Perspectivas dos pais acerca da interação socialde crianças com cicatrizes de queimaduras / Parents' perspectives on the social interactionof children with burn scars

As queimaduras provocam efeitos físicos e psicológicos devastadores nos indivíduos, sobretudo em crianças e adolescentes, e podem modificar a qualidade de vida da pessoa. O objetivo foi analisar o impacto das cicatrizes por queimaduras em crianças menores de oito anos na interação com amigos, família e escola, na perspectiva dos pais. Estudo quantitativo de corte transversal realizado com os pais de crianças <8 anos de idade, vítimas de queimaduras e internadas em um Centro de Tratamento de Queimados no norte do Paraná e acompanhadas ambulatorialmente, de 2017 a 2020. A coleta de dados ocorreu por meio de dois instrumentos: caracterização sociodemográfica e clínica; e Brisbane Burn Scar Impact Profile. Realizou-se análise descritiva e teste Qui-quadrado utilizando-se o SPSS®. Participaram 34 pais cujas crianças sofreram queimaduras, sendo 52,9% de 1 a 3 anos de idade, 58,8% sexo masculino, 82,2% por agente etiológico térmico e a internação foi de 73,5% devido à Superfície Corpórea Queimada ≤20%. Após a alta os pais identificaram que as cicatrizes de queimaduras tinham "um pouco" e "pouco" impacto nas cicatrizes nas relações de amizade e na interação social. Para os pais, prevaleceu a resposta "nada" de impacto, seguido por "um pouco" e "muito" na escola, nas brincadeiras, nos jogos e nas atividades diárias. Quanto às reações emocionais e ao humor, a maior parte dos pais considerou "nada". Nesse sentido, os pais responderam às questões quanto à própria percepção sobre as atividades diárias do seu filho e, em geral, a cicatriz de queimadura não impactou na qualidade de vida da criança.

Burns cause devastating physical and psychological effects on individuals, especially children and adolescents, and can change a person's quality of life. The objective was to analyze the impact of burn scars in children under eight years of age in the interaction with friends, family and school, from the parents' perspective. Quantitative cross-sectional study carried out with the parents of children <8 years old who were victims of burns and admitted to a Burn Treatment Center in northern Paraná and monitored on an outpatient basis, from 2017 to 2020. Data collection occurred using two instruments: sociodemographic and clinical characterization; Brisbane Burn Scar Impact Profile. Descriptive analysis and Chi-square test were performed using SPSS®. 34 parents participated whose children suffered burns, 52.9% aged 1 to 3 years old, 58.8% male, 82.2% due to thermal etiological agent and 73.5% hospitalization was due to Burned Body Surface ≤ 20%. After discharge, the parents identified that the burn scars had "a little" and "little" impact on the scars in friendship relationships and social interaction. For parents, the answer "nothing" of impact prevailed, followed by "a little" and "a lot" in school, play, games and daily activities. As for emotional reactions and mood, most parents considered "nothing" that impacted the child with burn scars. In this sense, parents answered questions regarding their own perception of their child's daily activities and, in general, the burn scar did not impact the child's quality of life.

Predation scars provide a new method to distinguish native and invasive crab predation on mollusc prey.

Crab species are increasingly important socioeconomic resources that are threatened by human exploitation, climate change, and invasive species, such as European green crabs (Carcinus maenas). However, the continued health of their populations is often uncertain given the limited long-term population data, necessitating alternate approaches to ensure their continued viability. Furthermore, C. maenas are one of the most highly invasive and destructive marine species globally, posing a threat to local ecosystems and species, including socioeconomically important crabs and their mollusc prey. Improved understanding of C. maenas invasions and their impacts on local crab and mollusc resources is therefore vitally important. Here, we present a new method for identifying species-level presence and relative abundances of important crab species, including invasive C. maenas, from the scars they leave on their prey. We conducted controlled manipulative feeding experiments in which individuals of Dungeness crabs (Metacarcinus magister), red rock crabs (Cancer productus), and C. maenas, were allowed to attack snails (Tegula funebralis) and produce sublethal shell damage. Resulting shell damage was photographed and landmarked for geometric morphometric analyses to determine any differences in the shape of shell damage between crab species. There were statistically significant differences between the shape of shell damage created by all three crab species (p < .0001). Shell damage formed a gradient from narrow/deep (C. productus) to shallow/wide (C. maenas) with M. magister as an intermediate form. Our method provides a novel, cost-effective tool for long-term species-specific reconstructions of crab populations and assessing the broader ecological impacts of C. maenas invasions that can inform management and mitigation for these three important crab species.

Oregano essential oil-infused mucin microneedle patch for the treatment of hypertrophic scar.

Hypertrophic scar (HS) manifests as abnormal dermal myofibroblast proliferation and excessive collagen deposition, leading to raised scars and significant physical, psychological, and financial burdens for patients. HS is difficult to cure in the clinic and current therapies lead to recurrence, pain, and side effects. In this study, a natural amphiphilic polymer mucin is used to prepare a dissolving microneedle (muMN) that is loaded with oregano essential oil (OEO) for HS therapy. muMN exhibits sufficient skin/scar tissue penetration, quick skin recovery time after removal, good loading of natural essential oil, fast dissolution and detachment from the base layer, and good biocompatibility to applied skin. In the rabbit HS model, OEO@muMN shows a significant reduction in scar thickness, epidermal thickness index, and scar elevation index. OEO@muMN also attenuates the mean collagen area fraction and decreases the number of capillaries in scar tissues. Biochemical Assay reveals that OEO@muMN significantly inhibits the expression of transforming growth factor-ß1 (TGF-ß1) and hydroxyproline (HYP). In summary, this study demonstrates the feasibility and good efficacy of using the anti-proliferative and anti-oxidative OEO for HS treatment. OEO@muMN is an efficient formulation that holds the potential for clinical anti-HS application. muMN is an efficient platform to load and apply essential oils transdermally.

Scar/WAVE drives actin protrusions independently of its VCA domain using proline-rich domains.

Cell migration requires the constant modification of cellular shape by reorganization of the actin cytoskeleton. Fine-tuning of this process is critical to ensure new actin filaments are formed only at specific times and in defined regions of the cell. The Scar/WAVE complex is the main catalyst of pseudopod and lamellipodium formation during cell migration. It is a pentameric complex highly conserved through eukaryotic evolution and composed of Scar/WAVE, Abi, Nap1/NCKAP1, Pir121/CYFIP, and HSPC300/Brk1. Its function is usually attributed to activation of the Arp2/3 complex through Scar/WAVE's VCA domain, while other parts of the complex are expected to mediate spatial-temporal regulation and have no direct role in actin polymerization. Here, we show in both B16-F1 mouse melanoma and Dictyostelium discoideum cells that Scar/WAVE without its VCA domain still induces the formation of morphologically normal, actin-rich protrusions, extending at comparable speeds despite a drastic reduction of Arp2/3 recruitment. However, the proline-rich regions in Scar/WAVE and Abi subunits are essential, though either is sufficient for the generation of actin protrusions in B16-F1 cells. We further demonstrate that N-WASP can compensate for the absence of Scar/WAVE's VCA domain and induce lamellipodia formation, but it still requires an intact WAVE complex, even if without its VCA domain. We conclude that the Scar/WAVE complex does more than directly activating Arp2/3, with proline-rich domains playing a central role in promoting actin protrusions. This implies a broader function for the Scar/WAVE complex, concentrating and simultaneously activating many actin-regulating proteins as a lamellipodium-producing core.

Combined biomaterial scaffold and neuromodulation strategy to promote tissue repair and corticospinal connectivity after spinal cord injury in a rodent model.

Spinal cord injury (SCI) damages the trauma site, leading to progressive and secondary structural defects rostral and caudal to the injury. Interruption of ascending and descending pathways produce motor, sensory, and autonomic impairments, driving the need for effective therapies. In this study, we address lesion site repair and promoting descending projections using a combined biomaterial-neuromodulation strategy in a rat model of cervical contusion SCI. To promote tissue repair, we used Chitosan fragmented physical hydrogel suspension (Cfphs), a biomaterial formulation optimized to mitigate inflammation and support tissue remodeling. To promote descending projections, we targeted the corticospinal motor system with dual motor cortex-trans-spinal direct current neuromodulation to promote spared corticospinal tract (CST) axon sprouting rostral and caudal to SCI. Cfphs, injected into the lesion site acutely, was followed by 10 days of daily neuromodulation. Analysis was made at the chronic phase, 8-weeks post-SCI. Compared with SCI only, Cfphs alone or in combination with neuromodulation prevented cavity formation, by promoting tissue remodeling at the injury site, abrogated astrogliosis surrounding the newly formed tissue, and enabled limited CST axon growth into the remodeled injury site. Cfphs alone significantly reduced CST axon dieback and was accompanied by preserving more CST axon gray matter projections rostral to SCI. Cfphs + neuromodulation produced sprouting rostral and caudal to injury. Our findings show that our novel biomaterial-neuromodulation combinatorial strategy achieves significant injury site tissue remodeling and promoted CST projections rostral and caudal to SCI.

Combined Stromal Vascular Fraction and Fractional CO2 Laser Therapy for Hypertrophic Scar Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Hypertrophic scars (HTSs) result from aberrant wound healing processes, leading to raised, thickened tissue with functional discomfort and cosmetic concerns. Current treatments, including corticosteroid injections and laser therapy, have limitations. Stromal vascular fraction (SVF) therapy and CO2 laser treatment offer promising avenues, with SVF therapy showing regenerative potential and CO2 laser therapy promoting precise tissue removal and wound healing. This study aims to investigate the combined application of SVF therapy and CO2 laser treatment for HTS, aiming to enhance treatment efficacy, tissue remodeling, and aesthetic outcomes, ultimately improving patient satisfaction in HTS management. METHOD: PubMed, Scopus, Embase, and Web of Science databases have been searched for relevant studies. The "R" software (version 4.3.1) along with the "tidyverse" and "meta" statistical packages utilized to analyze data related to the efficiency of this combined method. A random-effects model was fitted to the data. For each study, continuous outcomes were pooled by calculating the standardized mean difference, along with their 95% confidence intervals. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. RESULTS: Six articles fulfilled our inclusion criteria and were included in our review. Results from the pooled analysis of Vancouver Scar Scale (VSS) scores across three included studies indicated a significant impact of the SVF+CO2 method on VSS scores post-treatment (SMD=-3.0144; 95% CI:-4.3706 to -1.6583, p<0.0001). However, analysis of transepidermal water loss levels before and after treatment showed no significant difference (SMD=-2.7603; 95% CI: -6.8729 to 1.3522; p=0.1883). Comparatively, in a pooled analysis of two studies, the combined SVF+CO2 method demonstrated superior efficacy in VSS scores compared to other methods (SMD= -1.3573; 95% CI: -2.2475 to -0.4672, p = 0.0028), with moderate heterogeneity across studies (I^2=23.0%, p = 0.2545). CONCLUSION: The combined application of SVF and CO2 laser treatment shows significant promise in improving hypertrophic scars' appearance and texture. The SVF+CO2 method demonstrates superior efficacy compared to other modalities, suggesting its potential as a valuable therapeutic approach for hypertrophic scar management. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

New challenges in scar therapy: the novel scar therapy strategies based on nanotechnology.

The pathological mechanism of pathological scar is highly complex, encompassing the abnormalities of diverse cytokines, signaling pathways and regulatory factors. To discover more preferable scar treatment options, a variety of distinct approaches have been utilized clinically. Nevertheless, these treatments possess certain side effects and are inclined to relapse. Presently, pathological scar treatment remains a clinical conundrum, and there is an urgent demand for treatment methods that are safe, less traumatic and have lower recurrence rates. New drug delivery systems, novel therapeutic drugs and therapy strategies can enable drugs to permeate the skin effectively, decrease side effects, enhance drug efficacy and even achieve pain-free self-administration. Currently, novel nanotechnologies such as nanomicroneedles, photodynamics mediated by novel photosensitizers, bioelectrical stimulation and 3D printed dressings have been developed for the effective treatment of pathological scars. Additionally, innovative nanoscale fillers, including nano-fat and engineered exosomes, can serve as novel therapeutic agents for the efficient treatment of pathological scars. The intervention of nanomaterials can enhance drug absorption, stabilize and safeguard the active ingredients of drugs, delay or control drug release and enhance bioavailability. This article reviews these new treatment strategies for scar to explore novel approaches for efficient and safe for keloid treatment.

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Bikini line one-anastomosis gastric bypass (BLOGB): initial report.

BACKGROUND: This study introduces a new access method for one-anastomosis gastric bypass (OAGB) by placing ports at the bikini line. OBJECTIVE: To describe our initial experience and assess the feasibility, safety, and effectiveness of this novel access. SETTING: University Hospital. METHODS: This prospective case-control study included 72 patients: 42 were allocated to the bikini line one-anastomosis gastric bypass (BLOGB) group, and 30 were assigned to the control group. Exclusion criteria included a history of major abdominal surgery, hiatal hernia, extensive lower abdominal adhesions, or a body mass index (BMI) exceeding 55 kg/m2. RESULTS: The mean preoperative BMI of the study sample was 40.01 ± 2.84. Weight loss was satisfactory, with the highest percent excess weight loss (%EWL) observed at 12 months: 90.88 ± 7.90 and 91 ± 7.11 (p = 0.474) in both groups, respectively. Both groups showed no significant differences in operative complications, hospital stay, weight loss, or resolution of obesity-associated diseases. However, the BLOGB patients had a longer mean operative time of 110.71 ± 17.72 min compared to 98 ± 18.27 min in the control group (p = 0.002). Moreover, they experienced less postoperative pain and reported greater satisfaction with the appearance of their scars. CONCLUSION: BLOGB was found to be potentially feasible, safe, and effective, offering improved aesthetic outcomes and reduced postoperative pain. This approach may be suitable for a select group of patients concerned with scar appearance. However, large-scale studies are necessary to ensure that safety is not compromised in pursuit of aesthetic benefits.

Advanced Wound Healing and Scar Reduction Using an Innovative Anti-ROS Polysaccharide Hydrogel with Recombinant Human Collagen Type III.

Excessive fibrotic scar formation during skin defect repair poses a formidable challenge, impeding the simultaneous acceleration of wound healing and prevention of scar formation and hindering the restoration of skin integrity and functionality. Drawing inspiration from the structural, compositional, and biological attributes of skin, we developed a hydrogel containing modified recombinant human collagen type III and thiolated hyaluronic acid to address the challenges of regenerating skin appendages and improving the recovery of skin functions after injury by reducing fibrotic scarring. The hydrogel displayed favorable biocompatibility, antioxidant properties, angiogenic potential, and fibroblast migration stimulation in vitro. In a rat full-layer defect model, it reduced inflammation, promoted microvascular formation, and significantly enhanced the wound healing speed and effectiveness. Additionally, by upregulating fibrosis-associated genes, such as TGFB1, it facilitated collagen accumulation and a beneficial balance between type I and type III collagen, potentially expediting skin regeneration and functional recovery. In conclusion, the utilization of rhCol III-HS demonstrated considerable potential as a wound dressing, offering a highly effective strategy for the restoration and rejuvenation of complete skin defects.

Multifunctional Nanofiber Membranes Constructed by Microfluidic Blow-Spinning to Inhibit Scar Formation at Early Intervention Stage.

Pathological scarring has been a challenge in skin injury repair since ancient times, and prophylactic treatment in the early stages of wound healing usually results in delayed wound healing. In this study, poly(ethylene oxide) (PEO) and chitosan (CTS) were used as carrier materials to construct multifunctional pirfenidone (PFD)/CTS/PEO (PCP) nanofiber membranes (NFMs) loaded with PFD by microfluidic blow-spinning (MBS). MBS is a good method for quickly, safely, and greenly constructing large-area manufacturing of inexpensive NFMs. PCP NFMs were uniform in external morphology, with diameters ranging from 200 to 500 nm. The encapsulation efficiency of the drug-loaded PCP NFMs was above 80%, which had a good slow release, visualization, water absorption, and biocompatibility. The inhibitory effect of PCP NFMs on normal human dermal fibroblasts was dose-dependent and inhibited the expression of the transforming growth factor-ß1/SMAD family member 3 (TGF-ß1/SMAD3) signaling pathway. PCP NFMs showed significant antibacterial effects against both Staphylococcus aureus and Escherichia coli. In the rabbit ear scar experiment, the wound healed about 70% on day 5 and almost completely on day 10 after PCP-3 NFMs treatment, with the thinnest scar tissue, skin color, tenderness close to normal tissue, and a Vancouver scar scale score of less than 5. PCP-3 NFMs had good effects on anti-inflammatory, wound healing, and collagen-I deposition reducing effects. In conclusion, PCP-3 NFMs can both promote wound healing and intervene to inhibit pathological scarring in advance, making them a potential multifunctional wound dressing for early prevention and treatment of pathological scarring.

Shh regulates M2 microglial polarization and fibrotic scar formation after ischemic stroke.

BACKGROUND: Fibrotic scar formation is a critical pathological change impacting tissue reconstruction and functional recovery after ischemic stroke. The regulatory mechanisms behind fibrotic scarring in the central nervous system (CNS) remain largely unknown. While macrophages are known to play a role in fibrotic scar formation in peripheral tissues, the involvement of microglia, the resident immune cells of the CNS, in CNS fibrosis requires further exploration. The Sonic Hedgehog (Shh) signaling pathway, pivotal in embryonic development and tissue regeneration, is also crucial in modulating fibrosis in peripheral tissues. However, the impact and regulatory mechanisms of Shh on fibrotic scar formation post-ischemic stroke have not been thoroughly investigated. METHODS: This study explores whether Shh can regulate fibrotic scar formation post-ischemic stroke and its underlying mechanisms through in vivo and in vitro manipulation of Shh expression. RESULTS: Our results showed that Shh expression was upregulated in the serum of acute ischemic stroke patients, as well as in the serum, CSF, and ischemic regions of MCAO/R mice. Moreover, the upregulation of Shh expression was positively correlated with fibrotic scar formation and M2 microglial polarization. Shh knockdown inhibited fibrotic scar formation and M2 microglial polarization while aggravating neurological deficits in MCAO/R mice. In vitro, adenoviral knockdown or Smoothened Agonist (SAG) activation of Shh expression in BV2 cells following OGD/R regulated their polarization and influenced the expression of TGFß1 and PDGFA, subsequently affecting fibroblast activation. CONCLUSION: These results suggest that Shh regulates M2 microglial polarization and fibrotic scar formation after cerebral ischemia.

Post-surgical Hypertrophic Scar in a Patient With Unilateral Temporomandibular Joint Ankylosis.

Wound healing is nature's response to injury. It is a complex and dynamic process involving multiple biological systems aimed at restoring the integrity of damaged tissue. The temporomandibular joint (TMJ) is a critical anatomical structure that facilitates jaw movement and function. TMJ ankylosis is a pathological condition characterized by fusion of the mandibular condyle to the glenoid fossa resulting in severe restriction in mouth opening and significantly reduced mandibular movements. This condition affects the patient's quality of life by deteriorating major functions such as mastication, speech, oral hygiene, breathing, facial growth, and esthetics. Gap arthroplasty is the mainstay of treatment. There are various surgical approaches to TMJ such as Al-Kayat Bramley, Popowich's modification, Blair's inverted hockey stick, Dingman's, Thoma's, endaural, postauricular, and rhytidectomy incisions. Wound healing in the TMJ region poses unique challenges due to its complex anatomy and the high level of mechanical stress it endures. Following trauma to TMJ, hematomas are organized by fibrous granulation tissues and mesenchymal stem cells are recruited from adjacent bone by cytokines and chemokines such as bone morphogenetic proteins, transforming growth factor-beta and stromal cell-derived factor 1. These recruited mesenchymal cells differentiate into osteoprogenitors and osteoblasts to form new bone and fibroblasts to form a scar. In humans, scarring is the final outcome of the wound healing process, which has evolved to rapidly repair injuries. Scarring from injuries, surgeries, and burns places a significant burden on the healthcare system. Patients with major scars, especially children and adolescents, often experience long-term functional and psychological issues. This article aims to present a case of post-surgical hypertrophic scar in a patient after gap arthroplasty through Al-Kayat Bramley incision and the role of a multi-professional team to treat such wounds.

Multimodality Imaging for Rare Presentation of Placenta Increta in the First Trimester in a Patient with Previous Cesarean Section and Asherman Syndrome.

We report multi-modality imaging (Ultrasound and Magnetic Resonance Imaging) findings of a rare complication in a multi-gravida patient with history of Asherman syndrome presenting with placenta increta in a cesarean scar ectopic pregnancy. The appropriate diagnosis was established with imaging and patient was managed surgically with total abdominal hysterectomy and bilateral salpingectomy. Asherman syndrome and its management of hysteroscopic adhesiolysis are associated with increased odds of placenta accreta spectrum and postpartum hemorrhage. Patients with Asherman syndrome are considered high risk in pregnancy and should be closely monitored for placental site abnormalities during current and subsequent pregnancies.

Sporotrichosis caused by Sporotrix globosa in an elderly male farmer at the site of a cat scratch.

We report a case of sporotrichosis in an elderly male farmer at the site of a cat scratch scar. An 84-year-old Japanese farmer was scratched by his cat two months before his visit to our hospital. A skin biopsy was performed. Tissue culture revealed the presence of Sporothrix globosa. The patient was treated with oral itraconazole 200 mg/day for 13 months due to a slow healing ulceration, and the symptoms resolved. (71 words).

Patient-reported scar quality in paediatric and adult burn patients: A long-term multicentre follow-up study.

BACKGROUND: Burn scar maturation can take several years but is generally studied shortly after injury. Therefore, we investigated patient-reported scar quality up to 5-7 years post-burn. METHODS: Patients with ≤ 20 % total body surface area burned completed the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS 2.0) on the same scar at 3, > 18 months (median 28 months) and 5-7 years (median 63 months) post-burn. RESULTS: Fifty-eight patients (21 children; 37 adults) with a median total body surface area burned (TBSA) of 6.3 % participated. Average patient-reported scar quality (POSAS score) was generally worst at 3 months (median score: 4.2), best at 28 months (median score: 2.2) and intermediate at 63 months post-burn (median score: 3.4) (p < 0.001). Many patients (66 %) reported a median 1.8 point higher (worse) POSAS score at 63 months compared to 28 months post-burn, whereas 14 % reported an identical, and 21 % a lower (better) score. At any assessment, largest differences with normal skin were reported for scar colour. Univariate predictive factors of long-term patient-reported scar quality were scar quality at 3 months (p = 0.002) and 28 months post-burn (p < 0.001), full-thickness burn size (p = 0.033), length of hospital stay (p = 0.003), and number of surgeries (p < 0.001). CONCLUSION: Two-thirds of patients with burns up to 20 % TBSA scored the quality of their scars worse at 63 months compared to 28 months post-burn. Whether this corresponds to increased dissatisfaction with scars in the long term should be further investigated. These new insights add to the body of knowledge on scar maturation and underscores the importance of discussing patients' expectations.

Nanocellulose significantly reduces number of anesthetics, hospital days, and in-patient dressing changes compared to PU-Foam Dressing: A prospective cohort study in children.

BACKGROUND: Pediatric thermal injuries can have profound physical and psychological effects. Long-term care, including wound dressing selection, significantly impacts outcomes. This study compared treatment related variables and long-term results of bacterial nanocellulose (BNC) and polyurethane foam (PU-foam) dressings in pediatric burn care. METHODS: A prospective cohort study comparing BNC (2018-2020) and PU-foam (2016-2018) in pediatric burn patients. Data included demographics, wound characteristics, infection rates, treatment duration, anesthesia procedures, dressing changes, scar assessments (POSAS, VSS), colorimeter measurements, and quality of life (CDLQI). Regression analyses were performed to correct for differences in burn depth. RESULTS: After correction for burn depth, BNC showed a shorter hospital stay duration (p = 0.007), a lower number of procedures under general anesthesia (p<0.0001) and a reduced number of inpatient dressing changes (p = 0.006), compared to PU-foam, whereas wound infection rates did not differ between the treatment groups (p = 0.169). Scar outcomes (POSAS, VSS, colorimeter measurements) and quality of life (CDLQI) were comparable for both treatments. DISCUSSION: BNC dressing benefits include significantly fewer anesthesia procedures, a reduced number of inpatient dressing changes and a shorter hospital stays, supporting the use of BNC dressing. Long-term scar outcomes with BNC are comparable to established dressings like PU-foam. Further randomized trials are necessary to confirm these findings.

Single-cell sequencing analysis and bulk-seq identify IGFBP6 and TNFAIP6 as novel differential diagnosis markers for postburn pathological scarring.

BACKGROUND: If not accurately diagnosed and treated, postburn pathological scars, such as keloids and hypertrophic scars, can lead to negative clinical outcomes. However, differential diagnosis at the molecular level for postburn pathological scars remains limited. Using single-cell sequencing analysis, we investigated the genetic nuances of pathological scars at the cellular level. This study aimed to identify molecular diagnostic biomarkers to distinguish between postburn keloids and hypertrophic scars. METHODS: Single-cell sequencing, differential expression, and weighted co-expression network analyses were performed to identify potential key genes for discriminating between keloids and hypertrophic scars. Postburn clinical samples were collected from our centre to validate the expression levels of the identified key genes. RESULTS: Single-cell sequencing analysis unveiled 29 and 30 cell clusters in keloids and hypertrophic scars, respectively, predominantly composed of fibroblasts. Bulk differential gene analysis showed 96 highly expressed genes and 69 lowly expressed genes in keloids compared to hypertrophic scars. By incorporating previous research, Gene Set Enrichment Analysis was conducted to select fibroblasts as the focus of research. According to the single-cell data, 301 genes were stably expressed in fibroblasts from both types of pathological scars. Consistently, Weighted Gene Co-expression Network Analysis revealed that the blue module genes were mostly hub genes associated with fibroblasts. After intersecting fibroblast-related genes in single-cell data, Weighted Gene Co-expression Network Analysis-hub module genes, and bulk differential expression genes, insulin-like growth factor binding protein 6 and tumour necrosis factor alpha-induced protein 6 were identified as key genes to distinguish keloids from hypertrophic scars, resulting in diagnostic accuracies of 1.0 and 0.75, respectively. Immunohistochemical Staining and Quantitative Reverse Transcription PCR revealed that the expression levels of tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6 were significantly lower in postburn keloids than in hypertrophic scars- CONCLUSIONS: Tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6, exhibiting high diagnostic accuracy, provide valuable guidance for the differential diagnosis and treatment of postburn pathological scars.

The Causal Role of Uterine Fibroid in Keloid and Hypertrophic Scar: A Bidirectional Mendelian Randomization Study on European Populations.

BACKGROUND: The relationship between uterine fibroids and keloid/hypertrophic scars has been contradictory. Our research employs a bidirectional Mendelian Randomization (MR) approach to establish a clearer understanding of this potential causal link. OBJECTIVE: This study aimed to determine the effect of uterine fibroids on keloid/hypertrophic scars and the effect of keloid/hypertrophic scars on uterine fibroids. PURPOSE: We aimed to demonstrate the relationship between uterine fibroids and keloid/ hypertrophic scars. METHOD: Our bidirectional MR study utilized summarized data from genome-wide association studies (GWAS) focused on European populations. Our primary tool for establishing causality was the Inverse-Variance Weighted (IVW) method. To reinforce the IVW findings, we also applied four alternative MR methods: MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median. RESULT: The IVW method indicated a significant causal link, with uterine fibroids greatly raising the likelihood of developing keloids (Odds Ratio [OR] = 1.202, 95% Confidence Interval [CI]: 1.045-1.381; P=0.010) and hypertrophic scars (OR = 1.256, 95% CI: 1.039-1.519; P=0.018). Parallel results were observed with the MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median methods. Sensitivity analyses indicated robustness in these findings, with no evidence of heterogeneity or horizontal pleiotropy. Conversely, the reverse MR analysis did not demonstrate an increased risk of uterine fibroids due to keloids or hypertrophic scars. CONCLUSION: This study elucidates a significant causal effect of uterine fibroids on the development of keloid and hypertrophic scars, offering valuable insights into their pathogenesis and potential therapeutic targets.

Exosomal miR­194 from adipose­derived stem cells impedes hypertrophic scar formation through targeting TGF­ß1.

Hypertrophic scars, which result from aberrant fibrosis and disorganized collagen synthesis by skin fibroblasts, emerge due to disrupted wound healing processes. These scars present significant psychosocial and functional challenges to affected individuals. The current treatment limitations largely arise from an incomplete understanding of the underlying mechanisms of hypertrophic scar development. Recent studies, however, have shed light on the potential of exosomal non­coding RNAs interventions to mitigate hypertrophic scar proliferation. The present study assessed the impact of exosomes derived from adipose­derived stem cells (ADSCs­Exos) on hypertrophic scar formation using a rabbit ear model. It employed hematoxylin and eosin staining, Masson's trichrome staining and immunohistochemical staining techniques to track scar progression. The comprehensive analysis of the present study encompassed the differential expression of non­coding RNAs, enrichment analyses of functional pathways, protein­protein interaction studies and micro (mi)RNA­mRNA interaction investigations. The results revealed a marked alteration in the expression levels of long non­coding RNAs and miRNAs following ADSCs­Exos treatment, with little changes observed in circular RNAs. Notably, miRNA (miR)­194 emerged as a critical regulator within the signaling pathways that govern hypertrophic scar formation. Dual­luciferase assays indicated a significant reduction in the promoter activity of TGF­ß1 following miR­194 overexpression. Reverse transcription­quantitative PCR and immunoblotting assays further validated the decrease in TGF­ß1 expression in the treated samples. In addition, the treatment resulted in diminished levels of inflammatory markers IL­1ß, TNF­α and IL­10. In vivo evidence strongly supported the role of miR­194 in attenuating hypertrophic scar formation through the suppression of TGF­ß1. The present study endorsed the strategic use of ADSCs­Exos, particularly through miR­194 modulation, as an effective strategy for reducing scar formation and lowering pro­inflammatory and fibrotic indicators such as TGF­ß1. Therefore, the present study advocated the targeted application of ADSCs­Exos, with an emphasis on miR­194 modulation, as a promising approach to managing proliferative scarring.

A Strategy Involving Microporous Microneedles Integrated with CAR-TREM2-Macrophages for Scar Management by Regulating Fibrotic Microenvironment.

Dipeptidyl peptidase 4 (DPP4) positive fibroblasts play a pivotal role in scar development following skin injury. Heterogeneous vascular endothelial cells (ECs) within scarred areas retain the capacity to drive tissue regeneration and repair. Simultaneously, TREM2 macrophages play a crucial role in the progression and resolution of fibrosis by engaging in mutual regulation with ECs. However, effective strategies to inhibit scar formation through multi-factor regulation of the scar microenvironment remain a challenge. Here, CAR-TREM2-macrophages (CAR-TREM2-Ms) capable of targeting DPP4+ fibroblasts and modulating ECs subtype within the scar microenvironment are engineered to effectively prevent scarring. Hydrogel microporous microneedles (mMNs) are employed to deliver CAR-TREM2-Ms, which can effectively alleviate scar. Single-cell transcriptome sequencing (scRNA-seq) analysis reveals that CAR-TREM2-Ms can modify ECs fibrotic phenotype and regulate fibrosis by suppressing the profibrotic gene leucine-rich-alpha-2-glycoprotein 1 (Lrg1). In vitro experiments further demonstrate that CAR-TREM2-Ms improve the scar microenvironment by phagocytosing DPP4+ fibroblasts and suppressing TGFß secretion. This, in turn, inhibits the phenotypic conversion of LRG1 ECs and provides multifactorial way of alleviating scars. This study uncovers the evidence that mMNs attached to CAR-TREM2-Ms may exert vital influences on skin scarring through the regulation of the skin scar microenvironment, providing a promising approach for treating posttraumatic scarring.