No abstract

This study attempted to investigate the role and mechanism of endoplasmic reticulum (ER) stress in the islet dysfunction in mice after severe burns. C57BL/6 mice were randomly divided into the sham group, burn group, and burn+4-phenylbutyric acid (4-PBA) group. Mice were burned with full thickness of 30% total surface area (TBSA), and 4-PBA solution was intraperitoneally injected into mice in burn+4-PBA group. Glucose-stimulated insulin secretion (GSIS), Fasting blood glucose (FBG) and glucose tolerance were detected 24h post severe burns. The ER stress-related pathway markers BIP, XBP1, p-PERK, p-eIF2α, CHOP, ATF6, apoptosis-related protein Cleaved-Caspase 3, and islet cell apoptosis were measured. Mice were characterized with elevated FBG, decreased glucose tolerance and GSIS levels post severe burns. The expression of BIP, XBP1, p-PERK, p-eIF2α, CHOP, ATF6, Cleaved-Caspase 3, and islet cell apoptosis were increased significantly after severe burns. 4-PBA treatment contributed to decreased FBG, improved glucose tolerance, increased GSIS, inhibited islet ER stress, and reduced pancreatic islet cell apoptosis in mice post severe burns. ER stress occurs in islets of severely burned mice, which leads to increased apoptosis of islet cells, thus resulting in islet dysfunction.

Background: Wound healing is a dynamic, sequential, and complex physiological process, including a variety of cellular events, such as proliferation, adhesion, chemotaxis, and apoptosis. Skin fibroblasts (FBs) and keratinocytes (KCs) are the two most important cells involved in wound repair, and Relying on the proliferation and differentiation of keratinocytes to form epithelium to completely cover the wound is the ideal result for wound repair, so expanding the source of keratinocytes is a huge challenge. Objective: In this study, we examined the phenomenon that human neonatal foreskin fibroblasts (HFF) transdifferentiated into keratinocyte-like (KLCs) cells in conventional culture and evaluated the characteristics of KLCs and the potential mechanisms of the transdifferentiation process. Methods: The HFF and KCs were isolated with dynamic enzymolysis. HFF were routinely cultured in ordinary DMEM medium for more than 40 days, and observed the cell morphology. Western-blot, quantitative PCR (qPCR), immunofluorescence, and flow cytometry were adopted to assess the expression of the KCs markers cytokeratin 5, cytokeratin 14, cytokeratin 19, E-cadherin, Integrin β1 and the FBs marker Vimentin. Scratch wound assays, CCK-8 assays, and Transwell assays were conducted to test the function of KLCs. Mouse xenograft models were also used to evaluate the therapeutic effects and tumorigenicity of KLCs. High-throughput mRNA sequencing was also performed to explore the mechanism of cellular transformation. Results: HFF transdifferentiation started on day 25 and reached 98% by day 40. qPCR and Western-blot indicated significantly increased levels of the KCs markers (CK5, CK14, CK19, E-cadherin, and Integrin β1) in KLCs, and decreased FBs marker (Vimentin). Flow cytometry analysis demonstrated the number of cells expressing CK14 increased over time while the number of Vimentin-positive cells decreased. CCK8 results showed that the proliferation rates of KLCs and KCs were higher than HFF-1, but there was no obvious difference between KLCs and KCs. Scratch and Transwell assays revealed that the migration ability of KLCs and KCs was significantly lower than that of HFF. In vivo transplantation experiments indicated that there was no significant difference in the wound healing potential between KLCs and KCs. The transdifferentiation was regulated by the AKT/P53/WNT/LEF1 signaling pathway, and modulating the pathway could shorten the transdifferentiation time to 10 days. Conclusion: HFF can transdifferentiate into KLCs over time without intervention. This transdifferentiation process is regulated by the AKT/P53/WNT/LEF1 signaling pathway.

This study was designed to analyse the characteristics and aetiology of lowtemperature burns and explore the prevention and treatment strategies. In total, 206 patients hospitalised with low-temperature burns in a major burn center in Beijing from 2017 to 2021 were included. There were 35-49 cases per year, with an average of 41 ± 4.5 cases. The prevalence of low-temperature burns was higher in female than in male and are mainly resulted from two kinds of incidents: unintended burns from heat treatment (50.97%, 105/206) and improper use of heating devices to keep warm (43.69%, 90/206). Most cases occurred in autumn (33.01%, 68/206) and the least in spring (17.96%, 37/206); cases in summer (24.27%, 50/206) and winter (24.76%, 51/206) accounted for nearly a quadrant respectively. Low-temperature burns in summer were mainly unintended burns from heat treatment (80%, 40/50), whereas in autumn were mainly resulted from improper use of heating devices to keep warm (55.88%, 38/68), the difference was statistically significant (χ 2 = 42.801, P < .001). Of all the cases, the burn size ranged from 0.2% to 5% TBSA, mostly less than 1% (85.92%, 177/206); third-degree burns accounted for 98.54% (203/206). Patients admitted after 3 weeks post-injury accounted for 42.23% (87/206). All patients were cured, and most of them were by surgeries (70.87%, 146/206). The results of the study show that low-temperature burn injury features a predictable morbidity among different seasons, a higher prevalence in adult women and a frequent occurrence at home. The wounds of low-temperature burns are often small in size but deep in depth, and can be easily misdiagnosed as superficial burns. However, most low-temperature burn wounds require surgical treatment. The study also suggests that based on the characteristics and aetiology of low-temperature burns, targeted prevention and treatment measures should be mapped out.