Science of Advanced Materials
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2022
·Vol. 14
·期 7
·1175-1184
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IF 1.067
Mei Qing,Shou Diwen,Quan Ying,Cheng Jiemin,Pan Pan,Chen Huiting,Huang Hongli,Li Yongqiang,Xia Yu,Zhou Yongjian
Lipid deposition is a key predisposing factor of nonalcoholic fatty liver disease (NAFLD). FOXO1 is obviously expressed in polarized M1 macrophages and may cause liver cell steatosis. Thus, silencing FOXO1 during M1 macrophage polarization using small interfering RNA (siRNA) technology
may alleviate lipid deposition in liver cells. However, a lack of effective and biocompatible carriers is challenging for such siRNA-delivery to macrophages. To improve this, RGDfC peptide-modified selenium nanoparticles (RGDfC-Se NPs) were fabricated as a siFOXO1 delivery carrier system.
We showed that RGDfC-Se NPs effectively increased siFOXO1 cellular uptake and silenced FOXO1 expression in human peripheral blood monocyte-like macrophages (THP-1 cells). Additionally, RGDfC-Se@siFOXO1 blocked M1 polarization in these cells. Also, FOXO-1-suppressed cell supernatants extenuated
lipid deposition in LO2 liver cells probably by down-regulating the expression of lipid deposition-related fat metabolic enzymes acetyl-CoA carboxylase 1 and fatty acid synthase. Furthermore, our in vivo analyses showed that RGDfC-Se@siFOXO1 attenuated hepatic steatosis by inhibiting
M1 macrophage polarization in mouse liver tissue. Our studies represent a new strategy and clinic treatment target for NAFLD.
研究领域:
药理学
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分子生物学
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纳米技术
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肝病学
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DOI
高影响因子
Pharmacognosy Magazine
·
2023
·
IF 0.7
Jiang-Long Shi,Li-Yun Liu,Yu-Ting Dong,Tao Shen
BackgroundSeveral studies have demonstrated the anti-inflammatory properties of gastrodin. However, its specific role and mechanism in the context of osteoarthritis (OA) remain unclear.ObjectivesThe objective of this study was to explore the function and mechanism of gastrodin in both in vivo and in vitro OA models.Materials and MethodsIn this study, the targets of gastrodin against osteoarthritis were analyzed using bioinformatics methods. The effect of gastrodin on neutrophil infiltration and inflammatory cytokines in OA synovial tissue was evaluated using H&E staining. The levels of inflammatory cytokines were determined using ELISA and Q-PCR. The extracellular matrix degradation-related proteins and PI3K/AKT/FoxO1 signaling pathway were tested using western blotting.ResultsBioinformatics analysis predicted that the target of gastrodin against OA might act on the FoxO pathway. The use of gastrodin resulted in a significant reduction in the infiltration of neutrophils in the synovial tissue of rats, as observed through H&E staining. Additionally, gastrodin was found to attenuate IL-1β-induced inhibition of chondrocyte viability, pro-inflammatory cytokine production, and extracellular matrix degradation. This effect can be attributed to the suppression of PI3K/AKT/FoxO1 by gastrodin.ConclusionThese findings indicate that gastrodin is a treatment for OA.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Meng Chen,Yonglu Li,Xin Yu,Yaxuan Wang,Wen Chen,Xiang Ye,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Tetrastigma hemsleyanum Diels et Gilg, a rare herbal plant native to China, possesses high medicinal value. More researches have focused on the flavones in the tubers of Tetrastigma hemsleyanum whereas polysaccharides attract few attentions. In this study, a purified polysaccharide (TTP-1) with the average molecular weights of 478.33 kDa was extracted from Tetrastigma hemsleyanum and conducted multiple analysis to identify its structural information. In vitro , TTP-1 could suppress the inflammation, cytotoxicity, genotoxicity, mitochondrial dysfunction and oxidative damage induced by LPS in RAW264.7 cells. Meanwhile, TTP-1 could attenuate inflammation via COX-2, iNOS, MAPKs pathways and ameliorate oxidative damage through Nrf2-Keap1, Sirt1-FoxO1 pathways in RAW264.7 cells. In vivo , the inflammation induced by LPS triggered the suppression of survival ratio and growing development, as well as the restrain of athletic ability in Caenorhabditis elegans . The treatment of TTP-1 reversed the situation induced by LPS. In a word, TTP-1 could ameliorate LPS-induced inflammation both in vitro and in vivo .
研究领域:
药理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2026
·
IF 29.1
Jiacheng Lei,Ruihao Xue,Qingqing Liang,Ge Yang,Xiaokai Pan,Tianxiang Ren,Kaikai Zheng,Qiang Wei,Ze Gong,Xiaojing Liu
Stem cell aging critically limits the efficacy of regenerative biomaterials, yet how mechanical cues within the microenvironment modulate this process remains insufficiently understood. Here, we reveal that the nanoscale spacing of adhesive ligands imposes stiffness-dependent effects on mesenchymal stem cell (MSC) senescence. Wider spacing (distance 150 nm) accelerates aging on stiff hydrogels (50 kPa) but mitigates it on soft hydrogels (5 kPa), relative to dense spacing (distance 30 nm). Using a molecular clutch-based theoretical model, we demonstrate that ligand spacing and matrix stiffness cooperatively regulate cell behaviors through focal adhesion assembly. Enhanced focal adhesion formation amplifies stress fiber-generated traction forces and nuclear envelope tension, leading to increased chromatin accessibility and transcriptional activation of FOXO1, a central regulator of cellular senescence. These mechanistic insights are further validated in vivo. Collectively, these findings delineate a mechanotransduction mechanism through which nanoscale adhesive architecture and matrix stiffness cooperatively govern stem cell aging.
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高影响因子
Journal of Genetics and Genomics
·
2021
·
IF 4.275
Feifei Chen,Lei Guo,Jiehui Di,Man Li,Dong Dong,Dongsheng Pei
Numerous circular RNAs (circRNAs) have been identified as vital regulators in various cancers. The newly reported circular RNA ubiquitin-associated protein 2 (circUBAP2) is a critical player in cell growth and metastasis in various types of cancers, although its role in colorectal cancer (CRC) has yet to be fully elucidated. We find that circUBAP2 is upregulated in CRC tissues and cell lines to induce autophagy both in vitro and in vivo . The effects of circUBAP2 on migration, invasion, and proliferation may be partially related to autophagy. Mechanistically, we uncover that circUBAP2 can directly interact with miR-582-5p and subsequently act as a microRNA sponge to regulate the expression of the miR-582-5p target gene forkhead box protein O1 ( FOXO1 ) and downstream signaling molecules, which collectively advance the progression and metastasis of CRC. These results suggest that circUBAP2 acts as an oncogene via a novel circUBAP2/miR-582-5p/FOXO1 axis, providing a potential biomarker and therapeutic target for CRC management.
研究领域:
分子生物学
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癌症研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Liang Hang-fei,Yang Xiao,Li Hui-lin,Li Xuan,Tian Jia-ning,Su Hai-guo,Huang Min,Fang Jian-hong,Bi Hui-chang
Our previous study shows that activation of pregnane X receptor (PXR) exerts hepatoprotection against lithocholic acid (LCA)-induced cholestatic liver injury. In this study we investigated whether PXR activation could inhibit hepatocyte pyroptosis, as well as the underlying mechanisms. Male mice were treated with mouse PXR agonist pregnenolone 16α-carbonitrile (PCN, 50 mg·kg −1 ·d −1 , i.p.) for 7 days, and received LCA (125 mg/kg, i.p., bid) from D4, then sacrificed 12 h after the last LCA injection. We showed that LCA injection resulted in severe cholestatic liver injury characterized by significant increases in gallbladder size, hepatocellular necrosis, and neutrophil infiltration with a mortality rate of 68%; PCN treatment significantly inhibited hepatocyte pyroptosis during LCA-induced cholestatic liver injury, as evidenced by reduced serum lactic dehydrogenase (LDH) levels, TUNEL-positive cells and hepatocyte membrane damage. Furthermore, PXR activation suppressed both the NOD-like receptor protein 3 (NLRP3) inflammasome-induced canonical pyroptosis and the apoptosis protease activating factor-1 (APAF-1) pyroptosome-induced non-canonical pyroptosis. Inhibition of the nuclear factor kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways was also observed following PXR activation. Notably, dual luciferase reporter assay showed that PXR activation inhibited the transcriptional effects of NF-κB on NLRP3, as well as FOXO1 on APAF-1. Our results demonstrate that PXR activation protects against cholestatic liver injury by inhibiting the canonical pyroptosis through the NF-κB-NLRP3 axis and the non-canonical pyroptosis through the FOXO1-APAF-1 axis, providing new evidence for PXR as a prospective anti-cholestatic target.
研究领域:
肝病学
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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
MOLECULAR NEUROBIOLOGY
·
2025
·Vol. 63
·期 1
·1-14
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IF 4.3
Cai Minghui,Guo Qi,Li Jiaxin,Dai Xiaoqi,Su Huiyu,Zhang Wenwen,Qiang Na,Li Geng,Jin Zihan,Zhu Hui
The factors influencing hippocampal aging are complex, and it remains challenging to identify effective anti-aging drugs and reveal pharmacological mechanisms. This study investigates the effects of autophagy mediated by the SIRT1/FoxO1 signaling pathway on resveratrol resistance to H 2 O 2 -induced aging and apoptosis in mouse hippocampal neurons. HT22 cells were treated with resveratrol and H 2 O 2 to evaluate the effects of resveratrol on H 2 O 2 -induced aging and apoptosis. The levels of P21, P53, BAX, Cleaved Caspase-3, and Bcl-2 were measured to estimate aging and apoptosis. Western blot, immunofluorescence assays, and transmission electron microscopy observation were used to detect the regulation of resveratrol on autophagy. 3-Methyladenine was used to block autophagy, and EX-527 was used to inhibit SIRT1. The changes of autophagy factors and the levels of SIRT1/FoxO1 signaling pathway were assayed. H 2 O 2 treatment induced aging in HT22 cells, manifesting increased levels of P21 and P53 and decreased cell viability. H 2 O 2 treatment aggravated apoptosis, showing increased levels of BAX and Cleaved Caspase-3, decreased levels of Bcl-2, and increased apoptotic cells. Resveratrol alleviated aging and apoptosis in H 2 O 2 -induced HT22 cells. Mechanically, resveratrol activated autophagy by up-regulating the levels of LC3B Ⅱ/Ⅰ and Beclin1 and down-regulating P62 against aging and apoptosis, which was abolished by 3-Methyladenine. Western blot results showed resveratrol activated SIRT1/FoxO1 signaling pathway which was related to regulation of autophagy. EX-527 treatment suggested resveratrol could not activate autophagy when the SIRT1/FoxO1 signaling pathway was blocked. These findings indicated that resveratrol activated autophagy via SIRT1/FoxO1 signaling pathway to protect against H 2 O 2 -induced aging and apoptosis in HT22 cells.
研究领域:
神经科学
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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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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Wen Chen,Qiang Chu,Xiang Ye,Yuhao Sun,Yangyang Liu,Ruoyi Jia,Yonglu Li,Pengcheng Tu,Qiong Tang,Ting Yu,Chuan Chen,Xiaodong Zheng
Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans ( C. elegans ) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans , by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G’s beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.
研究领域:
环境科学
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毒理学
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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
JOURNAL OF HAZARDOUS MATERIALS
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2020
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IF 9.038
Qiang Chu,Wen Chen,Ruoyi Jia,Xiang Ye,Yonglu Li,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Acrylamide (ACR), as a raw material of polyacrylamide that used in water purification, was verified to possess various toxicity. Tetrastigma hemsleyanum (TH) is a medicinal plant widely used to anti-inflammation and anti-tumor in Chinese folks. However, more researches focused on the biological activities in tubers and the leaves were ignored. Thus, the protective effect of Tetrastigma hemsleyanum leaves extract (THLE) against ACR-induced toxicity in HepG2 cells and Caenorhabditis elegans ( C. elegans ) was explored in this study. In vitro , we observed that THLE attenuated ACR-induced toxicity in HepG2 cell via regulating Akt/mTOR/FOXO1/MAPK signaling pathway. Further research proved that 5-caffeoylquinic acid (5-CA) plays a major role in THLE’s amelioration effect of ACR toxicity. In vivo , it was found that THLE possesses the same protective effect in ACR-treated wild-type N2 C. elegans and daf-2 (-) (deficit in DAF-2) mutants. However, the anti-ACR toxicity effect of THLE in daf-16 (-) mutants (deficit in DAF-16 that homologous to FOXO family in human) was weakened. Our results indicated that THLE exhibited protective effects against ACR-induced toxicity both in HepG2 cells and C. elegans , while DAF-16/FOXO gene is involved in THLE’ protective effect via regulating the expression levels of downstream antioxidant genes.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2026
·
IF 6.2
Qing Liu,Zengying Sui,Shiyi Li,Miaomiao Wan,Meilan Xue,Xia Qiu,Hui Liang,Lirui Sun
Fucoidan is a sulfated polysaccharide derived from brown algae ( Saccharina japonica ), and exhibits immunomodulatory properties. Emerging evidence suggests a strong correlation between the development of food allergy and intestinal dysfunction. The present study aimed to investigate the potential anti-food allergy activity of fucoidan and to elucidate its mechanism at the intestinal barrier function. The ovalbumin (OVA)-induced allergy mouse model was established, exhibiting increased OVA-specific IgE, histamine, Th2 inflammatory response, and intestinal damage. Oral administration of fucoidan markedly alleviated allergic symptoms by inhibiting mast cell activation and modulating intestinal immune responses. Furthermore, fucoidan significantly ameliorated intestinal immunological dysregulation, maintained barrier integrity, modulated gut microbiota composition, and enhanced short-chain fatty acid (SCFA) production. Mechanistically, the protective effects of fucoidan were closely associated with activation of the AMPK/SIRT1/FOXO1 pathway, which correlated with improved intestinal barrier function. Collectively, these results demonstrate that fucoidan may protect against food allergy by enhancing intestinal barrier function, highlighting the potential of natural biological substances in addressing food allergy.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Shuang Zhang,Lushuang Yu,Yonglu Li,Yangyang Liu,Xiang Ye,Xiaodong Zheng
The tubers of Apios americana Medikus possess high nutritional value and have been used as food in many countries for a long time. However, few researches have focused on the tuber polysaccharides. In the present study, a purified polysaccharide (ATP-1) was isolated with the average molecular weights of 12.16 kDa. ATP-1 significantly suppressed the release of nitric oxide (NO) and inflammatory cytokines from LPS-induced RAW 264.7 cells, as well as oxidative stress and mitochondrial dysfunction. Meanwhile, ATP-1 reduced oxidative damage via the NF-κB, MAPKs and Nrf2-Keap1 signaling pathways in RAW264.7 macrophages. Furthermore, autophagy was activated by HMGB1-Beclin1, Sirt1-FoxO1 and Akt-mTOR signaling pathways, leading to a relief of oxidative stress, mitochondrial dysfunction, inflammation and an expression enhancement of autophagy-related proteins, such as LC3, Beclin1, Atg4, Atg5, and Atg7. In summary, our results suggested that ATP-1 might help to activate the anti-inflammation system，resulting in prevention of LPS-induced damage in RAW264.7 cells.
研究领域:
药理学
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免疫学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Wenxuan Liu,Xiangka Hu,Xiaorui Han,Kexin Zeng,Xuedong Ren,Yining Chang,Chunmei Dai
Ethnopharmacology relevance Tangningtongluo Tablets (TNTL), a novel Miao ethnic medicine for treating type 2 diabetes mellitus (T2DM) and its complications. However, its potential bioactive components and the pharmacological mechanisms underlying its therapeutic effects remain unclear. Aim of the study This study aims to preliminarily explore the protective effects of TNTL and its active components on pancreatic cells via the PI3K/Akt/FoxO1 pathway and further investigate the underlying mechanisms. Materials and methods LC-MS was employed to identify components in serum, and network pharmacology was used to forecast active components and their mechanisms. The protective effects and mechanisms of TNTL and its active components on pancreatic β-cells in diabetic mice were investigated using HE staining, MTT assay, EdU assay, TUNEL staining, Western blot analysis, and qPCR analysis. Results A total of 29 active components of TNTL were detected in rat serum. Network pharmacology results indicated that luteolin, catechin, and chlorogenic acid are key compounds of TNTL in regulating the PI3K/Akt/FoxO1 pathway. Compared with the model group, TNTL and its active components reduced ROS and MDA levels, increased SOD levels, and reduced pro-apoptotic factor expression to alleviate pancreatic β-cells damage. They also activated PI3K/Akt/FoxO1 signaling and decreased apoptotic proteins. Conclusion This study demonstrates that TNTL mitigates oxidative stress and reduces pancreatic β-cell apoptosis in diabetic mice through modulation of the PI3K/Akt/FoxO1 pathway.
研究领域:
药理学
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民族药理学
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网络药理学
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糖尿病研究
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细胞生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）