Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Si-Mai Shao,Kyung Hye Park,Ye Yuan,Zijuan Zhang,Yanwen You,Zhenqiang Zhang,Li Hao
The main characteristic of Alzheimer’s disease (AD) is the progressive decline of learning and memory ability. Electroacupuncture (EA) may improve AD-related learning and memory ability. However, the underlying molecular mechanism of action remains unclear. The objective of the present study was to assess the effects and the molecular mechanism of EA on learning and memory in an amyloid β25-35 (Aβ25-35) induced AD mouse model. The AD model was established by intracerebroventricular (ICV) administration of Aβ25-35 oligomers. AD mice were electroacupunctured with wisdom three-needle combined with Baihui (GV20) five times per week for three consecutive weeks. The Morris water maze (MWM) and Y maze tests were applied to evaluate spatial learning and memory ability. A transmission electron microscope (TEM) was used to measure mitochondria and autophagy of hippocampal neurons, and western blot was applied to observe molecular changes in the mice hippocampus. The results suggested that EA treatment significantly alleviated learning and memory impairment related to AD, reduced mitochondria damage, improved autophagy, increased mitochondrial protein 2 (Mfn2), Beclin 1, and LC3B, and decreased the expressions of fission protein 1 (Fis1) level. Furthermore, EA further upregulated the protein expression of phosphatidylinositol 3-kinase (PI3K) and the ratio of p-Akt/Akt in the hippocampus of AD mice. This study demonstrates that EA treatment attenuates cognitive deficits, modulates mitochondrial fusion and fission, and enhances autophagy via the PI3K/Akt pathway in a mouse AD model.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
European Review for Medical and Pharmacological Sciences
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2018
·
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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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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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
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Ying-Ying Wu,Yi-Lin Huang,Bin Dai,Jian-Wei Liu,Xu Han
Background/Aim. Abnormal proliferation and migration of vascular smooth muscle cells is one of the main causes of atherosclerosis (AS). Therefore, the suppression of abnormal proliferation and migration of smooth muscle cells are the important means for the prevention and inhibition of AS. The clinical effects of Guanxinping (GXP) tablets and preliminary clinical research on the topic have proved that GXP can effectively treat coronary heart disease, but its underlying mechanism remains unclear. This study aimed to confirm the inhibitory effect of GXP on the abnormal proliferation of mouse aortic vascular smooth muscle (MOVAS) cells and to explore the underlying mechanism. Methods. MOVAS cells were divided into two major groups: physiological and pathological groups. In the physiological group, MOVAS cells were directly stimulated with GXP, whereas in the pathological group, the cells were stimulated by endothelin-1 (ET-1) before intervention by GXP. At the same time, atorvastatin calcium, which effectively inhibits the abnormal proliferation of MOVAS cells, was used in the negative control group. CCK8 assay, scratch test, ELISA, Western blotting, and immunofluorescence staining were performed to observe the proliferation and migration of MOVAS cells and the expression levels of related factors after drug intervention in each group. Results. In the physiological group, GXP had no significant effect on the proliferation and migration of MOVAS cells and the related factors. In the pathological group, a high dose of GXP reduced the abnormal proliferation and migration of MOVAS cells. Further, it reduced the expression levels of PI3K; inhibited the phosphorylation of Akt (protein kinase B); upregulated IκB-α levels; prevented nuclear factor kappa B (NF-κB) from entering the nucleus; downregulated the expression of interleukin 6 (IL6), IL-1β, and iNOS; and upregulated the ratio of apoptosis-related factor Bax/Bcl-2. There was no significant difference between the high-dose GXP group and the atorvastatin calcium group (negative control group). Conclusion. Our findings revealed that GXP was able to inhibit the proliferation and migration of MOVAS cells by regulating the PI3K/Akt/NF-κB 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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DOI
PubMed
高影响因子
Cancer Biomarkers
·
2019
·Vol. 25
·期 2
·193-201
·
IF 2.859
Xu Jin-huan,Wang Yan,Xu Dong
Circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but its functional effects in breast cancer (BC) remains largely unclear. In this study, we aimed to explore the expressing pattern, clinical significance and potential function of a newly identified circRNA, hsa_circ_001569, in BC. RT-PCR was performed to detect the expression of hsa_circ_001569 in both BC tissues and cell lines. The associations between hsa_circ_001569 expression and clinicopathological features and prognosis in BC patients were statistically analyzed. Next, we investigated the effects of hsa_circ_001569 on the proliferation, apoptosis, migration and invasion in BC cells lines. The effects of abnormal hsa_circ_001569 expression on EMT pathway and PI3K/AKT pathway were determined using Western blot. We found that hsa_circ_001569 expression was significantly up-regulated in both BC tissues and cell lines. Overexpression of hsa_circ_001569 was associated with Lymph node metastasis, advanced clinical stage and shorter overall survival. Multivariate assay confirmed that hsa_circ_001569 expression was an independent prognostic factor for 5-year overall survival. Furthermore, functional investigations revealed that knockdown of hsa_circ_001569 significantly suppressed the growth and metastatic potentials of BC cells. Besides, molecular mechanistic study revealed that depression of hsa_circ_001569 impeded the activation of PI3K-AKT signaling in BC cells. Our results indicated that hsa_circ_001569 upregulation was associated with BC lymph-node metastasis, clinical stage, and poor prognosis. Hsa_circ_001569 might contribute to progression of BC by modulating PI3K-AKT pathway.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
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2026
·Vol. 31
·期 8
·
IF 4.1
Jinhui Zhang,Chao Wei,Dongyan Wang,Renmi He,Xiangdan Xiao,Jianwei Xu,Junhou Lu
Background: Glioblastoma is the most aggressive primary malignant brain tumor of the central nervous system and remains difficult to treat because of rapid progression, diffuse invasion, and frequent recurrence. This study aimed to identify a potential natural compound against glioblastoma using a reverse network pharmacology strategy and to investigate its anti-glioma effects and underlying mechanism. Methods: Glioblastoma-related targets were collected from public disease databases and integrated with differentially expressed genes from a public transcriptomic dataset to identify intersecting targets. Protein-protein interaction analysis, hub target screening, functional enrichment analysis, and reverse network pharmacology were performed to identify candidate compounds. Molecular docking and 100-ns molecular dynamics simulations were used to assess interactions between 20-hydroxyecdysone and pathway-related targets. Cell viability, colony formation, apoptosis, migration, and protein expression were examined in U251 and U87 glioma cells. Statistical differences were analyzed using a paired Student’s t-test for two-group comparisons or one-way analysis of variance (ANOVA) followed by Dunnett’s multiple-comparisons test for multi-group comparisons, as appropriate. Results: A total of 136 intersecting targets and 18 hub targets were identified. Functional enrichment analysis indicated that the phosphatidylinositol 3-kinase/protein kinase B signaling pathway was one of the key enriched pathways. Reverse network pharmacology identified 20-hydroxyecdysone as a candidate compound. Molecular docking showed relatively strong binding of 20-hydroxyecdysone to epidermal growth factor receptor, fms-related receptor tyrosine kinase 1, and integrin subunit alpha 5, and molecular dynamics simulations supported the stability of these complexes. In vitro experiments showed that 20-hydroxyecdysone inhibited cell viability, clonogenicity, and migration, while promoting apoptosis. It also reduced the phosphorylation levels of phosphatidylinositol 3-kinase, protein kinase B, and glycogen synthase kinase 3 beta at Ser9 without markedly altering total protein expression. Conclusion: Treatment with 20-Hydroxyecdysone showed anti-glioma activity in vitro and may exert its effects, at least in part, through suppression of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. These findings support its further evaluation as a potential therapeutic candidate for glioblastoma.
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DOI
高影响因子
Cell and Bioscience
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2026
·Vol. 16
·期 1
·88
·
IF 6.5
Chen Xin,Zhang Qing,Xie Fen,Zhai Huilan,Li Chuanhong,Zhou Weifeng,Zhang Nuobei
Background Hepatocellular carcinoma (HCC) is a lethal malignancy driven by cancer stem cells, which drive progression and therapeutic resistance. Nuclear pore protein ELYS is implicated in tumorigenesis, but its role in HCC stemness remains unclear. Methods Transcriptome sequencing identified ELYS-induced differentially expressed genes (DEGs). Functional impacts of ELYS on malignant phenotypes and stemness were assessed in vitro. Signaling pathway activation was confirmed using inhibitors of Hedgehog (GANT-61) and AKT (MK-2206 2HCl). Bioinformatics analysis, luciferase reporter, and ChIP assays elucidated the FOXO6-NUP205 axis. Xenograft models validated the findings in vivo. Clinical relevance was evaluated using TCGA-HCC data and immunohistochemistry in clinical samples. Results DEGs in ELYS-overexpressing cells were enriched in PI3K/AKT and Hedgehog (Hh) pathways. ELYS facilitated Gli-1 nuclear translocation by activating PI3K/AKT, placing it upstream of Hh. Bioinformatic and experimental analyses identified FOXO6 and its target NUP205 as key effectors. ELYS upregulated FOXO6, which directly activated NUP205 transcription. FOXO6 knockdown suppressed ELYS-induced effects on NUP205, Gli-1 nuclear translocation, and stemness factors. In vivo, ELYS promoted tumor growth and lung metastasis via PI3K/AKT/Hh. Clinically, ELYS, FOXO6, and NUP205 were overexpressed in HCC, correlating with advanced features and poor survival. Conclusion This study defines an oncogenic axis wherein ELYS promotes HCC stemness and metastasis by activating PI3K/AKT, triggering a FOXO6-NUP205 cascade to drive Hedgehog, representing a pivotal mechanism and therapeutic target. Graphical abstract
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DOI
高影响因子
IMMUNOLOGY
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2026
·
IF 5.4
Sisi Zhang,Zhou Jingxiang,Caixia Tan,Yuanyuan Xiao,Ju Zou,Biyue Tian,Anhua Wu,Chunhui Li
Clostridioides difficile infection (CDI) remains a major cause of antibiotic-associated colitis and is characterized by excessive intestinal inflammation, epithelial barrier disruption and impaired mucosal repair. Although sodium butyrate (NaB), a microbiota-derived short-chain fatty acid, has demonstrated anti-inflammatory and barrier-protective properties, the immunological mechanisms underlying its protective effects during CDI remain incompletely understood. In this study, we investigated the role of NaB in regulating macrophage polarization and epithelial repair using murine CDI models, primary bone marrow-derived macrophages, THP-1-derived macrophages, Caco-2 epithelial cells and macrophage–epithelial co-culture systems. NaB treatment significantly alleviated CDI-associated weight loss, colonic shortening, histopathological injury and inflammatory cytokine production while restoring epithelial barrier integrity and tight junction protein expression. Mechanistically, NaB promoted macrophage polarization towards an anti-inflammatory M2 phenotype, characterized by increased CD206 and IL-10 expression and reduced CD86 and IL-1β expression. These immunomodulatory effects were accompanied by suppression of PI3K/Akt/mTOR signalling in both colonic tissues and macrophages. Pharmacological inhibition and activation studies further supported the involvement of this pathway in NaB-mediated macrophage reprogramming. Importantly, conditioned medium from NaB-treated macrophages enhanced epithelial viability, migration and barrier-associated protein expression, whereas IL-10 neutralization partially abolished these protective effects, highlighting a critical role for macrophage–epithelial crosstalk. Collectively, our findings demonstrate that low-dose NaB protects against CDI-induced intestinal injury through coordinated regulation of macrophage polarization and epithelial barrier repair, at least in part via modulation of PI3K/Akt/mTOR signalling. These results identify NaB as a promising host-directed therapeutic strategy for CDI and provide new insights into microbiota-derived metabolite–immune interactions during intestinal inflammation.
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产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2026
·
IF 2.5
Hai Huang,Liwei Guo,Hansong Sun,Yunhong Liu,Jun Zhang,Weijie Tang,Xiaodong Xia,Yu Wang,Ni Chen,Dong Lv,Jing Yang
Objective To investigate the mechanism of action of saikosaponin D (SSD) on bladder cancer (BCa) and evaluate its synergistic antitumor efficacy with the chemotherapeutic agent gemcitabine (GEM). Methods MTT, colony formation, Transwell, and scratch wound healing assays detected SSD's effects on the proliferation, invasion, and migration of RT112 and T24 cells. Specific inhibitors identified cell death mode. Western blotting, immunohistochemistry, and flow cytometry verified ferroptosis-related protein expression and oxidative stress. Network pharmacology predicted core pathways, validated by examining PI3K/AKT pathway activity. Animal models evaluated the synergistic effect of SSD and GEM. Results In vitro, SSD dose-dependently inhibited the BCa cells proliferation, invasion, and migration, and upregulating E-cadherin whilst downregulating N-cadherin, Vimentin, and Snail. The effects were blocked by the ferroptosis inhibitor Fer-1. Network pharmacology identified the PI3K/AKT pathway as a core target. Moreover, SSD regulated the GPX4/SLC7A11/ACSL4, suppressed PI3K/AKT phosphorylation, and triggered lipid peroxidation and reactive oxygen species accumulation, partially reversed by a PI3K-specific phosphopeptide agonist. In vivo, SSD inhibited tumor growth, and its combination with GEM showed superior efficacy. The combination therapy most effectively downregulated SLC7A11, GPX4, Vimentin, N-cadherin and Snail, while upregulating the ACSL4 and E-cadherin. Conclusion SSD inhibits the malignant phenotype of BCa by targeting PI3K/AKT to trigger ferroptosis. Its synergistic effect with GEM from the dual mechanisms of ferroptosis sensitization and epithelial-mesenchymal transition inhibition, providing an innovative combination strategy based on natural product active ingredients to overcome bladder cancer chemoresistance.
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DOI
PubMed
高影响因子
Dose-Response
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2026
·
IF 2.8
AiJiao Sun,CuiYu Yu,FeiYan Zhu,Jing Chen,LiangChuan Chen,ZePing Hu,WeiBing Wang
BackgroundExtracellular matrix (ECM) deposition and excessive fibrosis are important factors in the deterioration of cardiac function after myocardial ischaemia‒reperfusion injury (I/RI). However, therapeutic strategies for inhibiting ECM deposition and excessive fibrosis have still not been elucidated.Methods and resultsSingle-nucleus RNA sequencing (snRNA-seq) revealed that the overexpression of type VI collagen-α 3 (Col6a3) in fibroblasts in the myocardial infarction area strongly promotes the process of myocardial fibrosis. Consistent results were not observed in the infarcted myocardial tissues of mice treated with 4,8-dicarboxyl-8,9-iridoid-1-glycoside (BIG). Echocardiography confirmed that BIG alleviated cardiac dysfunction in mice after myocardial I/RI, TTC and Evans blue double staining revealed that BIG reduced the myocardial infarction size and area at risk. BIG inhibited inflammatory responses, apoptosis, and matrix metalloproteinase (MMP) secretion both in vivo and in vitro. Immunofluorescence staining revealed that BIG downregulated the expressions of TGF‒β and Col6a3 in cardiac fibroblasts but not in cardiomyocytes. The PI3K-specific inhibitor LY294002 and AKT inhibitor were utilitzed to confirm that BIG suppressed myocardial fibrosis and alleviated cardiac dysfunction by activating the PI3K/AKT pathway.ConclusionsThe results provide valuable information for the treatment of myocardial fibrosis induced by myocardial I/RI and highlight the therapeutic potential of BIG in reducing collagen deposition.
✓ 已验证
DOI
PubMed
高影响因子
Animals
·
2026
·Vol. 16
·期 9
·1310
·
IF 3.2
Binwen Zhang,Zheng Wei,Mei Yang,Xin Wang,Qiang Shan,Zheng Cao
Simple SummaryMastitis is a common disease in dairy cows, with major pathogens includingStaphylococcus aureusandEscherichia coli. Although berberine has antibacterial and anti-inflammatory properties, it is poorly absorbed after oral administration. We developed a novel berberine-loaded hydrogel that can be applied to the udder, delivering the drug directly to the mammary tissue. Experimental results showed that this hydrogel is stable, safe, and capable of sustained drug release. Tests in a mouse model demonstrated that it effectively reduces bacteria-induced inflammation, protects the mammary barrier, and minimizes cell damage. Its mechanism of action is related to the regulation of intracellular NF-κB and PI3K/Akt signaling pathways. This study suggests that the hydrogel offers a new topical strategy for treating mastitis, solving the problem of poor oral absorption through local application. It holds promise for providing dairy cows with a more convenient and effective treatment option in the future.Mastitis is a common disease in dairy cows, mainly caused by Staphylococcus aureus and Escherichia coli. Berberine (BBR) has antibacterial and anti-inflammatory potential, but its application is limited due to poor oral absorption and difficulty in reaching mammary tissue. To address this, this study developed a BBR-loaded composite ethosome hydrogel (BBR-CEH) to achieve targeted mammary delivery through local transdermal administration. The experimental results showed that BBR-CEH has good chemical stability and biosafety. Subsequently, a mouse mastitis model was established by intraductal injection of 50 µL of bacterial mixture (E. coli:S. aureus= 1:1, each at 1 × 107CFU/mL). The results showed that after BBR-CEH treatment, the mRNA expression ofTNF-α(tumor necrosis factor-alpha),IL-6(interleukin-6), andIL-1β(interleukin-1 beta) was significantly decreased, the mRNA expression ofZO-1(zonula occludens-1),Occludin, andClaudin-4was significantly increased, andBax/Bcl-2(Bcl-2-associated X protein/B-cell lymphoma 2) was significantly reduced (p< 0.01), indicating alleviation of mastitis by reducing inflammation, improving tight junctions, and inhibiting apoptosis. Finally, network pharmacology and in vivo experiments confirmed that its mechanism involves the NF-κB (nuclear factor kappa-B) and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways. Thus, topical BBR-CEH may represent a promising new strategy for mastitis treatment.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
·
IF 8.7
Lili Fan,Shukun Qu,Chenxue Miao,Dongjie Wu,Yuan Rao,Weisong Xu,Yanping He,Guang Song
Oxidative stress is a key pathological factor that contributes to blood–brain barrier (BBB) disruption during ischemic injury. Panax notoginseng saponins (PNS), the primary bioactive components of Panax notoginseng , possess potent antioxidative and vasoprotective activities. This study aimed to elucidate the molecular mechanisms by which PNS regulate endothelial integrity and BBB permeability under oxidative stress conditions. Mouse brain microvascular endothelial cells (bEnd.3) were treated with hydrogen peroxide to induce oxidative damage, followed by intervention with PNS. Transcriptomic and proteomic analyses revealed that Akap12 (A-kinase anchoring protein 12) and Aquaporin 1 (AQP1) were key molecules involved in PNS-mediated endothelial protection. H₂O₂ exposure markedly suppressed Akap12 expression and inhibited the PI3K/AKT signaling pathway, leading to elevated AQP1 expression and increased BBB permeability. PNS treatment reversed these effects by restoring Akap12 expression, reactivating PI3K/AKT signaling, and reducing AQP1 levels. Functional validation further showed that AQP1 dysregulation altered the expression balance of tight junction proteins, including Claudin-5 and ZO-1, thereby impairing barrier function. Collectively, these findings demonstrate that PNS protect endothelial cells from oxidative injury by activating Akap12-dependent PI3K/AKT signaling and modulating AQP1-associated tight junction remodeling. This study provides new mechanistic insights into the molecular basis of PNS-mediated BBB protection and suggests potential therapeutic targets for oxidative or ischemic cerebrovascular diseases.
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PubMed
高影响因子
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