Thoracic research and practice最新文献

{"title":"Nanoparticle-Based Therapeutic Strategies in Respiratory Diseases: Current Approaches and Future Perspectives.","authors":"Ozge Cinar, Ilgin Kimiz-Gebologlu, Suphi S Oncel","doi":"10.4274/ThoracResPract.2025.s012","DOIUrl":"10.4274/ThoracResPract.2025.s012","url":null,"abstract":"<p><strong>Introduction: </strong>Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, tuberculosis, and acute respiratory distress syndrome (ARDS) remain major global health challenges, causing significant morbidity and mortality worldwide.<sup>1,2</sup> Despite the availability of pharmacological treatments such as bronchodilators, corticosteroids, antibiotics, and chemotherapeutics, most conventional drug administration routes (oral or intravenous) are often associated with critical limitations. These systemic delivery methods lead to the widespread distribution of drugs throughout the body rather than targeted accumulation at the site of infection or inflammation. This lack of specificity reduces the drug concentration at the affected region while increasing off-target toxicity in healthy tissues.<sup>3</sup> Furthermore, many orally administered drugs suffer degradation in the gastrointestinal tract or undergo first-pass metabolism in the liver, which significantly decreases the amount of active drug reaching the systemic circulation and ultimately the target lung tissues.<sup>4</sup> Many therapeutic drugs also have short half-lives, necessitating frequent dosing to maintain therapeutic levels, reducing patient compliance in chronic or long-term treatments.<sup>5</sup> Therefore, there is an urgent need for advanced drug delivery systems capable of improving pulmonary targeting, enhancing therapeutic efficacy, and minimizing systemic side effects. Nanotechnology offers a promising and innovative alternative platform for addressing these challenges. Nanoparticles, ranging from 1-100 nm and employed as drug delivery systems, display unique physical, chemical, and biological properties compared to their macro-scale counterparts. As a transformative field in biomedical science, nanotechnology enables the design of novel nanoformulations to overcome the major limitations of conventional treatments. Nano-based drug delivery systems can enhance solubility, extend drug half-life, and achieve localized accumulation in the lungs by penetrating mucosal barriers.<sup>6</sup> Different nanoparticle types, such as polymeric, lipid-based, and metallic nanoparticles, have been developed to optimize therapeutic efficiency and minimize side effects.<sup>7</sup> Considering liposomes, polymeric nanoparticles, solid lipid nanoparticles, and inorganic nanoparticles as representative platforms for pulmonary applications a comparison of conventional and nanotechnology-based drug delivery systems is important (Figure 1). Recent studies highlight the great potential of nanoparticle-based systems for respiratory diseases For example, inhalable reactive oxygen species (ROS)-responsive nanoparticles were designed to release anti-inflammatory drugs only in regions with high oxidative stress, reducing inflammation and tissue damage in COPD and ARDS models.<sup>8</sup> Similarly, glutathione (GSH)-triggered nanoparticles utilize","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"31-33"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145672422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occupational and Environmental Exposures: Trends in Publications, Diseases, and Experimental Models.","authors":"Omur Sert, Ozlem Yesil-Celiktas","doi":"10.4274/ThoracResPract.2025.s003","DOIUrl":"10.4274/ThoracResPract.2025.s003","url":null,"abstract":"<p><strong>Introduction: </strong>Environmental exposures such as silica dust, microplastics, and general dust have significant health impacts. We performed a PubMed-based analysis (2000-2025) of research trends on these exposures, associated diseases, and experimental models. Pulmonary fibrosis was the most studied disease, while animal models and conventional <i>in vitro</i> systems dominated experimental approaches. Organ-on-chip platforms remain scarcely used. The results highlight growing research interest and the need for advanced human-relevant models to study exposure effects on respiratory and systemic health. Diverse environmental agents (particulates, gases, volatile organic compounds, biological agents, and nanomaterials) disseminate through the atmosphere, water, and soil, resulting in human exposure via numerous pathways. The result of exposure is influenced by the physicochemical characteristics of the substance (dimensions, morphology, surface chemistry), the exposure dosage, the duration of exposure, and the exposure pathway.<sup>1</sup> Especially, fine-ultrafine particles in the atmosphere can penetrate through the upper and lower respiratory pathways due to their aerodynamic features; PM 2.5<sup>2</sup> or smaller particles can directly interact with epithelial cells at the alveolar level. The airway epithelium serves as the main defense mechanism against inhaled substances. Also orchestrate the homeostasis via physical and immunological defense mechanisms. To form the epithelial barrier, epithelial cells are connected to each other by cell-cell junctions (tight, gap, and adherents).<sup>3</sup> Due to the inhalation of 6-12 liters of air per minute, this tissue is subjected to a significant quantity of deleterious substances and pathogenic organisms.<sup>4</sup> Because of the lack of early diagnosis methods and the gaps that need to be addressed, particularly in studies conducted with animal models, the number of studies observing the effects of exosomes on the lungs and other organs is increasing. For example, pneumoconiosis, one of the world's most common occupational diseases, or silicosis, considered an occupational lung disease, is characterized by the inhalation of crystalline silica dust, inflammation, and progressive fibrosis.<sup>5</sup> On the other hand, physiological and anatomical mimicry models of the respiratory system have been proven to be essential for drug development and elucidating the pathophysiological mechanisms of diseases triggered by epigenetics and hereditary genetic factors. Lung epithelial models can be organized as monoculture/multicultural cells with supporting scaffolds such as trans-wells and bio-gels. Notably, as a novel study niche, organ-on-a-chips provide controllable physiological conditions that recapitulate tissue specific features.</p><p><strong>Material and methods: </strong>We performed a PubMed search (2000-2025) to quantify publications on occupational exposures (silica, coal dus","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"7-9"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145672508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A NAMs-Based Microphysiological System for Metastasis and Mechanobiology Studies.","authors":"Basar Dogan, Pelin Saglam-Metiner, Tuncay Goksel, Ozlem Yesil-Celiktas","doi":"10.4274/ThoracResPract.2025.s002","DOIUrl":"10.4274/ThoracResPract.2025.s002","url":null,"abstract":"<p><strong>Introduction: </strong>Lung and breast cancers are among the most common types of cancer worldwide, with approximately 2.5 million new cases occurring each year.<sup>1</sup> Lung cancer often remains asymptomatic until advanced stages, leading to delayed diagnosis and high mortality. Bone metastasis is a frequent complication of lung cancer; after breast and prostate cancers, lung cancer accounts for 30-40 % of bonemetastatic case.<sup>2</sup> As in other cancers, the tumor microenvironment (TME) plays a crucial role in the pathogenesis of lung cancer. Fibroblasts, endothelial cells, and immune cells, as well as the extracellular matrix (ECM), are the primary TME components.<sup>3</sup> The lung ECM, which consists largely of collagen, hardens under the influence of other proteins in the cancerous state, contributing to tumor prognosis.<sup>4</sup> Epithelial-mesenchymal transition (EMT) is one of the most important phenomena in the progression and metastatic process of lung cancer.<sup>5</sup> During EMT, epithelial cells lose their apical polarity, detach from the basement membrane, and transition to a mesenchymal phenotype. This initiates a cascade characterized by increased cellular invasiveness, called metastasis. EMT is triggered by signaling pathways such as TGF-β, HIF-1α, and Notch, and is generally characterized by a loss of E-cadherin and an increase in vimentin and N-cadherin.<sup>5</sup> This process enhances the ability to metastasize, particularly to distant organs such as bone. The bone microenvironment, with its rich calcium content, serves as an important signal transmitter for cancer cells. Osteoblasts, osteoclasts, bone matrix proteins, and local immune cells play a decisive role in the localization, dormancy, and reactivation of metastatic cells.<sup>6</sup> Lung-derived metastases may gain a proliferative advantage due to the high calcium concentration and growth factors in bone. Conventional 2D culture and animal models insufficiently reproduce the complex tumor-bone interactions, limiting translational progress.<sup>7,8</sup> Organ-on-a-chip models developed to evaluate therapeutic strategies mimic cell-cell and cell-matrix interactions at the physiological level through microfluidic systems.<sup>9</sup> These systems are compatible with New Approach Methodologies strategies, which include organoids, <i>in silico</i> studies, and omics technology, and offer platforms with high translational value from both ethical and scientific perspectives.<sup>10</sup> In this context, we developed a lung cancer metastasis-on-a-chip platform as a physiologically relevant <i>in vitro</i> alternative (Figure 1).</p><p><strong>Material and methods: </strong>Lung cancer metastasis-on-a-chip platform consists of two PDMS layers, where two tissue chambers represent the lung and bone compartments, and a single microchannel serve as the vascular lumen. The dual-chamber microfluidic system integrates lung cancer epithelial and stromal ","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"4-6"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of <i>Staphylococcus aureus</i> on Lung Cancer Cells.","authors":"Deniz Ece, Can Muftuoglu, Ufuk Mert, Gokhan Gurur Gokmen, Cagla Ozdenizer, Gunel Mukhtarova, Uygar Alaman, Tuncay Goksel, Ayse Caner","doi":"10.4274/ThoracResPract.2025.s009","DOIUrl":"10.4274/ThoracResPract.2025.s009","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer continues to be a leading cause of morbidity and mortality.^1,2 In addition to genetic, epigenetic, and stromal microenvironmental factors, the host microbiota, an integral part of the human body, significantly contributes to cancer development and progression.³ <i>Staphylococcus aureus</i> (<i>S. aureus</i>), a Gram-positive bacterium, is known to cause DNA damage through its toxins and may promote carcinogenesis and metastasis in various cancer types, including lung cancer.^4,5 The aim of our study was to establish a <i>S. aureus</i> infection model and investigate its molecular and cellular effects on lung cancer and normal bronchial epithelial cells.</p><p><strong>Material and methods: </strong>To establish an intracellular infection model, A549 lung cancer and BEAS-2B bronchial epithelial cell lines were infected with <i>S. aureus</i> at infection ratios of 1:25, 1:50, and 1:100 for 2 hours and treated with gentamicin for 2-4 hours to eliminate extracellular bacteria. Intracellular infection was visualized by Giemsa staining. Intracellular <i>S. aureus</i> load was determined by CFU analysis, and the infection index was calculated. The effect of <i>S. aureus</i> infection on cell cycle and cell death was analyzed using flow cytometry. Wound closure assay was performed to assess metastatic potential. Expression levels of key genes involved in cancer mechanisms were examined using reverse transcription quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>Intracellular <i>S. aureus</i> colonies were demonstrated in A549 and BEAS-2B cell lines at ratios of 1:25, 1:50, and 1:100 (Figure 1A, B). BEAS-2B cells were observed to be more infected than A549 cells (Figure 1C). According to the migration assay results, A549 cells infected with <i>S. aureus</i> showed a significant increase in migration capacity compared to the control group. This finding suggests that <i>S. aureus</i> infection increases cell migration in A549 cells. Cell cycle analysis revealed that infected A549 cells accumulated, particularly in the G2 phase, 24 h after infection. These results suggest that <i>S. aureus</i> infection differentially affects these two cell lines. Furthermore, RT-qPCR analysis revealed changes in the expression levels of genes involved in important cellular processes.</p><p><strong>Conclusion: </strong>This study demonstrates that <i>S. aureus</i> infection induces cell-type-specific responses in lung epithelial cells. BEAS-2B cells were more susceptible to colonization, while A549 cells exhibited increased migration and G2/M phase arrest, along with changes in gene expression associated with key cellular pathways. These findings suggest that <i>S. aureus</i> may contribute to pathological processes such as chronic infection or tumor progression at the cellular level.</p>","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"23-24"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered Humanoid-on-Chip Platforms: Tools for Evaluating the Effects of Environmental Exposure on Human Physiological Barriers.","authors":"Pelin Saglam-Metiner, Ozlem Goksel, Tuncay Goksel, Omer H Yilmaz, Esra Erdal, Ozlem Yesil-Celiktas","doi":"10.4274/ThoracResPract.2025.s001","DOIUrl":"10.4274/ThoracResPract.2025.s001","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Environmental pollutants; bioaerosols, chemicals and micro/nano-plastics (MNPs) can disrupt the mechano-biological processes of the human body, impairing structural, cellular, and molecular functions. Such disruptions may ultimately contribute to the onset of toxicity-associated pharmacokinetic disorders.&lt;sup&gt;1&lt;/sup&gt; Traditional &lt;i&gt;in vivo&lt;/i&gt; and 2D &lt;i&gt;in vitro&lt;/i&gt; models often fall short in accurately mimicking the complexity of human physiological responses to such environmental exposures. In response, recent advances in microfluidic organ-on-a-chip (OoC) platforms, organoid models, and induced pluripotent stem cell (iPSC) technologies have enabled the development of biomimetic, animal-free, and human-relevant &lt;i&gt;in vitro&lt;/i&gt; models. These systems increasingly replicate the molecular, structural, and functional characteristics of both healthy&lt;sup&gt;2&lt;/sup&gt; and diseased human tissues, providing powerful tools for toxicological, pharmacological, and pathophysiological research.&lt;sup&gt;3,4&lt;/sup&gt; To further enhance the predictive power of these models, multi-organ integration strategies are gaining attention particularly those emulating organ axis that are functionally and biochemically interconnected.&lt;sup&gt;5&lt;/sup&gt; Among these, the brain-lung-liver-intestine axis represents a critical multi-organ network that mediates systemic responses to external insults. For example, inhaled airborne pollutants can initiate inflammatory signaling in the lung, which may be translocated via the bloodstream to the liver and brain.&lt;sup&gt;6,7&lt;/sup&gt; Similarly, orally ingested MNPs or pharmaceuticals undergo metabolism in the intestine and liver, potentially generating bioactive metabolites that affect the central nervous system (CNS).&lt;sup&gt;5,8&lt;/sup&gt; Such complex inter-organ interactions are essential to understanding the full scope of environmental toxicity and human pathophysiology, yet are poorly captured in isolated organ models.&lt;sup&gt;5&lt;/sup&gt; Bioengineered humanoid-on-chip systems that incorporate the brain-lung-liver-intestine axis within a single fluidically linked microphysiological platform offer a novel solution. These integrated systems can simulate real-time organ-organ crosstalk under dynamic flow conditions, mimicking human circulatory, absorptive, and barrier functions with high fidelity.&lt;sup&gt;5,6,8&lt;/sup&gt; For instance, the intestine-on-chip component can model nutrient or xenobiotic absorption, followed by first-pass metabolism in the liver module,&lt;sup&gt;8&lt;/sup&gt; systemic immune or endocrine responses via the lung module,&lt;sup&gt;6&lt;/sup&gt; and downstream neuroinflammatory effects observed in the brain-on-chip compartment.&lt;sup&gt;5,7&lt;/sup&gt; Such systems also allow for the controlled exposure of specific organs to pollutants or therapeutics, enabling precise mechanistic dissection of toxicity pathways across the entire axis.&lt;sup&gt;9&lt;/sup&gt; By combining tissue-specific cellular architectures, mechanical cues (e.g., peristalsis, breathing motions), and physiologically relevant f","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"1-3"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-Scale Production and Therapeutic Evaluation of Exosomes for Cancer Treatment.","authors":"Ilgin Kimiz-Gebologlu, Suphi S Oncel","doi":"10.4274/ThoracResPract.2025.s011","DOIUrl":"10.4274/ThoracResPract.2025.s011","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Lung cancer remains one of the most prevalent and deadly malignancies worldwide, representing a major global health challenge. According to the latest global cancer statistics, lung cancer accounts for approximately 11.6% of all new cancer diagnoses and 19.8% of cancer-related deaths, making it the leading cause of cancer mortality.&lt;sup&gt;1&lt;/sup&gt; Current therapeutic strategies, including surgery, chemotherapy, radiotherapy, and targeted therapies, vary depending on the histological type and stage of the tumor. While these approaches have improved survival in select patient populations, their overall effectiveness remains unsatisfactory due to systemic toxicity, drug resistance, and tumor recurrence. Consequently, there is an urgent need to develop safer, more effective, and targeted therapeutic strategies capable of overcoming these limitations.&lt;sup&gt;2&lt;/sup&gt; Recent advances in immunotherapy and nanotechnology have transformed the landscape of cancer treatment, enabling precise modulation of tumor immunity and site-specific delivery of therapeutic agents. Among the various nanocarrier systems, such as liposomes, polymeric nanoparticles, developed to date, exosomes have attracted attention as a promising next-generation therapeutic tool for cancer diagnosis, treatment, and prognosis.&lt;sup&gt;3&lt;/sup&gt; Exosomes are naturally derived, cell-secreted nanovesicles with intrinsic biological functions. Exosomes are lipid bilayer vesicles with diameters typically ranging between 30 and 150 nm, secreted by most eukaryotic and prokaryotic cells under both physiological and pathological conditions. They are formed through the endosomal pathway and encapsulate a rich cargo of proteins, lipids, nucleic acids, and metabolites reflective of their cell of origin. Due to their endogenous origin, exosomes exhibit exceptional biocompatibility, low immunogenicity, and the ability to cross biological barriers such as the blood-brain barrier, features that confer them a distinct advantage over synthetic nanoparticles. Furthermore, their inherent role in intercellular communication allows them to mediate the transfer of bioactive molecules between cells, influencing diverse biological processes including immune regulation, angiogenesis, and metastasis.&lt;sup&gt;4,5&lt;/sup&gt; These properties position exosomes as promising candidates for both diagnostic and therapeutic applications in cancer. In recent years, the use of exosomes as liquid biopsy biomarkers for early detection of cancer has gained attention. Because exosomes can be readily isolated from non-invasive sources such as plasma, serum, or bronchoalveolar lavage fluid, they provide valuable molecular insights into tumor progression and response to therapy.&lt;sup&gt;6&lt;/sup&gt; Beyond diagnostics, exosomes also offer unique advantages as therapeutic delivery vehicles. Their natural targeting capabilities, long circulation time, and ability to encapsulate and protect therapeutic molecules such as small RNAs,","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"28-30"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Untargeted Metabolomic Profile in Breath Condensate Using LC-QTOF/MS and Investigation of Potential Lung Cancer-Specific Biomarkers.","authors":"Ebru Cakan Yildirim, Füsun Pelit, Korcan Korba, Murat Ali Salan, Tuncay Goksel, Levent Pelit","doi":"10.4274/ThoracResPract.2025.s006","DOIUrl":"10.4274/ThoracResPract.2025.s006","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Lung cancer remains the leading cause of cancer-related mortality worldwide, primarily due to late diagnosis and the lack of sensitive, non-invasive biomarkers for early detection. Conventional diagnostic methods such as imaging and biopsy are either invasive or incapable of identifying disease at its earliest stages. Therefore, there is a growing demand for analytical strategies that enable non-invasive, rapid, and reliable diagnosis of lung cancer.&lt;sup&gt;1&lt;/sup&gt; In recent years, exhaled breath condensate (EBC) has emerged as an attractive biological matrix in clinical metabolomics. EBC collection is completely non-invasive, painless, and repeatable, allowing real-time reflection of the metabolic status of the respiratory tract. It contains a variety of low-molecular-weight compounds, including volatile and non-volatile metabolites derived from airway and alveolar surfaces. Metabolomic profiling of EBC, particularly through high-resolution mass spectrometry, offers valuable insight into the biochemical alterations associated with lung cancer pathogenesis.&lt;sup&gt;2&lt;/sup&gt; Metabolomics, as a systems biology approach, enables comprehensive analysis of metabolites that serve as the final products of cellular processes. This field provides a functional readout of the physiological state and disease progression, bridging the gap between genotype and phenotype. The untargeted metabolomics approach-unlike targeted methods that focus on predefined molecules-captures the widest possible range of metabolites, making it ideal for exploratory biomarker discovery.&lt;sup&gt;3&lt;/sup&gt; The present study aimed to investigate potential lung cancer-specific biomarkers through untargeted metabolomic profiling of EBC samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Breath samples were collected from lung cancer patients and healthy controls, and data were analyzed using multivariate statistical approaches to identify significant metabolic differences between the two groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods: &lt;/strong&gt;EBC samples were collected in the morning after overnight fasting. Participants inhaled filtered air through their noses and exhaled through their mouths into a thermostat-controlled condenser system maintained at +4 °C for 15 minutes. Saliva contamination was prevented using a U-shaped glass trap. The collected condensate (approximately 2-2.5 mL) was transferred into Teflon tubes and stored at -80 °C until analysis. Metabolites were separated by LC-QTOF/MS, a high-resolution analytical platform suitable for untargeted metabolomics due to its excellent mass accuracy and sensitivity. Raw data were processed using Signpost MS software for peak alignment, normalization, and statistical comparison. Principal component analysis (PCA) and hierarchical clustering were applied to visualize group separation and identify metabolite patterns associated with lung cancer. The workflow of ","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"15-17"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSC-Exosomes as Novel Therapeutics in Asthma and Allergic Airway Inflammation.","authors":"Sevval Kurt, Ilgin Kimiz-Gebologlu, Suphi S Oncel","doi":"10.4274/ThoracResPract.2025.s013","DOIUrl":"10.4274/ThoracResPract.2025.s013","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Allergic respiratory diseases, including asthma and allergic rhinitis, are chronic inflammatory diseases that affect millions of people worldwide and constitute a significant health problem.&lt;sup&gt;1&lt;/sup&gt; These diseases are characterized by airway obstruction, mucus overproduction, eosinophilic infiltration, and airway hyperresponsiveness, which together lead to impaired respiratory function and reduced quality of life. Despite significant advances in pharmacotherapy, current treatments such as corticosteroids and bronchodilators mainly target symptom control rather than underlying immune dysregulation, often resulting in relapse or steroid resistance.&lt;sup&gt;2&lt;/sup&gt; Consequently, there is a growing need for novel, effective, and safe therapeutic strategies that address the root causes of airway inflammation rather than providing temporary relief. In recent years, extracellular vesicles, particularly exosomes (Exos), have emerged as key mediators of intercellular communication and as promising candidates for next-generation biologics. Exos are lipid bilayer nanosized vesicles (30-150 nm) secreted by almost all cell types, containing proteins, lipids, mRNAs, and microRNAs that reflect the physiological state of their parent cells.&lt;sup&gt;3&lt;/sup&gt; Their natural stability, biocompatibility, and ability to traverse biological barriers with minimal immunogenicity confer several advantages over synthetic nanocarriers. Due to their intrinsic targeting capacity and role in cell-cell signaling, Exos are increasingly explored for use in drug delivery, immune modulation, and regenerative medicine.&lt;sup&gt;4&lt;/sup&gt; Among various exosome sources, mesenchymal stem cell (MSC)-derived Exos have emerged as highly attractive candidates for cell-free therapies. MSCs are well-known for their immunoregulatory and regenerative capabilities, and their secreted Exos retain most of these biological functions. Importantly, MSC-Exos can interact with immune cells and modulate inflammatory signaling pathways, suggesting their potential as next-generation biotherapeutics in allergic airway diseases.&lt;sup&gt;5&lt;/sup&gt; The immunopathogenesis of allergic airway diseases is mainly driven by the imbalance between Th1 and Th2 immune responses, with Th2 cytokines such as interleukin (IL)-4, IL-5, and IL-13 playing central roles in eosinophilic inflammation and immunoglobulin E (IgE) production.&lt;sup&gt;6&lt;/sup&gt; MSC-Exos have been shown to mitigate these pathological processes through multiple mechanisms: attenuating Th2-dominated responses, downregulating pro-inflammatory cytokines, and promoting the expansion of regulatory T-cells (Tregs), which are crucial for maintaining immune tolerance.&lt;sup&gt;7&lt;/sup&gt; Furthermore, MSC-Exos promotes the polarization of M2 macrophages, a phenotype associated with tissue repair and resolution of inflammation. At the molecular level, Exos derived from MSCs deliver bioactive microRNAs that modulate critical signaling cascades, including NF-κB","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"34-36"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145672397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel Formulations to Investigate Lung Cancer Mechanism.","authors":"Aysel Saskara, Yagmur Arslan, Ozlem Yesil-Celiktas","doi":"10.4274/ThoracResPract.2025.s004","DOIUrl":"10.4274/ThoracResPract.2025.s004","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Lung cancer remains a leading cause of cancer-related deaths worldwide, largely due to late diagnosis and the complexity of the tumor microenvironment (TME).&lt;sup&gt;1&lt;/sup&gt; A key factor in lung cancer is the extracellular matrix (ECM), a 3D network composed of structural proteins, glycoproteins, proteoglycans, and growth factors that together regulate cell adhesion, proliferation, and signaling. ECM architecture and its changes are closely related to cancer mechanisms.&lt;sup&gt;2&lt;/sup&gt; Thus, physiological models that recapitulate ECM composition and mechanics are essential. 2D cultures fail to replicate the organization and biochemical and mechanical signals of the TME, whereas microfluidic platforms offer dynamic, 3D cell culture systems hydrogel-integrated.&lt;sup&gt;3&lt;/sup&gt; A broad range of biomaterials (synthetic, semi-synthetic, natural) is used to recapitulate the dynamics of ECM. Natural hydrogels such as collagen, gelatin methacrylate (GelMA), Matrigel, alginate, fibrin, and decellularized ECM (dECM) are widely used due to their inherent bioactivity and ability to support cell adhesion and proliferation.&lt;sup&gt;4&lt;/sup&gt; Synthetic hydrogels, such as polyethylene glycol (PEG) and polyacrylamide, provide tunable stiffness and control over matrix composition, while semi-synthetic hybrids (e.g., PEG-GelMA, GelMA-dECM) combine biological cues with structural stability (Figure 1).&lt;sup&gt;5&lt;/sup&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods: &lt;/strong&gt;Cancer cell lines A549 (adenocarcinoma), H1299 (non-small cell lung cancer), and H460 (large cell carcinoma) are frequently used in cancer modelling. Co-culture systems integrate fibroblasts, endothelial cells, and immune cells (e.g., macrophages) to simulate the TME and study cell-matrix-cell interactions. Patient-derived organoids preserve tumor heterogeneity, genetic mutations, and drug response profiles, representing a personalized &lt;i&gt;in vitro&lt;/i&gt; cancer model. Tumor spheroids embedded in hydrogels recapitulate diffusion gradients and are used to evaluate drug penetration and metastasis. Further, they can be integrated into microfluidic platforms or well plates. As a next step, it is important to investigate ECM rheology, determine mechanical structure and cytokine expression levels, and further validate cell-matrix interactions.&lt;sup&gt;6,7&lt;/sup&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;These models have shown that tumor cells embedded in hydrogels exhibit enhanced invasive behavior and increased expression of matrix metalloproteinases (enzymes responsible for ECM degradation and remodeling). From a biomechanical perspective, rheological analyses revealed that cancer-associated hydrogels typically exhibit higher storage modulus than healthy matrices, reflecting a stiffer microenvironment and increased collagen levels.&lt;sup&gt;8&lt;/sup&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Collectively, recent findings underscore the central role of the ECM and hydrogel-based systems in modeling lung cancer progression. The dev","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"10-11"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Scarcity to Survival: Adaptive Strategies of A549 Lung Cancer Cells Under Serum Starvation.","authors":"Gunel Mukhtarova, Cagla Ozdenizer, Deniz Ece, Ufuk Mert, Ayse Caner","doi":"10.4274/ThoracResPract.2025.s008","DOIUrl":"10.4274/ThoracResPract.2025.s008","url":null,"abstract":"<p><strong>Introduction: </strong>Serum plays a critical role in regulating fundamental biological processes, and variations in serum levels can directly influence tumor cell metabolic adaptations, stress responses, and traits associated with tumor progression. The lung adenocarcinoma cell line A549 serves as a widely used <i>in vitro</i> model for studying these mechanisms. This study aims to investigate how short- and long-term exposure to different serum concentrations affects A549 cell morphology, proliferation, migration, cell cycle dynamics, gene expression profiles, three-dimensional spheroid formation capacity, and molecular features related to stemness, metastatic potential, and drug resistance. Serum availability is a key determinant of tumor cell behavior, influencing proliferation, differentiation, and survival, while nutrient deprivation triggers adaptive mechanisms that enable cancer cells to endure stress conditions.^1,2.</p><p><strong>Material and methods: </strong>A549 cells were cultured under different serum concentrations [1%, 10%, and 20% fetal bovine serum (FBS)], with cells maintained in 10% FBS serving as the control group. To evaluate the effects of serum availability on cellular behavior, various assays were performed, including Giemsa staining for morphology, wound healing assay for migration, flow cytometric analysis of CD44 and CD133 for stemness, XTT assay with flavopiridol for drug resistance, colony formation assay for clonogenic capacity, three-dimensional spheroid formation assay, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) for gene expression profiling.</p><p><strong>Results: </strong>Significant differences in proliferation and morphology were observed in A549 cells depending on serum concentration. Cell cycle analyses showed that exposure to different serum concentrations caused significant changes in phase distribution. RT-qPCR results revealed significant expression differences in specific genes associated with cellular stress response and proliferation. These findings contribute to elucidating adaptive response mechanisms of tumor cells to nutritional conditions and provide an important approach for the development of <i>in vitro</i> tumor biology models.</p><p><strong>Conclusion: </strong>Serum deprivation triggers complex adaptive responses in A549 cells, influencing morphology, migration, stemness, drug sensitivity, and gene expression. Low-serum conditions promoted stress-adaptive and survival phenotypes relevant for modeling tumor microenvironments. These findings suggest that serum availability is a crucial determinant of cancer cell plasticity and behavior. Moreover, long-term adaptation to serum limitation may mimic the nutrient-restricted conditions of solid tumors, providing a valuable <i>in vitro</i> model for studying metabolic flexibility and therapy resistance mechanisms in lung cancer cells.</p>","PeriodicalId":75221,"journal":{"name":"Thoracic research and practice","volume":"26 Suppl 1","pages":"21-22"},"PeriodicalIF":0.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}