Meteorin regulates mesendoderm development by enhancing nodal expression

During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.open1113sciescopu

Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human breast cancer cell

AbstractEts-1 is a cellular homologue of the product of the viral ets oncogene of the E26 virus, and it functions as a tissue-specific transcription factor. It plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis, and apoptosis. Ets-1 controls the expression of critical genes involved in these processes by binding to ets binding sites present in the transcriptional regulatory regions. Here, we transiently overexpressed Ets-1 in MCF-7 and comprehensively searched for potential downstream targets of Ets-1 by cDNA microarray analysis. The expressions of several interferon-related genes including STAT1 and Nmi were augmented by the overexpression of Ets-1. RT-PCR and Western blotting confirmed the increase in the levels of STAT1 and Nmi mRNA and protein. In contrast, Ets-1 siRNA decreased the expression of STAT1 and Nmi proteins. As in our transient transfection experiments, stable overexpression of Ets-1, also increased the protein expression of STAT1 and Nmi in MCF-7 cells. Taken together, our results indicate that STAT1 and Nmi are downstream targets of Ets-1 in MCF-7 human breast cancer cells

Electrodeposition of CdTe thin films using nitrate precursor for applications in solar cells

Cadmium telluride (CdTe) thin films have been electrodeposited (ED) on glass/fluorine-doped tin oxide (FTO) substrates using simplified two-electrode system in acidic and aqueous solution containing Cd(NO3)2 4H2O and TeO2. The X-ray diffraction (XRD), optical absorption, photoelectrochemical (PEC) cell measurements, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) have been carried out to study the structural, optical, electrical and morphological properties of the CdTe layers. The XRD study shows that the ED-CdTe layers are polycrystalline with cubic crystal structure. Results obtained from optical absorption reveal that the bandgaps of the as-deposited and the CdCl2 treated CdTe layers are in the ranges ~1.50 to ~1.54 eV and ~1.46 to ~1.51 eV, respectively. Observation from PEC measurements indicates a p-, i- and n-type electrical conductivity for as-deposited CdTe layers grown in the cathodic voltage range (1,247–1,258) mV. The SEM images indicate noticeable change in CdTe grain size from ~85 to ~430 nm after CdCl2 treatment with uniform surface coverage of the glass/FTO substrate. The TEM images show the columnar growth structure for as-deposited and CdCl2 treated CdTe layers. The TEM images also indicate an increase in grain’s diameter from ~50 to ~200 nm after CdCl2 treatment

Scutellaria baicalensis

Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts of Scutellaria baicalensis and its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts of S. baicalensis. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts of S. baicalensis compared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts of S. baicalensis. L6 cells treated with flavonoids and extracts of S. baicalensis increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that the S. baicalensis extracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function

Influence of halloysite nanotubes on physical and mechanical properties of cellulose fibres reinforced vinyl ester composites

Natural fibres are generally added to polymer matrix composites to produce materials with the desirable mechanical properties of higher specific strength and higher specific modulus while at the same time to maintain a low density and low cost. The physical and mechanical properties of polymer composites can be enhanced through the addition of nanofillers such as halloysite nanotubes. This article describes the fabrication of vinyl ester eco-composites and eco-nanocomposites and characterizes these samples in terms of water absorption, mechanical and thermal properties. Weight gain test and Fourier transform infrared analysis indicated that 5% halloysite nanotube addition gave favourable reduction in the water absorption and increased the fibre–matrix adhesion leading to improved strength properties in the eco-nanocomposites. However, halloysite nanotube addition resulted in reduced toughness but improved thermal stability

Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma

Background Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma

Immunomodulatory Effects of Hypocrellin A on MHC-restricted Antigen Processing

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the H-2Kb-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways

Simultaneous control of magnetic topologies for reconfigurable vortex arrays

The topological spin textures in magnetic vortices in confined magnetic elements offer a platform for understanding the fundamental physics of nanoscale spin behavior and the potential of harnessing their unique spin structures for advanced magnetic technologies. For magnetic vortices to be practical, an effective reconfigurability of the two topologies of magnetic vortices, that is, the circularity and the polarity, is an essential prerequisite. The reconfiguration issue is highly relevant to the question of whether both circularity and polarity are reliably and efficiently controllable. In this work, we report the first direct observation of simultaneous control of both circularity and polarity by the sole application of an in-plane magnetic field to arrays of asymmetrically shaped permalloy disks. Our investigation demonstrates that a high degree of reliability for control of both topologies can be achieved by tailoring the geometry of the disk arrays. We also propose a new approach to control the vortex structures by manipulating the effect of the stray field on the dynamics of vortex creation. The current study is expected to facilitate complete and effective reconfiguration of magnetic vortex structures, thereby enhancing the prospects for technological applications of magnetic vortices.ope