RESUMO
Cigarette smoke (CS) is a risk factor for chronic obstructive pulmonary disease (COPD), which can exacerbate inflammation and oxidative stress. Pristimerin (Pris) is a natural compound with antioxidant and anti-inflammatory effects. We managed to evaluate the protective effects of Pris on CS-induced COPD. The CS-induced COPD mice model and cell model were constructed. The effects of Pris treatment on lung function, inflammatory cell infiltration, myeloperoxidase (MPO), and pathological changes of lung tissues in mice model were evaluated. The impacts of Pris treatment on inflammatory factors, chemokines, and oxidative stress parameters in mice lung tissues and cells were determined by kits. The viability of human bronchial epithelial cells after Pris treatment was tested by CCK-8. The activation of NF-κB pathway was confirmed by Western blot and immunofluorescence. CS treatment impaired lung function, reduced weight of mice, and enhanced inflammatory cell infiltration, MPO, and lung tissue damage, but these effects of CS were reversed by Pris treatment. Furthermore, Pris treatment downregulated the levels of malondialdehyde, IL-6, IL-1ß, TNF-α, CXCL1, and CXLC2, but upregulated superoxide dismutase and catalase levels. Pris treatment could overturn CS-induced activation of the NF-κB pathway. Pris alleviates CS-induced COPD by inactivating NF-κB pathway.
Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Animais , Fumar Cigarros/efeitos adversos , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Pulmão/metabolismo , Camundongos , NF-kappa B/metabolismo , Triterpenos Pentacíclicos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Nicotiana/metabolismoRESUMO
OBJECTIVE: To study the effect of lncRNA WT1-AS on oxidative stress injury (OSI) and apoptosis of neurons in Alzheimer's disease (AD) and its specific mechanisms related to the microRNA-375 (miR-375)/SIX4 axis and WT1 expression. RESULTS: After bioinformatic prediction, WT1-AS was found to be downregulated in Aß25-35treated SH-SY5Y cells, and WT1-AS overexpression inhibited WT1 expression. WT1 could target miR-375 to promote its expression. miR-375 bound to SIX4, and miR-375 overexpression inhibited SIX4 expression. WT1-AS inhibited OSI and apoptosis, while WT1 and miR-375 overexpression or SIX4 silencing reversed the WT1-AS effect on OSI and apoptosis. In vivo experiments revealed that WT1-AS improved learning/memory abilities and inhibited OSI and apoptosis in AD mice. CONCLUSION: Overexpression of WT1-AS can inhibit the miR-375/SIX4 axis, OSI and neuronal apoptosis in AD by inhibiting WT1 expression. METHODS: Related lncRNAs were identified, and miR-375 downstream targets were predicted. WT1-AS, WT1, miR-375 and SIX4 expression was detected in a cell model induced by Aß25-35. The binding of WT1 with miR-375 and that of miR-375 with SIX4 were further confirmed. Adenosine triphosphate (ATP), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) activities, and apoptosis levels were tested after mitochondrial membrane potential observation. Learning/memory abilities and neuronal apoptosis were tested in a mouse model.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/toxicidade , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , RNA Longo não Codificante/metabolismo , Transativadores/metabolismo , Proteínas WT1/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Animais , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Teste do Labirinto Aquático de Morris , Neurônios/metabolismo , Neurônios/patologia , RNA Longo não Codificante/genética , Transdução de Sinais , Transativadores/genética , Proteínas WT1/genéticaRESUMO
Epilepsy is a common type of neurological disorder with complex etiology. The mechanisms are still not clear. MicroRNAs are endogenous noncoding RNAs with many physiological activities. Multiple microRNAs were abnormally expressed in status epilepticus, including miR-210. In this study, we applied lithium chloride and pilocarpine to induce epileptic activity and aimed to disclose the potential mechanisms. Our data showed that miR-210 was significantly upregulated in hippocampus one day after modeling (P<0.05 vs control) and the high expression of miR-210 lasted for at least 30 days. By contrast, γ-aminobutyric acid (GABA) level significantly decreased concurrently after modeling (P<0.05 vs control). To question whether miR-210 could be a potential therapeutic target for epilepsy, miR-210 inhibitor was administrated through intrahippocampal injection after epilepsy modeling. Our data showed that morphological changes of hippocampal neurons and apoptosis triggered by epilepsy were mitigated by miR-210 inhibition. More importantly, the expressions of GABA-related proteins, including GABAA receptor α1, glutamate decarboxylase, and GABA transporter 1, were significantly elevated after epilepsy modeling in both mRNA and protein levels 3 days postmodeling (P<0.05 vs control), which were mitigated by miR-210 inhibitor treatment (P<0.05 vs model). In addition, epilepsy-induced upregulation of GABA transaminase was alleviated by miR-210 inhibitor. Taken together, these data implicated potential roles of miR-210 in lithium chloride-pilocarpine-induced epilepsy model and miR-210 could serve as a potential therapeutic target in status epilepticus.
RESUMO
The major histocompatibility complex (MHC) plays an important role in immune response. Avian MHCs are not well characterized, only reporting highly compact Galliformes MHCs and extensively fragmented zebra finch MHC. We report the first genomic structure of an endangered Pelecaniformes (crested ibis) MHC containing 54 genes in three regions spanning ~500â kb. In contrast to the loose BG (26 loci within 265â kb) and Class I (11 within 150) genomic structures, the Core Region is condensed (17 within 85). Furthermore, this Region exhibits a COL11A2 gene, followed by four tandem MHC class II αß dyads retaining two suites of anciently duplicated "αß" lineages. Thus, the crested ibis MHC structure is entirely different from the known avian MHC architectures but similar to that of mammalian MHCs, suggesting that the fundamental structure of ancestral avian class II MHCs should be "COL11A2-IIαß1-IIαß2." The gene structures, residue characteristics, and expression levels of the five class I genes reveal inter-locus functional divergence. However, phylogenetic analysis indicates that these five genes generate a well-supported intra-species clade, showing evidence for recent duplications. Our analyses suggest dramatic structural variation among avian MHC lineages, help elucidate avian MHC evolution, and provide a foundation for future conservation studies.
Assuntos
Aves/genética , Genoma , Complexo Principal de Histocompatibilidade/genética , Filogenia , Sequência de Aminoácidos , Animais , Sequência de Bases , Cromossomos Artificiais Bacterianos/metabolismo , Éxons/genética , Regulação da Expressão Gênica , Genômica , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/genética , Hibridização in Situ Fluorescente , Anotação de Sequência Molecular , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Sequências Repetitivas de Ácido Nucleico/genética , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
We present a case of gastric and intestinal Crohn's disease associated with extra-intestinal manifestations of fever, rash in the lower limbs in a 12 years old boy. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed for the diagnosis of the disease causing fever of unknown origin. Gastroscopy showed polypoid hyperplasia and ulcers in the stomach and their pathology suggested gastric Crohn's disease. Intestinal Crohn's disease was also diagnosed. Corticosteroids were temporarily effective. During 2 years of follow-up, there were clinical remissions and relapse confirmed by endoscopy in both the stomach and the small intestine.
Assuntos
Doença de Crohn/diagnóstico , Enterite/diagnóstico por imagem , Fluordesoxiglucose F18 , Gastrite/diagnóstico por imagem , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Criança , Diagnóstico Diferencial , Humanos , Masculino , Compostos RadiofarmacêuticosRESUMO
Defensins play a key role in the innate immunity of various organisms. Detailed genomic studies of the defensin cluster have only been reported in a limited number of birds. Herein, we present the first characterization of defensins in a Pelecaniformes species, the crested ibis (Nipponia nippon), which is one of the most endangered birds in the world. We constructed bacterial artificial chromosome libraries, including a 4D-PCR library and a reverse-4D library, which provide at least 40 equivalents of this rare bird's genome. A cluster including 14 ß-defensin loci within 129â kb was assigned to chromosome 3 by FISH, and one gene duplication of AvBD1 was found. The ibis defensin genes are characterized by multiform gene organization ranging from two to four exons through extensive exon fusion. Splicing signal variations and alternative splice variants were also found. Comparative analysis of four bird species identified one common and multiple species-specific duplications, which might be associated with high GC content. Evolutionary analysis revealed birth-and-death mode and purifying selection for avian defensin evolution, resulting in different defensin gene numbers among bird species and functional conservation within orthologous genes, respectively. Additionally, we propose various directions for further research on genetic conservation in the crested ibis.
Assuntos
Aves/genética , Genoma , Família Multigênica , Filogenia , beta-Defensinas/genética , Processamento Alternativo , Sequência de Aminoácidos , Animais , Aves/classificação , Aves/imunologia , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Sequência Conservada , Espécies em Perigo de Extinção , Éxons , Dosagem de Genes , Duplicação Gênica , Biblioteca Gênica , Loci Gênicos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Alinhamento de Sequência , Especificidade da Espécie , beta-Defensinas/imunologiaRESUMO
The in vivo antimutagenicity of Se-enriched rice was evaluated by bone marrow micronucleus and testicle chromosomal aberrations assay in mice exposed to cyclophosphamide (CP) and mitomycin C (MMC). Regular rice did not alter the occurrence of chemical-induced mutation. However, the addition of Se-enriched rice or selenite significantly inhibited the incidence of CP-induced micronuclei and MMC-induced chromosomal aberration in mice and the effect was dose-dependent. Providing selenite or Se-enriched rice also significantly increased the activity of glutathione peroxidase in liver and the selenium concentration in blood compared to regular rice. No significant differences were found in mice body weight gain. These results revealed the antimutagenic potential of Se-enriched rice against chemical-induced mutation.
Assuntos
Antimutagênicos/farmacologia , Ciclofosfamida/toxicidade , Mitomicina/toxicidade , Oryza , Selênio/farmacologia , Animais , Células da Medula Óssea , Aberrações Cromossômicas , Dieta , Feminino , Masculino , Camundongos , Testes para Micronúcleos , Selenito de Sódio/farmacologiaRESUMO
Two experiments were conducted to study the effect of the application of selenium on the selenium content of soybean and its products in two counties with selenium-deficient soil. Selenium-enriched soybean was produced by the application of sodium selenite and Se-enriched fertilizer. The selenium contents of soybeans, soybean protein and okra were determined by hydride-generation atomic fluorescence spectrometry. The results showed that the selenium contents of soybean, soybean protein, and okra were significantly increased by the application of sodium selenite and selenium-enriched fertilizer. Foliar application of selenium provided a higher efficiency for increasing the selenium content of soybean than soil application. Significant differences were found in that soybean cultivars exhibited different accumulation of selenium. There was no remarkable difference in soybean yield, soybean protein, and lipid between selenium and control. The selenium-enriched protein derived from selenium-enriched soybean could be used as a functional ingredient and soybean okra as a selenium-enriched feed for animals for increasing selenium intake.
Assuntos
Glycine max/química , Glycine max/efeitos dos fármacos , Selênio/análise , Selênio/farmacologia , China , Fertilizantes , Compostos de Selênio/análise , Compostos de Selênio/farmacologiaRESUMO
This research was to determine the effect of foliar application of selenium on increasing the antioxidant activity of tea harvested during the early spring tea producing season using a alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical scavenging method and the linoleic acid system. The results showed that the radical scavenging ability of the tea extracts followed this order during the first 60 min: selenium-enriched tea obtained by fertilization with selenate > BHT > selenium-enriched tea obtained by fertilization with selenite > alpha-tocopherol > regular tea. Se-enriched tea obtained by fertilization with selenate exhibited the highest inhibition percentage of 84.29% at 30 min. Se-enriched tea extracts provided higher hydrogen-donating capabilities than regular tea and contrasts with BHT and alpha-tocopherol at the concentration of 100 microg of solids/mL of ethanol. There was a little change in the sequence of radical scavenging ability during the later 60 min: Se-enriched tea obtained by fertilization with selenate > Se-enriched tea obtained by fertilization with selenite > BHT > regular tea > alpha-tocopherol. The individual activity of tea extracts and references measured by the linoleic acid system showed that the tea extracts, BHT, and alpha-tocopherol manifested almost the same patterns of activity as the DPPH method. Tea enriched in selenium by fertilization with selenate still exhibited the highest inhibition activity of lipid oxidation, whereas alpha-tocopherol showed the lowest inhibition. The antioxidant activity of Se-enriched green tea harvested during the early spring tea producing season is enhanced compared to regular tea.
Assuntos
Antioxidantes/análise , Camellia sinensis/química , Folhas de Planta/química , Estações do Ano , Selênio/administração & dosagem , Compostos de Bifenilo , Hidroxitolueno Butilado/química , Fertilizantes , Sequestradores de Radicais Livres/química , Peroxidação de Lipídeos , Peróxidos/análise , Picratos/química , Extratos Vegetais/química , alfa-Tocoferol/químicaRESUMO
A method of hydride generation atomic fluorescence spectrometry was applied to the determination of the selenium concentration of regular polished rice in China and selenium-enriched polished rice obtained by foliar application of selenium-enriched fertilizer in the forms of selenite and selenate. The average selenium content of regular rice was 0.025 +/- 0.011 microg g(-)(1). On the basis of a daily dietary rice intake of 300-500 g suggested by the China Nutrition Society, the total selenium intake from regular rice was calculated to be 7.5-12.5 microg per person per day for an adult. The selenium contents of rice were significantly increased to 0.471-0.640 microg g(-)(1) by foliar application of selenium-enriched fertilizer at rate of 20 g of Se ha(-)(1) in the forms of sodium selenite and sodium selenate. The selenium content of rice by application of a fertilizer of selenate was 35.9% higher than that by a fertilizer of selenite, which showed that Se-enriched fertilizer in selenate exhibited greater efficiency in increasing Se content in rice products. The Se-enriched rice products can increase daily Se intake on average by 100-200 microg of Se per day by the consumption of 400 g of rice products if the Se level of rice products is controlled at 0.3-0.5 microg of Se g(-)(1). Because rice is a staple food in China, selenium-enriched rice obtained by bioenrichment of selenium to increase the Se content of rice could be a good selenium source for the population in selenium-deficient regions.