Combination of Carbonic Anhydrase Isoform IX Inhibitors and Gefitinib Suppresses on the Invasive Potential of Non-Small Cell Lung Cancer Cells.

Human carbonic anhydrase IX (CAIX) plays a key role in maintaining pH homeostasis of malignant neoplasms, thus creating a favorable microenvironment for the growth, invasion, and metastasis of tumor cells. Recent studies have established that inhibition of CAIX expressed on the surface of tumor cells significantly increases the efficacy of classical chemotherapeutic agents and makes it possible to suppress the resistance of tumor cells to chemotherapy, as well as to increase their sensitivity to drugs (in particular, to reduce the required dose of cytostatic agents). In this work, we studied the ability of new CAIX inhibitors based on substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides, to potentiate the cytostatic effect of gefitinib (selective inhibitor of epidermal growth factor receptor tyrosine kinase domain) under hypoxic conditions.

Auxin Triggers AHR Pathway Activation in the Auxin-Inducible Degron System in Mammalian Cells.

The auxin-inducible degron (AID) system is widely used to study function of various proteins. The plant hormone auxin is used as an inducer in this system, which easily penetrates into the cells and causes proteasomal degradation of the protein of interest fused to a small degron tag. It is often assumed that as a plant hormone, auxin does not significantly affect physiology of animal cells.

Novel Rhamnose-Containing Glycopolymers from the Cell Wall of VKM Ac-1390.

VKM Ac-1390 (family Microbacteriaceae, class Actinomycetes) contains three rhamnose-containing glycopolymers in the cell wall, the structures of which were established by chemical and NMR spectroscopy methods. The first polymer, a rhamnomannan, consists of repeating tetrasaccharide units with xylopyranose side residues, →2)-α-[β-D-Xyl-(1→3)]-D-Rha-(1→3)-α-D-Man-(1→2)-α-D-Rha-(1→3)-α-D-Man-(1→. The second polymer found in minor amounts, is a rhamnan, →2)-α-D-Rha-(1→3)-α-D-Rha-(1→.

Characterization of Carbohydrate Specificity of Monoclonal Antibodies to Fungal Antigenic Markers Using Biotinylated Oligosaccharides as Coating Antigens.

Mannan and β-(1→3)-glucan are two polysaccharide markers that are characteristic for a number of fungal pathogens, including , which is the most common cause of invasive mycoses in humans. In this study, we examined epitope specificity of two monoclonal antibodies, CM532 and FG70, which recognize certain oligosaccharide fragments of these fungal polysaccharides. Using a panel of biotinylated oligosaccharides as coating antigens, we found that the CM532 antibody obtained by immunization with the pentamannoside β-Man-(1→2)-β-Man-(1→2)-α-Man-(1→2)-α-Man-(1→2)-α-Man KLH conjugate, selectively recognizes the trisaccharide β-Man-(1→2)-α-Man-(1→2)-α-Man epitope.

Post-Selection Design of Aptamers: Comparative Study of Affinity of the DNA Aptamers to Recombinant Extracellular Domain of Human Epidermal Growth Factor Receptors.

The current work presents comparative assessment of affinity of the designed DNA aptamers for extracellular domain of the human epidermal growth factor receptor (EGFR*). The affinity data of the 20 previously published aptamers are summarized. Diversity of the aptamer selection methods and techniques requires unification of the comparison algorithms, which is also necessary for designing aptamers used in the post-selection fitting to the target EGFR* protein.

Deciphering the Ligand-Binding Site in a DNA Aptamer Targeting Deoxynivalenol.

Food safety is one of the primary demands of modern society. Mycotoxins are toxic metabolites of food-contaminating fungi. Fungi enter the food chain by infecting crops and irreversibly contaminate them due to the structural stability of mycotoxins.

Activation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.

Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types.

Effects of the RNA-Binding Protein Sam68 on Poly(ADP-Ribose)polymerase 1 Activity.

Taking into account involvement of the RNA-binding proteins in regulation of activity of poly(ADP-ribose) polymerase 1 (PARP1), a key factor of DNA repair, the effect of the intrinsically disordered protein Sam68 (Src-associated substrate during mitosis of 68 kDa) on catalytic activity of this enzyme was studied. Plasmid containing coding sequence of the Sam68 protein was obtained. Using the obtained construct, conditions for the Sam68 expression in cells were optimized and procedure for protein purification was developed.

Metabolomic Profiles of Siberian Wood Frog in Hypoxia and Upon Reoxygenation.

Hypoxia poses a serious challenge for all animals; however, certain animals exhibit a remarkable resilience in the case of prolonged and severe hypoxia. The Siberian wood frog is a unique amphibian capable of surviving for up to several months at almost complete anoxia. We investigated changes in the metabolome of at the onset of hypoxia (day 1) and within 1 h of reoxygenation after a long-term hypoxia using H NMR.

Pathogenesis-Associated Bacterial Amyloids: The Network of Interactions.

Amyloids are protein fibrils with a characteristic cross-β structure that is responsible for the unusual resistance of amyloids to various physical and chemical factors, as well as numerous pathogenic and functional consequences of amyloidogenesis. The greatest diversity of functional amyloids was identified in bacteria. The majority of bacterial amyloids are involved in virulence and pathogenesis either via facilitating formation of biofilms and adaptation of bacteria to colonization of a host organism or through direct regulation of toxicity.

Troponins and Skeletal Muscle Pathologies.

Skeletal muscles account for ~30-40% of the total weight of human body and are responsible for its most important functions, including movement, respiration, thermogenesis, and glucose and protein metabolism. Skeletal muscle damage negatively impacts the whole-body functioning, leading to deterioration of the quality of life and, in severe cases, death. Therefore, timely diagnosis and therapy for skeletal muscle dysfunction are important goals of modern medicine.

Functional properties of aged hypothalamic cells.

The hypothalamus, in addition to controlling the main body's vital functions, is also involved in aging regulation. The aging process in the hypothalamus is accompanied by disturbed intracellular pathways, including Ca signaling and neuronal excitability in the brain. Intrinsic electrophysiological properties of individual neurons and synaptic transmission between cells is disrupted in the central nervous system of old animals.

Combined irradiation by gamma-rays and carbon-12 nuclei caused hyperlocomotion and change in striatal metabolism of rats.

Exposure to ionizing radiation during manned deep space missions to Mars could lead to functional impairments of the central nervous system, which may compromise the success of the mission and affect the quality of life for returning astronauts. Along with radiation-induced changes in cognitive abilities and emotional status, the effects of increased motor activity were observed. The mechanisms behind these phenomena still remain unresolved.

Transcriptome analysis reveals significant discrepancies between two in vitro models of host-trematode interaction.

Cell models emulating an in vitro parasitic infection can greatly improve our understanding of helminthiases. Nonetheless, it remains challenging to select an appropriate in vitro model to study molecular pathogenesis of infections by trematodes having a complex life cycle. Therefore, adequate models are in high demand.

The effects of autophagy-modifying drugs chloroquine and lithium on the skin melanoma microenvironment.

Background: Skin melanoma is a highly metastatic cancer with an increasing global incidence. Despite advancements in immunotherapy, new treatment strategies based on tumor biology are essential for improving outcomes and developing novel therapies. Autophagy plays a critical role in melanoma cell metabolism and affects the tumor microenvironment (TME).

Stress, resilience and sense of self-efficacy among Ukrainian, Polish, Romanian, and Slovak women during the Russian invasion of Ukraine.

Objectives: The aim of the current study was to determine the levels of stress, resilience and the sense of self-efficacy, as well as the influence of resilience and the sense of self-efficacy in shaping stress levels, in a sample of women from various countries of origin.

Methods: The study was carried out on a sample of Ukrainian (N = 82), Polish (N = 102), Slovak (N = 79), and Romanian (N = 42) women using the Sense of Stress Questionnaire, the General Self-Efficacy Scale and the Brief Resilience Scale.

Results: Highest total stress levels were found among Ukrainian women, while the lowest were found among Polish women.

Consumer-grade wearable devices in arrhythmia diagnostics for clinicians: where we are and where we are going.

Atrial arrhythmias, including atrial fibrillation (AF), are a major contributor to cardiovascular morbidity and mortality. Early detection and effective management are critical to mitigating adverse outcomes such as stroke, heart failure, and overall mortality. Wearable devices have emerged as promising tools for monitoring, detecting, and managing atrial arrhythmias near-continuously.

The endothelial surface layer-glycocalyx - Universal nano-infrastructure is fundamental to physiology, cell traffic and a complementary neural network.

The glycocalyx and its associated endothelial surface layer which lines all cell membranes and most tissues, dwarfs the phospholipid membrane of cells in extent. Its major components are sulphated polymers like heparan and chondroitin sulphates and hyaluronic acid. These form a fuzzy layer of unknown structure and function.

Can artificial intelligence lower the global sudden cardiac death rate? A narrative review.

Purpose Of Review: WHO defines SCD as sudden unexpected death either within 1 h of symptom onset (witnessed) or within 24 h of having been observed alive and symptom-free (unwitnessed). Sudden cardiac arrest is a major cause of mortality worldwide, with survival to hospital discharge for hospital cardiac arrest and in-hospital cardiac arrest being only 9.3 % and 21.

What Kills Mature Street and Park Trees in Cities? Systematic Quantitative Review of Published Case Studies.

Street and park trees often endure harsher conditions, including increased temperatures and drier soil and air, than those found in urban or natural forests. These conditions can lead to shorter lifespans and a greater vulnerability to dieback. This literature review aimed to identify confirmed causes of street and park tree dieback in urban areas from around the world.

Monocyte and Macrophage in Follicular Liquid: Predictive Markers of Embryo Quality in Women with Obesity and Infertility.

Background: Over the past five years, the pregnancy rate in assisted reproductive technology (ART) programs in Russia has remained relatively stable. The aim of this study was to assess the distribution of monocyte and macrophage subsets in the blood and follicular fluid of infertile women undergoing assisted reproductive technology.

Methods: The study involved 45 women with a mean age of 35 ± 4.

SERT-Deficient Mice Fed Western Diet Reveal Altered Metabolic and Pro-Inflammatory Responses of the Liver: A Link to Abnormal Behaviors.

Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).

Neural Correlates of Social Touch Processing: An fMRI Study on Brain Functional Connectivity.

Background: The significance of tactile stimulation in human social development and personal interaction is well documented; however, the underlying cerebral processes remain under-researched. This study employed functional magnetic resonance imaging (fMRI) to investigate the neural correlates of social touch processing, with a particular focus on the functional connectivity associated with the aftereffects of touch.

Methods: A total of 27 experimental subjects were recruited for the study, all of whom underwent a 5-minute calf and foot massage prior to undergoing resting-state fMRI.

Optical Based Methods for Water Monitoring in Biological Tissue.

Skin homeostasis is strongly dependent on its hydration levels, making skin water content measurement vital across various fields, including medicine, cosmetology, and sports science. Noninvasive diagnostic techniques are particularly relevant for clinical applications due to their minimal risk of side effects. A range of optical methods have been developed for this purpose, each with unique physical principles, advantages, and limitations.