Levels of Small Extracellular Vesicles Containing hERG-1 and Hsp47 as Potential Biomarkers for Cardiovascular Diseases.

The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.

SNAIL transcription factor increases the motility and invasive capacity of prostate cancer cells.

The incidence and mortality rates of prostate cancer (PCa) are increasing, and PCa is almost the second­leading cause of cancer­associated mortality in men. During tumor progression, epithelial cells decrease the number of adhesion molecules, change their polarity and position, rearrange their cytoskeleton and increase their migratory and invasive capacities. These changes are known under the concept of epithelial­mesenchymal transition (EMT). EMT is characterized by an upregulation of certain transcription factors, including SNAIL1, which represses genes that are characteristic of an epithelial phenotype, including E­cadherin, and indirectly increase the expression levels of genes, which are associated with the mesenchymal phenotype. It has been suggested that the transcription factor, SNAIL1, decreases the proliferation and increases the migratory and invasive capacities of PCa cell lines. The present study was performed using LNCaP and PC3 cell lines, in which the expression levels of SNAIL1 were increased or silenced through the use of lentiviral vectors. The expression levels of EMT markers were quantified using reverse transcription­quantitative polymerase chain reaction and western blot analysis. In addition, cell survival was analyzed using an MTS assay; cell proliferation was examined using an antibody targeting Ki­67; migration on plates with 8 µm pores to allow the passage of cells; and invasiveness was analyzed using a membrane chamber covered in dried basement membrane matrix solution. The levels of apoptosis were determined using a Caspase 3/7 assay containing a substrate modified by caspases 3 and 7. The results demonstrated that the overexpression and silencing of SNAIL1 decreased cell proliferation and survival. However, the overexpression of SNAIL1 decreased apoptosis, compared with cells with the SNAIL1­silenced cells, in which cell apoptosis increased. The migration and invasive capacities increased in the cells overexpressing SNAIL1, and decreased when SNAIL1 was silenced. In conclusion, PCa cells overexpressing SNAIL1 exhibited characteristics of an EMT phenotype, whereas the silencing of the SNAIL1 transcriptional repressor promoted an epithelial­like phenotype, with decreased migration and invasion, characteristic of mesenchymal cells.

Cholesterol levels after 3 days of high-dose simvastatin in patients at moderate to high risk for coronary events.

BACKGROUND: Elevated levels of low-density lipoprotein cholesterol (LDL-C) impair vascular function by a variety of mechanisms. HMG CoA reductase inhibitors (statins) improve endothelial function by lowering LDL-C and possibly by other "pleiotropic" effects. How rapidly statins can lower LDL-C has not been thoroughly studied. METHODS: We examined the lipid response to 3 days of high-dose simvastatin in a randomized prospective double-blind placebo-controlled crossover study. Twenty-seven subjects at moderate to high risk for coronary heart disease (CHD) received either simvastatin 80 mg/day for 3 days followed by placebo for 3 days or placebo followed by simvastatin. After a washout period of 10 to 14 days, subjects received the opposite treatment. Nonfasting blood lipid levels, including total cholesterol, direct LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides, were obtained before randomization and after each 3-day treatment period. RESULTS: The mean LDL-C level at baseline was 107 mg/dl and decreased 24% in patients receiving simvastatin and 5.6% in patients receiving placebo (P < 0.001). Statistically significant reductions were also achieved in the total cholesterol and cholesterol/HDL-C ratio: 14% and 12%, respectively. Changes in HDL-C and triglyceride levels were not significant. CONCLUSION: Treatment with simvastatin for only 3 days results in a 24% drop in the LDL-C level. As defined by ATPIII, this decrease is comparable to that necessary to lower the LDL-C from one risk level to a lower one and is, therefore, both clinically and statistically significant.

Vitrectomia en las inflamaciones del vitreo / Vitrectomy in vitreous inflammation

El autor presenta un estudio de 12 pacientes con diferentes endoftalmitis con inflamaciones del vítreo tratados con vitrectomía + antibióticos concluyendo que los resultados visuales dependen del empleo de la vitrectomía en el momento preciso, verificando previamente por el laboratorio la virulencia de los agentes patológicos