BRITISH JOURNAL OF PHARMACOLOGY
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2025
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IF 7.7
Yu-Chen Jiang,Jia Guo,Sai-Hu Liu,Xu Dai,Chen-Yu Wang,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Background and Purpose Vincamine has extensive biological and pharmaceutical activity. We examined the hepatoprotective effects and mechanisms by which vincamine suppresses hepatic fibrosis. Experimental Approach Hepatic stellate cells (HSCs), TGF- β stimulated, were cultured with either vincamine, farnesoid X receptor (NR1H4; FXR) agonist or antagonist. Further, C57BL/6 mice were given thioacetamide (TAA) to induce hepatic fibrosis and subsequently treated with vincamine or curcumin. Key Results Vincamine regulated the deposition of extracellular matrix (ECM), inflammatory factors and S100A4, and up-regulated FXR and TGR5 (GPBA receptor) in activated HSCs, by activating FXR. FXR deficiency blocked vincamine effect on FXR, TGR5, α -smooth muscle actin ( α -SMA) and IL1R1 in activated LX-2 cells. Vincamine corrected ECM imbalance, inflammatory secretion and FXR/TGR5 down-regulation in activated LX-2 cells with stimulating medium from LPS-primed THP-1 cells. S100A4 deficiency increased FXR and TGR5, and decreased IL-1β expression in activated THP-1. Further, S100A4 deficiency in activated macrophages could elevate FXR and TGR5 expression in activated LX-2, strengthening the impact of vincamine on α -SMA and IL-1β expression. Further, vincamine reduced serum ALT/AST levels, liver and intestinal histopathological changes, and caused ECM accumulation and protected the intestinal barrier in thioacetamide-induced hepatic fibrosis mice. Vincamine decreased inflammatory factors e.g. caspase 1 and IL-1β, and inhibited the S100A4-mediated FXR-TGR5 pathway. Conclusion and Implications Vincamine significantly reverses hepatic fibrosis via inhibiting S100A4 involved in the crosstalk between macrophages and HSCs, and by activating the FXR-TGR5 pathway. Targeting the S100A4-mediated FXR dependence on modulating the liver environment may be the key target of vincamine in inhibiting hepatic fibrosis. Graphical
研究领域:
药理学
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肝脏病学
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分子生物学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 9
·e202200447
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IF 2.745
Ling Guo,Yanling Jin,You Yang,Jing Liu,Chunyan Liu,Yan Zeng,Qulian Guo,Wenjun Liu
Purple sweet potato is considered an abundant, inexpensive, and ideal source of anthocyanins. Purple sweet potato anthocyanins (PSPAs) have been shown to possess high antimutagenicity and antitumor effects due to the abundance of acylated anthocyanins. However, the effect and underlying mechanism of PSPA effects in acute lymphoblastic leukemia (ALL), especially T-cell acute lymphoblastic leukemia (T-ALL), remain unclear. In this study, the antileukemic effects of PSPAs and the underlying molecular mechanisms were evaluated by in vitro and in silico assays. PSPAs extracted from ten cultivars were analyzed and quantified. Anthocyanins from Nanzi 018, which showed the best antileukemic effect, were selected to analyze the underlying mechanism. First, the PSPAs potently reduced cell viability and induced apoptosis. Additionally, the PSPAs sharply increased intracellular Ca 2+ levels, which resulted in calcium overload in T-ALL cells. Furthermore, on the basis of bioinformatics analyses, we focused on an osmotically regulated transcription factor, NFAT5. Molecular docking preliminarily indicated that PSPA molecules bound and interacted with the NFAT5 protein. Western blot analyses confirmed that PSPAs elicited calcium overload by nonosmotic regulation of NFAT5/S100A4-S100A9 pathway activation. Moreover, pretreatment with a NFAT5 inducer confirmed that PSPAs targeted NFAT5 and affected p38/NF-κB/Bcl-2/Caspase-3 axis activation. This study demonstrates that PSPAs exert their antileukemic effects through calcicoptosis induction by targeting NFAT5.
研究领域:
肿瘤学
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药理学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2019
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IF 4.259
Xue Biyun,Hou Gaopeng,Zhang Guixi,Huang Jingjing,Li Liangliang,Nan Yuchen,Mu Yang,Wang Lizhen,Zhang Lu,Han Ximeng,Ren Xiaolei,Zhao Qin,Wu Chunyan,Wang Jingfei,Zhou En-Min
Prevention and control of infection by porcine reproductive and respiratory syndrome virus (PRRSV) remains a challenge, due to our limited understanding of the PRRSV invasion mechanism. Our previous study has shown that PRRSV glycoprotein GP5 interacts with MYH9 C-terminal domain protein (PRA). Here we defined that the first ectodomain of GP5 (GP5-ecto-1) directly interacted with PRA and this interaction triggered PRA and endogenous MYH9 to form filament assembly. More importantly, MYH9 filament assembly was also formed in GP5-ecto-1-transfected MARC-145 cells. Notably, PRRSV infection of MARC-145 cells and porcine alveolar macrophages also induced endogenous MYH9 aggregation and polymerization that were required for subsequent PRRSV internalization. Moreover, overexpression of S100A4, a MYH9-specific disassembly inducer, in MARC-145 cells significantly resulted in diminished MYH9 aggregation and marked inhibition of subsequent virion internalization and infection by both PRRSV-1 and PRRSV-2 isolates. The collective results of this work reveal a novel molecular mechanism employed by MYH9 that helps PRRSV gain entry into permissive cells.
研究领域:
病毒学
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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
Immunity Inflammation and Disease
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2023
·Vol. 11
·期 2
·e730
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IF 3.2
Min Liu,Shuang Liu,Fajiu Li,Chenghong Li,Shi Chen,Xiaoyan Gao,Xiaojiang Wang
Objective Asthma is a chronic respiratory disease with an increasing incidence every year. microRNAs (miRNAs) have been demonstrated to have implications for asthma. However, limited information is available regarding the effect of miR-124-3p on this disease. Therefore, this study aimed to explore the possible effects of miR-124-3p and S100A4 on inflammation and epithelial–mesenchymal transition (EMT) in asthma using mouse models. Method Ovalbumin was used to induce asthmatic mouse models. Lung injury in mouse models was assessed, and the bronchoalveolar lavage fluid of mice was collected to determine the number of eosinophilic granulocytes and assess inflammation. The expression levels of miR-124-3p, S100A4, E-cadherin, N-cadherin, Snail1, vimentin, and TGF-β1/Smad2 signaling pathway-related proteins were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. In vitro experiments, cells were transfected with miR-124-3p mimics or inhibitors to test the expression of S100A4 by RT-qPCR and western blot analysis, and the mutual binding of miR-124-3p and S100A4 was validated by dual-luciferase reporter gene assay. Results Overexpression of miR-124-3p or inhibition of S100A4 expression attenuated bronchial mucus secretion and collagenous fibers and suppressed inflammatory cell infiltration. Additionally, upon miR-124-3p overexpression or S100A4 suppression, eosinophilic granulocytes were decreased, interleukin-4 (IL-4) and IL-13 expression levels were reduced in the bronchoalveolar lavage fluid, serum total IgE level was reduced, and the TGF-β1/Smad2 signaling pathway was suppressed. Mechanically, a dual-luciferase reporter gene assay verified the binding relationship between miR-124-3p and S100A4. Conclusion miR-124-3p can negatively target S100A4 to attenuate inflammation in asthmatic mouse models by suppressing the EMT process and the TGF-β/smad2 signaling pathway.
研究领域:
免疫学
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分子生物学
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呼吸医学
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DOI
PubMed
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2025
·Vol. 36
·期 3
·e70136
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IF 3.4
Ping Xie,Jing He,Yangjun Ou
Photothermal therapy is a promising adjunctive treatment technique requiring a nanoplatform with excellent biocompatibility, photothermal stability, and precise targeting capabilities. This study aims to develop such a nanoplatform by synthesizing two new manganese(II)-based coordination polymers. The polymers were created by integrating 1,4-bis(imidazol-1-yl)benzene with the ternary ligand tris( p -carboxyphenyl)phosphane oxide, resulting in the formulas {[Mn 3 (L) 2 (bib) 3 (H 2 O) 7 ]·12H 2 O} n (CP 1 ) and {[Mn(HL)(bib)]·H 2 O} n (CP 2 ). These structures, with large surface areas and porosity, enhance drug loading efficiency. Doxorubicin (DOX) was successfully incorporated into a biocompatible HA/CMCS hydrogel-CP composite (HA/CMCS-CPs@DOX), forming a robust nanotherapeutic platform. Under near-infrared light irradiation, these metal-hydrogel composites effectively induced localized hyperthermia, aiding ocular melanoma treatment. We evaluated the effect of HA/CMCS-CP 2 @DOX on the cell proliferation of the uveal melanoma cell line, and the regulatory effects of the system on lncRNA ARAP1-AS1/miR-149-3p/S100A4 were also explored.
研究领域:
材料科学
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癌症治疗
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药物递送系统
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分子生物学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）