European Review for Medical and Pharmacological Sciences
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2018
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IF 2.387
X. Lv,C.-Y. Li,P. Han,X.-Y. Xu
OBJECTIVE: MicroRNAs are a class of small non-coding RNAs that be involved in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the effects of miR-520a-3p in cell growth and metastasis.MATERIALS AND METHODS: The mimics and inhibitor of miR-520a-3p were used to identify the effects of miR-520a-3p on cell proliferation and apoptosis using methylthiazol tetrazolium (MTT) assay and flow-cytometric method, respectively. Transwell assay was used to evaluate the cell migration and invasion. The protein expression levels related PI3K/AKT/mTOR signaling pathways were measured by Western blot.RESULTS: The results showed that miR-520a-3p overexpression could significantly inhibit cell proliferation and induce apoptosis, suppress cell migration and invasion. MiR-520a-3p overexpression could markedly reduce the ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) compared with control. However, miR-520a-3p overexpression could increase caspase-3 expression compared with control group. After inhibited the expression of miR-520a-3p, the capacity of cell proliferation, migration and invasion were increased, cell apoptosis was inhibited compared with control group. The ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, MMP-2 and MMP-9 were increased compared with control group.CONCLUSIONS: Our study suggested that miR-520a-3p could suppress the NSCLC proliferation, migration and invasion through PI3K/AKT/mTOR signaling pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2019
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IF 4.825
Wensong Yao,Zhen Lin,Peiying Shi,Bing Chen,Gang Wang,Jianyong Huang,Yuxia Sui,Qicai Liu,Shaoguang Li,Xinhua Lin,Qicai Liu,Hong Yao
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and tends to have drug resistance. Delicaflavone (DLF), a novel anticancer agent of biflavonoid from Selaginella doederleinii Hieron , showed strong anti-CRC activities, which has not yet been reported. In this study, we investigated the effects and possible anti-CRC mechanism of DLF in vitro and in vivo . It was shown that DLF significantly inhibited the cells viability and induced G2/M phase arrest, apoptosis , the loss of mitochondrial membrane potential (Δψm), generation of ROS and increase of intracellular Ca 2+ in HT29 and HCT116 cells by MTT assay, TEM, flow cytometry and inverted fluorescence microscope. Western blot and qPCR assays results further confirmed DLF induced caspase-dependent apoptosis and inhibited PI3K/AKT/mTOR and Ras/MEK/Erk signaling pathways in CRC cells. Meanwhile, DLF significantly suppressed the tumor growth via activation of Caspase-9 and Caspase-3 protein and decrease of ki67 and CD34 protein without apparent side effects in vivo . In summary, these results indicated DLF induced ROS-mediated cell cycle arrest and apoptosis through ER stress and mitochondrial pathway accompanying with the inhibition of PI3K/AKT/mTOR and Ras/MEK/Erk signaling cascade. Thus DLF could be a potential therapeutic agent for CRC.
研究领域:
肿瘤学
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药理学
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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
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2026
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IF 4
Liu Hengxu,Xiong Rui,Zhang Shipeng,Zheng Quanyou,Lai Xiaodan
Fatigue is a widespread health problem, and abnormal autophagy in skeletal muscle cells is a key mechanism driving fatigue progression. The purpose of this study was to evaluate the effect of ginsenoside Rg3 (Rg3) on fatigue in ammonium chloride (NH 4 Cl)-induced C2C12 myoblasts cells and to elucidate its potential molecular mechanism. The potential anti-fatigue mechanism of Rg3 was predicted by network pharmacology and molecular dynamics simulations. C2C12 cells were treated with NH 4 Cl to construct an in vitro fatigue model and then treated with Rg3. CCK-8, live/dead staining, Giemsa staining, autolysosome staining, and Western blot were used to evaluate cell viability, myotube morphology, autophagic flow, and key protein expression. Network pharmacology analysis indicated that the anti-fatigue effect of Rg3 was associated with the PI3K/AKT/mTOR pathway-regulated autophagy. Molecular docking and molecular dynamics simulations confirmed that Rg3 binds strongly to PI3K. Cell experiments showed that Rg3 significantly attenuated cell death, myotube injury and abnormal autophagy in NH 4 Cl-induced C2C12 cells. Moreover, Rg3 effectively activated the PI3K/AKT/mTOR pathway. Our results indicated that the anti-fatigue effect of Rg3 may be associated with the attenuation of autophagy through activation of the PI3K/AKT/mTOR pathway. This provides a potential therapeutic candidate for fatigue intervention.
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高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
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2022
·Vol. 36
·期 7
·e24406
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IF 3.124
Zhihai Li,Qiaozhi Jin,Yana Sun
Background LINC00941 has been proved to be related to various tumors, but its relationship with laryngocarcinoma remains vague. Methods LINC00941 expression in laryngocarcinoma tumor and laryngocarcinoma cells was determined by real time-quantitative polymerase chain reaction (RT-qPCR). Besides, the five-year survival of laryngocarcinoma patients with different LINC00941 expression was analyzed with Kaplan–Meier survival analysis, and the clinical characteristics of laryngocarcinoma patients were also recorded. After transfection, cell viability, cell proliferation, apoptosis, cell cycle, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation, flow cytometry, cell scratch, and Transwell assays, respectively. Glycolysis was assessed by the colorimetric method. Expressions of proliferation-associated proteins, migration-associated proteins, glycolysis-associated proteins, and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signal pathway-associated proteins were detected by Western blot. Results In laryngocarcinoma tumor tissues and cells, LINC00941 was highly expressed. High expression of LINC00941 decreased the 5-year survival of laryngocarcinoma patients, and it was positively related to lymph node metastasis and clinical stages. LINC00941 overexpression decreased apoptosis but promoted cell viability, proliferation, cell-cycle progression, migration, and invasion, and glucose consumption and lactate production in laryngocarcinoma cells. Moreover, LINC00941 overexpression elevated expressions of Ki-67, PCNA, MMP2, N-Cadherin, HK2, PFKFB4, and PKM, activated the PI3K/AKT/mTOR signal pathway but reduced E-Cadherin expression, while LINC00941 silencing had the opposite effects. PKM overexpression reversed the effects of LINC00941 silencing on cellular and glycolytic phenotypes. Conclusion LINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma cells by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway.
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PubMed
高影响因子
BURNS
·
2024
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IF 3.2
Meiyue Yang,Zhibo Yang,Xiangjun Huang,Xiaoping Li,Fangqin Chou,Shuiqing Zeng
The aim of this study was to explore the effect and mechanism of formononetin (FMNT) in thermal-injured fibroblast proliferation, apoptosis, and oxidative stress. After the thermal injury, HSF cells showed inhibited proliferation, migration, and ECM synthesis, whereas increased apoptosis, ROS production, and inflammation. Specifically, after thermal injury, cell viability, migration distance, and protein levels of Collage I, Collage III, α-SMA, MMP1, and MMP3 were reduced; cell apoptosis rate and TUNEL-positive cell numbers were increased; the levels of Bax and Cleaved caspase-3 showed to be elevated, while Bcl-2 level showed to be reduced. Moreover, the thermal injured-HSF cells showed increased levels of ROS, MDA, LDH, TNF-α, and IL-1β, and decreased GSH, SOD, GSH-Px, and CAT. FMNT levels can partially eliminate the effects of thermal injury on HSF cells, as shown by promoting thermal injured-HSF cell proliferation and migration, and inhibiting cell apoptosis, ROS production, and inflammation. FMNT exerted no significant effect on normal HSF cells. Additionally, the level of the P13K/AKT/mTOR signaling-related proteins (p-P13K, p-AKT, and p-mTOR) was reduced in thermal injured-HSF cells, whereas FMNT could promote p-P13K, p-AKT, and p-mTOR levels. FMNT can partially alleviate the thermal injury-induced inhibition of fibroblast proliferation and migration; FMNT also inhibited the apoptosis, ROS level, and inflammation in thermal-injured cells. The effects of FMNT may be mediated by regulating the P13K/AKT/mTOR pathway.
研究领域:
药理学
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细胞生物学
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伤口愈合
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PubMed
高影响因子
FITOTERAPIA
·
2025
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IF 2.6
Ren-Fen Ma,Xin-Cheng Zhuang,Qian Wu,Hua Zhang
An intensive phytochemical study on the aerial parts of Euphorbia wallichii afforded ten lathyrane-type diterpenoids, including six formerly unreported ones ( 1 – 4 , 6 and 8 ). Their structures were determined via comprehensive spectroscopic analyses, and the absolute stereochemistries were assigned on the basis of electronic circular dichroism technique. Among these diterpenoids, compound 2 exhibited the best inhibitory activity on NO production and its potential anti-inflammatory mechanism was then explored by network pharmacology analysis. Further experimental validation demonstrated that diterpenoid 2 could exert its anti-inflammatory effect by suppressing pro-inflammatory factors and modulating PI3K/Akt/mTOR signaling pathway. In short, the present work confirms the promising potential of E. wallichii as a source of natural anti-inflammatory agents.
研究领域:
植物化学
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药理学
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药物化学
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天然产物研究
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高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 19
·55200-55213
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IF 5.8
Feng Huimiao,Zhou Ping,Liu Feixue,Zhang Wei,Yang Haitao,Li Xueqing,Dong Jingquan
Abamectin is a commonly used pesticide in agriculture and fisheries and poses a risk to aquatic species. However, the mechanism of its toxic effects on fish remains to be discovered. In this study, we explored the effects of abamectin exposure at different concentrations on the respiratory system of carp. Carp were divided into three groups, namely the control group, low-dose abamectin treatment group, and high-dose abamectin treatment group. Gill tissue was collected after abamectin exposure for histopathological, biochemical, tunnel, mRNA, and protein expression analysis. Histopathological analysis indicated that abamectin damaged the gill structure. Biochemical analysis showed that abamectin triggered oxidative stress with lowered antioxidant enzyme activities and increased MDA content. Moreover, abamectin led to enhanced INOS levels and pro-inflammatory transcription, activating inflammation. Tunnel results demonstrated that exposure to abamectin induced gill cell apoptosis through an exogenous pathway. In addition, exposure to abamectin activated the PI3K/AKT/mTOR pathway, leading to inhibition of autophagy. Overall, abamectin caused respiratory system toxicity in carp via triggering oxidative stress, inflammation, and apoptosis and inhibiting autophagy. The study suggests that abamectin has a profound toxicity mechanism in the respiratory system of carp, contributing to a better understanding of pesticide risk assessment in aquatic systems.
研究领域:
水生毒理学
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环境科学
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渔业
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
·
IF 7.5
Tao Long,Xue Chen,Yue Zhang,Yu-Jia Zhou,Yan-Ni He,Yun-Fei Zhu,Hai-Jun Fu,Lu Yu,Chong-Lin Yu,Betty Yuen-Kwan Law,Jian-Ming Wu,Da-Lian Qin,An-Guo Wu,Xiao-Gang Zhou
Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae , a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans . Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.
研究领域:
神经科学
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药理学
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中药学
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细胞生物学
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分子生物学
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PubMed
高影响因子
American Journal of Translational Research
·
2025
·Vol. 17
·期 10
·7749
·
IF 1.6
Xiaowen Li,Ruikang Guo,Lingling Liang,Hao Liang,Guangqi Zhou,Qinglan Lu,Yonghui Huang,Zhen Qi,Xiaojie Li
Objective: Periodontitis, a prevalent oral disease leading to alveolar bone defects, remains a primary cause of tooth loss in adults. The biologic mechanisms driving bone loss in periodontitis are still poorly understood, limiting the development of genetic treatment. This study investigates potential therapeutic targets for alveolar bone loss by analyzing transcriptomic data related to the osteogenic differentiation of induced pluripotent stem cells (iPSCs). Methods: Using in vitro and in vivo models, we examined the role of neuropeptide Y receptor Y1 (NPY1R) and the PI3K-AKT-mTOR (PAM) signaling pathway in osteogenic differentiation and bone loss. A combination of bioinformatics, molecular biology, and histologic techniques was employed to pinpoint key signaling events that influence bone remodeling in periodontitis and to identify potential intervention points. Results: Transcriptomic profiling during iPSC osteogenic differentiation revealed significant upregulation of neuropeptide Y (NPY) and NPY1R. Suppression of NPY1R reduced the osteogenic capacity of iPSCs. Activation of the PAM pathway was observed during osteogenesis, and treatment with LY294002, a PAM pathway inhibitor, led to decreased osteogenic activity. In vivo experiments using a rat periodontitis model confirmed increased expression of NPY1R and activation of the PAM pathway, suggesting a role in bone repair processes. Conclusion: The NPY/NPY1R axis and the PAM signaling pathway appear to regulate bone regeneration and may be involved in preventing alveolar bone loss in periodontitis. These findings provide a new direction for therapy targeting bone defects associated with periodontal disease.
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高影响因子
BIOORGANIC CHEMISTRY
·
2021
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IF 5.275
Yingying Ma,Xiaorong Yang,Hongwei Han,Zhongling Wen,Minkai Yang,Yahan Zhang,Jiangyan Fu,Xuan Wang,Tongming Yin,Guihua Lu,Jinliang Qi,Hongyan Lin,Xiaoming Wang,Yonghua Yang
Triple-negative breast cancer (TNBC) has an unfavorable prognosis attribute to its low differentiation, rapid proliferation and high distant metastasis rate. PI3K/Akt/mTOR as an intracellular signaling pathway plays a key role in the cell proliferation, migration, invasion, metabolism and regeneration. In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Through three rounds of screening by computer-aided drug design method (CADD), we preliminarily obtained sixteen novel anilide (dicarboxylic acid) shikonin esters and identified them as excellent compounds. CCK-8 assay results demonstrated that compound M9 exhibited better antiproliferative activities against MDA-MB-231, A549 and HeLa cell lines than shikonin (SK), especially for MDA-MB-231 (M9: IC 50 = 4.52 ± 0.28 μM; SK: IC 50 = 7.62 ± 0.26 μM). Moreover, the antiproliferative activity of M9 was better than that of paclitaxel. Further pharmacological studies showed that M9 could induce apoptosis of MDA-MB-231 cells and arrest the cell cycle in G2/M phase. M9 also inhibited the migration of MDA-MB-231 cells by inhibiting Wnt/β-catenin signaling pathway. In addition, western blot results showed that M9 could inhibit cell proliferation and migration by down-regulating PI3K/Akt/mTOR signaling pathway. Finally, a three-dimensional quantitative structure–activity relationship (3D-QSAR) model was also constructed to provide a basis for further development of shikonin derivatives as potential antitumor drugs through structure–activity relationship analysis. To sum up, M9 could be a potential candidate for TNBC therapy.
研究领域:
药理学
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肿瘤学
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药物化学
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细胞生物学
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药物设计
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PubMed
高影响因子
Molecular Cancer
·
2023
·Vol. 22
·期 1
·1-20
·
IF 37.3
Song Runjie,Ma Shuoqian,Xu Jiajia,Ren Xin,Guo Peilan,Liu Huijiao,Li Peng,Yin Fan,Liu Mei,Wang Qiang,Yu Lei,Liu Jiali,Duan Binwei,Rahman Nafis A.,Wołczyński Sławomir,Li Guangming,Li Xiangdong
Background hsa_circ_0001727 (circZKSCAN1) has been reported to be a tumor-associated circRNA by sponging microRNAs. Intriguingly, we found that circZKSCAN1 encoded a secretory peptide (circZKSaa) in the liver. The present study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression.Methods The circRNA profiling datasets (RNA-seq data GSE143233 and GSE140202) were reanalyzed and circZKSCAN1 was selected for further study. Mass spectrometry, polysome fractionation assay, dual-luciferase reporter, and a series of experiments showed that circZKSCAN1 encodes circZKSaa. Cell proliferation, apoptosis, and tumorigenesis in nude mice were examined to investigate the functions of circZKSaa. Mechanistically, the relationship between the circZKSaa and mTOR in HCC was verified by immunoprecipitation analyses, mass spectrometry, and immunofluorescence staining analyses.Results Receiver operating characteristic (ROC) analysis demonstrated that the secretory peptide circZKSaa encoded by circZKSCAN1 might be the potential biomarker for HCC tissues. Through a series of experiments, we found that circZKSaa inhibited HCC progression and sensitize HCC cells to sorafenib. Mechanistically, we found that the sponge function of circZKSCAN1 to microRNA is weak in HCC, while overexpression of circZKSaa promoted the interaction of FBXW7 with the mammalian target of rapamycin (mTOR) to promote the ubiquitination of mTOR, thereby inhibiting the PI3K/AKT/mTOR pathway. Furthermore, we found that the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5.Conclusion sThese results reveal that a novel circZKSCAN1-encoded peptide acts as a tumor suppressor on PI3K/AKT/mTOR pathway, and sensitizes HCC cells to sorafenib via ubiquitination of mTOR. These findings demonstrated that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.
研究领域:
分子生物学
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癌症研究
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遗传学
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高影响因子
PSYCHONEUROENDOCRINOLOGY
·
2025
·
IF 3.6
Zhaoke Ling,Qingqing Kong,Zhiqiang He,Xin Hao,Ruiyao Liu,Jie Liu,Yushi Wang,Jiao Liu,Wenlong Du,Yi Liu
The pathogenesis of depression is associated with synaptic impairment and dysfunction in autophagy processes. Mendelian randomization (MR) analysis revealed that six GWAS IDs revealed a significant association between Beclin-1 levels and depression risk. Besides, all SNPs had a positive effect on depression risk. Analyzing neurons from depressed individuals using single-cell RNA sequencing (scRNA-seq) uncovered decreased expression of AKT, mTOR, and genes linked to synaptic plasticity. The activation of the PI3K/AKT/mTOR signaling has been demonstrated to control autophagy and have a protective effect on the nervous system. Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter that can potentially treat various neurological disorders by improving neuronal synaptic plasticity. However, whether H 2 S regulates autophagy through PI3K/AKT/mTOR signaling, improves neuronal synaptic plasticity damage, and plays an antidepressant role is unclear. Our current research revealed that the reduction in the expression of p-PI3K, p-AKT, and p-mTOR proteins increase in neuronal autophagy activity and decline synaptic plasticity in mice with depression induced by chronic unpredictable mild stress (CUMS). Treatment with the exogenous hydrogen sulfide donor NaHS for one day and continuous treatment for one week improved the depression-like behaviors in the mice. Compared with those after one day of NaHS treatment, the above protein expression levels were restored and maintained, and the antidepressant effect was more significant after one week of continuous treatment with NaHS. Moreover, the PI3K inhibitor LY294002 was used to demonstrate that NaHS suppresses autophagy through activating the PI3K/AKT/mTOR signaling and ameliorates synaptic plasticity impairments. This study provides novel insights into the antidepressant mechanisms of H 2 S, highlighting its antidepressant therapeutic potential.
研究领域:
神经科学
·
分子生物学
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药理学
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DOI
PubMed
高影响因子
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