Structural Insight on the Selectivity of Calyx[4]Arene-Based Inhibitors of MgDependent Atp-Hydrolases.

Located in plasma membranes, ATP hydrolases are involved in several dynamic transport processes, helping to control the movement of ions across cell membranes. ATP hydrolase acts as a transport protein, converting energy from ATP hydrolysis into transport molecules against their concentration gradients. In addition to energy metabolism and active transport, ATP hydrolase is essential for maintaining cellular homeostasis and cell function.

Impairment of brain function in a mouse model of Alzheimer's disease during the pre-depositing phase: The role of α7 nicotinic acetylcholine receptors.

Alzheimer's disease (AD) is an age-dependent incurable neurodegenerative disorder accompanied by neuroinflammation, amyloid accumulation, and memory impairment. It begins decades before the first clinical symptoms appear, and identifying early biomarkers is key for developing disease-modifying therapies. We show now in a mouse model of AD that before any amyloid deposition the brains of 1.

α7 Nicotinic acetylcholine receptors regulate translocation of HIF-1α to the cell nucleus and mitochondria upon hypoxia.

Nicotinic acetylcholine receptors (nAChRs), initially characterized as ligand-gated ion channels mediating fast synaptic transmission, are now found in many non-excitable cells and mitochondria where they function in ion-independent manner and regulate vital cellular processes like apoptosis, proliferation, cytokine secretion. Here we show that the nAChRs of α7 subtype are present in the nuclei of liver cells and astrocytoma U373 cell line. As shown by lectin ELISA, the nuclear α7 nAChRs are mature glycoproteins that follow the standard rout of post-translational modifications in Golgi; however, their glycosylation profile is non-identical to that of mitochondrial nAChRs.

Mesenchymal stem cells as a potential therapeutic tool to cure cognitive impairment caused by neuroinflammation.

An established contribution of neuroinflammation to multiple brain pathologies has raised the requirement for therapeutic strategies to overcome it in order to prevent age- and disease-dependent cognitive decline. Mesenchymal stem cells (MSCs) produce multiple growth and neurotrophic factors and seem to evade immune rejection due to low expression of major histocompatibility complex class I molecules. Therefore, MSCs are widely used in experiments and clinical trials of regenerative medicine.

SARS-Cov-2 spike protein fragment 674-685 protects mitochondria from releasing cytochrome c in response to apoptogenic influence.

In spite of numerous studies, many details of SARS-Cov-2 interaction with human cells are still poorly understood. The 674-685 fragment of SARS-Cov-2 spike protein is homologous to the fragment of α-cobratoxin underlying its interaction with α7 nicotinic acetylcholine receptors (nAChRs). The interaction of 674-685 peptide with α7 nAChR has been predicted in silico.

AGE-RELATED MORPHO-FUNCTIONAL CHANGES IN RATS' PANCREAS UNDER HIGH-FAT DIET-INDUCED INSULIN RESISTANCE AND ITS PHARMACOLOGICAL TREATMENT.

Objective: The aim: To determine the set of structural and functional changes in pancreatic islets (PI) of obesity-induced insulin resistant (IR) rats of different age (young and old) fed with prolonged (6 month) high-fat diet (HFD) (58% of fat) and further treatment with N-Stearoylethanolamine (NSE), a bioactive N-Acylethanolamine.

Patients And Methods: Materials and methods: Alimentary obesity-induced IR model in rats of two age groups was used to investigate the influence of age and NSE treatment on pancreas morphology (using histological, histochemical and immunohistochemical techniques) and on several biochemical parameters associated with DM onset.

Results: Results: The NSE administration normalized pancreas morphology which was more affected in the old IR group; the signs of inflammation, edema, fibrosis and steatosis were somehow diminished and PI area became significantly increased.

Changing Functional Signatures of Microglia along the Axis of Brain Aging.

Microglia, the innate immune cells of the brain, are commonly perceived as resident macrophages of the central nervous system (CNS). This definition, however, requires further specification, as under healthy homeostatic conditions, neither morphological nor functional properties of microglia mirror those of classical macrophages. Indeed, microglia adapt exceptionally well to their microenvironment, becoming a legitimate member of the cellular brain architecture.

Mitochondrial α7 nicotinic acetylcholine receptors are displaced from complexes with VDAC1 to form complexes with Bax upon apoptosis induction.

Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in muscles and autonomic ganglia and regulate cytokine and neurotransmitter release in the brain and non-excitable cells. The α7 nAChRs localized in the outer membrane of mitochondria regulate cytochrome c release stimulated by apoptosis-inducing agents. However, the mechanisms through which nAChRs influence mitochondrial permeability remain obscure.

Mesenchymal Stem Cells or Interleukin-6 Improve Episodic Memory of Mice Lacking α7 Nicotinic Acetylcholine Receptors.

Nicotinic acetylcholine receptors of α7 subtype (α7 nAChRs) are involved in regulating cognition, inflammation and cell survival. Neuroinflammation is accompanied by the decrease of α7 nAChRs in the brain and impairment of memory. We show here that α7-/- mice possess pro-inflammatory phenotype and demonstrate worse episodic memory compared to wild-type mice.

Intravenously Injected Mesenchymal Stem Cells Penetrate the Brain and Treat Inflammation-Induced Brain Damage and Memory Impairment in Mice.

Neuroinflammation is regarded as one of the pathogenic factors of Alzheimer disease (AD). Previously, we showed that mice regularly injected with bacterial lipopolysaccharide (LPS) possessed the AD-like symptoms like episodic memory decline, elevated amounts of amyloid beta (Aβ) peptide (1-42), and decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain. The use of mesenchymal stem cells (MSCs), which can differentiate into multiple cell types, including neurons, is an attractive idea of regenerative medicine, in particular, for neurodegenerative disorders like AD.

Coronaridine congeners modulate mitochondrial α3β4* nicotinic acetylcholine receptors with different potency and through distinct intra-mitochondrial pathways.

In contrast to plasma membrane-expressed nicotinic acetylcholine receptors (nAChRs), mitochondrial nAChRs function in an ion-independent manner by triggering intra-mitochondrial kinases that regulate the release of cytochrome c (Cyt c), an important step in cellular apoptosis. The aim of this study is to determine the structural requirements for mitochondrial α3β4* nAChR activation by measuring the modulatory effects of two noncompetitive antagonists of these receptors, (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC], on Cyt c release from wild-type and α7-/- mice mitochondria. The sandwich ELISA results indicated that α3β4* nAChRs are present in liver mitochondria in higher amounts compared to that in brain mitochondria and that these receptors are up-regulated in α7-/- mice.

Nicotinic Acetylcholine Receptor α9 and α10 Subunits Are Expressed in the Brain of Mice.

The α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits are likely to be the evolutionary precursors to the entire cys-loop superfamily of ligand-gated ion channels, which includes acetylcholine, GABA, glycine and serotonin ionotropic receptors. nAChRs containing α9 and α10 subunits are found in the inner ear, dorsal root ganglia and many non-excitable tissues, but their expression in the central nervous system has not been definitely demonstrated. Here we show the presence of both α9 and α10 nAChR subunits in the mouse brain by RT-PCR and immunochemical approaches with a range of nAChR subunit-selective antibodies, which selectivity was demonstrated in the brain preparations of α7-/-, α9-/- and α10-/- mice.

Nicotine facilitates nicotinic acetylcholine receptor targeting to mitochondria but makes them less susceptible to selective ligands.

Several nicotinic acetylcholine receptor (nAChR) subtypes are expressed in mitochondria to regulate the internal pathway of apoptosis in ion channel-independent manner. However, the mechanisms of nAChR activation in mitochondria and targeting to mitochondria are still unknown. Nicotine has been shown to favor nAChR pentamer assembly, folding, and maturation on the way of biosynthesis.

Facile fabrication of luminescent organic dots by thermolysis of citric acid in urea melt, and their use for cell staining and polyelectrolyte microcapsule labelling.

Luminescent organic dots (O-dots) were synthesized via a one-pot, solvent-free thermolysis of citric acid in urea melt. The influence of the ratio of the precursors and the duration of the process on the properties of the O-dots was established and a mechanism of their formation was hypothesized. The multicolour luminescence tunability and toxicity of synthesized O-dots were extensively studied.

Impact of gadolinium-157 containing nanoscale magnetosensitive composites on morfofunctional properties of cells in vitro.

Objective - to investigate the morphofunctional cells properties under the action of magneticallybased nanocomposites containing gadolinium-157. Materials and methods. Experimental studies are performed in cell culture line L929 Nanocomposites based on magnetite modified by functional amino groups chemically fixed by diethylenetriaminepentaacetic acid (DTPA) and gadolinium - (Fe3O4/γ-APS/DTPA-Gd) were studied (1), also by meso-2,3-dimercaptosuccinic acid (DMSA) - (Fe3O4/DMSA-Gd), which binds to the hydroxyl group of magnetite surface (2); gadolinium was adsorbed from a solution of gadolinium sulfate.

Fibrin(ogen)olytic and platelet modulating activity of a novel protease from the Echis multisquamatis snake venom.

The variety of enzymes including serine proteases that possess fibrin(ogen)olytic and platelet modulating activity have been discovered in different snake venoms. In our work the fibrin(ogen)olytic and platelet modulating activity of a new protease from Echis multisquamatis snake venom was studied. It was shown that purified enzyme cleaved the ВβR42-A43 bond of fibrinogen during first contact with the substrate following much slower hydrolysis of C-terminus of fibrinogen Aα-chain.

Artificial gravity and functional plasticity of nerve system. L-[14C]-glutamate uptake by nerve terminals from rat cerebellum and cerebral hemispheres under hypergravity stress.

We have investigated the effects of altered gravity on the kinetic parameters of glutamate transport activity. We observed no differences in Km values for cerebellum and cerebral hemisphere nerve terminals (synaptosomes) between control rats- 18,2 +/- 7,6 micromoles (cerebellum), 10,7 +/- 2,5 micromoles (cerebral hemispheres) and animals exposed to hypergravity- 23,3 +/- 6,9 micromoles (cerebellum), 6,7 +/- 1,5 micromoles (cerebral hemispheres). The similarity of this parameter for the two studied groups of animals showed that affinity of glutamate transporter to substrate in cerebellum and cerebral hemispheres was not sensitive to hypergravity stress.

[Effect of low doses of radiation on vitamin A and E levels in rat liver].

It has been established that under intake of small doses of 137Cs by rat for 9 months the radioactivity of whole rat body was increased in irregular manner. Under this condition the level of fat-soluble vitamins A and E is decreased and the decrease is well correlated with a level of radionuclide accumulation by rat's body. The possible causes of decrease of the vitamins A and E level under intake of small doses of radionuclide are discussed.