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1.
Chin Med Sci J ; 37(4): 331-339, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36647592

RESUMO

Objective To investigate the expression of topoisomeraseⅡα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05). ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.


Assuntos
Carcinoma Hepatocelular , DNA Topoisomerases Tipo II , Neoplasias Hepáticas , Humanos , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Linfócitos T CD8-Positivos , Biologia Computacional , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Prognóstico , DNA Topoisomerases Tipo II/genética
2.
Sheng Li Xue Bao ; 74(5): 705-714, 2022 Oct 25.
Artigo em Zh | MEDLINE | ID: mdl-36319094

RESUMO

The purpose of this study was to investigate the effects of acute fear stress on the spatial memory and neuronal plasticity of medial prefrontal cortex (mPFC) neurons in mice, and to elucidate the mechanisms underlying mPFC plasticity and post-stress memory regulation. Male C57BL/6 mice (6 weeks old) were randomly divided into control group and stress group. Foot shock stress was applied to establish an acute fear stress model. Changes in spatial memory were examined by the Morris water maze test, and the dynamic changes in the spike encoding of pyramidal neurons and GABAergic neurons in the prelimbic cortex (PrL) and infralimbic cortex (IL) of mPFC were detected by whole-cell recording. The results showed that acute fear stress significantly enhanced the percentage of freezing and the number of freezing, reduced the average speed, decreased the escape latency during acquisition phase, extended the probing time in the first quadrant and shortened the probing time in the third quadrant during probe trial, increased inter-spike interval, energy barrier and absolute refractory period of GABAergic neurons in the PrL and pyramidal neurons in the IL, while decreased inter-spike interval, energy barrier and absolute refractory period of pyramidal neurons in the PrL and GABAergic neurons in the IL. These results suggest that acute fear stress can enhance the spatial memory of mice, elevate the excitability and function of the PrL, while deteriorate the excitability and function of the IL, and the underlying mechanism may involve the role of mPFC microcircuitry plasticity in spatial memory after stress.


Assuntos
Plasticidade Neuronal , Memória Espacial , Animais , Masculino , Camundongos , Medo , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal
3.
BMC Clin Pathol ; 14: 22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24855452

RESUMO

BACKGROUND: Whole blood gene expression-based molecular diagnostic tests are becoming increasingly available. Conventional tube-based methods for obtaining RNA from whole blood can be limited by phlebotomy, volume requirements, and RNA stability during transport and storage. A dried blood spot matrix for collecting high-quality RNA, called RNA Stabilizing Matrix (RSM), was evaluated against PAXgene® blood collection tubes. METHODS: Whole blood was collected from 25 individuals and subjected to 3 sample storage conditions: 18 hours at either room temperature (baseline arm) or 37°C, and 6 days at room temperature. RNA was extracted and assessed for integrity by Agilent Bioanalyzer, and gene expression was compared by RT-qPCR across 23 mRNAs comprising a clinical test for obstructive coronary artery disease. RESULTS: RSM produced RNA of relatively high integrity across the various tested conditions (mean RIN ± 95% CI: baseline arm, 6.92 ± 0.24; 37°C arm, 5.98 ± 0.48; 6-day arm, 6.72 ± 0.23). PAXgene samples showed comparable RNA integrity in both baseline and 37°C arms (8.42 ± 0.17; 7.92 ± 0.1 respectively) however significant degradation was observed in the 6-day arm (3.19 ± 1.32). Gene expression scores on RSM were highly correlated between the baseline and 37°C and 6-day study arms (median r = 0.96, 0.95 respectively), as was the correlation to PAXgene tubes (median r = 0.95, p < 0.001). CONCLUSION: RNA obtained from RSM shows little degradation and comparable RT-qPCR performance to PAXgene RNA for the 23 genes analyzed. Further development of this technology may provide a convenient method for collecting, shipping, and storing RNA for gene expression assays.

4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(1): 24-31, 2022 Jan.
Artigo em Zh | MEDLINE | ID: mdl-35078572

RESUMO

Objective To analyze the correlation between the expression of TOP2A gene and the proportion of CD4+T cells in hepatocellular carcinoma (HCC) and its clinical prognostic significance. Methods The expression of TOP2A mRNA in normal liver tissues and HCC tissues and its significance for survival and prognosis of HCC patients were analyzed by BioGPS, GEPIA and Kaplan-Meier Plotter databases. The coexpression gene of TOP2A and its GO function were analyzed using GENE and Metascape databases, along with the KEGG pathway enrichment analysis. The correlation between TOP2A and microsatellite instability (MSI) and DNA repair gene was analyzed by Sangerbox database. Then, the correlation between TOP2A gene and CD4+ T cells and various immune cells was analyzed by TISIDB and TIMER database, and analysis was also performed regarding the effect of CD4+ T cells on the survival and prognosis of HCC patients. Results TOP2A mRNA is not significantly expressed in normal liver tissues and CD4+ T cells, but is significantly expressed in HCC tissue, which is not conducive to the survival and prognosis of patients. The GO function of TOP2A coexpression gene is mainly enriched in cell mitosis and cell proliferation, while KEGG is mainly enriched in cell cycle and platinum drug resistance pathway. The expression of TOP2A is positively correlated with MSI, MSH2 and MSH6 of DNA repair gene, the purity of tumor cells and the numbers of various immune cells. All kinds of immune cells reported certain copy number variation in HCC, but only the numbers of CD4+ T cells showed a significant effect on the survival and prognosis of HCC patients. Conclusion There is a significant positive correlation between the expression of TOP2A mRNA and the number of CD4+T cells in HCC, which is not conducive to the survival and prognosis of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Linfócitos T CD4-Positivos , Carcinoma Hepatocelular/genética , Variações do Número de Cópias de DNA , Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Prognóstico , Linfócitos T
5.
J Food Biochem ; 46(12): e14379, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35976957

RESUMO

Diabetic nephropathy (DN) is a highly prevalent and severe diabetic complication. It is urgent to explore high efficiency and minor side effects therapy for DN. Chrysin is a natural flavonoid with various biological activities found in honey and propolis, and has considerable potential to improve DN. The study was designed to explore the effects and the specific underlying mechanism of chrysin for DN in high-fat-diet (HFD) and streptozotocin (STZ) induced DN mice. Firstly, the study revealed that chrysin effectively improved obesity, insulin resistance (IR), renal function, and pathological injury in DN mice. Secondly, the study found that chrysin improved the key indices and markers of lipid accumulation, oxidative stress, and inflammation which are closely related to the development or progression of DN. Moreover, chrysin markedly modulated lipid metabolism by regulating Adenosine 5' monophosphate-activated protein kinase (AMPK) and essential downstream proteins. Furthermore, AMPK inhibitor (Dorsomorphin) intervention partially suppressed the positive effects of chrysin on all testing indicators, indicating that activated AMPK is crucial for chrysin action on DN. The present study demonstrated that chrysin may improve DN by regulating lipid metabolism, and activated AMPK plays a critical role in the regulation of chrysin. PRACTICAL APPLICATIONS: The study verified the positive effects of chrysin on obesity, insulin resistance, kidney injury, renal function, lipid accumulation, inflammation, and oxidative stress, which are closely related to the development or progression of diabetic nephropathy (DN). Moreover, we explored that chrysin improves DN by regulating AMPK-mediated lipid metabolism. Furthermore, the AMPK inhibitor was used to confirm that activated AMPK plays a critical role in the effects of chrysin. These results could offer a full explanation and a potential option for adjuvant therapy of DN diabetes with chrysin.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Resistência à Insulina , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Estreptozocina/efeitos adversos , Metabolismo dos Lipídeos , Flavonoides/farmacologia , Inflamação , Lipídeos
6.
Curr Microbiol ; 62(3): 876-83, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21046395

RESUMO

A pathogenic bacterial strain, ST-1, was isolated from a naturally infected silkworm. The strain was identified on the basis of its physiological and biochemical properties and the results of sequence analysis of its 16S rRNA gene. The results of the 16S rRNA gene sequence analysis revealed that ST-1 shared the highest sequence identity (more than 99%) with Pseudomonas chlororaphis subsp. aurantiaca. ST-1 bacteria were gram-negative and 0.7-0.9 × 1.3-1.5 µm long, short rods with rounded ends. The strain could utilize sodium citrate, malonate, D-glucose, sucrose, D-fructose, D-mannose, and L-arabinose. Pathogenicity of ST-1 for silkworm could be depicted as a linear regression of the logarithm (y) of ST-1 concentration against probability (x) (y = 0.4040 + 0.0600x). The median lethal concentration (LC(50)) was 2.12 × 10(4) cfu/ml. In conclusion, ST-1 was identified as Ps. chlororaphis subsp. aurantiaca. This is the first report that Ps. aurantiaca is a pathogen for silkworm Bombyx mori.


Assuntos
Bombyx/microbiologia , Pseudomonas/isolamento & purificação , Pseudomonas/patogenicidade , Animais , Técnicas de Tipagem Bacteriana , Metabolismo dos Carboidratos , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Dados de Sequência Molecular , Filogenia , Pseudomonas/classificação , Pseudomonas/metabolismo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Análise de Sobrevida
7.
Undersea Hyperb Med ; 38(5): 335-43, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22013760

RESUMO

The spinal cord is one of the most commonly affected sites in decompression sickness (DCS). Alternative methods have long been sought to protect against DCS spinal cord dysfunction, especially when hyperbaric treatment is unavailable. Use of perfluorocarbon (PFC) emulsion with or without oxygen breathing has shown survival benefits in DCS animal models. The effectiveness of intravenous PFC emulsion with oxygen breathing on spinal cord function was studied. Somatosensory-evoked potentials (SSEPs) and histologic examination were chosen to serve as measures. After fast decompression (203 kPa/minute) from 709 kPa (for 60 minutes), male Sprague-Dawley rats randomly received: 1) air and saline; 2) oxygen (O2) and saline; 3) O2 and PFC emulsion. The incidence and average number of abnormal SSEP waves in survival animals that received O2 and PFC emulsion were significantly reduced (P < 0.05). Foci of demyelination, necrosis and round non-staining defects in white matter regions of the spinal cord could be found in severe DCS rats. We concluded that administration of PFC emulsion combined with oxygen breathing was beneficial for DCS spinal conductive dysfunction in rats.


Assuntos
Doença da Descompressão/complicações , Fluorocarbonos/administração & dosagem , Oxigenoterapia/métodos , Traumatismos da Medula Espinal/terapia , Animais , Terapia Combinada/métodos , Doenças Desmielinizantes/patologia , Emulsões , Potenciais Somatossensoriais Evocados/fisiologia , Infusões Intravenosas/métodos , Leucoencefalopatias/patologia , Masculino , Necrose , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
8.
Undersea Hyperb Med ; 37(3): 173-80, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20568547

RESUMO

Divers are at risk of decompression sickness (DCS) when the ambient pressure decrease exceeds a critical threshold. Hyperbaric oxygen (HBO2) preconditioning has been used to prevent various injuries, but the protective effect on DCS has not been well explored. To investigate the prophylactic effect of HBO2 on DCS, rats were pretreated with HBO2 (250 kPa-60 minutes) (all the pressures described here are absolute pressure) for 18 hours before a simulated air dive (700 kPa-100 minutes) with fast decompression to the surface at the rate of 200 kPa/min (n=33). During the following 30 minutes, the rats walked in a 3 m/minute rotating cage and were monitored for signs of DCS. The control rats were pretreated with normobaric air (n=30), normoxic hyperbaric nitrox (250 kPa, 8.4% O2) (n=13), or N(G)-nitro-L-arginine methyl ester (L-NAME) 30 minutes before HBO2 exposure (n=13). Nitric oxide (NO) levels were recorded immediately and 18 hours after HBO2 exposure in the brain and spinal cord. The incidence of DCS in rats pretreated with HBO2 was 30.3%, which was significantly lower than those treated with normobaric air (63.3%) (p<0.05) or hyperbaric nitrox (61.5%) (p<0.05). The onset time of DCS of the rats pretreated with HBO2 was significantly delayed compared with those treated with air (p<0.05). L-NAME nullified the HBO2 preconditioning effect. HBO2 increased NO level in the rat brain and spinal cord right after exposure; this effect was inhibited by L-NAME. Taken together, HBO2 preconditioning reduced the incidence of DCS in rats, and NO was involved in the prophylactic effect.


Assuntos
Doença da Descompressão/prevenção & controle , Oxigenoterapia Hiperbárica/métodos , Óxido Nítrico/metabolismo , Animais , Encéfalo/metabolismo , Doença da Descompressão/metabolismo , Inibidores Enzimáticos/administração & dosagem , Masculino , Atividade Motora/fisiologia , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/análise , Nitrogênio/administração & dosagem , Oxigênio/administração & dosagem , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Fatores de Tempo
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(4): 337-343, 2020 Apr.
Artigo em Zh | MEDLINE | ID: mdl-32519672

RESUMO

Objective To analyze the expression of pituitary tumor transforming gene 1 (PTTG1) in hepatocellular carcinoma (HCC) and its clinical prognostic implication. Methods Firstly, the Tumorsurvival and HCCDB databases were used to analyze the expression of PTTG1 gene and its co-expressed genes in HCC tissues. Secondly, cBioPortal, MetaScape, Kaplan-Meier Plotter databases were used to analyze the mutations, GO functions and KEGG of the co-expressed genes of PTTG1 in HCC, and to analyze the effects of co-expressed genes on the overall survival (OS) and prognosis of HCC patients. Finally, the TIMER database was used to analyze the expression of PTTG1 gene in the HCC immune microenvironment and its relationship with immune cells, and the impact of various immune cells on OS and prognosis of HCC patients. Results PTTG1 gene was highly expressed in HCC tissues and was not conducive to OS of HCC patients. PTTG1 had 19 significant co-expressed genes in HCC, and its co-expressed genes were also highly expressed in HCC, which was also not conducive to OS of HCC patients. The GO function of PTTG1 gene and its co-expressed genes was mainly enriched in cell division, mitosis and protein kinase binding, while KEGG was enriched in cell cycle, p53 signaling pathway and human T-lymphotropic virus (HTLV) infection. PTTG1 and its co-expressed genes were mutated to some extent in HCC, and significantly shortened OS and DFS in HCC patients. PTTG1 gene was positively correlated with the expression of various immune cells in the immune microenvironment of HCC, but the expression of various immune cells was also not conducive to OS of HCC patients. Conclusion High expression of PTTG1 is not conducive to survival and prognosis of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Securina/metabolismo , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , Prognóstico , Microambiente Tumoral
10.
J Food Sci ; 85(9): 2943-2951, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32702186

RESUMO

Inflammatory bowel disease (IBD) is a chronic intestinal disease, which was commonly found in westerners whereas is increasingly prevalent in Asia because of the changing eating habits. In previous research, we found that a water-soluble polysaccharide isolated from Auricularia auricular-judae (Bull.)-a kind of edible mushroom (Aap)-is composed of ß-1,3 glycosidic bonds, which is regarded as therapeutic or protective substance in enteritis. We therefore aimed to find the preventing effect of Aap on IBD. Here, we reported that pre-administration of Aap not only ameliorated weight loss, colon damage, and mucosal inflammation in colitis mice, but also prevented the damage of intestinal barrier by reducing the D-lactic acid and diamine oxidase level in plasma. Through high-throughput sequencing, we found that Aap changed gut microbiota composition. Furthermore, the preventing effect was transmissible via horizontal feces transfer from Aap-treated mice to normal mice. Our results indicated that oral administration of Aap is a promising protective substance of IBD. PRACTICAL APPLICATION: Our study proved that Auricularia auricula polysaccharide had substantial preventing effect on DSS-induced colitis in mice. This research might lay the theoretical foundation and technical support for the development of related functional foods. People could also enhance their gut immunity by eating Auricularia auricular in their daily life. Auricularia auricular as a highly nutritious agricultural product showed the broad significance in nutrition and food function.


Assuntos
Basidiomycota/química , Colite Ulcerativa/microbiologia , Colite Ulcerativa/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Fezes/microbiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação
11.
PLoS Genet ; 2(6): e93, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16789827

RESUMO

The differential expression of alleles occurs commonly in humans and is likely an important genetic factor underlying heritable differences in phenotypic traits. Understanding the molecular basis of allelic expression differences is thus an important challenge. Although many genes have been shown to display differential allelic expression, this is the first study to examine in detail the cumulative effects of multiple cis-regulatory polymorphisms responsible for allele-specific expression differences. We have used a variety of experimental approaches to identify and characterize cis-regulatory polymorphisms responsible for the extreme allele-specific expression differences of keratin-1 (KRT1) in human white blood cells. The combined data from our analyses provide strong evidence that the KRT1 allelic expression differences result from the haplotypic combinations and interactions of five cis-regulatory single nucleotide polymorphisms (SNPs) whose alleles differ in their affinity to bind transcription factors and modulate KRT1 promoter activity. Two of these cis-regulatory SNPs bind transcriptional activators with the alleles on the high-expressing KRT1 haplotype pattern having a higher affinity than the alleles on the low-expressing haplotype pattern. In contrast, the other three cis-regulatory SNPs bind transcriptional inhibitors with the alleles on the low-expressing haplotype pattern having a higher affinity than the alleles on the high-expressing haplotype pattern. Our study provides important new insights into the degree of complexity that the cis-regulatory sequences responsible for allele-specific transcriptional regulation have. These data suggest that allelic expression differences result from the cumulative contribution of multiple DNA sequence polymorphisms, with each having a small effect, and that allele-specific expression can thus be viewed as a complex trait.


Assuntos
Queratinas/genética , Sequência de Bases , DNA/sangue , DNA/genética , Primers do DNA , Regulação da Expressão Gênica , Genes Reporter , Humanos , Queratina-1 , Queratinas/sangue , Leucócitos/fisiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Transcrição Gênica
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(10): 903-909, 2019 Oct.
Artigo em Zh | MEDLINE | ID: mdl-31814567

RESUMO

Objective To investigate the expression of C-C motif chemokine ligand 23 (CCL23) in hepatocellular carcinoma (HCC) and its clinical significance for survival and prognosis. Methods GEPIA, HCCDB, MetaScape, TIMER, TISIDB, Kaplan-Meier Plotter and other online databases were used to analyze the expression level of CCL23 in HCC, the functional notes of co-expression gene and its gene ontology (GO), the enrichment of Kyoto gene and genome encyclopedia (KEGG), the correlation between tumor cell purity, the expression of CCL23 in immune cells and its significance for survival and prognosis of patients. Results The expression of CCL23 in all stages of HCC was negatively correlated with the purity of HCC tumor cells. The short prognosis of HCC patients with low expression of CCL23 was poor. The GO function and KEGG pathway of CCL23 co-expressed gene in HCC were mainly enriched in immune cell activation and complement system activation. CCL23 was the strongest chemokine factor in HCC, and it could bind to multiple receptors including CC chemokine receptor 1 (CCR1), CCR2, CCR7 and CXC chemokine receptor 6 (CXCR6) to exert chemokine effect on immune cells, among which CD8+ T cells and macrophages have the most obvious chemokine effect. Conclusion The low expression of CCL23 in HCC tissue is not conducive to the development of anti-tumor immune defense in HCC patients and significantly shortens the survival of HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Quimiocinas CC/genética , Neoplasias Hepáticas/genética , Linfócitos T CD8-Positivos , Carcinoma Hepatocelular/imunologia , Biologia Computacional , Humanos , Neoplasias Hepáticas/imunologia , Macrófagos , Receptores CCR1/metabolismo , Receptores CCR2/metabolismo , Receptores CCR7/metabolismo , Receptores CXCR6/metabolismo
13.
Hum Genet ; 122(6): 625-34, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17955261

RESUMO

Genomic imprinting is an epigenetic process in which the copy of a gene inherited from one parent (maternal or paternal) is consistently silenced or expressed at a significantly lower level than the copy from the other parent. In an effort to begin a systematic genome-wide screen for imprinted genes, we assayed differential allelic expression (DAE) at 3,877 bi-allelic protein-coding sites located in 2,625 human genes in 67 unrelated individuals using genotyping microarrays. We used the presence of both over- and under-expression of the reference allele compared to the alternate allele to identify candidate-imprinted genes. We found 61 genes with at least twofold DAE plus "flipping" of the more highly expressed allele between reference and alternate across heterozygous samples. Sixteen flipping genes were genotyped and assayed for DAE in an independent data set of lymphoblastoid cell lines from two CEPH pedigrees. We confirmed that PEG10 is paternally expressed, identified one gene (ZNF331) with multiple lines of data indicating it is imprinted, and predicted several additional imprinting candidate genes. Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted. With samples of mRNA from appropriate tissues and a collection of informative cSNPs, a genome-wide search using this methodology could expand the list of genes that undergo genomic imprinting in a tissue- or temporal-specific manner.


Assuntos
Mapeamento Cromossômico/métodos , Impressão Genômica , Negro ou Afro-Americano/genética , Alelos , Asiático/genética , Células Cultivadas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/fisiologia , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Polimorfismo de Nucleotídeo Único , População Branca/genética
14.
J Appl Physiol (1985) ; 104(4): 1185-91, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18174394

RESUMO

We studied the effect of hyperbaric oxygen (HBO) preconditioning on the molecular mechanisms of neuroprotection in a rat focal cerebral ischemic model. Seventy-two male Sprague-Dawley rats were pretreated with HBO (100% O(2), 2 atmospheres absolute, 1 h once every other day for 5 sessions) or with room air. In experiment 1, HBO-preconditioned rats and matched room air controls were subjected to focal cerebral ischemia or sham surgery. Postinjury motor parameters and infarction volumes of HBO-preconditioned rats were compared with those of controls. In experiment 2, HBO-preconditioned rats and matched room air controls were killed at different time points. Brain levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream target gene erythropoietin (EPO) analyzed by Western blotting and RT-PCR as well as HIF-1alpha DNA-binding and transcriptional activities were determined in the ipsilateral hemisphere. HBO induced a marked increase in the protein expressions of HIF-1alpha and EPO and the activity of HIF-1alpha, as well as the expression of EPO mRNA. HBO preconditioning dramatically improved the neurobehavioral outcome at all time points (3.0 +/- 2.1 vs. 5.6 +/- 1.5 at 4 h, 5.0 +/- 1.8 vs. 8.8 +/- 1.4 at 8 h, 6.4 +/- 1.8 vs. 9.7 +/- 1.3 at 24 h; P < 0.01, respectively) and reduced infarction volumes (20.7 +/- 4.5 vs. 12.5 +/- 3.6%, 2,3,5-Triphenyltetrazolium chloride staining) after cerebral ischemia. This observation indicates that the neuroprotection induced by HBO preconditioning may be mediated by an upregulation of HIF-1alpha and its target gene EPO.


Assuntos
Isquemia Encefálica/terapia , Eritropoetina/biossíntese , Oxigenoterapia Hiperbárica , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Precondicionamento Isquêmico , Animais , Comportamento Animal/efeitos dos fármacos , Western Blotting , Isquemia Encefálica/fisiopatologia , Infarto Cerebral/patologia , Infarto Cerebral/prevenção & controle , Circulação Cerebrovascular/fisiologia , DNA/biossíntese , DNA/genética , DNA/metabolismo , Eritropoetina/genética , Membro Anterior/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Fármacos Neuroprotetores , Oxigênio/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sais de Tetrazólio , Regulação para Cima/genética , Regulação para Cima/fisiologia
15.
Brain Res ; 1153: 204-13, 2007 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-17462608

RESUMO

It has been established that hyperbaric oxygen (HBO) treatment reduces brain edema, decreases infarct volume, contributes to neurological functional recovery and suppresses apoptosis in suture-induced focal cerebral ischemic animal models. In the present study, we evaluated the therapeutic effect of HBO in an endothelin-1-induced focal cerebral ischemia in rats and explored the associated mechanisms of HBO-induced brain protection. One hundred twenty male Sprague-Dawley rats (280 to 320 g) were randomly assigned to sham, focal cerebral ischemia and focal cerebral ischemia treated with HBO groups. Brain water content, neurological function, morphology and molecular biological markers were assessed. HBO (100% O2, 2.5 atmosphere absolute for 2 h) was initiated at 1 h after focal cerebral ischemia. Rats were killed at 24 h to harvest tissues for Western blot or for histology. In HBO-treated animals, an enhanced ratio of Bcl-2 and Bax and a reduced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in the hippocampus after focal cerebral ischemia were observed. These results indicate that HBO provides brain protection that is probably associated with the inhibition of HIF-1alpha and the elevation of Bcl-2.


Assuntos
Isquemia Encefálica/terapia , Endotelina-1 , Oxigenoterapia Hiperbárica/métodos , Análise de Variância , Animais , Edema Encefálico/etiologia , Edema Encefálico/terapia , Infarto Encefálico/etiologia , Infarto Encefálico/terapia , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/complicações , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo
16.
Aviat Space Environ Med ; 78(4): 368-73, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17484337

RESUMO

INTRODUCTION: The precise action of the immunological effects associated with hyperbaric exposure is poorly understood. This study's goal was to clarify the effects and etiology of deep air dives on the immune response. METHODS: Sprague-Dawley rats were exposed to 7-ATA air for 60 min twice daily for 3 consecutive days. Several markers of immune function, the degree of stress, and oxidative stress following or during the exposures were determined. Rats exposed to 1.47-ATA oxygen or 7-ATA nitrox (0.21-ATA oxygen + 6.79-ATA nitrogen) were taken as controls. RESULTS: Peripheral lymphocytes and CD3+ and CD4+CD3+ subsets in peripheral blood and spleen, plasma interleukin-2 level, and the responses of splenic lymphocytes to concanavalin A all decreased, antioxidant enzyme activities and the concentration of reduced glutathione both decreased, while the level of malondialdehyde increased following hyperbaric air exposures. All changes returned to normal in 3-5 d. Similar changes were observed following exposures to 1.47-ATA oxygen, but not to normoxic nitrox. Plasma levels of adrenocorticotropic hormone and corticosterone increased after one exposure and recovered to normal levels after three exposures in rats treated with either hyperbaric or normobaric air. Pretreatment of the animals with N-acetylcysteine, a potent free radical scavenger and antioxidant attenuated the effects of hyperbaric air on immune and antioxidant systems. CONCLUSIONS: These results are consistent with the hypothesis that repetitive exposure to 7-ATA air has a temporary immunosuppressive effect on rats, which is related to oxidative stress induced by the high partial pressure of oxygen in breathing gas.


Assuntos
Medicina Aeroespacial , Pressão Atmosférica , Descompressão/efeitos adversos , Oxigenoterapia Hiperbárica/efeitos adversos , Sistema Imunitário , Terapia de Imunossupressão , Narcose por Gás Inerte/etiologia , Estresse Oxidativo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Linfócitos T
17.
Onco Targets Ther ; 9: 5117-21, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27574452

RESUMO

PURPOSE: This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. PATIENTS AND METHODS: In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50-100 mg oral TMZ every day until the radiotherapy regimen was completed. RESULTS: The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). CONCLUSION: Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation.

18.
Cell Mol Immunol ; 1(1): 50-6, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16212921

RESUMO

Resveratrol (3,5,4'-trihydroxystilbene) (RV) is a constituent of grape seeds with anti-inflammatory and anti-oxidant activities. In this study, we examined the capacity of RV to modulate the function of G protein-coupled chemoattractant receptors, which play important roles in inflammation and immune responses. RV, over a non-cytotoxic concentration range, inhibited chemotactic and calcium mobilization responses of phagocytic cells to selected chemoattractants. At low micromolar concentrations, RV potently reduced superoxide anion production by phagocytic leukocytes in response to the bacterial chemotactic peptide fMLF, a high affinity ligand for formylpeptide receptor FPR, and A beta42, an Alzheimer's disease-associated peptide and a ligand for the FPR variant FPRL1. In addition, RV reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and the activation of nuclear factor NF-kappaB induced by formylpeptide receptor agonists. These results suggest that the inhibition of the function of chemoattractant receptors may contribute to the anti-inflammatory properties of RV. Thus, RV may be therapeutically promising for diseases in which activation of formylpeptide receptors contributes to the pathogenic processes.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Leucócitos/efeitos dos fármacos , Fagócitos/efeitos dos fármacos , Receptores de Formil Peptídeo/metabolismo , Estilbenos/farmacologia , Vitis/química , Cálcio/metabolismo , Quimiocina CXCL12 , Quimiocinas CXC/metabolismo , Fatores Quimiotáticos/metabolismo , Quimiotaxia de Leucócito/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Interleucina-8/metabolismo , Leucócitos/citologia , Leucócitos/metabolismo , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Peptídeos/metabolismo , Fagócitos/citologia , Fagócitos/metabolismo , Resveratrol , Superóxidos/metabolismo
19.
Artigo em Zh | MEDLINE | ID: mdl-25051823

RESUMO

OBJECTIVE: To understand the distribution of the river beach wetlands and Oncomelania snails in the lower reaches of the Yangtze River, and explore the countermeasures of snail control. METHODS: The river beach wetlands outside the Yangtze River levee were investigated and classified according to the hierarchical and classification system of wetlands of China. The snail survey was carried out in the beach wetlands of Runzhou section of lower reaches of the Yangtze River from 2004 to 2013. The change trend of snail areas and the densities was analyzed in the wetlands. RESULTS: The river beach of Runzhou section of lower reaches of the Yangtze River belongs to the riverine wetland. There was Oncomelania snail breeding except the permanent water area. At present, there were natural wetlands of 1303.0 hm2, human-made wetlands of 1479.0 hmb2 and wetland function changes of 1059.0 hm2 in the river beach of Runzhou section. There was the snail area of 181.4 hm2 in the natural wetland in 2013. The area of snail control by the molluscicide and environmental modification was 4624.55 hm2 from 2004 to 2013. The decline rates of snail areas and densities were 66.53% and 77.66% respectively. The existing Oncomelania snails were distributed in the natural wetlands. CONCLUSION: The human-made wetland is helpful to snail control. The snail control in the river beach wetlands should attach a great importance to the protection of wetland ecology.


Assuntos
Controle de Pragas/métodos , Rios , Caramujos/crescimento & desenvolvimento , Áreas Alagadas , Animais , China , Reservatórios de Doenças
20.
Artigo em Zh | MEDLINE | ID: mdl-25856896

RESUMO

OBJECTIVE: To evaluate the effect of comprehensive prevention and control of soil-transmitted nematodiasis in Runzhou District, Zhenjiang City, Jiangsu Province from 1997 to 2012. METHODS: The comprehensive prevention and control measures included the helminthicide, health education, improvement of water supplier and harmless toilets, and these measures were implemented continuously. At the same time, the infection rates of soil-transmitted nematodes, the local economic indicators, and the coverage rates of tap water and harmless toilets were surveyed. RESULTS: The mass chemotherapy was performed for 202 100 person-times and the diagnosed chemotherapy was performed for 2 006 person-times in Runzhou District from 1997 to 2012. The awareness rates of health knowledge were 57.18% in 1997, and 95.62% in 2012. The coverage rates of tap water and harmless toilets were 10.14% and 10.21% in 1997, and 100.0% and 90.38% in 2012, respectively. There were negative correlations between the awareness rate of per capita GDP, per capita net income, coverage rates of tap water, coverage rates of harmless toilets, health knowledge and the infection rate of soil-transmitted nematodes, respectively (r(per capitaGDP) = -0.526, P < 0.05; r(per capita net income) = -0.671, P < 0.01; r(coverage rates of tap water) = -0.936, P < 0.01; r(coverage rates of harmless toilets) = -0.922, P < 0.01; r(awareness) = -0.774, P < 0.01). The statistical analysis showed that the infection rate of soil-transmitted nematodes had a downward trend as an exponential curve in Runzhou District from 1997 to 2012 (y = 42.031 7e(-0.357 6x), R2 = 0.803 6, F = 57.28, P = 0.000). The infection rate of degradation by an annual rate was 29.18%. The infection rate in farmers was significantly higher than that in students (χ2 = 17.998, P < 0.01). There was no significant difference between men and women in the infection rate of soil-transmitted nematodes (χ2 = 3.627, P = 0.057). CONCLUSION: The comprehensive prevention and control measures and the development of social economy contribute to the steady decline of soil-transmitted nematode infections.


Assuntos
Controle de Doenças Transmissíveis/métodos , Nematoides/isolamento & purificação , Infecções por Nematoides/prevenção & controle , Solo/parasitologia , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , China/epidemiologia , Fezes/parasitologia , Feminino , Educação em Saúde , Humanos , Higiene , Masculino , Pessoa de Meia-Idade , Nematoides/fisiologia , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/parasitologia , Infecções por Nematoides/transmissão , Adulto Jovem
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