Leukotrienes

AIMS: The aim of this study was to investigate the effects of chlorogenic acid (CGA) on the intestinal microorganisms and metabolites in broilers during lipopolysaccharide (LPS)-induced immune stress. METHODS: A total of 312 one-day-old Arbor Acres (AA) broilers were randomly allocated to four groups with six replicates per group and 13 broilers per replicate: (1) MS group (injected with saline and fed the basal diet); (2) ML group (injected with 0.5 mg LPS/kg and fed the basal diet); (3) MA group (injected with 0...

In the last few years there has been an increased appreciation that pain perception in rheumatic and musculoskeletal diseases (RMDs) has several mechanisms which include nociceptive, inflammatory, nociplastic and neuropathic components. Studies in specific patient groups have also demonstrated that the pain experienced by people with specific diagnoses can present with distinctive components over time. For example, the pain observed in rheumatoid arthritis has been widely accepted to be caused by the activation of nociceptors, potentiated by the release of inflammatory mediators, including prostaglandins, leukotrienes and cytokine networks in the joint environment...

Arachidonic acid (AA) is a main component of cell membrane lipids. AA is mainly metabolized by three enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP450). Esterified AA is hydrolysed by phospholipase A2 into a free form that is further metabolized by COX, LOX and CYP450 to a wide range of bioactive mediators, including prostaglandins, lipoxins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. Increased mitochondrial oxidative stress is considered to be a central mechanism in the pathophysiology of the kidney...

Patients with severe eosinophilic asthma experience high risk of exacerbations and reduced quality of life. Benralizumab, a monoclonal antibody binding to IL-5 receptor α subunit, is an approved drug for its treatment. The objective was to describe clinical remission after benralizumab prescription in routine clinical practice. Retrospective multicenter study with data from four hospitals in Valencian Community (Spain) with asthma units between 2019 and 2020. Data was gathered at baseline and after 12 months...

Osteoporosis is a metabolic bone disease closely associated with oxidative stress. We had previously confirmed that the Viscozyme-assisted polysaccharide from Portulaca oleracea L (VPOP1) protects against antioxidant stress and evaluated the structure of VPOP1. In this study, we aimed to explore the anti-osteoporotic effects of VPOP1 on H2 O2 -induced osteoblast apoptosis. In addition, untargeted zebrafish metabolomics based on UPLC-Q-Orbitrap-HRMS was used to investigate the potential anti-osteoporotic mechanisms of VPOP1...

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft- versus -host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT)...

Treatment of tuberculosis (TB) is faced with several challenges including the long treatment duration, drug toxicity and tissue pathology. Host-directed therapy provides promising avenues to find compounds for adjunctively assisting antimycobacterials in the TB treatment regimen, by promoting pathogen eradication or limiting tissue destruction. Eicosanoids are a class of lipid molecules that are potent mediators of inflammation and have been implicated in aspects of the host response against TB. Here, we have explored the blood transcriptome of pulmonary TB patients to understand the activity of leukotriene B4, a pro-inflammatory eicosanoid...

Leukotriene A4 hydrolase (LTA4H) is the final and rate-limiting enzyme in the biosynthesis of pro-inflammatory leukotriene B4 (LTB4 ). Preclinical studies have provided strong evidence that LTA4H is an attractive drug target for the treatment of chronic inflammatory diseases. Here, we describe the transformation of compound 2 , a fragment-like hit, into the potent inhibitor of LTA4H 3 . Our strategy involved two key steps. First, we aimed to increase the polarity of fragment 2 to improve its drug-likeness, particularly its solubility, while preserving both its promising potency and low molecular weight...

Prostaglandin E2 (PGE2) signals differently through 4 receptor subtypes (EP1-EP4) to elicit diverse physiologic/pathologic effects. We previously reported that PGE2 via its EP3 receptor reduces cardiac contractility and male mice with cardiomyocyte-specific deletion of the EP4 receptor (EP4 KO) develop dilated cardiomyopathy. The aim of this study was to identify pathways responsible for this phenotype. We performed ingenuity pathway analysis (IPA) and found that genes differentiating WT mice and EP4 KO mice were significantly overrepresented in mitochondrial (adj...

BACKGROUND: The aim of this study is to evaluate the role of leukotriene B4, an inflammatory mediator, in the development of pulmonary hypertension in paediatric patients with CHD with left-right shunt. METHODS: The study included forty patients with CHD with left-right shunts. Based on haemodynamic data obtained from cardiac diagnostic catheterisation, 25 patients who met the criteria for pulmonary arterial hypertension were included in the patient group. The control group comprised 15 patients who did not meet the criteria...

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient's response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy...

OBJECTIVES: Montelukast is a well-known leukotriene receptor antagonist commonly used in treating allergic rhinitis and asthma. Omega-3 fatty acid is also known as an antiallergic and immunomodulator molecule. This study aimed to elucidate the efficacy of systemic montelukast and omega-3 fatty acid treatment in allergic rhinitis models in Wistar Hannover rats. METHODS: This research was conducted on 28 healthy Wistar Hannover rats weighing 250-350 g. After establishing the allergic rhinitis model, nasal symptoms were observed and scored, and the nasal mucosa of all rats was investigated histologically...

Pneumocystis pneumonia (PCP) is a fungal pulmonary disease with high mortality in immunocompromised patients. Neutrophils are essential in defending against fungal infections; however, their role in PCP is controversial. Here we aim to investigate the effects of neutrophil extracellular traps (NETs) on Pneumocystis clearance and lung injury using a mouse model of PCP. Intriguingly, although neutrophils play a fundamental role in defending against fungal infections, NETs failed to eliminate Pneumocystis, but instead impaired the killing of Pneumocystis...

Macrophages (MΦ) infected with human immunodeficiency virus (HIV)-1 or activated by its envelope protein gp120 exert neurotoxicity. We found previously that signaling via p38 mitogen-activated protein kinase (p38 MAPK) is essential to the neurotoxicity of HIVgp120-stimulated MΦ. However, the associated downstream pathways remained elusive. Here we show that cysteinyl-leukotrienes (CysLT) released by HIV-infected or HIVgp120 stimulated MΦ downstream of p38 MAPK critically contribute to neurotoxicity...

Background and aims: Granulocyte colony-stimulating factor (G-CSF) has been proposed as a therapeutic option for patients with ACLF, however clinical outcomes are controversial. We aimed at dissecting the role of G-CSF in an alcohol-induced murine model of ACLF. Methods : ACLF was triggered by a single alcohol binge (5 g/kg) in a bile duct ligation (BDL) liver fibrosis model. A subgroup of mice received two G-CSF (200 μg/kg) or vehicle injections prior to acute decompensation with alcohol. Liver, blood and brain tissues were assessed...

Inflammation plays a pivotal role in various pathological processes, ranging from routine injuries and infections to cancer. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are two major enzymes involved in the formation of lipid mediators of inflammation, such as prostaglandins and leukotrienes, through the arachidonic acid pathway. Despite the frequent use of nonsteroidal anti-inflammatory drugs for managing inflammatory disorders by inhibiting these enzymes, there is a wide spectrum of adverse effects linked to their usage...

It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes...

Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A4 (LTA4 ), were increased in CD4+ T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission...

LYS006 is a novel, highly potent and selective, new-generation leukotriene A4 hydrolase (LTA4H) inhibitor in clinical development for the treatment of neutrophil-driven inflammatory diseases. We describe the complex pharmacokinetic to pharmacodynamic (PD) relationship in blood, plasma, and skin of LYS006-treated nonclinical species and healthy human participants. In a randomized first in human study, participants were exposed to single ascending doses up to 100 mg and multiple ascending doses up to 80 mg b...

BACKGROUND: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. HYPOTHESIS: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery...