Search Results (463)

Background/Objectives: Levofloxacin (LVX) is a fluoroquinolone approved for the treatment of bacterial pneumonia, sinusitis, and prostatitis. Emerging in vitro and preclinical evidence suggests that efflux transporters are involved in LVX’s target tissue site distribution. Methods: The objective of this research was to characterize tissue exposure using a physiologically based pharmacokinetic (PBPK) model to be able to make more educated choices for optimal doses using target site pharmacokinetics data. Results: The final PBPK model in humans was applied to simulate free target site concentrations of LVX in lung and prostate, linking to minimum inhibitory concentrations (MIC) to assess appropriateness of currently approved dosing regimens for infections in both tissues. The clinical PBPK model was able to reproduce total plasma as well as free lung and prostate exposure of LVX in humans. Efflux transporters participate in LVX distribution to prostatic but not pulmonary tissue. Our results show a good penetration of LVX in both tissues with unbound partition coefficient (Kp,uu) equal to 0.79 and 0.72 for lung and prostate, respectively. Since LVX penetration in lung and prostate is similar, different sensitivities of the pathogens to LVX will dictate the effectiveness of the approved therapeutic regimen in the treatment of bacterial pneumonia, sinusitis, and prostatitis. Conclusions: Our research provides relevant insight into LVX’s target site exposure in lung and prostate. When integrated with pathogen-specific susceptibility data, these findings can be applied to refine current dosing regimens and help optimize the pharmacological treatment outcomes. Full article

Pseudomonas aeruginosa is a resilient Gram-negative pathogen frequently implicated in healthcare associated infections, particularly among immunocompromised individuals and those with chronic conditions such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), or cancer. It is well known for its high resistance to antibiotic treatment. This review briefly mentions P. aeruginosa’s resistance mechanisms, biofilm formation, and virulence factors, while primarily focusing on treatment challenges and recent advancements in therapeutic strategies aimed at overcoming resistance. Covered are novel non-antibiotic interventions such as quorum sensing inhibitors, quorum quenching agents, iron chelators, lectin and efflux pump inhibitors, as well as antimicrobial peptides and nanoparticles. Traditional medicine, phytochemicals, and probiotics are also evaluated. Additionally, this review explores the development of a viable vaccine, bacteriophage therapy, lactoferrin-hypothiocyanite combination, and topical use of electrochemical scaffolds. This review emphasizes the need for extensive safety studies and in vivo validation of these emerging non-antibiotic therapeutic strategies to determine their efficacy, pharmacological behavior, and clinical feasibility before they can be translated into practice. Many of these emerging treatments could play a vital role in future combination therapies by enhancing the efficacy of existing antibiotics and countering resistance and virulence mechanisms. Advancing these approaches from laboratory to clinical application remains a major challenge, making the development of approved therapies or vaccines a critical scientific and public health priority. Full article

Interstitial lung diseases (ILDs) encompass a heterogeneous group of disorders characterized by varying degrees of inflammation and fibrosis. Despite advances in understanding the pathogenesis, therapeutic options remain limited, particularly for patients with progressive phenotypes. Current international guidelines for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) emphasize the need for antifibrotic strategies and call for novel pharmacological interventions targeting key molecular pathways involved in fibrogenesis. This review provides a comprehensive overview of the most promising emerging pharmacological agents for ILDs, with particular attention to their mechanisms of action, efficacy, and safety profiles as reported in recent preclinical and clinical studies. The recent approval of Nerandomilast and the ongoing phase III trials of other agents mark a pivotal transition toward a new generation of antifibrotic therapies, aiming to achieve more effective disease control and improved patient outcomes. In view of an enlargement of active drugs aiming at controlling the disease with different mechanisms, the Authors underline the need for a “precision medicine” model to be applied to each ILD phenotyped patient, mirroring what already happens for other respiratory diseases. Full article

Background/Objectives: The most prevalent benign tumors in women are uterine fibroids. Most patients—more than half—do not exhibit any symptoms, but the most common clinical signs include irregular uterine bleeding, pelvic pain, gastrointestinal problems, increased frequency of urination, and, in some cases, infertility. Venous thromboembolism is a very rare consequence, especially when significant uterine fibroids are present. This syndrome usually develops because of pelvic vascular systems being compressed, which causes venous stasis. Pharmacological treatment, minimally invasive procedures, and surgical techniques are examples of therapy alternatives. The purpose of this study is to present, compare, and potentially elucidate the underlying mechanisms of VTE development in fibroids. Methods: we have synthesized findings from 24 documented instances of venous thromboembolism (VTE) linked to uterine fibroids. Results: the principal mechanism underlying thromboembolic events was identified as the mechanical compression of pelvic venous structures due to mass effect. Additionally, we recognized other pertinent risk factors, including oral contraceptive use, May-Thurner syndrome, myomatous erythrocytosis, and intravenous leiomyomatosis. None of the reviewed case reports provided evidence of confirmed inherited thrombophilia in the patients under investigation. The femoral and popliteal veins, primarily in the left leg, were most frequently impacted by thrombosis and the ensuing blockage. Imaging techniques confirmed that individuals suffered pulmonary embolisms in half of the cases. When the right treatment was given as soon as possible, most of VTEs had favorable outcome. In almost half of the cases examined, the patient had a hysterectomy. Since all symptoms were alleviated and the chance of additional thromboembolic consequences was reduced, this treatment strategy turned out to be the most successful. Conclusions: Clinicians should maintain a low threshold for venous imaging in women with large pelvic masses and unilateral limb symptoms. Despite being uncommon, VTE associated with UFs can cause serious morbidity. Mechanical venous compression is the main mechanism, which is often exacerbated by additional prothrombotic variables. Clinicians should maintain a low threshold for venous imaging in women with significant pelvic masses and unilateral limb symptoms, look for concurrent thrombophilia, and investigate early surgical consultation to address compressive etiologies when VTE is still unexplained. It would be simpler to ascertain the actual incidence and pinpoint risk variables that can be altered with standardized reporting of fibroid-associated VTE and prospective registries. Full article

Background: Preterm birth, affecting more than 13.4 million infants worldwide each year, remains one of the leading causes of neonatal morbidity and mortality. Among its complications, respiratory distress syndrome and bronchopulmonary dysplasia are predominant contributors to prolonged hospitalization and respiratory support needs. As advances in perinatal care have improved survival, attention has increasingly turned to optimizing respiratory function and reducing complications through non-pharmacological interventions. Respiratory physiotherapy has therefore gained recognition as a valuable adjunct to medical management in this population. Purpose: To provide a comprehensive synthesis of the current clinical evidence regarding respiratory physiotherapy techniques used in preterm neonates with respiratory distress syndrome or bronchopulmonary dysplasia. Summary of Evidence: The available literature describes several physiotherapeutic modalities—including prolonged slow expiration, postural treatment, Vöjta therapy, and gentle mechanical techniques—aimed at improving ventilation, gas exchange, and secretion clearance. Across diverse studies, these interventions have been associated with better oxygenation, improved heart and respiratory rates, shorter mechanical ventilation time, and reduced hospital stay, while showing no relevant adverse effects. Although methodological heterogeneity persists, the consistency of beneficial trends supports their integration into multidisciplinary neonatal care. Conclusions: Respiratory physiotherapy represents a safe and promising therapeutic complement for preterm neonates with respiratory distress syndrome or bronchopulmonary dysplasia. Techniques that combine postural control and controlled expiratory maneuvers appear particularly effective in enhancing pulmonary mechanics and recovery. Future research should focus on standardizing intervention protocols, identifying optimal timing and dosing, and evaluating the long-term respiratory and developmental outcomes of these physiotherapeutic strategies. Full article

Background/Objectives: The diagnosis and risk stratification of valvular heart disease have traditionally relied on resting echocardiography. However, in a significant portion of patients, resting findings do not fully reflect the hemodynamic severity of the condition, particularly in asymptomatic individuals with severe valvular disease or those with nonspecific symptoms. In this context, stress echocardiography emerges as a vital imaging modality, providing a dynamic assessment of valvular, ventricular, and pulmonary function under hemodynamic load (from physical exercise or pharmacological agents). Methods: We conducted a comprehensive synthesis and critical evaluation of the current landscape, recent advancements, and future directions regarding the application of stress echocardiography in valvular heart disease. Results: This comprehensive review explores the incremental role of stress echocardiography in valvular heart disease, analyzing the evolution of its clinical applications, from low-flow, low-gradient aortic stenosis to the evaluation of contractile reserve and exercise-induced pulmonary hypertension in mitral stenosis and regurgitation. We discuss standardized protocols, key parameters to monitor, and the diagnostic and prognostic outcomes from major clinical trials and current guidelines. Attention is given to stress echocardiography’s ability to unmask the true severity of the disease and to identify patients at high risk for adverse events, thereby guiding crucial clinical decisions, such as the optimal timing for surgical or transcatheter intervention. Conclusions: The review evaluates the limitations of modality and outlines future research directions, including its integration with new technologies like 3D echocardiography and speckle tracking techniques, to further optimize the role of stress echocardiography as a decision-making tool in the multidisciplinary management of valvular heart disease. Full article

Idiopathic pulmonary fibrosis is a chronic, progressive, interstitial lung disease for which specific and effective drug therapies are still lacking. Lathyrol is a diterpene compound with broad pharmacological activities that can be extracted from the traditional Chinese medicine Leptochloa chinensis (L.) Nees. To investigate the anti-pulmonary fibrosis effect of lathyrol and its underlying mechanism. In vivo, a mouse model of pulmonary fibrosis was induced by bleomycin, treated with intraperitoneal injections of lathyrol. In vitro, myofibroblast conversion was induced in three fibroblast cell lines by stimulating them with TGF-β1, followed by treatment with lathyrol. Transcriptomic analysis was performed to assess the regulation of signaling pathways and gene expression patterns modulated by lathyrol. The effects of lathyrol on PPARγ activation, as well as on the nuclear translocation and ubiquitination of phosphorylated Smad3, were examined. The interaction among Nedd4, PPARγ, and phosphorylated Smad3 was detected. In vivo, lathyrol ameliorated pathological fibrosis in the lungs of mice with pulmonary fibrosis and this effect was blocked by a PPARγ inhibitor. In vitro, lathyrol inhibited the transdifferentiation of fibroblasts into myofibroblasts, and these effects were suppressed by either inhibiting PPARγ activation or specifically silencing the PPARγ gene. Lathyrol inhibited the nuclear translocation of phosphorylated Smad3 and promoted its ubiquitination, while also enhancing the interaction among Nedd4, PPARγ, and phosphorylated Smad3. These effects were abolished following the specific silencing of either PPARγ or Nedd4. In conclusion, Lathyrol inhibits myofibroblast transformation by suppressing TGF-β/Smad pathway activation through PPARγ activation, thereby exerting its anti-pulmonary fibrosis effects. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease characterized by progressive scarring of the lungs. The available therapeutic strategies are limited and primarily focus on slowing disease progression rather than achieving fibrosis reversal. Cardamonin (CDN), a food-derived natural chalcone, has exhibited anti-fibrotic activity in liver and kidney fibrosis models; however, its role and underlying mechanism in IPF remain unelucidated. Herein, we integrated network pharmacology, machine learning, molecular simulations, and in vitro experiments. Network pharmacology identified 135 overlapping targets between CDN and IPF, which demonstrated a significant enrichment in the Phosphatidylinositol 3-Kinase/Protein Kinase B signaling pathway (PI3K/AKT). Machine learning further prioritized 6 core targets, with IGF1 emerging as a key candidate. Molecular docking revealed a favorable binding energy of −7.9 kcal/mol for the CDN-IGF1 complex. Subsequent 100 ns molecular dynamics simulations further confirmed its robust binding stability, yielding a mean binding free energy of −150.978 kcal/mol. In vitro, CDN significantly mitigated fibrosis in bleomycin (BLM)-challenged A549 cells, downregulating the expression of α-smooth muscle actin (α-SMA) and fibronectin. This effect was accompanied by a beneficial reversal of epithelial–mesenchymal transition (EMT), as indicated by increased E-cadherin levels and decreased vimentin expression. Mechanistically, CDN significantly suppressed the IGF1/PI3K/AKT axis; this inhibitory effect was partially reversed by exogenous IGF1 supplementation and further enhanced by the PI3K-specific inhibitor LY294002. This work provides the evidence that CDN alleviates BLM-induced pulmonary fibrosis by targeting the IGF1/PI3K/AKT-EMT axis. These findings lend support to a robust mechanistic basis for developing CDN as a potential therapeutic candidate for IPF. It should be noted that these conclusions are drawn from in vitro experiments using A549 cells, and further validation in primary alveolar epithelial cells and animal models is warranted to confirm their physiological relevance. Full article

KSRP (KH-type splicing regulatory protein) has emerged as a pivotal regulator of gene expression at multiple levels, acting as a transcription and splicing factor in the nucleus, and mediating AU-rich element (ARE)-dependent mRNA decay, translational silencing, and microRNA (miRNA) maturation in the cytoplasm. We and others have shown that KSRP acts as a regulator of immune responses, e.g., by dampening the expression of proinflammatory cytokines such as TNF-α, IL-6, IL-8, but also of NOS2, and facilitating the maturation of regulatory miRNAs, including let-7a, miR-129, and miR-155. This review aims to present current knowledge on the regulation of KSRP activity as conferred by miRNAs, phosphorylation, ubiquitination, SUMOylation, and interactions with long non-coding RNAs to enable dynamic responses towards inflammatory stimuli, and the effects of KSRP on innate immune reactions. Here, KSRP acts as an inhibitor by attenuating RIG-I-mediated antiviral signaling, cytokine production, and phagocytosis. In vivo, KSRP deficiency reduced arthritis severity but heightened inflammatory responses in sepsis and enhanced pathogen clearance in invasive pulmonary aspergillosis. These findings position KSRP as a dual regulator that limits tissue damage while constraining antimicrobial immunity. As a perspective, modulation of KSRP activity by applying pharmacological inhibitors may provide strategies to either suppress hyperinflammation in autoimmunity and sepsis or enhance host defense in immunocompromised states. Full article

Asthma is a chronic inflammatory disorder of the airways affecting over 260 million people worldwide and remains a major clinical and socioeconomic challenge. Despite substantial advances in pharmacological management (including inhaled corticosteroids, β₂-agonists, leukotriene receptor antagonists, and biologic therapies), many patients continue to experience uncontrolled symptoms or corticosteroid resistance. This persistent unmet need has prompted interest in adjunctive and alternative treatment strategies. Oxygen therapy during asthma exacerbations and worsening pulmonary obstruction is a standard life-saving procedure. However, various forms of oxygen therapy are being considered for long-term treatment to reduce the number of exacerbations. Experimental and preliminary clinical data indicate that oxygen therapy may offer multiple benefits, including improved oxygenation, anti-inflammatory effects, reduced oxidative stress, modulation of nitric oxide signaling, enhanced immune responses, and promotion of angiogenesis. These mechanisms may collectively alleviate airway inflammation and improve pulmonary function. Nevertheless, clinical evidence on hyperbaric oxygen therapy (HBOT) in asthma remains limited. Existing small-scale studies suggest its safety but provide inconclusive results regarding its efficacy. Potential adverse effects such as barotrauma, oxygen toxicity, and transient anxiety necessitate careful patient selection and standardized treatment protocols. Further large-scale, randomized controlled trials are required to determine the therapeutic value of HBOT and to define its role as an adjunctive therapy in the comprehensive management of asthma. Full article

Vascular dysfunction lies at the core of cardiovascular diseases—the leading cause of global morbidity and mortality. Despite their prevalence, therapeutic options remain limited, in part due to an incomplete understanding of the molecular mechanisms driving vascular pathology. The integrated stress response (ISR), an evolutionarily conserved signaling network activated by diverse stressors, represents a critical but underexplored mechanism in vascular biology. This review examines the dual roles of the core ISR kinases—PERK, GCN2, HRI and PKR—in vascular homeostasis and pathology, including atherosclerosis, pulmonary hypertension, and angiogenesis. We develop a conceptual framework in which the ISR functions as a context-dependent, double-edged sword: while PERK and PKR promote inflammation, apoptosis, and vascular re-modeling, GCN2 mediates protective effects. The outcome of ISR activation is shaped by cell type, stress duration and intensity, and downstream signaling bias (e.g., ATF4 vs. CHOP dominance). We further discuss pharmacological ISR modulators—including 2-aminopurine, C16, salubrinal, halofuginone, GSK2606414, and GSK2656157—which have demonstrated beneficial effects in preclinical models by suppressing inflammation, reducing apoptosis, and attenuating disease progression. Collectively, the ISR emerges as a critical regulatory node in vascular pathophysiology, and its selective, context-aware modulation represents a promising avenue for therapeutic intervention. Full article

Treating acute lung injury (ALI) presents significant challenges due to adverse drug reactions. This study systematically explored the protective effects and mechanisms of a flavonoid-rich extract from Bombyx batryticatus (FBB), a traditional Chinese medicine, in combating ALI. Through UPLC-MS/MS analysis, we identified 163 flavonoid components in FBB for the first time, including flavonoids, flavonols, and chalcones. Unlike single-component flavonoid therapies, FBB provides synergistic regulation across multiple targets and pathways. Network pharmacology predictions, supported by experimental validation, revealed that FBB primarily suppresses the expression of inflammatory factors (IL-1β, IL-6, TNF-α) and oxidative stress markers (iNOS, COX-2) by modulating the PI3K/Akt, MAPK, and NF-κB signaling pathways. FBB inhibits pro-inflammatory responses and upregulates chemokine receptors like Ccr1 and Ccr2, along with IL-2Rb, at the transcriptional level. This suggests its potential to promote inflammation resolution and tissue repair through immune microenvironment remodeling, rather than mere immunosuppression. Additionally, FBB demonstrated significant anti-apoptotic effects both in vitro and in vivo, effectively reducing pulmonary edema and vascular permeability. Its complex composition and multi-pathway synergistic mechanisms offer broader regulatory potential and unique therapeutic advantages in treating ALI compared to single flavonoid compounds or conventional hormone drugs like dexamethasone (DEX). This study reveals a novel mechanism by which FBB, a multi-component natural drug, exerts therapeutic effects in ALI, providing a theoretical and experimental foundation for developing flavonoid-based compound preparations from traditional Chinese medicine. Full article

Background: Interstitial lung diseases (ILDs) profoundly affect daily life, limiting mobility, independence, and emotional stability. While antifibrotic therapies may slow physiological decline, the living experience—characterized by breathlessness, cough, frailty, and psychological distress—remains insufficiently understood; this study therefore aimed to capture real-world patient perspectives on functional capacity, self-management, and mental health to identify treatable traits beyond conventional physiological measures. Materials and Methods: A cross-sectional quantitative online survey was conducted between September 2024 and January 2025 by Lungenfibrose e.V. in collaboration with the Center for Interstitial and Rare Lung Diseases (ZISL), Universities of Giessen and Marburg Lung Center (Giessen site). Patients with physician-confirmed ILD completed standardized instruments assessing dyspnea (MRC), cough intensity (VAS-Cough), frailty (CFS), and health-related quality of life (EQ-5D-5L). Data were analyzed descriptively across physical, functional, and psychosocial domains. Results: The majority of 69 respondents had idiopathic pulmonary fibrosis (64.7%) with a mean diagnostic delay of 1.4 ± 2.2 years; 69% were diagnosed within two years of symptom onset, and 77% were receiving antifibrotic therapy (nintedanib 57%, pirfenidone 19%). Functional limitations were substantial—55% were mobile for fewer than two hours per day, 73% reported mobility impairment, and oxygen use was common (51% during exertion, 26% at rest). Frailty increased over time (mean CFS 3.2 → 3.8), with 46% classified as fit, 36% vulnerable, and 18% frail. Dyspnea and cough remained burdensome (mean VAS-cough 40 ± 26; 58% moderate–severe), and health-related quality of life was reduced (mean EQ-VAS 56.5 ± 23.7), with high rates of anxiety/depression (78%), limitations in daily activities (76%), and pain/discomfort (74%). Despite overall satisfaction with care (mean 7.1 ± 2.5), respondents frequently reported unmet needs for psychological support and clearer communication about treatment and disease management. Conclusions: Despite antifibrotic therapy and structured specialist care, individuals living with ILD continue to face substantial physical and emotional challenges. Treatable traits—including frailty, dyspnea, inactivity, anxiety, and social isolation—emerge as key determinants of well-being. Multidisciplinary strategies integrating rehabilitation, psychosocial support, and patient education alongside pharmacological therapy are essential to preserve autonomy and improve quality of life in pulmonary fibrosis. Full article

Background/Objectives: The utility and value of graduated compression stockings (gCS) as an adjunct to pharmacological thromboprophylaxis, with and without low-molecular-weight heparins (LMWH) and other anticoagulants, in avoiding any thromboembolic (TE) event in the scenario of total joint replacement, fracture management, spine and pelvic surgery, and arthroscopic procedures, remains unclear. Because of the urgent need to decide whether gCS should stay in the portfolio of a national group of nine tertiary trauma centres, our research department was requested to answer the question of whether gCS provide any extra benefit in addition to modern TE prophylaxis in orthopaedic and trauma surgery through a prospectively registered rapid review (PROSPERO CRD42024621104). Methods: We searched PubMed, Ovid MEDLINE, Embase, CINAHL, and CENTRAL from 1 January 1980 to 1 March 2025, for randomised controlled trials (RCTs) and cohort studies comparing TE prophylaxis regimens, both with and without gCS, and modern pharmacological anticoagulants. The methodological quality of individual studies was rated by the Cochrane Collaborations’ Risk of Bias Version 2.0 (RoB-2) and the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tools, supplemented by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The reported cumulative incidence of any TE event (i.e., deep vein thrombosis, pulmonary embolism), as defined by individual trialists, was chosen as the primary endpoint, and expressed as the relative risk (RR) between intervention and control groups. Results: Fifteen investigations (13 RCTs and 2 observational studies) enrolling 7721 patients (mean age, 59 [SD 13] years; 3538 males [46%]) with various musculoskeletal conditions and injuries were included. Methodological quality was deemed sufficient to derive meaningful conclusions. The random-effects pooled RR across all studies was 1.15 (95% confidence interval [CI]: 0.80–1.64) in favour of the no-gCS control, but with substantial heterogeneity (I²: 73%). Only three studies investigated the effectiveness of gCS versus no prophylaxis (N = 246, RR: 0.72, 95% CI: 0.43–1.22). Seven studies (N = 5117) compared various combinations of pharmacological prophylaxis, with or without gCS, for a summary RR of 1.44 (95% CI: 0.76–2.72). Conclusions: The results of this rapid review neither show a clear benefit nor support the general use of gCS to prevent TE in orthopaedic and trauma surgery, especially if pharmacological prophylactic measures are established and suitable. Full article

Background/Objectives: Pulmonary fibrosis (PF) is a progressive interstitial lung disease with limited therapeutic options. Lepidium sativum (cress seeds) possess recognized antioxidant and anti-inflammatory properties, yet its potential antifibrotic activity has not been investigated. This study evaluated the phytochemical composition and antifibrotic efficacy of cress seed extract (CSE) and examined whether its effects are associated with modulation of the ncNRFR/let-7d pathway in methotrexate (Mtx)-induced PF. Methods: Comprehensive metabolite profiling was performed using GC–MS, HPLC, and UPLC–T-TOF–MS/MS. Antioxidant capacity and antiproliferative effects were assessed in vitro. Network pharmacology was used to identify CSE-related PF targets and regulatory pathways. In vivo, PF was induced in adult male Wistar rats by Mtx, followed by oral CSE administration (50–150 mg/kg). Biochemical markers of inflammation, oxidative stress, extracellular matrix deposition, EMT, and ncRNA expression (ncNRFR and let-7d) were quantified alongside histopathology and immunohistochemistry. Results: CSE contained diverse terpenes, phenolics, flavonoids, glucosinolates, and amino acid derivatives. It exhibited potent antioxidant activity and antiproliferative effects against A549 and Hep2 lung cancer cells. Network analysis identified 997 overlapping CSE–PF targets and highlighted IL6 and MMP1 as relevant miR-let-7d–associated nodes. In vivo, Mtx-induced marked fibrosis characterized by increased ncNRFR, reduced let-7d, elevated IL6, HMGB1, TGF-β, MMP1, collagen, and hydroxyproline, and reduced antioxidant enzyme activity. CSE treatment dose-dependently mitigated these alterations, improved histoarchitecture, and reduced collagen deposition. Conclusions: CSE showed antifibrotic, antioxidant, and anti-inflammatory activity in MTX-induced PF in rats and modulated the reciprocal expression patterns of ncNRFR and let-7d. These findings support CSE as a potential source of bioactive constituents for PF management and identify the putative ncNRFR–let-7d regulatory relationship as a novel pathway in fibrotic lung disease, warranting further mechanistic investigation. Full article