INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Siyuan Xu,Xinya Huang,Yanyan Wang,Jianping Liu,Wenli Zhang
Recombinant high-density lipoprotein (rHDL) as anti-atherosclerosis (AS) vehicle has unique advantages including multiple anti-atherogenic functions and homing features to plaques. However, rHDL may be converted into dysfunctional forms due to complex treatment during preparation. Herein, oxidation-induced dysfunction of non-split HDL and rHDL was initially investigated. It was found that although both non-split HDL and rHDL showed oxidative dysfunction behavior, non-split HDL demonstrated superior oxidation defense compared to rHDL due to its intact composition and avoidance of overprocessing such as split and recombination. Unfortunately, in vivo oxidative stress could compromise the functionality of HDL. Therefore, surface engineering of non-split HDL and rHDL with cascade antioxidant enzyme analogues Ebselen and mitochondrial-targeted TPGS-Tempo was conducted to construct a dual-line defense HDL nano system ( i.e. , T@E-HDLs/rHDL), aiming to restore plaque redox balance and preserving the physiological function of HDL. Results indicated that both T@E-HDLs and rHDLs performed without distinction and exhibited greater resistance to oxidative stress damage as well as better functions than unmodified HDLs in macrophage foam cells. Overall, the modification of dual antioxidants strategy bridges the gap between non-split HDL and rHDL, and provides a promising resolution for the dilemmas of oxidative stress in plaques and HDL self dysfunction.
研究领域:
心血管科学
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药学
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生物技术
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DOI
PubMed
高影响因子
Open Life Sciences
·
2020
·Vol. 15
·期 1
·1042-1048
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IF 0.69
Tao Jin,Lu Wang,Dongbo Li,Tao Yang,Yuefei Zhou
Testosterone is often used to improve the physiological function. But increased testosterone levels affect blood lipids and cause inflammation and oxidative stress, which are risk factors for vascular diseases. This study aimed at investigating the effects of testosterone on cerebral vascular injury using an established intracranial aneurysm (IA) model. Sixteen-week-old female C57Bl/6 mice were subcutaneously infused with testosterone propionate (TP; 5 mg/kg day) or plain soybean oil (controls) for 6 weeks. After 2 weeks of treatment, mice were given angiotensin II-elastase for another 4 weeks. The results showed that TP significantly increased cell apoptosis and reactive oxygen species production in cerebral artery, together with increases in plasma tumor necrosis factor-α (TNF-α) levels and in urinary 8-isoprostane levels. Plasma assays showed that 2 weeks after TP or soybean oil administration, the high-density lipoprotein (HDL) level was higher in the TP group than in controls. In vitro studies showed that testosterone increased TNF-α and monocyte chemotactic protein-1 mRNA and protein expression levels in RAW 264.7 macrophages. In summary, by reducing the HDL level, TP aggravates cerebral artery injury by increasing cell apoptosis, inflammation, and oxidative stress.
研究领域:
神经科学
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药理学
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血管生物学
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DOI
PubMed
高影响因子
INTEGRATED FERROELECTRICS
·
2018
·
IF 0.367
Wei Hong,Chuntian Zhang,Jing Sun,Shu Wu,Kaijun Zhang,Jinming Wang,Zhanmei Xiao,Heng Zhang,Qingshan Li,Guangzhong Xing
This paper first designed the molecular structure of the water-soluble polyurethane phase change material. Taking HDI (hexamethylene diisocyanate), PEG (polyethylene glycol), chain extender (DMPA (dimethylolpropionic acid), BDO (1,4- butanediol), EDA (ethylenediamine)), catalyst (DBTDL (February acid dibutyl tin)), neutralizing agent (TEA (triethylamine)) as the raw material, the paper then prepared the waterborne polyurethane phase change material, which is available for wet spinning process. The particle size, appearance, storage stability, water absorption, tensile strength and elongation at break of the WPUPCM emulsion were then tested. Moreover, the influences of reaction temperature, reaction time, R value (ie -NCO / -OH molar ratio), PEG relative molecular mass and DMPA content on the WPUPCM performance indicators were investigated. The study indicated that reaction temperature, reaction time, R value, PEG relative molecular mass and DMPA content show various influences on WPUPCM performance indicators. Therefore, in order to meet the requirements of practical application and determine optimal formulation and process parameters, further relevent studies based on comprehensive considerations of all factors are needed.
研究领域:
材料科学
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化学工程
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DOI
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
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脂质代谢
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临床生物化学
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PubMed
高影响因子
Cardiovascular Diabetology
·
2018
·Vol. 17
·期 1
·1-8
·
IF 5.235
Luo Mengdie,Zhang Ziyu,Peng Yani,Wang Shuai,Peng Daoquan
Background It is well known that angiopoietin-like protein 8 (ANGPTL8) exerts its effects on lipid metabolism through the inhibition of lipoprotein lipase and subsequent elevation of plasma triglyceride. However, it is not clear whether ANGPTL8 could affect lipid metabolism via other pathways. The study was aimed to investigate the effects of ANGPTL8 on the function of high-density lipoprotein (HDL), which plays a protective role in atherosclerosis progression.Methods Two hundred and ten subjects were recruited. Plasma ANGPTL8 was measured by enzyme-linked immunosorbent assays. Cholesterol efflux capacity was chosen as the biomarker of HDL function and measured via H3-cholesterol loading THP-1 cell models.Results ANGPTL8 exhibited no significant difference between CAD group and nonCAD group, but ANGPTL8 in DM group was significantly higher than that in the nonDM group [568.3 (406.2–836.8) vs 458.2 (356.8–755.6), P = 0.023]. Compared to controls, subjects in CAD group and DM group exhibited significantly lower cholesterol efflux capacity [CAD: 14.58 ± 2.06 vs 12.51 ± 2.83%, P < 0.0001; DM: 13.62 ± 2.57 vs 12.34 ± 3.16%, P = 0.0099]. ANGPTL8 was inversely correlated with cholesterol efflux capacity (r = − 0.188, P < 0.01). Regression analysis revealed that plasma ANGPTL8 was an independent contributor to cholesterol efflux capacity (standardized β = − 0.143, P = 0.023).Conclusion ANGPTL8 presents a negative effect on HDL-mediated cholesterol efflux capacity.
研究领域:
医学
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生物化学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Shuze Ren,Mahmoud Abou-Elsoud,Shasha Wang,Jiaojiao Chen,Xi Huang
Egg yolk proteins have garnered significant attention from researchers due to their outstanding functional properties, and physical modification methods serve as a key approach to enhancing the characteristics of these proteins. In this study, phosphorylated egg yolk high-density lipoprotein (HDL) was prepared using sodium tripolyphosphate (STP) to investigate the properties of the high-internal-phase emulsion formed after cross-linking with phosvitin (Pv), as well as its protective effect on curcumin. Phosphorylation significantly enhanced the functional properties of HDL, with the 6% STP treatment yielding the highest phosphorus content (7.32 mg/g) in the resulting phosphorylated HDL (P-HDL). Structural analyses confirmed covalent phosphate binding, which reduced HDL particle size, induced protein unfolding, and exposed hydrophobic regions, thereby improving its emulsifying capacity and thermal stability. A composite stabilizer composed of phosphorylated HDL (P-HDL) and Pv was developed to construct high internal phase emulsions (HIPEs). These HIPEs also exhibited superior performance in curcumin delivery, increasing its bioaccessibility to 38.10% compared with 15.40% in the control, while effectively inhibiting lipid oxidation during storage. This study provides a promising strategy for designing high-performance emulsion delivery systems.
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PubMed
高影响因子
DRUG DELIVERY
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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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Yuxin Zhao,Kai Liu,Long Xie,Jia Luo,Huan Gu,Xiaofang Li
Biomimetic HDL nanoparticles were prepared based on the natural structure of HDL for liver-target delivery. • Bromelain (BRO) and chondroitin sulfate (CS) were modified on the silybin-loaded HDL nanoparticles (BCSH). • BRO promoted nanoparticles penetration by disrupting the ECM barrier, while CS enhanced CD44-mediated aHSC uptake. • The BRO and CS modified HDL nanoparticles showed significantly increased liver accumulation in fibrotic mice. • BCSH suppressed HSC activation by inhibiting inflammation and oxidative stress, improving liver function in fibrotic mice. Activated hepatic stellate cells (aHSCs) play a central role in liver fibrosis by promoting excessive extracellular matrix (ECM) deposition, while oxidative products in fibrotic livers perpetuate their activation. The treatment of liver fibrosis remains challenging because the ECM barrier limits drug uptake by aHSCs. To overcome this challenge, we developed high-density lipoprotein (HDL) nanoparticles loaded with silybin (SIL), and modified them with chondroitin sulfate (CS) and bromelain (BRO). The resulting formulation, denoted as BRO/CS-SIL@HDL nanoparticles (BCSH), was designed to enhance hepatic enrichment, facilitate penetration through the collagen-rich ECM, and enable CD44 receptor-mediated targeting. BCSH showed efficient internalization even in the presence of a collagen barrier. BCSH treatment markedly reduced inflammation, oxidative stress, collagen deposition, and HSC activation. Then RNA seq was further performed to explore the potential molecular mechanisms underlying the therapeutic effects of the nanoparticles, revealing alterations in multiple signaling pathways and biological processes related to liver fibrosis. In conclusion, these results suggest that BCSH represents a promising therapeutic strategy for liver fibrosis. Download: Download high-res image (156KB) Download: Download full-size image
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高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-10
·
IF 4.38
Tang Xiaoyu,Mao Ling,Chen Jin,Zhang Tianhua,Weng Shuwei,Guo Xin,Kuang Jie,Yu Bilian,Peng Daoquan
In patients with coronary artery disease (CAD), further increasing the level of high-density lipoprotein (HDL) cholesterol (HDL-C) as an add-on to statins cannot reduce cardiovascular risk. And it has been reported that HDL functional metric—cholesterol efflux capacity (CEC) may be a better predictor of CAD risk than HDL-C. CEC measurement is time-consuming and not applicable in clinical settings. Thus, it is meaningful to explore an easily acquired index for evaluating CEC. Thirty-six CAD patients and sixty-one non-CAD controls were enrolled in this cross-sectional study. All CAD patients had acute coronary syndrome (ACS). CEC was measured using a [ 3 H] cholesterol loading Raw 264.7 cell model with apolipoprotein B-depleted plasma (a surrogate for HDL). Proton nuclear magnetic resonance (NMR) spectroscopy was used to assess HDL components and subclass distribution. CEC was significantly impaired in CAD patients (11.9 ± 2.3%) compared to controls (13.0 ± 2.2%, p = 0.022). In control group, CEC was positively correlated with enzymatically measured HDL-C levels (r = 0.358, p = 0.006) or with NMR-determined HDL-C levels (NMR-HDL-C, r = 0.416, p = 0.001). However, in CAD group, there was no significant correlation between CEC and HDL-C (r = 0.216, p = 0.206) or NMR-HDL-C (r = 0.065, p = 0.708). Instead, we found that the level of high-sensitivity C-reactive protein (hsCRP) was inversely associated with CEC (r = − 0.351, p = 0.036). Multiple regression analysis showed that the hsCRP level was associated with CEC after adjusting other cardiovascular risk factors and HDL-C, although the association would not reach significance if adjusting for multiple testing. NMR spectroscopy showed that HDL particles shifted to larger ones in patients with high hsCRP levels, and this phenomenon was accompanied by decreased CEC. In patients with CAD, the level of HDL-C cannot reflect HDL function. The impaired correlation between HDL-C and CEC is possibly due to an inflammation-induced HDL subclass remodeling. These hypothesis-generating data suggest that hsCRP levels, a marker of acute inflammation, may associate with HDL dysfunction in ACS subjects. Due to the design limited to be correlative in nature, not permitting causal inference and a larger, strictly designed study is still needed.
研究领域:
心血管病学
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临床医学
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分子生物学
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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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DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 8
·期 9
·3259-3270
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IF 3.247
Xiaozhou Zhou,Shiguo Chen,Xingqian Ye
The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.
研究领域:
药理学
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营养学
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分子生物学
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生物化学
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PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 4
·2635-2648
·
IF 3.9
Ying Li,Yingxin Tian,Qixue Wang,Xinyi Gu,Long Chen,Yiqun Jia,Shan Cao,Ting Zhang,Mingmei Zhou,Xiaojun Gou
Gynura segetum (Lour.) Merr. (GS), has been widely used in Chinese folk medicine and can promote circulation, relieve pain and remove stasis. In recent years, the hepatotoxicity caused by GS has been reported, however its mechanism is not fully elucidated. Metabolomic techniques are powerful means to explore the toxicological mechanism and therapeutic effects of traditional Chinese medicine. The purpose of this study was to establish a serum metabolomics method based on Gas Chromatography-Mass Spectrometry (GC-MS) to explore the hepatotoxicity mechanism of different exposure times and doses of GS in rats. Sprague Dawley (SD) rats were administered daily with distilled water, 7.5 g kg−1 GS, or 15 g kg−1 GS by intragastrical gavage for either 10 or 21 days. The methods adopted included enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) staining and GC-MS-based serum metabolomics. Serum biochemistry analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total bilirubin (TBIL) and total bile acid (TBA) significantly (P < 0.05) increased while the levels of albumin (ALB) and high-density lipoprotein (HDL) significantly (P < 0.05) decreased in GS-treated groups, compared with the control group. Interestingly, the ALT, AST, TG and ALB levels changed in a time- and dose-dependent manner. The results of H&E staining showed the degree of liver damage after administration of GS gradually deepened with the extension of administration time and the increase of the dose. According to the results of metabolomics analysis, 26 differential metabolites were identified, which were involved in 8 metabolic pathways including phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism and so on. Meanwhile, the number of differential metabolites in different GS-treated groups was associated with GS exposure time and dose. Therefore, we concluded that GS might induce hepatotoxicity depending on the exposure time and dose.
研究领域:
药理学
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毒理学
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代谢组学
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传统中药
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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）