This article is devoted to the synthesis of a new magnetic palladium catalyst that has been immobilized on A-TT-Pd coated-magnetic FeO nanoparticles. Such surface functionalization of magnetic particles is a promising method to bridge the gap between heterogeneous and homogeneous catalysis approaches. The structure, morphology, and physicochemical properties of the particles were characterized through different analytical techniques, including TEM, FT-IR, XRD, SEM, EDS, TGA-DTG, ICP, and VSM techniques.
View Article and Find Full Text PDFDysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites.
View Article and Find Full Text PDFBacterial infections and persistent inflammation can impede the intrinsic healing process of wounds. To combat this issue, researchers have delved into the potential use of carbon dots (CDs) in the regulation of inflammation and counteract infections. These CDs were synthesized using a microwave-assisted hydrothermal process and have demonstrated outstanding antibacterial and antibiofilm properties against Gram-positive and Gram-negative bacteria.
View Article and Find Full Text PDFThe activation of memory T cells is a very rapid and concerted cellular response that requires coordination between cellular processes in different compartments and on different time scales. In this study, we use ribosome profiling and deep RNA sequencing to define the acute mRNA translation changes in CD8 memory T cells following initial activation events. We find that initial translation enables subsequent events of human and mouse T cell activation and expansion.
View Article and Find Full Text PDFZika virus (ZIKV) and dengue virus (DENV) are members of the Flaviviridae family of RNA viruses and cause severe disease in humans. ZIKV and DENV share over 90% of their genome sequences, however, the clinical features of Zika and dengue infections are very different reflecting tropism and cellular effects. Here, we used simultaneous RNA sequencing and ribosome footprinting to define the transcriptional and translational dynamics of ZIKV and DENV infection in human neuronal progenitor cells (hNPCs).
View Article and Find Full Text PDFThe eIF4E translation initiation factor has oncogenic properties and concordantly, the inhibitory eIF4E-binding protein (4EBP1) is considered a tumor suppressor. The exact molecular effects of 4EBP1 activation in cancer are still unknown. Surprisingly, 4EBP1 is a target of genomic copy number gains (Chr.
View Article and Find Full Text PDFAgPO nanostructures (APNs) containing silver (Ag metal; of the noble metal families) have the potential to exhibit enzyme-mimetic activity. A nanostructure shape, including its surface facets, can improve the bioactivity of enzyme mimicry, yet the molecular mechanisms remain unclear. Herein, we report facet-dependent peroxidase and oxidase-like activity of APNs with both antibacterial and biofilm degrading properties through the generation of reactive oxygen species.
View Article and Find Full Text PDFPancreatic adenocarcinoma (PDAC) epitomizes a deadly cancer driven by abnormal KRAS signaling. Here, we show that the eIF4A RNA helicase is required for translation of key KRAS signaling molecules and that pharmacological inhibition of eIF4A has single-agent activity against murine and human PDAC models at safe dose levels. EIF4A was uniquely required for the translation of mRNAs with long and highly structured 5' untranslated regions, including those with multiple G-quadruplex elements.
View Article and Find Full Text PDFInhibition of the eIF4A RNA helicase with silvestrol and related compounds is emerging as a powerful anti-cancer strategy. We find that a synthetic silvestrol analogue (CR-1-31 B) has nanomolar activity across many cancer cell lines. It is especially active against aggressive MYC/BCL2 B cell lymphomas and this likely reflects the eIF4A-dependent translation of both MYC and BCL2.
View Article and Find Full Text PDFRocaglates, a class of natural compounds isolated from plants of the genus Aglaia, are potent inhibitors of translation initiation. They are proposed to form stacking interactions with polypurine sequences in the 5'-untranslated region (UTR) of selected mRNAs, thereby clamping the RNA substrate onto eIF4A and causing inhibition of the translation initiation complex. Since virus replication relies on the host translation machinery, it is not surprising that the rocaglate Silvestrol has broad-spectrum antiviral activity.
View Article and Find Full Text PDFThe oncogenic c-MYC (MYC) transcription factor has broad effects on gene expression and cell behavior. We show that MYC alters the efficiency and quality of mRNA translation into functional proteins. Specifically, MYC drives the translation of most protein components of the electron transport chain in lymphoma cells, and many of these effects are independent from proliferation.
View Article and Find Full Text PDFTranslation initiation is orchestrated by the cap binding and 43S preinitiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent mutations in papillary thyroid cancers are mutually exclusive with other drivers, including .
View Article and Find Full Text PDFUnlabelled: Recent reports have made important revelations, uncovering direct regulation of DNA damage response (DDR)-associated proteins and chromatin ubiquitination (Ubn) by macroautophagy/autophagy. Here, we report a previously unexplored connection between autophagy and DDR, via a deubiquitnase (DUB), USP14. Loss of autophagy in prostate cancer cells led to unrepaired DNA double-strand breaks (DSBs) as indicated by persistent ionizing radiation (IR)-induced foci (IRIF) formation for γH2AFX, and decreased protein levels and IRIF formation for RNF168, an E3-ubiquitin ligase essential for chromatin Ubn and recruitment of critical DDR effector proteins in response to DSBs, including TP53BP1.
View Article and Find Full Text PDFAim: The treatment of peritoneal dialysis related culture negative peritonitis is empirical which increases the cost of therapy and moreover antibiotic resistance. We aimed the study to isolate bacterial DNA from PD effluent and indentify bacteria causing peritonitis in culture negative situations. We have also studied the cytokine response with different bacteria causing peritonitis.
View Article and Find Full Text PDFMotivation: Deep sequencing based ribosome footprint profiling can provide novel insights into the regulatory mechanisms of protein translation. However, the observed ribosome profile is fundamentally confounded by transcriptional activity. In order to decipher principles of translation regulation, tools that can reliably detect changes in translation efficiency in case-control studies are needed.
View Article and Find Full Text PDFBrain abscess develops in response to a parenchymal infection. Intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) play vital role in central nervous system (CNS) diseases. We studied ICAM-1 (K469E) and MCP-1 (-2518 A>G) polymorphisms among brain abscess patients.
View Article and Find Full Text PDFBackground: Toll-like receptors (TLRs), expressed on cells of the innate immune system, are the first line of host defense. Recognition of bacterial pathogens by the peritoneum is mediated in part by TLR. In this study, we investigated the role of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) gene polymorphisms in end-stage renal disease (ESRD) patients on peritoneal dialysis (PD).
View Article and Find Full Text PDFObjective: Brain abscess develops in response to a parenchymal infection with pyogenic bacteria. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are the most crucial pro-inflammatory cytokines with both beneficial and destructive properties for the central nervous system. The present study evaluated the association of specific alleles/genotypes of TNF-α and IL-1β with brain abscess.
View Article and Find Full Text PDFAim: Cytokines play a critical role in the pathophysiology of end stage renal disease (ESRD). Tumour necrosis factor-a (TNF-α) is an important cytokine involved in initiation and progression of renal diseases. The present study evaluated the association of specific alleles/genotype of TNF-α with chronic renal failure (CRF) and ESRD.
View Article and Find Full Text PDFBackground: is an opportunistic human pathogen in debilitated patients with foreign plastic intravascular devices and peritoneal dialysis (PD) catheters. We performed a Medline search of the English-language literature on continuous ambulatory peritoneal dialysis (CAPD) peritonitis in end-stage renal disease (ESRD) and reviewed 13 cases.
Case Presentation: A 54-year-old male with ESRD secondary to chronic long-standing type II diabetes mellitus presented to the nephrology outpatient department with fever, abdominal pain and cloudy PD effluent.
The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance.
View Article and Find Full Text PDFBackground: Macroautophagy is a catabolic process that can mediate cell death or survival. Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment (TR) is known to induce autophagy. Here we investigated whether SQSTM1/p62 (p62) overexpression, as a marker of autophagic flux, was related to aggressiveness of human prostate cancer (PCa) and whether autophagy regulated the treatment response in sensitive but not resistant PCa cell lines.
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