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Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H2O2 generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction. [ABSTRACT FROM AUTHOR]

Background: Femoral fractures often lead to complications such as altered pulmonary hemodynamics. Right ventricular global longitudinal strain (RV GLS), which correlates with pulmonary hemodynamics, indicates the subclinical function of the right ventricle (RV). This study aimed to investigate the predictive value of RV GLS for the risk of adverse clinical composite outcomes in patients with femoral fractures. Methods: Data were obtained from a prospective single-center cohort of patients hospitalized for femoral fractures and followed up for at least 1 year between March 2021 and October 2022. The primary outcome was the development of an adverse composite clinical event, which included pneumonia, pulmonary oedema or effusion, pulmonary thromboembolism, and all-cause mortality within the 1-year period following surgery. Results: Among the 163 patients, 36 (22.09%) experienced adverse composite clinical events during 1-year follow-up. The adverse outcome group demonstrated poorer RV GLS and RV free wall strain values than the non-adverse outcome group. The optimal cut-off value of RV GLS for predicting composite adverse clinical events was −12.55%. The cumulative composite event-free survival rate was significantly lower in the RV GLS ≥ −12.55% group (log-rank p-value = 0.003). After adjusting for confounding factors, multivariate Cox proportional hazards regression analyses showed that RV GLS ≥ −12.55% independently increased the risk of composite adverse clinical events by 2.65-fold. Conclusions: Poor RV GLS is a significant predictor of adverse clinical outcomes in patients with femoral fractures. Specifically, an RV GLS value of ≥ −12.55% indicated a substantially increased risk of adverse events. [ABSTRACT FROM AUTHOR]

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9-based therapeutics, especially those that can correct gene mutations via homology directed repair (HDR), have the potential to revolutionize the treatment of genetic diseases. However, HDR-based therapeutics are challenging to develop because they require simultaneous in vivo delivery of Cas9 protein, guide RNA and donor DNA. Here, we demonstrate that a delivery vehicle composed of gold nanoparticles conjugated to DNA and complexed with cationic endosomal disruptive polymers can deliver Cas9 ribonucleoprotein and donor DNA into a wide variety of cell types, and efficiently correct the DNA mutation that causes Duchenne muscular dystrophy in mice via local injection, with minimal off-target DNA damage.