Relationship Between the Occurrence of Depression and (rs6877842, rs10719) and (rs11077) Single-Nucleotide Polymorphisms in the Polish Population: A Case-Control Study.

Although the epidemiology and symptoms of major depressive disorder (MDD) have been well-documented, the etiology and pathophysiology of the disease have not yet been fully explained. Depression arises from intricate interplay among social, psychological, and biological factors. Recently, there has been growing focus on the involvement of miRNAs in depression, with suggestions that abnormal miRNA processing locally at the synapse contributes to MDD.

Endoplasmic Reticulum Stress Differently Modulates the Release of IL-6 and IL-8 Cytokines in Human Glial Cells.

Endoplasmic reticulum (ER) stress is a significant player in the pathophysiology of various neurodegenerative and neuropsychiatric disorders. Despite the established link between ER stress and inflammatory pathways, there remains a need for deeper exploration of the specific cellular mechanisms underlying ER stress-mediated neuroinflammation. This study aimed to investigate how the severity of ER stress (triggered by different concentrations of tunicamycin) can impact the release of proinflammatory cytokines IL-6 and IL-8 from astrocytes and microglia, comparing the effects with those induced by well-known immunostimulants-tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS).

PPARγ, NF-κB and the UPR pathway as new molecular targets in the anti-inflammatory actions of NSAIDs: Novel applications in cancers and central nervous system diseases?

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, ibuprofen, or celecoxib have a well-established and unquestionable role in the human therapeutic arsenal, but still new perspectives are being discovered. This review presents new anti-inflammatory mechanisms of NSAIDs action, other than the classical one, i.e.

Ketamine - A New Antidepressant Drug with Anti-Inflammatory Properties.

Ketamine is a new, potent and rapid-acting antidepressant approved for therapy of treatment-resistant depression, which has a different mechanism of action than currently-available antidepressant therapies. It owes its uniquely potent antidepressant properties to a complex mechanism of action, which currently remains unclear. However, it is thought that it acts by modulating the functioning of the glutamatergic system, which plays an important role in the process of neuroplasticity associated with depression.

Antidepressant mechanisms of ketamine's action: NF-κB in the spotlight.

Ketamine recently approved for therapy of treatment-resistant depression shows a complex and not fully understood mechanism of action. Apart from its classical glutamatergic N-methyl-D-aspartate receptor antagonistic action, it is thought that anti-inflammatory properties of the drug are of clinical relevance due to the contribution of activated inflammatory mediators to the pathophysiology of depression and non-responsiveness of a group of patients to current antidepressant therapies. In a search of the mechanism underlying anti-inflammatory effects of ketamine, the nuclear factor kappa B transcription factor (NF-κB) has been proposed as a target for ketamine.

Gut Microbiota Metabolites Differentially Release Gliotransmitters from the Cultured Human Astrocytes: A Preliminary Report.

Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic acid is not well understood. In order to test this mechanism, a human astrocyte cell-line culture was treated with the compounds or without them, and the supernatants were collected for the analysis of ATP and glutamate gliotransmitter release with the use of luminescent and fluorescent methods, respectively.

Diclofenac Diminished the Unfolded Protein Response (UPR) Induced by Tunicamycin in Human Endothelial Cells.

Diclofenac belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), which are amongst the most frequently prescribed drugs to treat fever, pain and inflammation. Despite the presence of NSAIDs on the pharmaceutical market for several decades, epidemiological studies have shown new clinical applications of NSAIDs, and new mechanisms of their action were discovered. The unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress is involved in the pathophysiology of many diseases and may become a drug target, therefore, the study evaluated the effects of diclofenac on the tunicamycin-induced UPR pathways in endothelial cells.

The Importance of Endoplasmic Reticulum Stress as a Novel Antidepressant Drug Target and Its Potential Impact on CNS Disorders.

Many central nervous system (CNS) diseases, including major depressive disorder (MDD), are underpinned by the unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress. New, more efficient, therapeutic options for MDD are needed to avoid adverse effects and drug resistance. Therefore, the aim of the work was to determine whether UPR signalling pathway activation in astrocytes may serve as a novel target for antidepressant drugs.

Osteosarcoma cells in early and late stages as cancer in vitro progression model for assessing the responsiveness of cells to silver nanoparticles.

Understanding of biology of osteosarcoma malignant progression is indispensable for enhancement of conventional chemotherapy by the use of silver nanoparticles (AgNPs). We presented an in vitro model of cancer progression closely resembling processes occurring in vivo in terms of protein profile. A comparison of cytotoxic and genotoxic potential of AgNPs in Saos-2 cells in early stages of cancerous progression (early passages) with the cells in advanced stages (late passages) demonstrated significantly reduced responsiveness of the late passage cells to nanoparticles toxicity.

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells.

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2.

Dysfunction of endothelial cells exposed to nanomaterials assessed by atomic force spectroscopy.

The study of the impact of nanomaterials on endothelial cell elasticity with the atomic force spectroscopy (AFS) can be a significant model for assessing nanomaterials toxic effects in vitro. The mechanical properties of cells exposed to nanostructures can provide information not only about cellular nano and micro-structure, but also about cell physiology. The toxicity of nanostructures is an important issue which must be carefully considered when the optimal nanomaterial is defined.

Comprehensive Biological Evaluation of Biomaterials Used in Spinal and Orthopedic Surgery.

Biological acceptance is one of the most important aspects of a biomaterial and forms the basis for its clinical use. The aim of this study was a comprehensive biological evaluation (cytotoxicity test, bacterial colonization test, blood platelets adhesion test and transcriptome and proteome analysis of Saos-2 cells after contact with surface of the biomaterial) of biomaterials used in spinal and orthopedic surgery, namely, Ti6Al4V ELI (Extra Low Interstitials), its modified version obtained as a result of melting by electron beam technology (Ti6Al4V ELI-EBT), polyether ether ketone (PEEK) and polished medical steel American Iron and Steel Institute (AISI) 316L (the reference material). Biological tests were carried out using the osteoblasts-like cells (Saos-2, ATCC HTB-85) and bacteria (DH5α).

Endothelial cell aging detection by means of atomic force spectroscopy.

Endothelial cell aging is related to changes not only in cell phenotype, such as luminal changes, intimal and medial thickening, and increased vascular stiffness, but encompasses different cell responses to various substances including drugs or nanomaterials. In the present work, time- and dose-dependent elasticity changes evoked by silver nanoparticles in endothelial cells in early (below 15) passages were analyzed. Silver nanoparticle concentrations of 3, 3.

Designing laser-modified surface structures on titanium alloy custom medical implants using a hybrid manufacturing technology.

The hybrid technology combines an efficient material-removal process and implant surface treatment by the laser reducing time of manufacture process compared to currently used machining technologies. It also permits precise structuring of the implant material surface. Six structures of the Ti6Al4V ELI surface were designed and studied how the structure topography prepared with the hybrid technology affected the Escherichia coli adhesion to the surface and viability, as well as the growth, adhesion, and viability of human osteogenic Saos-2 cells cultured on the investigated surfaces.

Simultaneous transcriptome and proteome analysis of EA.hy926 cells under stress conditions induced by nanomaterials.

Today, the extensive and constantly growing number of applications in the field of nanotechnology poses a lot of questions about the potential toxicity of nanomaterials (NMs) toward cells of different origins. In our work we employed the tools of molecular biology to evaluate changes that occur in human endothelial cells at the transcriptomic and proteomic level, following 24 h of exposure to three different classes of NMs. Using microarray technology, we demonstrated that 24 h of exposure to silver nanoparticles (SNPs), multiwalled carbon nanotubes (MWCNTs) and polyamidoamine dendrimers (PAMAMs) leads to changes in 299, 1271, and 431 genes, respectively, influencing specific molecular pathways.

Human brain endothelial barrier cells are distinctly less vulnerable to silver nanoparticles toxicity than human blood vessel cells: A cell-specific mechanism of the brain barrier?

The blood-brain barrier (BBB) constitutes a distinctive and tightly regulated interface between the brain and the peripheral circulation. The objective of studies was to compare responses of human endothelial cells representing the model of blood vessels - EA.hy926 and HUVEC cells and the model of the brain endothelial barrier - HBEC5i cells to silver nanoparticles (SNPs).

Orexins protect neuronal cell cultures against hypoxic stress: an involvement of Akt signaling.

Orexins A and B are peptides produced mainly by hypothalamic neurons that project to numerous brain structures. We have previously demonstrated that rat cortical neurons express both types of orexin receptors, and their activation by orexins initiates different intracellular signals. The present study aimed to determine the effect of orexins on the Akt kinase activation in the rat neuronal cultures and the significance of that response in neurons subjected to hypoxic stress.

Orexins/hypocretins stimulate accumulation of inositol phosphate in primary cultures of rat cortical neurons.

Background: Orexins A and B (also named hypocretins 1 and 2) are hypothalamic peptides with pleiotropic activity. They signal through two G protein-coupled receptors: OX1R and OX2R. We have previously demonstrated that both types of orexin receptors are expressed in cultured rat cortical neurons, and stimulation of the predominant OX2R inhibits cyclic AMP synthesis.

Orexin A suppresses the growth of rat C6 glioma cells via a caspase-dependent mechanism.

Orexin A and orexin B (also known as hypocretins) are closely related peptides synthesized by hypothalamic neurons. They orchestrate diverse central and peripheral processes by stimulation of two G-protein coupled receptors, OX(1)R and OX(2)R. Recent studies have demonstrated the ability of orexins to promote a robust apoptosis in different cancer cells in culture and a potent growth reduction of human colon tumors in mice xenografts.

Orexins promote survival of rat cortical neurons.

Orexin A and B (hypocretin-1 and -2) are hypothalamic peptides that exert their biological functions by stimulation of two specific, membrane-bound receptors, OX(1)R and OX(2)R. Recently, we have demonstrated the expression of both types of orexin receptors in rat cortical neurons, with the OX(2)R level being markedly higher compared to OX(1)R. In the present study we investigated the receptor-mediated effects of orexin A, an agonist of OX(1)R and OX(2) R, orexin B and [Ala(11)-D-Leu(15)]orexin B, preferential agonists of OX(2)R, on survival of cultured neurons derived from rat cerebral cortex.

Orexins/hypocretins acting at Gi protein-coupled OX 2 receptors inhibit cyclic AMP synthesis in the primary neuronal cultures.

Orexins A and B are newly discovered neuropeptides with pleiotropic activity. They signal through two G protein-coupled receptors: OX(1) and OX(2). In this study, we examined the expression of orexin receptors and effects of the receptors' activation on cyclic AMP formation in the primary neuronal cell cultures from rat cerebral cortex.

VIP-induced neuroprotection of the developing brain.

Excitotoxicity is a key molecular mechanism of perinatal brain damage and is associated with cerebral palsy and long term cognitive deficits. VIP induces a potent neuroprotection against perinatal excitotoxic white matter damage. VIP does not prevent the initial appearance of white matter lesion but promotes a secondary repair with axonal regrowth.

Effects of PACAP and VIP on cAMP-generating system and proliferation of C6 glioma cells.

An identification of PAC1- and VPAC-type receptors in a great number of neoplastic cells gave rise to intensive studies on the biochemical and physiological role of the mentioned peptides in cancers. Our earlier studies focused on effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) in C6 glioma cells have shown their stimulatory receptor-mediated action on the cyclic adenosine monophosphate (cAMP)-generating system. In the present study, we demonstrated that truncated peptides, i.

Cyclic AMP formation in C6 glioma cells: effect of PACAP and VIP in early and late passages.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) exert their actions via common receptors, VPAC1 and VPAC2, which are equally sensitive to both peptides, while PACAP stimulates its specific PAC1-type receptors. Both peptides potently stimulate cAMP production in different biological systems. In the present article, we examined the effects of PACAP and VIP on cAMP formation in C6 rat glioma cells used between passages 12-28 (early) and 120-136 (late).

Constitutive activity of beta-adrenergic receptors in C6 glioma cells.

Alprenolol and propranolol (0.001-10 microM) significantly and concentration-dependently inhibited both isoprenaline-driven and basal (non-stimulated) cyclic adenosine monophosphate (cAMP) accumulation in the rat C6 glioma cells, showing high potency particularly in the latter condition (IC 50 values of 30 and 27 nM, respectively). In the rat cerebral cortical slices, these two tested beta-adrenoceptor antagonists inhibited the isoprenaline-evoked cAMP response, but had no effect on the nucleotide accumulation under basal (non-stimulated) conditions.