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
·
心血管疾病
·
药理学
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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
Biofabrication
·
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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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
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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产品关联
DOI
PubMed
高影响因子
Medical Molecular Morphology
·
2021
·Vol. 54
·期 4
·337-345
·
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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产品关联
DOI
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
·
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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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Jun Zhang,Tiantian Zuo,Jie Yang,Zongwei Hu,Zhihua Wang,Rui Xu,Siyu Ma,Yawen Wei,Qi Shen
The aggressive progression of breast cancer is impacted significantly by the tumor microenvironment (TME). The current chemotherapy normally causes cytotoxicity to tumor cells, while does not effectively modulate the TME. Thus, the chemotherapy effect of breast cancer is usually dissatisfactory. In this study, a kind of hierarchically releasing bio-responsive nanoparticles (R(D)/H(S) NPs), constructed by β-cyclodextrin-grafted heparin and pH-sensitive pseudorotaxane, were investigated to enhance the breast cancer chemotherapeutic efficacy through TME modulation. Doxorubicin (DOX) and transforming growth factor-β (TGF-β) receptor inhibitor (SB431542) loaded onto R(D)/H(S) NPs were released rapidly for the respective response to low pH in endosomes/lysosomes and heparanase (HPSE) in TME. Our results showed that R(D)/H(S) NPs effectively inhibited the formation of tumor-associated fibroblasts (TAFs) and reduced TGF-β and collagen I secretion. Besides, the immunosuppressive microenvironment was effectively reversed into immunogenic, characterized by increased CD8+ and CD4+ T cell infiltration, which distinctly inhibited breast cancer metastasis. Therefore, R(D)/H(S) NPs remodeled the TME by downregulating TAFs, TGF-β, and collagen I; activating the immune microenvironment; and then amplifying the chemotherapeutic efficacy of DOX.
研究领域:
肿瘤学
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纳米技术
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2022
·
IF 11.322
Yonghong Fan,Juan Pei,Xinxin Li,Yinhua Qin,Youqian Xu,Ming Ke,Jie Zhang,Yong Liu,Ju Tan,Mingcan Yang,Gang Li,Tianqing Li,Chuhong Zhu
Tissue-engineered vascular grafts (TEVGs) show great potential in clinics for treating vascular diseases. However, the complications including thrombosis, delayed endothelialization , and endothelial-to-mesenchymal transition (EndMT) induced pathological remodeling have been demonstrated to be the main cause of graft failure. Here, we have developed a multifunctional surface by immobilizing ALK5 inhibitor loaded covalent organic framework (COF) nanoparticles , recombinant CD47 protein, and vascular endothelial growth factor (VEGF). Such a surface can prevent thrombosis and stenosis in TEVGs. Immobilization of VEGF facilitated the recruitment of endothelial-forming cells to accelerate endothelialization. Grafting of CD47 endowed the TEVGs with stealth function to inhibit the adhesion and activation of platelets and macrophages, thereby suppressing thrombus formation and reducing the secretion of EndMT triggers (i.e. TNF-α and IL-1β). In addition, long-term in situ delivery of ALK5 inhibitor could block the TGF-β signaling pathway that mediated EndMT to prevent intima hyperplasia and endothelial dysfunction during graft remolding. This synergistic strategy is competent to support the formation of functional endothelium on the neo-intima, and has shown promising preliminary results in keeping the patency of TEVGs.
研究领域:
组织工程
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血管生物学
·
生物材料
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免疫学
·
分子生物学
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产品关联
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Yi Wang,Linhao Hou,Yiqian Huang,Pengfei Wei,Liya Sun,Yan Zhang,Xueqiao Yu,Shiqing Ma,Wei Jing,Bo Zhao,Huachong Ma
Chronic wounds in diabetes take a lifetime risk of developing into diabetic foot ulcers (DFUs). Conventional wound dressings and commercial products fail for ideal tissue regeneration in DFUs due to the incapacity to promote vascularization and prevent bacterial infections during wound repair. In this study, the small intestinal submucosa (SIS) with enriched vascularized bioactive factors, was chemically decorated by 2-methacryloyloxy ethyl phosphorylcholine (MPC) through Michael-type addition to be endowed anti-fouling ability, in order to treat chronic wound regeneration in diabetes. In the diabetic skin injury experiment, we established the animal model by 5-mm diameter defects in the SD rats and implanted the bio-patches to the located sites. The SIS-MPC bio-patch showed superior advantages in bacterial anti-adhesion (100-fold foul resistance than commercial patches), while maintained affinity for fibroblast growth and collagen formation, as demonstrated by immunohistochemical staining from the local tissues, outperforming commercial wound dressings in tissue regeneration, which was attributed to acceleration in neovascularization and inflammation modulation through TGF-β and MAPK pathway. This novel SIS-MPC bio-patch would be a promising candidate for medical translations into diabetes and chronic wound treatments.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
糖尿病研究
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产品关联
DOI
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
·
心血管疾病
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
·
2019
·Vol. 9
·期 1
·1-15
·
IF 3.355
Tan Jianxin,Wang Yajun,Wang Siliang,Wu Simeng,Yuan Zhe,Zhu Xike
Background Adipocyte accumulation is a predominant feature of age-related thymic involution, but the mechanisms responsible for thymic adipogenesis remain to be elucidated. The aim of this study was to identify key regulators in thymic adipogenesis. We used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation of OP9-DL1 cells, and investigated the differentially expressed proteins during adipogenic differentiation by using label-free quantitative proteomics. Furthermore, the effects of transforming growth factor β1 (TGF-β1) on rosiglitazone-induced adipogenic differentiation of OP9-DL1 cells as well as the underlying mechanisms were also investigated. Results Proteomic analysis identified 139 proteins differed significantly in rosiglitazone-treated cells compared with dimethyl sulphoxide (DMSO)-treated cells. Rosiglitazone-induced adipogenic differentiation was inhibited by TGF-β1 treatment in OP9-DL1 cells and primary thymic stromal cells. Real-time PCR analysis showed significant increases in PPARγ and fatty acid binding protein 4 mRNA levels in rosiglitazone-treated cells, which were inhibited by TGF-β1 treatment. TGF-β1 down-regulated PPARγ expression at both mRNA and protein levels in OP9-DL1 cells. Chromatin immunoprecipitation analysis demonstrated that TGF-β1 enhanced the binding of Smad2/3 and histone deacetylase 1, but reduced the binding of H3K14ac to the promoter of PPARγ gene. TGF-β1 partially reversed the inhibitory effects of rosiglitazone on the expression of Axin2 and β-catenin protein levels. TGF-β1 inhibited rosiglitazone-induced adipogenic transformation in OP9-DL1 cells by down-regulation of PPARγ and activation of the canonical Wnt/β-catenin signaling pathway. Conclusion Taken together, activation of TGF-β pathway may serve as a useful strategy to prevent thymic adiposity in age-related thymic involution.
研究领域:
免疫学
·
细胞生物学
·
蛋白质组学
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分子生物学
·
衰老研究
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·
IF 3.1
Sun Hui,Wang ZiTong,Tu BingHua,Shao ZiChen,Li YiDan,Han Di,Jiang YinJie,Zhang Peng,Zhang WeiChang,Wu YunYan,Wu XiaoMing,Liu Chi-Ming
Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.
研究领域:
药理学
·
内分泌学
·
糖尿病
·
前列腺健康
·
信号转导
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Liu Siqi,Guo Junfu,Cheng Xianda,Li Wenna,Lyu Shuangyu,Chen Xuanyi,Li Qingwei,Wang Hao
The transforming growth factor-βs (TGF-βs) are multifunctional cytokines capable of regulating a wide range of cellular behaviors and play a key role in maintaining the homeostasis of the immune system. The TGF-β subfamily, which is only present in deuterostomes, expands from a single gene in invertebrates to multiple members in jawed vertebrates. However, the evolutionary processes of the TGF-β subfamily in vertebrates still lack sufficient elucidation. In this study, the TGF-β homologs are identified at the genome-wide level in the reissner lamprey (Lethenteron reissneri), the sea lamprey (Petromyzon marinus), and the Japanese lamprey (Lampetra japonica), which are the extant representatives of jawless vertebrates with a history of more than 350 million years. The molecular evolutionary analyses reveal that the lamprey TGF-β subfamily contains two members representing ancestors of TGF-β2 and 3 in vertebrates, respectively, but TGF-β1 is absent. The transcriptional expression patterns show that the lamprey TGF-β2 may play a central regulatory role in the innate immune response of the lamprey since it exhibits a more rapid and significant upregulation of expression than TGF-β3 during lipopolysaccharide stimuli. The incorporation of BrdU assay reveals that the lamprey TGF-β2 recombinant protein exerts the bipolar regulation on the proliferation of the supraneural myeloid body cells (SMB cells) in the quiescent and LPS-activated state, while plays an inhibitory role in the proliferation of quiescent and activated leukocytes in lampreys. Furthermore, caspase-3/7 activity analysis indicates that the lamprey TGF-β2 protects SMB cells from apoptosis after serum deprivation, in contrast to promoting apoptosis of leukocytes. Our composite results offer valuable clues to the origin and evolution of the TGF-β subfamily and imply that TGF-βs are among the most ancestral immune regulators in vertebrates.
研究领域:
进化生物学
·
免疫学
·
分子生物学
·
基因组学
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DOI
PubMed
高影响因子
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