Non-Linear Association between Obstructive Sleep Apnea Risk and Lipid Profile: Data from the 2015-2018 National Health and Nutrition Examination Survey.

Background: The relationship between the multivariable apnea prediction (MAP) index and lipid levels was examined using a cross-sectional and retrospective study of National Health and Nutrition Examination Surveys (2015-2018). A total of 3195 participants with MAP scores were included in the analysis. Methods: The MAP index, an algorithm leveraging sleep apnea symptom frequency, body mass index (BMI), age, and sex, estimates the risk of obstructive sleep apnea (OSA). We investigated the associations between the MAP index and lipid profiles-specifically, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) -using weighted linear regression and restricted cubic splines (RCS) analysis. Additionally, mediation analysis was conducted to explore the potential mediating role of physical activity on the link between OSA risk, hyperlipidemia, and cardiovascular mortality. Results: A non-linear relationship was observed between OSA severity and lipid profiles, including elevated levels of TC, increased LDL-C, higher TG, and decreased HDL-C (All p for non-linearity < 0.05). The findings remained consistent across the stratified sensitivity analyses. Furthermore, physical activity served as a mediator in the association between the MAP index and both hyperlipidemia and cardiovascular mortality, accounting for 16.6% and 16.7% of the indirect effects, respectively. Conclusions: Participants at high risk for OSA demonstrated an increased prevalence of dyslipidemia. Additionally, engagement in physical activity was shown to have beneficial effects on lipid metabolism.

Oral anticoagulants increased 30-day survival in sepsis patients complicated with atrial fibrillation: a retrospective analysis from MIMIC-IV database.

Background: The severity of sepsis is associated with systemic clotting activation. Atrial fibrillation (AF) is the most commonly observed arrhythmia in patients with sepsis and can lead to a poor prognosis. The aim of this study is to elucidate the association between oral anticoagulants and survival from septic patients complicated with AF. Methods: The data of 8,828 septic patients, including 2,955 AF and 5,873 without AF, were all originated from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients with sepsis and AF are divided into OAC- group (n = 1,774) and OAC+ group (n = 1,181) based on OAC therapy. Septic patients with no AF were considered as the control group (n = 5,873, sepsis and no AF group). The main outcome endpoint was the survival rate of 30 day. The secondary outcome endpoint was the length of stay (LOS) from intensive care unit and hospital. Propensity score matching (PSM) was used to adjust the influence of superfluous factors, and a restricted mean survival time (RMST) analysis was used for calculating the benefit of survival time and survival rate. Analysis including univariate and multivariate logistic regression analysis was conducted to find prognosis-related predictors. Results: After PSM, the OAC+group had a higher 30-day survival rate compared to the OAC- group (81.59% vs. 58.10%; P < 0.001) in the ICU. Despite the higher survival, the hospital LOS (14.65 days vs. 16.66 days; P = 0.15) and ICU LOS (6.93 days vs. 5.92 days; P = 0.02) were prolonged at OAC+ group than OAC- group. No difference was found in survival rate of 30 day between the sepsis patients using warfarin and patients using NOAC (85.60% vs. 79.84%, P = 0.12). The sepsis patients using warfarin had a prolonged LOS in ICU and hospital compared with the sepsis patients using NOAC. In the vasopressor subgroup, patients who received NOAC therapy were associated with a reduced 30-day survival rate (73.57% vs. 84.03%; P = 0.04) and reduced LOS in ICU and hospital than those on warfarin therapy. Conclusion: This study demonstrated that oral anticoagulants may increase the 30-day survival rate of patients with sepsis and AF.

Magnetic vagus nerve stimulation alleviates myocardial ischemia-reperfusion injury by the inhibition of pyroptosis through the M2AChR/OGDHL/ROS axis in rats.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury is accompanied by an imbalance in the cardiac autonomic nervous system, characterized by over-activated sympathetic tone and reduced vagal nerve activity. In our preceding study, we pioneered the development of the magnetic vagus nerve stimulation (mVNS) system. This system showcased precise vagus nerve stimulation, demonstrating remarkable effectiveness and safety in treating myocardial infarction. However, it remains uncertain whether mVNS can mitigate myocardial I/R injury and its specific underlying mechanisms. In this study, we utilized a rat model of myocardial I/R injury to delve into the therapeutic potential of mVNS against this type of injury. RESULTS: Our findings revealed that mVNS treatment led to a reduction in myocardial infarct size, a decrease in ventricular fibrillation (VF) incidence and a curbing of inflammatory cytokine release. Mechanistically, mVNS demonstrated beneficial effects on myocardial I/R injury by inhibiting NLRP3-mediated pyroptosis through the M2AChR/OGDHL/ROS axis. CONCLUSIONS: Collectively, these outcomes highlight the promising potential of mVNS as a treatment strategy for myocardial I/R injury.

Exosomal thioredoxin-1 from hypoxic human umbilical cord mesenchymal stem cells inhibits ferroptosis in doxorubicin-induced cardiotoxicity via mTORC1 signaling.

Doxorubicin (DOX), a clinical chemotherapeutic drug, is often annoyed by its cardiotoxicity which involves ferroptosis in its pathological progress. Human umbilical cord mesenchymal stem cells (HucMSCs)-derived exosomes (HucMSCs-Exo) are proven effective in treating cardiovascular diseases. This study aimed to compare the therapeutic effects between normoxic HucMSCs-Exo (Exo) and hypoxic HucMSCs-Exo (Hypo-Exo) on DOX-induced ferroptosis and explore the underlying mechanisms. An acute cardiotoxicity model was successfully constructed by administrating two doses intraperitoneal injections of DOX (25 mg/kg in total). Exo and Hypo-Exo were extracted by ultracentrifugation and characterized. Compared with Exo, Hypo-Exo and Ferrostatin-1 (Fer-1) exerted superior effects on inhibiting DOX-induced ferroptosis, as evidenced by decreasing malondialdehyde (MDA), iron content and increasing glutathione (GSH) level as well as ferroptosis-related genes expression including prostaglandin-endoperoxide synthase 2 (Ptgs2) mRNA level and glutathione peroxidase 4 (GPX4) protein level. Based on quantitative proteomics analysis, we found that thioredoxin1 (Trx1) was remarkably upregulated in Hypo-Exo and exhibited anti-ferroptosis activity via activating the mechanistic target of rapamycin complex 1 (mTORC1) in neonatal rat cardiomyocytes (NRCMs). Trx1 knockdown and rapamycin (an mTORC1 inhibitor) partially abolished the protective effects of Hypo-Exo. Furthermore, our data indicated that solute carrier family 7 member 11 (SLC7A11) was critical for GPX4 protein synthesis. In conclusion, Hypo-Exo exhibited a better suppression of ferroptosis in DOX-induced cardiotoxicity. Trx1-mediated mTORC1 activation is critical for the Hypo-Exo anti-ferroptosis process, which involves increased GPX4 protein synthesis and decreased iron overload. This study indicated that Hypo-Exo may present a potential strategy against ferroptosis in DOX-induced cardiotoxicity.

In Vitro Effects of Hollow Gold Nanoshells on Human Aortic Endothelial Cells.

Gold nanoparticles are emerging as promising biomedical tools due to their unique nanoscale characteristics. Our purpose was to synthesize a hollow-shaped gold nanoparticle and to investigate its effect on human aortic endothelial cells (HAECs) in vitro. Hollow gold nanoshells with average 35-nm diameters and 10-nm shell thickness were obtained by galvanic replacement using quasi-spherical nanosilver as sacrifice-template. Our results showed that hollow gold nanoshells in the culture medium could be internalized into the cytoplasm of HAECs. No cytotoxicity effect of hollow gold nanoshells on HAECs was observed within the test concentrations (0-0.8 µg/mL) and test exposure period (0-72 h) by tetrazolium dye assay. Meanwhile, the release of cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without hollow gold nanoshells). The concentrations of vasodilators, nitric oxide, and prostacyclin I-2 were not changed, but the vasoconstrictor endothelin-1 was decreased by hollow gold nanoshells treatment in HAECs. HAECs exposed to hollow gold nanoshells resulted in suppressing expressions of genes involved in apoptosis and activating expressions of genes of adhesion molecules. Moreover, we demonstrated by in vitro endothelial tube formation that hollow gold nanoshells (0.8 µg/mL) could not inhibit angiogenesis by the HAECs. Altogether, these results indicate that the structure and major function of HAECs would not be disrupted by hollow gold nanoshell treatment.

Protective effects of drag-reducing polymers on ischemic reperfusion injury of isolated rat heart.

Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on ischemic reperfusion (I/R) injury of isolated rat hearts. Experiments were performed on isolated rat hearts subjected to 30 min of ischemia followed by 90 min of reperfusion in Langendorff preparations. Adult Wistar rats were divided into the following five groups: control group, I/R group, group III (I/R and 2×10(-7)  g/ml PEO reperfusion), group IV (I/R and 1×10(-6)  g/ml PEO reperfusion), and group V (I/R and 5×10(-6)  g/ml PEO reperfusion). Left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum rate of ventricular pressure increase and decrease ( ± dp/dtmax), heart rate (HR) and coronary flow were measured. Lactate dehydrogenase (LDH) and creatine kinase (CK) activity and coronary flow, myocardial infarction size and cardiomyocytes apoptosis were also assayed. Our results showed that PEO decreased LVEDP and increased LVSP, ± dP/dtmax in group IV and group V compared with the I/R group (all P <  0.05). The coronary flow significantly increased and the activities of LDH and CK in the coronary flow significantly decreased in group IV and group V compared with those in the I/R group (all P <  0.05). Cell apoptosis and myocardial infarction size were reduced in group IV and group V compared with the I/R group (all P <  0.05). Collectively, these results suggested that DRPs had a protective effect on cardiac I/R injury of isolated rat hearts and it may offer a new potential approach for the treatment of acute ischemic heart diseases.

The cytotoxicity evaluation of magnetic iron oxide nanoparticles on human aortic endothelial cells.

One major obstacle for successful application of nanoparticles in medicine is its potential nanotoxicity on the environment and human health. In this study, we evaluated the cytotoxicity effect of dimercaptosuccinic acid-coated iron oxide (DMSA-Fe2O3) using cultured human aortic endothelial cells (HAECs). Our results showed that DMSA-Fe2O3 in the culture medium could be absorbed into HAECs, and dispersed in the cytoplasm. The cytotoxicity effect of DMSA-Fe2O3 on HAECs was dose-dependent, and the concentrations no more than 0.02 mg/ml had little toxic effect which were revealed by tetrazolium dye assay. Meanwhile, the cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without DMSA-Fe2O3). However, the endocrine function for endothelin-1 and prostacyclin I-2, as well as the urea transporter function, was altered even without obvious evidence of cell injury in this context. We also showed by real-time PCR analysis that DMSA-Fe2O3 exposure resulted in differential effects on the expressions of pro- and anti-apoptosis genes of HAECs. Meanwhile, it was noted that DMSA-Fe2O3 exposure could activate the expression of genes related to oxidative stress and adhesion molecules, which suggested that inflammatory response might be evoked. Moreover, we demonstrated by in vitro endothelial tube formation that even a small amount of DMSA-Fe2O3 (0.01 and 0.02 mg/ml) could inhibit angiogenesis by the HAECs. Altogether, these results indicate that DMSA-Fe2O3 have some cytotoxicity that may cause side effects on normal endothelial cells.