铜绿假单胞菌的群体感应系统及其抑制剂研究进展

群体感应系统(quorum sensing system, QS)是一种微生物细胞与细胞间的交流系统。铜绿假单胞菌是该系统的典型代表,可调控细菌产生对抗生素的耐药、形成生物膜、产生毒力因子,并且减弱宿主的免疫应答。群体感应系统抑制剂(quorum sensing inhibitors, QSIs)在不影响细菌生长的前提下可降低细菌的毒性,且增强细菌生物膜对抗生素治疗的敏感性,这些特点使QSIs成为目前抗感染领域的研发热点。本文就铜绿假单胞菌的群体感应系统及QSIs的研究进展进行了综述。     

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.     

西达本胺增加慢性髓系白血病耐药株K562/ADM细胞对柔红霉素的敏感性

目的 观察西达本胺（CDM）能否影响人慢性髓系白血病耐药株K562/ADM细胞对柔红霉素（DNR）的敏感性,并探讨其可能的分子机制。方法 体外常规培养K562细胞和K562/ADM细胞,给予不同剂量CDM和（或）DNR处理48 h后,采用细胞计数试剂盒8（CCK-8）法检测CDM与DNR对K562和K562/ADM细胞的毒性作用,采用Chou-Talalay中效分析法对两药的联合效应进行评价,采用流式细胞术检测细胞增殖、细胞周期和凋亡,采用Western blotting方法检测组蛋白2AX（H2AX）、γH2AX（Ser139）、共济失调毛细血管扩张征突变基因（ATM）、p-ATM（Ser1981）、乳腺癌易感蛋白l（BRCA1）和p-BRCA1（Ser1524）的蛋白表达水平。 结果 DNR可剂量依赖性地抑制K562/ADM细胞活力（P<0.05）,半数抑制浓度（IC50）为11.76 μmol/L,耐药倍数为18.09;CDM可协同增强DNR对K562/ADM细胞的抑制作用置信区间（CI）（CI<1）,反转倍数为8.11;与对照组相比,DNR组细胞增殖率显著降低（P<0.05）,G2/M期细胞比例和凋亡率明显升高（P<0.05）,而无毒剂量的CDM可协同增强DNR引起的细胞增殖抑制、G2/M期阻滞和细胞凋亡（P<0.05）;耐药株K562/ADM细胞中ATM和BRCA1蛋白表达水平显著高于其亲代K562细胞（P<0.05）;DNR可上调K562/ADM细胞中H2AX、ATM和BRCA1蛋白的磷酸化水平（P<0.05）;CDM与DNR联用可使γH2AX蛋白水平进一步升高,但p-ATM和p BRCA1蛋白水平的变化则相反（P<0.05）。 结论 CMD可反转K562/ADM细胞对DNR的耐药性,这可能与上调H2AX蛋白的磷酸化水平以及下调ATM和BRCA1蛋白的磷酸化水平有关。     

Infection patterns,clinical significance,and genetic characteristics of Enterocytozoon bieneusi and Giardia duodenalis in dairy cattle in Jiangsu,China

The infection patterns and clinical significance of Enterocytozoon bieneusi and Giardia duodenalis in dairy cattle remain poorly investigated despite their common occurrence. Data on the genetic diversity are also needed to understand the transmission and human-infective potential of the two pathogens. In this study, fecal specimens from 1366 dairy cattle on a large farm were examined for the presence and genotype distribution of E. bieneusi and G. duodenalis by PCR and DNA sequencing. The overall infection rates of E. bieneusi and G. duodenalis were 13.0% and 20.6%, respectively. Pre-weaned calves had significantly higher infection rates of both pathogens than post-weaned and adult cattle (P < 0.001), with peak occurrence of the pathogens in animals of 7–12 weeks. In both pre- and post-weaned calves, animals with diarrhea were 2.1–3.0 times more likely to be infected with either pathogen than those without diarrhea (P < 0.01). The E. bieneusi identified belonged to five genotypes, including J (n = 138), I (n = 21), BEB4 (n = 10), Type IV (n = 1), and a novel genotype CHC17 (n = 1). Genotype J was the dominant one in all age groups, whereas genotype I was only identified in calves of 6–11 weeks. Genotyping of G. duodenalis at three genetic loci identified assemblage E (n = 278), assemblage A (n = 2), and concurrence of the two (n = 1). Altogether, 13, 7 and 10 subtypes of assemblage E were detected at the bg, gdh, and tpi loci, respectively, forming 65 multilocus genotypes. The formation of two major clusters of MLGs in eBURST analysis indicated that intra-assemblage genetic recombination of two dominant MLGs could have led to the high genetic heterogeneity within assemblage E on a single farm. Results of this study provide much needed data on the pathogenicity of E. bieneusi and G. duodenalis in pre- and post-weaned calves. The clinical significance of the two pathogens in dairy cattle warrants further investigations.