Respir Res. 2025 Mar 26;26(1):115. doi: 10.1186/s12931-025-03185-x.

ABSTRACT

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of global mortality, with acute exacerbations of COPD (AECOPD) significantly increasing the disease's morbidity and mortality. Among the pathogens implicated in AECOPD, Pseudomonas aeruginosa (P. aeruginosa) is increasingly recognized as a major co-infecting bacterium. Despite its clinical importance, the molecular mechanisms and therapeutic targets underlying AECOPD with P. aeruginosa infection remain inadequately understood.

METHODS: We employed a multi-omics approach, integrating proteomic analyses of bronchoalveolar lavage fluid (BALF) and plasma with transcriptomic analysis of peripheral blood. A discovery cohort of 40 AECOPD with P. aeruginosa infection patients and 20 healthy controls was analyzed, followed by validation in an independent cohort of 20 patients and 10 controls. Differentially expressed proteins (DEPs) and genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis (WGCNA), and immune infiltration analysis. Molecular docking simulations were conducted to explore potential therapeutic agents.

RESULTS: Our integrative analysis identified key biomarkers, which played critical roles in oxidative stress and neutrophil extracellular trap (NET) formation, both of which were pivotal in the pathogenesis of AECOPD with P. aeruginosa infection. The combined analysis of BALF, plasma, and peripheral blood underscored the interplay between local lung changes and systemic immune responses. Functional enrichment analyses highlighted significant pathways related to bacterial defense, inflammation, and immune activation. Validation in an independent cohort confirmed the diagnostic value of three key proteins (AZU1, MPO, and RETN), with high area under the curve (AUC) values in ROC analyses. Molecular docking indicated strong binding affinities of these proteins with Pioglitazone and Rosiglitazone, suggesting potential therapeutic utility.

CONCLUSIONS: This study provides a comprehensive understanding of the molecular mechanisms underlying AECOPD with P. aeruginosa infection, highlighting the pivotal roles of oxidative stress and NET formation in disease progression. The identified biomarkers offer promising diagnostic and therapeutic targets. Our findings pave the way for novel strategies to improve outcomes for AECOPD patients with P. aeruginosa infection. While the study design limits our ability to establish causality, these results provide important insights that warrant further investigation, particularly through longitudinal studies, to confirm the specific contributions of P. aeruginosa in exacerbations.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40140846 | PMC:PMC11948814 | DOI:10.1186/s12931-025-03185-x

Cancers (Basel). 2025 Mar 8;17(6):927. doi: 10.3390/cancers17060927.

ABSTRACT

INTRODUCTION: Liquid biopsies provide a less-invasive option to tissue biopsies for the early diagnosis, prognosis, and tailored therapy of colorectal cancer (CRC). CRC is a major cause of cancer-related death, and early identification is essential for improving patient outcomes.

REVIEW: Conventional diagnostic techniques, including colonoscopy and tissue biopsy, may be enhanced by liquid biopsies that examine circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and other indicators present in body fluids. These markers provide significant insights into tumor biology, heterogeneity, and therapeutic response. CTCs detected in early-stage CRC have prognostic significance for disease recurrence and survival, while ctDNA investigation may uncover genetic mutations, epigenetic alterations, and tumor development. The identification of ctDNA in minimal residual disease (MRD) postsurgery correlates with an elevated risk of recurrence and unfavorable prognosis, underscoring its use in assessing treatment effectiveness. Furthermore, non-coding RNAs (ncRNAs) contained inside EVs provide potential prospective biomarkers and therapeutic targets, facilitating diagnosis and treatment assessment. Notwithstanding the potential of liquid biopsies, obstacles persist in assay standardization, sensitivity enhancement, and the management of tumor heterogeneity. Additional extensive research is required to determine their function in clinical practice.

CONCLUSION: Overall, liquid biopsies serve as a potential instrument for real-time monitoring, evaluating therapy responses, and directing individualized therapeutic strategies in CRC patients.

PMID:40149264 | PMC:PMC11940745 | DOI:10.3390/cancers17060927

J Immunother Cancer. 2025 Mar 18;13(3):e011002. doi: 10.1136/jitc-2024-011002.

ABSTRACT

The intrinsic characteristics of metastatic tumors are of great importance in terms of the development of antimetastatic treatment strategies. Elucidation from a spatial immune perspective has the potential to provide a more comprehensive understanding of the mechanisms underlying immune escape, effectively addressing the limitations of relying solely on the analysis of immune cell subpopulation transcriptional profiles. Advances in spatial omics technology enable researchers to precisely analyze precious liver metastasis samples in a high-throughput manner, revealing spatial alterations in immune cell distribution induced by metastasis and exploring the molecular basis of the remodeling process. The aggregation of specific cell subpopulations in distinct regions not only modifies local immune characteristics but also concurrently affects global biological behaviors of liver metastatic tumors. Identifying specific spatial immune characteristics in pretreatment or early-stage treatment tissue samples may achieve accurate clinical predictions. Moreover, developing strategies that target spatial immune remodeling is a promising avenue for future antimetastatic therapy.

PMID:40107672 | PMC:PMC11927485 | DOI:10.1136/jitc-2024-011002

JHLT Open. 2024 Aug 23;6:100152. doi: 10.1016/j.jhlto.2024.100152. eCollection 2024 Nov.

ABSTRACT

Pulmonary arterial hypertension is a complex and heterogeneous condition, associated with a considerable diagnostic delay, diminished exercise capacity, and poor outcomes. In pulmonary arterial hypertension, biomarker research has become a subject of intense inquiry, and novel circulating biomarkers acknowledged in a multitude of mechanistic pathways are emerging. Beyond the widely used natriuretic peptides, novel biomarkers may provide deeper pathophysiological understanding, support clinical decision-making, and prompt the incorporation of precision medicine by enabling a more precise individual phenotyping. In this state-of-the-art review, the recent advances in circulating biomarkers in pulmonary arterial hypertension from a clinical perspective are discussed, with particular emphasis on the current state of knowledge, gaps in evidence, and future perspectives.

PMID:40145036 | PMC:PMC11935499 | DOI:10.1016/j.jhlto.2024.100152