Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

Serum uric acid is neuroprotective in Chinese patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator.

BACKGROUND: Exogenous uric acid (UA) is a neuroprotective antioxidant that reinforces the benefits of intravenous recombinant tissue plasminogen activator thrombolysis in animal thromboembolic stroke. However, whether serum uric acid (SUA) also increases the benefits of thrombolysis in Chinese patients with acute ischemic stroke (AIS) has yet to be fully defined. METHODS: A total of 216 consecutive AIS patients of Chinese origin treated with intravenous thrombolysis were enrolled in a prospective stroke registry. Demographic and clinical characteristics, conventional risk factors, important laboratory data, and neurologic course were prospectively recorded. Functional outcomes were assessed with the modified Rankin Scale (mRS) score on day 90 by telephone calls. Receiver operating characteristic curves and binary logistic regression models were used to examine the performance of SUA in predicting excellent outcomes (mRS, 0-1). RESULTS: SUA levels were significantly higher in patients with excellent outcomes than those in patients with poor outcomes (331.46 ± 103.39 versus 277.69 ± 105.62, P = .008). SUA had a modest power for predicting excellent outcomes as suggested by area under the curve of .665 ± .052, P = .003. In multivariate models, increased SUA levels (adjusted odds ratio, 1.005; 95% confidence interval, 1.002-1.009; P = .033) were associated with excellent outcomes independently of the effect of possible confounders. Spearman correlation tests indicated that there was an inverse correlation between SUA levels and stroke severity. CONCLUSIONS: Increased SUA levels are associated with excellent outcomes in Chinese patients with AIS treated with intravenous thrombolysis, giving additional support to administration of exogenous UA as an adjuvant to thrombolysis.

Salvianolate inhibits reactive oxygen species production in H(2)O(2)-treated mouse cardiomyocytes in vitro via the TGFß pathway.

AIM: To investigate the effects of salvianolate, a water-soluble active compound from Salvia miltiorrhiza Bunge, on reactive oxygen species (ROS) production in mouse cardiomyocytes in vitro. METHODS: Primary ventricular cardiomyocytes were prepared from neonatal mouse. The cell viability was determined using MTT assay. Culture medium for each treatment was collected for measuring the levels of NO, iNOS, total antioxidant capacity (TAOC) and transforming growth factor ß1 (TGFß1). TGFß1 and Smad2/3 expression in the cells was detected with Western blotting. RESULTS: H2O2 (1.25 mmol/L) did not significantly affect the cell viability, whereas the high concentration of salvianolate (5 g/L) alone dramatically suppressed the cell viability. Treatment of the cells with H2O2 (1.25 mmol/L) markedly increased ROS and iNOS production, and decreased the levels of NO, TAOC and TGFß1 in the culture medium. Furthermore, the H2O2 treatment significantly increased TGFß1 and Smad2/3 expression in the cells. Addition of salvianolate (0.05, 0.1, and 0.5 g/L) concentration-dependently reversed the H2O2-induced alterations in the culture medium; addition of salvianolate (0.05 g/L) reversed the H2O2-induced increases of TGFß1 and Smad2/3 expression in the cells. Blockage of TGFß1 with its antibody (1 mg/L) abolished the above mentioned effects of salvianolate. CONCLUSION: Salvianolate inhibits ROS and iNOS production and increases TAOC and NO levels in H2O2-treated cardiomyocytes in vitro via downregulation of Smad2/3 and TGFß1 expression. High concentration of salvianolate causes cytotoxicity in mouse cardiomyocytes.