Glioblastoma multiforme (GBM) is the common primary brain tumor classified the most malignant glioma. Long non-coding RNAs (LncRNAs) are important epigenetic regulators with critical roles in cancer ...initiation and progression. LncRNA HOTAIRM1 transcribes from the antisense strand of HOXA gene cluster which locus in chromosome 7p15.2. Recent studies have shown that HOTAIRM1 is involved in acute myeloid leukemia and colorectal cancer. Here we sought to investigate the role of HOTAIRM1 in GBM and explore its mechanisms of action.
The expressions of HOTAIRM1 and HOXA1 in GBM tissues and cells were determined by qRT-PCR, and the association between HOTAIRM1, HOXA1 transcription and tumor grade were analyzed. The biological function of HOTAIRM1 in GBM was evaluated both in vitro and in vivo. Chromatin immunoprecipitation (ChIP) assay and quantitative Sequenom MassARRAY methylation analysis were performed to explore whether HOTAIRM1 could regulate histone and DNA modification status of the HOXA1 gene transcription start sites (TSS) and activate its transcription. ChIP and RNA-ChIP were further performed to determine the molecular mechanism of HOTAIRM1 in epigenetic regulation of the HOXA1 gene.
HOTAIRM1 was abnormally up-regulated in GBM tissues and cells, and this up-regulation was correlated with grade malignancy in glioma patients. HOTAIRM1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration and invasion, and inducing cell apoptosis. In vivo experiments showed knockdown of HOTAIRM1 lessened the tumor growth. Additionally, HOTAIRM1 action as regulating the expression of the HOXA1 gene. HOXA1, as an oncogene, it's expression levels were markedly elevated in GBM tissues and cell lines. Mechanistically, HOTAIRM1 mediated demethylation of histone H3K9 and H3K27 and reduced DNA methylation levels by sequester epigenetic modifiers G9a and EZH2, which are H3K9me
and H3K27me
specific histone methyltransferases, and DNA methyltransferases (DnmTs) away from the TSS of HOXA1 gene.
We investigated the potential role of HOTAIRM1 to promote GBM cell proliferation, migration, invasion and inhibit cell apoptosis by epigenetic regulation of HOXA1 gene that can be targeted simultaneously to effectively treat GBM, thus putting forward a promising strategy for GBM treatment. Meanwhile, this finding provides an example of transcriptional control over the chromatin state of gene and may help explain the role of lncRNAs within the HOXA gene cluster.
Cerebral ischemia leads to reactive astrogliosis and glial scar formation. Glial scarring can impede functional restoration during the recovery phase of stroke. Salidroside has been shown to have ...neuroprotective effects after ischemic stroke, but its impact on long-term neurological recovery, especially whether it regulates reactive astrogliosis and glial scar formation, is unclear. In this study, male adult C57/BL6 mice were subjected to transient cerebral ischemia injury followed by intravenous salidroside treatment. Primary astrocytes were treated with lipopolysaccharide (LPS) or conditioned medium from cultured primary neurons subjected to oxygen-glucose deprivation (CM-OGD). Salidroside significantly improved long-term functional outcomes following ischemic stroke in the rotarod and corner tests. It also reduced brain glial scar volume and decreased expression of the glial scar marker, glial fibrillary acidic protein (GFAP) and inhibited astrocyte proliferation. In primary astrocyte cultures, salidroside protected astrocytes from CM-OGD injury-induced reactive astroglial proliferation, increasing the percentage of cells in G0/G1 phase and reducing the S populations. The inhibitory effect of salidroside on the cell cycle was related to downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA expression and increased p27Kip1 mRNA expression. Similar results were found in the LPS-stimulated injury model in astroglial cultures. Western blot analysis demonstrated that salidroside attenuated the CM-OGD-induced upregulation of phosphorylated Akt and glycogen synthase kinase 3β (GSK-3β). Taken together, these results suggested that salidroside can inhibit reactive astrocyte proliferation, ameliorate glial scar formation and improve long-term recovery, probably through its effects on the Akt/GSK-3β pathway.
Colorectal neoplasia differentially expressed (CRNDE), an oncogene, is highly expressed in many tumor cells and affects cellular proliferation, migration, invasion, and apoptosis. Its function and ...mechanism of action is a research hotspot. In this study, microarray analysis was performed to discover the differentially expressed genes in CRNDE over-expression cells. RT² Profiler PCR Array was used to study the expression of genes related to the toll-like receptor (TLR) pathway. We found that over-expression of CRNDE in astrocytes increased the expression of key factors in the toll-like receptor signaling pathway, especially toll-like receptor-3-mediated MyD88-independent pathway. Furthermore, it up-regulated expression levels of downstream transcription factor such as nuclear factor kappa B and numerous cytokines. In contrast, CRNDE knockdown in glioma U87MG cell line showed an opposite trend in the expression of the above-mentioned genes. We speculated that CRNDE might trigger inflammation to regulate tumorigenesis and tumor development through the toll-like receptor pathway.
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Molecular imprinting technology (MIT) aims to prepare polymers with tailor-made binding sites for the templates in shape, size and functional groups. However, many disadvantages of ...traditional MIT lead to some unsatisfactory results. Recently, surface molecular imprinting technique (SMIT) has aroused extensive attention and been applied in many fields, such as sensors, separation and purification, catalysis and biomedical areas owing to the desired selectivity, reduction of “embedding” phenomenon, fast mass transfer rate and binding kinetics. With the rapid development of SMIT, it faces a number of challenges, involving pure templates obtained, the higher cost of using noble metals, unclear recognition mechanism, low solubility of the templates in solvents, etc., which limit its practical applications in various aspects. This paper briefly reviews current status of the SMIT, particularly emphasis on the preparation of surface molecularly imprinted polymers (SMIPs, including interactions between templates and monomers, solid matrixes and synthetic strategies) and significant applications on sensors, separation and purification, catalysis and biomedical areas. Furthermore, some still existing challenges and future prospects in this research area are also highlighted.
We established a glioma biobank at Beijing Tiantan Hospital in November, 2010. Specialized residents have been trained to collect, store and manage the biobank in accordance with standard operating ...procedures.
One hundred samples were selected to evaluate the quality of glioma samples stored in the liquid nitrogen tank during different periods (from 2011 to 2015) by morphological examination, RNA integrity determination, DNA integrity determination and housekeeping gene expression determination.
The majority of samples (95%) had high RNA quality for further analysis with RIN ≥6. Quality of DNA of all samples were stable without significant degradation.
Storage conditions of our biobank are suitable for long-term (at least five years) sample preservation with high molecular quality.
20(S)-Ginsenoside Rh2 (20(S)-GRh2) exerts important pharmacological effects with regard to the control of human hepatocellular carcinoma (HCC). EZH2 is a potent histone methyltransferase of H3K27me3, ...which has been determined as an oncogene in many malignancies. The CDKN2A-2B gene cluster encodes three important tumor suppressors, P14, P15 and P16. In this study, the anticancer effect and molecular mechanism of 20(S)-GRh2 on HCC was investigated. Treatment of HCC cells with 20(S)-GRh2 inhibited cell proliferation, migration and induced cell cycle arrest at the G0/G1 phase, and inhibited tumor growth in vivo. We demonstrate for the first time that this effect was specifically mediated by down-regulating expression of EZH2. Further molecular mechanism study indicated that the decreased EZH2 promoted P14, P15 and P16 gene transcription through reducing H3K27me3 modification in the promoter of CDKN2A-2B gene cluster loci. Similarly, silencing of EZH2 by siRNA down-regulated P14, P15, P16 mRNA levels and inhibited HCC cell proliferation. Our results suggested that EZH2 could be a potentially therapeutic target by 20(S)-GRh2 in HCC, which provided a rationale for the development of drugs that inhibited histone methylase as a strategy against various cancers.
Amlodipine is a commonly used and effective drug for the treatment of hypertension. This work investigates imprinted membranes with functional molecular recognition properties prepared via the ...surface molecular imprinted technology. The surface molecular imprinted membrane are synthesized by taking (S)-amlodipine (S-ADP) as the template molecule, methacrylic acid (MAA) as the functional monomer, and N, N′-methylenebisacrylamide (MBA) as the cross-linker in the present of a surface-initiating system of –OH/Ce4+ constituted by the hydroxyl on the surface of basilemma polyvinyl alcohol (PVA) and ammonium cerium sulfate dissolved in solvent.
The imprinted layer is grafted onto the PVA membranes followed by the removal of the S-ADP template molecule, obtaining the S-ADP surface molecular imprinted membranes (S-ADP-SMIMs). The membrane is characterized by Fourier transform infrared reflection (FTIR), and scanning electron microscopy (SEM),13C Nuclear Magnetic Resonance spectroscopy (13C NMR) and X-ray photoelectron spectroscopy (XPS). The ability of enantioseparation and selective permeability of S-ADP-SMIMs is studies. As a result, the selectivity coefficient is 4.6 and the optical purity of adsorption liquid gets up to 80% for S-ADP-SMIMs. However, the non-surface molecular imprinted membrane (NSMIM) shows no selectivity. And the results of in vitro release experiments reveal that the cumulative amounts released of S-ADP and R-amlodipine (R-ADP) is 1459.01 μg cm−2 and 106.21 μg cm−2, respectively. In the skin permeation experiments, the optimal drug concentration is 4.0 mg/mL, Carbopol is determined 0.9% and 1% oleic acid is acted as excellent permeation enhancer. The cumulative amount transported reaches 1719.68 μg cm−2 for S-ADP, while a lower value of 228.17 μg cm−2 is measured for R-ADP. These results strongly suggest the formation of imprinted cavities, which offer selectivity for the transport of S-ADP. So, the imprinted membrane is universal for other chiral drugs. It makes it possible to selectively delivery dominant isomers exactly and efficiently.
S-ADP molecule-imprinted membranes was prepared by surface-initiating grafted polymerization. The selectivity coefficient of S-ADP-SMIMs reaches 4.6 and the optical purity of adsorption liquid gets up to 80%. The in vitro skin permeation amount reaches 1719.68 μg cm−2 for S-ADP, while a lower value of 228.17 μg cm−2 is measured for R-ADP. Display omitted
•Surface molecular imprinted membrane S-ADP-SMIMs has excellent enatioseparation•S-ADP-SMIMs is used as controlled release membrane for transdermal preparation.•S-ADP-SMIMs acts as a “gate” for selective release and permeation S-ADP.
A novel adsorbent with high adsorption capacity to remove cationic dyes was synthesized. Sodium 4-styrene sulfonate (SSS) was grafted polymerization on the surface of magnetic chitosan microspheres ...via -NH2/S2O82− surface initiating system, obtaining MCS-g-PSSS microspheres. The grafted microsphere was characterized by Fourier transforms infrared spectroscopy, X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, vibration sample magnetometer and the Brunauer-Emmett-Teller. Cationic dyes were adsorbed by MCS-g-PSSS and methylene blue(MB) was acted as a typical example. The adsorption performance was explored by varying experimental conditions. The results showed the maximal adsorption capacity was 989 mg/g at pH 1 at 25 °C. The pseudo-second order model was found to be applicable for the adsorption kinetics. The adsorption capacity increased with rising temperature and it decreased owing to adding of ions. The adsorption isotherms were the best fitted by Langmuir. MCS-g-PSSS for MB showed high adsorption capacity due to the strong electrostatic interactions and π-π stacking, which was explained by FTIR and XPS and was verified by DFT calculations. The degree of adsorption spontaneity increased with rising the temperature. The grafted MCS-g-PSSS microspheres had high adsorption capacity for various kinds of cationic dyes and excellent for remove MB in the aqueous solution.
Dyes bring a lot of benefits to our lives, however, as common organic pollutants, they have destructive influences on the environment. Firstly, glutaraldehyde crosslinked chitosan microspheres (GCS) ...are prepared via inverse-phase suspension polymerization. Then, GCS microspheres are acted as the base material, ammonium persulfate (Aps) as the initiator, sodium styrene sulfonate (SSS) as anionic functional monomer, functional microspheres (GCS-g-PSSS) are prepared by surface grafting polymerization. The amount of monomer and Aps, temperature and reaction time is respectively explored. The chemical structures and physicochemical properties of functional microspheres were characterized by FT-IR, zeta potential, scanning electron microscope and X-ray photoelectron spectroscopy. The adsorption kinetic at different temperature and initial concentration is studied and fitted. The adsorption isotherms of GCS-g-PSSS for MB are explored at different pH, temperature and salinity. The adsorption capacity of GCS-g-PSSS for MB is 820.1 mg/g at 318 K. The adsorption isotherms at different temperature are fitted by Langmuir, Freundlich, Dubinin-Radushkevich and Temkin. Thermodynamic parameters imply that adsorption is a spontaneous and endothermic process. And this adsorbent has good reusability. The adsorption ability of GCS-g-PSSS microspheres is also excellent for other cationic dyes. Thus, GCS-g-PSSS microspheres might serve as a promising adsorbent for contaminated water scavenging.
Interleukin-4 induced 1 protein (IL4I1), a secreted amino acid oxidase produced by antigen presenting cells, oxidizes phenylalanine to phenylpyruvate. It has been found that IL4I1 exerts an ...immunosuppressive function by inhibiting the proliferation and differentiation of T cells as well as limiting the proliferation of B cells. IL4I1 is involved in host defense against infection. As a gene related to poor prognosis in cancers, IL4I1 participates in tumor immune escape. IL4I1 promotes remyelination via regulation of the different phenotypes of microglia in the autoimmune demyelinating diseases, but the detailed mechanism still remains unknown. We summarize the role and mechanism of IL4I1 in the immune regulation to provide new ideas for the treatment of infections, cancers and autoimmune diseases.
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