structure, it has different functions in addition to connections with the central and peripheral nervous system. This article examines pathological responses produced by scars, analyzing definitions and differences. At the same time, it considers the subcutaneous fascias, as this connective structure is altered when there is a discontinuous cutaneous surface. The consequence is an ample symptomatology, which is not limited to the body area where the scar is located, such as a postural or trigeminal disorder.

Concepts: Nervous system, Scar, Wound healing, Collagen, Healing, Organ, Skin, Human anatomy

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Type I collagen is the most abundant protein in the human body. Its excessive synthesis results in fibrosis of various organs. Fibrosis is a major medical problem without an existing cure. Excessive synthesis of type I collagen in fibrosis is primarily due to stabilization of collagen mRNAs. We recently reported that intermediate filaments composed of vimentin regulate collagen synthesis by stabilizing collagen mRNAs. Vimentin is a primary target of Withaferin-A (WF-A). Therefore, we hypothesized that WF-A may reduce type I collagen production by disrupting vimentin filaments and decreasing the stability of collagen mRNAs. This study is to determine if WF-A exhibits anti-fibrotic properties in vitro and in vivo and to elucidate the molecular mechanisms of its action. In lung, skin and heart fibroblasts WF-A disrupted vimentin filaments at concentrations of 0.5-1.5 µM and reduced 3 fold the half-lives of collagen α1(I) and α2(I) mRNAs and protein expression. In addition, WF-A inhibited TGF-β1 induced phosphorylation of TGF-β1 receptor I, Smad3 phosphorylation and transcription of collagen genes. WF-A also inhibited in vitro activation of primary hepatic stellate cells and decreased their type I collagen expression. In mice, administration of 4 mg/kg WF-A daily for 2 weeks reduced isoproterenol-induced myocardial fibrosis by 50%. Our findings provide strong evidence that Withaferin-A could act as an anti-fibrotic compound against fibroproliferative diseases, including, but not limited to, cardiac interstitial fibrosis.

Concepts: Protein, Bone, Gene, Scar, Collagen, Fibrosis, Heart, In vitro

46

Although regeneration via the reprogramming of one cell lineage to another occurs in fish and amphibians, it is not observed in mammals. We discovered in mouse that during wound healing adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and non-adipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered BMP signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist, noggin, in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts when treated with either BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.

Concepts: DNA, Protein, Gene expression, Human, Scar, Wound healing, Chromosome, Cytoplasm

31

Striae gravidarum (stretch marks developing during pregnancy) occur in 50% to 90% of women. They appear as red or purple lines or streaks that fade slowly to leave pale lines or marks on the skin. The abdomen, breasts and thighs are commonly affected. The exact cause of stretch marks is unclear and no preparation has yet been shown to be effective in preventing the development of stretch marks. They are a source of significant anxiety for women, impacting on their quality of life.

Concepts: Pregnancy, Scar, Obstetrics, Stretch marks, Cocoa butter

30

Burn scars remain a serious physical and psychological problem for the affected people. Clinical studies as well as basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling has no influence on repigmentation of large hypopigmented scars. The goal of this study is to evaluate whether two established methods - needling (for improvement of scar quality) and non-cultured autologous skin cell suspension (for repigmentation) - can be successfully combined. Twenty subjects with mean age of 33 years (6-60 years) with scars from deep second and third degree burns have been treated. The average treated surface area was 94cm(2) (15-250cm(2)) and was focused on prominent areas such as the face, neck, chest and arm. Percutaneous collagen induction or “medical needling” was performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (NCASCS) was produced and applied using the ReNovaCell Autologous Cell Harvesting Device (Avita Medical), according to the manufacturer’s instructions. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, as well as with patient and observer ratings. Patient satisfaction/preference was also obtained. Taken together, the pigmentation ratings and objective measures indicate individual improvement in 17 of the study participants. The melanin increases seen 12 months after NCASCS treatment are statistically significant. Medical needling in combination with NCASCS shows promise for repigmentation of burn cars.

Concepts: Statistics, Patient, Scar, Collagen, Organ, Skin, Epidermis, Burn

28

BACKGROUND: Many Asians receive epicanthoplasty to improve their medial epicanthal fold.Excessive performance of such surgery may cause multiple unwanted results, but there is no report on any restoration method for an overcorrected result of epicanthoplasty. Accordingly, the authors have created a new method for reversely restoring the excessively corrected medial epicanthal fold using skin-redraping epicanthoplasty (Plast Reconstr Surg. 2007;119:703-710). METHODS: During the interval between January 2009 and April 2011, 35 patients received surgery for restoration of the epicanthal fold using the authors' method, which involves sufficiently elevating the skin flap and redraping it to reconstruct the epicanthal fold. This method is very simple to design and perform, and it effectively covers the excessively exposed lacrimal lake. In addition, it can be used independently of the type of prior epicanthoplasty. RESULTS: After the surgery, 2 patients experienced overcorrection, and we repeated the epicanthoplasty. In the other patients, there was no severe complication except for mild redness, a condition that improved after several months. The mean measured distance between the medial canthi after the surgery was 36.8 mm, corresponding to a total lengthening effect of 4.5 mm. This improved the aggressive facial expression caused by the exposed lacrimal lake, and the eyes no longer appeared to be too close together. Moreover, in the case of patients who had more visible scars due to prior epicanthoplasty on the medial epicanthal area, the overall scar length decreased. CONCLUSIONS: This method is simple in design and easy to perform. It can also control the degree of restoration with an additional advantage of reducing a prior scar. Using this method, we could effectively restore the overcorrected epicanthal fold.

Concepts: Causality, Scar, Eye, Skin, Oral and maxillofacial surgery, FN SCAR, 2011, Lacrimal lake

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To map skin temperature kinetics, and by extension skin blood flow throughout normal or abnormal repair of full-thickness cutaneous wounds created on the horse body and limb, using infrared thermography.

Concepts: Scar, Wound healing, Healing, Temperature, Horse, Black body, Thermography, Thermal radiation

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Burns are a significant health challenge and healing can result in scar formation. Chitosan, a derivative of chitin, has been used to promote wound healing. In this study we used gene expression profiling in a mouse model of full thickness cutaneous burn to assess the benefits of treating with a chitosan lactate dressing. Three days after wounding mice treated with chitosan showed increased expression of genes associated with formation of granulation tissue. At a later time point, seven days after wounding, genes that initially showed increased expression were now down-regulated, and there was increased expression of genes involved in remodeling suggesting that the chitosan treatment results in accelerated healing. Quantitative RT-PCR showed modulated mRNA levels for TGFβ1 by the chitosan dressing. TGFβ1 initially promotes healing but extended activity can result in scarring. Importantly we found that expression was elevated at day three, but decreased at day seven suggesting that chitosan treatment will not result in scar formation, and may even be beneficial in preventing scar formation. Additionally, the biphasic regulation of expression of TGFβ1 could be a powerful biomarker for future studies of the wound-healing potential of chitosan based and other treatments for burn wounds. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

Concepts: DNA, Gene, Gene expression, Transcription, Scar, Wound healing, Cellular differentiation, Burn

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The present study was designed to determine the role of topical treatment with curcumin (Cur) on burn wound healing in rats. The Wistar-albino rats were randomly allotted into one of three experimental groups: 4th, 8th and 12th day (post burn) and all groups include subgroups which Burn and Burn + Cur. Each group contains 12 animals. Burn wounds were made on the back of rat and Cur was administered topically. At the end of the study, all animals were sacrificed and the wound tissues removed for analyse to biochemical and histopathological changes. There was a significant increase in the hydroxyproline levels in the skin of the Cur groups. Cur treated wounds were found to heal much faster as indicated by improved rates of inflammatory cells, collagen deposition, angiogenesis, granulation tissue formation and epithelialization which were also confirmed by histopathological and biochemical examinations. Our data also indicate that there is a rise in the expression of proliferating cell nuclear antigen in skin tissues of Cur-treated rats in the Burn group. The results clearly substantiate the beneficial effects of the topical application of Cur in the acceleration of wound healing.

Concepts: Scar, Wound healing, Collagen, Extracellular matrix, Healing, Medical emergencies, Injuries, Granulation tissue

28

Hypertrophic scar (HS) is a cutaneous fibrotic disorder characterized by persistent inflammation, excessive proliferation of fibroblasts, and abundant accumulation of extracellular matrix (ECM) proteins. Pleiotrophin (PTN) is a highly conserved and secreted ECM-associated protein that belongs to a novel family of heparin-binding cytokines with multiple biological functions. The aim of this study was to detect and compare the expression and localization of PTN in HS tissues and normal skin tissues. Surgically removed HS tissue samples and site-matched normal skin specimens were obtained from 18 patients during the scar excision and reconstructive surgery. Semi-quantitative RT-PCR, Western blot analysis and immunohistochemistry were used to determine PTN gene expression and localization in skin tissues. Compared with the normal skin tissues, PTN was highly expressed at both mRNA and protein levels in HS tissues (P < 0.01). In immunohistochemical staining, PTN protein was localized in the cells of both epidermis and dermis in skin tissues, and there were increased staining intensity of PTN in HS tissues than in normal skin samples. In conclusion, elevated expression of PTN is likely to be involved in the pathogenesis of HS. Further studies are still required to elucidate the exact role of PTN in HS formation.

Concepts: Antibody, DNA, Gene, Gene expression, Molecular biology, Scar, Skin, Tissue