Rocaglamide regulates iron homeostasis by suppressing hepcidin expression.

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.

Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma.

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.

Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions.

BACKGROUND AND OBJECTIVE: Endothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients. METHODS: A total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro. RESULTS: Endothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05). CONCLUSION: NP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.

Eosinophilic bronchiectasis increases length and cost of hospitalization: a retrospective analysis in a hospital of southern China from 2012 to 2020.

BACKGROUND: The concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation. METHODS: A total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (< 300 cell/µL). Clinical characteristics, length of hospital stay (LOS), hospitalization cost and inflammatory markers were compared between the two groups. RESULTS: Eosinophilic bronchiectasis occurred in approximately 11.7% of all patients. 156 propensity score-matched pairs were identified with and without high eosinophil count. Eosinophilic bronchiectasis presented with a longer LOS [9.0 (6.0-12.5) vs. 5.0 (4.0-6.0) days, p < 0.0001] and more hospitalization cost [15,011(9,753-27,404) vs. 9,109(6,402-12,287) RMB, p < 0.0001] compared to those in non-eosinophilic bronchiectasis. The median white blood cell (WBC), lymphocyte, platelet (PLT) and C-reactive protein (CRP) levels in eosinophilic bronchiectasis were significantly increased. Multivariate logistic regression analysis confirmed that the high levels of eosinophil count (OR = 13.95, p < 0.0001), worse FEV1% predicted (OR = 7.80, p = 0.0003) and PLT (OR = 1.01, p = 0.035) were independent prognostic factors for length of hospital (LOS) greater than 7 days. CONCLUSION: Eosinophilic bronchiectasis patients had longer length of hospital stay and more hospitalization cost compared to those in non-eosinophilic bronchiectasis group, which might be associated with the stronger inflammatory reaction.

Corrosion Inhibition Mechanism of Water-Soluble Imidazoline on A572 Gr.65 Steel in 3.5 wt % NaCl Solution.

To optimize the economic advantages and corrosion-resisting property of A572 Gr.65 steels, the inhibition effect of water-soluble imidazoline on the sample surface with rare earth was explored in a 3.5 wt % NaCl solution. In this paper, the mechanism of corrosion and the adsorptive behavior of water-soluble imidazoline inhibitors on A572 Gr.65 steels with 47 ppm of rare earth in saltwater solution were discussed, along with the establishment of the adsorption model. Achievements proposed that the inhibition efficiency of water-soluble imidazoline was as high as 95.73% at 80 mg L-1 dosage following an anodic-dominated mixed-type inhibition mechanism. Besides, the scanning electron microscopy and X-ray diffraction analysis revealed that the corrosion inhibitor resulted in a smoother and more stable rust layer with a significant reduction of the γ-FeOOH. Theoretical calculations confirmed that imidazoline formed a unimolecular layer adsorption film on the steel surface, exhibiting adherence to both Langmuir and Frumkin adsorption isotherms, involving physical and chemical adsorption.

Simultaneous evaluation of the fractional exhaled nitric oxide and blood eosinophil count of T2-high endotype in patients with non-cystic fibrosis bronchiectasis.

OBJECTIVE: Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC. METHODS: This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO ≥25 ppb; BEC ≥200/µL). RESULTS: Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis. CONCLUSIONS: Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients.

Novel DNA Promoter Hypermethylation in Nasal Epithelium of Asthma.

BACKGROUND: Abnormal epigenetic alterations influenced by external factors and affecting DNA expression contribute to the development of asthma. However, the role of the nasal epithelium in airway inflammation remains unknown. OBJECTIVE: The objective of this study is to identify novel DNA promoter hypermethylation, which suppresses mRNA expression in nasal epithelial of asthma. METHODS: Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Gene expression and DNA promoter methylation sites in key correlated modules between asthma and normal were identified by weighted gene co-expression network analysis. Gene Oncology and Kyoto Encyclopedia of Genes and Genomes were conducted to analyse the function of genes. Further validation was performed in human BEAS-2B cells challenged by IL-4 or IL-13. RESULTS: Lightcyan, lightgreen, midnightblue, cyan and tan modules in the mRNA expression dataset showed a close relationship with asthma, in which genes were enriched in TNF, IL-17, ErbB, MAPK and Estrogen signalling pathways. Blue and turquoise modules in the methylation profiling dataset were associated with asthma. Forty nine lowly expressed genes were identified to be correlated with aberrant DNA hypermethylation of promoters. Among these genes, the mRNA levels of BCL10, GADD45B, LSR and SQSTM1 were downregulated in BEAS-2B cells challenged with IL-4 or IL-13. CONCLUSION: Four potential genes in the nasal epithelium, by hypermethylating their own DNA promoter, might mediate the inflammatory response in the pathogenesis of asthma. Analyzing epigenomic data by integrated bioinformatics helps to understand the role of DNA methylation in asthma, with the goal of providing new perspectives for diagnosis and therapy.

Ailanthone inhibits non-small cell lung cancer growth and metastasis through targeting UPF1/GAS5/ULK1 signaling pathway.

BACKGROUND: Targeting long non-coding RNAs (LncRNAs) is a novel and promising approach in cancer therapy. In our previous study, we investigated the effects of ailanthone (aila), the main active compound derived from the stem barks of Ailanthus altissima (Mill.) Swingle, on the growth of non-small cell lung cancer (NSCLC) cells. Although we observed significant inhibition of NSCLC cell growth of aila, the underlying mechanisms involving LncRNAs, specifically LncRNA growth arrest specific 5 (GAS5), remain largely unknown. METHODS: To further explore the impact of aila on NSCLC, we performed a series of experiments. Firstly, we confirmed the inhibitory effect of aila on NSCLC cell growth using multiple assays, including MTT, wound healing, transwell assay, as well as subcutaneous and metastasis tumor mice models in vivo. Next, we utilized cDNA microarray and RT-QPCR to identify GAS5 as the primary target of aila. To verify the importance of GAS5 in aila-induced tumor inhibition, we manipulated GAS5 expression levels by constructing GAS5 over-expression and knockdown NSCLC cell lines. Furthermore, we investigated the upstream and downstream signaling pathways of GAS5 through western blot and RT-QPCR analysis. RESULTS: Our results showed that aila effectively increased GAS5 expression, as determined by microarray analysis. We also observed that aila significantly enhanced GAS5 expression in a dose- and time-dependent manner across various NSCLC cell lines. Notably, over-expression of GAS5 led to a significant suppression of NSCLC cell tumor growth; while aila had minimal inhibitory effect on GAS5-knockdown NSCLC cells. Additionally, we discovered that aila inhibited ULK1 and autophagy, and this inhibition was reversed by GAS5 knockdown. Moreover, we found that aila up-regulated GAS5 expression by suppressing UPF1-mediated nonsense-mediated mRNA decay (NMD). CONCLUSION: In summary, our findings suggest that aila promotes GAS5 expression by inhibiting UPF1-mediated NMD, leading to the repression of ULK1-mediated autophagy and subsequent inhibitory effects on NSCLC cells. These results indicate that aila is a potent enhancer of GAS5 and holds promising potential for application in NSCLC therapy. However, our research is currently focused only on NSCLC. It remains to be determined whether aila can also inhibit the growth of other types of tumors through the UPF1/GAS5/ULK1 signaling pathway. In future studies, we can further investigate the mechanisms by which aila suppresses other types of tumors and potentially broaden the scope of its application in cancer therapy.

Two sensory neurons coordinate the systemic mitochondrial stress response via GPCR signaling in C. elegans.

Mitochondrial perturbations within neurons communicate stress signals to peripheral tissues, coordinating organismal-wide mitochondrial homeostasis for optimal fitness. However, the neuronal control of the systemic stress regulation remains poorly understood. Here, we identified a G-protein-coupled receptor (GPCR), SRZ-75, that couples with Gαq signaling in a pair of chemosensory ADL neurons to drive the mitochondrial unfolded protein response (UPRmt) activation in the intestine via the release of neuropeptides in Caenorhabditis elegans. Constitutive activation of Gαq signaling in the ADL neurons is sufficient to induce the intestinal UPRmt, leading to increased stress resistance and metabolic adaptations. Ablation of ADL neurons attenuates the intestinal UPRmt activation in response to various forms of neuronal mitochondrial dysfunction. Thus, GPCR and its Gαq downstream signaling in two sensory neurons coordinate the systemic UPRmt activation, representing a previously uncharacterized, but potentially conserved, neuronal signaling for organismal-wide mitochondrial stress regulation.

Protein disulfide isomerase PDI-6 regulates Wnt secretion to coordinate inter-tissue UPRmt activation and lifespan extension in C. elegans.

Coordination of inter-tissue stress signaling is essential for organismal fitness. Neuronal mitochondrial perturbations activate the mitochondrial unfolded-protein response (UPRmt) in the intestine via the mitokine Wnt signaling in Caenorhabditis elegans. Here, we found that the protein disulfide isomerase PDI-6 coordinates inter-tissue UPRmt signaling via regulating the Wnt ligand EGL-20. PDI-6 is expressed in the endoplasmic reticulum (ER) and interacts with EGL-20 through disulfide bonds that are essential for EGL-20 stability and secretion. pdi-6 deficiency results in misfolded EGL-20, which leads to its degradation via ER-associated protein degradation (ERAD) machinery. Expression of PDI-6 declines drastically with aging, and animals with pdi-6 deficiency have decreased lifespan. Overexpression of PDI-6 is sufficient to maintain Wnt/EGL-20 protein levels during aging, activating the UPRmt, and significantly extending lifespan in a Wnt- and UPRmt-dependent manner. Our study reveals that protein disulfide isomerase facilitates Wnt secretion to coordinate the inter-tissue UPRmt signaling and organismal aging.

Corrigendum: The Identification of Two RNA Modification Patterns and Tumor Microenvironment Infiltration Characterization of Lung Adenocarcinoma.

[This corrects the article DOI: 10.3389/fgene.2022.761681.].

Dietary S. maltophilia induces supersized lipid droplets by enhancing lipogenesis and ER-LD contacts in C. elegans.

Dietary and symbiotic bacteria can exert powerful influence on metazoan lipid metabolism. Recent studies have emerged that microbiota have a role in animal obesity and related health disorders, but the mechanisms by which bacteria influence lipid storage in their host are unknown. To reduce the complexity of the relationship between gut microbiota and the host, Caenorhabditis elegans (C. elegans) has been chosen as a model organism to study interspecies interaction. Here, we demonstrate that feeding C. elegans with an opportunistic pathogenic bacterium Stenotrophomonas maltophilia (S. maltophilia) retards growth and promotes excessive neutral lipid storage. Gene expression analysis reveals that dietary S. maltophilia induces a lipogenic transcriptional response that includes the SREBP ortholog SBP-1, and fatty acid desaturases FAT-6 and FAT-7. Live imaging and ultrastructural analysis suggest that excess neutral lipid is stored in greatly expanded lipid droplets (LDs), as a result of enhanced endoplasmic reticulum (ER)-LD interaction. We also report that loss of function mutations in dpy-9 in C. elegans confers resistance to S. maltophilia. Dietary S. maltophilia induces supersized LDs by enhancing lipogenesis and ER-LD contacts in C. elegans. This work delineates a new model for understanding microbial regulation of metazoan physiology.

The Identification of Two RNA Modification Patterns and Tumor Microenvironment Infiltration Characterization of Lung Adenocarcinoma.

Background: RNA modification plays an important role in many diseases. A comprehensive study of tumor microenvironment (TME) characteristics mediated by RNA modification regulators will improve the understanding of TME immune regulation. Methods: We selected 26 RNA modification "writers" of lung adenocarcinoma (LUAD) samples and performed unsupervised clustering analysis to explore RNA modification patterns in LUAD. Differentially expressed genes (DEGs) with RNA modification patterns were screened to develop a "writers" of RNA modification score (WM score) system. The infiltration ratio of TME cell subsets was analyzed by CIBERSORT. Results: We identified two RNA modification modes showing different characteristics of overall survival (OS) and TME cell infiltration. According to WM score, LUAD patients were divided into a high-WM score group and a low-WM score group. High-scored patients had a poor prognosis and higher tumor mutation burden (TMB), they were more sensitive to four LUAD therapies (erlotinib, XA V939, gefitinib, and KU-55933) and more clinically responsive to PD-L1 treatment. Those with a low WM score showed higher stromal scores, ESTIMATE scores, and survival chance. Conclusion: Our work revealed the potential role of RNA modification patterns in TME, genetic variation, targeted inhibitor therapy, and immunotherapy. Identifying RNA modification pattern of LUAD patients help understand the characteristics of TME and may promote the development of immunotherapy strategies.

Acute fibrinous and organizing pfneumonia: two case reports and literature review.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern characterized by the intra-alveolar fibrin deposition and organizing pneumonia. Its clinical characteristics are still not well known and there is no consensus on treatment yet. CASE PRESENTATION: We report two female cases in their fifties diagnosed with AFOP confirmed by a second lung biopsy. Case 1 was idiopathic AFOP with manifestation of 6-week fever, dyspnea, and cough, while case 2 was secondary to systemic lupus erythematosus and fever was the major symptom. Their chest CT scans revealed bilateral multiple consolidations, predominantly in the lower lobes. Both cases were initially diagnosed with pneumonia, but did not improve after treatment with broad-spectrum antibiotics. In both cases, transbronchial biopsy and bronchoalveolar lavage fluid examination were inconclusive and the pathological diagnosis was confirmed by percutaneous lung biopsy. Both patients had a good clinical response to prednisone. CONCLUSIONS: We report two rare AFOP cases to highlight the importance of awareness of this disease. We further perform the most comprehensive review to date in AFOP, including 150 patients since 2002. Consolidation was the most common imaging pattern, followed by ground-glass opacity and nodules. A lung biopsy is required for a definitive diagnosis. Corticosteroids is recommended as the most effective therapy, but treatment options should depend on the etiology and disease severity.

The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels.

The memory of stresses experienced by parents can be passed on to descendants as a forecast of the challenges to come. Here, we discovered that the neuronal mitochondrial perturbation-induced systemic mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans can be transmitted to offspring over multiple generations. The transgenerational activation of UPRmt is mediated by maternal inheritance of elevated levels of mitochondrial DNA (mtDNA), which causes the proteostasis stress within mitochondria. Furthermore, results from intercrossing studies using wild C. elegans strains further support that maternal inheritance of higher levels of mtDNA can induce the UPRmt in descendants. The mitokine Wnt signalling pathway is required for the transmission of elevated mtDNA levels across generations, thereby conferring lifespan extension and stress resistance to offspring. Collectively, our results reveal that the nervous system can transmit stress signals across generations by increasing mtDNA in the germline, enabling descendants to better cope with anticipated challenges.

A computed tomography (CT)-derived radiomics approach for predicting primary co-mutations involving TP53 and epidermal growth factor receptor (EGFR) in patients with advanced lung adenocarcinomas (LUAD).

BACKGROUND: Epidermal growth factor receptor (EGFR) co-mutated with TP53 could reduce responsiveness to tyrosine kinase inhibitors (TKIs) and worsen patients' prognosis compared to TP53 wild type patients in. EGFR: mutated lung adenocarcinomas (LUAD). To identify this genetically unique subset prior to treatment through computed tomography (CT) images had not been reported yet. METHODS: Stage III and IV LUAD with known mutation status of EGFR and TP53 from The First Affiliated Hospital of Sun Yat-sen University (May 1, 2017 to June 1, 2020) were collected. Characteristics of pretreatment enhanced-CT images were analyzed. One-versus-one was used as the multiclass classification strategy to distinguish the three subtypes of co-mutations: EGFR + & TP53 +, EGFR + & TP53 -, EGFR -. The clinical model, semantic model, radiomics model and integrated model were built. Area under the receiver-operating characteristic curves (AUCs) were used to evaluate the prediction efficacy. RESULTS: A total of 199 patients were enrolled, including 83 (42%) cases of EGFR -, 55 (28%) cases of EGFR + & TP53 +, 61 (31%) cases of EGFR + & TP53 -. Among the four different models, the integrated model displayed the best performance for all the three subtypes of co-mutations: EGFR - (AUC, 0.857; accuracy, 0.817; sensitivity, 0.998; specificity, 0.663), EGFR + & TP53 + (AUC, 0.791; accuracy, 0.758; sensitivity, 0.762; specificity, 0.783), EGFR + & TP53 - (AUC, 0.761; accuracy, 0.813; sensitivity, 0.594; specificity, 0.977). The radiomics model was slightly inferior to the integrated model. The results for the clinical and the semantic models were dissatisfactory, with AUCs less than 0.700 for all the three subtypes. CONCLUSIONS: CT imaging based artificial intelligence (AI) is expected to distinguish co-mutation status involving TP53 and EGFR. The proposed integrated model may serve as an important alternative marker for preselecting patients who will be adaptable to and sensitive to TKIs.

Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19.

BACKGROUND: The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. METHODS: A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected. RESULTS: On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells. CONCLUSIONS: A sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

The detrimental qualitative and quantitative alterations of circulating endothelial progenitor cells in patients with bronchiectasis.

BACKGROUND: Bronchiectasis is an independent risk factor for cardiovascular disease（CVD）and cardiac dysfunction. Endothelial progenitor cells (EPCs) play a crucial role in maintaining endothelial function, and is inversely correlated with cardiovascular risk factors or cardiac dysfunction. However, the relationship between EPCs and bronchiectasis is unknown. METHODS: Twenty-nine patients with stable bronchiectasis and 15 healthy controls were recruited. Fasting venous blood were collected for determining circulating EPC number and activity as well as systemic inflammatory cytokines. RESULTS: The number and migratory or proliferative activity of circulating EPCs in bronchiectasis patients were significantly reduced (p < 0.001). In high E-FACED group, the number of circulating EPCs evaluated by cell culture assay and EPC proliferation were decreased (p < 0.05). Similarly, the number and function of circulating EPCs were both reduced in low forced expiratory volume in 1 s (FEV1) or high mMRC group (p < 0.05). There was a significant correlation between circulating EPCs and bronchiectasis disease severity, according to the E-FACED score (p < 0.05), particularly to FEV1 (p < 0.05) and mMRC dyspnea score (p < 0.05). The count and activity of EPCs inversely correlated with hsCRP levels and IL-6 levels (p < 0.01). CONCLUSIONS: Deficiencies in the number and function of circulating EPCs are present in patients with bronchiectasis. The changes are related to disease severity and may be partly attributed to systemic inflammation. The current findings may provide novel surrogate evaluation biomarkers and potential therapeutic target for bronchiectasis.