INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yi Lu,Yibo Shan,Jianwei Zhu,Zhiming Shen,Wenxuan Chen,Hao Chen,Hongcan Shi
Patch tracheoplasty offers an alternative approach to repairing congenital tracheal stenosis without tension but poses a higher risk of restenosis, granulation tissue formation, and tracheal collapse. The use of tissue-engineered patches for tracheoplasty has been proposed as a solution. Studies suggest that decellularization methods are effective in preparing tracheal patches; however, further research is necessary to improve their efficiency and safety. This study introduces a novel decellularization method using 3-[(3Cholamidopropyl)dimethylammonio]propanesulfonate (CHAPS) and DNase to create a biocompatible tracheal matrix. To enhance the regeneration of epithelial regions within decellularized tracheal scaffolds, this study conducted experimental validations at various levels, both in vivo and in vitro, by introducing extracellular vesicles derived from adipose mesenchymal stem cells as an intervention measure. The ability to promote epithelial regeneration was validated both in vitro and in vivo by incorporating a GelMA hydrogel loaded with adipose-derived mesenchymal stem cell extracellular vesicles (ADMSC-EVs). Evaluation of HBE cell proliferation on tracheal patches treated with varying concentrations of ADMSC-EVs, along with migration and invasion experiments on ADMSC-EV-treated HBE cells, demonstrated enhanced epithelialization in vitro. The inflammatory response and vascular regeneration were assessed via subcutaneous implantation in rats for two weeks. In a rabbit tracheal defect model, the hydrogel loaded with ADMSC-EVs accelerated re-epithelialization in the patch area. This approach shows promise as a novel material for tracheal patching in clinical applications.
研究领域:
组织工程
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再生医学
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干细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 25
·4810-4822
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IF 7.571
Boyou Zhang,Fei Sun,Yi Lu,Zhihao Wang,Zhiming Shen,Lei Yuan,Qiang Wu,Cong Wu,Hongcan Shi
Long segment trachea defects are repaired by tracheal substitution, while decellularized technology has been effectively employed to prepare tissue engineering trachea (TET). However, its clinical application is restricted by the long preparation cycle, while poor vascularization is associated with the transplantation failure. In the present study, we used sodium lauryl ether sulfate (SLES) to develop a novel rapid decellularized tracheal preparation method, then constructed a TET with revascularization functions. Summarily, we decellularized rabbit trachea using various SLES concentrations. Results from histological analysis, immunohistochemical and DAPI staining, as well as DNA quantitative assay, revealed that 1–0.1% (v/v) SLES treatment not only entirely removed cellular components to reduce its immunogenicity, but also retained the tracheal matrix's gross structure. SEM images, safranine O-fast green staining, total collagen content assay and collagen II immunofluorescence revealed that low SLES concentrations preserved the bioactive components of the decellularized tracheal matrix. Next, we performed cytobiocompatible and cytotoxin assays to verify biocompatibility of the decellularized tracheal matrix, and is confirmed by the omentum transplantation of rats. Results from omentum transplantation revealed that the decellularized tracheal matrix had low immunogenicity and excellent biocompatibility. Its revascularization capacity was confirmed by histologic appearance and CD31 immunofluorescence. Based on these findings, we selected 0.1% (v/v) as the optimal SLES concentration for preparing a decellularized tracheal matrix. Next, we seeded allogeneic bone marrow stem cells (BMSC) onto the matrix to construct TET patches. In vivo tracheal defect reconstruction confirmed the biocompatibility and revascularization capacity of this novel TET, and the formation of a vascular network around the patch promoted submucosa and mucosa regeneration without significant stenosis, 4 weeks post-surgery. In conclusion, we used SLES to successfully develop a novel decellularized approach for the preparation of TET, which has low immunogenic and inflammatory responses, as well as excellent biocompatibility, and revascularization ability in vivo without additional exogenous cytokines.
研究领域:
组织工程
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再生医学
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生物医学工程
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移植学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-19
·
IF 12.6
Shen Zhiming,Shan Yibo,Lu Yi,Zhu Jianwei,Yuan Lei,Chen Wenxuan,Sun Fei,Wang Qi,Wang Yilun,Zhang Yaojing,Xu Xiangyu,Chen Yu,Ge Wei,Chen Wei,Si Panpan,Zhang Renquan,Shi Hongcan
Tracheal reconstruction presents a significant global clinical challenge due to the unique structure and function of the trachea, which complicates its repair. Key challenges include restoring tracheal function post-transplantation, managing surgical complications, and ensuring the long-term survival of transplanted tissue. Furthermore, adequate vascularization of the transplanted trachea, along with the repair of cartilage and epithelial cells, is critical for facilitating functional recovery and successful reconstruction. In this study, a decellularized tracheal matrix was extracted to preserve its natural bioactivity. Nanoclay and GelMA were then employed as carrier materials to integrate with the decellularized tracheal matrix, forming a hydrogel scaffold. Both nanoclay and GelMA offer tunable porous structures and surface properties that promote cell adhesion and proliferation, while providing sufficient mechanical support. By leveraging the biological functions of endothelial progenitor cell-derived exosomes, we successfully loaded exosomes onto the decellularized extracellular matrix, creating a novel cell-free tracheal scaffold for investigating tracheal defect repair. The scaffold exhibited excellent biocompatibility, promoting graft vascularization and facilitating the repair of tracheal cartilage and epithelium. These findings hold significant promise for advancing tracheal reconstruction surgery and offer valuable insights for future research in this area. Graphical abstract
研究领域:
组织工程
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再生医学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOSCIENCES
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2021
·Vol. 46
·期 1
·1-12
·
IF 1.826
Yang Mingzhu,Wang Li
Asthma has significant impacts on living quality particularly in children. Long noncoding RNA (lncRNA) MALAT1 plays a crucial role in neonatal respiratory diseases. Meanwhile, MALAT1 knockdown could induce viability and attenuate apoptosis of airway-related cells. However, the role of MALAT1 in neonatal asthma, asthma-related cell, and its possible mechanism is unclear. This study aims to investigate MALAT1 level in asthma and to identify the effects of MALAT1 on bronchial/tracheal smooth muscle cells (B/TSMCs). Newborn asthma modeling rat was constructed by introducing ovalbumin (OVA). MALAT1 levels in tissues or B/TSMCs were determined by RT-qPCR. Exogenous changes of MALAT1, RyR2 or miR-133a in B/TSMCs were fulfilled by cell transfection; cell apoptosis was measured by using Cell Death Detection ELISA kit and Hochest33342; IL-6, TNF-α and IL-1β level was detected by using corresponding ELISA kit; ryanodine receptor 2 (RyR2) mRNA and miR-133a level was determined by RT-qPCR; cleaved caspase-3 (c-caspase-3) and RyR2 expression was detected by Western blot; luciferase reporter assay was performed to confirm the target regulation of miR-133a on RyR2. We found that MALAT1 was significantly upregulated in tracheal tissues of newborn asthma modeling rats. In MALAT1-silenced or -overexpressed B/TSMCs, we found a synchronous change of cell apoptosis, inflammatory factor secretion (IL-6, TNF-α, and IL-1β) or RyR2 level, but a reverse change of miR-133a level with MALAT1. Besides, MALAT1 induced B/TSMCs apoptosis and inflammation increase could be partially reversed when RyR2 was silenced or when miR-133a was overexpressed. The luciferase reporter assay confirmed that RyR2 is a direct target gene of miR-133a in B/TSMCs. Finally, we conclude that MALAT1 knockdown could protect from B/TSMCs injury via regulating miR-133a/RyR2 axis.
研究领域:
呼吸医学
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分子生物学
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细胞生物学
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产品关联
DOI
高影响因子
Scientific Reports
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2016
·Vol. 6
·期 1
·1-12
·
IF 5.228
Sun Fei,Jiang Yuan,Xu Yanfei,Shi Hongcan,Zhang Siquan,Liu Xingchen,Pan Shu,Ye Gang,Zhang Weidong,Zhang Fangbiao,Zhong Chonghao
Decellularization techniques have been widely used as an alternative strategy for organ reconstruction. This study investigated the mechanical, pro-angiogenic and in vivo biocompatibility properties of decellularized airway matrices cross-linked with genipin. New Zealand rabbit tracheae were decellularized and cross-linked with genipin, a naturally derived agent. The results demonstrated that, a significant (p < 0.05) increase in the secant modulus was computed for the cross-linked tracheae, compared to the decellularized samples. Angiogenic assays demonstrated that decellularized tracheal scaffolds and cross-linked tracheae treated with 1% genipin induce strong in vivo angiogenic responses (CAM analysis). Seven, 15 and 30 days after implantation, decreased (p < 0.01) inflammatory reactions were observed in the xenograft models for the genipin cross-linked tracheae matrices compared with control tracheae and no increase in the IgM or IgG content was observed in rats. In conclusion, treatment with genipin improves the mechanical properties of decellularized airway matrices without altering the pro-angiogenic properties or eliciting an in vivo inflammatory response.
研究领域:
组织工程
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生物材料
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
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2019
·Vol. 20
·期 2
·1-11
·
IF 2.608
Liu Chunxia,Lin Ling,Huang Zhengwei,Wu Qiaoli,Jiang Junhuang,Lv Li,Yu Xiaoxia,Quan Guilan,Li Guocheng,Wu Chuanbin
Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease associated with the high morbidity and mortality. Long-term intermittent therapy by inhalable antibiotics has recently emerged as an effective approach for NCFB treatment. However, the effective delivery of antibiotics to the lung requires administering a high dose to the site of infection. Herein, we investigated the novel inhalable silk-based microparticles as a promising approach to deliver high-payload ciprofloxacin (CIP) for NCFB therapy. Silk fibroin (SF) was applied to improve drug-payload and deposit efficiency of the dry powder particles. Mannitol was added as a mucokinetic agent. The dry powder inhaler (DPI) formulations of CIP microparticles were evaluated in vitro in terms of the aerodynamic performance, particle size distribution, drug loading, morphology, and their solid state. The optimal formulation (highest drug loading, 80%) exhibited superior aerosolization performance in terms of fine particle fraction (45.04 ± 0.84%), emitted dose (98.10 ± 1.27%), mass median aerodynamic diameter (3.75 ± 0.03 μm), and geometric standard deviation (1.66 ± 0.10). The improved drug loading was due to the electrostatic interactions between the SF and CIP by adsorption, and the superior aerosolization efficiency would be largely attributed to the fluffy and porous cotton-like property and low-density structure of SF. The presented results indicated the novel inhalable silk-based DPI microparticles of CIP could provide a promising strategy for the treatment of NCFB.
研究领域:
药学
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呼吸医学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Zhiming Shen,Fei Sun,Yibo Shan,Yi Lu,Cong Wu,Boyou Zhang,Qiang Wu,Lei Yuan,Jianwei Zhu,Qi Wang,Yilun Wang,Wenxuan Chen,Yaojing Zhang,Wenlong Yang,Yiwei Fan,Hongcan Shi
Functional vascularization is crucial for maintaining the long-term patency of tissue-engineered trachea and repairing defective trachea. Herein, we report the construction and evaluation of a novel cell-free tissue-engineered tracheal scaffold that effectively promotes vascularization of the graft. Our findings demonstrated that exosomes derived from endothelial progenitor cells (EPC-Exos) enhance the proliferation, migration, and tube formation of endothelial cells. Taking advantage of the angiogenic properties of EPC-Exos, we utilized methacrylate gelatin (GelMA) as a carrier for endothelial progenitor cell exosomes and encapsulated them within a 3D-printed polycaprolactone (PCL) scaffold to fabricate a composite tracheal scaffold. The results demonstrated the excellent angiogenic potential of the methacrylate gelatin/vascular endothelial progenitor cell exosome/polycaprolactone tracheal scaffold. Furthermore, in vivo reconstruction of tracheal defects revealed the capacity of this composite tracheal stent to remodel vasculature. In conclusion, we have successfully developed a novel tracheal stent composed of methacrylate gelatin/vascular endothelial progenitor exosome/polycaprolactone, which effectively promotes angiogenesis for tracheal repair, thereby offering significant prospects for clinical and translational medicine.
研究领域:
组织工程
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生物医学工程
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再生医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2021
·
IF 5.165
Hong-Xia Song,Ting Lei,Fang Wu,Xiaoyu He,Jiang Wang
This article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). This article has been retracted at the request of the Editor-in-Chief. In investigating concerns brought up regarding the authenticity of the article, the editors reached out to the corresponding author for an explanation. The authors failed to reply. The editors therefore feel that the findings of the manuscript cannot be relied upon and that the article needs to be retracted.
研究领域:
配位化学
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医学应用
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材料科学
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DOI
高影响因子
Advanced Science
·
2021
·Vol. 9
·期 3
·2102460
·
IF 16.806
Rui Zheng,Mulong Du,Man Tian,Zhaozhong Zhu,Chengcheng Wei,Haiyan Chu,Cong Gan,Jiayuan Liang,Renjie Xue,Fang Gao,Zhenguang Mao,Meilin Wang,Zhengdong Zhang
Fine particulate matter less than 2.5 µm in diameter (PM 2.5 ) is a major risk factor for acute asthma attacks in children. However, the biological mechanism underlying this association remains unclear. In the present study, PM 2.5 -treated HBE cells-secreted extracellular vesicles (PM 2.5 -EVs) caused cytotoxicity in “horizontal” HBE cells and increased the contractility of “longitudinal” sensitive human bronchial smooth muscle cells (HBSMCs). RNA sequencing showed that let-7i-5p is significantly overexpressed in PM 2.5 -EVs and asthmatic plasma; additionally, its level is correlated with PM 2.5 exposure in children with asthma. The combination of EV-packaged let-7i-5p and the traditional clinical biomarker IgE exhibits the best diagnostic performance (area under the curve [AUC] = 0.855, 95% CI = 0.786–0.923). Mechanistically, let-7i-5p is packaged into PM 2.5 -EVs by interacting with ELAVL1 and internalized by both “horizontal” recipient HBE cells and “longitudinal” recipient-sensitive HBSMCs, with subsequent activation of the MAPK signaling pathway via suppression of its target DUSP1 . Furthermore, an injection of EV-packaged let-7i-5p into PM 2.5 -treated juvenile mice aggravated asthma symptoms. This comprehensive study deciphered the remodeling of the extracellular environment mediated by the secretion of let-7i-5p-enriched EVs during PM 2.5 -induced asthma attacks and identified plasma EV-packaged let-7i-5p as a novel predictor of childhood asthma.
研究领域:
环境健康
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分子生物学
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呼吸医学
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细胞生物学
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临床诊断
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产品关联
DOI
PubMed
高影响因子
AVIAN DISEASES
·
2025
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IF 1.3
Du Xiaowen,Zeng Mengting,Yang Wenzhuo,Jiang Yuting,Huang Guangyu,Ding Shiping,Jiang Danli,Yuan Zhaoxia
For decades, infectious bronchitis (IB), caused by the infectious bronchitis virus (IBV), has posed a significant threat to poultry health and is mainly controlled by vaccines. However, the currently available commercial vaccines do not provide adequate protection against new IBV strains that emerge due to ongoing evolution. Therefore, new antiviral strategies need to be explored. Cepharanthine (CEP), tetrandrine (TET), and berbamine hydrochloride (BBM) are natural plant-derived bis-benzylisoquinoline alkaloids (BBAs) with proven antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), porcine epidemic diarrhea virus (PEDV), and other viruses. Despite this, their potential antiviral activities against IBV remain unknown. As a proof-of-concept study, we aimed to investigate the inhibitory effects of CEP, TET, and BBM on the laboratory-adapted IBV Beaudette strain in Vero cells and of CEP in chicken embryos. Our research demonstrated that CEP, TET, and BBM effectively suppressed IBV infection in Vero cells, with CEP showing a particularly high selective index of 309.6. These compounds dose-dependently decreased IBV RNA levels and N protein expression and lowered intracellular and extracellular viral titers. Notably, CEP also exhibited antiviral activity against IBV infection in chicken embryos, resulting in reduced mortality and fewer lesions. While these findings highlight the potential of CEP, TET, and BBM as candidates for further development, further studies are required to evaluate their efficacy against field-prevalent IBV strains (e.g., Massachusetts, QX-like) and clarify the specific antiviral mechanisms.
研究领域:
病毒学
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药物开发
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兽医学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Huimei Zhao,Haiyan Zhang,Jianyu Shi,Yanru Liu,Jingao Yu,Yuangui Yang,Jingyu Weng,Zhongxing Song,Rui Zhou,Hong Min,Jian Yao,Mei Wang,Zhen Zhang
Ethnopharmacological relevance Asthma is a chronic inflammatory airway disease. Current treatments have limited efficacy and often cause severe side effects. Wuwei Shaji Powder (WSP), a traditional Mongolian remedy, is used for treating chronic pulmonary diseases, but its efficacy against asthma and underlying mechanisms are still unclear. Aim of the study To investigate the therapeutic effect of WSP on asthma and elucidate its molecular mechanisms. Materials and methods An ovalbumin (OVA)-induced allergic asthma model was established in rats. Ferroptosis or apoptosis was induced in BEAS-2B cells using Erastin or CdCl 2 . Various techniques including histopathological staining, ELISA, Western blot, flow cytometry, and transmission electron microscopy were employed to assess WSP's effects and mechanisms. Results WSP alleviated OVA-induced allergic asthma in rats without the immunosuppressive side effects observed with dexamethasone. WSP suppressed ferroptosis in bronchial epithelial cells both in vivo and in vitro. It reduced thiol- and sulfonic-based oxidative stress through Keap1 S-sulfhydration, disrupted the Keap1-Nrf2 interaction, and promoted Nrf2 nuclear translocation. Notably, we discovered that CdCl 2 can induce ferroptosis in BEAS-2B cells, and WSP prevented both ferroptosis and apoptosis in these cells. Conclusion WSP alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via S-sulfhydration of Keap1, providing new insights for its clinical application.
研究领域:
民族药理学
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呼吸系统疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2024
·
IF 12.4
Kai Ni,Bo Che,Rong Gu,Chunhong Wang,Hongyang Xu,Huiduo Li,Shiyan Cen,Mingzhi Luo,Linhong Deng
Rationale: Bitter taste receptors (TAS2Rs) are abundantly expressed in airway smooth muscle cells (ASMCs), which have been recognized as promising targets for bitter agonists to initiate relaxation and thereby prevent excessive airway constriction as the main characteristic of asthma. However, due to the current lack of tested safe and potent agonists functioning at low effective concentrations, there has been no clinically approved TAS2R-based drug for bronchodilation in asthma therapy. This study thus aimed at exploring TAS2R agonists with bronchodilator potential by BitterDB database analysis and cell stiffness screening. Methods: Bitter compounds in the BitterDB database were retrieved and analyzed for their working subtype of TAS2R and effective concentration. Compounds activating TAS2R5, 10, and 14 at < 100 μM effective concentration were identified and subsequently screened by cell stiffness assay using optical magnetic twisting cytometry (OMTC) to identify the most potent to relax ASMCs. Then the compound identified was further characterized for efficacy on various aspects related to relaxation of ASMCs, incl. but not limited to traction force by Fourier transform traction force microscopy (FTTFM), [Ca 2+ ] i signaling by Fluo-4/AM intensity, cell migration by scratch wound healing, mRNA expression by qPCR, and protein expressing by ELISA. The compound identified was also compared to conventional β-agonist (isoproterenol and salbutamol) for efficacy in reducing cell stiffness of cultured ASMCs and airway resistance of ovalbumin-treated mice. Results: BitterDB analysis found 18 compounds activating TAS2R5, 10, and 14 at < 100 μM effective concentration. Cell stiffness screening of these compounds eventually identified flufenamic acid (FFA) as the most potent compound to rapidly reduce cell stiffness at 1 μM. The efficacy of FFA to relax ASMCs in vitro and abrogate airway resistance in vivo was equivalent to that of conventional β-agonists. The FFA-induced effect on ASMCs was mediated by TAS2R14 activation, endoplasmic reticulum Ca 2+ release, and large-conductance Ca 2+ -activated K + (BK Ca ) channel opening. FFA also attenuated lipopolysaccharide-induced inflammatory response in cultured ASMCs. Conclusions: FFA as a potent TAS2R14 agonist to relax ASMCs while suppressing cytokine release might be a favorite drug agent for further development of TAS2R-based novel dual functional medication for bronchodilation and anti-inflammation in asthma therapy.
研究领域:
药理学
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呼吸病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）