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. 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. 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. 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.

Trophoblast stem cells (TSCs) have been confirmed to play a cardioprotective role in heart failure. However, whether TSC-derived exosomes (TSC-exos) can protect against cardiac injury remains unclear. In the present study, TSC-exos were isolated from the supernatant of TSCs using the ultracentrifugation method and characterized by transmission electron microscopy and western blotting. Utilizing the public Gene Expression Omnibus (GEO) database, we found that let-7i and Yes-associated protein 1 (YAP) could participate in the development of heart failure. In vitro, AC16 cardiomyocytes subjected to doxorubicin (DOX) were treated with TSC-exos or let-7i mimic. Flow cytometry showed that TSC-exos and let-7i both decreased cardiomyocyte apoptosis. In vivo, mice that were intraperitoneally injected into DOX received either PBS, TSC-exos, or AAV9-let7i^up for let-7i overexpression. Mice receiving TSC-exos and AAV9-let7i^up showed improved cardiac function and decreased inflammatory responses, accompanied by downregulated YAP signaling. Mechanistically, TSC-exos could transfer let-7i to cardiomyocytes and silence the YAP signaling pathway. In conclusion, TSC-exos could alleviate DOX-induced cardiac injury via the let-7i/YAP pathway, which sheds new light on the application of TSC-exos as a potential therapeutic tool for heart failure.

Background: Dyslipidemia is frequently exhibited in individuals with chronic kidney disease (CKD). Remnant cholesterol (RC), an emerging novel lipid marker, plays an elusive role in CKD progression. This study sought to investigate the association of RC with decreased kidney function or albuminuria in the general population of U.S. Method: Data were retrieved from the continuous 2001 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Individuals aged between 18 and 70 years were included. RC was divided into quartiles. Albuminuria was defined by albumin-to-creatinine ratio (ACR) ≥30 mg/g, while reduced kidney function was described as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m². Using a multivariable regression model, the association of RC with decreased eGFR or albuminuria was examined. The dose‒response relationship between RC and eGFR or ACR was also investigated using a restricted cubic spline (RCS) model. Results: A total of 1551 (10.98%) participants with impaired renal function or albuminuria were identified. After multivariate adjustment, RC was not significantly associated with kidney function decline or albuminuria (odds ratio (OR) 1.24, 95% confidence interval (95% CI): 0.95, 1.61). However, a significantly inverse correlation was observed between RC and eGFR in a dose‒response manner (β -2.12, 95% CI: -3.04, -1.21). This association remained consistent when stratifying data by gender, age, race, hypertension, diabetes and body mass index (BMI). Conclusion: A higher RC was significantly correlated with a lower eGFR in the general population. The role of RC in predicting kidney outcomes needed further investigation in prospective studies.

Cerebral venous sinus thrombosis (CVST) is a rare ischemic cerebrovascular disease. The aim of this retrospective observational study was to investigate the risk factors for complication of cerebral venous sinus thrombosis by seizures and to explore the impact of such seizures on clinical outcomes. Patients with cerebral venous sinus thrombosis with or without epileptic seizures were retrospectively analyzed and compared in terms of clinical variables, causative factors, clinical presentation, and imaging data. In all, 69 patients with cerebral venous sinus thrombosis were enrolled in this study, 32 (46.38%) of whom had experienced secondary seizures. Compared with those with no seizures, significantly more patients with secondary seizures had hemiplegia (37.50 vs. 15.63%; P = 0.020), bleeding (29.40 vs. 10.81%; P = 0.047), lesions involving the frontal (31.25 vs. 10.81%; P = 0.023) and temporal lobe (43.75 vs. 8.11%; P = 0.005), and thrombosis in the superior sagittal sinus (65.63 vs. 40.54%; P = 0.036). Multivariate logistic regression analysis showed focal neurological deficits (P = 0.004, odds ratio = 5.16, 95% CI 1.99–15.76) and thrombosis of the superior sagittal sinus (P = 0.039, odds ratio = 0.13, 95% CI 0.04–0.37) were independent risk factors for secondary seizures in patients with cerebral venous sinus thrombosis. In addition, mortality rate (9.38 vs. 5.41%; P = 0.469) and 90-day excellent prognosis rate (81.25 vs. 86.47%; P = 0.793) did not differ significantly between patients with and without epileptic seizures. The presence of focal neurological deficits and thrombosis of the superior sagittal sinus are independent risk factors for secondary seizures in patients with cerebral venous sinus thrombosis, whereas mortality and 90-day prognosis have no correlation with secondary seizures.

Cocaine-regulated and amphetamine-regulated transcript (CART) is a neuropeptide with reported neuroprotective effects in ischemic cerebral injury. However, its mechanism has not yet been elucidated. Herein, we investigated the role and mechanism of CART in synaptic plasticity in neurons after ischemic cerebral stroke. We found that the survival rate of the oxygen-glucose deprivation (OGD) neurons was increased after CART treatment. Moreover, CART treatment significantly attenuated ischemia-induced neuronal synaptic damage and increased synaptophysin expression. In addition, the number of presynaptic vesicles was increased and the postsynaptic density (PSD) was thickened after CART treatment. Mechanistically, CART treatment enhanced the expression of Arc mRNA in a cAMP response element binding protein (CREB) dependent manner in OGD neurons, and blockade of CREB by KG-501 eliminated the protective effect of CART. Collectively, CART protected the synaptic structure in neurons after ischemic cerebral injury by increasing the Arc expression via upregulating p-CREB.