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.
Review
Biochemistry & Molecular Biology
Carson J. Rohan, Rushabh P. Lohade, Chad Brewer, Jeffrey B. Travers
Summary: Thermal burn injuries in alcohol-intoxicated patients result in greater morbidity and mortality. This review highlights the roles of platelet-activating factor (PAF) and subcellular microvesicle particle (MVP) release in the pathology of intoxicated thermal burn injury (ITBI). The review provides a mechanism and potential therapeutic approaches for the increased toxicity and immunosuppressive outcomes of TBI in the presence of acute ethanol exposure.
Review
Biochemistry & Molecular Biology
Linyue Dong, Yiming Li, Huali Wu
Summary: Intracellular platelet activating-factor acetylhydrolase type II (PAF-AH II) is a monomeric enzyme with broad substrate specificity and various functions such as protection against oxidative stress, transacetylase activity, and producing lipid mediators. It has been proven to be involved in several diseases and has drawn attention from researchers.
CHEMISTRY AND PHYSICS OF LIPIDS
(2021)
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.
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
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)
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
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.
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
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
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.
Article
Chemistry, Medicinal
JiaYuan Xu, Wang Chen, ZiLi Feng, CongXue Duan, Bin Wang, ZhengDong Zhao
Summary: Ginkgolide B, a natural product, was modified to obtain 10 derivatives. These derivatives exhibited inhibitory activity against rabbit platelet aggregation induced by platelet activating factor, with 4 derivatives showing strong inhibitory activity.
MEDICINAL CHEMISTRY RESEARCH
(2022)
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
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.
Article
Chemistry, Medicinal
Noraziah Nordin, Juriyati Jalil, Mohd Faiz Abd Ghani, Adib Afandi Abdullah, Rozana Othman
Summary: Naturally derived flavonoids have been found to potentially act as promising PAF antagonists with some level of inhibitory activity. Further investigation is needed to develop new drug candidates for PAF-mediated diseases.
LETTERS IN DRUG DESIGN & DISCOVERY
(2022)
Article
Cell Biology
Kandahalli Venkataranganayaka Abhilasha, Mosale Seetharam Sumanth, Anita Thyagarajan, Ravi Prakash Sahu, Kempaiah Kemparaju, Gopal Kedihithlu Marathe
Summary: Bacterial toxins signaling through Toll-like receptors (TLRs) are involved in the pathogenesis of inflammatory diseases, with lipopolysaccharide (LPS) acting through TLR-4 and lipoteichoic acid (LTA), BLP, or Pam3CSK4 acting through TLR-2. The study suggests a potential role of PAF in TLR-mediated pathogenicity, with bacterial toxins shown to interact with PAF-R leading to cross-tolerance.
Article
Environmental Sciences
Isaie Sibomana, Joyce G. Rohan, David R. Mattie
Summary: This study investigated the potential toxicity of aircraft engine oils containing organophosphates on esterase activities, clinical chemistry parameters, and hippocampal electrophysiology in rats. The results showed gender differences in the effects of these oils, with significant impacts on AChE and BChE activities. Additionally, precautions should be taken to minimize long-term exposure to aircraft oil among maintenance workers.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2021)
Review
Medicine, Research & Experimental
Harshini Mallipeddi, Anita Thyagarajan, Ravi P. Sahu
Summary: The natural compound Withaferin-A has shown promising anti-tumoral activities against TNBC in both in-vitro and in-vivo experimental models, with studies indicating its potential to enhance chemotherapy efficacy. Derived from the ayurvedic medicinal plant Withania somnifera, Withaferin-A demonstrates anti-inflammatory and anti-cancer properties, highlighting its significance in the treatment of TNBC.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Nathan M. Gargas, Victoria T. Ethridge, Molly K. Miklasevich, Joyce G. Rohan
Summary: The study on Gulf War illness using a rat model showed significant effects on hippocampal function, behavior, and biochemical levels following exposure to GW chemicals, potentially leading to increased motor activity, changes in neuronal activity, and activation of immune response.
Review
Oncology
Sharlo Bayless, Jeffrey B. Travers, Ravi P. Sahu, Craig A. Rohan
Summary: Photodynamic therapy (PDT) is a treatment option for tumors and pre-cancerous lesions, but the immunosuppressive side effects can be blocked by inhibiting Tregs, MDSCs, and COX-2 to enhance treatment efficacy.
Article
Nutrition & Dietetics
Avinash S. Mahajan, Venkata S. Arikatla, Anita Thyagarajan, Tetyana Zhelay, Ravi P. Sahu, Michael G. Kemp, Dan F. Spandau, Jeffrey B. Travers
Summary: Dermal fibroblasts produce collagen and IGF-1, regulating cell proliferation and responses to stressors. The study shows that H2O2 induces cell senescence, while pretreatment with Cr or NAM can protect fibroblasts from this senescence. These findings suggest a potential strategy for preventing stress-induced senescence in aging skin.
Article
Biochemistry & Molecular Biology
Shreepa J. Chauhan, Anita Thyagarajan, Ravi P. Sahu
Summary: The study found that miR-149-5p can block PAFR-mediated lung cancer cell proliferation, while PAFR activation attenuates the cytotoxic effects of targeted therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anita Thyagarajan, Krishna Awasthi, Christine M. Rapp, R. Michael Johnson, Yanfang Chen, Kelly L. R. Miller, Jeffrey B. Travers, Ravi P. Sahu
Summary: Chemotherapy is the main treatment for various types of cancers, including skin cancer. However, it is limited by adverse effects. Recent studies have found that chemotherapy drugs can induce the generation of extracellular vesicles called microvesicle particles (MVP), which may involve specific receptors and enzymes. Experiments showed that topical application of gemcitabine can induce MVP generation in human and murine skin, and this process is dependent on specific receptors and enzymes.
Letter
Dermatology
Ericson John V. Torralba, Shikshita Singh, Robert F. Short, Christine M. Rapp, Karen M. Henkels, Ravi P. Sahu, Jeffrey B. Travers
SKIN RESEARCH AND TECHNOLOGY
(2023)
Letter
Dermatology
Anita Thyagarajan, Christine M. Rapp, Leah Schneider, Amie Lund, Jeffrey B. Travers, Ravi P. Sahu
SKIN RESEARCH AND TECHNOLOGY
(2023)
Review
Oncology
Aya Abunada, Zaid Sirhan, Anita Thyagarajan, Ravi P. Sahu
Summary: The evidence on HER2 directed therapy in breast cancer has been extensive in the past decade. Tyrosine kinase inhibitors have emerged as a significant treatment option for various malignancies. This literature commentary discusses the recent findings and clinical implications of TKI agents in improving outcomes for HER2 positive breast cancer.
WORLD JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Medicine, General & Internal
Zaid Sirhan, Anita Thyagarajan, Ravi P. Sahu
Summary: HER2 overexpression is common in breast cancer and is associated with poor prognosis. HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors have been used to treat HER2-positive breast cancer, but resistance mechanisms and limited treatment options after disease progression remain challenges. The recent FDA approval of tucatinib, a new tyrosine kinase inhibitor, for use in combination with immunotherapy and/or chemotherapy represents an important advancement in the treatment of advanced/metastatic HER2-positive breast cancer.
MILITARY MEDICAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Langni Liu, Azeezat A. Awoyemi, Katherine E. Fahy, Pariksha Thapa, Christina Borchers, Benita Y. Wu, Cameron L. McGlone, Benjamin Schmeusser, Zafer Sattouf, Craig A. Rohan, Amy R. Williams, Elizabeth E. Cates, Christina Knisely, Lisa E. Kelly, Ji C. Bihl, David R. Cool, Ravi P. Sahu, Jinju Wang, Yanfang Chen, Christine M. Rapp, Michael G. Kemp, R. Michael Johnson, Jeffrey B. Travers
Summary: UVB radiation is a major cause of skin cancer, inducing immunosuppression and the release of MVPs containing bioactive substances like PAFR agonists. Activation of PAFR in keratinocytes by UVB exposure leads to the generation of UVB-MVPs, which can affect systemic immunity in both mice and humans.
JOURNAL OF CLINICAL INVESTIGATION
(2021)