Search Results (454)

Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function has been proposed as a therapeutic strategy to prevent the progression of periodontal disease. Houttuynia cordata, a perennial herb traditionally used in Asian medicine, is recognized for its anti-inflammatory properties, with documented benefits in the cardiovascular, respiratory, and gastrointestinal systems. However, its potential therapeutic role in oral pathologies, such as periodontitis, remains underexplored. This study aimed to investigate the anti-inflammatory effects of H. cordata extract on interleukin (IL)-1β-stimulated primary gingival keratinocytes (PGKs) subjected to IL-1β-induced inflammatory stress, simulating the conditions encountered during orthodontic treatment. Methods: Inflammation was induced in PGKs using IL-1β, and the impact of H. cordata extract pretreatment was assessed using quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblotting. Results: H. cordata extract significantly downregulated the mRNA and protein expression levels of tumor necrosis factor-alpha, IL-8, and intercellular adhesion molecule-1 in IL-1β-stimulated PGKs without inducing cytotoxicity. Conclusions: These findings suggest that H. cordata holds promise as a preventive agent against periodontitis by attenuating inflammatory responses in gingival epithelial tissues. We believe that our findings will inform the development of prophylactic interventions to reduce periodontitis risk in patients undergoing orthodontic therapy. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Nasal irrigation (NI) is an effective, safe, low-cost strategy for treating and preventing upper respiratory tract diseases. High-volume, low-pressure saline irrigations are the most efficient method for removing infectious agents, allergens, and inflammatory mediators. This article reviews clinical evidence supporting NI use in various conditions: nasal congestion in infants, recurrent respiratory infections, acute and chronic rhinosinusitis, allergic and gestational rhinitis, empty nose syndrome, and post-endoscopic sinus surgery care. NI improves symptoms, reduces recurrence, enhances the efficacy of topical drugs, and decreases the need for antibiotics and decongestants. During the COVID-19 pandemic, NI has also been explored as a complementary measure to reduce viral load. Due to the safe profile and mechanical cleansing action on inflammatory mucus, nasal irrigations represent a valuable adjunctive treatment across a wide range of sinonasal conditions. Full article

The Pelargonium genus, encompassing over 280 species, remains markedly underexplored despite extensive traditional use for respiratory, gastrointestinal, and dermatological disorders. This review of aqueous, alcoholic, and hydroalcoholic extracts reveals critical research gaps: only 10 species have undergone chemical characterization, while 17 have been evaluated for biological activities. Phytochemical analysis identified 252 unique molecules across all studies, with flavonoids emerging as the predominant class (n = 108). Glycosylated derivatives demonstrated superior bioactivity profiles compared to non-glycosylated analogs. Phenolic acids (n = 43) and coumarins (n = 31) represented additional major classes. Experimental studies primarily documented antioxidant, antibacterial, and anti-inflammatory effects, with emerging evidence for antidiabetic, anticancer, and hepatoprotective activities. However, methodological heterogeneity across studies limits comparative analysis and comprehensive understanding. In silico target prediction analysis was performed on 197 high-confidence molecular structures. Glycosylated flavonols, anthocyanidins, flavones, and coumarins showed strong predicted interactions with key inflammatory targets (ALOX15, ALOX5, PTGER4, and NOS2) and metabolic regulators (GSK3A and PI4KB), providing mechanistic support for observed therapeutic effects and suggesting potential applications in chronic inflammatory and metabolic diseases. These findings underscore the substantial therapeutic potential of underexplored Pelargonium species and advocate for systematic research employing untargeted metabolomics, standardized bioassays, and compound-specific mechanistic validation to fully unlock the pharmacological potential of this diverse genus. Full article

Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial condition associated with significant systemic complications such as cardiovascular disease (CVD), metabolic disorders, muscle wasting, and sarcopenia. While Body Mass Index (BMI) is a well-established indicator of obesity and has prognostic value in COPD, its role in predicting disease outcomes is complex. Muscle wasting is prevalent in COPD patients and exacerbates disease severity, contributing to poor physical performance, reduced quality of life, and increased mortality. Additionally, COPD is linked to metabolic disorders, such as dyslipidemia and diabetes, which contribute to systemic inflammation and worse prognosis and, therefore, should be treated. The systemic inflammatory response plays a central role in the development of sarcopenia. In this review, we highlight the mixed efficacy of statins in managing dyslipidemia in COPD, considering side effects, including muscle toxicity in such a frail population. Alternative lipid-lowering therapies and nutraceuticals, in addition to standard treatment, have the potential to target hypercholesterolemia, which is a coexisting condition present in more than 50% of all COPD patients, without worsening muscle wasting. The interference between adipose tissue and lung, and particularly the potential protective role of adiponectin, an adipocytokine with anti-inflammatory properties, is also reviewed. Respiratory, metabolic and muscular health in COPD is comprehensively assessed. Identifying and managing dyslipidemia and paying attention to other relevant COPD comorbidities, such as sarcopenia and muscle wasting, is important to improve the quality of life and to reduce the clinical burden of COPD patients. Future research should focus on understanding the relationships between these intimate mechanisms to facilitate specific treatment for systemic involvement of COPD. Full article

Bronchopulmonary dysplasia (BPD) remains a significant complication of preterm birth, characterized by impaired alveolar and vascular development, chronic lung inflammation, and long-term respiratory morbidity. Corticosteroids, both systemic and inhaled, have been widely investigated as potential therapeutic agents due to their anti-inflammatory properties and their emerging role in modulating oxidative stress. This narrative review explores the current evidence regarding the use of inhaled and systemic corticosteroids in the prevention and management of BPD, analyzing their efficacy, safety profiles, and long-term outcomes. While systemic corticosteroids, particularly dexamethasone, have demonstrated benefits in reducing ventilator dependence and lung inflammation, concerns regarding adverse neurodevelopmental effects have limited their routine use. Inhaled steroids have been proposed as a safer alternative, but their role in altering the disease trajectory remains controversial. A better understanding of the optimal timing, dosage, and patient selection is essential to maximize benefits while minimizing risks. Future research should focus on optimizing dosing strategies and identifying subgroups of preterm infants who may derive the greatest benefit from corticosteroid therapy. Full article

Periodontitis is a prevalent chronic inflammatory disease that has been increasingly recognized for its systemic impacts, including its connection to respiratory diseases such as pneumonia, chronic obstructive pulmonary disease (COPD), Obstructive Sleep Apnea (OSA), asthma, lung cancer, and COVID-19. This review explores the potential role of periodontal pathobionts, particularly Porphyromonas gingivalis (Pg), Treponema denticola (Td), Fusobacterium nucleatum (Fn), Aggregatibacter actinomycetemcomitans (Aa), and Tannerella forsythia (Tf), in respiratory health. These pathobionts contribute to respiratory diseases by facilitating pathogen adhesion, inducing epithelial cell apoptosis, and promoting inflammation. The review also highlights the beneficial effects of periodontal treatment in reducing pathobiont burden and systemic inflammation, thereby mitigating the risk of respiratory complications. This interdisciplinary approach underscores the need to consider oral health as a critical component in managing and preventing respiratory diseases, with future research needed to further clarify these associations and develop targeted interventions. Full article

Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, and chronic respiratory conditions are the leading causes of death globally, largely driven by modifiable lifestyle factors. With growing interest in dietary strategies for NCDs prevention and management, functional foods like watercress (Nasturtium officinale) have attracted attention for their rich phytochemical content and potential health benefits. This narrative review synthesizes 88 sources published between 2019 and March 2025, exploring the effects of watercress bioactive compounds on major NCDs. Watercress is abundant in glucosinolates, isothiocyanates (especially phenethyl isothiocyanate), flavonoids, vitamins, and minerals. These compounds contribute to antioxidant, anti-inflammatory, and metabolic regulatory effects. Preclinical and clinical studies show that watercress supplementation may improve lipid profiles, reduce oxidative stress, and modulate inflammation in cardiovascular and respiratory conditions. It also appears to enhance insulin function and reduce blood glucose levels. In cancer models, watercress extracts exhibit antiproliferative, pro-apoptotic, and chemoprotective properties, with selective toxicity towards cancer cells and protective effects on normal cells. These findings highlight the therapeutic potential of watercress as a dietary adjunct in NCDs prevention and management, supporting the need for further clinical research. Full article

Asthma is defined as a chronic respiratory disease, the processes of which are mainly related to the hyperreactivity of the immune system. Airway hyperresponsiveness and remodeling are other hallmarks of asthma that are strongly involved in the progression of the disease. Moreover, asthma is associated with the occurrence of atopic dermatitis, chronic sinusitis, allergic rhinitis, and a high profile of T2-type cytokines, such as IL-4, IL-5 and IL-13. The hyperresponsiveness of the immune system is a consequence of aberrant levels of alarmins, endogenous molecules that induce pro-inflammatory responses. They are released as a result of a defect or cell death, leading to the initiation of an inflammatory reaction. High-mobility group box 1 (HMGB1), S100 proteins, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and IL-25 bind to various receptors, influencing the behavior of immune cells, resulting in stimulated migration and activation of these cells. In this review, we will discuss the potential role of alarmins in the pathogenesis of asthma. Full article

Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article

In chronic respiratory diseases (CRDs), oxidative stress and inflammation are closely linked, driving disease onset, progression, and comorbidities. Oxidative stress activates inflammatory pathways, while chronic inflammation promotes further reactive oxygen species (ROS) production, creating a vicious cycle leading to airway remodeling, reduced lung function, and exacerbations. This review highlights the central roles of inflammation and oxidative stress in chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). In COPD, chronic hypoxemia associates with emphysema, appearing with disease progression. In OSA, beyond systemic consequences, pulmonary inflammation and oxidative stress contribute to lung injury as well. Although COPD and OSA are distinct conditions, some patients present with “overlap syndrome”, a term used in this review to describe the coexistence of both. This combination poses unique diagnostic and therapeutic challenges. We also examine the role of hypoxia and its transcriptional effects via hypoxia-inducible factors (HIFs) in promoting oxidative stress and inflammation. Finally, we explore how artificial intelligence (AI) offers promising tools to improve diagnosis, monitoring, and management of CRDs and may help elucidate mechanistic links between hypoxia, inflammation, and oxidative stress, contributing to more personalized therapeutic strategies. Full article

Background: Multidrug-resistant bacteria (MDRB) represent a significant challenge in intensive care units (ICUs), as they limit treatment options, prolong hospital stays, and escalate healthcare costs. Respiratory ICUs are particularly affected due to the high prevalence of chronically ill patients with recurrent infections. Understanding the impact of culture positivity and MDRB on clinical outcomes and readmission rates is essential for enhancing patient care and addressing the growing burden of antimicrobial resistance. Methods: This retrospective study was conducted in a specialized respiratory ICU at a tertiary care hospital between 1 January 2019, and 1 January 2020. A total of 695 ICU admissions were analyzed, with patients grouped based on readmission status and culture results. Demographic, clinical, and laboratory data were reviewed. Statistical analyses were performed using appropriate tests, with p-values ≤ 0.05 considered statistically significant. Results: Among the 519 unique patients, 65 experienced ICU readmissions. Male patients were significantly more likely to be readmitted (p = 0.008). Culture positivity was predominantly observed in respiratory samples, with Klebsiella spp. identified as the most common pathogen. MDRB prevalence exceeded 60% in both groups, significantly prolonging ICU stays (p = 0.013). However, no significant differences in survival rates were observed between MDRB-positive and MDRB-negative groups. Notably, patients with readmissions had lower C-reactive protein (CRP) levels both during admission and at discharge compared to non-readmitted patients (p = 0.004). This paradox may reflect a subclinical inflammatory response associated with bacterial colonization rather than active infection, particularly in patients with chronic respiratory diseases. Conclusions: MDRB infections and culture positivity are key contributors to prolonged ICU stays, resulting in increased healthcare costs. Implementing effective strategies to manage MDRB infections is critical for improving outcomes in respiratory ICUs and reducing associated risks. This study underscores the growing burden of MDRB and highlights the importance of enhanced antimicrobial stewardship in respiratory ICUs. Full article

Background: The efficacy of EA575 in the treatment of respiratory diseases is described in various clinical studies, improving patients’ disease-related symptoms. However, mechanistic in vivo data proving its beneficial effects are limited. Methods: Focusing on the treatment of acute airway inflammation and accompanying cough, this study aimed to elucidate antitussive and mucoactive properties of EA575, applying two animal models. Animals were treated orally twice daily for 7 days, resulting in 43, 215.2, or 430.5 mg/kg bw/d of EA575. Antitussive effects were investigated within an acute lung inflammation model of bleomycin-treated guinea pigs after citric acid exposure. Hereby, the number of coughs, enhanced pause (penH), and bronchoalveolar lavage fluid (BALF) were investigated. Mucoactivity of EA575 was assessed within a murine model, determining phenol red concentration in BALF. Results: EA575 treatment within the acute lung inflammation model reduced cough events up to 56% while reducing inflammatory cell influx in BALF dose-dependently, e.g., reducing neutrophils in BALF up to 70.9%. This suggests a strong connection between anti-inflammatory and antitussive properties of EA575. Furthermore, penH decreased in a dose-dependent manner, suggesting an ease in respiration. Mucoactivity was shown by a dose-dependent increase in phenol red concentration in BALF up to 38.9%. Notably, EA575/salbutamol co-administration resulted in enhanced phenol red secretion compared to respective single administrations. Conclusions: These data highlight the benefits of EA575 in treating cough-related respiratory diseases, particularly when accompanied by sputum, as EA575 has been shown to obtain mucoactivity. Furthermore, the combinatory effect of EA575/salbutamol treatment provides a foundation for future research in the treatment of chronic respiratory diseases. Full article

Equine asthma is a chronic respiratory disease characterised by neutrophilic inflammation, airway hyperresponsiveness, and impaired pulmonary function. Obesity, increasingly prevalent among domestic horses, has been identified as a potential risk factor for exacerbating inflammatory conditions. This study aimed to explore whether obesity modifies neutrophil metabolism and inflammatory responses in horses affected by asthma. Six asthmatic horses in clinical remission were categorised into two groups: obese and non-obese, based on body condition score. Serum levels of interleukin-1β (IL-1β) and peripheral blood neutrophil counts were significantly higher in obese horses, indicating a heightened systemic inflammatory state. Neutrophils from obese horses displayed a stronger oxidative burst following zymosan stimulation and elevated IL-1β gene expression in response to lipopolysaccharide, suggesting a hyperinflammatory phenotype. Metabolomic profiling of neutrophils identified 139 metabolites, with notable differences in fatty acids, branched-chain amino acids, and tricarboxylic acid (TCA) cycle intermediates. Pathway enrichment analysis revealed significant alterations in fatty acid biosynthesis, amino acid metabolism, and glutathione-related pathways. Elevated levels of itaconate, citraconic acid, and citrate in obese horses indicate profound metabolic reprogramming within neutrophils. These results suggest that obesity promotes a distinct neutrophil phenotype marked by increased metabolic activity and heightened responsiveness to inflammatory stimuli. This altered profile may contribute to the persistence or worsening of airway inflammation in asthmatic horses. The findings underscore the importance of addressing obesity in the clinical management of equine asthma and open avenues for further research into metabolic-targeted therapies in veterinary medicine. Full article

Asthma is a chronic inflammatory respiratory disease well-known to demonstrate sexual dimorphism in incidence and severity, although the mechanisms causing these differences remain incompletely understood. RPS4X and RPS4Y1 are X and Y-chromosome-linked genes coding ribosomal subunits previously associated with inflammation, airway remodelling and asthma medication efficacy. Particularly, RPS4Y1 has been under-investigated within the context of disease, with little examination of molecular mechanisms and pathways regulated by this gene. The ribosome, a vital cellular machinery, facilitates the translation of mRNA into peptides and then proteins. Imbalance or dysfunction in ribosomal components may lead to malfunctioning proteins. Using CRISPR-Cas9 knockout cellular models for RPS4Y1 and RPS4X, we characterised the function of RPS4Y1 in the context of the asthma-relevant processes, inflammation and fibrosis. No viable RPS4X knockouts could be generated. We highlight novel molecular mechanisms such as specific translation of IL6 and tenascin-C mRNA by RPS4Y1 containing ribosomes. Furthermore, an RPS4Y1-centric gene signature correlates with clinical lung function measurements, specifically in adult male asthma patients. These findings inform the current understanding of sex differences in asthma, as females do not produce the RPS4Y1 protein. Therefore, the pathologically relevant functions of RPS4Y1 may contribute to the complex sexually dimorphic pattern of asthma susceptibility and progression. Full article