Integrative genomics analysis of various omics data and networks identify risk genes and variants vulnerable to childhood-onset asthma.

BACKGROUND: Childhood-onset asthma is highly affected by genetic components. In recent years, many genome-wide association studies (GWAS) have reported a large group of genetic variants and susceptible genes associated with asthma-related phenotypes including childhood-onset asthma. However, the regulatory mechanisms of these genetic variants for childhood-onset asthma susceptibility remain largely unknown. METHODS: In the current investigation, we conducted a two-stage designed Sherlock-based integrative genomics analysis to explore the cis- and/or trans-regulatory effects of genome-wide SNPs on gene expression as well as childhood-onset asthma risk through incorporating a large-scale GWAS data (N = 314,633) and two independent expression quantitative trait loci (eQTL) datasets (N = 1890). Furthermore, we applied various bioinformatics analyses, including MAGMA gene-based analysis, pathway enrichment analysis, drug/disease-based enrichment analysis, computer-based permutation analysis, PPI network analysis, gene co-expression analysis and differential gene expression analysis, to prioritize susceptible genes associated with childhood-onset asthma. RESULTS: Based on comprehensive genomics analyses, we found 31 genes with multiple eSNPs to be convincing candidates for childhood-onset asthma risk; such as, PSMB9 (cis-rs4148882 and cis-rs2071534) and TAP2 (cis-rs9267798, cis-rs4148882, cis-rs241456, and trans-10,447,456). These 31 genes were functionally interacted with each other in our PPI network analysis. Our pathway enrichment analysis showed that numerous KEGG pathways including antigen processing and presentation, type I diabetes mellitus, and asthma were significantly enriched to involve in childhood-onset asthma risk. The co-expression patterns among 31 genes were remarkably altered according to asthma status, and 25 of 31 genes (25/31 = 80.65%) showed significantly or suggestively differential expression between asthma group and control group. CONCLUSIONS: We provide strong evidence to highlight 31 candidate genes for childhood-onset asthma risk, and offer a new insight into the genetic pathogenesis of childhood-onset asthma.

Synergistic protection of Schizandrin B and Glycyrrhizic acid against bleomycin-induced pulmonary fibrosis by inhibiting TGF-ß1/Smad2 pathways and overexpression of NOX4.

Pulmonary fibrosis, a progressive and lethal lung disease, is a major therapeutic challenge for which new therapeutic strategies are warranted. Schisandrin B (Sch B) and Glycyrrhizic acid (GA) are the principal active ingredients of Schisandra chinensis and Glycyrrhiza glabra respectively, which have been reported to protect against lung injures. The present study was aimed at exploring the combinatorial therapeutic effects on bleomycin-induced pulmonary fibrosis. Lung fibrotic injuries were induced in mice by a single intratracheal instillation of 5mg/kg bleomycin (BLM). Then, these mice were administered with Sch B (100mg/kg) or/and GA (75mg/kg) for 28days. BLM-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues were attenuated to a higher degree by combinatorial treatment than by treatment of the individual agents. The expression of TGF-ß1 and the phosphorylation of its downstream target, Smad2 were enhanced by BLM, but weakened by Sch B or/and GA. Furthermore, the significant overexpression of NADPH oxidase 4 (NOX4) was observed in BLM-induced pulmonary fibrosis, which was inhibited by Sch B or/and GA. Our study reveals that the synergistic protection by Sch B and GA against BLM-induced pulmonary fibrosis is correlated to its anti-inflammatory, anti-oxidative and anti-fibrotic properties, involving inhibition of TGF-ß1/Smad2 signaling pathways and overexpression of NOX4.

Fabrication of Thermoresponsive Nanofibers for Cell Sorting and Aligned Cell Sheet Engineering.

Poly(N-isopropylacrylamide-co-N-hydroxysuccinimide ester) was synthesized by free radical polymerization followed by gelatin grafting to obtain biocompatible thermosensitive poly(N-isopropylacrylamide-co-N-hydroxysuccinimide ester)-g-gelatin. Electrospinning was then applied to fabricate aligned thermoresponsive poly(N-isopropylacrylamide-co-N-hydroxysuccinimide ester)-g-gelatin nanofiber mats. Cell coculture study showed that this kind of nanofiber mats performed different surface adhesion to rat fibroblast cells and phoenix cells at 37 degrees C, phoenix cells can then be sorted out firstly by gradient cooling treatment. The fibroblast cells that had attached on the nanofiber mats were allowed to proliferate to reach confluence. These fibroblast cells tended to elongate along with the oriented direction of the nanofibers during culture and finally formed oriented cell sheets. This kind of aligned cell sheet could easily detach from nanofiber mats by low temperature treatment. This technique is simple and can easily harvest target cells and aligned cell sheets with minimum invasion, which has the potential to be applied in tissue engineering and regenerative medicine.

[Response of leaf anatomical characteristics of Cyclobalanopsis gilva seedlings to drought stress].

In this study, the leaf anatomical characteristics and transpiration rate of one-year-old seedlings from three study areas including Qingyuan of Zhejiang Province, Dongkou and Jingzhou of Hunan Province were investigated using a pot planting experiment in which relative soil water content was kept as 75%-80% (control), 55%-60% (mild drought stress), 45%-50% (moderate drought stress), 30%-35% (severe drought stress), respectively. The results showed that drought stress significantly reduced the total thickness of the seedling leaves, the thickness of their upper and lower epidermis and the thickness of palisade tissue. The ratio of the palisade tissue to spongy tissue, stomatal length and width also decreased significantly, while the stomatal density increased significantly as the drought stress became more intense. The treatments of drought stress had no significant effect on the thickness of the main veins of the leaves although their xylem thickness varied depending on the seedlings from the different study sites. The change of leaf structure caused the change of physiological function. As drought stress was intensified, the transpiration rate of C. gilva seedlings decreased significantly. The ratio of the palisade tissue to spongy tissue, the thickness of the lower epidermis and stomatal density of the seedlings from Dongkou of Hunan Province were significantly greater, while the transpiration rate was significantly lower than those from other two study sites for all the drought stress treatments, implying that the C. gilva seedlings from Dongkou of Hunan Province had a stronger drought-resistance ability.

The effects and measures of auricular acupressure and interactive multimedia for smoking cessation in college students.

The earlier one starts to smoke, the more likely it is that one's tobacco use will increase. Either auricular acupressure or multimedia education could improve physiological health status and reduce smoking for young smokers. This study aimed to evaluate the effects of a 10-week auricular acupressure (AA) and interactive multimedia (IM) on smoking cessation in college smokers. A pre- and posttest control research design with two experiments (AA and IM) and one control was used. Thirty-two participants were in each of three groups. A significant difference from pretest to posttest among three groups was exhibited on carbon monoxide (CO), cotinine, and nicotine dependence. Scheffe's post hoc test found significances on CO in the AA between the IM and the control and cotinine and nicotine dependence between the AA and the control. After controlling the covariates, the main effect of the group was no difference in all outcomes. The interventions, especially AA, may contribute to a decrease of CO, cotinine, and nicotine dependence along with the time change. An analysis without controlling influences may overestimate interventional effects.

Diagnosis of multiple primary lung cancer: a systematic review.

A substantial percentage (8%) of all newly diagnosed cancer cases are in patients with previous tumours, with a similar trend in lung cancer. Cases of multiple primary lung cancer (MPLC) are increasing worldwide, due to improved diagnostic and surveillance mechanisms and the ageing population. Diagnosis of MPLC is complicated by difficulties in distinguishing it from lung cancer metastasis. Clinicopathological assessment, diagnosis and management have evolved, but remain severely limited by the lack of robust and dependable molecular markers for the differential diagnosis of metastasis and MPLC. This systematic review evaluates diagnostic criteria for MPLC, and the subsequent management and success rates. The incorporation of molecular biology techniques into the diagnostic process for MPLC is also discussed.

Pulmonary arterial hypertension and microRNAs--an ever-growing partnership.

Pulmonary arterial hypertension (PAH) is a debilitating condition with progressive remodeling of the pulmonary resistance vessels. PAH is characterized by multifocal, polyclonal lesions inhabited by cells that underwent phenotypic transition, resulting in altered cell proliferation and contractility, ultimately resulting in increased vascular resistance. Diagnosis of PAH is confounded by the fact that it is largely asymptomatic in the initial stages. In fact, idiopathic PAH patients >65 years of age cannot be diagnosed hemodynamically due to high pulmonary capillary wedge pressure. This highlights the need for defining more robust molecular biomarkers for PAH diagnosis and progression. Recent studies have indicated that microRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression, play a discrete role in vascular inflammation and in the etiology of cardiovascular pathologies inclusive of PAH and can potentially serve as diagnostic biomarkers. However, a cohesive understanding of global miRNA-mediated molecular events that control pulmonary vasculature plasticity is lacking which, if addressed systematically, can lead to detailed elucidation of the downstream cellular pathways that are affected by activation/silencing of silenced cognate transcripts. In turn, this can lead to not only robust biomarkers, but also to novel therapeutic strategies targeting more upstream regulators than the existing ones targeting more downstream effectors. The current review aims to provide a summary understanding of PAH, its associated pathophysiology, current knowledge of the role of miRNAs in PAH, and identifies grey areas that need further research for successful bench-to-bedside transition of these exciting new discoveries.

Comparative study of solitary thin-walled cavity lung cancer with computed tomography and pathological findings.

BACKGROUND: Solitary thin-walled cavity lung cancer is a specific form of lung cancer, the diagnosis of which remains a formidable challenge. OBJECTIVE: By comparing the computed tomography (CT) presentations and pathological findings, the purpose of present study was to explain the possible mechanism of thin-walled cavity formation and to improve the diagnostic accuracy for this disease. METHODS: The medical records of eighteen patients with solitary thin-walled cavity lung cancer were analyzed retrospectively. RESULTS: Chest CT demonstrated that solitary thin-walled cavities located at pulmonary periphery, and all these cavity lesions displayed suspected malignant signs. Pathological findings after surgery confirmed these lesions were adenocarcinoma, most of which were moderately or well differentiated. Microscopic findings showed tumor cells proliferated in the surface of thin-wall cavity in nine patients and infringed bronchiolar wall in five patients. No obvious necrotic tumor cell was observed in each patient. CONCLUSION: It was suggested some thin-walled cavities may be formed as a result of unidirectional check-valve mechanism. Together, a high index of awareness of this suspected CT signs is required for early diagnosis of this disease.