Nutrigenomics: SNPs correlated to detoxification, antioxidant capacity and longevity.

Nutritional genomics, also known as nutrigenomics, is the study of how a person's diet and genes interact with each other. The field of nutrigenomics aims to explain how common nutrients, food additives and preservatives can change the body's genetic balance towards either health or sickness. This study reviews the effects of SNPs on detoxification, antioxidant capacity, and longevity.

Nutrigenomics: SNPs Correlated to Lipid and Carbohydrate Metabolism.

Background: Nutrigenomics - the study of the interactions between genetics and nutrition - has emerged as a pivotal field in personalized nutrition. Among various genetic variations, single-nucleotide polymorphisms (SNPs) have been extensively studied for their probable relationship with metabolic traits.

Methods: Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject.

Nutrigenomics: SNPs correlated to minerals' deficiencies.

Nutrigenetics and nutrigenomics are two interrelated fields that explore the influence of genetic diversity on nutrient responses and function. While nutrigenetics investigates the effects of hereditary ge-netic variations on micronutrient metabolism, nutrigenomics examines the intricate relationship between diet and the genome, studying how genetic variants impact nutrient intake and gene expression. These disciplines offer valuable insights into predicting and managing chronic diseases through personalized nutritional approaches.

Structure-Based Design and Pharmacophore-Based Virtual Screening of Combinatorial Library of Triclosan Analogues Active against Enoyl-Acyl Carrier Protein Reductase of with Favourable ADME Profiles.

Cost-effective therapy of neglected and tropical diseases such as malaria requires everlasting drug discovery efforts due to the rapidly emerging drug resistance of the plasmodium parasite. We have carried out computational design of new inhibitors of the enoyl-acyl carrier protein reductase (ENR) of (ENR) using computer-aided combinatorial and pharmacophore-based molecular design. The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) complexation QSAR model was developed for triclosan-based inhibitors (TCL) and a significant correlation was established between the calculated relative Gibbs free energies of complex formation (∆∆Gcom) between ENR and TCL and the observed inhibitory potencies of the enzyme (IC50exp) for a training set of 20 known TCL analogues.

Methodology for clinical research.

A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device.

Optimization of an Inclusion Body-Based Production of the Influenza Virus Neuraminidase in .

Neuraminidase (NA), as an important protein of influenza virus, represents a promising target for the development of new antiviral agents for the treatment and prevention of influenza A and B. Bacterial host strain BL21 (DE3)pLysS containing the NA gene of the H1N1 influenza virus produced this overexpressed enzyme in the insoluble fraction of cells in the form of inclusion bodies. The aim of this work was to investigate the effect of independent variables (propagation time, isopropyl -d-1-thiogalactopyranoside (IPTG) concentration and expression time) on NA accumulation in inclusion bodies and to optimize these conditions by response surface methodology (RSM).

Antiviral agents against COVID-19: structure-based design of specific peptidomimetic inhibitors of SARS-CoV-2 main protease.

Despite the intense development of vaccines and antiviral therapeutics, no specific treatment of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently available. Recently, X-ray crystallographic structures of a validated pharmacological target of SARS-CoV-2, the main protease (M also called 3CL) in complex with peptide-like irreversible inhibitors have been published. We have carried out computer-aided structure-based design and optimization of peptidomimetic irreversible α-ketoamide M inhibitors and their analogues using MM, MD and QM/MM methodology, with the goal to propose lead compounds with improved binding affinity to SARS-CoV-2 M, enhanced specificity for pathogenic coronaviruses, decreased peptidic character, and favourable drug-like properties.

Bioengineered Scaffolds as Substitutes for Grafts for Urethra Reconstruction.

Urethral defects originating from congenital malformations, trauma, inflammation or carcinoma still pose a great challenge to modern urology. Recent therapies have failed many times and have not provided the expected results. This negatively affects patients' quality of life.

Structure-Based Design and in Silico Screening of Virtual Combinatorial Library of Benzamides Inhibiting 2-trans Enoyl-Acyl Carrier Protein Reductase of with Favorable Predicted Pharmacokinetic Profiles.

Background: During the previous decade a new class of benzamide-based inhibitors of 2-trans enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (Mt) with unusual binding mode have emerged. Here we report in silico design and evaluation of novel benzamide InhA-Mt inhibitors with favorable predicted pharmacokinetic profiles.

Methods: By using in situ modifications of the crystal structure of N-benzyl-4-((heteroaryl)methyl) benzamide (BHMB)-InhA complex (PDB entry 4QXM), 3D models of InhA-BHMBx complexes were prepared for a training set of 19 BHMBs with experimentally determined inhibitory potencies (half-maximal inhibitory concentrations IC50exp).

Virtual design of novel Plasmodium falciparum cysteine protease falcipain-2 hybrid lactone-chalcone and isatin-chalcone inhibitors probing the S2 active site pocket.

We report computer-aided design of new lactone-chalcone and isatin-chalcone (HLCIC) inhibitors of the falcipain-2 (PfFP-2). 3D models of 15 FP-2:HLCIC1-15 complexes with known observed activity (IC) were prepared to establish a quantitative structure-activity (QSAR) model and linear correlation between relative Gibbs free energy of enzyme:inhibitor complex formation (ΔΔG) and IC: pIC = -0.0236 × ΔΔG+5.

Methods and Current Trends in Determination of Neuraminidase Activity and Evaluation of Neuraminidase Inhibitors.

This review focuses on the methods and current trends in determination of neuraminidases (NAs) activity and evaluation of neuraminidase inhibitors (NAIs) by means of biochemical assays. These methods can be used, in principle, for any type of sialidase, with regard to substrate specificity and optimal conditions for enzymatic reaction. Considering the range of organisms producing sialidases, this review omits cell-based assays (plaque assays and study of cytopathic effect) and animal model studies, which are reviewed elsewhere concerning specific organisms.

Current state and prospects of biotechnology in Central and Eastern European countries. Part II: new and preaccession EU countries(CRO, RO, B&H, SRB).

Innovation holds the potential for economic prosperity. Biotechnology (BT) has proved to be a viable vehicle for the development and utilization of technologies, which has brought not only advances to society, but also career opportunities to nation-states that have enabling conditions. In this review, we assess the current state of BT-related activities within selected new and preaccession EU countries (NPA) of CEE region namely Croatia, Romania, Bosnia and Herzegovina and Serbia, examining educational programs, research activity, enterprises, and the financing systems.

Current state and prospects of biotechnology in Central and Eastern European countries. Part I: Visegrad countries (CZ, H, PL, SK).

Innovation is a key determinant of sustainable growth. Biotechnology (BT) is one such industry that has witnessed a revolution in innovative ideas leading to the founding of many new companies based on providing products, solutions and services, stretching from the food industry to environmental remediation, and new medicines. BT holds much promise for the development of national and local economies, however, this requires a strategic approach involving actors within government, industry, and academia working in concert to maximize this potential.

Oguchi type I caused by a homozygous missense variation in the SAG gene.

Oguchi disease, is a very rare form of night blindness caused by biallelic variations in the SAG or GRK1 genes, both involved in rod restoration after light stimuli. Here we report the clinical and genetic findings of an 8-year old boy with a history of reduced visual acuity, nyctalpia and hemeralopia. Clinical findings, in particular the Mizuo-Nakamura phenomenon, were compatible with a diagnosis of Oguchi disease.

Diarylcyclopropane hydroxamic acid inhibitors of histone deacetylase 4 designed by combinatorial approach and QM/MM calculations.

Inhibitors of histone deacetylase superfamily (HDAC), which induce cell cycle arrest, trigger cell death and reduce angiogenesis appear as promising anti-cancer drugs targeting the epigenetic regulation of gene expression. Approved HDAC inhibitors were found effective against haematological and solid malignancies, other HDACIs are currently in clinical trials for the treatment of neurological diseases or immune disorders. Among those, diarylcyclopropane hydroxamic acids (DCHA) were found to be potent and selective inhibitors of the class IIa HDACs, specifically HDAC4, a pharmacological target for the treatment of Huntington's disease and muscular atrophy.

Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients.

Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease.

How accurate is the description of ligand-protein interactions by a hybrid QM/MM approach?

During the last decades, the application of hybrid quantum mechanical/molecular mechanical (QM/MM) methods has been extended to the field of drug design. In principle, the approximate QM/MM approach offers a more complete description of drug-receptor non-covalent interactions. This is especially true when charge or proton transfer, chelation of metal ions or strong polarization of ligand and protein or surface chemical groups are involved.

Valorisation of softwood bark through extraction of utilizable chemicals. A review.

Softwood bark is an important source for producing chemicals and materials as well as bioenergy. Extraction is regarded as a key technology for obtaining chemicals in general, and valorizing bark as a source of such chemicals in particular. In this paper, properties of 237 compounds identified in various studies dealing with extraction of softwood bark were described.

Computer-Aided Design of Orally Bioavailable Pyrrolidine Carboxamide Inhibitors of Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis with Favorable Pharmacokinetic Profiles.

We have carried out a computational structure-based design of new potent pyrrolidine carboxamide (PCAMs) inhibitors of enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (MTb). Three-dimensional (3D) models of InhA-PCAMx complexes were prepared by in situ modification of the crystal structure of InhA-PCAM1 (Protein Data Bank (PDB) entry code: 4U0J), the reference compound of a training set of 20 PCAMs with known experimental inhibitory potencies (IC50(exp)). First, we built a gas phase quantitative structure-activity relationships (QSAR) model, linearly correlating the computed enthalpy of the InhA-PCAM complex formation and the IC50(exp).

Virtually Designed Triclosan-Based Inhibitors of Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis and of Plasmodium falciparum.

We report here new chemical structures of predicted nanomolar triclosan-based inhibitors (TCLs) of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) virtually proposed by computer-assisted molecular design. 3D models of InhA-TCL complexes were prepared by in situ modifications of the reference crystal structure (PDB entry 1P45) for a training set of 15 TCLs with known InhA inhibitory activities. A QSAR model was built leading to linear correlation between the calculated free energies of complexation (ΔΔGcom ) and experimental values IC50 (exp) : pIC50 =-0.

Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: the effect of different substitution patterns.

New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)-glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range.