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We previously reported the involvement of serotonin (5-HT) metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo. Here, we report cigarette smoke as a source of serotonin (5-HT) to the airways and aim at investigating the effects of 5-HT on oxidative stress and inflammation in human bronchial epithelial cells (BEAS-2B). A 5-HT analog was identified to be present in aqueous phase cigarette smoke using the LC-MS/MS approach, which was later confirmed by a 5-HT enzyme-linked immune assay (EIA). Furthermore, exposure to 5-HT caused a time-dependent elevation of intracellular ROS level, which was blocked in the presence of apocynin (a NOX inhibitor). In support, the immunoblot analysis indicated that there was an increase in the expression of NOX2 time-dependently. 5-HT-induced elevation of IL-8 at both mRNA and protein levels was observed, which was inhibited by TEMPOL (a free radical scavenger), and inhibitors for p38 MAPK (SB203580) and ERK (U0126), in line with the time-dependent phosphorylation of p38 MAPK and ERK. In conclusion, our findings suggest that 5-HT presented in bronchial epithelium of smokers may be involved in cigarette smoke-induced oxidative stress and inflammation via activation of p38 MAPK and ERK pathway after the formation of free radicals.  相似文献   
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Variation of polysaccharide concentration in irrigation-channel sediment was determined concurrently with biological, chemical and physical factors influencing the benthic algal community. Phenol-sulphuric acid method was used to measure polysaccharide concentration. Polysaccharide concentration, biomass of benthic algae, and species composition changed spatially and temporally. Fluctuations of total suspended solid (TSS) concentration and exposure of channel bed to direct sunlight had major effects on algal growth and polysaccharide production. Polysaccharide concentration was correlated to chlorophyll a concentration (r=0.73, P<0.001) and algal biomass (r=0.57, P<0.001). Fragilaria construens and Aulacoseira (Melosira) italica were the most common diatoms in the benthic flora. Chlorophyll a concentration in the sediment showed a strong negative correlation (r=-0.99, P<0.001) with the seasonal variation of TSS concentration in channel water. The polysaccharides produced by benthic microorganisms play a major role in clogging channel bed and thereby reducing seepage from earthen irrigation channels. Correlations between polysaccharide concentration and chlorophyll a (and algal biomass) further indicate the importance of benthic algae for polysaccharide production. Since availability of light to the algal flora is critical for the production of polysaccharides, the effect of clogging can be maximized by exposing the channel bed to direct sunlight during non-irrigation period (winter).  相似文献   
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A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA.  相似文献   
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The structure of monomeric human chemokine IL-8 (residues 1–66) was determined in aqueous solution by NMR spectroscopy. The structure of the monomer is similar to that of each subunit in the dimeric full-length protein (residues 1–72), with the main differences being the location of the N-loop (residues 10–22) relative to the C-terminal α-helix and the position of the side chain of phenylalanine 65 near the truncated dimerization interface (residues 67–72). NMR was used to analyze the interactions of monomeric IL-8 (1–66) with ND-CXCR1 (residues 1–38), a soluble polypeptide corresponding to the N-terminal portion of the ligand binding site (Binding Site-I) of the chemokine receptor CXCR1 in aqueous solution, and with 1TM-CXCR1 (residues 1–72), a membrane-associated polypeptide that includes the same N-terminal portion of the binding site, the first trans-membrane helix, and the first intracellular loop of the receptor in nanodiscs. The presence of neither the first transmembrane helix of the receptor nor the lipid bilayer significantly affected the interactions of IL-8 with Binding Site-I of CXCR1.  相似文献   
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Six male Quechua Indians (34.0 +/- 1.1 yr, 159.5 +/- 2.1 cm, 60.5 +/- 1.6 kg), life-long residents of La Raya, Peru (4,350-m altitude with an average barometric pressure of 460 Torr), were studied using noninvasive methods to determine the structural and functional changes in the cardiovascular system in response to a 6-wk deacclimation period at sea level. Cardiac output, stroke volume, and left ventricular ejection fractions were determined using radionuclide angiographic techniques at rest and during exercise on a cycle ergometer at 40, 60, and 90% of a previously determined maximal O2 consumption. Subjects at rest were subjected to two-dimensional and M-mode echocardiograms and a standard 12-lead electrocardiogram. Hemoglobin and hematocrit were measured on arrival at sea level by use of a Coulter Stacker S+ analyzer. After a 6-wk deacclimation period, all variables were remeasured using the identical methodology. Hemoglobin values decreased significantly over the deacclimation period (15.7 +/- 1.1 to 13.5 +/- 1.2 g/dl; P less than 0.01). The results indicate that the removal of these high-altitude-adapted natives from 4,300 m to sea level for 6 wk results in only minor changes to the cardiac structure and function as measured by these noninvasive techniques.  相似文献   
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Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.  相似文献   
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A survey was made of the presence, copy number and location of the Salmonella-specific DNA insertion element IS200, within the genomes of the 27 phage type strains of Salmonella enteritidis. All the phage type strains contained copies of IS200 revealed by genomic Southern blot hybridizations with a 300-bp DNA probe internal to the element. Restriction site variation around IS200 insertion sites was examined. Three fundamental patterns of hybridization corresponding to chromosomal IS200 loci were found. In terms of population genetics, these 'IS200 profiles' correspond to clonal lineages of recent evolutionary origin, and underline the phage-typing scheme for epidemiological subdivision of S. enteritidis. The molecular analysis is consistent with genetic selection pressures which are apparent in the observed epidemiological distribution of S. enteritidis, since each clonal lineage contained one of the phage types of major clinical importance in the U.K.  相似文献   
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