The upregulation of peripheral CD3-CD56+CD16+ natural killer cells correlates with Th1/Th2 imbalance in asthma patients during acute upper respiratory viral infections.

PURPOSE: The aim of this study is to clarify the changes of peripheral CD3-CD56+CD16+ NK cells and their correlation with Th1/Th2 immunity profiles in asthma during the phase of acute upper respiratory viral infections (AURVIs). METHODS: Peripheral venous blood and induced sputum samples were collected from 56 mild asthma patients, 49 asthma patients with AURVIs and 50 healthy subjects. Peripheral CD3-CD56+CD16+ NK cells were monitored by flow cytometry during the course of acute viral infections. Meanwhile, the induced sputum Th2 cytokines IL-4 and IL-5, and Th1 cytokine IFN-γ were also detected by ELISA assay. RESULTS: The asthmatics had lower levels of peripheral CD3-CD56+CD16+ NK cells populations as well as higher induced sputum cytokines (IL-4, IL-5 and IFN-γ) compared to healthy controls at baseline. Upon upper respiratory viral infections, peripheral CD3-CD56+CD16+ NK cells numbers in asthma patients sharply elevated on day 3 and slowly decreased by day 14, in accordance with induced sputum IFN-γ changes. IL-4 and IL-5 levels spiked much later (day 8) and lasted until day 14. Compared with asthma alone group, the IFN-γ/IL-4 and IFN-γ/IL-5 ratios of the asthma patients with AURVIs on day 1 were higher and peaked on day 3. The changes of peripheral CD3-CD56+CD16+ NK cells proportions positively correlated with the IFN-γ/IL-4 and IFN-γ/IL-5 ratios on day 1 to day 3 in asthma subsequent to upper respiratory viral infections. CONCLUSIONS: Our findings showed an imbalanced Th1/Th2 immunity in airways of asthma with acute upper respiratory viral infections. Upregulated peripheral CD3-CD56+CD16+ NK cells play a crucial role in biased Th1 immunity of airways in asthma during the acute phase of viral infections. The anti-viral Th1 immunity by targeting NK cells may be a possible therapeutic option for virus-induced asthma exacerbation.

Diagnostic efficacy of visual subtypes and low attenuation area based on HRCT in the diagnosis of COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Current gold standard criteria, pulmonary function tests (PFTs) may result in underdiagnosis of potential COPD patients. Therefore, we hypothesize that the combination of high-resolution computed tomography (HRCT) and clinical basic characteristics will enable the identification of more COPD patients. METHODS: A total of 284 patients with respiratory symptoms who were current or former smokers were included in the study, and were further divided into 5 groups of GOLD grade I-IV and non-COPD according to PFTs. All patients underwent inspiratory HRCT scanning and low attenuation area (LAA) was measured. Then they were divided into seven visual subtypes according to the Fleischner Society classification system. Non-parametric tests were used for exploring differences in basic characteristics and PFTs between different groups of enrolled patients and visual subtypes. Binary logistic regression was to find the influencing factors that affected the patients' outcome (non-COPD vs GOLD I-IV). The area under the receiver operating characteristic curve (AUC-ROC) was to explore the diagnostic efficacy of LAA, visual subtypes, and combined basic characteristics related to COPD for COPD diagnosis. Finally, based on the cut-off values of ROC analysis, exploring HRCT features in patients who do not meet the diagnostic criteria but clinically suspected COPD. RESULTS: With the worsening severity of COPD, the visual subtypes gradually progressed (p < 0.01). There was a significant difference in LAA between GOLD II-IV and non-COPD (p < 0.0001). The diagnostic efficacy of LAA, visual subtypes, and LAA combined with visual subtypes for COPD were 0.742, 0.682 and 0.730 respectively. The diagnostic efficacy increased to 0.923-0.943 when basic characteristics were added (all p < 0.001). Based on the cut-off value of ROC analysis, LAA greater than 5.6, worsening of visual subtypes, combined with positive basic characteristics can help identify some potential COPD patients. CONCLUSION: The heterogeneous phenotype of COPD requires a combination of multiple evaluation methods. The diagnostic efficacy of combining LAA, visual subtypes, and basic characteristics achieves good consistency with current diagnostic criteria.

Solar ultraviolet B radiation promotes α-MSH secretion to attenuate the function of ILC2s via the pituitary-lung axis.

The immunomodulatory effects of ultraviolet B (UVB) radiation in human diseases have been described. Whether type 2 lung inflammation is directly affected by solar ultraviolet (UV) radiation is not fully understood. Here, we show a possible negative correlation between solar UVB radiation and asthmatic inflammation in humans and mice. UVB exposure to the eyes induces hypothalamus-pituitary activation and α-melanocyte-stimulating hormone (α-MSH) accumulation in the serum to suppress allergic airway inflammation by targeting group 2 innate lymphoid cells (ILC2) through the MC5R receptor in mice. The α-MSH/MC5R interaction limits ILC2 function through attenuation of JAK/STAT and NF-κB signaling. Consistently, we observe that the plasma α-MSH concentration is negatively correlated with the number and function of ILC2s in the peripheral blood mononuclear cells (PBMC) of patients with asthma. We provide insights into how solar UVB radiation-driven neuroendocrine α-MSH restricts ILC2-mediated lung inflammation and offer a possible strategy for controlling allergic diseases.

[Cloning and characterization of cDNA encoding Psammosilene tunicoides squalene synthase].

The total triterpene saponins of Psammosilene tunicoides have significant pharmacologic activity. Psammosilene tunicoides squalene synthase (PSS) is a gateway enzyme to regulate the biosynthesis of total triterpene saponins extracted from the root of Psammosilene tunicoides which is an endangered species. In this paper, cDNA encoding of PSS was cloned by the degenerate primer PCR and rapid-amplification of cDNA ends (RACE). The full-length of cDNA of PSS is 1663 bp, with an open reading frame (ORF) of 1 245 bp, encoding 414 amino acid polypeptide (calculated molecular mass, 47.69 kDa), 5'UTR (untranslated region) and 3'UTR are 260 bp and 158 bp, respectively. The deduced amino acid sequence of PSS has higher homology with the known squalene synthases of several species such as Panax notoginseng (83%), Panax ginseng (82%) and Glycyrrhiza glabra (82%) than that with Schizosacharomyces pombe (35%), Candida albicans (39%) and Homo sapiens (47%). The characterization of PSS was done by a series of methods, such as prokaryotic expression, the activity of enzyme in vitro, capillary gas chromatography (GC) and capillary gas chromatography mass spectrometry (GC-MS). The results showed that the cell-free extract of E. coli transformed with the recombinant plasmid can effectively convert farnesyl diphosphate into squalene in vitro. GenBank accession number is EF585250. Our research provided important base for the study of Psammosilene tunicoides secondary metabolism and metabolic engineering.

Pathogenic mechanisms of lung adenocarcinoma in smokers and non-smokers determined by gene expression interrogation.

Cigarette smoking is the leading risk factor for lung cancer, which accounts for the highest number of cancer-related mortalities worldwide in men and women. Individuals with a history of smoking are 15-30 times more likely to develop lung cancer compared with those who do not smoke. However, our understanding of the underlying molecular mechanisms that contribute to lung tumorigenesis in smokers versus non-smokers remains incomplete. In order to investigate such mechanisms, the present study aimed to systemically interrogate microarray datasets from tumor biopsies and matching normal tissues from stage I and II lung adenocarcinoma patients who had never smoked or were current smokers. The gene expression analysis identified 422 (99 upregulated and 323 downregulated) and 534 (174 upregulated and 360 downregulated) differentially-expressed genes from the never-smokers and current smokers, respectively, and the two groups shared 277 genes that exhibited similar trends of alteration. These genes encode regulators that are involved in a variety of cellular functions, including collagen metabolism and homeostasis of caveolae plasma membranes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes characterization indicated that biological pathways, including extracellular matrix-receptor interaction and cell migration and proliferation, were all affected in the lung cancer patients regardless of the smoking status. However, smoking induced a unique gene expression pattern characterized by upregulation of cell cycle regulators (CDK1, CCNB1 and CDC20), as well as significantly affected biological networks, including p53 signaling pathways. Taken together, these findings suggest novel mechanistic insights, and provide an improved understanding of the smoking-induced molecular alterations that contribute to the pathogenesis of lung adenocarcinoma.

Sonographic Features of Endobronchial Ultrasonography Predict Intrathoracic Lymph Node Metastasis in Lung Cancer Patients.

BACKGROUND: Intrathoracic lymph node sampling by endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) has become a standard of care in staging lung cancer. This study aimed to assess the efficacy of utilizing the individual sonographic features of lymph nodes for predicting metastasis in lung cancer patients. METHODS: From January 2010 to May 2012, we retrospectively studied 459 metastatic lymph nodes in 298 lung cancer patients and 176 reactive lymph nodes in 90 patients with nonspecific inflammation. Digital videos of the lymph nodes were obtained during EBUS-TBNA and categorized according to the following characteristics: size, shape, margin, central hilar structure, echogenicity, necrosis sign, matting, calcification, and vascular patterns. The sonographic findings were compared with the final pathology results and clinical follow-up. RESULTS: Multivariate analysis revealed five independent predictive factors for lymph node metastasis: long axis, round shape, absence of central hilar structure, presence of matting, and nonhilar vascular pattern perfusion. An aggregate score system based on the odds ratio was developed and reduced the criteria to four factors: presence of matting, nonhilar vascular pattern perfusion, absence of central hilar structure, and round shape. It showed at least two of four independent predictive factors could obtain the best performance for predicting metastatic lymph nodes and yield a high sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 93.03%, 55.68%, 84.55%, 75.38%, and 82.68%, respectively. CONCLUSIONS: Sonographic features of the EBUS images can differentiate metastatic from reactive lymph nodes, so it may help predict intrathoracic lymph nodes metastasis in lung cancer patients.