Heme oxygenase-1 induction mitigates burn-associated early acute kidney injury via the TLR4 signaling pathway.

OBJECTIVES: Early acute kidney injury (AKI) after burn contributes to disastrous prognoses for severely burned patients. Burn-induced renal oxidative stress and secondary proinflammatory mediator release contribute to early AKI development, and Toll-like receptor (TLR) 4 regulates inflammation. Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that plays a vital role in protecting against ischemia-induced organ injury via its antioxidant properties and regulation of inflammation. We investigated the potential effect of HO-1 induction in preventing burn-induced early AKI and its related mechanism. METHODS: A classic major-burn rat model was established using a 100 °C water bath, and hemin was injected intraperitoneally immediately after the injury to induce HO-1. Histological staining and blood tests were used to assess AKI progression based on structural changes and function. Renal levels of HO-1, oxidative stress, proinflammatory mediators and TLR4-related signals were detected using ELISA, immunostaining, qRT-PCR, and western blotting. The selective TLR4 inhibitor TAK242 and TLR4 inducer LPS were introduced to determine the roles of HO-1 in burn-related renal inflammation and the TLR4 pathway. RESULTS: Hemin improved burn-induced renal histological damage and dysfunction, and this beneficial effect was related to reduced renal oxidative stress and the release of proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6 and intracellular adhesion molecule-1 (ICAM-1). Hemin downregulated the expression of TLR4 and the subsequent phosphorylation of IKKα/ß, IκBα, and NF-κB p65;. TAK242 exerted an effect similar to but weaker than hemin; and LPS reversed the antiinflammatory effect of hemin and the regulation of TLR4 signals. These results suggested that the TLR4 signaling pathway mediated the HO-1-facilitated regulation of renal inflammation after burn. CONCLUSION: The present study demonstrated that HO-1 induction prevented burn-induced early AKI by targeting renal inflammation, which was mediated via regulation of the TLR4/NF-κB signaling pathway.

Locally activated mitophagy contributes to a "built-in" protection against early burn-wound progression in rats.

AIMS: Deep burn-wounds undergo a dynamic progression in the initial or periburn area after insults, and the zone of stasis is the crucial region suffering the deterioration, considered as salvageable. Few studies explored the role of mitochondria in this process. This study is to clarify a possible "built-in" protection of mitophagy. MAIN METHODS: A classic "comb" scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission-electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator. KEY FINDINGS: We found that burn-caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was involved in the aforementioned changes. Furthermore, we detected mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. SIGNIFICANCE: We demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a therapeutic target due to its possible regulation on BNIP3- or PARKIN-mediated mitophagy.

Clinical decision model for the reconstruction of 175 cases of scalp avulsion/defect.

PURPOSE: It has been reported widely on various methods of repairing scalp avulsion/defect, including anastomotic vessels for total scalp avulsion and dermal grafts (skin grafting, latissimus dorsi or anterior serratus flap, "visor flap" repair.). The long-term retrospective study, however, with large sample size remains rare; and there is no report on decision-making tree for repairing emergency scalp avulsion/defects under critical conditions. METHODS: The decision-making model is provided for surgeons to design the scalp reconstruction based on the retrospective analysis of 175 cases of scalp avulsion/scalp defect. In this 10-year retrospective study, 175 cases of the repair of scalp avulsion and scalp defects in a single center were analyzed. The clinical decision model was generated based on representative cases. RESULTS: For patients with scalp avulsion/defects, a comprehensive examination and evaluation on systemic injury and complication should be conducted first for saving lives and reducing trauma effects. To make more reasonable clinical decisions, it is also required to determine the location, size, depth of scalp defect the injury area of cranial periosteum, injury of blood vessel or other adjacent organs, and whether the scalp can be reused. Meanwhile, it is necessary to evaluate whether the patient can tolerate long-term anastomotic vascular surgery according to the vital signs and physical status. CONCLUSION: The primary treatment goal is to decrease traumatic effects and save patient's life while repairing and reconstructing scalp avulsions and scalp defects. In addition, it is necessary to comprehensively consider the anatomical, functional and cosmetic characteristics of scalp, surgical equipment, team technical skillsets and patient's own pursuit to optimize a reasonable surgical solution.

A Retrospective Multicenter Study of 1898 Liquefied Petroleum Gas-Related Burn Patients in Eastern China From 2011 to 2015.

Liquefied petroleum gas (LPG) is a widely used environment-friendly fuel. Previous studies have shown an increasing number of LPG-related burns. Our study was designed to evaluate the epidemiologic pattern of these injuries and provide recommendations for burn prevention. This retrospective study included all patients with LPG-related burns from eight burn centers in Zhejiang Province, China between 2011 and 2015. Database variables included patient demographics, accident characteristics, and injury characteristics. The association between different categorical variables was identified using the chi-square test. And the association between two or more means of quantitative variables was analyzed by the one-way analysis of variance or t-test. A total of 1898 patients were included, 47.31% were males and 52.69% were females. The predominant age group was 31 to 70 years (74.50%), and the majority were poorly educated and the incidence peaked from June to September. The most common place of occurrence was home (74.08%) and gas leak (96.52%) was the most common cause. The four limbs (43.33%) were the most frequently affected areas; the mean burn area was 25.19 ± 20.97% of the total body surface area and most patients (46.89%) suffered from moderate burns. The mean length of hospital stay was 17.66 ± 16.55 days and the majority of patients (89.36%) recovered with a 0.84% mortality rate. Our findings reflected that the increase in incidence rate was alarming, and the causes resulting in LPG-related burns have not gained much attention yet. Therefore, this calls for simple but strict measures aiming at each hazardous step during the use of LPG to prevent these burn injuries.