Efficient polymer nanoparticle-mediated delivery of gene editing reagents into human hematopoietic stem and progenitor cells

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Comparison of P25 and nanobelts on Kruppel-like factor-mediated nitric oxide pathways in human umbilical vein endothelial cells

Recently, we reported that titanium dioxide (TiO₂) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO₂ nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.     

Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml^-1 or < 300 ng.ml^-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127–141 [120–172]) g.l^-1, 143 (133–150 [120–179]) g.l^-1, p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77–82 [9–85]) days vs. 81 (79–83 [0–85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.     

尿酸性肾病中医分型与氧化应激指标的相关性研究

目的：探讨尿酸性肾病中医分型与氧化应激相关性。方法：采用回顾性分析方法对2017年12月至2019年9月北京中医药大学第三附属医院收治的尿酸性肾病患者105例进行研究，选择同时期正常健康者105例作为对照，参考《中药新药临床研究指导原则》将105例尿酸性肾病和临床常见证型相结合，分成脾肾气虚18例、气阴两虚证19例、肝肾阴虚16例、阴阳两虚12例、湿热蕴结19例、瘀血阻滞17例、痰浊内阻13例，均在入院次日清晨空腹抽取静脉血，检测氧化应激氧化应激、肾功能损害指标，比较不同组别在氧化应激指标含量水平变化情况，比较中医分型和氧化应激、肾功能损害指标水平变化。结果：1）尿酸性肾病组总抗氧化能力（T-ACO）、晚期蛋白氧化物（AOPP）、血清丙二醇（MDA）、超氧化物歧化酶（SOD）含量水平分别为（19.45±3.42）U/mL、（42.45±3.53）μmol/L、（4.52±1.23）nmol/L、（76.78±5.64）U/mL，正常对照组则分别为（10.76±1.31）U/mL、（20.84±1.28）μmol/L、（2.13±0.76）nmol/L、（130.85±16.75）U/mL，尿酸性肾病组T-ACO、AOPP、MDA较正常对照组显著偏高，SOD显著偏低（P<0.05）。2）虚证中阴阳两虚证SOD含量上较其他证型均偏低，而MDA、T-AOC、AOPP、胱抑素C（CysC）、β2微球蛋白、尿微量白蛋白（UMALB）、蛋白尿发生率则较其他证型均偏高，差异均有统计学意义（P<0.05），实证中瘀血阻滞证SOD含量较其他证型均偏低，而MDA、T-AOC、AOPP则较其他证型均偏高，差异均有统计学意义（P<0.05）。结论：尿酸性肾病中医分型的阴阳两虚证、瘀血阻滞证氧化应激水平、肾损害指标均显著升高，可结合该实验室检查进行临床干预。     

The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.     

FeNO预测肺癌患者放射性肺炎的临床价值

目的:观察肺癌患者放疗后一氧化氮分数（FeNO）的增加能否提示放射性肺损伤。方法:本研究中，我们评估了FeNO变化与放疗后呼吸症状、CT扫描改变和剂量体积直方图（DVH）参数之间的关系。测量65例肺癌患者放疗前及放疗后4、5、6、10周和4、7.5月的FeNO。结果:在放疗后，11名肺癌患者（17%）自述有明显的呼吸道症状，21名（32%）患者有超过1/3的被照射肺区表现出放射性肺炎样图像。13名患者（20%）的FeNO增加超过10 ppb。以FeNO增加超过10 ppb为标准诊断放疗相关呼吸症状的灵敏度和特异性分别为18%和83%。FeNO变化与放疗后DVH参数或CT扫描改变之间无显著相关性。3名患者（5%）在第4、5周持续表现出异常高水平的FeNO（2或3倍，高达55 ppb），随后出现了显著的呼吸症状和/或放射性肺炎图像。结论:放疗期间的连续FeNO监测预测肺癌患者放射性肺炎症状或图像的能力较差。然而，三名患者表现出的特定模式值得研究。     

基于二氧化硅纳米粒子的抗肿瘤药物递送系统研究进展CSCD

近年来癌症治疗受到广泛关注,二氧化硅纳米颗粒因其独特的理化性质在肿瘤诊疗领域展现巨大潜力。基于二氧化硅纳米粒子的药物输送系统可被动或主动靶向肿瘤组织,并通过刺激响应的方式实现药物在肿瘤部位的可控释放,有效提高抗肿瘤药物在肿瘤部位的浓度,提高治疗效率。同时,二氧化硅纳米粒子通过负载造影剂可实现生物成像功能,用于肿瘤组织定位及药物追踪,实现更高效的抗肿瘤治疗。本文介绍了二氧化硅纳米粒子的制备方式,并对二氧化硅纳米粒子在药物靶向递送系统及生物成像领域中的研究进展进行综述。     

Biofunctionalization of magnetite nanoparticles with stevioside: effect on the size and thermal behaviour for use in hyperthermia applications

Controlling the magnetic properties of a nanoparticle efficiently via its particle size to achieve optimized heat under alternating magnetic field is the central point for magnetic hyperthermia-mediated cancer therapy (MHCT). Here, we have shown the successful use of stevioside (a natural plant-based glycoside) as a promising biosurfactant to control the magnetic properties of Fe₃O₄ nanoparticles by controlling the particle size. The biocompatibility and cellular uptake efficiency by rat C6 glioma cells and calorimetric magnetic hyperthermia profile of the nanoparticles were further examined. Our finding suggests superior properties of stevioside-coated magnetite nanoparticles in comparison to polysorbate-80 and oleic acid coated nanomagnets as far as particle size reduction, biocompatibility, hyperthermic effect, and cellular uptake by the glioblastoma cancer cells are concerned. The stevioside-coated nanomagnets exhibiting the maximum temperature rise were further investigated as heating agents in in vitro magnetic hyperthermia experiments (405?kHz, 168?Oe), showing their efficacy to induce cell death of rat C6 glioma cells after 30?min at a target temperature T?=?43?°C.     

Iron intake,oxidative stress-related genes and breast cancer risk

Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case–control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER–/PR– breast cancer risk (all p_trend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR_{>18 vs. 0 mg/day} = 0.68, 95% CI: 0.51–0.91), and dietary heme iron was associated with an increased risk, particularly the ER–/PR– subtype (OR_{highest vs. lowest quintile} = 1.69, 95% CI: 1.16–2.47; p_trend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (p_interaction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.