The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study.

Background: Hypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC). Methods: EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease. Results: Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation. Conclusion: The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.

Patient-Derived Organoids as Therapy Screening Platforms in Cancer Patients.

Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs-on-a-chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. Furthermore, this work introduces tools for data processing and analysis of organoids, along with their microenvironment. These tools aim to achieve enhanced readouts. Finally, this work explores the challenges and future perspectives of using PDOs in drug development and personalized screening for cancer patients.

Quality-of-Life Bronchiectasis Respiratory Symptom Scale Predicts the Risk of Exacerbations in Adults with Bronchiectasis: A Prospective Observational Study.

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.

Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. METHODS: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). RESULTS: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. CONCLUSION: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis. TRIAL REGISTRATION:  This study is registered with ClinicalTrials.gov, number NCT04490447.

Potential Therapeutic Strategies for Targeting Y-Box-Binding Protein 1 in Cancers.

As one of the most conservative proteins in evolution, Y-box-binding protein 1 (YB-1) has long been considered as a potential cancer target. YB-1 is usually poorly expressed in normal cells and exerts cellular physiological functions such as DNA repair, pre-mRNA splicing and mRNA stabilizing. In cancer cells, the expression of YB-1 is up-regulated and undergoes nuclear translocation and contributes to tumorigenesis, angiogenesis, tumor proliferation, invasion, migration and chemotherapy drug resistance. During the past decades, a variety of pharmacological tools such as siRNA, shRNA, microRNA, circular RNA, lncRNA and various compounds have been developed to target YB-1 for cancer therapy. In this review, we describe the physiological characteristics of YB-1 in detail, highlight the role of YB-1 in tumors and summarize the current therapeutic methods for targeting YB-1 in cancer.

Targeting galectins in T cell-based immunotherapy within tumor microenvironment.

Over the past few years, tumor immunotherapy has emerged as an innovative tumor treatment and owned incomparable advantages over other tumor therapy. With unique complexity and uncertainty, immunotherapy still need helper to apply in the clinic. Galectins, modulated in tumor microenvironment, can regulate the disorders of innate and adaptive immune system resisting tumor growth. Considering the role of galectins in tumor immunosuppression, combination therapy of targeted anti-galectins and immunotherapy may be a promising tumor treatment. This brief review summarizes the expression and immune functions of different galectins in tumor microenvironment and discusses the potential value of anti-galectins in combination with checkpoint inhibitors in tumor immunotherapy.

The clinical characteristics and prognosis of ABPA are closely related to the mucus plugs in central bronchiectasis.

INTRODUCTION: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. OBJECTIVES: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs. METHODS: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. RESULTS: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. CONCLUSIONS: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

Graphene Oxide-Based Biosensors for Liquid Biopsies in Cancer Diagnosis.

Liquid biopsies use blood or urine as test samples, which are able to be continuously collected in a non-invasive manner. The analysis of cancer-related biomarkers such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA, and exosomes provides important information in early cancer diagnosis, tumor metastasis detection, and postoperative recurrence monitoring assist with clinical diagnosis. However, low concentrations of some tumor markers, such as CTCs, ctDNA, and microRNA, in the blood limit its applications in clinical detection and analysis. Nanomaterials based on graphene oxide have good physicochemical properties and are now widely used in biomedical detection technologies. These materials have properties including good hydrophilicity, mechanical flexibility, electrical conductivity, biocompatibility, and optical performance. Moreover, utilizing graphene oxide as a biosensor interface has effectively improved the sensitivity and specificity of biosensors for cancer detection. In this review, we discuss various cancer detection technologies regarding graphene oxide and discuss the prospects and challenges of this technology.

Remote Magnetic Control of Autophagy in Mouse B-Lymphoma Cells with Iron Oxide Nanoparticles.

Autophagy is the spontaneous degradation of intracellular proteins and organelles in response to nutrient deprivation. The phagocytosis of iron oxide nanoparticles (IONPs) results in intracellular degradation that can be exploited for use in cancer treatment. Non-invasive magnetic control has emerged as an important technology, with breakthroughs achieved in areas such as magneto-thermal therapy and drug delivery. This study aimed to regulate autophagy in mouse B-lymphoma cells (A20) through the incorporation of IONPs-quantum dots (QDs). We hypothesized that with the application of an external magnetic field after phagocytosis of IONPs-QDs, autophagy of intracellular IONPs-QDs could be regulated in a non-invasive manner and subsequently modulate the regulation of inflammatory responses. The potential of this approach as a cancer treatment method was explored. The application of IONPs and an external magnetic force enabled the non-invasive regulation of cell autophagy and modulation of the self-regulatory function of cells. The combination of non-invasive magnetic fields and nanotechnology could provide a new approach to cancer treatment.

Enhanced Osteogenic Differentiation of Stem Cells on Phase-Engineered Graphene Oxide.

Graphene oxide (GO) has attracted significant interest as a template material for multiple applications due to its two-dimensional nature and established functionalization chemistries. However, for applications toward stem cell culture and differentiation, GO is often reduced to form reduced graphene oxide, resulting in a loss of oxygen content. Here, we induce a phase transformation in GO and demonstrate its benefits for enhanced stem cell culture and differentiation while conserving the oxygen content. The transformation results in the clustering of oxygen atoms on the GO surface, which greatly improves its ability toward substance adherence and results in enhanced differentiation of human mesenchymal stem cells toward the osteogenic lineage. Moreover, the conjugating ability of modified GO strengthened, which was examined by auxiliary osteogenic growth peptide conjugation. Overall, our work demonstrates GO's potential for stem cell applications while maintaining its oxygen content, which could enable further functionalization and fabrication of novel nano-biointerfaces.

Simultaneous drug delivery and cellular imaging using graphene oxide.

Graphene oxide (GO), a derivative of graphene, and its related nanomaterials have attracted much attention in recent years due to the excellent biocompatibility and large surface area of GO with abundant oxygen functional groups, which further enable it to serve as a nano-bio interface. Herein, we demonstrate the induction of blue fluorescence in GO suspensions via a mild thermal annealing procedure. Additionally, this procedure preserves the oxygen functional groups on the graphene plane which enables the conjugation of cancer drugs without obvious cytotoxicity. Consequently, we demonstrate the capability of GO to simultaneously play the dual-role of a: (i) cellular imaging agent and (ii) drug delivery agent in CT26 cancer cells without the need for additional fluorescent protein labeling. Our method offers a simple, controllable strategy to tune and enhance the fluorescence property of GO, which shows potential for biomedical applications and fundamental studies.

Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes.

Macrolides antibiotics have been effectively used in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using P. aeruginosa agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance, and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment. Plasma IL-18 levels were determined from patients who were diagnosed with bronchiectasis isolated with or without P. aeruginosa and treated with azithromycin for 3-5 days. Azithromycin treatment enhanced bacterial clearance and attenuated lung injury in mice chronically infected with P. aeruginosa, which resulted from the inhibition of caspase-1-dependent IL-1ß and IL-18 secretion. In vitro, azithromycin and erythromycin inhibited NLRC4 and NLRP3 inflammasomes activation. Plasma IL-18 levels were higher in bronchiectasis patients with P. aeruginosa isolation compared with healthy controls. Azithromycin administration markedly decreased IL-18 secretion in bronchiectasis patients. The results of this study reveal that azithromycin and erythromycin exert a novel anti-inflammatory effect by attenuating inflammasomes activation, which suggests potential treatment options for inflammasome-related diseases.

Combined inhaled corticosteroid and long-acting ß2-adrenergic agonist therapy for noncystic fibrosis bronchiectasis with airflow limitation: An observational study.

BACKGROUND AND OBJECTIVE: There is presently no clear evidence on the effect of combined treatment for non-cystic fibrosis (non-CF) bronchiectasis with inhaled corticosteroid (ICS) and long-acting ß2-adrenergic agonist (LABA). The objective of this study is to assess the efficacy and safety of salmeterol-fluticasone combined inhaled therapy for non-CF bronchiectasis with airflow limitation. METHODS: An observational study was performed in 120 non-CF bronchiectasis patients diagnosed by high-resolution computed tomography (HRCT) scanning of the chest. Patients received either routine therapy or salmeterol-fluticasone (100/500 µg daily) combined inhaled therapy on the basis of routine therapy. Clinical symptoms, health-related quality of life (HRQL), lung function, short-acting ß2-adrenergic agonist (SABA) use, and safety were monitored throughout the study. RESULTS: OF the 120 subjects, 60 received combined inhaled therapy and 60 received routine therapy. Compared to the control group, the combined inhaled therapy group showed significant improvement in their clinical symptom scores (-2.21 vs. -0.31, P = 0.002) and a reduction in number of weekly SABA usage (-4.2 vs. 0.1, P < 0.01). In addition, patients in the inhaled therapy group achieved a significant improvement in HRQL based on mMRC (-1.51 vs. -0.31, P < 0.005) and SGRQ (-7.83 vs. -2.16, P < 0.01) scoring accompanied with no severe adverse events. There were fewer exacerbation frequencies in the combined inhaled therapy group over the 12 months of treatment compared to the control group (1 [0-2] vs. 2 [1-4], P = 0.017). Furthermore, stratified analysis indicated that combined inhaled therapy partially improve lung function for patients for whom it is severely impaired and those with pseudomonas aeruginosa isolated. CONCLUSION: Our results show that salmeterol-fluticasone combined inhaled therapy should be effective and safe for non-CF bronchiectasis patients especially for those patients with poor lung function or pseudomonas aeruginosa isolated.

Asthma and bronchiectasis exacerbation.

Bronchiectasis and asthma are common respiratory diseases worldwide. However, the influence of asthma on bronchiectasis remains unclear. The objective of this study is to analyse the effects of asthma on bronchiectasis exacerbation.Data from inpatients diagnosed with bronchiectasis with or without asthma at Shanghai Pulmonary Hospital (Shanghai, China) between January 2013 and December 2014 were retrospectively collected and analysed. 249 patients with only bronchiectasis and 214 patients with both bronchiectasis and asthma were included in the study. Follow-up records were used to evaluate the effect of asthma on bronchiectasis exacerbation.The variables found to be independently associated with bronchiectasis exacerbations were age (OR 1.07, 95% CI 1.03-1.11; p<0.001), duration of symptoms (OR 1.06, 95% CI 1.03-1.09; p<0.001), the presence of asthma (OR 2.6, 95% CI 1.15-5.88; p=0.021), forced expiratory volume in 1 s <50% predicted (OR 4.03, 95% CI 1.75-9.26; p=0.001), isolation of Pseudomonas aeruginosa in sputum (OR 2.41, 95% CI 1.00-5.79; p=0.05) and lung lesion extension to more than two lobes (OR 2.73, 95% CI 1.16-6.45; p=0.022).The existence of asthma was associated with an independent increase in risk of bronchiectasis exacerbation.

Efficacy and safety of long-term inhaled antibiotic for patients with noncystic fibrosis bronchiectasis: a meta-analysis.

BACKGROUND AND AIMS: The evidence supported the use of nebulized antibiotics in non-cystic fibrosis (non-CF) bronchiectasis is indefinite. A meta-analysis was performed to determine the efficacy and safety of long-term inhaled antibiotics for patients with non-CF bronchiectasis. METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were searched up to March 20, 2014. Reduction of sputum bacterial density, eradication of sputum Pseudomonas aeruginosa, the risk of exacerbations and other clinical outcomes related to inhalation treatment were analyzed. RESULTS: Three hundred seventy articles were searched. Eight randomized controlled trials recruiting 539 patients were included in this meta-analysis. Long-term inhaled antibiotics showed an obvious reduction of the sputum bacterial density [weighted mean difference = 2.85, 95% confidence interval (CI): 1.6-4.09, P < 0.00001] and augment eradication of sputum P. aeruginosa [odds ratio (OR) = 6.6, 95% CI: 2.93-14.86, P < 0.00001]. No evidences showed higher risk of P. aeruginosa resistance after inhaled therapy. In addition, nebulized therapy reduced the amount of patients with exacerbation (OR = 0.46, 95% CI: 0.21-1.00, P = 0.05). However, patients with inhaled antibiotics were more likely to suffer wheeze (OR = 6.74, 95% CI: 2.22-20.52, P = 0.0008) and bronchospasm (OR = 2.84, 95% CI: 1.11-7.25, P = 0.03). CONCLUSION: For patients with non-CF bronchiectasis, long-term inhaled antibiotics can effectively reduce the sputum bacterial density, increase P.A eradication and attenuate the risk of exacerbation, however, accompanied with higher risk of wheeze and bronchospasm.

Distribution of Major Pathogens from Sputum and Bronchoalveolar Lavage Fluid in Patients with Noncystic Fibrosis Bronchiectasis: A Systematic Review.

OBJECTIVE: Noncystic fibrosis (non-CF) bronchiectasis remains as a common health problem in Asia. Pathogens' distribution in airways of patients with non-CF bronchiectasis is important for doctors to make right decision. DATA SOURCES: We performed this systematic review on the English language literatures from 1966 to July 2014, using various search terms included "pathogens" or "bacteria" or "microbiology" and "bronchiectasis" or "non-cystic fibrosis bronchiectasis" or "non-CF bronchiectasis" or "NCFB." STUDY SELECTION: We included studies of patients with the confirmed non-CF bronchiectasis for which culture methods were required to sputum or bronchoalveolar lavage fluid (BALF). Weighted mean isolation rates for Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Stapylococcus aureus, Moxarella catarrhails were compared according to different methodology. RESULTS: The total mean bacterial culture positive rates were 63%. For studies using sputum samples, the mean positive culture rates were 74%. For studies using BALF alone or BALF and sputum, it was 48%. The distributions of main bacterial strains were 29% for H. influenzae, 28% for P. aeruginosa, 11% for S. pneumoniae, 12% for S. aureus, and 8% for M. catarrhails with methodology of sputum. Meanwhile, the bacterial distributions were 37% for H. influenzae, 8% for P. aeruginosa, 14% for S. pneumoniae, 5% for S. aureus, and 10% for M. catarrhails with methodology of BALF alone or BALF and sputum. Analysis of the effect of different methodology on the isolation rates revealed some statistically significant differences. CONCLUSIONS: H. influenzae accounted for the highest percentage in different methodology. Our results suggested that the total positive culture rates and the proportion of P. aeruginosa from sputum and BALF specimens had significant differences, which can be used in further appropriate recommendations for the treatment of non-CF bronchiectasis.

The existence of bronchiectasis predicts worse prognosis in patients with COPD.

Bronchiectasis is prevalent in patients with COPD. The objective of this study was to assess the clinical characteristics and prognostic value of bronchiectasis in patients with COPD in China. Data from patients diagnosed with COPD at the Shanghai Pulmonary Hospital between January 2009 and December 2013 were retrospectively collected and analyzed. SPSS statistical software was used to analyze the data. Data from 896 patients with COPD were analyzed. Bronchiectasis was present in 311 patients. The isolation of pseudomonas aeruginosa (PA) from sputum was the variable most significantly associated with the presence of bronchiectasis in patients with COPD (hazard ratio (HR), 2.93; 95% confidence interval (CI), 1.35-6.37; P = 0.007). During follow-up (median of 21 months; interquartile range: 10-39 months), there were 75 deaths, of which 39 were in the bronchiectasis group. The presence of bronchiectasis (HR, 1.77; 95% CI, 1.02-3.08; P = 0.043) was associated with an increase in all-cause mortality in patients with COPD. These results suggest that bronchiectasis in patients with COPD was associated with the isolation of PA from the sputum. Bronchiectasis was an independent risk factor for all-cause mortality in patients with COPD.