Hsa_circ_0006571 promotes spinal metastasis through sponging microRNA-138 to regulate sirtuin 1 expression in lung adenocarcinoma

Copyright © 2009 - 2021 AME Publishing Company. All rights reserved. Open Access Statement:This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/Background: Circular RNAs (circRNAs) are known to participate in lung cancer. However, their role in spinal metastasis (SM) of lung adenocarcinoma remains elusive. In this study, we determined that hsa_circ_0006571 serves as a sponge for miR-138, which targets sirtuin 1 (Sirt1) in the development of SM. Methods: A human circRNA microarray was performed to compare SM and lung adenocarcinoma samples. The expression of hsa_circ_0006571 and miR-138 was determined using quantitative polymerase chain reaction (qPCR) in vitro and in vivo. Cell proliferation was performed by Cell Counting Kit-8 (CCK-8) and apoptosis was analyzed by Annexin V/PI staining. RNA-pulldown and RNA immunoprecipitation (RIP) were used to analyze the interaction between hsa_circ_0006571. Tumor metastasis was determined through a xenograft experiment in vivo. Results: Hsa_circ_0006571 was observed to be significantly upregulated in SM tissues through circRNA microarray and qPCR. We detected a lower expression of miR-138 in SM tissues compared with lung adenocarcinoma. Hsa_circ_0006571 silencing suppressed lung cancer cell proliferation and migration while promoting apoptosis. Hsa_circ_0006571 interacted with miR-138 to promote expression of Sirt1, leading to activation of epithelial-mesenchymal transition (EMT). Xenograft experiments showed that downregulation of hsa_circ_0006571 delayed the SM of lung adenocarcinoma cells via the miR-138-Sirt1 axis. Conclusions: Hsa_circ_0006571 promoted tumor cell migration and invasion via the miR-138/Sirt1 pathway. Our observations indicate that circRNAs are possible novel therapeutic targets for SM of lung adenocarcinoma.This work was supported by the National Natural Science Foundation of China (81572629, 81772855 and 81701370).info:eu-repo/semantics/publishedVersio

Superconductivity Induced by Site-Selective Arsenic Doping in Mo5_5Si3_3

Arsenic doping in silicides has been much less studied compared with phosphorus. In this study, superconductivity is successfully induced by As doping in Mo$_5$Si$_3$. The superconducting transition temperature ($T_c$) reaches 7.7 K, which is higher than those in previously known W$_5$Si$_3$-type superconductors. Mo$_5$Si$_2$As is a type-II BCS superconductor with upper and lower critical fields of 6.65 T and 22.4 mT, respectively. In addition, As atoms are found to selectively take the 8$h$ sites in Mo$_5$Si$_2$As. The emergence of superconductivity is possibly due to the shift of Fermi level as a consequence of As doping, as revealed by the specific heat measurements and first-principles calculations. Our work provides not only another example of As doping, but also a practical strategy to achieve superconductivity in silicides through Fermi level engineering.Comment: Supporting Information available at the corresponding DO

Strong-Coupling Superconductivity with TcT_c ∼\sim 10.8 K Induced by P Doping in the Topological Semimetal Mo5_5Si3_3

By performing P doping on the Si sites in the topological semimetal Mo$_5$Si$_3$, we discover strong-coupling superconductivity in Mo$_5$Si$_{3-x}$P$_x$ (0.5 $\le$ $x$ $\le$ 2.0). Mo$_5$Si$_3$ crystallizes in the W$_5$Si$_3$-type structure with space group of $I4/mcm$ (No. 140), and is not a superconductor itself. Upon P doping, the lattice parameter $a$ decreases while $c$ increases monotonously. Bulk superconductivity is revealed in Mo$_5$Si$_{3-x}$P$_x$ (0.5 $\le$ $x$ $\le$ 2.0) from resistivity, magnetization, and heat capacity measurements. $T_c$ in Mo$_5$Si$_{1.5}$P$_{1.5}$ reaches as high as 10.8 K, setting a new record among the W$_5$Si$_3$-type superconductors. The upper and lower critical fields for Mo$_5$Si$_{1.5}$P$_{1.5}$ are 14.56 T and 105 mT, respectively. Moreover, Mo$_5$Si$_{1.5}$P$_{1.5}$ is found to be a fully gapped superconductor with strong electron-phonon coupling. First-principles calculations suggest that the enhancement of electron-phonon coupling is possibly due to the shift of the Fermi level, which is induced by electron doping. The calculations also reveal the nontrivial band topology in Mo$_5$Si$_3$. The $T_c$ and upper critical field in Mo$_5$Si$_{3-x}$P$_x$ are fairly high among pseudobinary compounds. Both of them are higher than those in NbTi, making future applications promising. Our results suggest that the W$_5$Si$_3$-type compounds are ideal platforms to search for new superconductors. By examinations of their band topologies, more candidates for topological superconductors can be expected in this structural family.Comment: 15 pages, 5 figures. Supplementary Information availabe at the corresponding DO

Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?

Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation of immune cells plays a critical role in BBB disruption after ischemic stroke. Infiltrating blood-borne immune cells (neutrophils, monocytes, and T lymphocytes) increase BBB permeability, as they cause microvascular disorder and secrete inflammation-associated molecules. In contrast, they promote BBB repair and angiogenesis in the latter phase of ischemic stroke. The profound immunological effects of cerebral immune cells (microglia, astrocytes, and pericytes) on BBB disruption have been underestimated in ischemic stroke. Post-stroke microglia and astrocytes can adopt both an M1/A1 or M2/A2 phenotype, which influence BBB integrity differently. However, whether pericytes acquire microglia phenotype and exert immunological effects on the BBB remains controversial. Thus, better understanding the inflammatory mechanism underlying BBB disruption can lead to the identification of more promising biological targets to develop treatments that minimize the onset of life-threatening complications and to improve existing treatments in patients. However, early attempts to inhibit the infiltration of circulating immune cells into the brain by blocking adhesion molecules, that were successful in experimental stroke failed in clinical trials. Therefore, new immunoregulatory therapeutic strategies for acute ischemic stroke are desperately warranted. Herein, we highlight the role of circulating and cerebral immune cells in BBB disruption and the crosstalk between them following acute ischemic stroke. Using a robust theoretical background, we discuss potential and effective immunotherapeutic targets to regulate BBB permeability after acute ischemic stroke

Cord blood stem-cell-derived dendritic cells generate potent antigen-specific immune responses and anti-tumour effects

A B S T R A C T The aim of the present study was to investigate whether CBSCs [(umbilical) cord blood stem cells] can be a new source of DCs (dendritic cells), which can generate more potent antigen-specific immune responses and anti-tumour effects. CBSCs and PBMCs (peripheral blood mononuclear cells) were collected, cultured and differentiated into DCs. Surface markers, secreting cytokines, antigen-presentation activity, antigen-specific cell-mediated immunity and cytotoxic killing effects induced by these two DC origins were evaluated and compared. CBSCs were expanded ∼17-fold by ex vivo culture. The expression of surface markers in CBSC-derived DCs were higher than those in PBMC-derived DCs treated with LPS (lipopolysaccharide). The CBSC-derived DCs mainly secreted IL (interleukin)-6, IL-10 and TNF (tumour necrosis factor)-α, whereas PBMC-derived DCs mainly secreted IL-5 and IFN (interferon)-γ . The CBSC-derived DCs had better antigen-presentation abilities when stimulated with LPS or TNF-α, induced higher numbers of IFN-γ -secreting antigen-specific CD8 + T-cells, as assessed using an ELISpot (enzymelinked immunosorbent spot) assay, and stimulated more potent antigen-specific CTL (cytotoxic T-cell) activities (P < 0.01, one-way ANOVA). CBSC-derived DCs had quicker and greater ERK (extracellular-signal-regulated kinase) and Akt phosphorylation, and weaker p38 phosphorylation, than PBMC-derived DCs when stimulated with LPS. In conclusion, CBSC-derived DCs have the ability to induce stronger antigen-specific immunity and more potent anti-tumour effects and therefore could be a good source of DCs for use in DC-based cancer vaccines and immunotherapy

Influence of Genetic Background and Tissue Types on Global DNA Methylation Patterns

Recent studies have shown a genetic influence on gene expression variation, chromatin, and DNA methylation. However, the effects of genetic background and tissue types on DNA methylation at the genome-wide level have not been characterized extensively. To study the effect of genetic background and tissue types on global DNA methylation, we performed DNA methylation analysis using the Affymetrix 500K SNP array on tumor, adjacent normal tissue, and blood DNA from 30 patients with esophageal squamous cell carcinoma (ESCC). The use of multiple tissues from 30 individuals allowed us to evaluate variation of DNA methylation states across tissues and individuals. Our results demonstrate that blood and esophageal tissues shared similar DNA methylation patterns within the same individual, suggesting an influence of genetic background on DNA methylation. Furthermore, we showed that tissue types are important contributors of DNA methylation states

Carbon dots-based dual-emission ratiometric fluorescence sensor for dopamine detection

The detection of Dopamine (DA) is significant for disease surveillance and prevention. However, the development of the precise and simple detection techniques is still at a preliminary stage due to their high tester requirements, time-consuming process, and low accuracy. In this work, we present a novel dual-emission ratiometric fluorescence sensing system based on a hybrid of carbon dots (CDs) and 7-amino-4-methylcoumarin (AMC) to quickly monitor the DA concentration. Linked via amide bonds, the CDs and AMC offered dual-emissions with peaks located at 455 and 505 nm, respectively, under a single excitation wavelength of 300 nm. Attributed to the fluorescence of the CDs and AMC in the nanohybrid system can be quenched by DA, the concentration of DA could be quantitatively detected by monitoring the ratiometric ratio change in fluorescent intensity. More importantly, the CDs-AMC-based dual-emission ratiometric fluorescence sensing system demonstrated a remarkable linear relationship in the range of 0–33.6 μM to detection of DA, and a low detection limit of 5.67 nM. Additionally, this sensor successfully applied to the detection of DA in real samples. Therefore, the ratiometric fluorescence sensing system may become promising to find potential applications in biomedical dopamine detection

Biocleavable Polycationic Micelles as Highly Efficient Gene Delivery Vectors

An amphiphilic disulfide-containing polyamidoamine was synthesized by Michael-type polyaddition reaction of piperazine to equimolar N, N′-bis(acryloyl)cystamine with 90% yield. The polycationic micelles (198 nm, 32.5 mV), prepared from the amphiphilic polyamidoamine by dialysis method, can condense foreign plasmid DNA to form nanosized polycationic micelles/DNA polyelectrolyte complexes with positive charges, which transfected 293T cells with high efficiency. Under optimized conditions, the transfection efficiencies of polycationic micelles/DNA complexes are comparable to, or even higher than that of commercially available branched PEI (Mw 25 kDa)

A Modified Sagittal Spine Postural Classification and Its Relationship to Deformities and Spinal Mobility in a Chinese Osteoporotic Population

BACKGROUND: Abnormal posture and spinal mobility have been demonstrated to cause functional impairment in the quality of life, especially in the postmenopausal osteoporotic population. Most of the literature studies focus on either thoracic kyphosis or lumbar lordosis, but not on the change of the entire spinal alignment. Very few articles reported the spinal alignment of Chinese people. The purpose of this study was threefold: to classify the spinal curvature based on the classification system defined by Satoh consisting of the entire spine alignment; to identify the change of trunk mobility; and to relate spinal curvature to balance disorder in a Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: 450 osteoporotic volunteers were recruited for this study. Spinal range of motion and global curvature were evaluated noninvasively using the Spinal-Mouse® system and sagittal postural deformities were characterized. RESULTS: We found a new spine postural alignment consisting of an increased thoracic kyphosis and decreased lumbar lordosis which we classified as our modified round back. We did not find any of Satoh's type 5 classification in our population. Type 2 sagittal alignment was the most common spinal deformity (38.44%). In standing, thoracic kyphosis angles in types 2 (58.34°) and 3 (58.03°) were the largest and lumbar lordosis angles in types 4 (13.95°) and 5 (-8.61°) were the smallest. The range of flexion (ROF) and range of flexion-extension (ROFE) of types 2 and 3 were usually greater than types 4 and 5, with type 1 being the largest. CONCLUSIONS/SIGNIFICANCE: The present study classified and compared for the first time the mobility, curvature and balance in a Chinese population based on the entire spine alignment and found types 4 and 5 to present the worst balance and mobility. This study included a new spine postural alignment classification that should be considered in future population studies

DNA methylation and methyl-CpG binding proteins: developmental requirements and function

DNA methylation is a major epigenetic modification in the genomes of higher eukaryotes. In vertebrates, DNA methylation occurs predominantly on the CpG dinucleotide, and approximately 60% to 90% of these dinucleotides are modified. Distinct DNA methylation patterns, which can vary between different tissues and developmental stages, exist on specific loci. Sites of DNA methylation are occupied by various proteins, including methyl-CpG binding domain (MBD) proteins which recruit the enzymatic machinery to establish silent chromatin. Mutations in the MBD family member MeCP2 are the cause of Rett syndrome, a severe neurodevelopmental disorder, whereas other MBDs are known to bind sites of hypermethylation in human cancer cell lines. Here, we review the advances in our understanding of the function of DNA methylation, DNA methyltransferases, and methyl-CpG binding proteins in vertebrate embryonic development. MBDs function in transcriptional repression and long-range interactions in chromatin and also appear to play a role in genomic stability, neural signaling, and transcriptional activation. DNA methylation makes an essential and versatile epigenetic contribution to genome integrity and function