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… Read more: 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… Read more: 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… Read more: 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… Read more: 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… Read more: 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 4.0
  Absztrakt 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… Read more: Explainable deep recurrent neural networks for the batch analysis of a pharmaceutical tableting process in the spirit of Pharma 4.0
• UV–VIS imaging-based investigation of API concentration fluctuation caused by the sticking behaviour of pharmaceutical powder blends 
  Absztrakt Surface powder sticking in pharmaceutical mixing vessels poses a risk to the uniformity and quality of drug formulations. This study explores methods for evaluating the amount of pharmaceutical powder mixtures adhering to the metallic surfaces. Binary powder blends consisting of amlodipine and microcrystalline cellulose (MCC) were used to investigate the effect of the mixing order on the adherence… Read more: UV–VIS imaging-based investigation of API concentration fluctuation caused by the sticking behaviour of pharmaceutical powder blends 
• 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… Read more: 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… Read more: 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… Read more: 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… Read more: 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… Read more: Novel Piperazine Derivatives of Vindoline as Anticancer Agents 
• Furandicarboxylic Acid (FDCA): Electrosynthesis and Its Facile Recovery From Polyethylene Furanoate (PEF) via Depolymerization
  Absztrakt 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… Read more: 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… Read more: A silica-supported organocatalyst for polycarbonate methanolysis under mild and economic conditions 
• Covalent immobilization of an enzyme on a layered silicate to catalyze the self-degradation of PCL 
  Absztrakt A lipase from Burkholderia cepacia was covalently linked to the surface of Laponite® layered silicate after its activation with glycidoxy moieties on two different routes. The modified silicate was embedded into poly-ε-caprolacton (PCL) for the preparation of self-degradable biopolymers. The activated silicate was characterized by thermogravimetry (TGA) and infrared spectroscopy (FTIR), the location of the linker… Read more: Covalent immobilization of an enzyme on a layered silicate to catalyze the self-degradation of PCL 
• Immobilization of human tyrosine hydroxylase onto magnetic nanoparticles – A novel formulation of a therapeutic enzyme 
  Absztrakt Human tyrosine hydroxylase (hTH) has key role in the production of catecholamine neurotransmitters. The structure, function and regulation of hTH has been extensively researched area and the possibility of enzyme replacement therapy (ERT) involving hTH through nanocarriers has been raised as well. However, our understanding on how hTH may interact with nanocarriers is still lacking. In this work, we attempted to investigate… Read more: Immobilization of human tyrosine hydroxylase onto magnetic nanoparticles – A novel formulation of a therapeutic enzyme 
• N-Functionalization of β-aminophosphonates: cytotoxic effects of the new derivatives 
  Absztrakt β-Aminophosphonates obtained by the Michael addition of primary amines to the double bond of diethyl vinylphosphonate proved to be suitable starting materials (amine components) in the Kabachnik–Fields reaction with formaldehyde and dialkyl phosphites or secondary phosphine oxides to afford N-phosphonylmethyl- and N-phosphinoylmethyl-β-aminophosphonates. On the other hand, the starting aminophosphonates were modified by N-acylation using acid chlorides. The N-acyl… Read more: N-Functionalization of β-aminophosphonates: cytotoxic effects of the new derivatives 
• Synthetic and mechanistic studies of the multicomponent reaction of 2-(phenylethynyl)benzaldehyde, primary amine and diphenylphosphine oxide 
  Absztrakt The synthesis of potentially biologically active phosphinoyl functionalized N-(2-(phenylethynyl)benzyl)amine, 1,2-dihydro-isoquinoline and 2H-isoindoline via a multicomponent reaction of 2-(phenylethynyl)benzaldehyde, amine and diphenylphosphine oxide is described for the first time. Depending on the catalyst and the conditions used, the same one-pot three-component reaction can selectively lead to the mentioned three different products. The formation of the cyclic products was… Read more: Synthetic and mechanistic studies of the multicomponent reaction of 2-(phenylethynyl)benzaldehyde, primary amine and diphenylphosphine oxide 
• Flow Synthesis of Capsaicin and Capsaicinoid Analogues 
  Absztrakt Capsaicin and its derivatives are special alkaloids responsible for the pungency of spicy pepper fruits and are mainly used in the pharmaceutical, food, and cosmetic industries. Until now, only batch syntheses of capsaicin and some of its analogues have been described; the drawbacks, such as long reaction time, variable yields, and chemical waste emission,… Read more: Flow Synthesis of Capsaicin and Capsaicinoid Analogues 
• Influence of Trp-Cage on the Function and Stability of GLP-1R Agonist Exenatide Derivatives 
  Absztrakt Exenatide (Ex4), a GLP-1 incretin mimetic polypeptide, is an effective therapeutic agent against diabetes and obesity. We highlight the indirect role of Ex4’s structure-stabilizing Trp-cage (Tc) motif in governing GLP-1 receptor (GLP-1R) signal transduction. We use various Ex4 derivatives to explore how Tc compactness influences thermal stability, aggregation, enhancement of insulin secretion, and GLP-1R… Read more: Influence of Trp-Cage on the Function and Stability of GLP-1R Agonist Exenatide Derivatives 
• LoCoHD: a metric for comparing local environments of proteins 
  Absztrakt Protein folds and the local environments they create can be compared using a variety of differently designed measures, such as the root mean squared deviation, the global distance test, the template modeling score or the local distance difference test. Although these measures have proven to be useful for a variety of tasks, each fails… Read more: LoCoHD: a metric for comparing local environments of proteins 
• Synthesis of small protein domains by automated flow chemistry 
  Absztrakt 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… Read more: Synthesis of small protein domains by automated flow chemistry 
• Opening Amyloid-Windows to the secondary structure of proteins: The amyloidogenecity increases tenfold inside beta-sheets 
  Absztrakt Methods from artificial intelligence (AI), in general, and machine learning, in particular, have kept conquering new territories in numerous areas of science. Most of the applications of these techniques are restricted to the classification of large data sets, but new scientific knowledge can seldom be inferred from these tools. Here we show that an… Read more: Opening Amyloid-Windows to the secondary structure of proteins: The amyloidogenecity increases tenfold inside beta-sheets 
• Unveiling the Oxazolidine Character of Pseudoproline Derivatives by Automated Flow Peptide Chemistry 
  Absztrakt Pseudoproline derivatives such as Thr(ΨPro)-OH are commonly used in peptide synthesis to reduce the likelihood of peptide aggregation and to prevent aspartimide (Asi) formation during the synthesis process. In this study, we investigate notable by-products such as aspartimide formation and an imine derivative of the Thr(ΨPro) moiety observed in flow peptide chemistry synthesis. To… Read more: Unveiling the Oxazolidine Character of Pseudoproline Derivatives by Automated Flow Peptide Chemistry 
• Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology 
  Absztrakt Aggregation-prone-motifs (APRs) of proteins are short segments, which – as isolated peptides – form diverse amyloid-like crystals. We introduce two APRs – designed variants of the incretin mimetic Exendin-4 – that both display crystal-phase polymorphism. Crystallographic and spectroscopic analysis revealed that a single amino-acid substitution can greatly reduce topological variability: while LYIQWL can form… Read more: Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology 
• Cyclodextrin derivatives decrease Transient Receptor Potential Vanilloid 1 and Ankyrin 1 ion channel activation via altering the surrounding membrane microenvironment by cholesterol depletion –  
  Absztrakt Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) are nonselective cation channels expressed in primary sensory neurons and several other non-neuronal structures such as immune cells, keratinocytes, and vascular smooth muscle cells. They play important roles in nociception, pain processing and their chanellopathies are associated with the development of several pathological conditions.… Read more: Cyclodextrin derivatives decrease Transient Receptor Potential Vanilloid 1 and Ankyrin 1 ion channel activation via altering the surrounding membrane microenvironment by cholesterol depletion –  
• Polymer-based laminar probes with an ultra-long flexible spiral-shaped cable for in vivo neural recordings, Sensors and Actuators B: Chemical 
  Absztrakt Compared to conventional rigid silicon probes, flexible penetrating neural implants exhibit improved mechanical compliance with brain tissue, enabling high-quality neural recordings over extended periods of time. However, the length of the implantable shank and extension cable of most flexible devices falls short of clinical electrodes used in diagnostics and treatment of neurological disorders. In this study, we demonstrate… Read more: Polymer-based laminar probes with an ultra-long flexible spiral-shaped cable for in vivo neural recordings, Sensors and Actuators B: Chemical 
• Synthesis and estrogenic activity of BODIPY-labeled estradiol conjugates. 
  Absztrakt Novel BODIPY–estradiol conjugates have been synthesized by selecting position C-3-O for labeling. The conjugation strategy was based on Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) or etherification. Estradiol derivatives used as azide partners bearing an ω-azidoalkyl function through C4–C8-long linkers have been prepared. CuAAC reactions of estradiol azides with BODIPY alkyne furnished fluorescent 3-O-labeled conjugates bearing the triazole ring as a coupling… Read more: Synthesis and estrogenic activity of BODIPY-labeled estradiol conjugates. 
• Efficient Refinement of Complex Structures of Flexible Histone Peptides Using Post-Docking Molecular Dynamics Protocols. 
  Absztrakt Histones are keys to many epigenetic events and their complexes have therapeutic and diagnostic importance. The determination of the structures of histone complexes is fundamental in the design of new drugs. Computational molecular docking is widely used for the prediction of target–ligand complexes. Large, linear peptides like the tail regions of histones are challenging… Read more: Efficient Refinement of Complex Structures of Flexible Histone Peptides Using Post-Docking Molecular Dynamics Protocols. 
• Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis: Effects on Disease Progression and Inflammatory Biomarkers. 
  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
• Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability. 
  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
• Lipid raft disruption as an opportunity for peripheral analgesia. 
  Absztrakt Chronic pain conditions are unmet medical needs, since the available drugs, opioids, non-steroidal anti-inflammatory/analgesic drugs and adjuvant analgesics do not provide satisfactory therapeutic effect in a great proportion of patients. Therefore, there is an urgent need to find novel targets and novel therapeutic approaches that differ from classical pharmacological receptor antagonism. Most ion channels… Read more: Lipid raft disruption as an opportunity for peripheral analgesia. 
• Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model. 
  Absztrakt The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons.… Read more: Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model. 
• Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice. 
  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
• Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis. 
  Absztrakt Background and aims Smoking is recognised as an independent risk factor in the development of chronic pancreatitis (CP). Cystic fibrosis transmembrane conductance regulator (CFTR) function and ductal fluid and bicarbonate secretion are also known to be impaired in CP, so it is crucial to understand the relationships between smoking, pancreatic ductal function and the… Read more: Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis. 
• Gastric Carcinogenesis and Potential Role of the Transient Receptor Potential Vanilloid 1 (TRPV1) Receptor: An Observational Histopathological Study. 
  Absztrakt The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided… Read more: Gastric Carcinogenesis and Potential Role of the Transient Receptor Potential Vanilloid 1 (TRPV1) Receptor: An Observational Histopathological Study. 
• Antibody-mediated autoimmunity in symptom-based disorders: position statement and proceedings from an international workshop. 
  Absztrakt A 2-day closed workshop was held in Liverpool, United Kingdom, to discuss the results of research concerning symptom-based disorders (SBDs) caused by autoantibodies, share technical knowledge, and consider future plans. Twenty-two speakers and 14 additional participants attended. This workshop set out to consolidate knowledge about the contribution of autoantibodies to SBDs. Persuasive evidence for… Read more: Antibody-mediated autoimmunity in symptom-based disorders: position statement and proceedings from an international workshop. 
• Topiramate inhibits adjuvant-induced chronic orofacial inflammatory allodynia in the rat. 
  Absztrakt Chronic orofacial pain disorders are common debilitating conditions, affecting the trigeminal system. Its underlying pathophysiological mechanisms are still unclear and the therapy is often unsatisfactory, therefore, preclinical models are crucial to identify the key mediators and novel treatment options. Complete Freund’s adjuvant (CFA)-induced orofacial inflammatory allodynia/hyperalgesia is commonly used in rodents, but it has… Read more: Topiramate inhibits adjuvant-induced chronic orofacial inflammatory allodynia in the rat. 
• Progress on the development of Class A GPCR‐biased ligands
  Absztrakt Class A G protein-coupled receptors (GPCRs) continue to garner interest for their essential roles in cell signalling and their importance as drug targets. Although numerous drugs in the clinic target these receptors, over 60% GPCRs remain unexploited. Moreover, the adverse effects triggered by the available unbiased GPCR modulators, limit their use and therapeutic value.… Read more: Progress on the development of Class A GPCR‐biased ligands
• Site-Selective Antibody Conjugation with Dibromopyrazines. 
  Absztrakt In recent years, antibody conjugates have evolved as state-of-the-art options for diagnostic and therapeutic applications. During site-selective antibody conjugation, incomplete rebridging of antibody chains limits the homogeneity of conjugates and calls for the development of new rebridging agents. Herein, we report a dibromopyrazine derivative optimized to reach highly homogeneous conjugates rapidly and with high… Read more: Site-Selective Antibody Conjugation with Dibromopyrazines. 
• Mapping protein binding sites by photoreactive fragment pharmacophores 
  Absztrakt Fragment screening is a popular strategy of generating viable chemical starting points especially for challenging targets. Although fragments provide a better coverage of chemical space and they have typically higher chance of binding, their weak affinity necessitates highly sensitive biophysical assays. Here, we introduce a screening concept that combines evolutionary optimized fragment pharmacophores with… Read more: Mapping protein binding sites by photoreactive fragment pharmacophores 
• Contribution of Noncovalent Recognition and Reactivity to the Optimization of Covalent Inhibitors : A Case Study on KRasG12C 
  Absztrakt Covalent drugs might bear electrophiles to chemically modify their targets and have the potential to target previously undruggable proteins with high potency. Covalent binding of drug-size molecules includes a noncovalent recognition provided by secondary interactions and a chemical reaction leading to covalent complex formation. Optimization of their covalent mechanism of action should involve both… Read more: Contribution of Noncovalent Recognition and Reactivity to the Optimization of Covalent Inhibitors : A Case Study on KRasG12C 
• Synthesis and Systematic Investigation of Lepidiline A and Its Gold(I), Silver(I), and Copper(I) Complexes Using In Vitro Cancer Models and Multipotent Stem Cells 
  Absztrakt The imidazole alkaloid lepidiline A from the root of Lepidium meyenii has a moderate to low in vitro anticancer effect. Our aim was to extend cytotoxicity investigations against a panel of cancer cells, including multidrug-resistant cancer cells, and multipotent stem cells. Lepidiline A is a N-heterocyclic carbene precursor, therefore a suitable ligand source for metal complexes.… Read more: Synthesis and Systematic Investigation of Lepidiline A and Its Gold(I), Silver(I), and Copper(I) Complexes Using In Vitro Cancer Models and Multipotent Stem Cells 
• Characterisation of Canine and Feline Breast Tumours, Their Metastases, and Corresponding Primary Cell Lines Using LA-REIMS and DESI-MS Imaging 
  Absztrakt Breast cancer, a complex disease with a significant prevalence to form metastases, necessitates novel therapeutic strategies to improve treatment outcomes. Here, we present the results of a comparative molecular study of primary breast tumours, their metastases, and the corresponding primary cell lines using Desorption Electrospray Ionisation (DESI) and Laser-Assisted Rapid Evaporative Ionisation Mass Spectrometry… Read more: Characterisation of Canine and Feline Breast Tumours, Their Metastases, and Corresponding Primary Cell Lines Using LA-REIMS and DESI-MS Imaging 
• Mesenchymal Stem Cells Increase Drug Tolerance of A431 Cells Only in 3D Spheroids, Not in 2D Co-Cultures 
  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
• Copper(II) Complexes with Isomeric Morpholine-Substituted 2-Formylpyridine Thiosemicarbazone Hybrids as Potential Anticancer Drugs Inhibiting Both Ribonucleotide Reductase and Tubulin Polymerization: The Morpholine Position Matters 
  Absztrakt The development of copper(II) thiosemicarbazone complexes as potential anticancer agents, possessing dual functionality as inhibitors of R2 ribonucleotide reductase (RNR) and tubulin polymerization by binding at the colchicine site, presents a promising avenue for enhancing therapeutic effectiveness. Herein, we describe the syntheses and physicochemical characterization of four isomeric proligands H2L3–H2L6, with the methylmorpholine substituent at… Read more: Copper(II) Complexes with Isomeric Morpholine-Substituted 2-Formylpyridine Thiosemicarbazone Hybrids as Potential Anticancer Drugs Inhibiting Both Ribonucleotide Reductase and Tubulin Polymerization: The Morpholine Position Matters 
• The mutagenic consequences of defective DNA repair
  Absztrakt Multiple separate repair mechanisms safeguard the genome against various types of DNA damage, and their failure can increase the rate of spontaneous mutagenesis. The malfunction of distinct repair mechanisms leads to genomic instability through different mutagenic processes. For example, defective mismatch repair causes high base substitution rates and microsatellite instability, whereas homologous recombination deficiency is characteristically associated with deletions and chromosome instability. This review presents… Read more: The mutagenic consequences of defective DNA repair
• Inflammation and Colorectal Cancer: A Meta-Analysis of the Prognostic Significance of the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)
  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
• Harnessing Hyperthermia : Molecular, Cellular, and Immunological Insights for Enhanced Anticancer Therapies
  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 novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia
  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
• Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors 
  Absztrakt Identifying genes with prognostic significance that can act as biomarkers in solid tumors can help stratify patients and uncover novel therapy targets. Here, our goal was to expand our previous ranking analysis of survival-associated genes in various solid tumors to include colon cancer specimens with available transcriptomic and clinical data. A Gene Expression Omnibus search was performed to identify available… Read more: Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors 
• The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity 
  Absztrakt The clinical success of PARP1/2 inhibitors (PARPi) prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARPi. We show that the sensitivity of POLE4 knockouts is not due to compromised response to DNA… Read more: The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity 
• The human factor H protein family – an update.
  Absztrakt Complement is an ancient and complex network of the immune system and, as such, it plays vital physiological roles, but it is also involved in numerous pathological processes. The proper regulation of the complement system is important to allow its sufficient and targeted activity without deleterious side-effects. Factor H is a major complement regulator,… Read more: The human factor H protein family – an update.
• Phosphoryl- or phosphinoyl-functionalized benzo[de]isoquinolinones: Synthesis, experimental design, mechanism and biological activity
  Absztrakt A propylphosphonic anhydride (T3P®)-mediated new multicomponent method was developed for the synthesis of benzo[de]isoquinolinones bearing a phosphonate or a phosphine oxide moiety as a new family of compounds. The one-pot three-component reaction of 1,8-naphthalaldehydic acid, primary amines and dialkyl phosphites or secondary phosphine oxides was carried out under mild conditions at low or ambient… Read more: Phosphoryl- or phosphinoyl-functionalized benzo[de]isoquinolinones: Synthesis, experimental design, mechanism and biological activity
• Efficient synthesis of diethyl, dialkyl α-hydroxy-propylenebisphosphonates and related 5-phosphonoyl-1,2-oxaphospholane 2-oxides
  Absztrakt A series of new dialkyl α-diethylphosphonoylethyl-α-hydroxy-ethylphosphonates were prepared using the Pudovik reaction of the corresponding γ-oxophosphonate with dialkyl phosphites performed on the surface of Al2O3/KF. The adducts revealed unexpected reactivity in the attempted O-acylation reaction, and provided the corresponding 5-phosphonoyl-1,2-oxaphospholane 2-oxides. On treatment with Cs2CO3, instead of the expected rearrangement a cyclization reaction leading… Read more: Efficient synthesis of diethyl, dialkyl α-hydroxy-propylenebisphosphonates and related 5-phosphonoyl-1,2-oxaphospholane 2-oxides
• Exploring RAD18-dependent replication of damaged DNA and discontinuities: A collection of advanced tools.
  Absztrakt DNA damage tolerance (DDT) pathways mitigate the effects of DNA damage during replication by rescuing the replication fork stalled at a DNA lesion or other barriers and also repair discontinuities left in the newly replicated DNA. From yeast to mammalian cells, RAD18-regulated translesion synthesis (TLS) and template switching (TS) represent the dominant pathways of DDT. Monoubiquitylation of… Read more: Exploring RAD18-dependent replication of damaged DNA and discontinuities: A collection of advanced tools.
• Electrophilic MiniFrags Revealed Unprecedented Binding Sites for Covalent HDAC8 Inhibitors
  Absztrakt Screening of ultra-low-molecular weight ligands (MiniFrags) successfully identified viable chemical starting points for a variety of drug targets. Here we report the electrophilic analogues of MiniFrags that allow the mapping of potential binding sites for covalent inhibitors by biochemical screening and mass spectrometry. Small electrophilic heterocycles and their N-quaternized analogues were first characterized in… Read more: Electrophilic MiniFrags Revealed Unprecedented Binding Sites for Covalent HDAC8 Inhibitors
• Free Energy Calculations in Covalent Drug Design
  Absztrakt Covalent inhibition has been attracting significant attention in drug discovery. Here we present the free energy-based computational modeling of both reversible and irreversible covalent inhibitors. The specific features of reversible inhibition are discussed emphasizing the difference between the two-state noncovalent and the three-state reversible covalent inhibition. Computational approaches and approximations to calculate the free… Read more: Free Energy Calculations in Covalent Drug Design
• Molecular Mechanism of Labelling Functional Cysteines by Heterocyclic Thiones
  Absztrakt Heterocyclic thiones have recently been identified as reversible covalent warheads, consistent with their mild electrophilic nature. Little is known so far about their mechanism of action in labelling nucleophilic sidechains, especially cysteines. The vast number of tractable cysteines promotes a wide range of target proteins to examine; however, our focus was put on functional… Read more: Molecular Mechanism of Labelling Functional Cysteines by Heterocyclic Thiones
• On-DNA Synthesis of Multisubstituted Indoles
  Absztrakt The increasing role of the DNA-encoded library technology in early phase drug discovery represents a significant demand for DNA-compatible synthetic methods for therapeutically relevant heterocycles. Herein, we report the first on-DNA synthesis of multisubstituted indoles via a cascade reaction of Sonogashira coupling and intramolecular ring closure. Further functionalization by Suzuki coupling at the third… Read more: On-DNA Synthesis of Multisubstituted Indoles
• Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents
  Absztrakt Slow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report… Read more: Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents
• Study protocol of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA)
  Absztrakt –   Szerzők Bankó, Éva M ; Weiss, Béla ; Hevesi, István ; Manga, Annamária ; Vakli, Pál ; Havadi-Nagy, Menta ; Kelemen, Rebeka ; Somogyi, Eszter ; Homolya, István ; Bihari, Adél et al. Megjelenés dátuma 2024 Megjelenés adatai IDEGGYOGYASZATI SZEMLE / CLINICAL NEUROSCIENCE 77 : 1-2 pp. 51-59. , 9 p. (2024)
• Dietary approaches for exploiting metabolic vulnerabilities in cancer
  Absztrakt Renewed interest in tumor metabolism sparked an enthusiasm for dietary interventions to prevent and treat cancer. Changes in diet impact circulating nutrient levels in the plasma and the tumor microenvironment, and preclinical studies suggest that dietary approaches, including caloric and nutrient restrictions, can modulate tumor initiation, progression, and metastasis. Cancers are heterogeneous in their metabolic dependencies and preferred… Read more: Dietary approaches for exploiting metabolic vulnerabilities in cancer
• Blood oxygen regulation via P2Y12R expressed in the carotid body
  Absztrakt Background Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor (P2Y12R) has been implicated in CB; however, the exact role of the receptor in O2 sensing and signal transduction is unknown. Methods The presence of P2Y12R was… Read more: Blood oxygen regulation via P2Y12R expressed in the carotid body
• Amide isomerization pathways: Electronic and structural background of protonation- and deprotonation-mediated cistrans interconversions
  Absztrakt 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… Read more: 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+ Ion
  Absztrakt 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… Read more: 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 Complexes
  Absztrakt 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… Read more: 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 SPPS
  Absztrakt 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… Read more: Acetyl group for proper protection of βsugaramino acids used in SPPS
• Synthesis of small protein domains by automated flow chemistry
  Absztrakt 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… Read more: Synthesis of small protein domains by automated flow chemistry
• Proteotranscriptomic Discrimination of Tumor and Normal Tissues in Renal Cell Carcinoma
  Absztrakt 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… Read more: 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 inhibitors
  Absztrakt 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… Read more: 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 levels
  Absztrakt 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… Read more: 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 cells
  Absztrakt 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… Read more: 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 mining
  Absztrakt 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… Read more: 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 therapies
  Absztrakt 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… Read more: 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 Technique
  Absztrakt 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… Read more: 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-phosphinates
  Absztrakt 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… Read more: 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 PVC
  Absztrakt 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… Read more: Reusable Glucose-Based Crown Ethers Anchored to PVC
• MeSesamol, a bio-based and versatile polar aprotic solvent for organic synthesis and depolymerization
  Absztrakt 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… Read more: 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 reaction
  Absztrakt 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… Read more: 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 acylation
  Absztrakt 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… Read more: 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 Hybrids
  Absztrakt 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… Read more: 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 imaging
  Absztrakt 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… Read more: 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 Fluid
  Absztrakt 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… Read more: 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 Networks
  Absztrakt 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.… Read more: 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 Variant
  Absztrakt 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… Read more: 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 Cells
  Absztrakt 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… Read more: 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 therapy
  Absztrakt 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… Read more: 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 mice
  Absztrakt 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… Read more: 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 illnesses
  Absztrakt 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… Read more: 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,… Read more: SH2db, an information system for the SH2 domain 
• Covalent fragment approaches targeting non-cysteine residues
  Absztrakt 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… Read more: Covalent fragment approaches targeting non-cysteine residues
• Activation-Free Sulfonyl Fluoride Probes for Fragment Screening
  Absztrakt 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,… Read more: Activation-Free Sulfonyl Fluoride Probes for Fragment Screening
• Effective Synthesis, Development and Application of a Highly Fluorescent Cyanine Dye for Antibody Conjugation and Microscopy Imaging
  Absztrakt 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… Read more: 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 networks
  Absztrakt 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… Read more: 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 recordings
  Absztrakt 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… Read more: 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 mode
  Absztrakt 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… Read more: 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… Read more: 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 D
  Absztrakt 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… Read more: 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… Read more: Hydrogen peroxide production by epidermal dual oxidase 1 regulates nociceptive sensory signals