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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
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《Cancer cell》2022,40(2):153-167.e11
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Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T2-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T2-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T2-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T2 relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T2 was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T2 relaxation time was derived (R2 = 0.98): T2 (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T2-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T2-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis. 相似文献
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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
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《Vaccine》2022,40(32):4296-4300
Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19. 相似文献
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Kevin Kyung Ho Choi Santosh Sanagapalli 《World journal of gastrointestinal oncology》2022,14(3):568-586
Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations. 相似文献
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Xiumei Jiang Xiaowei Zhang Patrick Gray Jiwen Zheng Timothy R. Croley Peter P. Fu 《journal of environmental science and health part c-environmental carcinogenesis & ecotoxicology reviews》2019,37(2):116-131
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