JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
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2022
·Vol. 110
·期 8
·1956-1967
·
IF 3.405
Yameng Yu,Boya Ma,Chen Guo,Xinbang Jiang,Zhuang Liu,Yamin Chai,Lichun Wang,Yunzheng Du,Biao Wang,Nan Li,Lailiang Ou
Lowering of low-density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane-mimetic LDL adsorbent (PVA@COOH-PE) via directional immobilization of phospholipid onto macro-porous cross-linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid-packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high-density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH-PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia.
研究领域:
生物医学工程
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材料科学
·
血液学
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产品关联
DOI
PubMed
高影响因子
CLINICAL BIOCHEMISTRY
·
2020
·
IF 2.573
Tianhua Zhang,Xiaoyu Tang,Ling Mao,Jin Chen,Jie Kuang,Xin Guo,Danyan Xu,Daoquan Peng,Bilian Yu
Background The mechanism for an abnormal pattern of triglyceride (TG) metabolism in response to a meal still needs further investigation. Extensive pieces of evidence have shown that apolipoprotein CIII (apoCIII) is a critical modulator of plasma TG metabolism mostly by inhibiting the hydrolysis of TG. Little is known about the role of apoCIII contained in high density lipoprotein (HDL) in plasma TG metabolism after a meal. Methods Fasting and 4-hour postprandial peripheral venous blood were collected in 91 subjects selected from our hospital. Serum lipid parameters, apoCIII levels and HDL subcomponents were tested by standard laboratory procedures, ELISA, and nuclear magnetic resonance (NMR), respectively. The t -test, and Non-parametric tests were performed to examine differences between groups, Pearson’s correlation and multiple regression analysis were used to assess the correlations between apoCIII (HDL-associated or nonHDL-associated) and postprandial TG. Results There was a significant increase in TG after a meal compared to fasting status [155.40(96.70–251.07) mg/dl .vs. 118.53(83.38–173.29)mg/dl, p < 0.001]. However, the total apoCIII levels were unchanged before (11.56(7.89–16.22) mg/dl) and after a meal (11.66(7.75–16.02)mg/dl, p = 0.124), while a significant increase in HDL-associated apoCIII (HDL-apoCIII) was observed from fasting (5.25(3.92–7.83)mg/dl) to post-meal (6.46(4.57–8.76)mg/dl, p = 0.001). Unlike nonHDL-apoCIII, HDL-apoCIII was positively correlated with both fasting and postprandial plasma TG in subjects with baseline plasma TG > 118.53 mg/dl (R = 0.503, p < 0.001 for fasting, R = 0.584, p < 0.001 for postprandial). Besides, in the subjects who had an abnormal TG response to a meal, which was defined as postprandial plasma TG increase of>30% compared to baseline TG levels, postprandial HDL-apoCIII was also increased significantly [5.37(3.52–7.02)mg/dl .vs. 6.64(4.61–8.86)mg/dl, p = 0.001]. The enrichment of apoCIII in HDL led to changes of TG, cholesterol, free cholesterol, phospholipid and apoAII contents in HDL particles defined by NMR. Conclusion Enrichment of apoCIII in HDL particles potentially plays an independent role in postprandial hypertriglyceridemia.
研究领域:
心脏病学
·
脂质代谢
·
临床生物化学
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DOI
PubMed
高影响因子
Polymers
·
2025
·Vol. 17
·期 5
·625
·
IF 4.9
Yunpeng Zhang,Danni Liu,Yaoqi Wang,Qi Sun,Dong Mei,Xiaoling Wang,Yan Su,Siyu Liu,Chunying Cui,Shuang Zhang
Atherosclerosis (AS) is an important causative agent of cardiovascular diseases, and the occurrence and development of AS is accompanied by oxidative stress, so antioxidant therapy has become one of the strategies for the treatment of AS. This study aimed to design and construct an apolipoprotein ApoA1-modified inorganic–organic composite nanosystem for AS therapy, in which ApoA1 was modified onto carboxylated CeO2/Mn3O4by covalent bonding, resulting in an inorganic–organic nanocomplex with a structure similar to that of high-density lipoprotein. The nanocomplex could effectively deliver the antioxidant nanoparticles to the AS plaque through the specific recognition between ApoA1 and the macrophage at the AS lesion site. For one thing, the nanocomplex could alleviate the oxidative stress environment of the AS site through the highly efficient antioxidant effect of CeO2/Mn3O4, which played a therapeutic role in the treatment of AS. For another, it could effectively eliminate the formed lipid plaques and maximally alleviate and treat AS by utilizing the cholesterol efflux effect of ApoA1.
研究领域:
心血管疾病
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纳米医学
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材料科学
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治疗开发
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
·
2024
·
IF 3.9
Wei Chen,Yuan Chen,Baoye Song,Lei Zhai,Geru Tao,Bingxiang Wang,Boyan Liu,Hao Wang,Cindy X. Zhang,Hong-mei Gu,Deling Yin,Shucun Qin,Da-wei Zhang
Surfeit locus protein 4 (SURF4) acts as a cargo receptor to mediate endoplasmic reticulum export of various cargos. We have shown that SURF4 is essential for secretion of hepatic very low-density lipoprotein and intestinal chylomicron. Knockdown of hepatic Surf4 also significantly reduces the development of atherosclerosis and liver fibrosis without causing overt liver damage. However, constitutive global Surf4 knockout results in embryonic lethality. To further understand the physiological role of Surf4 , we generated tamoxifen-inducible global Surf4 knockout mice. We found that conditional knockout of Surf4 in adult mice ( Surf4 ig-ko ) significantly reduced mouse body weight. Male and female Surf4 ig-ko mice died approximately 30 and 50 days after tamoxifen administration, respectively. Triglyceride secretion and serum levels of total cholesterol, triglycerides, free fatty acids, apolipoprotein B-100, and apolipoprotein-48 were significantly reduced in Surf4 ig-ko mice compared with Surf4 flox mice. Proteomics analysis of mouse serum samples revealed 308 proteins with significantly altered expression in Surf4 ig-ko mice that have unique functions and are involved in various biological processes. In addition, Surf4 ig-ko mice exhibited lipid accumulation in the intestine but not in the liver. However, in Surf4 ig-ko mice, liver weight was significantly reduced, and serum transaminase activity was significantly increased, indicating liver damage. Therefore, SURF4 is essential for survival in adult mice, suggesting that the therapeutic use of SURF4 requires precise tissue/cell type-specific targeting.
研究领域:
分子生物学
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脂质代谢
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遗传学
·
生理学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2022
·
IF 3.898
Yang Liu,Qiu Han,Guiliang Li,Haibo Lin,Fu Liu,Gang Deng,Dingfeng Lv,Weijie Sun
Precluding the excessive lipoproteins from plasma rapidly and effectively is highly needed for biomedical detection and reducing plasma product scrap in blood donation stations. The current centrifugation procedure is high-cost and time-consuming. Herein, we fabricated an anionic microfiltration polyethersulfone (PES) membrane modified by interface swelling and implanting of acrylic acid (AA) for screening out large particle lipoprotein chylomicron (CM) and adsorbing cationic very low-density lipoproteins (VLDL). To improve the separation efficiency, a two-stage filtration through carboxylated polyethersulfone microfiltration membranes with the mean pore size of 0.45 and 0.22 μm respectively were conducted. Attenuated total reflection Fourier transform infrared technique (ATR-FTIR), water contact angle (WCA), Zeta potential and scanning electron microscope (SEM) were employed to characterize the modified membrane. To test the effectiveness of this membrane, plasma flux and concentration variation of plasma components were examined to study the purification effectiveness. Furthermore, the hemocompatibility of modified membranes was tested to confirm its practicability on blood-contacting materials. The carboxylated polyethersulfone microfiltration membrane shows its promising potential application to purify chylous plasma.
研究领域:
生物医学工程
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膜技术
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血液处理
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血浆分离
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DOI
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2021
·Vol. 69
·期 1
·59-66
·
IF 1.645
Dong-Dong Li,Pan Yu,Hui Xu,Zhen-Zhong Wang,Wei Xiao,Lin-Guo Zhao
Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9-O-cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.
研究领域:
药理学
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药物发现
·
化学
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DOI
PubMed
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Jin Li,Mengmeng Han,Jianfei Li,Zhiming Ge,Qianqian Wang,Kai Zhou,Xiaoxing Yin
Reconstituted high density lipoprotein (rHDL) has been regarded as a promising brain-targeting vehicle for anti-glioma drugs under the mediation of apolipoprotein A-I (apoA-I). However, some stability issues relating to drug leakage and consequent reduced targeting efficiency in the course of discoidal rHDL (d-rHDL) circulating in blood hinder its broad application. The objective of the study was to develop a novel stabilized d-rHDL by replacing cholesterol and apoA-I with mono-cholesterol glutarate (MCG) modified apoA-I (termed as mA) and to evaluate its allosteric behavior and glioma targeting. MCG was synthesized through esterifying the hydroxyl of cholesterol with glutaric anhydride and characterized by FI-IR and 1H NMR. d-rHDL assembled with mA (termed as m-d-rHDL) presented similar properties such as minute particle size and disk-like appearance resembling nascent HDL. Morphological transformation observation and in vitro release plots convinced that the modification of cholesterol could effectively inhibit the remolding of d-rHDL. The uptake of m-d-rHDL by LCAT-pretreated bEND.3 cells was significantly higher than that of d-rHDL, thereby serving as another proof for the capability of m-d-rHDL in enhancing targeting property. Besides, apoA-I anchoring into m-d-rHDL played a critical role in the endocytosis process into bEND.3 cells and C6 cells, which implied the possibility of traversing blood brain barrier and accumulating in the brain and glioma. These results suggested that the modification toward cholesterol to improve the stability of d-rHDL is advantageous, and that this obtained m-d-rHDL revealed great potential for realization of suppressing the remolding of d-rHDL in the brain-targeted treatment of glioma for drug delivery.
研究领域:
药剂学
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神经科学
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药物递送系统
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癌症研究
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Hua-Jie Chen,Yusi Hu,Peiyu Yao,Di Ning,Yu-Peng Zhang,Zhi-Gang Wang,Shu-Lin Liu,Dai-Wen Pang
Cardiovascular disease is one of the main causes of death in the world, which is closely associated with dyslipidemia. Dyslipidaemia is usually manifested as a relatively higher level of low-density lipoprotein (LDL) and lower level of high-density lipoprotein (HDL). Thus, the quantitative detection of the LDL and HDL particles is of great importance to predict the risk of cardiovascular diseases. However, the traditional methods can only indirectly reflect the HDL/LDL particle concentrations by detecting the cholesterol or proteins in HDL/LDL particles and are always laborious and time-consuming. Thus, the accurate and efficient approach for the detection of intact HDL and LDL particles is still lacking so far. We developed an enzyme- and isolation-free method to measure the concentration of HDL and LDL based on DNAzyme and hybridization chain reaction (HCR)-based signal amplification. This method can be used to directly and accurately detect the concentration of “actual” HDL and LDL particles instead of the cholesterol in HDL and LDL, with limits of detection of 10 and 30 mg/dL, respectively, which also satisfied the lipoprotein analysis in clinical samples. Therefore, this HCR–DNAzyme platform has great potential in clinical applications and health management.
研究领域:
医学诊断
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分子生物学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 11
·2534
·
IF 6.525
Bo Wei,Yuanfang Li,Meiying Ao,Wenxiang Shao,Kun Wang,Tong Rong,Yun Zhou,Yong Chen
Previously, we found that exogenous ganglioside GM3 had an antiatherosclerotic efficacy and that its antiatherosclerotic efficacy could be enhanced by reconstituted high-density lipoprotein (rHDL). In this study, we hypothesized that GM3-functionalized rHDL (i.e., GM3-rHDL) as a nanocarrier can promote the efficacy of traditional antiatherosclerotic drugs (e.g., statins). To test this hypothesis, lovastatin (LT) was used as a representative of statins, and LT-loaded GM3-rHDL nanoparticle (LT-GM3-rHDL or[email protected]; a mean size of ~142 nm) and multiple controls (e.g., GM3-rHDL without LT, LT-loaded rHDL or LT-rHDL, and other nanoparticles) were prepared. By using two different microsphere-based methods, the presences of apolipoprotein A-I (apoA-I) and/or GM3 in nanoparticles and the apoA-I-mediated macrophage-targeting ability of apoA-I/rHDL-containing nanoparticles were verified in vitro. Moreover, LT-GM3-rHDL nanoparticle had a slowly sustained LT release in vitro and the strongest inhibitory effect on the foam cell formation of macrophages (a key event of atherogenesis). After single administration of rHDL-based nanoparticles, a higher LT concentration was detected shortly in the atherosclerotic plaques of apoE−/−mice than non-rHDL-based nanoparticles, suggesting the in vivo plaque-targeting ability of apoA-I/rHDL-containing nanoparticles. Finally, among all nanoparticles LT-GM3-rHDL induced the largest decreases in the contents of blood lipids and in the areas of atherosclerotic plaques at various aortic locations in apoE−/−mice fed a high-fat diet for 12 weeks, supporting that LT-GM3-rHDL has the best in vivo antiatherosclerotic efficacy among the tested nanoparticles. Our data imply that GM3-functionalized rHDL (i.e., GM3-rHDL) can be utilized as a novel nanocarrier to enhance the efficacy of traditional antiatherosclerotic drugs (e.g., statins).Keywords:ganglioside GM3;atherosclerosis;reconstituted high-density lipoprotein (rHDL);lovastatin (LT);drug delivery system;statins;ApoA-I
研究领域:
药理学
·
心血管疾病
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纳米技术
·
药物递送
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2016
·
IF 2.243
Evgen Multia,Heli Sirén,Karl Andersson,Jörgen Samuelsson,Patrik Forssén,Torgny Fornstedt,Katariina Öörni,Matti Jauhiainen,Marja-Liisa Riekkola
Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins . Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy Distribution (AED) calculations provided information on the heterogeneity of the interactions without any a priori model assumptions. The AED calculations evidenced a homogenous binding site distribution for the interactions. Quartz Crystal Microbalance (QCM) studies were used to evaluate thermodynamics and kinetics of the Low-Density Lipoprotein (LDL) and anti-apoB-100 Mab interactions. High affinity and selectivity were observed, and the emerging data sets were analysed with so called Interaction Maps. In thermodynamic studies, the interaction between LDL and anti-apoB-100 Mab was found to be predominantly enthalpy driven. Both techniques were also used to study antibody interactions with Intermediate-Density (IDL) and Very Low-Density (VLDL) Lipoproteins. By screening affinity constants for IDL-VLDL sample in a single injection we were able to distinguish affinity constants for both subpopulations using the numerical Interaction Map tool.
研究领域:
生物化学
·
分子生物学
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DOI
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2017
·Vol. 24
·期 9
·2242-2248
·
IF 5.317
Dandan Jiang,Xiqian Li,Qiong Jia
Graphical A facile synthetic strategy based on host–guest interactions was developed to prepare multilayer cucurbit[6]uril-based magnetic nanoparticles, MNPs-(HA-DAH 5 /HA-CB[6] 5 ). The compound was employed as a blood purification material for the removal of LDL from plasma because it had good blood compatibilitiy and could be easily separated with an external magnet. Efficient removal of low density lipoprotein (LDL) is a key challenge due to its high level in plasma as a primary risk factor in the pathogenesis of atherosclerotic cardiovascular disease. In this work, a facile synthesis strategy based on host–guest interactions was developed to prepare multilayer cucurbit[6]uril-based magnetic nanoparticles, MNPs-(HA-DAH 5 /HA-CB[6] 5 ). The compound was employed as a blood purification material for the removal of LDL from plasma because it had good blood compatibility and could be easily separated with an external magnet. The efficient removal of LDL was attributed to the electrostatic interactions between the positive charged apoB-100 domain of LDL and the negative charged adsorbent. Moreover, the prepared material exhibited high recyclability and could release LDL in physiological saline for recyclable use. MNPs-(HA-DAH 5 /HA-CB[6] 5 ) offered promising perspectives and broad applications in extracorporeal treatment for the removal of LDL.
研究领域:
生物医学工程
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材料科学
·
心血管疾病研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Xiaozhou Huang,Yuxi Wen,Yihan Chen,Yuanyuan Liu,Chao Zhao
Diabetes mellitus, characterized by hyperglycemia and insulin resistance, is a disorder of the endocrine metabolic system which has emerged as a common chronic disease worldwide. Euglena gracilis polysaccharides have ideal development potential in the treatment of diabetes. However, their structure and bioactivity are largely unclear. A novel purified water-soluble polysaccharide (EGP-2A-2A) from E. gracilis with a molecular weight of 130.8 kDa consisted of xylose, rhamnose, galactose, fucose, glucose, arabinose, and glucosamine hydrochloride. The SEM image for EGP-2A-2A suggested a rough surface with the presence of globule-like protrusions. Methylation and NMR spectral analyses revealed that EGP-2A-2A was mainly composed of →6)-β-D-Gal p -(1 → 2)-α-D-Glc p -(1 → 2)-α-L-Rha p -(1 → 3)-α-L-Ara f -(1 → 6)-β-D-Gal p -(1 → 3)-α-D-Ara f -(1 → 3)-α-L-Rha p -(1 → 4)-β-D-Xyl p -(1 → 6)-β-D-Gal p -(1 → with complex branching structure. EGP-2A-2A significantly increased glucose consumption and glycogen content in IR-HeoG2 cells and modulates glucose metabolism disorders by regulating PI3K, AKT, and GLUT4 signaling pathways. EGP-2A-2A significantly suppressed TC, TG, and LDL-c levels, and enhanced that of HDL-c. EGP-2A-2A ameliorated abnormalities caused by disorders of glucose metabolism and the hypoglycemic activity of EGP-2A-2A may be mainly positively related to its high glucose content and the β-configuration in the main chain. These results suggested that EGP-2A-2A played an important role in alleviating disorders of glucose metabolism through insulin resistance and has the potential for development as a novel functional food with nutritional and health benefits.
研究领域:
生物化学
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分子生物学
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营养学
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药理学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）