查找使用阿拉丁产品的科研文献

Concanavalin A inhibits human liver cancer cell migration by regulating F‑actin redistribution and assembly via MAPK signaling pathway

Haoran Jiang,Xianxin Wen,Xue Zhang,Bingyu Zhang

Concanavalin A (Con A), the first and most typical representative of the legume lectin family, has a potent anti‑liver cancer effect by inducing cell apoptosis and autophagy. However, its function in human liver cancer cell migration remains unclear. The present study investigated the effect of Con A on the viability and migration of human liver cancer cells with different metastatic abilities. It was found that Con A could reduce the viability of human liver cancer cells (HCCLM3, MHCC97L and HepG2) and human hepatocytes (MIHA). In addition, Con A could inhibit human liver cancer cell migration specifically without affecting hepatocytes. Sugar inhibition assay showed that glucose‑related sugar binding sites played an important role in the inhibition of Con A on human liver cancer cell migration. In addition, Con A could affect HCCLM3 migration by activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway. Moreover, Con A could regulate fibrous actin (F‑actin) redistribution and assembly via the MAPK signaling pathway. However, Con A had no significant effect on the activation of matrix metalloproteinase (MMP)‑2 and MMP‑9 in HCCLM3 cells. In conclusion, Con A may bind to glucose‑related receptor protein, activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway, further contracting cells and reducing the content of F‑actin of single cells to inhibit HCCLM3 cell migration. These results would deepen the links between human liver cancer cell migration and related glycoproteins or signaling molecules, and may provide a new perspective for Con A as a potential anticancer agent.

Tea polyphenols alleviates acetochlor-induced apoptosis and necroptosis via ROS/MAPK/NF-κB signaling in Ctenopharyngodon idellus kidney cells

Xia Zhao,Xu Shi,Qingqing Liu,Xiaojing Li

Overuse of acetochlor pollutes soil and rivers, causing threats to the ecosystem. Studies found that acetochlor exposure could damage multiple organs and tissues in fish and mammal. Tea polyphenols (TP), a natural antioxidant that extracted from tea, has been widely used in food and feed additions. However, the mechanism by which acetochlor causes tissue damage is unclear, and its mitigating agent has yet to be developed. Therefore, we established acetochlor exposure and TP mitigation models by treating Ctenopharyngodon idellus kidney (CIK) cells with 20 μM acetochlor and/or 2.5 μg/mL TP for 24 h, and detected the programmed cell death and its related pathways. The results showed that acetochlor exposure modified antioxidant enzyme activities, induced oxidative stress, resulted in the decline of MMP and ATP levels, enhanced glycolysis and lactate accumulation, and triggered apoptosis and necroptosis in CIK cells. However, TP could inhibit CYP450s expression, activate Nrf2 pathway, enhance antioxidant capacity, further effectively alleviate acetochlor-induced CIK cell death. Overall, the present study proved that acetochlor exposure triggered mitochondrial damage and lactate accumulation-mediated apoptosis and necroptosis through CYP450s/ROS/MAPK/NF-κB pathway. Furthermore, TP could alleviate effectively cell death through relieving oxidative stress and lightening Warburg-like effect.

Integrated Identification of Macrophage NF-κB, p38 MAPK and AKT1 Signalling as Candidate Targets of Zerumbone in Experimental Periodontitis

Characterised by progressive alveolar bone loss, periodontitis arises from immune dysregulation and is classified as a chronic inflammatory condition. Zerumbone (Zer) has anti-inflammatory properties; however, its mechanism within the periodontal context remains unclear. We investigated the therapeutic effects and potential molecular targets of Zer by integratingin vivoefficacy assessment (using male C57BL/6 mice), network pharmacology, molecular docking, and molecular dynamics simulations, together with analysis of public single-cell transcriptomic data, with mechanistic validation using RAW 264.7 macrophages stimulated with LPS. In vivo, Zer attenuated bone resorption, preserved collagen integrity, reduced the number of TRAP-positive osteoclasts, and mitigated inflammation without hepatorenal toxicity. Network pharmacology predictedNFKB1,MAPK14, andAKT1as potential core targets, while IL-17 pathway enrichment suggested the involvement ofIL17A; single-cell data localisedNFKB1/MAPK14/AKT1to macrophages and showed thatIL17Ais predominantly expressed in T cells. In vitro, Zer dose-dependently suppressed LPS-driven phosphorylation of NF-κB p65, p38 MAPK and AKT1, correlating with reduced pro-inflammatory cytokine release and an M1-to-M2 phenotypic shift. In vivo, Zer also reduced gingival IL-17A expression. However, as IL-17A is primarily produced by T cells and our in vitro experiments were conducted exclusively in macrophages, this observation remains correlative and does not establish a direct T-cell-mediated effect. Collectively, these findings suggest that Zer ameliorates periodontitis partly through suppression of macrophage NF-κB and p38 MAPK signalling, with reduced AKT1 phosphorylation observed alongside these effects; however, whether AKT1 causally contributes to these effects remains to be determined. In addition, the potential impact on T-cell-associated IL-17A responses warrants further investigation.

Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

Wei Jiang,Tao Luo,Sheng Li,Yue Zhou,Xiu-Yin Shen,Feng He,Jie Xu,Hua-Qiao Wang

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.

Coenzyme Q10 prevents RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways

Zheng Delu,Cui Chenli,Ye Chengsong,Shao Chen,Zha Xiujing,Xu Ying,Liu Xu,Wang Can

Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.

Adolescent exposure to organophosphate insecticide malathion induces spermatogenesis dysfunction in mice by activating the HIF-1/MAPK/PI3K pathway

Shouchun Xiao,Jingna Cui,Yue Cao,Yaru Zhang,Jiaxing Yang,Li Zheng,Fanrong Zhao,Xueke Liu,Zhiqiang Zhou,Donghui Liu,Peng Wang

Chemical-caused reproductive dysfunction has emerged as a global public health concern. This study investigated the adverse effects of the organophosphorus pesticide malathion on reproductive function in adolescent male mice at environmentally relevant concentrations. The results indicated that eight-week malathion exposure reduced testis weight, caused sex and thyroid hormone disorders, and induced testicular spermatogenic epithelium damage and oxidative stress. Testicular RNA sequencing indicated that malathion significantly affected testicular energy metabolism, hypoxia-inducible factor 1 (HIF-1) signaling, and steroid hormone biosynthesis pathways. Malathion significantly increased the gene and protein expression of HIF-1α by upregulating key genes in the mitogen-activated protein kinase (MAPK) pathway ( Map2k2 , Mapk3 , and Eif4e2 ) and the phosphatidylinositol 3-kinase (PI3K) pathway ( Pik3r2 and Akt1 ). Furthermore, malathion downregulated HIF-1α degradation-regulating genes while upregulating anaerobic metabolism and inflammation-related genes, thereby inhibiting normoxia and promoting hypoxia processes. Testicular hypoxia subsequently induced steroid hormone biosynthesis disorders and spermatogenesis dysfunction. Molecular docking verified that malathion interfered with HIF-1α and steroid hormone synthases (CYP11A1, CYP17A1 and CYP19A1) by forming hydrogen bonds and hydrophobic interactions with these proteins. This study presents the first evidence that malathion triggers spermatogenesis dysfunction in mice through activating the HIF-1/MAPK/PI3K pathway, providing a comprehensive understanding of the reproductive toxicity risks associated with organophosphorus pesticides.

Polysaccharide from Ganoderma atrum delay senescence and enhance stress resistance through modulating IIS and MAPK pathway in Caenorhabditis elegans

Jiayan Xie,Mengni Shu,Xinyi Chen,Jianhua Xie,Yi Chen,Xiaobo Hu,Chunchao Nie,Danyan Liu,Qiang Yu

Ganoderma atrum is an edible and medicinal fungi in oriental countries with various bioactivities, such as antioxidant, anti-inflammatory and anti-aging properties. The study was to evaluate the effects of polysaccharide from Ganoderma atrum (PSG) on lifespan, healthspan (locomotion, pumping, lipofuscin, ROS, chemotaxis and intestinal permeability) and defense system (stress resistance, antioxidant enzymes activities), as well as to investigate its anti-aging mechanism in Caenorhabditis elegans . The findings indicated that PSG prolonged the lifespan (optimal concentration at 400 μg/mL, with an increased average lifespan by 23.10 %) and improved senescence-related physiological indicators of worms. Furthermore, the lipid accumulation was reduced, while stress resistance and antioxidant enzymes activities were enhanced after PSG intervention. Meanwhile, studies with mutants demonstrated that DAF-16/FOXO and SKN-1/Nrf-2 were required for lifespan-extension, which might be attributed to the IIS and MAPK pathways. Overall, these demonstrated that PSG was a potential dietary supplement to promote health and ameliorate aging-associated pathologies.

Phenethyl isothiocyanate inhibits the carcinogenic properties of hepatocellular carcinoma Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways

Jiao Du,Yuting Zhang,Jiajia Chen,Libo Jin,Liying Pan,Pengyu Lei,Sue Lin

Background Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatment options. Phenethyl isothiocyanate (PEITC) is a bioactive substance present primarily in the cruciferous vegetables. PEITC has exhibited anti-cancer properties in various cancers, including lung, bile duct, and prostate cancers. It has been demonstrated that PEITC can inhibit the proliferation, invasion, and metastasis of SK-Hep1 cells, while effectively inducing apoptosis and cell cycle arrest in HepG2 cells. However, knowledge of its anti-carcinogenic effects on Huh7.5.1 cells and its underlying mechanism remains elusive. In the present study, we aim to evaluate the anti-carcinogenic effects of PEITC on human HCC Huh7.5.1 cells. Methods MTT assay and colony formation assay was performed to investigate the anti-proliferative effects of PEITC against Huh7.5.1 cells. The pro-apoptosis effects of PEITC were determined by Annexin V-FITC/PI double staining assay by flow cytometry (FCM), mitochondrial transmembrane potential (MMP) measurement, and Caspase-3 activity detection. A DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was conducted to estimate the DNA damage in Huh7.5.1 cells induced by PEITC. Cell cycle progression was determined by FCM. Transwell invasion assay and wound healing migration assay were performed to investigate the impact of PEITC on the migration and invasion of Huh7.5.1 cells. In addition, transcriptome sequencing and gene set enrichment analysis (GSEA) were used to explore the potential molecular mechanisms of the inhibitory effects of PEITC on HCC. Quantitative real-time PCR (qRT-PCR) analysis was performed to verify the transcriptome data. Results MTT assay showed that treatment of Huh7.5.1 cells with PEITC resulted in a dose-dependent decrease in viability, and colony formation assay further confirmed its anti-proliferative effect. Furthermore, we found that PEITC could induce mitochondrial-related apoptotic responses, including a decrease of mitochondrial transmembrane potential, activation of Caspase-3 activity, and generation of intracellular reactive oxygen species. It was also observed that PEITC caused DNA damage and cell cycle arrest in the S-phase in Huh7.5.1 cells. In addition, the inhibitory effect of PEITC on the migration and invasion ability of Huh7.5.1 cells was assessed. Transcriptome sequencing analysis further suggested that PEITC could activate the typical MAPK, PI3K-Akt, and p53 signaling pathways, revealing the potential mechanism of PEITC in inhibiting the carcinogenic properties of Huh7.5.1 cells. Conclusion PEITC exhibits anti-carcinogenic activities against human HCC Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways. Our results suggest that PEITC may be useful for the anti-HCC treatment.

Luteolin attenuates experimental dry eye disease via dual modulation of macrophage JAK-STAT signaling and corneal epithelial MAPK pathways

Zhirui Du,Xueqiao Yan,Lin Cheng,Haiyu Shen,Guoguo Zhi,Baojie Li,Qian Yu

Background Dry eye disease (DED) is a multifactorial ocular condition marked by tear film instability, inflammation, and oxidative stress. Current therapies, including artificial tears and immunosuppressants, offer limited long-term benefit and potential side effects. Natural flavonoids such as luteolin possess anti-inflammatory and antioxidant properties, yet their therapeutic potential in DED remains underexplored. Purpose This study aimed to evaluate the therapeutic efficacy and mechanisms of luteolin in experimental DED. Methods Flavonoids were initially screened using lipopolysaccharide-stimulated RAW264.7 macrophages. A benzalkonium chloride-induced DED mouse model was treated with topical luteolin or cyclosporine A. Ocular surface evaluations included tear secretion, corneal fluorescein staining, and goblet cell density. Inflammatory and oxidative markers were examined via histology, immunofluorescence, and qPCR. RNA sequencing and network pharmacology were used to identify target pathways. In vitro studies with RAW264.7 cells and hyperosmolarity-stressed human corneal epithelial cells further validated mechanism-specific effects. Target engagement was further validated using pathway-specific pharmacological inhibitors. Ocular safety and pharmacokinetics were also assessed. Results Luteolin showed superior anti-inflammatory activity among tested flavonoids. It improved tear production, reduced epithelial damage, and preserved goblet cells. Mechanistically, it modulated macrophage-driven inflammation through JAK-STAT signaling and mitigated oxidative epithelial damage by suppressing the MAPK pathway. Transcriptomic and pharmacological analyses confirmed its dual immunomodulatory and cytoprotective roles. Combined STAT1/3 and MAPK inhibition mimicked its therapeutic effects. Topical luteolin was well-tolerated and achieved corneal bioavailability. Conclusions Luteolin provides a dual protective effect in DED by targeting inflammation and oxidative stress, supporting its development as a safe and effective disease-modifying therapy.

Duchesnea indica (Andr.) Focke extracts exerted anti-inflammatory effect via inhibiting MAPK/ERK pathway in LPS-stimulated RAW264.7 cells

Haipeng Feng,Qianqian Qiao,Jingyan Zhang,Kang Zhang,Lei Wang,Jianxi Li

Duchesnea indica (Andr.) Focke ( DIF ), a medicinal plant from the Rosaceae family, possesses therapeutic properties such as heat-clearing and detoxification, dispersion of stasis detumescence, blood-cooling, and hemostatic effect. The latest research unveiled a diverse array of pharmacologically active compounds from DIF, showcasing a broad spectrum of pharmacological effects. However, there was limited attention given to the comprehensive investigation of its high molecular weight compounds, particularly polysaccharides. In this study, DIF extracts were prepared by water-extraction and alcohol-precipitation method and the pharmacological effect was detected. The results demonstrated that the total polysaccharide content, reducing sugar content, total flavonoid content, and total polyphenol content in DIF extracts were 32.62 ± 0.91 %, 13.41 ± 0.18 %, 1.07 ± 0.07 %, and 12.16 ± 0.27 %, respectively. Although the total antioxidant activity of DIF extracts were significantly low than that of the vitamin C group, its ability to scavenge ABTS, DPPH, and superoxide anion radicals was similar to that of the vitamin C group. Furthermore, DIF extracts demonstrated significant inhibition on NO and MDA levels while simultaneously enhancing SOD activity in LPS-stimulated RAW264.7 cells. Finally, DIF extracts significantly reduced the mRNA level of pro-inflammation cytokines interleukin ( IL )-6, IL-1β, inducible nitric oxide synthase ( iNOS ), cyclooxygenase-2 ( COX-2 ) and tumor necrosis factor ( TNF ) -α , and directly inhibited the phosphorylation level of extracellular regulated kinase and mitogen-activated protein kinase ( ERK-MAPK ) pathway. Taken together, these results indicated that DIF extracts exhibited an anti-inflammatory and antioxidant effect in LPS-induced RAW264.7 mouse macrophages by directly inhibiting ERK-MAPK signaling pathway. Based on these findings, DIF extracts provided new insights into the treatment and prevention of diseases related to oxidative stress and inflammation.

The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells

Yang Yuan,Huang Jin,Li Jianzhong,Yang Huansheng,Yin Yulong

Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated. Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes. Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.

A novel finding relates to the involvement of ATF3/DOCK8 in Alzheimer's disease pathogenesis

Wenqiang Zhang,Fei Teng,Xifa Lan,Peihui Liu,Aiming Wang,Fan Zhang,Zhiqiang Cui,Jingwei Guan,Xiaohong Sun

BackgroundThe involvement of microglia is likely to be pivotal in the pathogenesis of Alzheimer's disease (AD) by modulating the deposition of amyloid-β (Aβ) plaques. The deletion of Dedicator of cytokinesis 8 (DOCK8) has a protective effect in mouse with neurodegenerative diseases.ObjectiveTo explore the underlying mechanism of DOCK8 in AD.MethodsIn present study, we first the detected the expression of DOCK8 in the hippocampal tissue of APP/PS1 mice. Then, the expression of DOCK8 was knocked down in the hippocampal tissue of APP/PS1 mice, and the effects of DOCK8 down-regulation on cognitive function, the microglia migration around Aβ plaques, and the cell division cycle 42 (Cdc42)/p38 mitogen-activated protein kinase (MAPK) signaling pathway were detected. Next, the effects of DOCK8 knockdown on Aβ-induced migration and activation of BV-2 cells as well as the MAPK signaling pathway were detected. Finally, the transcriptional regulation of DOCK by transcription factor 3 (ATF3) was detected by a dual luciferase reporter assay.ResultsDOCK8 expression exerts a significant upregulation in the hippocampus of APP/PS1 mice. However, following the DOCK8 knockdown, there was a significant recovery in the results of the behavioral tests and a notable reduction in microglial expression. Moreover, the high expression of DOCK8 mediated by ATF3 successfully triggered the Cdc42/p38 MAPK signaling pathway, thereby enhancing the migration and recruitment of microglia towards senile plaques, accelerating the production of Aβ plaques.ConclusionsATF3-mediated high expression of DOCK8 accelerates the production of Aβ plaques, and participates in the pathogenesis of AD.