Observation of Enhanced Magnetic Pinning in Sm3+ Substituted Nanocrystalline MnZn Ferrites Prepared by Propellant Chemistry Route

We report the effect of Sm3+ substitution on the structural and magnetic properties of nanocrystalline Mn0.5Zn0.5SmyFe2-yO4 (y = 0.00, 0.01, 0.03 and 0.05) samples prepared by propellant chemistry route using a mixture of fuels. Rietveld refinement of XRD patterns confirmed the formation of cubic spinel phase with space group View the MathML source. The lattice parameter values decreased with Sm3+ substitution up to y = 0.03, but with a noticeable increase for the sample with y = 0.05. In all the samples, entire amount of Zn2+ and Sm3+ were found to be present at the A and B sites, respectively. A distribution of Mn2+ ions at the tetrahedral (A) and the octahedral (B) sites of the spinel Mn0.5Zn0.5Fe2O4 was observed. The microstructures of the samples were observed using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). For all the samples, the average crystallite size decreased with increase in Sm3+ concentration, as determined using Williamson-Hall method. The FTIR spectra showed prominent absorption bands at ∼540 and ∼390 cm−1 corresponding to the stretching vibrations of the metal ion complexes at the tetrahedral (A) and the octahedral (B) sites, respectively. Magnetic properties such as saturation magnetization (Ms), remanence (Mr) and magneton number (ηB) were found to decrease, while the coercivity (Hc) and reduced remanence (Mr/Ms) of the samples were found to increase with increasing Sm3+ content. The increase in Hc with increase in Sm3+ concentration is interpreted as the enhanced pinning of the magnetic moments at the magnetic defects created by Sm3+ ions, which is further confirmed by Mössbauer spectroscopy through a nearly constant magnetic hyperfine field. This results in an increase in the magnetic particle size in spite of decreasing average crystallite size. Our work suggests that, Sm3+ substitution can be used to alter the magnetic hardness of Mnsingle bondZn ferrites and to enable them to be used as potential materials for various technological applications

Severe Oleander Poisoning Presenting with Hyperkalaemia and Unusual Electrocardiographic Changes

Background: Hyperkalaemia in oleander (Nerium oleander) poisoning has been associated with a poor prognosis. Different electrocardiographic (ECG) presentations are possible because of vagotonia and hyperkalaemia. Methods/Results: We report a series of three cases of oleander poisoning in which ECG showed unusual hyperkalaemia features, such as bradyarrhythmia, sinoatrial block, atrioventricular block and junctional rhythm. Conclusions: If arterial blood gas analysis or laboratory values indicate hyperkalaemia in oleander poisoning, the hyperkalaemia should be treated immediately, even if the ECG does not show typical hyperkalaemia features

Case Report - Unusual metastasis in colorectal cancer

Metastasis from colorectal carcinoma occurs by either lymphatic or hematogenous spread. The most common sites of colorectal metastasis are the liver and lung. Involvement of the skin, muscles and bones are quite rare. The prognosis in such patients is usually poor. Herewith, we are reporting a case of colonic carcinoma who had cutaneous metastasis, muscular involvement and diffuse skeletal metastasis. At the end, she had brain metastasis, but liver and lung involvement was not observed till the end

The long noncoding RNA SPRIGHTLY acts as an intranuclear organizing hub for pre-mRNA molecules

Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence cancerous condition are poorly understood. The aberrant expression of SPRIGHTLY lncRNA, encoded within the drosophila gene homolog Sprouty-4 intron, is correlated with a variety of cancers, including human melanomas. We demonstrate by SHAPE-seq and dChIRP that SPRIGHTLY RNA secondary structure has a core pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre-mRNAs: SOX5, SMYD3, SND1, MEOX2, DCTN6, and RASAL2, all of which have cancer-related functions. Hemizygous knockout of SPRIGHTLY by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 in melanoma cells significantly decreases SPRIGHTLY lncRNA levels, simultaneously decreases the levels of its interacting pre-mRNA molecules, and decreases anchorage-independent growth rate of cells and the rate of in vivo tumor growth in mouse xenografts. These results provide the first demonstration of an lncRNA’s three-dimensional coordinating role in facilitating cancer-related gene expression in human melanomas

Exosome-mediated MIR211 modulates tumor microenvironment via the DUSP6-ERK5 axis and contributes to BRAFV600E inhibitor resistance in melanoma

The microRNA MIR211 is an important regulator of melanoma tumor cell behavior. Previous studies suggested that in certain tumors, MIR211 acted as a tumor suppressor while in others it behaved as an oncogenic regulator. When MIR211 is expressed in BRAFV600E-mutant A375 melanoma cells in mouse xenografts, it promotes aggressive tumor growth accompanied by increased cellular proliferation and angiogenesis. We demonstrate that MIR211 is transferred to adjacent cells in the tumor micro-environment via exosomes. Cross-species genome-wide transcriptomic analysis showed that human tumor-derived MIR211 interacts with the mouse transcriptome in the tumor microenvironment, and activates ERK5 signaling in human tumor cells via the modulation of a feedback loop. Human miR211 directly inhibits human DUSP6 protein phosphatase at the post-transcriptional level. We provide support for the hypothesis that DUSP6 inhibition conferred resistance of the human tumor cells to the BRAF inhibitor vemurafenib and to the MEK inhibitor cobimetinib, with associated increases in ERK5 phosphorylation. These findings are consistent with a model in which MIR211 regulates melanoma tumor proliferation and BRAF inhibitor resistance by inducing ERK5 signaling within the complex tumor microenvironment. We propose that the MIR211-ERK5 axis represents an important and sensitive regulatory arm in melanoma with potential theranostic applications

Exosome-mediated MIR211 modulates tumor microenvironment via the DUSP6-ERK5 axis and contributes to BRAFV600E inhibitor resistance in melanoma

The microRNA MIR211 is an important regulator of melanoma tumor cell behavior. Previous studies suggested that in certain tumors, MIR211 acted as a tumor suppressor while in others it behaved as an oncogenic regulator. When MIR211 is expressed in BRAFV600E-mutant A375 melanoma cells in mouse xenografts, it promotes aggressive tumor growth accompanied by increased cellular proliferation and angiogenesis. We demonstrate that MIR211 is transferred to adjacent cells in the tumor micro-environment via exosomes. Cross-species genome-wide transcriptomic analysis showed that human tumor-derived MIR211 interacts with the mouse transcriptome in the tumor microenvironment, and activates ERK5 signaling in human tumor cells via the modulation of a feedback loop. Human miR211 directly inhibits human DUSP6 protein phosphatase at the post-transcriptional level. We provide support for the hypothesis that DUSP6 inhibition conferred resistance of the human tumor cells to the BRAF inhibitor vemurafenib and to the MEK inhibitor cobimetinib, with associated increases in ERK5 phosphorylation. These findings are consistent with a model in which MIR211 regulates melanoma tumor proliferation and BRAF inhibitor resistance by inducing ERK5 signaling within the complex tumor microenvironment. We propose that the MIR211-ERK5 axis represents an important and sensitive regulatory arm in melanoma with potential theranostic applications

Molecular Mechanisms Governing IL-24 Gene Expression

Interleukin-24 (IL-24) belongs to the IL-10 family of cytokines and is well known for its tumor suppressor activity. This cytokine is released by both immune and nonimmune cells and acts on non-hematopoietic tissues such as skin, lung and reproductive tissues. Apart from its ubiquitous tumor suppressor function, IL-24 is also known to be involved in the immunopathology of autoimmune diseases like psoriasis and rheumatoid arthritis. Although the cellular sources and functions of IL-24 are being increasingly investigated, the molecular mechanisms of IL-24 gene expression at the levels of signal transduction, epigenetics and transcription factor binding are still unclear. Understanding the specific molecular events that regulate the production of IL-24 will help to answer the remaining questions that are important for the design of new strategies of immune intervention involving IL-24. Herein, we briefly review the signaling pathways and transcription factors that facilitate, induce, or repress production of this cytokine along with the cellular sources and functions of IL-24

Attenuated IL-2 muteins leverage the TCR signal to enhance regulatory T cell homeostasis and response in vivo

Interleukin-2 (IL-2), along with T-cell receptor (TCR) signaling, are required to control regulatory T cell (Treg) homeostasis and function in vivo. Due to the heightened sensitivity to IL-2, Tregs retain the ability to respond to low-dose or attenuated forms of IL-2, as currently being developed for clinical use to treat inflammatory diseases. While attenuated IL-2 increases Treg selectivity, the question remains as to whether a weakened IL-2 signal sufficiently enhances Treg suppressive function(s) toward disease modification. To understand this question, we characterized the in vivo activity and transcriptomic profiles of two different attenuated IL-2 muteins in comparison with wildtype (WT) IL-2. Our study showed that, in addition to favoring Tregs, the attenuated muteins induced disproportionately robust effects on Treg activation and conversion to effector Treg (eTreg) phenotype. Our data furthermore suggested that Tregs activated by attenuated IL-2 muteins showed reduced dependence on TCR signal, at least in part due to the enhanced ability of IL-2 muteins to amplify the TCR signal in vivo. These results point to a new paradigm wherein IL-2 influences Tregs’ sensitivity to antigenic signal, and that the combination effect may be leveraged for therapeutic use of attenuated IL-2 muteins