A molecular approach to maggot debridement therapy with Lucilia sericata and its excretions/secretions in wound healing

Chronic wounds caused by underlying physiological causes such as diabetic wounds, pressure ulcers, venous leg ulcers and infected wounds affect a significant portion of the population. In order to treat chronic wounds, a strong debridement, removal of necrotic tissue, elimination of infection and stimulation of granulation tissue are required. Maggot debridement therapy (MDT), which is an alternative treatment method based on history, has been used quite widely. MDT is an efficient, simple, cost-effective and reliable biosurgery method using mostly larvae of Lucilia sericata fly species. Larvae can both physically remove necrotic tissue from the wound site and stimulate wound healing by activating molecular processes in the wound area through the enzymes they secrete. The larvae can stimulate wound healing by activating molecular processes in the wound area through enzymes in their excretions/secretions (ES). Studies have shown that ES has antibacterial, antifungal, anti-inflammatory, angiogenic, proliferative, hemostatic and tissue-regenerating effects both in vivo and in vitro. It is suggested that these effects stimulate wound healing and accelerate wound healing by initiating a direct signal cascade with cells in the wound area. However, the enzymes and peptides in ES are mostly still undefined. Examining the molecular content of ES and the biological effects of these ingredients is quite important to illuminate the molecular mechanism underlying MDT. More importantly, ES has the potential to have positive effects on wound healing and to be used more as a therapeutic agent in the future, so it can be applied as an alternative to MDT in wound healing

The Effects of the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin, Cannabinoid Agonist WIN 55,212-2, and Nitric Oxide Synthase Inhibitor N omega-Nitro-L-Arginine Methyl Ester Hydrochloride on the Serotonin and Dry Skin-Induced Itch

Introduction: In many types of itch, the interaction between immune system cells, keratinocytes, and sensory nerves involved in the transmission of itch is quite complex. Especially for patients with chronic itching, current treatments are insufficient, and their quality of life deteriorates significantly. Objective: In this study, we aimed to investigate the role of the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), cannabinoid agonist WIN 55,212-2, and nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) in pruritus. Methods: We created a serotonin (5-HT)-induced (50 mu g/mu L/mouse, i.d.) acute and acetone-ether-water (AEW)-induced chronic itching models. 17-AAG (1, 3, and 5 mg/kg, intraperitoneally [i.p.]), WIN 55,212-2 (1 mg/kg, i.p.), and L-NAME (1 mg/kg, i.p.) were applied to Balb/c mice. Results: We found that 17-AAG suppressed the scratches of mice, depending on the dose. The itch behavior was reduced by WIN 55,212-2, but L-NAME showed no antipruritic effect at the administered dose. The combined application of these agents in both pruritus models showed synergism in terms of the antipruritic effect. Our results showed that NO did not play a role in the antipruritic effect of WIN 55,212-2 and 17-AAG. Increased plasma IgE levels with AEW treatment decreased with the administration of 17-AAG (5 mg/kg, i.p.) and WIN 55,212-2. Conclusion: These results demonstrate that Hsp90 may play a role in the peripheral pathway of pruritus, and cannabinoid agonists and Hsp90 inhibitors can be used together in the treatment of pruritus

Topical application of metformin accelerates cutaneous wound healing in streptozotocin-induced diabetic rats

Background Diabetic chronic wound, which is one of the diabetic complications caused by hyperglycemia, characterized by prolonged inflammation has become one of the most serious challenges in the clinic. Hyperglycemia during diabetes not only causes prolonged inflammation and delayed wound healing but also modulates the activation of nuclear factor-kappa B (NF-kappa B) and the expression of matrix metalloproteinases (MMPs). Although metformin is the oldest oral antihyperglycemic drug commonly used for treating type 2 diabetes, few studies have explored the molecular mechanism of its topical effect on wound healing. Therefore, we aimed to investigate the molecular effects of topical metformin application on delayed wound healing, which's common in diabetes. Methods and results In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-kappa B p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline. As a result of our study, we showed that topically applied metformin accelerates wound healing by suppressing NF-kappa B p65 activity and diminishing the expression of MMP2 and MMP9. Conclusions Diabetic wounds treated with metformin healed even faster than those in the control group that mimicked standard wound healing