LIFE SCIENCES
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2018
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IF 3.234
Han Zhang,Fenfen Qin,Anlong Liu,Qinmei Sun,Qisheng Wang,Shuwu Xie,Shengfeng Lu,Dong Zhang,Zhigang Lu
Aims Electro-acupuncture (EA) is frequently recommended as a complementary therapy for premature ovarian failure (POF) in the clinical. However, little information exists about its potential treatment mechanisms. The study was designed to observe the effect of EA to ovarian function and fertility in POF mice model, and investigated its potential mechanisms on PI3K/AKT/mTOR signaling pathway. Materials and methods Forty-five female C57/BL6 mice were divided into the Control, the Model and the EA group. The ovaries morphology of mice was observed by hematoxylin and eosin (HE) staining, and all follicles were counted under microscope. The protein expression of PI3K, phospho-PI3K, AKT, phospho-AKT, mTOR, phospho-mTOR, S6, phospho-S6, 4E-BP1 and phospho-4E-BP1 were detected by western blotting. The data was presented as the ratio of phosphorylation protein to total protein. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ) and anti-Mullerian hormone (AMH) levels were measured by enzyme-linked immunosorbent assay (ELISA). The fertility was observed by giving treated mice 8 weeks for breeding. Key findings We found that primordial follicle counts were increased in EA group compared to Model group. The phosphorylation of PI3K, AKT, mTOR, 4E-BP1 and S6K in EA group significantly reduced compared to Model group. Serum FSH and LH levels in EA group were decreased compared to Model group, while, serum E 2 and AMH levels in EA group were increased compared with Model group. The litter size in EA group was improved compared to Model group. Significance The effects of EA on the PI3K/AKT/mTOR signaling pathway may represent one of the mechanisms involved in attenuating the mice POF.
研究领域:
生殖生物学
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针灸疗法
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信号转导
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PubMed
高影响因子
NEUROCHEMICAL RESEARCH
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2016
·Vol. 41
·期 7
·1635-1644
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IF 2.472
Zou Yunjun,Wang Bo,Fu Wan,Zhou Shouhong,Nie Yaxiong,Tian Shaowen
It is widely accepted that environmental stress is a risk factor for mental disorders. Glucocorticoid hormones play a vital role in the regulation of physiological response to stress. High concentrations of corticosterone can induce cellular damage in PC12 cells, which possess typical neuronal features. Apelin and its receptor APJ are widely distributed in the central nervous system including limbic structures involved in stress responses. Previous studies have suggested that apelin has a neuroprotective function. However, the effect of apelin on corticosterone-induced neuronal damage remains to be elucidated. In the present study, we explored the potential protective activity of apelin-13 in PC12 cells treated with corticosterone and its underling mechanisms. The viability of the cells, the apoptosis of the cells, the level of phosphorylation of Akt (p-Akt) and extracellular signal-regulated kinases (p-ERKs) and cleaved caspase-3 expression were detected by MTT, Hoechst staining and flow cytometer assays and Western blotting. Results showed that corticosterone induced cells viability loss, cell apoptosis, down-regulation of p-Akt and p-ERKs and up-regulation of cleaved caspase-3. The effects induced by corticosterone were attenuated by apelin-13 pretreatment. Furthermore, apelin-13-mediated anti-viability loss, antiapoptosis and caspase-3 suppression activities were blocked by specific inhibitors of phosphatidylinositol 3-kinase (PI3K) (LY294002) and ERKs (PD98059). The data suggest that apelin-13 protects PC12 cells from corticosterone-induced apoptosis through activating PI3K/Akt and ERKs signaling pathways.
研究领域:
神经科学
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细胞生物学
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药理学
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高影响因子
Scientific Reports
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2017
·Vol. 7
·期 1
·1-13
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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
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药理学
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分子生物学
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传统中药
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PubMed
高影响因子
MATERIALS & DESIGN
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2026
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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
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高影响因子
MATERIALS & DESIGN
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2026
·
IF 8.2
Peng Cao,Shuoyi Hui,Kaituo Liu,Lin Tong,Chenxing Zhang,Mingfan Xi,Xingyu Zhu,Daojiang Yu,Guozhong Lyu
Dihydromyricetin-loaded membranes sustain local delivery in diabetic wounds. • The membranes reduce inflammation and promote fibroblast migration. • Repair is linked to phosphoinositide 3-kinase/protein kinase B signaling. • Treatment speeds wound closure, collagen deposition, and angiogenesis. Diabetic wounds remain a major clinical challenge because of persistent inflammation, impaired angiogenesis, and delayed tissue repair. Here, we developed a dihydromyricetin (DHM)-loaded polyvinylpyrrolidone/polyvinyl butyral electrospun nanofiber membrane (PBDEM) as a local therapeutic dressing for diabetic wound treatment. PBDEM improved DHM dispersion and local retention, enabled sustained release, and showed favorable biocompatibility. By integrating network pharmacology, GEO transcriptomic analysis, molecular docking, molecular dynamics simulation, and in vitro and in vivo validation, we identified PI3K/AKT signaling as a key pathway associated with PBDEM action. In vitro , PBDEM reduced high-glucose-induced pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), increased anti-inflammatory factors (TGF-β1 and IL-10), and promoted fibroblast migration. In diabetic mice, PBDEM alleviated early inflammation, accelerated wound closure, and enhanced collagen deposition and angiogenesis. These findings indicate that PBDEM is an active local drug-delivery platform that promotes diabetic wound healing through PI3K/AKT-associated immune regulation. Download: Download high-res image (146KB) Download: Download full-size image
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高影响因子
Journal of Ovarian Research
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2025
·Vol. 18
·期 1
·296
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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
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分子内分泌学
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发育生物学
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营养生物化学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2026
·Vol. 58
·期 1
·1-25
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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.
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高影响因子
Food & Function
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2025
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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
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营养科学
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分子信号传导
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发育生理学
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代谢紊乱
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DOI
PubMed
高影响因子
Translational Oncology
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2025
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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.
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高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Zuo Wanyun,Liu Na,Zeng Yunhong,Xiao Zhenghui,Wu Keke,Yang Fan,Li Biao,Song Qingqing,Xiao Yunbin,Liu Qiming
Luteolin is a flavonoid compound with a variety of pharmacological effects. In this study, we explored the effects of luteolin on monocrotaline (MCT) induced rat pulmonary arterial hypertension (PAH) and underlying mechanisms. A rat PAH model was generated through MCT injection. In this model, luteolin improved pulmonary vascular remodeling and right ventricular hypertrophy, meanwhile, luteolin could inhibit the proliferation and migration of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB (PDGF-BB) in a dose-dependent manner. Moreover, our results showed that luteolin could downregulate the expression of LATS1 and YAP, decrease YAP nuclear localization, reduce the expression of PI3K, and thereby restrain the phosphorylation of AKT induced by PDGF-BB. In conclusion, luteolin ameliorated experimental PAH, which was at least partly mediated through suppressing HIPPO-YAP/PI3K/AKT signaling pathway. Therefore, luteolin might become a promising candidate for treatment of PAH.
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PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
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2022
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IF 3.461
Zi-Xiao Wang,Shuai Wang,Xue-Peng Qiao,Wen-Bo Li,Jian-Tao Shi,Yi-Ru Wang,Shi-Wu Chen
PI3Ks and HDACs play essential roles in the occurrence and progression of leukemia. Herein, a series of novel pyrazin-2(1 H )-one derivatives were rationally designed and synthesized as novel dual PI3K and HDAC inhibitors based on scaffold replacement and heterozygous strategies. Most of the target compounds showed potent inhibitory potency to PI3Kα and HDAC6. Especially, compound 9q displayed PI3Kα and HDAC6 inhibitory with IC 50 values of 372 nM and 4.5 nM, and anti-proliferative activity against MV4-11 cells with IC 50 value of 0.093 ± 0.012 μM. Further mechanistic studies revealed that 9q induced apoptosis, arrested the cell cycle in the G2/M phase, promoted the acetylation of α-tubulin, and blocked the PI3K/AKT/mTOR signal way in MV4-11 cells. All the results demonstrated that 9q was a promising lead candidate for further development of novel PI3K/HDAC dual inhibitors for leukemia treatment.
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PubMed
高影响因子
NEPHROLOGY
·
2023
·
IF 2.5
Ziyuan Liu,Huilong Xiang,Qin Deng,Wanting Fu,Yang Li,Zejun Yu,Yinsheng Qiu,Zhinan Mei,Lingyun Xu
Aim Inflammation and apoptosis are main pathological processes that lead to the development of hyperuricemic nephropathy (HN). This study aims to explore whether baicalin (BA) and baicalein (BAI) can relieve the damage through PI3K/AKT/NF-κB signal pathway and provide more reliable and precise evidence for the treatment of HN. Methods HN mice were induced by yeast extract with potassium oxonate (PO), and HK-2 cells were induced by monosodium urate (MSU). Molecular docking, western blot, q-PCR, and other methods were used to explore the changes of various indicators in HN mice and HK-2 cells. Results Molecular docking results showed that BA and BAI had good binding ability with PI3K, AKT, p65 and IκBα. BA and BAI significantly ameliorated the levels of renal function, decreased the p-PI3K, p-AKT and p-p65 expression, down-regulated the BAX/BCL2 and CASP3, and blunted the mRNA levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-18 in both renal tissue of HN mice and HK-2 cells induced by MSU. BA and BAI also decreased the oxidative stress level of MSU-induced HK-2 cells. Conclusion BA and BAI were confirmed to attenuate HN through alleviating renal inflammatory and apoptosis in cells and tissues by inhibiting PI3K/AKT/NF-κB pathway. BA and BAI were expected to be developed as new anti-HN drugs.
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高影响因子
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