m6A reader IGF2BP1 accelerates apoptosis of high glucose-induced vascular endothelial cells in a m6A-HMGB1 dependent manner.

Emerging evidence indicates that N6-methyladenosine (m6A) plays a critical role in vascular biological characteristic. In diabetes mellitus pathophysiology, high glucose (HG)-induced vascular endothelial dysfunction is associated with diabetes vascular complications. Nevertheless, the underlying mechanism of high glucose (HG)-related m6A regulation on vascular endothelial cells is still unclear. Results indicated that m6A reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was up-regulated in HG-treated human umbilical vascular endothelium cells (HUVECs) comparing to normal group. Functionally, results indicated that IGF2BP1 knockdown recovered the proliferation of HUVECs inhibited by HG-administration. Besides, IGF2BP1 knockdown reduced the apoptosis induced by HG-administration. Mechanistically, IGF2BP1 interacted with HMGB1 mRNA and stabilized its expression of m6A-modified RNA. Therefore, these findings provided compelling evidence demonstrating that m6A reader IGF2BP1 contributes to the proliferation and apoptosis of vascular endothelial cells in hyperglycaemia, serving as a target for development of diabetic angiopathy therapeutics.

Molecular imbalance mechanism of skin and blood leucocytes in severe burn patients at different burn times.

Background: Severe burns are a leading cause of injuries worldwide and are usually accompanied by considerable morbidity and mortality. The purpose of this study was to investigate the changes of gene expression in blood and skin at different times after severe burn. Methods: Firstly, the gene expression profiles of different burn time samples in GSE19743 and GSE8056 were analyzed. Secondly, the maladjusted gene network was identified by protein-protein interaction (PPI) network, and the genes in the network were enriched and analyzed. In addition, the key dysfunctional genes were identified by betweenness algorithm, and evaluated by survival analysis, Cox analysis, receiver operating characteristic (ROC) analysis. Finally, crosstalk analysis and enrichment analysis were carried out between the blood- and skin-specific differentially expressed genes (DEGs) at different burn times. Results: The results showed that there were common DEGs in the blood and skin at different burn times. Importantly, we screened out the key dysfunctional genes BIRC5, NCAM1, PCNA, TOP2A, and VEGFA, which were related to the course of burns. Enrichment analysis showed that these maladjusted genes were mainly involved in the immune inflammation-related signal pathway. Additionally, significant crosstalk was identified between blood- and skin-specific genes at different burn times, especially in the blood. The signal pathways involved in specific genes represent their own pathological characteristics. Conclusions: Both blood and skin tissues express common pathological changes and unique molecular mechanisms at different times after burn injury. The results of this study provide guidance for clinical personalized treatment.

Promoting repair of highly purified stromal vascular fraction gel combined with advanced platelet-rich fibrin extract for irradiated skin and soft tissue injury.

Background: To evaluate the effect of highly purified stromal vascular fraction gel (SVFG) combined with advanced platelet-rich fibrin extract (APRFE) in treatment of irradiated skin and soft tissue injury. Methods: The subcutaneous fat and whole blood of 4 rabbits were collected to isolate the SVFG and APRFE, respectively. Forty-eight rabbits were divided into 4 groups to prepare irradiated skin injury models with 25 Gy for 24 hours; corresponding dose were performed subcutaneously injected into wounds. In group A, the rabbits were treated with 0.3 mL APRFE combined with 1 mL SVFG. In group B, the rabbits were treated with 1 mL SVFG. In group C, the rabbits were treated with 0.3 mL APRFE, and group D was treated with 1 mL normal saline. The wound healing was detected on the 2, 5, 9 and 14 d after intervention. The wounds tissue was cut for hematoxylin and eosin (HE) staining to observe the structure and Masson staining to observe the collagen content. The expression of CD31 in each group was detected by immunohistochemistry (IHC), the protein and mRNA levels of K19, hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), interleukin 8 (IL-8) and interleukin 10 (IL-10) were detected respectively by Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) on 7, 14 and 28 d after intervention. Results: It is revealed that wound healing rates from 5 to 14 d in group A was significantly higher than that of control. The wounds healing rates in group B and C were significantly higher than that of control after 12 d. Masson staining results showed that the collagen content in group A was significantly higher than that of the other 3 groups on the 7, 14 and 28 d. The results of IHC showed that the expression of CD31 in group A was significantly higher than that of the other 3 groups on 7, 14 and 28 d. WB and RT-PCR results showed that relative expression levels of K19, HIF-1α, VEGF, IL-10 in group A were significantly higher than that of the other 3 groups on 7, 14 and 28 d. However, the relative expression levels of IL-8 in group A was significantly lower than that of the other 3 groups on 7, 14 and 28 d. Conclusions: SVFG combined with APRFE can promote the repair of irradiated skin and soft tissue injury by accelerating angiogenesis, promoting collagen synthesis and reducing inflammation.