Inflammation-Responsive Hydrogel Accelerates Diabetic Wound Healing through Immunoregulation and Enhanced Angiogenesis.

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.

Development of a Wound Epithelialization Healing Model: Reducing the Impact of Contraction Healing on the Wound Surface.

Animal experiments are important in trauma-related studies because they simulate in vivo effects. Rodents are a good choice for preparing trauma models; however, contractile healing in rodents results in a healing pattern that differs considerably from that in humans. Therefore, this study developed a new rodent model that avoids contractile healing of the skin around the wound using an anticontraction ring, and the skin in the wound's center remains intact and acts as a source for epithelialized diffusion healing. Cell proliferation, migration, revascularization, and collagen secretion did not differ between the novel and conventional full-skin defect trauma models. However, the healing rate at various stages significantly differed between the 2 groups owing to differences in the healing patterns. And without effective treatment, the experimental group cannot heal. The stabilities of the novel and conventional methods were good regardless of operator or batch. In summary, this new animal trauma model provides a stable experimental environment similar to that in humans, which may promote trauma-related research.

Trehalose promotes functional recovery of keratinocytes under oxidative stress and wound healing via ATG5/ATG7.

Wounds are in a stressed state, which precludes healing. Trehalose is a stress metabolite that protects cells under stress. Here, we explored whether trehalose reduces stress-induced wound tissue damage. A stress model was prepared by exposing human keratinocytes to hydrogen peroxide (H2O2), followed by trehalose treatment. Trehalose effects on expression of the autophagy-related proteins ATG5 and ATG7 and cell proliferation and migration were evaluated. For in vivo verification, a wound model was established in Sprague-Dawley rats, to measure the effects of trehalose wound-healing rate and reactive oxygen species (ROS) content. Histological changes during wound healing and trehalose's effects on ATG5 and ATG7 expression, necrosis, and apoptosis were examined·H2O2 stress increased ATG5 and ATG7 expression in vitro, but this was insufficient to prevent stress-induced damage. Trehalose further increased ATG5/ATG7 levels, which restored proliferation and increased migration by depolymerizing the cytoskeleton. However, trehalose did not exert these effects after ATG5 and ATG7 knockout. In vivo, the ROS content was higher in the wound tissue than in normal skin. Trehalose increased ATG5/ATG7 expression in wound tissue keratinocytes, reduced necrosis, depolymerized the cytoskeleton, and promoted cell migration, thereby promoting wound healing.

Advancing translational research in neuroscience through multi-task learning.

Translational research in neuroscience is increasingly focusing on the analysis of multi-modal data, in order to account for the biological complexity of suspected disease mechanisms. Recent advances in machine learning have the potential to substantially advance such translational research through the simultaneous analysis of different data modalities. This review focuses on one of such approaches, the so-called "multi-task learning" (MTL), and describes its potential utility for multi-modal data analyses in neuroscience. We summarize the methodological development of MTL starting from conventional machine learning, and present several scenarios that appear particularly suitable for its application. For these scenarios, we highlight different types of MTL algorithms, discuss emerging technological adaptations, and provide a step-by-step guide for readers to apply the MTL approach in their own studies. With its ability to simultaneously analyze multiple data modalities, MTL may become an important element of the analytics repertoire used in future neuroscience research and beyond.

Synergistic Effects of Quercetin-Modified Silicone Gel Sheet in Scar Treatment.

Both silicone gel and quercetin are effective in scar treatment but have different action mechanisms. Quercetin is mainly applied in the gel form and can lead to poor adhesion of silicone gel sheet; therefore, they cannot be combined in clinical use. In this study, a silicone gel sheet that releases quercetin in a sustained manner for 48 hours was successfully developed. Four round scars (Ø: 1 cm) were made in the ears of New Zealand albino rabbits (n = 10). After scar healing, the rabbits were divided into four groups: blank control group with no treatment, silicone gel sheet group with dressing change every 2 days, quercetin group with dressing change three times daily, and combination treatment group with dressing change every 2 days. Scar assessment was performed 3 months later. Transepidermal water loss showed no difference between the combination treatment group and the silicone gel sheet group, but was lower than that in the quercetin group and the blank control group. Immunohistochemistry of CD 31 and proliferating cell nuclear antigen showed the following results: combination treatment group < silicone gel sheet group = quercetin group < blank control group. Polymerase chain reaction results showed that the expression of type-I and type-III collagen in the combination treatment group and the quercetin group was significantly lower than that in the other two groups. Thus, quercetin-modified silicone gel sheet combines the advantages of the two treatments and is more effective at inhibiting cell proliferation in scar tissue than either of the two treatments alone.

Comparative effectiveness of different therapies for treating striae distensae: A systematic review and network meta-analysis.

BACKGROUND: Striae distensae (SD) are common and aesthetically undesirable dermal lesions. The aim of this study is to comprehensively evaluate the effectiveness of different therapies in treating striae distensae using network meta-analysis. METHODS: A systematic search of electronic databases up to December 1, 2019 was conducted. Randomized controlled trails (RCTs) examining the effectiveness of different methods in treating striae distensae were included. The primary outcomes are clinical effective rate and patient's satisfaction degree. Risk of bias was assessed by the Cochrane risk of bias tool. Network meta-analysis was based on Bayesian framework. RESULTS: Fourteen trails that met the criteria with 651 subjects were included. The results of the network meta-analysis show that topical tretinoin combined bipolar radiofrequency showed the highest probability of being the best method to improve the clinical effectiveness and patient satisfaction rate of treating SD (84.5% and 95.7% respectively), closely followed by bipolar radiofrequency (75.3% and 84.3% respectively). Among laser treatment, CO2 fractional laser is superior to other lasers in the clinical effectiveness and patient satisfaction (72.0% and 58.1% respectively). Statistics showed the topical tretinoin was the worst-performing option in improving the clinical effectiveness and patient satisfaction rate of SD treatment (5.4% and 5.1% respectively). CONCLUSION: Based on the results of network meta-analysis, we recommend treating striae distensae with bipolar radio frequency combined topical tretinoin. The commonly used CO2 fractional laser can be considered as alternative treatment candidate. Additional large-scale RCTs are necessary to obtain more precise estimates of their relative efficacy.

Modification and utility of a rat burn wound model.

This study aimed to improve the conventional rat burn wound model and to validate its utility. In total, 60 Sprague-Dawley rats were divided equally into the control and experimental groups. Altogether, 60 burn wound models with zones of stasis were created in each group. Gross visual assessments of the burn wounds were performed at 0, 24, and 48 hours after burn creation. The rates of necrosis in the zones of stasis were calculated, and the blood flow from the wounds was examined. Wound tissues were collected 48 hours after the burn and subjected to hematoxylin and eosin staining to determine whether the models were successfully established. The model success rates were calculated. The success rate of the burn wound models was significantly different between the control group and the experimental group (93.33% [56/60] vs 100%; P = .042). The Cronbach's alpha values and the respective correlation coefficients indicated that the stability of the zones of stasis in the models on the two sides of the spine was higher in the experimental group than in the control group. The standard deviations of the rate of necrosis, blood flow, and density of necrotic cells and apoptosis cell density, and inflammatory factor content in the zones of stasis were smaller in the experimental group than in the control group at 48 hours after model construction. This suggested that the stability of repeated procedures was higher in the experimental group than in the control group. The novel device for creating burns in animal models facilitated the effective creation of zones of stasis for rat burn wound models. Both the model success rate and stability were higher compared with the conventional model construction method. In addition, the use of the novel device can better align with the requirements of self-controlled studies.

Development of a PHMB hydrogel-modified wound scaffold dressing with antibacterial activity.

Current wound scaffold dressing constructs can facilitate wound healing but do not exhibit antibacterial activity, resulting in high infection rates. We aimed to endow wound scaffold dressing with anti-infective ability by polyhexamethylenebiguanide (PHMB). We prepared PHMB hydrogel at varying concentrations (0.25%, 0.5%, 1%, 2%) and assessed release and cytotoxicity. PHMB hydrogel was added to the wound scaffold dressing to generate a PHMB hydrogel-modified wound scaffold dressing. Wound healing and infection prevention were evaluated using a full-thickness skin defect model in rats. In vitro, the hydrogel PHMB release time positively correlated with PHMB concentration, with 1% allowing sufficiently long release time to encompass the high-incidence period (3-5 days) of infection following wound scaffold dressing implantation. Implantation of 1% PHMB hydrogel into the skin did not cause adverse responses. in vitro cytotoxicity assays showed the PHMB hydrogel-modified wound scaffold dressing did not significantly affect proliferation of fibroblasts or vascular endothelial cells, 99.90% vs 99.84% for fibroblasts and 100.21% vs 99.28% for vascular endothelial cells at 21 days. Transplantation of PHMB hydrogel-modified wound scaffold dressing/unmodified wound scaffold dressing on the non-infected wounds of rats yielded no significant difference in relative vascularization rate, 47.40 vs 50.87 per view at 21 days, whereas bacterial content of the wound tissue in the PHMB hydrogel-modified wound scaffold dressing group was significantly lower than the unmodified wound scaffold dressing group, (1.80 ± 0.35) × 103 vs (9.34 ± 0.45) × 103 at 14 days. Prevalence of persistent wound infection in the rats receiving PHMB hydrogel-modified wound scaffold dressing transplantation onto infected wounds was significantly lower than the unmodified wound scaffold dressing group, 30% vs 100%. PHMB hydrogel-modified wound scaffold dressing exhibited suitable antibacterial ability, and its biological activity did not significantly differ from that of the unmodified wound scaffold dressing, thereby allowing it to effectively prevent infection following wound scaffold dressing implantation.

Burn-Related Dysregulation of Inflammation and Immunity in Experimental and Clinical Studies.

The purpose of this study was to evaluate burn-related variations of inflammation and immunity. Fifty-five mice were divided randomly into sham burn and burn groups. Eighty-seven hospitalized burn patients were also reviewed. In mice, neutrophils and monocytes were elevated significantly on post burn day (PBD 1). Lymphocytes were reduced on PBDs 1 and 3. Levels of serum tumor necrosis factor-α and interleukin-6 were highest on PBD 1. Interleukin-1ß levels were the highest on PBD 3. On PBD 3, CD4CD25T regulatory cells/CD4 cells in spleen were higher. On PBDs 1, 3, 7, and 14, percentage of splenic dendritic cells were significantly lower than the sham burn group. In patients, neutrophils and monocytes were significantly elevated on PBD 1. Levels declined but remained elevated at most days to PBD 7. Lymphocytes in burn groups 1 and 2 were reduced on PBDs 1 and 3, respectively. Our results exhibited that severe burn injury initiated a hyperinflammatory response and immunosuppression. PBDs 1 to 3 were important for changes in inflammation and immunosuppression.

Role of cytokines in host defense against Staphylococcus aureus skin infection.

Wound infection caused by Staphylococcus aureus (S. aureus) is a critical clinical problem due to long hospitalization times, significant morbidity and mortality, as well as considerable medical resource consumption. With the emergence of methicillin-resistant S. aureus (MRSA) strains, current antibiotic treatments are becoming ineffective in combatting S. aureus infection. Thus, a novel therapeutic strategy is required. Recent studies discovered that several cytokines in the infected wound area play protective roles against S. aureus infection. This review summarizes recent discoveries regarding the role of cytokines-mediated responses in host defense against S. aureus skin infection, and discusses their implications for future immunotherapy and vaccine development.

Risk Factors for Acute Kidney Injury in Patients With Burn Injury: A Meta-Analysis and Systematic Review.

Acute kidney injury (AKI) is a fatal complication of burn injury. Few systematic reviews to date have focused on the risk factors predisposing to AKI in patients with burn injury. The aim of this article is to identify the risk factors for the occurrence of AKI in burn patients, thus providing theoretical evidence for prevention and treatment. We performed a systematic review and meta-analysis of studies determining the prevalence, risk factors, and outcomes of AKI in patients with burn injury. An electronic search (up to April 2016) was performed using Pubmed, Embase, Web of Knowledge, and the Cochrane Library databases. Finally, a total of 18 articles (nine prospective cohort, seven retrospective cohort, two case-control) meeting the eligibility criteria were included. The pooled incidence of AKI was 39.6% (95% confidence interval = 34.7-44.4%). Significant risk factors for the occurrence of AKI included age (odds ratio [OR] = 3.78 [1.28-6.27]), TBSA (OR = 15.66 [11.01-20.31]), full-thickness TBSA (OR = 15.66 [11.01-20.31]), flame burn (OR = 1.56 [1.09-2.25]), inhalation injury (OR = 2.97 [1.80-4.89]), abbreviated burn severity index on admission (OR = 2.42 [1.87-2.98]), sequential organ failure assessment score on admission (OR = 2.69 [1.39-3.98]), baseline blood urea nitrogen (OR = 2.11 [0.72-3.51]), serum creatinine (OR = 2.69 [1.39-3.98]), and sepsis (OR = 4.42 [1.75-11.18]). In addition, burn patients with AKI are more likely to have long stay in intensive care unit and high mortality. AKI is a common complication and occurs at a remarkable rate in burn patients. We identified 10 variables as independent risk factors for the development of AKI in burn patients. Our findings may help clinicians to develop effective preventive and therapeutic strategies and provide appropriate, timely initial treatment.

Blood transfusions in severe burn patients: Epidemiology and predictive factors.

BACKGROUND: Blood is a vital resource commonly used in burn patients; however, description of blood transfusions in severe burns is limited. The purpose of this study was to describe the epidemiology of blood transfusions and determine factors associated with increased transfusion quantity. METHODS: This is a retrospective study of total 133 patients with >40% total body surface area (TBSA) burns admitted to the burn center of Changhai hospital from January 2008 to December 2013. The study characterized blood transfusions in severe burn patients. Univariate and Multivariate regression analyses were used to evaluate the association of clinical variables with blood transfusions. RESULTS: The overall transfusion rate was 97.7% (130 of 133). The median amount of total blood (RBC and plasma), RBC and plasma transfusions was 54 units (Interquartile range (IQR), 20-84), 19 units (IQR, 4-37.8) and 28.5 units (IQR, 14.8-51.8), respectively. The number of RBC transfusion in and outside operation room was 7 (0, 14) and 11 (2, 20) units, and the number of plasma was 6 (0.5, 12) and 21 (11.5, 39.3) units. A median of one unit of blood was transfused per TBSA and an average of 4 units per operation was given in the series. The consumption of plasma is higher than that of RBC. On multivariate regression analysis, age, full-thickness TBSA and number of operations were significant independent predictors associated with the number of RBC transfusion, and coagulopathy and ICU length showed a trend toward RBC consumption. Predictors for increased plasma transfusion were female, high full-thickness TBSA burn and more operations. CONCLUSIONS: Severe burn patients received an ample volume of blood transfusions. Fully understanding of predictors of blood transfusions will allow physicians to better optimize burn patients during hospitalization in an effort to use blood appropriately.