Precise Therapy Using the Selective Endogenous Encapsidation for Cellular Delivery Vector System

Interindividual variability in drug response is a major problem in the prescription of pharmacological treatments. The therapeutic effect of drugs can be influenced by human genes. Pharmacogenomic guidelines for individualization of treatment have been validated and used for conventional dosage forms. However, drugs can often target non-specific areas and produce both desired and undesired pharmacological effects. The use of nanoparticles, liposomes, or other available forms for drug formulation could help to overcome the latter problem. Virus-like particles based on retroviruses could be a potential envelope for safe and efficient drug formulations. Human endogenous retroviruses would make it possible to overcome the host immune response and deliver drugs to the desired target. PEG10 is a promising candidate that can bind to mRNA because it is secreted like an enveloped virus-like extracellular vesicle. PEG10 is a retrotransposon-derived gene that has been domesticated. Therefore, formulations with PEG10 may have a lower immunogenicity. The use of existing knowledge can lead to the development of suitable drug formulations for the precise treatment of individual diseases

Factors Determining Ticagrelor-Induced Dyspnea in Patients with Acute Coronary Syndrome

(1) Background: The aim of this study was to determine clinical and genetic factors predicting the development of dyspnea in patients receiving ticagrelor. (2) Methods: A total of 277 patients with acute myocardial infarction (with and without ST-segment elevation), who underwent coronary angiography and PTCA with stent implantation and treated with antiplatelet drugs (ticagrelor and aspirin), were enrolled in this study. Platelet aggregation (induction with high-sensitivity ADP, ADP HS) testing was performed using a MULTIPLATE analyzer and reagents for the determination of P2Y12 receptor activity. Venous blood samples were collected for genotyping. (3) Results: Patients experiencing ticagrelor-related dyspnea had lower ADP HS. ROC curve analysis showed that an ADP HS cut-off of ≤19.5 U was associated with the development of dyspnea. The ADP HS value of ≤19.5 U and any dose of atorvastatin lower than 80 mg (or no atorvastatin) increased the risk of dyspnea by more than 4 and 2 times, respectively (OR = 4.07, p ≤ 0.001 and OR = 2.25; p = 0.008). (4) Conclusion: A lower ADP HS value possibly indicates greater ticagrelor activity and a higher plasma concentration of this drug. Atorvastatin might have an impact on the occurrence of ticagrelor-related dyspnea by affecting ticagrelor metabolism. No impact of any genetic variant on the development of dyspnea was determined

Human Placental Mesenchymal Stem Cells and Derived Extracellular Vesicles Ameliorate Lung Injury in Acute Respiratory Distress Syndrome Murine Model

This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like lung injury in mice using intranasal LPS instillation and evaluated histological changes, neutrophil accumulation via immunohistochemistry, bronchoalveolar lavage fluid cell count, total protein, and cytokine concentration, as well as lung gene expression changes at three time points: 24, 72, and 168 h. We found that both P-MSCs and EV treatments reduced the histological evidence of lung injury, decreased neutrophil infiltration, and improved alveolar barrier integrity. Analyses of cytokines and gene expression revealed that both treatments accelerated inflammation resolution in lung tissue. Biodistribution studies indicated negligible cell engraftment, suggesting that intraperitoneal P-MSC therapy functions mostly through soluble factors. Overall, both P-MSC and EV therapy ameliorated LPS-induced lung injury. Notably, at the tested dose, EV therapy was more effective than P-MSCs in reducing most aspects of lung injury