MATERIALS & DESIGN
·
2021
·
IF 7.991
Yang Lei,Xiaorong Lan,Zhoukun He,Anlin Yin,Wanyu Jin,Qinsheng Hu,Yunbing Wang
The bioprosthetic heart valve (BHV) has attracted considerable attention in clinical practice. However, complications of the BHV such as thrombosis, calcification, and early deterioration after implantation have limited further applications. In the present study, we provide a strategy to fabricate an anti-biofouling BHV by constructing interpenetrating polymer network structures on both inner and outer valve materials. We systematically investigated the morphologies, wetting properties, elemental compositions, stability of the extracellular matrix, transparency, mechanical properties, and anti-biofouling properties (e.g., anti-cell adhesion, resistance to bovine serum albumin protein adsorption, anticoagulant properties, and anti-calcification properties) of the modified BHV via both in vitro and in vivo experiments. Compared to the BHV without coating treatment, treated with heparin, or treated with a hydrophobic polydimethylsiloxane coating, the BHV treated with a hydrophilic coating containing both polyacrylic acid and polydimethylsiloxane exhibited better multifarious anti-biofouling properties. Our findings provide a method for the preparation of multi-antifouling medical materials with better synergistic hemocompatibility and anti-calcification.
研究领域:
生物医学工程
·
材料科学
·
心血管医学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Chen Jinyong,Ren Tanchen,Xie Lan,Hu Haochang,Li Xu,Maitusong Miribani,Zhou Xuhao,Hu Wangxing,Xu Dilin,Qian Yi,Cheng Si,Yu Kaixiang,Wang Jian`an,Liu Xianbao
Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790—an anti-calcification drug—to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient ( Ldlr −/− ) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.
研究领域:
心血管疾病
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药物递送
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·
IF 4.5
Yujing Wang,Min Xiao,Feng Cai,Yang Li,Tianli Shi,Xiaoyan Zhou,Shuhong Tian,Denggao Huang
Vascular calcification (VC) is a common complication of chronic kidney disease (CKD). VC is a gene-regulated process similar to osteogenic differentiation. There are still no convincing schemes to prevent and reduce the development of VC. It has been reported that hypoxia-inducing factor 1α (HIF-1α) and endothelin-1(ET-1) are related to VC. In this study, we found that the expression of ET-1 and HIF-1α was enhanced after VC, the interaction between HIF-1α and ET-1 was confirmed by CO-IP and luciferase experiments. We found that ET-1 was an upregulated differential gene of calcified vascular smooth muscle cells (VSMCs) through gene sequencing. However, hypoxia-inducing factor 2α (HIF-2α) and HIF-1α have antagonistic effects on each other. HIF-1α is a pro-inflammatory cytokine, and HIF-2α can improve inflammation and fibrosis. Roxadustat, as a selective PHD3 inhibitor, preferentially activates HIF-2α. It is still unclear whether roxadustat improves VC in CKD by regulating the expression of HIF-2α/HIF-1α. Alizarin red staining and western blot as well as immunohistochemical results showed that roxadustat could significantly reduce the degree of vascular and VSMCs calcification in CKD rats. Serum HIF-1α and ET-1 were significantly decreased after roxadustat treatment. In addition, western blot results showed that roxadustat could decrease the expression of HIF-1α and ET-1 in vascular tissues and calcified VSMC, but HIF-2α expression significantly increased. Interestingly, our study confirmed that activation of HIF-1α or inhibition of HIF-2α reversed the ameliorating effect of roxadustat on VC, proving that the effect mediated by roxadustat is HIF-2α/HIF-1α dependent. We have demonstrated for the first time that roxadustat improves VC in CKD rats by regulating HIF-2α/HIF-1α, thus providing a new idea for the application of roxadustat in VC of CKD.
研究领域:
药理学
·
肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
·
2025
·
IF 4.7
Long Li,Quanyou Chai,Chunling Guo,Junyi Wei,Yuqiao Qin,Huimin Liu,Zhaoyang Lu
Aim Vascular calcification (VC) is a major adverse cardiovascular event in chronic kidney disease (CKD) patients. N6-methyladenosine (m6A) modification is vital for many biological processes, but its function and possible molecular mechanisms in VC are poorly understood. This study aimed to clarify the function and molecular mechanisms of N6-adenosine-methyltransferase-like 3 (METTL3) in VC. Methods and results The results of the bioinformatic analysis showed that METTL3 expression was significantly upregulated in calcified VSMCs. This finding was corroborated by phosphate-induced VSMCs calcification models and 5/6 nephrectomy-induced CKD mouse VC models. Afterward, Alizarin Red S staining and m6A dot blot analysis demonstrated METTL3 overexpression elevated m6A levels and encouraged calcification in VSMCs and mouse aortic rings, while METTL3 knockdown decreased m6A levels and inhibited calcium deposition in these experimental models. Furthermore, METTL3 promoted VC via the PTEN/AKT pathway, and MeRIP verified that METTL3 induced PTEN mRNA degradation by modifying it with m6A. In addition, molecular docking simulations and DARTS assays revealed that quercetin is a natural small-molecule inhibitor of METTL3. The current investigation demonstrated that quercetin mitigated VC by reducing METTL3-dependent m6A levels in vivo and in vitro. Conclusion In conclusion, this study unraveled the pathogenic mechanism of METTL3-mediated m6A modification in VC and provided new insights to establish METTL3 as a therapeutic target for VC.
研究领域:
分子生物学
·
心血管疾病
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Catalysis
·
2025
·
IF 13.1
Lixin Kang,Haoran Li,Kexin Lin,Shen Hu,Song Liu,Yuben Qiao,Ying Wang,Aitao Li
The biocatalytic production of 25-hydroxyvitamin D3 (25(OH)VD3, calcidiol) represents a superior alternative to traditional chemical synthesis. However, the reported VD3 hydroxylases generally exhibit suboptimal catalytic efficiency, limiting their practical applications. In this study, a cytochrome P450 CYP107Pdh from Pseudonocardia dioxanivorans_CB1190, which displays unique C26 hydroxylation activity on VD3, was identified. Then, structure-guided loop engineering combined with binding pocket reshaping was conducted on CYP107Pdh, leading to the generation of the quintuple variant 89_90insIP/T112A/V161L/G186V (M4). This variant shifted the regioselectivity from 91% C26 in the wild type (WT) to 81% C25 for calcidiol production. In addition, variant M4 showed a remarkable enhancement in catalytic activity, achieving a catalytic efficiency (kcat/Km) that is 75-fold higher than that of the WT. Computational analyses revealed that the regioselectivity shift and activity improvement are primarily attributed to a conformational transition in the substrate-binding pocket from an open to a more closed state, which optimizes substrate binding and facilitates efficient 25-hydroxylation of VD3. Finally, a semipreparative biotransformation yielded 2.64 g of crystalline calcidiol (95% purity) from a 1-L reaction, thereby expanding the enzyme library of VD3 hydroxylases and underscoring its potential for industrial-scale production of calcidiol.
研究领域:
生物化学
·
酶工程
·
药物合成
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Xinyun Pu,Xu Peng,Shubin Shi,Shaoxiong Feng,Xu Wei,Xi Gao,Xixun Yu
Valvular heart disease (VHD) poses a significant threat to human health, and the transcatheter heart valve replacement (THVR) is the best treatment for severe VHD. Currently, the glutaraldehyde cross-linked commercial bioprosthetic heart valves (BHVs) remain the first choice for THVR. However, the cross-linking by glutaraldehyde exhibits several drawbacks, including calcification, inflammatory reactions, and difficult endothelialization, which limits the longevity and applicability of BHVs. In this study, λ-carrageenan with anticoagulant function was modified by carboxymethylation into carboxymethyl λ-carrageenan (CM-λC); subsequently, CM-λC was used as a cross-linking agent to stabilize decellularized bovine pericardial tissue through amide bonds formed by a 1-(3-(Dimethylamino)propyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide (EDC/NHS)-catalyzed reaction between the amino functional groups within pericardium and the carboxyl group located on CM-λC. Lastly, the inclusion complex (CD/Rutin) (formed by encapsulating the rutin molecule through the hydrophobic cavity of the mono-(6-ethylenediamine-6-deoxy)-β-cyclodextrin) was immobilized onto above BHVs materials (λCar-BP) through the amidation reaction. The treated sample exhibited mechanical properties and collagen stability similar to those of GA-BP, except for improved flexibility. Because of the presence of sulfonic acid groups and absence of aldehyde group as well as the Rutin release from CD/Rutin immobilized onto BHVs, the hemocompatibility, anti-inflammatory, HUVEC-cytocompatibility, and anticalcification properties, of the CM-λC-fixed BP modified with CD/Rutin was significantly better than that of GA-BP. In summary, this nonaldehyde-based natural polysaccharide cross-linking strategy utilizing the combination of CM-λC and CD/Rutin provides a novel solution to obtain BHVs with durable and stable anticoagulant, anticalcification, and anti-inflammatory properties, and has a wide range of potential applications in improving the various properties of BHVs.
研究领域:
医学材料学
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心血管病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Physiological Investigation
·
2024
·Vol. 67
·期 2
·69
·
IF 0
Wang Chunli,Xu Mingzhi,Bai Yafei,Pan Mingjiao,Qi Yonghui,Chen Ruman
Vascular calcification (VC), a major complication in chronic kidney disease (CKD), is predominantly driven by osteoblastic differentiation. Recent studies have highlighted the crucial role of microRNAs in CKD’s pathogenesis. Here, our research focused on the effects of miR-204-5p and its molecular mechanisms within VC. We initially found a notable decrease in miR-204-5p levels in human aortic vascular smooth muscle cells stimulated with inorganic phosphate, using this as a VC model in vitro. Following the overexpression of miR-204-5p, a decrease in VC was observed, as indicated by alizarin red S staining and measurements of calcium content. This decrease was accompanied by lower levels of the osteogenic marker, runt-related transcription factor 2, and higher levels of α-smooth muscle actin, a marker of contractility. Further investigation showed that calcium/calmodulin-dependent protein kinase 1 (CAMK1), which is a predicted target of miR-204-5p, promotes VC. Conversely, overexpressing miR-204-5p reduced VC by suppressing CAMK1 activity. Overexpressing miR-204-5p also effectively mitigated aortic calcification in an in vivo rat model. In summary, our research indicated that targeting the miR-204-5p/CAMK1 pathway could be a viable strategy for mitigating VC in CKD patients.
研究领域:
分子生物学
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病理学
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心血管科学
·
遗传学
✓ 已验证
DOI
JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
·
2020
·
IF 4.495
Jian Guo,Binbin Tong,Jie Jian,Jianguo Chen,Taosheng Zhou,Xunzhong Shang,Jinrong Cheng
Large transduction coefficient ( d 33 × g 33 ) is difficult to obtain in piezoelectric ceramics because these two parameters show opposite trends with compositional modifications. Herein, the Pb(Zr 0.53 Ti 0.47 )O 3 ceramic powders were calcinated under different temperatures (A:830 °C, B:860 °C, and C:890 °C), and then mixed together according to different weight ratios (1A:1B:1C, 1A:2B:1C, 1A:2B:3C and 3A:2B:1C) for ceramics preparation. Both d 33 and g 33 are improved successfully, and the transduction coefficient with the weight ratio of 1A:2B:3C reaches up to 17,500 × 10 −15 m 2 /N, which is 60 % higher than that with the powders calcinated under 830 °C, and at least twice those of commercial PZT-4, PZT-5A and PZT-8 ceramics. The improved transduction coefficient is owing to the enhanced piezoelectric constant and spontaneous polarization resulted from the increased grain size, relative density and the fraction of tetragonal phase. These results indicate that this is a simple but effective way to tailor the transduction coefficient in piezoelectric ceramics .
研究领域:
材料科学
·
物理学
✓ 已验证
DOI
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-20
·
IF 17.694
Wang Zhen-Xing,Luo Zhong-Wei,Li Fu-Xing-Zi,Cao Jia,Rao Shan-Shan,Liu Yi-Wei,Wang Yi-Yi,Zhu Guo-Qiang,Gong Jiang-Shan,Zou Jing-Tao,Wang Qiang,Tan Yi-Juan,Zhang Yan,Hu Yin,Li You-You,Yin Hao,Wang Xiao-Kai,He Ze-Hui,Ren Lu,Liu Zheng-Zhao,Hu Xiong-Ke,Yuan Ling-Qing,Xu Ran,Chen Chun-Yuan,Xie Hui
Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called “calcification paradox”. Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.
研究领域:
骨骼生物学
·
干细胞生物学
·
血管生物学
·
老年学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Shanshan Song,Xina Yu,Changming Xie,Zhanhua Li,Ying Zhang,Yan Liu,Zhongjue Qiu,Tiantian Wang,Hongna Su,Hui Huang,Pei Luo
Panaxynol (PA), a bioactive compound found in carrots and other Apiaceae plants, holds promise for managing diabetes-related vascular complications. This study investigated the long-term effects of PA on diabetes-induced vascular calcification (DVC) in db/db mice for up to 9 weeks. The impact of PA on DVC was evaluated both in vivo and in vitro using immunohistochemical staining, Western blotting, micro-computed tomography, and other analytical techniques. Results demonstrated that PA significantly attenuated arterial calcification and collagen hyperplasia in the aorta. Additionally, PA elevated levels of the lipid signaling molecule 14,15-EET, which preserved the vascular structure and function by reducing inflammatory macrophage infiltration in perivascular adipose tissue. This protective effect was partially attributed to the PA-mediated inhibition of soluble epoxide hydrolase (sEH) through Sirt6 activation. These findings highlight PA as a potential natural therapeutic strategy for mitigating diabetic vascular complications and offer an alternative to conventional pharmacological approaches.
研究领域:
生物学
·
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials
·
2024
·Vol. 17
·期 17
·4409
·
IF 3.1
Yuxiang Chen,Shengping Wu,Hanhui Huang,Feng Rao,Lang Yang
This study aims to compare the effects of three calcium compounds on the workability, setting time and mechanical properties of red mud (RM)–blast furnace slag (BFS)-based geopolymers. The crystalline phase, hydration process and microstructure of RM-BFS-based geopolymers were characterized by X-ray diffraction (XRD), heat evolution, X-ray photoelectron spectroscopy (XPS), and scanning electron microscope (SEM) tests. The results showed that an appropriate amount of calcium compounds can improve the flowability and compressive strength of the geopolymers, but the excessiveness causes a decrease in strength due to rapid hardening. Other than calcium carbonate, both calcium oxide and calcium chloride played important roles in accelerating the setting times of RM-BFS-based geopolymers. The acceleration in the setting times of geopolymers could be attributed to the calcium hydroxide produced by the dissolution of the calcium compounds, which also provides nucleation sites for the geopolymerization reaction. This study gives new insights into the effect of calcium on the setting times and mechanical properties of geopolymers in the geopolymerization process.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jianming Zhao,Abudureheman Bahatibieke,Guodong Liu,Jinming Li,Junfei Li,Feilong Zhao,Bohao Yao,Yajie Xie,Yudong Zheng
Injury to cardiac valves is a major contributor to mortality associated with cardiovascular diseases. Artificial valves are preferred for their mimicry of natural valve efficiency in optimizing hemodynamics and minimizing associated complications. To endure the substantial pressures of the cardiovascular system, these valves require exceptional fatigue resistance, calcification resistance, and blood compatibility. To address these demands, we have designed and synthesized a silane uniformly integrated polyurea-polyurethane elastomer (PSCU). The PSCU features a highly responsive hydrogen bond network, conferred by the integration of oxygen-containing spirochemical rings and polyurethane urea segments, which forms orientation to prevent material fatigue damage. Concurrently, PSCU has almost no adverse effects on the blood due to the uniform integration of silane, and long-term use will not cause calcification. In vivo evaluations have confirmed PSCU’s exceptional biocompatibility and stability, with no observable tissue inflammation or material accumulation. Moreover, fluid dynamics studies have demonstrated PSCU’s superior mechanical attributes, maintaining effective unidirectional blood flow under a sustained 60 mmHg pressure gradient. This breakthrough material represents a significant advancement in the field of cardiovascular medicine, offering enhanced durability and reliability for artificial heart valves.
研究领域:
生物材料学
·
心血管医学
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）