Klebsiella pneumoniae has emerged as a leading cause of pyogenic liver abscess (PLA), driven by hypervirulent and multidrug‑resistant (MDR) strains that pose major diagnostic and therapeutic challenges. This organism exhibits extensive capsular diversity (K1‑K80), with serotypes K1, K2, K5, K20, K54 and K57 being the most associated with invasive infections and severe clinical outcomes. Increasing convergence between hypervirulence and MDR determinants threatens effective management worldwide. Pharmacological and safety limitations of current antibiotics, including nephrotoxicity of colistin, hepatotoxicity of tigecycline and poor drug penetration into abscess cavities, further complicate treatment and encourage exploration of non‑traditional strategies such as anti‑virulence or immunomodulatory approaches. Recent advancements in rapid diagnostic tools such as metagenomic sequencing, MALDI‑TOF and point‑of‑care PCR assays offer promising prospects for early detection and antimicrobial optimization. Pharmacokinetic challenges at the abscess site and the emergence of hybrid hvKp‑MDR strains emphasize the urgency of precision‑guided therapy and robust global surveillance. K. pneumoniae‑associated PLA thus represents an evolving global health threat and understanding serotype diversity, antibiotic limitations and diagnostic innovations is essential for developing more effective preventive and therapeutic strategies. The present review provides current insights into the epidemiology, pathogenesis and therapeutic challenges of K. pneumoniae‑associated PLA, while highlighting translational opportunities and research priorities to counter the escalating dual threat of hypervirulence and resistance. .

Cigarette smoking is a major driver of airway and systemic inflammation and contributes to the development and progression of chronic obstructive pulmonary disease (COPD). This study compared peripheral blood inflammatory markers and immune cell profiles in smokers with and without COPD and in non-smoking controls. In this cross-sectional study, blood samples were collected from 80 participants (n = 20/group): non-smoker controls (NS), smokers with normal lung function (NLFS), current smokers with COPD (COPD-CS), and ex-smokers with COPD (COPD-ES). Total white cell count (WCC) and leukocyte differentials (neutrophils, lymphocytes, monocytes, eosinophils) were measured using an automated haematology analyser (Sysmex XN2000). Systemic inflammatory markers were measured using C-reactive protein (CRP, Roche Cobas Pro) and erythrocyte sedimentation rate (ESR, Diesse VES-MATIC Easy). Lung function parameters (including FEV1, FVC, DLco, FEF25–75

Early airflow changes associated with tobacco smoking often occur without observable obstruction or symptoms. Spirometry, the gold standard, has limitations in detecting early disease highlighting the need for sensitive diagnostic methods. We aimed to evaluate the utility of the forced oscillation technique (FOT) and biomarkers in detecting early airway abnormalities in smokers and patients with chronic obstructive pulmonary disease (COPD), and to explore the correlation between FOT parameters, spirometry measures, and biomarkers of airway inflammation. A cross-sectional study was conducted on 71 participants divided into three groups: patients with COPD (CP, n = 27), normal lung function smokers (NS, n = 22), and healthy controls (HC, n = 22). Lung function was assessed using spirometry and FOT, with biomarkers of inflammation (MMP-9, TIMP-1, and TIMP-2) measured from venous blood samples. Statistical analyses included group comparisons and correlation between lung function parameters and biomarker levels. Patients with COPD had significantly lower spirometry and higher FOT values compared with NS and HC (P < 0.01). In contrast, NS participants had similar spirometry values to HC, except for FEF25-75% and peak expiratory flow (PEF). The NS group exhibited significantly higher values for R5 compared with HC (P < 0.05). FOT parameters, particularly R5, demonstrated comparable diagnostic accuracy with spirometry in smokers, and all other parameters showed excellent discriminatory ability in patients with COPD. MMP-9 correlated positively with percentage predicted FOT parameters, R5-R20 and AX, and X5 (r' = 0.29, 0.30, and 0.31; P = 0.02, 0.04, and 0.02, respectively) in the combined group of smokers and patients with COPD and positively with percentage predicted Fres (r' = 0.30; P = 0.01) when all groups were analyzed together. FOT may be a sensitive and complementary measure to detect early airway changes in smokers and patients with COPD. MMP-9 correlating with FOT further supports the role of FOT combined with biomarkers in detecting early airway abnormalities in smokers and earlier stages of COPD.NEW & NOTEWORTHY This study highlights the utility of the forced oscillation technique (FOT) and biomarkers in detecting early airway changes in smokers and patients with COPD. FOT, along with biomarkers for airway remodeling can provide a sensitive measure and insight into early airway dysfunction, complementing traditional spirometry. These findings underscore the importance of early detection of airway abnormalities and the potential of FOT as a clinical tool for managing at-risk populations.

INTRODUCTION:COPD is a progressive respiratory condition marked by persistent airflow limitation and chronic inflammation, mainly caused by cigarette smoking. Although current inhaled therapies improve symptoms and reduce exacerbations, they do not substantially modify disease progression, emphasizing the need for novel therapeutic approaches. AREAS COVERED:This review provides a comprehensive overview of the effectiveness and mechanisms of biologic therapies in the management of COPD. We discuss the mechanistic rationale, clinical efficacy, and limitations of currently approved and emerging biologics, highlighting their relevance to distinct inflammatory endotypes of COPD. The role of small-airway disease in COPD is highlighted, together with advances in drug formulation and inhaled delivery technologies. Challenges related to drug delivery, particularly the influence of particle size on distal airway deposition, are examined, along with recent innovations in nanotechnology and comparative considerations of systemic versus inhaled therapeutic approaches. Relevant literature was identified through searches of PubMed (MEDLINE), Embase, Web of Science, and Google Scholar. Studies available in print or online up to June 2025 were considered. EXPERT OPINION:Biologic therapies offer promise for selected COPD phenotypes; however, their long-term impact will depend on precision medicine, optimized airway-targeted delivery, and integration with established inhaled treatments to achieve meaningful disease modification.

Abstract Pulmonary vascular remodelling is common in patients with chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factors (VEGFs) are key mediators in angiogenesis and vascular remodelling and exist in different isoforms. VEGF-A is the most potent angiogenic member binding to VEGF receptor 2 (VEGFR2). There are, however, few studies on other isoforms, as VEGF-C, and its receptor VEGFR3 in COPD and subsequent impact of cAMP therapies on VEGF isoforms. Our aim was to evaluate the VEGF isoform synthesis in primary distal lung fibroblasts from control subjects (non-smokers (n=6) and ex-smokers (n=4), and COPD subjects with GOLD stage II (n=4) or GOLD stage IV (n=6), and the expression of VEGFR2 and VEGFR3 in human lung tissue. Primary lung fibroblasts were exposed to the cAMP generating therapies formoterol, iloprost, or roflumilast, the adenylyl cyclase activator forskolin or to transforming growth factor (TGF)-b1. VEGF isoforms were evaluated with ELISA. VEGF-C release was not significantly altered by TGF-β1, in contrast to the increased levels of VEGF-A, in all fibroblasts. VEGF-C was significantly decreased by iloprost, forskolin and formoterol, whereas VEGF-A was significantly increased by iloprost and forskolin, with differences in release pattern between and within fibroblasts from control and COPD subjects. Exposure to VEGF-C specifically towards VEGFR3 decreased proliferative rate in human lung fibroblasts and bronchial epithelial cells. VEGFR2 and VEGFR3 were both present in parenchymal lung tissue and VEGFR2 in pulmonary blood vessels. in both healthy and COPD, whereas there was elevated expression of VEGFR3 in bronchial epithelium. In conclusion, TGF-β1 and cAMP generating compounds have significant effects on VEGF-C and VEGF-A synthesis, which appear dysregulated in lung fibroblasts from ex-smokers and patients with COPD. Increased VEGFR3 expression in the bronchial epithelium in lung tissue, and studies into their functional impact, warrants further investigations.

Mitotic regulators play an essential role in cell cycle progression by ensuring correct chromosomal alignment, segregation, DNA replication, repair, and division, thereby maintaining genomic stability. Aberrant activity of cell cycle kinases, including aurora kinase B (AURKB) and cyclin-dependent kinase 1 (CDK1), might lead to disrupted mitotic checkpoints, causing aneuploidies and uncontrolled proliferation, which are critical hallmarks of cancers. Targeted inhibition of cell cycle kinases is an attractive strategy to combat cancers with minimal side effects. This study employed a comprehensive multi-staged computational approach to discover dual-targeting inhibitors against AURKB and CDK1, which are reported as key promoters of tumorigenesis. High-throughput screening of phytochemicals available in the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database was conducted to identify common lead/s from top hits. Jervine (IMPHY000366), a steroid alkaloid, emerged as a common compound depicting high binding affinity and ligand efficiency for AURKB and CDK1. In addition, this compound qualified all drug-like filters. After structure analysis, the docked complex was subjected to 300 ns MD simulation studies, confirming structural integrity in AURKB and CDK1 upon binding of Jervine. H-bonding pattern, secondary structural content, free energy landscape, and principal component analysis further supported Jervine’s strong and stable affinity for AURKB and CDK1. Lastly, MMPBSA showed a higher negative free energy in the presence of Jervine than VX-680 when complexed with AURKB. Finally, our results suggest that Jervine is a potent, dual-targeting kinase inhibitor with favourable pharmacokinetic and therapeutic properties, warranting further experimental validation for anticancer drug development.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality globally, driven by marked molecular and cellular heterogeneity that complicates diagnosis and treatment. Despite advances in targeted therapies and immunotherapies, treatment resistance frequently emerges, and clinical benefits remain limited to specific molecular subtypes. To improve early detection and dynamic monitoring, novel diagnostic strategies—including liquid biopsy, low-dose computed tomography scans (CT) with radiomic analysis, and AI-integrated multi-modal platforms—are under active investigation. Non-invasive sampling of exhaled breath, saliva, and sputum, and high-throughput profiling of peripheral T-cell receptors and immune signatures offer promising, patient-friendly biomarker sources. In parallel, multi-omic technologies such as single-cell sequencing, spatial transcriptomics, and proteomics are providing granular insights into tumor evolution and immune interactions. The integration of these data with real-world clinical evidence and machine learning is refining predictive models and enabling more adaptive treatment strategies. Emerging therapeutic modalities—including antibody–drug conjugates, bispecific antibodies, and cancer vaccines—further expand the therapeutic landscape. This review synthesizes recent advances in NSCLC diagnostics and treatment, outlines key challenges, and highlights future directions to improve long-term outcomes. These advancements collectively improve personalized and effective management of NSCLC, offering hope for better-quality survival. Continued research and integration of cutting-edge technologies will be crucial to overcoming current challenges and achieving long-term clinical success.

Sphingosine kinase 1 (SphK1) is an essential enzyme in sphingolipid metabolism, catalyzing the phosphorylation of sphingosine to produce sphingosine-1-phosphate (S1P), a bioactive lipid with diverse roles in cell proliferation, survival, and migration. Dysregulation of the SphK1/S1P axis is implicated in a variety of pathological conditions, including inflammatory, metabolic, and neurodegenerative diseases. Targeting SphK1 represents a promising therapeutic strategy, particularly in oncology and inflammation-related pathologies. In this study, we investigated the potential of three natural compounds, Baicalin (BA), Naringenin (NR), and Noscapine (NS) as SphK1 inhibitors. Through combined molecular docking, molecular dynamics simulations, binding studies and enzyme inhibition assays, we identified these compounds as effective SphK1 inhibitors. BA, NR, and NS exhibited binding affinities characterized by IC50 values of 26.542, 32.157, and 28.134 μM, respectively. These molecules bind to the active site of SphK1 with favorable binding energies with strong non-covalent interactions. This study provides structural and functional insights into potential of BA, NR, and NS to target SphK1 selectively, which can function as lead compounds for developing novel anti-cancer therapy with minimal off-target effects, offering avenues for developing drugs with enhanced specificity and affinity for this enzyme.

Background: Genome sequencing is transforming infectious-disease diagnostics, surveillance, and precision therapy by enabling rapid, high-resolution pathogen identification, transmission tracking, and genomic-informed antimicrobial stewardship. Methods: We review contemporary sequencing platforms (short- and long-read), targeted and metagenomic approaches, and operational workflows that connect laboratory outputs to clinical and public health decision-making. We highlight strengths and limitations of genomic AMR prediction, the role of plasmids and mobile elements in resistance and virulence, and practical steps for clinical translation, including validation, reporting standards, and integration with electronic health records. Results: Comparative and population genomics reveal virulence determinants and host–pathogen interactions that correlate with clinical outcomes, improving risk stratification for high-risk infections. Integrating sequencing with epidemiological and clinical metadata enhances surveillance, uncovers cryptic transmission pathways, and supports infection control policies. Despite these advances, clinical implementation faces technical and interpretative barriers, as well as challenges related to turnaround time, data quality, bioinformatic complexity, cost, and ethical considerations. These issues must be addressed to realize routine, point-of-care sequencing. Conclusions: Emerging solutions, including portable sequencing devices, standardized pipelines, and machine-learning models, promise faster, more actionable results and tighter integration with electronic health records. The widespread adoption of sequencing in clinical workflows has the potential to shift infectious disease management toward precision medicine, thereby improving diagnostics, treatment selection, and public health responses.

The WHO recently published a Tobacco Knowledge Summary (TKS) which is prepared with the objective to summarize the current evidence on the association between tobacco use and asthma. This is also intended as an advocacy tool to widely include health care professionals in the fight for tobacco control and prevention of tobacco related adverse health effects. This article expands on the evidence outlined in the TKS, providing a more comprehensive and clinically focused analysis, aimed at lung-specialist audience. It emphasizes six key messages aimed at guiding healthcare providers and governments in advocating for the health of people living with asthma and the broader population: (1) Babies born to mothers who smoke have smaller lungs and an increased risk of developing asthma during childhood. Pregnant women should receive targeted support to quit tobacco use. (2) Children exposed to second-hand tobacco smoke have an increased risk of developing asthma. (3) Smoking during adolescence and adulthood increases the risk of developing asthma and exacerbates the condition, as well as causing other lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. (4) For people living with asthma, smoking worsens symptoms and can make treatment with medications less effective. All smokers with asthma should be supported to quit smoking. (5) E-cigarettes, heated tobacco products and other nicotine-delivery devices likely also carry risks. Governments should implement effective tobacco control measures to protect all individuals, including those who are vulnerable. (6) The tobacco and nicotine industries’ aggressive tactics in the marketing of their products specifically target children, adolescents and young adults. Protecting youth from these harmful tactics is a top priority.

INTRODUCTION:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by distorted alveolar structure and reduced lung compliance, and impaired ventilation-perfusion. Small airway disease (SAD) is  often termed a 'quietzone' due to its asymptomatic nature. Around 30-40% of IPF patients exhibit SAD, which is associated with worse prognosis, higher fibrosis and emphysema scores, and elevated mortality risk. We used PubMed and Google Scholar for literature search. AREAS COVERED:This review explores the pathophysiology of small airways in IPF, focusing on 1. Risk factors, including age, gender, smoking and occupational dust exposure, and ozone. 2. Diagnostic challenges: SAD is difficult to detect through traditional spirometry or high-resolution computed tomography  imaging due to resolution limitations.  3. Early physiological changes of small airways include airway wall thickening, lumen distortion, and reduced terminal bronchioles, preceding microscopic fibrosis, occurs in the early process of IPF. 4. Pathological mechanisms: The review examines the underlying mechanisms driving small airway disease in IPF. EXPERT OPINION:A comprehensive approach is essential to improve the understanding and management of SAD in IPF. Priorities include identifying therapeutic targets, advanced imaging and functional assessments. Forced oscillation technique should be introduced for early detection for small airway abnormalities in IPF.

Introduction:Asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is a term used to describe a patient with coexisting clinical features of asthma and COPD. We have previously reported that epithelial to mesenchymal transition (EMT) is active in the lungs of patients with COPD however, EMT in ACO remains an unexplored area. We hypothesize that EMT is an active process in ACO. Methods:In this cross-sectional study, large airway endobronchial biopsy (EBB) tissues from patients with asthma (14), COPD (22), current (CS) and ex-smokers (ES), and ACO (12) were immunohistochemically stained for EMT markers (E and N cadherin, vimentin, S100A4, and Collagen IV) and compared with 12 current smokers with normal lung function (NLFS) and 10 non-smoking healthy control (HC) subjects. In addition, air-liquid interface (ALI) cell cultures were performed and cells from patients with ACO and HC were treated with TGF-β, IL-13 and cigarette smoke extract (CSE). Later cells from ALI cultures were lysed for Immunoblotting. Immunostained tissues were enumerated for percent expression of E and N-Cadherin in the epithelium, vimentin and S100A4 positive cells both in the epithelium and reticular basement membrane (RBM). Additionally, the degree of RBM fragmentation was evaluated, a key tissue structural marker of EMT. Results:Compared to healthy controls and asthmatics, ACO had the greatest fragmentation of RBM (P < 0.01). ACO also had substantially decreased percentage expression of E-cadherin (P <0.01), increase percentage of N-cadherin expression, and higher vimentin and S100A4 positive basal cells, in comparison to healthy controls. In the RBM of ACO, S100A4 positive cells (P <0.05) and Vimentin-positive cells were markedly higher in comparison to HC. Similar changes were observed with western blots in response to Th-2 cytokine IL-13, CSE and EMT activator TGF-β. Conclusions:These data are suggestive of active EMT in ACO. Additionally, 50% of the patients with ACO were on 800 mcg/day inhaled corticosteroid (ICS) treatment which may have abrogated some EMT activity; however, it suggests protective effects of ICS as we previously reported in COPD. Studies with larger cohorts are needed to further confirm ICS effects in ACO.

The WHO recently published a Tobacco Knowledge Summary (TKS) synthesizing current evidence on tobacco and COPD, aiming to raise awareness among a broad audience of health care professionals. Furthermore, it can be used as an advocacy tool in the fight for tobacco control and prevention of tobacco-related disease. This article builds on the evidence presented in the TKS, with a greater level of detail intended for a lung-specialist audience. Pulmonologists have a vital role to play in advocating for the health of their patients and the wider population by sharing five key messages: (1) Smoking is the leading cause of COPD in high-income countries, contributing to approximately 70