Cationic Albumin‐Conjugated Chelating Agent as a Novel Brain Drug Delivery System in Neurodegeneration

The critical role of metal ions and in particular iron in oxidative stress and protein aggregation offers chelation therapy as a sensible pharmaceutical strategy in oxidative stress‐induced neuronal damages. In this research, we conjugated an iron‐chelating agent, deferasirox, to cationized human serum albumin molecules in order to develop a novel brain delivery system for the management of neurodegenerative disorders due to the significant role of oxidative stress‐induced neuronal injury in such diseases. Cationized albumin is known to be able to transport to brain tissue via adsorptive‐mediated transcytosis. The developed structures were molecularly characterized, and their conjugation ratio was determined. PC12 cell line was utilized to evaluate the neuroprotective features of these newly developed molecules in the presence of hydrogen peroxide neuronal damage and to identify the mechanisms behind the observed neuronal protection including apoptotic and autophagic pathways. Furthermore, a rat model of Alzheimer's disease was utilized to evaluate the impact of conjugated structures in vivo. Data analysis revealed that the conjugated species were able to hinder apoptotic cell death while enhancing autophagic process. The developed conjugated species were also able to attenuate amyloid beta‐induced learning deficits when administered peripherally.     

Increased Circulating Levels of Vitamin D Binding Protein in MS Patients

Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS.     

3种人血清白蛋白降解多肽片段的血液相容性研究

目的 研究3种人血清白蛋白降解多肽片段(PF1-123、PF124-298、PF299-585)的血液相容性.方法 分别考察3种多肽片段对新鲜人血的溶血率、对血细胞形态的影响、全血凝固时间以及血浆复钙时间,测试其血液相容性.结果 PF1-123、PF124-298和PF299-585对新鲜人血的溶血率分别为0.52％±0.47％、0.39％±0.33％、0.32％±0.23％,对血细胞形态均无不良影响,说明3种多肽片段均符合医用材料的溶血率要求;3种多肽片段的全血凝固时间曲线以及血浆复钙时间曲线与人血清白蛋白相似,说明其与血液接触后不会激活相关因子而促成凝血.结论 PF1-123、PF124-298和PF299-585具有良好的血液相容性.     

人血白蛋白在原发性肝癌肝切除术后的应用分析

目的 对东方肝胆外科医院原发性肝癌行肝切除术后使用人血白蛋白的情况进行合理性评价。 方法 回顾分析2012年6月至2013年6月期间150例原发性肝癌患者行肝切除术后应用人血白蛋白治疗的临床资料,比较患者术后应用人血白蛋白前后临床指标、生化指标,及人血白蛋白用药剂量相关因素分析,评价该院人血白蛋白的用药合理性。 结果 在统计的150份病历中,白蛋白总用量11 212.5 g(897瓶),总金额527 744元,占药品总费用的近20%,占住院总费用的近10%。患者在术后使用人血白蛋白后肝功能异常指标阳性率降低(P<0.05),人血白蛋白的使用剂量与患者用药前肝功能的Child-Pugh评分存在正相关(P<0.05)。 结论 该院原发性肝癌肝切除术后使用人血白蛋白较为合理,可达到预期的治疗效果。     

原发性高血压患者血压变异性与尿微量白蛋白/尿肌酐比值研究

目的：探讨原发性高血压患者血压变异性（BPV）与尿微量白蛋白/尿肌酐的关系。方法：103例符合入选标准的原发性高血压患者作为高血压组,并选96例健康体检者作为对照组,予24h监测动态血压、血压变异性及尿微量白蛋白,比较两组血压变异性与尿微量白蛋白/尿肌酐的关系。结果：各组患者在年龄、性别、吸烟史、总胆固醇、甘油三酯、空腹血糖以及体重指数等指标方面比较无差异性(P>0.05),高血压组患者昼间SBPV、夜间SBPV和24h SBPV均显著高于对照组(P<0.01);高血压组尿微量白蛋白、尿微量白蛋白/尿肌酐比值显著高于对照组(P<0.05)。结论：血压变异程度与尿微量白蛋白/尿肌酐具有相关性,可预测高血压早期的肾功能损害。     

棉酚与人血清白蛋白相互作用及其分子模拟研究

摘 要 目的： 探讨棉酚与人血清白蛋白(HSA)的相互作用。方法: 采用荧光光谱方法研究在生理条件下,棉酚与人血清白蛋白（HSA）的相互作用,并采用分子对接软件模拟棉酚与人血清白蛋相互作用。结果:棉酚与HSA的结合常数为2.390 6×10⁵ L·mol^-1 (293K) 和3.576 8×10³ L·mol^-1（303K）, 具有一个结合位点,结合反应的主要作用力为氢键和范德华力,结合位置更接近于人血清白蛋白的酪氨酸残基,分子模拟分析也证实此结果。结论: 棉酚对人血清白蛋白的荧光猝灭机制属于静态荧光猝灭。     

西红康对实验性糖尿病肾病大鼠肾脏结构和功能的影响

目的：考察西红康对实验性糖尿病肾病大鼠肾脏结构和功能的影响。方法32只 Wistar 大鼠（雄性）随机分为模型组、西红康组、糖适平阳性组和正常对照组,每组8只,建立糖尿病肾病大鼠模型,对大鼠进行8周的治疗,检测记录治疗前后大鼠的血糖、体重和尿微量白蛋白,分别采用光学显微镜及透射电镜观察大鼠肾脏的结构变化。结果给药前,各组动物的血糖、体重和尿微量白蛋白中均无统计学差异（P ＞0．05）。给药8周后,血糖水平、体重和尿微量白蛋白指标,阳性组和西红康组相对于模型组均有统计学差异（P ＜0．05）。正常组大鼠肾脏肾小球结构完整,肾脏系膜细胞、滤过膜内皮细胞和足细胞均结构正常,模型组大鼠肾小球体积增大,系膜细胞发生中度增生,毛细血管基底膜结构模糊,内皮细胞胞质局部融合,阳性组和西红康组均能不同程度降低肾小球大小,缓解系膜细胞增生,毛细血管基底膜结构更为清晰,内皮细胞胞质融合程度下降。结论西红康可减轻实验性糖尿病肾病大鼠肾脏病理损害,改善肾脏功能。     

Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin

We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A_299–585 (A_299–585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A_299–585 via a succinic acid spacer to give TPS-PF-A_299–585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A_299–585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A_299–585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A_299–585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A_299–585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A_299–585 to be a useful carrier for targeting TP to the kidney.     

Comparative examination of adsorption of serum proteins on HSA- and PLGA-based nanoparticles using SDS–PAGE and LC–MS

The behavior of nanosized drug carrier systems under cell culture conditions and therefore also the destiny in the body are highly influenced by the protein corona, which is formed upon entering a biological environment. Some of the adsorbed proteins, named opsonins, lead to a shortened plasma circulation half-life of the nanoparticles. Others are attributed to promote the transport of nanoparticles into other compartments of the body, just to mention two examples. Hence, detailed knowledge concerning the composition of the protein corona is of great importance. The aim of this work was to investigate the influence of the nanoparticle starting material and the surface modification on the composition of the adsorbed serum proteins in a cell culture environment. Therefore, positively charged nanoparticles based on the biodegradable polymer poly(dl-lactide-co-glycolide) (PLGA) stabilized with didodecyldimethylammonium bromide (DMAB) and negatively charged nanoparticles based on human serum albumin (HSA) were prepared and modified with hydrophilic polymers. By incubating the nanoparticles with fetal bovine serum (FBS) the adsorption of serum proteins on the colloidal system was investigated. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) a semi-quantitative analysis of the protein corona was performed and after enzymatic in-solution-digestion the adsorbed proteins were identified using high resolution LC–MS. Our study accentuates the influence of the core material, surface charge, and surface modification on the amount and nature of the adsorbed proteins. The combination of SDS–PAGE and LC–MS turns out to be a simple and reliable method to investigate the protein corona of nanoparticles.     

Prognostic significance of the combination of preoperative hemoglobin,albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients.