JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2022
·Vol. 36
·期 7
·e24406
·
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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Chinese Journal of Natural Medicines
·
2025
·
IF 4.9
Lushan Xu,Chenggang Li,ChenChen Zhao,Zibu Wang,Zhi Zhang,Xin Shu,Xiang Cao,Shengnan Xia,Xinyu Bao,Pengfei Shao,Yun Xu
Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro . Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
研究领域:
神经科学
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药理学
·
免疫学
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PubMed
高影响因子
BURNS
·
2024
·
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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FITOTERAPIA
·
2025
·
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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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 19
·55200-55213
·
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
·
渔业
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BIOMEDICINE & PHARMACOTHERAPY
·
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
·
中药学
·
细胞生物学
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分子生物学
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BIOORGANIC CHEMISTRY
·
2021
·
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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Aging-US
·
2020
·
IF 4.831
Yan Sun,Shiting Dai,Jin Tao,Yunlong Li,Ziqi He,Quan Liu,Jiawen Zhao,Yaoliang Deng,Juening Kang,Xuepei Zhang,Sixing Yang,Yunlong Liu
Oxidative stress and autophagy are the key promoters of calcium oxalate (CaOx) nephrolithiasis. Taurine is an antioxidant that plays a protective role in the pathogenesis of kidney disease. Previous studies found that taurine suppressed cellular oxidative stress, and inhibited autophagy activation. However, the effect of taurine on CaOx kidney stone formation remains unknown. In the present work, we explored the regulatory effects of taurine on CaOx crystals-induced HK-2 cell injury. Results showed that pretreatment with taurine significantly enhanced the viability of HK-2 cells and ameliorated kidney tissue injury induced by CaOx crystals. Taurine also markedly reduced the levels of inflammatory cytokines, apoptosis, and CaOx crystals deposition. Furthermore, we observed that taurine supplementation alleviated CaOx crystals-induced autophagy. Mechanism studies showed that taurine reduced oxidative stress via increasing SOD activity, reducing MDA concentration, alleviating mitochondrial oxidative injury, and decreasing the production of intracellular ROS. Taurine treatment also effectively activated Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cells both in vitro and in vivo . In summary, the current study shows that taurine inhibits ROS-dependent autophagy via activating Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cell and kidney injury, suggesting that taurine may serve as an effective therapeutic agent for the treatment of CaOx nephrolithiasis.
研究领域:
肾病学
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细胞生物学
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分子生物学
·
药理学
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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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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Helin Chen,Yanyan Wang,Jie Luo,Min Kang,Jin Hou,Ruoping Tang,Ling Zhao,Fei Shi,Gang Ye,Xiaoli He,Hengmin Cui,Hongrui Guo,Yinglun Li,Huaqiao Tang
Nano-copper has been increasingly employed in various products. In previous studies, we showed that nano-copper caused damage in the rat testis, but it remains unclear whether the toxic reaction can affect the reproductive function. In this study, following 28 d of exposure to nano-copper at a dose of 44, 88, and 175 mg/kg/day, there was a decrease in sperm quality, fructose content, and the secretion of sex hormones. Nano-copper also increased the level of oxidative stress, sperm malformation rate, and induced abnormal structural changes in testicular tissue. Moreover, Nano-copper upregulated the expression of apoptosis-related protein Bax and autophagy-related protein Beclin, and downregulated the expression of Bcl2 and p62. Furthermore, nano-copper (175 mg/kg) downregulated the protein expression of AMPK, p-AKT, mTOR, p-mTOR, p-4E-BP1, p70S6K, and p-p70S6K, and upregulated the protein expression of p-AMPK. Therefore, nano-copper induced damage in testicular tissues and spermatogenesis is highly related to cell apoptosis and autophagy by regulating the Akt/mTOR signaling pathway. In summary, excess exposure to nano-copper may induce testicular apoptosis and autophagy through AKT/mTOR signaling pathways, and damage the reproductive system in adult males, which is associated with oxidative stress in the testes.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
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AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
·
2019
·Vol. 316
·期 2
·C198
·
IF 3.553
Zhen Luo,Xue Xu,Takami Sho,Jing Zhang,Weina Xu,Jianbo Yao,Jianxiong Xu
Significant embryo loss remains a serious problem in pig production. Reactive oxygen species (ROS) play a critical role in embryonic implantation and placentation. However, the potential mechanism of ROS on porcine trophectoderm (pTr) cell fate during the peri-implantation period has not been investigated. This study aimed to elucidate the effects of ROS on pTr cell phenotypes and the regulatory role in cell attachment and differentiation. Herein, results showed that exogenous H2O2 inhibited pTr cell viability, arrested the cell cycle at S and G2/M phases, and increased cell apoptosis and autophagy protein light chain 3B and Beclin-1, whereas these effects were reversed by different concentrations of N-acetyl-l-cysteine (NAC) posttreatment. In addition, NAC abolished H2O2-induced autophagic flux, inhibited intracellular and mitochondrial ROS, and restored expression of genes important for mitochondrial DNA and biogenesis, cell attachment, and differentiation. NAC reversed H2O2-activated MAPK and Akt/mammalian target of rapamycin pathways in dose-dependent manners. Furthermore, analyses with pharmacological and RNA interference approaches suggested that autophagy regulated cell apoptosis and gene expression of caudal-related homeobox 2 and IL-1β. Collectively, these results provide new insights into the role of the ROS-induced autophagy in pTr cell apoptosis, attachment, and differentiation, indicating a promising target for decreasing porcine conceptus loss during the peri-implantation period.
研究领域:
生殖生物学
·
细胞生物学
·
分子生物学
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Journal of Integrative Neuroscience
·
2021
·Vol. 20
·期 1
·67-75
·
IF 2.117
Dong-Xing Liu,Di Zhang,Wei-Min Hu,Yan-Fang Chang,Xiao-Hui Wang,Lin Li
Overactivation of the PI3-K/Akt/mTOR signaling pathway and inhibition of autophagy in the brain are involved in Alzheimer’s disease. The present paper’s goal was to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. We treated the human neuroblastoma SH-SY5Y cell line with Aβ1-42 as an Alzheimer’s disease in vitro model to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. Further, SH-SY5Y cells damaged by Aβ1-42 were treated with geniposide. Akt/mTOR-related proteins and autophagy-associated proteins were measured to reveal the molecular mechanisms by which geniposide protects against Aβ1-42-induced toxicity. Results showed that Akt and mTOR’s geniposide inhibited phosphorylation induced by Aβ1-42, enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by Aβ1-42. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against Aβ toxicity.
研究领域:
神经科学
·
药理学
·
细胞生物学
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高影响因子
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