Ceria Nanozyme Coordination with Curcumin for Treatment of Sepsis-induced Cardiac Injury by Inhibiting Ferroptosis and Inflammation.

INTRODUCTION: Sepsis-induced cardiac injury is the leading cause of death in patients. Recent studies have reported that reactive oxygen species (ROS)-mediated ferroptosis and macrophage-induced inflammation are the two main key roles in the process of cardiac injury. The combination of ferroptosis and inflammation inhibition is a feasible strategy in the treatment of sepsis-induced cardiac injury. OBJECTIVES: In the present study, ceria nanozyme coordination with curcumin (CeCH) was designed by a self-assembled method with human serum albumin (HSA) to inhibit ferroptosis and inflammation of sepsis-induced cardiac injury. METHODS AND RESULTS: The formed CeCH obtained the superoxide dismutase (SOD)-like and catalase (CAT)-like activities from ceria nanozyme to scavenge ROS, which showed a protective effect on cardiomyocytes in vitro. Furthermore, it also showed ferroptosis inhibition to reverse cell death from RSL3-induced cardiomyocytes, denoted from curcumin. Due to the combination therapy of ceria nanozyme and curcumin, the formed CeCH NPs could also promote M2 macrophage polarization to reduce inflammation in vitro. In the lipopolysaccharide (LPS)-induced sepsis model, the CeCH NPs could effectively inhibit ferroptosis, reverse inflammation, and reduce the release of pro-inflammatory factors, which markedly alleviated the myocardial injury and recover the cardiac function. CONCLUSION: Overall, the simple self-assembled strategy with ceria nanozyme and curcumin showed a promising clinical application for sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation. Acknowledgments: This study was supported by grants of the National Natural Science Foundation of China (82100398); the Nanjing Medical Science and Technique Development Foundation (YKK21068); Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2023-LCYJ-PY-24); the Jiangsu Research Hospital Association for Precision Medication (JY202120); the Jiangsu Pharmaceutical Association for Jinpeiying Project (J2021001); China Postdoctoral Science Foundation (2022M721576).

Effect of continuous furosemide infusion on outcome of acute kidney injury.

OBJECTIVE: To evaluate the clinical effects of continuous intravenous infusion with high-dose furosemide on early acute kidney injury (AKI) complicated with acute lung edema. METHODS: Ninety patients who had been treated by furosemide at routine dose for 12 hour but with unsatisfactory outcomes were selected and subjected to continuous intravenous infusion with high-dose furosemide. The dose was adjusted according to hourly urine output. Serum levels of urea nitrogen, creatinine and potassium, pH, oxygenation index and mechanical ventilation time before and 6, 12, 24, 48 and 72 hour after treatment were compared. RESULTS: The urine outputs before and 6, 12, 24, 48 and 72 hour after treatment were (10.71 ± 1.81), (164.52 ± 21.42), (189.71 ± 29.61), (181.33 ± 23.52), (176.82 ± 24.80) and (164.52 ± 18.91) ml/h respectively. Compared with data before treatment, the serum levels of urea nitrogen, creatinine and potassium significantly decreased while pH and oxygenation index significantly increased after six hour of treatment (P<0.05). After treatment, the kidney functions of 80 patients (88.9%) were completely recovered, without obvious adverse reactions. CONCLUSION: For patients with early AKI complicated with acute pulmonary edema who cannot be cured by diuretic agent at routine dose, high-dose furosemide increases urine output and improves success rate.

Panaxatriol saponins promotes angiogenesis and enhances cerebral perfusion after ischemic stroke in rats.

BACKGROUND: Panaxatriol saponins (PTS), an extract from the traditional Chinese herb Panax notoginseng, which has been used to treat ischemic stroke for many years in China. However, the mechanism underlying the effects of PTS remains unclear. This study aimed to determine whether PTS can protect against ischemic brain injury by promoting angiogenesis and to explore the possible mechanism by which it promotes angiogenesis. METHODS: Middle cerebral artery occlusion (MCAO) was induced in rats, and neurological deficit scores and brain infarct volumes were assessed. Micro-Positron emission tomography (PET) was adopted to assess cerebral perfusion, and real-time PCR and western blotting were used to evaluate vascular growth factor and Sonic hedgehog (Shh) pathway component levels. Immunofluorescence staining was used to determine capillary densities in ischemic penumbrae. RESULTS: We showed that PTS improved neurological function and reduced infarct volumes in MCAO rats. Micro-PET indicated that PTS can significantly increase 18F-fluorodeoxyglucose (18F-PDG) uptake by ischemic brain tissue and enhance cerebral perfusion after MCAO surgery. Moreover, PTS was able to increase capillary densities and enhance angiogenesis in ischemic boundary zones and up-regulate vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1) expression by activating the Shh signaling pathway. CONCLUSION: These findings indicate that PTS exerts protective effects against cerebral ischemic injury by enhancing angiogenesis and improving microperfusion.

Icariin inhibits neurotoxicity of beta-amyloid by upregulating cocaine-regulated and amphetamine-regulated transcripts.

beta-Amyloid peptide (Abeta) is one of the main protein components of senile plaques contributing to Alzheimer's disease and it can induce neuronal apoptosis. In this study, it was found that icariin, a flavonoid extracted from Chinese Herba-Epimedii, inhibited Abeta42-induced neurotoxicity in a dose-dependent manner. The peak dose of icariin was 160 microg/ml. In addition, mRNA and protein expressions of cocaine and amphetamine-regulated transcript (CART) were increased in Abeta42-treated neurons in the presence of 80 microg/ml icariin. Moreover, CART-RNA interference was able to reverse neuroprotection of icariin on Abeta42. Furthermore, the expression of CART can be suppressed by extracellular signal-regulated kinase inhibitor instead of p38/JNK inhibitors, suggesting that icariin may be developed into therapeutic agents for Alzheimer's disease and other neurodegenerative diseases.