The efficacy and safety of botulinum toxin B (BTX-B) for treatment of Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud's phenomenon were blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numbness visual analogue scale scores and Raynaud's score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numbers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud's phenomenon and digital ulcers in patients with SSc without serious adverse events.

Cutaneous ischemia-reperfusion (I/R) injury is associated with the early pathogenesis of cutaneous pressure ulcers (PUs). The objective of this study was to investigate the effect of mesenchymal stem cells (MSCs) injection on the formation of PUs after I/R injury and determine the underlying mechanisms. We found that the subcutaneous injection of MSCs into areas of I/R injured skin significantly suppressed the formation of PUs. I/R-induced vascular damage, hypoxia, oxidative DNA damage, and apoptosis were decreased by MSCs injection. Oxidative stress signals detected after I/R in OKD48 (Keap1-dependent oxidative stress detector, No-48-luciferase) mice were decreased by the injection of MSCs. In cultured fibroblasts, MSCs-conditioned medium significantly inhibited oxidant-induced reactive oxygen species (ROS) generation and apoptosis. Furthermore, endoplasmic reticulum (ER) stress signals detected after I/R in ERAI (ER stress-activated indicator) mice were also decreased by the injection of MSCs. These results suggest that the injection of MSCs might protect against the development of PUs after cutaneous I/R injury by reducing vascular damage, oxidative cellular damage, oxidative stress, ER stress, and apoptosis.

BTX-B injection might have protective effects against PU formation after cutaneous I/R injury by reducing vascular damage, hypoxia-induced oxidative and ER stress, and apoptosis.

MSCs-derived MFG-E8 might accelerate diabetic wound healing by promoting angiogenesis, the clearance of apoptotic cells, and the infiltration of M2 macrophages, and by suppressing inflammatory cytokines in wound area.

No abstract