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1.
Front Oncol ; 9: 852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552177

RESUMO

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (NF-κB) signaling pathway, tumor necrosis factor receptor-1 (TNFR1) signaling pathway, and tumorigenesis-related tryptase secreted by mast cells, we summarize the anticancer properties of NM in existing studies both in vitro and in vivo. In addition, the efficacy and side effects of NM in cancer patients are summarized in detail. To further clarify NM's antitumor activities, clinical trials devoted to validating the clinical applications and underlying mechanisms are needed in the future.

2.
Cancer Biomark ; 24(4): 449-459, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30909186

RESUMO

OBJECTIVE: Sirtuins (SIRT) are NAD+-dependent protein deacetylases that are involved in the regulation of cancer-associated pathways. However, the biological role of these deacetylases remains elusive in glioblastoma (GBM). Here, we evaluated the effects of 7 sirtuins regarding their occurrence and prognostic value for GBM. METHODS: In this research, the effects of SIRT5 on the occurrence and prognosis of GBM were evaluated using integrative bioinformatics analyses. RESULTS: Based on comprehensive analyses of data obtained from web-based bioinformatics platforms, the data demonstrate that only SIRT5 expression is statistically decreased in GBM tissues. The clinical relevance analysis shows that downregulation of SIRT5 is significantly correlated with a shorter survival time. Moreover, the expression levels of SIRT5 were confirmed to be negatively associated with DNA methylation status. In addition, a protein-protein interaction network was constructed to determine the relationship of genes coexpressed with SIRT5. Functional enrichment analysis revealed that SIRT5 was potentially involved in epithelial-mesenchymal transition and in regulating cell communications. CONCLUSIONS: Collectively, our results indicate that SIRT5 acts as a potential suppresser during tumorigenesis, and suggest that SIRT5 may be a promising prognostic biomarker of GBM.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/mortalidade , Sirtuínas/genética , Biologia Computacional/métodos , Ilhas de CpG , Metilação de DNA , Perfilação da Expressão Gênica , Genômica/métodos , Glioblastoma/patologia , Humanos , Prognóstico
3.
Int J Phytoremediation ; 18(2): 103-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26605425

RESUMO

The root powder of long-root Eichhornia crassipes, as a new kind of biodegradable adsorbent, has been tested for aqueous adsorption of Pb, Zn, Cu, and Cd. From FT-IR, we found that the absorption peaks of phosphorous compounds, carbonyl, and nitrogenous compounds displayed obvious changes before and after adsorption which illustrated that plant characteristics may play a role in binding with metals. Surface properties and morphology of the root powders have been characterized by means of SEM and BET. Energy spectrum analysis showed that the metals were adsorbed on root powders after adsorption. Then, optimum quantity of powder, pH values, and metal ion concentrations in single-system and multi-system were detected to discuss the characteristics and mechanisms of metal adsorption. Freundlich model and the second-order kinetics equation could well describe the adsorption of heavy metals in single-metal system. The adsorption of Pb, Zn, and Cd in the multi-metal system decreased with the concentration increased. At last, competitive adsorption of every two metals on root powder proved that Cu and Pb had suppressed the adsorption performance of Cd and Zn.


Assuntos
Eichhornia/química , Recuperação e Remediação Ambiental/métodos , Metais Pesados/química , Poluentes Químicos da Água/química , Adsorção , Biodegradação Ambiental , Recuperação e Remediação Ambiental/instrumentação , Microscopia Eletrônica de Varredura , Raízes de Plantas/química , Pós/química , Espectroscopia de Infravermelho com Transformada de Fourier
4.
PLoS One ; 7(10): e47441, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23071808

RESUMO

Vulnerability for anxiety and depressive disorders is thought to have origins in early life and is increasingly recognized to involve deficits in GABAergic neurotransmission. Mice that were rendered heterozygous for the γ2 subunit gene of GABA(A) receptors (GABA(A)Rs) show behavioral, cognitive, neuroendocrine and pharmacologic features expected of a mouse model of melancholic anxious depression, including reduced survival of adult-born hippocampal neurons. Here we embarked on elucidating the developmental substrate underlying this phenotype, focusing on the Elevated Plus Maze and Forced Swim Test as relevant behavioral paradigms. In a first series of experiments using hemizygous tamoxifen-induced genetic inactivation of a floxed γ2 genomic locus we show that reducing the gene dosage at postnatal days (P)13/14 but not P27/28 results in altered behavior in both of these tests in adulthood, reminiscent of the anxious-depressive phenotype previously described for global heterozygous mice. However, in contrast to global heterozygous mice, the behavioral changes induced by γ2 subunit knockdown at P13/14 occurred without changes in adult hippocampal neurogenesis, indicating that altered neurogenesis is not an absolute prerequisite for anxiety- and depression-related behavior in this model. In a separate series of experiments using a pharmacological approach, acute but transient potentiation of GABA(A)Rs with diazepam uncovered distinct developmental vulnerabilities for altered behavior in the Elevated Plus Maze and Forced Swim Test, respectively. Specifically, diazepam given during P10-16 but not during later weeks resulted in increased anxiety-like behavior in adulthood, while diazepam administered during P29-35 but not earlier nor later resulted in increased immobility behavior in adulthood. We conclude that anxiety-like behavior in the Elevated Plus Maze and behavioral despair-like immobility in the Forced Swim Test are controlled by separate postnatal critical periods characterized by distinct developmental sensitivity to manipulation of GABAergic transmission via γ2 subunit-containing GABA(A)Rs.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Depressão/fisiopatologia , Neurônios GABAérgicos/fisiologia , Receptores de GABA-A/genética , Transmissão Sináptica/fisiologia , Fatores Etários , Análise de Variância , Animais , Transtornos de Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Depressão/metabolismo , Diazepam/farmacologia , Sinergismo Farmacológico , Feminino , Dosagem de Genes/genética , Técnicas de Silenciamento de Genes , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Aprendizagem em Labirinto/fisiologia , Camundongos , Receptores de GABA-A/metabolismo , Tamoxifeno/farmacologia
6.
Biol Psychiatry ; 68(6): 512-20, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20579975

RESUMO

BACKGROUND: The gamma-aminobutyric acid (GABA) Type A receptor deficits that are induced by global or forebrain-specific heterozygous inactivation of the gamma2 subunit gene in mouse embryos result in behavior indicative of trait anxiety and depressive states. By contrast, a comparable deficit that is delayed to adolescence is without these behavioral consequences. Here we characterized gamma2-deficient mice with respect to hypothalamic-pituitary-adrenal (HPA) axis abnormalities and antidepressant drug responses. METHODS: We analyzed the behavioral responses of gamma2(+/-) mice to desipramine and fluoxetine in novelty suppressed feeding, forced swim, tail suspension, and sucrose consumption tests as well as GABA(A) receptor deficit- and antidepressant drug treatment-induced alterations in serum corticosterone. RESULTS: Baseline corticosterone concentrations in adult gamma2-deficient mice were elevated independent of whether the genetic lesion was induced during embryogenesis or delayed to adolescence. However, the manifestation of anxious-depressive behavior in different gamma2-deficient mouse lines was correlated with early onset HPA axis hyperactivity during postnatal development. Chronic but not subchronic treatment of gamma2(+/-) mice with fluoxetine or desipramine normalized anxiety-like behavior in the novelty suppressed feeding test. Moreover, desipramine had antidepressant-like effects in that it normalized HPA axis function and depression-related behavior of gamma2(+/-) mice in the forced swim, tail suspension, and sucrose consumption tests. By contrast, fluoxetine was ineffective as an antidepressant and failed to normalize HPA axis function. CONCLUSIONS: Developmental deficits in GABAergic inhibition in the forebrain cause behavioral and endocrine abnormalities and selective antidepressant drug responsiveness indicative of anxious-depressive disorders such as melancholic depression, which are frequently characterized by HPA axis hyperactivity and greater efficacy of desipramine versus fluoxetine.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo/tratamento farmacológico , Desipramina/farmacologia , Fluoxetina/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de GABA-A/metabolismo , Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/farmacologia , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Corticosterona/sangue , Transtorno Depressivo/sangue , Transtorno Depressivo/genética , Desipramina/administração & dosagem , Modelos Animais de Doenças , Feminino , Fluoxetina/administração & dosagem , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Camundongos , Camundongos Knockout , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Receptores de GABA-A/genética , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/farmacologia
7.
J Am Soc Mass Spectrom ; 20(4): 723-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19200748

RESUMO

Protein citrullination is emerging as an important signaling mechanism that modulates a variety of biological processes. This protein modification constitutes only a 1 Da mass shift, and can be readily confused with other common protein modifications that yield an identical mass shift. In an attempt to develop a robust methodology for detection of protein citrullination sites, we analyzed synthetic citrulline-containing peptides by electrospray ionization tandem mass spectrometry. Collision-induced dissociation (CID) spectra revealed abundant neutral loss of 43 Da from citrullinated peptide precursor ions, which was reconciled by elimination of the HNCO moiety (isocyanic acid) from the citrulline ureido group. The elimination occurs readily in multiple charge states of precursor ions and also in b and y ions. HNCO loss in CID spectra provides a novel diagnostic marker for citrullination, and its utility was demonstrated by the discovery of Arg197 as the specific site of citrullination on nucleophosmin upon peptidylarginine deiminase 4 treatment.


Assuntos
Cromatografia Líquida , Citrulina/química , Cianatos/química , Peptídeos/química , Espectrometria de Massas em Tandem , Humanos , Hidrolases , Proteínas Nucleares , Processamento de Proteína Pós-Traducional , Desiminases de Arginina em Proteínas
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 28(2): 127-30, 2007 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-17649680

RESUMO

OBJECTIVE: To identify the epidemical characteristics of suicidal tendency among middle-school students in cities of China and to explore the main factors leading to suicidal tendency in adolescents. METHODS: Multi-stage cluster sampling method was used to select 9015 students in grades 1, 2, 3 and 4 respectively from 25 general middle schools in Beijing, Hangzhou, Wuhan and Urumqi of China in June 2006 and field investigation was carried out through "China Global School-based Student Health Survey (GSHS) Questionnaire". RESULTS: Among the students in the four cities, the incidence rates of suicidal ideation were from 14.4% to 20.8% with an average of 17.4%. The incidence rates of suicidal plan were from 6.8% to 9.7% with an average of 8.2% and were different among cities. 15.0% of the boys had suicidal ideation and 6.7% of them made a suicidal plan comparing to 19.7% of girls having had suicidal ideation and 9.5% of them made a suicidal plan. The two kinds of suicidal tendency in girls were all higher than those in boys. City, age, gender, grade, days and type of being bullied, depression, close friends and having received health education on coping with stresses were factors influencing suicidal tendency of students. Days of being bullied and suicidal tendency showed a dose-response relation. CONCLUSION: Suicidal tendency seemed common in middle-school students. Training on 'coping the issue' should be strengthened and harmonious environment should be improved in middle-schools.


Assuntos
Estudantes/psicologia , Suicídio/estatística & dados numéricos , Adolescente , China/epidemiologia , Coleta de Dados , Feminino , Humanos , Incidência , Masculino , Suicídio/psicologia , População Urbana
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