The biochemical mechanisms of cell injury and myocardial cell death after myocardial infarction remain unresolved. Cyclooxygenase 2 (COX-2), a key enzyme in prostanoid synthesis, is expressed in human ischemic myocardium and dilated cardiomyopathy, but it is absent in healthy hearts. To assess the role of COX-2 in cardiovascular physiopathology, we developed transgenic mice that constitutively express functional human COX-2 in cardiomyocytes under the control of the α-myosin heavy chain promoter. These animals had no apparent phenotype but were protected against ischemia-reperfusion injury in isolated hearts, with enhanced functional recovery and diminished cellular necrosis. To further explore the phenotype of this animal model, we carried out a differential proteome analysis of wild-type vs. transgenic cardiomyocytes. The results revealed a tissue-specific proteomic profile dominated by mitochondrial proteins. In particular, an increased expression of respiratory chain complex IV proteins was observed. This correlated with increased catalytic activity, enhanced respiratory capacity, and increased ATP levels in the heart of COX-2 transgenic mice. These data suggest a new link between COX-2 and mitochondria, which might contribute to the protective cardiac effects of COX-2 against ischemia-reperfusion injury.

A hypertonic solution of Ibuprofen (Ibu) was designed to nebulize, associating a low concentration of Ibu with L-Arginine (AR), to increase solubility and serve as a nitric oxide donor. To provide preclinical research human bronchial epithelial cells derived from a cystic fibrosis patient homozygous for the ΔF508 CFTR mutation (CFBE41o-) and mouse RAW 264.7 macrophages were pre-treated with Ibu (10-100 μM), AR (20 and 200 μM), or the combination Ibu-AR (10-100 μM). After Angiotensin II (AngII) or LPS/Interferon ϒ (IFN) stimulation, Reactive Oxygen Species (ROS) generation, Nitric Oxide (NO) formation, and the expression of inflammatory markers were determined. Ibu-AR (10/20 μM) significantly reduced ROS generation stimulated by AngII (p < 0.01) in CFBE41o- cells preserved the NO pathway and inhibited LPS-stimulated nitrite generation (p < 0.001). In macrophages, the combination Ibu-Ar, in a ratio of 1:2-1:6, efficiently scavenged excessive ROS generated by LPS, and significantly induced NO generation (p < 0.001), but inhibited nitrite formation. In LPS/IFNϒ-activated Raw, gene signature of M1polarization including tumor necrosis factor (TNF-α), NADPH Oxidase 2 (NOX-2), MCP-1, and inducible nitric oxide synthase (iNOS) were significantly downregulated by Ibu-AR, as well TNF-α, IL-6, and iNOS protein expressions. The inhibitory effect produced by Ibu-AR on M1 macrophages was associated with the inhibition of p-ERK1/2 and p-STAT3. Ibu-AR represents an effective therapeutic strategy for reducing oxidative stress, preserving NO bioavailability, and modulating inflammation in chronic inflammatory diseases.

Mutation landscapes and signatures have been thoroughly studied in SARS-CoV-2. Here, we analyse those patterns and link their changes to the viral replication tissue in the respiratory tract. Surprisingly, a substantial difference in those patterns is observed in samples from vaccinated patients. Hence, we propose a model to explain where those mutations could originate during the replication cycle.

Mutation landscapes and signatures have been thoroughly studied in SARS-CoV-2. Here, we analyse those patterns and link their changes to the viral replication niche. Surprisingly, those patterns look to be also modified after vaccination. Hence, by deductive reasoning we identify the steps of the coronavirus infection cycle in which those mutations initiate.

Cardiovascular disease is the leading cause of death worldwide. In the same sense,coronary artery bypass graft (CABG) surgery is one of the most frequently performedcardiac surgery procedures worldwide. In clinical practice, myocardial revascularizationcan be followed by a procedure called endarterectomy to reinforce the sanitation ofthe vessel with decreased flow and improved irrigation. However, there is sufficientevidence in the medical literature that reports serious adverse events due to theapplication of endarterectomy, the most feared complication being the perioperativeinfarction itself, which is why it has fallen into disuse. This work aims to disseminateour experience regarding coronary endarterectomy to be valued as an interventiontool within a complex spectrum like diffuse coronary disease. La enfermedad cardiovascular es la principal causa de muerte en todo el mundo. Elbypass coronario es uno de los procedimientos de cirugía cardíaca realizados conmayor frecuencia en todo el mundo, aunque en ocasiones suele no ser suficiente pararestaurar la irrigación. En la práctica médica, la revascularización miocárdica puedeser seguida por un procedimiento denominado endarterectomía coronaria (EC) parareforzar el saneamiento del vaso con flujo disminuido y mejorar la irrigación. Sinembargo, suficiente evidencia en la literatura médica reporta serios eventos adversospor la aplicación de la EC, la complicación más temida es el infarto perioperatorio,razón por la cual ha caído en desuso. El objetivo de este trabajo es difundir laexperiencia de nuestro equipo quirúrgico sobre la aplicación de EC en situaciones derevascularización miocárdica dentro de un espectro complejo como es la enfermedadcoronaria difusa.