Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.     

Development of curcumin loaded sodium hyaluronate immobilized vesicles (hyalurosomes) and their potential on skin inflammation and wound restoring

In the present work new highly biocompatible nanovesicles were developed using polyanion sodium hyaluronate to form polymer immobilized vesicles, so called hyalurosomes. Curcumin, at high concentration was loaded into hyalurosomes and physico-chemical properties and in vitro/in vivo performances of the formulations were compared to those of liposomes having the same lipid and drug content. Vesicles were prepared by direct addition of dispersion containing the polysaccharide sodium hyaluronate and the polyphenol curcumin to a commercial mixture of soy phospholipids, thus avoiding the use of organic solvents. An extensive study was carried out on the physico-chemical features and properties of curcumin-loaded hyalurosomes and liposomes. Cryogenic transmission electron microscopy and small-angle X-ray scattering showed that vesicles were spherical, uni- or oligolamellar and small in size (112–220 nm).The in vitro percutaneous curcumin delivery studies on intact skin showed an improved ability of hyalurosomes to favour a fast drug deposition in the whole skin. Hyalurosomes as well as liposomes were biocompatible, protected in vitro human keratinocytes from oxidative stress damages and promoted tissue remodelling through cellular proliferation and migration. Moreover, in vivo tests underlined a good effectiveness of curcumin-loaded hyalurosomes to counteract 12-O-tetradecanoilphorbol (TPA)-produced inflammation and injuries, diminishing oedema formation, myeloperoxydase activity and providing an extensive skin reepithelization. Thanks to the one-step and environmentally-friendly preparation method, component biocompatibility and safety, good in vitro and in vivo performances, the hyalurosomes appear as promising nanocarriers for cosmetic and pharmaceutical applications.     

Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.     

异基因造血干细胞移植患者生活质量变化轨迹及影响因素研究

目的 探讨异基因造血干细胞移植患者3年内的生活质量变化轨迹及影响因素。方法 采用便利抽样法,选取2016年7月—2017年10月于苏州市某三级甲等医院行异基因造血干细胞移植的患者作为调查对象,在患者移植前（入仓前1~2 d）、移植后1个月、3个月、半年、1年、1年半及3年时采用一般资料调查表及癌症治疗功能评价-骨髓移植测评量表进行调查。 结果 异基因造血干细胞移植患者的癌症治疗功能评价-骨髓移植测评量表总分在移植后1个月时降至最低,此后呈逐渐上升趋势,半年时基本恢复至移植前水平,3年时总分显著高于移植前,差异具有统计学意义（P<0.05）。生理健康、功能健全及干细胞移植3个维度得分与癌症治疗功能评价-骨髓移植测评量表总分变化轨迹一致,呈波动上升型;情绪稳定维度在移植前得分最低,随移植时间延长逐渐上升;社交/家庭健全维度移植前得分与移植后各时间点得分比较,差异无统计学意义（P>0.05）。多元线性回归分析结果显示,影响患者移植后3年时生活质量的主要因素为居住地（t=3.175,P=0.002）、家庭人均月收入（t=3.320,P=0.001）、移植相关并发症（t=-6.955,P<0.001）及患者是否回归工作/学习（t=2.706,P=0.008）。 结论 异基因造血干细胞移植患者总体生活质量呈波动上升趋势,癌症治疗功能评价-骨髓移植测评量表5个维度间的恢复时间及变化轨迹存在差异。至移植后3年时,居住地为农村、家庭人均月收入较低、患有移植相关并发症及尚未回归工作/学习的患者生活质量更差。护理人员可根据患者生活质量变化轨迹动态调整护理措施,为其提供更为精准的延续性护理。     

G蛋白信号调节因子-13通过调控β-catenin抑制结直肠癌细胞增殖、迁移和侵袭

目的：探究G蛋白信号调节因子-13（RGS13）在结直肠癌（CRC）进展中的作用。方法：使用TCGA数据库和实时荧光定量聚合酶链反应（RT-qPCR）在mRNA水平分析CRC组织和细胞中RGS13 的表达量，使用免疫组织化学染色（IHC）和蛋白质印迹法（Western blot）在蛋白水平进一步分析。用ATP细胞活力检测实验、软琼脂克隆集落形成实验和细胞迁移侵袭实验检测RGS13对CRC细胞增殖、迁移和侵袭的影响，并通过Western blot、RT-qPCR等实验探究其下游分子机制。结果：RGS13在CRC组织与细胞系中低表达（P ＜0.01），RGS13 表达越低，患者的无病生存期越短（P =0.017）。RGS13 的下调可显著促进CRC细胞的增殖、迁移与侵袭（P ＜0.01），表明RGS13在CRC进展中发挥抑癌作用。机制上，RGS13通过下调Wnt/β-catenin信号通路中β-catenin的蛋白水平，进而降低癌基因c-Myc、MMP7 和CCND1等的表达水平（P ＜0.01），发挥对CRC的抑制作用。结论：RGS13可能通过下调β-catenin发挥抑制CRC进展的重要作用。     

Immunohistochemical Expression of Cyclin D1 and Ki-67 in Primary and Metastatic Oral Squamous Cell Carcinoma

Objective: The aim of current study was to investigate the expression of Cyclin D1 and Ki-67 in primary and metastatic oral squamous cell carcinoma (OSCC) and their different histological grades. Methods: Paraffin embedded 30 oral squamous cell carcinoma (15 each of primary and cervical lymph node metastatic OSCC) were included in the study. Cyclin D1 and Ki 67 expressions were evaluated by immunohistochemistry and compared in primary and lymph node metastasis of OSCC and their histological grades. The data was analyzed using SPSS software. Results: The mean age of patients with primary OSCC was 53.47 ±16.67 years and 61.47 ±11.94 years in patients with metastasis. Males were comparatively affected more than females with tongue as the most common site involved in both primary and metastatic tumours. The mean size of primary and metastatic tumour biopsies were 1.16 mm and 3.93 mm respectively. Comparison of the expression of Cyclin D1 in these primary and metastatic OSCC revealed a statistically significant difference (p = 0.003) whereas it was insignificant for Ki-67 (p = 0.715). Conclusion: Cyclin D1 can be a useful marker in predicting aggressive or metastatic behaviour of OSCC on premier biopsies.     

Nitric oxide donors offer protection to RBC from storage lesion

BackgroundRed blood cell (RBC), which is the most commonly transfused blood component, due to its ability to save a life in absence of any other blood components, can be stored up to maximum 6 weeks by following standard preservation procedure. During storage, RBC undergoes various biophysical and biochemical changes (commonly known as storage lesion) for which blood transfusion with “old RBC” shows a lot of clinical problems especially relevant to critically ill patients. Recent research on S-nitrosylation of haemoglobin to improve oxygen delivery of banked blood revealed the important role of nitric oxide (NO) in protecting storage lesion.Materials and methodsIn the present study, we used various “NO donating” chemicals with different NO release dynamics and chemistries in RBC storage cocktails to test the effects of NO on storage lesion. Changes in different storage markers were evaluated after 7 days storage of pre-treated RBC.ResultsAll the NO donors have shown protection against hemolysis. However, S-nitroso glutathione (GSNO) ranks first in shielding RBCs from storage lesion and additionally, it helps in elevating the value of 2, 3-di phosphoglycerate (2, 3-DPG), improving the RBC membrane fluidity and decreasing the adhesion towards endothelial monolayer.DiscussionPresent study reveals that NO released from NO donors confers protection against storage lesions of the RBC. Further, the study confirms that pre-treatment with GSNO, a NO donor and a nitrosylating agent, ensures the best protection to RBC during low temperature storage, when compared to other NO donor treatments.