PUBLICATIONS

• The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway
  Abstract 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… Read more: 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 Pathways
  Abstract 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… Read more: Friend or Foe: The Relativity of (Anti)oxidative Agents and Pathways
• The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway
  Abstract 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… Read more: The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway
• Edge computing on TPU for brain implant signal analysis
  Abstract 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… Read more: Edge computing on TPU for brain implant signal analysis
• Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells
  Abstract 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… Read more: Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells
• New Transcriptomic Biomarkers of 5-Fluorouracil Resistance
  Abstract 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… Read more: New Transcriptomic Biomarkers of 5-Fluorouracil Resistance
• 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 
  Abstract 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… Read more: 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 
• Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4) 
  Abstract 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… Read more: 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 triple function of the capsaicin-sensitive sensory neurons: In memoriam János Szolcsányi
  Abstract 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… Read more: The triple function of the capsaicin-sensitive sensory neurons: In memoriam János Szolcsányi
• Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency.
  Abstract 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… Read more: Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency.
• Safe and Efficient Continuous-Flow Synthesis and Batchwise Hydrolysis of Ethyl 5-Acetyl-1H-pyrazole-3-carboxylate: A Key Synthon of Darolutamide 
  Abstract 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… Read more: Safe and Efficient Continuous-Flow Synthesis and Batchwise Hydrolysis of Ethyl 5-Acetyl-1H-pyrazole-3-carboxylate: A Key Synthon of Darolutamide 
• Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer Cells
  Abstract 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… Read more: Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer Cells
• The regulatory role of the CD2AP/TKS4 interaction in EMT and its potential as a biomarker for colon cancer 
  Abstract 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.… Read more: The regulatory role of the CD2AP/TKS4 interaction in EMT and its potential as a biomarker for colon cancer 
• IL-1 mediates chronic stress-induced hyperalgesia accompanied by microglia and astroglia morphological changes in pain-related brain regions in mice
  Abstract 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… Read more: IL-1 mediates chronic stress-induced hyperalgesia accompanied by microglia and astroglia morphological changes in pain-related brain regions in mice
• A novel fusion protein system for the production of nanobodies and the SARS-CoV-2 spike RBD in a bacterial system
  Abstract 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… Read more: A novel fusion protein system for the production of nanobodies and the SARS-CoV-2 spike RBD in a bacterial system
• Improved acylation of pseudoproline: masked threonine in flow peptide chemistry
  Abstract 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… Read more: Improved acylation of pseudoproline: masked threonine in flow peptide chemistry
• Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation
  Abstract 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… Read more: Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation
• DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis
  Abstract 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… Read more: DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis
• P2 receptor-mediated signaling in physiological and pathological brain development
  Abstract 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… Read more: P2 receptor-mediated signaling in physiological and pathological brain development
• 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.
  Abstract 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… Read more: 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.
• Relationship between bibliometric indicators and university ranking positions
  Abstract 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.… Read more: Relationship between bibliometric indicators and university ranking positions
• Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors
  Abstract 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… Read more: Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors
• Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer 
  Abstract 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… Read more: Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer 
• Analysis of a large cohort of pancreatic cancer transcriptomic profiles to reveal the strongest prognostic factors 
  Abstract 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… Read more: Analysis of a large cohort of pancreatic cancer transcriptomic profiles to reveal the strongest prognostic factors 
• miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer
  Abstract 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… Read more: miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer
• Spatial predictors of immunotherapy response in triple-negative breast cancer
  Abstract 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… Read more: Spatial predictors of immunotherapy response in triple-negative breast cancer
• Novel peptide calcitonin gene-related peptide antagonists for migraine therapy
  Abstract 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… Read more: Novel peptide calcitonin gene-related peptide antagonists for migraine therapy
• Supporting grant reviewers through the scientometric ranking of applicants 
  Abstract 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… Read more: Supporting grant reviewers through the scientometric ranking of applicants 
• Hemokinin1 is a mediator of chronic restraint stressinduced pain
  Abstract 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… Read more: Hemokinin1 is a mediator of chronic restraint stressinduced pain
• An atlas of genetic determinants of forearm fracture 
  Abstract 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… Read more: An atlas of genetic determinants of forearm fracture 
• NATURE GENETICS 55 : 11 pp. 1820-1830. , 11 p. (2023)
  Abstract 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… Read more: NATURE GENETICS 55 : 11 pp. 1820-1830. , 11 p. (2023)
• Site-Selective Antibody Conjugation with Dibromopyrazines. 
  Abstract 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. 
• Progress on the development of Class A GPCR‐biased ligands
  Abstract 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
• Topiramate inhibits adjuvant-induced chronic orofacial inflammatory allodynia in the rat. 
  Abstract 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. 
• Antibody-mediated autoimmunity in symptom-based disorders: position statement and proceedings from an international workshop. 
  Abstract 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. 
• Gastric Carcinogenesis and Potential Role of the Transient Receptor Potential Vanilloid 1 (TRPV1) Receptor: An Observational Histopathological Study. 
  Abstract 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. 
• Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis. 
  Abstract 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. 
• 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. 
  Abstract Bone cancer and its related chronic pain are huge clinical problems since the available drugs are often ineffective or cannot be used long term due to a broad range of side effects. The mechanisms, mediators and targets need to be identified to determine potential novel therapies. Here, we characterize a mouse bone cancer model… Read more: 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. 
• Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model. 
  Abstract 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. 
• Lipid raft disruption as an opportunity for peripheral analgesia. 
  Abstract 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. 
• Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability. 
  Abstract Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the… Read more: Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability. 
• Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis: Effects on Disease Progression and Inflammatory Biomarkers. 
  Abstract Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund’s adjuvant (CFA)-induced chronic arthritis rat… Read more: Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis: Effects on Disease Progression and Inflammatory Biomarkers. 
• Efficient Refinement of Complex Structures of Flexible Histone Peptides Using Post-Docking Molecular Dynamics Protocols. 
  Abstract 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. 
• Synthesis and estrogenic activity of BODIPY-labeled estradiol conjugates. 
  Abstract 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. 
• Polymer-based laminar probes with an ultra-long flexible spiral-shaped cable for in vivo neural recordings, Sensors and Actuators B: Chemical 
  Abstract 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 
• Cyclodextrin derivatives decrease Transient Receptor Potential Vanilloid 1 and Ankyrin 1 ion channel activation via altering the surrounding membrane microenvironment by cholesterol depletion –  
  Abstract 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 –  
• Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology 
  Abstract 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 
• Unveiling the Oxazolidine Character of Pseudoproline Derivatives by Automated Flow Peptide Chemistry Unveiling the Oxazolidine Character of Pseudoproline Derivatives by Automated Flow Peptide Chemistry 
  Abstract 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 Unveiling the Oxazolidine Character of Pseudoproline Derivatives by Automated Flow Peptide Chemistry 
• Opening Amyloid-Windows to the secondary structure of proteins: The amyloidogenecity increases tenfold inside beta-sheets 
  Abstract 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 
• Synthesis of small protein domains by automated flow chemistry 
  Abstract 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 
• LoCoHD: a metric for comparing local environments of proteins 
  Abstract 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 
• Influence of Trp-Cage on the Function and Stability of GLP-1R Agonist Exenatide Derivatives 
  Abstract 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 
• Flow Synthesis of Capsaicin and Capsaicinoid Analogues 
  Abstract 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 
• Synthetic and mechanistic studies of the multicomponent reaction of 2-(phenylethynyl)benzaldehyde, primary amine and diphenylphosphine oxide 
  Abstract 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 
• N-Functionalization of β-aminophosphonates: cytotoxic effects of the new derivatives 
  Abstract 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 
• Immobilization of human tyrosine hydroxylase onto magnetic nanoparticles – A novel formulation of a therapeutic enzyme 
  Abstract 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 
• Covalent immobilization of an enzyme on a layered silicate to catalyze the self-degradation of PCL 
  Abstract 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 
• A silica-supported organocatalyst for polycarbonate methanolysis under mild and economic conditions 
  Abstract 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 
• Furandicarboxylic Acid (FDCA): Electrosynthesis and Its Facile Recovery From Polyethylene Furanoate (PEF) via Depolymerization
  Abstract 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
• Novel Piperazine Derivatives of Vindoline as Anticancer Agents 
  Abstract 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 
• Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments 
  Abstract 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 
• In-line indirect concentration measurement of ultralow dose API during twin-screw wet granulation based on NIR and Raman spectroscopy 
  Abstract 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 
• Development of Continuous Additive-Controlled MSMPR Crystallization by DoE-Based Batch Experiments 
  Abstract 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 
• UV imaging for the rapid at-line content determination of different colourless APIs in their tablets with artificial neural networks 
  Abstract 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 
• UV–VIS imaging-based investigation of API concentration fluctuation caused by the sticking behaviour of pharmaceutical powder blends 
  Abstract 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 
• Explainable deep recurrent neural networks for the batch analysis of a pharmaceutical tableting process in the spirit of Pharma 4.0
  Abstract 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
• Bioequivalence prediction with small-scale biphasic dissolution and simultaneous dissolution-permeation apparatus—An aripiprazole case study 
  Abstract 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 
• Raman and NIR spectroscopy-based real-time monitoring of the membrane filtration process of a recombinant protein for the diagnosis of SARS-CoV-2 
  Abstract 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 
• SARS-CoV-2 Nucleocapsid Protein Is Not Responsible for Over-Activation of Complement Lectin Pathway 
  Abstract 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 
• The interlacing anti-cancer effect of pharmacologic ascorbate, chloroquine and resveratrol 
  Abstract 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 
• The High‐Affinity Chymotrypsin Inhibitor Eglin C Poorly Inhibits Human Chymotrypsin‐Like Protease: Gln192 and Lys218 Are Key Determinants 
  Abstract 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 
• Mapping protein binding sites by photoreactive fragment pharmacophores 
  Abstract 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 
  Abstract 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 
  Abstract 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 
  Abstract 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 
  Abstract Mesenchymal stem cells (MSCs) are an integral part of the tumor microenvironment (TME); however, their role is somewhat controversial: conflicting reports suggest that, depending on the stage of tumor development, MSCs can either support or suppress tumor growth and spread. Additionally, the influence of MSCs on drug resistance is also ambiguous. Previously, we showed… Read more: Mesenchymal Stem Cells Increase Drug Tolerance of A431 Cells Only in 3D Spheroids, Not in 2D Co-Cultures 
• 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 
  Abstract 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
  Abstract 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)
  Abstract The overall prognosis for colorectal cancer (CRC) remains challenging as the survival time varies widely, even in patients with the same stage of disease. Recent studies suggest prognostic relevance of the novel markers of systemic inflammation, the systemic immune–inflammation index (SII), and the systemic inflammation response index (SIRI). We conducted a comprehensive meta-analysis to… Read more: 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)
• Harnessing Hyperthermia : Molecular, Cellular, and Immunological Insights for Enhanced Anticancer Therapies
  Abstract Hyperthermia, the raising of tumor temperature (≥39°C), holds great promise as an adjuvant treatment for cancer therapy. This review focuses on 2 key aspects of hyperthermia: its molecular and cellular effects and its impact on the immune system. Hyperthermia has profound effects on critical biological processes. Increased temperatures inhibit DNA repair enzymes, making cancer… Read more: Harnessing Hyperthermia : Molecular, Cellular, and Immunological Insights for Enhanced Anticancer Therapies
• A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia
  Abstract Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in patients with acute myeloid leukemia (AML). STAT3 exists in two distinct alternatively spliced isoforms, the full-length isoform STAT3α and the C-terminally truncated isoform STAT3β. While STAT3α is predominantly described as an oncogenic driver, STAT3β has been suggested to act as a tumor… Read more: A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia
• Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors 
  Abstract 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 
  Abstract 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.
  Abstract 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
  Abstract 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
  Abstract 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.
  Abstract 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
  Abstract 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
  Abstract 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
  Abstract 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
• Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents
  Abstract 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)
  Abstract –   Authors Bankó, Éva M ; Weiss, Béla ; Hevesi, István ; Manga, Annamária ; Vakli, Pál ; Havadi-Nagy, Menta ; Kelemen, Rebeka ; Somogyi, Eszter ; Homolya, István ; Bihari, Adél et al. Release date 2024 Release details IDEGGYOGYASZATI SZEMLE / CLINICAL NEUROSCIENCE 77 : 1-2 pp. 51-59. , 9 p. (2024)
• Dietary approaches for exploiting metabolic vulnerabilities in cancer
  Abstract 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
  Abstract 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
  Abstract 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
• Hemokinin-1 induces transcriptomic alterations in pain-related signaling processes in rat primary sensory neurons independent of NK1 tachykinin receptor activation
  Abstract 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… Read more: Hemokinin-1 induces transcriptomic alterations in pain-related signaling processes in rat primary sensory neurons independent of NK1 tachykinin receptor activation
• Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice
  Abstract 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… Read more: Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice
• Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice – Copy
  Abstract 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… Read more: Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice – Copy
• Hydrogen peroxide production by epidermal dual oxidase 1 regulates nociceptive sensory signals 
  Abstract 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 
• Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor D
  Abstract 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