Bioactive Materials
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2022
·
IF 16.874
Qiang Wei,Dachuan Liu,Genglei Chu,Qifan Yu,Zhao Liu,Jiaying Li,Qingchen Meng,Weishan Wang,Fengxuan Han,Bin Li
Annulus fibrosus (AF) repair remains a challenge because of its limited self-healing ability. Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair. Although the unique and beneficial characteristics of decellularized extracellular matrix (ECM) in tissue repair have been demonstrated, the poor mechanical property of ECM hydrogels largely hinders their applications in tissue regeneration. In the present study, we combined polyethylene glycol diacrylate (PEGDA) and decellularized annulus fibrosus matrix (DAFM) to develop an injectable, photocurable hydrogel for AF repair. We found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous structure. Transforming growth factor-β1 (TGF-β1) was further incorporated into PEGDA/DAFM hydrogels, and it could be continuously released from the hydrogel. The in vitro experiments showed that TGF-β1 facilitated the migration of AF cells. Furthermore, PEGDA/DAFM/TGF-β1 hydrogels supported the adhesion, proliferation, and increased ECM production of AF cells. In vivo repair performance of the hydrogels was assessed using a rat AF defect model. The results showed that the implantation of PEGDA/DAFM/TGF-β1 hydrogels effectively sealed the AF defect, prevented nucleus pulposus atrophy, retained disc height, and partially restored the biomechanical properties of disc. In addition, the implanted hydrogel was infiltrated by cells resembling AF cells and well integrated with adjacent AF tissue. In summary, findings from this study indicate that TGF-β1-supplemented DAFM hydrogels hold promise for AF repair.
研究领域:
生物医学工程
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组织工程
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骨科
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2022
·
IF 6.064
Gao Haijun,Huo Lele,Mo Xiaojin,Jiang Bin,Luo Yanping,Xu Bin,Li Jingzhong,Ma Xingming,Jing Tao,Feng Zheng,Zhang Ting,Hu Wei
Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 μg/ml than albendazole with IC50 = 3.71 and 21.22 μg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.
研究领域:
寄生虫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Nutrition
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2022
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IF 6.59
Xiaoxiao Xu,Chuang Ma,Hang Wu,Yuanqiao Ma,Zejin Liu,Peijie Zhong,Chaolei Jin,Wenjuan Ning,Xiao Wu,Yijie Zhang,Jichang Han,Junpeng Wang
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
研究领域:
肺科学
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细胞生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Kuaitian Wang,Mengqi Jian,Yuhang Chen,Mengdi Du,Zhenhua Wang,Bo Xu,Ning Tang,Yongqiang Cheng,Jing Gan
The aim of this study was to determine the osteogenic activity and mechanism of soybean peptide VVELLKAFEEKF (SOP) and the potential relationship between SOP and transforming growth factor-β1 (TGF-β1). The results show that SOP promotes MC3T3-E1 cell proliferation by altering cell progression. SOP induced cell differentiation and mineralization in a dose-dependent manner at 0.7–7 μM. Moreover, SOP stimulates osteoblast differentiation, which may be achieved through the activation of p38-MAPK and Smad2/3 signaling pathways. Furthermore, treatment with a TβRI inhibitor (SB525334) inhibited the phosphorylation levels of p38 and Smad2/3, which indicates the involvement of TβRI in the process of osteoblast differentiation caused by SOP. Besides, in non-FBS-cultured MC3T3-E1 cells, SOP and TGF-β1 promoted the phosphorylation of Smad2/3 and alkaline phosphatase (ALP) activity, but the effect was lost when SOP was incubated separately, indicating that SOP stimulated osteoblast differentiation by promoting TGF-β1 activity. In vivo, SOP significantly restores bone mineral density loss and behavioral deficits in a model of glucocorticoid-induced osteoporosis (GIOP) in zebrafish. These results suggest that SOP may have the function of promoting bone remodeling and may be used as a potential active factor for functional food development to prevent osteoporosis.
研究领域:
生物学
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药理学
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医学研究
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Zhang Dan,Su Ying,Sun Peng,Liu Xingzhi,Zhang Lin,Ling Xuwei,Fan Yuhui,Wu Kang,Shi Qin,Liu Jisheng
Hydrogel-based tissue engineering has been widely used to repair cartilage injury. However, whether this approach can be applied to treat nasal septum cartilage defects remains unclear. In this study, three gelatin methacrylate-based scaffolds loaded with transforming growth factor (TGF)-β1 (GelMA-T) were prepared, and their effects on repair of nasal septum cartilage defects were examined. In vitro, the GelMA-T scaffolds showed good biocompatibility and promoted the chondrogenic differentiation of bone mesenchymal stem cells. Among three scaffolds, the 10% GelMA-T scaffold promoted chondrogenic differentiation most effectively, which significantly improved the expression of chondrocyte-related genes, including Col II, Sox9, and ACAN. In vivo, 10% GelMA-T scaffolds and 10% GelMA-T scaffolds loaded with bone mesenchymal stem cells (BMSCs; 10% GelMA-T/BMSCs) were transplanted into a nasal septum cartilage defect site in a rabbit model. At 4, 12, and 24 weeks after surgery, the nasal septum cartilage defects exhibited more complete repair in rabbits treated with the 10% GelMA-T/BMSC scaffold as demonstrated by hematoxylin & eosin, safranine-O, and toluidine blue staining. We showed that GelMA-T/BMSCs can be applied in physiological and structural repair of defects in nasal septum cartilage, providing a potential strategy for repairing cartilage defects in the clinic.
研究领域:
组织工程
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再生医学
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生物医用材料
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骨科
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2021
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IF 4.749
Genbin Wu,Binbin Sun,Chunfeng Zhao,Zhuoying Wang,Songsong Teng,Mengkai Yang,Zhi Cui,Guoliang Zhu,Yinxian Yu
Tendon adhesion formation is associated with the aberrant expression of many genes, and interfering with the expression of these genes can prevent adhesion and promote tendon repair. Recent studies have found that silencing the transforming growth factor β-1 (TGF-β1) gene can reduce the occurrence of tendon adhesions. The development of tissue engineering and three-dimensional (3D) printing technology have provided new solutions for tendon repair. In this study, TGF-β1 gene silencing microRNA (miRNA) based RNAi plasmid was loaded on a 3D tendon scaffold using 3D printing technology. In vitro experiments confirmed the sustained release of plasmid and the good biocompatibility of the printed tendon scaffold. Subsequently, the TGF-β1 gene silencing plasmid loaded tendon scaffold was implanted in a chicken tendon defect model to evaluate the effect of the scaffold in vivo. The results from biomechanical tests and histological examinations showed that the scaffold not only promoted tendon regeneration but also prevented tendon adhesion, which was conducive to the recovery of biofunction. Evaluation of protein expression showed that the loaded plasmids prevented tendon adhesion and promoted tendon functional repair via silencing of the TGF-β1 gene.
研究领域:
组织工程
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再生医学
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分子生物学
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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
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2018
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IF 3.118
Yichuan Xiao,Jiantao Ye,Ying Zhou,Junjun Huang,Xiawen Liu,Biyun Huang,Liu Zhu,Bo Wu,Genshui Zhang,Yi Cai
AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways. It has been shown that activation of AMPK could inhibit fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby suppressing cardiac fibrosis. Baicalin , the major component found in skullcap, possesses multiple protective effects on the cardiovascular system. However, little is known about the effect of baicalin on cardiac fibrosis and the molecular mechanism by which baicalin exerts its anti-fibrotic effects has not been investigated. In this study, we revealed that baicalin could inhibit cell proliferation , collagen synthesis , fibronectin (FN) and Connective tissue growth factor (CTGF) protein expression in cardiac fibroblasts induced by angiotensin Ⅱ (Ang Ⅱ). It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC). Moreover, baicalin inhibited transforming growth factor-β (TGF-β)/Smads signaling pathway stimulated with Ang Ⅱ through activating AMPK. Subsequently, we also demonstrated that baicalin attenuated Ang Ⅱ-induced Smad3 nuclear translocation, and interaction with transcriptional coactivator p300, but promoted the interaction of p300 and AMPK. Taken together, these results provide the first evidence that the effect of baicalin against cardiac fibrosis may be attributed to its regulation on AMPK/TGF-β/Smads signaling, suggesting the therapeutic potential of baicalin on the prevention of cardiac fibrosis and heart failure.
研究领域:
心脏病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
GENE
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2024
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IF 2.6
Wen Zhong,Huanan Jia,Haiyan Zhu,Yuan Tian,Wei Huang,Qiyue Yang
Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 μM or 40 μM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-β-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-β and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-β/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.
研究领域:
老年学
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药理学
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肌肉生物学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
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2018
·Vol. 234
·期 7
·11440-11450
·
IF 3.923
Zheng-Yu Liu,Hong-Wei Pan,Yan Cao,Jiao Zheng,Yu Zhang,Yi Tang,Jin He,Yong-Jun Hu,Chang-Lu Wang,Qiong-Chao Zou,Qing-Hua Fu,Le Zhang,Jian-Qiang Peng,Jing Ling,Ning Peng,Jing-Jing Rong,Zhao-Fen Zheng
microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA-330 (miR-330) on left ventricular remodeling via the TGF-β1/Smad3 signaling pathway by targeting the sex-determining region Y (SRY) in mice with myocardial ischemia–reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia–reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR-330, SRY, transforming growth factor-β (TGF-β1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR-330 in MIRI with the involvement of SRY and TGF-β1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR-330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR-330, TGF-β1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR-330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF-β1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR-330 could suppress left ventricular remodeling to inhibit the activation of the TGF-β1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.
研究领域:
心脏病学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Ye Liu,Jiufeng Zhao,Xingrui Mu,Junyu Deng,Xingqian Wu,Wenjie He,Yiqiu Liu,Rifang Gu,Felicity Han,Xuqiang Nie
Ethnopharmacological relevance Centella asiatica (L.) Urban is an ethnobotanical herb. The main bioactive components of Centella asiatica are pentacyclic triterpenoid glycosides , namely asiaticoside and hydroxyasiaticoside. Asiaticoside possess a diverse array of pharmacological properties, such as wound-healing, anti-inflammatory, antioxidant, anti-allergic, antidepressant, anxiolytic, anti-fibrotic, antibacterial, anti-arthritic, anti-tumor, and immunomodulatory activities. Aim of the study The purpose of this investigation is to explore potential therapeutic interventions for the delayed healing of wounds in diabetic patients (DW) facilitated by Asiaticoside-Nitric Oxide. To clarify the key molecular mechanism of miRNA-21-5p in DW wound repair and to deepen the understanding of DW disease pathogenesis. Materials and methods Firstly, miRNA microarray technology, bioinformatics, and RT-qPCR were used to analyze DW patients' and normal controls' skin tissue samples. Secondly, in order to investigate the role of miRNA-21-5p, a hyperglycemic model was established using HaCaT cells. Overexpressing as well as interfering HaCaT cell lines were constructed by lentiviral infection to further explore the proliferative and migratory effects of Asiaticoside-Nitric Oxide. The next step was to search for potential target genes of miRNA-21-5p and verify them with dual-luciferase reporter assay. Finally, the expression levels of target genes and proteins were detected through the utilization of RT-qPCR and Western blotting under the influence of Asiaticoside-Nitric Oxide. Results A library of miRNAs and target genes expressed explicitly in DW patients and rats was established. The study confirmed the upregulation of miRNA-21-5p in DW patients and identified its involvement in signaling pathways related to chronic ulcer wound repair. Overexpression of LV-miRNA-21-5p significantly promoted cell proliferation , while treatments of Asiaticoside-Low dose (AC-L) and Asiaticoside-Medium dose (AC-M) enhanced proliferation and migration, particularly when combined with nitroprusside (SNP). Further analysis revealed potential target genes of miRNA-21-5p, such as TGF-β1, SMAD7, and TIMP3. Their interaction with miRNA-21-5p was confirmed through dual luciferase assays. The study found that anti-DW drugs increased the expression of TGF-β1 and SMAD7 while inhibiting TIMP3 expression in a high-glucose environment. Conclusions The research concluded that miRNA-21-5p plays a crucial role in the delayed healing of diabetic wounds, and that the combination treatment of AC + SNP shows promise in promoting wound healing in DW rats. Target genes, including TGF-β1, SMAD7, and TIMP3, may contribute to the regulatory mechanisms involved in diabetic wound healing. These findings provide valuable insights for developing novel therapeutic approaches for DW.
研究领域:
药理学
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分子生物学
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糖尿病研究
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伤口愈合
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民族药理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
·
IF 3.997
Meng Xiao,Jiangwei Xiao,Gang Wu,Yu Ke,Liming Fang,Chunlin Deng,Hua Liao
Protein adsorption on biomaterial surfaces is clinically applied to increase therapeutic effects; however, this adsorption is possibly accompanied by conformational changes and results in loss of protein bioactivity or adverse reactions. In this research, a transforming growth factor β1 (TGF-β1) affinitive peptide HSNGLPL was grafted onto biopolymer surface to stabilize TGF-β1 spatial conformation after adhesion. The peptide with azide end group was combined with the propynyl pendant group on polyurethane via copper-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction. The final polymer was characterized by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy, which indicated that the affinitive peptide was introduced to the polymer. Quartz crystal microbalance with dissipation (QCM-D) was performed to monitor TGF-β1 adsorption and desorption on the surfaces coated with polyurethane with and without peptide combination. Results showed that TGF-β1 adhered on polyurethane surface and formed a compact and rigid layer. This layer showed spatial structural change but presented a loose and diffuse layer on the peptide-grafted polyurethane surface, indicating stable spatial conformation after adherence. Similar regulations were observed on the two surfaces where BSA layer was coated in advance. In vivo animal experiments revealed that immune reactions and tissue regenerations occurred earlier on peptide-modified polyurethane than on polyurethane, which did not undergo peptide grafting. This finding confirmed that affinitive interactions may preserve TGF-β1 bioactivity on polymer surface after adsorption.
研究领域:
生物材料
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生物医学工程
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蛋白质工程
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组织工程
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DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 24
·4267
·
IF 5.1
Jing Xu,Wen-Zhao Wen,Jun-Hui Zhao,Jun-Rong Guo,Zhuo-Ya Zhang,Ping Xiong
Citri grandis exocarpium ( Citri grandis ) has been consumed by human beings for fifteen hundred years. It is commonly consumed as a health drink and dietary supplement in China. However, its nutritional and healthcare functions are still not fully understood. Objective: Our previous study found that oral administration of Citri grandis extract can significantly decrease the blood lipid levels of hyperlipidemic mice fed a high-fat diet. The aim of this study was to confirm the preventative effects of Citri grandis extract against atherosclerosis. Methods: Atherosclerotic lesion models were induced in HUVECs and apoE −/− C57BL/6J mice. ApoE −/− mice fed a high-fat diet were orally administered Citri grandis extract (0.4, 0.8, and 1.6 g/kg/d BW) and Simvastatin (1 mg/kg/d BW) on the first day of model establishment. After a 16-week treatment, serum samples and aorta and liver tissues were collected. Observation of pathological changes in aortic and liver tissues was performed using a light microscope with oil red O, H&E, Masson’s trichrome staining, and TEM. Biochemical detection was employed to determine the serum levels of TC, TG, LDL-C, and HDL-C as well as the activities of AST and ALT. In addition, expression studies of TGF-β, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1 were performed via qPCR and Western blot analysis. Results: Compared with cholesterol-induced HUVECs, Citri grandis extract significantly enhanced cell viability, attenuated the morphological changes in HUVECs, and reduced LDH release. Furthermore, after treatment with Citri grandis extract, the levels of TC, TG, and LDL-C significantly decreased in the atherosclerosis model apoE −/− mice after 16 weeks, and aortic plaque, lipid deposition, and endothelial injury were obviously ameliorated. The mRNA and protein expression of TGF-β, PPAR-γ, LXR-α, and ABCA1 in aortic and liver of atherosclerosis apoE −/− mice were upregulated ( p < 0.05, p < 0.01), while those of PI3K and Akt1 were suppressed ( p < 0.05, p < 0.01). Conclusions: Citri grandis extract can significantly decrease the high circulating lipid levels and the liver lipid deposition of high-fat-diet-fed apoE −/− mice and reduce aorta lipid accumulation and atherosclerotic plaques by regulating the expression of TGF-β1, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1. Citri grandis extract can be used as a healthcare dietary supplement for the prevention of abnormal lipid metabolism and atherosclerosis.
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PubMed
高影响因子
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