Reactive Metabolite-induced Protein Glutathionylation: a Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity

Published date : 13 Jul 2018

Although covalent protein binding is established as the pivotal event underpinning acetaminophen (APAP) toxicity, its mechanistic details remain unclear. In this study, we demonstrated that APAP induces widespread protein glutathionylation in a time-, dose- and bioactivation-dependent manner in HepaRG cells.

type
Journal Paper
journal
Molecular & Cellular Proteomics, 2018, Jul 13, doi: 10.1074/mcp.RA118.000875
Impact Factor
5.232

Homologous Lympho-Epithelial Kazal-type Inhibitor Domains Delay Blood Coagulation by Inhibiting Factor X and XI with Differential Specificity

Published date : 12 Jul 2018

Despite being initially identified in the blood filtrate, LEKTI is a 15-domain Kazal-type inhibitor mostly known in the regulation of skin desquamation. In the current study, screening of serine proteases in blood coagulation cascade showed that LEKTI domain 4 has inhibitory activity toward only FXIa, whereas LEKTI domain 6 inhibits both FXIa and FXaB (bovine FXa). Nuclear magnetic resonance structural and dynamic experiments plus molecular dynamics simulation revealed that LEKTI domain 4 has enhanced backbone flexibility at the reactive-site loop.

type
Journal Paper
journal
Structure, 26, Pg 1178-1186, Sept 4, 2018, doi: 10.1016/j.str.2018.05.018, PMID: 30017565
Impact Factor
4.907

PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells

Published date : 09 Jul 2018

Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target. Here, we describe an RNAi screen for SASP regulators. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Among the screen candidates was PTBP1.

type
Journal Paper
journal
Cancer Cell, Vol. 34, Issue 1, Pg 85-102, 9 July 2018, doi: 10.1016/j.ccell.2018.06.007,
Impact Factor
22.844

Calmidazolium Chloride and Its Complex with Serum Albumin Prevent Huntingtin Exon1 Aggregation

Published date : 06 Jul 2018

Huntington's disease (HD) is a genetic disorder caused by a CAG expansion mutation in Huntingtin gene leading to polyglutamine (polyQ) expansion in the N-terminus side of Huntingtin (Httex1) protein. Neurodegeneration in HD is linked to aggregates formed by Httex1 bearing expanded polyQ. Initiation and elongation steps of Httex1 aggregation are potential target steps for the discovery of therapeutic molecules, for yet untreatable and cruel, HD. Here we report Httex1 aggregation inhibition by calmidazolium chloride (CLC) by acting on the initial aggregation event.

type
Journal Paper
journal
Molecular Pharmaceutics, 2018, Aug 6, 15 (8), pp 3356–3368, doi:10.1021/acs.molpharmaceut.8b00380


Impact Factor
4.556

Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide

Published date : 05 Jul 2018

Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN.

type
Journal Paper
journal
Proceedings of the National Academy of Sciences of the United States of America (PNAS), July 24, 2018, Vol. 115, no. 30, Pg E7119-E7128, doi: 10.1073/pnas.1801253115
Impact Factor
9.504

Synthesizing retinal and neuronal images with generative adversarial nets

Published date : 04 Jul 2018

This paper aims at synthesizing multiple realistic-looking retinal (or neuronal) images from an unseen tubular structured annotation that contains the binary vessel (or neuronal) morphology. The generated phantoms are expected to preserve the same tubular structure, and resemble the visual appearance of the training images. Inspired by the recent progresses in generative adversarial nets (GANs) as well as image style transfer, our approach enjoys several advantages.

type
Journal Paper
journal
Medical Image Analysis, 2018 Jul 4;49:14-26. doi: 10.1016/j.media.2018.07.001
Impact Factor
5.356

Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors and status of novel antivirals

Published date : 03 Jul 2018

A total of 13672 viruses, collected by World Health Organization recognised National Influenza Centres between May 2016 and May 2017, were assessed for neuraminidase inhibitor susceptibility by four WHO Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance Epidemiology and Control of Influenza. The 50% inhibitory concentration (IC50) was determined for oseltamivir and zanamivir for all viruses, and for peramivir and laninamivir in a subset (n = 8457).

type
Journal Paper
journal
Antiviral Research 2018 Jul 3;157:38-46. doi: 10.1016/j.antiviral.2018.07.001
Impact Factor
4.307

Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub

Published date : 26 Jun 2018

Infection and tissue damage induces assembly of supramolecular organizing centres (SMOCs)), such as the Toll-like receptor (TLR) MyDDosome, to co-ordinate inflammatory signaling. SMOC assembly is thought to drive digital all-or-none responses, yet TLR activation by diverse microbes induces anything from mild to severe inflammation. Using single-molecule imaging of TLR4-MyDDosome signaling in living macrophages, we find that MyDDosomes assemble within minutes of TLR4 stimulation.

type
Journal Paper
journal
eLife, 2018 Jan 24;7. pii: e31377. doi: 10.7554/eLife.31377
Impact Factor
7.616