Molecular Analysis of HLA Genes in Romanian Patients with Chronic Hepatitis B Virus Infection.

Hepatitis B, a persistent inflammatory liver condition, stands as a significant global health issue. In Romania, the prevalence of chronic hepatitis B virus (CHB) infection ranks among the highest in the European Union. The HLA genotype significantly impacts hepatitis B virus infection progression, indicating that certain HLA variants can affect the infection's outcome. The primary goal of the present work is to identify HLA alleles and specific amino acid residues linked to hepatitis B within the Romanian population. The study enrolled 247 patients with chronic hepatitis B; HLA typing was performed using next-generation sequencing. This study's main findings include the identification of certain HLA alleles, such as DQB1*06:03:01, DRB1*13:01:01, DQB1*06:02:01, DQA1*01:03:01, DRB5*01:01:01, and DRB1*15:01:01, which exhibit a significant protective effect against HBV. Additionally, the amino acid residue alanine at DQB1_38 is associated with a protective role, while valine presence may signal an increased risk of hepatitis B. The present findings are important in addressing the urgent need for improved methods of diagnosing and managing CHB, particularly when considering the disease's presence in diverse population groups and geographical regions.

Ideonella sakaiensis Can Metabolize Bisphenol A as a Carbon Source.

Bisphenol A and its analogues represent a significant environmental and public health hazard, particularly affecting the endocrine systems of children and newborns. Due to the growing need for non-pathogenic biodegradation microbial agents as environmentally friendly and cost-effective solutions to eliminate endocrine disruptors, this study aimed to investigate the degradation of bisphenol A by Ideonella sakaiensis, based on its currently understood unique enzymatic machinery that is already well known for degrading polyethylene terephthalate. The present study provides novel insights into the metabolic competence and growth particularities of I. sakaiensis. The growth of I. sakaiensis exposed to bisphenol A exceeded that in the control conditions, starting with 72 h in a 70% nutrient-rich medium and starting with 48 h in a 100% nutrient-rich medium. Computational modeling showed that bisphenol A, as well as its analogue bisphenol S, are possible substrates of PETase and MHETase. The use of bisphenol A as a carbon and energy source through a pure I. sakaiensis culture expands the known substrate spectra and the species' potential as a new candidate for bisphenol A bioremediation processes.

Harnessing Code Interpreters for Enhanced Predictive Modeling: A Case Study on High-Density Lipoprotein Level Estimation in Romanian Diabetic Patients.

Diabetes is a condition accompanied by the alteration of body parameters, including those related to lipids like triglyceride (TG), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs). The latter are grouped under the term dyslipidemia and are considered a risk factor for cardiovascular events. In the present work, we analyzed the complex relationships between twelve parameters (disease status, age, sex, body mass index, systolic blood pressure, diastolic blood pressure, TG, HDL, LDL, glucose, HbA1c levels, and disease onset) of patients with diabetes from Romania. An initial prospective analysis showed that HDL is inversely correlated with most of the parameters; therefore, we further analyzed the dependence of HDLs on the other factors. The analysis was conducted with the Code Interpreter plugin of ChatGPT, which was used to build several models from which Random Forest performed best. The principal predictors of HDLs were TG, LDL, and HbA1c levels. Random Forest models were used to model all parameters, showing that blood pressure and HbA1c can be predicted based on the other parameters with the least error, while the less predictable parameters were TG and LDL levels. By conducting the present study using the ChatGPT Code Interpreter, we show that elaborate analysis methods are at hand and easy to apply by researchers with limited computational resources. The insight that can be gained from such an approach, such as what we obtained on HDL level predictors in diabetes, could be relevant for deriving novel management strategies and therapeutic approaches.

Aspartame Safety as a Food Sweetener and Related Health Hazards.

Aspartame is the methyl-ester of the aspartate-phenylalanine dipeptide. Over time, it has become a very popular artificial sweetener. However, since its approval by the main food safety agencies, several concerns have been raised related to neuropsychiatric effects and neurotoxicity due to its ability to activate glutamate receptors, as well as carcinogenic risks due to the increased production of reactive oxygen species. Within this review, we critically evaluate reports concerning the safety of aspartame. Some studies evidenced subtle mood and behavioral changes upon daily high-dose intake below the admitted limit. Epidemiology studies also evidenced associations between daily aspartame intake and a higher predisposition for malignant diseases, like non-Hodgkin lymphomas and multiple myelomas, particularly in males, but an association by chance still could not be excluded. While the debate over the carcinogenic risk of aspartame is ongoing, it is clear that its use may pose some dangers in peculiar cases, such as patients with seizures or other neurological diseases; it should be totally forbidden for patients with phenylketonuria, and reduced doses or complete avoidance are advisable during pregnancy. It would be also highly desirable for every product containing aspartame to clearly indicate on the label the exact amount of the substance and some risk warnings.

Silver Carp (Hypophthalmichthys molitrix) (Asian Silver Carp) Presence in Danube Delta and Romania-A Review with Data on Natural Reproduction.

The Danube River has a large hydrographical basin, being the second largest river in Europe. The main channel flows through seven European countries with many species of fish inhabiting it. In this review we focused on the invasive species silver carp (Hypophthalmichthys molitrix), which plays an important ecological and economic role in its original habitat, but since introduced in Europe's rivers, the species has posed a serious ecological risk under global warming. In this review paper, we gathered data regarding silver carp, such as when and how it entered the Danube Delta and the water temperature suitable for its growth and reproduction, mainly in the context of global warming, as well as the nature of nutrition and the ecological risk the species poses.

Epithelial Sodium Channel Inhibition by Amiloride Addressed with THz Spectroscopy and Molecular Modeling.

THz spectroscopy is important for the study of ion channels because it directly addresses the low frequency collective motions relevant for their function. Here we used THz spectroscopy to investigate the inhibition of the epithelial sodium channel (ENaC) by its specific blocker, amiloride. Experiments were performed on A6 cells' suspensions, which are cells overexpressing ENaC derived from Xenopus laevis kidney. THz spectra were investigated with or without amiloride. When ENaC was inhibited by amiloride, a substantial increase in THz absorption was noticed. Molecular modeling methods were used to explain the observed spectroscopic differences. THz spectra were simulated using the structural models of ENaC and ENaC-amiloride complexes built here. The agreement between the experiment and the simulations allowed us to validate the structural models and to describe the amiloride dynamics inside the channel pore. The amiloride binding site validated using THz spectroscopy agrees with previous mutagenesis studies. Altogether, our results show that THz spectroscopy can be successfully used to discriminate between native and inhibited ENaC channels and to characterize the dynamics of channels in the presence of their specific antagonist.

Dynamic analysis of the interactions between Si/SiO2 quantum dots and biomolecules for improving applications based on nano-bio interfaces.

Due to their outstanding properties, quantum dots (QDs) received a growing interest in the biomedical field, but it is of major importance to investigate and to understand their interaction with the biomolecules. We examined the stability of silicon QDs and the time evolution of QDs - protein corona formation in various biological media (bovine serum albumin, cell culture medium without or supplemented with 10% fetal bovine serum-FBS). Changes in the secondary structure of BSA were also investigated over time. Hydrodynamic size and zeta potential measurements showed an evolution in time indicating the nanoparticle-protein interaction. The protein corona formation was also dependent on time, albumin adsorption reaching the peak level after 1 hour. The silicon QDs adsorbed an important amount of FBS proteins from the first 5 minutes of incubation that was maintained for the next 8 hours, and diminished afterwards. Under protein-free conditions the QDs induced cell membrane damage in a time-dependent manner, however the presence of serum proteins attenuated their hemolytic activity and maintained the integrity of phosphatidylcholine layer. This study provides useful insights regarding the dynamics of BSA adsorption and interaction of silicon QDs with proteins and lipids, in order to understand the role of QDs biocorona.

Advanced Structure-activity Relationships Applied to Mentha spicata L. Subsp. spicata Essential Oil Compounds as AChE and NMDA Ligands, in Comparison with Donepezil, Galantamine and Memantine - New Approach in Brain Disorders Pharmacology.

BACKGROUND: Alzheimer's disease (AD) therapy is based on several natural and synthetic compounds that act as acetylcholinesterase (AChE) and N-methyl-D-aspartate receptor (NMDA) ligands that have limited efficiency in relieving AD symptoms. Recent studies show that inhibitors isolated from Mentha spicata L. subsp. spicata are promising for AD therapy. OBJECTIVE: We aimed to identify novel and more potent phytopharmaceutical compounds for AD treatment by taking into account the compounds from Mentha spicata L. subsp. spicata essential oil. METHOD: We generated structure-activity relationship (SAR) models that predict the biological activities of 14 Mentha spicata L. subsp. spicata compounds on AChE and NMDA by comparing their molecular features with those of the three conventional ligands: donepezil, galantamine and memantine. RESULTS: The most relevant descriptors for predicting the biological activities of considered compounds are solvent accessible area and their subdivided, hydrophobicity, energy of frontier molecular orbitals and counts of the aromatic ring and rotatable bounds. 1,8-cineole, the main compound from Mentha spicata L. subsp. spicata essential oil, resulted to be similar with memantine and dissimilar with donepezil in respect to hidrophobicity (logP1,8-cineole=2.95, logPmemantine=2.81, logPdonepezil=4.11), the energy of LUMO (eLUMO1,8-cineole=3.01 eV, eLUMOmemantine=3.35 eV, eLUMOdonepezil=-0.35 eV) and the solvent accessible surface areas over all hydrophobic (SA_H1,8-cineole= 350 Å2, SA_Hmemantine= 358 Å2, SA_Hdonepezil= 655 Å2) or polar atoms (SA_P1,8-cineole= 4 Å2, SA_Pmemantine=10 Å2, SA_Pdonepezil=44.62 Å2). CONCLUSION: Our results point towards 1,8-cineole as a good candidate for NMDA antagonism, with a weaker AChE inhibitory effect. Our results may be useful in establishing new therapeutic strategies for neurological disorders.

Efficiency of vanilla, patchouli and ylang ylang essential oils stabilized by iron oxide@C14 nanostructures against bacterial adherence and biofilms formed by Staphylococcus aureus and Klebsiella pneumoniae clinical strains.

Biofilms formed by bacterial cells are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence and chronicization of the microbial infections and to therapy failure. The purpose of this study was to combine the unique properties of magnetic nanoparticles with the antimicrobial activity of three essential oils to obtain novel nanobiosystems that could be used as coatings for catheter pieces with an improved resistance to Staphylococcus aureus and Klebsiella pneumoniae clinical strains adherence and biofilm development. The essential oils of ylang ylang, patchouli and vanilla were stabilized by the interaction with iron oxide@C14 nanoparticles to be further used as coating agents for medical surfaces. Iron oxide@C14 was prepared by co-precipitation of Fe+2 and Fe+3 and myristic acid (C14) in basic medium. Vanilla essential oil loaded nanoparticles pelliculised on the catheter samples surface strongly inhibited both the initial adherence of S. aureus cells (quantified at 24 h) and the development of the mature biofilm quantified at 48 h. Patchouli and ylang-ylang essential oils inhibited mostly the initial adherence phase of S. aureus biofilm development. In the case of K. pneumoniae, all tested nanosystems exhibited similar efficiency, being active mostly against the adherence K. pneumoniae cells to the tested catheter specimens. The new nanobiosystems based on vanilla, patchouli and ylang-ylang essential oils could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with anti-adherence and anti-biofilm properties.

Molecular screening of carbapenemase-producing Gram-negative strains in Romanian intensive care units during a one year survey.

This is the first study, to our knowledge, performed on a significant number of strains (79 carbapenem-resistant Enterobacteriaceae and 84 carbapenem-resistant non-fermenting Gram-negative rods, GNRs) isolated from tissue samples taken from patients in the intensive care units of two large hospitals in Bucharest, Romania, between 2011 and 2012. The results revealed a high prevalence and great diversity of carbapenemase genes (CRG), in both fermenting and non-fermenting Gram-negative carbapenem-resistant strains. The molecular screening of carbapenem-resistant GNRs revealed the presence of worldwide-distributed CRGs (i.e. blaOXA-48 and blaNDM-1 in Enterobacteriaceae and blaOXA-23, blaVIM-4, blaOXA-10-like, blaOXA-60-like, blaSPM-like and blaGES-like in non-fermenting GNRs), reflecting the rapid evolution and spread of carbapenemase producers, particularly in hospitals. Rapid identification of the colonized or infected patients is required, as are epidemiological investigations to establish the local or imported origin of the respective strains.

Mitotic checkpoint proteins Mad1 and Mad2 - structural and functional relationship with implication in genetic diseases.

In normal cells, the accuracy of chromosome segregation which assures cells euploidy depends on mitosis mechanics and on proper functioning of a specific complex of proteins represented by the error-checking spindle assembly checkpoint (SAC). SAC proteins are deeply involved in correct cell divisions, but some of these, such as mitotic arrest-deficient proteins (Mad1 and Mad2), are critical. Mad1 and Mad2 are involved in preventing "wrong" cellular divisions which lead to cellular aneuploidy and are recognized as inductors of genetic disorders, as well as activators of oncoproteins. To clarify aneuploidy involvement in the evolution of cancer or other genetic disorders, structural and functional specificity of spindle checkpoint proteins have been analyzed, but the process is still poorly understood. In order to better understand SAC proteins involvement in initiation of cancer and other genetic disorders, here we review studies that conducted to relevant structural and functional information regarding these proteins. The results of these studies suggest that minor changes in structure and functionality of SAC proteins are able to generate aneuploidy. Therefore, a deeper understanding of Mad1 and Mad2 structural changes obtained by experimental and theoretical studies could open new perspectives of genetic medicine.

Pharmacological descriptors related to the binding of Gp120 to CD4 corresponding to 60 representative HIV-1 strains.

The standardization of HIV-1 strains for vaccine tests include the use of viral reference panels. We determined a series of pharmacological descriptors (molecular surfaces, volumes, electrostatic energies, solvation energies, number of atoms, number of hydrogen donors or acceptors and number of rigid bonds) for the gp120 CD4-binding sites structures in the unliganded state from a reference panel of 60 diverse strains of HIV-1. We identified the descriptors that varied significantly between the strains, the outliner strains for each descriptor set and the possible correlations between the descriptors. Our results improve the knowledge about gp120, its molecular and possible neutralization properties.