Review
Biochemistry & Molecular Biology
Julia E. M. Upton, Eyal Grunebaum, Gordon Sussman, Peter Vadas
Summary: Platelet-activating factor (PAF) plays a crucial role in multiple inflammatory conditions, contributing to platelet aggregation and activation as well as allergic and nonallergic inflammatory diseases. Recent research has highlighted its significance in various medical conditions, including severe pediatric anaphylaxis, blood-brain barrier permeability, reproduction, ocular diseases, and cardiovascular risk. The investigation of PAF as both a biomarker and therapeutic target continues to provide potential for targeted and effective treatments for inflammatory conditions.
Article
Cell Biology
Eileen Deuster, Ivi Hysenaj, Maja Kahaly, Elisa Schmoeckel, Doris Mayr, Susanne Beyer, Thomas Kolben, Anna Hester, Fabian Kraus, Anca Chelariu-Raicu, Alexander Burges, Sven Mahner, Udo Jeschke, Fabian Trillsch, Bastian Czogalla
Summary: In patients with ovarian cancer, high expression of PAFR affects overall and recurrence-free survival, while rupatadine, an antagonist, effectively inhibits proliferation and migration of ovarian cancer cells.
Review
Cell Biology
Pu Rong, Jie-Li Wang, Angelina Angelova, Zakaria A. Almsherqi, Yuru Deng
Summary: This article explores the relationship between plasmalogens and Platelet-Activating Factor (PAF), suggesting the potential role of plasmalogenic analogs of PAF as modulators and PAF antagonists. The metabolic interconversion of these lipids is discussed as an important factor in preventing and relieving PAF-mediated inflammation, and the possibility of plasmalogen analogs as a new class of bioactive anti-inflammatory drugs is proposed. Additionally, the competition between PAF and its natural plasmalogenic analogs for binding to the PAF receptor is proposed as a mechanistic model and potential therapeutic perspective.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Mary A. Smal, Brian A. Baldo
Summary: Experiments identified a fatty acid inhibitor in human saliva that can effectively inhibit PAF-induced platelet aggregation. The cis-unsaturated fatty acids showed strong inhibitory effects, especially on ADP-induced PA, suggesting a potential regulatory role in certain diseases.
Review
Endocrinology & Metabolism
Jeffrey B. Travers, Joyce G. Rohan, Ravi P. Sahu
Summary: PAF, a glycerophosphocholine lipid mediator, plays a crucial role in pathologic processes and can be transmitted through MVP to activate the PAF receptor and generate more PAF. Studying the PAF family of lipid mediators is essential for understanding the relationship among diverse cutaneous, cancerous, neurologic, and systemic pathologic processes.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Marie-Eve Tremblay, Zakaria A. Almsherqi, Yuru Deng
Summary: Fatty acids and phospholipids play essential roles in the structure and function of cell membranes. Recent research has focused on two subclasses of ether phospholipids, platelet activating factor (PAF) and its precursor plasmalogen, due to their association with several chronic inflammatory, neurodegenerative, and metabolic disorders. Inflammatory conditions often involve an excess of PAF or decreased levels of plasmalogens. The exact mechanisms of plasmalogens in inflammation are not yet fully understood. Anti-inflammatory responses are likely mediated by the plasmalogen signaling pathway, while pro-inflammatory responses involve the release of arachidonic acid from membrane phospholipids, particularly derived from the hydrolysis of plasmalogens. Changes in plasmalogen levels can affect cell membrane properties and impact signaling pathways involved in inflammatory cascades and immune responses. Plasmalogen replacement therapy shows promise as an anti-inflammatory strategy for treating chronic diseases with an inflammatory component.
Article
Food Science & Technology
Filio Petsini, Agathi Ntzouvani, Maria Detopoulou, Vasiliki D. Papakonstantinou, Nick Kalogeropoulos, Elizabeth Fragopoulou, Tzortzis Nomikos, Meropi D. Kontogianni, Smaragdi Antonopoulou
Summary: Eating farmed fish fed with an olive-pomace enriched diet affects PAF metabolism and markers of inflammation and oxidative stress, but has similar effects to conventionally fed farmed fish.
Article
Medicine, General & Internal
Jordi Roca-Ferrer, Maria Perez-Gonzalez, Isam Alobid, Valeria Tubita, Mireya Fuentes, Marina Bantula, Rosa Munoz-Cano, Antonio Valero, Inaki Izquierdo, Joaquim Mullol, Jacopo Galli
Summary: This study aimed to assess the role of the Platelet-Activating Factor (PAF)/receptor (PAFR) system in chronic rhinosinusitis with nasal polyps (CRSwNP). The study found that PAFR protein was expressed in nasal mucosa and nasal polyps, and Lyso-PAF concentrations were higher in nasal polyps of asthmatic patients. These findings suggest that the PAF/PAFR system may play a role in CRSwNP pathogenesis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Carolyn J. English, Anna E. Lohning, Hannah L. Mayr, Mark Jones, Dianne P. Reidlinger
Summary: Traditionally, cardiovascular disease (CVD) risk has been assessed through blood lipids and the inflammatory marker C-reactive protein (hsCRP). However, recent research has shown that the pro-inflammatory markers platelet-activating factor (PAF) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) can also indicate vascular damage in the absence of traditional risk factors. This study investigated the relationship between PAF, Lp-PLA(2), hsCRP, and traditional risk factors for CVD among 100 adults. The results showed that PAF, Lp-PLA(2), and hsCRP were independently correlated with various CVD risk factors, suggesting their involvement in different atherogenic pathways.
Review
Nutrition & Dietetics
Carolyn J. English, Hannah L. Mayr, Anna E. Lohning, Dianne P. Reidlinger
Summary: Atherosclerosis is a chronic inflammation disease and recent research has identified two novel inflammatory biomarkers: platelet-activating factor (PAF) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)). The study found that Mediterranean, heart healthy, and vegetarian dietary patterns were associated with improved levels of PAF and Lp-PLA(2), while Western dietary patterns were less favorable. More well-designed studies are needed to confirm these findings and identify other dietary patterns that improve inflammation.
Article
Multidisciplinary Sciences
Junke Liu, Hengmin Tang, Chanjuan Xu, Shengnan Zhou, Xunying Zhu, Yuanyuan Li, Laurent Prezeau, Tao Xu, Jean-Philippe Pin, Philippe Rondard, Wei Ji, Jianfeng Liu
Summary: This study reveals that the assembly of platelet-activating factor receptor (PAFR) into dimers and oligomers can significantly influence its signaling mode. Oligomerization enhances G protein coupling, while restraining beta-arrestin recruitment and internalization.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Yue Liao, Susann Badmann, Till Kaltofen, Doris Mayr, Elisa Schmoeckel, Eileen Deuster, Mareike Mannewitz, Sarah Landgrebe, Thomas Kolben, Anna Hester, Susanne Beyer, Alexander Burges, Sven Mahner, Udo Jeschke, Fabian Trillsch, Bastian Czogalla
Summary: The study investigated the role of platelet-activating factor acetylhydrolase in BRCA1 mutant ovarian cancer and its interaction with the Wnt signaling pathway. Results suggest that PAF-AH may have a protective role and negatively regulate the Wnt/beta-catenin pathway in ovarian cancer, particularly in BRCA1 mutant cases. Further research is needed to explore the potential use of PAF-AH as a biomarker for predicting disease risk and prognosis in ovarian cancer patients.
Review
Nutrition & Dietetics
Rajendran Harishkumar, Sakshi Hans, Janelle E. Stanton, Andreas M. Grabrucker, Ronan Lordan, Ioannis Zabetakis
Summary: This review discusses the role of platelet-activating factor (PAF) and its receptor in inflammatory diseases and atherosclerotic cardiovascular diseases, with a focus on how inhibiting PAF-R can reduce cardiovascular disease risk. Research suggests that dietary factors may modulate PAF metabolism and PAF-R function to regulate disease development.
Article
Immunology
Soodeh Mahdian, Reihaneh Pirjani, Raha Favaedi, Monireh Movahedi, Ashraf Moini, Maryam Shahhoseini
Summary: The study compared the levels of aPL and PAF among RIF and fertile women, finding that Anti Cardiolipin antibody IgG levels were above normal in a small portion of RIF patients. Differences in the correlation of aPL and PAF levels in the two groups suggest that the same changes may have different effects on RIF and fertile women.
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2021)
Article
Food Science & Technology
Mingming Li, Xin Zhang, Jiapeng Li, Linggao Liu, Qiujin Zhu, Chao Qu, Yunhan Zhang, Shouwei Wang
Summary: This study investigated the isolation, purification, and identification of potential cardioprotective bioactive peptides from dry-cured pork coppa. The results showed that M1F2 peptide had a higher inhibitory effect on cardiovascular inflammation compared to M2F2. Nano-liquid chromatography-tandem mass spectrometry identified a total of 30 peptides, among which LTDKPFL, VEAPPAKVP, KVPVPAPK, IPVPKK, and PIKRSP were found to be promising platelet-activating factor acetyl hydrolase inhibitory peptides. Overall, bioactive peptides produced during the processing of dry-cured pork coppa have positive effects on human health.
Article
Biochemistry & Molecular Biology
Alexandros Tsoupras, Vassili N. Kouvelis, Katherine M. Pappas, Constantinos A. Demopoulos, Milton A. Typas
Summary: In this study, the lipids of the entomopathogenic fungus B. bassiana were found to exhibit strong anti-inflammatory and anti-thrombotic effects, particularly against platelet-activating factor (PAF). Lipid fractions derived from phenolics/glycolipids, Sphingomyelins, and Phosphatidylcholines (PC) showed potent anti-PAF activity. The presence of these bioactive lipids in B. bassiana opens up new possibilities for its potential applications.
PROSTAGLANDINS & OTHER LIPID MEDIATORS
(2022)
Article
Chemistry, Medicinal
Alexandros Tsoupras, Chloe Brummell, Ciara Kealy, Karolis Vitkaitis, Shane Redfern, Ioannis Zabetakis
Summary: The beneficial effects of fish-derived lipid bioactives, including omega-3 (n-3) polyunsaturated fatty acids, lipid vitamins, carotenoids, and polar lipid bioactives, have been extensively studied for their potential in preventing chronic disorders, particularly inflammation and cardiovascular diseases. This article reviews recent findings on the lipid content, bio-functionality, and cardio-protective benefits of commonly consumed fish species. The recovery and utilization of lipid bioactives from fish by-products and fishing by-catch are also highlighted for their industrial and environmental significance. The effects of heat treatments during fish processing on the structures and functionality of these marine lipid bioactives are discussed, as well as the need for novel green extraction technologies and low temperature processing methods to minimize undesirable changes in the lipid profile.
Article
Food Science & Technology
Daniel Granato, Marcio Carocho, Lillian Barros, Ioannis Zabetakis, Andrei Mocan, Alexandros Tsoupras, Adriano Gomes Cruz, Tatiana Colombo Pimentel
Summary: This review integrates concepts of food science, technology, nutrition, circular economy, and sustainability to explore the technological applications of bioactive ingredients obtained from agro-industrial side-streams in dairy food formulations. By incorporating these ingredients, the nutritional value of traditional dairy products can be enhanced, contributing to circularity within food systems and human health.
TRENDS IN FOOD SCIENCE & TECHNOLOGY
(2022)
Article
Immunology
Athanasios Papakyriakou, Anastasia Mpakali, Efstratios Stratikos
Summary: This study investigates the heterodimerization topology between endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) using computational molecular dynamics calculations. The proposed model involves the exon 10 loop, suggesting a potential role and significance of ERAP1/ERAP2 molecular interactions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Dionisios Vourloumis, Ioannis Mavridis, Alexandros Athanasoulis, Ioannis Temponeras, Despoina Koumantou, Petros Giastas, Anastasia Mpakali, Victoria Magrioti, Jacqueline Leib, Peter van Endert, Efstratios Stratikos, Athanasios Papakyriakou
Summary: A highly selective synthetic method for functionalization of the alpha-hydroxy-beta-amino acid scaffold of an aminopeptidase inhibitor has been discovered. Structural studies revealed that interactions with the GAMEN loop play a key role in the potency and selectivity of the inhibitor. This study suggests that alpha-hydroxy-beta-amino acid derivatives could serve as useful drug leads for aminopeptidases.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Petros Giastas, Athanasios Papakyriakou, George Tsafaras, Socrates J. Tzartos, Marios Zouridakis
Summary: The beta 3 subunit of nicotinic acetylcholine receptors (nAChRs) has been considered an accessory subunit, but recent research suggests that it may have a functional role. The crystal structure of the beta 3 extracellular domain (ECD) shows distinctive features that hinder the binding site cavity, and molecular dynamics simulations demonstrate that the site cannot efficiently accommodate nicotine. These findings support the accessory role of the beta 3 subunit.
Article
Food Science & Technology
Alexandros Tsoupras
Summary: The antioxidant properties of vitamin C and phenolic compounds in citrus fruits are well-established. This study evaluates the anti-inflammatory and antithrombotic effects of vitamin C and citrus fruit juices on platelets and leukocytes, demonstrating their potential as functional foods with protective health benefits against inflammation and thrombosis.
Editorial Material
Biochemistry & Molecular Biology
Theoharis C. Theoharides, Smaragdi Antonopoulou, Constantinos A. Demopoulos
Article
Oncology
Mantas Grigalavicius, Somayeh Ezzatpanah, Athanasios Papakyriakou, Tine Therese Henriksen Raabe, Konstantina Yannakopoulou, Theodossis A. Theodossiou
Summary: In a metabolic study, it was found that the addition of b-aminolevulinic acid (5-ALA) to glioblastoma multiforme (GBM) cells inhibited glycolysis and reduced adenosine triphosphate (ATP) production. The inhibitory effect is believed to be due to the competitive inhibition of lactate dehydrogenase (LDH) by 5-ALA. The inhibition of LDH by 5-ALA was found to be comparable to established LDH inhibitors oxamate (OXM) and tartronate (TART). 5-ALA-induced glycolysis inhibition resulted in cell death in different metabolic phenotypes of GBM cells, with better outcomes in the Warburg-type cells. Furthermore, the inhibition of LDH by 5-ALA enhanced the outcome of photodynamic therapy (PDT) in GBM cells.
Article
Biochemistry & Molecular Biology
Alessandro Agnarelli, Andrea Lauer Betran, Athanasios Papakyriakou, Viviana Vella, Mark Samuels, Panagiotis Papanastasopoulos, Christina Giamas, Erika J. Mancini, Justin Stebbing, John Spencer, Chiara Cilibrasi, Angeliki Ditsiou, Georgios Giamas
Summary: Recently, the oncogenic role of LMTK3 has been established in different tumors, making it a potential target for cancer therapy. In this study, a highly specific small molecule inhibitor for LMTK3, called C36, was identified and shown to have significant therapeutic effects in cancer cell lines. The binding affinity between LMTK3 and C36 was demonstrated through microscale thermophoresis, and C36 was found to inhibit the activity of LMTK3 by binding to both the ATP- and substrate-binding sites. Treatment with C36 led to decreased proliferation and increased apoptosis in breast cancer cells, highlighting the potential of LMTK3 inhibitors for cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Athena Andreou, Athanasios Papakyriakou, Maria I. Zervou, George N. Goulielmos, Elias E. Eliopoulos
Summary: The IFIH1 gene encodes MDA5, a cytoplasmic RNA helicase involved in innate immunity. The missense variant rs35667974 of IFIH1 is protective for some autoimmune diseases but increases the risk for others. This study shows that the rs35667974 variant affects the catalytic activity of MDA5 in the presence of 2'-O methylation, leading to reduced negative feedback on cytokine signaling and selectively protecting against autoimmunity.
JOURNAL OF MOLECULAR EVOLUTION
(2023)
Review
Chemistry, Medicinal
Dimitris Georgiadis, Nikolaos Skoulikas, Athanasios Papakyriakou, Efstratios Stratikos
Summary: Phosphinic peptides are important bioactive compounds used in the study of Zn-metalloproteases in the field of biology and pharmacology. They mimic the structure of natural substrates during proteolysis and act as mechanism-based inhibitors. Phosphinic peptides serve as tool compounds for rational drug design and the exploration of biological pathways.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Smaragdi Antonopoulou, Constantinos A. Demopoulos
Summary: Atherosclerosis is a progressive vascular disease caused by inflammation and oxidation. The Mediterranean diet, especially olive oil, has been recognized as a healthy dietary pattern. This review focuses on the effects of olive oil microconstituents in atherosclerosis, particularly their inhibitory activity against Platelet-Activating Factor (PAF) actions. The anti-atherogenic effect of olive oil is attributed to the synergistic action of its microconstituents, including polar lipids, polyphenols, and alpha-tocopherol. Daily moderate intake of olive oil in a balanced diet is significant for healthy adults.
Article
Biochemistry & Molecular Biology
Antigoni Margariti, Vasiliki D. Papakonstantinou, George M. Stamatakis, Constantinos A. Demopoulos, Christina Machalia, Evangelia Emmanouilidou, Gregor Schnakenburg, Maria-Christina Nika, Nikolaos S. Thomaidis, Athanassios I. Philippopoulos
Summary: This study investigates the antiplatelet and anti-inflammatory activities of a series of complexes. It is found that certain complexes exhibit potent inhibitory effects on platelet aggregation induced by Platelet-Activating Factor (PAF) and also affect the metabolic enzymatic pathways of PAF, resulting in anti-inflammatory properties.
Article
Biotechnology & Applied Microbiology
Kyeesha Glenn-Davi, Alison Hurley, Eireann Brennan, Jack Coughlan, Katie Shiels, Donal Moran, Sushanta Kumar Saha, Ioannis Zabetakis, Alexandros Tsoupras
Summary: The effects of fermentation on the anti-inflammatory and anti-platelet properties of dairy and plant-based alternatives were evaluated. Fermented products exhibited stronger anti-inflammatory and anti-platelet potency, with polar lipids showing the most significant effects. Fermentation altered the fatty acid content, increasing the unsaturated fatty acids and enhancing the functional properties of these bioactives.
FERMENTATION-BASEL
(2022)
Article
Biochemistry & Molecular Biology
Michael Ramek, Jasmina Sabolovic
Summary: This paper investigates the geometries, energy landscapes, and magnetic parameters of copper(II) amino acid compounds using density functional theory calculations. The results show that certain conformers with histaminate-like and glycine-like modes have low Gibbs free energies and high metal-binding affinities. The predicted conformations reproduce the experimental electron paramagnetic resonance parameters.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Wei Tian, Wen Zhong, Zengyan Yang, Ling Chen, Shijie Lin, Yanping Li, Yuxing Wang, Peilin Yang, Xing Long
Summary: A series of novel dibutyltin complexes based on salen-like ligands were synthesized and characterized. Complex S03 showed excellent in vitro anticancer activity and induced cancer cell death through multiple mechanisms. This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Natalie C. Korkola, Martin J. Stillman
Summary: Many proteins require a metal cofactor for their function, and these metals play a role in protein folding. The study found that the metallation rates of different metal binding pathways are influenced by pH, with the less cooperative pathway being more affected by low pH conditions. Specific mixtures of structures are formed in the initial steps of metallation, and unfolding the disordered apo-MT structure hinders the formation of these preliminary structures. The compact conformation of the native apo-MT allows for rapid formation of metal-thiolate structures with high affinity, providing protection from oxidation.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Boxuan Yang, Xitong Song, Binju Wang
Summary: The diiron active site plays a crucial role in catalytic transformations in both biological and chemical systems. Recent advancements in the field include the synthesis of biomimetic diiron catalysts inspired by the active structure of soluble methane monooxygenase (sMMO), which have been successfully applied to the dehydrogenation of indolines.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Christina N. Banti, Angeliki A. Piperoudi, Catherine P. Raptopoulou, Vassilis Psycharis, Constantinos M. Athanassopoulos, Sotiris K. Hadjikakou
Summary: Two copper(I) polymorphs with mitochondria-targeting properties were successfully prepared via metal ion conjugation. These compounds showed promising activities in DNA binding, enzyme inhibition, and cancer cell inhibition. The molecular mechanisms of action were investigated.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
