Chronic obstructive pulmonary disease (COPD) is a systemic condition with significant extrapulmonary comorbidities. White adipose tissue (WAT) dysfunction, driven by cigarette smoke (CS) exposure, may contribute to systemic inflammation and disease progression. This study investigates whether oxidative stress mediates lung–adipose tissue cross-talk in COPD and whether targeting this pathway can mitigate both pulmonary and metabolic dysfunction. Male BALB/c mice were exposed to CS for 8 or 24 weeks, with or without apocynin, an NADPH oxidase inhibitor. Lung and WAT tissues were analysed for inflammation, oxidative stress, adipokine expression, and mitochondrial function. Phosphoproteomic profiling was performed on lung tissue. In vitro, conditioned media from CS-exposed bronchial epithelial cells and oxidatively primed adipocytes were used to assess reciprocal effects on adipocytes and epithelial cells. CS exposure induced airway inflammation, glucose intolerance, dyslipidaemia, and WAT dysfunction, including increased lipolysis, oxidative stress, and adipokine imbalance. Apocynin treatment reduced oxidative stress, normalised adipokine profiles, and restored mitochondrial markers in WAT. Phosphoproteomic analysis revealed activation of MAPK, TNF, and Apelin signalling pathways in the lungs. Conditioned media experiments confirmed bidirectional cross-talk: epithelial-derived factors impaired adipocyte function, while dysfunctional adipocytes triggered oxidative stress and apoptosis in bronchial epithelial cells.CS-induced oxidative stress drives a pathological feedback loop between the lungs and WAT, contributing to COPD progression and systemic metabolic dysfunction. Targeting redox-sensitive pathways may offer therapeutic strategies to disrupt this lung-adipose axis and improve outcomes in COPD.

Usutu virus is an emerging mosquito-borne flavivirus with an expanding geographic distribution and increasing public health relevance, yet no licensed vaccine is currently available. This study used an integrated reverse vaccinology strategy to identify conserved immunogenic regions from the Envelope protein and NS5 protein, and construct a multi-epitope vaccine. Following sequential computational screening, the retained T-cell and B-cell epitopes satisfied the predefined selection criteria, while selected T-cell epitopes achieved an estimated 96.41% global population coverage. The final vaccine consisted of 240 amino acids and incorporated an adjuvant together with peptide linkers. Computational characterization indicated favorable physicochemical features and a refined three-dimensional model with improved stereochemical characteristics. Receptor-binding analyses predicted favorable interactions with TLR2 and TLR4, producing weighted docking scores of −1326.1 and −1230.2, respectively. Molecular dynamics simulation further characterized the temporal behavior of the vaccine–TLR2 complex, while MM-GBSA analysis yielded an estimated binding energy of −74.78 kcal/mol. C-ImmSim predicted enhanced humoral and cellular immune-response patterns following repeated antigen administration, including increased simulated antibody levels and changes in immune-cell populations. All findings in this study are based on in silico analyses and represent computational predictions rather than experimentally confirmed results. Further experimental validation is required to verify the predicted properties, immunogenicity, and protective potential of the proposed vaccine candidate.

MARK4 is a serine/threonine kinase implicated in neurodegenerative disorders and cancer, making it an attractive target for therapeutic intervention and drug repurposing. In this study, we investigated the inhibition and interaction of ibuprofen with MARK4 using an integrated experimental and computational approach employing steady-state fluorescence and UV-vis spectroscopy, circular dichroism, molecular docking, and molecular dynamics simulations. The ATPase assays showed that ibuprofen produces dose-dependent inhibition of MARK4 ATPase activity. The ATPase activity of MARK4 was inhibited by >93% with an IC₅₀ of 4.02 ± 0.33 µM. The fluorescence titrations demonstrated quenching of MARK4 intrinsic fluorescence upon addition of ibuprofen. The thermodynamic analysis indicated spontaneous binding with favorable entropy and involvement of hydrophobic forces in the binding. The observed reduction in ellipticity suggests alterations in the secondary structure of MARK4 upon ibuprofen binding. The binding energy from docking was obtained as −7.0 kcal/mol. Ibuprofen was docked within the ATP or inhibitor binding site, with two hydrogen bonds. MD simulations confirmed the dynamic stability of the MARK4–ibuprofen complex over 100 ns. The complex retained overall compactness, with nominal increases in RMSD and RMSF relative to the apo protein. The findings demonstrate the potential of ibuprofen to inhibit MARK4 ATPase activity, which may further guide drug discovery.

Pulmonary rehabilitation (PR) improves exercise tolerance and dyspnoea in chronic obstructive pulmonary disease (COPD) but does not address the elevated cardiovascular disease (CVD) risk. Vascular dysfunction, an early CVD feature, is driven by oxidative stress—a shared pathogenic mechanism in COPD and CVD. Carnosine, a bioactive dipeptide with antioxidant and pH-buffering properties, may enhance muscle performance and protect against vascular injury. The present study sought to determine whether carnosine supplementation combined with exercise training could modify early CVD features in a preclinical COPD model. Male BALB/c mice were exposed to room air or cigarette smoke (CS; 9 cigarettes/day, 5 days/week, 8 weeks) with or without carnosine (1 mg/ml in drinking water) and with or without treadmill exercise training (50% maximal speed; 30 min/day, 5 days/week). After 8 weeks, blood pressure, exercise capacity, resting heart rate, lung inflammation, systemic oxidative stress, aortic endothelial function, and platelet activation were assessed. CS impaired weight gain, reduced exercise capacity, elevated resting heart rate, and induced airway inflammation (P <0.0001). CS also caused severe endothelial dysfunction and platelet activation (P <0.0001). Exercise alone did not reverse these vascular abnormalities. In contrast, carnosine plus exercise restored weight gain, exercise capacity, and heart rate; preserved endothelial function; and prevented platelet adhesion and activation, without altering airway inflammation. Exercise training alone is insufficient to counteract CS-induced vascular injury. Carnosine supplementation provides synergistic vascular protection, highlighting its potential as an adjunct to PR to mitigate oxidative stress-driven CVD risk in COPD.