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1.
Immunity ; 54(11): 2595-2610.e7, 2021 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-34506733

RESUMEN

Fungal airway infection (airway mycosis) is an important cause of allergic airway diseases such as asthma, but the mechanisms by which fungi trigger asthmatic reactions are poorly understood. Here, we leverage wild-type and mutant Candida albicans to determine how this common fungus elicits characteristic Th2 and Th17 cell-dependent allergic airway disease in mice. We demonstrate that rather than proteinases that are essential virulence factors for molds, C. albicans instead promoted allergic airway disease through the peptide toxin candidalysin. Candidalysin activated platelets through the Von Willebrand factor (VWF) receptor GP1bα to release the Wnt antagonist Dickkopf-1 (Dkk-1) to drive Th2 and Th17 cell responses that correlated with reduced lung fungal burdens. Platelets simultaneously precluded lethal pulmonary hemorrhage resulting from fungal lung invasion. Thus, in addition to hemostasis, platelets promoted protection against C. albicans airway mycosis through an antifungal pathway involving candidalysin, GP1bα, and Dkk-1 that promotes Th2 and Th17 responses.


Asunto(s)
Plaquetas/inmunología , Candida albicans/fisiología , Candidiasis/complicaciones , Candidiasis/inmunología , Susceptibilidad a Enfermedades , Interacciones Huésped-Patógeno/inmunología , Hipersensibilidad/complicaciones , Hipersensibilidad/inmunología , Subgrupos de Linfocitos T/inmunología , Plaquetas/metabolismo , Hipersensibilidad/metabolismo , Activación de Linfocitos/inmunología , Subgrupos de Linfocitos T/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Células Th2/inmunología , Células Th2/metabolismo
2.
Artículo en Inglés | MEDLINE | ID: mdl-39079117

RESUMEN

Impaired airway epithelial barrier and decreased expression of E-cadherin are key features of severe asthma. As a gatekeeper of the mucosa, E-cadherin can be cleaved from the cell surface and released into the apical lumen as a soluble form (sE-cadherin).This study was aimed to investigate the role of sE-cadherin in severe asthma.Induced sputum was obtained from healthy subjects and patients with asthma. Two murine models of severe asthma were established using either TDI (toluene diisocyanate) or OVA (ovalbumin)/CFA (complete Freund's adjuvants). The role of sE-cadherin in severe asthma was evaluated by intraperitoneal injection of DECMA-1, a neutralizing antibody against sE-cadherin. Mice or THP-1-derived macrophages were treated with recombinant sE-cadherin to explore the pro-inflammatory mechanism of sE-cadherin.Severe asthma patients had a significantly higher sputum sE-cadherin level than the health subjects with mild to moderate asthma, which were positively correlated with sputum HMGB1 level and glucocorticoid dosage required for daily control. Allergen exposure markedly increased sE-cadherin level in the bronchoalveolar lavage fluid in mice. Treatment of DECMA-1 significantly attenuated allergen-induced airway inflammation and hyperresponsivenes in both models of severe asthma. While exposure to recombinant sE-cadherin dramatically up-regulated VEGF expression in THP-1-derived macrophages, and increased neutophlil and eosinophil infiltration into the airway as well as the release of VEGF and IL-6 in mice, both of which can be suppressed by pharmacological inhibition of ERK signaling.Taken together, our data indicated that sE-cadherin contributed to the airway inflammation of severe asthma in an ERK-depedent pathway.

3.
BMC Pulm Med ; 24(1): 98, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408986

RESUMEN

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.


Asunto(s)
Bronquiectasia , Eosinofilia , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Humanos , Estudios Retrospectivos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Progresión de la Enfermedad , Hospitalización , Recuento de Leucocitos , Eosinófilos , Bronquiectasia/epidemiología , Bronquiectasia/complicaciones , Eosinofilia/epidemiología , Eosinofilia/complicaciones , Hospitales
4.
Int Arch Allergy Immunol ; 184(11): 1135-1142, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37586352

RESUMEN

INTRODUCTION: Asthma is a chronic disease that affects populations worldwide. The purpose of this study was to investigate the expression of TCN1 in sputum and its correlation with inflammation and lung function in asthma. METHODS: We recruited 141 subjects, detected TCN1 mRNA level by quantitative reverse transcription polymerase chain reaction, detected TCN1 protein expression by Western blot, detected TCN1 protein level by enzyme-linked immunosorbent assay, and analyzed the correlation between TCN1 and fraction of exhaled nitric oxide (FeNO), IgE, EOS%, lung functions, and some Th2 cytokines. The diagnostic value of TCN1 was evaluated by receiver operating characteristics curve. The expression of TCN1 was further confirmed by human bronchial epithelial cell in vitro. RESULTS: Compared with the health group, the expression of TCN1 in induced sputum cells increased in asthma group and was correlated with FeNO, IgE, and EOS%. TCN1 level was also elevated in the induced sputum supernatant of asthma patients. The protein level of TCN1 in induced sputum supernatant was correlated with FeNO, IgE and PC-20, forced expiratory volume in the first second (FEV1)%pred, FEV1/FVC, and some cytokines (IL-4, IL-5, IL-10, IL-13, MUC5AC). TCN1 was also differentially expressed in patients with different severity of asthma. Four weeks after ICS treatment, the expression of TCN1 in induced sputum supernatant increased. In vitro, the protein level of TCN1 in human bronchial epithelial cells' supernatant increased after stimulated with IL-4 and IL-13. CONCLUSION: The expression of TCN1 was increased in asthma patients' sputum, and was positively correlated with some inflammatory markers, negatively correlated with lung function. TCN1 may be used as a potential biomarker for the diagnosis and treatment of asthma.


Asunto(s)
Asma , Interleucina-13 , Humanos , Asma/metabolismo , Citocinas/metabolismo , Eosinófilos/metabolismo , Volumen Espiratorio Forzado , Inmunoglobulina E/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Óxido Nítrico/metabolismo , Esputo
5.
Int Arch Allergy Immunol ; 184(5): 460-470, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36689923

RESUMEN

INTRODUCTION: circRNA played a role in a variety of diseases. This paper aimed to explore the differentially expressed circRNA in induced sputum cells of asthma patients, so as to provide new potential biomarkers and new ideas for the study of asthma. METHODS: All subjects were from the First Affiliated Hospital of Sun Yat-sen University. Differentially expressed circRNAs of asthma patients were screened by high-throughput sequencing. qRT-PCR was used to verify the expression of differential circRNAs. The association between circRNA and asthma was explored by analyzing the correlation between circRNA and clinical data and some cytokines of asthma patients. The possible ceRNA network was analyzed and predicted by online software, and the expression of each molecule in the network was preliminary verified by qRT-PCR in induced sputum cells and 16HBE cell. RESULTS: We screened a total of 49 circRNAs differentially expressed in asthma patients (including 12 circRNAs with elevated expression and 37 circRNAs with decreased expression), among which has_circSORT1 and has_circSERPINB1 were significantly elevated. Correlation analysis showed that has_circSORT1 was correlated with FeNO, EOS%, IL-17A, IFN-γ, and PC20, and has_circSERPINB1 was correlated with IL-6, IL-17A, IFN-γ, FEV1%, and FVC%. The possible existence of has_circSORT1/has-miR-185-3p/ZNFX1, a ceRNA regulatory network, in induced sputum cells of asthma patients was hypothesized by online software prediction and qRT-PCR in sputum cells and 16HBE. CONCLUSION: Differentially expressed circRNAs existed in induced sputum cells of asthma patients, among which has_circSORT1 and has_circSERPINB1 were significantly upregulated and may be involved in the process of asthma disease, which could be expected to be a potential biomarker for asthma diagnosis. In addition, a ceRNA regulatory network, has_circSORT1/has-miR-185-3p/ZNFX1, may exist in asthma.


Asunto(s)
Asma , MicroARNs , Humanos , ARN Circular/genética , MicroARNs/genética , MicroARNs/metabolismo , Esputo , Interleucina-17 , Biomarcadores/análisis , Asma/diagnóstico , Asma/genética
6.
Chin J Cancer Res ; 35(5): 511-525, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37969955

RESUMEN

Objective: DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer. This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4 gene (PTGER4) DNA methylation in plasma, appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers. Methods: We developed a multimodal prediction model with a training set of 257 individuals. The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects. In addition, we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal. Results: There were significant differences between the early-stage lung cancers and benign groups in the methylation levels. The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693, 0.497 and 0.864, respectively, while the AUCs of PTGER4 were 0.559, 0.739 and 0.619, respectively. With the highest AUC of 0.894, the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set. Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations. Conclusions: The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs. A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

7.
BMC Immunol ; 23(1): 23, 2022 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-35578178

RESUMEN

BACKGROUND: Asthma is a common chronic airway disease in the world. The purpose of this study was to explore the expression of IL1-RL1 in sputum and its correlation with Th1 and Th2 cytokines in asthma. METHODS: We recruited 132 subjects, detected IL1-RL1 protein level in sputum supernatant by ELISA, and analyzed the correlation between the expression level of IL1-RL1 and fraction of exhaled nitric oxide (FeNO), IgE, peripheral blood eosinophil count (EOS#), and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-33 and TSLP) and Th1 cytokines (IFN-γ, IL-2, IL-8). The diagnostic value of IL1-RL1 was evaluated by ROC curve. The expression of IL1-RL1 was further confirmed by BEAS-2B cell in vitro. RESULTS: Compared with the healthy control group, the expression of IL1-RL1 in sputum supernatant, sputum cells and serum of patients with asthma increased. The AUC of ROC curve of IL1-RL1 in sputum supernatant and serum were 0.6840 (p = 0.0034), and 0.7009 (p = 0.0233), respectively. IL1-RL1 was positively correlated with FeNO, IgE, EOS#, Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-33 and TSLP) and Th1 cytokines (IFN-γ, IL-2, IL-8) in induced sputum supernatant. Four weeks after inhaled glucocorticoids (ICS) treatment, the expression of IL1-RL1 in sputum supernatant and serum was increased. In vitro, the expression of IL1-RL1 in BEAS-2B was increased after stimulated by IL-4 or IL-13 for 24 h. CONCLUSION: The expression of IL1-RL1 in sputum supernatant, sputum cells and serum of patients with asthma was increased, and was positively correlated with some inflammatory markers in patients with asthma. IL1-RL1 may be used as a potential biomarker for the diagnosis and treatment of asthma.


Asunto(s)
Asma , Proteína 1 Similar al Receptor de Interleucina-1 , Asma/inmunología , Biomarcadores/metabolismo , Citocinas/metabolismo , Eosinófilos , Humanos , Inmunoglobulina E/inmunología , Proteína 1 Similar al Receptor de Interleucina-1/biosíntesis , Proteína 1 Similar al Receptor de Interleucina-1/inmunología , Interleucinas/inmunología , Óxido Nítrico/inmunología
8.
J Gene Med ; 24(2): e3397, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34751492

RESUMEN

BACKGROUND: Aberrant expression of m6A-related proteins contributes to the occurrence and progression of non-small cell lung cancer (NSCLC). Current studies mainly focus on single m6A regulatory genes and their underlying mechanisms, and the expression of multiple m6A regulatory proteins in NSCLC remains unclear. Therefore, it is necessary to systematically examine these proteins, particularly in clinical specimens. METHODS: Bioinformatic analysis was used to determine the expression of m6A regulatory genes and their correlation with common gene mutations, such as TP53, EGFR and KRAS, using The Cancer Genome Atlas (TCGA) and the AE-meta databases. Immunohistochemistry was employed to analyze the protein expression of m6A regulatory proteins in 61 benign lung tissues and 316 NSCLC tissues. Statistical analysis was performed to calculate the correlation between the expression of m6A regulatory proteins and clinicopathological features, survival, and common gene mutations in lung carcinoma patients. RESULTS: Analysis of the mRNA levels of 13 core m6A regulators, using information from TCGA and the AE-meta databases, revealed that YTHDF1 levels were upregulated in NSCLC compared to those in adjacent normal tissues. Immunohistochemical staining showed that the expression of METTL3, ALKBH5, YTHDC2 and YTHDF1 was significantly upregulated in NSCLC tissues. Further analyses demonstrated a positive correlation between differentially expressed m6A regulatory proteins, including METTL3, ALKBH5, YTHDC2 and YTHDF1, and the poor clinicopathological features and survival of NSCLC patients. According to the statistics of NSCLC patients enrolled in the present study, the protein levels of METTL3 in patients with EGFR exon-19 mutation were higher than those in patients with wild-type EGFR. CONCLUSIONS: Our results indicate that m6A regulators, including METTL3, ALKBH5, YTHDC2 and YTHDF1, could serve as predictive markers of NSCLC, which will facilitate the early detection and diagnosis of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adenosina/genética , Adenosina/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Genes Reguladores , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Metiltransferasas/genética
9.
Int Arch Allergy Immunol ; 183(6): 673-681, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35172310

RESUMEN

INTRODUCTION: Asthma is a common chronic respiratory disease. This study aimed to explore the expression level of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in induced sputum supernatant, induced sputum cells, and serum of asthma patients. METHODS: The protein levels of CEACAM5 in induced sputum supernatant and serum were detected by enzyme-linked immunosorbent assay. The expression of CEACAM5 in induced sputum cells was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We analyzed the correlations between CEACAM5 expression and the clinical characteristics (FeNO and IgE) of asthma. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CEACAM5 in asthma. The expression level of CEACAM5 in 16HBE and BEAS-2B cells was detected by qRT-PCR. RESULTS: The expression of CEACAM5 in induced sputum supernatant, induced sputum cells, and serum of asthma patients was significantly upregulated. Asthma patients with high CEACAM5 expression in induced sputum supernatant had higher levels of FeNO, IgE, and IL-13. The expression levels of CEACAM5 in induced sputum supernatant and induced sputum cells were positively correlated with FeNO and IgE. The ROC curve showed that CEACAM5 had a good diagnostic value in asthma. CEACAM5 expression was upregulated in BEAS-2B and 16HBE cells after IL-4 or IL-13 stimulation for 48 h. CONCLUSION: The expression levels of CEACAM5 in induced sputum supernatant, induced sputum cells, and serum of asthma patients were significantly increased. CEACAM5 may be involved in eosinophilic inflammation of asthma and may be used as a diagnostic biomarker and therapeutic target of asthma.


Asunto(s)
Asma , Interleucina-13 , Asma/tratamiento farmacológico , Biomarcadores/metabolismo , Antígeno Carcinoembrionario/metabolismo , Antígeno Carcinoembrionario/uso terapéutico , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Eosinófilos/metabolismo , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/uso terapéutico , Humanos , Inmunoglobulina E , Interleucina-13/metabolismo , Óxido Nítrico/metabolismo , Esputo
10.
Int Arch Allergy Immunol ; 183(11): 1216-1225, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36063806

RESUMEN

INTRODUCTION: CXCL14 involved in inflammatory processes was upregulated in the asthma expression profile datasets in our pilot study. However, the expression of CXCL14 in induced sputum and its potential clinical role in asthma were poorly reported. OBJECTIVE: We sought to detect CXCL14 expression in airway epithelium and induced sputum cells of asthma and explore its potential clinical implications. METHODS: The expression of CXCL14 in asthma was analyzed using R software based on multiple microarray datasets, including GSE43696, GSE63142, GSE67940, and GSE76262. Subsequent verification of the CXCL14 expression pattern in induced sputum and bronchial epithelium cells was performed by qRT-PCR and ELISA. Besides, the correlations between CXCL14 and eosinophilic inflammation indicators (FeNO, EOS#, and IgE), Th2 signature genes (SERPINB2, POSTN, and CLCA1), inflammatory cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, TSLP, IL-8, IL-17A, IFN-γ, and IL-2), and airway obstruction indicators (pulmonary function and mucin secretion) were further explored. RESULTS: The expression of CXCL14 in epithelium and sputum cells was upregulated in asthma and positively correlated with clinical eosinophilic indicators. The protein levels of CXCL14 were positively associated with Th2 signature genes (SERPINB2, POSTN, and CLCA1) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, and TSLP). Increased expression of CXCL14 was also observed in BEAS-2B cells stimulated by the cytokine IL-4. Furthermore, the expression of CXCL14 was positively correlated with MUC5AC secretion and negatively associated with pulmonary function. CONCLUSIONS: Upregulated CXCL14 in asthma was positively correlated with inflammatory indicators and negatively correlated with pulmonary function, which indicated that upregulated CXCL14 might act as a pathogenic gene through involvement in Th2 inflammation in asthma.


Asunto(s)
Obstrucción de las Vías Aéreas , Asma , Eosinofilia , Humanos , Esputo , Interleucina-13/metabolismo , Interleucina-33/metabolismo , Interleucina-10/metabolismo , Interleucina-5 , Proyectos Piloto , Interleucina-4/metabolismo , Asma/metabolismo , Eosinofilia/metabolismo , Citocinas/metabolismo , Inflamación/genética , Inflamación/metabolismo , Obstrucción de las Vías Aéreas/metabolismo , Quimiocinas CXC/metabolismo
11.
BMC Pulm Med ; 22(1): 86, 2022 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-35287655

RESUMEN

BACKGROUND: Baculoviral IAP repeat-containing 3 (BIRC3) which encodes a member of the IAP family of proteins upregulated in the asthma expression profile dataset. However, there was few research on studying the clinical implication of BIRC3 in asthma. OBJECTIVE: To validate BIRC3 expression and its clinical implications in induced sputum of asthma. METHODS: Based on the GSE76262 (118 asthma cases and 21 healthy controls) dataset, differentially expressed genes were screened using R software. Subsequently, BIRC3 mRNA and protein were clinically verified in induced sputum samples through quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Besides, the correlations between BIRC3 expression and asthmatic eosinophilic/allergic inflammation indicators (FeNO, IgE, and EOS%), pulmonary function (FEV1, FEV1% pred, FVC% pred, and FEV1/FVC), and inflammatory cytokines (IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP) were analyzed. Finally, BIRC3 mRNA was detected in human primary bronchial epithelial cells stimulated by cytokines (IL-4 or IL-13). RESULTS: BIRC3 was screened as a candidate gene in the GSE76262, which was highly expressed in asthma. Highly expressed BIRC3 was positively correlated with eosinophilic and allergic indicators, including FeNO, blood eosinophil, and serum IgE. Moreover, BIRC3 protein was positively associated with inflammation cytokines, like IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP, while negatively correlated with FEV1, FEV1%pred, FVC% pred, and FEV1/FVC. Furthermore, the expression of BIRC3 could be induced in primary bronchial epithelial cells treated by cytokines IL-4 or IL-13. CONCLUSIONS: BIRC3 significantly increased in induced sputum of asthma and positively correlated with airway eosinophilic and peripheral blood allergic inflammation, type 2 cytokines, and airway obstruction. Increased BIRC3 might be involved in the pathogenesis of asthma by affecting the eosinophilic and allergic inflammation.


Asunto(s)
Asma , Esputo , Proteína 3 que Contiene Repeticiones IAP de Baculovirus/genética , Proteína 3 que Contiene Repeticiones IAP de Baculovirus/metabolismo , Citocinas/metabolismo , Eosinófilos/metabolismo , Humanos , Pruebas de Función Respiratoria , Esputo/metabolismo
12.
Am J Physiol Lung Cell Mol Physiol ; 321(1): L6-L16, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33881353

RESUMEN

Macrophage migration inhibitory factor (MIF) inhibition can attenuate pulmonary fibrosis, but the antifibrotic mechanism is unclear. Here we investigated the antifibrotic effect of MIF knockdown in rats with bleomycin (BLM)-induced pulmonary fibrosis. The results showed that MIF inhibition attenuated lung injury and extracellular matrix deposition; significantly reduced the levels of cytokines including transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), hydroxyproline (hyp), fibroblast growth factor 23 (FGF23), and secreted phosphoprotein 1 (Spp1); and inhibited the expression of CD68, F4/80, and α-smooth muscle actin (α-SMA) protein. MIF inhibition is associated with reduction of proinflammatory mediators and macrophage infiltration in lungs. In addition, MIF knockdown in the day 14 group was significantly better than MIF knockdown in day 1 group in terms of the above mentioned cytokines TGF-ß1, IL-17, TNF-α. MIF knockdown in day 14 group showed a better trend than MIF knockdown in day 1 group in inhibition of hyp and α-SMA formation. Furthermore, MIF inhibition downregulated the FGF23, Spp1, anti-integrin alpha 10 (Itga10), laminin subunit alpha 1 (Lama1), thrombospondin 2 (THBS2), and Serpin family B member 5 (SERPINB5) mRNA levels and the p-Smad2/3 protein level. MIF knockdown may inhibit fibrosis through the TGF-ß1/Smads signaling pathway. In addition, MIF inhibition protects against vascular remodeling via Thbs2 and Serpinb5 signaling. In summary, our study showed that knockdown of MIF can significantly inhibit lung inflammation and fibrosis in rats with BLM-induced pulmonary fibrosis. The future development of inhibitors targeting MIF may contribute to the treatment of pulmonary fibrosis.


Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Bleomicina/toxicidad , Oxidorreductasas Intramoleculares/antagonistas & inhibidores , Factores Inhibidores de la Migración de Macrófagos/antagonistas & inhibidores , Fibrosis Pulmonar/prevención & control , Animales , Masculino , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal
13.
Respir Res ; 22(1): 263, 2021 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-34629055

RESUMEN

BACKGROUND: Inhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger). METHODS: C57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 µg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined. RESULTS: In comparison to mice challenged only with A. niger, addition of LPS (1 µg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies. CONCLUSIONS: In contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.


Asunto(s)
Alveolitis Alérgica Extrínseca/microbiología , Aspergillus niger/patogenicidad , Hiperreactividad Bronquial/microbiología , Lipopolisacáridos , Pulmón/microbiología , Aspergilosis Pulmonar/microbiología , Esporas Fúngicas/patogenicidad , Alveolitis Alérgica Extrínseca/inducido químicamente , Alveolitis Alérgica Extrínseca/inmunología , Alveolitis Alérgica Extrínseca/fisiopatología , Animales , Aspergillus niger/inmunología , Hiperreactividad Bronquial/inducido químicamente , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/fisiopatología , Broncoconstricción , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Exposición por Inhalación , Pulmón/inmunología , Pulmón/fisiopatología , Ratones Endogámicos C57BL , Aspergilosis Pulmonar/inmunología , Aspergilosis Pulmonar/fisiopatología , Esporas Fúngicas/inmunología , Linfocitos T Colaboradores-Inductores/inmunología
14.
BMC Infect Dis ; 21(1): 79, 2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33461503

RESUMEN

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.


Asunto(s)
COVID-19/inmunología , Citocinas/sangre , Linfocitos , Adulto , Anciano , Linfocitos B , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos , COVID-19/sangre , Femenino , Humanos , Interleucina-10 , Células Asesinas Naturales/inmunología , Recuento de Linfocitos , Subgrupos Linfocitarios , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad
15.
BMC Cancer ; 20(1): 520, 2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32503451

RESUMEN

BACKGROUND: According to the proportion of glandular and squamous pathological components, adenosquamous carcinoma (ASC) could be divided into adenocarcinoma (AC) and squamous cell carcinoma (SCC) predominant subtypes. Due to its rarity, no study investigating the impact of different subtypes on the clinical features, radiologic findings and prognosis characteristics of ASC has been reported. METHODS: Sixty eight patients who underwent surgical resection for lung adenosquamous carcinoma in our institute between January 2006 and March 2017 were retrospectively reviewed. Data regarding the clinical features, radiologic findings and prognosis characteristics were collected. RESULTS: Thirty nine patients of the study cohort were with AC-predominant ASC and 29 with SCC-predominant ASC. There was no significant difference between the two subgroups in age, gender, smoking history, serum carcinoembryonic antigen (CEA) level and T,N classification. Air bronchogram was found more frequently in AC-predominant ASC than in SCC-predominant ASC (P = 0.046). Multivariate analysis identified pathological subtype (P = 0.022) and CT findings of peripheral location (P = 0.009) to be independent prognostic factors. CONCLUSIONS: AC-predominant ASC were more commonly presented with air bronchogram, and were with a better prognosis than SCC-predominant ASC.


Asunto(s)
Carcinoma Adenoescamoso/mortalidad , Neoplasias Pulmonares/mortalidad , Pulmón/patología , Anciano , Broncografía , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/patología , Carcinoma Adenoescamoso/cirugía , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonectomía , Pronóstico , Estudios Retrospectivos
16.
Sleep Breath ; 23(4): 1283-1289, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30900058

RESUMEN

PURPOSE: Previous studies revealed that the concomitant prevalence of obstructive sleep apnea (OSA) and venous thromboembolism (VTE) was high, but the results were inconclusive due to various limitations. We aimed to systematically review the literature on the prevalence of OSA in patients with VTE. METHODS: Relevant studies were identified on multiple electronic databases through July 2018. The DerSimonian-Laird random effects model was used to calculate the pooled prevalence of OSA, moderate-to-severe OSA, and severe OSA in VTE patients, respectively. Sensitivity analysis was performed based on diagnostic methods of OSA and races. RESULTS: A total of 11 studies comprising 895 patients were available for the meta-analysis, but one study was excluded because of the between-study heterogeneity in the following analysis. The pooled prevalence of OSA, moderate-to-severe OSA, and severe OSA in VTE patients were 70% (95% CI = 65%, 75%), 41% (95% CI = 29%, 54%), and 19% (95% CI = 15%, 23%), respectively. Sensitivity analysis indicated that the prevalence was similar in different diagnostic methods, but the contributions of races to OSA were complex. Although the lower prevalence of all OSA and moderate-to-severe OSA as compared with Western countries, Asian countries have similar or even a little bit higher prevalence of severe OSA. CONCLUSIONS: Findings from this meta-analysis supported that the prevalence of OSA in VTE patients was strikingly high. Screening for OSA in patients with VTE is necessary for developing effective treatment strategies.


Asunto(s)
Apnea Obstructiva del Sueño/epidemiología , Tromboembolia Venosa/epidemiología , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prevalencia , Pronóstico , Apnea Obstructiva del Sueño/diagnóstico , Tromboembolia Venosa/diagnóstico
17.
Int Arch Allergy Immunol ; 176(2): 124-132, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29642055

RESUMEN

The T helper 2 (Th2)-type response was considered the hypostasis of allergic airway diseases, including asthma and allergic rhinitis (AR). However, more recent studies have suggested that allergic airway inflammation also depends on innate immunity and is closely related to group 2 innate lymphoid cells (ILC2s). This study evaluated the ILC2 levels of asthma subjects, patients with asthma and AR, and healthy individuals, regarding how to investigate the relationship between clinical data and ILC2 levels. It was found that asthma patients and asthma with AR patients had higher ILC2 levels compared to healthy subjects. ILC2s were positively correlated with the percentage of eosinophils in patients with asthma and AR, but not with pulmonary function. ILC2 levels were higher in mild asthma subjects than in patients with severe asthma. This study provides a new interpretation of the pathogenesis of allergic airway inflammation and may provide a new direction for the diagnosis and assessment of allergic airway diseases.


Asunto(s)
Asma/inmunología , Eosinófilos/inmunología , Linfocitos/inmunología , Adulto , Asma/etiología , Asma/fisiopatología , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino
18.
Nucleic Acids Res ; 43(21): 10474-91, 2015 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-26405199

RESUMEN

PIWI interacting RNAs (piRNAs) are highly expressed in germline cells and are involved in maintaining genome integrity by silencing transposons. These are also involved in DNA/histone methylation and gene expression regulation in somatic cells of invertebrates. The functions of piRNAs in somatic cells of vertebrates, however, remain elusive. We found that snoRNA-derived and C (C')/D' (D)-box conserved piRNAs are abundant in human CD4 primary T-lymphocytes. piRNA (piR30840) significantly downregulated interleukin-4 (IL-4) via sequence complementarity binding to pre-mRNA intron, which subsequently inhibited the development of Th2 T-lymphocytes. Piwil4 and Ago4 are associated with this piRNA, and this complex further interacts with Trf4-Air2-Mtr4 Polyadenylation (TRAMP) complex, which leads to the decay of targeted pre-mRNA through nuclear exosomes. Taken together, we demonstrate a novel piRNA mechanism in regulating gene expression in highly differentiated somatic cells and a possible novel target for allergy therapeutics.


Asunto(s)
Complejo Multienzimático de Ribonucleasas del Exosoma/metabolismo , Regulación de la Expresión Génica , Interleucina-4/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Asma/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Regulación hacia Abajo , Células HEK293 , Humanos , Interleucina-4/metabolismo , Intrones , Precursores del ARN/metabolismo , Estabilidad del ARN , ARN Interferente Pequeño/química , ARN Nucleolar Pequeño/química , Células Th2/inmunología
19.
Antimicrob Agents Chemother ; 58(1): 511-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24189261

RESUMEN

The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.


Asunto(s)
Azitromicina/efectos adversos , Azitromicina/uso terapéutico , Enfermedad Crónica/tratamiento farmacológico , Enfermedades Pulmonares/tratamiento farmacológico , Humanos
20.
Nutrients ; 16(16)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39203827

RESUMEN

Research on dietary fatty acids (FAs) and lung health has reported skeptical findings. This study aims to examine the causal relationship between circulating FAs and Chronic Obstructive Pulmonary Disease (COPD) onset and exacerbation, using a two-sample Mendelian Randomization (MR) analysis. Strong and independent genetic variants of FAs were obtained from the UK Biobank of European ancestry. The exposure traits included saturated FA (SFA), poly- and mono-unsaturated FA (PUFA and MUFA), omega-3 and omega-6 PUFA, docosahexaenoic acid (DHA), and linoleic acid (LA), all expressed as total FA (TFA) percentages. Summary statistics for COPD outcomes were obtained from the FinnGen consortium including COPD, COPD hospitalization, COPD/asthma-related infections, COPD-related respiratory insufficiency, and COPD/asthma/interstitial lung disease (ILD)-related pneumonia. The inverse-variance weighted (IVW) was the primary MR approach. MR-Egger regression and MR-PRESSO were utilized to evaluate heterogeneity and pleiotropy. MR-PRESSO tests suggested no obvious horizontal pleiotropy. MR results by the IVW approach indicated that the genetically high SFA/TFA levels were associated with an increased risk of COPD/asthma/ILD-related pneumonia (OR: 1.275, 95%CI: 1.103-1.474, p for FDR = 0.002). No significant relationship was observed between other types of FAs and COPD outcomes. Our MR analysis suggests that there is weak evidence that the genetically predicted high SFA/TFA was associated with an increased risk of pneumonia.


Asunto(s)
Ácidos Grasos Insaturados , Análisis de la Aleatorización Mendeliana , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Ácidos Grasos Insaturados/sangre , Ácidos Grasos/sangre , Asma/genética , Asma/sangre , Asma/epidemiología , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Femenino , Masculino , Ácidos Grasos Omega-3/sangre
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