Mitophagy induced by nanoparticle–peptide conjugates enabling an alternative intracellular trafficking route

The intracellular behaviors of nanoparticles are fundamentally important for the evaluation of their biosafety and the designs of nano carrier-assisted drug delivery with high therapeutic efficacy. It is still in a great need to discover how functionalized nanoparticles are transported inside the cells, for instance, in a complicated fashion of translocation between different types of cell organelles. Here we report a new understanding of the interactions between nanoparticles and cells by the development of polyoxometalates nanoparticle–peptide conjugates and investigation of their intracellular trafficking behaviors. The as-prepared nanoparticles are featured with a unique combination of fluorescence and high contrast for synchrotron X-ray-based imaging. Functional surface modification with peptides facilitates effective delivery of the nanoparticles onto the target organelle (mitochondria) and subsequent intracellular trafficking in a dynamic mode. Interestingly, our experimental results have revealed that autophagy of mitochondria (mitophagy) can be induced by NP-peptide as a cellular response for recycling the damaged organelles, through molecular mediation associated with the change of mitochondrial membrane potential. The biological effects induced by NP-peptide reciprocally affect the distribution patterns and fates of nanoparticles in the cell metabolism by providing an alternative route of intracellular trafficking. The new understanding of the mutual activities between nanoparticles and cells will enrich our approaches in the development of nanobiotechnology and nano-medicine for disease treatments.     

Plant sterols and casein-derived tripeptides attenuate blood pressure increase in spontaneously hypertensive rats

In this study, we investigated the synergistic effects of plant sterols (PS) and casein-derived tripeptides on arterial tone and blood pressure in experimental hypertension. We hypothesized that PS and tripeptides could have positive, synergistic effects on the development of hypertension and endothelial dysfunction in young spontaneously hypertensive rats (SHR). Six-week-old male SHR were divided into 3 groups to receive milk products containing PS, or PS with tripeptides, or a control containing no active components for 8 weeks. Systolic blood pressure (SBP) was measured weekly, and vascular reactivity measurements with isolated mesenteric arteries were performed at the end of the study. Biochemical measurements for several parameters were performed by enzyme-linked immunosorbent assay using plasma samples. Levels of angiotensin-converting enzyme 1, cyclooxygenase-2, endothelial nitric oxide synthase, and P-selectin messenger RNA expressions were determined from aortic tissue by real-time polymerase chain reaction. The study showed that long-term treatment with PS + tripeptides attenuated the development of hypertension in SHR (SBP, 187 ± 5 mm Hg vs 169 ± 4 mm Hg in control group; P < .01). Plant sterols alone did not affect SBP significantly. Endothelial dysfunction was observed in all SHR; however, treatment with PS resulted in poorer endothelium-dependent and nitric oxide–mediated relaxation compared with other groups. Aortic cyclooxygenase-2 and P-selectin were significantly down-regulated in PS and PS + tripeptides groups when compared with the control group. The expression of endothelial nitric oxide synthase was significantly lower in PS than in PS + tripeptides group. In conclusion, long-term treatment with PS has a slight but not significant antihypertensive effect. Plant sterols do not provide any beneficial effects on endothelial function in hypertensive rats; however, treatment with both PS and tripeptides showed mild anti-inflammatory effects.     

结缔组织生长因子在胃癌组织中的表达及其与预后的关系

目的：检测结缔组织生长因子（CTGF）在胃癌组织中的表达并探讨CTGF表达在患者预后判断中的意义。方法：应用免疫组织化学染色方法检测108例胃癌组织中CTGF的表达情况,分析CTGF表达与患者临床病理特征、术后生存时间之间的关系。结果：CTGF高表达常见于发生淋巴结转移的病例（P=0.038）,CTGF表达水平低的患者术后五年生存率（48.4%）显著高于表达水平高的患者（23.9%,双侧log-rank检验,P=0.003 5）。Cox回归分析证明患者TNM分期（P〈0.001）、肿瘤分化（P=0.027）和CTGF表达水平（P=0.016）是胃癌的独立预后因子。结论：胃癌组织中CTGF高表达与发生淋巴结转移和患者预后不良显著相关。     

内源性多肽在妊娠期糖尿病中的研究进展

妊娠期糖尿病（gestational diabetes mellitus,GDM）是一种常见的妊娠期并发症,其发病率在全球范围内日益增高。目前临床上对GDM的诊疗手段仍存在一定的局限性,难以在妊娠前或妊娠早期及时发现并调整生活方式避免GDM的发生、发展。内源性多肽是生物体内普遍存在的一类生命活动调控物质,具有分子质量低、活性高、易于合成和改造等优点作为药物的良好分子基础,是近年来的研究热点。越来越多的研究表明内源性多肽在疾病的预测、诊断和治疗方面都发挥着重要作用,且其在GDM中的研究也日益受到更多的关注。就GDM相关多肽的研究进展进行了综述。     

肾上腺髓质素前体肽内不同片段间的相互作用

肾上腺髓质素(adrenomedullin,ADM)是1993年由Kitamura等[1]发现的一种心血管活性肽.ADM除具有强大的舒张血管、降低血压、抑制血管平滑肌细胞(vascular smooth muscle cells,VSMC)迁移、增殖作用外,还有利钠、利尿和心脏保护等作用,在维持循环稳态和心血管疾病中具有重要意义[1].随后人们发现ADM前体(preproADM,185个氨基酸残基)在体内经内源性肽酶降解后产生的另外3个片段也具有生物学效应:肾上腺髓质素原N末端20肽(preproADM22-41,proADM N terminal20 peptide,PAMP)具有弱的舒张血管、降低血压作用[2];preproADM153-185具有升高血压、促进VSMC增殖的作用[3];preproADM45-92亦具有弱的舒张血管、轻度降低血压的作用[3,4 ].     

利用噬菌体多肽库筛选卵巢癌细胞特异性结合肽

目的:利用噬菌体7肽库进行体外快速差减筛选(biopanning and rapid analysis of selective interactive ligands,BRASIL),从而获得卵巢癌细胞株HO-8910细胞表面特异性结合肽。方法:以中国仓鼠卵巢细胞株CHO为吸附细胞,卵巢癌细胞株HO-8910为靶细胞,利用噬菌体展示技术联合差减筛选策略,经过连续5轮生物淘洗,随机挑选13个噬菌体单克隆进行DNA测序,利用噬菌体竞争结合实验、ELISA实验、细胞免疫染色、细胞免疫荧光、合成多肽的竞争抑制实验鉴定阳性噬菌体的亲和性及特异性。结果:筛选出的噬菌体NPMIRRQ与卵巢癌细胞株HO-8910有较高的亲和性及特异性。结论:阳性噬菌体表面展示的多肽NPMIRRQ可能为卵巢癌的早期诊断和转移复发监测提供新思路。