Introduction While studies using various materials to overcome ischemia-reperfusion (IR) injury are becoming increasingly common, studies on the effects of botulinum toxin A (BoTA) on IR injury in musculocutaneous flaps are still limited. The purpose of this study was to examine our hypotheses that BoTA provide protection of musculocutaneous flap from ischemia-reperfusion injury. Method Five days after pretreatment injection (BoTA versus normal saline), a right superior musculocutaneous flap (6 × 1.5 cm in size) was made. Ischemia was created by a tourniquet strictly wrapping the pedicle containing skin and muscle for 8 h. After ischemia, the tourniquet was cut, and the musculocutaneous flap was reperfused. Results The overall survival percentage of flap after 8 h of pedicle clamping followed by reperfusion was 87.32 ± 3.67% in the control group versus 95.64 ± 3.25% in the BoTA group (p < 0.001). The BoTA group had higher expression of CD34, HIF-1α, VEGF, and NF-kB comparing to control group in qRT-PCR analysis. Conclusions In this study, we found that local BoTA preconditioning yielded significant protection against IR injury in a rat musculocutaneous flap model.
Objective: Inactivation of poly(ADP-ribose) polymerase 1 ( PARP1 ) has been found to have protective effect in several fibrotic diseases. But the effect is not studied yet in keloids. Herein, we evaluated the therapeutic effect of PARP1 inhibitor, rucaparib, for keloids. Approach: The protein expressions of PARP1 and smad3 were evaluated with western blotting in keloids and controls. The effect of rucaparib was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and migration assay. We further analyzed the effect of rucaparib on patient-derived keloid xenograft murine model. Results: The protein expressions of PARP1 and smad3 were significantly higher in keloid tissue. Rucaparib (20 μM) significantly suppressed the proliferation of keloid fibroblasts. Moreover, the combination of rucaparib (20 μM) and triamcinolone (50 μM) showed additive suppressive effect on keloid fibroblasts. Migration assay showed that rucaparib (10 μM) significantly suppressed the migration of keloid fibroblasts. Fibrosis markers in keloid fibroblasts significantly decreased after rucaparib treatment (20 μM). In patient-derived keloid xenograft model, rucaparib significantly reduced the size of keloid tissue. Innovation and Conclusion: The study data suggest PARP1 might be a novel therapeutic target for keloid disease. PARP1 inhibitor, rucaparib, might be a promising therapeutic drug for the treatment of keloid disease.
BackgroundIdentifying novel and safe immunosuppressants is of crucial importance. Recently, there have been several studies revealing that botulinum toxin A significantly alleviates ischemia-reperfusion injuries.Emerging evidence shows that ischemia-reperfusion injuries contribute to innate immune activation, promoting rejection and inhibiting tolerance. Therefore, we hypothesized that a pretreatment with botulinum toxin A might decrease allograft rejection in a rat transplantation model. MethodsTwenty-four Lewis rats were randomly assigned to two groups consisting of 12 rats each, depending on whether skin allograft was performed after pretreatment with botulinum toxin A (BoTA group) or with normal saline (control group). The experimental group was pretreated with a subcutaneous injection of botulinum toxin A (10 IU), while the control group was pretreated with normal saline 5 days prior to surgery. The donor Brown-Norway rat dorsal skin was subsequently grafted to the recipient Lewis rats. The recipient wounds, measuring 2 cm × 2 cm, were made via dorsal skin excision through the panniculus carnosus. The donor skins of the same dimensions were obtained and transplanted onto the wounds and sutured with 4-0 nylon sutures. Mean graft survival time was measured in both groups. Quantitative reverse-transcriptase polymerase chain reaction and western blotting were performed to evaluate the gene/protein expression of CD4 and VEGF. ResultsThe mean graft survival time in the BoTA group was significantly longer than that of the control group (p=0.004). The relative mRNA and protein expression of CD4 was significantly lower in the BoTA group (p<0.001), while the relative mRNA and protein expression of VEGF was significantly higher in the BoTA group (p<0.001). ConclusionIn conclusion, our results show that botulinum toxin A prolongs the survival of skin allografts in a rat transplantation model.
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