In chronic obstructive pulmonary disease (COPD), dysregulated calcium homeostasis, oxidative stress, and mucus hypersecretion converge to suppress ciliary beat frequency (CBF), thereby compromising mucociliary clearance (MCC). These mechanisms are subject to pharmacological modulation. Long-acting muscarinic antagonists (LAMAs) exert direct cilia-stimulatory effects and may counteract pathogen-induced mucin overproduction without impairing clearance. Long-acting β₂-agonists (LABAs) enhance ciliary activity through the cAMP–PKA–dynein (cyclic adenosine monophosphate–protein kinase A–dynein) signalling pathway. Inhaled corticosteroids (ICSs), although largely neutral on CBF, provide indirect protection by suppressing IL-13–driven inflammation. Phosphodiesterase (PDE)-4 inhibitors sustain intracellular cAMP and promote ciliary motility, though their clinical use remains limited by adverse effects. Emerging evidence suggests that dual and triple therapies may provide additive or synergistic benefits for preserving mucociliary function. Clinically, ex vivo CBF interpretation may be influenced by ongoing pharmacotherapy and tissue sampling site. Nasal brush samples may predominantly reflect systemic rather than inhaled therapy. Moreover, differences in PDE isoform expression between nasal and bronchial epithelium further complicate direct extrapolation of results. Rigorous patient stratification by treatment regimen is therefore essential to reconcile inconsistencies reported across studies. Ultimately, preservation of MCC in COPD depends on a delicate balance between oxidative stress and pharmacological modulation of ciliary function.

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most prevalent and biologically aggressive subtype of renal cell carcinoma, characterized by pronounced immunogenicity and extensive remodeling of the tumor microenvironment. Chronic inflammation and dysregulated cytokine signaling contribute substantially to tumor progression. Signal transducer and activator of transcription 3 (STAT3) represents a central molecular hub integrating cytokine- and hypoxia-driven pathways. This review aims to summarize current evidence on the cytokine–STAT3 signaling axis in ccRCC and to evaluate its translational relevance for biomarker development. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science databases. Experimental, translational, and clinical studies addressing cytokine signaling, STAT3 activation, tumor microenvironment interactions, and biomarker development in ccRCC were evaluated. Particular attention was given to studies analyzing cytokine profiles in tumor tissue, plasma, and urine, as well as their associations with STAT3 activation and clinicopathological parameters. Results: Accumulating evidence indicates that ccRCC exhibits a complex, compartment-specific cytokine signature involving interleukins, chemokines, and tumor necrosis factor (TNF)-related cytokines. Among these mediators, IL-6, IL-8, and selected chemokines such as CXCL10 appear particularly relevant due to their associations with tumor progression, immune modulation, and clinical outcome. Many of these mediators converge on persistent STAT3 activation, which promotes tumor cell survival, angiogenesis, immune suppression, and metastatic potential. Tissue-based analyses demonstrate correlations between altered cytokine expression and STAT3 activation, while urinary cytokine profiles reflect tumor-associated inflammatory processes in a non-invasive manner. Plasma cytokines appear to capture broader systemic inflammatory responses. Conclusions: The cytokine–STAT3 axis represents a biologically plausible signaling network associated with tumor progression and immune modulation in ccRCC. By integrating evidence from cytokine profiling in tumor tissue, plasma, and urine with current knowledge of STAT3 signaling, this review highlights the importance of compartment-specific inflammatory signatures in understanding ccRCC biology and their potential relevance for biomarker discovery. Integrative approaches combining cytokine profiling with functional assessment of STAT3 activation may improve disease characterization and support the development of diagnostic and prognostic biomarkers, although rigorous clinical validation remains necessary.

Allergic airway diseases, including allergic asthma, involve a complex interplay between inflammation and structural remodeling, leading to impaired airway function. The p38 mitogen-activated protein kinase (p38 MAPK) pathway is a key regulator of inflammatory signaling; however, its role in airway function and remodeling remains incompletely understood. This study investigated the effects of the p38 MAPK inhibitor doramapimod in an ovalbumin-induced guinea pig model of allergic airway inflammation. Doramapimod (1 and 3 mg/kg, intraperitoneally) significantly attenuated airway hyperresponsiveness, reduced cough responses, and increased tracheal ciliary beat frequency. Treatment also reduced levels of selected type 2-associated cytokines, including interleukin-4, interleukin-5, interleukin-13, as well as interferon gamma. In addition, doramapimod reduced inflammatory cell infiltration, decreased the number of MUC5AC-positive epithelial cells, and reduced collagen deposition. Collagen type III levels were reduced, whereas transforming growth factor beta 1 levels remained unchanged. Notably, doramapimod did not affect histamine- or carbachol-induced contractile responses in isolated tracheal rings obtained from healthy guinea pigs. These findings demonstrate that treatment with doramapimod, a p38 MAPK inhibitor, attenuates airway inflammation and remodeling while improving functional features of allergic airway disease. Together, these results support further investigation of p38 MAPK inhibition as a potential therapeutic strategy for allergic airway disease.