BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Min Chen,Xiaodong Wang,Bo Hu,Jian Zhou,Xin Wang,Wei Wei,Hua Zhou
Echinacoside is a natural ingredient with various pharmacological activities . In this study, we investigated the protective effects of echinacoside on cardiomyocytes (rat H9c2 cells) in an anoxia/reperfusion (A/R) model. Further, the regulatory function of sodium-calcium exchanger protein 3 (SLC8A3/NCX3) as well as the protein kinase B (AKT) signaling were studied. The present results indicated that echinacoside protected against A/R-induced apoptosis in a dose manner, which was characterized by a decrease in the apoptosis and caspase 3 protein levels in H9c2 cells. Further, Ca 2+ uptake were dose-dependently reduced in H9c2 cells by echinacoside under A/R conditions. Whereas, relative mRNA expression of SLC8A3 and protein levels of SLC8A3 and p-AKT showed opposite tendency. On the one hand, the A/R-induced abnormalities in H9c2 cells were remarkably ameliorated by activated p-AKT and over-expression of SLC8A3 but aggravated by inhibited p-AKT, and the aggravated effection were ameliorated by echinacoside. Moreover, protein levels of SLC8A3 were positively regulated by p-AKT signaling. On the other hand, apoptosis and Ca 2+ uptake as well as protein levels of caspase 3 were significantly increased by SLC8A3 silencing in H9c2 cells under normoxic conditions, and this symptom was remarkably reversed by echinacoside or Nimodipine (an antagonis of Ca 2+ ) treatment . Collectively, echinacoside has showed a cardioprotective effect against A/R treatment in a dose dependent manner in vitro, and this cardioprotective effect was potentially achieved via up-regulating p-AKT and SLC8A3.
研究领域:
药理学
·
心脏病学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Zhaopeng Yan,Bin Zang,Xiaoying Gong,Jiangyue Ren,Rui Wang
Aims Acute pancreatitis (AP) is usually complicated with multiple organ insufficiency, including renal injury. Hyperlipidemia is regarded as a risk factor to induce AP. High-fat diet-induced hyperlipidemic pancreatitis (HP) increased nowadays and showed more severe symptoms and complications than other AP. However, detailed mechanisms or mediators involved in HP complicated with acute renal injury were less studied. Here, we aimed to study how miR-214 expresses in the HP and whether miR-214 has functions to regulate pathological kidney damages induced by HP. Main methods Sprague-Dawley rats were adopted to establish HP model complicated with acute renal injury through long-term high-fat diet and sodium taurocholic injection. Models were injected with LV-rno-miR-214-3p or LV-anti-rno-miR-214-3p to exogenously regulate miR-214-3p to study its impacts on HP via a series of molecular and histological experiments. Key findings MiR-214-3p was found to be up-regulated in the kidney, pancreas and serum of HP rats and also could intensify the pathological alterations, kidney and pancreas damages and fibrosis induced by HP. Inflammatory response in HP was enhanced when miR-214-3p was overexpressed. Besides, miR-214-3p up-regulation was showed to inhibit PTEN expression but increased P-Akt levels in the HP kidney, which might be a possible mechanism to induce severe symptoms of pancreatitis. Knockdown of miR-214-3p showed opposite effects. Significance MiR-214-3p is indicated to exacerbate the tissue damages and inflammatory response caused by HP complicated with acute renal injury, which may provide a novel therapeutic perspective targeting miR-214-3p to treat HP with acute renal injury.
研究领域:
分子生物学
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病理学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Yuan Yuan,Li Jinmeng,Chen Yanhong,Cai Qingshan,Xu Yingying,Lin Luting,Lang Yazhen,Guo Suhang,Zhang Ruoying,Cai Xinjun
Multidrug-resistant tuberculosis (MDR-TB) remains a main global health concern as there is no comprehensive therapeutic intervention yet and numerous adverse effects follow the therapeutic process. In recent years, linezolid has been frequently used for treating MDR-TB. However, peripheral neuropathy associated with linezolid has reduced patient compliance. The current study explored the mechanism underlying linezolid-induced peripheral neuropathy in MDR-TB. Autophagy plays a neuroprotective role against peripheral nerve injury. We hypothesized that autophagy might also play a neuroprotective role against linezolid-induced peripheral neuropathy. In this study, we collected 12 questionnaires from MDR-TB patients in our hospital, and 10 of them developed linezolid-induced pain. The pain is mainly concentrated in the feet and accompanied by numbness. Subsequently, we used Sprague-Dawley (SD) rats and Schwann cells (SCs) to explore the mechanism. We found that linezolid causes a sparse arrangement of sciatic nerve tissue with associated loss of neurons, myelin sheaths, and down-regulation of LC3B expression. These results were also confirmed by in vitro experiments, showing that linezolid inhibited the proliferation of SCs. And the expression of P-AKT and P62 was elevated, and the expression of LC3B declined compared with the control group. Moreover, chloroquine (CQ), an autophagy inhibitor, also exhibited experimental results similar to linezolid. In summary, we conclude that linezolid-induced peripheral neuropathy is associated with the inhibition of autophagy flux.
研究领域:
药理学
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神经科学
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传染病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Yao Guo,Jing Cui,Xueyi Liang,Taoyu Chen,Chong Lu,Tao Peng
Pancreatic cancer (PC) is a serious threat to human health, with most patients diagnosed at the advanced stages of the disease. Treatment with gemcitabine (GEM) leads to PC GEM resistance. In addition, cancer stem cell (CSC)-derived exosomes play an important role in cancer progression. We aimed to investigate the role and mechanism of action of PC stem cell-derived exosomes in PC drug resistance and progression. CSC-derived exosomes increased the proportion of F4/80+/CD86 + cells and levels of M2 polarization factors. miR-210 is expressed in CSC-derived exosomes. Thus, following co-culture, miR-210 was taken up by macrophages. Transfection or the addition of miR-210 mimics increased the proportion of F4/80+/CD206 + cells and levels of M2 polarization factors. Further, the miR-210 targets inhibited the levels of FGFRL1. The FGFRL1 overexpression plasmid also inhibited miR-210-mediated M2 polarization. After co-culture of THP-M2 cells with PC cells and treatment with GEM, the survival rate, migration rate, and levels of MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR in PC cells increased. And THP-M2 increased the tumor volume and MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR levels. Overall, miR-210 from PC stem cell-derived exosome targets and inhibits FGFRL1 to promote macrophage M2 polarization, which activates the p-PI3K/p-AKT/p-mTOR pathway and increases GEM resistance.
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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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Ziyou Huai,Zijian Li,Wei Xue,Shujing Li,Yinjiu Huang,Xin Cao,Qinjun Wei,Yuanyuan Wang
Curcumin, extracted from Zingiberaceae and Araceae rhizomes, is clinically used for its anti-inflammatory, antibacterial, antioxidant, and anti-cancer properties. Its safety and potential make it a promising base for designing enhanced derivatives. The focus now is on optimizing curcumin and synthesizing more potent 1,4-pentadien-3-ones, which have anti-cancer activities. In the realm of triple-negative breast cancer (TNBC), an aggressive and invasive form with high metastatic potential, the need for innovative treatments is acute. The challenges posed by chemotherapy resistance, recurrence, and TNBC’s heterogeneity have emphasized the necessity for novel therapeutic approaches. Our strategy involved the integration of a quinoxaline ring into 1,4-pentadien-3-one , followed by subsequent modifications. In this study, N17 demonstrated the ability to induce cell death and effectively suppress cell proliferation in breast cancer cells. These observed anti-cancer effects were attributed to the inhibition of p-AKT(S473), a key regulator implicated in both cell apoptosis and the modulation of epithelial-mesenchymal transition process in breast cancer cells. Furthermore, our investigation indicated N17 achieves its inhibitory effects on p-AKT(S473) by specifically targeting the CSNK1G3 protein. Remarkably, N17 not only impedes the EMT process but also triggers apoptosis through the CSNK1G3/AKT signaling axis. These findings provide the critical role of CSNK1G3 as an anti-cancer regulator in TNBC, establishing N17 as a pharmacological intervention with immense promise for treating cancer metastasis.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 43
·30190-30201
·
IF 3.9
Huien Chen,Xinyu Liu,Meixia Xie,Xiaoting Zhong,Chunyan Yan,Minghua Xian,Shumei Wang
Rehmannia glutinosa (RG) as a Chinese herbal medicine can be used both in medicine and food. As the main component of RG, the polysaccharides have a hypoglycemic effect, however, the hypoglycemic activity of RG homopolysaccharides remains unknown. We isolated and purified two polysaccharides, RGP70-1-1 and RGP70-1-2 (4.9 kDa and 2.8 kDa) from RG. The structural characteristics, including monosaccharide composition, linkage, and configuration were analyzed by FT-IR, HPLC, GC-MS, NMR spectroscopy, Congo test, and SEM. RGP70-1-1 and RGP70-1-2 consist of four monosaccharides (glucose, mannose, arabinose, and galactose). RGP70-1-1 contains 14 connection modes, with the linkages including L-Araf-(1→, →3)-L-Araf-(1→, →5)-L-Araf-(1→, →3,5)-L-Araf-(1→, →2,5)-L-Araf-(1→, D-Manp-(1→, →2)-D-Manp-(1→, →4)-D-Manp-(1→, D-Galp-(1→, →4)-D-Galp-(1→, →4,6)-D-Galp-(1→, →6)-D-Glcp-(1→, →4,6)-D-Glcp-(1→, →3,6)-D-Glcp-(1→. The linkages of RGP70-1-2 is including →5)-L-Araf-(1→, →3,5)-L-Araf-(1→, →4)-D-Manp-(1→, →3,6)-D-Manp-(1→, D-Galp-(1→, →6)-D-Galp-(1→, D-Glcp-(1→, →6)-D-Glcp-(1→, →4,6)-D-Glcp-(1→. Furthermore, RGP70-1-1 and RGP70-1-2 can inhibit α-glucosidase and α-amylase. RGP70-1-1 stimulated GLP-1 secretion in STC-1 cells and was related to the up-regulation of PI3K and p-AKT protein expression. The findings revealed a natural product with potential hypoglycemic activity, which may be used as a GLP-1 secretagogue and a beneficial functional food ingredient for T2D.
研究领域:
药理学
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生物化学
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药物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Iranian Journal of Basic Medical Sciences
·
2017
·
IF 1.424
Jimei Bu,Hengbing Zu
Objective(s): In previous studies, researchers observed that doxepin could improve cognitive processes and has protective effects on the central nervous system. Thus, this study was designed to analyze the effects of doxepin on β-amyloid (Aβ)-induced memory impairment and neuronal toxicity in rat and to explore the underlying mechanism. Materials and Methods: Rats were treated with Aβ1-42 and doxepin was injected to validate its effects on cognitive function. The Morris water maze test was performed to detect memory function. Aβ1-42-treated SH-SY5Y human neuroblastoma cell line was also used to detect the effects of doxepin and to explore the underlying mechanism. Western blotting analysis was used to detect the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. Results: After treated with 1 mg/kg of doxepin, Aβ1-42-treated rats showed markedly lower escape latency and higher platform-finding strategy score. Low doses of doxepin significantly reversed the effects of Aβ1-42 on the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. In vitro experiment showed the consistent results. Besides, PI3K inhibitor (LY294002) treatment could markedly reversed the effects of doxepin on Aβ1-42-treated SH-SY5Y cells. Conclusion: Our results demonstrated that doxepin could protect against the Aβ1-42-induced memory impairment in rats. The protective effect of doxepin was associated with the enhancement of PSD-95 and synapsin 1 expression via PI3K/AKT/mTOR signaling pathway.
研究领域:
神经科学
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药理学
·
认知科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Yanzhi Wang,Cancan Sun,Leaf Huang,Mengqian Liu,Lu Li,Xiping Wang,Linchao Wang,Shanshan Sun,Haiwei Xu,Gege Ma,Lei Zhang,Jiaxin Zheng,Hongmin Liu
The potential of combination therapy using nanoparticle delivery systems in improving triple-negative breast cancer treatment efficacy remains to be explored. Here, we report a novel nanoparticle system using a cholesterol biguanide conjugate hydrochloride (CBH) as both a drug and carrier to load magnolol (MAG). Poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) and aminoethyl anisamide-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (AEAA-PEG-PLGA) were added to form nanoparticles. Nanoparticles accumulated most in tumor tissues when the weight ratio of AEAA-PEG-PLGA to mPEG-PLGA was 4:1. MAG and CBH exerted a synergistic inhibitory effect on 4 T1 cells. An in vitro study showed that nanoparticles displayed the highest tumor cell uptake rate, highest apoptosis rate, and strongest inhibitory effect on tumor cell migration and monoclonal formation. CBH might promote nanoparticle uptake by cells and lysosomal escape. After intravenous administration to mice with 4 T1 breast tumors in situ , the nanoparticles inhibited tumor growth without obvious toxicity. Western blot results showed that nanoparticles altered the levels of p53, p-AKT, and p-AMPK in the tumor tissue. Moreover, cell apoptosis was found in the same area of H&E-stained and TUNEL-stained tumors treated with the nanoparticles. Collectively, this nanoparticle system provides a novel combination drug delivery strategy for treating triple-negative breast cancer.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2017
·
IF 2.399
Lin Yu,Xiaofeng Wu,Min Chen,Huarong Huang,Yan He,Huaqian Wang,Dongli Li,Zhiyun Du,Kun Zhang,Susan Goodin,Xi Zheng
Background : Docetaxel is the first-line treatment for castration-resistant prostate cancer (CRPC). The limited survival benefit associated with the quick emergence of resistance and systemic toxicity diminishes its efficacy in high-dose monotherapy. YK-4-279 is a small molecule inhibitor of ETV1 that plays an important role in the progression of prostate cancer. The aim of this study was to evaluate the hypothesis that the combination of docetaxel and YK-4-279 will have a synergistic effect on inhibiting growth and accelerating apoptosis in human prostate cancer cells. Methods : Cell growth assessed using CCK-8 and trypan blue exclusion assays. Cell apoptosis was determined by morphological assessment in cells stained with propidium iodide. Standard scratch migration and Matrigel-coated transwell invasion assays were used to assess cell migration and invasion, respectively. Western blotting was used to investigate the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in prostate cancer cells. Results : The combination of low-dose docetaxel and YK-4-279 synergistically inhibited growth and induced apoptosis in human prostate cancer cells. The combination also more efficiently suppressed the migration and invasion of LNCaP and PC-3 cells. The combination of low-dose docetaxel and YK-4-279 caused a stronger decrease in the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in LNCaP cells and of p-Akt, Bcl-2, and p-STAT3 in PC-3 cells compared with either drug alone. Conclusions : These data suggest that the combination of docetaxel and YK-4-279 may be an effective approach for inhibiting the growth and metastasis of prostate cancer. This could permit a decrease in the docetaxel dose necessary for patients with CRPC and thereby lower its systemic toxicity.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Suwen Liu,Jincheng Yu,Mengfan Fu,Xinfang Wang,Xuedong Chang
Hawthorn polyphenol extract (HPE) is beneficial for patients with type 2 diabetes (T2D). However, the mechanism underlying its beneficial effects remains unclear. We investigated the inhibitory effects and mechanisms of HPE on insulin resistance, inflammation, and aortic injury in T2D rats, using metformin (MF) as a positive control. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) was used to determine the primary polyphenols in HPE. Hematoxylin & Eosin (H&E) staining was used to evaluate pathological conditions of the skeletal muscle, liver, and aorta vessels in each group. The levels of serum and intestinal tissue oxidative stress, tumor necrosis factor α (TNF-α), and inflammatory interleukin-6 (IL-6) were also assessed. Western blotting was used to evaluate protein expression levels in the associated molecular pathway. Volatile organic compounds (VOCs) from colon contents were determined using headspace-gas chromatography-ion mobility chromatography. Our results showed that supplementation with 300 mg HPE/kg body weight over four weeks significantly improved total cholesterol (TC), total triglyceride (TG), insulin, and lipopolysaccharide (LPS) levels in diabetic rats ( p < 0.01). The lesions of skeletal muscle, liver, and aorta in diabetic rats were significantly improved. HPE supplementation also significantly downregulated the inflammatory factors (IL-6, TNF-α, and MCP-1) in the liver of diabetic rats via the SIRT1/AMPK/NF-κB signaling pathway. Furthermore, HPE significantly reduced insulin resistance in T2D rats by upregulating the phosphorylation of glucose absorption protein (GLUT4) and insulin resistance-associated proteins, p-IRS1, p-AKT, and p-PI3K, in the rat liver ( p < 0.01). The findings show that HPE could also alleviate aortic injury by activating SIRT1 and regulating the NF-κB and Wnt2/β-catenin signaling pathways. Overall, the results of this study suggest that both HPE and MF have similar inhibitory effects on T2D in rats and that HPE could be used as a functional food component in the adjuvant treatment of T2D.
研究领域:
药理学
·
内分泌学
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2022
·
IF 3.94
Hui Yu,Ruxin Zheng,Fei Lei,Wanyue Wang,Weikang Guo,Lu Zhang,Yunduo Liu,Xiuwei Chen,Yaoxian Wang
This study aimed to synthesize silica-coated gold (Au@SiO 2 ) nanoparticles coupled to antibodies against the scavenger receptor class B type I (SR-BI) and investigate their potential ability of visual tracking and treatment of cervical cancer. The fluorescein isothiocyanate (FITC)-labeled Au@SiO 2 -SR-BI antibody was synthesized, followed by characterization determination. The expression and location of SR-BI protein in cervical cancer cells were respectively detected by western blot and immunofluorescence assays. The effects of nanoparticles on cancer cells were determined by adsorption assay and apoptosis detection, respectively. The effects of nanoparticles on tumor formation in nude mice were determined. The particle sizes of Au@SiO 2 ranged from 2-2.5 μm, and the particle size distribution was relatively uniform. MS751 showed the highest expression of SR-BI. SR-BI was located in the cytomembrane. There were more FITC-Au@SiO 2 -SR-BI nanoparticles on the surface of the cells compared to FITC-Au@SiO 2 . Significant apoptosis was observed in the FITC-Au@SiO 2 -SR-BI-treated group in both MS751 and H8 cells. Photothermal ablation of solid tumors was observed when FITC-Au@SiO 2 -SR-BI was activated using 808 nm wave. Expressions of the apoptosis-related markers including BCL2, BCLX, and p-AKT were significantly decreased, while those of caspase 3 and caspase 8 were significantly increased. The study presented a novel antibody-conjugated Au@SiO 2 nanoparticle specifically targeting molecular receptors on cancer cell membranes. Antibody-conjugated Au@SiO 2 nanoparticles may have therapeutic potential for the treatment of cervical cancer.
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 10
·1523
·
IF 4.7
Mengyao Zhang,Huiqian Liu,Linlin Xu,Xizi Zhang,Wei Chen,Chengtao Wang
Histamine, a bioactive component in certain foods such as Huangjiu has been associated with liver injury and disrupted intestinal balance. This study explored the potential therapeutic effects of fucoidan (FCD) in mitigating histamine-induced imbalances in mice. We found that FCD mitigated liver injury, reducing transaminases, oxidative stress, and inflammation. Histological improvements included decreased cell infiltration and necrosis. FCD restored tight junction proteins and suppressed inflammation-related genes. Western blot analysis revealed FCD’s impact on TGF-β1,p-AKT, AKT, CYP2E1, Grp78, NLRP3, Cas-1, and GSDMD. Gut LPS levels decreased with FCD. Gut microbiota analysis showed FCD’s modulation effect, reducing Firmicutes and increasing Bacteroides. FCD demonstrates potential in alleviating histamine-induced liver injury, regulating inflammation, and influencing gut microbiota. Further research exploring higher dosages and additional parameters is warranted.
研究领域:
药理学
·
肝病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）