百草枯对A549细胞中解整合素-金属蛋白酶17表达的影响

目的构建体外百草枯（paraquat,PQ）细胞纤维化模型,观察PQ对A549细胞中解整合素-金属蛋白酶17（ADAM17）表达的影响,探讨ADAM17在PQ中毒致肺纤维化中的作用。方法体外培养A549细胞,分为正常对照组、不同浓度PQ组,应用CCK-8检测细胞活力,筛选PQ浓度和时间,显微镜下观察细胞形态,ELISA测定各组纤维化标志物I型胶原（type I collagen,Col I）和纤连蛋白（fibronectin,FN）的表达,建立细胞纤维化模型;免疫细胞化学检测A549细胞中ADAM17的分布情况,RT-PCR和Western blot分别半定量检测ADAM17 mRNA及蛋白水平的表达情况。结果（1）随着PQ浓度增加及作用时间延长,A549细胞活力呈下降趋势,差异有统计学意义（P〈0.05）,呈剂量依赖性和时间依赖性。（2）正常的A549细胞融合呈铺路石样生长,排列比较紧密,经PQ诱导后细胞排列较松散,细胞间连接变疏松,部分细胞溶解、死亡。（3）ELISA显示,随PQ浓度增加,Col I和FN表达增强,差异有统计学意义（P〈0.05）;随PQ时间延长,Col I和FN表达也逐渐增强,差异有统计学意义（P〈0.05）,成功建立PQ细胞纤维化模型。（4）免疫细胞化学显示,ADAM17在A549细胞胞浆表达。（5）RT-PCR和Western blot表明,随着PQ浓度增加,ADAM17 mRNA及蛋白水平表达明显增加,差异有统计学意义（P〈0.05）,以PQ 200 umol/L时最为明显。随着PQ作用时间延长,ADAM17 mRNA及蛋白表达水平也明显增加,差异有统计学意义（P〈0.05）,在24 h达到高峰。结论百草枯可引起肺泡上皮细胞形态学改变,导致细胞损伤,成功建立细胞的纤维化模型,对A549细胞的毒性作用具有剂量和时间依赖性。ADAM17在PQ诱导的A549细胞中过表达,可能参与了百草枯诱导的肺纤维化过程。     

A visible fluorescent nanovaccine based on functional genipin crosslinked ovalbumin protein nanoparticles

Accurate and efficient antigen delivery is crucial for inducing a strong and long-term immune response. A visible protein nanovaccine made from antigen could provide a novel and promising technology for secure and efficient delivery of the antigen with imaging visualization. In this study, a functional nanovaccine based on genipin crosslinked ovalbumin (OVA) fluorescent nanoparticles with chitosan (CS-OVA-NPs) was developed. The nanovaccine can carry abundant antigens by self-crosslinking without additional carriers. The fluorescence imaging technique was applied to monitor and reveal the process of antigen delivery in vivo based on the fluorescence of genipin with a non-invasive and real-time manner. This functional OVA nanovaccine can enhance the uptake of OVA in Dendritic Cells (DCs) and further promote DCs to maturate in vitro. In vivo study further indicated CS-OVA-NPs could trigger antigen-specific immune responses, which demonstrated that this fluorescent nanovaccine provided a novel design approach for accurate and efficient vaccine delivery.     

Correction to: Association between IL-35 and coronary arterial lesions in children with Kawasaki disease

Clinical and Experimental Medicine - The article Association between IL‑35 and coronary arterial lesions in children with Kawasaki disease, written by Ya Su, Siqi Feng, Li Luo, Ruixi Liu and...     

Increased levels of circulating fibroblast growth factor 21 in children with Kawasaki disease

Clinical and Experimental Medicine - The purpose of this study was to examine the serum levels of fibroblast growth factor 21 (FGF21) in children with acute Kawasaki disease (KD) and to investigate...     

ARL4C stabilized by AKT/mTOR pathway promotes the invasion of PTEN-deficient primary human glioblastoma

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency in primary human glioblastoma (GBM) is associated with increased invasiveness and poor prognosis with unknown mechanisms. Therefore, how loss of PTEN promotes GBM progression remains to be elucidated. Herein, we identified that ADP-ribosylation factor like-4C (ARL4C) was highly expressed in PTEN-deficient human GBM cells and tissues. Mechanistically, loss of PTEN stabilized ARL4C protein due to AKT/mTOR pathway-mediated inhibition of ARL4C ubiquitination. Functionally, ARL4C enhanced the progression of GBM cells in vitro and in vivo. Moreover, microarray profiling and GST pull-down assay identified that ARL4C accelerated tumor progression via RAC1-mediated filopodium formation. Importantly, targeting PTEN potently inhibited GBM tumor progression in vitro and in vivo, whereas overexpression of ARL4C reversed the tumor progression impaired by PTEN overexpression. Clinically, analyses with patients' specimens validated a negative correlation between PTEN and ARL4C expression. Elevated ARL4C expression but PTEN deficiency in tumor was associated with poorer disease-free survival and overall survival of GBM patients. Taken together, ARL4C is critical for PTEN-deficient GBM progression and acts as a novel prognostic biomarker and a potential therapeutic candidate. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

A cross-sectional serum investigation of a clustering hepatitis C virus infection in Southwest China

Serum samples were collected in a village with a clustering hepatitis C virus (HCV) infection. HCV antibody, HCV RNA loads, liver function indexes, HCV envelope antibody, and neutralizing activity were assessed. Among 851 adult sera, 342 samples were positive for anti-HCV. Of these positive samples, 254 (74.3%) were HCV RNA positive (≥800 copies/mL). None of the 69 children's sera were positive for HCV antibody or RNA. Among the HCV antibody positive sera, alanine aminotransferase, and aspartate aminotransferase levels increased with the higher virus loads, but decreased when virus loads were higher than 1 × 10 ⁶ copies/mL. HCV envelope antibody and neutralizing antibody levels increased with viral load.     

Enhanced conversion of sterols to steroid synthons by augmenting the peptidoglycan synthesis gene pbpB in Mycobacterium neoaurum

Some species of mycobacteria have been modified to transform sterols to valuable steroid synthons. The unique cell wall of mycobacteria has been recognized as an important organelle to absorb sterols. Some cell wall inhibitors (e.g., vancomycin and glycine) have been validated to enhance sterol conversion by interfering with transpeptidation in peptidoglycan biosynthesis. Therefore, two transpeptidase genes, pbpA and pbpB, were selected to rationally modify the cell wall to simulate the enhancement effect of vancomycin and glycine on sterol conversion in a 22‐hydroxy‐23,24‐bisnorchol‐4‐ene‐3‐one (4‐HBC) producing strain (WIII). Unexpectedly, the pbpA or pbpB gene augmentation was conducive to the utilization of sterols. The pbpB augmentation strain WIII‐pbpB was further investigated for its better performance. Compared to WIII, the morphology of WIII‐pbpB was markedly changed from oval to spindle, indicating alterations of the cell wall. Biochemical analysis indicated that the altered cell wall properties of WIII‐pbpB might contribute to the positive effect on sterol utilization. The productivity of 4‐HBC was enhanced by 28% in the WIII‐pbpB strain compared to that of WIII. These results demonstrated that the modification of peptidoglycan synthesis can improve the conversion of sterols to steroid synthons in mycobacteria.     

低温常压等离子技术在肿瘤学中的应用

等离子医学是研究等离子技术在医学领域应用的一门新兴科学。简述低温常压等离子技术,着重介绍其在肿瘤学中的应用。在肿瘤学领域中,等离子技术通过直接处理肿瘤细胞,产生大量活性物质引起肿瘤细胞的凋亡、坏死和自噬,从而发挥对肿瘤组织的直接致死性作用;等离子技术也可通过活化液体,使活化液体具备细胞毒性作用,从而发挥对肿瘤组织的间接致死性作用;同时等离子技术也具有诸多对肿瘤组织的非致死性作用;此外等离子技术也可参与构建化疗药物的缓释系统,协助药物跨生物膜转运,与传统化疗药物产生协同抗肿瘤的作用等,在肿瘤药物学领域发挥重要作用。