Synthesis and Biological Properties of Polyphenol-Containing Linear and Dendrimeric Cationic Peptides.

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers.

Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy.

Background: IgE cross-sensitization to major birch pollen allergen Bet v 1 and pathogenesis-related (PR10) plant food allergens is responsible for the pollen-food allergy syndrome.

Methods: We designed a recombinant protein, AB-PreS, consisting of non-allergenic peptides derived from the IgE-binding sites of Bet v 1 and the cross-reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB-PreS was expressed in E.

Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes.

Background: The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail.

Objective: To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation.

Methods: Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG and IgG reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis.

Thermochemical Study of the Interaction of Cytosine and Uracil with Peptides in a Buffered Saline: Complex Formation with beta-Endorphin 30-31 (Human), L-Glutathion (Reduced) and α-L-Alanyl-L-Tyrosine.

The complex formation of uracil and cytosine with glycyl-L-glutamic acid (β-endorphin 30-31), γ-L-glutamyl-L-cysteinyl-glycine (glutathione reduced), α-L-alanyl-L-tyrosine, and α-L-alanyl-α-L-alanine in a buffered saline has been studied using dissolution calorimetry. The values of the reaction constant, the change in Gibbs energy, enthalpy, and entropy were obtained. It is shown that the ratio of the enthalpy and entropy factors depends on the charge of the peptide ion, and the number of H-bond acceptors in the peptide structure.

Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation.

Background: Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation MIR 19® (siR-7-EM/KK-46) targeting a conserved sequence in known SARS-CoV-2 variants for treatment of COVID-19.

Methods: We conducted an open-label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled siR-7-EM/KK-46 (3.

Effect of Genetic Polymorphism of the CYP2D6 Gene on the Efficacy and Safety of Fluvoxamine in Major Depressive Disorder.

Background: Previous studies have shown that cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of fluvoxamine, the activity of which is highly dependent, inter alia, on the polymorphism of the gene encoding it. The objective of our study was to investigate the effect of 1846G>A polymorphism of the CYP2D6 gene on the efficacy and safety of fluvoxamine, using findings on CYP2D6 enzymatic activity and on CYP2D6 expression level in patients with depressive disorders comorbid with alcohol use disorder.

Study Question: Efficacy and safety of fluvoxamine depend on the polymorphism of CYP2D6 gene in patients with major depressive disorder.

Silencing of SARS-CoV-2 with modified siRNA-peptide dendrimer formulation.

Background: First vaccines for prevention of Coronavirus disease 2019 (COVID-19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to evaluate the anti-SARS-CoV-2 effect of siRNA both in vitro and in vivo.

Methods: To identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS-CoV-2 genes fused with the firefly luciferase reporter gene and SARS-CoV-2-infected cells was used.

Lipidomic analysis as a tool for identifying susceptibility to various skin diseases.

This review is about the significance of the use of lipidomic analysis for identifying susceptibility to skin diseases. Exactly this article describes the use of lipidomic analysis in different studies to detect abnormalities in the lipid composition of the skin to diagnose and prevent various dermatological diseases.

Linear and dendrimeric antiviral peptides: design, chemical synthesis and activity against human respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the most common viral pathogens. It is especially dangerous for newborns and young children. In some cases it could lead to severe bronchiolitis, pneumonia with hospitalization or even a lethal outcome.

Analytical Strategies in Lipidomics for Discovery of Functional Biomarkers from Human Saliva.

Human saliva is increasingly being used and validated as a biofluid for diagnosing, monitoring systemic disease status, and predicting disease progression. The discovery of biomarkers in saliva biofluid offers unique opportunities to bypass the invasive procedure of blood sampling by using oral fluids to evaluate the health condition of a patient. Saliva biofluid is clinically relevant since its components can be found in plasma.

Antihypertensive Effect Of Amlodipine In Co-Administration With Omeprazole In Patients With Hypertension And Acid-Related Disorders: Cytochrome P450-Associated Aspects.

Background: CYP2C19 and CYP3A are the main enzymes involved in omeprazole metabolism, while CYP3A is the principal enzyme family for amlodipine biotransformation. Concomitant use of these drugs in patients with hypertension and acid-related disorders (ARD) might lead to drug-drug interaction.

Purpose: The aim of the study was to find if adding omeprazole for treating ARD to amlodipine long-term therapy of hypertension influenced blood pressure of CYP2C19 polymorphism carriers.

Influence of Al on the Structure and in Vitro Behavior of Hydroxyapatite Nanopowders.

Nanopowders of aluminum-substituted (0-20 mol %) hydroxyapatite (HA) with the average size of 40-60 nm were synthesized by the precipitation method from nitrate solutions. A series of samples were studied by various analytical tools to elucidate the peculiarities of Al introduction. Electron paramagnetic resonance and pulsed electron-nuclear double resonance data demonstrate that incorporation of Al resulted in a decrease in the concentration of impurity carbonate anions and lead to an increase in the number of protons in the distant environment of the impurity nitrogen species.

A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells.

One of the urgent problems of gene therapy is the search for effective transfection methods. Synthetic cationic peptides (CPs) are considered to be one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of the architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field.

CYP3A and CYP2C19 activity in urine in relation to CYP3A4, CYP3A5, and CYP2C19 polymorphisms in Russian peptic ulcer patients taking omeprazole.

Background: Proton pump inhibitors (PPIs) are metabolized by cytochrome P450. CYP2C19 is the main isoenzyme for the majority of PPI, whereas CYP3A family is a secondary enzyme for PPI biotransformation.

Purpose: The aim of the study was to find if , and genotypes are connected with CYP3A and CYP2C19 activities in Russian peptic ulcer patients taking omeprazole.

Which cytochrome P450 metabolizes phenazepam? Step by step in silico, in vitro, and in vivo studies.

Background: Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam's metabolic liver pathways and other pharmacokinetic features.

Methods: To determine phenazepam's metabolic pathways, the study was divided into three stages: in silico modeling, in vitro experiment (cell culture study), and in vivo confirmation.

Influence of and gene polymorphisms on pharmacokinetics of apixaban in patients with atrial fibrillation and acute stroke.

Introduction: Difficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke.

Patients And Methods: Pharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al.

Do and gene polymorphisms and low CYP3A4 isoenzyme activity have an impact on stent implantation complications in acute coronary syndrome patients?

Aim: The aim of this study was to determine the impact of and gene polymorphisms and CYP3A4 isoenzyme activity on stent implantation complications among patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).

Patients And Methods: Seventy-six patients (median age 63, range 37-91 years) with an ACS who underwent PCI were screened for and gene polymorphisms with real-time polymerase chain reaction: , , and . CYP3A4 isoenzyme activity was determined by urine cortisol and 6-beta-hydroxycortisol levels.

Urine metabolic ratio of omeprazole in relation to CYP2C19 polymorphisms in Russian peptic ulcer patients.

Background: CYP2C19 is known to be the main enzyme of biotransformation of proton pump inhibitors (PPIs), whereas the gene is highly polymorphic. Genotyping and phenotyping together represent more reliable data about patient's CYP2C19 activity.

Purpose: The aim of the study was to investigate the applicability of urine metabolic ratio of omeprazole for CYP2C19 phenotyping in Russian peptic ulcer patients with different genotypes.

Catalytic activity of human indoleamine 2,3-dioxygenase (hIDO1) at low oxygen.

A cytokine-inducible extrahepatic human indoleamine 2,3-dioxygenase (hIDO1) catalyzes the first step of the kynurenine pathway. Immunosuppressive activity of hIDO1 in tumor cells weakens host T-cell immunity, contributing to the progression of cancer. Here we report on enzyme kinetics and catalytic mechanism of hIDO1, studied at varied levels of dioxygen (O2) and L-tryptophan (L-Trp).

Tyrosine oxidation in heme oxygenase: examination of long-range proton-coupled electron transfer.

Heme oxygenase is responsible for the degradation of a histidine-ligated ferric protoporphyrin IX (Por) to biliverdin, CO, and the free ferrous ion. Described here are studies of tyrosyl radical formation reactions that occur after oxidizing Fe(III)(Por) to Fe(IV)=O(Por(·+)) in human heme oxygenase isoform-1 (hHO-1) and the structurally homologous protein from Corynebacterium diphtheriae (cdHO). Site-directed mutagenesis on hHO-1 probes the reduction of Fe(IV)=O(Por(·+)) by tyrosine residues within 11 Å of the prosthetic group.

Computational modeling of oxygen isotope effects on metal-mediated O2 activation at varying temperatures.

Oxygen equilibrium isotope effects ((18)O EIEs) upon the formation of metal superoxide and peroxide structures from natural abundance O(2) are reported. The (18)O EIEs determined over a range of temperatures are compared to those calculated on the basis of vibrational frequencies. Considering all vibrational modes in a "full frequency model" is found to reproduce the empirical results better than "cut-off" models which consider only the most isotopically sensitive modes.

Inner-sphere mechanism for molecular oxygen reduction catalyzed by copper amine oxidases.

Copper and topaquinone (TPQ) containing amine oxidases utilize O2 for the metabolism of biogenic amines while concomitantly generating H2O2 for use by the cell. The mechanism of O2 reduction has been the subject of long-standing debate due to the obscuring influence of a proton-coupled electron transfer between the tyrosine-derived TPQ and copper, a rapidly established equilibrium precluding assignment of the enzyme in its reactive form. Here, we show that substrate-reduced pea seedling amine oxidase (PSAO) exists predominantly in the Cu(I), TPQ semiquinone state.

Isotopic probing of molecular oxygen activation at copper(I) sites.

Copper-dioxygen (CuO2) adducts are frequently proposed as intermediates in enzymes, yet their electronic and vibrational structures have not always been understood. [Cu(eta1-O2)TMG3tren]+ (TMG3tren = 1,1,1-tris{2-[N2-(1,1,3,3-tetramethylguanidino)]ethyl}amine) features end-on (eta1) O2 coordination in the solid state. Described here is an investigation of the compound's solution properties by nuclear magnetic resonance spectroscopy, density functional calculations, and oxygen isotope effects.