Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro−/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin.

The prevalence of psoriasis is increasing, and poses a serious risk to human health and quality of life. Psoriasis, a chronic immune‑mediated skin disease with epidermal hyperkeratosis and parakeratosis, is associated with numerous complications, including metabolic syndromes that are regulated by sirtuins (SIRTs) via deacetylation. As they serve a necessary function in inflammation and metabolism, SIRTs are considered to link inflammation and metabolic syndrome. Previous studies have indicated that SIRTs serve a function in the pathophysiology of psoriasis, but to date no detailed research has been conducted investigating the expression levels and patterns of SIRTs in psoriasis. The present study investigated the abnormal expression of SIRTs in psoriasis and provided a theoretical foundation for the treatment and prognosis of psoriasis. Tumor necrosis factor (TNF)‑α‑stimulated HaCaT cells and an imiquimod‑induced psoriasis mouse model were used to produce in vitro and in vivo models, respectively. Psoriasis clinical specimens (psoriasis area and severity index >10; n=22) and normal group specimens (n=22) were obtained from human subjects. The mRNA and protein expression levels in human and mouse skin lesions and TNF‑α‑stimulated HaCaT cells were detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting, and compared with the control groups. The expression patterns of SIRT proteins were investigated using immunofluorescence (IF) staining. The expression levels of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 were downregulated while those of SIRT6 and SIRT7 were upregulated in skin lesions and TNF‑α‑stimulated HaCaT cells compared with the control group as determined by RT‑qPCR, western blotting and IF. Statistically significant differences were observed in vivo and in vitro. P‑values of SIRT1‑7 mRNA are less than 0.05 in RT‑qPCR, and the P‑values of SIRT1‑7 proteins are less than 0.05 except for SIRT4 in the western blot analysis. SIRTs serve notable functions in severe psoriasis dermatitis, with the overexpression of SIRT6 and SIRT7 potentially induced by the adaptive immune response, and the downregulation of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 may be a result of an internal environment imbalance in vivo. Psoriasis is an inflammation and metabolism‑associated disease mediated by the SIRT family. The present results provide a novel potential mechanism and strategy for the treatment of psoriasis by modulating the function and expression of SIRTs.