The protective effects of high-dose ascorbic acid (250 mg/kg) on the myocardium were observed in 85 patients undergoing Cardiopulmonary Bypass (CPB). The changes in serum Malonyldialdehyde (MDA). Creatine Phosphokinase (CPK), Creatine Phosphokinase isozyme (CPK-MB) and Lactic Dehydrogenase (LDH) in group B (n = 45, receiving ascorbic acid) were lower (p < 0.05) than in group A (n = 40, no ascorbic acid) during and after CPB. The MDA remained at a higher level two days postoperatively; CPK and CPK-MB, the sensitive and specific reflectors of myocardial injury, recovered very slowly in the control group (A) after the operation. The hearts in all the patients of group B resuscitated automatically intraoperatively while five cases (12.5%) needed defibrillation in group A. The cardiac index (CI) measured in ICU in group B was higher than in group A (p < 0.05). The patients needed shorter ICU and hospital stays in group B than in group A. The results indicate that ascorbic acid can act as a scavenger of free radicals to decrease the peroxidation of the lipids present in the cell membrane and remove the radicals to protect the myocardium from ischemia-reperfusion injury effectively during and after open-heart operation.

Chronic foot wounds are a leading cause of morbidity and hospitalization for patients with diabetes. Negative pressure wound therapy (NPWT) is known to promote healing of diabetic foot wounds, but the underlying molecular mechanisms remain elusive. We propose to gain molecular insights into the wound healing promoting signals underlying the effects of NPWT on diabetic foot wounds in humans. We assessed 30 patients with diabetic foot ulcers. Of these cases, 15 were treated with NPWT, while 15 patients were treated with traditional gauze therapy. Granulated tissue was harvested before and after treatment in both patient groups and histologically analyzed with hematoxylin & eosin as well as Masson's trichrome staining methods. Immunohistochemistry and Western blot analysis was performed to evaluate expression of basic fibroblast growth factor (bFGF) and extracellular signal-regulated kinase (ERK)1/2, previously associated with promoting cellular growth and/or wound healing. Unlike controls, the wounds in the NPWT-treated diabetic patients developed characteristic features of granulated tissue with increased collagen deposition. Immunohistochemical analysis also revealed an increase in bFGF levels in NPWT-treated patients. Western blot analysis further showed a significant up-regulation of bFGF and phosphorylated ERK1/2 protein levels in the NPWT-treated diabetic patients vs. controls. Our studies reveal that NPWT is associated with an up-regulation of bFGF and ERK1/2 signaling, which may be involved in promoting the NPWT-mediated wound healing response.

Diabetic hyperglycemia aggravates the prognosis of intracerebral hemorrhagic stroke (ICH) in the clinic. In addition to hematoma expansion and increased inflammation, how diabetic hyperglycemia affects the outcomes of ICH is still unclear. We found that streptozotocin-induced diabetic hyperglycemia not only increased neutrophil infiltration, but also changed the gene expression profile of neutrophils, including lactoferrin (Ltf) encoding gene Ltf . Peroxisome proliferator-activated receptor γ (PPARγ) transcribed Ltf and the lack of neutrophilic Ltf transcription and secretion exacerbated neuronal ferroptosis by accumulating intraneuronal iron. Furthermore, the administration of recombinant Ltf protected against neuronal ferroptosis and improved neurobehavior in hyperglycemic ICH mice, and vice versa . These results indicate that supplementing Ltf or inhibiting neuronal ferroptosis are promising potential strategies to improve the acute outcomes of diabetic ICH in the clinic.

Oligodendrocyte progenitor cells (OPCs) differentiate to myelin-producing mature oligodendrocytes and enwrap growing or demyelinated axons during development and post central nervous diseases. Failure of remyelination owing to cell death or undifferentiation of OPCs contributes to severe neurologic deficits and motor dysfunction. However, how to prevent the cell death of OPCs is still poorly understood, especially in hemorrhagic diseases. In the current study, we injected autologous blood into the mouse lateral ventricular to study the hemorrhage-induced OPC cell death in vivo. The integrity of the myelin sheath of the corpus callosum was disrupted post intraventricular hemorrhage (IVH) assessed by using magnetic resonance imaging, immunostaining, and transmission electron microscopy. Consistent with the severe demethylation, we observed massive cell death of oligodendrocyte lineages in the periventricular area. In addition, we found that ferroptosis is the major cell death form in Hemin-induced OPC death by using RNA-seq analysis, and the mechanism was glutathione peroxidase 4 activity reduction-resulted lipid peroxide accumulation. Furthermore, inhibition of ferroptosis rescued OPC cell death in vitro, and in vivo attenuated IVH-induced white matter injury and promoted recovery of neurological function. These data demonstrate that ferroptosis is an essential form of OPC cell death in hemorrhagic stroke, and rescuing ferroptotic OPCs could serve as a therapeutic target for stroke and related diseases.

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