CHEMICAL RESEARCH IN TOXICOLOGY
·
2016
·
IF 3.025
Xiaomin Xia,Qiong Shi,Xiufang Song,Juanli Fu,Zixuan Liu,Yawen Wang,Yuxin Wang,Chuanyang Su,Erqun Song,Yang Song
Our previous studies suggested that tetrachlorobenzoquinone (TCBQ) elicits pro-inflammatory activities; however, the mechanism of its toxicity toward vascular endothelial cell has not been characterized. Although TCBQ has been shown to stimulate interleukin-1 beta (IL-1β) expression, it is unknown whether TCBQ regulates post-translational IL-1β activation. Using human umbilical vein endothelial cells, we discovered that TCBQ not only promotes the expression of NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) components [composed of NLRP3, adaptor molecule apoptosis-associated speck like protein containing a caspase activation and recruitment domain (ASC), and pro-caspase 1] but also participates in priming the NLRP3 inflammasome. Activation of the NLRP3 inflammasome results in the maturation and release of IL-1β. Further experiments showed that K+ efflux, reactive oxygen species (ROS) production, and mitochondrial DNA damage may be involved in NLRP3 inflammasome activation mediated by TCBQ. Moreover, TCBQ downregulates the ubiquitination of NLRP3, further facilitating the activation of the NLRP3 inflammasome. These results suggest that the NLRP3/IL-1β signaling pathway plays an important role in TCBQ-induced endothelial cell pro-inflammatory responses, which may point to potential therapeutic approaches against TCBQ-mediated toxicity.
研究领域:
毒理学
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免疫学
·
细胞生物学
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血管生物学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
Liwenyu Chen,Yi Yu,Min Lin,Ming Liang,Chen Yang,Xutian Kan,Xiaoliang Lin,Jin Qi
Schisandra chinensis (Turcz.) Baill, a traditional Chinese medicine with significant nourishing functions, has a regulatory effect on the cardiovascular system, digestive system, central nervous system, and endocrine and immune systems. It can protect the cardiovascular system, improve immunity, and has anti-oxidant and anti-aging properties. This study aimed to identify the chisandra chinensis components that increased NAD+ levels, by using spectrum-effect analysis and experimental validations. First, the quality of the S. chinensis extract was analyzed by HPLC-MS. The extract of S. chinensis increased the NAD+ levels of HUVECs during oxygen and glucose deprivation injury, and protected HUVEC s from injury from superoxide dismutase (SOD) and aging. The relationships of spectral effects were studied by partial least square regression. Coupled with target cell extraction, the material basis for increasing NAD+ levels in S. chinensis was obtained. The pharmacological activity of S. chinensis was verified at the cellular level. The related enzymes of the NAD+ synthesis and decomposition pathways were identified, showing that S. chinensis increased the level of NAD+ by increasing the activity of related enzymes in the synthesis pathways of NMNAT1, NMNAT2, NMNAT3, and NAMPT, but had no effect on the decomposition pathway. Finally, four constituents were confirmed, in vitro, to be the basis of S. chinensis -induced increases in the levels of NAD+. The EC 50 values of the four constituents were also determined.
研究领域:
药理学
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心血管生物学
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植物化学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Jun Zhang,Zhen Zou,Bin Wang,Ge Xu,Qiong Wu,Yuchan Zhang,Zhiyi Yuan,Xi Yang,Chao Yu
s The increasing use of copper oxide nanoparticles (CuONPs) has led to major concerns regarding both the predominant physicochemical properties and the potential toxic effects on the environment and human health. The objective of this study is to explore the possible mechanisms underlying the toxicity of CuONPs in vascular endothelial cells. We found that CuONPs induced the cell death in human umbilical vein endothelial cells (HUVECs) through a caspase-independent pathway. Our results also demonstrated that CuONPs were prevalently deposited within lysosomes . The lysosomal deposition of CuONPs led to lysosomal dysfunction, resulting in the impairment of autophagic flux and the accumulation of undegraded autophagosomes . Nevertheless, blockage of the lysosomal deposition of CuONPs could significantly attenuate HUVEC cell death. Interestingly, we found that the inhibition of lysosomal deposition of CuONPs reduced the release of Cu ions , which has been considered as the crucial factor for the toxicity of CuONPs. In summary, our results indicate that the lysosomal deposition of CuONPs (along with the enhanced release of Cu ions form CuONPs) triggers CuONPs-induced HUVEC cell death. Our findings provide an insight into the mechanism of toxicity to the cardiovascular system induced by toxic metal oxide nanoparticles exposure.
研究领域:
纳米技术
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毒理学
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2025
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IF 2.5
Xiang Ming,Lin Xiangdong,Chen Haiying
Coronary heart disease (CHD) is a disease caused by organic and functional coronary artery stenosis, resulting in a reduced oxygen supply to the heart. This study aimed to investigate the mechanism via which Luteolin regulates the Sirt1 / Nrf2 pathway to inhibit ferroptosis in human umbilical vein endothelial cells (HUVEC) associated with CHD. An ox-LDL-induced HUVEC cell model with Sirt1 silencing and Luteolin treatment was established. The silencing efficiency of Sirt1 was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The results of molecular docking and DARTS experiments showed that Luteolin could effectively bind Sirt1 . Subsequently, we measured the expression of Nrf2 and Sirt1 , cell viability, MDA, GSH, Fe 2+ levels, lipid ROS content, expression of ferroptosis-related proteins GPX4, FTH, FTL, and cell migration parameters. The results showed that Luteolin could activate the Sirt1 / Nrf2 axis and effectively inhibit ox-LDL-induced ferroptosis in HUVEC. Experimental results revealed that Luteolin could enhance HUVEC cell viability, decrease MDA, Fe 2+ , and ROS levels, increase GSH levels, promote the expression of HO-1, GPX4, FTH, FTL, inhibit the expression of ACSL4 and TFRC, and enhance the migration capability of HUVEC cells. Moreover, silencing Sirt1 reversed the effects of Luteolin on the activation of Sirt1 and Nrf2 , confirming the dependence of these effects on the Sirt1 / Nrf2 signaling pathway. In conclusion, this study indicates that Luteolin could inhibit ferroptosis in HUVEC in CHD by modulating the Sirt1 / Nrf2 axis, providing a basis for further research on strategies for preventing and treating CHD and related diseases.
研究领域:
药理学
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分子生物学
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心脏病学
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细胞生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
LIPIDS
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2016
·Vol. 52
·期 1
·27-35
·
IF 1.892
Pan Yao,Liu Benxin,Deng Zeyuan,Fan Yawei,Li Jing,Li Hongyan
The effects of two fatty acids, oleic acid (OLA) and elaidic acid (ELA) on normal human umbilical vein endothelial cells (HUVEC) and non-rafts HUVEC were investigated in this study. The expression levels of inflammatory cytokines (ICAM-1, VCAM-1 and IL-6) were analyzed. Western blot was used to analyze the expression levels of inflammation-related proteins (NF-κB, ERK1/2) and toll-like receptors 4 (TLR4). The results showed that the levels of nuclear translocation of NF-κB p65 and phosphorylated ERK1/2 were significantly decreased only in non-lipid rafts cells pretreated with trans fatty acid (TFA). The expression of TLR4 in the ELA-treated normal cells was higher than that in non-lipid rafts HUVEC. When the lipid rafts was destroyed by methyl-β-cyclodextrin, the levels of nuclear translocation of NF-κB p65, phosphorylated ERK1/2 and TLR4 were decreased significantly. Therefore, lipid rafts may be involved in TFA induced-inflammation in HUVEC through blocking the inflammatory signal pathway. Lipid rafts might be a platform for specific receptors such as TLR4 for TFA to activate the pro-inflammation on cell membranes.
研究领域:
细胞生物学
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分子生物学
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心血管研究
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DOI
PubMed
高影响因子
Current Research in Food Science
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2022
·
IF 6.269
Xuan Chen,Liufeng Zheng,Bing Zhang,Zeyuan Deng,Hongyan Li
Oxidative stress is a potential factor in the promotion of endothelial dysfunction. In this research, flavonoids (quercetin, luteolin) combined with carotenoids (lycopene, lutein), especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production. RNA-seq analysis indicated quercetin-lycopene combination downregulated inflammatory genes induced by H 2 O 2 , such as IL-17 and NF-κB. The expression of NF-κB p65 was activated by H 2 O 2 but inhibited by the quercetin-lycopene combination. Moreover, the quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity. SIRT1 inhibitor EX-527 attenuated the inhibitory effects of quercetin, lycopene, and their combination on the expression of p65, Nox4 enzyme, and ROS. Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress, potentially contributing to the prevention of cardiovascular disease.
研究领域:
药理学
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分子生物学
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细胞生物学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Haifeng Wang,Yi Huang,Chenhui Zhou,Fanyong Gong,Jianyong Wang,Hao Liu,Wenhui Zhao,Yuxiang Zhao,Xiang Gao
In recent years, the use of nanocarriers to deliver bioactive peptides has become a new strategy to promote angiogenesis. The aim of this study was to develop a QKCMP peptide delivery system based on triangular DNA origami nanostructure (tDONs) carrier to improve the bioactivity and targeting of the peptide. The main objective of this study was to design and prepare QKCMP peptide-TDOns complexes and to evaluate their angiogenesis promoting effects in vitro and in vivo. tDONs were synthesized and purified, and then QKCMP peptide was loaded into tDONs. A variety of characterization techniques were used to evaluate the physicochemical properties of the complexes, including particle size, morphology, and RNA release efficiency. The effects of QKCMP peptid-TDons on proliferation, apoptosis, migration and angiogenesis of human umbilical vein endothelial cells (HUVEC) were evaluated by CCK8, EdU, Annexin V-FITC/PI, PI staining and Transwell assay. At the same time, its promoting effect on angiogenesis was further verified in zebrafish and mouse models. The successful preparation of QKCMP peptide-TDONS showed good biocompatibility and stability. The results of in vitro experiments showed that QKCMP peptide-TDons significantly promoted HUVEC proliferation, inhibited apoptosis, and activated endothelial cell function. Zebrafish experiments showed that QKCMP peptid-TDons effectively enhanced angiogenesis and promoted rapid repair of carotid vascular endothelium in mouse models.
研究领域:
生物医学工程
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分子生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Sheng Ding,Siyu Liu,Shaoyang Kang,Shuwei Wang,Nan Jiang,Yuwei Li,Chunxiao Zhou,Hantao Lou,Chuangnian Zhang,Pingsheng Huang,Wenshuai Liu,Zujian Feng,Weiwei Wang,Deling Kong,Ningbei Yin
Diabetic wound healing poses a major clinical challenge. One of the promising therapy, the flap transplantation surgery exhibited unsatisfactorily low flap survival due to the intertwined pathological barriers: impaired angiogenesis, excessive oxidative stress, and persistent inflammation, leading to poor tissue repair. While the therapeutic platforms based on extracellular vesicles (EVs) emerges as a promising treatment, its efficacy is often limited by the inadequate yield and rapid in vivo clearance. To address this challenge, this study developed a strategy centered on preconditioning human umbilical vein endothelial cells (HUVECs) with high glucose (HG) stress to produce HG-preconditioned extracellular vesicles (hEVs), which significantly improve production, enrich regenerative cargoes (e.g., HIF-1α, VEGF), and enhance homologous cellular internalization. The hEVs derived from HUVECs were encapsulated by microfluidically fabricated gelatin methacryloyl (GelMA) microgels to create GelMA@hEVs. The biodegradable and biocompatible GelMA microgels enabled a sustained hEVs release profile. Therefore, GelMA@hEVs exhibited significant efficacy improvement in promoting endothelial cell proliferation, migration, and tube formation critical for vascularization, mitigating reactive oxygen species, and modulating macrophage polarization toward a pro-reparative phenotype. Mechanistically, these therapeutic effects relied on activating the HIF-1α/VEGF pathway, a core axis for angiogenesis dysregulated in diabetes. In diabetic ischaemic flap models, GelMA@hEVs significantly improved flap survival, restored vascular perfusion, and facilitated tissue regeneration without systemic toxicity. Altogether, this work provides a generalizable strategy for diabetic ischaemic flap repair by combining engineered EVs as bioactive cargo with a microgel scaffold for sustained delivery, offering a promising in situ tissue engineering solution.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhiwan Chen,Mengfei Yuan,Haojing Li,Lihua Li,Binghong Luo,Lu Lu,Qi Xiang,Shan Ding
The inflammation of chronic wounds plays a key hindering role in the wound healing process. Slowing down the inflammatory response is significant for the repair of chronic wounds. Studies have revealed that succinate can inactivate gastrin D (GSDMD) and prevent cell pyroptosis. Chitosan has anti-inflammatory properties and is commonly used as wound healing material. Therefore, we used succinic anhydride to modify chitosan and found that N-succinylated chitosan (NSC) was more effective in inhibiting inflammation. The results showed that the stimulation of TNF-α and high glucose induces overexpression of capase-1 and TNF-α in human umbilical vein endothelial cells (HUVEC), and down-expression of CD31. However, the expression of capase-1 and TNF-α decreased, while the expression of CD31, VEGF and IL-10 was up-regulated significantly in dysfunctional HUVEC cells after treated by NSC. Moreover, NSC can speed wound healing, histological examination results showed that wounds treated with NSC exhibited faster epithelial tissue regeneration and thicker collagen deposition. Overall, this study results suggested that NSC has the function of restoring the physiological functions of dysfunctional HUVEC cells induced by high glucose and TNF-α, and can accelerate wound healing, indicating that NSC has good potential to be applied in inflammatory chronic wounds such as diabetic foot.
研究领域:
药理学
·
伤口愈合
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炎症
·
细胞生物学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Yunxin Zhang,Jianlong Liu,Wei Jia,Xuan Tian,Peng Jiang,Zhiyuan Cheng,Jinyong Li
This study is aimed at identifying the roles of AGE/RAGE and ET-1 in deep vein thrombosis (DVT). Advanced glycation end products (AGEs) in glycated human serum albumin (M-HSA) were detected by ELISA. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis, followed by ELISA for the detection of inflammatory cytokine level and oxidative stress level in HUVECs. Immunofluorescence was performed to detect ET-1 and eNOS expression. The expression of specific proteins was assayed by western blot. As a result, decreased HUVEC viability was observed after stimulation with M-HSA, whereas RAGE inhibitor improved it. Cell apoptosis showed the opposite trend. Additionally, M-HSA-induced inflammatory cytokine release and oxidative stress of HUVECs were both alleviated by RAGE inhibitor. RAGE inhibitor also increased the levels of NO and eNOS while decreasing the level of ET-1 in M-HSA-stimulated HUVECs. Furthermore, decreased protein expression of Bax, cleaved-caspase3, RAGE, p65, ET-1 and iNOS was observed after treatment with RAGE inhibitor, in addition to increased protein expression of Bcl-2 and eNOS. In conclusion, blocking AGE/RAGE pathway downregulates ET-1, thereby mitigating HUVEC damage in DVT.
研究领域:
心血管疾病
·
分子生物学
·
细胞生物学
·
血栓形成
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DOI
PubMed
高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 1
·22
·
IF 5.4
Xia Zheng,Xiaofei Liu,Zhuo Wang,Rui Li,Qiaoli Zhao,Bingbing Song,Kit-Leong Cheong,Jianping Chen,Saiyi Zhong
Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (Na2SeO3) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 9
·2187
·
IF 3.098
Hui Wang,Wenxi Zhang,Yatao Cheng,Xinyu Zhang,Nannan Xue,Gaorong Wu,Meng Chen,Kang Fang,Wenbo Guo,Fei Zhou,Herong Cui,Tao Ma,Penglong Wang,Haimin Lei
In the clinic some anti-tumor drugs have shown damage to normal blood vessels, which could lead to vascular diseases. Therefore, it is necessary to evaluate the effects of anti-tumor drugs on normal blood vessels at the beginning of the drug design process. In this study, ligustrazine (TMP) and flavonoids were selected as raw materials. Sixteen novel TMP-flavonoid derivatives were designed and synthesized. Interestingly, compounds14and16were obtained by hydrolysis of a dihydroflavone to a chalcone under alkaline conditions. The cytotoxicity of the TMP-flavonoid derivatives was evaluated on five human tumor cell lines and one classical type of normal endothelial cell lines (HUVEC-12) by an MTT assay. Part of the derivatives showed better anti-tumor activities than the corresponding raw materials. Among them, compound14exhibited the closest activity to the positive control against the Bel-7402 cell line (IC50= 10.74 ± 1.12 μM; DDP IC50= 6.73 ± 0.37 μM) and had no toxicity on HUVEC-12 (IC50> 40 μM). Subsequently, fluorescence staining and flow cytometry analysis indicated that compound14could induce apoptosis of Bel-7402 cell lines. Moreover, the structure-activity relationships of these derivatives were briefly discussed.Keywords:TMP-flavonoid derivatives;anti-tumor;human tumor cell lines;HUVEC-12;fluorescence staining;flow cytometry
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
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）