Search Results (265)

Obstructive sleep apnea syndrome (OSAS) in children and adolescents is a prevalent and multifactorial disorder associated with significant short- and long-term health consequences. While adenotonsillectomy (AT) remains the first-line treatment, a substantial proportion of patients—especially those with obesity, craniofacial anomalies, or comorbid conditions—exhibit persistent or recurrent symptoms, underscoring the need for individualized and multimodal approaches. This review provides an updated and comprehensive overview of current and emerging treatments for pediatric OSAS, with a focus on both surgical and non-surgical options, including pharmacological, orthodontic, and myofunctional therapies. A narrative synthesis of recent literature was conducted, including systematic reviews, randomized controlled trials, and large cohort studies published in the last 10 years. The review emphasizes evidence-based indications, mechanisms of action, efficacy outcomes, safety profiles, and limitations of each therapeutic modality. Adjunctive and alternative treatments such as rapid maxillary expansion, mandibular advancement devices, myofunctional therapy, intranasal corticosteroids, leukotriene receptor antagonists, and hypoglossal nerve stimulation show promising results in selected patient populations. Personalized treatment plans based on anatomical, functional, and developmental characteristics are essential to optimize outcomes. Combination therapies appear particularly effective in children with residual disease after AT or with specific phenotypes such as Down syndrome or maxillary constriction. Pediatric OSAS requires a tailored, multidisciplinary approach that evolves with the child’s growth and clinical profile. Understanding the full spectrum of available therapies allows clinicians to move beyond a one-size-fits-all model, offering more precise and durable treatment pathways. Emerging strategies may further redefine the therapeutic landscape in the coming years. Full article

The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18–55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant (p < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways. Full article

Bladder dysfunction is among the most drastic and quality-of-life-reducing conditions after spinal cord injury (SCI). Neuroinflammation in the lower urinary tract (LUT) after SCI could be a key driver of neurogenic bladder dysfunction and tissue fibrosis. Leukotrienes, a group of highly active lipid mediators, are potent inflammatory mediators. Here, we explored the potential of early montelukast (MLK) therapy, a cysteinyl leukotriene receptor 1 antagonist, on LUT function and structure four weeks after severe SCI in rats. Rats (strain Lewis, female, n = 50) received a permanent bladder catheter, followed by a complete T9 spinal cord transection. MLK was given daily, starting on day one post-injury. Bladder and locomotor function were regularly assessed. Bladder tissue was histologically and immunhistochemically analyzed. Post-SCI, MLK concentrations in plasma and cerebrospinal fluid were clinically relevant. MLK improved bladder functionality. MLK had no impact on smooth muscle alignment and uroepithelial integrity at this early SCI time point. This pilot study gave first insights into early, continuous oral MLK treatment with the first promising results of preserved LUT function and possible subsequent improved tissue integrity. Full article

Neurodegenerative diseases are characterised by the progressive loss of neurons, leading to a decline in specific brain functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most prevalent, affecting approximately 60 million people worldwide. The pathogenesis of these diseases is complex, combining inflammatory, oxidative, and excitotoxic processes that result in neuronal dysfunction and death. Despite recent advances, there is currently no cure for AD and PD. Available therapies demonstrate limited efficacy, highlighting the continuing need for novel therapeutic approaches. Ergolide, a naturally occurring sesquiterpene lactone from the Inula brittanica plant, has shown immunoregulatory properties in systemic immune cells and potential applications in certain cancers. This study examines whether the therapeutic effects of ergolide extend to the brain. We explored its mechanisms of action in vitro, and its capacity to restore behavioural integrity in zebrafish models of inflammation and neurotoxicity in vivo. We report the ability of ergolide to attenuate inflammatory cytokine and nitric oxide (NO) production from microglia in response to toll-like receptor activation. We further propose a role for the NFκB and cysteinyl leukotriene (CysLT) pathways in ergolide-mediated regulation of microglial activation. Ergolide did not protect against oxidative-induced neuronal death in vitro or mitigate seizure activity in zebrafish. Instead, we revealed a pro-oxidant and cytotoxic effect on neuroblastoma cells. Importantly, ergolide improved survival and alleviated the dysfunction in sensorimotor behaviour in a zebrafish model of inflammation. Our findings reveal a neuroprotective effect of ergolide, likely stemming from its immunoregulatory capacity. We also support further investigation of the CysLT pathway as a therapeutic target for neuroinflammatory-related disease. Full article

The aim of this narrative review is to explore possible connections that might lead to both obesity and asthma; it will explain factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, lung function, the genetics/genomics of obese asthma, risk of exacerbation, atopy, and response to treatment. It highlights the role that obesity plays as a risk factor for and disease modifier of asthma, understanding the evidence supporting lifestyle changes in influencing disease progression. Pathophysiological mechanisms in obesity-related asthma have influences on the course of disease pathology. Due to these factors, the child with obese asthma needs a specific therapeutic approach taking into account the common unresponsiveness to bronchodilators, increased requirements for controller medications, poorer steroid effectiveness, and better response to leukotriene receptor (LTR) inhibitors. Therapeutic strategies centered on prevention are suggested and the development of resources to assist families with weight loss strategies and lifestyle changes is shown to be useful for effective weight control and optimal asthma management. Obese children with asthma generally should receive interventions that encourage daily physical activity, weight loss, and normalization of nutrient levels, and monitoring of common obesity-related sequelae should be considered by healthcare providers managing obese children with difficult to control asthma. Recognizing and identifying an asthmatic patient is not always easy and a detailed medical history of the patient, with particular attention paid to their presenting and past symptoms, and a complete physical examination play pivotal and fundamental roles in determining the final diagnosis. Full article

Background/Objectives: Montelukast (MLK), a leukotriene receptor antagonist, has been associated with neuropsychiatric side effects. This study aimed to rationally modify MLK’s structure to reduce these risks by optimizing its interactions with dopamine D2 (DRD2) and serotonin 5-HT1A receptors using computational molecular simulation techniques. Methods: A library of MLK derivatives was designed and screened using structural similarity analysis, molecular docking, molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations, and ADME-Tox predictions. Structural similarity analysis, based on Tanimoto coefficient fingerprinting, compared MLK derivatives to known neuropsychiatric drugs. Docking was performed to assess initial receptor binding, followed by 100 ns MD simulations to evaluate binding stability. MM/PBSA calculations quantified binding affinities, while ADME-Tox profiling predicted pharmacokinetic and toxicity risks. Results: Several MLK derivatives showed enhanced DRD2 and 5-HT1A binding. MLK_MOD-42 and MLK_MOD-43 emerged as the most promising candidates, exhibiting MM/PBSA binding free energies of −31.92 ± 2.54 kcal/mol and −27.37 ± 2.22 kcal/mol for DRD2 and −30.22 ± 2.29 kcal/mol and −28.19 ± 2.14 kcal/mol for 5-HT1A, respectively. Structural similarity analysis confirmed that these derivatives share key pharmacophoric features with atypical antipsychotics and anxiolytics. However, off-target interactions were not assessed, which may influence their overall safety profile. ADME-Tox analysis predicted improved oral bioavailability and lower neurotoxicity risks. Conclusions: MLK_MOD-42 and MLK_MOD-43 exhibit optimized receptor interactions and enhanced pharmacokinetics, suggesting potential neuropsychiatric applications. However, their safety and efficacy remain to be validated through in vitro and in vivo studies. Until such validation is performed, these derivatives should be considered as promising candidates with optimized receptor binding rather than confirmed safer alternatives. Full article

Upper gastrointestinal bleeding from erosive gastritis remains associated with high mortality in septic or postoperative patients. While stress ulcer bleeding has declined, it still occurs in septic patients and is considered a manifestation of intestinal failure within multi-organ failure syndrome. The integrity of the gastric mucosal barrier plays a crucial role in protection against this condition. Somatostatin (SS) appears as a biomolecule with cytoprotective properties. We aimed to investigate whether SS treatment protected the gastric mucosa in a rat model of lipopolysaccharide (LPS)-induced sepsis. Rats received LPS (10 mg/kg) intraperitoneally, followed by saline or SS (200 μg/kg; 5 mL/kg) treatment after 30 min (early treatment group) or 120 min (late treatment group). Control rats received only saline. Two hours after saline or SS administration (total procedure duration of 150 or 240 min), gastric lavage, gastric mucosa, and plasma samples were collected for analysis. SS treatment mitigated the LPS-induced gastric mucosal barrier disruption preserving phosphatidylcholine (PC) levels, as well as decreasing leukocyte infiltration marker myeloperoxidase (MPO), inflammation-related enzyme phospholipase A2 (PLA2), and lipid peroxidation indicator malondialdehyde (MDA). SS also reduced arachidonic acid-related metabolites thromboxane B2 (TXB2) and leukotriene B4 (LTB4) while increasing prostaglandin I2 (PGI2). SS treatment effectively maintained gastric mucosal integrity, reducing inflammation, and modulating arachidonic acid metabolites. These findings suggest that SS may serve as a therapeutic agent for preserving gastric mucosal integrity and reducing inflammation in LPS-induced gastric injury. Full article

Air pollution has been widely recognized as a risk factor for neurological disorders, and the gut microbiome may play a mediating role. However, current evidence remains limited. In this study, a mouse model was employed with continuous exposure to real-time air pollution from conception to late adolescence. Effects of growth-stage air pollution exposure on the gut microbiome, host metabolites, and brain tissue were assessed. Pathological damage in the hippocampus and cortex was observed. Fecal metagenomic sequencing revealed alterations in both compositions and functions of the gut microbiome. Metabolic disturbances in unsaturated fatty acids and glycerophospholipids were identified in the intestine, serum, and brain tissues, with significant changes in metabolites (e.g., gamma-linolenic acid, alpha-linolenic acid, docosahexaenoic acid (DHA), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Serum levels of the pro-inflammatory mediator leukotriene C4 were also elevated. Correlation analysis identified a group of different gut microbiome species that were associated with host metabolites. Furthermore, mediation analysis showed that intestinal and serum metabolites mediated the associations between the key gut microbiome and brain microbiome. These findings indicate that the metabolic crosstalk in the gut–brain axis mediates the neuronal damage in mice induced by growth-stage air pollution exposure, potentially through pathways involving lipid metabolism and inflammation. Full article

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting inflammation and PUFAs mitigating it. Oxylipins, bioactive molecules derived from the oxidation of PUFAs, play crucial roles in immune regulation across various organisms, including plants, fungi, and bacteria. These molecules, such as prostaglandins, leukotrienes, and resolvins, regulate immune responses during infection and inflammation. The production of oxylipins extends beyond mammals, with fungi and bacteria synthesizing these molecules to modulate immune responses, promoting both defense and pathogenesis. This review delves into the multifaceted effects of oxylipins, exploring their impact on host and microbial interactions, with a focus on their potential for therapeutic applications in modulating infection and immune response. Full article

Chronic lymphocytic leukemia (CLL) cells depend on microenvironment niches for proliferation and survival. The adhesion of tumor cells to stromal cells in such niches triggers the activation of signaling pathways crucial for their survival, including B-cell receptor (BCR) signaling. While inhibitors of Bruton’s tyrosine kinase (BTKi) have shown efficacy in patients with CLL by disrupting these interactions, acquired resistance and toxicity remain a challenge during long-term therapy. Thus, identifying additional therapeutic modalities is important. Previously, we demonstrated that 5-lipoxygenase (5-LOX) pathway inhibitors reduced mantle cell lymphoma (MCL) cell adhesion to stromal cells, motivating us to investigate their potential in the context of CLL. We employed an ex vivo co-culture model to study CLL cell adhesion to stromal cells in the absence and presence of 5-LOX pathway inhibitors (zileuton and MK886) as well as the BTKi ibrutinib that was included for comparative purposes. Our findings demonstrated that different CLL samples adhere to stromal cells differentially. We observed a variable decrease in CLL cell adhesion to stromal cells following the inhibition of the 5-LOX pathway across a spectrum of patient samples that was distinct to the spectrum for ibrutinib. Positive and negative correlations were shown between the clinical and genetic features of the CLL samples and their level of adherence to stromal cells in both the absence and presence of the tested inhibitors. These results suggest the 5-LOX pathway as a candidate for assessment as a new therapeutic target in CLL. Full article

This study aimed to evaluate the effects of aspirin eugenol ester (AEE) on growth performance, oxidative liver damage, inflammation, and liver metabolomics in broilers under high-stocking-density (HSD) stress. A total of 360 broilers were divided into four groups: normal density (ND, 14/m²), high density (HD, 22/m²), ND-AEE (ND + 0.01% AEE), and HD-AEE (HD + 0.01% AEE). HSD decreased total antioxidant capacity, increased malondialdehyde (MDA) levels, and elevated the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) mRNA, which contributed to the reduced performance of broilers. Specifically, HSD caused abnormalities in linoleic acid metabolism, leading to elevated levels of Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4) synthesis, which aggravated inflammation, increased liver lipid levels, and impaired ATP production. AEE counteracted the decline in broiler production performance induced by HSD by enhancing total antioxidant capacity, reducing MDA levels, protecting the liver from oxidative damage, and maintaining mitochondrial oxidative phosphorylation. AEE positively regulated the linoleic acid metabolism by promoting the synthesis of γ-linolenic acid and phosphatidylcholine, which reduced the synthesis of COX-2 and mPGES-1. AEE alleviated the metabolic imbalance caused by HSD stress and enhanced the efficiency of mitochondrial fatty acid oxidation, which reduced excess lipid accumulation in the liver and promoted ATP production. In summary, this study provides strong support for the dietary addition of AEE to alleviate liver oxidative damage, inflammation, and energy metabolism disorders caused by HSD stress. Full article

Many polyunsaturated fatty acids within cells exhibit diverse physiological functions. Particularly, arachidonic acid is the precursor of highly bioactive prostaglandins and leukotrienes, which are pro-inflammatory mediators. However, polyunsaturated fatty acids, such as arachidonic, docosahexaenoic, and eicosapentaenoic acids, can be metabolized into specialized proresolving mediators (SPMs), which have anti-inflammatory properties. Given that pro-inflammatory mediators and SPMs are produced via similar enzymatic pathways, SPMs can play a crucial role in mitigating excessive tissue damage induced by inflammation. Mast cells are immune cells that are widely distributed and strategically positioned at interfaces with the external environment, such as the skin and mucosa. As immune system sentinels, they respond to harmful pathogens and foreign substances. Upon activation, mast cells release various pro-inflammatory mediators, initiating an inflammatory response. Furthermore, these cells secrete factors that promote tissue repair and inhibit inflammation. This dual function positions mast cells as central regulators, balancing between the body’s defense mechanisms and the need to minimize tissue injury. This review investigates the production of SPMs by mast cells and their subsequent effects on these cells. By elucidating the intricate relationship between mast cells and SPMs, this review aims to provide a comprehensive understanding of the mechanism by which these cells regulate the delicate balance between tissue damage and repair at inflammatory sites, ultimately contributing to the resolution of inflammatory responses. Full article

Background and Objectives: Acute pancreatitis (AP) is an inflammatory disease where there is autodigestion of the pancreas by prematurely activated enzymes which may lead to a systemic inflammatory response. The aim of our study was to investigate the levels of circulating serum leukotriene B4 (LTB4), lipoxin A4 (LXA4), and resolvin D1 (RvD1) in pancreatitis due to gallstones in the etiologic investigation of AP. Materials and Methods: A total of 147 patients with AP (n: 49), AC (n: 49), and combined AP + AC (n: 49) will be included in the study. Healthy volunteers (n: 49) will be included as the control group. Results: RvD1 levels were significantly lower in patient groups compared to controls, while LXA4 levels were lower in patients with combined AP + AC (145.24 ng/L) compared to both controls (312.36 ng/L) and other patient groups. LTB4 levels were elevated in all patient groups compared to controls (335.56 ng/L vs. 65.56 ng/L) and were highest in combined AP + AC. Significant correlations were identified: RvD1 showed a negative correlation with LTB4 (r =−0.676; p < 0.001) and a positive correlation with LXA4 (r = 0.563, p < 0.001). ROC analysis demonstrated high diagnostic accuracy, with LXA4 and LTB4 achieving perfect differentiation (AUC: 1.0) between control and combined AP + AC cases. Conclusions: Our study showed that serum RvD1 and LXA4 levels have powerful anti-inflammatory properties in accordance with the literature. LTB4 may represent new, effective indicators to predict the severity of AP and the presence of necrosis in patients with AP. Despite its low sensitivity and specificity, RvD1 could be used as a complementary marker to the current scoring systems for the initial assessment of AP prognosis. These findings provide a new mechanistic understanding of how RvD1 attenuates inflammation to facilitate resolution, which could help develop novel therapeutic strategies for diseases caused by unresolved inflammation. It is easily obtainable and can provide additional prognostic information to clinicians. Full article

The purpose of this review is to propose that lipoxin A4 (LXA4), derived from arachidonic acid (AA), a potent anti-inflammatory, cytoprotective, and wound healing agent, may be useful to prevent and manage diabetic retinopathy (DR). LXA4 suppresses inappropriate angiogenesis and the production of pro-inflammatory prostaglandin E2 (PGE2), leukotrienes (LTs), 12-HETE (12-hydroxyeicosatetraenoic acid), derived from AA by the action of 12-lioxygenase (12-LOX)) interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the expression of NF-κB, inducible NO (nitric oxide) synthase (iNOS), cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF)—factors that play a role in DR. Thus, the intravitreal injection of LXA4 may form a new approach to the treatment of DR and other similar conditions such as AMD (age-associated macular degeneration) and SARS-CoV-2-associated hyperinflammatory immune response in the retina. The data for this review are derived from our previous work conducted in individuals with DR and from various publications on LXA4, inflammation, and DR. Full article

Background/Objectives: Halitosis is primarily caused by the activity of oral microorganisms. In this study, we employed metagenomic sequencing and metabolomic approaches to investigate the differences in salivary microbiota and metabolite profiles between individuals with halitosis and periodontitis and healthy controls. Additionally, we expanded the study to examine how oral malodorous compounds interact with human oral squamous carcinoma (HSC-4) cells. Methods: Saliva samples were collected and analyzed using Ultra-High Performance Liquid Chromatography–Mass Spectrometry (UHPLC-MS) to identify metabolites. We then assessed the correlations between the microbiota and metabolites. Furthermore, the impact of oral malodorous substances on HSC-4 cells was investigated by evaluating apoptosis, antioxidant activity, and inflammatory properties. Results: The microbiota and metabolite profiles showed significant differences between the halitosis with periodontitis group and the periodontally healthy group. The halitosis with periodontitis group exhibited significantly higher relative abundances of eight genera: Tannerella, Selenomonas, Bacteroides, Filifactor, Phocaeicola, Fretibacterium, Eubacterium saphenum, and Desulfobulbus. In contrast, the periodontally healthy group showed significantly higher relative abundances of Family XIII UCG-001, Haemophilus, and Streptobacillus. Two metabolites, 2,3-dihydro-1H-indole and 10,11-dihydro-12R-hydroxy-leukotriene E4, were significantly higher in individuals with halitosis and periodontitis. In the treatment of HSC-4 cells with metabolites, dimethyl sulfide (DMS) did not show significant effects while indole appeared to induce cell death in HSC-4 cells by triggering apoptotic pathways. Additionally, both indole and DMS affected the inflammatory and antioxidant properties of HSC-4 cells. Conclusions: This study provides insights into the mechanisms of halitosis by exploring the correlations between microbiota and metabolite profiles. Furthermore, oral metabolites were shown to impact the cellular response of HSC-4 cells. Full article