Optimisation of dispersive liquid-liquid microextraction for plasma sample preparation in bioanalysis of CDK4/6 inhibitors in therapeutic combinations for breast cancer treatment.

Cyclin D dependent kinase 4 and 6 (CDK 4/6) inhibitors are novel anticancer drugs used in therapeutic combinations with endocrine therapy for breast cancer treatment. Their determination in patient plasma is of high interest as a prerequisite for possible therapeutic drug monitoring. Dispersive liquid-liquid microextraction (DLLME) shows great potential in bioanalytical sample preparation.

Streptococcus pneumoniae disrupts the structure of the golgi apparatus and subsequent epithelial cytokine response in an HO-dependent manner.

Background: Lung infections caused by Streptococcus pneumonia are a global leading cause of death. The reactive oxygen species HO is one of the virulence factors of Streptococcus pneumoniae. The Golgi apparatus is essential for the inflammatory response of a eukaryotic cell.

Vulnerability and tuberculosis treatment outcomes in urban settings in England: A mixed-methods study.

Background: Evidence on factors contributing to poor treatment outcome and healthcare priorities in vulnerable populations affected by tuberculosis (TB) in urban areas of England other than London is needed to inform setting-specific prevention and care policies. We addressed this knowledge gap in a cohort of TB patients and healthcare providers in Birmingham and Leicester, UK.

Methods: A mixed-methods study was performed.

Analysis of rare fusions in NSCLC: Genomic architecture and clinical implications.

Objectives: Molecular diagnosis for targeted therapies has been improved significantly in non-small-cell lung cancer (NSCLC) patients in recent years. Here we report on the prevalence of rare fusions in NSCLC and dissect their genomic architecture and potential clinical implications.

Materials And Methods: Overall, n = 5554 NSCLC patients underwent next-generation sequencing (NGS) for combined detection of oncogenic mutations and fusions either at primary diagnosis (n = 5246) or after therapy resistance (n = 308).

The vascular perspective on acute and chronic lung disease.

The pulmonary vasculature has been frequently overlooked in acute and chronic lung diseases, such as acute respiratory distress syndrome (ARDS), pulmonary fibrosis (PF), and chronic obstructive pulmonary disease (COPD). The primary emphasis in the management of these parenchymal disorders has largely revolved around the injury and aberrant repair of epithelial cells. However, there is increasing evidence that the vascular endothelium plays an active role in the development of acute and chronic lung diseases.

Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis.

Background: TP53, encoding the tumor suppressor p53, is frequently mutated in various cancers, producing mutant p53 proteins (mutp53) which can exhibit neomorphic, gain-of-function properties. The latter transform p53 into an oncoprotein that promotes metastatic tumor progression via downstream effectors such as ENTPD5, an endoplasmic reticulum UDPase involved in the calnexin/calreticulin cycle of N-glycoprotein biosynthesis. Elucidating the mechanisms underlying the pro-metastatic functions of the mutp53-ENTPD5 axis is crucial for developing targeted therapies for aggressive metastatic cancer.

The Prognostic Value of Blood Eosinophil Level in AECOPD is Influenced by Corticosteroid Treatment During Hospitalization.

Purpose: Blood eosinophil is a promising biomarker for phenotyping patients with acute exacerbation of COPD (AECOPD). We aimed to evaluate the prognostic value of eosinophil on short- and long-term outcomes stratified by corticosteroid treatment among AECOPD inpatients.

Patients And Methods: In this retrospective cohort study, we included patients hospitalized for AECOPD from July 2013 to June 2021 in Beijing, China.

The Role of the Redox Enzyme p66Shc in Biological Aging of the Lung.

The mitochondrial adaptor protein p66Shc has been suggested to control life span in mice via the release of hydrogen peroxide. However, the role of p66Shc in lung aging remains unsolved. Thus, we investigated the effects of p66Shc on the aging of the lung and pulmonary circulation.

Hepatorenal dysfunction in patients with chronic thromboembolic pulmonary hypertension.

Background: Cardiac interactions with organs such as the liver or kidneys have been described in different cardiovascular diseases. However, the clinical relevance of hepatorenal dysfunction in chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We determined the association of hepatorenal dysfunction (measured using the Model for End-stage Liver Disease Sodium [MELDNa] score) with right heart function and survival in patients with CTEPH.

ADPGK-AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth.

Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role in tumor-associated macrophages (TAMs) is still largely unknown. We found that the lncRNA ADPGK-AS1 was substantially upregulated in artificially induced M2-like human macrophages, macrophages exposed to lung cancer cells in vitro, and TAMs from human lung cancer tissue. ADPGK-AS1 is partly located within mitochondria and binds to the mitochondrial ribosomal protein MRPL35.

The lung mesenchyme in development, regeneration, and fibrosis.

Mesenchymal cells are uniquely located at the interface between the epithelial lining and the stroma, allowing them to act as a signaling hub among diverse cellular compartments of the lung. During embryonic and postnatal lung development, mesenchyme-derived signals instruct epithelial budding, branching morphogenesis, and subsequent structural and functional maturation. Later during adult life, the mesenchyme plays divergent roles wherein its balanced activation promotes epithelial repair after injury while its aberrant activation can lead to pathological remodeling and fibrosis that are associated with multiple chronic pulmonary diseases, including bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease.

Prognostic Impact of the Immune-Cell Infiltrate in N1-Positive Non-Small-Cell Lung Cancer.

Introduction: The tumoral immune milieu plays a crucial role for the development of non-small-cell lung cancer (NSCLC) and may influence individual prognosis. We analyzed the predictive role of immune cell infiltrates after curative lung cancer surgery.

Materials And Methods: The tumoral immune-cell infiltrate from 174 patients with pN1 NSCLC and adjuvant chemotherapy was characterized using immunofluorescence staining.

Stem/Progenitor Cells and Related Therapy in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly seen in preterm infants, and is triggered by infection, mechanical ventilation, and oxygen toxicity. Among other problems, lifelong limitations in lung function and impaired psychomotor development may result. Despite major advances in understanding the disease pathologies, successful interventions are still limited to only a few drug therapies with a restricted therapeutic benefit, and which sometimes have significant side effects.

Decellularized Lung Extracellular Matrix Scaffold Promotes Human Embryonic Stem Cell Differentiation towards Alveolar Progenitors.

Objective: Efficient production of functional and mature alveolar epithelial is a major challenge for developing any cell replacement therapy for lung degenerative diseases. The extracellular matrix (ECM) pro-vides a dynamic environment and mediates cellular responses during development and maintenance of tissue functions. The decellularized ECM (dECM) which retains its native-like structure and bio-chemical composition can provide the induction of embryonic stem cell (ESC) differentiation toward the tissue-specific lineages during culture.

Supranormal lung function: Prevalence, associated factors and clinical manifestations across the lifespan.

Background And Objective: It is now well established that there are different life-long lung function trajectories in the general population, and that some are associated with better or worse health outcomes. Yet, the prevalence, clinical characteristics and risk factors of individuals with supranormal FEV or FVC values (above the upper-limit of normal [ULN]) in different age-bins through the lifetime in the general population are poorly understood.

Method: To address these questions, we investigated the prevalence of supranormal FEV and FVC values in the LEAD (Lung, hEart, sociAl and boDy) study, a general population cohort in Austria that includes participants from 6 to 82 years of age.

Evaluation of diagnostic accuracy of dual-energy computed tomography in patients with chronic thromboembolic pulmonary hypertension compared to V/Q-SPECT and pulmonary angiogram.

Purpose: The relevance of dual-energy computed tomography (DECT) for the detection of chronic thromboembolic pulmonary hypertension (CTEPH) still lies behind V/Q-SPECT in current clinical guidelines. Therefore, our study aimed to assess the diagnostic accuracy of DECT compared to V/Q-SPECT with invasive pulmonary angiogram (PA) serving as the reference standard.

Methods: A total of 28 patients (mean age 62.

Decoding the role of fatty acids and their metabolites in lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and life‑threatening interstitial lung disease of familial or sporadic onset. The incidence and prevalence of IPF range from 0.09 to 1.

Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control.

Background: Patients with type-2 (T2) cytokine-low severe asthma often have persistent symptoms despite suppression of T2 inflammation with corticosteroids.

Objectives: We sought to analyze whole blood transcriptome from 738 samples in T2-biomarker-high/-low patients with severe asthma to relate transcriptomic signatures to T2 biomarkers and asthma symptom scores.

Methods: Bulk RNA-seq data were generated for blood samples (baseline, week 24, week 48) from 301 participants recruited to a randomized clinical trial of corticosteroid optimization in severe asthma.