Induced pluripotent stem cell (iPSC)-derived motor neurons provide a powerful platform for studying motor neuron diseases. These cells enable human-specific modeling of disease mechanisms and high-throughput drug screening. While commercially available iPSC-derived motor neurons offer a convenient alternative to time-intensive differentiation protocols, their electrophysiological properties and maturation require comprehensive evaluation to validate their utility for research and therapeutic applications. In this study, we characterized the electrophysiological properties of commercially available iPSC-derived motor neurons. Immunofluorescence confirmed the expression of motor neuron-specific biomarkers, indicating successful differentiation and maturation. Electrophysiological recordings revealed stable passive membrane properties, maturation-dependent improvements in action potential kinetics, and progressive increases in repetitive firing. Voltage-clamp analyses confirmed the functional expression of key ion channels, including high- and low-voltage-activated calcium channels, TTX-sensitive and TTX-insensitive sodium channels, and voltage-gated potassium channels. While the neurons exhibited hallmark features of motor neuron physiology, high input resistance, depolarized resting membrane potentials, and limited firing capacity suggest incomplete electrical maturation. Altogether, these findings underscore the potential of commercially available iPSC-derived motor neurons as a practical resource for MND research, while highlighting the need for optimized protocols to support prolonged culture and full maturation.

• Klíčová slova
• Motor neuron, action potential, calcium current, iPSC, potassium current, sodium current,
• MeSH
• akční potenciály MeSH
• buněčná diferenciace MeSH
• elektrofyziologické jevy MeSH
• indukované pluripotentní kmenové buňky * cytologie   metabolismus   MeSH
• lidé MeSH
• motorické neurony * cytologie   metabolismus   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Super- and low-shedding phenomena have been observed in genetically homogeneous hosts infected by a single bacterial strain. To decipher the mechanisms underlying these phenotypes, we conducted an experiment with chicks infected with Salmonella Enteritidis in a non-sterile isolator, which prevents bacterial transmission between animals while allowing the development of the gut microbiota. We investigated the impact of four commensal bacteria called Mix4, inoculated at hatching, on chicken systemic immune response and intestinal microbiota composition and functions, before and after Salmonella infection. Our results revealed that these phenotypes were not linked to changes in cell invasion capacity of bacteria during infection. Mix4 inoculation had both short- and long-term effects on immune response and microbiota and promoted the low-shedder phenotype. Kinetic analysis revealed that Mix4 activated immune response from day 4, which modified the microbiota on day 6. This change promotes a more fermentative microbiota, using the aromatic compounds degradation pathway, which inhibited Salmonella colonization by day 11 and beyond. In contrast, control animals exhibited a delayed TNF-driven pro-inflammatory response and developed a microbiota using anaerobic respiration, which facilitates Salmonella colonization and growth. This strategy offers promising opportunities to strengthen the barrier effect against Salmonella and possibly other pathogens.

• Klíčová slova
• Salmonella, carrier-state, chicken, excretion, immune response, microbiota, super-shedder, virulence,
• MeSH
• Bacteria * imunologie   klasifikace   genetika   MeSH
• kur domácí imunologie   mikrobiologie   MeSH
• nemoci drůbeže * mikrobiologie   imunologie   prevence a kontrola   MeSH
• Salmonella enteritidis * imunologie   růst a vývoj   fyziologie   MeSH
• salmonelová infekce u zvířat * imunologie   mikrobiologie   prevence a kontrola   MeSH
• střevní mikroflóra * imunologie   MeSH
• symbióza MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

In this study, we synthesized magnetic graphene oxide nanoparticles functionalized with polyvinyl alcohol (GO-PVA-Fe3O4) for effective delivery of anticancer drug and its cytotoxic potential against human breast cancer cells MDAMB. Initially, GO was synthesized using a modified Hummer's method. Subsequently, the GO was functionalized with the biocompatible polymer PVA to enhance its aqueous stability and surface reactivity. Magnetic nanoparticles (Fe3O4) were then grafted onto the PVA-functionalized GO via a chemical co-precipitation method, resulting in the formation of a stable magnetic nanocomposite. The anticancer drug 5-fluorouracil (5FU) was loaded onto the surface of the nanocarrier by non-covalent interaction. The developed nanocomposite (GO-PVA-Fe3O4-5FU) showed high drug loading capacity of 14.17 % mg mg-1 along with pH-responsive drug release of anticancer drug 5FU. 5-FU has demonstrated around 30.40 % drug release which is about 2.5 times higher than the drug release at pH 7.4 that demonstrated improved and passive targeted drug release at cancer microenvironment. Cellular cytotoxicity of the developed nanocarrier with the drug showed biocompatibility and higher cytotoxicity against MDAMB with an IC50 value of 23.65 ± 3.72 µg/mL as compared to the nanocarrier without drug loading. Therefore, the obtained results demonstrate potential of the synthesized nanocarriers as effective platforms for drug delivery. Overall, the GO-based magnetic nanocomposites exhibited promising characteristics for passive targeted drug delivery applications, offering improved biocompatibility, pH-responsive controlled release, and suitability for prospective cancer therapeutics.

• Klíčová slova
• 5FU, Anticancer, Cytotoxicity, Drug release, Magnetic graphene oxide,
• MeSH
• fluoruracil * aplikace a dávkování   chemie   farmakologie   MeSH
• grafit * chemie   aplikace a dávkování   MeSH
• hydrofobní a hydrofilní interakce MeSH
• koncentrace vodíkových iontů MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• magnetické nanočástice * chemie   MeSH
• nádorové buněčné linie MeSH
• nádory prsu * farmakoterapie   MeSH
• nanokompozity * chemie   aplikace a dávkování   MeSH
• nosiče léků chemie   MeSH
• polyvinylalkohol chemie   MeSH
• protinádorové antimetabolity * aplikace a dávkování   chemie   MeSH
• protinádorové látky * aplikace a dávkování   chemie   MeSH
• uvolňování léčiv MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluoruracil * MeSH
• grafit * MeSH
• graphene oxide MeSH Prohlížeč
• magnetické nanočástice * MeSH
• nosiče léků MeSH
• polyvinylalkohol MeSH
• protinádorové antimetabolity * MeSH
• protinádorové látky * MeSH

In the present study, the primary action of native cyclodextrins (CDs) on lysozyme protein as binding ligand and secondary as aggregation inhibitor were probed. Thermally induced denaturation using differential scanning calorimetry (DSC) was measured in the presence of native α-, β- and γ-CDs. The denaturation process in CD absence was reversible to 60-80 % at pH≤6 with maximum Tm at pH=4. Denaturation in the presence of native α-CD at pH from 2 to 10, at the least stable and partially reversible conditions in presence of β-CD and γ-CDs at single pH 2 only, was measured. The protein thermal stability decreases in the presence of CDs, with the most evident for β-CD, followed by α-CD and almost no effect for γ-CD. The reversibility in the presence of α-CD was similar to that in its absence. The best protection performance against heat-induced denaturation was found at pH 2 for β-CD. The heat capacity data for α-CD at acidic pH were fitted by the protein-ligand binding model in the whole temperature and ligand concentration ranges studied. The decrease in thermal stability for α-CD at all pH, β- and γ-CD at pH 2 were fitted linearly as a function of ligand concentration. The CD-to-lysozyme binding parameters obtained in this work and from the literature for other CDs are briefly discussed using the concept of cyclodextrin cavity size, charge distribution, solvent accessible surface area and amino acid hydrophobicity.

• Klíčová slova
• Cyclodextrin, Differential scanning calorimetry, Inclusion complex lysozyme binding model,
• MeSH
• cyklodextriny * chemie   farmakologie   MeSH
• denaturace proteinů MeSH
• diferenciální skenovací kalorimetrie MeSH
• koncentrace vodíkových iontů MeSH
• kur domácí MeSH
• muramidasa * chemie   metabolismus   MeSH
• stabilita enzymů účinky léků   MeSH
• teplota * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklodextriny * MeSH
• muramidasa * MeSH

Endothelial cells, the gatekeepers of vascular permeability, play a pivotal role in vascular homeostasis by controlling inflammatory responses and hemostatic balance. However, their role is not limited to the circulatory system, since they also mediate organ function through numerous signaling pathways and cellular interactions. Recent studies have shown that endothelial cells not only constitute a heterogeneous population but also exhibit adaptive capacity, particularly in response to mechanical or biochemical stimuli. A growing body of research on endothelial cells also highlights their involvement in various pathological conditions, including cardiovascular diseases, inflammatory disorders, and cancer. Furthermore, endothelial progenitor cells represent a valuable therapeutic option in regenerative medicine, and ongoing clinical trials are investigating their use in the treatment of ischemic diseases, myocardial infarction, and organ fibrosis. This manuscript reviews the physiology and pathophysiology of endothelial cells, focusing on recent findings and clinical applications relevant to new therapeutic approaches.

• Klíčová slova
• Endothelial cells, Endothelial dysfunction, Regenerative medicine, Vascular homeostasis,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Local anesthetics are routinely used for pain management, yet their broader effects on cancer cells remain incompletely understood. Here, we investigate the impact of ropivacaine hydrochloride and lidocaine hydrochloride monohydrate on SaOS-2 human osteosarcoma cells using a series of in vitro assays. Our findings indicate that both anesthetics markedly reduce cell viability and proliferation, as measured by XTT and Colony formation assays, respectively. Mechanistic studies reveal significant disruption of mitochondrial function, evidenced by decreased membrane potential, enhanced mitochondrial superoxide production, and pronounced mitochondrial fragmentation. Concurrently, the expression of matrix metalloproteinases (MMP-2 and MMP-9) is downregulated, while pro-apoptotic markers (Caspase-3, Caspase-9, and BAX) are upregulated. Neither agent alters Vimentin or E-cadherin expression, suggesting a limited effect on epithelial-mesenchymal transition pathways. Notably, lidocaine and ropivacaine also inhibit SaOS-2 cell migration and invasion, as demonstrated by Scratch, single-cell migration, and Transwell invasion assays. Furthermore, both agents suppress alkaline phosphatase activity, a hallmark associated with osteosarcoma differentiation and metastatic potential. Taken together, these results support the conclusion that ropivacaine and lidocaine exert broad anti-tumor effects by impairing both mitochondrial homeostasis and the invasive phenotype in osteosarcoma cells. Their capacity to mitigate core hallmarks of malignancy underscores the need for further investigation into local anesthetics as potential adjuvant therapies for osteosarcoma.

• Klíčová slova
• Lidocaine, Local anesthetics, Osteosarcoma, Ropivacaine, SaOS-2,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The specific structure of low-processed foods places unique demands on technological processes. The study examines an alternative protocol to preserve the quality of shredded radish during cold storage - applying pre-storage treatments with the probiotic Lactiplantibacillus plantarum (SP) alone or in combination with the prebiotic inulin (SPI). RESULTS: Shredded radish samples were soaked in the functional solutions and, after cold storage, were further tested in terms of colour changes, microbiological quality, nutritional value and antioxidant properties. The treatments not only improve microbiological safety and enhance colour stability but also maintain nutritional value without any adverse effects. The SPI-treated samples showed a 56% reduction in coliforms compared to the control and were rich in probiotics (6.74 log10CFU g-1). Both treatments reduced browning, which was especially visible in the SPI samples (40%). Compared to fresh samples, the application of SPI significantly increased the levels of glucoraphenin (2.19-fold), glucobrassicin (2.48-fold), gluconapoleiferin 1 and 2 isomers (2.97- and 2.17-fold) and oxodihydroxyoctadecenoic acid (29-fold). These changes were reflected in the improved antioxidant properties, including reducing, antiradical and lipid-protecting capacities. Treatments slightly decreased starch and protein content but without any negative impact on digestibility. CONCLUSION: The results confirm that the pre-storage treatments described may be an alternative to traditional preservation methods and are practical tools for extending the shelf life and overall quality of shredded radish. © 2025 Society of Chemical Industry.

• Klíčová slova
• antioxidant properties, nutrients, prebiotic, pre‐storage treatment, probiotic, untargeted metabolomics, white radish,
• MeSH
• antioxidancia * analýza   metabolismus   chemie   MeSH
• barva MeSH
• inulin * analýza   metabolismus   MeSH
• konzervace potravin * metody   MeSH
• Lactobacillus plantarum * metabolismus   MeSH
• Maillardova reakce MeSH
• metabolomika MeSH
• nutriční hodnota MeSH
• potravinářská mikrobiologie MeSH
• prebiotika analýza   MeSH
• probiotika * analýza   metabolismus   MeSH
• Raphanus * chemie   mikrobiologie   metabolismus   MeSH
• skladování potravin MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• antioxidancia * MeSH
• inulin * MeSH
• prebiotika MeSH

Microtubules (MTs) undergo diverse posttranslational modifications that regulate their structural and functional properties. Among these, polyglutamylation-a dominant and conserved modification targeting unstructured tubulin C-terminal tails-plays a pivotal role in defining the tubulin code. Here, we describe a mechanism by which tubulin tyrosine ligase-like 11 (TTLL11) expands and diversifies the code. Cryo-electron microscopy revealed a unique bipartite MT recognition strategy wherein TTLL11 binding and catalytic domains engage adjacent MT protofilaments. Biochemical and cellular assays identified previously uncharacterized polyglutamylation patterns, showing that TTLL11 directly extends the primary polypeptide chains of α- and β-tubulin in vitro, challenging the prevailing paradigms emphasizing lateral branching. Moreover, cell-based and in vivo data suggest a cross-talk between polyglutamylation and the detyrosination/tyrosination cycle likely linked to the TTLL11-mediated elongation of the primary α-tubulin chain. These findings unveil an unrecognized layer of complexity within the tubulin code and offer mechanistic insights into the molecular basis of functional specialization of MT cytoskeleton.

• MeSH
• elektronová kryomikroskopie MeSH
• lidé MeSH
• mikrotubuly metabolismus   MeSH
• molekulární modely MeSH
• peptidsynthasy * metabolismus   chemie   genetika   MeSH
• posttranslační úpravy proteinů MeSH
• tubulin * metabolismus   chemie   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• peptidsynthasy * MeSH
• tubulin polyglutamylase MeSH Prohlížeč
• tubulin * MeSH

BAF (SWI/SNF) chromatin remodelers engage binding partners to generate site-specific DNA accessibility. However, the basis for interaction between BAF and divergent binding partners has remained unclear. Here, we tested the hypothesis that scaffold proteins augment BAF's binding repertoire by examining β-catenin (CTNNB1) and steroidogenic factor 1 (SF-1, NR5A1), a transcription factor central to steroid production in human cells. BAF inhibition rapidly opposed SF-1/β-catenin enhancer occupancy, impairing SF-1 target activation and SF-1/β-catenin autoregulation. These effects arise due to β-catenin's role as a molecular adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast to exclusively IDR-driven mechanisms, adapter function is mediated by direct association of ARID1A with β-catenin's folded Armadillo repeats. β-catenin similarly linked cBAF to YAP1, SOX2, FOXO3, and CBP/p300, reflecting a general IDR-mediated mechanism for modular coordination between factors. Molecular visualization highlights β-catenin's adapter role for interaction of cBAF with binding partners.

• Klíčová slova
• IDRs, adrenocortical carcinoma, chromatin remodeling, co-activators, scaffold proteins, steroid hormones, transcription factors, transcription regulators, unstructured protein,
• MeSH
• adaptorové proteiny signální transdukční metabolismus   genetika   MeSH
• beta-katenin * metabolismus   genetika   chemie   MeSH
• DNA vazebné proteiny * metabolismus   genetika   chemie   MeSH
• fosfoproteiny metabolismus   genetika   MeSH
• HEK293 buňky MeSH
• jaderné proteiny * metabolismus   genetika   MeSH
• lidé MeSH
• protein FOXO3 metabolismus   genetika   MeSH
• signální proteiny YAP MeSH
• signální transdukce MeSH
• steroidogenní faktor 1 * metabolismus   genetika   MeSH
• transkripční faktory p300-CBP metabolismus   genetika   MeSH
• transkripční faktory * metabolismus   genetika   chemie   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vnitřně neuspořádané proteiny * metabolismus   genetika   MeSH
• zesilovače transkripce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• ARID1A protein, human MeSH Prohlížeč
• beta-katenin * MeSH
• CTNNB1 protein, human MeSH Prohlížeč
• DNA vazebné proteiny * MeSH
• fosfoproteiny MeSH
• jaderné proteiny * MeSH
• NR5A1 protein, human MeSH Prohlížeč
• protein FOXO3 MeSH
• signální proteiny YAP MeSH
• steroidogenní faktor 1 * MeSH
• transkripční faktory p300-CBP MeSH
• transkripční faktory * MeSH
• vnitřně neuspořádané proteiny * MeSH
• YAP1 protein, human MeSH Prohlížeč

Conventional Ag-decorated TiO2 coatings suffer from low adsorption capacity and burst release kinetics, limiting long-term antibacterial efficacy and risking cytotoxicity. An entirely different payload release approach can be based on metal-organic frameworks (MOFs), which offer tunable porosity, high surface area, and internal diffusion channels. Here, we report a thermally stabilized Ti-based MOF [NH2-MIL-125(Ti)] functionalized with Ag+ via reactive deposition, enabling high Ag loading (∼14.7 wt %) and sustained release. Annealing at 250 °C enhances aqueous stability, allowing diffusion-governed Ag+ delivery over >48 h, with 77% of the Ag still present in the MOF after a 24 h release. The system exhibits dose-dependent antibacterial activity in powders and comparable efficacy in coatings, with a more gradual release profile. This scalable platform is promising for long-acting coatings, wound interfaces, and implantable materials.

• Klíčová slova
• NH2-MIL-125, antibacterial activity, metal−organic-frameworks (MOFs), silver,
• MeSH
• antibakteriální látky * chemie   farmakologie   MeSH
• Escherichia coli účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• porézní koordinační polymery * chemie   MeSH
• poréznost MeSH
• Staphylococcus aureus účinky léků   MeSH
• stříbro * chemie   farmakologie   MeSH
• titan * chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• porézní koordinační polymery * MeSH
• stříbro * MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč