Journal of Functional Foods
·
2020
·
IF 3.701
Fenfen Li,Danfei Huang,Weiyu Yang,Xiaozhen Liu,Shaoping Nie,Mingyong Xie
The preventive role of polysaccharide from the seeds of Plantago asiatica L. (PLCP) against reproductive system injury induced by nonylphenol (NP) was investigated. Male Sprague-Dawley rats were exposed orally to NP 1 h after PLCP intragastric administration continuously for 45 days. The results showed that NP induced significant decrease in relative weight of testes and epididymis, changed testicular histomorphology, and disrupted hormone secretions. Moreover, oxidative stress occurred after NP exposure by overproduction of Malondialdehyde, lipid peroxidation, inducible nitric oxide synthase, and low activities of superoxide dismutase and catalase. Furthermore, the induction of apoptosis and disturbance of PI3K/Akt/mTOR pathway by NP were also proved. Interestingly, PLCP alleviated NP toxicity by improving antioxidant enzymes, recovering hormone secretions, inhibiting apoptosis and autophagy, which involves PI3K/Akt/mTOR pathway. These findings provide a good direction that PLCP may be a good candidate to help body defend against toxic substance, particularly endocrine disrupting chemicals induced reproductive toxicity.
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高影响因子
CHEMICAL PAPERS
·
2024
·Vol. 78
·期 14
·7943-7950
·
IF 2.1
Li Zhigang,Liu Xuzhuo,Wang Chunlong,Song Hanbing,Zhang Jie
In this study, we synthesized zinc selenide (ZnSe)-polyacrylamide (PAM) nanomaterials for their potential application in treating knee osteoarthritis (KOA). Initially, we characterized the newly prepared material through various techniques including Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption–desorption to confirm its identity as the desired product. The results demonstrated that ZnSe-PAM nanomaterial exhibited excellent water solubility, biocompatibility, and stability, along with a large surface area, making it suitable for use as a drug carrier. Subsequently, the material was loaded with the drug 1 to obtain ZnSe-PAM@1. Cellular and thermosensitive experiments were then conducted, revealing that this nanomaterial could facilitate drug release by generating heat, thereby reducing the level of microRNA-146a-5P and blocking the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/extracellular (PI3K/Akt/mTOR/ERK) signal-regulated kinase signaling pathway, thus alleviating the symptoms of KOA. These findings present a new direction for drug intervention in KOA and highlight the potential of developing ZnSe-PAM nanomaterials as novel drug carriers.
研究领域:
材料科学
·
医学
·
生物技术
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.1
Shaoying Gong,Tianju Yang,Ruoyu Wu,Qinghai Sheng,Tangwei Zhang,Ming Xiao,Miao Wang,Yongxin She,Jing Wang,A.M. Abd El-Aty
Nonylphenol (NP) is known to damage the intestinal epithelial barrier (IEB), although its mechanisms remain unclear. Arabinogalactan (AG) is a natural polysaccharide with intestinal protective properties. This study explored the mechanisms of NP-induced IEB damage and evaluated the protective potential of AG in a Caco-2 cell monolayer model. The results revealed that NP induces inflammation and oxidative stress through the PI3K/AKT/mTOR signaling pathway, thereby inhibiting tight junction (TJ) gene and protein expression and ultimately leading to IEB damage. Conversely, AG enhanced TJ expression and suppressed inflammation and oxidative stress by activating the PI3K/AKT/mTOR signaling pathway, thus alleviating NP-induced IEB damage. This research provides new insights into the molecular mechanisms of NP-induced IEB damage and highlights the potential of AG as a functional food ingredient for promoting intestinal health. Moreover, our study provides a theoretical basis for supporting policies aimed at restricting NP residues in food and offers a potential dietary reference for high-risk populations exposed to NP-contaminated environments.
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高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2020
·Vol. 393
·期 9
·1739-1752
·
IF 2.05
Song Lin,Yao Lifen,Zhang Limei,Piao Zhongyuan,Lu Yichan
Autophagy, a lysosomal degradative pathway, is crucial for the pathogenesis of Alzheimer’s disease (AD). Schizandrol A (SchA) shows multiple pharmacological effects. However, the potential effects and mechanisms of SchA on amyloid-β (Aβ)-induced autophagy remain unclear. In this study, differentiated SH-SY5Y cells or primary hippocampal neurons were pretreated with SchA (2 μg/ml) for 1 h before subjected to Aβ 1–42 (10 μM) for 24 h to test its effects on cell viability, apoptosis, oxidative stress, and autophagy. Then an mTOR inhibitor (rapamycin) and a PI3K inhibitor (LY294002) were employed to explore the role of PI3K/AKT/mTOR pathway. The results showed that SchA significantly inhibited Aβ 1–42 -triggered reduction of viable cells, increases of apoptotic cell number and pro-apoptotic protein expressions, as well as alterations of oxidative stress markers. In addition, the increases of LC3-II/LC3-I and Beclin-1 and decrease of p62 were suppressed by SchA. At the molecular level, we found that the inactivation of PI3K/AKT/mTOR pathway was ameliorated by SchA. Inhibition of PI3K/AKT/mTOR pathway deteriorated the protective effects of SchA against Aβ 1–42 -induced autophagy activation, cell death, and apoptosis. In conclusion, we demonstrate that SchA attenuates Aβ 1–42 -induced autophagy through activating PI3K/AKT/mTOR signaling pathway. SchA may be a novel drug for the prevention and treatment of AD.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Jihang Dai,Yu Sun,Duoyun Chen,Yaxin Zhang,Lianqi Yan,Xiaolei Li,Jingcheng Wang
Fibroblasts excessive proliferation was considered as a decisive reason for epidural fibrosis , which was known as a serious complication of lumbar laminectomy. As a traditional Chinese medicine , triptolide (TP) was used to be proved effective in preventing several fibrosis scar formation diseases. However, little is known about the effect of TP on preventing epidural fibrosis and its possible mechanism. Here, we performed in vitro and in vivo experiments to detect the possible mechanism of TP in preventing epidural fibrosis. In vitro, the effect of TP on impacting fibroblasts proliferation activities was detected by CCK-8, cell cycle assay and EdU incorporation assay. Also, the expressions of cell proliferation protein markers and the expressions of p-PI3K, p-AKT, p-mTOR were detect by Western blot . Besides, the effect of TP on inducing fibroblast apoptosis and autophagy was tested by Western blots, flow cytometry, TUNEL staining , Transmission electron microscope (TEM) analysis and LC3 immunofluorescent staining. The results suggested that TP could suppress the activation of PI3K/AKT/mTOR signaling pathway. Meanwhile, TP could inhibit fibroblast proliferation and induce fibroblast apoptosis as well as autophagy, which was known as two cellular self-destructions. Furthermore, we speculated the possible molecular pathway, through which that TP could inhibit fibroblast proliferation, induce fibroblast apoptosis and autophagy. We used PI3-kinase activator (740Y-P) to activate the PI3K/AKT/mTOR signaling. Activation of PI3K/AKT/mTOR signaling pathway increase the proliferation of fibroblasts and suppressed the autophagy and apoptosis induced by TP. In vivo, we built epidural fibrosis models in rats and locally applied TP of various concentrations. Hematoxylin–eosin (HE) and Masson's trichrome were used to detect the effect of TP on reducing epidural fibrosis. And the results showed that TP could significantly reduce the surgery-induced epidural fibrosis. In conclusion, the results above shown that TP could reduce epidural fibrosis formation, and the potential mechanism might through inhibiting fibroblast proliferation and stimulating apoptosis and autophagy via suppressing PI3K/AKT/mTOR signaling pathway. It might provide a novel thought for reducing surgery-induced epidural fibrosis.
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高影响因子
MOLECULES
·
2024
·Vol. 29
·期 17
·3990
·
IF 4.2
Shuang Tian,Yinxu Zhao,Siqi Deng,Liman Hou,Juan Song,Ming Wang,Ming Bu
In the following study, a series of new lupeol-3-carbamate derivatives were synthesized, and the structures of all the newly derived compounds were characterized. The new compounds were screened to determine their anti-proliferative activity against human lung cancer cell line A549, human liver cancer cell line HepG2, and human breast cancer cell line MCF-7. Most of the compounds were found to show better anti-proliferative activity in vitro than lupeol. Among them, obvious anti-proliferation activity (IC50= 5.39~9.43 μM) was exhibited by compound3iagainst all three tumor cell lines. In addition, a salt reaction was performed on compound3k(IC50= 13.98 μM) and it was observed that the anti-proliferative activity and water solubility of compound3k·CH3I(IC50= 3.13 μM), were significantly enhanced subsequent to the salt formation process. The preliminary mechanistic studies demonstrated that apoptosis in HepG2 cells was induced by compound3k·CH3Ithrough the inhibition of the PI3K/AKT/mTOR pathway. In conclusion, a series of new lupeol-3-carbamate derivatives were synthesized via the structural modification of the C-3 site of lupeol, thus laying a theoretical foundation for the design of this new anticancer drug.
研究领域:
药理学
·
肿瘤学
·
药物化学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yawen Yu,XinLiu Duan,Xiaorong Wang,Mingyan Yang,Ling Weng,Dalei Li,Teng Liu,Baifang Gong,Zhixia Wang,Huaying Fan
Ginseng-derived exosome-like nanoparticles (GENs) have been considered as new candidates for tumor therapy. However, maintaining the retention and stability of exosomes in vivo is a major challenge in clinical application of GENs. Here, we prepared hydrogels using modified hyaluronic acid (HA) and carboxymethyl chitosan (CMCS). We investigated whether the combination of GENs with hydrogels could improve the stability of GENs and enhance their retention in tumor tissues, thereby enhancing their tumor therapeutic effect. In vitro experiments showed that hydrogels significantly increased the uptake of GENs by cells and increased tumor apoptosis rate. In vivo experiments showed that hydrogels significantly increased the retention of GENs in tumor tissues and improved the antitumor ability of GENs. Meanwhile, we evaluated the anti-tumor mechanism of GENs. The results showed that GENs and GENs@Hydrogels induced 4T1 cell apoptosis through the PTEN/PI3K/Akt/mTOR pathway and caspase-dependent pathway. In addition, GENs and GENs@Hydrogels down-regulate PD-L1 level in tumor tissues, up-regulate MHC-I level, and increase the abundance of CD8+T cells, which have immune regulation ability. In conclusion, GENs@Hydrogels has been shown to be a successful candidate for the treatment of breast cancer (BC) with its promising potential to modulate immunity and inhibit tumor progression.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
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高影响因子
MOLECULAR BIOLOGY
·
2024
·
IF 1.5
Yang S. J.,Ying J. L.,Xie W. J.
Abstract Microglia phagocytosis plays an important role in the pathogenesis of neurodegeneration. Defects or dysfunction of microglia phagocytosis were observed in neurodegenerative diseases, with different targets and associated receptors influencing the microglia response. Moreover, non-canonical LC3-associated (microtubule-associated protein 1 light chain 3) phagocytosis was extensively studied recently as a novel form of phagocytosis on macrophages, but little on microglia. Here, we investigated changes in phagocytic function of microglia activated by lipopolysaccharide (LPS) as well as rapamycin-regulated phagocytosis. Phagocytosis in mouse BV2 cells and primary microglia was analyzed by flow cytometry and immunofluorescence. Phagocytosis-related mechanisms in BV2 cells were analyzed using Western blotting and real-time polymerase chain reaction. Rapamycin was shown to reduce LPS-induced phagocytosis of microglia and at the same time stimulate LС3-dependent phagocytosis by regulating Atg3 , Atg4 and Atg7 expression. In addition, in BV2 cells, the PI3K/AKT/mTOR pathway may be involved in phagocytosis. These results suggest that phagocytosis of microglia is a complex process, and the increase in phagocytosis should not be considered as a maturation of phagocytic function. The data will provide new insights into the mechanisms of phagocytosis and neuroimmunity.
研究领域:
神经科学
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免疫学
·
细胞生物学
·
药理学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Qiang Chu,Meng Chen,Dongxiao Song,Xixi Li,Yunyun Yang,Zihuan Zheng,Yonglu Li,Yangyang Liu,Lushuang Yu,Zheng Hua,Xiaodong Zheng
Oxidative stress is a critical cause for the progression of neurodegenerative diseases, indicating that screening natural antioxidant and pharmacological targeting of mechanism need more attention. Natural plant polysaccharides are the primary group of natural antioxidants showing mighty antioxidant activity. Therefore, a polysaccharide (AFP-2) from flowers of Apios americana Medik was isolated, purified and characterized. Then, a H 2 O 2 -induced PC12 cells oxidative stress model was established to investigate the neuroprotective role of AFP-2 and to clarify the potential mechanism of action against H 2 O 2 -induced neurotoxicity. It was found that AFP-2 reduced ROS production and mitochondrial damage caused by hydrogen peroxide in PC12 cells. In addition, data from transmission electron microscope and western blot displayed that AFP-2 significantly activated autophagy in PC12 cells via Akt-mTOR pathway. These results together qualify AFP-2 as an interesting natural polysaccharide worth further investigation as a neuroprotective agent.
研究领域:
神经科学
·
药理学
·
分子生物学
·
天然产物化学
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PubMed
高影响因子
STEROIDS
·
2020
·
IF 1.948
Jingwen Xu,Mingmei Zhang,Xiaoying Lin,Yihai Wang,Xiangjiu He
Allium chinense , as a side dish on Asian table, is often used in folk medicine for its health benefits. (25R)-5α-spirostan-3β-yl-3-O-acetyl-O-β- d -glucopyranosyl-(1 → 2)-O-[β- d -glucopyranosyl-(1 → 3)]-O-β- d -glucopyranosyl-(1 → 4)-β- d -galactopyranoside (A-24) is a bioactive steroidal saponin isolated from Allium chinense . Previously, we have shown that A-24 has cytotoxic effects on cancer cells, but not on normal cells. To further explore the underlying mechanisms, in this study, we investigated the anticancer activity of A-24 in human gastric cancer cell lines in terms of cell proliferation, colony formation, cell cycle, induction of apoptosis/autophagy, and PI3K/Akt/mTOR pathway. A-24 showed dose-dependent cytotoxicity in SGC-7901 and AGS cell lines, it induced intrinsic mitochondrial pathway of apoptosis as well as autophagy, G2/M phase arrest and modulation of cyclinB1, p-cdc2, p-wee1 and p-Histone H3 expression. Furthermore, A-24 downregulated the phosphorylation of Akt at Ser473 and mTOR at Ser2448 in PI3K/Akt/mTOR pathway, and its downstream substrates p-p70S6K and p-4EBP1 in a dose-dependent manner. In addition, the pre-treatment of tumor cells with 3-methyladenine (3-MA) and LY294002 increased A-24-induced apoptosis. Collectively, these findings highlight the significance of downregulation of PI3K/Akt/mTOR pathway in A-24-induced apoptosis and autophagy, and the potential application of A-24 as a novel candidate in the treatment of human gastric adenocarcinoma.
研究领域:
药理学
·
肿瘤学
·
细胞生物学
·
分子生物学
·
生物化学
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PubMed
高影响因子
CURRENT CANCER DRUG TARGETS
·
2022
·Vol. 22
·期 1
·86-95
·
IF 2.907
Yiyan SongYang,Yang Songyisha,Li Dejia,Li Wen
Background: Non-Small-Cell Lung Cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of all lung cancer cases and resulting in high morbidity and mortality. Previous studies have demonstrated that 1,25-dihydroxy-vitamin-D3 (vitamin D) exhibited
anti-cancer activity against breast and prostate cancer. Objectives: The aim of the current study is to investigate the effect of vitamin D on NSCLC and its underlying mechanism. Methods: The effects of vitamin D on stemness maintenance and the Warburg effect in NSCLC cells were
investigated both in vitro and in vivo. Results and Discussion: In vitro experiments revealed that vitamin D inhibited glycolysis and stemness maintenance in A549 and NCI-H1975 cells. Both in vitro and in vivo experiments indicated that vitamin D attenuated the expression of metabolism-related
enzymes associated with the Warburg effect (GLUT1, LDHA, HK2, and PKM2). In addition, vitamin D down-regulated the expression of stemness-related genes (Oct-4, SOX-2, and Nanog) and the expression of PI3K, AKT, and mTOR. Conclusion: Overall, these findings suggest that vitamin D suppresses
the Warburg effect and stemness maintenance in NSCLC cells via the inactivation of PI3K/AKT/mTOR signaling, thereby inhibiting the progression of NSCLC. The current study indicates that vitamin D is a potential candidate in therapeutic strategies against NSCLC.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
·
细胞生物学
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PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2026
·
IF 4.6
Zhihui Jiang,Yufei Du,Yilin Zhu,Jingyan Wu,Shengming Ma,Shaoting Weng,Kunpeng Zhang
Dimethyl phthalate (DMP), a widespread environmental pollutant, poses serious risks to aquatic organisms. This study investigated the mechanisms of DMP-induced oxidative stress and autophagy in zebrafish gill tissues, and evaluated the protective effect of 1,8-cineole. Zebrafish models were established for DMP exposure alone, 1,8-cineole treatment alone, and combined exposure. Using histopathology, transmission electron microscopy, fluorescence staining, antioxidant enzyme activity assays, real-time quantitative PCR, and Western blot, we systematically analyzed the impacts of DMP on gill morphology, oxidative stress levels, autophagy-related gene and protein expression, and the PI3K/AKT/mTOR signaling pathway. Results revealed that DMP exposure significantly induced oxidative stress and autophagy in gill tissues and suppressed PI3K/AKT/mTOR pathway activity. In contrast, 1,8-cineole treatment effectively alleviated DMP-induced oxidative damage and autophagy activation, while partially restoring PI3K/AKT/mTOR signaling. This study is the first to demonstrate that 1,8-cineole mitigates DMP-induced autophagy injury in gills by modulating the PI3K/AKT/mTOR pathway, offering a theoretical foundation and a potential green strategy for protecting aquatic organisms from phthalate toxicity.
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高影响因子
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