Unveiling structural components of dibenzofuran-based MMP-12 inhibitors: a comparative classification-dependent analysis with molecular docking-based virtual screening and molecular dynamics simulation.

Unlabelled: The implication of matrix metalloproteinase-12 (MMP-12) in various major disorders including cancer, COPD, cardiovascular disorders, and neurological diseases makes it a potential target for drug discovery. Contemplating the significance of MMP-12, a number of MMP-12 inhibitors were designed, synthesized and tested throughout the world but the non-selective nature of most of those molecules can lead to adverse drug interactions. In contradiction, the dibenzofuran (DBF) and dibenzothiophene (DBT) derivatives showed highly potent and selective MMP-12 inhibition.

Sepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial.

Purpose: We hypothesised that the biological heterogeneity of sepsis may highlight sepsis subtypes with differences in response to intravenous vitamin C treatment in the Lessening Organ Dysfunction with VITamin C (LOVIT) trial. Our aims were to identify sepsis subtypes and to test whether sepsis subtypes have differences in treatment effect to vitamin C and describe putative biological effects of vitamin C treatment.

Methods: We measured biomarkers of inflammation, at baseline and at 7 days post-randomisation, in 457/863 (53.

Imaging distinct neuronal populations with a dual channel miniscope.

Miniature fluorescence microscopes (miniscopes) are one of the most powerful and versatile tools for recording large scale neural activity in freely moving rodents with single cell resolution. Recent advances in the design of genetically encoded calcium indicators (GECIs) allow to target distinct neuronal populations with non-overlapping emission spectral profiles. However, conventional miniscopes are limited to a single excitation, single focal plane imaging, which does not allow to compensate for chromatic aberration and image from two spectrally distinct calcium indicators.

Anticoagulation Among Patients Hospitalized for COVID-19 : A Systematic Review and Prospective Meta-analysis.

Background: Reported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent.

Purpose: To estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes.

Data Sources: Randomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.

An overview of matrix metalloproteinase-12 in multiple disease conditions, potential selective inhibitors, and drug designing strategies.

Matrix metalloproteases (MMPs) are the proteolytic enzymes accountable for extracellular matrix (ECM) modification through their Zn-dependent catalytic activity. Among these, MMP-12 is one of the crucial MMPs that contributes to various disease states including different types of cancers and other major pathophysiological conditions including COPD, asthma, emphysema, skin diseases, arthritis, vascular diseases, and neurological disorders. The majority of the MMP-12 inhibitors should have three constitutional pharmacophoric features (i.