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1.
目的 对比研究朝鲜淫羊藿酸性多糖酯化还原前后的理化特性,并探讨其改善油酸诱导的肝癌HepG2细胞脂质堆积活性的差异。方法 采用高效凝胶渗透色谱法测定朝鲜淫羊藿酸性多糖(EFPA)的均一性和分子量,高效液相色谱法测定EFPA和酯化还原后朝鲜淫羊藿酸性多糖(EFPA-R)的单糖组成;采用油酸(OA)处理HepG2细胞诱导建立脂质蓄积模型,不同浓度EFPA与EFPA-R(10、30、100、300 μg·mL-1)分别和OA共同作用于细胞24 h,采用CCK-8试剂盒测定细胞存活率,油红O染色观察细胞内脂滴蓄积情况,并采用试剂盒测定细胞内总胆固醇(TC)、甘油三酯(TG)含量。结果 EFPA为成分均一的多糖组分,分子量为125.8 kDa,由甘露糖、葡萄糖、半乳糖、葡萄糖醛酸和阿拉伯糖组成,摩尔比为1.7∶7.4∶1.4∶1.8∶1.0,葡萄糖占比最大,EFPA-R由甘露糖、葡萄糖、半乳糖和阿拉伯糖组成,摩尔比为0.8∶10.6∶2.1∶1.0;在10-300 μg·mL-1范围内,EFPA和EFPA-R对HepG2细胞的抑制作用较弱,作为给药浓度;与空白组相比,模型组细胞中TC、TG含量显著升高(P < 0.01),细胞内红色脂滴显著增多,与模型组相比,EFPA可显著降低细胞中TC、TG含量(P < 0.01),明显减少细胞内红色脂滴(P < 0.05或P < 0.01),EFPA-R干预后细胞则无明显变化。结论 EFPA可明显改善HepG2细胞脂质堆积情况,且呈现剂量依赖性,而半乳糖醛酸(GalA)的存在可能是其抑制HepG2细胞脂质蓄积的关键因素。  相似文献   
2.
《Cancer cell》2022,40(2):153-167.e11
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Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL.  相似文献   
6.
Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H2O2. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.  相似文献   
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Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.  相似文献   
9.
Introduction: Ischemic stroke is becoming a primary cause of disability and death worldwide. To date, therapeutic options remain limited focusing on mechanical thrombolysis or administration of thrombolytic agents. However, these therapies do not promote neuroprotection and neuro-restoration of the ischemic area of the brain.

Areas covered: This review highlights the option of minimal invasive, intra-arterial, administration of biological agents for stroke therapy. The authors provide an update of all available studies, discuss issues that influence outcomes and describe future perspectives which aim to improve clinical outcomes. New therapeutic options based on cellular and molecular interactions following an ischemic brain event, will be highlighted.

Expert opinion: Intra-arterial administration of biological agents during trans-catheter thrombolysis or thrombectomy could limit neuronal cell death and facilitate regeneration or neurogenesis following ischemic brain injury. Despite the initial progress, further meticulous studies are needed in order to establish the clinical use of stem cell-induced neuroprotection and neuroregeneration.  相似文献   

10.

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
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