Background: Ustekinumab, a human-derived monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23, has excellent clinical efficacy and safety in treating psoriasis, with a long half-life. However, no reports have described the use of human skin/serum samples to elucidate its molecular mechanisms. Material/Methods: Twenty-four psoriasis patients were enrolled in our double-blind study and randomly divided into placebo and ustekinumab-administered groups. Dynamic changes in psoriasis area-severity index scores, and mRNA and protein levels of p35 and p40 were analyzed at 3 time points (before treatment and during the 12 th and 24 th weeks of treatment). Results: Ustekinumab initially increased and then decreased p35 mRNA expression, but increased p40 mRNA levels throughout the study. The p35 protein levels were not significantly altered, while p40 protein levels were increased after the first 2 injections but decreased after the third injection. Conclusions: We concluded that 2 equilibria influence the efficacy of ustekinumab against psoriasis. First, because of the dual roles of p35 in psoriasis pathogenesis, homeostasis occurs between p35 and p40 expression levels. The second balance lies between the upregulation of p40 mRNA levels and the ability of ustekinumab to neutralize the function of the elevated p40 protein.
Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, the molecular mechanisms have not been fully elucidated. Objectives: to explicitly demonstrate the relationship between adipose-derived stem cells alleviating keloids and alterations of Col-1, Col-3, CTGF, and P-4-HB. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into two groups, one co-cultured with adipose-derived stem cells and the other grown independently. We compared the wound-healing rates, fibroblast survival rates, apoptosis rates, mRNA expressions, and protein levels of Col-1, Col-3, CTGF, and P-4-HB between separated groups. Results: We found no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate at the baseline. With adipose-derived stem cells, wound-healing rate and survival rate of normal fibroblasts were promoted, whereas in keloid fibroblasts, they were reduced. The apoptosis rate of normal fibroblasts and keloid fibroblasts were restrained, with the restraint in keloid fibroblasts being more evident. The protein levels of Col-3, CTGF, and P-4-HB were lower in keloid fibroblasts co-cultured with adipose-derived stem cells than in normal fibroblasts under similar conditions. Conclusions: Adipose-derived stem cells strongly suppressed keloid fibroblasts' proliferative and invasive behavior. However, adipose-derived stem cells negatively regulated keloid fibroblast apoptosis. Adipose-derived stem cells can be a potential keloid therapy worth further investigation.
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