Search Results (708)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with limited therapeutic options and increasing global incidence, with a median survival of only 2–5 years. The clinical utility of macrophage polarization to regulate the progression of pulmonary fibrosis remains understudied. This study determined the efficacy of nintedanib and pexidartinib (PLX3397) combination therapy for treating IPF. Combination treatment effectively inhibited the progression of radiation-induced pulmonary fibrosis (RIPF) and prolonged survival in bleomycin-treated mice. Micro-CT analysis revealed a significant tissue repair efficacy. The therapy significantly normalized the abnormal vascular structure observed during RIPF and bleomycin-induced pulmonary fibrosis progression and was accompanied by a decrease in the M2 population. Polarized M1 macrophages enhanced normalized tube formation of irradiated endothelial cells (ECs) in vitro; M2 macrophages increased adhesion in irradiated ECs and abnormal tube formation. Single-cell RNA sequencing data from patients with IPF further supports colony stimulating factor (CSF) 1 upregulation in macrophages and downregulation of capillary EC markers. This study highlights a promising combination strategy to overcome the therapeutic limitations of monotherapy with nintedanib for the treatment of IPF. Full article

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Background: Pulmonary involvement is the most common prognosis-related organ involvement in idiopathic inflammatory myopathy (IIM). Owing to the large number of antibodies, the evidence for lung involvement and rare antibodies is limited. In everyday clinical practice, the interpretation of positive myositis antibodies represents a challenge. Methods: This study is a retrospective monocentric analysis. The data collection regarding positive myositis antibodies and possible pulmonary involvement was carried out from July 2019 to May 2022. Data analysis revealed positive results for one of the following antibodies: EJ, PL7, OJ, PL12, Mi-2α, TIF1γ, MDA5, SAE, NXP2, SRP, Ku, PM-Scl100 and PM-Scl75. In our analysis, patients with IIM, patients with inflammatory rheumatic disease other than IIM and patients without inflammatory rheumatic disease are described. The results of high-resolution computed tomography (HRCT), pulmonary function tests, echocardiographic examinations and their associated clinical findings are examined. Results: In the entire cohort, 209 patients with positive myositis antibodies were detected. In total, 22 (10.5%) patients had interstitial lung disease (ILD) patterns on HRCT. In the subgroup of patients with IIM, a significantly higher proportion of patients with lung involvement (n = 13, 35.1%) was found than in the group with other inflammatory rheumatic diseases (IRDs) (n = 6, 6.7%) or in the group without IRDs (n = 3, 3.7%). When the antibody groups were considered, the PL12-positive patients had the largest proportion of ILD (42%), followed by the MDA5-positive patients (40%). Conclusions: In patients with IIM, myositis antibodies are highly relevant for assessing the risk of lung involvement. In groups with other IRD or without IRD, antibody detection does not represent this high relevance for lung involvement. A differentiated assessment of the various MSAs or MAAs detected, as well as clinical parameters, allows for further important risk assessment for prognosis-relevant lung involvement. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease characterized by chronic inflammation, vascular remodeling, and immune dysregulation. COVID-19, caused by SARS-CoV-2, shares several systemic immunohematologic disturbances with IPF, including cytokine storms, endothelial injury, and prothrombotic states. Unlike general comparisons of viral infections and chronic lung disease, this review offers a focused analysis of the shared hematologic and immunologic mechanisms between COVID-19 and IPF. Our aim is to better understand how SARS-CoV-2 infection may worsen disease progression in IPF and identify converging pathophysiological pathways that may inform clinical management. We conducted a narrative synthesis of the peer-reviewed literature from PubMed, Scopus, and Web of Science, focusing on clinical, experimental, and pathological studies addressing immune and coagulation abnormalities in both COVID-19 and IPF. Both diseases exhibit significant overlap in inflammatory and fibrotic signaling, particularly via the TGF-β, IL-6, and TNF-α pathways. COVID-19 amplifies coagulation disturbances and endothelial dysfunction already present in IPF, promoting microvascular thrombosis and acute exacerbations. Myeloid cell overactivation, impaired lymphocyte responses, and fibroblast proliferation are central to this shared pathophysiology. These synergistic mechanisms may accelerate fibrosis and increase mortality risk in IPF patients infected with SARS-CoV-2. This review proposes an integrative framework for understanding the hematologic and immunologic convergence of COVID-19 and IPF. Such insights are essential for refining therapeutic targets, improving prognostic stratification, and guiding early interventions in this high-risk population. Full article

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease associated with high morbidity and mortality. Both pulmonary and extrapulmonary comorbidities significantly influence disease progression and patient outcomes. Despite current therapeutic options, effective treatments remain limited. Quercetin, a naturally occurring flavonoid, has emerged as a promising compound due to its antioxidant, anti-inflammatory, and antifibrotic properties. Preclinical and clinical studies have demonstrated its ability to modulate key molecular pathways involved in IPF, including Nrf2, SIRT1/AMPK, and the regulation of fibrosis-associated microRNAs (miRNAs). Furthermore, quercetin shows therapeutic potential across a range of IPF-related comorbidities, including chronic obstructive pulmonary disease, pulmonary hypertension, lung cancer, cardiovascular disease, diabetes, and psychiatric disorders. Under these conditions, quercetin acts via epigenetic modulation of miRNAs and regulation of oxidative stress and inflammatory signaling pathways. This review highlights the multifunctional role of quercetin in IPF and its comorbidities, emphasizing its gene regulatory mechanisms and potential as an adjunctive or alternative therapeutic strategy. 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 neutrophil-to-lymphocyte ratio (NLR) is a simple, inexpensive and easily accessible inflammatory biomarker that reflects the balance between innate and adaptive immunity. In recent years, NLR has emerged as a potential prognostic and disease severity marker for different diseases, including idiopathic pulmonary fibrosis (IPF), a progressive and fatal interstitial lung disease with a highly variable course and poor prognosis. Several studies have highlighted that NLR can be associated with several clinical outcomes such as lung function decline, increased risk of hospitalization, acute exacerbation of IPF, and mortality over time. It might also correlate with overall survival in the course of antifibrotic therapy and validated prognostic score as a gender–age–physiology score. Despite these findings, the clinical use of NLR remains limited due to its non-specific nature, the lack of standardized cut-off values, and high variability related to demographic factors, comorbidities and medications. Hence, NLR may display the underlying immune dysregulation in IPF and could be exploited as a non-invasive tool for risk stratification and disease monitoring. Further studies are needed to confirm and validate its use in IPF and to establish reliable cut-off values in clinical applications. Full article

Interstitial pneumonia is a general term for diseases in which inflammation occurs mainly in the interstitium of the lung. It is also pointed out that interstitial pneumonia reduces alveolar function and makes it difficult to take in oxygen through inspiration, causing symptoms such as dyspnea and coughing, which may eventually lead to respiratory failure. At present, there is no effective treatment, and only conservative treatment exists. This time, we report that the therapeutic effect was confirmed in patients with interstitial pneumonia who took platinum palladium. In this case, improvement tendencies were observed in patients with Idiopathic pulmonary fibrosis (IPF), but improvement tendencies were also observed in many other lung diseases. In order to explore the mechanism, AMPK was measured at the in vitro level, and blood KL-6 and hydrogen peroxide levels in the patient were measured at the in vivo level. AMPK values were significantly elevated by more than 800%, and KL-6 and hydrogen peroxide levels were also significantly decreased by drinking platinum palladium. Platinum palladium exhibits a strong antioxidant effect and is the only substance in the world that can approach all four types of active oxygen. In addition, when it was actually administered to patients, there were cases of dramatic improvement, and it was confirmed that KL-6, a parameter of lung function, decreased in 16 out of 32 patients, and furthermore, oxygen inhalation was completed. Patients were also seen. It was suggested that increasing the number of cases in the future may help improve interstitial pneumonia. Full article

Emerging evidence suggests a significant association between monocytes and the pathophysiology and prognosis of idiopathic pulmonary fibrosis (IPF). This review aims to systematically evaluate current knowledge regarding blood monocyte counts and their relationship with the etiology, progression, and prognosis of IPF. We conducted a systematic search in the PubMed database for articles published through 17 February 2025, using the MeSH terms “lung diseases, interstitial” and “monocytes,” which yielded 314 results. After filtering for full-text articles in English (n = 242), we included only studies focusing on blood monocyte counts with clinical implications in IPF. Articles relating to other cell types or non-IPF lung diseases were excluded. Our systematic search identified 12 relevant articles. Monocytes play an essential role in regulating inflammatory responses and resolution across multiple diseases, with established but incompletely understood contributions to lung fibrosis development in IPF. Correlations have been demonstrated between elevated blood monocyte counts and the following: (1) the presence and progression of interstitial lung abnormalities, (2) the progression from an indeterminate usual interstitial pneumonia (UIP) pattern on CT scans to definitive IPF, and (3) worse lung function parameters, an increased risk of acute exacerbations, and reduced overall survival in IPF patients. Monocytes serve as critical orchestrators throughout IPF’s natural history—from early interstitial changes to disease progression and acute exacerbations. Targeting monocyte recruitment pathways and reprogramming their differentiation represents a promising therapeutic approach, while circulating monocyte counts offer potential as accessible biomarkers for disease progression and treatment response. Future research should characterize stage-specific monocyte phenotypes to enable precision-targeted interventions. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive interstitial lung disease with an unknown etiology. It is often accompanied by skeletal muscle mass loss. Chest wall muscles play a crucial role in respiratory movements and form part of the skeletal muscles. The aim of this study is to evaluate the relationship between chest wall muscle thickness and pulmonary function test (PFT) results, as well as other prognostic markers, in patients with IPF. Materials and Methods: A retrospective analysis was conducted on 108 patients diagnosed with IPF and 53 control subjects. Chest wall muscle thickness was measured on thoracic computed tomography (CT) images at specific anatomical levels. PFT parameters, the Gender-Age-Physiology (GAP) index, number of acute exacerbations, and mortality data were evaluated in relation to muscle thickness. Results: IPF patients had significantly reduced thickness in the bilateral external scapular muscles at both the aortic and pulmonary trunk levels compared to controls. Bilateral pectoral muscle thickness at the aortic level was positively correlated with forced vital capacity (FVC) and negatively correlated with the number of exacerbations. Internal scapular muscle thickness at the aortic level showed a significant positive correlation with diffusion capacity of the lung for carbon monoxide (DLCO) and a negative correlation with both GAP scores and exacerbation frequency. External scapular muscle thickness at the pulmonary trunk level was positively associated with PFT parameters and inversely correlated with the GAP index, exacerbations, and mortality. Conclusions: In patients with IPF, the bilateral external scapular muscle thickness at the aortic and pulmonary trunk levels was significantly reduced compared to controls. Significant associations were found between some chest wall muscle thicknesses and the GAP index, pulmonary function, acute exacerbations, and mortality, underscoring the prognostic value of baseline muscle measurements. Measurement of chest wall muscle thickness using routine thoracic CT scans may offer additional prognostic value in IPF. Incorporating this parameter into clinical evaluation may help identify patients who could benefit from supportive interventions, such as nutritional therapy or pulmonary rehabilitation. Full article

The uncontrolled fibrosis of lung tissue can lead to premature death in patients suffering from idiopathic pulmonary fibrosis (IPF), and it complicates the course of chronic obstructive pulmonary disease (COPD) and emphysema. It is also a risk factor for developing lung cancer. Antifibrotic drugs, such as nantedanib and pirfenidone, are able to slow down the progression of pulmonary fibrosis, but more effective treatment is still needed to reverse it. Studies on the pathogenesis of tissue fibrosis have demonstrated that integrins play a crucial role affecting the development of pulmonary fibrosis, for example, by activating transforming growth factor-β (TGF-β). Taking the above into consideration, targeting specific integrins could offer promising opportunities for managing fibroplastic changes in lung tissue. Integrins are a type of transmembrane molecule that mediate interactions between cells and extracellular matrix (ECM) molecules. This review discusses the role of integrins in the pathogeneses of respiratory diseases and carcinogenesis, as well as presents promising approaches to the drug therapy of pulmonary fibrosis of various etiologies based on integrin inhibition. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited therapeutic options. Current therapies (pirfenidone, nintedanib) exhibit modest efficacy and significant side effects, underscoring the need for novel strategies targeting early pathogenic drivers. Saroglitazar (SGZ), a dual PPARα/γ agonist with anti-inflammatory properties approved for diabetic dyslipidemia, has not been explored for IPF. We aimed to investigate SGZ’s therapeutic potential in pulmonary fibrosis and elucidate its mechanisms of action. Materials and Methods: Using a bleomycin (BLM)-induced murine pulmonary fibrosis model, we administered SGZ therapeutically. A histopathological assessment (H&E, Masson’s trichrome, collagen I immunofluorescence), Western blotting, and qRT-PCR analyzed the fibrosis progression and inflammatory markers. Flow cytometry evaluated the macrophage polarization. In vitro studies used RAW264.7 macrophages stimulated with BLM/LPS and MRC-5 fibroblast co-cultures. The NF-κB/NLRP3 pathway activation was assessed through protein and gene expression. Results: SGZ significantly attenuated BLM-induced histopathological hallmarks, including alveolar wall thickening, collagen deposition, and inflammatory infiltration. Fibrotic markers (OPN, α-SMA) and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) were downregulated in the SGZ-treated mice. Mechanistically, SGZ suppressed the M1 macrophage polarization (reduced CD86⁺ populations) and inhibited the NF-κB/NLRP3 pathway activation in the alveolar macrophages. In the RAW264.7 cells, SGZ decreased the NLRP3 inflammasome components (ASC, cleaved IL-1β) and cytokine secretion. Co-cultures demonstrated that the SGZ-treated macrophage supernatants suppressed the fibroblast activation (α-SMA, collagen I) in MRC-5 cells. Conclusions: SGZ attenuates pulmonary fibrosis by suppressing macrophage-driven inflammation via NF-κB/NLRP3 inhibition and disrupting the macrophage–fibroblast crosstalk. These findings nominate SGZ as a promising candidate for preclinical optimization and future clinical evaluation in IPF. Full article

The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves complex interactions between epithelial, mesenchymal, immune, and endothelial cells, often aggravated by lipid metabolism dysfunction, mitochondrial, and peroxisomal abnormalities. Changes in lipid metabolism may drive fibrotic processes, suggesting the potential of lipid biomarkers for disease monitoring. We compared here the cholesterol metabolism and very-long-chain fatty acid profiles of patients with IPF with healthy controls. The IPF patients’ lipidic profiles were also evaluated according to disease severity and progression rate. This prospective, observational study involved 50 IPF patients at disease diagnosis before antifibrotic treatment initiation and 50 age- and gender-matched healthy controls. Using a serum lipidomic profile, we focused on cholesterol synthesis, mitochondrial and peroxisomal markers, inflammatory lipids, and oxidative stress markers. Disease severity was evaluated using the Gender-Age-Physiology (GAP) index, while the prognosis was assessed by classifying patients as rapid or slow progressors based on a 24-month follow-up. IPF patients exhibited lower levels of cholesterol synthesis precursors (e.g., lathosterol), mitochondrial oxysterols, and inflammatory mediators (e.g., arachidonic acid) compared to controls. Reduced levels of these biomarkers were also associated with higher disease severity and rapid disease progression. Conversely, some peroxisomal markers (e.g., brassidic acid and nervonic acid) showed altered trends depending on disease severity. Our findings indicate that patients with IPF, compared to healthy controls, may show lipidomic alterations, particularly a reduction in cholesterol precursors and docosahexaenoic acids, which are also associated with IPF severity and progression. While preliminary, this study suggests lipidomics to be a promising tool to stratify IPF severity and prognosis. Full article

Growth Differentiation Factor 15 (GDF15), also known as non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) or macrophage inhibitory cytokine 1 (MIC-1), is a stress- and inflammation-induced cytokine distantly related to the TGF-β superfamily. Its highly elevated levels showed close association with various pathological conditions, making it an emerging biomarker of disease prognosis. However, most GDF15-mediated effects under normal physiology and various pathological conditions are poorly understood. This is partly because the only known GDF15 receptor is exclusively localized in the brain, and how GDF15 functions peripherally is currently unknown. Mounting recent evidence has shown GDF15’s critical role in fibrosis in multiple organs, such as the liver, lung, and kidney. Evidence further suggests that it can either contribute to fibrosis by promoting inflammation and fibroblast activation or confer protective effects by modulating the immune response and mitigating fibrosis severity. Thus, the exact role of GDF15 in fibrosis can vary depending on the organ involved and the specific disease context. For example, increased GDF15 in idiopathic pulmonary fibrosis (IPF) promotes fibrosis via fibroblast activation and collagen deposition. Conversely, GDF15 might have a protective role in liver fibrosis, with decreased GDF15 levels causing increased fibrosis severity, while GDF15 treatment ameliorates fibrosis. Due to its close association with fibrosis, GDF15 is being investigated as a potential biomarker for disease severity and monitoring treatment response. However, further research unraveling its mechanisms of action is needed to explore the potential of GDF15 as a therapeutic target for treating fibrosis, either by modulating its expression or utilizing its immunomodulatory properties. This review marshals the limited studies addressing the recently appreciated differential role of GDF15 in regulating the fibrotic process in different organs. The review also discusses the aspects of further research needed to highlight GDF 15 as a novel predictor and therapeutic target for fibrosis in different organs. Full article