
PUBLIKÁCIÓK
- The High‐Affinity Chymotrypsin Inhibitor Eglin C Poorly Inhibits Human Chymotrypsin‐Like Protease: Gln192 and Lys218 Are Key Determinants Absztrakt Eglin C, a small protein from the medicinal leech, has been long considered a general high-affinity inhibitor of chymotrypsins and elastases. Here, we demonstrate that eglin C inhibits human chymotrypsin-like protease (CTRL) weaker by several orders of magnitude than other chymotrypsins. In order to identify the underlying structural aspects of this unique deviation, we… További információ: The High‐Affinity Chymotrypsin Inhibitor Eglin C Poorly Inhibits Human Chymotrypsin‐Like Protease: Gln192 and Lys218 Are Key Determinants
- The interlacing anti-cancer effect of pharmacologic ascorbate, chloroquine and resveratrol Absztrakt Currently, a diagnosis with KRAS mutant pancreatic ductal adenocarcinoma (PDAC) means a death warrant, so finding efficient therapeutic options is a pressing issue. Here, we presented that pharmacologic ascorbate, chloroquine and resveratrol co-treatment exerted a synergistic cytotoxic effect on PDAC cell lines. The observed synergistic cytotoxicity was a general feature in all investigated cancer… További információ: The interlacing anti-cancer effect of pharmacologic ascorbate, chloroquine and resveratrol
- SARS-CoV-2 Nucleocapsid Protein Is Not Responsible for Over-Activation of Complement Lectin Pathway Absztrakt The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral structural protein that is abundant in the circulation of infected individuals. Previous published studies reported controversial data about the role of the N protein in the activation of the complement system. It was suggested that the N protein directly… További információ: SARS-CoV-2 Nucleocapsid Protein Is Not Responsible for Over-Activation of Complement Lectin Pathway
- Raman and NIR spectroscopy-based real-time monitoring of the membrane filtration process of a recombinant protein for the diagnosis of SARS-CoV-2 Absztrakt This research shows the detailed comparison of Raman and near-infrared (NIR) spectroscopy as Process Analytical Technology tools for the real-time monitoring of a protein purification process. A comprehensive investigation of the application and model development of Raman and NIR spectroscopy was carried out for the real-time monitoring of a process-related impurity, imidazole, during the tangential flow filtration of Receptor-Binding… További információ: Raman and NIR spectroscopy-based real-time monitoring of the membrane filtration process of a recombinant protein for the diagnosis of SARS-CoV-2
- Bioequivalence prediction with small-scale biphasic dissolution and simultaneous dissolution-permeation apparatus—An aripiprazole case study Absztrakt Both biphasic dissolution and simultaneous dissolution-permeation (D-P) systems have great potential to improve the in vitro-in vivo correlation compared to simple dissolution assays, but the assay conditions, and the evaluation methods still need to be refined in order to effectively use these apparatuses in drug development. Therefore, this comprehensive study aimed to compare the predictive accuracy… További információ: Bioequivalence prediction with small-scale biphasic dissolution and simultaneous dissolution-permeation apparatus—An aripiprazole case study
- Explainable deep recurrent neural networks for the batch analysis of a pharmaceutical tableting process in the spirit of Pharma 4.0Absztrakt Due to the continuously increasing Cost of Goods Sold, the pharmaceutical industry has faced several challenges, and the Right First-Time principle with data-driven decision-making has become more pressing to sustain competitiveness. Thus, in this work, three different types of artificial neural network (ANN) models were developed, compared, and interpreted by analyzing an open-access dataset… További információ: Explainable deep recurrent neural networks for the batch analysis of a pharmaceutical tableting process in the spirit of Pharma 4.0
- UV imaging for the rapid at-line content determination of different colourless APIs in their tablets with artificial neural networks Absztrakt This paper presents a novel high-resolution and rapid (50 ms) UV imaging system, which was used for at-line, non-destructive API content determination of tablets. For the experiments, amlodipine and valsartan were selected as two colourless APIs with different UV induced fluorescent properties according to the measured solid fluorescent spectra. Images were captured with a LED-based UV illumination (385–395 nm) of… További információ: UV imaging for the rapid at-line content determination of different colourless APIs in their tablets with artificial neural networks
- Development of Continuous Additive-Controlled MSMPR Crystallization by DoE-Based Batch Experiments Absztrakt Additive-controlled crystallization is a promising method to improve crystal morphology and produce solid drug particles with the desired technological and pharmacological properties. However, its adaptation to continuous operation is a hardly researched area. Accordingly, in this work, we aimed to come up with a methodology that provides the systematic and fast development of a… További információ: Development of Continuous Additive-Controlled MSMPR Crystallization by DoE-Based Batch Experiments
- In-line indirect concentration measurement of ultralow dose API during twin-screw wet granulation based on NIR and Raman spectroscopy Absztrakt Twin-screw wet granulation (TWSG) is a promising continuous alternative of pharmaceutical wet granulation. One of its benefits is that the components dissolved in the granulation liquid are distributed homogeneously in the granules. This provides an elegant way to manufacture products with ultralow drug doses. Near-infrared (NIR) and Raman spectroscopy are well-established process analytical technology… További információ: In-line indirect concentration measurement of ultralow dose API during twin-screw wet granulation based on NIR and Raman spectroscopy
- Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments Absztrakt In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone… További információ: Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments
- Novel Piperazine Derivatives of Vindoline as Anticancer Agents Absztrakt A series of novel vindoline–piperazine conjugates were synthesized by coupling 6 N-substituted piperazine pharmacophores at positions 10 and 17 of Vinca alkaloid monomer vindoline through different types of linkers. The in vitro antiproliferative activity of the 17 new conjugates was investigated on 60 human tumor cell lines (NCI60). Nine compounds presented significant antiproliferative effects. The most potent… További információ: Novel Piperazine Derivatives of Vindoline as Anticancer Agents
- Furandicarboxylic Acid (FDCA): Electrosynthesis and Its Facile Recovery From Polyethylene Furanoate (PEF) via DepolymerizationAbsztrakt Replacing fossil fuels with renewable, bio-based alternatives is inevitable for the modern chemical industry, in line with the 12 principles of green chemistry. 2,5-Furandicarboxylic acid (FDCA) is a promising platform molecule that can be derived from 5-hydroxymethyl furfural (HMF) via sustainable electrochemical oxidation. Herein, we demonstrate TEMPO-mediated electrooxidation of HMF to FDCA in ElectraSyn… További információ: Furandicarboxylic Acid (FDCA): Electrosynthesis and Its Facile Recovery From Polyethylene Furanoate (PEF) via Depolymerization
- A silica-supported organocatalyst for polycarbonate methanolysis under mild and economic conditions Absztrakt In the pursuit of circular economies aimed at eliminating waste and pollution, chemical recycling emerges as a promising avenue for transforming plastics into monomers. This study addresses the need for economically viable and mild depolymerisation methods, focusing on poly(bisphenol A carbonate) (BPA-PC), an engineering plastic with the monomer bisphenol A (BPA), a known xenoestrogen. Improving BPA-PC… További információ: A silica-supported organocatalyst for polycarbonate methanolysis under mild and economic conditions
- Amide isomerization pathways: Electronic and structural background of protonation- and deprotonation-mediated cistrans interconversionsAbsztrakt The cis-trans isomerization of amide bonds leads to wide range of structural and functional changes in proteins and can easily be the rate-limiting step in folding. The trans isomer is thermodynamically more stable than the cis, nevertheless the cis form can play a role in biopolymers’ function. The molecular system of N-methylacetamide · 2H2O is complex enough to reveal energetics of the cis-trans isomerization at coupled… További információ: Amide isomerization pathways: Electronic and structural background of protonation- and deprotonation-mediated cistrans interconversions
- NMR-Chemical-Shift-Driven Protocol Reveals the Cofactor-Bound, Complete Structure of Dynamic Intermediates of the Catalytic Cycle of Oncogenic KRAS G12C Protein and the Significance of the Mg2+ IonAbsztrakt In this work, catalytically significant states of the oncogenic G12C variant of KRAS, those of Mg2+-free and Mg2+-bound GDP-loaded forms, have been determined using CS-Rosetta software and NMR-data-driven molecular dynamics simulations. There are several Mg2+-bound G12C KRAS/GDP structures deposited in the Protein Data Bank (PDB), so this system was used as a reference, while… További információ: NMR-Chemical-Shift-Driven Protocol Reveals the Cofactor-Bound, Complete Structure of Dynamic Intermediates of the Catalytic Cycle of Oncogenic KRAS G12C Protein and the Significance of the Mg2+ Ion
- Inhibitor Design Strategy for Myostatin: Dynamics and Interaction Networks Define the Affinity and Release Mechanisms of the Inhibited ComplexesAbsztrakt Myostatin, an important negative regulator of muscle mass, is a therapeutic target for muscle atrophic disorders such as muscular dystrophy. Thus, the inhibition of myostatin presents a strategy to treat these disorders. It has long been established that the myostatin prodomain is a strong inhibitor of the mature myostatin, and the minimum peptide of… További információ: Inhibitor Design Strategy for Myostatin: Dynamics and Interaction Networks Define the Affinity and Release Mechanisms of the Inhibited Complexes
- Acetyl group for proper protection of βsugaramino acids used in SPPSAbsztrakt The synthesis of D-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc-GlcAPC(Ac)-OH, β-SAAs consisting of only 4–5 synthetic steps. Their active ester and amide bond formation… További információ: Acetyl group for proper protection of βsugaramino acids used in SPPS
- Synthesis of small protein domains by automated flow chemistryAbsztrakt The most fundamental topological units of proteins are their autonomously folded domains. The rapid and reliable chemical synthesis of domains in the range of 5–10 kDa in size, remains a challenge. Their bacterial expression is cumbersome, especially when chemical changes, post-translational modifications or the incorporation of non-natural residues are involved. Here, we report an… További információ: Synthesis of small protein domains by automated flow chemistry
- Proteotranscriptomic Discrimination of Tumor and Normal Tissues in Renal Cell CarcinomaAbsztrakt Clear cell renal carcinoma is the most frequent type of kidney cancer, with an increasing incidence rate worldwide. In this research, we used a proteotranscriptomic approach to differentiate normal and tumor tissues in clear cell renal cell carcinoma (ccRCC). Using transcriptomic data of patients with malignant and paired normal tissue samples from gene array… További információ: Proteotranscriptomic Discrimination of Tumor and Normal Tissues in Renal Cell Carcinoma
- Substrate specificity of human chymotrypsin-like protease (CTRL) characterized by phage display-selected small-protein inhibitorsAbsztrakt Chymotrypsin-like protease (CTRL) is one of the four chymotrypsin isoforms expressed in the human exocrine pancreas. Human genetic and experimental evidence indicate that chymotrypsins B1, B2, and C (CTRB1, CTRB2 and CTRC) are important not only for protein digestion but also for protecting the pancreas against pancreatitis by degrading potentially harmful trypsinogen. CTRL has not been reported to play a similar role, possibly… További információ: Substrate specificity of human chymotrypsin-like protease (CTRL) characterized by phage display-selected small-protein inhibitors
- Complement inhibition can decrease the haemostatic response in a microvascular bleeding model at multiple levelsAbsztrakt Background: Haemostasis is a crucial process by which the body stops bleeding. It is achieved by the formation of a platelet plug, which is strengthened by formation of a fibrin mesh mediated by the coagulation cascade. In proinflammatory and prothrombotic conditions, multiple interactions of the complement system and the coagulation cascade are known to aggravate… További információ: Complement inhibition can decrease the haemostatic response in a microvascular bleeding model at multiple levels
- Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cellsAbsztrakt Therapy resistance has long been considered to occur through the selection of pre-existing clones equipped to survive and quickly regrow, or through the acquisition of mutations during chemotherapy. Here we show that following in vitro treatment by chemotherapy, epithelial breast cancer cells adopt a transient drug tolerant phenotype characterized by cell cycle arrest, epithelial-to-mesenchymal transition… További információ: Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cells
- Discovery and biocatalytic characterization of opine dehydrogenases by metagenome miningAbsztrakt Enzymatic processes play an increasing role in synthetic organic chemistry which requires the access to a broad and diverse set of enzymes. Metagenome mining is a valuable and efficient way to discover novel enzymes with unique properties for biotechnological applications. Here, we report the discovery and biocatalytic characterization of six novel metagenomic opine dehydrogenases… További információ: Discovery and biocatalytic characterization of opine dehydrogenases by metagenome mining
- Nanoformulation of lipase from Porcine pancreas by electrospinning as a novel alternative for enzyme-based per os therapiesAbsztrakt Pancreatic enzyme replacement therapy (PERT) treats pancreatic insufficiency, causing a lack of digestive enzymes due to pancreatic damage or dysfunction. However, traditional PERT faces challenges such as poor stability and limited efficiency of the enzymes. Lipase from Porcine pancreas (PpL) is commonly applied for PERT, however only classic formulas such as tablets or capsules produced from… További információ: Nanoformulation of lipase from Porcine pancreas by electrospinning as a novel alternative for enzyme-based per os therapies
- Combined Nanofibrous Face Mask: Co-Formulation of Lipases and Antibiotic Agent by Electrospinning TechniqueAbsztrakt The application of enzyme-based therapies has received significant attention in modern drug development. Lipases are one of the most versatile enzymes that can be used as therapeutic agents in basic skin care and medical treatment related to excessive sebum production, acne, and inflammation. The traditional formulations available for skin treatment, such as creams, ointments… További információ: Combined Nanofibrous Face Mask: Co-Formulation of Lipases and Antibiotic Agent by Electrospinning Technique
- Reusable Glucose-Based Crown Ethers Anchored to PVC – CopyEnantioseparation of P-Stereogenic 1-Adamantyl Arylthiophosphonates and Their Stereospecific Transformation to 1-Adamantyl Aryl-H-phosphinatesAbsztrakt A focused library of 1-adamantyl arylthiophosphonates was prepared in racemic form. An enantioseparation method was developed for P-stereogenic thiophosphonates using (S)-1-phenylethylamine as the resolving agent. Under optimized conditions, three out of the five arylthiophosphonates were prepared in enantiopure form (ee > 99%). The subsequent desulfurization of optically active arylthiophosphonates gave the corresponding H-phosphinates without significant erosion of… További információ: Reusable Glucose-Based Crown Ethers Anchored to PVC – CopyEnantioseparation of P-Stereogenic 1-Adamantyl Arylthiophosphonates and Their Stereospecific Transformation to 1-Adamantyl Aryl-H-phosphinates
- Reusable Glucose-Based Crown Ethers Anchored to PVCAbsztrakt The recovery and reuse of the enantioselective catalysts produced by tedious work are important not only from the perspective of green chemistry, but also from the point of view of productivity. Some of the carbohydrate-based crown ethers prepared in our research group were able to generate significant asymmetric induction in certain cases. However, they… További információ: Reusable Glucose-Based Crown Ethers Anchored to PVC
- MeSesamol, a bio-based and versatile polar aprotic solvent for organic synthesis and depolymerizationAbsztrakt Applications of polar aprotic solvents are inevitable in the chemical industry, but few nonhazardous alternatives are available. Herein, we propose methyl sesamol (MeSesamol) as a promising new bio-based alternative for polar aprotic solvents and demonstrate its versatile applications. MeSesamol was derived from natural resources using environmentally friendly and facile procedures, such as methylation using… További információ: MeSesamol, a bio-based and versatile polar aprotic solvent for organic synthesis and depolymerization
- Synthesis and anticancer activity of phosphinoylated and phosphonoylated N-heterocycles obtained by the microwave-assisted palladium acetate-catalyzed Hirao reactionAbsztrakt A literature survey showed that different derivatives with the 9-phenyl-9H-carbazole or the dihydroindoline scaffold may be of biological activity including cytotoxic effect. Driven by this experience, P-functionalized derivatives of these N-heterocycles were synthesized. Three N-heterocycles, 9-(4-bromophenyl)-9H-carbazole, 3-bromo-9-phenyl-9H-carbazole and 1-(5-bromoindolin-1-yl)ethan-1-one, were coupled with dialkyl phosphites and diarylphosphine oxides using Pd(OAc)2 (10 %) as the catalyst precursor and triethylamine as… További információ: Synthesis and anticancer activity of phosphinoylated and phosphonoylated N-heterocycles obtained by the microwave-assisted palladium acetate-catalyzed Hirao reaction
- Cytotoxyc activity of α-aminophosphonic derivatives coming from the tandem Kabachnik–Fields reaction and acylationAbsztrakt Encouraged by the significant cytotoxic activity of simple α-aminophosphonates, a molecular library comprising phosphonoylmethyl- and phosphinoylmethyl-α-aminophosphonates, a tris derivative, and N-acylated species was established. The promising aminophosphonate derivatives were subjected to a comparative structure–activity analysis. We evaluated 12 new aminophosphonate derivatives on tumor cell cultures of different tissue origins (skin, lung, breast, and prostate). Several… További információ: Cytotoxyc activity of α-aminophosphonic derivatives coming from the tandem Kabachnik–Fields reaction and acylation
- Synthesis and In Vitro Anticancer Evaluation of Flavone—1,2,3-Triazole HybridsAbsztrakt Hybrid compounds of flavones, namely chrysin and kaempferol, and substituted 1,2,3-triazole derivatives, were synthesized by click reaction of the intermediate O-propargyl derivatives. 4-Fluoro- and 4-nitrobenzyl-1,2,3-triazole-containing hybrid molecules were prepared. The mono- and bis-coupled hybrids were investigated on 60 cell lines of 9 common cancer types (NCI60) in vitro as antitumor agents. Some of them proved… További információ: Synthesis and In Vitro Anticancer Evaluation of Flavone—1,2,3-Triazole Hybrids
- In-line particle size measurement during granule fluidization using convolutional neural network-aided process imagingAbsztrakt This paper presents a machine learning-based image analysis method to monitor the particle size distribution of fluidized granules. The key components of the direct imaging system are a rigid fiber-optic endoscope, a light source and a high-speed camera, which allow for real-time monitoring of the granules. The system was implemented into a custom-made 3D-printed… További információ: In-line particle size measurement during granule fluidization using convolutional neural network-aided process imaging
- Development and Comparison of Alternative Methods for the Purification of Adalimumab Directly from Harvested Cell Culture FluidAbsztrakt Research background. Protein A affinity chromatography is a well-established method currently used in the pharmaceutical industry. However, the high costs usually associated with chromatographic separation of protein A and the difficulties in continuous operation make the investigation of alternative purification methods very important. Experimental approach. In this study, extraction/back-extraction and precipitation/dissolution methods were developed and optimised. They… További információ: Development and Comparison of Alternative Methods for the Purification of Adalimumab Directly from Harvested Cell Culture Fluid
- Comparing the Performance of Raman and Near-Infrared Imaging in the Prediction of the In Vitro Dissolution Profile of Extended-Release Tablets Based on Artificial Neural NetworksAbsztrakt In this work, the performance of two fast chemical imaging techniques, Raman and near-infrared (NIR) imaging is compared by utilizing these methods to predict the rate of drug release from sustained-release tablets. Sustained release is provided by adding hydroxypropyl methylcellulose (HPMC), as its concentration and particle size determine the dissolution rate of the drug.… További információ: Comparing the Performance of Raman and Near-Infrared Imaging in the Prediction of the In Vitro Dissolution Profile of Extended-Release Tablets Based on Artificial Neural Networks
- Application of a Receptor-Binding-Domain-Based Simple Immunoassay for Assessing Humoral Immunity against Emerging SARS-CoV-2 Virus VariantAbsztrakt We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of the His-tagged RBD proteins of the virus variants were stably engineered into HEK cells secreting the protein into the supernatant, and RBD purification was performed by Ni-chromatography and buffer exchange by membrane… További információ: Application of a Receptor-Binding-Domain-Based Simple Immunoassay for Assessing Humoral Immunity against Emerging SARS-CoV-2 Virus Variant
- Development of a Large-Scale Pathogen Screening Test for the Biosafety Evaluation of Canine Mesenchymal Stem CellsAbsztrakt Background The action of mesenchymal stem cells (MSCs) is the subject of intense research in the field of regenerative medicine, including their potential use in companion animals, such as dogs. To ensure the safety of canine MSC batches for their application in regenerative medicine, a quality control test must be conducted in accordance with… További információ: Development of a Large-Scale Pathogen Screening Test for the Biosafety Evaluation of Canine Mesenchymal Stem Cells
- Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapyAbsztrakt DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the piggyBac and Sleeping Beauty systems—the only DNA transposons currently employed in clinical trials—during therapeutic intervention, we treated the mouse model of tyrosinemia type I with liver-targeted gene delivery using both transposon vectors. For… További információ: Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy
- The antidepressant effect of short- and long-term zinc exposition is partly mediated by P2X7 receptors in male miceAbsztrakt Background: As a member of the purinergic receptor family, divalent cation-regulated ionotropic P2X7 (P2rx7) plays a role in the pathophysiology of psychiatric disorders. This study aimed to investigate whether the effects of acute zinc administration and long-term zinc deprivation on depression-like behaviors in mice are mediated by P2X7 receptors. Methods: The antidepressant-like effect of elevated zinc… További információ: The antidepressant effect of short- and long-term zinc exposition is partly mediated by P2X7 receptors in male mice
- Editorial: Purinergic signalling in the central nervous system and its pharmacological importance in neurological and psychiatric illnessesAbsztrakt This Research Topic aims to honour the 80th birthday of Professor Peter Illes, who is a member of the European Academy of Sciences, the founder/first president of the German Purine Club, and honorary president of the Chinese Purine Club. His connections with China explain that a number of Chinese scientists contributed with articles to… További információ: Editorial: Purinergic signalling in the central nervous system and its pharmacological importance in neurological and psychiatric illnesses
- SH2db, an information system for the SH2 domain Absztrakt SH2 domains are key mediators of phosphotyrosine-based signalling, and therapeutic targets for diverse, mostly oncological, disease indications. They have a highly conserved structure with a central beta sheet that divides the binding surface of the protein into two main pockets, responsible for phosphotyrosine binding (pY pocket) and substrate specificity (pY + 3 pocket). In recent years,… További információ: SH2db, an information system for the SH2 domain
- Covalent fragment approaches targeting non-cysteine residuesAbsztrakt Covalent fragment approaches combine advantages of covalent binders and fragment-based drug discovery (FBDD) for target identification and validation. Although early applications focused mostly on cysteine labeling, the chemistries of available warheads that target other orthosteric and allosteric protein nucleophiles has recently been extended. The range of different warheads and labeling chemistries provide unique opportunities… További információ: Covalent fragment approaches targeting non-cysteine residues
- Activation-Free Sulfonyl Fluoride Probes for Fragment ScreeningAbsztrakt SuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Accordingly, sulfonyl fluorides label multiple nucleophilic amino acid residues, making these reagents popular in both chemical biology and medicinal chemistry applications. The reactivity of sulfonyl fluorides nominates this warhead chemotype as a candidate for an external,… További információ: Activation-Free Sulfonyl Fluoride Probes for Fragment Screening
- Effective Synthesis, Development and Application of a Highly Fluorescent Cyanine Dye for Antibody Conjugation and Microscopy ImagingAbsztrakt An asymmetric cyanine-type fluorescent dye was designed and synthesized via a versatile, multi-step process, aiming to conjugate with an Her2+ receptor specific antibody by an azide–alkyne click reaction. The aromaticity and the excitation and relaxation energetics of the fluorophore were characterized by computational methods. The synthesized dye exhibited excellent fluorescence properties for confocal microscopy, offering efficient… További információ: Effective Synthesis, Development and Application of a Highly Fluorescent Cyanine Dye for Antibody Conjugation and Microscopy Imaging
- Synaptic alterations and neuronal firing in human epileptic neocortical excitatory networksAbsztrakt Epilepsy is a prevalent neurological condition, with underlying neuronal mechanisms involving hyperexcitability and hypersynchrony. Imbalance between excitatory and inhibitory circuits, as well as histological reorganization are relatively well-documented in animal models or even in the human hippocampus, but less is known about human neocortical epileptic activity. Our knowledge about changes in the excitatory signaling… További információ: Synaptic alterations and neuronal firing in human epileptic neocortical excitatory networks
- Seeing beyond the spikes: reconstructing the complete spatiotemporal membrane potential distribution from paired intra- and extracellular recordingsAbsztrakt Although electrophysiologists have been recording intracellular neural activity routinely ever since the ground-breaking work of Hodgkin and Huxley, and extracellular multichannel electrodes have also been used frequently and extensively, a practical experimental method to track changes in membrane potential along a complete single neuron is still lacking. Instead of obtaining multiple intracellular measurements on… További információ: Seeing beyond the spikes: reconstructing the complete spatiotemporal membrane potential distribution from paired intra- and extracellular recordings
- Thermal neuromodulation using pulsed and continuous infrared illumination in a penicillin‐induced acute epilepsy modeAbsztrakt Infrared neuromodulation (INM) is a promising neuromodulation tool that utilizes pulsed or continuous-wave near-infrared (NIR) laser light to produce an elevation of the background temperature of the neural tissue. The INM-based cortical heating has been proven as an effective modality to induce changes in neuronal activities. In this paper, we investigate the effect of… További információ: Thermal neuromodulation using pulsed and continuous infrared illumination in a penicillin‐induced acute epilepsy mode
- Studying the Association of TKS4 and CD2AP Scaffold Proteins and Their Implications in the Partial Epithelial–Mesenchymal Transition (EMT) Process Absztrakt Colon cancer is a leading cause of death worldwide. Identification of new molecular factors governing the invasiveness of colon cancer holds promise in developing screening and targeted therapeutic methods. The Tyrosine Kinase Substrate with four SH3 domains (TKS4) and the CD2-associated protein (CD2AP) have previously been linked to dynamic actin assembly related processes and… További információ: Studying the Association of TKS4 and CD2AP Scaffold Proteins and Their Implications in the Partial Epithelial–Mesenchymal Transition (EMT) Process
- Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor DAbsztrakt Complement factor D (FD) is a serine protease present predominantly in the active form in circulation. It is synthesized as a zymogen (pro-FD), but it is continuously converted to FD by circulating active MASP-3. FD is a unique, self-inhibited protease. It has an extremely low activity toward free factor B (FB), while it is… További információ: Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor D
- Hydrogen peroxide production by epidermal dual oxidase 1 regulates nociceptive sensory signals Absztrakt Keratinocytes of the mammalian skin provide not only mechanical protection for the tissues, but also transmit mechanical, chemical, and thermal stimuli from the external environment to the sensory nerve terminals. Sensory nerve fibers penetrate the epidermal basement membrane and function in the tight intercellular space among keratinocytes. Here we show that epidermal keratinocytes produce hydrogen peroxide upon the activation of the NADPH… További információ: Hydrogen peroxide production by epidermal dual oxidase 1 regulates nociceptive sensory signals
- Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in miceAbsztrakt The Transient Receptor Potential Vanilloid 1 (TRPV1) non-selective cation channel predominantly expressed in primary sensory neurons of the dorsal root and trigeminal ganglia mediates pain and neurogenic inflammation. TRPV1 mRNA and immunoreactivity were described in the central nervous system (CNS), but its precise expression pattern and function have not been clarified. Here we investigated Trpv1 mRNA… További információ: Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice
- Hemokinin-1 induces transcriptomic alterations in pain-related signaling processes in rat primary sensory neurons independent of NK1 tachykinin receptor activationAbsztrakt The tachykinin hemokinin-1 (HK-1) is involved in immunological processes, inflammation, and pain. Although the neurokinin 1 receptor (NK1R) is described as its main target, several effects are mediated by currently unidentified receptor(s). The role of HK-1 in pain is controversial, depending on the involvement of peripheral and central sensitization mechanisms in different models. We… További információ: Hemokinin-1 induces transcriptomic alterations in pain-related signaling processes in rat primary sensory neurons independent of NK1 tachykinin receptor activation
- NATURE GENETICS 55 : 11 pp. 1820-1830. , 11 p. (2023)Absztrakt Objectives It has previously been shown that the peptide (34Pro,35Phe)CGRP27–37 is a potent calcitonin gene-related peptide, CGRP receptor antagonist, and in this project we aimed to improve the antagonist potency through the structural modification of truncated C-terminal CGRP peptides. Methods Six peptide analogues were synthesized and the anti-CGRP activity confirmed using both in vitro and in vivo studies. Key… További információ: NATURE GENETICS 55 : 11 pp. 1820-1830. , 11 p. (2023)
- An atlas of genetic determinants of forearm fracture Absztrakt Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm… További információ: An atlas of genetic determinants of forearm fracture
- Hemokinin1 is a mediator of chronic restraint stressinduced painAbsztrakt The Tac4 gene-derived hemokinin-1 (HK-1) binds to the NK1 receptor, similarly to Substance P, and plays a role in acute stress reactions and pain transmission in mice. Here we investigated Tac4 mRNA expression in stress and pain-related regions and its involvement in chronic restraint stress-evoked behavioral changes and pain using Tac4 gene-deleted (Tac4-/-) mice compared to C57Bl/6 wildtypes… További információ: Hemokinin1 is a mediator of chronic restraint stressinduced pain
- Supporting grant reviewers through the scientometric ranking of applicants Absztrakt Introduction Comparing the scientific output of different researchers applying for a grant is a tedious work. In Hungary, to help reviewers to rapidly rank the scientific productivity of a researcher, a grant decision support tool was established and is available at www.scientometrics.org. In the present study, our goal was to assess the impact of this… További információ: Supporting grant reviewers through the scientometric ranking of applicants
- Novel peptide calcitonin gene-related peptide antagonists for migraine therapyAbsztrakt Objectives It has previously been shown that the peptide (34Pro,35Phe)CGRP27–37 is a potent calcitonin gene-related peptide, CGRP receptor antagonist, and in this project we aimed to improve the antagonist potency through the structural modification of truncated C-terminal CGRP peptides. Methods Six peptide analogues were synthesized and the anti-CGRP activity confirmed using both in vitro and in vivo studies. Key… További információ: Novel peptide calcitonin gene-related peptide antagonists for migraine therapy
- Spatial predictors of immunotherapy response in triple-negative breast cancerAbsztrakt Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell–cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately… További információ: Spatial predictors of immunotherapy response in triple-negative breast cancer
- miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast CancerAbsztrakt Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel… További információ: miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer
- Analysis of a large cohort of pancreatic cancer transcriptomic profiles to reveal the strongest prognostic factors Absztrakt Pancreatic adenocarcinoma remains a leading cause of cancer-related deaths. In order to develop appropriate therapeutic and prognostic tools, a comprehensive mapping of the tumor’s molecular abnormalities is essential. Here, our aim was to integrate available transcriptomic data to uncover genes whose elevated expression is simultaneously linked to cancer pathogenesis and inferior survival. A comprehensive… További információ: Analysis of a large cohort of pancreatic cancer transcriptomic profiles to reveal the strongest prognostic factors
- Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer Absztrakt Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with clinical features of high metastatic potential, susceptibility to relapse, and poor prognosis. TNBC lacks the expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is characterized by genomic and transcriptional heterogeneity and… További információ: Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer
- Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumorsAbsztrakt Immune-checkpoint inhibitors show promising effects in the treatment of multiple tumor types. Biomarkers are biological indicators used to select patients for a systemic anticancer treatment, but there are only a few clinically useful biomarkers such as PD-L1 expression and tumor mutational burden, which can be used to predict immunotherapy response. In this study, we… További információ: Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors
- Relationship between bibliometric indicators and university ranking positionsAbsztrakt A growing interest for demonstrating prestige and status of higher education institutions has spurred the establishment of several international ranking systems. A major percentage of these rankings include parameters related to scientific productivity. Here, we examined the differences between diverse rankings as well as correlation with bibliometric parameters and disciplines for the top universities.… További információ: Relationship between bibliometric indicators and university ranking positions
- Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL. Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL.Absztrakt Translesion DNA synthesis (TLS) facilitates replication over damaged or difficult-to-replicate templates by employing specialized DNA polymerases. We investigate the effect on spontaneous mutagenesis of three main TLS control mechanisms: REV1 and PCNA ubiquitylation that recruit TLS polymerases and PRIMPOL that creates post-replicative gaps. Using whole-genome sequencing of cultured human RPE-1 cell clones, we find… További információ: Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL. Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL.
- P2 receptor-mediated signaling in physiological and pathological brain developmentAbsztrakt The purinergic pathway mediates both pro-inflammatory and anti-inflammatory responses, whereas the breakdown of adenosine triphosphate (ATP) is in a critical equilibrium. Under physiological conditions, extracellular ATP is maintained at a nanomolar concentration. Whether released into the medium following tissue damage, inflammation, or hypoxia, ATP is considered a clear indicator of cell damage and a… További információ: P2 receptor-mediated signaling in physiological and pathological brain development
- DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesisAbsztrakt DNA mismatch repair (MMR) corrects mismatched DNA bases arising from multiple sources including polymerase errors and base damage. By detecting spontaneous mutagenesis using whole genome sequencing of cultured MMR deficient human cell lines, we show that a primary role of MMR is the repair of oxygen-induced mismatches. We found an approximately twofold higher mutation… További információ: DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis
- Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formationAbsztrakt A large group of hormones are stored as amyloid fibrils in acidic secretion vesicles before they are released into the bloodstream and readopt their functional state. Here, we identify an evolutionarily conserved hexapeptide sequence as the major aggregation-prone region (APR) of gastrointestinal peptides of the glucagon family: xFxxWL. We determine nine polymorphic crystal structures… További információ: Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation
- Improved acylation of pseudoproline: masked threonine in flow peptide chemistryAbsztrakt Pseudoproline derivatives are incorporated into polypeptides as aggregation disrupters during synthesis, from which the unmodified side chains can be recovered during the final step (resin cleavage). However, direct coupling to pseudoproline is challenging and thus dipeptides of pseudoproline, Fmoc-Xaa-Yaa(ΨMe,Mepro)-OH, are traditionally introduced, which requires the entire library of Fmoc-Xaa-Thr(ΨMe,Mepro)-OH in stock, making this approach… További információ: Improved acylation of pseudoproline: masked threonine in flow peptide chemistry
- A novel fusion protein system for the production of nanobodies and the SARS-CoV-2 spike RBD in a bacterial systemAbsztrakt Antibodies are key proteins of the immune system, and they are widely used for both research and theragnostic applications. Among them, camelid immunoglobulins (IgG) differ from the canonical human IgG molecules, as their light chains are completely missing; thus, they have only variable domains on their heavy chains (VHHs). A single VHH domain, often… További információ: A novel fusion protein system for the production of nanobodies and the SARS-CoV-2 spike RBD in a bacterial system
- IL-1 mediates chronic stress-induced hyperalgesia accompanied by microglia and astroglia morphological changes in pain-related brain regions in miceAbsztrakt Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model. Female and… További információ: IL-1 mediates chronic stress-induced hyperalgesia accompanied by microglia and astroglia morphological changes in pain-related brain regions in mice
- The regulatory role of the CD2AP/TKS4 interaction in EMT and its potential as a biomarker for colon cancer Absztrakt Background Colon cancer is a leading cause of death worldwide. Although several biomarkers have been developed, more sensitive and specific methods are needed for its early detection. TKS4 and CD2AP scaffold proteins have been already linked to dynamic actin assembly-related processes, such as colon cancer cell migration, although their co-instructive role during tumour-formation remains unknown.… További információ: The regulatory role of the CD2AP/TKS4 interaction in EMT and its potential as a biomarker for colon cancer
- Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer CellsAbsztrakt Multidrug resistance (MDR) in cancer is one of the major obstacles of chemotherapy. We have recently identified a series of 8-hydroxyquinoline Mannich base derivatives with MDR-selective toxicity, however with limited solubility. In this work, a novel 5-nitro-8-hydroxyquinoline-proline hybrid and its Rh(η5-C5Me5) and Ru(η6–p-cymene) complexes with excellent aqueous solubility were developed, characterized, and tested against… További információ: Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer Cells
- Safe and Efficient Continuous-Flow Synthesis and Batchwise Hydrolysis of Ethyl 5-Acetyl-1H-pyrazole-3-carboxylate: A Key Synthon of Darolutamide Absztrakt A safe and metal-free process using ethyl glycinate hydrochloride as the starting material has been developed for the preparation of ethyl 5-acetyl-1H-pyrazole-3-carboxylate, a key intermediate for the synthesis of potential blockbuster drug substance darolutamide. In the key step, the toxic and explosive intermediate, ethyl diazoacetate was generated and used in situ. Reaction parameters were optimized… További információ: Safe and Efficient Continuous-Flow Synthesis and Batchwise Hydrolysis of Ethyl 5-Acetyl-1H-pyrazole-3-carboxylate: A Key Synthon of Darolutamide
- Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency.Absztrakt G12C mutant KRas is considered druggable by allele-specific covalent inhibitors due to the nucleophilic character of the oncogenic mutant cysteine at position 12. Discovery of these inhibitors requires the optimization of both covalent and noncovalent interactions. Here, we report covalent fragment screening of our electrophilic fragment library of diverse non-covalent scaffolds equipped with 40 different electrophilic… További információ: Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency.
- The triple function of the capsaicin-sensitive sensory neurons: In memoriam János SzolcsányiAbsztrakt This paper is dedicated to the memory of János Szolcsányi (1938–2018), an outstanding Hungarian scientist. Among analgesics that act on pain receptors, he identified capsaicin as a selective lead molecule. He studied the application of capsaicin and revealed several physiological (pain, thermoregulation) and pathophysiological (inflammation, gastric ulcer) mechanisms. He discovered a new neuroregulatory system… További információ: The triple function of the capsaicin-sensitive sensory neurons: In memoriam János Szolcsányi
- Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4) Absztrakt Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn… További információ: Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4)
- The heptapeptide somatostatin analogue TT-232 exerts analgesic and anti-inflammatory actions via SST4 receptor activation: In silico, in vitro and in vivo evidence in mice Absztrakt Since the conventional and adjuvant analgesics have limited effectiveness frequently accompanied by serious side effects, development of novel, potent pain killers for chronic neuropathic and inflammatory pain conditions is a big challenge. Somatostatin (SS) regulates endocrine, vascular, immune and neuronal functions, cell proliferation through 5 Gi protein-coupled receptors (SST1-SST5). SS released from the capsaicin-sensitive peptidergic… További információ: The heptapeptide somatostatin analogue TT-232 exerts analgesic and anti-inflammatory actions via SST4 receptor activation: In silico, in vitro and in vivo evidence in mice
- New Transcriptomic Biomarkers of 5-Fluorouracil ResistanceAbsztrakt The overall response rate to fluoropyrimidine monotherapy in colorectal cancer (CRC) is limited. Transcriptomic datasets of CRC patients treated with 5-fluorouracil (5FU) could assist in the identification of clinically useful biomarkers. In this research, we aimed to analyze transcriptomic cohorts of 5FU-treated cell lines to uncover new predictive biomarker candidates and to validate the… További információ: New Transcriptomic Biomarkers of 5-Fluorouracil Resistance
- Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer CellsAbsztrakt The ever-increasing number of recording sites of silicon-based probes imposes a great challenge for detecting and evaluating single-unit activities in an accurate and efficient manner. Currently separate solutions are available for high precision offline evaluation and separate solutions for embedded systems where computational resources are more limited. We propose a deep learning-based spike sorting system, that utilizes both… További információ: Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells
- Edge computing on TPU for brain implant signal analysisAbsztrakt The ever-increasing number of recording sites of silicon-based probes imposes a great challenge for detecting and evaluating single-unit activities in an accurate and efficient manner. Currently separate solutions are available for high precision offline evaluation and separate solutions for embedded systems where computational resources are more limited. We propose a deep learning-based spike sorting system, that utilizes both… További információ: Edge computing on TPU for brain implant signal analysis
- The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK PathwayAbsztrakt Ferroptosis represents a typical process that has dual functions in cell fate decisions since the reduction and/or inhibition of ferroptosis is desirable for the therapies of diseases such as neurological disorders, localized ischemia-reperfusion, kidney injury, and hematological diseases, while the enhanced ferroptosis of cancer cells may benefit patients with cancer. The JNK pathway also… További információ: The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway
- Friend or Foe: The Relativity of (Anti)oxidative Agents and PathwaysAbsztrakt An element, iron, a process, the generation of reactive oxygen species (ROS), and a molecule, ascorbate, were chosen in our study to show their dual functions and their role in cell fate decision. Iron is a critical component of numerous proteins involved in metabolism and detoxification. On the other hand, excessive amounts of free… További információ: Friend or Foe: The Relativity of (Anti)oxidative Agents and Pathways
- A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex. Absztrakt The structure of porcine AAP (pAAP) in a covalently bound complex with meropenem was determined by cryo-EM to 2.1 Å resolution, showing the mammalian serine-protease inhibited by a carbapenem antibiotic. AAP is a modulator of the ubiquitin-proteasome degradation system and the site of a drug–drug interaction between the widely used antipsychotic, valproate and carbapenems.… További információ: A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex.
- A Novel Cell-Based Model for a Rare Disease: The Tks4-KO Human Embryonic Stem Cell Line as a Frank-Ter Haar Syndrome Model System ZEEBONE, Y. Y.; KOVÁCS, M.; BÓTA, B.; ZDENĚK, V.; TAUBNER, T.; HALAS, V. Dietary fumonisin may compromise the nutritive value of feed and distort copper and zinc digestibility and retention in weaned piglets JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION 107 : 2 pp. 504-517. Paper: 13724 , 14 p. (2023) Munkacsoport: Élelmiszerbiztonság
- Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling ZEEBONE, YARSMIN YUNUS ; BÓTA, BRIGITTA; HALAS, VERONIKA; LIBISCH, BALÁZS; OLASZ, FERENC; PAPP, PÉTER; KERESZTÉNY, TIBOR; GERŐCS, ANNAMÁRIA; ALI, OMERALFAROUG; KOVÁCS, MELINDA ET AL. Gut-Faecal Microbial and Health-Marker Response to Dietary Fumonisins in Weaned Pigs TOXINS 15 : 5 Paper: 328 , 18 p. (2023) Munkacsoport: Élelmiszerbiztonság
- A Comprehensive Evaluation of the Performance of Prediction Algorithms on Clinically Relevant Missense Variants. ALI, OMERALFAROUG ; SZABÓ, ANDRÁS Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24 : 21 Paper: 15693 , 64 p. (2023) Munkacsoport: Élelmiszerbiztonság
- Cryo-EM structure of acylpeptide hydrolase reveals substrate selection by multimerization and a multistate serine-protease triad. ALI, OMERALFAROUG ; SZABÓ, ANDRÁS Fumonisin Distorts the Cellular Membrane Lipid Profile: A Mechanistic Insight TOXICOLOGY 506 Paper: 153860 (2024) Munkacsoport: Élelmiszerbiztonság
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