Theranostic nanoplatform to target macrophages enables the inhibition of atherosclerosis progression and fluorescence imaging of plaque in ApoE(−/−) mice

Abstract Background Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. Therefore, the early diagnosis and inhibition of atherosclerotic plaque progress still be a vital task. Results In this study, we presented the development of composite mesoporous silica nanoparticle (Ru(bpy)3@SiO2-mSiO2, CMSN)-based nanomedicines (NMs) (Ru(bpy)3@SiO2-mSiO2@SRT1720@AntiCD36, CMSN@SRT@Anti) for accurate diagnosis and treatment of atherosclerosis (AS). In vitro cell experiments showed that both RAW264.7 and oxidized low density lipoprotein (ox-LDL)-stimulated RAW264.7 cells could significantly uptake CMSN@SRT@Anti. Conversely, little fluorescence signal could be observed in CMSN@SRT group, showing the excellent targeting ability of CMSN@SRT@Anti to Class II scavenger receptor, CD36 on macrophage. Additionally, such fluorescence signal was significantly stronger in ox-LDL-stimulated RAW264.7 cells, which might benefit from the upregulated expression of CD36 on macrophages after ox-LDL treatment. For another, compared with free SRT1720, CMSN@SRT@Anti had a better and more significant effect on the inhibition of macrophage foaming process, which indicated that drug-carrying mesoporous silicon with targeting ability could enhance the efficacy of SRT1720. Animal experimental results showed that after the abdominal injection of CMSN@SRT@Anti, the aortic lesions of ApoE-/-mice could be observed with obvious and persistent fluorescence signals. After 4 weeks post-treatment, the serum total cholesterol, aortic plaque status and area were significantly improved in the mouse, and the effect was better than that in the free SRT1720 group or the CMSN@SRT group. Conclusions The designed CMSN@SRT@Anti with excellent biocompatibility, high-performance and superior atherosclerosis-targeting ability has great potential for accurate identification and targeted therapy of atherosclerotic diseases. Graphic abstract

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Theranostic Nanoplatform to Target Macrophages Enables the Inhibition of Atherosclerosis Progression and Fluorescence Imaging of Plaque

10.21203/rs.3.rs-533800/v1 ◽

2021 ◽

Author(s):

Qi Wang ◽

Yong Wang ◽

Siwen Liu ◽

Xuan Sha ◽

Xiaoxi Song ◽

...

Keyword(s):

Atherosclerotic Plaque ◽

High Performance ◽

Human Life ◽

Silica Nanoparticle ◽

Raw264.7 Cells ◽

Fluorescence Signal ◽

Accurate Identification ◽

Mesoporous Silicon ◽

Aortic Plaque ◽

Targeting Ability

Abstract Background: Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. Therefore, the early diagnosis and inhibition of atherosclerotic plaque progress still be a vital task. Results: In this study, we presented the development of composite mesoporous silica nanoparticle (CMSN) - based nanomedicines (NMs) (Ru(bpy)3@SiO2-mSiO2@SRT1720@ AntiCD36, CMSN@SRT@Anti) for accurate diagnosis and treatment of atherosclerosis. In vitro cell experiments showed that both RAW264.7 and ox-LDL-stimulated RAW264.7 cells could significantly uptake CMSN@SRT@Anti. Conversely, little fluorescence signal could be observed in CMSN@SRT group, showing the excellent targeting ability of CMSN@SRT@Anti to CD36 on macrophage. Additionally, such fluorescence signal was significantly stronger in ox-LDL-stimulated RAW264.7 cells, showing the ox-LDL can promote the upregulation of CD36 expression on macrophages to produce a stronger binding signal. For another, compared with free SRT1720, CMSN@SRT@Anti had a better and more significant effect on the inhibition of macrophage foaming process, which indicated that drug-carrying mesoporous silicon with targeting ability could enhance the efficacy of SRT1720. Animal experimental results showed that after the abdominal injection of CMSN@SRT@Anti, the aortic lesions of ApoE-/-mice could be observed with obvious and persistent fluorescence signals. After 4 weeks post- treatment, the serum total cholesterol, aortic plaque status and area were significantly improved in the mouse, and the effect was better than that in the free SRT1720 group or the CMSN@SRT group. Conclusions: The designed CMSN@SRT@Anti with excellent biocompatibility, high-performance and superior atherosclerosis-targeting ability has great potential for accurate identification and targeted therapy of atherosclerotic diseases.

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928 The more low-density lipoprotein cholesterol decreases by statin, the more fibrous component increases in a coronary atherosclerotic plaque: a prospective randomized study with intravascular ultrasound-radiofrequency analysis

European Heart Journal ◽

10.1016/s0195-668x(03)94220-5 ◽

2003 ◽

Vol 24 (5) ◽

pp. 153

Author(s):

N KOMIYAMA

Keyword(s):

Intravascular Ultrasound ◽

Atherosclerotic Plaque ◽

Low Density Lipoprotein ◽

Randomized Study ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Prospective Randomized Study ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Coronary Atherosclerotic Plaque

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Tanshinone IIA Promotes Macrophage Cholesterol Efflux and Attenuates Atherosclerosis of apoE-/- Mice by Omentin-1/ABCA1 Pathway

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190404125213 ◽

2019 ◽

Vol 20 (5) ◽

pp. 422-432 ◽

Cited By ~ 3

Author(s):

Yu-lin Tan ◽

Han-xiao Ou ◽

Min Zhang ◽

Duo Gong ◽

Zhen-wang Zhao ◽

...

Keyword(s):

Atherosclerotic Plaque ◽

Lipid Content ◽

Plasma Levels ◽

Cholesterol Efflux ◽

Density Lipoprotein ◽

Tanshinone Iia ◽

Lipoprotein Cholesterol ◽

Mrna Levels ◽

Cellular Lipid ◽

Oil Red O

Background: Tanshinone IIA (Tan IIA) and Omentin-1 have a protective role in the cardiovascular system. However, if and how Tan IIA and Omentin-1 regulate cholesterol metabolism in macrophages has not been fully elucidated. Objective: To investigate the possible mechanisms of Tan IIA and Omentin-1 on preventing macrophage cholesterol accumulation and atherosclerosis development. Methods: The effect of Tan IIA on the protein and mRNA levels of Omentin-1 and ATP-binding cassette transporter A1 (ABCA1) in macrophages was examined by Western blot and qRT-PCR assay, respectively. Cholesterol efflux was assessed by liquid scintillation counting (LSC). Cellular lipid droplet was measured by Oil Red O staining, and intracellular lipid content was detected by high performance liquid chromatography (HPLC). In addition, the serum lipid profile of apoE−/− mice was measured by enzymatic method. The size of atherosclerotic lesion areas and content of lipids and collagen in the aortic of apoE−/− mice were examined by Sudan IV, Oil-red O, and Masson staining, respectively. Results: Tan IIA up-regulated expression of Omentin-1 and ABCA1 in THP-1 macrophages, promoting ABCA1-mediated cholesterol efflux and consequently decreasing cellular lipid content. Consistently, Tan IIA increased reverse cholesterol transport in apoE−/− mice. Plasma levels of high-density lipoprotein cholesterol (HDL-C), ABCA1 expression and atherosclerotic plaque collagen content were increased while plasma levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic plaque sizes were reduced in Tan IIA-treated apoE−/− mice. These beneficial effects were, however, essentially blocked by knockdown of Omentin-1. Conclusion: Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1 pathway, reducing the development of aortic atherosclerosis.

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The Physiological Roles of Vitamin E and Hypovitaminosis E in the Transition Period of High-Yielding Dairy Cows

Animals ◽

10.3390/ani11041088 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1088

Author(s):

Satoshi Haga ◽

Hiroshi Ishizaki ◽

Sanggun Roh

Keyword(s):

Dairy Cows ◽

High Performance ◽

Molecular Mechanisms ◽

Transition Period ◽

Disease Risk ◽

Serum Vitamin ◽

Physiological Role ◽

Density Lipoprotein ◽

Alpha Tocopherol ◽

Transition Dairy Cows

Levels of alpha-tocopherol (α-Toc) decline gradually in blood throughout prepartum, reaching lowest levels (hypovitaminosis E) around calving. Despite numerous reports about the disease risk in hypovitaminosis E and the effect of α-Toc supplementation on the health of transition dairy cows, its risk and supplemental effects are controversial. Here, we present some novel data about the disease risk of hypovitaminosis E and the effects of α-Toc supplementation in transition dairy cows. These data strongly demonstrate that hypovitaminosis E is a risk factor for the occurrence of peripartum disease. Furthermore, a study on the effectiveness of using serum vitamin levels as biomarkers to predict disease in dairy cows was reported, and a rapid field test for measuring vitamin levels was developed. By contrast, evidence for how hypovitaminosis E occurred during the transition period was scarce until the 2010s. Pioneering studies conducted with humans and rodents have identified and characterised some α-Toc-related proteins, molecular players involved in α-Toc regulation followed by a study in ruminants from the 2010s. Based on recent literature, the six physiological factors: (1) the decline in α-Toc intake from the close-up period; (2) changes in the digestive and absorptive functions of α-Toc; (3) the decline in plasma high-density lipoprotein as an α-Toc carrier; (4) increasing oxidative stress and consumption of α-Toc; (5) decreasing hepatic α-Toc transfer to circulation; and (6) increasing mammary α-Toc transfer from blood to colostrum, may be involved in α-Toc deficiency during the transition period. However, the mechanisms and pathways are poorly understood, and further studies are needed to understand the physiological role of α-Toc-related molecules in cattle. Understanding the molecular mechanisms underlying hypovitaminosis E will contribute to the prevention of peripartum disease and high performance in dairy cows.

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Novel Carbon Dots Derived from Glycyrrhizae Radix et Rhizoma and Their Anti-Gastric Ulcer Effect

Molecules ◽

10.3390/molecules26061512 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1512

Author(s):

Yuhan Liu ◽

Meiling Zhang ◽

Jinjun Cheng ◽

Yue Zhang ◽

Hui Kong ◽

...

Keyword(s):

Gastric Ulcer ◽

Photoelectron Spectroscopy ◽

Carbon Dots ◽

High Performance ◽

Raw264.7 Cells ◽

Mice Model ◽

X Ray ◽

Glycyrrhizae Radix ◽

Transmission Electron ◽

High Resolution Tem

Glycyrrhizae Radix et Rhizoma (GRR) is one of the commonly used traditional Chinese medicines in clinical practice, which has been applied to treat digestive system diseases for hundreds of years. GRR is preferred for anti-gastric ulcer, however, the main active compounds are still unknown. In this study, GRR was used as precursor to synthesize carbon dots (CDs) by a environment-friendly one-step pyrolysis process. GRR-CDs were characterized by using transmission electron microscopy, high-resolution TEM, fourier transform infrared, ultraviolet-visible and fluorescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. In addition, cellular toxicity of GRR-CDs was studied by using CCK-8 in RAW264.7 cells, and the anti-gastric ulcer activity was evaluated and confirmed using mice model of acute alcoholic gastric ulcer. The experiment confirmed that GRR-CDs were the spherical structure with a large number of active groups on the surface and their particle size ranged from 2 to 10 nm. GRR-CDs had no toxicity to RAW264.7 cells at concentration of 19.5 to 5000 μg/mL and could reduce the oxidative damage of gastric mucosa and tissues caused by alcohol, as demonstrated by restoring expression of malondialdehyde, superoxide dismutase and nitric oxide in serum and tissue of mice. The results indicated the explicit anti-ulcer activity of GRR-CDs, which provided a new insights for the research on effective material basis of GRR.

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Comparative Research of Chemical Profiling in Different Parts of Fissistigma oldhamii by Ultra-High-Performance Liquid Chromatography Coupled with Hybrid Quadrupole-Orbitrap Mass Spectrometry

Molecules ◽

10.3390/molecules26040960 ◽

2021 ◽

Vol 26 (4) ◽

pp. 960

Author(s):

Haibo Hu ◽

Yau Lee-Fong ◽

Jinnian Peng ◽

Bin Hu ◽

Jialin Li ◽

...

Keyword(s):

Mass Spectrometry ◽

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

High Performance ◽

High Resolution Mass Spectrometry ◽

Scientific Development ◽

Multivariate Statistical ◽

Accurate Identification ◽

Orbitrap Mass Spectrometry ◽

Q Exactive

The roots of Fissistigma oldhamii (FO) are widely used as medicine with the effect of dispelling wind and dampness, promoting blood circulation and relieving pains, and its fruits are considered delicious. However, Hakka people always utilize its above-ground parts as a famous folk medicine, Xiangteng, with significant differences from literatures. Studies of chemical composition showed there were multiple aristolactams that possessed high nephrotoxicity, pending evaluation research about their distribution in FO. In this study, a sensitive, selective, rapid and reliable method was established to comparatively perform qualitative and semi-quantitative analysis of the constituents in roots, stems, leaves, fruits and insect galls, using an Ultra-High-Performance Liquid Chromatography coupled with Hybrid Quadrupole Orbitrap Mass Spectrometry (UPLC-Q-Exactive Orbitrap MS, or Q-Exactive for short). To make more accurate identification and comparison of FO chemicals, all MS data were aligned and screened by XCMS, then their structures were elucidated according to MSn ion fragments between the detected and standards, published ones or these generated by MS fragmenter. A total of 79 compounds were identified, including 33 alkaloids, 29 flavonoids, 11 phenylpropanoids, etc. There were 54 common components in all five parts, while another 25 components were just detected in some parts. Six toxic aristolactams were detected in this experiment, including aristolactam AII, AIIIa, BII, BIII, FI and FII, of which the relative contents in above-ground stems were much higher than roots. Meanwhile, multivariate statistical analysis was performed and showed significant differences both in type and content of the ingredients within all FO parts. The results implied that above-ground FO parts should be carefully valued for oral administration and eating fruits. This study demonstrated that the high-resolution mass spectrometry coupled with multivariate statistical methods was a powerful tool in compound analysis of complicated herbal extracts, and the results provide the basis for its further application, scientific development of quality standard and utilization.

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Antihyperglycemic and Antilipidemic Properties of a Tea Infusion of the Leaves from Annona cherimola Miller on Streptozocin-Induced Type 2 Diabetic Mice

Molecules ◽

10.3390/molecules26092408 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2408

Author(s):

Jesús Martínez-Solís ◽

Fernando Calzada ◽

Elizabeth Barbosa ◽

Miguel Valdés

Keyword(s):

High Performance ◽

Density Lipoprotein ◽

Organ Damage ◽

Tea Infusion ◽

Annona Cherimola ◽

End Of Treatment ◽

Tea Infusions ◽

Array Detection ◽

Treatment Of Diabetes

The antihyperglycemic and antilipidemic effects of the tea infusion extracts of leaves from Annona cherimola Miller (IELAc-0.5, IELAc-1.5, and IELAc-3.0) were evaluated on normoglycemic (NG) and streptozocin-induced diabetic (STID) mice. In the acute test, IELAc-1.5 at 300 mg/kg bodyweight (bw) exhibited antihyperglycemic activity on STID mice since the first hour of treatment. Then, its antidiabetic potential was analyzed in a subchronic evaluation. IELAc-1.5 was able to reduce the blood glucose level, glycated hemoglobin (HbA1c), cholesterol (CHO), and triglycerides (TG); high-density lipoprotein (HDL) showed an increase at the end of treatment. IELAc-1.5 did not modify the urine profile at the end of the evaluation, and neither toxicity nor macroscopic organ damage were observed in acute and subchronic assays. In addition, a major flavonol glycoside present in the tea infusion extracts was identified using high-performance liquid chromatography with diode array detection (HPLC-DAD). The analysis of the tea infusion extracts by HPLC revealed that rutin was the major component. This study supports the use of tea infusions from Annona cherimola for the treatment of diabetes and suggests that rutin could be responsible, at least in part, for their antidiabetic properties.

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