The transient receptor potential (TRP) channels regulate physiological and pathological processes. Changes in their activity and sensitivity may be involved in the pathophysiology of asthma. The present study investigates the effect of an inhaled TRPV4 channel blocker HC-067047 in an experimental guinea pig model of ovalbumin-induced allergic asthma. We monitored the effect of 50 nM, 100 nM, and 150 nM HC-067047 concentrations on airway defense reflexes in vivo and tracheal smooth muscle contractility in vitro. The anti-inflammatory action of HC-067047 was investigated by analysis of chronic inflammation markers from lung homogenates. The results suggest that HC-067047 can suppress airway defense reflexes in vivo and acetylcholine-induced contractility in vitro. Immunological analysis revealed that TRPV4 channel blockade leads to a decrease in the levels of inflammatory cytokines. An effect on airway defence reflexes and airway inflammation was observed using tested concentrations (50 mM, 100 mM, 150 mM) of HC-067047. The effects of HC-067047 on both airway defense reflexes and inflammation underline the role of TRPV4 channels in asthma and uncover therapeutic targets for developing innovative drugs in asthma therapy.

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Calcium (Ca²⁺)-activated chloride (Cl^-) channels, such as TMEM16A, are inferred to be involved in asthma. Therefore, the present study investigated the therapeutic potential of TMEM16A inhibition in a guinea pig model of ovalbumin (OVA)-induced allergic asthma. Guinea pigs were treated with a specific blocker, CaCCinh-A01 (10 μM), administered via inhalation. A significant reduction in cough reflex sensitivity and specific airway resistance was observed in animals treated with CaCCinh-A01, highlighting its potential to improve airway function. Despite a reduction in ciliary beating frequency (CBF), CaCCinh-A01 reduced airway mucus viscosity by decreasing the production of mucin-5AC (MUC5AC). The nonspecific reduction in the Th1/Th2 cytokine spectrum following CaCCinh-A01 treatment indicated the suppression of airway inflammation. Additionally, markers associated with airway remodeling were diminished, suggesting that CaCCinh-A01 may counteract structural changes in airway tissues. Therefore, inhibition appears to mitigate the pathological aspects of asthma, including airway hyperresponsiveness, inflammation, and remodeling. However, further studies are required to comprehensively evaluate the potential of TMEM16A as a therapeutic target for asthma.

Wild fruits are distributed worldwide, but are consumed mainly in developing countries, where they are an important part of the diet. Still, in many other countries, they are consumed only locally. Blackthorn (Prunus spinosa L.) is an underutilized species rich in fibres and phenolic compounds, making it suitable as a potential functional food for supporting human health. Cold (Cw) and hot (Hw) water-extracted (poly)phenolic polysaccharide–protein complexes, differing in carbohydrate, phenolic and protein contents, were isolated from blackthorn fruits and characterized. The complexes exhibited molecular weights of 235,200 g/mol (Cw) and 218,400 g/mol (Hw), and were rich in pectic polymers containing galacturonic acid, arabinose, galactose and rhamnose, indicating a dominance of homogalacturonan (HG) [→4)-α-D-GalA(1→4)-α-D-GalA(1→]n and a low content of RGI [→2)-α-L-Rha(1→4)-α-D-GalA(1→2)-α-L-Rha(1→]n sequences associated with arabinan or arabinogalactan. Minor content of glucan, probably starch-derived, was also solubilized. Pectic polysaccharides were highly esterified and partly acetylated. Pharmacological testing was performed in male Dunkin–Hartley guinea pigs, a model with human-like airway reflexes. Both complexes affected airway defense mechanisms. Particularly, Hw significantly suppressed citric acid-induced cough, similar to codeine, and reduced bronchoconstriction comparably to salbutamol in a dose-dependent manner. These findings support further exploration of Hw as a natural antitussive and bronchodilatory agent.

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.

Background: The family of calcium-activated chloride channels, TMEM16, plays a significant role in contributing to the pathogenesis of airway inflammatory diseases. Targeting these ion channels and aiming to modulate them may provide an interesting new approach to the therapy of these potentially fatal diseases. Methods: We tested this hypothesis in both healthy and ovalbumin (OVA)-sensitized male Dunkin-Hartley guinea pigs. The ion channel activity was modulated by TMEM16A-nonselective (benzbromarone) and TMEM16A-selective blockers (CaCCinh-A01). In vivo airway reactivity, induced by histamine and methacholine, was expressed as specific airway resistance (sRaw) values. The number of citric acid-induced coughs was counted using a double-chambered body plethysmograph, and the frequency of ciliary beating (CBF) was assessed in vitro by brushing method. For comparison, salbutamol and codeine were tested under the same conditions. Results: The results showed significant differences in the responses of unsensitized and sensitized airways to both TMEM16 blockers administered. CaCCinh-A01 and benzbromarone significantly reduced the number of cough efforts in the group of OVA-sensitized guinea pigs. Significant improvement in sRaw values could be observed in OVA-sensitized TMEM16 blocker–treated animals compared to salbutamol when challenged with inhalational histamine, and the outcome was similar to salbutamol when challenged with methacholine. CBF was significantly inhibited in animals sensitized to OVA treated with selective inhibition of TMEM16A. Conclusions: The results demonstrated that treatment with blockers of TMEM16 can reduce both cough effort and sRaw, and the difference between TMEM16A-selective and TMEM16A-nonselective blocking is only negligibly in favor of CaCCinh-A01. It is also worthwhile to note the impairment of CBF in OVA-sensitized animals treated with CaCCinh-A01.