JOURNAL OF MOLECULAR MEDICINE-JMM
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2023
·
IF 4.7
Chen Yinghui,Wu Yizhuo,Feng Weiqi,Luo Xueyang,Xiao Bing,Ding Xiaowei,Gu Yongjia,Lu Yanan,Yu Yu
Abstract The ductus arteriosus (DA), bridging the aorta and pulmonary artery, immediately starts closing after birth. Remodeling of DA leads to anatomic obstruction to prevent repatency. Several histological changes, especially extracellular matrices (ECMs) deposition and smooth muscle cells (SMCs) migration bring to anatomic closure. The genetic etiology and mechanism of DA closure remain elusive. We have previously reported a novel copy number variant containing Vav2 in patent ductus arteriosus (PDA) patients, but its specific role in DA closure remains unknown. The present study revealed that the expression of Vav2 was reduced in human patent DA, and it was less enrichment in the adjacent aorta. Matrigel experiments demonstrated that Vav2 could promote SMC migration from PDA patient explants. Smooth muscle cells with Vav2 overexpression also presented an increased capacity in migration and downregulated contractile-related proteins. Meanwhile, SMCs with Vav2 overexpression exhibited higher expression of collagen III and lessened protein abundance of lysyl oxidase, and both changes are beneficial to DA remodeling. Overexpression of Vav2 resulted in increased activity of Rac1, Cdc42, and RhoA in SMCs. Further investigation noteworthily found that the above alterations caused by Vav2 overexpression were particularly reversed by Rac1 inhibitor. A heterozygous, rare Vav2 variant was identified in PDA patients. Compared with the wild type, this variant attenuated Vav2 protein expression and weakened the activation of downstream Rac1, further impairing its functions in SMCs. In conclusion, Vav2 functions as an activator for Rac1 in SMCs to promote SMCs migration, dedifferentiation, and ECMs production. Deleterious variant potentially induces Vav2 loss of function, further providing possible molecular mechanisms about Vav2 in PDA pathogenesis. These findings enriched the current genetic etiology of PDA, which may provide a novel target for prenatal diagnosis and treatment. Key messages
Although we have proposed the potential association between Vav2 and PDA incidence through whole exome sequencing, the molecular mechanisms underlying Vav2 in PDA have never been reported. This work, for the first time, demonstrated that Vav2 was exclusively expressed in closed DAs.
Moreover, we found that Vav2 participated in the process of anatomic closure by mediating SMCs migration, dedifferentiation, and ECMs deposition through Rac1 activation.
Our findings first identified a deleterious Vav2 c.701C>T variant that affected its function in SMCs by impairing Rac1 activation, which may lead to PDA defect. Vav2 may become an early diagnosis and an effective intervention target for PDA clinical therapy.
研究领域:
心血管生物学
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遗传学
·
分子生物学
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发育生物学
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Tong Zhang,Tian Liang,Qichao Pan,Shouyan Zhang,Shuhua Zhang,Zhi Geng,Bo Zhu
Blood-contacting catheters are highly susceptible to thrombus formation, making heparin coating essential for reducing clinical complications. However, the limitations of heparin coatings have spurred significant efforts to develop alternative strategies. This study demonstrates a cost-efficient, mechanically viable, and universal zwitterion coating approach for long and complex catheters with near-zero fouling, super anticoagulation, and selective biocapturing. Leveraging the synergistic action of side groups, a wet-adhesive initiator-bearing polymer rapidly assembles on catheter surfaces in aqueous environments, facilitating the grafting of superhydrophilic and zwitterionic polymers onto catheter inner walls. This strategy demonstrates broad adaptability, successfully applying to ten substrates and showing exceptional versatility in modifying catheters and joints of various shapes and sizes. These coatings exhibit near-zero protein fouling across a broad pH range, and superior resistance to blood cells and bacteria. Furthermore, they maintain excellent stability under simulated bloodstream without compromising anticoagulant performance. Beyond antifouling properties, this method enables the construction of highly selective bio-interaction networks on catheter inner walls, allowing precise capture of circulating tumor cells from blood. This zwitterion coating technique, with its rapid modification, robust anticoagulant properties, and customizable bio-functionality, provides an attractive solution for, beyond catheters, a wide range of medical devices that must perform in challenging biological environments.
研究领域:
生物医学工程
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材料科学
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血液学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Cewen Hu,Bin Liu,Xinyue Huang,Zhilong Wang,Kaiqi Qin,Luyi Sun,Zengjie Fan
Muscle atrophy resulting from peripheral nerve injury (PNI) poses a threat to a patient’s mobility and sensitivity. However, an effective method to inhibit muscle atrophy following PNI remains elusive. Drawing inspiration from the sea cucumber, we have integrated microneedles (MNs) and microchannel technology into nerve guidance conduits (NGCs) to develop bionic microneedle NGCs (MNGCs) that emulate the structure and piezoelectric function of sea cucumbers. Morphologically, MNGCs feature an outer surface with outward-pointing needle tips capable of applying electrical stimulation to denervated muscles. Simultaneously, the interior contains microchannels designed to guide the migration of Schwann cells (SCs). Physiologically, the incorporation of conductive reduced graphene oxide and piezoelectric zinc oxide nanoparticles into the polycaprolactone scaffold enhances conductivity and piezoelectric properties, facilitating SCs’ migration, myelin regeneration, axon growth, and the restoration of neuromuscular function. These combined effects ultimately lead to the inhibition of muscle atrophy and the restoration of nerve function. Consequently, the concept of the synergistic effect of inhibiting muscle atrophy and promoting nerve regeneration has the capacity to transform the traditional approach to PNI repair and find broad applications in PNI repair.
研究领域:
生物医学工程
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神经科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Peipei Zhang,Yang Gao,Shaohai Li,Shaoliang Zhao,Hai Wang,Pengcheng Yu,Guanghui Gao,Yuanrui Wang
Medical catheters require lubrication and antimicrobial properties to reduce complications, such as tissue trauma and bacterial infections. Coating hydrogel on the catheter surface is a promising strategy; however, it usually faces the challenge of weak interfacial adhesion, thus leading to coating delamination or fracture and failure. Here, a waterborne polyurethane (WPU)-triggered surface bonding strategy was presented to construct hydrogel coatings, which involved two key steps: (i) coating a sticky WPU layer on the catheter surface and (ii) dip-coating the WPU-coated catheter with a monomer solution consisting of quaternary ammonium chitosan (QCS), sulfobetaine methacrylate (SBMA), N-vinylpyrrolidone (NVP), and zinc sulfate heptahydrate (ZnSO4·7H2O) for growing the hydrogel layer by ultraviolet initiation. The hydrogel coating demonstrated tough adhesion performance to the catheter, and the interfacial bonding strength achieved 536 N/m. Meanwhile, the hydrogel coating had a variable thickness adjusted by QCS and possessed excellent hydrophilicity (WCA = 24.6°) and low surface friction properties (COF = 0.0357) based on the formation of the hydration layer. Furthermore, the introduction of ZnSO4·7H2O endowed the hydrogel coating with prominent antimicrobial properties against Escherichia coli (Gram-negative bacteria) and Bacillus subtilis (Gram-positive bacteria). This approach paves an avenue for fabricating hydrogel coatings with strong interface stability, controllable thickness, lubrication, and antibacterial properties.
研究领域:
生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 12
·5035-5043
·
IF 5.251
Lin Liu,Hengchong Shi,Huan Yu,Rongtao Zhou,Jinghua Yin,Shifang Luan
Catheter-associated infections (CAIs) caused by bacterial colonization are significant problems in clinics. Thus, effective antibacterial coatings for biomedical catheters to prevent bacterial infections are urgently needed. Ideal coatings should include the advantage of potent antibacterial properties and being easily and economically modified on the catheter surface. Due to their advantages of adhesive capability on various substrates, an increasing number of coatings based on plant polyphenols have been developed. However, the hydrophilicity of plant polyphenols limits their utilization in coatings. Herein, hydrophobic tannic acid (TA) was synthesized via the one-step electrostatic assembly of TA and benzalkonium chloride (BAC) with the green solvent water as the medium. The as-prepared hydrophobic TA (TBA) facilely formed a stable and colorless coating on the luminal and outer surface of biomedical catheters with broad-spectrum antibacterial activity and biocompatiblity. It was demonstrated that the TBA-coated surfaces displayed excellent bactericidal activity toward Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and more than 99% of the above bacteria were killed by the TBA-coated films. The test of the coated catheters in vitro also showed the excellent antibacterial activity of both the outer and luminal surfaces of the catheter. Moreover, in an in vivo mouse model, the coated catheters relatively prevented bacterial colonization compared to the uncoated catheters. Meantime, no significant cytotoxicity and host response for Cell Counting Kit-8 (CCK-8) and tissue compatibility in vivo were observed, indicating the better biocompatibility of the TBA coating. This preparation method overcomes the limitation of the traditional hydrophilic tannic acid as a coating and provides a new method for preventing medical indwelling device-associated infections.
研究领域:
生物医学工程
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材料科学
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微生物学
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医疗器械
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 17
·3808-3815
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IF 7
Tiankun Hui,Chen Wang,Liangmin Yu,Chuanli Zhou,Meng Qiu
Treatment of large gaps in peripheral nerves is a major clinical challenge. Artificial nerve guidance conduits (NGCs) have provided new opportunities for guiding nerve regeneration. In this study, multifunctional black phosphorus (BP) hydrogel NGCs loaded with neuregulin 1 (Nrg1) were fabricated to support peripheral-nerve regeneration: they exhibited good flexibility and nerve regeneration-related cell induction, promoted Schwann-cell proliferation and accelerated neuron-branch elongation. Nrg1 induced the proliferation and migration of Schwann cells, which had beneficial roles in promoting nerve regeneration. In vivo immunofluorescence studies revealed BP hydrogel NGCs loaded with Nrg1 promoted sciatic-nerve regeneration and axon remyelination. Our method has great potential for promoting treatment of peripheral-nerve injuries.
研究领域:
神经科学
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生物材料
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组织工程
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 24
·9039
·
IF 4.927
Yijie Zhang,Zhiwen Jiang,Yanting Wang,Lixin Xia,Shuqin Yu,Hongjian Li,Wei Zhang,Wanshun Liu,Kai Shao,Baoqin Han
Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.Keywords:chitosan;carboxymethyl chitosan;nerve conduit;biocompatibility
研究领域:
生物医学工程
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神经科学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Ziwei Kan,Ye Chen,Qianyun Zhang,Luyi Pan,Aiying Chen,Ding Wang,Yi Wang,Guangming Wan,Bin He
The catheters coating can be effective in reducing bloodstream infection and thrombosis, which are the major complications in blood contact catheters. However, the surface functional coating is difficult to be implemented due to the high surface stretching force from the minor-caliber. In this work, we propose a covalent bonding coating of polydopamine/titanium dioxide quantum dots (PDA/TiO 2 QDs) on polyurethane (PU) catheters, which can fulfill a dual-function of antibacterial and antithrombosis. The PDA/TiO 2 QDs layer was prepared by dip-coating, where the intermediate transition layer of PDA was reacted with the internal hydroxyls of PU surface by pre-oxidation and bonds with the external TiO 2 QDs coating. The surface microstructures are analyzed by SEM, TEM and XPS methods, and the antimicrobial and anticoagulant performances are investigated by bacterial plate count and platelet adhesion tests. The oxidizing and hydrophilic effect of the top layer of TiO 2 QDs were enhanced by the QD-sized particles. The antibacterial activities of the PDA/TiO 2 QDs coating on PU catheters against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ), especially to S. aureus , are evidenced by bacterial plate count test, reaching good bactericidal rates of 49.9 % against E. coli and 83.7 % against S. aureus , respectively. Platelet adhesion test and whole blood dynamic circulation modeling demonstrate that the PDA/TiO 2 QDs coating effectively inhibits platelet adhesion due to an excellent hydrophilicity of TiO 2 QDs surface, and thereafter reduce thrombus formation.
研究领域:
材料科学
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生物材料
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生物医学工程
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表面化学
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DOI
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Fan Zhang,Liping Nan,Jia-Qi Fang,Lei Liu,Bo Xu,Xue-Han Jin,Shuhao Liu,Shengfu Liu,Kaihang Song,Zhijie Weng,Feng Chen,Jian-Guang Wang,Jun-Jian Liu
The Nerve Guide Conduit (NGC)offers a promising alternative to traditional methods for regenerating peripheral nerves. The efficacy of nerve regeneration and functional recovery is heavily dependent on the electrical, chemical, and physical properties of the NGC. A bionic Melt electrowriting (MEW) NGC loaded with Placental derived mesenchymal Stem Cells (PDMSCs) has been developed. Our study introduces a novel approach by utilizing Schwann cells induced from placental mesenchymal stem cells (PDMSCs), showcasing their potential in enhancing nerve regeneration when integrated with conductive nerve guidance conduits. Schwann cells (SCs) are crucial for nerve regeneration, and while various stem cells, including Bone Marrow Stromal Cells (BMSCs), have been investigated as sources of SCs for NGC loading, they are often limited by ethical concerns and restricted availability. PDMSCs, however, offer the advantages of widespread sourcing and the unique ability to differentiate into SCs, making them an attractive alternative for NGC applications. This NGC utilizes of an electrostatic direct writing technique employing Polycaprolactone (PCL) for the sheath and acrimped fiber scaffold made of polypyrrole (PPY) incorporating PDMSCs for itsinternal structure. The bionic PC-NGC loaded with PDMSCs, exhibits favorable characteristics including permeability, mechanical stability, and electrical conductivity. The PPY component effectively transmitsphysiological nerve signals, thereby promoting nerve regeneration, while the PDMSCs differentiateinto Schwann cells, creating a conducive environment for nerve regeneration. This research innovatively combines PDMSCs, known for their wide availability and SC differentiation potential, with a bionic NGC to enhance the treatment of peripheral nerve injuries (PNI). In vitro evaluations have confirmed the excellent biocompatibility of the materials used. Animal experiments usinga rat model with sciatic nerve injury demonstratedthat the PC-NGC significentlyfacilitated peripheral nerve regeneration. This was evidenced by improvements in axonal myelination, increased musclemass, enhanced sciatic nerve function index, and positive electrophysiologicalfindings. These outcomes arecomparable to those achieved through autologous transplantation. Characterized by its layered oriented fibers, the bionic PC-NGC integrates multi-scale and multifunctional biomaterials with PDMSCPDMSCs to effectively address peripheral nerve injuries (PNI). The useof thisprinted NGC stimulatesneuronal cell growth, thereby accelerating nerve regeneration. This innovative approach in tissue engineering presentsa promising clinical treatment strategy for PNI.
研究领域:
组织工程学
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再生医学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2025
·Vol. 44
·期 1
·1-25
·
IF 12.8
Wang Pengyu,Guo Weihua,Liu Shuyue,Li Shouyi,Li Jiaqi,Ding Bowen,Yin Fengyi,Yang Yang,Li Xingjiang,Cao Pei,Ma Chaozhe,Zhang Wanying,Song Yidan,Geng Yating,Liu Lantao,Hu Jing,Hao Jihui,Feng Yukuan
Background Copper accumulation triggers mitochondrial-driven cell death, known as cuproptosis, offering a promising mechanism for targeted cancer therapy. Recent studies have highlighted the critical role of intratumoral copper levels in regulating the expression of programmed cell death ligand-1 (PD-L1), suggesting that copper-induced cuproptosis not only enhances cancer cell death but may also amplify the effects of anti-PD-L1 antibodies (αPD-L1). However, in tumors where monotherapy with αPD-L1 shows limited efficacy, particularly in pancreatic ductal adenocarcinoma (PDAC), the role of copper-induced cuproptosis in enhancing αPD-L1 treatment efficacy and its underlying mechanisms remain unclear. Meanwhile, inadequate tumor drug accumulation and glycolysis significantly restrict the efficacy of cuproptosis. To address these challenges, we have synthesized a novel nanozyme, Pt@PCN-Cu, designed to stabilize intracellular copper accumulation and effectively induce cuproptosis. Additionally, we aim to determine whether this strong induction of cuproptosis can synergize with αPD-L1 to enhance cancer therapy, ultimately paving the way for novel strategies to improve PDAC treatment. Methods Pt@PCN-Cu was synthesized via a one-pot method, and its therapeutic potential was assessed in combination with αPD-L1 for the treatment of PDAC. Initially, the material’s properties were characterized, and its efficient cellular uptake was confirmed. Anti-tumor efficacy was evaluated by inducing cuproptosis in PDAC cell lines and xenograft models. RNA sequencing (RNA-seq) was utilized to identify key regulators involved in the modulation of PD-L1 expression by cuproptosis. Lastly, the therapeutic efficacy of Pt@PCN-Cu combined with αPD-L1 was evaluated in vivo, focusing on tumor growth inhibition and immune modulation within the tumor microenvironment (TME). Results Pt@PCN-Cu demonstrates excellent physicochemical properties and remarkable cascade catalytic activity, providing a solid foundation for further in vitro and in vivo studies. In vitro, Pt@PCN-Cu efficiently transports copper and induces cuproptosis primarily through mitochondrial dysfunction. Mechanistic studies show that Pt@PCN-Cu triggers the dissociation of hexokinase 2 (HK2) from mitochondria, leading to a reduction in HK2 activity. This decline in HK2 activity impairs glycolysis, a metabolic pathway essential for tumor energy metabolism, which in turn results in elevated PD-L1 levels. In vivo, Pt@PCN-Cu demonstrates excellent safety and accumulates at the tumor site in a subcutaneous PDAC mouse model, inducing cuproptosis. Moreover, the combination of Pt@PCN-Cu with αPD-L1 further enhanced its therapeutic efficacy and effectively reprogrammed the immunosuppressive TME. Conclusion This study presents strong evidence confirming the safety and therapeutic potential of Pt@PCN-Cu in PDAC treatment. Importantly, Pt@PCN-Cu not only induces cuproptosis but also significantly enhances antitumor efficacy in combination with αPD-L1 by regulating PD-L1 expression through HK2 modulation. These findings underscore a more effective and innovative approach for treating PDAC.
研究领域:
肿瘤学
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分子生物学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xu Zhang,Mingzhe Wang,Lin Liu,Huan Yu,Yang Liu,Xiaozheng Duan,Lei Wang,Hengchong Shi,Shifang Luan
Interventional cardiovascular catheters (ICCs) are prone to complications such as venous thrombosis and occlusion during clinical applications, primarily due to the gradual adhesion and accumulation of cells, proteins, and microorganisms on their surfaces. Heparin sodium (HS) represents a typical clinically antithrombotic agent, whereas its hydrophilicity usually limits stable binding to hydrophobic catheter surfaces. Herein, we propose an easy-operating one-step strategy for fabricating hydrophobic-modified heparin based on electrostatic assembly between ethyl lauroyl arginate (ELA), a cationic antimicrobial compound, and anionic HS. The resulting ELA-HS complex shows water-insoluble and alcohol-soluble features, which can form a uniform and robust coating driven by electrostatic and hydrophobic interactions upon a series of catheters with diverse shapes and multi-cavity structures via solvent immersion. Molecular dynamics (MD) simulation elucidated the formation mechanism of hydrophobic-modified heparin, as well as the assembly mechanism between the coating and substrates. Importantly, this obtained ELA-HS coating with adaptive dissociation effectively resists the adsorption of fibrinogen and significantly reduces the adhesion of blood cells, including platelets, lymphocytes, and monocytes. Leveraging ELA’s inherent bactericidal properties, the coating also demonstrates substantial antibacterial efficacy, reducing bacterial colonization by over 99% whether gram-negative Escherichia coli ( E.coli. ) and gram-positive Staphylococcus aureus ( Sa. ). In vivo validation further confirms the coating’s dual functionality in preventing thrombosis and microbial infection, even in stringent acute models of canine jugular vein implantation. This ELA-HS modification strategy offers a practical solution to enhance the hemocompatibility and infection resistance of interventional catheters, addressing critical clinical challenges associated with thrombosis and bacterial adhesion.
研究领域:
生物医学工程
·
材料科学
·
心血管医学
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产品关联
DOI
高影响因子
Journal of Materials Research and Technology-JMR&T
·
2021
·
IF 5.039
Yuzhe Chen,Wenxuan Zhao,Honglian Dai
Chitosan (CS) is a type of natural polysaccharide, widely used as a biomaterial on account of its great biocompatibility and the multitudes of functional groups on the long chitosan chain, making it easy for property augmentations. Nevertheless, the lack of workability and mechanical capacity limits the applications. Herein, electrospinning was chosen to fabricate oriented chitosan/polyethylene oxide (PEO) nanofibres decorated by integrin-targeting polypeptides (RGD, Arg-Gly-Asp), which is essential for cell adhesion. At the same time, porous PLGA-PEG membranes were taken as a shell of the composite film, which can provide mechanical support for the scaffold. Adequate topological anisotropic information from oriented nanofibres helps the scaffold simulate the natural axon structure, which can induce accelerated regeneration of neurotmesis. Moreover, β-Tricalcium Phosphate (β-TCP) nanoparticles were brought into nanofibers to neutralize the acidic environment produced by the degeneration of PLGA-PEG. Cell viability tests at the in vitro level and dorsal root ganglion (DRG, 1-day sucking SD rat) co-culture detection proved that the scaffold possesses excellent biocompatibility while guiding oriented regeneration of damaged nerves. In this study, a CS-RGD/PEO/β-TCP/PLGA-PEG porous composite scaffold with low cytotoxicity was fabricated. The scaffold can not only lead to the oriented growth of nerves but also has selectivity, which can help nutrient exchange while inhibiting the invasion of fibrous tissue.
研究领域:
生物医学工程
·
材料科学
·
神经再生
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）