Blocking the MIR155HG/miR-155 axis reduces CTGF-induced inflammatory cytokine production and α-SMA expression via upregulating AZGP1 in hypertrophic scar fibroblasts.

Hypertrophic scarring (HS) is a pathological condition characterized by excessive fibrosis and inflammation, resulting in excessive extracellular matrix formation in the skin. MIR155HG, a long non-coding RNA, is abnormally upregulated in fibrotic tissues; however, its underlying mechanism is poorly understood. Using single-cell sequencing data, we analyzed connective tissue growth factor (CTGF) expression in various cell types in HS and normal skin tissues and MIR155HG expression in clinical samples. To investigate the mechanism of fibrosis, an in vitro model using CTGF-treated hypertrophic scar fibroblasts (HSFBs) was established and qRT-PCR, western blotting and ELISA assays were performed to investigate the expression of interleukin (IL)-1ß, IL-6, and mesenchymal markers α-smooth muscle actin (α-SMA). CTGF stimulates MIR155HG level through phosphorylated STAT3 binding to the MIR155HG promoter. We analyzed the methylation of MIR155HG, assessed the levels of miR-155-5p/-3p in CTGF-treated HSFBs and identified differentially expressed genes among HS and NS samples using the Gene Expression Omnibus RNA sequencing data. The binding between miR-155-5p/-3p and AZGP1 was confirmed using a dual-luciferase assay and inflammatory cytokine production and α-SMA expression were investigated in rescue experiments. The findings revealed that CTGF elevated inflammatory cytokine production, α-SMA and MIR155HG expression in HSFBs. MIR155HG is upregulated in HS tissues due to low DNA methylation. Mechanistically, miR-155-5p/-3p was directly bound to MIR155HG 3'UTR. MIR155HG silencing inhibited cytokine production and α-SMA expression by repressing the generation of miR-155-5p/-3p in CTGF-treated HSFBs. Bioinformatics analysis and luciferase reporter assays revealed that miR-155-5p/-3p targets AZGP1. In addition, transfection with plasmids carrying AZGP1 cDNA significantly inhibited the signaling activity of miR-155-5p/-3 p-overexpressing HSFBs. Our findings highlight the importance of the MIR155HG/miR-155/AZGP1 axis in regulating cytokine production and α-SMA in HS.

Autologous nanofat harvested from donor site of full-thickness skin or skin flap grafting for the treatment of early postburn scarring: a case series.

Introduction: Postburn scarring often presents a specific reconstructive challenge from both functional and cosmetic perspectives. The purpose of this study was to investigate whether autologous nanofat harvested from the donor site of full skin or a skin flap can be reused for the treatment of early postburn scaring. Methods: From July 2018 to April 2022, patients with early postburn scarring underwent scar reconstruction surgery with full-thickness skin or a skin flap for a contour deformity and/or scar contracture, and autologous nanofat grafting was performed during the same operation. The Vancouver Scar Score (VSS) and the itch and pain scores were evaluated at the preoperation time point as well as at 2-3 weeks and 3-months postoperation. A comparison was made among the same patients at different time points. Results: A total of 17 patients, aged from 18 months to 62 years old were included in this analysis. The VSS was reduced from 10.00 ± 2.12 to 7.41 ± 1.277 at the 2-3-week postoperation time point, and to 5.53 ± 1.37 at the 3-month postoperation time point. The pain and itch score were reduced from 4.65 ± 1.37 and 6.35 ± 1.27, to 3.70 ± 1.10 and 4.94 ± 1.30 at the 2-3-week postoperation time point, and to 3.00 ± 1.28 and 3.94 ± 0.97 at the 3-month postoperation time point respectively. The VSS and pain and itch scores showed a statistically significant reduction (P < 0.05) at the 2-3-week and 3-month postoperative follow-ups compared with the preoperation time point. Conclusion: Autologous nanofat grafting from donor sites of full thickness skin or skin flap may be a promising treatment for an early postburn scaring as it promotes scar softening, improves itching and pain within the scar. However, this is a small case series with only 17 patients. Further conclusions need to be drawn through expanded samples for randomized controlled clinical trials. Lay Summary: Hypertrophic scarring is the most common complication after partial thickness burn injury, and the complex pathogenesis and prolonged dynamic process render treatments only marginally effective. In the past few decades, with the technological advances of liposuction and fat grafting, nanofat grafting has been used in a variety of surgical fields, including wound healing, scleroderma, facial rejuvenation, and neuralgia. However, the role of nanofat grafting is not well documented in the prevention and treatment of early postburn scarring. Full-thickness skin grafting or skin flap transplantation is the most common method for the reconstruction of a hypertrophic scaring until now. In the current study, we harvested subcutaneous fat during the preparation of the full-thickness skin or skin flap, prepared nanofat and injected it in the scar located at a nonsurgical site. Comparison of the pre- and postoperation scores for scar color, scar thickness, scar stiffness, and scar regularity showed that the postoperation scores were decreased significantly and that there was a significant improvement in scar pigmentation and thickness as well astheaesthetic outcome after treatment. Most importantly, reductions in the scores for pain and itching could be assessed objectively. It seems that the nanofat grafting is a potential method for prevention and treatment for early postburn scaring.

Emerging trends in the application of hydrogel-based biomaterials for enhanced wound healing: A literature review.

Currently, there is a rising global incidence of diverse acute and chronic wounds, underscoring the immediate necessity for research and treatment advancements in wound repair. Hydrogels have emerged as promising materials for wound healing due to their unique physical and chemical properties. This review explores the classification and characteristics of hydrogel dressings, innovative preparation strategies, and advancements in delivering and releasing bioactive substances. Furthermore, it delves into the functional applications of hydrogels in wound healing, encompassing areas such as infection prevention, rapid hemostasis and adhesion adaptation, inflammation control and immune regulation, granulation tissue formation, re-epithelialization, and scar prevention and treatment. The mechanisms of action of various functional hydrogels are also discussed. Finally, this article also addresses the current limitations of hydrogels and provides insights into their potential future applications and upcoming innovative designs.

Reconstruction of Scalp Defects Using Rotational Flaps After Revascularization Surgery in Patients with Moyamoya Disease.

OBJECTIVE: Treating scalp defects after revascularization surgery is difficult because the scalp microcirculation is severely compromised. We aimed to review the clinical effects of using rotational flaps in scalp defect reconstruction and explore risk factors for wound-related complications (WRC) after reconstruction surgery. METHODS: We retrospectively identified patients with scalp defects after combined revascularization surgery who were surgically treated with rotational flap reconstruction at our institution between January 2018 and December 2022. We analyzed treatment results in different surgical technique and revascularization strategy cohorts, including direct bypass superficial temporal artery branch selection, indirect bypass types, and skin incisions. RESULTS: Eleven patients were included. The superficial temporal artery parietal branch was selected for direct bypass surgery in 10 (90.9%) patients, 4 (40%) of whom had WRC after flap reconstruction. Five types of indirect bypass surgeries were performed; three patients treated by encephalo-duro-myo-arterio-perio-synangiosis and 1 patient treated by encephalo-duro-myo-perio-synangiosis had WRC after flap reconstruction. Question mark (n = 6, 54.5%), curved (n = 4, 36.65%), and Y-shaped (n = 1, 9.1%) incisions were used; in the first three incision cohorts, 2 patients in each cohort had WRC after flap reconstruction. CONCLUSIONS: Patients had the following commonalities that may be risk factors for WRC after flap reconstruction: 1) wounds with nonviable bone exposure after revascularization surgery; 2) three or more tissues used as donor tissues and donor tissues containing the periosteum; and 3) thin scalp around the defect.

Non-coding RNAs in hypertrophic scars and keloids: Current research and clinical relevance: A review.

Hypertrophic scars (HS) and keloids (KD) are lesions that develop as a result of excessive fibroblast proliferation and collagen deposition in response to dermal injury, leading to dysregulation of the inflammatory, proliferative, and remodeling phases during wound healing. HS and KD affect up to 90 % of the population and are associated with lower quality of life, physical health, and mental status in patients. Efficient targeted treatment represents a significant challenge, primarily due to our limited understanding of their underlying pathogenesis. Non-coding RNAs (ncRNAs), which constitute a significant portion of the human transcriptome with minimal or no protein-coding capacity, have been implicated in various cellular physiologies and pathologies and may serve as diagnostic indicators or therapeutic targets. NcRNAs have been found to be aberrantly expressed and regulated in HS and KD. This review provides a summary of the expression profiles and molecular mechanisms of three common ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in HS and KD. It also discusses their potential as biomarkers for the diagnosis and treatment of these diseases and provides novel insights into epigenetic-based diagnosis and treatment strategies for HS and KD.

Self-supervised neural network-based endoscopic monocular 3D reconstruction method.

Based on deep learning, monocular visual 3D reconstruction methods have been applied in various conventional fields. In the aspect of medical endoscopic imaging, due to the difficulty in obtaining real information, self-supervised deep learning has always been a focus of research. However, current research on endoscopic 3D reconstruction is mainly conducted in laboratory environments, lacking experience in dealing with complex clinical surgical environments. In this work, we use an optical flow-based neural network to address the problem of inconsistent brightness between frames. Additionally, attention modules and inter-layer losses are introduced to tackle the complexity of endoscopic scenes in clinical surgeries. The attention mechanism allows the network to better focus on pixel texture details and depth differences, while the inter-layer losses supervise the network at different scales. We have established a complete monocular endoscopic 3D reconstruction framework and conducted quantitative experiments on a clinical dataset using the cross-correlation coefficient as a metric. Compared with other self-supervised methods, our framework can better simulate the mapping relationship between adjacent frames during endoscope motion. To validate the generalization performance of our framework, we tested the model trained on the clinical dataset on the SCARED dataset and achieved equally excellent results.

Laparoscopic harvest and free transplantation of great omentum flap for extensive tissue defects in complex wounds.

Introduction: The repair of extensive tissue defects remains a challenge, although great progress has been made in reconstructive surgery. The transplantation of a single huge flap or several flaps in combination will inevitably result in donor-site morbidity. Here we report our experience in the repair of these wounds with laparoscopically harvested great omentum flaps. Methods: Twelve patients with extensive tissue defects caused by deep burn injury, avulsion injury, and open fracture underwent free omental flap transplantation and split-thickness skin grafting. The patient demographics, wound characteristics, and complications postsurgical operation were recorded. Prior to omentum flap transplantation, these patients underwent debridement, vacuum sealing drainage treatment, and/or fixation of fractures. All omentum flaps harvested using laparoscopic technique were anastomosed to recipient vessels, and split-thickness skin grafting was performed 14 days after omental flap transplantation. Results: The mean defect size was 471 cm2 and the mean omental flap size was 751.1 cm2. Among all 12 cases, the omental flaps survived well except for distal partial necrosis in one case. Skin grafting was also achieved in all cases, and all patients achieved complete wound coverage. All donor sites achieved primary healing without major complications. The mean follow-up time was 30 months with satisfactory appearance and functional outcome. Conclusion: For the reconstruction of extensive tissue defects in complex wounds, the free transfer of an omental flap may be an ideal option because of its well-vascularized and pliable tissue with reliable vascular anatomy, as well as minimized donor-site morbidity.

Insufficient SIRT1 in macrophages promotes oxidative stress and inflammation during scarring.

Macrophage is a critical regulator in wound healing and scar formation, and SIRT1 is related to macrophage activation and polarization, while the specific mechanism is still unclear. To explore the specific effects of SIRT1 in scarring, we established a skin incision mouse model and LPS-induced inflammation cell model. The expression of SIRT1 in tissue and macrophage was detected, and the level of SIRT1 was changed to observe the downstream effects. LPS-induced macrophages with or without SIRT1 deficiency were used for TMT-based quantitative proteomic analysis. SIRT1 was suppressed in scar while increased in macrophages of scar tissue. And macrophages were proven to be necessary for wound healing. In the early stage of wound healing, knockout of SIRT1 in macrophage could greatly strengthen inflammation and finally promote scarring. NADH-related activities and oxidoreductase activities were differentially expressed in TMT-based quantitative proteomic analysis. We confirmed that ROS production and NOX2 level were elevated after LPS stimulation while the Nrf2 pathway and the downstream proteins, such as Nqo-1 and HO-1, were suppressed. In contrast, the suppression of SIRT1 strengthened this trend. The NF-κB pathway was remarkably activated compared with the control group. Insufficient increase of SIRT1 in macrophage leads to over activated oxidative stress and activates NF-κB pathways, which then promotes inflammation in wound healing and scarring. Further increasing SIRT1 in macrophages could be a promising method to alleviate scarring. KEY MESSAGES: SIRT1 was suppressed in scar while increased in macrophages of scar tissue. Inhibition of SIRT1 in macrophage leads to further activated oxidative stress. SIRT1 is negatively related to oxidative stress in macrophage. The elevation of SIRT1 in macrophage is insufficient during scarring.

Competitive binding of CD226/TIGIT with poliovirus receptor regulates macrophage polarization and is involved in vascularized skin graft rejection.

End-stage organ failure often requires solid organ transplantation. Nevertheless, transplant rejection remains an unresolved issue. The induction of donor-specific tolerance is the ultimate goal in transplantation research. In this study, an allograft vascularized skin rejection model using BALB/c-C57/BL6 mice was established to evaluate the regulation of the poliovirus receptor signaling pathway using CD226 knockout or T cell immunoglobulin and ITIM domain (TIGIT)-crystallizable fragment (Fc) recombinant protein treatment. In the TIGIT-Fc-treated and CD226 knockout groups, graft survival time prolonged significantly, with a regulatory T cell proportion increase and M2-type macrophage polarization. Donor-reactive recipient T cells became hyporesponsive while responding normally after a third-party antigen challenge. In both groups, serum interleukin (IL)-1ß, IL-6, IL-12p70, IL-17A, tumor necrosis factor-α, interferon gamma, and monocyte chemoattractant protein-1 levels decreased, and the IL-10 level increased. In vitro, M2 markers, such as Arg1 and IL-10, were markedly increased by TIGIT-Fc, whereas iNOS, IL-1ß, IL-6, IL-12p70, tumor necrosis factor-α, and interferon gamma levels decreased. CD226-Fc exerted the opposite effect. TIGIT suppressed TH1 and TH17 differentiation by inhibiting macrophage SHP-1 phosphorylation and enhanced ERK1/2-MSK1 phosphorylation and nuclear translocation of CREB. In conclusion, CD226 and TIGIT competitively bind to poliovirus receptor with activating and inhibitory functions, respectively. Mechanistically, TIGIT promotes IL-10 transcription from macrophages by activating the ERK1/2-MSK1-CREB pathway and enhancing M2-type polarization. CD226/TIGIT-poliovirus receptor are crucial regulatory molecules of allograft rejection.

MicroRNA let-7d attenuates hypertrophic scar fibrosis through modulation of iron metabolism by reducing DMT1 expression.

Hypertrophic scar is an unavoidable result of wound healing following burns and trauma, which remains a challenging problem for clinicians. Previously, we demonstrated that exosomal microRNAs (miRs) of human amniotic epithelial cells accelerated wound healing and inhibited scar formation. However, the underlying mechanism is still unclear. In this particular study, we found that miR-let-7d reduced collagen deposition, and this was accompanied by decreased level of iron content in myofibroblasts. Importantly, inhibition of miR-let-7d in myofibroblasts accelerated collagen deposition and promoted cell proliferation. In addition, bioinformatics prediction combined with classical dual-luciferase reporter gene assay demonstrated that the cellular iron importer divalent metal transporter 1 (DMT1) was a target gene of miR-let-7d, and the miR-let-7d mimics inhibited the expression of DMT1 in myofibroblasts. Moreover, silencing of DMT1 with small interfering RNA (siRNA) reduced the deposition of extracellular matrix. Consistent with the results in vitro, the miR-let-7d mimics effectively ameliorated hypertrophic scar fibrosis in a rabbit ear hypertrophic scar model. Taken together, our results indicated for the first time that miR-let-7d attenuated hypertrophic scar fibrosis through modulation of iron metabolism by reducing iron uptake through DMT1, which may provide a novel therapeutic strategy for hypertrophic scar.

Feasibility, comparability and outcomes of three acquainted facial island flaps for periorbital defects reconstruction.

Severe coloboma of ocular malignant neoplasms post-resection poses a reconstructive challenge to surgeons. To compare the practicability, manipulability and outcomes of temporal (myocutaneous) flaps (TFs), forehead (supratrochlear artery/supraorbital artery) flaps (FFs) and buccal (facial artery) flaps (BFs) for periorbital defects reconstruction, a retrospective case series was conducted and evaluated between March 2014 and March 2021. Patient demographics and clinical parameters including age, gender, pathological diagnosis, operative methods, flap selection, operation time, aesthetic satisfaction and follow-up period were collected. The differences in complications were compared and assessed of the three flaps, including flap survival, venous congestion and donor site healing. Totally, 68 patients who underwent periorbital reconstructive operations because of common ocular malignant tumours were reviewed in this study. As for aesthetic satisfaction, a score more than "moderately dissatisfied" was obtained in 21 patients with TFs (95.5%), and of which the scores in FFs group were 12 cases (60%) and 16 cases with BFs reconstruction (61.5%) (P < .05). Severe microvascular complications underwent re-exploration operation occurred in one patient with FFs (1.5%) (P > .05). Notable flap necrosis was observed in two patients with BFs repair (2.9%) and in one case with FFs repair (1.5%), with no statistical difference between the three flap selections (P > .05). Moderate venous congestion occurred in one patient with TFs (1.5%), which was fully meliorated non-surgically. The three familiar facial island flaps are considered as minor trauma and time-saving process for reconstructing the extensive periorbital defects with comparable ranks of complications.

Adipose-Derived Stem Cell Exosomes Inhibit Hypertrophic Scaring Formation by Regulating Th17/Treg Cell Balance.

Aiming to reveal the role of ADCS-Exos in secretion of inflammatory factors, Th17 and regulatory T (Treg) cell differentiation from naïve CD4+ T cells in hypertrophic scaring formation and maturation is explored. ELISA, qRT-PCR, and immunoblotting are performed to assay the local inflammatory factors IL-6, IL-10, IL-17A, and TNF-α, and transcriptional factors of RORϒt and Foxp3, in scaring tissue from patients and mice wound models treated with or without ADCS-Exos. Immunohistochemistry staining and immunoblotting are conducted to assay the extracellular matrix (ECM) deposition in vitro and in vivo. The results show that IL-6, IL-10, IL-17A, TNF-α, RORϒt, and Foxp3 are increased on mRNA and protein levels in hypertrophic scaring compared with atrophic scaring and normal skin. Naïve CD4+ T cells treated with ADCS-Exos in vitro can produce significantly less IL-6, IL-17A, TNF-α, and RORϒt and more IL-10 and Foxp3 on mRNA and protein levels. In addition, mice in ADSC-Exos-treated group demonstrate less collagen deposition; decreased IL-17A, TNF-α, and RORϒt; and increased IL-10 and Foxp3 production.

Autologous Scar-Related Tissue Combined with Skin Grafting for Reconstructing Large Area Burn Scar.

BACKGROUND: This study introduced a novel method to reconstruct large areas of scarring caused by burns via combining autologous scar-related tissue with spit-thickness skin grafting (ASTCS). METHODS: 25 patients underwent reconstruction after scar resection surgeries around the joints were analyzed between Jan 2012 and Jan 2018. Patient demographics and clinical parameters were collected, autologous scar-related tissue was modified to meshed structure, and the split-thickness skin was acquired from the scalp. The scar was resected and punched by a meshing machine with a thickness of 0.3-0.5 mm at a ratio of 1:1. The secondary wounds were covered by the epidermis from a donor site. The surgical areas were bandaged for 7-10 days before the first dressing change. RESULTS: 25 patients (mean [SD] age, 26.4 [18.8] years; 16 [64%] men) underwent wounds reconstructive operations due to scar resection were reviewed. Wound location of 9 (22%), 8 (19.5%), 9 (22%), 7 (17.1%) and 8 (19.5%) cases were reconstructed in axillary, hand and wrist, popliteal fossa, elbow and neck, respectively. 39 sites of transplanted tissues survived well, and 2 sites were cured after two weeks of dressing changes. Except the analysis of injury causes, nutritional status, wound area and hospital days, patients with scar deformities in joint areas achieved satisfactory function by assessing the Vancouver Burn Skin Score and the Barthel Index Scale Scores after 12-month follow-up. CONCLUSIONS: Combining autologous scar-related tissue with skin grafting provided a novel method for treating large areas of burn scars with better functional outcomes.

The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species.

Background: Acute lung injury (ALI) is a common complication following severe burns. The underlying mechanisms of ALI are incompletely understood; thus, available treatments are not sufficient to repair the lung tissue after ALI. Methods: To investigate the relationship between the Notch pathway and burn-induced lung injury, we established a rat burn injury model by scalding and verified lung injury via lung injury evaluations, including hematoxylin and eosin (H&E) staining, lung injury scoring, bronchoalveolar lavage fluid and wet/dry ratio analyses, myeloperoxidase immunohistochemical staining and reactive oxygen species (ROS) accumulation analysis. To explore whether burn injury affects Notch1 expression, we detected the expression of Notch1 and Hes1 after burn injury. Then, we extracted pulmonary microvascular endothelial cells (PMVECs) and conducted Notch pathway inhibition and activation experiments, via a γ-secretase inhibitor (GSI) and OP9-DLL1 coculture, respectively, to verify the regulatory effect of the Notch pathway on ROS accumulation and apoptosis in burn-serum-stimulated PMVECs. To investigate the regulatory effect of the Notch pathway on ROS accumulation, we detected the expression of oxidative-stress-related molecules such as superoxide dismutase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 2, NOX4 and cleaved caspase-3. NOX4-specific small interfering RNA (siRNA) and the inhibitor GKT137831 were used to verify the regulatory effect of the Notch pathway on ROS via NOX4. Results: We successfully established a burn model and revealed that lung injury, excessive ROS accumulation and an inflammatory response occurred. Notch1 detection showed that the expression of Notch1 was significantly increased after burn injury. In PMVECs challenged with burn serum, ROS and cell death were elevated. Moreover, when the Notch pathway was suppressed by GSI, ROS and cell apoptosis levels were significantly increased. Conversely, these parameters were reduced when the Notch pathway was activated by OP9-DLL1. Mechanistically, the inhibition of NOX4 by siRNA and GKT137831 showed that the Notch pathway reduced ROS production and cell apoptosis by downregulating the expression of NOX4 in PMVECs. Conclusions: The Notch pathway reduced ROS production and apoptosis by downregulating the expression of NOX4 in burn-stimulated PMVECs. The Notch-NOX4 pathway may be a novel therapeutic target to treat burn-induced ALI.

Exosomes Derived From Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation-Induced Brain Injury by Activating the SIRT1 Pathway.

OBJECTIVE: Studies have shown that the therapeutic effects of mesenchymal stem cells (MSCs) are mediated in a paracrine manner, mainly through extracellular vesicles such as exosomes. Here, we designed a study to investigate whether exosomes derived from adipose-derived mesenchymal stem cells (ADMSC-Exos) had protective effects in a rat model of radiation-induced brain injury and in microglia. METHODS: Male adult Sprague-Dawley (SD) rats were randomly divided into three groups: the control group, the radiation group (30 Gy), and the radiation + exosomes group (30 Gy + 100 ug exosomes). Meanwhile, microglia were divided into four groups: the control group, the radiation group (10 Gy), the radiation + exosomes group (10 Gy + 4 ug exosomes), and radiation + exosomes + EX527 group (10 Gy + 4 ug exosomes + 100 nM EX527). Tissue samples and the levels of oxidative stress and inflammatory factors in each group were compared. RESULTS: Statistical analysis showed that after irradiation, ADMSC-Exos intervention in vivo significantly reduced the levels of caspase-3, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and promoted the recovery of superoxide dismutase (SOD), catalase (CAT), IL-4, and IL-10. Moreover, ADMSC-Exos intervention inhibited microglial infiltration and promoted the expression of SIRT1. Furthermore, the results in vitro showed that the above effects of ADMSC-Exos could be reversed by SIRT-1 inhibitor EX527. CONCLUSION: This study demonstrated that ADMSC-Exos exerted protective effects against radiation-induced brain injury by reducing oxidative stress, inflammation and microglial infiltration via activating the SIRT1 pathway. ADMSC-Exos may serve as a promising therapeutic tool for radiation-induced brain injury.

Memristor-Based Neural Network Circuit of Emotion Congruent Memory With Mental Fatigue and Emotion Inhibition.

Most memristor-based neural networks only consider a single mode of memory or emotion, but ignore the relationship between emotion and memory. In this paper, a memristor-based neural network circuit of emotion congruent memory is proposed and verified by the simulation results. The designed circuit consists of a memory module, an emotion module and an association neuron module. Varieties of memory and emotion functions are considered. The functions such as learning, forgetting, variable rate and emotion generation are implemented by the circuit. Furthermore, mental fatigue and emotion inhibition which are two important self-protective measures of the brain are realized in this paper on the basis of emotion congruent memory. Finally, the paper also considers the congruence between emotion and memory materials and the regulation of emotion on memory. The neural network circuit of emotion congruent memory can provide more references for the application of memristor.

Early intervention by Z-plasty combined with fractional CO2 laser therapy as a potential treatment for hypertrophic burn scars.

The aim of this study is to determine whether Z-plasty combined with fractional CO2 laser therapy can be a potential management option for hypertrophic burn scars in the proliferation stage. A total of 105 patients (46 male and 59 female patients) diagnosed with hypertrophic scars under tension but without any functional limitations were enrolled in this study. The Vancouver Scar Scale (VSS) score and scar height were analyzed and compared. The VSS scores for all scars were improved in all groups after treatment. The scar height was also significantly decreased in each group after treatment (P < 0.05). In the C group, the scar height decreased significantly to 2.62 ±â€¯0.21 mm, which was the maximum extent at the ≦ 6 month time point compared to the decrease in the other groups. Compared to the > 12 month time point for the C group, there was a significant difference between the ≦ 6 month time point for the L group and the > 12 month time point for the Z group. The proportion of satisfied patients was highest at 89.47% at the ≦6 month time point in the C group and lowest at 65.52% at the > 12 month time point in the L group. Six representative cases are presented. Z-plasty can decrease the thickness of a hypertrophic burn scar, which not only reduces the scar tension but also makes it easy to treat the scar with a fractional CO2 laser. Subsequent treatment with a fractional CO2 laser can better improve the color and texture of the scar.

A retrospective study to identify the optimal parameters for pulsed dye laser in the treatment of hypertrophic burn scars in Chinese children with Fitzpatrick skin types III and IV.

For over several decades, 595-nm pulsed dye laser (PDL) has been used effectively, reducing erythema and improving the pliability and texture of burn scars. Children usually tolerate PDL treatment as it is non-invasive and causes only mild pain compared to other laser treatments. However, currently, there are limited data on scar management in children who underwent PDL treatment, especially for Fitzpatrick skin types III and IV. The objective of the study was to identify the optimal parameters for the PDL treatment that induce inhibitory effects on scar tissue in children with Fitzpatrick skin types III and IV. Besides, the study assessed the usefulness of high-frequency ultrasound (20 MHz) and laser Doppler flowmetry in assessing these lesions. A total of 165 (79 males and 86 females) children with hypertrophic scars treated by PDL were assessed by the Vancouver scar scale (VSS), high-frequency ultrasound (20 MHz), and laser Doppler flowmetry. The parameters used for the 595-nm PDL treatment were pulse duration of 0.45 ms, fluence between 5 and 9 J/cm2, a spot size of 7 mm, and treatment intervals from 3 to 8 weeks. There were no significant differences between pretreatment and post-treatment in terms of the distribution of sex, type of skin color, and low and high fluences. While the mean scores of all scar parameters based on VSS, except thickness and pliability between pre and post-treatment, showed significant differences in ≤3-year-old children vs. to >3-year-old children, except for the subscore, a significant improvement was observed when PDL was initiated within 4 to 6 months of the scar age. In Chinese children with Fitzpatrick skin types III and IV, early intervention, appropriate treatment intervals, and low fluence of PDL were optimal parameters in treating hypertrophic burn scars. The combined high-frequency ultrasound and laser Doppler flowmetry assessment of scars helped assess these lesions and compare the efficacy of different treatment modalities.

IL-10 alleviates lipopolysaccharide-induced skin scarring via IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts.

Hypertrophic scar (HS) is a severe fibrotic skin disease. It has always been a major problem in clinical treatment, mainly because its pathogenesis has not been well understood. The roles of bacterial contamination and prolonged wound inflammation were considered significant. IL-10 is a potent anti-inflammatory cytokine and plays a pivotal role in wound healing and scar formation. Here, we investigate whether IL-10 alleviates lipopolysaccharide (LPS)-induced inflammatory response and skin scarring and explore the possible mechanism of scar formation. Our results showed that the expression of TLR4 and pp65 was higher in HS and HS-derived fibroblasts (HSFs) than their counterpart normal skin (NS) and NS-derived fibroblasts (NSFs). LPS could up-regulate the expression of TLR4, pp65, Col I, Col III and α-SMA in NSFs, but IL-10 could down-regulate their expression in both HSFs and LPS-induced NSFs. Blocking IL-10 receptor (IL-10R) or the phosphorylation of STAT3, their expression was up-regulated. In addition, in vitro and in vivo models results showed that IL-10 could alleviate LPS-induced fibroblast-populated collagen lattice (FPCL) contraction and scar formation. Therefore, IL-10 alleviates LPS-induced skin scarring via IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts by reducing ECM proteins deposition and the conversion of fibroblasts to myofibroblasts. Our results indicate that IL-10 can alleviate the LPS-induced harmful effect on wound healing, reduce scar contracture, scar formation and skin fibrosis. Therefore, the down-regulation of inflammation may lead to a suitable scar outcome and be a better option for improving scar quality.

PINK1/PRKN-dependent mitophagy in the burn injury model.

Burn injury leads to mitochondrial dysfunction and autophagy, also known as mitophagy. The alleviation of mitochondrial damage may be a potential method for the treatment of burn injury and complications. In this animal study, we analyzed the expression of mitochondrial damage- and mitophagy-related factors, specifically PINK1 and PRKN. The results showed mitochondria damage in the skin; compared with the normal control group, genes involved in the mitochondrial damage, such as Nrf-1, UQCRC2, CYC1, and NDUFA9, as well as in the mitophagy, including PINK1, PRKN, MFN1, and USP30, were differentially expressed. Furthermore, PINK1 interacted with PRKN and participated in mitophagy in the skin. In conclusion, our data reveal more about the mechanism underlying mitophagy in burns, providing a potential clinical treatment.