Cardiovascular disease (CVD) remains a leading cause of death globally. Understanding and characterizing the biochemical context of the cardiovascular system in health and disease is a necessary preliminary step for developing novel therapeutic strategies aimed at restoring cardiovascular function. Bioactive lipids are a class of dietary-dependent, chemically heterogeneous lipids with potent biological signaling functions. They have been intensively studied for their roles in immunity, inflammation, and reproduction, among others. Recent advances in liquid chromatography-mass spectrometry techniques have revealed a staggering number of novel bioactive lipids, most of them unknown or very poorly characterized in a biological context. Some of these new bioactive lipids play important roles in cardiovascular biology, including development, inflammation, regeneration, stem cell differentiation, and regulation of cell proliferation. Identifying the lipid signaling pathways underlying these effects and uncovering their novel biological functions could pave the way for new therapeutic strategies aimed at CVD and cardiovascular regeneration.
Background: Fragmented QRS (fQRS) and Q waves are ECG findings in patients with myocardial scar. fQRS is more sensitive than pathological Q waves in detecting myocardial fibrosis in patients with coronary artery disease (CAD). Cardiac magnetic resonance (CMR) imaging is used for the diagnosis and for quantifying scar tissue in patients with HCM. Our aim was to correlate ECG parameters like fQRS and Q waves with the presence of late gadolinium enhancement (LGE) assessed by contrast CMR imaging to elucidate ECG markers which might predict scar tissue in HCM. Methods: This study is a retrospective analysis which included 39 patients who were diagnosed/suspected to have HCM on echocardiography and referred for contrast CMR imaging at our centre between 2010 and 2016. Presence of fQRS was correlated with scar demonstrated by LGE on CMR. Results: Twenty four (66.67%) patients had asymmetrical septal hypertrophy, 7 (19.44%) patients had apical involvement while 5 (13.89%) had concentric pattern. Only 4 (11.11%) patients had pathological Q waves in contiguous leads on surface ECG while fQRS in two contiguous leads was present in 23 (63.89%) patients. Presence of fQRS was more in patients with LGE on CMR than those without (84.61 versus 10%, p<.001). When presence of LGE in specific segments (anterior, lateral and inferior) was correlated with corresponding ECG leads, all the three segments showed significant correlation. The overall sensitivity, specificity, PPV and NPV of fQRS for predicting scar tissue were 84.6, 90.0, 95.6 and 69.2%, respectively. Conclusion: fQRS on surface ECG can be used as an indirect marker to predict the presence of fibrosis in HCM.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds are under clinical investigation for various diseases. In particular, marine natural compounds are gaining more attention in the new drug development process. The present study aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the 4 SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds, namely, chrysophaentin A (−6.6 kcal/mol), geodisterol sulfates (−6.6 kcal/mol), hymenidin (−6.4 kcal/mol), plinabulin (−6.4 kcal/mol), and tetrodotoxin (−6.3 kcal/mol) expressed minimized binding energy and molecular interactions, such as covalent and hydrophobic interactions, with the SARS CoV-2 main protease. Using molecular dynamic studies, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (ROG), and hydrogen bond (H-Bond) values were calculated for the SARS-CoV-2 main protease with a hymenidin docked complex. Additionally, in silico drug-likeness and pharmacokinetic property assessments of the compounds demonstrated favorable druggability. These results suggest that marine natural compounds are capable of fighting SARS-CoV-2. Further in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.
Magnesium (Mg 2+ ) is the most abundant divalent cation in cells, yet the mechanisms mediating its organellar transport remain poorly defined. We identify endoplasmic reticulum (ER) Mg 2+ adenosine triphosphatase (ATPase) (ERMA) as the transporter that drives Mg 2+ uptake into the ER lumen, establishing the ER as a bi-ionic intracellular reservoir. MagFRET biosensors targeted to the ER demonstrate that ERMA mediates dynamic ER Mg 2+ storage and robust adenosine 5′-triphosphate–dependent Mg 2+ uptake reaching 15 to 30 millimolar. Cryo–electron microscopy structures of human and mouse ERMA reveal a P-type ATPase fold with an unwound transmembrane 4 (TM4) that coordinates Mg 2+ via the unique PILP backbone and the TM5 residue Q1110, whose mutation markedly impairs ERMA-mediated Mg 2+ uptake. Functional reconstitution of domain mutants, ERMA-SERCA chimeras, and pathogenic variants confirm ERMA as an ER-resident Mg 2+ pump and gatekeeper of ER Mg 2+ ionic equilibrium.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds is under clinical investigation for various diseas-es. Especially, marine natural compounds are gaining more attention in the new drug develop-ment process. The present study has aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the four SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds namely Chrysophaentin A (-6.6 kcal/mol), Geodisterol sulfates (-6.6 kcal/mol), Hymenidin (-6.4 kcal/mol), Plinabulin (-6.4 kcal/mol) and Tetrodotoxin (-6.3 kcal/mol) expressed the minimized binding energy and molecular interactions such as covalent and hydrophobic interactions to the SARS CoV-2 Main Protease. Using Molecular dynamic stud-ies, the Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (ROG), and Hydrogen bonds (H-Bonds) values were calculated for SARS-CoV-2 Main Protease with Hymenidin docked complex. Additionally, in silico Druglikeness and pharmaco-kinetic property assessments of the compounds demonstrated favorable druggability. These re-sults suggested that marine natural compounds are capable of fighting SARS-CoV-2. Further, in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.