International Wound Journal
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2022
·Vol. 19
·期 5
·1023-1038
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IF 3.099
Dong Zheng,Tong Chen,Long Han,Songwei Lv,Jianjian Yin,Kaiyuan Yang,Yuji Wang,Nanwei Xu
The cartilage repair and regeneration show inadequate self-healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell-carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell-based cartilage-regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal-sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell-based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF-β1 and efficiently regulate cartilage-specific and inflammatory-related gene expressions. Finally, the cartilage-regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF-β1-SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration.
研究领域:
生物材料学
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再生医学
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组织工程学
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PubMed
高影响因子
TOXICOLOGY LETTERS
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2022
·
IF 4.271
Shuhong Guan,Hui Liu,Jun Zhou,Qiudi Zhang,Hui Bi
Transforming growth factor (TGF)-β1-induced fibrotic changes in alveolar epithelium is a critical event in pulmonary fibrosis . Herein, we recognized that lncRNA mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) was abnormally upregulated within human idiopathic pulmonary fibrosis (IPF) lung tissue, bleomycin (BLM)-caused pulmonary fibrotic model mice and TGF-β1-stimulated mice type II alveolar epithelial cells. In vivo , MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro , MIR100HG knockdown attenuated TGF-β1-induced fibrotic changes in mice type II alveolar epithelial cells. Through direct binding, MIR100HG knockdown upregulated microRNA-29a-3p (miR-29a-3p) expression; through serving as competing endogenous RNA for miR-29a-3p, MIR100HG knockdown downregulated TGF-beta activated kinase 1/MAP3K7 binding protein 1 (Tab1) expression. Finally, under TGF-β1 stimulation, Tab1 knockdown attenuated TGF-β1-induced fibrotic changes and partially attenuated the effects of miR-29a-3p inhibition. In conclusion, we demonstrated the aberrant upregulation of lncRNA MIR100HG in BLM-caused lung fibrogenesis and TGF-β1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-β1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy.
研究领域:
肺科学
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分子生物学
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细胞生物学
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药理学
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PubMed
高影响因子
NEUROREPORT
·
2024
·
IF 1.6
Guo Jianlian,Xu Yong,Liu Jie,Hou Xueqi
This project is conceived to reveal the role of lidocaine in the process of Alzheimer’s disease (AD) and its possible downstream targets. After the employment of AD cell model in mice hippocampal neuronal HT-22 cells in the presence of amyloid-β1-42 (Aβ1-42), Cell Counting Kit-8 method investigated cell viability. Oxidative damage was assayed based on a dichloro-dihydro-fluorescein diacetate fluorescent probe and commercially available kits. The 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide fluorescent probe estimated mitochondrial function. Terminal-deoxynucleotidyl transferase mediated nick end labeling, western blotting, and immunofluorescence appraised the apoptotic level. Western blot also ascertained the alternations of nerve growth factors (NGF)-protein kinase B (Akt) pathway-related proteins. Aβ1-42 concentration dependently triggered the viability loss, oxidative damage, and apoptosis in HT-22 cells. Lidocaine promoted the viability and reduced the mitochondrial impairment and mitochondria-dependent apoptosis in Aβ1-42-treated HT-22 cells in a concentration-dependent manner. Besides, lidocaine activated the NGF-Akt pathway and NGF absence blocked NGF-Akt pathway, aggravated mitochondrial dysfunction as well as mitochondria-dependent apoptosis in lidocaine-administrated HT-22 cells in response to Aβ1-42. Altogether, these observations concluded that lidocaine might stimulate NGF-Akt pathway to confer protection against mitochondrial impairment and apoptosis in Aβ1-42-mediated cellular model of AD.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Ruxia Liu,Ting Zhou,Xinsheng Li,Quan Zou,Jiaojiao Yu,Jingjing Ye,Wenhui Wang,Yan Zhou,Shao-Kai Sun
Pulmonary hypertension (PH) is a life-threatening cardiovascular disease with a lack of effective treatment options. Nanozymes, though promising for PH therapy, pose safety risks due to their metallic nature. Here, a non-metallic nanozyme is reported for the treatment of monocrotaline (MCT)-induced PH with a therapeutic mechanism involving the ROS/TGF-β1 signaling. The synthesized melanin-polyvinylpyrrolidone-polyethylene glycol (MPP) nanoparticles showcase ultra-small size, excellent water solubility, high biocompatibility, and remarkable antioxidant capacity. The MPP nanoparticles are capable of effectively eliminating ROS in isolated pulmonary artery smooth muscle cells (PASMCs) from PH rats, and significantly reduce PASMC proliferation and migration. In vivo results from a PH model demonstrate that MPP nanoparticles significantly increase pulmonary artery acceleration time, decrease wall thickening and PCNA expression in lung tissues, as evidenced by echocardiograpy, histology and immunoblot analysis. Additionally, MPP nanoparticles treatment improve running capacity, decrease Fulton index, and attenuate right ventricular fibrosis in MCT-PH rats by using treadmill test, picrosirius red, and trichrome Masson staining. Further transcriptomic and biochemical analyses reveal that inhibiting ROS-driven activation of TGF-β1 in the PA is the mechanism by which MPP nanoparticles exert their therapeutic effect. This study provides a novel approach for treating PH with non-metallic nanozymes based on a well-understood mechanism.
研究领域:
纳米技术
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心血管疾病
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药理学
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生物医学工程
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DOI
PubMed
高影响因子
Biofabrication
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2020
·Vol. 12
·期 2
·025030
·
IF 8.213
Chong Wang,Haibing Yue,Wei Huang,Xudong Lin,Xiaoqiong Xie,Zhi He,Xiao He,Sanbiao Liu,Lu Bai,Bingheng Lu,Yen Wei,Min Wang
Due to the increasing aging population and the high probability of sport injury among young people nowadays, it is of great demand to repair/regenerate diseased/defected osteochondral tissue. Given that osteochondral tissue mainly consists of a subchondral layer and a cartilage layer which are structurally heterogeneous and mechanically distinct, developing a biomimetic bi-phasic scaffold with excellent bonding strength to regenerate osteochondral tissue is highly desirable. Three-dimensional (3D) printing is advantageous in producing scaffolds with customized shape, designed structure/composition gradients and hence can be used to produce heterogeneous scaffolds for osteochondral tissue regeneration. In this study, bi-layered osteochondral scaffolds were developed through cryogenic 3D printing, in which osteogenic peptide/β-tricalcium phosphate/poly(lactic-co-glycolic acid) water-in-oil composite emulsions were printed into hierarchically porous subchondral layer while poly(D,L-lactic acid-co-trimethylene carbonate) water-in-oil emulsions were printed into thermal-responsive cartilage frame on top of the subchondral layer. The cartilage frame was further filled/dispensed with transforming growth factor-β1 loaded collagen I hydrogel to form the cartilage module. Although the continuously constructed osteochondral scaffolds had distinct microscopic morphologies and varied mechanical properties at the subchondral zone and cartilage zone at 37 °C, respectively, the two layers were closely bonded together, showing excellent shear strength and peeling strength. Rat bone marrow derived mesenchymal stem cells (rBMSCs) exhibited high viability and proliferation at both subchondral- and cartilage layer. Moreover, gradient rBMSC osteogenic/chondrogenic differentiation was obtained in the osteochondral scaffolds. This proof-of-concept study provides a facile way to produce integrated osteochondral scaffolds for concurrently directing rBMSC osteogenic/chondrogenic differentiation at different regions.
研究领域:
生物医学工程
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组织工程
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再生医学
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生物材料
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
·
IF 5.8
Li Shen,Shiyan Fu,Yonglai Chen,Wenrun Li,Suiyi Liu,Zhi Li,Jie Li,Yong Li,Yonghong Ran,Jing Zhang,Lu Qiao,Yuhui Hao
Radiation-induced pulmonary fibrosis (RIPF), one type of pulmonary interstitial diseases, is frequently observed following radiation therapy for chest cancer or accidental radiation exposure. Current treatments against RIPF frequently fail to target lung effectively and the inhalation therapy is hard to penetrate airway mucus. Therefore, this study synthesized mannosylated polydopamine nanoparticles (MPDA NPs) through one-pot method to treat RIPF. Mannose was devised to target M2 macrophages in the lung through CD 206 receptor. MPDA NPs showed higher efficiency of penetrating mucus, cellular uptake and ROS-scavenging than original polydopamine nanoparticles (PDA NPs) in vitro. In RIPF mice, aerosol administration of MPDA NPs significantly alleviated the inflammatory , collagen deposition and fibrosis. The western blot analysis demonstrated that MPDA NPs inhibited TGF-β1/Smad3 signaling pathway against pulmonary fibrosis. Taken together this study provide a novel M2 macrophages-targeting nanodrugs through aerosol delivery for the prevention and targeted treatment for RIPF.
研究领域:
药理学
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纳米技术
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肺科学
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放射生物学
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治疗学
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DOI
PubMed
高影响因子
Medical Molecular Morphology
·
2021
·Vol. 54
·期 4
·337-345
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IF 2.309
Xu Sijia,Dong Wenxin,Shi Yu
The purpose of this study is to explore whether LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, influencing the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation. PICSAR and miR-485-5p expressions were detected by qPCR. Cell proliferation was examined by CCK-8. Protein expressions were determined by western blot. Immunofluorescence detected the Ki-67 expression. Dual-luciferase followed by immunoprecipitation was performed to verify the interaction between PICSAR and miR-485-5p. Interference with PICSAR inhibited the abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and the excessive deposition of ECM. It was also confirmed in our study that MiR-485-5p is a direct target of PICSAR in HSFs. Additionally, inhibition of miR-485-5p reversed the effect of PICSAR knockdown in HSFs. LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, promoting the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation.
研究领域:
分子生物学
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细胞生物学
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伤口愈合
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 7
·6172
·
IF 5.6
Tianxiao Sun,Haihua Li,Yan Zhang,Guixin Xiong,Yuerun Liang,Fang Lu,Rong Zheng,Qi Zou,Jiejie Hao
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by lung inflammation and excessive deposition of extracellular matrix components. Transforming growth factor-β1 (TGF-β1) induced epithelial–mesenchymal transformation of type 2 lung epithelial cells leads to excessive extracellular matrix deposition, which plays an important role in fibrosis. Our objective was to evaluate the effects of 3-cyclopropylmethoxy-4-(difluoromethoxy) benzoic acid (DGM) on pulmonary fibrosis and aimed to determine whether EMT plays a key role in the pathogenesis of pulmonary fibrosis and whether EMT can be used as a therapeutic target for DGM therapy to reduce IPF. Firstly, stimulation of in vitro cultured A549 cells to construct EMTs with TGF-β1. DGM treatment inhibited the expression of proteins such as α-SMA, vimentin, and collagen Ⅰ and increased the expression of E-cadherin. Accordingly, Smad2/3 phosphorylation levels were significantly reduced by DGM treatment. Secondly, models of tracheal instillation of bleomycin and DGM were used to treat rats to demonstrate their therapeutic effects, such as improving lung function, reducing lung inflammation and fibrosis, reducing collagen deposition, and reducing the expression of E-cadherin. In conclusion, DGM attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats.Keywords:IPF;A549;EMT;TGF-β1/Smad;ECM
研究领域:
药理学
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呼吸医学
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细胞生物学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 4
·2155-2162
·
IF 2.784
Tao Song,Jingdong Zhao,Tongbai Jiang,Xing Jin,Yubin Li,Xinrong Liu
The present study investigated the effects of formononetin (FMN) against balloon injury‑induced neointima formation in vivo and platelet‑derived growth factor (PDGF)‑BB‑induced proliferation and migration of vascular smooth muscle cells (VSMCs) in vitro, and explored the underlying mechanisms. A rat model of carotid artery injury was established, in order to examine the effects of FMN on balloon injury‑induced neointima formation. Histological observation of the carotid artery tissues was conducted by hematoxylin and eosin staining. VSMC proliferation during neointima formation was observed by proliferating cell nuclear antigen staining. Subsequently, rat aortic VSMCs were isolated, and the effects of FMN on PDGF‑BB‑induced VSMC proliferation and migration were determined using Cell Counting Kit‑8 and Transwell/wound healing assays, respectively. Immunohistochemical and immunocytochemical staining was applied to measure the expression of transforming growth factor (TGF)‑β in carotid artery tissues and VSMCs, respectively. SMAD family member 3 (Smad3)/phosphorylated (p)‑Smad3 expression was examined by western blotting. FMN treatment significantly inhibited the abnormal proliferation of smooth muscle cells in neointima, and alterations to the vascular structure were attenuated. In addition, pretreatment with FMN effectively inhibited the proliferation of PDGF‑BB‑stimulated VSMCs (P<0.05). FMN also reduced the number of cells that migrated to the lower surface of the Transwell chamber and decreased wound‑healing percentage (P<0.05). The expression levels of TGF‑β were decreased by FMN treatment in vivo and in vitro, and Smad3/p‑Smad3 expression was also markedly inhibited. In conclusion, FMN significantly protected against balloon injury‑induced neointima formation in the carotid artery of a rat model; this effect may be associated with the regulation of VSMC proliferation and migration through altered TGF‑β1/Smad3 signaling.
研究领域:
药理学
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心血管疾病
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2018
·Vol. 17
·期 1
·251-259
·
IF 1.41
Meng Wang,Hui Li,Yaxin Zhao,Chuanfeng Lv,Guanghua Zhou
Rhynchophylline (Rhy) is a major active component of Uncaria rhynchophylla and exhibits the potential to inhibit the proliferation of airway smooth muscle cells (ASMCs). In the current study, it was hypothesized that Rhy serves a key role in the anti‑asthma effect of Uncaria rhynchophylla by inhibiting transforming growth factor‑β1 (TGF‑β1)‑mediated activation of Smad and mitogen‑activated protein kinase (MAPK) signaling. Allergic asthma was induced in mice using ovalbumin (OVA), and the effect of Rhy treatment on inflammatory and allergic responses in the bronchoalveolar lavage fluid (BALF) and serum of mice was determined. Subsequently, the changes in TGF‑β1‑induced Smad and MAPK signaling following Rhy administration were detected to determine the mechanism associated with this treatment. In addition, TGF‑β1 was employed to induce hyperplasia of ASMCs, and the effect of Rhy on proliferation of ASMCs, and Smad and MAPK signaling in vitro was also assessed. The administration of Rhy attenuated the recruitment of eosinophils in BALF induced by OVA, which was associated with the suppressed production of immunoglobulin E, interleukin (IL)‑13, IL‑4 and IL‑5. At the molecular level, the administration of Rhy suppressed the expression levels of TGF‑β1, Smad4, p‑Smad2 and p‑Smad3, while it induced the expression of Smad7, indicating the inhibitory effect of Rhy on TGF‑β1‑mediated Smad and MAPK signaling. Furthermore, Rhy inhibited the proliferation of ASMCs and, similar to the results of the in vivo assay, it blocked the pro‑hyperplasia signaling transduction in vitro. In conclusion, the current study demonstrated the anti‑asthma effect of Rhy, which depended on the inhibition of TGF‑β1‑mediated Smad and MAPK signaling.
研究领域:
药理学
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免疫学
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呼吸医学
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细胞生物学
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DOI
PubMed
高影响因子
Nature Communications
·
2026
·
IF 18.1
Wu Fan,An Yanxin,Zhao Yuqing,Yu Jiazhi,Wu Gaoyi,Tay Franklin R.,Jiao Yang,Wang Jing
Reconstruction of large segmental bone defects remains challenging because current grafting strategies often fail to coordinate angiogenesis, neurogenesis, and osteogenesis. Here we developed a functional scaffold (peptide/Talin1 plasmid/PLA–HA/GelMA, PTPG) capable of simultaneously delivering peptides and Talin1 plasmids. We hypothesized that this scaffold enables neurovascularized bone regeneration through bidirectional activation of integrin β1 (ITGB1). The REDV–IKVAV (Arg-Glu-Asp-Val-Gly-Gly-Gly-Ile-Lys-Val-Ala-Val) peptide triggers “outside-in” ITGB1 signaling in endothelial and Schwann cells, while Talin1 plasmid-mediated “inside-out” activation. This PTPG scaffold synergistically enhances cell proliferation, migration and secretion, which are eliminated by ITGB1 silencing. In vivo, PTPG scaffold promotes aligned neurovascular networks guiding bone deposition. Single-cell RNA sequencing demonstrates enrichment of endothelial H-type signatures and repair-associated Schwann cell phenotypes, with activation of ITGB1–focal adhesion kinase–paxillin signaling. Collectively, this scaffold integrates structural support with peptide and genetic cues to promote coordinated angiogenesis, neurogenesis, and osteogenesis, offering a promising strategy for functional bone regeneration.
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Huan Chen,Jin Liu,Jia Zhang,Yuqian Chen,Yan Wang,Yuanjie Qiu,Huizhong Hu,Limin Chai,Qianqian Zhang,Qingting Wang,Manxiang Li
Bromodomain-containing protein 4 (BRD4) is recognized as a member of the bromodomain and extraterminal (BET) family that is involved in the airway inflammation and airway remodeling of asthma. However, the underlying mechanisms of BRD4 in airway smooth muscle cells (ASMCs) proliferation and airway remodeling remain unclear. Primary cultured rat ASMCs and ovalbumin (OVA)-induced rat asthma models were applied to address these issues in the present study. We showed that transforming growth factor β1 (TGF-β1) increased the protein expression of ubiquitin specific peptidase 22 (USP22), which deubiquitinated BRD4 therefore increased its expression, and then resulted in the upregulation of glioma-associated oncogene homolog 1 (GLI1) and osteopontin (OPN) leading to ASMCs proliferation. We further confirmed that induction of TGF-β1 sequentially upregulated USP22, BRD4, GLI1 and OPN leading to airway remodeling in OVA-induced rat asthma models, targeting TGF-β1/USP22/BRD4/GLI1/OPN pathway axis effectively attenuated airway remodeling and asthma development. Our study provides novel sights to understand the role of TGF-β1/USP22/BRD4/GLI1/OPN axis in airway remodeling, and targeting this pathway might have potential value for the prevention and treatment of asthma.
研究领域:
医学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）