Alternating Cationic-Hydrophobic Peptide/Peptoid Hybrids: Influence of Hydrophobicity on Antibacterial Activity and Cell Selectivity

The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent antibacterial activity (e. g., MICs of 2–8 μg/mL against E. coli) and low toxicity toward mammalian cells (<10 % hemolysis at 400 μg/mL and IC₅₀>800 μg/mL for HepG2 viability). Most peptidomimetics retained activity against drug-resistant strains. These findings corroborate the hypothesis that for related peptidomimetics two hydrophobicity thresholds may be identified: i) it should exceed a certain level in order to confer antibacterial activity, and ii) there is an upper limit, beyond which cell selectivity is lost. It is envisioned that once identified for a given subclass of peptide-like antibacterials such thresholds can guide further optimisation.     

咖啡酸的化学改性及产物抗氧化性的研究

以咖啡酸和氨基酸乙酯盐酸盐为原料,1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)及1-羟基苯并三唑(HOBt)为催化剂,合成咖啡酰甘氨酸乙酯、咖啡酰丙氨酸乙酯、咖啡酰丝氨酸乙酯、咖啡酰苏氨酸乙酯4种产物。利用核磁共振氢谱(~1H NMR)和高效液相色谱-质谱(HPLC-MS)对产物结构进行表征,考察了咖啡酸化学改性产物对DPPH自由基及羟基自由基活性的抑制率及对红细胞膜的刺激性,并与咖啡酸单体进行了比较。结果表明,通过在咖啡酸中引入甘氨酸乙酯、丙氨酸乙酯、丝氨酸乙酯和苏氨酸乙酯后,4种咖啡酸酰胺类产物均呈现较好的抑制DPPH自由基、羟基自由基活性的效果;咖啡酰丝氨酸乙酯清除DPPH自由基能力较强,其IC_(50)值为13.5 μmol/L;咖啡酰丙氨酸乙酯清除羟基自由基能力较强,其IC_(50)值为0.214 mmol/L。红细胞溶血试验结果表明,4种咖啡酸酰胺类衍生物的红细胞溶血率均低于咖啡酸单体。     

Oxidative capacity and hemolytic activity of settled dust from moisture‐damaged schools

Exposure to moisture‐damaged indoor environments is associated with adverse respiratory health effects, but responsible factors remain unidentified. In order to explore possible mechanisms behind these effects, the oxidative capacity and hemolytic activity of settled dust samples (n = 25) collected from moisture‐damaged and non‐damaged schools in Spain, the Netherlands, and Finland were evaluated and matched against the microbial content of the sample. Oxidative capacity was determined with plasmid scission assay and hemolytic activity by assessing the damage to isolated human red blood cells. The microbial content of the samples was measured with quantitative PCR assays for selected microbial groups and by analyzing the cell wall markers ergosterol, muramic acid, endotoxins, and glucans. The moisture observations in the schools were associated with some of the microbial components in the dust, and microbial determinants grouped together increased the oxidative capacity. Oxidative capacity was also affected by particle concentration and country of origin. Two out of 14 studied dust samples from moisture‐damaged schools demonstrated some hemolytic activity. The results indicate that the microbial component connected with moisture damage is associated with increased oxidative stress and that hemolysis should be studied further as one possible mechanism contributing to the adverse health effects of moisture‐damaged buildings.     

A novel leukodepletion filter from electrospun poly(ethylene-vinyl alcohol) membranes and evaluation of its efficiency

The authors describe the fabrication and evaluation of a novel leukodepletion filter using novel poly(ethylene-vinyl alcohol) membranes through electrospinning. The membranes were biocompatible and nonhemolytic. A prototype of the filter was developed by stacking the membranes in a poly(methyl methacrylate) case. Upon whole blood filtration, the filter could achieve 100% leukodepletion while capturing 8% red blood cells and 91% platelets. The length of filtration through the developed filter was high when compared to that of marketed filter while overall performance of the filter was comparable to that of the marketed filter.     

羧基化氧化石墨烯-镧复合物抗凝血性能的研究

将稀土La(3+)离子接枝到羧基化的氧化石墨烯片层上,制备了一种功能化的氧化石墨烯(GeneO-La).利用红外光谱和透射电镜等手段对所合成的GeneO-La复合物进行了表征;将功能化的氧化石墨烯应用到抗凝血体系中,研究其抗凝血性能.结果表明,La(3+)已经通过配位作用吸附在羧基化的氧化石墨烯片层上.通过溶血实验和血...     

医用高氮无镍奥氏体不锈钢的制备与生物相容性研究

主要探讨不同含氮量的无镍奥氏体不锈钢材料对血管内皮细胞及血小板粘附的影响。通过溶血率和血小板粘附试验考察不同含氮量的无镍奥氏体不锈钢材料的血液相容性;通过MTT试验和细胞粘附试验考察不同含氮量的无镍奥氏体不锈钢材料的细胞相容性。结果表明不同含氮量的无镍奥氏体不锈钢材料的溶血率都低于国家标准的5%,对血小板粘附的影响不显著;粘附在高氮无镍奥氏体不锈钢材料表面的血管内皮细胞数量均多于钛合金材料,且细胞生长状态良好;细胞毒性试验表明,不同含氮量的高氮无镍奥氏体不锈钢材料和对照组钛合金材料对血管内皮细胞没有产生明显的毒副作用。     

pH值对透明质酸钠溶液溶血性测定的影响

目的探讨pH值对透明质酸钠(HA)溶液溶血性的影响。方法调整0.4%HA溶液的pH值,以1%羊血悬浮液检测溶血性。结果0.4%HA溶液的pH<4时,溶血检测阳性;调整pH 5.5~8.0时,溶血阴性。结论0.4%HA溶液在pH<4时,其溶血性检测结果为假阳性。检测时应将HA溶液的pH调至5.5~8.0。     

Tailor-made pH-sensitive polyacrylic acid functionalized mesoporous silica nanoparticles for efficient and controlled delivery of anti-cancer drug Etoposide

A multifaceted therapeutic platform has been proposed for controlled delivery of Etoposide (ETS) leading to a synergistic advantage of maximum therapeutic efficacy and diminished toxicity. A state of the art pH responsive nanoparticles (NPs) MSNs-PAA consisting of mesoporous silica nanoparticles core and polymeric shell layers, were developed for controlled release of model anti-cancer drug ETS. Graft onto strategy was employed and amination served as an interim step, laying a vital foundation for functionalization of the MSN core with hydrophilic and pH responsive polyacrylic acid (PAA). MCM-41-PAA were investigated as carriers for loading and regulated release of ETS at different pH for the first time. The PAA-MSNs contained 20.19% grafted PAA as exhibited by thermogravimetric analysis (TGA), which enormously improved the solubility of ETS in aqueous media. The synthesized PAA-MSNs were characterized by various techniques viz, SEM-EDS, TEM, BET, FT-IR and powder XRD. ETS was effectively loaded into the channels of PAA-MSN via electrostatic interactions. The cumulative release was much rapid at extracellular tumor (6.8) and endosomal pH (5.5) than that of blood pH (7.4). Hemolysis study was done for the prepared NPs. MTT assay results showed that the drug-loaded ETS-MCM-41-PAA NPs were more cytotoxic to both prostate cancer cells namely PC-3 and LNCaP than free ETS, which was attributed to their slow and sustained release behavior. The above results confirmed that PAA-MSN hold a great potential as pH responsive carriers with promising future in the field of cancer therapy.