Search Results (14)

Background: Neuropsychiatric disorders such as Alzheimer’s disease (AD), bipolar disorder (BD), and depression exhibit shared glutamatergic abnormalities, although their upstream molecular mechanisms remain poorly defined. Magnesium (Mg²⁺) serves as a key regulator of N-methyl-D-aspartate (NMDA) receptor function; however, the role of Mg²⁺ transporters, particularly SLC41A1, has not been systematically investigated. As NMDA receptor dysregulation contributes to emotional and cognitive impairments, elucidating Mg²⁺-NMDA signaling may enable the development of novel therapeutic strategies. Methods: We integrated Mendelian randomization, locus colocalization, human brain transcriptomics, functional enrichment, and co-expression analyses to determine whether SLC41A1 functions as a cross-disorder molecular driver. In addition, in vitro electrophysiological experiments using field potential recordings in hippocampal Schaffer-CA1 synapses were conducted to validate its functional role in NMDA receptor-mediated synaptic transmission. Results: Genetically elevated SLC41A1 expression increased the risk of AD, BD, depression, and alcohol dependence, with strong colocalization analyses supporting shared causal variants. Transcriptomic profiling revealed SLC41A1 upregulation in AD and BD, with enrichment in magnesium transport, mitochondrial function, and synaptic signaling pathways. Co-expression networks across GTEx brain regions demonstrated strong correlations with NMDA-related genes (e.g., GRINA, CAMK2G, GRIN2C). Under NMDAR-selective recording conditions, both imipramine treatment and SLC41A1 knockdown significantly reduced NMDAR-mediated fEPSP amplitudes, supporting a role for SLC41A1 in regulating NMDA receptor-dependent synaptic responses. Conclusions: This study identifies SLC41A1 as a magnesium-centered, transdiagnostic therapeutic target that links Mg²⁺ homeostasis to NMDA-dependent synaptic dysfunction. These findings provide a mechanistic foundation for developing SLC41A1-modulating or magnesium-based therapeutic approaches for mood and cognitive disorders. Full article

Xyloglucan is a highly promising ‘green’ polymer that has found its application in the food and pharmaceutical industries. Due to its molecular structure similarity to mucin, it has remarkable mucoadhesion properties, which has led to a high research interest in this excipient for the development of transmucosal delivery systems. Thermosensitivity is another promising property of xyloglucan derivatives, which is mainly exhibited by synthetic block copolymers such as pluronics and PLGA derivatives. Delivery systems whose mechanism of active ingredient release is based on temperature sensitivity are widely used in many medical fields, ranging from antitumour therapy to intranasal delivery. Thus, conducting research on the possibility of obtaining and using a new mucoadhesive, fully biocompatible and affordable polymer—xyloglucan—is a promising task. Full article

This current article was dedicated to the determination of the composition of phenolic compounds in extracts of four species of the genus Filipendula in order to establish a connection between the composition of polyphenols and biological effects. A chemical analysis revealed that the composition of the extracts studied depended both on the plant species and its part (leaf or flower) and on the extractant used. All four species of Filipendula were rich sources of phenolic compounds and contained hydrolyzable tannins, condensed tannins, phenolic acids and their derivatives, and flavonoids. The activities included data on those that are most important for creating functional foods with Filipendula plant components: the influence on blood coagulation measured by prothrombin and activated partial thromboplastin time, and on the activity of the digestive enzymes (pancreatic amylase and lipase). It was established that plant species, their parts, and extraction methods contribute meaningfully to biological activity. The most prominent result is as follows: the plant organ determines the selective inhibition of either amylase or lipase; thus, the anticoagulant activities of F. camtschatica and F. stepposa hold promise for health-promoting food formulations associated with general metabolic disorders. Full article

Calendula officinalis L. is a well-known plant widely used in traditional medicine due to the presence of various biologically active compounds. The main raw material for the production of medicinal preparations is the inflorescence, which consists of ligulate and tubular flowers. However, the characteristics of the metabolome of these flowers are not fully understood. This study identified and compared the levels of major metabolites in the ligulate and tubular flowers of two C. officinalis cultivars, ‘Golden Sea’ (GS) and ‘Paradise Garden’ (PG). The metabolome was analysed using ultra-performance liquid chromatography with photodiode array detection and a Q Exactive Orbitrap high-resolution mass spectrometer. It was found that the tubular flowers of both PG and GS cultivars had higher levels of lipids, phenolamides and caffeoylquinic acids and lower levels of triterpenoid glycosides than the ligulate flowers. It was also shown that the inflorescences of the GS, which had a 35% higher proportion of tubular flowers, contained 30% more phenolic compounds and 50% more lipids than the PG. Thus, the results obtained extend our understanding of the features in the metabolomes of ligulate and tubular flowers and suggest that the quality of inflorescences of C. officinalis cultivars, as a source of medicinal preparations, is strongly influenced by the proportion of ligulate and tubular flowers. Full article

Essential oils (EOs) are of commercial importance for medicine, food, cosmetics, the perfume industry, and agriculture. In plants, EOs, like the wax cover, serve as protection against abiotic stresses, such as high temperatures and water deficiency. The use of spraying with exogenous hormones of aromatic plants affects the accumulation and composition of volatile compounds, as well as tolerance to abiotic stress. As a result of cytokinin treatment with 6-BAP (6-benzylaminopurine) (200 mg L^−l) of Anetum graveolens L. “Uzory” and “Rusich” varieties, several responses to its action were revealed: a change in the division of leaf blades, inhibition of flowering, an increase in the content of EO and its main components α-phellandrene and p-cymene in leaves, and limonene in umbels and fruits. It was revealed that the increased accumulation of EO in dill leaves was longer with sufficient moisture. In contrast, under conditions of heat and water deficiency, the effect of 6-BAP treatment on accumulations of the EO in leaves was short-lived and did not appear on umbels and fruits. The study of the cytokinin effect on a fine structure of a wax cover on the adaxial side of leaves by scanning electron microscopy revealed a change in its elements (from amorphous layers with scales to thin tubules), which probably increased the sensitivity of leaves to water deficiency and, consequently, led to a decrease in the biosynthetic activity of leaf tissue. Thus, 6-BAP had an impact on the adaptive properties of dill plants, prolonging the “youth” of vegetative organs and the ability to EO biosynthesis under conditions of sufficient moisture. Full article

Increasing awareness of climate issues in recent decades has led to new policies on buildings’ energy consumption and energy performance. The European Union (EU) directive 2010/31/EC, i.e., the energy performance of buildings directive (EPBD), is one of the measures initiated to achieve climate and energy goals by reducing energy use and greenhouse gas emissions in the building sector. The EPBD required all new buildings to be nearly zero-energy buildings (nZEBs) by 2021. Nearly zero-energy buildings (nZEBs) are buildings with a very-high-energy performance and nearly zero or low-energy requirements covered to a very significant extent by energy from renewable sources produced on-site or nearby. The utilisation of solar photovoltaic (PV) panels is a common approach for achieving the nZEB standard. The carbon footprint of PV panels is often not discussed as a parameter. This paper aimed to analyse the environmental performance of an existing nearly zero-energy university building in a Norwegian use case scenario. This analysis is performed by assessing annual electricity and heat consumption from both energetic and environmental perspectives. The energy required for the building during the studied period is then used to analyse the environmental and energy performance of the building. When it comes to the environmental assessment, the commercial software SimaPro was used. The proposed revision EPBD and nZEB definition from 2021 suggests that nZEBs should also consider operational greenhouse gas emissions and life-cycle global warming potential from 2027. The life cycle assessment (LCA) of the building’s energy sources looks at the global warming potential (GWP) and greenhouse gas (GHG) emissions, and how they compare to Norwegian grid electricity. The results of the analysis highlights potential challenges to justifying the use of alternative energy sources to fulfil the criteria of nZEBs. When installing solar PV, it is important to consider the energy mix of the country where the solar PVs are produced. To solely consider the energy performance of the building, the installation of solar PV panels in countries with a high share of renewable energy may result in a reduced impact in terms of emission reduction from a life cycle perspective. Full article

The red raspberry is one of the world’s most popular berries. The main direction of its breeding has switched to nutritional quality, and the evaluation of raspberry germplasm for antioxidant content and activity is very important. As berries, raspberry leaves contain valuable bioactive compounds, but the optimal time for their collection is unknown. We evaluated 25 new breeding lines and standard raspberry cultivars for their polyphenolic content and antioxidant capacity. The antioxidant activity of berries correlated better with the content of total phenolics (0.88 and 0.92) and flavonoids (0.76 and 0.88) than with anthocyanins (0.37 and 0.66). Two breeding lines were significantly superior to the standard cultivars and can be used in further breeding. Leaves collected in three phenological phases of the raspberry contained more phenolics (5.4-fold) and flavonoids (4.1-fold) and showed higher antioxidant activities (2.4-fold in FRAP assay, 2.2-fold in ABTS) than berries. The optimal time for harvesting raspberry leaves is the fruit ripening stage, with exceptions for some cultivars. Genetic diversity analysis using microsatellite (SSR) markers from flavonoid biosynthesis genes divided the genotypes into five clusters, generally in agreement with their kinships. The relationship between genetic data based on metabolism-specific SSR markers and the chemical diversity of cultivars was first assessed. The biochemical and genetic results show a strong correlation (0.78). This study is useful for further the improvement of raspberry and other berry crops. Full article

Increasing awareness of climate issues and environmental policy has been a key factor behind the continuous transition of energy systems at different levels. This paper aimed to analyse the energy system of Viken county, located in Norway. An energy system model using the energy system analysis tool EnergyPLAN was developed. Based on the reference year 2018, two future scenarios which focus on changes in the transport sector for the year 2030 and 2050 were designed. Besides changes in the transport sector, the integration of renewable energy sources is considered in the future scenarios. The results of the analysis regarding the future scenario shows substantial CO${}_2$ reduction as a result of energy-carrier switching within the transport sector. The integration of new energy sources, in this case, solar PV and wind power, helps to offset increased import dependency. The primary energy supply decrease and the share of renewable energy increases significantly. Full article

Androgenic alopecia (AGA) is the most common type of progressive hair loss in man. The search for reliable predictors of the conservative treatment’s effectiveness is an urgent problem today. Forty-eight patients with AGA, stages I–IV by the Norwood–Hamilton scale, were treated for 4 months with 5% topical minoxidil joints with corrections for trace element and vitamin imbalances. In most cases, the positive therapy’s effect was shown in the parietal but not in the occipital area, whereas that effect was observed in others. The attempts to associate the therapy’s effectiveness with initially defined genetic, hormonal, and metabolic parameters showed the absence of differences between groups with positive and negative outcomes. Among the studied nutrient parameters (Zn, Cu, Mg, Ca, Fe, and Se, as well as vitamins B12, E, D, and folic acid), differences between these groups was shown in zinc content only. The starting point from a zinc plasma level above 10 µmol/L likely provides the success of the subsequent conservative therapy and correlates with an increase in the hair density and diameter in the parietal area. The integral predictive value of the Zn plasma level was assessed as 72.3% (positive predictive value: −88%; and negative predictive value: −55%). Full article

Research Highlights: Long-term exposure of paper birch to elevated carbon dioxide (CO₂) and ozone (O₃) modified metabolite content of over-wintering buds, but no evidence of reduced freezing tolerance was found. Background and Objectives: Atmospheric change may affect the metabolite composition of over-wintering buds and, in turn, impact growth onset and stress tolerance of perennial plant species in spring. Materials and Methods: Low molecular weight compounds of paper birch (Betula papyrifera) buds, including lipophilic, polar and phenolic compounds were analyzed, and freezing tolerance (FT) of the buds was determined prior to bud break after 11 growing seasons exposure of saplings to elevated concentrations of CO₂ (target concentration 560 µL L⁻¹) and O₃ (target concentration 1.5 × ambient) at the Aspen FACE (Free-Air CO₂ and O₃ Enrichment) facility. Results: The contents of lipophilic and phenolic compounds (but not polar compounds) were affected by elevated CO₂ and elevated O₃ in an interactive manner. Elevated O₃ reduced the content of lipids and increased that of phenolic compounds under ambient CO₂ by reallocating carbon from biosynthesis of terpenoids to that of phenolic acids. In comparison, elevated CO₂ had only a minor effect on lipophilic and polar compounds, but it increased the content of phenolic compounds under ambient O₃ by increasing the content of phenolic acids, while the content of flavonols was reduced. Conclusions: Based on the freezing test and metabolite data, there was no evidence of altered FT in the over-wintering buds. The impacts of the alterations of bud metabolite contents on the growth and defense responses of birches during early growth in spring need to be uncovered in future experiments. Full article

Ischemic stroke is known to cause the accumulation of misfolded proteins and loss of calcium homeostasis leading to impairment of endoplasmic reticulum (ER) function. The unfolded protein response (UPR) is an ER-located and cytoprotective pathway that aims to resolve ER stress. Transmembrane BAX inhibitor-1 motif-containing (TMBIM) protein family member TMBIM3/GRINA is highly expressed in the brain and mostly located at the ER membrane suppressing ER calcium release by inositol-1,4,5-trisphosphate receptors. GRINA confers neuroprotection and is regulated by erythropoietin (EPO) after murine cerebral ischemia. However, the role of GRINA and the impact of EPO treatment on the post-ischemic UPR have not been elucidated yet. We subjected GRINA-deficient (Grina^−/−) and wildtype mice to transient (30 min) middle cerebral artery occlusion (tMCAo) followed by 6 h or 72 h of reperfusion. We administered EPO or saline 0, 24 and 48 h after tMCAo/sham surgery. Oxygen–glucose deprivation (OGD) and pharmacological stimulation of the UPR using Tunicamycin and Thapsigargin were carried out in primary murine cortical mixed cell cultures. Treatment with the PERK-inhibitor GSK-2606414, IRE1a-RNase-inhibitor STF-083010 and EPO was performed 1 h prior to either 1 h, 2 h or 3 h of OGD. We found earlier and larger infarct demarcations in Grina^−/− mice compared to wildtype mice, which was accompanied by a worse neurological outcome and an abolishment of EPO-mediated neuroprotection after ischemic stroke. In addition, GRINA-deficiency increased apoptosis and the activation of the corresponding PERK arm of the UPR after stroke. EPO enhanced the post-ischemic activation of pro-survival IRE1a and counteracted the pro-apoptotic PERK branch of the UPR. Both EPO and the PERK-inhibitor GSK-2606414 reduced cell death and regulated Grina mRNA levels after OGD. In conclusion, GRINA plays a crucial role in post-ischemic UPR and the use of both GSK-2606414 and EPO might lead to neuroprotection. Full article

The Glutamate Receptor Ionotropic NMDA-Associated Protein 1 (GRINA) belongs to the Lifeguard family and is involved in calcium homeostasis, which governs key processes, such as cell survival or the release of neurotransmitters. GRINA is mainly associated with membranes of the endoplasmic reticulum, Golgi, endosome, and the cell surface, but its presence in the nucleus has not been explained yet. Here we dissect, with the help of different software tools, the potential roles of GRINA in the cell and how they may be altered in diseases, such as schizophrenia or celiac disease. We describe for the first time that the cytoplasmic N-terminal half of GRINA (which spans a Proline-rich domain) contains a potential DNA-binding sequence, in addition to cleavage target sites and probable PY-nuclear localization sequences, that may enable it to be released from the rest of the protein and enter the nucleus under suitable conditions, where it could participate in the transcription, alternative splicing, and mRNA export of a subset of genes likely involved in lipid and sterol synthesis, ribosome biogenesis, or cell cycle progression. To support these findings, we include additional evidence based on an exhaustive review of the literature and our preliminary data of the protein–protein interaction network of GRINA. Full article

The etiopathogenesis of neurodegenerative diseases is characterized by the death of neurons. Human periodontal ligament stem cells (hPDLSCs), coming from neuronal crest, can potentially become neuronal cells because of their embryologic origin. In this study, we performed an RNA-seq analysis of hPDLSCs in order to determine whether their transcriptomic profile revealed genes encoded for ion channel receptors. Next, each found gene was enriched by the information of pathways stored in the Reactome database. Our results show that the hPDLSCs express GABBR1 and GABBR2, CHRNA1, GRINA genes, respectively associated with GABA_B, NMDA and nACh receptors. In particular, the two subunits of GABA_B receptor are expressed in hPDLSCs. Further, the proteic extract for GABA_BR1, GABA_BR2 and AChRα1 confirmed their expression in hPDLSCs. Our results show that hPDLSCs express physiologically genes associated with ion channel receptors maintaining multipotent features which are useful for neurogenesis. Full article

Nearly 20 different transcripts of the human androgen receptor (AR) are reported with two currently listed as Refseq isoforms in the NCBI database. Isoform 1 encodes wild-type AR (type 1 AR) and isoform 2 encodes the variant AR45 (type 2 AR). Both variants contain eight exons: they share common exons 2–8 but differ in exon 1 with the canonical exon 1 in isoform 1 and the variant exon 1b in isoform 2. Splicing of exon 1 or exon 1b is reported to be mutually exclusive. In this study, we identified a novel exon 1b (1b/TAG) that contains an additional TAG trinucleotide upstream of exon 1b. Moreover, we identified AR transcripts in both normal and cancerous breast and prostate cells that contained either exon 1b or 1b/TAG spliced between the canonical exon 1 and exon 2, generating nine-exon AR transcripts that we have named isoforms 3a and 3b. The proteins encoded by these new AR variants could regulate androgen-responsive reporters in breast and prostate cancer cells under androgen-depleted conditions. Analysis of type 3 AR-GFP fusion proteins showed partial nuclear localization in PC3 cells under androgen-depleted conditions, supporting androgen-independent activation of the AR. Type 3 AR proteins inhibited androgen-induced growth of LNCaP cells. Microarray analysis identified a small set of type 3a AR target genes in LNCaP cells, including genes known to modulate growth and proliferation of prostate cancer (PCGEM1, PEG3, EPHA3, and EFNB2) or other types of human cancers (TOX3, ST8SIA4, and SLITRK3), and genes that are diagnostic/prognostic biomarkers of prostate cancer (GRINA3, and BCHE). Full article