COMPUTERS IN BIOLOGY AND MEDICINE
·
2024
·
IF 7
Jianan Li,Yan Sun,Haoran Bi
Diazinon (DZN), a persistent organophosphate insecticide, has been associated with neurotoxic effects, particularly in the hippocampus. However, the specific molecular mechanisms of DZN-induced hippocampal toxicity remain unknown. In this study, we analyzed the mRNA and miRNA expression patterns of HT22 cells following exposure to DZN (125 μM), and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted subsequently. The integration of miRNA sequencing (miRNA-seq) and mRNA sequencing (mRNA-seq) data identified 33 differentially expressed miRNAs (DEMIs, 15 up-regulated and 18 down-regulated) and 271 differentially expressed mRNAs (DEMs, 69 up-regulated and 202 down-regulated) targeted by the DEMIs. Moreover, the 3 most central mRNAs (ITGAV, FN1, and EGFR) and 7 associated miRNAs (mmu-miR-700-5p, mmu-miR-26a-2-3p, mmu-miR-452-3p, mmu-miR-25-3p, mmu-miR-582-5p, mmu-miR-467a-5p, and mmu-miR-467b-5p) were screened and validated using quantitative real-time PCR. Furthermore, the GO analysis revealed that the identified DEMs were enriched in biological adhesion extracellular matrix, and growth factor binding, while the KEGG analysis suggested that the enriched DEMs were involved in ECM-receptor interaction, mTOR signaling pathway, MAPK signaling pathway, and AMPK signaling pathway. Our results may aid in elucidating the underlying mechanisms associated with DZN-induced hippocampal toxicity and provide valuable insights into the pathogenesis of neurotoxicity triggered by other organophosphorus pesticides.
研究领域:
神经毒理学
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分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Nian-Yuan Xu,Jun Li,Mei-Ling Wang,Xue-Yu Chen,Ruizhi Tang,Xi-Qiu Liu
The current research models of breast cancer are usually limited in their capacity to recapitulate the tumor microenvironment in vitro. The lack of an extracellular matrix (ECM) oversimplifies cell–cell or cell–ECM cross-talks. Moreover, the lack of tumor-associated macrophages (TAMs), that can comprise up to 50% of some solid neoplasms, poses a major problem for recognizing various hallmarks of cancer. To address these concerns, a type of direct breast cancer cells (BCCs)–TAMs coculture organoid model was well developed by a sequential culture method in this study. Alginate cryogels were fabricated with appropriate physical and mechanical properties to serve as an alternative ECM. Then, our previous experience was leveraged to polarize TAMs inside of the cryogels for creating an in vitro immune microenvironment. The direct coculture significantly enhanced BCCs organoid growth and cancer aggressive phenotypes, including the stemness, migration, ECM remodeling, and cytokine secretion. Furthermore, transcriptomic analysis and protein–protein interaction networks implied certain pathways (PI3K-Akt pathway, MAPK signaling pathway, etc.) and targets (TNF, PPARG, TLR2, etc.) during breast cancer progression in a TAM-leading immune microenvironment. Future studies to advance treatment strategies for BCC patients may benefit from using this facile model to reveal and target the interactions between cancer signaling and the immune microenvironment.
研究领域:
肿瘤学
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生物医学工程
·
细胞生物学
·
免疫学
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组织工程
✓ 已验证
DOI
PubMed
高影响因子
Tissue Engineering Part C-Methods
·
2024
·Vol. 30
·期 3
·113-129
·
IF 2.7
Xiaoxiao Li,Weikang Zhao,Dandan Zhou,Pei Li,Chen Zhao,Qiang Zhou,Yiyang Wang
The decellularized extracellular matrix (ECM) of cartilage is a widely used natural bioscaffold for constructing tissue-engineered cartilage due to its good biocompatibility and regeneration properties. However, current decellularization methods for accessing decellularized cartilaginous tissues require multiple steps and a relatively long duration to produce decellularized cartilage. In addition, most decellularization strategies lead to damage of the microstructure and loss of functional components of the cartilaginous matrix. In this study, a novel decellularization strategy based on a hydrostatic pressure (HP) bioreactor was introduced, which aimed to improve the efficiency of producing integral decellularized cartilage pieces by combining physical and chemical decellularization methods in a perfusing manner. Two types of cartilaginous tissues, auricular cartilage (AC) and nucleus pulposus (NP) fibrocartilage, were selected for comparison of the effects of ordinary, positive, and negative HP-based decellularization according to the cell clearance ratio, microstructural changes, ECM components, and mechanical properties. The results indicated that applying positive HP improved the efficiency of producing decellularized AC, but no significant differences in decellularization efficiency were found between the ordinary and negative HP-treated groups. However, compared with the ordinary HP treatment, the application of the positive or negative HP did not affect the efficiency of decellularized NP productions. Moreover, neither positive nor negative HP influenced the preservation of the microstructure and components of the AC matrix. However, applying negative HP disarranged the fibril distribution of the NP matrix and reduced glycosaminoglycans and collagen type II contents, two essential ECM components. In addition, the positive HP was beneficial for maintaining the mechanical properties of decellularized cartilage. The recellularization experiments also verified the good biocompatibility of the decellularized cartilage produced by the present bioreactor-based decellularization method under positive HP. Overall, applying positive HP-based decellularization resulted in a superior effect on the production of close-to-natural scaffolds for cartilage tissue engineering.Impact statementIn this study, we successfully constructed a novel hydrostatic pressure (HP) bioreactor and used this equipment to produce decellularized cartilage by combining physical and chemical decellularization methods in a perfusing manner. We found that positive HP-based decellularization could improve the production efficiency of integral decellularized cartilage pieces and promote the maintenance of matrix components and mechanical properties. This new decellularization strategy exhibited a superior effect in the production of close-to-natural scaffolds and positively impacts cartilage tissue engineering.
研究领域:
组织工程
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生物医学工程
·
软骨生物学
·
机械工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS Pathogens
·
2024
·Vol. 20
·期 9
·e1012483
·
IF 5.5
Xi Luo,Litian Zhang,Xiaoyuan Xie,Liyan Yuan,Yanqiang Shi,Yinbo Jiang,Wujian Ke,Bin Yang
Fibronectin (FN) is an essential component of the extracellular matrix (ECM) that protects the integrity of the microvascular endothelial barrier (MEB). However, Treponema pallidum subsp . pallidum ( Tp ) breaches this barrier through elusive mechanisms and rapidly disseminates throughout the host. We aimed to understand the impact of Tp on the surrounding FN matrix of MEB and the underlying mechanisms of this effect. In this study, immunofluorescence assays (IF) were conducted to assess the integrity of the FN matrix surrounding human microvascular endothelial cell-1 (HMEC-1) with/without Tp co-culture, revealing that only live Tp exhibited the capability to mediate FN matrix disaggregation in HMEC-1. Western blotting and IF were employed to determine the protein levels associated with the FN matrix during Tp infection, which showed the unaltered protein levels of total FN and its receptor integrin α5β1, along with reduced insoluble FN and increased soluble FN. Simultaneously, the integrin α5β1-binding protein–intracellular vimentin maintained a stable total protein level while exhibiting an increase in the soluble form, specifically mediated by the phosphorylation of its 39 th residue (pSer39-vimentin). Besides, this process of vimentin phosphorylation, which could be hindered by a serine-to-alanine mutation or inhibition of phosphorylated-AKT1 (pAKT1), promoted intracellular vimentin rearrangement and FN matrix disaggregation. Moreover, within the introduction of additional cellular FN rather than other Tp -adhered ECM protein, in vitro endothelial barrier traversal experiment and in vivo syphilitic infectivity test demonstrated that viable Tp was effectively prevented from penetrating the in vitro MEB or disseminating in Tp -challenged rabbits. This investigation revealed the active pAKT1/pSer39-vimentin signal triggered by live Tp to expedite the disaggregation of the FN matrix and highlighted the importance of FN matrix stability in syphilis, thereby providing a novel perspective on ECM disruption mechanisms that facilitate Tp dissemination across the MEB.
Treponema pallidum subsp . pallidum ( Tp ), dominating the global concerned disease—syphilis, can mediate various pathogenic processes through its dissemination, during which the vascular endothelial barrier plays a vital role in the pathogen-host interaction. Tp alters the characteristics of the barrier components, including vascular endothelial cell and the surrounding extracelluar matrix (ECM), while the initial step of Tp dissemination involves breaching the ECM and moving toward the surface within unknown mechanisms. Here, we demostrated that live Tp triggered the pAKT1/pSer39-vimentin signals in microvascular endothelial cells, which promoted the redistribution of vimentin around the perinucleus. And pSer39-vimentin facilitated the detachment of intergrein α5β1 from fibronectin (FN), which is an essential component of ECM for Tp adhesion. Furthermore, we discovered that pAKT1 inhibition or addition of cellular FN could delay the FN matrix disaggregation, ultimately preventing live Tp from traversing the microvascular endothelial barrier. These results provide insights into ECM disruption employed by Tp and identify potential therapeutic targets against syphilis.
研究领域:
微生物学
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传染病学
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细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Shan Yu,Yiyuan Duan,Xingang Zuo,Xinyi Chen,Zhengwei Mao,Changyou Gao
Cell migration plays an important role in many physiological and biological processes, which is influenced by both physicochemical properties of surrounding matrix and signal gradient generated by neighboring/remote cells. Here we aim to develop a co-culture system of immune cells and smooth muscle cells (SMCs) based on the combination of Transwell and cell-responsive hydrogels. This model can be used to study the cell invasion into hydrogels in dynamic physiological conditions , with better mimicking of the in vivo microenvironment . Methacrylic anhydride-modified hyaluronic acid (MA-HA) macromolecules were crosslinked by matrix metalloproteinases (MMPs) sensitive peptides (MMP SP) to fabricate a cell-degradable hydrogel mimicking dynamic extracellular matrix (ECM). The migration of SMCs into the MMP-sensitive hydrogel was investigated under the existence of U937 cells, a type of macrophage-like cells. The invasion distance of SMCs in the MMP-sensitive hydrogels was much longer than that in the MMP-insensitive ones both in vitro and in vivo . The impact of hydrogel degradability and inductive signal gradient generated by U937 cells on cell invasion was compared, revealing that the degradability plays a major role in regulating cell invasion into the 3D hydrogels. Further mechanism investigation revealed that the expressions of cell migration-related genes and proteins were significantly up-regulated in the MMP-sensitive hydrogels compared to those in the MMP-insensitive hydrogels.
研究领域:
生物医学工程
·
细胞生物学
·
组织工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2022
·
IF 11.322
Shuyi Li,Rongli Deng,Xuenong Zou,Qiong Rong,Jiali Shou,Zilong Rao,Wanqiu Wu,Gang Wu,Daping Quan,Miao Zhou,Tim Forouzanfar
Periosteum is crucial to the initial healing of bone defects because it provides a stable periosteum-specific microenvironment and abundant osteogenic cells towards bone repair. However, the usage of autologous periosteum is restricted for limited availability. Xenogeneic decellularized periosteum (DP) preserves periosteum-specific cues but the hardly-controlled physicochemical properties render it inconvenient to use widely. Our study aimed to fabricate a tissue-engineered periosteum (TEP) with a continuous periosteum-specifically bioactive surface and tailored physicochemical properties by co-axial electrospinning of poly(ε-caprolactone) (PCL)/periosteal decellularized extracellular matrix (dECM) to promote bone defects healing. Before use, DP was confirmed for effective removal of residual DNA and well preservation of biological components, e.g., collagen and glycosaminoglycans . After optimization of fabrication processes, PCL/dECM co-axially electrospun membrane (PEC) bore an exquisite core-shell structure, which was effectively equipped with composite advantages of dECM and PCL. Notably, PEC stood out in terms of tensile strength and long-term durability within a physiological environment compared to that of the dECM uniaxial electrospun membrane (ECM). Besides, PEC exhibited remarkably better cell proliferation , migration, bio-mineralization, and osteogenic properties as compared to that of the electrospun PCL membrane. Moreover, PEC-TEP could significantly enhance the recovery of critical-sized bone defects in rats than that of PCL-TEP. To the best of our knowledge, biomimetic PEC-TEP was fabricated and used for the first time to repair bone defects. This novel strategy is promising to fabricate a dECM-based advanced membrane for tissue engineering .
研究领域:
组织工程
·
生物材料
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2022
·Vol. 10
·期 3
·2204479
·
IF 17.521
Qian Sun,Fang Pei,Man Zhang,Bo Zhang,Ying Jin,Zhihe Zhao,Qiang Wei
Remarkable exertions are directed to reveal and understand topographic cues that induce cell mechanical sensitive responses including lineage determination. Extracellular matrix (ECM) is the sophisticated ensemble of diverse factors offering the complicated cellular microenvironment to regulate cell behaviors. However, the functions of only a few of these factors are revealed; most of them are still poorly understood. Herein, the focus is on understanding the curved structure in ECM network for regulating stem cell mechanotransduction. A curved nanofiber network mimicking the curved structure in ECM is fabricated by an improved electrospinning technology. Compared with the straight fibers, the curved fibers promote cell bridge formation because of the cytoskeleton tension. The actomyosin filaments are condensed near the curved edge of the non-adhesive bridge in the bridging cells, which generates higher myosin-II-based intracellular force. This force drives cell lineage commitment toward osteogenic differentiation. This study enriches and perfects the knowledge of the effects of topographic cues on cell behaviors and guides the development of novel biomaterials.
研究领域:
生物材料
·
细胞生物学
·
组织工程
·
纳米技术
·
干细胞研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Hou Xiaodong,Shen Yuting,Huang Bin,Li Qiuyan,Li Shaoyue,Jiang Tingting,Shan Xuexia,Xu Weichen,Liu Shuo,Wu Shengbo,Zhao De,Zhu Anqi,Sun Liping,Xu Huixiong,Yue Wenwen
Preclinical studies demonstrating high cure rates with PD1/PD-L1 combinations have led to numerous clinical trials, but emerging results are disappointing. These combined immunotherapies are commonly employed for patients with refractory tumors following prior treatment with cytotoxic agents. Here, we uncovered that the post-chemotherapy tumor presents a unique mechanical microenvironment characterized by an altered extracellular matrix (ECM) elasticity and increased stiffness, which facilitate the development of aggressive tumor phenotypes and confer resistance to checkpoint blocking therapy. As thus, we rationally designed an in situ nanocomposite hydrogel system, LOS&FeOX@Gel, which enabled effective and specific delivery of the therapeutic payloads (losartan [LOS] and oxaliplatin [OX]) into tumor. We demonstrate that sustained release of LOS effectively remodels the tumor mechanical microenvironment (TMM) by reducing ECM deposition and its associated “solid stress”, thereby augmenting the efficacy of OX and its immunological effects. Importantly, this hydrogel system greatly sensitized post-chemotherapy tumor to checkpoint blocking therapy, showing synergistic therapeutic effects against cancer metastasis. Our study provides mechanistic insights and preclinical rationale for modulating TMM as a potential neoadjuvant regimen for tumor to optimize the benefits of chemo-immunotherapy, which lays the groundwork for leveraging “mechanical-immunoengineering” strategies to combat refractory tumors. Graphical Abstract
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2020
·
IF 7.242
Gaoyang Guo,Linhe Jin,Binggang Wu,Haiyang He,Fan Yang,Liangpeng Xu,Yang Lei,Yunbing Wang
With the coming of an aging society and the emergence of transcatheter valve technology, the implantation of bioprosthetic heart valves (BHVs) in patients with valvular disease has significantly increased worldwide. Currently, most clinically available BHVs are crosslinked with glutaraldehyde (GLUT). However, the GLUT treated BHV is less durable due to the combined effect of multiple factors such as cytotoxicity, immune responses, and calcification. In this study, the in-situ polymerization of sulfonic monomers with a decellularized extracellular matrix (ECM) was performed to simultaneously achieve the crosslinking and functionalization of ECM. Subsequently, the feasibility of the hybrid ECM used as leaflet material of BHV was evaluated. In in-vitro tests, the results indicated that the hybrid ECM fixed collagen efficiently and the introduction of sulfonic polymer promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). In in-vivo tests, after being implanted in SD rats and mice, the hybrid ECM significantly inhibited immune response and calcification compared with the non-hybrid counterpart and GLUT crosslinked tissue. These results indicated that the hybrid ECM exhibited more competitive stability and better biocompatibility compared to these features in GLUT-crosslinked valve. Therefore, the sulfonic polymer hybrid ECM provides a potential material for more durable BHV and the in-situ polymerization strategy can serve as a general treatment method for tissue crosslinking as well as tailoring the biophysical properties of ECM.
研究领域:
生物医学工程
·
组织工程
·
心血管医学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2024
·
IF 3.9
Xin Hao,Ting Du,Feng Yang,Yilan Wang,Huatao He,Menghan Yang,Meiying Hong,Guanxiong Wang,Deqing Huang,Yaolei Wang
Recently, in vitro models of intestinal mucosa have become important tools for drug screening and studying the physiology and pathology of the intestine. These models enable the examination of cellular behavior in diseased states or in reaction to alterations in the microenvironment, potentially serving as alternatives to animal models. One of the major challenges in constructing physiologically relevant in vitro models of intestinal mucosa is the creation of three-dimensional (3D) microstructures that accurately mimic the integration of intestinal epithelium and vascularized stroma. Here, core-shell alginate (Alg) microspheres were generated to create the compartmentalized extracellular matrix (ECM) microenvironment needed to simulate the epithelial and vascularized stromal compartments of the intestinal mucosa. We demonstrated that NIH-3T3 and human umbilical vein endothelial cells (HUVECs) embedded in the core of the microspheres can proliferate and develop a vascular network, while human colorectal adenocarcinoma cells (Caco-2) can form an epithelial monolayer in the shell. Compared to Caco-2 monolayer encapsulated within the shell, the presence of the vascularized stroma enhances their proliferation and functionality. As such, our core-shell Alg microspheres provide a valuable method for generating in vitro models of vascularized intestinal mucosa with epithelial and vascularized stroma arranged in a spatially relevant manner and demonstrating near-physiological functionality.
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2019
·Vol. 10
·期 1
·1-11
·
IF 11.878
Hong Yi,Zhou Feifei,Hua Yujie,Zhang Xianzhu,Ni Chengyao,Pan Dihao,Zhang Yiqing,Jiang Deming,Yang Long,Lin Qiuning,Zou Yiwei,Yu Dongsheng,Arnot David E.,Zou Xiaohui,Zhu Linyong,Zhang Shufang,Ouyang Hongwei
Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60–160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.
研究领域:
生物材料
·
组织工程
·
止血
·
外科技术
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Xiaomeng Li,Shuaibing Liu,Shanshan Han,Qingqing Sun,Jianmin Yang,Yuhang Zhang,Yongchao Jiang,Xiaofeng Wang,Qian Li,Jianglin Wang
Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through three-dimensional (3D) and spatiotemporal changes in vivo. The matrix stiffness as a crucial factor during bone tissue development is dynamic stiffening. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment. Here, we create a dynamic and controllable stiffening 3D biomimetic model to regulate the osteoblastic differentiation of MSCs with a dual-functional gelatin macromer that can generate a double-network hydrogel by sequential enzymatic and light-triggered crosslinking reactions. Our findings showed that these dynamic hydrogels allowed cells to spread and volume expansion prior to secondary crosslinking and to sense high stiffness after stiffening. The MSCs in the dynamic hydrogels, especially the hydrogel stiffened at the late period, presented the significantly elevated osteogenic ECM secretion, gene expression, and YAP/TAZ nuclear localization. In vivo evaluation of animal experiments further indicated that the enhancement of dynamic stiffening on osteogenesis of MSCs substantially promoted bone remodeling. Consequently, this work reveals that the 3D dynamic stiffening microenvironment as a critical biophysical cue not only mediates the stem cell fate in vitro, but also augments bone restoration in vivo. This article is protected by copyright. All rights reserved
研究领域:
生物材料
·
组织工程
·
再生医学
·
细胞生物学
·
生物力学
✓ 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）