Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain.

Background: Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, which carries 12.

Trace amine signaling in zebrafish models: CNS pharmacology, behavioral regulation and translational relevance.

Tyramine, β-phenylethylamine, octopamine and other trace amines are endogenous substances recently recognized as important novel neurotransmitters in the brain. Trace amines act via multiple selective trace amine-associated receptors (TAARs) of the G protein-coupled receptor family. TAARs are expressed in various brain regions and modulate neurotransmission, neuronal excitability, adult neurogenesis, cognition, mood, locomotor activity and olfaction.

New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors.

In this study, new 2-indolinone-indole hybrid compounds (4a-s) carrying a benzoyl moiety were synthesized and their cytotoxic effects were examined against pancreatic (MIA-PaCa-2) and colon (HT-29 and HCT-116) cancer cells by MTT assays. Most of the tested compounds exhibited a better inhibitory activity and safety profile than the reference standard sunitinib malate against MIA-PaCa-2 and HCT-116 cancer cells. Compound 4e displayed the greatest cytotoxic effect on HCT-116 cell with an IC value of 0.

Development of Primer Panels for Whole-Genome Amplification and Sequencing of Human Seasonal Coronaviruses: hCoV-OC43, hCoV-HKU1, hCoV-229E, and hCoV-NL63.

Human seasonal coronaviruses (hCoVs) are a group of viruses that affect the upper respiratory tract. While seasonal patterns and the annual variability of predominant hCoV species are well-documented, their genetic and species diversity in St. Petersburg and across Russia remains largely unexplored.

Studying the Oncolytic Activity of Strains Against Hepatoma, Glioma, and Pancreatic Cancer and .

Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A (GAS) strains for tumor treatment.

Omics Data Integration Uncovers mRNA-miRNA Interaction Regions in Genes Associated with Chronic Venous Insufficiency.

Chronic venous insufficiency (CVI), a chronic vascular dysfunction, is a common health problem that causes serious complications such as painful varicose veins and even skin ulcers. Identifying the underlying genetic and epigenetic factors is important for improving the quality of life of individuals with CVI. In the literature, many genes, variants, and miRNAs associated with CVI have been identified through genomic and transcriptomic studies.

Angiotensin IV Receptors in the Rat Prefrontal Cortex: Neuronal Expression and NMDA Inhibition.

Background: N-methyl-D-aspartate type glutamate receptors (NMDARs) are fundamental to neuronal physiology and pathophysiology. The prefrontal cortex (PFC), a key region for cognitive function, is heavily implicated in neuropsychiatric disorders, positioning the modulation of its glutamatergic neurotransmission as a promising therapeutic target. Our recently published findings indicate that AT receptor activation enhances NMDAR activity in layer V pyramidal neurons of the rat PFC.

Perspectives and Limitations of Mesenchymal Stem Cell-Based Therapy for Corneal Injuries and Retinal Diseases.

The eye represents a highly specialized organ, with its main function being to convert light signals into electrical impulses. Any damage or disease of the eye induces a local inflammatory reaction that could be harmful for the specialized ocular cells. Therefore, the eye developed several immunoregulatory mechanisms which protect the ocular structures against deleterious immune reactions.

Prospective memory performance and its resting-state functional connectivity correlates in individuals with memory complaints.

This study aimed to investigate prospective memory (PM) in patients with memory complaints but without dementia (PWD) and correlate findings with resting-state functional connectivity (rsFC) alterations. We hypothesized that PM impairment would be evident at a certain relatively early point in the continuum and specific rsFC patterns would be the neuroimaging signature of this impairment. Sixty PWD participated in the study.

Antiedemic Effect of the Myosin Light Chain Kinase Inhibitor PIK7 in the Rat Model of Myocardial Ischemia Reperfusion Injury.

Myocardial ischemia-reperfusion injury increases myocardial microvascular permeability, leading to enhanced microvascular filtration and interstitial fluid accumulation that is associated with greater microvascular obstruction and inadequate myocardial perfusion. A burst of reactive oxygen species and inflammatory mediators during reperfusion causes myosin light chain kinase (MLCK)-dependent endothelial hyperpermeability, which is considered a preventable cause of reperfusion injury. In the present study, a single intravenous injection of MLCK peptide inhibitor PIK7 (2.

Identification of the subventricular tegmental nucleus as brainstem reward center.

Rewards are essential for motivation, decision-making, memory, and mental health. We identified the subventricular tegmental nucleus (SVTg) as a brainstem reward center. In mice, reward and its prediction activate the SVTg, and SVTg stimulation leads to place preference, reduced anxiety, and accumbal dopamine release.

A cortico-subcortical loop for motor control via the pontine reticular formation.

Movement and locomotion are controlled by large neuronal circuits like the cortex-basal ganglia (BG)-thalamus loop. Besides the inhibitory thalamic output, the BG directly control movement via specialized connections with the brainstem. Whether other parallel loops with similar logic exist is presently unclear.

The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.

Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced alterations in behaviour.

A single exposure to a stressful event can result in enduring changes in behaviour. Long-term modifications in neuronal networks induced by stress are well explored but the initial steps leading to these alterations remain incompletely understood. In this study, we found that acute stress exposure triggers an immediate increase in the firing activity of calretinin-positive neurons in the paraventricular thalamic nucleus (PVT/CR+) that persists for several days in mice.

Comparative Study of Functionalized Carbosilane Dendrimers for siRNA Delivery: Synthesis, Cytotoxicity, and Biophysical Properties.

Efficient and safe carriers of genetic material are crucial for advancing gene therapy. Three new series of cationic dendritic nanocarriers based on a carbosilane scaffold, differentiated by peripheral modifications: saccharide (CS-glyco), amine (CS-N), and phosphonium dendrimers (CS-P) were designed for binding, protecting, and releasing polyanionic compounds like therapeutic siRNA. Besides introducing synthetic methodology, this study brings a unique direct interstructural comparison of 16 dendritic nanovector's characteristics, addressing a gap in typical research that focuses on uniform structural types.

Using Zebrafish Models to Study Epitranscriptomic Regulation of CNS Functions.

Epitranscriptomic regulation of cell functions involves multiple post-transcriptional chemical modifications of coding and non-coding RNA that are increasingly recognized in studying human brain disorders. Although rodent models are presently widely used in neuroepitranscriptomic research, the zebrafish (Danio rerio) has emerged as a useful and promising alternative model species. Mounting evidence supports the importance of RNA modifications in zebrafish CNS function, providing additional insights into epitranscriptomic mechanisms underlying a wide range of brain disorders.

Differential effects of chronic unpredictable stress on behavioral and molecular (cortisol and microglia-related neurotranscriptomic) responses in adult leopard (leo) zebrafish.

Stress plays a key role in mental, neurological, endocrine, and immune disorders. The zebrafish (Danio rerio) is rapidly gaining popularity as s model organism in stress physiology and neuroscience research. Although the leopard (leo) fish are a common outbred zebrafish strain, their behavioral phenotypes and stress responses remain poorly characterized.

Synaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex.

Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3.

Absolute number of three populations of interneurons and all GABAergic synapses in the human hippocampus.

The human hippocampus, essential for learning and memory, is implicated in numerous neurological and psychiatric disorders, each linked to specific neuronal subpopulations. Advancing our understanding of hippocampal function requires computational models grounded in precise quantitative neuronal data. While extensive data exist on the neuronal composition and synaptic architecture of the rodent hippocampus, analogous quantitative data for the human hippocampus remain very limited.

The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer diagnosed in children. While the majority of patients survive with conventional treatment, chemotherapeutic agents have adverse effects and the potential for relapse persists even after full recovery. Given their pivotal function in anti-cancer immunity, there has been a surge in research exploring the potential of natural killer (NK) cells in immunotherapy, which has emerged as a promising avenue for treating leukemia.

Prophylaxis by a reversible cholinesterase inhibitor and the NMDA receptor antagonist treatment as combinatorial countermeasure against nerve agent poisoning in mice model.

The current pharmacological pretreatment and medical treatment of nerve agent poisoning is an insufficiently addressed medical task. The prophylactic efficacy of a novel compound acting dually as an acetylcholinesterase inhibitor and NMDA receptor antagonist (K1959) and the therapeutic efficacy of a novel NMDA receptor antagonist (K2060) were evaluated in the NMRI mice model of nerve agent poisoning by tabun, soman and sarin. Their added value to the standard antidotal treatment (a combination of oxime reactivator and atropine) was also analyzed.

Laser-Induced Olfactory Bulbectomy in Adult Zebrafish as a Novel Putative Model for Affective Syndrome: A Research Tribute to Brian Leonard.

Inducing multiple neurobehavioural and neurochemical deficits, olfactory bulbectomy (OBX) has been developed as a rodent model of depression with potential for antidepressant drug screening. However, the generality of this model in other vertebrate taxa remains poorly understood. A small freshwater teleost fish, the zebrafish (Danio rerio), is rapidly becoming a common model species in neuroscience research.

Whole-Exome Sequencing: Discovering Genetic Causes of Granulomatous Mastitis.

Granulomatous mastitis (GM) is a rare, benign, but chronic and recurrent inflammatory breast disease that significantly impacts physical and psychological well-being. It often presents symptoms such as pain, swelling, and discharge, leading to diagnostic confusion with malignancy. The etiology of GM remains unclear, though autoimmune and multifactorial components are suspected.

Status of IKZF1 Deletions in Diagnose and Relapsed Pediatric B-ALL Patients.

IKZF1 deletions (ΔIKZF1) are common in precursor B-cell acute lymphoblastic leukemia (B-ALL) and are assumed to have a prognostic impact. We aimed to determine the prognostic implications of ΔIKZF1 and CRLF2 overexpression in pediatric B-ALL. Furthermore, we sought to compare the multiplex polymerase chain reaction (PCR) assay with standard multiplex ligand-dependent probe amplification (MLPA) methods to ascertain IKZF1 status in a clinical context.

Ghrelin recruits the endocannabinoid system to modulate food reward.

Ghrelin enhances feeding by activating the growth hormone secretagogue receptor (GHSR). In the brain, GHSRs are expressed in regions responsible for regulating food motivation including the ventral tegmental area (VTA). Endogenous cannabinoids also promote food seeking behaviors through the cannabinoid receptor 1 type (CB-1Rs) in brain regions including the VTA.