Maturity-Onset Diabetes of the Young 10 (MODY10): A Comprehensive Review of Genetics, Clinical Features, and Therapeutic Advances.

Maturity-onset diabetes of the young type 10 (MODY10) is a monogenic diabetes subtype caused by heterozygous mutations in the insulin gene (), leading to defective proinsulin processing, endoplasmic reticulum (ER) stress, and β-cell dysfunction. Current management relies on sulfonylureas or insulin therapy, but these fail to address the underlying genetic defect. Recent research has elucidated the molecular mechanisms of MODY10, including ER stress induced by proinsulin misfolding, activation of the unfolded protein response (UPR), and β-cell apoptosis.

Chromosomal Aberrations in Induced Pluripotent Stem Cells: Identification of Breakpoints in the Large Gene and Histone Gene Cluster.

Genome instability in induced pluripotent stem cells (IPSC) poses a significant challenge for their use in research and medicine. Cataloging and precisely describing all the identified aberrations that arise during cell reprogramming, expansion, and differentiation is essential for improving approaches to instability prevention and ensuring genetic quality control. We report the karyotypic analysis of 65 cell lines derived from skin fibroblasts, urinal sediment, and peripheral blood mononuclear cells of 33 individuals, 82% of whom suffer from monogenic genetic disorders not associated with genetic instability.

[The role of neuroinflammation in the development of seizure activity and autonomic disorders in patients with epilepsy].

The literature review provides data on the role of neuroinflammation, including microglial and astrocyte dysfunction, in the development of increased neuronal excitability and excitotoxicity, which can lead to increased seizure activity. The ability of reactive astrocytes to uptake glutamate through specific transporters is reduced, leading to increased cell excitability, excitotoxicity, and, consequently, the occurrence of epileptogenic activity. In general, neuroinflammation is associated with the activation of neuroplasticity, which can be of a maladaptive (aberrant) nature.

Behavioral Characteristics of Female Rats on the Model of Pain Syndrome in the Maxillofacial Region.

Changes in behavioral parameters in the open field and elevated plus maze tests were studied in female rats with experimental osteoarthritis of the temporomandibular joint (TMJ) caused by intra-articular injection of sodium monoiodoacetate (16 mg/kg). In the elevated plus maze, the animals with experimental pain syndrome demonstrated the following dynamics of behavioral parameters: the latency of leaving the central platform and the time spent in closed arms increased, while the number of visits to closed arms and numbers of head dips and rearings decreased on day 25 of the experiment in comparison with the baseline levels. In the open-field, the latency of the first movement and grooming time increased and the number of objects explored decreased by day 26.

Effect of Glutamate Antibodies on ASCL1 Gene Expression in Aging Mice with Spatial Memory Impairment Caused by Amyloid Fibrils of the Proinflammatory Protein S100A9.

Immunological correction of cognitive processes impaired due to the action of neurotoxic amyloidogenic forms of proinflammatory protein S100A9, a promoter of the inflammatory-amyloid cascade occurring in Alzheimer's disease, is poorly understood. Chronic intranasal administration of S100A9 fibrils leads to suppression of spatial memory formation in the Morris water maze in 12-month-old C57BL/6J mice and to an increase in activity of the ASCL1 gene involved in neurogenesis at the stage of cell differentiation, in the hippocampus and prefrontal cortex. In the case of combined administration of S100A9 fibrillar structures and antibodies to glutamate, the duration of the latency of reaching the platform in the water maze as well as ASCL1 gene expression in the hippocampus and prefrontal cortex returned to normal, but not in the cerebellum where a decrease in ASCL1 gene activity was observed.

Startle response and its prepulse modification in health and under different psychopathologies: Could we find any specific patterns?

The startle response (SR) is a generalized defensive response elicited by the presentation of a sudden intense stimulus. The presentation of a less intense signal (prepulse) before the central stimulus (pulse) affects the amplitude and latency of SR differently depending on the prepulse lead interval. The most studied form of such changes is prepulse inhibition (PPI), a decrease in SR amplitude at lead intervals of 50-500 ms.

A Case of Salt-Wasting Congenital Adrenal Hyperplasia Caused by a Rare Intronic Variant in the Gene.

This case report describes a novel intronic mutation, :c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency, and expands the known mutation spectrum associated with this condition. The patient, born full-term to unrelated parents, presented with adrenal failure within the first month of life, characterized by acute adrenal crisis symptoms such as vomiting, dehydration, weight loss, hypotension, and electrolyte imbalances.

Thiamine Compounds Alleviate Oxidative Stress, Over-Expression of Pro-Inflammatory Markers and Behavioral Abnormalities in a Mouse Predation Model of PTSD.

Experiences of life-threatening stimuli can induce post-traumatic stress disorder (PTSD), which is associated with long-lasting behavioral and neurochemical abnormalities. Despite its increased global incidence, the current treatment options for PTSD remain limited, highlighting the need for novel therapeutic strategies. As oxidative stress and neuroinflammation contribute to PTSD, the use of powerful antioxidants such as thiamine (B1 vitamin) compounds may counteract disease development.

Secretome and Cellular Composition of Peripheral Blood Mononuclear Cells Cultured in the Presence of Cell Feeder or Interleukins.

Peripheral blood mononuclear cells-derived immune cells are widely used in clinical practice, in particular for cancer therapy. The growth conditions are critical for the composition and functional activity of cells. Mononuclear cells were cultured for 15 days under different conditions: in the presence of K562 cell feeder expressing 4-1BBL and mbIL-21I, or without feeder, but in the presence of L-21 or with different combinations of cytokines (IL-2, IL-15, IL-21, and IL-12) without the feeder and the cytokine profile (48 cytokines) of the culture medium in the middle (day 7) and at the end (day 14) of culturing was compared.

Selection of UTRs in mRNA-Based Gene Therapy and Vaccines.

The untranslated regions (UTRs) of messenger RNAs (mRNAs) play a crucial role in regulating translational efficiency, stability, and tissue-specific expression. The review describes various applications and challenges of UTR design in the development of gene therapy and mRNA-based therapeutics. UTRs affect critical biological functions, such as mRNA stability, modulation of protein synthesis, and attenuation of immune response.

The delayed effect of the neuroprotector fabomotizole on the brain proteome in rats with the rotenone model of parkinsonism.

Fabomotizole is an original anxiolytic agent developed at the Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies that acts on a number of important receptor systems of the brain. In a model of Parkinson's disease induced in rats by a course of rotenone administration, fabomotizole attenuated manifestations of behavioral impairments and influenced the profile and relative content of brain proteins. Five days after the last administration of rotenone, the fabomotizole effect on the behavioral reactions of rats persisted.

Experimental Animal Models of Phenylketonuria: Pros and Cons.

Phenylketonuria (PKU) is a common inherited metabolic disorder characterised by impaired metabolism of the amino acid phenylalanine. The disease results from a mutation in the phenylalanine hydroxylase (PAH) enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). The absence or inactivity of this enzyme results in significantly elevated levels of Phe in the blood, which can lead to severe neurological conditions, including intellectual disability, epilepsy, and other developmental disorders.

[The known and new ideas about the mechanism of action and the spectrum of effects of Mexidol].

The review presents the results of studies concerning the multimodal mechanism of action of the Russian original drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), which provides its neuroprotective effect and a wide range of clinical effects. The Mexidol molecule is represented by two related and functionally significant components: 2-ethyl-6-methyl-3-hydroxypyridine and succinate. The presence of 3-hydroxypyridine in the structure of Mexidol is associated with the antioxidant and membranotropic activity of the drug, the ability to reduce glutamate excitotoxicity, and modulate the work of receptors and ion channels.

Reassortment Dynamics: Phylogeography and Evolution of H4N9 Influenza Viruses.

A characteristic feature of influenza A viruses is their high capacity for reassortment, significantly increasing their genetic diversity. This can lead to the formation of influenza A virus variants with unique phenotypic characteristics, particularly those with pandemic potential. Representatives of the H4N9 subtype are low-pathogenic influenza A (LPAI) viruses.

Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line.

The remarkable biophysical properties of metastatic migrating cells, such as their exceptional motility and deformability, enable them to migrate through physical confinements created by neighboring cells or extracellular matrix. This study explores the adaptive responses of breast cancer (BC) cell sublines derived from the highly aggressive, metastatic triple-negative MDA-MB-231 and the non-metastatic MCF7 human BC cell lines, after undergoing three rounds of confined migration (CM) stress. Our findings demonstrate that CM elicits common and cell-type specific adaptive responses in BC cell sublines.

A novel FBXW11 variant in a patient with neurodevelopmental, jaw, eye, and digital syndrome.

Neurodevelopmental, jaw, eye, and digital syndrome (NEDJED) is a rare autosomal dominant condition that has demonstrated diverse phenotypes. This is the second case report published on this condition, covering the disease history of an 8 year old patient with a severe manifestation of the disease. The patient was born with hydrocephalus, and demonstrated major developmental delay as he aged.

Activation of the Complement System and Changes in the Content of Modified Lipoproteins in Antiorthostatic Hypokinesia in Humans and Mice.

The correlation between the total activity of the complement system (TACS) and the content of modified LDL (mLDL) in blood serum when modeling microgravity in Earth conditions was evaluated. Healthy volunteers were placed in a state of antiorthostatic hypokinesia for 21 days. Microgravity in ICR mice was modeled by tail suspension for 14 days.

Antivirotics based on defective interfering particles: emerging concepts and challenges.

Viruses are obligate parasites, that use the host's internal metabolic systems for their own reproduction. This complicates the search for molecular targets to prevent the spread of viral infection without disrupting the vital functions of human cells. Defective interfering particles (DIPs) are natural competitors of viruses for important resources of viral reproduction.

Effect of Soybean Trypsin Inhibitor on Biochemical Parameters of the Blood under Conditions of Water and Food Deprivation in Rats.

We have previously demonstrated multidirectional changes in trypsin activity and some serum biochemical parameters in rats under conditions of water and food deprivation with following satiation. In the present study, administration of soybean trypsin inhibitor (STI) to animals subjected to water and food deprivation caused a moderate decrease in trypsin activity and an increase in the serum concentration of total protein, which attested to deceleration of protein metabolism. Significant changes in the content of cholesterol and triglycerides against the background of STI administration were also found indicating intensification of lipid and energy metabolism.

Sanger validation of WGS variants.

With the development of next-generation sequencing (NGS) technologies it became possible to simultaneously analyze millions of variants. Despite the quality improvement, it is generally still required to confirm the variants before reporting. However, in recent years the dominant idea is that one could define the quality thresholds for "high quality" variants which do not require orthogonal validation.

Study of the Pharmacological Activity Spectrum of the New Original NT-3 Mimetic Dipeptide GTS-302.

Unlabelled: The association of the pathogenesis of neurodegenerative diseases, depression, anxiety, and cognitive disorders with neurotrophin-3 deficiency determines the prospect of creating drugs with a similar mechanism of action. Since the use of full-length NT-3 is limited by unsatisfactory pharmacokinetic properties, the creation of low-molecular mimetics of neurotrophin-3 that are active when administered systemically is relevant. The Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies has created a dimeric dipeptide mimetic of the 4th loop of NT-3, hexamethylenediamide bis-(N-γ-oxybutyryl-L-glutamyl-L-asparagine) with the laboratory code GTS-302, which activates TrkC and TrkB receptors.

Analgesic Activity of the Low Molecular Weight Neurotrophin-3 Dipeptide Mimetic GTS-301.

It was previously shown that the original dipeptide mimetic of the 4th loop of neurotrophin-3 (NT-3) hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301), like the full-length neurotrophin, predominantly activates the tyrosine kinase receptor TrkC and has a neuroprotective effect in vitro at concentrations of 10-10 M, as well as antidiabetic (0.1 and 0.5 mg/kg) and antidepressant (5 and 10 mg/kg) effects after systemic administration in rodents.

Quantitative Analysis of Pseudogene-Associated Errors During Germline Variant Calling.

A pseudogene is a non-functional copy of a protein-coding gene. Processed pseudogenes, which are created by the reverse transcription of mRNA and subsequent integration of the resulting cDNA into the genome, being a major pseudogene class, represent a significant challenge in genome analysis due to their high sequence similarity to the parent genes and their frequent absence in the reference genome. This homology can lead to errors in variant identification, as sequences derived from processed pseudogenes can be incorrectly assigned to parental genes, complicating correct variant calling.

Creation of Long-Term Physical Stability of Amorphous Solid Dispersions N-Butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide, Resistant to Recrystallization Caused by Exposure to Moisture.

Amorphous solid dispersion (ASD) technology is often used as a promising strategy to improve the solubility of active pharmaceutical ingredients (APIs). ASDs allow APIs to be dispersed at the molecular level in a polymer carrier, destroying the crystalline structure of the APIs and, thanks to the polymer, providing long-term supersaturation in solution. However, stability issues are an obstacle to the development of new medications with ASD.