In vitro and in vivo burn healing study of standardized propolis: Unveiling its antibacterial, antioxidant and anti-inflammatory actions in relation to its phytochemical profiling.

BACKGROUND: Natural propolis has been used since decades owing to its broad-spectrum activities. Burn injuries are a global health problem with negative impacts on communities. Bacterial infections usually accompany burns, which demand implementation of antibiotics. Antibiotics abuse led to emergence of microbial drug resistance resulting in poor treatment outcomes. In such instances, the promising alternative would be natural antimicrobials such as propolis. OBJECTIVE: Full chemical profiling of propolis and evaluation of in vitro antibacterial, antioxidant and anti-inflammatory activities as well as in vivo burn healing properties. METHODS: Chemical profiling of propolis was performed using Liquid chromatography (UHPLC/MS-PDA and HPLC-PDA). In vitro assessment was done using Disc Diffusion susceptibility test against Staphylococcus aureus and infected burn wound mice model was used for in vivo assessment. In vitro antioxidant properties of propolis were assessed using DPPH, ABTS and FRAP techniques. The anti-inflammatory effect of propolis was assessed against lipopolysaccharide/interferon-gamma mediated inflammation. RESULTS: UHPLC/MS-PDA results revealed identification of 71 phytochemicals, mainly flavonoids. Upon flavonoids quantification (HPLC-PDA), Pinocembrin, chrysin and galangin recorded high content 21.58±0.84, 22.73±0.68 and 14.26±0.70 mg/g hydroalcoholic propolis extract, respectively. Propolis showed concentration dependent antibacterial activity in vitro and in vivo burn healing via wound diameter reduction and histopathological analysis without signs of skin irritation in rabbits nor sensitization in guinea pigs. Propolis showed promising antioxidant IC50 values 46.52±1.25 and 11.74±0.26 µg/mL whereas FRAP result was 445.29±29.9 µM TE/mg. Anti-inflammatory experiment results showed significant increase of Toll-like receptor 4 (TLR4), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels. Nitric oxide and iNOS were markedly increased in Griess assay and western blot respectively. However, upon testing propolis against LPS/IFN-γ-mediated inflammation, TLR4, IL-6 and TNF-α expression were downregulated at transcriptional and post-transcriptional levels. CONCLUSION: Propolis proved to be a promising natural burn healing agent through its antibacterial, antioxidant and anti-inflammatory activities.

Malignant melanoma arising in a burn scar.

Secondary malignancies are rare but devastating complications of longstanding burn scars. Squamous cell carcinoma is the most common, followed by basal cell carcinoma and melanomas. There are fewer than 50 total reported cases of malignant melanomas arising in burn scars. We report a case of malignant melanoma arising within a longstanding burn scar confirmed by histology, FISH, and PRAME staining to further characterize melanomas arising in burn scars and to illustrate the diagnostic challenges they present.

"Simmer pus and grow flesh" method promotes chronic wound healing in rats via bFGF-Wnt ß-catenin signaling pathway.

The purpose of this study was to explore the mechanism of "simmer pus and grow meat" method based on bFGF regulating WNT / ß-Catenin signaling pathway. Of 100 SPF rats, 25 were randomly selected as blank group, and 75 rats were established chronic infectious wound model and divided into blank group, model group (normal saline treatment, n = 25), experimental group (purple and white ointment treatment, n = 25), and wet burn ointment group (wet burn treatment, n = 25). The wound healing rate of rats was compared. The protein expressions of PCAN, VEGF, bFGF, ß-Catenin, GSK-3ß and C-Myc in granulation tissues were detected. On the 7th day, the wound healing rate of the model group was lower than that of the other 3 groups (P<0.05), and the wound healing rate of the positive control group was higher than that of the experimental group and the control group (P<0.05). The expressions of bFGF, GSK-3ß and C-MyC in model group were higher than those in control group (P<0.05). The ß-catenin protein expression in the model group was lower than that in the control group (P<0.05), and the ß-catenin protein expression in the experimental group and the positive control group was higher than that in the model group (P<0.05). The expressions of PCAN and VEGF in model group were lower than those in model group (P<0.05). We found that Zibai ointment promotes chronic wound healing by modulating the bFGF/Wnt/ß-Catenin signaling pathway.

Analysis of cases of suicide by self-immolation in the post-mortem material of the Department of Forensic Medicine in Cracow. / Analiza przypadków samobójstw przez podpalenie w materiale sekcyjnym Zakladu Medycyny Sadowej w Krakowie.

Aim: Analysis of self-immolation cases and distribution of the resulting burns and their degree. Material and methods: The study included 16 cases from the Department of Forensic Medicine, Jagiellonian University Medical College in Cracow from 2000-2022 in which the cause of death was self-immolation. Based on the analysis of photographs and autopsy reports, drawings were made showing the exact distribution and nature of the injuries, moreover, the approximate percentage of body surface area affected was determined as well as the frequency of involvement of specific areas of the body, and the presence of previous diseases and mental disorders including previous suicide attempts. Results: 81% of victims were male. Two age groups were predominant among the cases analyzed, namely, individuals around the age of 20, and those between 50 and 60 years of age. 44% of the deceased had burns exceeding 80% of total body surface. The most frequently involved body areas were the extremities and chest as well as head and neck. Fourth-degree burns were most prevalent on the head and neck, third-degree burns prevailed on the upper and lower extremities, second-degree burns were mostly found on the chest, and first-degree burns - on the lower extremities. There were no cases of fourth-degree burns of the buttocks. 38% of the subjects had a history of substance abuse, 56% suffered from mental illnesses, whereas 31% attempted suicide in the past. Conclusions: The distribution of burns in self-immolation cases is inhomogeneous. The most frequently affected area was the head, neck, chest and extremities, most likely due to victims dousing themselves with a flammable substance from the top of the head through the chest. In all cases, the immediate cause of death was burn disease, regardless of the size of the body surface area affected by the burns. The majority of victims had a history of mental illness, substance abuse or suicide attempts.

Synchronous carcinoma and sarcoma in a burn scar: a treatment conundrum.

Marjolijn's ulcer is a malignant ulcer in a burn scar. Types of malignancy are squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Soft tissue sarcoma case reports indicate only one type of cancer. We present a patient in her 60s with a 10-year-old burn scar developing a biopsy-proven squamous cell carcinoma on the lateral aspect of the left thigh with metastatic superficial inguinal node. A wide excision and grafting of ulcer with ilioinguinal dissection done on left side. On the 12th postoperative day 2, subcutaneous swellings adjacent to the grafted area developed, on biopsy revealed to be pleomorphic sarcoma. PET CT scan revealed tumour deposits in the muscles of the left lower limb, liver and lung. There are no case reports of synchronous carcinoma and sarcoma in a burn scar. The case is reported for its rarity and the decision-making dilemma.

Rapid formed temperature-sensitive hydrogel for the multi-effective wound healing of deep second-degree burn with shikonin based scar prevention.

Burns are a significant public health issue worldwide, resulting in prolonged hospitalization, disfigurement, disability and, in severe cases, death. Among them, deep second-degree burns are often accompanied by bacterial infections, insufficient blood flow, excessive skin fibroblasts proliferation and collagen deposition, all of which contribute to poor wound healing and scarring following recovery. In this study, SNP/MCNs-SKN-chitosan-ß-glycerophosphate hydrogel (MSSH), a hydrogel composed of a temperature-sensitive chitosan-ß-glycerophosphate hydrogel matrix (CGH), mesoporous carbon nanospheres (MCNs), nitric oxide (NO) donor sodium nitroprusside (SNP) and anti-scarring substance shikonin (SKN), is intended for use as a biomedical material. In vitro tests have revealed that MSSH has broad-spectrum antibacterial abilities and releases NO in response to near-infrared (NIR) laser to promote angiogenesis. Notably, MSSH can inhibit excessive proliferation of fibroblasts and effectively reduce scarring caused by deep second-degree burns, as demonstrated by in vitro and in vivo tests.

Quantitative color analysis of burned bone to predict DNA quantity, quality, and genotyping success.

Badly burned skeletal remains are commonly submitted to forensic laboratories for victim identification via DNA analysis methods. Burned skeletal remains present many challenges for DNA analysis as they can contain low amounts of DNA which can also be damaged and degraded, resulting in partial or no STR profiles. Therefore, a simple, but effective screening method that identifies which samples may provide the most successful STR or mtDNA typing results for identification would enable forensic laboratories to save time, money, and resources. One metric that can be used and a screening method is the color of burned bone, as bone color changes with exposure to fire as temperature and length of exposure increase. This research developed a quantitative screening method based on the surface color of burned bone. The different visual bone colors (light brown, dark brown, black, gray, and white) were quantified using the Commission on Illumination L*a*b color space. These values were then compared to DNA yield, STR, and mtDNA profile completeness to identify whether the L*a*b values can predict genotyping success. A Bayesian network was constructed to determine the probability of STR typing success, given a set of L*a*b values. Results demonstrated that samples with an a* value greater than or equal to one and b* value greater than eight (light brown and dark brown burned samples) were the most predictive of STR typing success and mtDNA typing success. A decision tree for processing burned bones was constructed based on the color value thresholds.

Current Approaches to Wound Repair in Burns: How far Have we Come From Cover to Close? A Narrative Review.

Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.

Topical Noneuphoric Phytocannabinoid Elixir 14 Reduces Inflammation and Mitigates Burn Progression.

INTRODUCTION: Thermal injuries are caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and mitigating burn wound progression for improved healing outcomes. Previous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure. Therefore, the purpose of this study was to investigate whether a topical application of Noneuphoric Phytocannabinoid Elixir 14 (NEPE14) containing a full complement of phytocannabinoids (< 0.3% delta-9-tetrahydrocannabinol or cannabidiol) and other phytochemicals would mitigate burn wound progression in the treatment of deep partial-thickness burn wounds. METHODS: Deep partial-thickness burns were created on the dorsum of four anesthetized pigs and treated with NEPE14, Vehicle control, Silverlon, or gauze. The burns were assessed on postburn days 4, 7, and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), MolecuLight imagery (qualitative bacterial load), and biopsies for histology and immunohistochemistry (interleukin six and tumor necrosis factor-α). RESULTS: Topical treatment with NEPE14 significantly (P < 0.001) decreased inflammation (interleukin six and tumor necrosis factor-α) in comparison to control groups. It was also demonstrated that the reduction in inflammation led to mitigation of burn wound progression. In terms of wound healing and presence of bacteria, no statistically significant differences were observed. CONCLUSIONS: Topical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.

Segmentation and classification of skin burn images with artificial intelligence: Development of a mobile application.

AIM: This study was conducted to determine the segmentation, classification, object detection, and accuracy of skin burn images using artificial intelligence and a mobile application. With this study, individuals were able to determine the degree of burns and see how to intervene through the mobile application. METHODS: This research was conducted between 26.10.2021-01.09.2023. In this study, the dataset was handled in two stages. In the first stage, the open-access dataset was taken from https://universe.roboflow.com/, and the burn images dataset was created. In the second stage, in order to determine the accuracy of the developed system and artificial intelligence model, the patients admitted to the hospital were identified with our own design Burn Wound Detection Android application. RESULTS: In our study, YOLO V7 architecture was used for segmentation, classification, and object detection. There are 21018 data in this study, and 80% of them are used as training data, and 20% of them are used as test data. The YOLO V7 model achieved a success rate of 75.12% on the test data. The Burn Wound Detection Android mobile application that we developed in the study was used to accurately detect images of individuals. CONCLUSION: In this study, skin burn images were segmented, classified, object detected, and a mobile application was developed using artificial intelligence. First aid is crucial in burn cases, and it is an important development for public health that people living in the periphery can quickly determine the degree of burn through the mobile application and provide first aid according to the instructions of the mobile application.

Efficiency of the fatty acids extracted from the microalga Parachlorella kessleri in wound-healing.

Wound healing is a physiological process that results in the reconstruction and restoration of granulation tissue, followed by scar formation. We explored the impact of fatty acids in the form of oils on wound healing since they are part of membrane phospholipids and participate in the inflammatory response. This work investigated the efficiency of fatty acids extracted from microalga Parachlorella kessleri in treating excisional wounds and burns and evaluated their antioxidant activity. The rationale behind this investigation lies in the integral role fatty acids play in membrane phospholipids and their involvement in the inflammatory response. Among different nitrogen sources, glycine showed the highest biomass and lipid productivity (0.08 g L-1 d-1 and 58.37 µgml-1 day-1, respectively). Based on the percentage of polyunsaturated fatty acids that increased by 50.38 % in the Glycine culture of P. kessleri, both total antioxidant capacity and DPPH radical scavenging activity were higher in the Glycine culture than control culture. In 30 anaesthetized male mice divided into 6 groups, using either a burn or an excision, two identical paravertebral full-thickness skin lesions were created. Either oils of P. kessleri (extracted from control and glycine culture) ointments or the vehicle (placebo cream) were applied twice daily to the excisional wounds of mice, while mebo cream was used for burn wounds as well as P. kessleri oil. P. kessleri oils (control or glycine culture) showed a significant effect on the reduction of excisional wounds and burns. Histopathological analysis showed that angiogenesis, collagen fiber formation, and epidermis creation were some of the healing indicators that improved. The key elements for this healing property are omega -3 fatty acids, and both P. kessleri oils extracted from control and glycine culture have significant wound-healing effects. Oil of glycine culture of P. kessleri, however, displayed superior results in this regard.

Tranexamic acid reduces inflammation, edema and burn wound conversion in a rodent model.

Burn wound conversion is the observed process where superficial partial thickness burns convert into deep partial or full thickness burn injuries. This conversion process often involves surgical excision to achieve timely wound healing. Unfortunately, the pathophysiology of this phenomenon is multifactorial and poorly understood. Thus, a therapeutic intervention that may prevent secondary progression and cell death in burn-injured tissue is desirable. Recent work by our group and others has established that tranexamic acid (TXA) has significant anti-inflammatory properties in addition to its well-known anti-fibrinolytic effects. This study investigates TXA as a novel therapeutic treatment to mitigate burn wound conversion and reduce systemic inflammation. Sprague-Dawley rats were subjected to a hot comb burn contact injury. A subset of animals underwent a similar comb burn with an adjacent 30%TBSA contact injury. The interspaces represent the ischemic zones simulating the zone of stasis. The treatment group received injections of TXA (100 mg/kg) immediately after injury and once daily until euthanasia. Animals were harvested for analyses at 6 h and 7 days after injury. Full-thickness biopsies from the ischemic zones and lung tissue were assessed with established histological techniques. Plasma was collected for measurement of damage associated molecular patterns (DAMPs), and liver samples were used to study inflammatory cytokines expression. Treatment with TXA was associated with reduced burn wound conversion and decreased burn-induced systemic inflammatory response syndrome (SIRS). Lung inflammation and capillary leak were also significantly reduced in TXA treated animals. Future research will elucidate the underlying anti-inflammatory properties of TXA responsible for these findings.

Pilot Application of SEM/EDX Analysis on Suspected Cigarette Burns in a Forensic Autopsy Case of Child Abuse.

ABSTRACT: Cigarette burn lesions present forensic scenarios that are often difficult to investigate, both from a morphological diagnostic point of view and with regard to the mode of infliction, especially if the victim is unable to speak or has died. Although there may be the suspicion for a lesion to be produced by a lit cigarette, to date one can only rely on the morphological aspects that characterize it, and there is a lack of tools to reach the most evidence-based diagnosis possible. This limitation arose when managing a forensic autopsy case of possible child abuse that resulted in the death of the child, characterized by the presence of 3 suspicious cigarette burn lesions. We therefore decided to perform scanning electron microscopy/energy-dispersive x-ray (SEM/EDX) spectrometry analysis on these lesions and on the cigarette butt found at the crime scene. At the same time, SEM/EDX was applied to the analysis of an unlit cigarette in its entirety (obtained from the same source package as the cigarette butt), a positive control skin sample with an iatrogenic cigarette burn injury, and a negative control skin sample. Among the various compounds highlighted on compositional analysis, only sulfuric anhydride (SO 3 ) and phosphoric anhydride (P 2 O 5 ) showed a highly significant distribution pattern by being found in the autopsy samples, the cigarette butt, the tobacco of the unlit cigarette, and the positive skin control. Considering this, cigarette burns appear to follow Locard's principle as well, and similarly to other lesions, SEM/EDX allowed the diagnosis of cigarette burn lesions, already suspected morphologically, to be corroborated. Therefore, SEM/EDX is confirmed as a helpful tool in forensic pathology investigations.

Iterative refinement of a histologic algorithm for burn depth categorization based on 798 consecutive burn wound biopsies.

INTRODUCTION: Our group previously reported a burn biopsy algorithm (BBA-V1) for categorizing burn wound depth. Here, we sought to promulgate a newer, simpler version of the BBA (BBA-V2). METHODS: Burn wounds undergoing excision underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn wounds assessed as likely to heal by 21 days were imaged within 72 h of injury and at 21 days. A sample of 798 burn wound biopsies were classified by both BBAV1 and BBAV2 algorithms. For nonoperative burn wounds, the proportion of healing versus nonhealing pixels at 21 days after injury were compared. RESULTS: The 798 biopsies were classified by BBAV1 as 24% SPT, 47% DPT, 28% FT and by BBAV2 as 3% SPT, 67% DPT, and 30% FT (p < 0.0001). Overall, the proportion of biopsies whose wound reclassification changed from a nonoperative to operative pathway was 21% (95% CI: 18-24%). Nonoperative wounds judged at injury as being SPT contained 12.8 million pixels. Repeat 21-day imaging revealed 11.3 million healed pixels (accuracy = 89.6% (95% CI: 89.59-89.62)). CONCLUSIONS: BBA-V2 was associated with a significantly higher concordance with visual assessment for burn wounds clinically judged as deep partial and full thickness.

Tripterine Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting ROS/JNK Signaling.

Keloids are benign skin tumors characterized by excessive fibroblast proliferation and collagen deposition. The current treatment of keloids with hormone drug injection, surgical excision, radiotherapy, physical compression, laser therapy, cryotherapy often have unsatisfactory outcomes. The phytochemical compounds have shown great potential in treating keloids. Tripterine, a natural triterpene derived from the traditional Chinese medicine Thunder God Vine (Tripterygium wilfordii), was previously reported to exhibit an anti-scarring bioactivity in mouse embryonic fibroblast NIH/3T3 cells. Accordingly, our study was dedicated to explore its role in regulating the pathological phenotypes of keloid fibroblasts. Human keloid fibroblasts were treated with tripterine (0-10 µM) for 24 hours. Cell viability, proliferation, migration, apoptosis, and extracellular matrix (ECM) deposition were determined by CCK-8, EdU, wound healing, Transwell, flow cytometry, western blotting, and RT-qPCR assays. The effects of tripterine treatment on reactive oxygen species (ROS) generation and JNK activation in keloid fibroblasts were assessed by DCFH-DA staining and western blotting analysis. Tripterine at the concentrations higher than 4 µM attenuated the viability of human keloid fibroblasts in a dose-dependent manner. Treatment with tripterine (4, 6, and 8 µM) dose-dependently inhibited cell proliferation and migration, promoted cell apoptosis, reduced α-SMA, Col1, and Fn expression, induced ROS production, and enhanced JNK phosphorylation in keloid fibroblasts. Collectively, tripterine ameliorates the pathological characteristics of keloid fibroblasts that are associated with keloidformation and growth by inducing ROS generation and activating JNK signalingpathway.

Use of adipose derived stem cells accelerates the healing process in third-degree burns.

INTRODUCTION: Burns are defined as a traumatic injury, usually of thermal origin, that affects the epithelial and adjacent tissue and is classified according to the depth reached. Tissue repair involved in this type of injury is often a challenge both due to its severity and the multiplicity of complications. Regenerative medicine has focused on the use of low-level laser photobiomodulation therapy (LLLT) and adipose-derived stem cells (ADSC), especially in the early stages of the process, to promote better healing and shorten repair time. Therefore, aim of this study was to evaluate the action of LLLT (660 nm) and ADSC in the repair process of burned skin tissue and investigate the association of the techniques (LLLT and ADSC). MATERIALS AND METHODS: An in vivo study was carried out using 96 rats (Wister) with a scald burn model at a temperature of 95ºC, exposing the animal's back for 14 s. Animals were randomized into seven groups and three periods, five, 14 and 21 days. The groups included GC: Control group, ADSC-: Group treated with CD49d negative cells, ADSC+ : Group treated with positive CD49d cells, CULT: Group treated with conventional isolation cells, LLLT: Group treated only with LLLT Low Power Laser, ADSC-LLLT: Group treated with CD49d negative cells and LLLT. ADSC+LLLT: Group treated with positive CD49d cells and LLLT. The groups treated with LLLT (660 nm; 5 J/cm2) received irradiation three times a week, on alternate days for five, 14 and 21 days, according to the time of biopsy. ADSC-treated groups received one to three applications of the cells in a total volume of 1000 µL starting soon after the surgical debridement of the burn. Photographic monitoring was carried out at 5, 14 and 21 days after the beginning of the experiment to assess the degree of lesion contraction. Macroscopic, morphometric and histopathological analyzes were performed. RESULTS: We showed significant re-epithelialization as well as an improvement in the healing process in the ADSC+, LLLT and ADSC+LLLT groups. We observed effects in the reduction of the inflammatory phase, increase in angiogenesis, decrease in oedema, greater collagen deposition, and better organization of the extracellular matrix compared to the other treatments. Moreover, the immunomagnetic separation of ADSC cells through the expression of the CD49d protein proved to be a useful means to obtain a more homogeneous population of cells with a role in tissue regeneration compared to the ADSC- and CULT groups. CONCLUSION: In conclusion, the association of ADSC+ with LLLT was effective in accelerating the burn repair process, stimulating cell proliferation and formation of more normal skin tissue.

Rete ridges are decreased in dyschromic burn hypertrophic scar: A histological study.

Dyschromic hypertrophic scar (HTS) is a common sequelae of burn injury, however, its mechanism has not been elucidated. This work is a histological study of these scars with a focus on rete ridges. Rete ridges are important for normal skin physiology, and their absence or presence may hold mechanistic significance in post-burn HTS dyschromia. It was posited that hyper-, and hypo-pigmented areas of scars have different numbers of rete ridges. Subjects with dyschromic burn hypertrophic scar were prospectively enrolled (n = 44). Punch biopsies of hyper-, hypo-, and normally pigmented scar and skin were collected. Biopsies were paraffin embedded, sectioned, stained with H&E, and imaged. The number of rete ridges were investigated. Burn hypertrophic scars that healed without autografts were first investigated. The number of rete ridges was higher in normal skin compared to HTS that was either hypo- (p < 0.01) or hyper-pigmented (p < 0.001). This difference was similar despite scar pigmentation phenotype (p = 0.8687). Autografted hyper-pigmented scars had higher rete ridge ratio compared to non-autografted hyper-pigmented HTS (p < 0.0001). Burn hypertrophihc scars have fewer rete ridges than normal skin. This finding may explain the decreased epidermal adherence to underlying dermis associated with hypertrophic scars. Though, contrary to our hypothesis, no direct link between the extent of dyschromia and rete ridge quantity was observed, the differences in normal skin and hypertrophic scar may lead to further understanding of dyschromic scars.

C-TYPE LECTIN-2D RECEPTOR CONTRIBUTES TO HISTONE-INDUCED VASCULAR BARRIER DYSFUNCTION DURING BURN INJURY.

ABSTRACT: Severe burns are associated with massive tissue destruction and cell death where nucleus histones and other damage-associated molecular patterns are released into the circulation and contribute to the pathogenesis of multiple-organ dysfunction. Currently, there is limited information regarding the pathophysiology of extracellular histones after burns, and the mechanisms underlying histone-induced vascular injury are not fully understood. In this study, by comparing the blood samples from healthy donors and burn patients, we confirmed that burn injury promoted the release of extracellular histones into the circulation, evidenced by increased plasma levels of histones correlating with injury severity. The direct effects of extracellular histones on human endothelial monolayers were examined, and the results showed that histones caused cell-cell adherens junction discontinuity and barrier dysfunction in a dose-related manner. Like burn patients, mice subjected to a scald burn covering 25% total body surface area also displayed significantly increased plasma histones. Intravital microscopic analysis of mouse mesenteric microcirculation indicated that treatment with a histone antibody greatly attenuated burn-induced plasma leakage in postcapillary venules, supporting the pathogenic role of extracellular histones in the development of microvascular barrier dysfunction during burns. At the molecular level, intrigued by the recent discovery of C-type lectin domain family 2 member D (Clec2d) as a novel receptor of histones, we tested its potential involvement in the histone interaction with endothelial cells. Indeed, we identified abundant expression of Clec2d in vascular endothelial cells. Further proximity ligation assay demonstrated a close association between extracellular histones and endothelial expressing Clec2d. Functionally, in vivo administration of an anti-Clec2d antibody attenuated burn-induced plasma leakage across mesenteric microvessels. Consistently, Clec2d knockdown in endothelial cells partially inhibited histone-induced endothelial barrier dysfunction. Together, our data suggest that burn injury-induced increases in circulating histones contribute to microvascular leakage and endothelial barrier dysfunction via a mechanism involving the endothelial Clec2d receptor.

The effect of topical magnesium on healing of pre-clinical burn wounds.

BACKGROUND: Magnesium (Mg) is an essential factor in the healing process. This study aimed to evaluate the effect of Mg creams on healing burn wounds in the rat model. METHODS: To induce burns under general anaesthesia, a 2 × 2 cm2, 100 °C plate was placed for 12 s between the scapulas in 100 male adult Sprague Dawley rats. Animals were divided into five groups (n = 20); positive control (induced burn without treatment); vehicle control (received daily Eucerin cream base topically); comparative control (induced burn and treated daily with Alpha burn cream topically); Treatment 1 and 2 (received daily Mg cream 2% and 4% topically, respectively). All animals were bled for hematological assessment of malondialdehyde (MDA) and TNF-α and sacrificed on days 0, 1, 7, 14, and 21 after interventions for biomechanical, histological, and stereological studies. RESULTS: Stereologically speaking, in treatment groups an increase in dermal collagen volume and fibroblasts was noticed. In treatment groups, the length of vessels, angiogenesis, and skin stretch increased, but the wound area, MDA, and TNF-α level decreased. CONCLUSION: Mg cream was effective in healing burns.

Re-recognition of the role of roughness in keloid assessment.

BACKGROUND: Under visual observation, keloids are more rough than normal skin. This roughness may be used to assess the activity and severity of keloids but lacks the support of objective and accurate evidence. The purpose of this study was to verify the role of roughness in the development of keloids and to clarify the advantage of roughness in the comprehensive assessment of keloids. METHODS: Patients with keloids who attended Peking Union Medical College Hospital were recruited. Keloids were classified into progressive, stable, and atrophic stages based on the change in size over the past year and blood perfusion. The keloids were evaluated using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The roughnesses of the keloid and normal skin were measured using the Phaseshift Rapid In vivo Measurement Of the Skin (PRIMOS), and blood perfusion was measured using laser speckle contrast imaging (LSCI). RESULTS: Thirty-three patients with a total of 81 keloids were included. The surface roughness values Sa, Sq, and Sz of the keloid region were 243.70 (143.85-328.05), 316.20 (179.85-475.20), and 1708.20 (1098.30-4087.20), respectively, which were 4.87, 4.80, and 3.08 times higher than those of normal skin. There were significant differences in roughness among the different keloid stages. A significantly strong correlation between roughness and other assessed indices was found. CONCLUSIONS: Roughness as a morphological characteristic is of great value in the evaluation of keloids. It is recommended as an important examination for keloids.