盐酸洛美沙星与人血清白蛋白相互作用的荧光光谱

应用荧光光谱法研究了生理条件下盐酸洛美沙星(LOM)与人血清白蛋白(HSA)相互作用机制。研究表明:盐酸洛美沙星对HSA内源荧光的猝灭机制属于形成复合物所引起的静态猝灭,猝灭速率常数Kq为3.37×1012L.mol-1.S-1;结合常数为1.23×105,结合位点数为1.11,并根据F rster非辐射能量转移理论,计算出盐酸洛美沙星与HSA相互结合时其供体-受体间的结合距离(R=2.44 nm)和能量转移效率(E=0.209)。通过HSA与抗菌药物盐酸洛美沙星结合反应,探讨了药物盐酸洛美沙星在生物体内与蛋白质相互作用的生物学效应及其作用机理,讨论了共存Cu2+、Fe3+、Zn2+对盐酸洛美沙星与HSA结合反应的影响。     

Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections

Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups.     

Antiproliferative and Pro-Apoptotic Effects of a Phenolic-Rich Extract from Lycium barbarum Fruits on Human Papillomavirus (HPV) 16-Positive Head Cancer Cell Lines

The in vitro antiproliferative activity of a phenolic-rich extract from Lycium barbarum fruits against head and neck HPV16 squamous cell carcinoma (OSCC) has been demonstrated, indicating for the first time that L. barbarum extract inhibits human papillomavirus (HPV) type 16 cell lines. Ethanol extract of L. barbarum was used for cell viability evaluation on SCC090, CAL27, and HGnF cell lines. After 24 and 48 h, the cell cycle effect of L. barbarum extract (at 1.0, 10, and 100 µg/mL) was measured via flow cytometry. In addition, the mRNA expression on E6/E7 and p53 via RT-PCR and the expression of p16, p53, Ki-67, and Bcl-2 via immunohistochemistry were also determined. Untreated cells, 20 µM cisplatin, and a Camellia sinensis-derived extract were used as negative and positive controls, respectively. We demonstrated that the studied L. barbarum extract resulted in G₀/G₁ arrest and S phase accumulation in SCC090 at 1.0 and 10 μg/mL. A reduction in mRNA levels of E6/E7 oncogenes (p < 0.05) with p53 overexpression was also observed through PCR, while immunohistochemical analyses indicated p16 overexpression (p > 0.05) and a decrease in p53 overexpression. The observed effects were associated with anticancer and immunomodulatory phenolics, such as flavonols/flavan-3-ols and tyramine-conjugated hydroxycinnamic acid amides, identified in the studied extract. These findings revealed that the phenolic-rich extract of L. barbarum fruits has promising properties to be considered further for developing new therapies against oral and oropharyngeal HPV lesions.     

Zinc and Copper Ions Induce Aggregation of Human β-Crystallins

Cataracts are defined as the clouding of the lens due to the formation of insoluble protein aggregates. Metal ions exposure has been recognized as a risk factor in the cataract formation process. The γ and β crystallins are members of a larger family and share several structural features. Several studies have shown that copper and zinc ions induce the formation of γ-crystallins aggregates. However, the interaction of metal ions with β-crystallins, some of the most abundant crystallins in the lens, has not been explored until now. Here, we evaluate the effect of Cu(II) and Zn(II) ions on the aggregation of HβA1, as a representative of the acidic form, and HβB2, as a representative of the basic β-crystallins. We used several biophysical techniques and computational methods to show that Cu(II) and Zn(II) induce aggregation following different pathways. Both metal ions destabilize the proteins and impact protein folding. Copper induced a small conformational change in HβA1, leading to high-molecular-weight light-scattering aggregates, while zinc is more aggressive towards HβB2 and induces a larger conformational change. Our work provides information on the mechanisms of metal-induced aggregation of β-crystallins.     

丝素蛋白修饰改性的聚羟基脂肪酸酯支架上人体平滑肌细胞的生长

聚三羟基丁酸脂和聚三羟基己酸脂的共聚物(PHBHH_x)是一种具有良好强度和韧性的生物可降解高分子材料, 可作为组织工程心脏瓣膜支架的选择材料之一. 但其生物相容性尚不甚理想. 为此, 本工作利用丝素蛋白修饰改性高分子多孔支架, 以提高支架的生物相容性. 并将人体平滑肌细胞接种在该复合支架上进行体外培养, 以证实改性效果. 其中, 用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)方法测试细胞生长, 评估复合支架的细胞相容性. 并用扫描电子显微镜观察细胞在支架上的生长形态. 结果显示, 丝素蛋白修饰改性后的复合支架更有利于细胞的粘附与生长, 平滑肌细胞在支架上表现出良好的生长形态. 这表明, 丝素能够改善多孔支架的生物相容性, 使PHBHH_x/丝素蛋白复合物能更适宜作为组织工程心脏瓣膜的支架材料. 结果对于进一步研究细胞外间质在复合支架上的生长以及体外培养的组织重建有重要的参考意义.     

资本配置视角下财产保险公司承保决策分析

探讨了产险公司在资本和收益双重约束条件下的承保决策问题．首先,从保险理论和实践的角度选择了TVaR资本配置方法,然后构造综合资本、收益双重因素的承保决策模型并进行了实证分析,结论显示从资本的角度进行承保决策是可行的．     

营运资本与公司综合治理对公司价值影响研究

拓展Faulkender和Wang(2006)模型,引入公司综合治理水平变量,分析了公司综合治理水平和营运资本对公司价值的影响.运用我国A股市场2008~2013年数据进行实证,证实公司综合治理水平与营运资本对企业价值影响显著;边际营运资本价值小于边际现金价值,企业在现有营运资本水平下增加营运资本投资,将降低企业超额收益率,减少企业投资价值;商业性企业比工业性企业、高治理效率企业比低治理效率企业、受融资约束企业比不受融资约束企业具有更高的边际营运资本价值.     

基于CAPM框架下的创业企业风险资本融资契约设计

从组合的视角出发,考虑创业企业家的风险厌恶程度,通过等价利率将创业企业的风险资本融资契约适应到CAPM框架下,利用纳什议价解刻画双方在信息不对称下的均衡解,基于风险-收益的角度建立了最优融资契约设计模型,为创业企业融资提供了契约设计和风险资本类型选择的一个依据,并通过算例说明了模型的可行性。研究还表明,创业企业引入风险资本优于纯债务融资,而股权的分配则取决于双方的议价力。同时,风险厌恶程度越低的创业企业家越趋向于选择独立的风险投资机构;风险厌恶程度越高的创业企业家越趋向于选择公司背景的风险投资机构;而风险厌恶程度不高,考虑后期贷款的创业企业家则趋向于选择银行背景的风险投资机构。