Characteristics of the Swedish Population Cohort Born in 1932–1970.

<p>Characteristics of the Swedish Population Cohort Born in 1932–1970.</p

Population characteristics of Parkinson Cases and controls.

#<p>Chi-Square tests for categorical variables, t-tests for continuous variables *number of participants that provided data.</p

Study population within the Swedish Multi-generation Register (MGR).

<p>The study population included individuals who were born in Sweden during 1932–1970, with available information on maternal links in the MGR, alive and free of PD, lived in Sweden, and were 40 years or older on January 1, 2002, or turned 40 years during the study period.</p

Incidence of influenza-like illness (ILI) by year of birth.

<p>National burden of ILI in Sweden from 1932 to 1970, data in 1947–1949 were excluded due to low report rates.</p

miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1

<div><p>MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways.</p></div

H&E staining shows pathological alterations that are characteristic of acute lung injury at 6 h after LPS instillation.

<p><i>A</i>: The gross appearance showed yellow FITC-Dextran on the pulmonary surface after i.n. instillation with 10 mg of FITC-Dextran/kg body weight (b.w.) for 1 hour. The lungs of the LPS model group showed red dots and swelling. <i>B</i>: Representative normal lung histology. <i>C</i>: Lung edema (arrow) and alveolar wall thickening (arrow head) in the ALI mice. <i>D</i>: Infiltration of many inflammatory cells (arrow shows neutrophils) in the ALI mice induced with i.n. instillation with 0.5 mg of LPS/kg b.w. for 6 h (n = 4). B, C, D the magnification is 400X.</p

Pulmonary Permeability Assessed by Fluorescent-Labeled Dextran Instilled Intranasally into Mice with LPS-Induced Acute Lung Injury

<div><p>Background</p><p>Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI). However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran) intranasally.</p><p>Methods/Principal Findings</p><p>For the mouse model of direct ALI, lipopolysaccharide (LPS) was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model.</p><p>Conclusion/Significance</p><p>In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations <i>in vivo</i>. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.</p></div

Representative examples of Cav-1 expression in GC.

<p><b>A:</b> Negative Cav-1 expression in tumor cells and fibroblasts; <b>C:</b> Positive Cav-1 signal in tumor cells and fibroblasts; <b>E:</b> Positive Cav-1 signal was observed in fibroblasts, but negative in tumor cells; <b>G:</b> Positive Cav-1 signal in tumor cells, but negative in fibroblasts. (The white arrow shows the tumor cells and the white triangle shows the fibroblasts; <b>A-G:</b> 200× magnification; <b>B, D, F</b> and <b>H</b> are H&E staining; the parallel two pictures are serial sections respectively).</p

Lung permeability evaluation in the i.p. or i.n. LPS-induced ALI model by FITC-Albumin and FITC-Dextran assay.

<p><i>A</i>: The FI value of plasma FITC-Albumin (5 mg/kg b.w., via i.n. instillation) in the ALI induced i.n. by LPS (0.5 mg/kg b.w.). <i>B</i>: Similar fold changes were found between FITC-Dextran (10 mg/kg b.w., via i.n. instillation) and EB (20 mg/kg b.w., via i.v. instillation) in the 6 h and 24 h LPS (4 mg/kg b.w., via i.n. instillation) groups compared to the control groups. <i>C</i>: Lung inflammatory lesions and thickened alveolar septa observed in ALI induced by LPS i.p. (15 mg/kg b.w.) (200X magnification). <i>D</i>: The concentration of plasma FITC-Dextran is significantly increased in the LPS i.p. group compared to the control group, with 10 mg of FITC-Dextran/kg b.w. via i.n. instillation (n = 3, *P<0.05, **P<0.01).</p