Science Advances
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2020
·Vol. 6
·期 48
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IF 13.117
Yun Xu,Guodong Shi,Jincheng Tang,Ruoyu Cheng,Xiaofeng Shen,Yong Gu,Liang Wu,Kun Xi,Yihong Zhao,Wenguo Cui,Liang Chen
Current homogeneous bioscaffolds could hardly recapture the regenerative microenvironment of extracellular matrix. Inspired by the peculiar nature of dura matter, we developed an extracellular matrix–mimicking scaffold with biomimetic heterogeneous features so as to fit the multiple needs in dura mater repairing. The inner surface endowed with anisotropic topology and optimized chemical cues could orchestrate the elongation and bipolarization of fibroblasts and preserve the quiescent phenotype of fibroblasts indicated by down-regulated α–smooth muscle actin expression. The outer surface could suppress the fibrotic activity of myofibroblasts via increased microfiber density. Furthermore, integrin β1 and Yes-associated protein molecule signaling activities triggered by topological and chemical cues were verified, providing evidence for a potential mechanism. The capability of the scaffold in simultaneously promoting dura regeneration and inhibiting epidural fibrosis was further verified in a rabbit laminectomy model. Hence, the so-produced heterogeneous fibrous scaffold could reproduce the microstructure and function of natural dura.
研究领域:
生物材料学
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再生医学
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细胞生物学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Dan Wang,Yimeng Zou,Tianqi Zhao,Weiyue Cao,Jiachi Han,Qing Wu,Zhitong Li,Xinyu Li,Peijing Liu,Lin Bai,Guiping Ren
Background The blood FGF21 expression has been previously suggested to increase in patients developing atopic dermatitis (AD) and asthma. However, its impact on atopic march is rarely analyzed. The present work focused on investigating the role of Fibroblast Growth Factor 21(FGF21) in atopic march mice and its underlying mechanisms. Methods The models were induced with Diisononyl phthalate (DINP) and OVA in wild-type C57BL/6 and FGF21 −/− mice. RAW264.7 cells were induced by LPS with/without FGF21 or KLB-SiRNA for in vitro analyses. Results The data indicated that there were more severe allergic reactions including IgE levels and the proportion of mast cells in the blood of FGF21 −/− mice in relative to WT model mice during the progression from AD to asthma. However, exogenous administration of FGF21 inhibited allergies. In this study, we reported that FGF21 mitigated AD-like lesions and Th1/2 or Th17/Treg cell imbalance in AD mice, and significantly decreased TSLP, IL-33, IL-4, IL-5, IL-13 and IL-17A expression on skin. During the asthma phase, FGF21 improved airway remodeling by downgrading inflammatory factors IL-4, IL-5, IL-13 and IL-17A; fibrotic markers α-SMA and Collagen I; and oxidative products MDA and ROS in wild-type model mice. Compared with WT model mice, the adverse consequences were aggravated in FGF21 −/− asthmatic mice. From the mechanistic perspective, FGF21 suppressed NF-κB/NLRP3, TGF-β1/Smad3 and JNK signaling pathways and increased Nrf2 expression in vivo and in vitro. In addition, β-Klotho knockdown attenuated the ameliorative impact of FGF21 on cellular damage. Blocking AMPKα in the LPS-treated RAW264.7 cells inhibited the reduction of FGF21 and the phosphorylation of JNK. Conclusions To conclude, FGF21 alleviated atopic march by inhibiting Th2/17 immune response, and reduced airway remodeling by regulating NF-κB/NLRP3, TGF-β1/Smad3 and AMPKα/JNK pathways. Moreover, this study provides a rationale and novel ideas for applying FGF21 in treating AD and asthma.
研究领域:
免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2024
·
IF 8.7
Deguang Wu,Jian Li,Chengxinqiao Wang,Zhiwen Su,Hao Su,Yan Chen,Bo Yu
Transforming growth factor-β1 (TGF-β1) is essential for cartilage regeneration, but its susceptibility to enzymatic denaturation and high cost limit its application. Herein, we report Ac-LIANAKGFEFEFKFK-NH 2 (LKP), a self-assembled peptide nanofiber hydrogel that can mimic the function of TGF-β1. The LKP hydrogel is simple to synthesize, and in vitro experiments confirmed its good biocompatibility and cartilage-promoting ability. However, LKP hydrogels suffer from poor mechanical properties and are prone to fragmentation; therefore, we prepared a series of injectable hydrogel composite scaffolds (SF-GMA/LKP) by combining LKP with glycidyl methacrylate (GMA)-modified silk fibroin (SF). SF-GMA/LKP composite scaffolds instantaneously induced in-situ filling of cartilage defects and, at the same time, relied on the interaction between LKP and SF-GMA interaction to prolong the duration of action of LKP. The SF-GMA/LKP10 and SF-GMA/LKP20 composite scaffolds had the best effect on neocartilage and subchondral bone reconstruction. This composite hydrogel scaffold can be used for high-quality cartilage repair.
研究领域:
生物材料
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组织工程
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2019
·
IF 3.585
Guangxu Cao,Shuang Li,Hezhan Shi,Peidi Yin,Jialing Chen,Huifeng Li,Ying Zhong,Li-Ting Diao,Bin Du
Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant features of TIF. MicroRNAs play critical roles during EMT in TIF. However, whether miRNAs can be used as therapeutic targets in TIF therapy remains undetermined. We found that miR-30e, a member of the miR-30 family, is deregulated in TGF-β1-induced PTCs, TIF mice and human fibrotic kidney tissues. Moreover, transcription factors that induce EMT, such as snail, slug, and Zeb2, were direct targets of miR-30e. Using a cell-based miR-30e promoter luciferase reporter system, Schisandrin B (Sch B) was selected for the enhancement of miR-30e transcriptional activity. Our results indicate that Sch B can decrease the expression of snail, slug, and Zeb2, thereby attenuating the EMT of PTCs during TIF by upregulating miR-30e, both in vivo and in vitro. This study shows that miR-30e can serve as a therapeutic target in the treatment of patients with TIF and that Sch B may potentially be used in therapy against renal fibrosis
研究领域:
肾病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Liang Zhou,Feng Cai,Hongyi Zhu,Yichang Xu,Jincheng Tang,Wei Wang,Ziang Li,Jie Wu,Zhouye Ding,Kun Xi,Liang Chen,Yong Gu
Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.
研究领域:
生物材料
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纳米技术
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再生医学
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骨科
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炎症
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Tong Yuling,Liu Liping,Wang Ruilin,Yang Tao,Wen Jianxia,Wei Shizhang,Jing Manyi,Zou Wenjun,Zhao Yanling
The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed in vivo. In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-β1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1β. In addition, BBR down-regulated the expression of TGF-β1 axis-related signals such as TGF-β1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-β1/PI3K signal pathway.
研究领域:
药理学
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胃肠病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
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2022
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IF 10.334
Xiaohua Xie,Xiaofeng Wu,Dongsheng Zhao,Ying Liu,Qiyue Du,Yitian Li,Yaping Xu,Yuhang Li,Yan Qiu,Yungang Yang
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9–5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-β1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.
研究领域:
药理学
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肺科学
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免疫学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Zhihong Deng,Lifeng Zhao,Xiuxue Li,Chang-Yun Wang,Yue Zhou,Mengfei Li,Yingfei Li,Xianjun Fu
Appropriate topical dressings for burn treatments are important to accelerate skin wound recovery and prevent external infections. This study aimed to evaluate the effect and investigate the mechanism of folium crataegi ( Crataegus pinnatifida Bge. ) for the treatment of burn wounds, as well as to compare the therapeutic effects of aqueous extracts ( HLW ) and alcoholic extracts ( HLE ) from folium crataegi . The results demonstrated that both HLW and HLE groups exhibited a higher wound contraction rate than the silver sulfadiazine ( SSD ) ointment group. Moreover, HLW showed more significant wound repair effects than HLE . HLW significantly increased levels of EGF and FGF-2 in wound tissue, as well as TGF-β1 , VEGF , CAT and IL-10 in serum. Folium crataegi extract, especially aqueous extracts, exerted good anti-inflammatory, anti-oxidant and anti-bacterial effects by upregulating the expression of lag3 , txn1 and slpi , respectively. Folium crataegi extract significantly inhibits the expression of npas2 , a key gene in the circadian rhythm pathway. In conclusion, this research illustrated that the folium crataegi extract, especially aqueous extracts, had better therapeutic effects on skin burns through multiple ways, possibly including a novel mechanism related to circadian rhythm pathway. These findings suggest that folium crataegi could be a valuable source of compounds for enhancing skin regeneration through multiple ways.
研究领域:
药理学
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烧伤治疗
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伤口愈合
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 12.6
Ce Li,Yichao Yuan,Yaqing Bao,Yeling Ni,Nan Chen,Jigang Piao,Lu Wang,Zhihong Zhu
Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by progressive fibrosis and poor prognosis, with no current therapies capable of reversing the fibrotic changes. The aberrant repair driven by fibroblast activation and an inflammatory microenvironment results in irreversible IPF. In this work, a macrophage-derived apoptotic body delivery system (SA + NAC@AB) co-loaded with sodium arsenite (SA) and N-acetylcysteine (NAC) was developed to exert synergistic antifibrotic activity against IPF via coordinated regulation of TGF-β1 signaling and inflammation. Apoptotic bodies derived from macrophages inherit inflammation-homing capability, enabling targeted delivery to fibrotic lesions. In vivo evaluation in a bleomycin-induced IPF mouse model demonstrated that SA + NAC@AB effectively targeted the lungs, significantly improved body weight and survival, and alleviated pulmonary fibrosis. Immunofluorescence and Western blot analyzes revealed that SA + NAC@AB reduced Smad2/3 phosphorylation and M2 macrophage polarization, indicating regulation of the TGF-β1/Smad2/3 pathway and inflammation as part of its mechanism of action. Furthermore, in vitro studies validated the enhanced efficacy of SA + NAC@AB, which significantly promoted fibroblast uptake, thereby potentiating its inhibitory effects on fibroblast viability, as well as TGF-β1-induced migration and differentiation. In conclusion, our study demonstrates that SA + NAC@AB represents an effective therapeutic strategy for IPF, offering a promising novel approach by modulating both the TGF-β1/Smad2/3 signaling pathway and the inflammatory response.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
·
IF 4.7
Lijun Fang,Linmao Lyu,Hongyu Zhong,Jiamao Lin,Pengtao Ren,Yu Wang,Yunhong Yin,Mengyu Zhang,Yiqing Qu
Idiopathic pulmonary fibrosis (IPF) is a kind of chronic and progressive interstitial lung disease of unclear aetiology. A key aspect of IPF is transforming growth factor-β1 (TGF-β1)-induced mitophagy dysfunction and senescence in lung fibroblasts. Mesenchyme homeobox 1 (MEOX1) is a critical transcription factor in the regulation of cell differentiation. However, the role of MEOX1 in the pathogenesis of lung fibrosis and mitophagy has not been clarified. In this study, RNA-sequencing analysis was employed to identify the differentially expressed genes in TGF-β1-treated lung fibroblasts and IPF lung tissue. In vivo , the mouse model of lung fibrosis was established by intratracheal injection of bleomycin (BLM), and fibroblast-specific knockdown of MEOX in mice was achieved by intratracheal injection of adeno-associated viruse-shMEOX1. And in vitro experiments were also carried out on human lung fibroblasts. Our results indicated that fibroblast-specific knockdown of MEOX1 protected mice from BLM-induced pulmonary fibrosis, connective tissue growth factor (CTGF) expression, and lung fibroblast activation, as well as mitophagy deficiency and senescence. In vitro , MEOX1 knockdown abolished TGF-β1-induced mitophagy deficiency by downregulating CTGF expression, thereby inhibiting senescence, over-activation and collagen production in lung fibroblasts. Furthermore, we also found that TGF-β1 upregulated the expression of MEOX1 through the NOX4-ROS-Smad pathway. In conclusion, MEOX1 knockdown may ameliorate pulmonary fibrosis by regulating mitophagy and senescence and may be a potential therapeutic target for IPF and other types of interstitial lung diseases.
研究领域:
分子生物学
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细胞生物学
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呼吸病学
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遗传学
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生物信息学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2024
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IF 4.1
Qiulu Li,Kaixin Ping,Yannan Xiang,Ying Sun,Zunhan Hu,Shujuan Liu,Xinying Guan,Mian Fu
Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 μg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-β1 and il-10 , while significantly down-regulated the gene expression levels of tnf-α , il-6 and il-1β . These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.
研究领域:
水生毒理学
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药理学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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