Dimethyl Fumarate Protects against Lipopolysaccharide- (LPS-) Induced Sepsis through Inhibition of NF-κB Pathway in Mice.

Sepsis is one of the most severe complications and causes of mortality in the clinic. It remains a great challenge with no effective treatment for clinicians worldwide. Inhibiting the release of proinflammatory cytokines during sepsis is considered as an important strategy for treating sepsis and improving survival. In the present study, we have observed the effect of dimethyl fumarate (DMF) on lipopolysaccharide- (LPS-) induced sepsis and investigated the possible mechanism. By screening a subset of the Johns Hopkins Drug Library, we identified DMF as a novel inhibitor of nitric oxide synthesis in LPS-stimulated RAW264.7 cells, suggesting that DMF could be a potential drug to treat sepsis. To further characterize the effect of DMF on LPS signaling, TNF-α, MCP-1, G-CMF, and IL-6 expression levels were determined by using cytokine array panels. In addition, an endotoxemia model with C57BL/6 mice was used to assess the in vivo efficacy of DMF on sepsis. The survival rate was assessed, and HE staining was performed to investigate histopathological damage to the organs. DMF was found to increase the survival of septic mice by 50% and attenuate organ damage, consistent with the reduction in IL-10, IL-6, and TNF-α (inflammatory cytokines) in serum. In vitro experiments revealed DMF's inhibitory effect on the phosphorylation of p65, IκB, and IKK, suggesting that the primary inhibitory effects of DMF can be attributed, at least in part, to the inhibition of phosphorylation of IκBα, IKK as well as nuclear factor-κB (NF-κB) upon LPS stimulation. The findings demonstrate that DMF dramatically inhibits NO and proinflammatory cytokine production in response to LPS and improves survival in septic mice, raising the possibility that DMF has the potential to be repurposed as a new treatment of sepsis.

Research trends on platelet-rich plasma in the treatment of wounds during 2002-2021: A 20-year bibliometric analysis.

Platelet-rich plasma (PRP) has attracted attention because of its potential to accelerate the wound healing process. However, resources for evaluating research trends in the treatment of wounds with PRP were limited. In this study, we aimed to make a bibliometric analysis of the literature related to PRP in the treatment of wounds and explore the research status, hotspots and frontiers in this field in recent 20 years. Studies about PRP treatment for wounds from 2002 to 2021 were retrieved from the Science Citation Index Expanded (SCI-E) of Web of Science (WOS) database. Visualisation softwares such as VOSviewer and SCImago Graphica, and CiteSpace were used to analyse the research trends and features. A total of 1748 studies were identified in the SCI-Expanded from 2002 to 2021. The number of publications on PRP in the treatment of wounds has shown an increasing trend, from 6 (in 2002) to 228 (in 2021). The papers published in the United States have led in times cited (14637) and H-index (63). Though Italy was slightly lower than China in the number of publications, the H-index and average cited (47, 28.45) were higher than that of China (38, 27.01). The strongest keyword was "fibrin" (strength = 13.07), and the longest burst duration keyword was "thrombin" (began in 2002 and ended in 2014). The largest 10 co-citation clusters are as follows: endothelial cell proliferation (#0), regenerative medicine-associated treatment (#1), diabetic wound healing (#2), autologous derived (#3), platelet-rich fibrin (#4), tissue engineering (#5), regenerative potential (#6), clinical randomised trial (#7), histologic observation (#8), and wound bacteria (#9). The United States has made the most outstanding contribution in this field. Chinese researchers need to enhance the quality of publications further. Wound Repair Regen. is the most noteworthy journal. The mechanism of growth factors of PRP, combination therapy, preparation of PRP, and related clinical trials may be topics that need attention.

Lentivirus-mediated subcutaneous JAM-A modification promotes skin wound healing in a mouse model by strengthening the secretory function and proliferation of fibroblasts.

A better understanding of the molecular regulation of wound healing may provide novel therapeutic targets. A previous study revealed that junctional adhesion molecule A (JAM-A)-modified mesenchymal stem cells promoted wound healing. However, whether direct JAM-A modification in the skin wound edge area accelerates the wound repair process is not clear. We determined whether JAM-A modification at the skin wound edge accelerated the wound healing process. We established JAM-A modification mouse wound models and mouse primary fibroblast cell models. Wound pictures were taken to compare the wound size. H&E staining was performed to monitor the morphology of the wound and quality of the newborn skin. CCK-8 assays and immunofluorescence (IF) for Ki67 were used to measure the cell proliferation of mouse primary fibroblasts. Quantitative real-time PCR, immunohistochemistry, IF, and Western blot analysis were used to detect bFGF and EGF expression in vivo and in vitro. The JAM-A-overexpressing group exhibited a smaller residual wound size than the control group at Day 7. Thicker epidermal layers and more hair follicle-like structures were found in the JAM-A-overexpressing group at Day 21. Cell proliferation capacity was higher in JAM-A-modified mouse fibroblasts. Elevated levels of bFGF and EGF were found in the JAM-A-modified group in vivo and in vitro. JAM-A modification significantly promoted fibroblast proliferation and wound healing. Increased levels of bFGF and EGF growth factors may be part of the mechanism.

Amniotic epithelial cells accelerate diabetic wound healing by protecting keratinocytes and fibroblasts from high-glucose-induced senescence.

Human amniotic epithelial cells (hAECs), one of the stem cells identified from the human placenta, possess numerous advantages and have been considered as an attractive and available cell source for regenerative medicine. Accumulating evidence has showed that cellular senescence was one of the pathogenic hubs of diabetic wound chronicity. Keratinocytes and fibroblasts are the primary cells involved in wound healing. Therefore, in this study, we aimed to investigate the anti-senescence effects of hAECs on keratinocytes and fibroblasts in diabetic wounds. Sustained hyperglycemia impaired cell function and accelerated senescence in vitro. However, this phenotype was rescued by hAECs-conditioned medium (hAECs-CM), with increased migration and proliferation in keratinocytes and fibroblasts and enhanced collagen synthesis and α-smooth muscle actin (α-SMA) production in fibroblasts. In addition, hAECs-CM dramatically inhibited intracellular reactive oxygen species (ROS) and senescence-associated ß-galactosidase (SA-ß-gal) in keratinocytes and fibroblasts under high-glucose (HG) condition. Moreover, hAECs-CM could downregulate the increased RAGE and P21 induced by continuous HG stimulation. Intradermal injection of hAECs in diabetic wounds promoted re-epithelialization and granulation tissue formation, accompanied by decreased P21+ cells and increased PCNA+ cells in epidermis and dermis, as well as promoted collagen deposition and α-SMA expression. Furthermore, CM-Dil-labeled hAECs survived to Day 5 but disappeared by Day 10 in diabetic wounds. These findings indicated that hAECs could inhibit diabetes-induced premature senescence and enhance the function of keratinocytes and fibroblasts via paracrine effects, partly by inhibiting RAGE/P21 signaling pathway. Thus, hAECs targeting cellular senescence induced by a hyperglycemic environment may be a new strategy for the treatment of diabetic wounds.

Ablative fractional carbon dioxide laser improves quality of life in patients with extensive burn scars: A nested case-control study.

BACKGROUND AND OBJECTIVES: Ablative fractional carbon dioxide laser (CO2 -AFL) for small-area burn scar management shows encouraging outcomes. Few studies, however, focused on comprehensive outcomes following CO2 -AFL treatment for extensive burn scars. This study evaluated whether CO2 -AFL surgery improved the quality of life (QoL) for burn survivors with extensive hypertrophic scars. METHODS: A retrospective nested case-control study was initiated to analyze the efficacy of CO2 -AFL treatment for patients with large-area burn scars. Patients with extensive burn scars (≥30% total body surface area [TBSA]) were registered in our hospital from March 2016 to October 2018. Patients undergoing CO2 -AFL surgery were divided into CO2 -AFL group, and patients undergoing conventional surgery were matched in a 1:1 ratio as the conventional surgery group according to the burned area. The questionnaires were collected and followed up. The 36-Item Short Form Health Survey (SF-36) and Burns Specific Health Scale-Brief (BSHS-B) were the primary parameters. Secondary parameters included the Pittsburgh Sleep Quality Index (PSQI), University of North Carolina "4P" Scars Scale (UNC4P), Patient Scars Assessment Scale for Patient (POSAS-P), and Douleur Neuropathique 4 questions (DN4). RESULTS: 23 patients (55.96 ± 21.59% TBSA) were included in CO2 -AFL group and 23 patients (57.87 ± 18.21% TBSA) in conventional surgery group. Both the BSHS-B total score (CO2 -AFL vs. conventional surgery: 115.35 ± 29.24 vs. 85.43 ± 33.19, p = 0.002) and the SF-36 total score (CO2 -AFL vs. conventional surgery: 427.79 ± 118.27 vs. 265.65 ± 81.66, p < 0.001) for the CO2 -AFL group were higher than those for the conventional surgery group. Parameters for the CO2 -AFL group were lower than those for the conventional surgery group in all of the following comparisons: PSQI total score (CO2 -AFL vs. conventional surgery: 7.70 ± 3.74 vs. 12.26 ± 4.61, p = 0.001), POSAS-P total score (CO2 -AFL vs. conventional surgery: 26.48 ± 6.60 vs. 33.04 ± 4.56, p < 0.001), UNC4P total score (CO2 -AFL vs. conventional surgery: 5.57 ± 1.97 vs. 7.26 ± 1.81, p = 0.004), and DN4 score (CO2 -AFL vs. conventional surgery: 3 [2-5] vs. 5 [4-8], p = 0.004). CONCLUSIONS: Compared to conventional surgery, whole scar CO2 -AFL surgery dramatically improved physical and mental health as well as QoL for people with extensive burn scars. Additionally, CO2 -AFL enhanced the evaluation of scars including their appearance, pain, itching, and a host of other symptoms.

Long noncoding RNA H19 act as a competing endogenous RNA of Let-7g to facilitate IEC-6 cell migration and proliferation via regulating EGF.

Intestinal mucosal injury is one of the most significant complications of burns. In our previous study, it was found that autophagy could alleviate burn-induced intestinal injury, but the underlying mechanisms are still unclear. Irregular expression of long noncoding RNAs (lncRNAs) is present in many diseases, including burns. However, the relationship between lncRNAs and intestinal mucosal injury requires further elucidation. In this study, we established a burn mice model and detected the expression level of autophagy-related proteins. Then, H19 content after autophagy intervention was tested in vitro and in vivo. The interaction of H19 with Let-7g and that of Let-7g with epidermal growth factor (EGF) were verified by dual-luciferase reporter assays. We found that the expression of the autophagy-associated proteins LC3-II and Beclin-1 was raised in the intestinal tract of the burn mice model. Similarly, the transfection of H19 raised autophagy levels. H19 was elevated after autophagy intervention in vitro and in vivo. H19 overexpression was able to promote IEC-6 cell migration and proliferation. Let-7g was suppressed by the overexpression of H19 and the combination of Let-7g mimic was able to abolish the physiological effect of H19. Moreover, the suppression of Let-7g increased the expression of EGF protein, which heightened IEC-6 cell migration and proliferation. Besides this, dual-luciferase assays revealed that Let-7g was a direct target of H19 as well as the EGF gene. Taken together, autophagy-mediated H19 increases in mouse intestinal tract after severe burn and functions as a sponge to Let-7g to regulate EGF, which suggests that H19 serves as a potential therapeutic target and biomarker for intestinal mucosal injury after burns.

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.

Acute Respiratory Distress Syndrome Induced by White Smoke Inhalation: a Potential Animal Model For Evaluating Pathological Changes and Underlying Mechanisms.

BACKGROUND/AIMS: White smoke inhalation (WSI) is an uncommon but potentially deadly cause of acute respiratory distress syndrome (ARDS). However, no clinical treatment protocol has been established for the treatment of WSI-induced ARDS. Therefore, it is necessary to investigate the effects of WSI in ARDS and the mechanisms underlying the effects of WSI to determine a novel therapeutic target. METHODS: On the basis of the duration of continued inhalation of white smoke (3 min, 5 min, and 7 min), rats were divided into three groups (WSI-3 min, WSI-5 min, and WSI-7 min). The survival rate, pathological change, and computed tomography (CT) score were evaluated to determine the modeling conditions. In the established WSI-5 min models, evaluations were performed to evaluate the following: arterial blood gas levels, lung wet/dry weight ratio, the expression of inflammatory cytokines, and the effect of NF-κB signaling pathway. RESULTS: The survival rate of rats at 72 h post-WSI in the WSI-3 min, WSI-5 min, and WSI-7 min groups was 83.33%, 75%, and 25%, respectively. Results from evaluation of H&E staining, CT scan, arterial blood gas levels, and lung wet/dry weight ratio suggest that the pathological changes in the rat in the WSI-5 min and WSI-7 min groups are very similar to those in patients with ARDS induced by WSI. Additionally, the expression of INF-γ, TGF-ß1, TNF-α, and IL-1ß were increased, and the NF-κB signaling pathway was activated in the WSI-5 min group. CONCLUSION: The rat model of WSI-5 min can be used as a WSI-induced ALI model for further experiments. The NF-κB signaling pathway may be a potential therapeutic target for the treatment of WSI- induced ARDS.

Therapeutic efficacy of early photobiomodulation therapy on the zones of stasis in burns: An experimental rat model study.

This study aimed to investigate the role of photobiomodulation therapy in preventing zones of stasis in burn wounds. We hypothesized that photobiomodulation therapy could promote tissue formation and release of nitric oxide (NO), and reduce inflammatory responses, thereby dilating local microvessels, reducing necrosis and apoptosis. Thirty rats were randomly divided into control group (CG) and laser group (LG). The zone of stasis was formed by applying a brass comb to the skin resulting in four rectangular burns separated by three unburned interspaces. The left side was laser wound (LW), while the right side was shielded wound (SW). The LW of LG was immediately subjected to photobiomodulation therapy, followed by once-daily 30-minutes photobiomodulation therapy sessions. Skin ultrasound and Doppler angiography analyses were used to evaluate the statuses of the zones of stasis at 1, 24, and 96 hours after injury. Harvested burn wound tissue was subjected to hematoxylin-eosin staining and HMGB1, caspase 3, and thrombomodulin immunohistochemistry, and the contents of NO and TNF-α were measured in stasis tissue. Thrombomodulin, HMGB1, and caspase 3 immunohistochemistry revealed significantly lower positive staining rates in the LW of LG rats relative to the others at 96 hours (p < 0.05), as well as a significantly higher skin blood flow relative to the others (p < 0.05). The NO content was significantly higher in the LW of LG, compared with other wounds, at 24 and 96 hours after injury (p < 0.05). The TNF-α level was significantly lower in the LW of LG than in other wounds at 96 hours (p < 0.05). Early, local photobiomodulation therapy can effectively ameliorate injury progression in the zone of stasis. However, these beneficial effects are limited to the directly irradiated sites.

Risk factors for hypertrophic burn scar pain, pruritus, and paresthesia development.

Hypertrophic scar pain, pruritus, and paresthesia symptoms are major and particular concerns for burn patients. However, because no effective and satisfactory methods exist for their alleviation, the clinical treatment for these symptoms is generally considered unsatisfactory. Therefore, their risk factors should be identified and prevented during management. We reviewed the medical records of 129 postburn hypertrophy scar patients and divided them into two groups for each of three different symptoms based on the University of North Carolina "4P" Scar Scale: patients with scar pain requiring occasional or continuous pharmacological intervention (HSc pain, n = 75) vs. patients without such scar pain (No HSc pain, n = 54); patients with scar pruritus requiring occasional or continuous pharmacological intervention (HSc pruritus, n = 63) vs. patients without such scar pruritus (No HSc pruritus, n = 66); patients with scar paresthesia that influenced the patients' daily activities (HSc paresthesia, n = 31) vs. patients without such scar paresthesia (No HSc paresthesia, n = 98). Three multivariable logistic regression models were built, respectively, to identify the risk factors for hypertrophic burn scar pain, pruritus, and paresthesia development. Multivariable analysis showed that hypertrophic burn scar pain development requiring pharmacological intervention was associated with old age (odds ratio [OR] = 1.046; 95% confidence interval [CI], 1.011-1.082, p = 0.009), high body mass index (OR = 1.242; 95%CI, 1.068-1.445, p = 0.005), 2-5-mm-thick postburn hypertrophic scars (OR = 3.997; 95%CI, 1.523-10.487, p = 0.005), and 6-12-month postburn hypertrophic scars (OR = 4.686; 95%CI, 1.318-16.653, p = 0.017). Hypertrophic burn scar pruritus development requiring pharmacological intervention was associated with smoking (OR = 3.239; 95%CI, 1.380-7.603; p = 0.007), having undergone surgical operation (OR = 2.236; 95%CI, 1.001-4.998; p = 0.049), and firm scars (OR = 3.317; 95%CI, 1.237-8.894; p = 0.017). Finally, hypertrophic burn scar paresthesia development which affected the patients' daily activities was associated with age (OR = 1.038; 95%CI, 1.002-1.075; p = 0.040), fire burns (OR = 0.041; 95%CI, 0.005-0.366; p = 0.004, other burns vs. flame burns), and banding and contracture scars (OR = 4.705; 95%CI, 1.281-17.288, p = 0.020).

Toll-like receptor 4 protects against stress-induced ulcers via regulation of glucocorticoid production in mice.

Stress-induced gastric ulcer is an important life-threatening condition, while the molecular basis of its development is incompletely understood. Toll-like receptor 4 (TLR4), an innate immune pattern recognition receptor, can induce pro-inflammatory transcription, aggravating a stress ulcer. The present study found that TLR4 played a protective role in a mouse model of water immersion (23 °C) restraint stress. Wild-type (WT) and TLR4-/- male mice were respectively divided into five groups (5 per group), and exposed to the stressor for 0, 0.5, 1, 2, or 4 hours. Gastric ulcer index, determined post mortem, increased with time in both types of mice but was greater in TLR4-/- mice. Furthermore, increased serum cortisol and corticosterone concentrations were observed in WT mice only, and such increases were detected only in WT mice 4 h after lipopolysaccharide (LPS) treatment (2 mg/kg, intraperitoneal injection). Moreover, the administration of cortisol alleviated the gastric injury in TLR4-/- mice. Western blotting showed expression in the adrenal of P450scc (CYP11A1), the first rate-limiting enzyme in the synthesis of steroids, was increased 4 h after water immersion restraint stress or LPS treatment in WT mice, but was conversely decreased in TLR4-/- mice after either stressor. Furthermore, in adrenal glands of TLR4-/- mice, structural distortion of mitochondria (which contain CYP11A1) was found with electron microscopy, and lack of lipid-storing droplets was found using light microscopy on adrenal cryosections stained with Oil red O. These data indicate that TLR4 plays a protective role in stress-induced gastric ulcer that is exerted via impacting synthesis of glucocorticoid in the adrenal gland.

Interleukin-33 increases antibacterial defense by activation of inducible nitric oxide synthase in skin.

Interleukin-33 (IL-33) is associated with multiple diseases, including asthma, rheumatoid arthritis, tissue injuries and infections. Although IL-33 has been indicated to be involved in Staphylococcus aureus (S. aureus) wound infection, little is known about how IL-33 is regulated as a mechanism to increase host defense against skin bacterial infections. To explore the underlying intricate mechanism we first evaluated the expression of IL-33 in skin from S. aureus-infected human patients. Compared to normal controls, IL-33 was abundantly increased in skin of S. aureus-infected patients. We next developed a S. aureus cutaneous infection mouse model and found that IL-33 was significantly increased in dermal macrophages of infected mouse skin. The expression of IL-33 by macrophages was induced by staphylococcal peptidoglycan (PGN) and lipoteichoic acid (LTA) via activation of toll-like receptor 2(TLR2)-mitogen-activated protein kinase (MAPK)-AKT-signal transducer and activator of transcription 3(STAT3) signaling pathway as PGN and LTA failed to induce IL-33 in Tlr2-deficient peritoneal macrophages, and MAPK,AKT, STAT3 inhibitors significantly decreased PGN- or LTA-induced IL-33. IL-33, in turn, acted on macrophages to induce microbicidal nitric oxygen (NO) release. This induction was dependent on inducible nitric oxide synthase (iNOS) activation, as treatment of macrophages with an inhibitor of iNOS, aminoguanidine, significantly decreased IL-33-induced NO release. Moreover, aminoguanidine significantly blocked the capacity of IL-33 to inhibit the growth of S. aureus, and IL-33 silencing in macrophages significantly increased the survival of S. aureus in macrophages. Furthermore, the administration of IL-33-neutralizing antibody into mouse skin decreased iNOS production but increased the survival of S. aureus in skin. These findings reveal that IL-33 can promote antimicrobial capacity of dermal macrophages, thus enhancing antimicrobial defense against skin bacterial infections.

JAM-A promotes wound healing by enhancing both homing and secretory activities of mesenchymal stem cells.

The homing ability and secretory function of mesenchymal stem cells (MSCs) are key factors that influence cell involvement in wound repair. These factors are controlled by multilayer regulatory circuitry, including adhesion molecules, core transcription factors (TFs) and certain other regulators. However, the role of adhesion molecules in this regulatory circuitry and their underlying mechanism remain undefined. In the present paper, we demonstrate that an adhesion molecule, junction adhesion molecule A (JAM-A), may function as a key promoter molecule to regulate skin wound healing by MSCs. In in vivo experiments, we show that JAM-A up-regulation promoted both MSC homing to full-thickness skin wounds and wound healing-related cytokine secretion by MSCs. In vitro experiments also showed that JAM-A promoted MSC proliferation and migration by activating T-cell lymphoma invasion and metastasis 1 (Tiam1). We suggest that JAM-A up-regulation can increase the proliferation, cytokine secretion and wound-homing ability of MSCs, thus accelerating the repair rate of full-thickness skin defects. These results may provide insights into a novel and potentially effective approach to improve the efficacy of MSC treatment.

The effects of porcine pulmonary surfactant on smoke inhalation injury.

BACKGROUND: Our previous study, consistent with others, demonstrated that administering an exogenous surfactant was a potential therapy for acute lung injury and acute respiratory distress syndrome. However, the underlying mechanisms remain largely unknown. In the present study, we investigated the effect of instilled porcine pulmonary surfactant (PPS) on rat inhalation injury model induced by smoke and the possible mechanism. MATERIALS AND METHODS: Fifteen Sprague-Dawley rats were equally randomized to three groups as follows (n = 5 in each group): sham control group (C group), inhalation injury group (II group), and inhalation injury + PPS treatment group (PPS group). Lung tissues were assayed for wet/dry ratio, histologic, terminal dUTP nick-end labeling staining, and Western blotting examinations. The myeloperoxidase activity was tested in lung tissues as well. Bronchoalveolar lavage fluid was collected to determine the total protein concentrations, inflammatory cytokines, surfactant protein A (SP-A), and SP-D. RESULTS: Our present work exhibited that PPS had therapeutic effects on smoke inhalation injury reflected by significant increase of PaO2 values, improved edema status, decreased vascular permeability, amelioration of lung histopathology, and reduction of inflammatory response. In addition, PPS treatment could increase endogenous SP-A levels both in lung tissue and bronchoalveolar lavage fluid. Further correlation analysis showed that SP-A was negatively correlated with both myeloperoxidase activity and interleukin 8 levels. CONCLUSIONS: These results indicate that PPS can attenuate smoke-induced inhalation injury at least partly through stimulating production of endogenous SP-A and inhibiting the release of proinflammatory cytokines such as interleukin 8. The increasing production of endogenous SP-A may be due to the antioxidant effect of PPS, which contains no SP-A.

Using negative pressure wound therapy on microskin autograft wounds.

BACKGROUND: Microskin autografts with conventional wrap and compression are used extensively in the treatment of skin and tissue defects. This comparative study aimed at investigation of the clinical application of negative pressure wound therapy (NPWT) in combination with microskin autografts for repair of acute and chronic wounds. METHODS: A prospective case-control study was performed from December 1, 2010-December 31, 2013 in Changhai Hospital, Shanghai. We compared a study group of patients received microskin autografting covered by NPWT with that of a control group of patients received microskin autografting covered by a conventional gauze. RESULTS: A total of 81 patients were in this study, 27 patients were allocated to the study group and 54 patients to the control group. The study group exhibited significant low infection rate and pain score during removal of inner layer at first dressing change after skin grafting compared with those of the control group (P < 0.05). The time interval between skin grafting and first postoperative change was longer in the study group than that in the control group (P < 0.01), the study group showed a significant shorter 95% wound healing time (P < 0.05), and survival rate of microskin autografts in the study group was higher than that in the control group (P < 0.05). CONCLUSIONS: NPWT is beneficial for wound closure after microskin autografts, which prolongs the interval between skin transplantation and first postoperative dressing change, reduces pain during removal of inner layer dressing, increases skin graft survival rate, and shortens wound healing time. Therefore, NPWT can be recommended for repair of acute and chronic wounds with microskin autografts.

BurnCalc assessment study of computer-aided individual three-dimensional burn area calculation.

BACKGROUND: Accurate estimation of a burned area is crucial to decisions about fluid resuscitation, surgical options, nutritional support, and prognosis. Widely used clinical methods to estimate a burn area are two-dimensional. They do not consider age, sex, body mass, physical deformities, or other relevant factors. Computer-aided methods have improved the accuracy of estimating burned areas by including data analysis and reducing subjective differences. Three-dimensional (3D) scanning allows us to determine body dimensions rapidly and reproducibly. We describe an individualized, cost-efficient, portable 3D scanning system, BurnCalc, that can create an individual 3D model and then calculate body surface area (BSA) and the burn area accurately and quickly. METHODS: The BurnCalc system was validated by verifying the accuracy and stability of BSA calculation. We measured 10 regular objects in experiment 1, using Student's t-test and the intraclass correlation coefficient (ICC) in the analysis. In experiment 2, artificial paper patches of known dimensions were attached to various parts of the body of 40 volunteers. Their sizes were then calculated using BurnCalc. The BurnCalc data were compared to actually measured values to verify accuracy and stability. Total BSAs of these 40 volunteers were also calculated by BurnCalc and compared to those derived from an accepted formula. In experiment 3, four experts using Chinese Rule-of-Nines or Rule-of-Palms methods calculated the percentages of the total BSA in 17 volunteers. Student's t-test and ICC, respectively, were used to compare the results obtained with the BurnCalc technique. RESULTS: Statistically, in experiment 1, p = 0.834 and ICC = 0.999, demonstrating that there was no difference between the BurnCalc and real measurements. Also, the hypothesis of null difference among measures (experiment 2) was true because p > 0.05 and ICC = 0.999, indicating that calculations of the total BSA and the burn area were more accurate using the BurnCalc technology. The reliability of the BurnCalc program was 99.9%. In experiment 3, only the BurnCalc method exhibited values of p > 0.05 (p = 0.774) and ICC = 0.999. CONCLUSIONS: BurnCalc technology produced stable, accurate readings, suggesting that BurnCalc could be regarded as a new standard clinical method.

Deficiency of Smad3 results in enhanced inducible nitric oxide synthase-mediated hypotension in lipopolysaccharide-induced endotoxemia.

BACKGROUND: Smad3 is a principal intracellular mediator of signaling for transforming growth factor ß, a cytokine involved in pleiotropic pathophysiological processes including inflammation and immunity. The function of Smad3 in regulating inducible nitric oxide synthase (iNOS) expression and septic shock has not been characterized. METHODS: Smad3(-/-) (referred hereafter as KO) and wild-type (WT) mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce the septic hypotension. Mortality, blood pressure, and plasma levels of nitrite were measured. The iNOS messenger RNA and protein levels in lung, kidney, and spleen were also analyzed. RESULTS: Mice lacking functional Smad3 respond to LPS with greater mortality than their WT littermates. The high mortality of KO mice is accompanied by enhanced hypotension after intraperitoneal injection of LPS. Both KO and WT mice displayed an increase in plasma nitrite during the experimental period; however, LPS administration caused more dramatic changes in KO mice than WT mice. Likewise, the iNOS messenger RNA and protein levels in lung, kidney, and spleen were more strongly increased in KO mice than in WT mice after LPS administration. CONCLUSIONS: Defects in the Smad3 gene may increase susceptibility to the development of septic hypotension because of enhanced iNOS production.

Consensus on the treatment of second-degree burn wounds (2024 edition).

Second-degree burns are the most common type of burn in clinical practice and hard to manage. Their treatment requires not only a consideration of the different outcomes that may arise from the dressing changes or surgical therapies themselves but also an evaluation of factors such as the burn site, patient age and burn area. Meanwhile, special attention should be given to the fact that there is no unified standard or specification for the diagnosis, classification, surgical procedure, and infection diagnosis and grading of second-degree burn wounds. This not only poses great challenges to the formulation of clinical treatment plans but also significantly affects the consistency of clinical studies. Moreover, currently, there are relatively few guidelines or expert consensus for the management of second-degree burn wounds, and no comprehensive and systematic guidelines or specifications for the treatment of second-degree burns have been formed. Therefore, we developed the Consensus on the Treatment of Second-Degree Burn Wounds (2024 edition), based on evidence-based medicine and expert opinion. This consensus provides specific recommendations on prehospital first aid, nonsurgical treatment, surgical treatment and infection treatment for second-degree burns. The current consensus generated a total of 58 recommendations, aiming to form a standardized clinical treatment plan.

Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis.

Diabetic wounds, characterized by prolonged inflammation and impaired vascularization, are a serious complication of diabetes. This study aimed to design a gelatin methacrylate (GelMA) hydrogel for the sustained release of netrin-1 and evaluate its potential as a scaffold to promote diabetic wound healing. The results showed that netrin-1 was highly expressed during the inflammation and proliferation phases of normal wounds, whereas it synchronously exhibited aberrantly low expression in diabetic wounds. Neutralization of netrin-1 inhibited normal wound healing, and the topical application of netrin-1 accelerated diabetic wound healing. Mechanistic studies demonstrated that netrin-1 regulated macrophage heterogeneity via the A2bR/STAT/PPARγ signaling pathway and promoted the function of endothelial cells, thus accelerating diabetic wound healing. These data suggest that netrin-1 is a potential therapeutic target for diabetic wounds.