Search Results (935)

Background: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. Methods: The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. Results: A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. Conclusions: TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine. Full article

Fine particulate matter (PM_2.5) exposure has been linked to increased lung damage due to compromised vascular barrier function, while 3-deoxysappanchalcone (3-DSC), a chalcone derived from Caesalpinia sappan, is known for its pharmacological benefits such as anti-cancer, anti-inflammatory, and antioxidant effects; however, its potential role in mitigating PM_2.5-induced pulmonary damage remains unexplored. To confirm the inhibitory effects of 3-DSC on PM_2.5-induced pulmonary injury, this research focused on evaluating how 3-DSC influences PM_2.5-induced disruption of the barrier of the endothelial cells (ECs) in the lungs and the resulting pulmonary inflammation. Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were assessed in PM_2.5-treated ECs and mice. This study demonstrated that 3-DSC effectively neutralized the reactive oxygen species (ROS) generated by PM_2.5 exposure in the lung endothelial cells, suppressing ROS-triggered p38 MAPK activation while enhancing Akt signaling pathways critical to preserving vascular barrier function. In animal models, 3-DSC administration markedly decreased vascular permeability, attenuated the influx of immune cells into the lung tissue, and lowered inflammatory mediators like cytokines in the airways of PM_2.5-exposed mice. These data suggest that 3-DSC might exert protective effects on PM_2.5-induced inflammatory lung injury and vascular hyperpermeability. Full article

Cadmium (Cd)-induced pulmonary toxicity is closely associated with ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation (LPO). Luteolin (Lut) is a natural flavonoid compound that exists in many plants. In this study, we used human bronchial epithelial BEAS-2B cells to explore the impact of ferroptosis in the inhibition of Cd-induced BEAS-2B cells proliferation. BEAS-2B cells were exposed to Cd (5 μM) with/without Lut (10 μM), ferroptosis modulators (Ferrostatin-1 (Fer-1)/Erastin), or nuclear factor erythroid 2-related factor 2 (Nrf2) regulators (tert-butylhydroquinone (TBHQ)/ML385). Viability, iron content, reactive oxygen species (ROS), LPO, mitochondrial membrane potential (MMP), and glutathione peroxidase (GSH-PX) activity were assessed. Exposure to Cd significantly decreased cell viability, increased intracellular iron levels, ROS production, and LPO activity, while simultaneously reducing MMP and GSH-PX activity. Fer-1 mitigated Cd-induced cytotoxicity, but Erastin intensified these effects. Mechanistically, Cd exposure suppressed the Nrf2/Solute Carrier Family 7 Member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway, which plays a crucial role in maintaining redox homeostasis. Activation of Nrf2 using TBHQ mitigated oxidative stress and upregulated the expression of key proteins within this pathway, while inhibition of Nrf2 with ML385 exacerbated cellular damage. Notably, Lut treatment could significantly alleviate Cd-induced cytotoxicity, oxidative stress, and downregulation of Nrf2/SLC7A11/GPX4 proteins. These findings demonstrate that ferroptosis is a critical mechanism underlying Cd-mediated lung epithelial injury and identify Lut as a promising therapeutic candidate via its activation of Nrf2-driven antioxidant defense mechanisms. This study provides novel insights into molecular targets for the prevention and treatment of Cd-associated pulmonary disorders. Full article

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, primarily driven by chronic airway inflammation due to cigarette smoke exposure. Despite its burden, however, current anti-inflammatory therapies offer limited efficacy in preventing disease progression. Plasminogen activator inhibitor-1 (PAI-1), as a key regulator of fibrinolysis, has recently been implicated in structural airway changes and persistent inflammation in patients with COPD. This study aimed to investigate the ability of the PAI-1 inhibitor TM5441 to attenuate airway inflammation and structural lung damage induced by a cigarette smoke extract (CSE) in a mouse model. Mice received intratracheal CSE or vehicle on days 1, 8, and 15, and were sacrificed on day 22. TM5441 (20 mg/kg) was administered orally from days 1 to 22. The CSE significantly increased the mean linear intercept, destructive index, airway resistance, and reductions in dynamic compliance. The CSE also increased the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid, systemic PAI-1 activity, and neutrophil elastase mRNA and protein expression in the lungs. TM5441 treatment significantly suppressed these changes without affecting coagulation time. These findings suggest that TM5441 may be a novel therapeutic agent for COPD by targeting PAI-1-mediated airway inflammation and emphysema. Full article

Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients. Full article

The broad-spectrum insect growth regulator (IGR) and insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP; also known as pyriproxyfen) is increasingly being used to address public health programs for vector control, initiated by the spread of Zika virus in 2015–2016. While considered relatively safe for humans under normal conditions, limited toxicology data are available. Current studies were undertaken to address the data gap regarding potential immunotoxicity of MPEP, with particular emphasis on host resistance to viral infection. Hsd:Harlan Sprague Dawley SD^® rats were treated for 28 days by oral gavage with doses of 0, 62.5, 125, 250 or 500 mg/kg/day of MPEP in corn oil. There was a dose-dependent increase in liver weights which is consistent with the liver playing a dominant role in MPEP metabolism. However, no histological correlates were observed. Following treatment, rats were subjected to a battery of immune tests as well as an established rat model of influenza virus infection to provide a comprehensive assessment of immune function and host resistance. While several of the immune tests showed minor exposure-related changes, evidenced by negative dose–response trends, most did not show significant differences in any of the MPEP treatment groups relative to vehicle control. Most notable was a negative trend in pulmonary mononuclear cell phagocytosis with increases in dose of MPEP. There was also a positive trend in early humoral immune response (5 days after immunization) to keyhole limpet hemocyanin (KLH) as evidenced by increased serum anti-KLH IgM antibodies which was followed later (14 days following immunization) by decreasing trends in anti-KLH IgM and IgG antibody levels. However, MPEP treatment had no effect on the ability of rats to clear the influenza virus nor the T-dependent IgM and IgG antibody response to the virus. The lack of effects of MPEP on host resistance to influenza suggests the immune effects were minimal and unlikely to present a hazard with respect to susceptibility to respiratory viral infection. Full article

Background: Acute lung injury (ALI) is driven by inflammatory cascades and reactive oxygen species (ROS) generation, with the progression to severe cases markedly increasing mortality. Sinapine thiocyanate (ST), a bioactive natural compound isolated from Sinapis Semen Albae (SSA), demonstrates both anti-inflammatory and antioxidant pharmacological activities. However, no monotherapeutic formulation of ST has been developed to date. A dry powder inhaler (DPI) enables targeted pulmonary drug delivery with excellent stability profiles and high inhalation efficiency. Methods: ST was purified and prepared as inhalable dry powder particles via an antisolvent crystallization technique. The therapeutic mechanisms of ST against ALI were elucidated by network pharmacology and pharmacokinetic analyses, with the therapeutic efficacy of the ST DPI in ALI mitigation being validated using LPS-induced rat models. Results: The ST DPI showed ideal aerodynamic characteristics. Notably, ST exhibited a three-compartment (triexponential) pharmacokinetic profile following both intravenous tail vein injection and inhalation administration. Furthermore, the inhaled formulation displayed a prolonged systemic residence time, which confers therapeutic advantages for pulmonary disease management. Furthermore, the inhalation administration of ST demonstrated a 2.7-fold increase in AUC compared with oral gavage, with a corresponding enhancement in systemic exposure. The ST DPI formulation demonstrated significant therapeutic efficacy against ALI in rats by downregulating inflammatory cytokines and modulating oxidative stress levels, mechanistically achieved through the MAPK-mediated regulation of cellular apoptosis via a positive feedback loop. Conclusions: The unique triexponential plasma level profiles of an ST DPI provide a promising pharmacokinetics-based therapeutic strategy for ALI, leveraging its marked efficacy in attenuating inflammation, oxidative stress, and pulmonary injury. Full article

Background and Objectives: Pediatric pulmonary medicine relies heavily on accurate lung function assessment, yet conventional spirometry presents challenges in children due to cooperation requirements. In this context, the interrupter resistance technique (Rint), a method used in pediatric pulmonology, offers a potentially more feasible alternative for evaluating airway resistance in younger populations. This study aimed to assess the feasibility and clinical concordance between expiratory interrupter resistance (Rint(e)) and standard spirometry in healthy children under 8 years, thus contributing to the development of age-appropriate pulmonary function testing in pediatric medicine. Materials and Methods: A cross-sectional study was conducted on 200 healthy children (aged 2–8 years) in Tunisia. Pulmonary measurements were taken using a handheld device for both Rint(e) and spirometry. Feasibility rates were calculated, and correlations between the techniques were statistically analyzed. Results: Rint(e) showed significantly higher feasibility than spirometry (82.5% vs. 34.5%, p < 0.05). While older children had higher success rates with both techniques, feasibility was independent of sex, BMI, and passive smoking exposure. Moderate negative correlations were found between log Rint(e) and FEV1/FVC indices. Conclusions: In pediatric pulmonary assessment, Rint(e) demonstrated higher feasibility than spirometry among young children, making it a practical complementary method in clinical settings. However, due to only moderate correlation with spirometric indices, Rint(e) cannot yet replace spirometry in diagnostic use. Its integration into pediatric medicine may help address the gap in functional respiratory evaluation for children under the age of 8. Full article

The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need for effective therapeutic strategies to mitigate spike protein-stimulated lung inflammation, we examined the anti-inflammatory properties of luteolin and ethanolic extract from Harrisonia perforata (Blanco) Merr. root. The ethanolic extract of H. perforata root (HPEE) contained a high concentration of luteolin flavonoid (143.53 ± 1.58 mg/g extract). Both HPEE (25–100 μg/mL) and luteolin (4.5–36 μM) significantly inhibited inflammation stimulated by the Wuhan (W) and Omicron (O) spike protein S1, as evidenced by a dose-dependent significant decrease in IL-6, IL-1β, and IL-18 secretion in A549 lung epithelial cells (p < 0.05). Furthermore, pretreatment with HPEE or luteolin prior to spike protein exposure (100 ng/mL) significantly, in a dose-dependent manner, repressed the inflammatory mRNA expression (p < 0.05). Mechanistic study revealed that HPEE and luteolin suppressed NLRP3 inflammasome signaling activation by reducing their machinery protein expressions. Additionally, they inhibited the ERK/JNK/p38 MAPK signaling activation, resulting in decreased inflammatory mRNA expression and cytokine release. These findings suggest that H. perforata root extract and its major flavonoid luteolin exert potent anti-inflammatory effects and may offer therapeutic potential against spike protein-induced lung inflammation. Full article

Background: Polluted soils represent a major problem in many industrialized countries that urgently requires appropriate health risk assessment. The One Health concept that considers a close relationship between human and animal health and ecosystems relies, among other techniques, on continuous monitoring through the use of animal species as bioindicators. In this context, terrestrial gastropods, already recognized as relevant indicators due to their anatomo-physiology, provide a reliable model to study the pneumotoxic effects of pollutants. On the other hand, risk assessment is based on multi-biomarker studies. Therefore, omic approaches seem particularly useful since they can simultaneously detect numerous early biological changes. Methods: In this study, Helix aspersa maxima was exposed to naphthalene, a highly volatile aromatic hydrocarbon responsible for numerous respiratory disorders. Pulmonary membrane extracts and hemolymph samples were analyzed by ¹H-NMR spectroscopy after single or repeated exposures to naphthalene. Results: Numerous metabolic changes were observed, which could be related to membrane lesions, energy, anti-inflammatory, and tumorigenesis pathways. Conclusions: Our findings highlight the potential of combining animal indicator and omics techniques to predict respiratory health risks in cases of exposure to polluted soils. Full article

In endothelial cells, high-dose irradiation induces numerous dysfunctions including alteration in junctional proteins such as VE-Cadherin, apoptosis and enhanced adhesiveness linked to overexpression of adhesion molecules like Intercellular Adhesion Molecule 1 (ICAM-1). Such endothelial dysfunctions can lead to altered tissue perfusion, development of tissue inflammation through increased endothelial permeability, and ultimately organ damage. As intracellular cyclic AMP (cAMP) levels are known to control intercellular junctions or apoptosis in the endothelium, we investigated here the effect of the Phosphodiesterase 4 inhibitor Roflumilast, a drug increasing cAMP levels, on irradiation-induced endothelial dysfunctions in human pulmonary microvascular endothelial cells (HPMECs). Using continuous impedance measurements in confluent endothelial cell monolayers, Roflumilast was found to rapidly reinforce the endothelial barrier and to prevent irradiation-induced barrier disruption. In accordance, irradiation-induced alteration in membrane VE-Cadherin-composed adherens junctions was prevented by Roflumilast treatment after irradiation, which was correlated with its protective effect of the actin cytoskeleton. Post-irradiation treatment with Roflumilast also protected HPMECs from irradiation-induced late apoptosis, but was without effect on irradiation-induced ICAM-1 overexpression. Overall, our results indicate that the beneficial effects of Roflumilast after irradiation are linked to the strengthening/protection of the endothelial barrier and reduced apoptosis, suggesting that this medicine may be useful for the treatment of endothelial damages after exposure to a high dose of radiation. Full article

Background/Objectives: Pediatric asthma is a leading cause of emergency department visits, and air pollution is a known primary environmental trigger. Although worldwide air pollutants have been associated with asthma exacerbations, limited data have been reported in the Eastern Province of Saudi Arabia. This study aimed to investigate the relationship between air pollution and pediatric asthma admissions among children aged 2 to 14 years old at King Fahd Hospital of the University Hospital (KFHU). Methods: This is a retrospective cohort study, over 366 days, including 1750 pediatric asthma-related ER visits and daily concentrations of air pollutants (PM_2.5, PM₁₀, NO₂, SO₂, CO, and O₃) and meteorological factors (temperature and humidity). Various statistical models, such as Poisson regression and ARIMA, were applied to determine the association between pollutants levels and hospital ER visits. The data were visit-based in nature, and it was not possible to follow up with repeat visits or for admission status for individual patients. Results: Elevated levels of PM_2.5, NO₂, and CO were significantly associated with more pediatric asthma ER visits, mainly on the same day and with short lags. PM_2.5 displayed the strongest association, consistent with its deeper pulmonary penetration and greater toxicity. Also, PM₁₀ levels were inversely associated with ER visits, possibly due to particle size and deposition location differences. Significantly correlated with increased ER visits are lower ambient temperature and higher humidity. Conclusions: This study offers strong evidence on the relationship between air pollution and pediatric asthma events, in turn highlighting the vital importance of air quality regulation, public health policies, and clinical vigilance for environmental exposures. Full article

Chronic obstructive pulmonary disease (COPD) is an escalating global health burden, with a disproportionate impact on low- and middle-income countries (LMICs). Although tobacco smoking is a well-established risk factor, emerging evidence highlights the significant role of non-smoking exposure in driving the prevalence of COPD in these regions. This narrative review synthesizes current data on key non-smoking contributors, including household air pollution, ambient urban pollution, occupational exposure, early-life respiratory insults, chronic infections, and socioeconomic adversity. These risk factors are associated with distinct COPD phenotypes, often marked by increased airway inflammation, reduced emphysema, and variable airflow limitation. Such presentations are particularly common among women and younger populations in LMICs. However, diagnostic and therapeutic challenges persist, owing to limited disease awareness, under-resourced health systems, restricted access to essential medications, and financial constraints impacting adherence. Despite the proven effectiveness of non-pharmacological measures and public health interventions, their implementation remains inadequate because of infrastructural and funding limitations. Bridging these gaps requires region-specific clinical guidelines, improved diagnostic infrastructure, expanded access to affordable treatment, and culturally sensitive interventions. Future priorities include identifying robust biomarkers, refining disease definitions to accommodate non-smoking phenotypes, and advancing implementation science to improve interventions. A coordinated, context-aware global response is essential to reduce the growing burden of COPD in LMICs and to ensure equitable respiratory health outcomes. Full article

Background: Chronic Obstructive Pulmonary Disease (COPD) exhibits some phenotypic differences between patients with biomass smoke inhalation (COPD-B) and tobacco smoking (COPD-T). COPD-B is characterized by less emphysema but more airway disease and vascular pulmonary remodeling, which are related to mast cells in lung tissues in COPD-T. Our objective was to describe the differences between the number of mast cells in COPD-B and COPD-T patients. Methods: A cross-sectional study was conducted on lung tissue resections for suspected cancer obtained between 2014 and 2021 from patients with documented COPD due to wood smoke or tobacco exposure. Histological samples were analyzed for mast cell count, CD34+ expression, and structural changes in lung tissue and pulmonary circulation. Results: A total of 20 histological samples were analyzed, with significant differences found in mast cell count [median 8 (p25-75, 5–11) vs. 2 (p75-25, 0–6), p = 0.016] and severe peribronchiolar fibrosis (60% vs. 10%, p = 0.04) between COPD-B and COPD-T patients. A positive correlation [Spearman rho = 0.879 (95% CI 0.71–0.96), p < 0.001] was observed between mast cell count and a gradual increase in pulmonary artery diameter. Conclusions: These preliminary findings suggest histological differences and the presence of mast cells between COPD-B and COPD-T, which should be confirmed in a larger number of samples and patients. Full article

Background: Effective early risk stratification in COVID-19 remains a critical challenge in emergency care, particularly due to the limitations of RT-PCR testing, including delayed processing and false negatives. There is an unmet need for imaging tools that are fast, reliable, and safe for repeated use in acute clinical settings. Methods: In this prospective, multicenter study, over 1000 patients hospitalized with suspected or confirmed COVID-19 were initially screened. A total of 555 patients with PCR-confirmed infection were ultimately included for analysis. All participants underwent low-dose chest CT (LDCT) at admission. Pulmonary involvement was assessed using the chest CT severity score (CTSS) based on a unified protocol. CTSS values were analyzed in relation to ICU admission, in-hospital mortality, demographic data, oxygen saturation, dyspnea scores, and laboratory markers (CRP, LDH, lymphocyte, and neutrophil counts). Imaging was interpreted by board-certified radiologists under harmonized reporting standards. Results: CTSS values ≥13 and ≥15 were significantly associated with ICU admission and in-hospital mortality, respectively (p < 0.01). Strong correlations were observed between the CTSS and CRP, LDH, and dyspnea scores, with negative correlations to oxygen saturation and lymphocyte count. The standardized LDCT protocol ensured consistent image quality and minimized radiation exposure. Conclusions: LDCT combined with the CTSS provides a robust, reproducible, and radiation-sparing method for emergency risk stratification in COVID-19. Its high clinical utility supports deployment in frontline triage systems and future AI-enhanced diagnostic workflows. Full article