Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Objective To investigate the clinical efficacy of acupuncture at Huatuo jiaji points plus point Shixuan bloodletting in treating cervical spondylotic radiculopathy.Methods One hundred patients with cervical spondylotic radiculopathy were randomly allocated to treatment and control groups, 50 cases each. The treatment group received acupuncture at Huatuo jiaji points plus point Shixuan bloodletting and the control group, acupuncture at Huatuo jiaji points alone. Plasma viscosity was measured in the two groups before and after treatment. The clinical therapeutic effects were compared between the two groups.Results There was a statistically significant pre-/post-treatment difference in plasma viscosity in the two groups (P<0.05). There was a statistically significant post-treatment difference in plasma viscosity between the treatment and control groups (P<0.05). The total efficacy rate was 94.0% in the treatment group and 84.0% in the control group; there was a statistically significant difference between the two groups (P<0.05).Conclusion Acupuncture at Huatuo jiaji points plus point Shixuan bloodletting is an effective way to treat cervical spondylotic radiculopathy.

Objective To observe the effect of acupuncture at the muscle region of meridians plus tuina on facial nerve function in peripheral facial paralysis. Method Sixty patients with peripheral facial paralysis (recovery stage) were randomized into a treatment group (intervened by acupuncture at the muscle region of meridians plus tuina) and a control group (intervened by conventional acupuncture), 30 cases in each group. Result The facial nerve electromyography (EMG) showed that the action potential latency and amplitude were changed significantly after the treatment in both groups (P<0.05), indicating that the two methods were both effective in recovering facial nerve function, while acupuncture at the muscle region of meridians plus tuina produced a more significant treatment effect compared to conventional acupuncture. In the treatment group, same treatment with different intervention times produced significantly different effects on the Toronto facial grading system (TFGS) (P<0.05), indicating that the earlier the intervention, the more significant the therapeutic efficacy. Conclusion Acupuncture at the muscle region of meridians plus tuina can produce a more significant effect in recovering facial nerve function in peripheral facial paralysis compared to conventional acupuncture.