Analysis of the expression profile of Dickkopf-1 gene in human glioma and the association with tumor malignancy

<p>Abstract</p> <p>Background</p> <p>Gliomas represent the most common primary malignant brain tumors, yet little is known about the molecular pathogenesis of these tumors. The highly-regulated Wnt signal transduction pathway is essential for normal developmental processes, and defects in the pathway are closely linked to oncogenesis. Dickkopf-1 (DKK-1) is a secreted protein that acts as a potent inhibitor of the Wnt pathway. The aim of this study was to examine the expression profile of DKK-1 gene in human glioma and its association with tumor malignancy.</p> <p>Methods</p> <p>We determined the expression levels of DKK-1 transcript and protein in 12 glioblastoma cell lines, medulloblastoma cells, low-grade glioma cells, and human astrocyte cells by semiquantitative RT-PCR and ELISA. A total of 47 tumor biopsy specimens and 11 normal brain tissue samples from patients with cerebral trauma internal decompression were embedded in paraffin blocks and used for immunostaining. Twenty-six primary tumors and 7 corresponding brain samples were stored in liquid nitrogen and used for RT-PCR. We further examined serologic concentrations and cerebral fluid levels of DKK-1 in patients with tumors.</p> <p>Results</p> <p>DKK-1 could only be detected in 12 human glioblastoma cell lines, not in a panel of other tumor and normal cell lines. The difference between glioma patients and healthy individuals was significant. Kendall's tau-c association analysis also revealed the increased DKK-1 protein expression in tumor tissues of higher pathologic classification. The levels of cerebral fluid DKK-1 protein were significantly higher in glioma patients than in healthy donors or in neuronal benign tumor patients, suggesting that the DKK-1 molecule in cerebral fluids can be applicable to detect the presence of glioma and be developed as a novel prognostic treatment.</p> <p>Conclusion</p> <p>The Wnt antagonist DKK-1 gene may have important roles in glioma tumorigenesis and act as a novel biomarker in human malignant glioblastoma.</p

Effects of selenium adaptation on intestinal morphology, antioxidant-relate genes expression and intestinal microflora of grass carp (Ctenopharyngodon idella)

In the study, the effects of selenium on intestinal tissue morphology, antioxidant-related genes, and intestinal flora of grass carp (Ctenopharyngodon idella) were studied. For this purpose, 180 healthy grass carps (20.0±2.0 g) were randomly divided into three groups with three replicates each: the corresponding amount of anhydrous sodium selenite was added to make experimental water solutions of different concentrations, including 0 μg/L Se4+ (control group), 200 μg/L Se4+ group and 300 μg/L Se4+ group. The experiment was carried out for 42 days. The obtained results showed that: at the end of the experiment, the 200 μg/L Se4+ adaptation can have beneficial effects on the intestinal villi height and goblet cells. The CuZnSOD and CAT genes mRNA levels of grass carp intestine were strongly upregulated in the 200ug/L Se4+ group. 200ug/L selenium could increase the expression level of the Hsp70 gene in the intestinal tract of grass carp after 42 days of adaptation. At the genus level, the most abundant sequence in the gut of Se-treated grass carp was Pseudomonas, while Aeromon, Flavobacterium, and Defluviimonas were more abundant in the control group. In conclusion, this study demonstrates that 200ug/L Se4+ selenium adaptation can positively affect gut morphology and antioxidant responses and can alter the gut microbiota structure of grass carp. The results will provide a theoretical basis for further research on the effect of selenium on aquatic animals

Elevated expression of Dickkopf-1 increases the sensitivity of human glioma cell line SHG44 to BCNU

<p>Abstract</p> <p>Background</p> <p>Studies have shown that Dickkopf-1 (DKK-1) is involved in tumorigenesis. Recently, we found that 9 out of 12 human glioma cell lines had high level of DKK-1 protein while the other 3 had very low or non-detectable level of DKK-1. The aim of this study is to further examine the function of DKK-1 in glioma cells.</p> <p>Materials and methods</p> <p>The glioma cell line SHG₄₄was obtained from a patient with grade II-III astrocytoma. SHG₄₄cells were transfected with a human DKK-1 gene. Transfection of the empty vector pcDNA3.1 was used as negative control. Sensitivity to BCNU was measured by Annexin-V staining. Expression of bax, bcl-2 and caspase-3 of three groups was determined by immunohistochemistry.</p> <p>Results</p> <p>The tranfection was confirmed by PCR, RT-PCR and Western blot. More apoptotic cell death was observed in the DKK-1 transfected cells, comparing to the non-transfected cells, or cells with empty vector. The expression of bax and caspase-3 of the SHG₄₄-DDK-1 increased, whereas the expression of bcl-2 decreased</p> <p>Conclusion</p> <p>Our results indicated that DKK-1 has a pro-apoptotic function of in glioma.</p

Learning Two-Stream CNN for Multi-Modal Age-related Macular Degeneration Categorization

This paper tackles automated categorization of Age-related Macular Degeneration (AMD), a common macular disease among people over 50. Previous research efforts mainly focus on AMD categorization with a single-modal input, let it be a color fundus image or an OCT image. By contrast, we consider AMD categorization given a multi-modal input, a direction that is clinically meaningful yet mostly unexplored. Contrary to the prior art that takes a traditional approach of feature extraction plus classifier training that cannot be jointly optimized, we opt for end-to-end multi-modal Convolutional Neural Networks (MM-CNN). Our MM-CNN is instantiated by a two-stream CNN, with spatially-invariant fusion to combine information from the fundus and OCT streams. In order to visually interpret the contribution of the individual modalities to the final prediction, we extend the class activation mapping (CAM) technique to the multi-modal scenario. For effective training of MM-CNN, we develop two data augmentation methods. One is GAN-based fundus / OCT image synthesis, with our novel use of CAMs as conditional input of a high-resolution image-to-image translation GAN. The other method is Loose Pairing, which pairs a fundus image and an OCT image on the basis of their classes instead of eye identities. Experiments on a clinical dataset consisting of 1,099 color fundus images and 1,290 OCT images acquired from 1,099 distinct eyes verify the effectiveness of the proposed solution for multi-modal AMD categorization

Theoretical and Experimental Analysis of Auctions with Negative Externalities

We investigate a private value auction in which a single "entrant" on winning imposes a negative externality on two "regular" bidders. In an English auction, when all bidders are active "regulars" free ride, exiting before price reaches their value. In a first-price sealed-bid auction incentives for free riding and aggressive bidding coexist, limiting free riding. We find substantial, though incomplete, free riding in the clock auction. In first-price auctions, regular bidders bid more aggressively than the "entrant" and both bid higher than in auctions with no externality. Predictions regarding revenue, efficiency, and successful entry between the two auctions are satisfied

Theoretical and Experimental Analysis of Auctions with Negative Externalities

We investigate a private value auction in which a single "entrant" on winning imposes a negative externality on two "regular" bidders. In an English auction, when all bidders are active "regulars" free ride, exiting before price reaches their value. In a first-price sealed-bid auction incentives for free riding and aggressive bidding coexist, limiting free riding. We find substantial, though incomplete, free riding in the clock auction. In first-price auctions, regular bidders bid more aggressively than the "entrant" and both bid higher than in auctions with no externality. Predictions regarding revenue, efficiency, and successful entry between the two auctions are satisfied

Bidirectional causality between immunoglobulin G N-glycosylation and metabolic traits: A mendelian randomization study

Although the association between immunoglobulin G (IgG) N-glycosylation and metabolic traits has been previously identified, the causal association between them remains unclear. In this work, we used Mendelian randomization (MR) analysis to integrate genome-wide association studies (GWASs) and quantitative trait loci (QTLs) data in order to investigate the bidirectional causal association of IgG N-glycosylation with metabolic traits. In the forward MR analysis, 59 (including nine putatively causal glycan peaks (GPs) for body mass index (BMI) (GP1, GP6, etc.) and seven for fasting plasma glucose (FPG) (GP1, GP5, etc.)) and 15 (including five putatively causal GPs for BMI (GP2, GP11, etc.) and four for FPG (GP1, GP10, etc.)) genetically determined IgG N-glycans were identified as being associated with metabolic traits in one- and two-sample MR studies, respectively, by integrating IgG N-glycan-QTL variants with GWAS results for metabolic traits (all P \u3c 0.05). Accordingly, in the reverse MR analysis of the integrated metabolic-QTL variants with the GWAS results for IgG N-glycosylation traits, 72 (including one putatively causal metabolic trait for GP1 (high-density lipoprotein cholesterol (HDL-C)) and five for GP2 (FPG, systolic blood pressure (SBP), etc.)) and four (including one putatively causal metabolic trait for GP3 (HDL-C) and one for GP9 (HDL-C)) genetically determined metabolic traits were found to be related to the risk of IgG N-glycosylation in one- and two-sample MR studies, respectively (all P \u3c 0.05). Notably, genetically determined associations of GP11 BMI (fixed-effects model-Beta with standard error (SE): 0.106 (0.034) and 0.010 (0.005)) and HDL-C GP9 (fixed-effects model-Beta with SE: –0.071 (0.022) and –0.306 (0.151)) were identified in both the one- and two-sample MR settings, which were further confirmed by a meta-analysis combining the one- and two-sample MR results (fixed-effects model-Beta with 95% confidence interval (95% CI): 0.0109 (0.0012, 0.0207) and –0.0759 (–0.1186, –0.0332), respectively). In conclusion, the comprehensively bidirectional MR analyses provide suggestive evidence of bidirectional causality between IgG N-glycosylation and metabolic traits, possibly revealing a new richness in the biological mechanism between IgG N-glycosylation and metabolic traits. © 2022 THE AUTHOR

Dynamic Control of a Multistate Chiral Supramolecular Polymer in Water

Natural systems transfer chiral information across multiple length scales through dynamic supramolecular interaction to accomplish various functions. Inspired by nature, many exquisite artificial supramolecular systems have been developed, in which controlling the supramolecular chirality holds the key to completing specific tasks. However, to achieve precise and non-invasive control and modulation of chirality in these systems remains challenging. As a non-invasive stimulus, light can be used to remotely control the chirality with high spatiotemporal precision. In contrast to common molecular switches, a synthetic molecular motor can act as a multistate chiroptical switch with unidirectional rotation, offering major potential to regulate more complex functions. Here, we present a light-driven molecular motor-based supramolecular polymer, in which the intrinsic chirality is transferred to the nanofibers, and the rotation of molecular motors governs the chirality and morphology of the supramolecular polymer. The resulting supramolecular polymer also exhibits light-controlled multistate aggregation-induced emission. These findings present a photochemically tunable multistate dynamic supramolecular system in water and pave the way for developing molecular motor-driven chiroptical materials

Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta-analysis

Prospective studies have shown that abnormally circulating cholesterol is associated with the risk of dementia. However, whether the association is causal or not remains unclear. We attempt to infer the causal association in a MR meta-analysis by using ApoE gene polymorphisms as instrument variables. Studies with dementia risk (27 studies) or circulating lipid levels (7 studies) were included, with totally 3136 dementia patients and 3103 healthy controls. The analyses showed that carriers of ε2 allele significantly were of decreased risk of AD (OR = 0.70; 95% CI: 0.58–0.84; P \u3c 0.01), whereas carriers of ε4 allele were of increased risk of AD (OR = 3.62; 95% CI: 3.03–4.32; P \u3c 0.05), compared to these of ε3 allele. Circulating TC was significantly reduced in carriers of ε2 allele (WMD = − 0.29 mmol/L; 95% CI: −0.54 to −0.03; P \u3c 0.05) and increased in carriers of ε4 allele (WMD = 0.42 mmol/l; 95% CI: 0.001–0.84; P \u3c 0.05). In addition, carriers of ε4 allele had reduction in circulating HDL-C (WMD = − 0.04 mmol/L; 95% CI: − 0.07 to −0.001; P \u3c 0.05). In comparing allele ε2 with ε3, the predicted OR of having AD for 1 mg/dL increment in circulating TC was 0.97 (95% CI: 0.86–0.98; P \u3c 0.05). Comparing allele ε4 with ε3, the predicted OR for a 1 mg/dL increment in TC was 1.08 (95% CI: 1.05–17.58; P \u3c 0.05), and reduction in HDL-C was 2.30 (95% CI: 1.51–43.99; P \u3c 0.05). Our findings demonstrate that high circulating TC and reduced HDL-C levels might be potential risk factors of the development of AD