Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate

Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.     

Drug therapies for polymyalgia rheumatica: a pharmacotherapeutic update

Introduction: Polymyalgia rheumatica (PMR), a common disease in individuals older than 50 in the western world, is characterized by bilateral inflammatory pain involving the shoulder girdle and less commonly the neck and pelvic girdle. The main goals of the currently available treatment are to induce remission and prevent relapse.

Areas covered: This review briefly presents the main epidemiological and clinical features of PMR and discusses in depth both its classical management as well as new therapies used in PMR.

Expert opinion: In general, patients with isolated PMR experience a rapid response (in less than seven days) to 12.5–25 mg/prednisone/day. Methotrexate is the conventional disease-modifying antirheumatic drug most commonly used for disease management, especially for relapses of the disease. However, this agent often yields a modest effect. Randomized controlled trials do not support the use of antitumor necrosis factor agents in PMR. Several case series and retrospective studies have highlighted the efficacy of the anti-interleukin-6 receptor antibody tocilizumab in PMR. However, controlled trials are needed to fully establish the efficacy of this biologic agent in PMR. The potential beneficial effect of the Janus-kinase inhibitors remains to be determined.     

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl₄, FeCl₂), whereas Na₂SeO₃ supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.     

运动对超重/肥胖型葡萄糖耐量减低患者炎症相关蛋白表达水平的影响

目的:研究运动对超重／肥胖型葡萄糖耐量减低(IGT)患者血循环中炎症相关蛋白--白细胞介素-6(IL-6)、可溶性内皮细胞选择素(sE-selectin)水平的影响。方法:60例超重／肥胖型IGT患者入选为期12周的随机对照研究,对照组予以单纯生活方式干预,运动组在此基础上增加运动强度及时间。观察血中IL-6、sE-selectin及体重变化。结果:超重／肥胖型ICT患者的血循环中IL-6、sE-Selectin明显升高,与正常人组比较,差异有显著性意义(P均<0.01)。经12周的干预治疗研究IGT患者体重减轻,运动组减轻体重较对照组更明显4.82±2.12kg,2.35±2.14kg(P<0.01)。伴随着血糖和体重的下降IL-6、sE-selectin明显降低,运动组改善更明显。相关分析显示:sE-selectin与体重指数(BMI)及糖化血红蛋白(HbAlc)之间分别存在显著的正相关(P均<0.01)。结论:超重／肥胖型IGT患者已有炎症因子的异常表达,而运动干预能使这些异常得到显著改善。     

芦黄颗粒对实验性动脉粥样硬化家兔C反应蛋白和白细胞介素-6水平的影响

目的:观察中药复方芦黄颗粒对实验性家兔动脉粥样硬化(AS)炎性细胞因子水平的影响,探讨该方防治AS的机制.方法:40只新西兰白兔随机分为5组:假手术组、模型组、血脂康对照组、芦黄颗粒高剂量组、芦黄颗粒低剂量组.采用高脂饲料喂饲及动脉内膜球囊损伤法建立兔AS模型,制模成功后给予相应的药物8周,分别测定各组C反应蛋白(CRP)和白细胞介素-6(IL-6)的浓度.结果:与假手术组比较,模型组CRP和IL-6均明显升高(P<0.01和P<0.05),芦黄颗粒高剂量组血清CRP和IL-6水平均明显低于模型组(P<0.05和P<0.01),与血脂康对照组比较差异无显著性.芦黄颗粒低剂量组CRP水平与模型组比较差异无显著性.结论:芦黄颗粒可能通过抗炎机制,发挥抑制AS的作用.     

PFKFB3基因在前列腺癌中的表达及其对前列腺癌细胞糖酵解及生长的影响

目的探讨6-磷酸果糖激酶-2/果糖双磷酸酶-2同工酶3（PFKFB3）基因在前列腺癌中的表达及其对前列腺癌细胞糖酵解及生长的影响。 方法收集我院病理科前列腺增生和前列腺癌蜡块组织,应用免疫组化技术检测PFKFB3的表达水平。通过荧光定量PCR和Western blot实验检测正常前列腺上皮细胞（RWPE-1）和四种前列腺癌细胞系（PC3、LNCaP、DU145、C4-2）中PFKFB3的表达。应用RNA干扰技术敲低PFKFB3表达,采用细胞糖酵解试剂盒、CCK-8和克隆形成实验检测PFKFB3对前列腺癌细胞的糖酵解和增殖活性的影响。 结果与前列腺增生组织相比,前列腺癌组织中的PFKFB3表达量明显增高[（59.7±0.25） vs （3.08±0.16）,P<0.05],且病理Gleason评分越高,PFKFB3表达量也越高。同样PFKFB3在不同前列腺癌细胞系中均明显高表达。抑制PFKFB3基因表达后,前列腺癌细胞的糖酵解和增殖能力显著降低。 结论PFKFB3基因在前列腺癌恶性进展中表达上调,促进肿瘤细胞的糖酵解和增殖,靶向PFKFB3可能为前列腺癌分子诊断和治疗提供潜在的应用价值。     

无管化微通道经皮肾镜取石术对肾结石患者的疗效及对CRP、IL-6、PCT水平的影响

目的研究无管化微通道经皮肾镜取石术对肾结石患者的疗效及对CRP、IL-6、PCT水平的影响。方法回顾性分析2015年4月至2017年4月本院收治的肾结石患者463例,按手术方式的不同分成研究组109例和对照组354例。对照组采用标准通道经皮肾镜取石术治疗,研究组予以无管化微通道经皮肾镜取石术治疗。分别比较两组结石清除率,各项手术指标水平,治疗前后血清CRP、IL-6、PCT水平,术后并发症发生情况,手术前后生活质量评分情况。结果研究组结石清除率高于对照组,但组间差异无统计学意义(P>0.05)。研究组手术时间、术中出血量、术后置管时间、住院时间均明显低于对照组(P<0.05)。术后研究组血清CRP、IL-6、PCT水平(0.92±0.31)nmol/L、(42.73±13.69)ng/L、(0.72±0.25)ng/L,均明显低于对照组的(1.33±0.40)nmol/L、(51.20±15.04)ng/L、(0.97±0.66)ng/L(P<0.05)。研究组术后并发症发生率为4.59%(5/109),明显低于对照组的18.93%(67/354)(P<0.05)。术后研究组各项SF-36评分均明显高于对照组,组间对比差异有统计学意义(P<0.05)。结论无管化微通道经皮肾镜取石术可能成为治疗肾结石的有效手段之一,对患者早日康复,减少并发症的发生以及改善预后均可能具有一定的积极促进作用。