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Rationale
Biomass is the energy source for cooking and heating for billions of people worldwide. Despite their prevalent use and their potential impact on global health, the effects of these fuels on lung biology and function remain poorly understood.Methods
We exposed human small airway epithelial cells and C57BL/6 mice to dung biomass smoke or cigarette smoke to compare how these exposures impacted lung signaling and inflammatory and proteolytic responses that have been linked with disease pathogenesis.Results
The in vitro exposure and siRNA studies demonstrated that biomass and cigarette smoke activated ERK to up regulate IL-8 and MMP-1 expression in human airway epithelial cells. In contrast to cigarette smoke, biomass also activated p38 and JNK within these lung cells and lowered the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Similarly, in the lungs of mice, both biomass and cigarette smoke exposure increased macrophages, activated ERK and p38 and up regulated MMP-9 and MMP-12 expression. The main differences seen in the exposure studies was that mice exposed to biomass exhibited more perivascular inflammation and had higher G-CSF and GM-CSF lavage fluid levels than mice exposed identically to cigarette smoke.Conclusion
Biomass activates similar pathogenic processes seen in cigarette smoke exposure that are known to result in the disruption of lung structure. These findings provide biological evidence that public health interventions are needed to address the harm associated with the use of this fuel source. 相似文献3.
Histopathological effects of cisplatin,doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats
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Hassan I El-Sayyad Mohamed F Ismail F M Shalaby RF Abou-El-Magd Rajiv L Gaur Augusta Fernando Madhwa HG Raj Allal Ouhtit 《International journal of biological sciences》2009,5(5):466-473
Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs. 相似文献
4.
Joana RF Abreu Daphne de Launay Marjolein E Sanders Aleksander M Grabiec G Marleen van de Sande Paul P Tak Kris A Reedquist 《Arthritis research & therapy》2009,11(4):R121-13
Introduction
Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases (MMPs). Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to contribute to inflammation and joint destruction in RA, and abrogation of Ras family signaling is therapeutic in animal models of RA. Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to contribute to spontaneous MMP production in melanoma cancer cells. Here, we examine the potential relationship between RasGRF1 expression and MMP production in RA, reactive arthritis, and inflammatory osteoarthritis synovial tissue and FLS. 相似文献5.
6.
Three wheat samples collected in 1987 in Central Poland and naturally infected withFusarium spp were analyzed for the presence ofFusarium spp andFusarium toxins. Heads were separated into three fractions: kernels with visibleFusarium damage, healthy looking kernels, and chaff + rachis. The samples contained deoxynivalenol (2.0 – 40.0μg/g), nivalenol (O.O1μg/g), 4,7-dideoxynivalenol (0.10 – 0.15μg/g). 15-acetyldeoxynivalenol (0.10–2.00 μg/g), 3-acetyldeoxynivalenol (O/1Oμg/g), and zearalenone (0.01–2.00μg/g). This is the first report about 15 - acetyldeoxynivalenol in European wheat and the co-occurrence of 3 - acetyldeoxynivalenol and 15-acetyldeoxynivalenol in the same sample of contaminated cereals. 相似文献
7.
Dastmalchi K Flores G Wu SB Ma C Dabo AJ Whalen K Reynertson KA Foronjy RF D Armiento JM Kennelly EJ 《Bioorganic & medicinal chemistry》2012,20(14):4549-4555
The edible fruits of Myrciaria vexator McVaugh (Myrtaceae), from northern South America, are eaten in certain locales, either fresh or processed into jellies and drinks. Activity-guided fractionation of M. vexator resulted in identification of ellagic acid (1), cyanidin-3-O-glucoside (2), delphinidin-3-O-glucoside (3), 2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid (4), and jaboticabin (5), and latter two compounds are being reported for the first time in this species. Ellagic acid was further examined, and found to inhibit cigarette smoke extract induced MMP-1 expression in vitro, and may be of significance in the treatment of chronic obstructive pulmonary (COPD). Other compounds identified for the first time from M. vexator include cyanidin-3-O-galactoside (6), cyanidin-3-O-arabinoside (7), cyanidin-3-O-rutionoside (8), petunidin (9), peonidin-3-O-galactoside (10) malvidin (11), hyperoside (12), querecetin-3-O-glucoside (13), and guajaverin (14), methyl protocatechuate (15), and protocatechuic acid (16). 相似文献
8.
Multiple duplications of yeast hexose transport genes in response to selection in a glucose-limited environment 总被引:11,自引:2,他引:9
When microbes evolve in a continuous, nutrient-limited environment, natural
selection can be predicted to favor genetic changes that give cells greater
access to limiting substrate. We analyzed a population of baker's yeast
that underwent 450 generations of glucose-limited growth. Relative to the
strain used as the inoculum, the predominant cell type at the end of this
experiment sustains growth at significantly lower steady-state glucose
concentrations and demonstrates markedly enhanced cell yield per mole
glucose, significantly enhanced high-affinity glucose transport, and
greater relative fitness in pairwise competition. These changes are
correlated with increased levels of mRNA hybridizing to probe generated
from the hexose transport locus HXT6. Further analysis of the evolved
strain reveals the existence of multiple tandem duplications involving two
highly similar, high- affinity hexose transport loci, HXT6 and HXT7.
Selection appears to have favored changes that result in the formation of
more than three chimeric genes derived from the upstream promoter of the
HXT7 gene and the coding sequence of HXT6. We propose a genetic mechanism
to account for these changes and speculate as to their adaptive
significance in the context of gene duplication as a common response of
microorganisms to nutrient limitation.
相似文献
9.
Alison M Wallace Becky A Mercer Jianqing He Robert F Foronjy Domenico Accili Andrew J Sandford Peter D Paré Jeanine M D’Armiento 《Respiratory research》2012,13(1):79
Background
Prior studies have demonstrated that the distal 1.5 kb of the MMP-1 promoter is fundamental in directing the induction of the MMP-1 gene by cigarette smoke.Methods
To characterize the genetic variants in the MMP-1 cigarette smoke-responsive element, deep re-sequencing of this element was performed on DNA samples from participants in the Lung Health Study. Furthermore, evidence of Sp1 binding to the MMP-1 promoter was assessed using chromatin immunoprecipitation assays and the influence of cigarette smoke exposure on this interaction was evaluated in cultured human small airway epithelial cells.Results
Ten polymorphisms (four novel) were detected in the cigarette smoke-responsive element. Chromatin immunoprecipitation assays to assess the protein-DNA interactions at Sp1 sites in the MMP-1 promoter showed increased binding to the Sp1 sites in the cigarette smoke-responsive element in small airway epithelial cells treated with cigarette smoke extract. In contrast, a Sp1 site outside of the element exhibited the opposite effect. None of the polymorphisms were more prevalent in the fast decliners versus the slow decliners (fast decliners = mean −4.14% decline in FEV1% predicted per year vs. decline in FEV1% predicted per year).Conclusions
Sequencing analyses identified four novel polymorphisms within the cigarette smoke-responsive element of the MMP-1 promoter. This study identifies functional activity within the cigarette smoke-responsive element that is influenced by cigarette smoke and examines this region of the promoter within a small patient population. 相似文献10.
Loss of phylogenetic information in chorion gene families of Bombyx mori gene conversion 总被引:1,自引:0,他引:1
Regier JC; Weigmann BM; Leclerc RF; Friedlander TP 《Molecular biology and evolution》1994,11(1):72-87
The silkmoth chorion has provided a stimulating model for the study of
evolution and developmental regulation of gene families. Previous attempts
at inferring relationships among chorion sequences have been based on
pairwise comparisons of overall similarity, a potentially problematic
approach. To remedy this, we identified the alignable regions of low
sequence variability and then analyzed this restricted database by
parsimony and neighbor-joining methods. At the deepest level, the chorion
sequence tree is split into two branches, called "alpha" and "beta." Within
each branch, early- and late-expressing genes each constitute monophyletic
groups, while the situation with middle-expressing genes remains uncertain.
The HcB gene family appears to be the most basal beta-branch group, but
this conclusion is qualified because the effect of gene conversion on
branching order is unknown. Previous studies by Eickbush and colleagues
have strongly suggested that ErA, HcA, and HcB families undergo gene
conversion within a gene family, whereas the ErB family does not. The
occurrence of conversion correlates with a particular tree structure;
namely, branch lengths are much greater at the base of the family than at
higher internodes and terminal branches. These observations raise the
possibility that chorion gene families are defined by gene conversion
events (reticulate evolution) rather than by descent with modification
(synapomorphy).
相似文献