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为提高Western Blotting结果的可靠性,以蛋白溶出率和凝胶电泳蛋白条带完整性为指标,比较提取液种类、研磨方式、酶抑制剂种类及其体积分数和提取时间对南美白对虾肝胰腺蛋白提取效果的影响。采用优化后的提取方法获得高质量蛋白样品,并采用Western Blotting法分析无水环境胁迫后南美白对虾肝胰腺组织中细胞凋亡信号通路相关蛋白的表达水平。结果表明:RIPA裂解液作为提取溶剂所得的蛋白溶出率高于水提和磷酸盐缓冲液,电动匀浆和液氮研磨所得蛋白条带更完整,4%蛋白酶磷酸酶混合抑制剂能有效抑制肝胰腺内源酶引起的蛋白降解;采用Western Blotting法分析无水保活期间南美白对虾肝胰腺蛋白,发现低温诱导休眠的同时会引起细胞轻微凋亡,且凋亡水平呈应激时间依赖性增加,环境胁迫解除后有所回调。 相似文献
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目的观察化脓隐秘杆菌自然感染奶牛脾脏组织的病理学变化,并检测组织细胞中Caspase-3、Caspase-8、Caspase-9、Bax和Bcl-2的表达,以确定化脓隐秘杆菌感染对奶牛脾脏组织细胞凋亡的影响。方法筛检2头化脓隐秘杆菌阴性健康奶牛(对照)和5头自然感染化脓隐秘杆菌的奶牛,收集脾脏组织样本,采用本课题组国家发明专利方法,进行石蜡制片和HE染色,观察脾脏组织病理学变化;采用免疫组织化学方法与本课题组国家发明专利方法相结合,检测奶牛脾脏组织中与细胞正负凋亡相关的调节基因Bax和Bcl-2及凋亡通路蛋白Caspase-3、Caspase-8和Caspase-9的表达情况。结果肉眼观察可见化脓隐秘杆菌自然感染奶牛脾脏肿大、柔软,有出血;病理组织学观察可见脾脏组织出血,水肿,淋巴细胞数量减少,有坏死;脾脏淋巴细胞Caspase-3、Caspase-9和Bax表达阳性,与对照组相比,差异有统计学意义(P <0.05),少量淋巴细胞Caspase-8和Bcl-2表达阳性,与对照组相比,差异无统计学意义(P> 0.05)。结论化脓隐秘杆菌能够引起奶牛脾脏淋巴细胞发生坏死和凋亡;可通过调节脾脏中淋巴细胞Bcl-2家族的活性,引起其Bax和Bcl-2比率改变,增加淋巴细胞线粒体内外膜通透性,导致与凋亡相关因子的释放,激活Caspase-9,进一步激活Caspase-3,从而引起脾脏中淋巴细胞发生凋亡。 相似文献
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So Young Kim Cheol Park Min Yeong Kim Seon Yeong Ji Hyun Hwangbo Hyesook Lee Su Hyun Hong Min Ho Han Jin-Woo Jeong Gi-Young Kim Chang-Gue Son JaeHun Cheong Yung Hyun Choi 《International journal of molecular sciences》2021,22(9)
Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC. 相似文献
6.
Cheng-Chin Huang Ching-Yao Yang Chin-Chuan Su Kai-Min Fang Cheng-Chieh Yen Ching-Ting Lin Jui-Min Liu Kuan-I Lee Ya-Wen Chen Shing-Hwa Liu Chun-Fa Huang 《International journal of molecular sciences》2021,22(9)
4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway. 相似文献
7.
Mohammad Bani Ismail Peramaiyan Rajendran Hamad Mohammed AbuZahra Vishnu Priya Veeraraghavan 《International journal of molecular sciences》2021,22(8)
Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity. 相似文献
8.
Oxana Kazakova Irina Smirnova Elena Tretyakova Ren Csuk Sophie Hoenke Lucie Fischer 《International journal of molecular sciences》2021,22(4)
Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI50) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC50) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI50 level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI50 level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group. 相似文献
9.
Zaidatul Akmal Othman Zaida Zakaria Joseph Bagi Suleiman Victor Udo Nna Aminah Che Romli Wan Syaheedah Wan Ghazali Mahaneem Mohamed 《International journal of molecular sciences》2021,22(8)
Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role. 相似文献
10.
Prof. Chiara Brullo Dr. Federica Rapetti Prof. Silvana Alfei Dr. Irena Maric Dr. Francesca Rizzelli Dr. Marina Mapelli Dr. Camillo Rosano Dr. Maurizio Viale Prof. Olga Bruno 《ChemMedChem》2020,15(11):961-969
Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. 相似文献