Search Results (151)

Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of lung fibrosis with cardiac MRI-derived measures of right ventricular (RV) function improves the diagnostic accuracy of PH in patients with ILD. Methods: We retrospectively analyzed 72 ILD patients who underwent chest CT, cardiac MRI, and right heart catheterization (RHC). Lung fibrosis was quantified using a Gaussian Histogram Normalized Correlation (GHNC) software that computed the proportions of diseased lung, ground-glass opacity (GGO), honeycombing, reticulation, consolidation, and emphysema. MRI was used to assess RV end-systolic volume (RVESV), ejection fraction, and RV longitudinal strain. PH was defined as a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg and pulmonary vascular resistance ≥ 3 Wood units on RHC. Results: Compared to patients without PH, those with PH (n = 21) showed significantly reduced RV strain (−13.4 ± 5.1% vs. −16.4 ± 5.2%, p = 0.026) and elevated RVESV (74.2 ± 18.3 mL vs. 59.5 ± 14.2 mL, p = 0.003). CT-derived indices also differed significantly: diseased lung area (56.4 ± 17.2% vs. 38.4 ± 12.5%, p < 0.001), GGO (11.8 ± 3.6% vs. 8.65 ± 4.3%, p = 0.005), and honeycombing (17.7 ± 4.9% vs. 12.8 ± 6.4%, p = 0.0027) were all more prominent in the PH group. In receiver operating characteristic curve analysis, diseased lung area demonstrated an area under the curve of 0.778 for detecting PH. This increased to 0.847 with the addition of RVESV, and further to 0.854 when RV strain was included. Combined models showed significant improvement in risk reclassification: net reclassification improvement was 0.700 (p = 0.002) with RVESV and 0.684 (p = 0.004) with RV strain; corresponding IDI values were 0.0887 (p = 0.03) and 0.1222 (p = 0.01), respectively. Conclusions: Combining CT-based fibrosis quantification with cardiac MRI-derived RV functional assessment enhances the non-invasive diagnosis of PH in ILD patients. This integrated imaging approach significantly improves diagnostic precision and may facilitate earlier, more targeted interventions in the management of ILD-associated PH. Full article

Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited treatment options for pulmonary hypertension in patients with interstitial lung disease (PH-ILD), this study aimed to evaluate the use of sotatercept in CTD-PAH patients with concomitant ILD. Methods: Eligible patients (n = 7) had a confirmed diagnosis of CTD-PAH with concomitant ILD. The patients were already receiving background PAH therapy. Baseline hemodynamic and clinical measurements were reassessed after 24 weeks of sotatercept therapy. The variables assessed included six-minute walk distance (6MWD), pulmonary vascular resistance (PVR), echocardiographic right ventricular systolic pressure (eRVSP), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, and supplemental oxygen requirements. Results: The study included seven patients with a mean age of 57 years (range: 39–73 years). After 24 weeks, the mean 6MWT distance increased from 211 m to 348 m (p < 0.01). Mean PVR decreased from 7.77 WU at baseline to 4.53 WU (p < 0.01). Mean eRVSP decreased from 79.43 mmHg to 54.14 mmHg (p < 0.01). NT-proBNP decreased from 3056.86 pg/mL to 1404.29 pg/mL (p < 0.01). The WHO functional class and supplemental oxygen requirements improved in all patients. Conclusions: Sotatercept was tolerated in patients with CTD-PAH and ILD, with no evidence of adverse respiratory effects. When added to foundational PAH therapy, sotatercept resulted in significant improvements across multiple parameters. These findings suggest that sotatercept may be a promising therapeutic option as an adjunctive treatment in this patient population. 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

Inhaled treprostinil is approved for the treatment of pulmonary hypertension-associated interstitial lung disease (PH-ILD); however, it has not shown significant benefit in patients with a pulmonary vascular resistance (PVR) < 4 WU. As such, treatment for non-severe PH-ILD remains controversial. A total of 16 patients with non-severe PH-ILD were divided into two groups based on changes in PVR during exercise: a dynamic PVR group (n = 10), characterized by an increase in PVR with exertion, and a static PVR group (n = 6), with no increase in PVR with exercise. The dynamic PVR group received inhaled treprostinil, while the static PVR group was monitored off therapy. Baseline and 16-week follow-up values were compared within each group. At 16 weeks, the dynamic PVR group demonstrated significant improvements in mean 6 min walk distance (6MWD) (+32.5 m, p < 0.05), resting PVR (−1.04 WU, p < 0.05), resting mean pulmonary arterial pressure (mPAP) (−5.8 mmHg, p < 0.05), exercise PVR (−1.7 WU, p < 0.05), exercise mPAP (−13 mmHg, p < 0.05), and estimated right ventricular systolic pressure (−9.2 mmHg, p < 0.05). In contrast, the static PVR group remained clinically stable. These observations suggest that an exercise-induced increase in PVR, identified through Level 3 CPET, may help select patients with non-severe PH-ILD who are more likely to benefit from early initiation of inhaled treprostinil. Full article

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and concomitant interstitial lung disease (ILD) are particularly challenging to manage due to concerns about ventilation–perfusion mismatch with systemic vasodilators. In this case series, we evaluated the effects of selexipag in eight prostacyclin-naïve CTD-PAH patients with concomitant ILD. Clinical, functional, and laboratory data were collected at baseline and after 16 weeks of treatment. After 16 weeks of treatment, the mean six-minute walk distance increased by 101.75 m (p < 0.05), and the mean estimated right ventricular systolic pressure decreased significantly (p < 0.05). Mean N-terminal pro b-type natriuretic peptide levels declined by 63%, though this reduction did not reach statistical significance. Importantly, supplemental oxygen requirements trended downward (p < 0.05) and pulmonary function tests remained stable. Pulmonary vasodilators have long been unsuccessfully studied in PH-ILD patients until the INCREASE trial. While other systemic agents used in PAH have not shown as much success as inhaled treprostinil in treating PH-ILD, our case series highlights the potential role of selexipag in patients with concomitant CTD-PAH and ILD. Further investigation of selexipag in pure Group 3 PH-ILD patients is warranted. Full article

The most serious complications of systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) include lung fibrosis (LF) and pulmonary hypertension (PH). The aim of this study was to find any association between the serological profile and the incidence of these complications. The tested group included 121 persons (87 SSc, 34 MCTD); mean age 55.6 ± 13.4 years. Patients were qualified for the LF presence group based on HRCT. Likelihood of PH was determined using echocardiography. The presence of antinuclear antibodies (ANA) was assessed using indirect immunofluorescence, ANA-profile, sclerosis-profile (using EUROIMMUN kits), and antiphospholipid antibodies (aPL) (using the ELISA method). Distribution of individual antibody types was at a level similar to the previously described groups in the Polish population and differed from the American and African population. A positive correlation was found between LF and the presence of anti-Scl-70 (p = 0.024) antibodies, negative correlation was found between LF and the presence of anti-histone (p = 0.03), anti-centromere A (p = 0.009), anti-centromere B (p = 0.014), and anti-nucleosomes (p = 0.03) antibodies. No correlation between the presence of aPL and the above complications was found. The prevalence of individual antibody types in SSc and MCTD may have ethnic and geographical grounds. Scl-70 antibodies correlate positively with LF. Anti-centromere, anti-histone, and anti-nucleosome antibodies reduce its risk. No correlation between aPL and the occurrence of LF and elevated PH risk was found. Full article

Pulmonary hypertension (PH) is a progressive lung disease characterized by abnormal pulmonary vascular pressure and right ventricular (RV) dysfunction. Atrial arrhythmias, including atrial fibrillation (AF) and atrial flutter, are common in patients with PH and significantly contribute to disease progression and mortality. A bidirectional pathophysiological link exists between PH and AF, encompassing shared mechanisms such as endothelial dysfunction, DNA damage, autophagy, inflammation, and oxidative stress, as well as mutual risk factors, including diabetes, obesity, heart disease, and aging. Despite these shared pathways, limited research has been conducted to fully understand the intertwined relationship between PH and AF, hindering the development of effective treatments. In this review, we provide a comprehensive overview of the epidemiology of PH, the molecular mechanisms underlying the development of AF in PH, and the overlap in their pathophysiology. We also identify novel druggable targets and propose mechanism-based therapeutic approaches to treat this specific patient group. By shedding light on the molecular connection between PH and AF, this review aims to fuel the design and validation of innovative treatments to address this challenging comorbidity. Full article

Background/Objectives: Nanocarrier particle design for treating chronic pulmonary diseases presents several challenges, including anatomical and physiological barriers. Drug-repurposing technology using monodispersed spherical silica is one of the innovative ways to deliver drugs. In the present study, the anticancer potential of combinational cisplatin/ribavirin was explored for targeted lung cancer therapeutics. Methods: Monodispersed spherical silica (80 nm) capable of diffusing into the tracheal mucus region was chosen and doped with 10 wt% superparamagnetic iron oxide nanoparticles (SPIONs). Subsequently, it was wrapped with chitosan (Chi, 0.6 wt/vol%), functionalized with 5% wt/wt cisplatin (Cp)/ribavarin (Rib) and angiotensin-converting enzyme 2 (ACE-2) (1.0 μL/mL). Formulations are based on monodispersed spherical silica or halloysite and are termed as (S/MSSiO₂/Chi/Cp/Rib) or (S/Hal/Chi/Cp/Rib), respectively. Results: X-ray diffraction (XRD) and diffuse reflectance UV-visible spectroscopy (DRS-UV-vis) analysis of S/MSSiO₂/Chi/Cp/Rib confirmed the presence of SPION nanoclusters on the silica surface (45% coverage). The wrapping of chitosan on the silica was confirmed with a Fourier transformed infrared (FTIR) stretching band at 670 cm⁻¹ and ascribed to the amide group of the polymer. The surface charge by zetasizer and saturation magnetization by vibrating sample magnetometer (VSM) were found to be −15.3 mV and 8.4 emu/g. The dialysis membrane technique was used to study the Cp and Rib release between the tumor microenvironment and normal pH ranges from 5.5 to 7.4. S/MSSiO₂/Chi formulation demonstrated pH-responsive Cp and Rib at acidic pH (5.6) and normal pH (7.4). Cp and Rib showed release of ~27% and ~17% at pH 5.6, which decreases to ~14% and ~3.2% at pH 7.4, respectively. To assess the compatibility and cytotoxic effect of our nanocomposites, the cell viability assay (MTT) was conducted on cancer lung cells A549 and normal HEK293 cells. Conclusions: The study shows that the designed nanoformulations with multifunctional capabilities are able to diffuse into the lung cells bound with dual drugs and the ACE-2 receptor. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by excessive extracellular matrix (ECM) production and tissue stiffening, resulting in impaired lung function. Sodium hydrogen exchanger isoform 1 (NHE1) is a key mediator of intracellular and extracellular pH regulation, influencing fibroblast activation, motility, and proliferative pathways. This study investigates the role of NHE1 in actin stress fiber formation, fibroblast-to-myofibroblast differentiation, and cytokine secretion in IPF progression. Methods: Fibroblasts were treated with profibrotic agonists, including transforming growth factor-beta (TGFβ), lysophosphatidic acid (LPA), and serotonin (THT), in the presence or absence of the NHE1-specific inhibitor, EIPA. Actin stress fibers were visualized using phalloidin staining, while α-smooth muscle actin (α-SMA) expression and cytokine secretion (TGFβ, IL-6, and IL-8) were quantified using immunostaining and ELISA. Intracellular pH changes were measured using BCECF-AM fluorescence. Results: Profibrotic agonists induced significant actin stress fiber formation and α-SMA expression in fibroblasts, both of which were abolished by EIPA. NHE1 activity was shown to mediate intracellular alkalization, a critical factor for fibroblast activation. Cytokine secretion, including TGFβ, IL-6, and IL-8, was enhanced by agonist treatments but reduced with NHE1 inhibition. Chronic TGFβ exposure increased intracellular pH and sustained myofibroblast differentiation, which was partially reversed by EIPA. Conclusions: NHE1 is indicated to play a novel and potential role in processes supporting profibrotic agonists driving fibroblast activation and IPF progression. Targeting NHE1 could present a potential therapeutic approach to disrupt profibrotic pathways and mitigate IPF severity. Full article

Background/Objectives: Chronic lower respiratory tract inflammation can result from exposure to bacterial particles, leading to the activation of the NLRP3 inflammasome pathway. These effects may cause irreversible respiratory damage, contributing to persistent lung injury and chronic obstructive pulmonary disease (COPD), as observed in long COVID or bacterial pneumonia in older adults’ patients. Given its profound impact, the NLRP3 inflammasome has emerged as a key therapeutic target for mitigating aberrant inflammatory responses. Methods: In this study, we investigated the anti-inflammatory effects of Kum Akha black rice, a functional food, on the attenuation of NLRP3 inflammasome pathway using lipopolysaccharide-induced A549 lung epithelial cells and a C57BL/6NJcl mouse model. The anthocyanin-rich fraction from Kum Akha black rice germ and bran extract (KA1-P1) was obtained using a solvent-partitioned extraction technique. Results: KA1-P1 exhibited a high anthocyanin content (74.63 ± 1.66 mg/g extract) as determined by the pH differential method. The HPLC analysis revealed cyanidin-3-O-glucoside (C3G: 45.58 ± 0.48 mg/g extract) and peonidin-3-O-glucoside (P3G: 6.92 ± 0.29 mg/g extract) as its anthocyanin’s active compounds. Additionally, KA1-P1 demonstrated strong antioxidant activity, as assessed by DPPH and ABTS assays. KA1-P1 (12.5–100 μg/mL) possessed inhibitory effects on LPS + ATP-induced A549 lung cells inflammation through the significant suppressions of NLRP3, IL-6, IL-1β, and IL-18 mRNA levels and the inhibition of cytokine secretions in a dose-dependent manner (p < 0.05). Mechanistic analysis revealed that KA1-P1 downregulated key proteins in the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). Furthermore, in vivo studies demonstrated that KA1-P1 significantly diminished LPS-induced lower respiratory inflammation in C57BL/6NJcl mice, as evidenced by the reduced bronchoalveolar lavage fluid and blood levels of inflammatory cytokines (IL-6, IL-1β, and IL-18) and diminished histopathological inflammatory lung lesions. Conclusions: Overall, our findings suggest that the anti-inflammatory properties of KA1-P1 may support its application as a functional supplement or promote the consumption of pigmented rice among the elderly to mitigate chronic lower respiratory tract inflammation mediated by the NLRP3 inflammasome pathway. Full article

Great progress has been made in the treatment of pulmonary arterial hypertension (WHO group 1 PAH) over the past two decades, which has significantly improved the morbidity and mortality in this patient population. Likewise, the more recent availability of antifibrotic medications for interstitial lung disease (ILD) have also been effective in slowing down the progression of disease. There is no known cure for either of these disease states. When this combination coexists, treatment can be challenging. Interstitial lung disease is a heterogenous group of chronic inflammatory and/or fibrotic parenchymal lung disorders. A subset of patients with ILD, not related to connective tissue disease, can initially present with inflammatory-predominant disease which progresses to irreversible fibrosis. This population of patients is also at risk for developing pulmonary hypertension (PH) or World Health Organization (WHO) group 3 PH. This coexistence of ILD and PH is associated with early morbidity and mortality. The early identification, diagnosis, and treatment of this combination of ILD and PH is vital. Medications available for both ILD and PH require an individualized approach with the intention of slowing down disease progression. Referral to expert centers for clinical trials and transplant evaluation is recommended. The combination of PH-ILD can be challenging to diagnose and treat effectively. Patients require a thorough clinical evaluation to enable the most accurate diagnosis. A vital part of that evaluation is the early recognition of PH. Medications can help improve disease progression along with clinical trials that will further improve our gaps in knowledge. Full article

Pulmonary hypertension associated with interstitial lung disease (ILD-PH) frequently complicates the course of patients with fibrotic ILD. In this narrative review, the authors assess current diagnostic tools and management considerations in ILD-PH patients. ILD-PH is associated with increased morbidity and mortality and may be suggested by the presence of symptoms out of proportion to the extent of the ILD. There are other clues to the presence of PH in the context of ILD including the need for supplemental oxygen, a reduced DLCO especially if accompanied by a disproportionately higher forced vital capacity, imaging demonstrating an enlarged pulmonary artery or a dilated right ventricle, or objective evidence of a reduced exercise capacity. While echocardiography is one screening tool, right heart catheterization remains the gold standard for the diagnosis of PH. When appropriate, treatment with inhaled treprostinil, or possibly other pulmonary vasodilators, may be indicated. Full article

Background/Objectives: Pulmonary hypertension (PH) is associated with increased morbidity and mortality in chronic obstructive pulmonary disease (COPD). The ratio of the functional vital capacity (FVC) to diffusing capacity of the lung for carbon monoxide (DLCO) has demonstrated predictive and prognostic efficacy in PH due to lung disease, including COPD. However, forced expiratory volume in 1 s (FEV1) is used to grade COPD severity. We aimed to determine whether FEV1/DLCO predicts PH severity in COPD-PH. Methods: This is a retrospective analysis of patients with COPD-PH diagnosed via right heart catheterization and pulmonary function testing. Linear regression assessed the correlation of FEV1/DLCO with RHC parameters. Receiver operating characteristic (ROC) analysis was performed to assess the predictive effectiveness of FEV1/DLCO for severe PH. Results: Among 212 patients with COPD-PH, the FEV1/DLCO ratio positively correlated with mean pulmonary artery pressure (mPAP; r = 0.6, p < 0.001) and pulmonary vascular resistance (PVR; r = 0.56, p < 0.001). In ROC analysis, FEV1/DLCO was effective at predicting severe PH (AUC 0.60, p = 0.02). Those with a FEV1/DLCO ratio > 1.66 had a decreased rate of transplant-free survival as compared to those with a lower ratio (40.8% vs. 59.2%, p = 0.01). Conclusions: Among patients with COPD-PH, FEV1/DLCO correlates well with mPAP and PVR. The FEV1/DLCO ratio may effectively predict severe PH and may predict transplant-free survival in COPD-PH. Full article

Objectives: To investigate the role of blood eosinophils in predicting PH in end-stage lung disease. Methods: We conducted a retrospective study of adults with CF, COPD, and ILD who underwent RHC during lung transplant evaluations (2010–2022). Patients were classified by the 2022 ECS/ERS PH guidelines with pulmonary function and laboratory tests, including hemograms. The eosinophil threshold was set at 0.30 G/L. Results: We analyzed 663 patients (n = 89 CF, n = 294 COPD, and n = 280 ILD). Severe PH was more common in ILD (16%) than in CF (4%) and COPD (7%) (p = 0.0002), with higher eosinophil levels in ILD (p = 0.0002). No significant correlation was found between eosinophil levels and hemodynamic parameters (PAPm, PVR, and CI) across CF, COPD, and ILD (PAPm: p = 0.3974, p = 0.4400 and p = 0.2757, respectively; PVR: p = 0.6966, p = 0.1489 and p = 0.1630, respectively; CI: p = 0.9474, p = 0.5705 and p = 0.5945, respectively), nor was a correlation observed in patients not receiving OCS. Linear regression analysis confirmed the lack of association (PAPm: p = 0.3355, p = 0.8552 and p = 0.4146, respectively; PVR: p = 0.6924, p = 0.8935 and p = 0.5459, respectively; CI: p = 0.4260, p = 0.9289 and p = 0.5364, respectively), controlling for 6-MWD, Nt-proBNP, and ICS/OCS dosages. ROC analysis indicated eosinophils were ineffective in distinguishing PH severity levels across these diseases (AUC 0.54, 0.51, and 0.53, respectively). The analysis of eosinophil levels measured 18 ± 6 months prior to baseline found no predictive correlation with the presence of PH either. Eosinophil levels did not differ significantly among PH groups, but eosinophilic COPD was linked to more unclassified PH, higher CO, and greater lung volumes than non-eosinophilic COPD. Conclusions: In our cohort of end-stage CF, COPD, and ILD patients, blood eosinophilia did not predict the presence of PH but was associated with hemodynamic parameters and lung volumes in COPD. Full article

Chitosan nanoparticles (CNPs) were synthesized in this study to enhance the limited bioactivity and stability of Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) and effectively deliver it to target tissues. Under optimized conditions, stable encapsulation of GRC was achieved by setting the chitosan (CHI)-to-tripolyphosphate (TPP) ratio to 4:1 and adjusting the pH of TPP to 2, resulting in a zeta potential of +22.77 mV, which indicated excellent stability. As the concentration of GRC increased, the encapsulation efficiency decreased, whereas the loading efficiency increased. Fourier-transform infrared (FT-IR) spectroscopy revealed shifts in the amide I and II bands of CHI from 1659 and 1578 to 1639 cm⁻¹, indicating hydrogen bonding and successful encapsulation of GRC encapsulated with CNPs (GCN). X-ray diffraction (XRD) examination revealed the transition of the nanoparticles from a crystalline to an amorphous state, further confirming successful encapsulation. In vivo experiments demonstrated that GCN treatment significantly reduced lung injury scores in fine particulate matter (PM_2.5)-exposed mice (p < 0.05) and alleviated lung epithelial barrier damage by restoring the decreased expression of occludin protein (p < 0.05). In addition, GCN decreased the PM_2.5-induced upregulation of MMP-9 and COL1A1 mRNA expression levels, preventing extracellular matrix (ECM) degradation and collagen accumulation (p < 0.05). GCN exhibited antioxidant effects by reducing the mRNA expression of nitric oxide synthase (iNOS) and enhancing both the protein and mRNA expression of superoxide dismutase (SOD-1) caused by PM_2.5, thereby alleviating oxidative stress (p < 0.05). In A549 cells, GCN significantly reduced PM_2.5-induced reactive oxygen species (ROS) production compared with GRC (p < 0.05), with enhanced intracellular uptake confirmed using fluorescence microscopy (p < 0.05). In conclusion, GCN effectively alleviated PM_2.5-induced lung damage by attenuating oxidative stress, suppressing apoptosis, and preserving the lung epithelial barrier integrity. These results emphasize its potential as a therapeutic candidate for preventing and treating the lung diseases associated with PM_2.5 exposure. Full article