Active wound dressings are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected skin wound healing. As the wide use of antibiotics leads to drug resistance we present here a new concept of wound dressings based on the polycaprolactone nanofiber scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as antibacterial agent. Firstly, we demonstrated in vitro that LPPO released from NANO exerted antibacterial activity while not impairing proliferation/differentiation of fibroblasts and keratinocytes. Secondly, using a mouse model we showed that NANO loaded with LPPO significantly reduced the Staphylococcus aureus counts in infected wounds as evaluated 7 days post-surgery. Furthermore, the rate of degradation and subsequent LPPO release in infected wounds was also facilitated by lytic enzymes secreted by inoculated bacteria. Finally, LPPO displayed negligible to no systemic absorption. In conclusion, the composite antibacterial NANO-LPPO-based dressing reduces the bacterial load and promotes skin repair, with the potential to treat wounds in clinical settings.
Transforming growth factor beta 1 (TGF-β1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-β1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluo-rescence). We demonstrated that TGF-β1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-β1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.
Background/Aim: We have previously shown that the water extract of Agrimonia eupatoria L. (AE) is a valuable source of polyphenols with excellent antioxidant properties and has clinical potential for the prevention and/or adjuvant therapy of cardiovascular complications associated with diabetes. Inspired by our previously published data, in the present study we examined whether AE improves skin wound healing in a series of in vitro and in vivo experiments. Materials and Methods: In detail, we investigated the ability of the AE extract to induce fibroblast to myofibroblast conversion, extracellular matrix (ECM) deposition, and keratinocyte proliferation/ differentiation, in vitro. In parallel, in an animal model, we measured wound tensile strength (TS) and assessed the progression of open wounds using basic histology and immunofluorescence. Results: The AE extract induced the myofibroblast-like phenotype and enhanced ECM deposition, both in vitro and in vivo. Furthermore, the wound TS of skin incisions and the contraction rates of open excisions were significantly increased in the AE-treated group. Conclusion: The present data show that AE water extract significantly improves the healing of open and sutured skin wounds. Therefore, our data warrant further testing in animal models that are physiologically and evolutionarily closer to humans.In recent decades, interest in the potential health benefits of phytomedicine has increased. Many of the health effects of extracts are associated with the presence of polyphenols (1, 2). In this context, we previously identified the presence of several 1236
Fibroblasts are actively involved in the formation of granulation tissue and/or tumor stroma. These cells possess the potential to differentiate into myofibroblasts acquiring a highly contractile -smooth muscle actin (SMA). Considering TGFas the main inducer of myofibroblast differentiation and horse chestnut extract (HCE) as an effective modulator of the wound healing, we have new evidence to demonstrate canonical TGF--canonical/non-SMAD signaling in normal fibroblasts, isolated from healthy human skin (human dermal fibroblasts -HDFs), and their malignant counterparts (CAFs) isolated from basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) using western blot and immunofluorescence. Our study revealed that HCE stimulated the deposition of fibronectin by BCC fibroblasts (BCCFs), an effect not seen in other studied fibroblasts. Moreover, HCE in combination with TGF--stress fibers, particularly visible in CAFs. Interestingly, the TGF-e canonical SMAD signaling in HDFs and BCCFs, whereas treatment of SCC fibroblasts (SCCFs) resulted in activation of the non-canonical AKT and/or ERK1/2 signaling. In conclusion, we observed specific differences in signaling between HDFs and CAFs that should be considered when developing new therapeutic approaches targeting wound/tumor microenvironments.
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