Article
Endocrinology & Metabolism
C. Indolfi, A. Klain, G. Di Nardo, C. Cuppari, A. Ceravolo, D. Concolino, R. De Sarro, A. Salpietro, F. Decimo, M. Miraglia del Giudice
Summary: This article discusses the strong link between asthma and infections, as well as the potential mechanisms for translating these infections into asthma.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2022)
Article
Pharmacology & Pharmacy
Borden A. Emily, Furey Matthew, Gattone J. Nicholas, Hambardikar D. Vedangi, Liang Xiao Hua, Scoma R. Ernest, Abou Samra Antonella, D-Gary R. Lakeshia, Dennis J. Dayshaun, Fricker Daniel, Garcia Cindy, Jiang ZeCheng, Khan A. Shariq, Kumarasamy Dheenadhayalan, Kuppala Hasmitha, Ringrose Savannah, Rosenheim J. Evan, Van Exel Kimberly, Vudhayagiri Hemanth Sai, Zhang Jiarui, Zhang Zhaowen, Guitart-Mampel Mariona, Urquiza Pedro, Solesio E. Maria
Summary: Mitochondrial dysfunction is a common feature in neurodegenerative diseases such as Alzheimer's Disease and Parkinson's Disease, with inorganic polyphosphate (polyP) potentially being a promising pharmacological target against these conditions. Further research is needed to fully understand the role of polyP in neurodegeneration and its effects on cellular and mitochondrial physiology.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Stanislas Martin, Audrey Foulon, Wissam El Hage, Diane Dufour-Rainfray, Frederic Denis
Summary: This study aimed to investigate the role of the oropharyngeal microbiome in the pathophysiology of schizophrenia and explore the possible bidirectional link between the oral microbiota and the brain in the context of dysbiosis-related neuroinflammation. The findings suggested the presence of phageoma in patients with schizophrenia and the involvement of periodontal disease in the development of inflammation in schizophrenia. Additionally, saliva could potentially serve as a substrate for characterizing different stages of schizophrenia. However, the current knowledge on this topic is limited and more research is needed to clarify these unresolved questions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Economics
Michalis Drouvelis, Graeme Pearce
Summary: In this paper, the link between intelligence and lying is studied using two experimental paradigms: the die rolling paradigm and the mind game paradigm. The behavior of subjects is compared based on their intelligence in each paradigm, under situations where lying benefits the subject or a charitable cause. The results indicate that lying increases when it benefits a charitable cause, and there is limited evidence that more intelligent individuals increase lying when it benefits a charity. These findings are consistent with models of self-image concerns and have potential implications for the existing literature on lying.
JOURNAL OF ECONOMIC BEHAVIOR & ORGANIZATION
(2023)
Article
Immunology
Aayushi Balda, Irshad Wani, Tamsheel Fatima Roohi, Suman, K. L. Krishna, Seema Mehdi, Abhishek P. R. Nadiga, Manasa Makkapati, Awaise Iqbal Baig
Summary: Psoriasis, a chronic auto-immune-mediated disease, is associated with a significant risk of malignancies, especially skin tumors. This review examines the relationship between psoriasis and cancer risk, discusses the significance of inflammation in cancer, and explores the various classes of drugs used to treat psoriasis and how they increase the risk of cancer. The review also discusses possible mechanisms associated with inflammation and psoriasis, as well as the risk of cancer in other cutaneous auto-inflammatory diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Friederike K. Warns, Mehmet Gultas, Astrid L. van Asten, Tobias Scholz, Martina Gerken
Summary: Tail biting is a well-known issue in modern pig production, influenced by various external and internal factors. Research showed that tail biting behavior increases in the middle and end of the rearing period, with most animals observed as both biters and victims. Tail-biting pigs tend to display submissive behavior, possibly compensating for resource access with tail biting. Early identification of predisposed pigs could help reduce tail biting and its consequences. Further research should focus on pigs' personality traits for better early detection of potential tail biters.
Review
Medicine, General & Internal
Alessandro Ferretti, Mattia Gatto, Margherita Velardi, Giovanni Di Nardo, Thomas Foiadelli, Gianluca Terrin, Manuela Cecili, Umberto Raucci, Massimiliano Valeriani, Pasquale Parisi
Summary: The relationship between migraines and allergies is still not well understood, although there is an epidemiological link between them. Genetic and biological factors contribute to both migraines and allergic disorders. The histaminergic system, particularly the H3 and H4 receptors, may play a role in the pathophysiology of both conditions. Antihistamine drugs could potentially be helpful in treating migraines and allergic disorders. Further research is needed to fully understand the mechanistic link between these two common and debilitating conditions.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Dorota Wronka, Anna Karlik, Julia O. Misiorek, Lukasz Przybyl
Summary: The human intestinal microbiota plays a crucial role in digestion, nutrient generation, and the host's overall health. Imbalances in the microbiota have been implicated in various diseases, including neurodegenerative disorders such as Parkinson's and Alzheimer's disease. However, little is known about the composition and interactions of the microbiome in Huntington's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Enric Sanchez, Marta Sanchez, Carolina Lopez-Cano, Marcelino Bermudez-Lopez, Jose Manuel Valdivielso, Cristina Farras-Salles, Reinald Pamplona, Gerard Torres, Didac Mauricio, Eva Castro, Elvira Fernandez, Albert Lecube
Summary: This study assessed the impact of obesity on the accumulation of advanced glycation end-products (AGEs) and found that AGE levels were associated with abdominal adiposity but not total body fat. Furthermore, elevated AGE levels were related to cardiovascular risk factors.
Letter
Endocrinology & Metabolism
Miao-Miao Sang, Zi-Lin Sun, Tong-Zhi Wu
Summary: Patients with inflammatory bowel disease (IBD) have an increased risk of diabetes, and IBD therapies may significantly modulate blood glucose, indicating a mechanistic connection between IBD and diabetes.
WORLD JOURNAL OF DIABETES
(2022)
Article
Medicine, General & Internal
Raymond E. E. Garrett, Carlos H. H. Palacio, David Bar-Or
Summary: Metabolic causes and renal tubular injury are potential factors contributing to Long COVID symptoms. In this study, we propose three mechanisms including creatine phosphate metabolism, un-reclaimed glomerular filtrate, and injury to COVID-specific proximal tubule cells, which may play a major role in Long COVID. This research aims to improve diagnostics and therapy for long-haul sufferers.
FRONTIERS IN MEDICINE
(2023)
Article
Dermatology
Fatmanur Hacinecipoglu, Muzeyyen Gonul, Seyda Ozdemir, Omer Faruk Demir
Summary: This study investigates the role of intestinal permeability in the etiopathogenesis of alopecia areata (AA) and its association with disease severity. The results show that there is no significant relationship between serum zonulin levels and the severity of AA.
JOURNAL OF COSMETIC DERMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Giuseppe Murdaca, Alessandra Gerosa, Francesca Paladin, Lorena Petrocchi, Sara Banchero, Sebastiano Gangemi
Summary: The importance of both the microbiome and vitamin D in health and disease is increasingly recognized. Microbiome studies have shown unique patterns in autoimmune diseases and dysbiosis is associated with allergies. Vitamin D deficiency affects the microbiome and immune system, highlighting the need for further research in allergic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Agriculture, Dairy & Animal Science
Pietro Asproni, Eva Mainau, Alessandro Cozzi, Ricard Carreras, Cecile Bienboire-Frosini, Eva Teruel, Patrick Pageat
Summary: This study found that farm pigs can be affected by inflammation of the vomeronasal organ, and pigs with this alteration exhibit an increased number of skin lesions caused by fights with other pigs. These results highlight a potential association between vomeronasal organ dysfunction and aggressive behavior in farm animals, which has implications for animal welfare.
Article
Immunology
Federica Saponaro, Maria Franzini, Chukwuma Okoye, Rachele Antognoli, Beatrice Campi, Marco Scalese, Tommaso Neri, Laura Carrozzi, Fabio Monzani, Riccardo Zucchi, Alessandro Celi, Aldo Paolicchi, Alessandro Saba
Summary: This study investigated the relationship between vitamin D levels and inflammatory markers in COVID-19 patients. The findings suggest that hypovitaminosis D is associated with higher levels of inflammatory markers and is related to disease severity and prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Scarpino, Laszlo Petri, Damijan Knez, Timea Imre, Peter abranyi-Balogh, Gyorgy G. Ferenczy, Stanislav Gobec, Gyorgy M. Keseru
Summary: WIDOCK is a virtual screening protocol that supports the selection of diverse electrophiles as covalent inhibitors by incorporating ligand reactivity into AutoDock4. It applies the reactive docking method, extends it into a virtual screening tool, and introduces easy experimental or computational parametrization and a ligand-focused evaluation scheme for validation against therapeutically relevant targets. The protocol has shown high sensitivity in retrieving experimental actives and better performance compared to standard covalent docking tools.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2021)
Article
Chemistry, Organic
Andras Gy Nemeth, Bence Marlok, Attila Domjan, Qinghe Gao, Xinya Han, Gyorgy M. Keseru, Peter Abranyi-Balogh
Summary: A novel one-pot aqueous reaction for the synthesis of 2-iminothiazolines and 2-aminothiazoles using isocyanides, amines, sulfur, and 2'-bromoacetophenones is presented. The procedure features excellent step- and atom-economy, enabling chromatography-free preparation of diversely substituted derivatives.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Physical
Levente M. Mihalovits, Gyorgy G. Ferenczy, Gyorgy M. Keseru
Summary: The recent rise of targeted covalent inhibitors in drug discovery presents new opportunities and challenges for quantum chemical reactivity calculations. These calculations are crucial in determining inhibitory potency by predicting intrinsic reactivities of covalent ligands. Mixed quantum mechanical/molecular mechanical potentials provide a comprehensive description of covalent ligand binding mechanisms, while efficient QM/MM predictions of ligand reactivities are highly useful in covalent drug discovery.
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Anita Racz, Roberta Palko, Dorottya Csanyi, Zsuzsanna Riedl, David Bajusz, Gyorgy M. Keseru
Summary: This study discovered a series of new MELK inhibitors through virtual screening, and disclosed the synthesis and bioactivity of this class of compounds for the first time, providing a new direction for anti-cancer drug development.
Review
Pharmacology & Pharmacy
Nikolett Peczka, Zoltan Orgovan, Peter Abranyi-Balogh, Gyorgy Miklos Keseru
Summary: This review provides an overview of electrophilic warheads used for protein labeling in chemical biology and medicinal chemistry. The warheads are discussed based on targeted residues, mechanism, and selectivity, and analyzed using multiple datasets. Despite the availability of numerous electrophilic warheads, only a fraction of them are used in current drug discovery projects. Recent studies have identified new tractable residues, but the discovery of new warheads for these residues is still needed.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Cell Biology
Levente Kollar, Martina Gobec, Matic Proj, Lara Smrdel, Damijan Knez, Timea Imre, Agnes Gomory, Laszlo Petri, Peter Abranyi-Balogh, Dorottya Csanyi, Gyoergy G. Ferenczy, Stanislav Gobec, Izidor Sosic, Gyoergy M. Keseru
Summary: Constitutive- and immunoproteasomes are vital components of the protein homeostasis system. Selective inhibition of immunoproteasomes shows promise for treating various diseases, and two series of compounds targeting proteasomes have been described in this study. The compounds exhibit significant inhibitory activities against specific subunits of the proteasomes, highlighting their potential for developing selective immunoproteasome inhibitors or compounds targeting multiple subunits.
Article
Chemistry, Medicinal
Ilona Bereczki, Henrietta Papp, Anett Kuczmog, Monika Madai, Veronika Nagy, Attila Agocs, Gyula Batta, Marton Milankovits, Eszter Ostorhazi, Janko Kos, Aron Zsigmond, Istvan Hajdu, David Bajusz, Jan Hodek, Jan Weber, Ferenc Jakab, Pal Herczegh, Aniko Borbas, Ana MitroviC, Zsolt Lorincz, Gyorgy Miklos Keserii
Summary: The prolonged global pandemic of COVID-19 has driven the need for the development of new drugs targeting SARS-CoV-2, with the glycopeptide antibiotic teicoplanin and certain apocarotenoids showing promising antiviral potential. The study suggests that these compounds could be further explored as potential antivirals against SARS-CoV-2.
Review
Pharmacology & Pharmacy
David Bajusz, Gyorgy M. Keseru
Summary: Experimental and virtual screening are complementary approaches that should be integrated in lead discovery settings. Virtual screening can access extremely large synthetically feasible chemical space that can be effectively searched on GPU clusters or cloud architectures. Experimental screening provides reliable datasets by quantitative HTS applications, and DNA-encoded libraries (DEL) have enlarged the chemical space covered by these technologies. These developments, together with the use of artificial intelligence methods, represent new options for their efficient integration. The case studies discussed here demonstrate the benefits of complementary strategies, such as focused and iterative screening.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Medicinal
Amanda E. Wakefield, David Bajusz, Dima Kozakov, Gyoergy M. Keseru, Sandor Vajda
Summary: Despite the limited number of GPCR structures cocrystallized with allosteric inhibitors, protein mapping has revealed the presence of druggable sites at the same locations in a large variety of GPCRs. These sites cluster at nine distinct locations and can be specifically targeted for allosteric modulation across GPCRs. The FTMap server facilitates protein mapping and is freely available for academic and governmental use.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Peter Abranyi-Balogh, Aaron Keeley, Gyorgy G. Ferenczy, Laszlo Petri, Timea Imre, Katarina Grabrijan, Martina Hrast, Damijan Knez, Janez Ilas, Stanislav Gobec, Gyorgy M. Keseru
Summary: The second generation of heterocyclic electrophiles, the quaternized analogue of the heterocyclic covalent fragment library, showed improved reactivity and MurA inhibitory potency. Quantum chemical reaction barrier calculations, GSH reactivity assay, and thrombin counter screen were used to explain the improved reactivity and selectivity of the N-methylated heterocycles and compare the two generations of heterocyclic electrophiles.
Article
Biochemistry & Molecular Biology
Laszlo Petri, Peter Aabranyi-Balogh, Noemi Csorba, Aaron Keeley, Jozsef Simon, Ivan Randelovic, Jozsef Tovari, Gitta Schlosser, Daniel Szabo, Laszlo Drahos, Gyoergy M. Keseru
Summary: SuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Sulfonyl fluorides can label multiple nucleophilic amino acid residues, making them popular in both chemical biology and medicinal chemistry applications. In this study, a small sulfonyl fluoride library was synthesized and characterized, resulting in the identification of a 3-carboxybenzenesulfonyl fluoride warhead for tagging nucleophilic residues. Coupling diverse fragments to this warhead could yield a library of sulfonyl fluoride bits (SuFBits) for screening against protein targets, facilitated by mass spectrometry identification of weak fragments.
Article
Biochemistry & Molecular Biology
David Bajusz, Gaspar Pandy-Szekeres, Agnes Takacs, Elvin D. de Araujo, Gyorgy M. Keseru
Summary: SH2db is a comprehensive structural database and webserver for SH2 domain structures, providing search, browse, and download functions. It assists researchers in their day-to-day work and serves as a valuable resource for SH2 domain-related research.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Physical
Levente M. Mihalovits, Levente Kollar, David Bajusz, Damijan Knez, Kristof Bozovicar, Timea Imre, Gyorgy G. Ferenczy, Stanislav Gobec, Gyorgy M. Keseru
Summary: This study investigates the mechanism of covalent labeling of cysteines using heterocyclic thiones as reversible covalent warheads. The main protease of SARS-CoV-2 harboring Cys145 was chosen as the target, and molecular dynamics simulations and experimental validations were conducted.
Review
Pharmacology & Pharmacy
Noemi Csorba, Peter Abranyi-Balogh, Gyorgy M. Keseru
Summary: Covalent fragment approaches combine the advantages of covalent binders and fragment-based drug discovery (FBDD) for target identification and validation. Recent studies have expanded the chemistries of different warheads to target protein nucleophiles other than cysteine residues. This review discusses these newly developed amino-acid-specific and promiscuous warheads, as well as emerging labeling chemistries. The applications of covalent fragments in the development of molecular glues and proteolysis-targeting chimeras (PROTACs) are highlighted, along with their utility in chemical proteomics-based target identification and validation.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Chemistry, Organic
Andras Gy. Nemeth, Renata Szabo, Krisztina Nemeth, Gyorgy M. Keseru, Peter Abranyi-Balogh
Summary: This study discovered the reactivity of easily accessible electron deficient alkenes towards sulfur and developed a new pseudo-multicomponent reaction for the preparation of polysulfides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Karlie R. Sharma, Christine M. Colvis, Griffih P. Rodgers, Douglas M. Sheeley
Summary: There are many genes within the druggable genome that have not been studied, and the US National Institutes of Health's program provides resources to explore these genes, with the potential for rapid impact on human health.
DRUG DISCOVERY TODAY
(2024)
Review
Pharmacology & Pharmacy
Mohammad Sameer Khan, B. H. Jaswanth Gowda, Waleed H. Almalki, Tanuja Singh, Amirhossein Sahebkar, Prashant Kesharwani
Summary: Mitochondria-specific functional liposomes hold great potential for cancer therapy. This review discusses the association between mitochondria and tumor formation, as well as the advantages of liposomes in delivering drugs to mitochondria.
DRUG DISCOVERY TODAY
(2024)
Review
Pharmacology & Pharmacy
Choong Yong Ung, Cristina Correia, Hu Li, Christopher M. Adams, Jennifer J. Westendorf, Shizhen Zhu
Summary: With increasing human life expectancy, the global medical burden of chronic diseases is growing. Chronic diseases often involve malfunctioning of multiple organs, and understanding the interorgan crosstalk is crucial to understanding the etiology of chronic diseases. Researchers have proposed the locked-state model (LoSM) and cutting-edge systems biology and artificial intelligence strategies to decipher chronic multiorgan locked states. The findings have important clinical implications for improving treatments for chronic diseases.
DRUG DISCOVERY TODAY
(2024)
