SCN4 is an autosomal recessive disease caused by mutations in the G6PC3 gene. The clinical, molecular, and immunological features; function of neutrophils; and prognosis of patients with SCN4 have not been fully elucidated.

Diabetic foot ulcer (DFU) frequently leads to non-traumatic amputation and finally even death. However, the mechanism of DFU is not fully understood. Interleukin 25 (IL-25), an alarmin cytokine that responds to tissue injury, has been reported to participate in tissue regeneration and maintaining glucose homeostasis. However, the role of IL-25 in diabetic wound healing remains unknown. Here, we showed that interleukin 17 receptor B (IL-17RB), the functional receptor of IL-25, was significantly inhibited in the wound skin of both diabetic patients with DFU and streptozotocin (STZ)-induced diabetic mice. Topical administration of recombinant IL-25 protein improved angiogenesis and collagen deposition in the wound bed and thus ameliorated delayed diabetic wound healing. IL-25 increased endothelial-specific CD31 expression in diabetic wounds and exogenous IL-25 protected endothelial cells from high glucose-impaired cell migration and tube formation in vitro. We further revealed that IL-25-mediated-IL-17RB signaling rescued the downregulation of Wnt/β-catenin pathway both in vivo in diabetic mice and in vitro in HUVECs and induced the phosphorylation of AKT and ERK 1/2 in HUVECs under high glucose conditions. This study defines a positive regulatory role of IL-25-mediated-IL-17RB signaling in diabetic wound healing and suggests that induction of IL-25-mediated-IL-17RB signaling may be a novel therapeutic strategy for treating poor healing diabetic wounds.

Despite extensive research, urosepsis remains a life-threatening, high-mortality disease. Currently, animal models of urosepsis widely accepted by investigators are very scarce. This study aimed to establish a standardized and reproducible model of urosepsis in rats. Forty adult Wistar rats were randomly divided into four groups according to the concentration of injected E. coli suspensions: Sham, Sep 3×, Sep 6×, and Sep 12×. Because the ureter is so thin and fragile, no conventional needle can be inserted into the ureter, which is probably why rats are rarely used to develop models of urosepsis. To solve this problem, the left ureter was ligated in the first procedure. After 24 hours, the left ureter above the ligation was significantly dilated, then saline or different concentrations of E. coli at 3 ml/kg were injected into the left renal pelvis using a 30G needle. The left ureter was subsequently ligated again at a distance of 1 cm from the renal hilum to maintain high pressure in the renal pelvis. Following injection of E. coli or saline for 24 h, three rats from each group were sacrificed and their organs (lung, liver, and right kidney) were collected. In contrast, the remaining seven rats continued to be observed for survival. At 10 days after E. coli injection, rats in the sep12× group had a higher mortality rate (100%) compared to the sep3× group (28.6%) or the sep6× group (71.4%). The significant changes in peripheral blood WBC count, serum IL-6 and TNF-α levels were also in the sep12× group. In addition, rats in the sepsis group showed multi-organ dysfunction, including damage to the lungs, liver, and kidneys. The establishment of a standardized rat model of urosepsis may be of great value for studying the pathophysiological of urosepsis.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by extensive skin fibrosis. There are no effective treatments due to the severity, multiorgan presentation, and variable outcomes of the disease. Here, integrated bioinformatics was employed to discover tissue-specific expressed hub genes associated with SSc, determine potential competing endogenous RNAs (ceRNA) regulatory networks, and identify potential targeted drugs.