Computational Drug Discovery in Diaphragm dysfunction via Text Mining and Biomedical Database.

The diaphragm, which is crucial for ventilation, is the primary muscle responsible for inspiration. Patients with severe burns who experience diaphragmatic dysfunction have an increased risk of mortality. Unfortunately, there are currently no effective medications available to prevent or treat this condition. The objective of our study is to utilize bioinformatics to identify potential genes and drugs associated with diaphragmatic dysfunction. In this study, text mining techniques were utilized to identify genes associated with diaphragmatic dysfunction and recovery. Common genes were then analyzed using GO and KEGG pathway analysis, as well as protein-protein interaction (PPI) network analysis. The obtained hub genes were processed using Cytoscape software, and their expression levels in diaphragmatic dysfunction were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in severe burn rats. Genes that were confirmed were then examined in drug-gene interaction databases to identify potential drugs associated with these genes. Our analysis revealed 96 genes that were common to both the "Diaphragm dysfunction" and "Functional Recovery" text mining concepts. Gene enrichment analysis identified 19 genes representing ten pathways. qRT-PCR showed a significant increase in expression levels of 13 genes, including CCL2, CCL3, CD4, EGF, HGF, IFNG, IGF1, IL17A, IL6, LEP, PTGS2, TGFB1, and TNF, in samples with diaphragmatic dysfunction. Additionally, we found that a total of 56 drugs targeted 5 potential genes. These findings provide new insights into the development of more effective drugs for treating diaphragmatic dysfunction, and also present substantial opportunities for researching new target pharmacology and promoting drugs in the pharmaceutical industry.

[New research direction of organ dysfunction caused by hemorrhagic shock: mechanisms of mitochondrial quality control].

Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Basic and clinical study of the effect of exogenous hyaluronic acid on the quality of acellular dermal matrix combined with thin intermediate split thickness skin graft.

BACKGROUND: To promote wound recovery in the recipient region, we studied the impact of exogenous hyaluronic acid (HA) on acellular dermal matrix (ADM) paired with thin intermediate-thickness skin transplant. METHODS: This study contains animal and clinical experiments. 50 Japanese big ear rabbits were separated into HA1, HA2, PADM, TS, and NS groups. Clinical part included 50 scar patients dividing into 5 groups (TS + HA + ADM 1, TS + ADM2, TS, TS + ADM and normal skin (NS)). RESULTS: In the animal trial, after 56 days, the grafts contracted least in the HA2 group; HA2 had the highest microvascular density (MVD), HA concentration, and collagen I and III expression. In clinical work, ADM > HA + ADM2 > HA + ADM1 > TS > NS; Type I and III collagen: HA + ADM1 and HA + ADM2 were higher than ADM; HA content: TS > HA + ADM1 > HA + ADM 2 > ADM. CONCLUSIONS: ADM, exogenous hyaluronic acid mixed with thin skin autograft has better biomechanical qualities and therapeutic impact than acellular dermal matrix alone, and the reconstructive result is near to self-thick skin autograft in all indexes.

Epidemiological and Clinical Characteristics of 471 Elderly Burn Patients in China: A Burn Center-based Study.

Burns are characterized by difficult treatment, poor prognosis, and high mortality especially in elderly patients. The aim of this paper is to study the epidemiological and clinical characteristics of elderly burn patients admitted to a major burn center from 2016 to 2020. The data of 471 elderly burn patients admitted to our burn center from January 2016 to December 2020 were retrospectively analyzed. Demographic and clinical variables of different age groups were statistically analyzed, and variables related to length of stay (LOS) and hospitalization costs were analyzed through linear regression models. The mean age of included patients was 69.03 years. Scald injuries accounted for 42.7% of all burns with the extremities being the most commonly affected anatomic site (46.5%). Approximately 67.5% and 5.9% of all patients suffered from full-thickness burns and inhalation injuries, respectively. These patients required more surgical procedures, longer operation durations, and higher costs compared with other burn patients. The mean LOS was 17 days with a mortality rate of 2.1%. There were statistically significant differences in the etiological characteristics and clinical manifestations of burn patients in different age groups. Individualized targeted prevention and treatment strategies should be performed according to the clinical characteristics and relevant risk factors of each patient.

miR-181c, a potential mediator for acute kidney injury in a burn rat model with following sepsis.

BACKGROUND: The miRNA profile is changed after burn or sepsis and is involved in regulating inflammatory reactions. However, the function and molecular mechanism of miRNAs in regulating burn sepsis-induced acute kidney injury (AKI) are still unclear. METHODS: In this study, animal and cell sepsis models were established after burned rats were injected with lipopolysaccharide (LPS) or NRK-52E cells treated with LPS, respectively. Cytokine expression, inflammatory cell infiltration, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1) levels were analysed after the indicated treatments. RESULTS: Burn sepsis increased the expression of inflammatory factors (TNF-α and IL-1ß) and chemokines (MIP-1α, MIP-2 and MCP-1). Moreover, burn sepsis promoted macrophage and neutrophil infiltration into the kidney and upregulated the levels of Scr and KIM-1 in the kidney and urine. Ectopic expression of miR-181c significantly reduced LPS-induced TLR4 protein expression, suppressed KIM-1 mRNA levels and subsequently inhibited the activation of inflammatory genes (TNF-α and IL-1ß) and chemokine genes (MIP-1α, MIP-2 and MCP-1). CONCLUSIONS: Our results demonstrated that miR-181c could suppress TLR4 expression, reduce inflammatory factor and chemokine secretion, mitigate inflammatory cell infiltration into the kidney and downregulate KIM-1 expression, which might ultimately attenuate burn sepsis-induced AKI.

Establishment of a Bama miniature pig burn model with different burn depths.

Background: The skin morphological characteristics of the Bama miniature pig are very similar to those of humans; thus, the Bama miniature pig is an ideal choice for establishing a skin burn model. Methods: In this study, 6 ordinary, male, Bama miniature pigs (weight: 23-28 kg and length: 71-75 cm) were used to establish burn models. A mixture of 1 mg of Ketamine and Sumianxin II was used for Bama miniature pigs anesthetizing, and 1 mg of Pentobarbital sodium was added as necessary. The different burn depths were made using a continuous pressure of 1 kg and contact times of 0 s, 10 s, 15 s, 20 s, 25 s, 30 s, 35 s, 40 s, and 45 s by the newly invented electronic burn instrument. The burned tissues were collected and examined with hematoxylin and eosin (H&E) and Masson staining. Results: Burning for 10-15 s caused a first-degree burn; the blood vessels in the superficial dermis were dilated and congested, and necrosis occurred above the basal layer of the epidermis. Burning for 20-25 s caused a superficial partial-thickness burn; the whole epidermal layer was necrotic, and the collagen fibers were slightly deformed. Burning for 30-35 s caused a deep partial-thickness burn; the whole epidermal layer and dermal layers were necrotic with leukocyte infiltration zones, and the collagen fibers were disordered, degenerated, and necrotized. Burning for 40-45 s caused a third-degree burn; the skin layers and adipose tissues were necrotic, and the thick blood vessels in the skin adipose tissues were full of disintegrated and agglutinated red blood cells. Conclusions: Stable burn depth models of Bama miniature pigs were constructed using a new and innovative electronic burn instrument. Our findings provide a basis for further research on the burn mechanism and evaluations of therapeutic drugs.

Effect of blended protein nutritional support on reducing burn-induced inflammation and organ injury.

BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.

Protective effect of restrictive resuscitation on vascular endothelial glycocalyx in pigs with traumatic hemorrhagic shock.

Background: Hemorrhagic shock is the leading cause of early traumatic death. Research and discussion on restrictive fluid resuscitation have been ongoing for many years. The purpose of this study was to explore whether restrictive resuscitation can inhibit the shedding of vascular endothelial glycocalyx in the prehospital treatment of traumatic hemorrhagic shock pigs. Methods: Landrace pigs were randomly divided into a restrictive resuscitation group (restrictive group) and a conventional resuscitation group (conventional group), with 6 pigs in each group. The gunshot caused a rupture of the pig's receding right femoral artery, and the average arterial pressure was 40-45 mmHg stable for 30 minutes, which was defined as a successful shock model. The end point of resuscitation in the restrictive group was a mean arterial pressure (MAP) of 55-60 mmHg for 30 minutes, and the end point of resuscitation in the conventional group was a MAP of 70-75 mmHg for 30 minutes. The results of arterial blood gas analysis, hemodynamic indicators, endothelial glycocalyx damage and shedding marker Syndecan1 and soluble thrombomodulin (sTM) expression levels were compared between the two groups of experimental pigs after resuscitation. Results: The two groups of experimental pigs had the same baseline levels before injury in age, body weight, blood loss, cardiac output index, cardiac function index (CFI), extravascular lung water index (ELWI), and pulmonary vascular permeability index (PVPI). The arterial blood gas analysis of the two experimental pigs showed no significant difference in carbon dioxide partial pressure, oxygen partial pressure, blood oxygen saturation, or blood lactic acid after resuscitation. The difference in cardiac output index and CFI at the end of resuscitation between the two groups was not statistically significant; the absolute value and percentage of Syndecan1 level increase in the restrictive resuscitation group were lower than those in the conventional resuscitation group, and the difference was statistically significant. Conclusions: Compared with full resuscitation in a short period of prehospital treatment, restrictive resuscitation can achieve a similar effect in maintaining tissue oxygen supply and can reduce the loss of vascular endothelial glycocalyx to a certain extent.

Human Umbilical Cord-Derived Mesenchymal Stem Cells Alleviate Acute Lung Injury Caused by Severe Burn via Secreting TSG-6 and Inhibiting Inflammatory Response.

OBJECTIVES: To investigate whether hUC-MSCs attenuated severe burn-induced ALI and the effects were based on TSG-6 secreted from hUC-MSCs. METHOD: A rat model was established and evaluated as follows: cytokine expression was measured by ELISA, and both inflammatory cell infiltration and lung injury were assessed by immunohistochemistry assay. RESULTS: In vitro, TSG-6 levels in serum from the burn group were significantly increased compared with those from the sham group. In vivo, TSG-6 levels of lung tissues and serum in the burn+hUC-MSC group were significantly increased compared with those in the burn group. Both in lung tissues and in serum, increased levels of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) were remarkably decreased, but the anti-inflammatory cytokine IL-10 increased after hUC-MSC administration (p < 0.05). These significant positive effects after hUC-MSC transplantation did not occur in the burn+siTSG-6 group. CONCLUSION: The intratracheal implantation of hUC-MSCs has been an effective treatment for severe burn-induced ALI via promoting TSG-6 secretion and inhibiting inflammatory reaction in lung tissue.

Usage of Negative Pressure Wound Therapy in Pseudoepitheliomatous Hyperplasia Secondary to Burn Injury: A Case Series.

Pseudoepitheliomatous hyperplasia (PEH) is a reactive epithelial proliferation secondary to a wide range of stimuli, including traumatic injury, inflammation, infection, and tumors of the skin. PEH secondary to burn injury is rarely reported. We report three cases of PEH patients after burn injury. All three cases were confirmed with the existence of bacterial infection, and all these cases were second- or third-degree burns. All three patients were treated with negative pressure wound therapy after wound debridement or tangential excision. All the wounds healed without split-thickness skin grafting and recurrence.

A narrative review of changes in microvascular permeability after burn.

OBJECTIVE: We aimed to review and discuss some of the latest research results related to post-burn pathophysiological changes and provide some clues for future study. BACKGROUND: Burns are one of the most common and serious traumas and consist of a series of pathophysiological changes of thermal injury. Accompanied by thermal damage to skin and soft tissues, inflammatory mediators are released in large quantities. Changes in histamine, bradykinin, and cytokines such as vascular endothelial growth factor (VEGF), metabolic factors such as adenosine triphosphate (ATP), and activated neutrophils all affect the body's vascular permeability. METHODS: We searched articles with subject words "microvascular permeability", "burn" "endothelium", and "endothelial barrier" in PubMed in English published from the beginning of database to Dec, 2020. CONCLUSIONS: The essence of burn shock is the rapid and extensive fluid transfer in burn and non-burn tissue. After severe burns, the local and systemic vascular permeability increase, causing intravascular fluid extravasation, leading to a progressive decrease in effective circulation volume, an increase in systemic vascular resistance, a decrease in cardiac output, peripheral tissue edema, multiple organ failure, and even death. There are many cells, tissues, mediators and structures involved in the pathophysiological process of the damage to vascular permeability. Ulinastatin is a promising agent for this problem.

Preparation and evaluation of chitosan-polyvinyl alcohol/polyhexamethylene guanidine hydrochloride antibacterial dressing to accelerate wound healing for infectious skin repair.

BACKGROUND: Wound infections, especially multidrug-resistant (MDR) bacterial infections, are a major challenge in clinical medicine. METHODS: In this study, a new type of antibacterial sponge was prepared from a solution containing a chitosan-polyvinyl alcohol (CTS-PVA) emulsion with added polyhexamethylene guanidine hydrochloride (PHMG) in a homogeneous medium using lyophilization technology. The antibacterial ability of and CTS-PVA/PHMG sponge against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Acinetobacter baumannii in vitro. The structure and physical properties were characterized. The sponge dressing was tested in a Pseudomonas aeruginosa-infected full-thickness mouse skin wound defect model. The effects were evaluated by wound area measurement and histological analysis. RESULTS: The CTS-PVA/PHMG sponge showed broad-spectrum antibacterial ability, including for MDR bacterial stains from clinical sources, while maintaining excellent physicochemical properties, including a high swelling degree and good moisture retention capability. Scanning electron microscopy images displayed the surface morphology of the CTS-PVA/PHMG sponge dressing. The detection of the wound healing rate and histological analysis supported that the new dressing can alleviate the inflammation and accelerate the healing speed of infected wounds and in vivo. CONCLUSIONS: CTS-PVA/PHMG sponge shows broad-spectrum antibacterial activity, which can provide a new pathway for clinical prevention and treatment of superbug-infected wounds.

Classification of Achilles tendon shortening induced by scar contracture and corresponding treatment strategies for pediatric patients - A single unit experience.

BACKGROUND: Achilles tendon shortening of pediatric patients caused by scar contracture poses a challenge for us. It always impairs walking function. In this article, we attempted to introduce a new classification of Achilles tendon shortening of pediatric patients and corresponding treatment strategies in our single center. METHODS: From 2001 to 2018, 65 patients (aging from 13 to 17-years-old, 34 females and 31 males, 21 cases with unilateral Achilles tendon shortening and 44 cases with bilateral Achilles tendon shortening) were recruited. The causes included trauma (n = 13), scald (n = 20) and burn (n = 32). The distance between the heel and the ground was from 3 to 18 cm. They were classified into three types: ≤5 cm, mild, n = 9; 5-10 cm, moderate, n = 30; ≥10 cm, serious, n = 26. They had a history from 7 months to 4 years (28 cases with less than 1.5 years and 37 cases with more than 1.5 years). Treatment methods: Scar-Achilles-Tendon (SAT) flaps and skin graft were used for moderate cases before special external fixation shoes were used for fixation for at least 6 months. External special shoes fixation was used for mild cases except 5cases still received SAT flap and skin graft. In serious cases, bone extraction was used for at least 6 months before receiving SAT flap and skin graft. RESULTS: The distance between the heel and the ground was 0 cm after treatment in 54 cases (mild, n = 9; moderate, n = 28; serious, n = 18). Recurrence was found in 11 cases (mild, n = 0; moderate, n = 5; serious, n = 6) after six months follow-up. There were 13 cases of tangential excision of eschar and 8 cases of escharectomy (P < 0.05) with flap necrosis affection. Among them, 9 cases with a medical history of less than 1.5 years had partial necrosis, 6 cases with a medical history of more than 1.5 years had partial flap necrosis(P < 0.05). Local necrosis was covered by skin graft again. Bone exposure was found in 5 serious cases. It was repaired by negative pressure therapy first and then skin graft was used. The walking ability (P < 0.05) and function (P < 0.05) of lower limbs were statistically improved after treatment. CONCLUSIONS: Different methods can be used according to the shortening degree of Achilles tendon of pediatric patients based on the new classification, which may be useful for future clinical work.

Effect of precise partial scab removal on the repair of deep partial-thickness burn wounds in children: a retrospective study.

BACKGROUND: The choice of treatment methods for children with deep partial-thickness burn wounds (DPBWs) is an issue that requires careful consideration from surgeons. The purpose of this study was to evaluate the efficacy of precise partial scab removal (PPSR) in the treatment of DPBWs in children. METHODS: We retrospectively analyzed the clinical data of 78 children with DPBWs. The children were divided into a PPSR group (n=37) and a routine dressing change (RDC) group (n=41). In the PPSR group, an electric dermatome was used to cut the scab in the early post-injury period. The thickness scale of the electric dermatome was set to 0.1 mm. The scab was removed to the base with scattered bleeding points. There was still a small amount of necrotic tissue in the base of the wound. For the acellular dermal matrix, the first dressing change was about 1 week after surgery. The RDC group was given conventional wound-dressing treatment. The wound dressing was changed with epidermal growth factor, silver-zinc antibacterial cream, and dressing change. The frequency of dressing change was adjusted once a day or once every other day depending on the condition of wound secretions. The hospitalization time, wound-healing time, fever duration, antibiotic use time, number of subsequent operations, and overall hospitalization expenses were compared between the two groups. RESULTS: The wound-healing time of the PPSR group was 19.86±6.4 days, and the wound-healing time of the RDC group was 24.15±7.12 days (P=0.0068). The duration of fever in the PPSR group and RDC group was 2.62±1.99 and 4.44±3.10 days, respectively (P=0.0032). The antibiotic use time in the PPSR group and RDC group was 4.0±1.33 and 4.83±1.88 days, respectively (P=0.0292). The overall hospitalization cost of the PPSR group and RDC group was yuan renminbi ¥37,852.84±10,894.64 and ¥38,047.46±19,450.37, respectively (P=0.9573). CONCLUSIONS: PPSR can shorten wound-healing time, reduce the frequency of dressing changes, shorten the time of fever in children, lower the frequency of antibiotic use, and decrease number of dressing changes on the wound.

Using rational strategies for children's scars based on more than 5 years assessment after burn.

BACKGROUND: Paediatric patients with scars after burn are regularly encountered. Discussion of rational strategies for management are of value. The objective of the study was to describe development and utilisation of strategies for paediatric burn scars up to five years after injury. METHODS: We included 164 cases aged from 5 to 8 years old in our study; all had burn scar deformities. RESULTS: Assessments were made up to December 31, 2019. The following strategies were used: sequential treatment, reconstruction based on facial aesthetic units, predicting the effect of surgery on development, releasing skin tension and application of photoelectric technology or other non-surgical measures. CONCLUSIONS: Using rational strategies for paediatric burn scars is very important.

Down-Regulation of miR-301a-3p Reduces Burn-Induced Vascular Endothelial Apoptosis by potentiating hMSC-Secreted IGF-1 and PI3K/Akt/FOXO3a Pathway.

Vascular endothelium dysfunction plays a pivotal role in the initiation and progression of multiple organ dysfunction. The mesenchymal stem cell (MSC) maintains vascular endothelial barrier survival via secreting bioactive factors. However, the mechanism of human umbilical cord MSC (hMSC) in protecting endothelial survival remains unclear. Here, we found IGF-1 secreted by hMSC suppressed severe burn-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and alleviated the dysfunction of vascular endothelial barrier and multiple organs in severely burned rats. Severe burn repressed miR-301a-3p expression, which directly regulated IGF-1 synthesis and secretion in hMSC. Down-regulation of miR-301a-3p decreased HUVECs apoptosis, stabilized endothelial barrier permeability, and subsequently protected against multiple organ dysfunction in vivo. Additionally, miR-301a-3p negatively regulated PI3K/Akt/FOXO3 signaling through IGF-1. Taken together, our study highlights the protective function of IGF-1 against the dysfunction of multiple organs negatively regulated by miR-301a-3p, which may provide the theoretical foundation for further clinical application of hMSC.

Plasma glucagon-like peptide 1 was associated with hospital-acquired infections and long-term mortality in burn patients.

BACKGROUND: Although glucagon-like peptide 1 levels have been closely associated with inflammation and mortality in septic patients, the clinical importance of glucagon-like peptide 1 on hospital-acquired infections and long-term mortality after burn injury remains unexplored. METHODS: Plasma samples from 144 burn patients were collected on admission to determine total glucagon-like peptide 1, interleukin 6, and monocyte chemotactic protein-1 levels. Hospital-acquired infections were determined by positive microbial culture. One-year mortality was assessed by telephone interview. Factors associated with glucagon-like peptide 1 were determined by multivariable linear logistic regression. Predicting the clinical importance of glucagon-like peptide 1 on the development of hospital-acquired infections and mortality were determined by Cox proportional hazards models and further by receiver operating characteristic curve analysis. Kaplan-Meier analyses were performed to examine whether the mean glucagon-like peptide 1 level of the cohort could discriminate the hospital-acquired infections-free survival. RESULTS: Median burn size was 41% (19%-70%) of total body surface area. Hospital-acquired infections developed in 36 (25%) patients after a mean of 10 ± 1 days after injury. Interleukin 6, monocyte chemotactic protein-1, and blood urea nitrogen levels and thrombin time were independently associated with increased glucagon-like peptide 1 levels. Levels of glucagon-like peptide 1 (median, interquartile range) were greater in patients who developed hospital-acquired infections than in those who did not (237 pmol/L, 76-524 vs 80 pmol/L, 51-158; P < .001) and in patients who died (536 pmol/L, interquartile range: 336-891 pmol vs 98 pmol/L, 47-189; P < .001). Although the glucagon-like peptide 1 level could not predict hospital-acquired infections-free survival in individual patients, it could predict 1-year mortality independently (P = .021). Moreover, a glucagon-like peptide 1 level of 200 pmol/L could discriminate hospital-acquired infections-free survival (P < .001). CONCLUSION: Admission glucagon-like peptide 1 level can discriminate hospital-acquired infections-free survival and predict long-term mortality in a group of patients with burn injury. Our data suggests that glucagon-like peptide 1 may be a predictive biomarker for hospital-acquired infections and mortality in burn patients.

Effect of celecoxib in treatment of burn-induced hypermetabolism.

BACKGROUND: Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step of prostanoid biosynthesis. Under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that exacerbate injury and metabolic disturbance. The present study was performed to investigate the effect of Celecoxib (the inhibitor of COX-2) treatment on lipolysis in burn mice. METHODS: One hundred male BALB/c mice were randomly divided into sham group, burn group, celecoxib group, and burn with celecoxib group (25 mice in each group). Thirty percent total body surface area (TBSA) full-thickness injury was made for mice to mimic burn injuries. Volume of oxygen uptake (VO2), volume of carbon dioxide output (VCO2), respiratory exchange ratio (RER), energy expenditure (EE), COX-2 and uncoupled protein-1 (UCP-1) expression in brown adipose tissue (BAT) were measured for different groups. RESULTS: Adipose tissue (AT) activation was associated with the augmentation of mitochondria biogenesis, and UCP-1 expression in isolated iBAT mitochondria. In addition, VO2, VCO2, EE, COX-2, and UCP-1 expression were significantly higher in burn group than in burn with celecoxib group (P<0.05). CONCLUSION: BAT plays important roles in burn injury-induced hypermetabolism through its morphological changes and elevating the expression of UCP-1. Celecoxib could improve lipolysis after burn injury.

MIR-190B Alleviates Cell Autophagy and Burn-Induced Skeletal Muscle Wasting via Modulating PHLPP1/Akt/FoxO3A Signaling Pathway.

INTRODUCTION: Cell autophagy is an important material recycling process and is involved in regulating many vital activities under both physiological and pathological conditions. However, the mechanism of autophagy regulating burn-induced skeletal muscle wasting still needs to be elucidated. METHODS: The rat burn model with 30% total body surface area and L6 cell line were used in this study. An immunofluorescence assay was used to detect autophagic levels. MicroRNA array and real-time PCR were employed to measure miR-190b levels, and its influence on PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) protein translation was estimated using luciferase reporter assay. The expression levels of autophagy-related proteins were analyzed by Western blot. Skeletal muscle wasting was evaluated by the ratio of tibias anterior muscle weight to body weight. RESULTS: Our study demonstrates that burn injury promotes expression of the autophagy-related proteins light chain 3 (LC3) and Beclin-1, suppresses expression of Akt and Forkhead box O (FoxO) 3a protein phosphorylation, and increases PHLPP1 protein level which is required for Akt dephosphorylation. miR-190b, the regulator of PHLPP1 protein translation, also significantly decreases after burn injury. Ectopic expression of miR-190b in L6 myoblast cell downregulates PHLPP1 protein expression, elevates Akt and FoxO3a phosphorylation, and subsequently reduces cell autophagy. Finally, suppressing autophagy with 3-methyladenine represses the protein expression of LC3 and Beclin-1 and mitigates burn-induced skeletal muscle wasting. CONCLUSION: Burn injury induced skeletal muscle cell autophagy and subsequently resulted in skeletal muscle wasting via regulating miR-190b/PHLPP1/Akt/FoxO3a signaling pathway.

The microRNA expression profile in rat lung tissue early after burn injury.

BACKGROUND: Severe burn causes acute lung injury in many victims, but the related mechanisms have been barely investigated. microRNAs (miRNAs) important regulators in numerous physiological and pathophysiological process. However, the roles of miRNAs in burn lung injury are untested. METHODS: Six healthy male Sprague-Dawley rats were randomly assigned into burn and sham groups. Lung injury was evaluated by hematoxylin and eosin (HE) staining at 24 h after injury. Differentially expressed miRNAs were determined by array hybridization and verified by real-time quantitative polymerase chain reaction (RT-qPCR). Bioinformatics analysis was undertaken to predict the target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were employed to identify potentially related biological processes and pathways, respectively. Neutrophil infiltration and apoptosis of the lung were confirmed by immunohistochemical staining of myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: HE sections showed obvious lung injury, and 21 upregulated and three downregulated miRNAs were detected. Target genes of these miRNAs were most highly enriched in inflammation and apoptosis related GO biological processes and pathways. Inflammation and apoptosis were confirmed by MPO and TUNEL staining. CONCLUSION: The differentially expressed miRNAs most likely participate in burn-induced lung injury by being involved in inflammation and apoptosis.