Search

Background and purpose: We used two‐sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid‐modifying drugs on intracranial aneurysm (IA). Methods: Genetic variants for the effects of high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A1, low‐density lipoprotein cholesterol (LDL‐C), apolipoprotein B, and triglycerides and targets for lipid‐modifying drugs were selected from the genome‐wide discovery analyses of the UK Biobank. Summary‐level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. Results: Univariate MR analyses showed that the HDL‐C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715–0.932, p = 0.003) and ruptured IA (rIA; OR = 0.775, 95% CI = 0.663–0.906, p = 0.001). The multivariate MR–inverse variance weighted analysis showed that the HDL‐C was negatively correlated with IA (OR = 0.655, 95% CI = 0.434–0.988, p = 0.043) and rIA (OR = 0.563, 95% CI = 0.347–0.913, p = 0.02), and the LDL‐C was negatively correlated with IA (OR = 0.402, 95% CI = 0.191–0.848, p = 0.017) and rIA (OR = 0.376, 95% CI = 0.160–0.883, p = 0.025). Using genetic proxies of known lipid‐modifying drugs, we found that the increased HDL‐C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR = 0.852, 95% CI = 0.747–0.973, p = 0.018), and the decreased LDL‐C with 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase proxies was associated with increased risk of IA (OR = 1.772, 95% CI = 1.080–2.908, p = 0.024) and rIA (OR = 1.856, 95% CI = 1.022–3.371, p = 0.042). Conclusions: Genetically determined HDL‐C and LDL‐C reduce the risk of IA and rIA. The effects of different lipid‐modifying drugs on IA need to be further investigated. [ABSTRACT FROM AUTHOR]

Timely and accurate diagnosis of acute ischemic stroke (AIS) and simultaneous functional imaging of cerebral oxygen saturation (sO 2) are essential to improve the survival rate of stroke patients but remains challenging. Herein, we developed a pH-responsive manganese (Mn)-based nanoplatform as a magnetic resonance/photoacoustic (MR/PA) dual-modal contrast agent for AIS diagnosis. The Mn-based nanoplatform was prepared via a simple and green biomimetic method using bovine serum albumin (BSA) as a scaffold for fabrication of MnCO 3 NPs as the T 1 MR contrast agent and accommodation of indocyanine green (ICG) as the PA probe. The obtained MnCO 3 @BSA-ICG NPs were biocompatible and exhibited a pH-responsive longitudinal relaxation rate and a concentration-dependent PA signal. In vivo MR/PA dual-modal imaging demonstrated that MnCO 3 @BSA-ICG NPs quickly and efficiently led to the MR/PA contrast enhancements in the infarcted area while not in the normal region, allowing a timely and accurate diagnosis of AIS. Moreover, PA imaging could directly monitor the sO 2 level, enabling a functional imaging of AIS. Therefore, MnCO 3 @BSA-ICG NPs could be applied as a potential MR/PA contrast agent for timely and functional imaging of AIS. [Display omitted] • MnCO 3 @BSA-ICG NPs were applied as a MR/PA dual-modal contrast agent for AIS imaging. • MnCO 3 @BSA-ICG NPs exhibited a pH-responsive longitudinal relaxation rate. • MnCO 3 @BSA-ICG NPs led to a rapid MR/PA contrast enhancements in the infarcted area. • MnCO 3 @BSA-ICG NPs enabled directly monitor the sO 2 level in the infarcted area. [ABSTRACT FROM AUTHOR]

It is becoming more and more important to effectively integrate multiple complementary diagnostic imaging and synergistic therapies into a nano-platform, but it is still challenging. Here, we used bovine serum albumin (BSA) as a template to prepare ultra-small Ag/Gd 2 O 3 (Ag/Gd@BSA) hybrid nanoparticles with high water dispersion by a biomineralization strategy for magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging-guided photothermal therapy (PTT). Compared with commercial MR and CT contrast agents, we showed that these well-characterized BSA-templated nanotheranostics possessed higher r 1 relaxivity (5.84 mM -1 s -1 ) and HU values. In addition, these nanotheranostics have an excellent NIR absorption feature and outstanding photothermal conversion efficiency (47.4%) in the solution phase. The in vivo imaging experiment demonstrated that the Ag/Gd@BSA hybrid nanoparticles could serve as tri-modality imaging contrast agents to enable precise diagnosis of tumors. Meanwhile, it was also revealed that Ag/Gd@BSA had ability to be an ideal nanotherapeutic agent to achieve a satisfactory tumor treatment effect through PTT. Also, we showed the good biocompatibility of Ag/Gd@BSA nanoparticles. Overall, these results indicated that Ag/Gd@BSA was an effective nanotheranostic, which could accurately identify tumor sites and realize complete tumor elimination, having great potential in clinical transformation.

In acute ischemic stroke therapy, potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species (ROS) during ischemic reperfusion. Herein, a novel 2D neuroprotective agent (AFGd-LDH) is reported, comprising Gd-containing layered double hydroxide nanosheets (Gd-LDH, as a drug nanocarrier/MRI contrast agent), atorvastatin (ATO, as a neuroprotective drug) and the ferritin heavy subunit (FTH, as a blood brain barrier transport agent). Experiments revealed AFGd-LDH to possess outstanding antioxidant activity, neuroprotective properties, blood‒brain barrier transit properties, and biocompatibility. In vitro studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be ∼90%, surpassing CeO 2 (50%, a ROS scavenger) and edaravone (52%, a clinical neuroprotective drug). Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion, reducing the infarct area by 67% and lowering the neurological deficit score from 3.2 to 0.9. AFGd-LDH also offered outstanding MRI performance, thus enabling simultaneous imaging and ischemia reperfusion therapy., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors.)