Integrative analysis of DNA methylation and gene expression through machine learning identifies stomach cancer diagnostic and prognostic biomarkers

DNA methylation is an early event in tumorigenesis. Here, by integrative analysis of DNA methylation and gene expression and utilizing machine learning approaches, we introduced potential diagnostic and prognostic methylation signatures for stomach cancer. Differentially-methylated positions (DMPs) and differentially-expressed genes (DEGs) were identified using The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) data. A total of 256 DMPs consisting of 140 and 116 hyper- and hypomethylated positions were identified between 443 tumour and 27 nontumour STAD samples. Gene expression analysis revealed a total of 2821 DEGs with 1247 upregulated and 1574 downregulated genes. By analysing the impact of cis and trans regulation of methylation on gene expression, a dominant negative correlation between methylation and expression was observed, while for trans regulation, in hypermethylated and hypomethylated genes, there was mainly a negative and positive correlation with gene expression, respectively. To find diagnostic biomarkers, we used 28 hypermethylated probes locating in the promoter of 27 downregulated genes. By implementing a feature selection approach, eight probes were selected and then used to build a support vector machine diagnostic model, which had an area under the curve of 0.99 and 0.97 in the training and validation (GSE30601 with 203 tumour and 94 nontumour samples) cohorts, respectively. Using 412 TCGA-STAD samples with both methylation and clinical data, we also identified four prognostic probes by implementing univariate and multivariate Cox regression analysis. In summary, our study introduced potential diagnostic and prognostic biomarkers for STAD, which demands further validation.     

Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a homing receptor preferentially expressed on gut-associated endothelial cells that plays a central role in leukocyte traffic into the mucosal immune compartment. Although the molecular mechanisms underlying endothelial ICAM-1 or E-selectin expression have been intensively investigated, the mechanisms that regulate human MAdCAM-1 expression have not been defined. We report MAdCAM-1 gene and protein expression in primary cultures of human intestinal microvascular endothelial cells (HIMEC) that was not demonstrated in human umbilical vein endothelial cells. Similar to ICAM-1 and E-selectin expression, MAdCAM-1 gene expression in HIMEC was inducible with TNF-, IL-1, or LPS activation. However, in striking contrast to ICAM-1 and E-selectin expression, MAdCAM-1 mRNA and protein expression in HIMEC was heavily dependent on culture duration and/or cellular density, suggesting a prominent role for cell-cell interaction among these endothelial cells in the expression of the mucosal addressin. MAdCAM-1 expression was inhibited by both SN-50 (NF-B inhibitor) and LY-294002 [phosphatidylinositol 3-kinase (PI3-K) inhibitor], whereas ICAM-1 and E-selectin expression was inhibited by SN-50 but not by LY-294002. The Akt phosphorylation by TNF- or LPS was greater at higher cell density, demonstrating a pattern similar to that of MAdCAM-1 expression. NF-B activation was not affected by cellular density in HIMEC. MAdCAM-1 expression in human gut endothelial cells is regulated by distinct signaling mechanisms involving both NF-B and PI3-K/Akt. These data also suggest that PI3-K/Akt is involved in the gut-specific differentiation of HIMEC, which results in expression of the mucosal addressin MAdCAM-1. cell adhesion molecules; nuclear factor-B; phosphatidylinositol 3-kinase     

Influence of synthesis parameters on the optical and photocatalytic properties of solvo/hydrothermal CuS and ZnS nanoparticles

Copper sulfide and zinc sulfide nanostructures were synthesized using a solvo/hydrothermal method and a thio Schiff base ligand, N‐benzylidene ethanethioamide, as a source of sulfide ions. The effects of different synthesis parameters including the type of solvent, temperature, and duration of reactions on the morphology of the CuS and ZnS products were investigated using field emission scanning microscopy and transmission electron microscopy, respectively. The structural aspects of the samples were characterized using powder X‐ray diffraction, Fourier transform infrared spectroscopy, and energy dispersive X‐ray analysis. The optical properties of the samples were studied through their optical absorption and photoluminescence spectra. The photocatalytic ability of the as‐synthesized sulfides was explored by studying the colour removal of methylene blue under ultraviolet light irradiation.     

The advance anticancer role of polymeric core-shell ZnO nanoparticles containing oxaliplatin in colorectal cancer

We evaluated the activity of core-shell ZnO nanoparticles (ZnO-NPs@polymer shell) containing Oxaliplatin via polymerization through in vitro studies and in vivo mouse models of colorectal cancer. ZnO NPs were synthesized in situ when the polymerization step was completed by co-precipitation. Gadolinium coordinated-ZnONPs@polymer shell (ZnO-Gd NPs@polymer shell) was synthesized by exploiting Gd's oxophilicity (III). The biophysical properties of the NPs were studied using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy, Ultraviolet-visible spectroscopy (UV-Vis), field emission electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy, dynamic light scattering, and z-potential. (3-(4,5-Dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide) (MTT) was used to determine the antiproliferative activity of ZnO-Gd-OXA. Moreover, a xenograft mouse model of colon cancer was exerted to survey its antitumor activity and effect on tumor growth. In the following, the model was also evaluated by histological staining (H-E; Hematoxylin & Eosin and trichrome staining) and gene expression analyses through the application of RT-PCR/ELISA, which included biochemical evaluation (MDA, thiols, SOD, CAT). The formation of ZnO NPs, which contained a crystallite size of 16.8 nm, was confirmed by the outcomes of the PXRD analysis. The Plate-like morphology and presence of Pt were obtained in EDX outcomes. TEM analysis displayed the attained ZnO NPs in a spherical shape and a diameter of 33 ± 8.5 nm, while the hydrodynamic sizes indicated that the particles were highly aggregated. The biological results demonstrated that ZnO-Gd-OXA inhibited tumor growth by inducing reactive oxygen species and inhibiting fibrosis, warranting further research on this novel colorectal cancer treatment agent.     

Climate change,unpredictable cold waves and possible brakes on plant migration

Aim Increases in annual mean temperature in the course of current climate change are expected to facilitate mass species migration towards higher altitudes and latitudes. However, this migration may be slowed, or even temporarily reversed, by infrequent and unpredictable episodes of low winter temperatures. Iran experienced a severe cold wave in January and February 2008, giving an opportunity to observe the effects on a large number of woody plant species, many growing further north than their natural ranges. Location The study was carried out in the National Botanical Garden of Iran (35°44′20.06″ N; 51°10′25.66″ E). Method To estimate the damage caused to each individual woody plant in the garden, we adopted the following protocol; at the start of the growing season, at the end of March and beginning of April 2008, all woody species were inspected for damage. In the case of evergreens this took the form of obvious damage to foliage, usually manifested as severe browning. In the case of deciduous species, damage was recognized by the failure of all or part of the plant to produce new leaves; all affected individual plants were labelled. In July all labelled plants were rechecked and, based on whole or partial above‐ground die‐back, a final list of damaged individuals was produced. Results As expected, the majority of native and exotic species introduced from cold temperate habitats showed no freezing injuries. Many woody species in the garden were damaged or killed, despite their previous survival and growth, in many cases for up to 40 years. The majority of taxa (101 out of a total of 145) that suffered freezing‐induced damage were evergreens. Main conclusions The results indicate that despite an increase in mean annual temperature, unpredictable lethal cold waves may retard the expansion of plants towards higher altitudes and latitudes. Broadleaved evergreen species from warm climates were particularly badly affected, with many species suffering high rates of mortality.     

Nebkhas of Salvadora persica and their effect on the growth and survival of Prosopis cineraria,Tamarix aphylla,and Capparis decidua trees and shrubs

Few studies were published on the effect of nebkhas (phytogenic mounds) on species diversity and soil resources, but no detailed study has been conducted yet on possible specific influence of nebkhas on growth and survival of the plants associated with them. We studied the nebkhas of Salvadora persica and their effect on growth and survival of three woody species (Prosopis cineraria, Tamarix aphylla, and Capparis decidua) in the Ommanian coast of Hormozgan Province in the south of Iran. The results showed that mean height and mean canopy diameter of P. cineraria and T. aphylla trees and shrubs inhabiting nebkhas of Salvadora persica were considerably higher than those of plants of these species growing outside nebkhas. The reverse occurred in the case of C. decidua. Generally, the percentages of stems with dead parts were significantly lower in plants inhabiting the nebkha sites in comparison to comparable ones growing outside the nebkhas. Salvadora persica nebkhas are enriched with more soil nutrients in comparison to inter-nebkha sites. Soil accumulated per each hectare in the nebkhas of the study area dominated by trees of Salvadora persica amounted to 237.6 m³. This indicates the great importance of nebkhas in the protection of soil and the associating species.