EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Design, Development and Immunogenicity Study of a Multi-Epitope Vaccine Prototype Against SARS-CoV-2.

SARS-CoV-2 caused the COVID-19 pandemic, which overwhelmed global healthcare systems. Over 776 million COVID-19 cases and more than 7 million deaths were reported by WHO in September 2024. COVID-19 vaccination is crucial for preventing infection and controlling the pandemic.

Angular-Substituted [1,4]Thiazino[3,4-a]Isoquinolines: Biological Evaluation and In Silico Studies on DPP-IV Inhibition.

Recent studies have discovered that aryl-substituted pyrido[2,1-a]isoquinolines have the potential to be highly active DPP IV inhibitors. In previous studies, we reported a novel synthetic approach for the construction of their sulfur-containing bioisosteric [1,4]thiazino[3,4-a]isoquinolines analogues, incorporating an additional aryl substituent. The present study aims to investigate the DPP IV inhibitory activity and cytotoxicity of the synthesized molecules by in vitro assay.

Detrimental effect of prenatal progesterone exposure on anxiety and depressive-like responses in adult male and female rat offspring: Role of plasma, hippocampal corticosterone and hippocampal progesterone receptors.

In clinical practice, the use of exogenous progesterone (Pro) is often required in assisted reproduction programs due to reduced levels of the hormone and the risk of miscarriage. Exposure to the hormone reduces anxiety in rodents, but the long-term effects of prenatal exposure in adult offspring are unknown. Therefore, the present study was designed to investigate the effect of prenatal Pro treatment on anxiety- and depression-like behavior and the effect on plasma, hippocampal corticosterone (CORT) and hippocampal progesterone receptor (PR) in young adult male and female rat offspring.

AChE inhibitory activity of N-substituted natural galanthamine derivatives.

Galanthamine derivatives are known for their AChE inhibitory activity. Among them, galanthamine has been approved for treatment of Alzheimer's disease. N-Acetylnorgalanthamine (narcisine) and N-(2'-methyl)allylnorgalanthamine (the most potent natural AChE inhibitor of galanthamine type) were synthetized using N-norgalanthamine as a precursor.

In Silico Identification of Peanut Peptides Suitable for Allergy Immunotherapy in HLA-DRB1*03:01-Restricted Patients.

Peanut allergy, a prevalent and potentially severe condition affecting millions worldwide, has been linked to specific human leukocyte antigens (HLAs), suggesting increased susceptibility. Employing an immunoinformatic strategy, we developed a "logo model" based on amino acid frequencies in the peptide binding core and used it to predict peptides originating from 28 known peanut allergens binding to HLA-DRB1*03:01, one of the susceptibility alleles. These peptides hold promise for immunotherapy in HLA-DRB1*03:01 carriers, offering reduced allergenicity compared to whole proteins.

The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress.

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth.

Stress cardiomyopathy following thyroidectomy in a postmenopausal patient: A case report.

Introduction And Importance: First described in 1990 in Japan, Stress cardiomyopathy (SC) is characterized by transient systolic and diastolic left ventricular (LV) dysfunction with a variety of wall-motion abnormalities. It predominantly affects postmenopausal women and is often preceded by an emotional or physical trigger. SC is an increasingly recognized form of transient LV dysfunction that is often completely reversible.

Inhibitor Trapping in Kinases.

Recently, we identified a novel mechanism of enzyme inhibition in N-myristoyltransferases (NMTs), which we have named 'inhibitor trapping'. Inhibitor trapping occurs when the protein captures the small molecule within its structural confines, thereby preventing its free dissociation and resulting in a dramatic increase in inhibitor affinity and potency. Here, we demonstrate that inhibitor trapping also occurs in the kinases.

The role of melatonin deficiency induced by pinealectomy on motor activity and anxiety responses in young adult, middle-aged and old rats.

Background: Aging affects anxiety levels in rats while the pineal gland, via its hormone melatonin, could modulate their inherited life "clock." The present study aimed to explore the impact of plasma melatonin deficiency on anxiety responses and the possible involvement of the hypothalamic-pituitary-adrenocortical (HPA) axis and heat shock proteins (Hsp) 70 and 90 in the frontal cortex (FC) and the hippocampus in young adult, middle-aged and elderly rats with pinealectomy.

Results: Melatonin deficiency induced at different life stages did not affect the lifespan of rats.

Clinical and virological profile of locally acquired acute hepatitis E in South Bulgaria.

Introduction: Acute hepatitis E virus (HEV) infection is recognized as a zoonosis in several European countries. We describe the characteristics and outcomes of locally acquired acute HEV hepatitis.

Methodology: A prospective study was conducted among adult patients with acute HEV hepatitis at the University Hospital in Plovdiv, South Bulgaria between January 2020 and May 2022.

Severe SARS-CoV-2 and respiratory syncytial virus co-infection in two children.

The Coronavirus Disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) affects mainly older adults. Those with comorbidities are at a higher risk of severe disease and even death. The symptomatic infection rate of children is lower, manifestations are milder, and severe forms are scarce.

The Serum ACE2, CTSL, AngII, and TNFα Levels after COVID-19 and mRNA Vaccines: The Molecular Basis.

Background: The SARS-CoV-2 virus as well as the COVID-19 mRNA vaccines cause an increased production of proinflammatory cytokines.

Aim: We investigated the relationship between ACE2, CTSL, AngII, TNFα and the serum levels of IL-6, IL-10, IL-33, IL-28A, CD40L, total IgM, IgG, IgA and absolute count of T- and B-lymphocytes in COVID-19 patients, vaccinees and healthy individuals.

Methods: We measured the serum levels ACE2, AngII, CTSL, TNFα and humoral biomarkers (CD40L, IL-28A, IL-10, IL-33) by the ELISA method.

ALPPS Procedure for the Treatment of Bilobar Multiple Liver Metastasis from Colorectal Cancer: First Case in RN Macedonia.

: ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy), is a recently developed procedure, first performed by HJ Schlitt in Regensburg, Germany. The technique developed two stages of hepatectomy. The ALPPS procedure has been introduced to increase the volume of future liver remnant, much more than the other technique, such as PVE (portal vein embolization).

Comparative Analysis of Anticonvulsant Activity of and 5,5'-Diphenylhydantoin Schiff Bases.

Recently, the four 5,5'-diphenylhydantoin Schiff bases, possessing different aromatic species () were synthesized, characterized, and evaluated for anticonvulsant activity in combination with phenytoin. In the present study, the and compounds were selected, based on their anticonvulsant potency, and compared with their isomers, prepared after a one-hour exposure to the UV source, for their anticonvulsant potency in the maximal electroshock (MES) test and the kainate (KA)-induced status epilepticus (SE) test in mice. In the MES test, the compound exhibited superior to phenytoin and isomer activity in the three tested doses, while the compound entirely suppressed the electroshock-induced seizure spread at the highest dose of 40 mg/kg.

Biorenewable Oxypropylated Pentane-1,2,5-triol as a Source for Incorporation in Rigid Polyurethane Foams.

In this study, as a product from the efficient Achmatowicz rearrangement and mild subsequent hydrogenation-reduction reactions of biorenewable C5 alcohols derived from lignocellulose, pentane-1,2,5-triol was successfully used after oxypropylation in the preparation of rigid polyurethane foams-one of the most important classes of polymeric materials. Despite the broad range of applications, the production of polyurethanes is still highly dependent on petrochemical materials considering the need of renewable raw materials and new process technologies for the production of polyol or isocyanate components as a key point for the sustainable development of polyurethane foams. The synthesized oxypropylated pentane-1,2,5-triol was analyzed using proton NMR spectroscopy, hydroxyl number, and viscosity, whereas the newly obtained foams incorporated with up to 30% biorenewable polyol were characterized using compressive stress, thermogravimetry, dynamic mechanical analysis, and scanning electron microscopy.

Hepatitis E Virus (HEV) Infection among Hemodialysis Patients from Southern Bulgaria.

Viral hepatitis B and C are widely recognized problems in hemodialysis (HD) patients. There have been increasing reports of the importance of the hepatitis E virus (HEV) in recent years, but the worldwide data on the seroprevalence of HEV among them are conflicting. The aim of the present study was to assess the seroprevalence of HEV in HD patients and to analyze the predictors of seropositivity.

DNA Methylation Patterns in Relation to Acute Severity and Duration of Anxiety and Depression.

Depression and anxiety are common mental disorders that often occur together. Stress is an important risk factor for both disorders, affecting pathophysiological processes through epigenetic changes that mediate gene-environment interactions. In this study, we explored two proposed models about the dynamic nature of DNA methylation in anxiety and depression: a stable change, in which DNA methylation accumulates over time as a function of the duration of clinical symptoms of anxiety and depression, or a flexible change, in which DNA methylation correlates with the acute severity of clinical symptoms.

Inhibitor Trapping in N-Myristoyltransferases as a Mechanism for Drug Potency.

Predicting inhibitor potency is critical in drug design and development, yet it has remained one of computational biology's biggest unresolved challenges. Here, we show that in the case of the N-myristoyltransferase (NMT), this problem could be traced to the mechanisms by which the NMT enzyme is inhibited. NMT adopts open or closed conformations necessary for orchestrating the different steps of the catalytic process.

Correction: Grancharov et al. Flexible Polymer-Organic Solar Cells Based on P3HT:PCBM Bulk Heterojunction Active Layer Constructed under Environmental Conditions. 2021, , 6890.

The authors would like to correct a mistake in Figure 3 as published in the original publication [...

The CCP4 suite: integrative software for macromolecular crystallography.

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces.

Docking-Based Prediction of Peptide Binding to MHC Proteins.

Major histocompatibility complex (MHC) proteins are the most polymorphic and polygenic proteins in humans. They bind peptides, derived from cleavage of different pathogenic antigens, and are responsible for presenting them to T cells. The peptides recognized by the T cell receptors are denoted as epitopes and they trigger an immune response.