OncoTargets and Therapy
·
2022
·
IF 4.345
Rong Wang,Danni Deng,Naiyuan Shao,Yuan Xu,Lian Xue,Ya Peng,Yatian Liu,Feng Zhi
Background Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced. Therefore, developing new agents to treat GBM is important.Aim This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved.Results According to MTT assay results, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner. Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner. Moreover, Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption. Finally, Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phosphorylation (p38 and JNK, but not ERK) to regulate apoptotic proteins (Bax, Bcl-2, Cytochrome c, Caspase-3, and PARP).Conclusion In summary, Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM; these results indicate that Evo may be regarded as a new approach for GBM treatment.
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Xiao-Ping Zhao,Xiao-Li Zheng,Min Huang,Ya-Jia Xie,Xiao-Wen Nie,Ali Adnan Nasim,Xiao-Jun Yao,Xing-Xing Fan
Although some important advances have been achieved in clinical and diagnosis in the past few years, the management of non-small cell lung cancer (NSCLC) is ultimately dissatisfactory due to the low overall cure and survival rates. Epidermal growth factor (EGFR) has been recognized as a carcinogenic driver and is a crucial pharmacological target for NSCLC. DMU-212, an analog of resveratrol, has been reported to have significant inhibitory effects on several types of cancer. However, the effect of DMU-212 on lung cancer remains unclear. Therefore, this study aims to determine the effects and underlying mechanism of DMU-212 on EGFR-mutant NSCLC cells. The data found that the cytotoxicity of DMU-212 on three EGFR-mutant NSCLC cell lines was significantly higher than that of normal lung epithelial cell. Further study showed that DMU-212 can regulate the expression of cell cycle-related proteins including p21 and cyclin B1 to induce G2/M phase arrest in both H1975 and PC9 cells. Moreover, treatment with DMU-212 significantly promoted the activation of AMPK and simultaneously down-regulated the expression of EGFR and the phosphorylation of PI3K, Akt and ERK. In conclusion, our study suggested that DMU-212 inhibited the growth of NSCLCs via targeting of AMPK and EGFR.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
Science Advances
·
2024
·Vol. 10
·期 10
·
IF 11.7
Liming Zheng,Sheng Zhao,Yixuan Li,Jiankun Xu,Wenjin Yan,Baosheng Guo,Jianbin Xu,Lifeng Jiang,Yifeng Zhang,Hui Wei,Qing Jiang
The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.
研究领域:
医学
·
生物材料学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Shuying Li,Hongbing Jiang,Kun Qiao,Wenjun Gui,Guonian Zhu
Silkworm ( Bombyx mori ) is one of the most important economic insects in the world, while pesticides impact its economic benefits. Tebuconazole is a fungicide that has been frequently detected in agriculture systems at concentrations that affect endocrine function in organisms. In the present study, silkworm larvae at different instar stages were exposed to tebuconazole, respectively. Cocoon weight, cocoon shell weight and cocoon shell rate were significantly decreased by 6.8%, 11.8% and 4.4% respectively, after exposure to 0.40 mg/L tebuconazole at 2nd -3rd instar stage. Vacuolization was found in the exposure silkworm under histopathological study at all stages exposures, indicating potential damage to silk gland. Downregulation of genes transcription ( Fibh , Fibl , P25 , Ser2 , Ser3 ) involved with protein synthesis in the silk gland were further observed, and the results showed significant decreasing in mRNA expression among the tebuconazole treatments. Ecdysteroid levels in silkworm were changed with pronounced decreases after exposed to tebuconazole. In contrast, exposure to tebuconazole significantly increased juvenile hormone 1 concentrations and the maximum increasing fold of juvenile hormone 1 was up to 3.73 which was observed at stage I exposure. In addition, co-exposure to 2 and 10 mg/L forskolin able to mitigate tebuconazole-induced downregulate of mRNA expression of Sgf1 in the present study, indicating the potential mechanism of tebuconazole-induced chronic toxicity in silkworm may relative to PI3K/AKT/TORC1/Sgf1 pathway.
研究领域:
昆虫学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2025
·Vol. 18
·期 1
·296
·
IF 4.2
Wen Jianzhong,Li Wenqian,Wang Zhijuan,Zhang Luchun,Huang Yating,Weng Mengjie,Chen Ye,Hou Zuyao,Zhang Meijia,Chen Yuezhou
Background Vitamins, as essential trace organic compounds for the human body, are crucial substances in the maintenance of normal reproductive function. Nevertheless, the effects of vitamins on the activation of primordial follicles and the underlying mechanisms remain unclear. Methods We used the in vitro culture model of newborn mouse ovaries to identify the vitamins that promote primordial follicle activation and study the mechanism of vitamin B6. The mechanism of VB6 was verified by in vivo injection model of newborn mice, oral feeding of adolescent mice, and in vitro culture model of human ovarian tissue. Results Thiamine monochloride (VB1), riboflavin (VB2), nicotinic acid (VB3), D-pantothenic acid (VB5), pyridoxine (VB6), folic acid (VB9), vitamin B12, L-ascorbic acid (VC), and tocopherol (VE) increased the number of growing follicles in the cultured newborn mouse ovaries. Next, we studied the molecular mechanism by using VB6. VB6 increased the protein levels of phosphorylated protein kinase B (p-Akt) and forkhead box O3a (p-FOXO3a), as well as the proportion of primordial follicle oocytes with FOXO3a nuclear export in the cultured mouse ovaries. The addition of PI3K inhibitor LY294002 blocked VB6-induced increase of growing follicles. Furthermore, intraperitoneal injection of VB6 in newborn mice and oral administration of VB6 to adolescent mice significantly increased the number of growing follicles and the protein levels of p-Akt. Importantly, VB6 also significantly increased the number of growing follicles and the protein levels of p-Akt in the cultured human ovarian tissues. Conclusion Our findings indicate that VB6 promotes primordial follicle activation through the PI3K/Akt signaling pathway.
研究领域:
生殖生物学
·
分子内分泌学
·
发育生物学
·
营养生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Chang Hong,Li Chun,Wang Qiyan,Lu Linghui,Zhang Qian,Zhang Yi,Zhang Na,Wang Yong,Wang Wei
The ancient traditional Chinese medicine Qishenkeli (QSKL) is widely used in the treatment of heart failure (HF) in China. Previous studies have shown that QSKL has definite effects on HF. The purpose of this study is to identify the regulation of QSKL on apoptosis and clarify the underlying mechanism. An apoptosis model of H9C2 cells was induced by oxygen-glucose deprivation/recovery (OGD/R). An animal model of HF was induced by ligation of left anterior descending (LAD) coronary artery in rat. We found that QSKL reduced intracellular ROS generation, increased mitochondrial membrane potential and protected H9C2 cells against OGD/R-induced apoptosis. In vivo results showed that QSKL administration could improve cardiac functions, decrease fibrotic area, infarct size and apoptotic rate in HF model. QSKL regulated the expressions of key apoptotic molecules, including increasing Bcl-2/Bax ratio, reducing the expressions of P53, Bax and Cleaved-caspase-3. Interestingly, QSKL also regulated the phosphorylated expressions of PI3K and Akt without significantly affecting PTEN. Taken together, the protective and anti-apoptotic effects of QSKL could be mediated partly through modulating the PI3K/Akt-P53 apoptotic pathway.
研究领域:
心脏病学
·
药理学
·
分子生物学
·
传统中药
✓ 已验证
DOI
PubMed
高影响因子
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
·
2025
·
IF 4.8
Xiaoqiang Liu,Luojia Liu,Qiaoling Wang,Lufan Xia,Fangqing Zuo,Jinrui Yang,Kaibang Zheng,Yunfan Tang,Jingjing Guo,Xiaoping Yu,Boye Qi,Hanghang Zhou,Ying Chen,Jiaping Zhang,Xuanfen Zhang
Skin cutaneous melanoma (SKCM), the most aggressive form of cutaneous malignancy globally, remains poorly understood in terms of its molecular drivers. Although the copper metabolism MURR1 domain (COMMD) protein family has been associated with oncogenesis, its functional relevance in SKCM is undefined. In this study, we identified COMMD4 as a prognostic biomarker of SKCM and showed that it is positively correlated with the adverse clinical outcomes of patients. COMMD4 gene knockout (COMMD4-KO) impaired the proliferative, migratory, and invasive capacities of SKCM cells in vitro and suppressed xenograft tumor growth in vivo. Mechanistically, COMMD4-KO induced G2/M phase arrest by disrupting p21-CDK1-cyclinB1 and impeded epithelial-mesenchymal transition (EMT) by reversing the E/N cadherin switch. We also demonstrate that COMMD4 activates PI3K-AKT signaling by binding PI3K-p85 to release PI3K-p110, thereby driving G2/M transition and EMT. Reactivation of PI3K-AKT signaling in COMMD4-KO cells rescued oncogenic phenotypes. By integrative Connectivity Map analysis and functional validation, we identified triamterene as a pharmacological inhibitor targeting the COMMD4-PI3K-AKT axis, which suppressed the progression of SKCM effectively in vitro and vivo. Our findings establish the COMMD4-PI3K-AKT axis as a novel and critical regulator of SKCM progression and repurpose triamterene as a promising therapeutic agent against SKCM. Graphical COMMD4 activates the PI3K-AKT signaling through binding PI3K-p85 to release PI3K-p110, driving the G2/M phase transition via p21-CDK1/cyclin B1 axis and facilitating the EMT by switching cadherin expression from the E to the N type, ultimately promoting the progression of SKCM.
研究领域:
肿瘤学
·
分子生物学
·
癌症信号通路
·
药理学
·
皮肤病学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2026
·Vol. 58
·期 1
·1-25
·
IF 8.5
Hui Fang,Min Shu,Jiaju Wang,Heng Tian,Jianguo Zhang,Ying Hu,He Li,Huan Zhou,Kangsheng Gu,Zhenhua Ren
International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2026
·
IF 8.2
Yanchuan Pu,junjie Zhao,Jianhang Zhao,Jinpeng Lou,Tao Jin,Haiyan Zhao,Wenji Wang
Tea polyphenols preserves chondrocyte homeostasis by mitigating mitochondrial stress. • Tea polyphenols protects chondrocytes by suppressing the PI3K/Akt signaling pathway. • Cartilage-affinity liposomes enhance local retention and in vivo efficacy of Tp. Tea polyphenols (Tp) have been reported to possess anti-inflammatory and antioxidant properties, but their application in osteoarthritis (OA) therapy is limited by poor bioavailability and lack of mechanistic clarity. Here, we show that Tp attenuates IL1β-induced chondrocyte inflammation, oxidative stress, and catabolic gene expression (MMP13, MMP3, ADAMTS5) while restoring COL2 levels. Transcriptomic analysis identifies the PI3K/Akt pathway as a key mediator of Tp’s chondroprotective effects, which was confirmed using the PI3K/Akt agonist YS-49. Tp also preserves mitochondrial membrane potential and reduces mitochondrial ROS production. To improve intra-articular delivery, we developed a cartilage-affinity peptide-modified liposomal nanocarrier (LipTp-T) with favorable size, stability, high encapsulation efficiency, and good biosafety. The peptide modification enhances chondrocyte uptake and prolongs joint retention beyond one week. In a mouse OA model, LipTp-T outperforms free Tp in preserving cartilage integrity, lowering OARSI scores, and suppressing ADAMTS5 and MMP13 expression, while consistently inhibiting the PI3K/Akt axis. Collectively, these findings demonstrate that Tp protects against OA by suppressing the PI3K/Akt pathway, and that cartilage-targeted liposomal delivery significantly enhances its therapeutic efficacy. Download: Download high-res image (193KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
Translational Oncology
·
2025
·
IF 4.1
Ying Shi,Hongda An,Wenshuang Wang,Dong Nan,Yingzhe Cui,Mingyuan He,Jianxiu Lian,Xiaoxiao Zhang,Jing Peng,Xiuhua Yang,Pengfei Liu
Purpose Glioblastoma (GBM), an extremely lethal and aggressive cancer with a poor prognosis and limited therapeutic outcomes, exhibits strong resistance to standard therapies owing to anoikis resistance indicating the need for novel treatments. In this study, we used thermoradiotherapy as an integrative approach for GBM to sensitize its resistance to anoikis. Experimental Design The therapeutic effects of thermoradiotherapy were assessed using cell counting kit-8, colony formation, Transwell, and anoikis assays. Proteomic analysis was performed to identify potential therapeutic targets for thermoradiotherapy. The impact of certain therapeutic target on GBM proliferation, metastasis, and anoikis was identified using EdU, colony formation, Transwell, and anoikis assays. Western blotting and qRT-PCR were used to explore the relevant molecular mechanisms. Results Thermoradiotherapy inhibited proliferation and metastasis of GBM, and reverses anoikis resistance to improve therapeutic outcomes. Proteomic analysis revealed ITGA5 as a prospective therapeutic target. In vitro and in vivo studies identified that ITGA5 promoted GBM proliferation, metastasis, and anoikis resistance by regulating PI3K/AKT pathway activation. Conclusions This study presents a novel thermoradiotherapy for GBM, integrating potent antitumour efficacy and negligible side effects. ITGA5 is a underlying therapeutic target for thermoradiotherapy which related to proliferation, metastasis, and anoikis resistance of GBM.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Chunyang Wang,Yimei Tang,Yanlin Zhang,Ziying Li,Jun Wang,Jinming Peng,Jie Peng
Maternal obesity impairs placental angiogenesis, increasing the risks of gestational metabolic disorders and fetal developmental compromise. Odd-chain saturated fatty acids (OCS-FAs), particularly pentadecanoic acid (PA, C15:0), demonstrate protective metabolic properties, yet their roles in placental angiogenesis remain unexplored. In this study, pregnant mice were fed a high-fat diet (HFD, 60% kcal) or isocaloric HFD supplemented with 1% (w/w) PA ethyl-ester (HFD + PA). Porcine iliac artery endothelial cells (PIEC) were used to assess angiogenic mechanisms in vitro. Our results showed that PA supplementation induced mild glucose intolerance (elevated 90/120 min glycemia, P < 0.05) without altering the body composition, fasting insulin, HOMA-IR, or plasma lipids (TG, T-CHO, HDL/LDL). PA augmented labyrinth zone (LZ) vascularization (P = 0.052) and upregulated fetal T-CHO transport (P = 0.002). RNA-seq revealed PA-activated PI3K-AKT signaling and enhanced the pro-angiogenic factor expression (HIFα, Lrp1, Flt4, MMP2/14, P < 0.05). Immunohistochemistry confirmed PI3K activation and increased CD31 endothelium in LZ. PA promoted PIEC tube formation (12.5 µM, P < 0.01) in vitro, while heptadecanoic acid (HA, C17:0) had no such effect and inhibited PIEC (12.5–25 µM, P < 0.01). PA's pro-angiogenic effect was abolished by PI3K inhibitor 3-MA (P < 0.01). In conclusion, PA promotes placental angiogenesis by activating the placental PI3K-AKT signaling, despite mild maternal glucose intolerance. These findings highlight PA's potential as a functional nutrient for mitigating gestational metabolic complications.
研究领域:
生殖生物学
·
营养科学
·
分子信号传导
·
发育生理学
·
代谢紊乱
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2021
·
IF 1.645
Bai-ling Sun,En-bo Cai,Yan Zhao,Yu Wang,Li-min Yang,Jing-Yao Wang
Arctigenin(ARG) , a natural lignans compound isolated from Arctium lappa L. In this study, the anti-tumor effect of ARG on prostate cancer cell PC-3M and the mechanism of apoptosis and autophagy induced by PI3K/Akt/mTOR signaling pathway were discussed, and further confirmed by the joint treatment of ARG and PI3K inhibitor LY294002. Here, the effect of ARG on cell viability was evaluated in PC-3M cells by CCK-8 assay. After the treatment of ARG, colony formation assay was used to detect the anti-proliferation effect. Annexin V-FITC/PI kit and DAPI staining were used to detect the apoptosis level, and cell cycle changes were analyzed by flow cytometry. The expression of autophagy was detected by acridine orange staining. In addition, the expression levels of apoptosis and autophagy-related proteins were analyzed by western blot. The result showed that different concentrations of ARG inhibited the proliferation of PC-3M cells. DAPI staining and flow cytometry showed that ARG induced PC-3M cell apoptosis and arrested cell in G0/G1 phase. Acridine orange staining showed that ARG induced autophagy in PC-3M cells. Western blot experiments showed that ARG inhibited the expression of Bcl-2 , promoted the expression of Bax and cleaved caspase-3. At the same time, the expression of autophagy-related proteins LC3B-II and Beclin-1 increased after ARG treatment, but P62 decreased. In addition, further studies have shown that treatment with LY294002 enhanced the effects of ARG on the expression of proteins associated with apoptosis and autophagy , indicating that ARG may induce apoptosis and autophagy through PI3K/Akt/mTOR pathway.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）