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

The Impact of CYP4F2 rs3093135 TT variant on bleeding and thrombosis in dual antiplatelet therapy users

Introduction: Dual antiplatelet therapy (DAPT) of thienopyridines (ticagrelor or clopidogrel) and aspirin is recommended for patients with acute coronary syndromes for a period of 12 months after percutaneous coronary intervention (PCI) and stent implantation. Individual patients` genetic and non-genetic factors may determine bleeding and thrombosis during DAPT. As it was showed already, CYP4F2 rs2108622 may significantly affect antiplatelet treatment with clopidogrel. Our most recent data showed, that CYP4F2 rs3093135 TT variant carriers, users of ticagrelor, had lower platelet aggregation values than non-carriers. Aim: To determine the impact of CYP4F2 rs3093135 TT variant on bleeding and trombosis in patients treated with dual thienopyridine (ticagrelor or clopidogrel) and aspirin antiplatelet therapy after percutaneous coronary intervention (PCI) and stent implantation. Methods: This prospective study was carried out with the patients hospitalized with acute coronary syndromes at the Department of Cardiology of Hospital of Health Sciences, Lithuania between January 2013 till December 2016. All the patients received dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel and aspirin for at least of 6 months after PCI and stent implantation. From a total of (n=378) patients receiving DAPT, only the patients with CYP4F2 rs3093135 TT variant (n=33) were selected into this study. Bleeding was defined according to Bleeding Academic Research Consortium (BARC) classification. Results: From a total of 33 patients, carriers of CYP4F2 rs3093135 TT variant, 9 (27.3%) patients received ticagrelor and 24 (72.7%) were treated with clopidogrel. Only 2 patients who used ticagrelor had no bleeding events. Seven patients had type 1 or 2 bleeding according to BARC classification and one patient had a major type 3a gastrointestinal bleeding and required a blood tranfusion. The bleeding events were not documented in clop[...]

Assessment of absorption of glycated nail proteins in patients with diabetes mellitus and diabetic retinopathy

Background and objectives: Glycation occurs in a variety of human tissues and organs. Knowledge about the relationship between predictive biochemical factors such as absorption of glycated nail proteins and severity of type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) remains limited. Materials and Methods: The study group consisted of patients with type 2 DM and DR (n = 32) and a control group (n = 28). Each patient underwent a comprehensive ophthalmic examination. The glycation process in nail clippings was evaluated in stages of in vitro glycation and deglycation stages. ATR–FTIR spectroscopy was used to calculate the infrared absorption in the region of interest. The absorption of solutions with nail clippings was evaluated by NanoDrop spectrophotometry. Absorption spectra di erences before and after the exposure to fructosamine 3-kinase were compared between DM patients with DR and the control group. [...]

Išemine širdies liga sergančių pacientų identifikavimas pagal CYP2C19*2 genotipą

Išemine širdies liga sergantiems pacientams, ku-riems išsivysto stento trombozė arba gydant anti-agregantais nustatomas didelis trombocitų reakty-vumas, siekėme nustatyti patologinį CYP2C19*2 alelį, taikydami naują greitai genotipą nustatantį metodą. Iš viso tyrime dalyvavo 35 pacientai. Visi pacientai buvo ištirti dėl CYP2C19*2 naudojant Spartan RX CYP2C19 tyrimų paketą. CYP2C19*1*1 genetinis variantas nustatytas 63 %, *1*2 – 34 %, *2*2 – 2 % tirtų pacientų. Vyrų ir moterų grupėse skirtingi genotipai pasiskirstė panašiai. CYP2C19*2 alelį, lemiantį blogesnį klopidogrelio antitromboci-tinį efektą, greitu genotipo identifikacijos metodu galima nustatyti greičiau nei per valandąObjective. The task was to identify the defective CYP2C19*2 allele by using a novel fast-genotyping method in the patients having coronary artery disease who developed stent thrombosis or high on-treatment platelet reactivity. Materials and methods. A total of 35 patients were included in the study. All the patients were screened for CYP2C19*2 using Spartan RX CYP2C19 Assay Package. Results. CYP2C19*1*1 variant was found in 63%, *1*2 in 34%, *2*2 in 3% of patients. The distribution of genotypes was similar in men and women. Conclusions. By using the bedside technique, CYP2C19*2, which is responsible for a poorer effect of clopidogrel, might be identified in less than an hourBiologijos katedraLietuvos sveikatos mokslų universitetasVytauto Didžiojo universiteta

Retinal and Choroidal Thinning—A Predictor of Coronary Artery Occlusion?

Introduction. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) allowed visualization of retina and choroid to nearly the capillary level; however, the relationship between systemic macrovascular status and retinal microvascular changes is not yet known well. Aim. Our purpose was to assess the impact of retinal optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters on prediction of coronary heart disease (CHD) in acute myocardial infarction (MI) and chronic three vessel disease (3VD) groups. Methods. This observational study included 184 patients—26 in 3VD, 76 in MI and 82 in healthy participants groups. Radial scans of the macula and OCTA scans of the central macula (superficial (SCP) and deep (DCP) capillary plexuses) were performed on all participants. All participants underwent coronary angiography. Results. Patients in MI groups showed decreased parafoveal total retinal thickness as well as GCL+ retinal thickness. Outer circle total retinal thickness and GCL+ retinal thickness were lowest in the 3VD group. The MI group had thinner, while 3VD the thinnest, choroid. A decrease in choroidal thickness and vascular density could predict 3VD. Conclusions. A decrease in retinal and choroidal thickness as well as decreased vascular density in the central retinal region may predict coronary artery disease. OCT and OCTA could be a significant, safe, and noninvasive tool for the prediction of coronary artery disease

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

Effects of Combined Treatment with Sodium Dichloroacetate and Sodium Valproate on the Genes in Inflammation- and Immune-Related Pathways in T Lymphocytes from Patients with SARS-CoV-2 Infection with Pneumonia: Sex-Related Differences

The study presents data on the anti-inflammatory effects of a combination of sodium dichloroacetate and sodium valproate (DCA–VPA) on the expression of inflammation- and immune response-related genes in T lymphocytes of SARS-CoV-2 patients. The study aimed to assess the effects of DCA–VPA on the genes of cytokine activity, chemokine-mediated signaling, neutrophil chemotaxis, lymphocyte chemotaxis, T-cell chemotaxis, and regulation of T-cell proliferation pathways. The study included 21 patients with SARS-CoV-2 infection and pneumonia: 9 male patients with a mean age of 68.44 ± 15.32 years and 12 female patients with a mean age of 65.42 ± 15.74 years. They were hospitalized between December 2022 and March 2023. At the time of testing, over 90% of sequences analyzed in Lithuania were found to be of the omicron variant of SARS-CoV-2. The T lymphocytes from patients were treated with 5 mmol DCA and 2 mmol VPA for 24 h in vitro. The effect of the DCA–VPA treatment on gene expression in T lymphocytes was analyzed via gene sequencing. The study shows that DCA–VPA has significant anti-inflammatory effects and apparent sex-related differences. The effect is more potent in T cells from male patients with SARS-CoV-2 infection and pneumonia than in females

SARS-CoV-2 infection, sex-related differences, and a possible personalized treatment approach with valproic acid: a review

Sex differences identified in the COVID-19 pandemic are necessary to study. It is essential to investigate the efficacy of the drugs in clinical trials for the treatment of COVID-19, and to analyse the sex-related beneficial and adverse effects. The histone deacetylase inhibitor valproic acid (VPA) is a potential drug that could be adapted to prevent the progression and complications of SARS-CoV-2 infection. VPA has a history of research in the treatment of various viral infections. This article reviews the preclinical data, showing that the pharmacological impact of VPA may apply to COVID-19 pathogenetic mechanisms. VPA inhibits SARS-CoV-2 virus entry, suppresses the pro-inflammatory immune cell and cytokine response to infection, and reduces inflammatory tissue and organ damage by mechanisms that may appear to be sex-related. The antithrombotic, antiplatelet, anti-inflammatory, immunomodulatory, glucose- and testosterone-lowering in blood serum effects of VPA suggest that the drug could be promising for therapy of COVID-19. Sex-related differences in the efficacy of VPA treatment may be significant in developing a personalised treatment strategy for COVID-19

Matrix metalloproteinase-3 gene polymorphism and dilatative pathology of ascending thoracic aorta

Matrix metalloproteinase-3 (MMP-3) degrades extracellular matrix and may lead to development of dilatative pathology of ascending thoracic aorta. Expression of MMP-3 depends upon the 5A/6A polymorphism in the promoter region. An increased number of 5A alleles leads to high expression of MMP-3. Thus, objective of the study was to determine whether the 5A/6A polymorphism in the promoter region of MMP-3 gene is associated with the development of dilatative pathology of ascending thoracic aorta. We studied 76 patients (age ranged from 31 to 81 years; median age, 64 years) who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n=604) aged 25–64 years, all from Lithuania. DNA was analyzed by using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position – 1171 of the MMP3 gene promoter. The prevalence of MMP-3 genotypes was similar in the group of dilatative pathology of ascending thoracic aorta and random sample of population. The frequency of 5A allele did not differ significantly between both groups and was 0.506 and 0.514, respectively. Male carriers of 5A/5A genotype were significantly younger compared with those with the 6A/6A genotype. In conclusion, the frequency of MMP-3 promoter 5A/6A genotypes did not differ between the group of patients with dilatative pathology of ascending thoracic aorta and the random sample of population, but the males with dilatative pathology of ascending thoracic aorta and 5A/5A genotype required aortic reconstruction surgery at the younger age than the males carrying 6A/ 6A genotype in the MMP-3 promoter region