Polo-like kinase 1 siRNA-607 induces mitotic arrest and apoptosis in human nasopharyngeal carcinoma cells

Polo-like kinase (Plk) 1 is overexpressed in many human malignancies including nasopharyngeal carcinoma, indicating its potential as a therapeutic target. Recently, using a simple cellular morphologybased strategy, we have identified several novel effective siRNAs against Plk1 including Plk1 siRNA- 607. In this study, we further investigated the effects of Plk1 siRNA-607 in human nasopharyngeal carcinoma cell line, HNE-1. Real time RT-PCR and Western blot indicated that Plk1 siRNA-607 transfection resulted in a significant inhibition in Plk1 expression in the HNE-1 cells. Furthermore, cell cycle, cell growth and apoptosis analysis clearly indicated that Plk1 siRNA-607 caused a dramatic mitotic cell cycle arrest followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth and viability of the nasopharyngeal carcinoma cells. Given that Plk1 has been widely accepted as a novel efficient target for cancer therapy, these results suggested that Plk1 siRNA-607 could be further developed for the treatment of human nasopharyngeal carcinoma.Key words: Nasopharyngeal carcinoma, Plk1, RNA silencing, cell cycle, apoptosis

Negative CT Contrast Agents for the Diagnosis of Malignant Osteosarcoma

© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The current positive computed tomography (CT) contrast agents (PCTCAs) including clinical iodides, present high CT density value (CT-DV). However, they are incapable for the accurate diagnosis of some diseases with high CT-DV, such as osteosarcoma. Because bones and PCTCAs around osteosarcoma generate similar X-ray attenuations. Here, an innovative strategy of negative CT contrast agents (NCTCAs) to reduce the CT-DV of osteosarcoma is proposed, contributing to accurate detection of osteosarcoma. Hollow mesoporous silica nanoparticles, loading ammonia borane molecules and further modified by polyethylene glycol, are synthesized as NCTCAs for the diagnosis of osteosarcoma. The nanocomposites can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, resulting in nearly 20 times reduction of CT density in osteosarcoma. This helps form large CT density contrast between bones and osteosarcoma, and successfully achieves accurate diagnosis of osteosarcoma. Meanwhile, The NCTCAs strategy greatly expands the scope of CT application, and provides profound implications for the precise clinical diagnosis, treatment, and prognosis of diseases

The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor

The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In this study, we investigated the effect of different N-glycosylation of S1 protein on its binding to ACE2. Using real-time surface plasmon resonance assay the negative effects were demonstrated by the considerable increase of binding affinities of de-N-glycosylated S1 proteins produced from three different expression systems including baculovirus-insect, Chinese hamster ovarian and two variants of human embryonic kidney 293 cells. Molecular dynamic simulations of the S1 protein-ACE2 receptor complex revealed the steric hindrance and Coulombic repulsion effects of different types of N-glycans on the S1 protein interaction with ACE2. The results should contribute to future pathological studies of SARS-CoV-2 and therapeutic development of Covid-19, particularly using recombinant S1 proteins as models

Shape Retrieval of Non-rigid 3D Human Models

3D models of humans are commonly used within computer graphics and vision, and so the ability to distinguish between body shapes is an important shape retrieval problem. We extend our recent paper which provided a benchmark for testing non-rigid 3D shape retrieval algorithms on 3D human models. This benchmark provided a far stricter challenge than previous shape benchmarks. We have added 145 new models for use as a separate training set, in order to standardise the training data used and provide a fairer comparison. We have also included experiments with the FAUST dataset of human scans. All participants of the previous benchmark study have taken part in the new tests reported here, many providing updated results using the new data. In addition, further participants have also taken part, and we provide extra analysis of the retrieval results. A total of 25 different shape retrieval methods are compared

Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Aβ42 Uptake and Lysosomal Trafficking

Alzheimer's disease (AD) is characterized by the presence of early intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular amyloid deposition in vulnerable brain regions. It has been hypothesized that endosomal/lysosomal dysfunction might be associated with the pathological accumulation of intracellular Abeta42 in the brain. Our previous findings suggest that the LDL receptor-related protein 1 (LRP1), a major receptor for apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain. However, direct evidence of neuronal endocytosis of Abeta42 through LRP1 is lacking.Here we show that LRP1 endocytic function is required for neuronal Abeta42 uptake. Overexpression of a functional LRP1 minireceptor, mLRP4, increases Abeta42 uptake and accumulation in neuronal lysosomes. Conversely, knockdown of LRP1 expression significantly decreases neuronal Abeta42 uptake. Disruptions of LRP1 endocytic function by either clathrin knockdown or by removal of its cytoplasmic tail decreased both uptake and accumulation of Abeta42 in neurons. Finally, we show that LRP1-mediated neuronal accumulation of Abeta42 is associated with increased cellular toxicity.These results demonstrate that LRP1 endocytic function plays an important role in the uptake and accumulation of Abeta42 in neuronal lysosomes. These findings emphasize the central function of LRP1 in neuronal Abeta metabolism

Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

© 2015 Macmillan Publishers Limited. All rights reserved. microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevityaging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo