Population Studies and Molecular Mechanisms of Human Radioadaptive Capabilities: Is It Time to Rethink Radiation Safety Standards?

The evolution of man on Earth took place under conditions of constant exposure to background ionizing radiation (IR). From this point of view, it would be reasonable to hypothesize the existence of adaptive mechanisms that enable the human organism to safely interact with IR at levels approximating long-term natural background levels. In some situations, the successful operation of molecular mechanisms of protection against IR is observed at values significantly exceeding the natural background level, for example, in cancer cells.

Boosting Lipofection Efficiency Through Enhanced Membrane Fusion Mechanisms.

Gene transfection is a fundamental technique in the fields of biological research and therapeutic innovation. Due to their biocompatibility and membrane-mimetic properties, lipid vectors serve as essential tools in transfection. The successful delivery of genetic material into the cytoplasm is contingent upon the fusion of the vector and cellular membranes, which enables hydrophilic polynucleic acids to traverse the hydrophobic barriers of two intervening membranes.

The Placenta as the Main Source of Serotonin in Ontogenetic Dynamics: Inflammation-Induced Modulation of Placental Serotonin Can Be Prevented by Immunoglobulin Administration.

Placental serotonin is recognized as a key component of feto-placental physiology and can be influenced by environmental factors such as maternal diet, drugs, stress, and immune activation. In this study, we compared the contribution of placental and fetal sources to the maintenance of serotonin levels required for normal fetal development during ontogenetic dynamics. Our results demonstrated the leading role of the placenta at almost all stages of development.

Non-Invasive Nanometer Resolution Assessment of Cell-Soft Hydrogel System Mechanical Properties by Scanning Ion Conductance Microscopy.

Biomimetic hydrogels have garnered increased interest due to their considerable potential for use in various fields, such as tissue engineering, 3D cell cultivation, and drug delivery. The primary challenge for applying hydrogels in tissue engineering is accurately evaluating their mechanical characteristics. In this context, we propose a method using scanning ion conductance microscopy (SICM) to determine the rigidity of living human breast cancer cells MCF-7 cells grown on a soft, self-assembled Fmoc-FF peptide hydrogel.

Proton-Translocating NADH-Ubiquinone Oxidoreductase: Interaction with Artificial Electron Acceptors, Inhibitors, and Potential Medicines.

Proton-translocating NADH-ubiquinone oxidoreductase (complex I) catalyzes the oxidation of NADH by ubiquinone accompanied by the transmembrane transfer of four protons, thus contributing to the formation of a proton motive force () across the coupling membranes of mitochondria and bacteria, which drives ATP synthesis in oxidative phosphorylation. In recent years, great progress has been achieved in resolving complex I structure by means of X-ray crystallography and high-resolution cryo-electron microscopy, which has led to the formulation of detailed hypotheses concerning the molecular mechanism of coupling of the redox reaction to vectorial proton translocation. To test and probe proposed mechanisms, a comprehensive study of complex I using other methods including molecular dynamics and a variety of biochemical studies such as kinetic and inhibitory analysis is required.

Trehalose Interferes with the Photosynthetic Electron Transfer Chain of Permeating the Bacterial Chromatophore Membrane.

Disaccharide trehalose has been proven in many cases to be particularly effective in preserving the functional and structural integrity of biological macromolecules. In this work, we studied its effect on the electron transfer reactions that occur in the chromatophores of the photosynthetic bacterium . In the presence of a high concentration of trehalose, following the activation of the photochemistry by flashes of light, a slowdown of the electrogenic reactions related to the activity of the photosynthetic reaction center and cytochtome (cyt) complexes is observable.

New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis.

The Special Issue "New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis" collects eight articles that have developed advanced approaches to the chemo-, regio- and stereoselective synthesis of novel important compounds, scaffolds, synthons, and practically valuable products [...

The N-Terminal Mutations of cMyBP-C Affect Calcium Regulation, Kinetics, and Force of Muscle Contraction.

The cardiac myosin binding protein-C (cMyBP-C) regulates cross-bridge formation and controls the duration of systole and diastole at the whole heart level. As known, mutations in cMyBP-C increase the cross-bridge number and rate of their cycling, hypercontractility, and myocardial hypertrophy. We investigated the effects of the mutations D75N and P161S of cMyBP-C related to hypertrophic cardiomyopathy on the mechanism of force generation in isolated slow skeletal muscle fibers.

Multiple Myeloma: Genetic and Epigenetic Biomarkers with Clinical Potential.

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells and accounts for approximately 10% of all hematologic malignancies. The clinical outcomes of MM can exhibit considerable variability. Variability in both the genetic and epigenetic characteristics of MM undeniably contributes to tumor dynamics.

The Gene Related to the Family Genes: An Evolutionary View on Origin and Function.

has two paralogs, and , related to the evolutionarily conserved family genes. In mammals, the family consists of , encoding transcription co-factors involved in the regulation of development and cell fate determination. The function of and in remains unclear.

Novel Peptidomimetic Cyclo-{E(I)-E(W)}Na (CP-88) with Hematopoietic Activity Sustained in Invasive and Oral Administration: Experimental and Preclinical Evaluation.

Over the last decades, significant progress has been made in studying agonistic and antagonistic hematopoietic peptides. The main disadvantage of this class of peptides is their low stability with noninvasive administration methods, which limits the widespread use of hematopoiesis-regulated peptide drugs in medical practice. The aim of this work is to study novel peptidomimetics with hematopoietic activity sustained in invasive and oral administration.

Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in the Gene.

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the () and () genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models.

Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue.

Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting liver tissue integrity and improve the liver condition after infusion.

Transcription Factors ClrB and XlnR and Their Effect on the Transcription of Cellulase Genes in the Filamentous Fungus .

The filamentous fungus (anamorph ) has been shown to be an efficient producer of secreted cellulases, used in biorefinery processes. Understanding the mechanisms of regulation of cellulase gene expression in the fungus is a current task in industrial biotechnology, since it allows for targeted changes in the composition of the complex secreted by the fungus. Expression of cellulase genes in fungi is regulated mainly at the level of transcription via pathway-specific transcription factors (TF), the majority of which belong to the Zn(II)2Cys6 family of zinc binuclear cluster proteins.

Branched Linkers for Homogeneous Antibody-Drug Conjugates: How Long Is Long Enough?

Homogeneous antibody-drug conjugates (ADCs) exhibit significantly improved pharmacological properties compared to their heterogeneous counterparts. Site-specific conjugation of the payload to the IgG required for homogeneity can be achieved using enzymes. One example is microbial transglutaminase (MTGase), which can selectively perform transamidation on the Q295 residue of human Fc when N297 glycans are removed.

Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.

Prenatal hypoxia, often accompanied by maternal glucocorticoid stress, can predispose offspring to neurological disorders in adulthood. If placental ischemia (PI) primarily reduces fetal oxygen supply, the maternal hypoxia (MH) model also elicits a pronounced fetal glucocorticoid exposure. Here, we compared MH and PI in rats to distinguish their unique and overlapping effects on embryonic and newborn brain development.

The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.

Doxorubicin (DOX), a cornerstone chemotherapeutic agent, effectively combats various malignancies but is marred by significant cardiovascular toxicity, including endothelial damage, chronic heart failure, and vascular remodeling. These adverse effects, mediated by oxidative stress, mitochondrial dysfunction, inflammatory pathways, and dysregulated autophagy, underscore the need for precise therapeutic strategies. Emerging research highlights the critical role of microRNAs (miRNAs) in DOX-induced vascular remodeling and cardiotoxicity.

Novel Selectable Marker Sesquiterpenoid Antibiotic Pentalenolactone.

Antibiotic resistance has been and remains a major problem in our society. The main solution to this problem is to search and study the mechanisms of antibiotic action. Many groups of secondary metabolites, including antimicrobial ones, are produced by the phylum.

Expanding Horizons of CRISPR/Cas Technology: Clinical Advancements, Therapeutic Applications, and Challenges in Gene Therapy.

CRISPR-Cas technology has transformed the field of gene editing, opening new possibilities for treatment of various genetic disorders. Recent years have seen a surge in clinical trials using CRISPR-Cas-based therapies. This review examines the current landscape of CRISPR-Cas implementation in clinical trials, with data from key registries, including the Australian New Zealand Clinical Trials Registry, the Chinese Clinical Trial Register, and ClinicalTrials.

Interaction of Cyclosporin C with Dy Ions in Acetonitrile and in Complex with Dodecylphosphocholine Micelles Determined by NMR Spectroscopy.

The spectral characteristics of cyclosporin C (CsC) with the addition of Dy ions in acetonitrile (CDCN) and CsC with Dy incorporated into dodecylphosphocholine (DPC) micelle in deuterated water were investigated by high-resolution NMR spectroscopy. The study was focused on the interaction between Dy ions and CsC molecules in different environments. Using a combination of one-dimensional and two-dimensional NMR techniques, we obtained information on the spatial features of the peptide molecule and the interaction between CsC and the metal ion.

Increased Levels of hsa-miR-199a-3p and hsa-miR-382-5p in Maternal and Neonatal Blood Plasma in the Case of Placenta Accreta Spectrum.

Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its impact on neonatal outcomes and respiratory morbidity, as well as the underlying pathogenetic mechanism, has not yet been extensively studied. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for the prevention of respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, microRNA (miRNA) profiling by small RNA deep sequencing and quantitative real-time PCR was performed on 160 blood plasma samples from preterm infants (gestational age: 33-36 weeks) and their mothers who had been diagnosed with or without PAS depending on the timing of the antenatal RDS prophylaxis.

The Role of the Serotonergic System in Time Perception: A Systematic Review.

Time perception is a fundamental cognitive function essential for adaptive behavior and shared across species. The neural mechanisms underlying time perception, particularly its neuromodulation, remain debated. In this review, we examined the role of the serotonergic system in time perception (at the scale of seconds and minutes), building a translational bridge between human and non-human animal studies.

Brown and Beige Adipose Tissue: One or Different Targets for Treatment of Obesity and Obesity-Related Metabolic Disorders?

The failure of the fight against obesity makes us turn to new goals in its treatment. Now, brown adipose tissue has attracted attention as a promising target for the treatment of obesity and associated metabolic disorders such as insulin resistance, dyslipidemia, and glucose tolerance disorders. Meanwhile, the expansion of our knowledge has led to awareness about two rather different subtypes: classic brown and beige (inducible brown) adipose tissue.

Antisolvent 3D Printing of Gene-Activated Scaffolds for Bone Regeneration.

The use of 3D-printed gene-activated bone grafts represents a highly promising approach in the fields of dentistry and orthopedics. Bioresorbable poly-lactic-co-glycolic acid (PLGA) scaffolds, infused with adenoviral constructs that carry osteoinductive factor genes, may provide an effective alternative to existing bone grafts for the reconstruction of extensive bone defects. This study aims to develop and investigate the properties of 3D scaffolds composed of PLGA and adenoviral constructs carrying the BMP2 gene (Ad-BMP2), both in vitro and in vivo.

Artificial Tertiary Lymphoid Structures: Exploring Mesenchymal Stromal Cells as a Platform for Immune Niche Formation.

Constructing artificial tertiary lymphoid structures (TLSs) opens new avenues for advancing cancer immunotherapy and personalized medicine by creating controllable immune niches. Mesenchymal stromal cells (MSCs) offer an ideal stromal source for such constructs, given their potent immunomodulatory abilities and accessibility. In this study, we explored the potential of adipose-derived MSCs to adopt TLS-supportive phenotypes and facilitate lymphocyte organization.