[Detection of some markers of the early phase of the inflammatory and reparative process in mechanical skin injuries]. / Vyyavlenie nekotorykh markerov rannei fazy vospalitel'no-reparativnogo protsessa pri mekhanicheskikh povrezhdeniyakh kozhi.

OBJECTIVE: To examine the applicability of IHC staining method: with TGF-ß1 antibodies (serial examination, statistically processed results) and with mast cell tryptase antibodies for injuries vitality determination. MATERIAL AND METHODS: 261 skin autopsy samples with mechanical injuries from 29 persons were divided to 3 groups (87 in each group): vital injuries, postmortal injuries, control non-injured samples. A routine histological examination using standard H&E stain and IHC both with TGF-ß1 and mast cells tryptase antibodies was performed. RESULTS AND CONCLUSION: The positive TGF-ß1 staining (score 2-3) was found in keratinocytes in vitally injured skin and the negative or weak one (score 0-1) was found in control postmortally injured and non-injured samples. Additionally, dermal TGF-ß1 expression was found in some vitally injured skin samples. The difference between vitally injured skin and control samples was statistically significant (p<0.05). No significant difference of dermal mast cells density in groups 1, 2, 3 was found.

Injerto de piel libre como tratamiento exitoso de una úlcera de Marjolin / Free skin graft as a successful treatment of a Marjolin ulcer

Introducción: la úlcera de Marjolin hace referencia a la aparición de un carcinoma de células escamosas ulcerado sobre un área previamente lesionada, crónicamente inflamada o con cicatrices. Se estima que solo el 1,7 % de las heridas crónicas se malignizan. Caso clínico: se trata de una mujer de 76 años que presentó una úlcera venosa crónica en la región maleolar de diez años de evolución que se había extendido. Se realizó una biopsia insicional y se obtuvo un carcinoma de células escamosas, por lo que se realizó la resección del tejido afectado, cubriendo el área con injerto autólogo de piel libre, fenestrado, de espesor parcial, y posteriormente se realizaron curas durante la hospitalización y el manejo ambulatorio, con lo que se obtuvieron resultados satisfactorios. Discusión: la resección-desbridamiento quirúrgico de la úlcera de Marjolin y el cierre con injerto libre de piel permitió la evolución satisfactoria y la cicatrización de las lesiones.(AU)

Introduction: Marjolin’s ulcer refers to the appearance of ulcerated squamous cell carcinoma on a previously injured,chronically inflamed or scarred area; it is estimated that only 1.7 % of chronic wounds become malignant.Case report: this is a 76-year-old woman who presented a chronic venous ulcer in the malleolar region of ten years ofevolution that had spread. An incisional biopsy was taken, resulting in squamous cell carcinoma, for which resectionof the affected tissue was performed: the area was covered with a free, fenestrated, partial-thickness autologous skingraft. Later, cures were carried out during hospitalization and ambulatory management, obtaining satisfactory results.Discussion: the surgical resection-debridement of the Marjolin ulcer and the closure with a free skin graft allowed thesatisfactory evolution and healing of the lesions.(AU)

Improved in vitro wound healing in response to a superoxidised solution.

OBJECTIVE: This study assessed wound healing in response to a superoxidised solution using an in vitro wound healing model. METHOD: Prewounded reconstructed full-thickness human skin models were treated with 10µl of either superoxidised solution (Hydrocyn aqua, Bactiguard South East Asia Sdn. Bhd., Malaysia) or Dulbecco's phosphate buffered saline (DPBS) and incubated at 37°C for up to seven days, with additional treatments added every 48 hours. On days 0, 1, 2, 5 and 7, triplicate samples were taken for specific immunostaining against cytokeratin 14 and vimentin. At each timepoint, horizontal and vertical wound diameters were measured to demonstrate wound closure. Maintenance media was taken at the same timepoints for the measurement of secreted proinflammatory cytokines interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-ɑ. RESULTS: At day 1, the superoxidised solution induced significantly lower diameter measurements compared with baseline data at day 0. Both treatment groups demonstrated significantly lower diameter measurements by day 2 when compared with the baseline; however, the average wound size of samples treated with the superoxidised solution was significantly lower when compared to the DPBS-treated group (p<0.05). No significant difference in expression of any proinflammatory was identified at any timepoint. CONCLUSION: Application of the superoxidised solution resulted in significantly improved wound closure over the first 48 hours in comparison to DPBS-treatment. Furthermore, application of the superoxidised solution did not induce significant proinflammatory effects, despite the significantly reduced wound diameter.

Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.

Wound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employed in wound-repairing activities. This work investigates the mesenchymal stem cells in the combined capacity of the bone marrow (BMMSC) for wound healing and Cystoseira sp. Algae extract in immunosuppressed rats. High-resolution liquid chromatography / MS investigation of Cystoseira extract revealed the prevalence of fatty acids that have wound-soothing potential. From constructed PPI network for wound healing and further analysis through molecular docking and molecular dynamics (MD) simulation experiments suggested that cystalgerone metabolite may be responsible for the wound healing-promoting effect of Cystoseira extract. According to the CD marker characterization of the BMMSC, 98.21% of them expressed CD90, and 97.1% expressed CD105. Sixteen d after immunity suppression (by 40 mg/kg hydrocortisone daily), an incision was made in the dorsal skin of the rat. The treatments were applied for 16 d and samples were taken from the tested groups on the 8th, 14th, and 16th days. The BMMSCs / Cystoseira group showed significantly improved wound closure, thickness, density of new layers, and skin elasticity than the control group (p < 0.001). The BMMSCs / Cystoseira combination significantly reduced the oxidative indicators, pro-inflammatory cytokines, and immune markers, according to the RT-PCR gene expression study. In order to delve deeper into the complex interconnections among wound healing-related biological targets and pinpoint key factors in this complex process, we engaged in network pharmacology and computational research. Subsequently, we conducted a comprehensive computational analysis, including reverse docking, free energy (ΔG) computation, and molecular dynamics simulations, on the molecular structures of the annotated compounds. The purpose of this investigation was to identify potential new targets for these chemicals as well as any potential interactions they may have with different signaling pathways related to the wound healing process. Our research indicates that the primary compounds of Cystoseira holds potential wound healing therapeutic activity. Although more safety testing and clinical studies are required, the combination has great potential for regenerative medicine and could be a revolutionary advance in the healing of the wounds of immunosuppressed patients.

Decellularized Placental Sponge Seeded with Human Mesenchymal Stem Cells Improves Deep Skin Wound Healing in the Animal Model.

Skin injuries lead to a large burden of morbidity. Although numerous clinical and scientific strategies have been investigated to repair injured skin, optimal regeneration therapy still poses a considerable obstacle. To address this challenge, decellularized extracellular matrix-based scaffolds recellularized with stem cells offer significant advancements in skin regeneration and wound healing. Herein, a decellularized human placental sponge (DPS) was fabricated using the decellularization and freeze-drying technique and then recellularized with human adipose-derived mesenchymal cells (MSCs). The biological and biomechanical properties and skin full-thickness wound healing capacity of the stem cells-DPS constructs were investigated in vitro and in vivo. The DPS exhibited a uniform 3D microstructure with an interconnected pore network, 89.21% porosity, a low degradation rate, and good mechanical properties. The DPS and MSCs-DPS constructs were implanted in skin full-thickness wound models in mice. An accelerated wound healing was observed in the wounds implanted with the MSCs-DPS construct when compared to DPS and control (wounds with no treatment) during 7 and 21 days postimplantation follow-up. In the MSCs-DPS group, the wound was completely re-epithelialized, the epidermis layer was properly organized, and the dermis and epidermis' bilayer structures were restored after 7 days. Our findings suggest that DPS is an excellent carrier for MSC culture and delivery to skin wounds and now promises to proceed with clinical evaluations.

[Analysis of the types and functions of CD34+ cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing].

Objective: To analyze the types and functions of CD34+ cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing. Methods: This study was an experimental study. The CD34+ cell lineage tracing mouse was produced, and the visualization of CD34+ cells under the fluorescent condition was realized. Six male CD34+ cell lineage tracing mice aged 7-8 weeks (designated as diabetic group) were intraperitoneally injected with streptozotocin to establish a diabetic model, and full-thickness skin defect wounds were prepared on their backs when they reached 13 weeks old. Another 6 male CD34+ cell lineage tracing mice aged 13 weeks (designated as control group) were also subjected to full-thickness skin defect wounds on their backs. On post-injury day (PID) 4, wound tissue was collected from 3 mice in control group and 2 mice in diabetic group, and digested to prepare single-cell suspensions. CD34+ cells were screened using fluorescence-activated cell sorting, followed by single-cell RNA sequencing. The Seurat 4.0.2 program in the R programming language was utilized for dimensionality reduction, visualization, and cell clustering analysis of CD34+ cell types, and to screen and annotate the marker genes for each CD34+ cell subpopulation. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis was performed to analyze the differentially expressed genes (DEGs) of CD34+ fibroblasts (Fbs), smooth muscle cells (SMCs), keratinocytes (KCs), and chondrocyte-like cells (CLCs) in the wound tissue of two groups of mice for exploring cellular functions. Results: On PID 4, CD34+ cells in the wound tissue of both groups of mice were consisted of 7 cell types, specifically endothelial cells, Fbs, KCs, macrophages, T cells, SMCs, and CLCs. Among these, Fbs were further classified into 5 subpopulations. Compared with those in control group, the proportions of CD34+ endothelial cells, Fbs subpopulation 1, Fbs subpopulation 4, KCs, and CLCs in the wound tissue of mice were increased in diabetic group, while the proportions of CD34+ Fbs subpopulation 2, Fbs subpopulation 3, and SMCs were decreased. The marker genes for annotating CD34+ CLCs, endothelial cells, Fbs subpopulation 1, Fbs subpopulation 2, Fbs subpopulation 3, Fbs subpopulation 4, Fbs subpopulation 5, KCs, macrophages, SMCs, and T cells were respectively metastasis-associated lung adenocarcinoma transcript 1, fatty acid binding protein 4, Gremlin 1, complement component 4B, H19 imprinted maternally expressed transcript, Dickkopf Wnt signaling pathway inhibitor 2, fibromodulin, keratin 5, CD74 molecule, regulator of G protein signaling 5, and inducible T-cell co-stimulator molecule. KEGG and GO enrichment analysis revealed that, compared with those in control group, DEGs with significant differential expression (SDE) in CD34+ Fbs from the wound tissue of mice in diabetic group on PID 4 were significantly enriched in terms related to inflammatory response, extracellular matrix (ECM) organization, regulation of cell proliferation, and aging (with Pvalues all <0.05), DEGs with SDE in CD34+ SMCs were significantly enriched in terms related to cell migration, apoptotic process, positive regulation of transcription, and phagosome (with P values all <0.05), DEGs with SDE in CD34+ KCs were significantly enriched in terms related to mitochondrial function, transcription, and neurodegenerative diseases (with P values all <0.05), and DEGs with SDE in CD34+ CLCs were significantly enriched in terms related to rhythm regulation, ECM, and viral infection (with P values all <0.05). Conclusions: CD34+ cells display high heterogeneity in the healing process of full-thickness skin defect wounds in both normal mice and diabetic mice. The significantly enriched functions of DEGs with SDE in CD34+ cell subpopulations in the wound tissue of the two mouse groups are closely related to the wound healing process.

Insights and mechanics-driven modeling of human cutaneous impact injuries.

Cutaneous damage mechanisms related to dynamic fragment impacts are dependent on the impact angle, impact energy, and fragment characteristics including shape, volume, contact friction, and orientation. Understanding the cutaneous injury mechanism and its relationship to the fragment parameters is lacking compromising damage classification, treatment, and protection. Here we develop a high-fidelity dynamic mechanics-driven model for partial-thickness skin injuries and demonstrate the influence of fragment parameters on the injury mechanism and damage sequence. The model quantitatively predicts the wound shape, area, and depth into the skin layers for selected impact angles, kinetic energy density, and the fragment projectile type including shape and material. The detailed sequence of impact damage including epidermal tearing that occurs ahead of the fragments initial contact location, subsequent stripping of the epidermal/dermal junction, and crushing of the underlying dermis are revealed. We demonstrate that the fragment contact friction with skin plays a key role in redistributing impact energy affecting the extent of epidermal tearing and dermal crushing. Furthermore, projectile edges markedly affect injury severity dependent on the orientation of the edge during initial impact. The model provides a quantitative framework for understanding the detailed mechanisms of cutaneous damage and a basis for the design of protective equipment.

Application of Aleppo pine extract for skin burn treatment.

OBJECTIVE: To investigate the Pinus halepensis extracts and determine its healing and antibacterial effects, and to evaluate the treatment of skin burns. METHODS: Aqueous and ethanolic extracts and topical based on Aleppo pine plant extracts were prepared. Thirty male and female Wistar rats were used to study the cutaneous toxicity of extracts from the bark of P. halepensis. The extracts' healing potential for burn wounds were also assessed by evaluating the clinical and macroscopic aspects of the wounds. The antibacterial activity of crude extracts of P. halepensis as well as its wound healing abilities was verified in this investigation. RESULTS: In animals with acute dermal toxicity, there were no signs of treatment-related toxicity or death. The extracts of these plants could be transformed into phytomedicines for the treatment of infected wounds. The results demonstrated that formulated ointments are successful in treating second-degree burns in rats and may be suitable for the short-term therapeutic treatment of second-degree burns. CONCLUSION: This study successfully answered our problem, regarding the efficacy of our extract for treating second-degree burns in rats. Further studies are needed to confirm these results by identifying the molecules responsible for these activities and examining their mechanism of action.

Comparative evaluation of two different xenogenic acellular matrices on full-thickness skin wound healing.

OBJECTIVE: The purpose of the study was to compare the healing potential of bubaline small intestinal matrix (bSIM) and fish swim bladder matrix (FSBM) on full-thickness skin wounds in rabbits. METHOD: Four full-thickness skin wounds (each 20×20mm) were created on the dorsum of 18 rabbits that were divided into three groups based on treatment: untreated sham control (I), implanted with double layers of bSIM (II) and implanted with double layers of FSBM (III). Macroscopic, immunologic and histologic observations were made to evaluate wound healing. RESULTS: Gross healing progression in the bSIM and FSBM groups showed significantly (p<0.05) less wound contraction compared with the sham group. The IgG concentration in rabbit sera was significantly (p<0.05) lower in the FSBM group compared with the bSIM group by enzyme-linked immunosorbent assay. The stimulation index of peripheral blood lymphocytes was significantly (p<0.05) lower in the FSBM group compared with the bSIM group by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Implantation of FSBM resulted in improved re-epithelialisation, neovascularisation and fibroplasia. CONCLUSION: The FSBM is a more effective dermal substitute when compared with the bSIM for full-thickness skin wound repair in rabbit.

Fitofotodermatosis: el peligro del sol y las plantas para la piel / Phytofotodermatosis: the danger of the sun and plants for the skin

Presentamos el caso de un paciente que padeció una reacción cutánea intensa tras el contacto con los frutos y las hojas de una higuera y posterior exposición solar. Se trata de una reacción no inmunológica llamada fitofotodermatosis. Es una erupción inflamatoria de la piel que se produce tras el contacto con sustancias fototóxicas (furocumarinas o psoralenos) y que puede llegar a ser de gran intensidad. Por ello requiere una anamnesis exhaustiva y su conocimiento por parte del equipo médico de Atención Primaria y pediatría, ya que su diagnóstico diferencial puede ser muy complejo.(AU)

We report the case of a patient who developed an intense skin reaction after contact with the fruits and leaves of a fig tree and subsequent sun exposure. This is a non-immunological reaction called phytophotodermatosis. It is an inflammatory skin rash that occurs after contact with phototoxic substances (furocoumarins or psoralens) and could be very intense. That is why it requires an in-depth history; its knowledge by primary care physicians and paediatricians, is important because the differential diagnosis could be very complex.(AU)

Cutaneous Radiation Injuries: REAC/TS Clinical Experience.

The Radiation Emergency Assistance Center/Training Site (REAC/TS) is one of the US Department of Energy (DOE)/National Nuclear Security Administration (NNSA) Nuclear Emergency Response Team (NEST) assets and has been responding to radiological incidents since 1976. REAC/TS is in the Oak Ridge Institute for Science and Education (ORISE). A critical part of the REAC/TS mission is to provide emergency response, advice, and consultation on injuries and illnesses caused from ionizing radiation. Fortunately, radiation injuries are not frequent, but when they occur, they are more likely to be cutaneous radiation injuries (CRI) or internal contamination. In this paper, we will review selected cases from the REAC/TS experience in order to illustrate cutaneous patterns of injury and treatment options.

[Research advances on the role of microRNA engineered exosomes in diabetic wounds].

Diabetic wounds are a common complication in patients with diabetes, which is difficult to treat. Current treatment methods for diabetic wounds include debridement, functional dressing coverage, negative pressure therapy, bone cement filling, and skin grafting, etc. MicroRNA (miRNA) engineered exosomes have shown promising potential in diabetic wound repair due to the ability to alleviate inflammation, stimulate angiogenesis, and promote collagen deposition and re-epithelialization. Related researches are being actively carred out. This paper reviews the pathophysiological characteristics of diabetic wounds, the characteristics of miRNA and exosomes, the engineering methods for exosomes loaded with miRNA, and the mechanism of miRNA engineered exosomes in promoting healing of diabetic wounds, aiming to provide a reference basis for the future clinical application of miRNA engineered exosomes in diabetic wounds.