CURRENT NEUROVASCULAR RESEARCH
·
2021
·Vol. 18
·期 1
·102-112
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IF 1.99
Chu Miao,Liu Huimiao,Xiong Zhaohui,Ju Chaojuan,Zhao Lina,Li Kangning,Tian Shiqi,Gu Ping
Background: Parkinson’s disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons. Canopy fibroblast growth factor signaling regulator 2 (CNPY2) is down-regulated in this disease, but its functions are unknown. Objective: This study
investigates the effects and regulation of CNPY2 in the apoptosis of neurons in PD. Methods: We established a PD model in vivo by a five consecutive days-injection of 1-methyl-4- phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to mice. In vitro, the human SH-SY5Y neuroblastoma cells, after
differentiation, were treated with 1-Methyl-4-phenylpyridinium iodide (MPP+) for modeling. The cells were transfected with a recombinant vector overexpressing CNPY2 followed by MPP+ treatment. Expression of CNPY2 and proteins related to apoptosis was detected by real-time PCR, western blot,
or immunofluorescence staining. The ROS level and mitochondrial membrane potential were determined by flow cytometry. Cell viability and apoptosis were measured by MTT assay and TUNEL staining. Results: CNPY2 level was down-regulated both in the brain and retina of PD mice and also inhibited
in neurons by MPP+ in vitro. Overexpression of CNPY2 repressed the level of Bax and cleaved caspase-3, enhanced Bcl-2 level, and promoted neurite length under MPP+ treatment. CNPY2 overexpression reduced the accumulation of ROS and mitochondria dysfunction in neurons. The AKT/ GSK3β signaling
pathway was activated by overexpressed CNPY2 to inhibit MPP+-induced neuronal apoptosis, which was confirmed using an AKT inhibitor MK-2206 2HCl. Conclusion: CNPY2 alleviates oxidative stress, mitochondria dysfunction, and apoptosis of neurons induced by MPP+ by activating the AKT/ GSK3β
signaling pathway.
研究领域:
神经科学
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分子生物学
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神经退行性疾病
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DOI
PubMed
高影响因子
CLINICAL & EXPERIMENTAL METASTASIS
·
2025
·Vol. 42
·期 5
·1-20
·
IF 3.2
Liu Jinren,Wang Xiangni,Cui Yixin,Lu Jiajia,He Zhirou,Xu Yulin,Li Rongrong,Xu Guimin,Gao Lingge,Fan Xiaolin,Wu Xili,Shi Xingmin,Zhang Guanjun
Ovarian cancer remains a significant challenge in oncology due to its aggressive nature, late-stage diagnosis, and high rates of chemoresistance, particularly to platinum-based therapies like cisplatin. The epithelial-mesenchymal transition (EMT) is a key driver of ovarian cancer metastasis and drug resistance, highlighting the need for novel therapeutic strategies. Cold atmospheric plasma (CAP) and plasma-activated liquids (PAL), including plasma-activated medium (PAM) and saline (PAS), have emerged as promising anticancer agents, generating reactive oxygen and nitrogen species (RONS) that selectively target cancer cells. This study investigates the potential of PAL to inhibit the invasion and metastasis of cisplatin-resistant ovarian cancer cells and explores its synergistic effects with cisplatin. In vitro , PAM reduced proliferation, migration, and invasion of cisplatin-resistant ovarian cancer cells (A2780/DDP and SKOV3/DDP) while downregulating EMT-related proteins (N-cadherin, β-catenin, vimentin). H 2 O 2 in PAM inhibit the PI3K/AKT/GSK3β pathway, promoting degradation of EMT regulators Snail, Slug, and β-catenin. Combining PAM with cisplatin enhanced therapeutic efficacy, reducing cell viability and metastatic potential. In vivo studies using an orthotopic mouse model further confirmed that PAS combined with low-dose cisplatin effectively suppressed tumor growth and metastasis with minimal side effects. These findings underscore the potential of PAL as an adjuvant therapy for cisplatin-resistant ovarian cancer, offering a novel approach to overcome drug resistance and inhibit metastasis. Future research should focus on optimizing treatment protocols and elucidating the molecular mechanisms underlying the synergistic effects of PAL and cisplatin.
研究领域:
肿瘤学
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等离子体医学
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分子生物学
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癌症研究
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Huang Yuechang,Zhang Xingmin,Li Qian,Zheng Wende,Wu Panpan,Wu Rihui,Chen Wen-Hua,Li Chen
Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic β-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3β proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3β signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.
研究领域:
药理学
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内分泌学
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代谢性疾病
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Licong Yang,Yabin Wang,Zhiwei Li,Xiaohua Wu,Jingtao Mei,Guodong Zheng
The pathology of Alzheimer's disease (AD) is highly correlated with obesity-induced insulin resistance. Resveratrol (Res) is a natural phenol that demonstrates a neuroprotective effect, but the bioactivity of Res is low in vivo . Here, chitosan (CS) was cross-linked with sodium tripolyphosphate (TPP) to encapsulate low water solubility Res. Next, a brain-targeted peptide (TG: TGNYKALHPHNG) was modified on the surface of Res-loaded CS/TPP nanoparticles (TG-Res-CS/TPP-NPs) to specifically deliver Res to the brain. Morris water maze results indicated that cognitive impairments were ameliorated by TG-Res-CS/TPP-NPs in obesity-related AD mice. Obesity-related insulin resistance promotes Tau phosphorylation and Aβ aggregation in the brain. Administration of TG-Res-CS/TPP-NPs alleviated lipid deposition-induced insulin resistance and decreased the level of phosphorylated Tau and Aβ aggregation via the JNK/AKT/GSK3β pathway. Additionally, TG-Res-CS/TPP-NPs transported across blood-brain barrier which in turn increased glucose transporter expression levels, antioxidant enzyme activity and inhibited microglial cell activation . Thus, TG-Res-CS/TPP-NPs were more effective than Res-CS/TPP-NPs at regulating glucose homeostasis , oxidative stress and neuroinflammation in the brain. Moreover, inflammatory , lipid metabolism and oxidative stress-related gut microbiota including Helicobacter , Colidextribacter , Anaerotruncus , Parasutterella , Allobaculum , Alloprevotella , Alistipes , Bifidobacterium and Candidatus_Saccharimonas were also regulated by TG-Res-CS/TPP-NPs. This work indicates the potential use of TG-Res-CS/TPP-NPs for the delivery of Res.
研究领域:
药理学
·
神经科学
·
分子生物学
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生物技术
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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