Publications by authors named "Paul Jordan"

Article Synopsis
  • mPGES-1 is highlighted as a key target for developing treatments for inflammation and pain, with the study introducing new benzimidazole compounds that effectively inhibit this enzyme.
  • One of the compounds, AGU654, showed exceptional selectivity for mPGES-1 over other related enzymes, with a low inhibition concentration (IC = 2.9 nM) and promising bioavailability.
  • AGU654 was able to reduce PGE production from activated immune cells without affecting other prostaglandins, and it also demonstrated success in alleviating fever and pain in guinea pig models, indicating its potential for managing inflammatory diseases.
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A library of degradable poly(2-alkyl-2-oxazoline) analogues (dPOx) with different length of the alkyl substituents was characterized in detail by gradient elution liquid chromatography. The hydrophobicity increased with increased side chain length as confirmed by a hydrophobicity row, established by reversed-phase liquid chromatography. Those dPOx were cytocompatible and formed colloidally stable nanoparticle (NP) formulations with positive zeta potential.

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Article Synopsis
  • L-(+)-Muscarine (1)-producing mushrooms are extremely dangerous, as consuming them can lead to serious health issues, including death, yet their metabolic properties remain poorly understood.
  • Research identified 4'-phosphomuscarine (2) as a key natural compound in the mycelium of Clitocybe rivulosa, using advanced techniques to confirm its structure, and it was also found in other mushroom species.
  • Muscaridine (3), another related compound, shows weak activation of the muscarinic acetylcholine receptor, highlighting the need for better understanding in emergency medicine to gauge the true risks associated with these toxic mushrooms.
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Here, we present a protocol for primary, human immune cell isolation and stimulation for lipid mediator profiling. We describe steps for the isolation of monocytes from human leukocyte concentrates via density centrifugation and differentiation/polarization toward M1- or M2-monocyte-derived macrophages (MDMs). We detail stimulation approaches of MDMs with live bacteria or influenza A virus for lipid mediator profiling and sample preparation for subsequent analysis, such as enzyme expression, mRNA analysis, or surface marker determination.

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Gliotoxin (GT), a secondary metabolite and virulence factor of the fungal pathogen Aspergillus fumigatus, suppresses innate immunity and supports the suppression of host immune responses. Recently, we revealed that GT blocks the formation of the chemotactic lipid mediator leukotriene (LT)B in activated human neutrophils and monocytes, and in rodents in vivo, by directly inhibiting LTA hydrolase. Here, we elucidated the impact of GT on LTB biosynthesis and the entire lipid mediator networks in human M1- and M2-like monocyte-derived macrophages (MDMs) and in human tissue-resident alveolar macrophages.

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Beneficial health effects of omega-3 polyunsaturated fatty acids (-3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve -3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory disorders. Here, we explored a synbiotic strategy to increase circulating SPM precursor levels.

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Selective inhibition of microsomal prostaglandin E synthase-1 (mPGES-1) is implicated as a new therapeutic modality for the development of new-generation anti-inflammatory drugs. Here, we present the discovery of new and potent inhibitors of human mPGES-1, i.e.

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The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur-containing amino lipids (SALs) involved in biofilm formation and marine surface colonization processes. Despite their physiological relevance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved, hindering progress in biochemical and functional investigations.

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Hybrid nanoparticles (HNPs) were designed by combining a PLGA core with a lipid shell that incorporated PEG-Lipid conjugates with various functionalities (-RGD, -cRGD, -NH, and -COOH) to create targeted drug delivery systems. Loaded with a neutral lipid orange dye, the HNPs were extensively characterized using various techniques and investigated for their uptake in human monocyte-derived macrophages (MDMs) using FC and CLSM. Moreover, the best-performing HNPs (i.

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Background: In times of physical stress, the body orchestrates a multisystemic regulatory response. The hormones epinephrine and norepinephrine play a role in the immediate regulation chain, while cortisol is involved in delayed regulation. The release of those stress hormones in response to exercise has previously been reported to elicit diverse immune reactions.

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Introduction: Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening colonoscopy every 10 years vs annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data.

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Respiratory influenza A virus (IAV) infections are major health concerns worldwide, where bacterial superinfections substantially increase morbidity and mortality. The underlying mechanisms of how IAV impairs host defense remain elusive. Macrophages are pivotal for the innate immune response and crucially regulate the entire inflammatory process, occurring as inflammatory M1- or pro-resolving M2-like phenotypes.

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Frankincense preparations are frequently used as traditional anti-inflammatory remedies in folk medicine with increasing popularity. Boswellic acids (BAs), especially 3-O-acetyl-11-keto-βBA (AKBA), are unique anti-inflammatory principles of frankincense, with multiple pharmacological actions and target proteins. We recently showed that AKBA favorably impacts lipid mediator (LM) networks in innate immune cells, by modulation of lipoxygenase (LOX) activities.

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The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds. However, the study designs and methods are highly diverse, presenting different hlAD disease patterns that occur after sensitization and repeated challenge with DNCB on dorsal skin. In addition, there is a lack of information about the progression of the disease during the experiment and the achieved pheno- and endotypes, especially at the timepoint when therapeutic treatment is initiated.

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Lipoxygenases (LOX) transform arachidonic acid (AA, C20:4) and docosahexaenoic acid (DHA, C22:6) into bioactive lipid mediators (LMs) that comprise not only pro-inflammatory leukotrienes (LTs) but also the specialized pro-resolving mediators (SPMs) that promote inflammation resolution and tissue regeneration. The 5-LOX-activating protein (FLAP) is known to provide AA as a substrate to 5-LOX for generating LTs, such as LTB, a potent chemoattractant and activator of phagocytes. Notably, 5-LOX is also involved in the biosynthesis of certain SPMs, namely, lipoxins and D-resolvins, implying a role of FLAP in SPM formation.

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5-Lipoxygenase-activating protein (FLAP) is a regulator of cellular leukotriene biosynthesis, which governs the transfer of arachidonic acid (AA) to 5-lipoxygenase for efficient metabolism. Here, the synthesis and FLAP-antagonistic potential of fast synthetically accessible 1,2,4-triazole derivatives based on a previously discovered virtual screening hit compound is described. Our findings reveal that simple structural variations on 4,5-diaryl moieties and the 3-thioether side chain of the 1,2,4-triazole scaffold markedly influence the inhibitory potential, highlighting the significant chemical features necessary for FLAP antagonism.

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Cannabinoids are phytochemicals from cannabis with anti-inflammatory actions in immune cells. Lipid mediators (LM), produced from polyunsaturated fatty acids (PUFA), are potent regulators of the immune response and impact all stages of inflammation. How cannabinoids influence LM biosynthetic networks is unknown.

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Glucocorticoids (GC) are potent anti-inflammatory agents, broadly used to treat acute and chronic inflammatory diseases, e.g., critically ill COVID-19 patients or patients with chronic inflammatory bowel diseases.

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Objectives: Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids and precursors of oxygenated lipid mediators with diverse functions, including the control of cell growth, inflammation and tumourigenesis. However, the molecular pathways that control the availability of PUFAs for lipid mediator production are not well understood. Here, we investigated the crosstalk of three pathways in the provision of PUFAs for lipid mediator production: (i) secreted group X phospholipase A (GX sPLA) and (ii) cytosolic group IVA PLA (cPLAα), both mobilizing PUFAs from membrane phospholipids, and (iii) adipose triglyceride lipase (ATGL), which mediates the degradation of triacylglycerols (TAGs) stored in cytosolic lipid droplets (LDs).

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In dermatological research, 2,4-dinitrochlorbenzene (DNCB)-induced atopic dermatitis (AD) is a standard model as it displays many disease-associated characteristics of human AD. However, the reproducibility of the model is challenging due to the lack of information regarding the methodology and the description of the phenotype and endotype of the mimicked disease. In this study, a DNCB-induced mouse model was established with a detailed procedure description and classification of the AD human-like skin type.

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In the last decades, inflammation has been recognized as being closely connected to cancer, and joint strategies encompassing chemotherapeutic and anti-inflammatory agents have been extensively studied. In this work, a series of novel cisplatin and oxaliplatin-based Pt(IV) complexes comprising non-steroidal anti-inflammatory drugs (NSAIDs) and their carboxyl ester analogues as axial moieties were synthesized. Several of the cisplatin-based Pt(IV) complexes 22-30 showed increased cytotoxicity in the human cancer cell lines CH1/PA-1, SW480 and A549 compared to the Pt(II) drug.

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Tuberculosis caused by Mycobacterium tuberculosis is a leading cause of death globally and a major health concern. In humans, macrophages are the first line invaded by M. tuberculosis.

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Background & Aims: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs.

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Dextran-based polymers, such as ethoxy acetalated dextran (Ace-DEX), are increasingly becoming the focus of research as they offer great potential for the development of polymer-based nanoparticles as drug delivery vehicles. Their major advantages are the facile synthesis, straightforward particle preparation and the pH-dependent degradation of the particles that can be fine-tuned by the degree of acetalation of the polymer. In this study we have shown that Ace-DEX can not only compete against the commonly used and FDA-approved polymer poly(lactic--glycolic acid) (PLGA), but even has the potential to outperform it in its encapsulation properties, , for the herein used anti-inflammatory leukotriene biosynthesis inhibitor BRP-187.

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