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1.
Cell Death Discov ; 8(1): 178, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35396503

RESUMO

Myocardial infarction (MI) is a fatal heart disease that affects millions of lives worldwide each year. This study investigated the roles of HIF-1α/lncRNA-TUG1 in mitochondrial dysfunction and pyroptosis in MI. CCK-8, DHE, lactate dehydrogenase (LDH) assays, and JC-1 staining were performed to measure proliferation, reactive oxygen species (ROS), LDH leakage, and mitochondrial damage in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Enzyme-linked immunoassay (ELISA) and flow cytometry were used to detect LDH, creatine kinase (CK), and its isoenzyme (CK-MB) levels and caspase-1 activity. Chromatin immunoprecipitation (ChIP), luciferase assay, and RNA-immunoprecipitation (RIP) were used to assess the interaction between HIF-1α, TUG1, and FUS. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to measure HIF-1α, TUG1 and pyroptosis-related molecules. Hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC), and terminal deoxynucleotidyl transferase dUTP risk end labelling (TUNEL) staining were employed to examine the morphology, infarction area, and myocardial injury in the MI mouse model. Mitochondrial dysfunction and pyroptosis were induced in H/R-treated cardiomyocytes, accompanied by an increase in the expression of HIF-α and TUG1. HIF-1α promoted TUG1 expression by directly binding to the TUG1 promoter. TUG1 silencing inhibited H/R-induced ROS production, mitochondrial injury and the expression of the pyroptosis-related proteins NLRP3, caspase-1 and GSDMD. Additionally, H/R elevated FUS levels in cardiomyocytes, which were directly inhibited by TUG1 silencing. Fused in sarcoma (FUS) overexpression reversed the effect of TUG1 silencing on mitochondrial damage and caspase-1 activation. However, the ROS inhibitor N-acetylcysteine (NAC) promoted the protective effect of TUG1 knockdown on H/R-induced cardiomyocyte damage. The in vivo MI model showed increased infarction, myocardial injury, ROS levels and pyroptosis, which were inhibited by TUG1 silencing. HIF-1α targeting upregulated TUG1 promotes mitochondrial damage and cardiomyocyte pyroptosis by combining with FUS, thereby promoting the occurrence of MI. HIF-1α/TUG1/FUS may serve as a potential treatment target for MI.

2.
Mitochondrial DNA B Resour ; 7(2): 317-319, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35141408

RESUMO

The complete mitochondrial genome (mitogenome) of Dacus haikouensis Wang and Cheng 2002 (Diptera: Tephritidae: Dacinae) was sequenced and annotated. The mitochondrial genome is 15,291 bp (GenBank No. MZ087939), containing 73.0% AT, which is the classical structure for insect mitogenome. Additionally, the phylogenetic tree confirmed that Dacus haikouedsis clustered with Dacus longicornis and Dacus conopsoides. The current study would enrich the mitogenomes of the fruit flies.

3.
Mol Biol Evol ; 39(2)2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34893856

RESUMO

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.


Assuntos
Genoma , Carneiro Doméstico , Animais , Ásia , Europa (Continente) , Variação Genética , Irã (Geográfico) , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Ovinos/genética , Carneiro Doméstico/genética
4.
Insects ; 12(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34940191

RESUMO

The cigarette beetle Lasioderma serricorne (Fabricius) is a major pest of stored products worldwide, especially tobacco and foods, causing huge economic losses. This study aimed to experimentally investigate the population dynamics of this pest at different temperatures and provide theoretical input for its control. Populations of L. serricorne were established under laboratory conditions at five temperatures (21 °C, 24 °C, 27 °C, 30 °C, and 33 °C). Results showed that an increasing temperature significantly affected the developmental time, longevity, oviposition period, and fecundity of L. serricorne. Both the longevity and fecundity of adult beetles were significantly reduced as the temperature increased. High temperatures significantly reduced the total duration of the preoviposition period but prolonged the oviposition period of L. serricorne. Increasing the temperatures from 21 °C to 33 °C significantly influenced the life table parameters of L. serricorne. The intrinsic increase rate (r), finite increase rate (λ), and gross reproductive rate (GRR) all increased with a greater rearing temperature, but mean generation time (T) was significantly shortened. To our best knowledge, this is the first report to detail the entire life history of the cigarette beetle in response to different temperatures when reared on tobacco dry leaves. This finding may provide basic information on the occurrence of L. serricorne in a warehouse setting and its mass rearing.

5.
Mitochondrial DNA B Resour ; 5(1): 780-781, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33366748

RESUMO

The complete mitochondrial genome (mitogenome) of the Bactrocera cheni (Diptera: Tephritidae: Dacinae) are sequenced and annotated. The mitochondrial genome is 15,945 bp (GenBank No. MN883026), with A + T% for the whole sequence = 73.0% (38.9% A, 16.4% C, 10.6% G, and 34.1% T), which is the classical structure for insect mitogenome. All PCGs started with ATN except ATP8; 9 PCGs use TAA as the stop codon, and others use TAG as the stop codon. The phylogenetic tree confirms that B. cheni and B. tsuneonis are not clade into one branch with strongly supported. And Pairwise Identity is 80.0% between B. cheni and B. tsuneonis. Based this study, we supported that B. cheni and B. tsuneonis are two different species clearly.

6.
Curr Biol ; 30(20): 4085-4095.e6, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32822607

RESUMO

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.


Assuntos
DNA Mitocondrial/genética , Genoma/genética , Polimorfismo de Nucleotídeo Único/genética , Carneiro Doméstico/genética , Cromossomo Y/genética , Animais , Cruzamento , Linhagem da Célula/genética , Mapeamento Cromossômico , Variação Genética/genética , Masculino , Mitocôndrias/genética , Fenótipo , Filogenia , Ovinos , Carneiro Doméstico/classificação , Sequenciamento Completo do Genoma
7.
Nat Commun ; 11(1): 2815, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499537

RESUMO

Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.


Assuntos
Criação de Animais Domésticos/métodos , Animais Selvagens/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Carneiro Doméstico/genética , Alelos , Animais , Cruzamento , Feminino , Frequência do Gene , Variação Genética , Genética , Genômica , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Desequilíbrio de Ligação , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único , Seleção Genética , Análise de Sequência de DNA , Ovinos , Especificidade da Espécie , Sequenciamento Completo do Genoma
8.
Biochem Cell Biol ; 98(2): 90-98, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31013434

RESUMO

To date, surgical resection is the mainstay for the treatment of colorectal cancer (CRC). Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents, has been reported to be involved in modulating the malignancy of a variety of human cancers. However, the underlying mechanisms remain poorly understood. In this study, using a cell counting kit (CCK-8), flow cytometry, and caspase-3 cleavage assays, we found that propofol promoted cell apoptosis and inhibited cell proliferation in both Colo205 and SW620 cells, through the down-regulation of HOXA11-AS and up-regulation of let-7i. Moreover, gain-of-function studies of HOXA11-AS or loss-of-function studies of let-7i also revealed a negative correlation between HOXA11-AS and let-7i in propofol-mediated biological functions of CRC cells. Furthermore, our mechanistic experiments revealed that HOXA11-AS acts as a molecular sponge for let-7i, thereby regulating the expression of ABCC10. We investigate the theory that propofol suppresses colorectal cancer tumorigenesis by modulating the HOXA11-AS-let-7i-ABCC10 regulatory network, indicating the potential for propofol to control CRC development.


Assuntos
Anestésicos Intravenosos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/patologia , Proteínas de Homeodomínio/genética , MicroRNAs/metabolismo , Propofol/farmacologia , RNA Longo não Codificante/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Oligonucleotídeos Antissenso/genética , Ligação Proteica
9.
Mitochondrial DNA B Resour ; 4(2): 2355-2356, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-33365541

RESUMO

The complete mitochondrial genome (mitogenome) of the fruit fly species Dacus trimacula (Diptera: Tephritidae: Dacinae) are sequenced and annotated. The mitochondrial genome is 15,851 bp (GenBank No. MK940811) has an A + T content of 72.8% (A 39.2%; C 17.0%; G 10.2%, and T 33.6%), which is the classical structure for insect mitogenome. All PCGs started with ATN and stopped with TAN. The phylogenetic tree confirms that D. trimacula clustered with D. longicornis as the sister group to Zeugodacus. This study enriches the mitogenomes of the fruit flies.

10.
Mitochondrial DNA B Resour ; 4(2): 3750-3751, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33366173

RESUMO

The complete mitochondrial genome (mitogenome) of the Bactrocera ruiliensis (Diptera: Tephritidae: Dacinae) is sequenced and annotated. The mitochondrial genome is 15,870 bp (GenBank No. MN477221) and has an A + T content of 73.3% (A 39.2%; C 16.2%; G 10.3%, and T 34.4%), which is the classical structure for insect mitogenome. All PCGs started with ATN, except ATP8, which is started with TTG; 12 PCGs use TAR (TAA/TAG) as the stop codon, except COX1, which ends with single T--. The phylogenetic tree confirms that B. ruiliensis clustered with other Bactrocera species. This study enriches the mitogenomes of the fruit flies.

11.
Front Genet ; 9: 118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29692799

RESUMO

Reproduction is an important trait in sheep breeding as well as in other livestock. However, despite its importance the genetic mechanisms of litter size in domestic sheep (Ovis aries) are still poorly understood. To explore genetic mechanisms underlying the variation in litter size, we conducted multiple independent genome-wide association studies in five sheep breeds of high prolificacy (Wadi, Hu, Icelandic, Finnsheep, and Romanov) and one low prolificacy (Texel) using the Ovine Infinium HD BeadChip, respectively. We identified different sets of candidate genes associated with litter size in different breeds: BMPR1B, FBN1, and MMP2 in Wadi; GRIA2, SMAD1, and CTNNB1 in Hu; NCOA1 in Icelandic; INHBB, NF1, FLT1, PTGS2, and PLCB3 in Finnsheep; ESR2 in Romanov and ESR1, GHR, ETS1, MMP15, FLI1, and SPP1 in Texel. Further annotation of genes and bioinformatics analyses revealed that different biological pathways could be involved in the variation in litter size of females: hormone secretion (FSH and LH) in Wadi and Hu, placenta and embryonic lethality in Icelandic, folliculogenesis and LH signaling in Finnsheep, ovulation and preovulatory follicle maturation in Romanov, and estrogen and follicular growth in Texel. Taken together, our results provide new insights into the genetic mechanisms underlying the prolificacy trait in sheep and other mammals, suggesting targets for selection where the aim is to increase prolificacy in breeding projects.

12.
Mol Med Rep ; 16(6): 8589-8594, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28990107

RESUMO

Bone marrow stromal cells (BMSCs) can differentiate into osteoblasts. The present study investigated the osteogenic effects of estradiol, as well as the role of the c­Jun N­terminal kinase (JNK) signaling pathway in promoting estradiol­enhanced osteogenesis of rat (r)BMSCs. rBMSCs were treated for 7 days with or without estradiol and further treated with or without the JNK­specific inhibitor SP600125. The role of estrogen during rBMSC osteogenesis was evaluated by alkaline phosphatase activity and mineralized nodule formation using the Gomori method and Alizarin red S staining, respectively. Subsequently, the mRNA expression levels of transforming growth factor-ß1 (TGF­ß1) and core­binding factor α1 (Cbfα1) were evaluated by reverse transcription­quantitative polymerase chain reaction, and TGF­ß1, Cbfα1 and phosphorylated (p)­JNK protein expression was detected by western blotting. All groups treated with SP600125 expressed low levels of TGF­ß1 and Cbfα1 mRNA and protein, and low p­JNK protein expression. Compared with the control cells, rBMSCs cultured with estradiol exhibited a significant upregulation in the expression levels of osteogenic genes and proteins. The present study demonstrated that estradiol enhanced osteogenic differentiation of rBMSCs and that the JNK signaling pathway was involved in this process, providing insights into the molecular mechanisms involved in rBMSC osteogenesis upon estradiol stimulation.


Assuntos
Estradiol/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/enzimologia , Osteogênese/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/metabolismo , Forma Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Citometria de Fluxo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Minerais/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
13.
Mol Biol Evol ; 34(9): 2380-2395, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28645168

RESUMO

China has a rich resource of native sheep (Ovis aries) breeds associated with historical movements of several nomadic societies. However, the history of sheep and the associated nomadic societies in ancient China remains poorly understood. Here, we studied the genomic diversity of Chinese sheep using genome-wide SNPs, mitochondrial and Y-chromosomal variations in > 1,000 modern samples. Population genomic analyses combined with archeological records and historical ethnic demographics data revealed genetic signatures of the origins, secondary expansions and admixtures, of Chinese sheep thereby revealing the peopling patterns of nomads and the expansion of early pastoralism in East Asia. Originating from the Mongolian Plateau ∼5,000‒5,700 years ago, Chinese sheep were inferred to spread in the upper and middle reaches of the Yellow River ∼3,000‒5,000 years ago following the expansions of the Di-Qiang people. Afterwards, sheep were then inferred to reach the Qinghai-Tibetan and Yunnan-Kweichow plateaus ∼2,000‒2,600 years ago by following the north-to-southwest routes of the Di-Qiang migration. We also unveiled two subsequent waves of migrations of fat-tailed sheep into northern China, which were largely commensurate with the migrations of ancestors of Hui Muslims eastward and Mongols southward during the 12th‒13th centuries. Furthermore, we revealed signs of argali introgression into domestic sheep, extensive historical mixtures among domestic populations and strong artificial selection for tail type and other traits, reflecting various breeding strategies by nomadic societies in ancient China.


Assuntos
Filogeografia/métodos , Carneiro Doméstico/genética , Animais , Animais Domésticos/genética , Cruzamento , China , DNA Mitocondrial/genética , Extremo Oriente , Variação Genética/genética , Genoma/genética , Genômica/métodos , Haplótipos , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Ovinos/genética , Migrantes , Cromossomo Y/genética
14.
Huan Jing Ke Xue ; 38(6): 2280-2286, 2017 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965344

RESUMO

To assess the pollution levels, characteristics, and the pollution sources and occupational inhalation exposure of polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs)in the workshops,ambient air samples in different types of incinerators of two municipal solid waste incinerators(MSWI) were collected and analyzed. The results showed that ① The I-TEQ concentration ranged from 0.034-2.152 pg·m-3in the two waste incineration plants, and the most sites' I-TEQ exceeded the ambient air quality standard. Besides, the I-TEQ concentration behind the incineration plant was higher than others. ② The dioxins in incineration plant were dominated by OCDD and 1,2,3,4,6,7,8-HpCDD. For MSWI A, the flue gas and the fly ash had major effect on PCDD/Fs, while the dioxins pollution in MSWI B was only affected by the fly ash. ③ Occupational inhalation exposure of PCDD/Fs was 0.01-1.10 pg·(kg·d)-1 in incineration plant, some occupational inhalation exposure values exceeded the evaluation standard, and the areas behind the incinerators were evaluated to have a high exposure risk.

15.
Leuk Lymphoma ; 57(6): 1311-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26372888

RESUMO

Decitabine (DAC) is commonly used for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Previous studies have indicated DAC sequentially combined with idarubicin was an effective treatment for myeloid neoplasms. Therefore, a clinical study was conducted of the sequential combination of DAC followed by low-dose idarubicin/cytarabine in high-risk myeloid neoplasms. A total of 30 patients with a diagnosis of high-risk MDS, AML evolving from MDS or relapsed/refractory AML were enrolled in the study. DAC was administered 20 mg/m(2) daily for 3 consecutive days. Idarubicin (3 mg/m(2)/day) was administered 24 h after the last administration of DAC for 5-7 consecutive days, combined with cytarabine (30 mg/m(2)/day) for 7-14 days. The overall complete remission rate was 66.67%. The results demonstrate that epigenetic priming with decitabine followed by low-dose idarubicin/ytarabine has an increased anti-leukemia effect compared to traditional chemotherapy in high-risk myeloid neoplasms.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/análogos & derivados , Epigênese Genética/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/uso terapêutico , Aberrações Cromossômicas , Citarabina/administração & dosagem , Decitabina , Progressão da Doença , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/diagnóstico , Recidiva , Indução de Remissão , Resultado do Tratamento
16.
Mol Med Rep ; 12(5): 6815-20, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26329131

RESUMO

Several biological properties of icariin have been identified, including its anticancer effect. However, the potential mechanisms underlying the effect of icariin on HepG2 hepatocellular carcinoma cells remain to be elucidated. The aim of the present study was to examine the effects of icariin on the proliferation and cytoskeleton of HepG2 cells. A 3­(4,5­dimethylthiazol­2­yl)­2,5 diphenyltetrazolium bromide assay was used to assess the antiproliferative effects of icariin and to determine the optimal concentration and treatment schedule of icariin on the HepG2 cells. Cell cycle analysis was performed using fluorescence activated cell sorting, the protein expression of B­cell lymphoma (Bcl)­2 was determined using immunohistochemical and western blot analyses, and F­actin in the cells was examined using confocal microscopy. The chemotherapeutic drug, oxaliplatin, was used as a positive control. The results demonstrated that the optimal concentration of icarrin to produce an antiproliferative effect on HepG2 cells was 10­5 mol/l, and the optimal treatment duration was 72 h. The icariin group had a significantly higher proportion of cells in the G0/G1 phase, compared with the control group, treated with high glucose Dulbecco's modified Eagles medium with 10% fetal bovine serum (P<0.05). The proportion of HepG2 cells in the S phase was significantly lower in the oxaliplatin (24.19%; P<0.05) and icariin (21.07%; P<0.01) groups, compared with the control group (28.62%). Icariin markedly decreased the expression of Bcl­2, compared with the control (P<0.01), and disrupted the polymerization of F­actin filaments in the HepG2 cells. Therefore, the present study demonstrated that, at an optimum concentration of 10­5 mol/l, icariin inhibited the proliferation of the HepG2 cells, promoted apoptosis by decreasing the expression of Bcl­2, and disrupted the actin cytoskeleton.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Citoesqueleto/metabolismo , Flavonoides/farmacologia , Actinas/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular , Células Hep G2 , Humanos , Concentração Inibidora 50 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
17.
Zhonghua Yi Xue Za Zhi ; 93(24): 1881-5, 2013 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-24124739

RESUMO

OBJECTIVE: To explore the pathophysiological changes in the functional connectivity of posterior cingulate cortex (PCC) with other brain regions in children with attention-deficit or hyperactivity disorder (ADHD) on resting-state functional magnetic resonance imaging(fMRI) and explore the neural mechanisms of ADHD at the point of relationships between brain regions. METHODS: Thirty children with ADHD from the Third Affiliated Hospital of Soochow University from June 2008 to April 2010 and another 30 age-and-gender-matched controls from a normal primary school over the same period underwent resting-state fMRI scans. And blood oxygenation level dependent (BOLD) signal was acquired to calculate the functional connectivity of PCC with other brain regions controls. Significant differences of connectivity between groups were analyzed with REST software. RESULTS: The pattern of functional connectivity of PCC for the ADHD group was similar to that of the control group. Significant positive functional connectivity with PCC was observed in the default mode of network (DMN) while negative functional connectivity was present in dorsolateral prefrontal cortex, anterior cingulate, parietal cortex and basal ganglia(all P < 0.05, corrected). Compared to the controls, the ADHD group exhibited decreased positive connectivity with PCC in bilateral medial prefrontal cortex (0.07 ± 0.20 vs 0.33 ± 0.23, t = -5.47), right posterior cingulate gyrus(0.25 ± 0.28 vs 0.48 ± 0.30, t = -3.44), right inferior temporal gyrus (-0.05 ± 0.19 vs 0.22 ± 0.22, t = -4.61) and cerebellar posterior lobe (-0.04 ± 0.21 vs 0.17 ± 0.16, t = -3.99), while decreased negative functional connectivity with PCC was observed in left insula (-0.10 ± 0.26 vs -0.30 ± 0.19, t = 3.71), right inferior parietal lobule (0.02 ± 0.18 vs -0.23 ± 0.17, t = 5.20), left postcentral gyrus (0.08 ± 0.26 vs -0.17 ± 0.25, t = 4.06), left superior temporal gyrus (-0.04 ± 0.25 vs -0.27 ± 0.17, t = 4.27), right superior temporal gyrus (-0.08 ± 0.25 vs -0.31 ± 0.21, t = 3.80) and left fusiform gyrus (-0.01 ± 0.25 vs -0.18 ± 0.17, t = 3.57)(all P < 0.05, corrected). CONCLUSIONS: The connectivity of DMN between brain regions is abnormal in ADHD group. And the strengthen of negative relationship between DMN and task activated network becomes reduced. It is surmised that the decreased internal synchronization of default network and disrupted balance between DMN and prefrontal-parietal attentional networks may be important neural mechanisms of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Giro do Cíngulo/fisiopatologia , Imageamento por Ressonância Magnética , Adolescente , Estudos de Casos e Controles , Criança , Humanos , Vias Neurais
18.
Zhonghua Yi Xue Za Zhi ; 93(20): 1555-8, 2013 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-24028722

RESUMO

OBJECTIVE: To explore the mathematics cognitive function of children with attention deficit hyperactivity disorder and explore neural mechanisms with event-related potential(ERP) and behaviors. METHODS: Behavior data and ERP elicited by performing mental calculation tasks were recorded in 27 children with ADHD and 29 normal controls from July to October 2012 at Third Affiliated Hospital of Soochow University.The differences of behaviors and N2 component of ERP were compared and analyzed. RESULTS: The reaction time of the children with ADHD were longer than the control group in addition, subtraction and multiplication ((949 ± 144) vs (829 ± 166) ms, (981 ± 129) vs (856 ± 170) ms, (944 ± 136) vs (825 ± 172) ms, all P < 0.05). While the correct rate were less than normal control in all three arithmetic operations (0.80% (0.72%, 0.88%) vs 0.90% (0.85%,0.96%), 0.78% (0.64%,0.85%) vs 0.90% (0.84%,0.93%), 0.86% (0.74%,0.92%) vs 0.93%(0.90%,0.98%), all P < 0.05). N2 component could be elicited by all subjects in forehead. The amplitude of N2 of children with ADHD were significantly lower than control group in all three arithmetic operations at left frontal (F3: (-3.5 ± 5.2) vs (-6.7 ± 3.5)µV, (-3.8 ± 4.0) vs (-7.4 ± 4.5)µV, -5.8 (-7.6,1.6) vs -6.4(-10.3, -4.9) µV, all P < 0.05) and Fz ((-4.3 ± 6.4) vs ( -7.4 ± 4.2) µV, (-5.0 ± 5.4) vs (-7.9 ± 4.6)µV, -5.2(-9.7, -0.6) vs -7.9 (-10.5, -5.1)µV, all P < 0.05), the latency of ADHD group were prolonger than controls in subtraction operations at right and left frontal ((328 ± 36) vs (307 ± 27)ms, 325 (307,354)vs 309 (280, 330)ms) and frontal electrodes ((331 ± 35) vs (311 ± 30) ms, all P < 0.05). In addition and multiplication operations, there was no significant difference in latency (all P > 0.05). CONCLUSIONS: The children with ADHD have weak capacities of inhibition irrelevant information and paying attention to control. Their deficits in mental arithmetics may be due to the difficulties of selecting the best strategy during cognitive tasks.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Cognição , Estudos de Casos e Controles , Criança , Potenciais Evocados , Feminino , Humanos , Masculino , Matemática
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(5): 1117-20, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22040954

RESUMO

This study was aimed to explore the effect of homoharringtonine in combination with AG490 on JAK2-STAT5 associated signal pathway in HEL cells, and analyze its mechanism so as to provide theoretical basis for therapy of chronic myeloproliferative neoplasma by new program. The cell survival rates were tested by MTT, apoptosis was tested by flow cytometry after HEL cells were treated by 20 ng/ml HHT, 100 µmol/L AG490 and 20 ng/ml HHT in combination with 100 µmol/L AG490, while the signal proteins such as P-JAK2, P-STAT5 and BCL-xL activated by abnormal activated JAK2 were tested by Western blot. The results showed that both HHT and AG490 could inhabit the HEL cell proliferation after being treated for 24 hours, and Annexin V-PI double staining confirmed early apoptosis while HHT effect was more obvious, Western blot showed that the expressions of P-JAK2 and P-STAT5 were down-regulated, while the total protein levels of JAK2 and STAT5 were stable. It is concluded that HHT combined with AG490 can obviously inhibit the proliferation and induce early apoptosis of HEL cells, and there is synergistic effect between the two drugs. HHT possibly acts as a broad-spectrum PTK inhibitor and synergistically with AG490 inhibits the phosphorylation of signal proteins caused by JAK2V617F, thus down-regulating the transcription of STAT5.


Assuntos
Harringtoninas/farmacologia , Janus Quinase 2/metabolismo , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tirfostinas/farmacologia , Linhagem Celular Tumoral , Mepesuccinato de Omacetaxina , Humanos
20.
Zhonghua Yi Xue Za Zhi ; 89(19): 1313-7, 2009 May 19.
Artigo em Chinês | MEDLINE | ID: mdl-19615183

RESUMO

OBJECTIVE: To investigate the characteristics of cognitive development in elementary school children using rest-fMRI methods. METHODS: Twenty-nine normal school children were divided into three groups according to their ages (8, 10 & 12 years old) and received the resting-state fMRI scans. A regional homogeneity (ReHo) approach was used to analyze blood oxygen level-dependent fMRI (BOLD-fMRI) data in resting state. The fMRI data were processed with software SPM2 and REST 1.2. RESULTS: Compared with younger groups (10 vs 8, 12 vs 10, 12 vs 8), the elder groups showed more increases in superior temporal gyrus (Z = 2.83, Z = 3.21), middle temporal gyrus (Z = 3.74, Z = 3.19, Z = 4.26), inferior temporal gyrus (Z = 3.01) and lentiform nucleus (Z = 3.31). In addition, the ReHo differences were demonstrated in superior frontal gyrus (Z = 3.21), middle frontal gyrus (Z = 3.19, Z = 3.22), medial frontal gyrus (Z = 3.15), lingual gyrus (Z = 3.43) and cerebellum (Z = 3.11, Z = 2.97) increased more in 12 years old group (12 vs 10, 12 vs 8). And the precuneus (Z = 2.95) and posterior cingulate (Z = 2.64) had increasing ReHo values with the age growth (12 vs 8). CONCLUSION: The function of execution control, accommodation of attention, visual spatial integration and default mode network became gradually developed with increasing age.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Cognição , Imageamento por Ressonância Magnética/métodos , Criança , Desenvolvimento Infantil , Feminino , Humanos , Masculino
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