Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1⁺), myeloid-committed progenitors (CD11b⁺, Gr-1⁺), and lymphoid-committed progenitors (CD45⁺, CD3e⁺). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1⁺ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b⁺ and Gr-1⁺ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45⁺ and CD3e⁺ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.     

Codelivery of Adriamycin and P-gp Inhibitor Quercetin Using PEGylated Liposomes to Overcome Cancer Drug Resistance

Transmembrane protein P-gp's overexpression at the drug-resistant cell membrane is the most important characteristic of multidrug resistance (MDR). Quercetin (QUE) can effectively suppress the function of P-gp to reverse MDR. This study uses QUE as the P-gp inhibitor andfilm-ultrasound technique with ammonium sulfate transmembrane gradient method to prepare long-circulating liposomes simultaneously encapsulating QUE and Adriamycin (doxorubicin) (AMD/DOX). The optimal conditions for the preparation of AMD_QUE_long-circulating liposomes (SLs) are as follows: hydrogenated soybean phospholipids (HSPC):cholesterol:DSPE-PEG 2000 = 73.07:24.36:2.57 mol/mol, QUE:HSPC = 1:20 mol/mol, AMD:HSPC = 1:7.9 w/w (NH₄₎₂SO₄ 0.15 mol/L, drug loaded (AMD) at 55°C for 25 min). The average encapsulation efficiency of AMD and QUE was 97.49% and 95.50%, respectively. The average particle size is 85 nm (n = 3), and the average zeta potential is ?14.9 mV. First, the pharmacokinetic study proved that codelivery liposomes enveloping QUE and AMD (AMD_QUE_SL) can obviously increase the blood concentration of AMD (C_max: 140.50 ± 32.37 μg/mL) and extend the half-life period of AMD in plasma (t_1/2:14.02 ± 1.54 h). Second, AMD_QUE_SL can obviously enhance the cell toxicity to AMD-resistant cell strains (HL-6/ADR and MCF-7/ADR), and the reverse effects on the resistance of HL-6/ADR and MCF-7/ADR is increased to 4.81-fold and 3.21-fold, respectively. Third, according to the in vivo pharmacodynamic study, the relative tumor volume and relative tumor growth of the AMD_QUE_SL group were the lowest. The inhibition rate of tumor growth of this group was the highest. It can be concluded that AMD_QUE_SL can effectively reverse MDR, lower cardiac toxicity of AMD in clinical treatment, and improve the clinical treatment effect of AMD.     

Development of innovative paclitaxel-loaded small PLGA nanoparticles: Study of their antiproliferative activity and their molecular interactions on prostatic cancer cells

Taxanes, including paclitaxel, are anti-cancer drugs approved for the treatment of prostate cancer but which have limited clinical application due to their hydrophobicity, their low therapeutic index and the emergence of chemoresistance. These side effects may be avoided through the use of new drug delivery systems such as nanoparticles, and paclitaxel-loaded PLGA nanoparticles up to 200 nm in size have shown encouraging results. As it is known that size affects the tissular penetration and distribution of tumors via the enhanced permeability and retention effect, so nanoparticles smaller than 100 nm are potentially interesting vehicles for improving paclitaxel delivery and efficacy.     

Parameters and pitfalls to consider in the conduct of food additive research,Carrageenan as a case study

This paper provides guidance on the conduct of new in vivo and in vitro studies on high molecular weight food additives, with carrageenan, the widely used food additive, as a case study. It is important to understand the physical/chemical properties and to verify the identity/purity, molecular weight and homogeneity/stability of the additive in the vehicle for oral delivery. The strong binding of CGN to protein in rodent chow or infant formula results in no gastrointestinal tract exposure to free CGN. It is recommended that doses of high Mw non-caloric, non-nutritive additives not exceed 5% by weight of total solid diet to avoid potential nutritional effects. Addition of some high Mw additives at high concentrations to liquid nutritional supplements increases viscosity and may affect palatability, caloric intake and body weight gain. In in vitro studies, the use of well-characterized, relevant cell types and the appropriate composition of the culture media are necessary for proper conduct and interpretation. CGN is bound to media protein and not freely accessible to cells in vitro. Interpretation of new studies on food additives should consider the interaction of food additives with the vehicle components and the appropriateness of the animal or cell model and dose–response.     

吸烟对牙周病治疗效果的影响

目的　探讨吸烟对牙周病治疗效果的影响。方法　收集在我科就诊的牙周病患者 84例 ,其中吸烟组 33例 ,非吸烟组 5 1例 ,均进行系统的牙周病治疗 ,治疗前和治疗后 6个月分别记录软垢指数 (DI)、牙石指数(CI)、牙周病指数 (PDI)。比较吸烟和不吸烟牙周病患者的治疗效果和预后。结果　两组患者治疗后DI、CI、PDI均有所下降 ,但吸烟组下降程度明显低于不吸烟组 (P <0 0 5 )。结论　吸烟患者牙周病治疗效果较非吸烟患者差。因此 ,戒烟应是牙周病预防和治疗的一个重要方面     

血流能量图及微血管密度与乳腺癌腋窝淋巴结转移的相关性

目的:探讨血流能量图angio(Power Doppler Imaging,PDI)及微血管密度(microvessel density,MVD)与乳腺癌腋淋巴转移的相关性。方法:术前观察74例乳腺癌的血流信号及血流能量图特征;术后标本采用免疫组化检测癌巢内MVD值,比较PDI与MVD两种方法与乳腺癌腋淋巴结转移的关系。结果:43个有腋淋巴结转移(LN+)组肿块以Ⅱ、Ⅲ级血流为主,血流主要分布在肿块周边多呈"爪"分布,血流信号较无腋淋巴结转移(LN-)组31个肿块明显丰富(P<0.05)。LN+组MVD值>LN-组(P<0.05)。癌巢内MVD值随Adler血流分级的增高和肿块体积的增大而测值增高(P<0.05),且随组织学级别的增加而显著增大(P<0.05)。结论:乳腺癌的PDI及MVD值与腋淋巴结转移密切相关,二者结合可作为评估乳腺癌患者预后的重要指标。     

Social–emotional delays at 2 years in extremely low gestational age survivors: Correlates of impaired orientation/engagement and emotional regulation

Background

Premature infants are less socially and emotionally competent at school age than infants born at term.

Aims

To evaluate the correlates of social and emotional delays at 2 years of age among prematurely born children.

Study design

This is a prospective cohort study.

Subjects

904 children born at < 28 weeks gestation during 2002–2004 and enrolled in the ELGAN study who survived until age 2 years and returned for a developmental assessment.

Outcome measures

The Bayley Behavior Rating Scale (BRS), a neurological examination, and the Bayley Scales of Infant Development II (BSID-II).

Results

Fully 31% of children had a non-optimal (14%) or questionable (17%) (NO/Q) BRS score for Emotional Regulation (ER), and 27% had a non-optimal (13%) or questionable (14%) score for Orientation/Engagement (O/E). Children with NO/Q scores on ER and O/E were more likely than others to have MDI and PDI scores < 70 and be unable to walk. Antecedents of NO/Q OE scores included multi-fetal pregnancy, while antecedents of NO/Q scores for both ER and O/E included indicators of socioeconomic disadvantage, and male sex.

Conclusions

Over 25% of children born extremely premature exhibit socio-emotional delays during developmental assessment at age 2 years. Antecedents of these delays include sociodemographic characteristics, as well as those common antecedents of other impairments commonly observed among extremely preterm infants.