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1.
Hereditas ; 156: 34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708719

RESUMO

Background: Cadmium (Cd) is a ubiquitous environmental toxicant for aquatic animals. The freshwater crab, Sinopotamon henanense (S. henanense), is a useful model for monitoring Cd exposure since it is widely distributed in sediments whereby it tends to accumulate several toxicants, including Cd. In the recent years, the toxic effects of Cd in the hepatopancreas of S. henanense have been demonstrated by a series of biochemical analysis and ultrastructural observations as well as the deep sequencing approaches and gene expression profile analysis. However, the post-transcriptional regulatory network underlying Cd toxicity in S.henanense is still largely unknown. Results: The miRNA transcriptional profile of the hepatopancreas of S. henanense was used to investigate the expression levels of miRNAs in response to Cd toxicity. In total, 464 known miRNAs and 191 novel miRNAs were identified. Among these 656 miRNAs, 126 known miRNAs could be matched with the miRNAs of Portunus trituberculatus, Eriocheir sinensis and Scylla paramamosain. Furthermore, a total of 24 conserved miRNAs were detected in these four crab species. Fifty-one differentially expressed miRNAs were identified in the Cd-exposed group, with 31 up-regulated and 20 down-regulated. Eight of the differentially expressed miRNAs were randomly selected and verified by the quantitative real-time PCR (qRT-PCR), and there was a general consistency (87.25%) between the qRT-PCR and miRNA transcriptome data. A total of 5258 target genes were screened by bioinformatics prediction. GO term analysis showed that, 17 GO terms were significantly enriched, which were mainly related to the regulation of oxidoreductase activity. KEGG pathway analysis showed that 18 pathways were significantly enriched, which were mainly associated with the biosynthesis, modification and degradation of proteins. Conclusion: In response to Cd toxicity, in the hepatopancreas of S. henanense, the expressions of significant amount of miRNAs were altered, which may be an adaptation to resist the oxidative stress induced by Cd. These results provide a basis for further studies of miRNA-mediated functional adaptation of the animal to combat Cd toxicity.

2.
Toxicology ; 423: 112-122, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152847

RESUMO

Cadmium (Cd) is one of the environmental pollutants, which has multiple toxic effects on fetuses and placentas. Placental fatty acid (FA) uptake and transport are critical for the fetal and placental development. We aimed to analyze the triglyceride (TG) level, the expression patterns of several key genes involved in FA uptake and transport, and the molecular mechanisms for the altered gene expressions in placentas in response to Cd treatment. Our results showed that the placental TG level was significantly decreased in the Cd-exposed placentas. Fatty acid transporting protein 1 (FATP1), FATP6 and fatty acid binding protein 3 (FABP3) were significantly down-regulated in the placentas from Cd-exposed mice. The expression level of phospho-p38 MAPK was increased by Cd treatment, while the protein level of total p38 MAPK remained unchanged. The expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) and the hypoxia-inducible factor-1α (HIF-1α) were significantly decreased in the Cd-exposed placentas. The methylation levels of the promoter regions of FATP1, FATP6 and FABP3 showed no significant differences between the treatment and control groups. In addition, the circulating non-esterified fatty acid (NEFA), total cholesterol (TC), and TG levels were not decreased in the maternal serum from the Cd-exposed mice. Therefore, our results suggest Cd exposure dose not reduce the maternal FA supply, but reduces the placental TG level. Cd treatment also downregulates the placental expressions of FATP1, FATP6 and FABP3, respectively associated with p38-MAPK, p38 MAPK/PPAR-γ and HIF-1α pathways.

3.
J Colloid Interface Sci ; 545: 200-208, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30884425

RESUMO

Rational design and facile synthesis of two-dimensional (2D) materials still remain a great challenge. Herein, a facile process was proposed to construct 2D porous hybrid nanosheets, with ultrathin antimony nanoplates (with a thickness of ca. 0.5 nm) being anchored on acetone-derived graphene-like carbon porous nanosheets, by an aldol reaction and subsequent carbothermal reduction method using acetone and antimony acetate as the starting raw materials. The novel structural and compositional characteristics afford the 2D porous hybrid nanosheets with impressive boosting electrochemical sodium storage properties in terms of excellent cycling stability, high reversible specific capacity, and superior rate performance. The present work would provide significant value for the development of both synthetic methodology of 2D materials and their application as electrode active materials for energy storage and conversion.

4.
Int J Mol Sci ; 20(2)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669342

RESUMO

Adenosine deaminases acting on RNA (ADAR) are enzymes that regulate RNA metabolism through post-transcriptional mechanisms. ADAR1 is involved in a variety of pathological conditions including inflammation, cancer, and the host defense against viral infections. However, the role of ADAR1p150 in vascular disease remains unclear. In this study, we examined the expression of ADAR1p150 and its role in viral myocarditis (VMC) in a mouse model. VMC mouse cardiomyocytes showed significantly higher expression of ADAR1p150 compared to the control samples. Coimmunoprecipitation verified that ADAR1p150 forms a complex with Dicer in VMC. miRNA-222, which is involved in many cardiac diseases, is highly expressed in cardiomyocytes in VMC. In addition, the expression of miRNA-222 was promoted by ADAR1p150/Dicer. Among the target genes of miRNA-222, the expression of phosphatase-and-tensin (PTEN) protein was significantly reduced in VMC. By using a bioinformatics tool, we found a potential binding site of miRNA-222 on the PTEN gene's 3'-UTR, suggesting that miRNA-222 might play a regulatory role. In cultured cells, miR-222 suppressed PTEN expression. Our findings suggest that ADAR1p150 plays a key role in complexing with Dicer and promoting the expression of miRNA-222, the latter of which suppresses the expression of the target gene PTEN during VMC. Our work reveals a previously unknown role of ADAR1p150 in gene expression in VMC.


Assuntos
Adenosina Desaminase/metabolismo , Infecções por Coxsackievirus/complicações , Enterovirus Humano B , MicroRNAs/genética , Miocardite/etiologia , Miocardite/metabolismo , PTEN Fosfo-Hidrolase/genética , Ribonuclease III/metabolismo , Animais , Sobrevivência Celular/genética , Células Cultivadas , Infecções por Coxsackievirus/patologia , Infecções por Coxsackievirus/virologia , Modelos Animais de Doenças , Enterovirus Humano B/fisiologia , Expressão Gênica , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Imuno-Histoquímica , Masculino , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/virologia , Ligação Proteica , Interferência de RNA
5.
Artigo em Inglês | MEDLINE | ID: mdl-30419307

RESUMO

PURPOSE: Postmastectomy radiotherapy (PMRT) showed heterogeneous effects on survival outcome of patients with T1-2N1 breast cancer. A reliable model to estimate individuals' risk of locoregional recurrence (LRR) and the potential benefit derived from PMRT is in need. METHODS AND MATERIALS: We retrospectively analyzed 1141 patients with T1-2N1 breast cancer who underwent mastectomy between January 2001 and December 2012. Based on the Fine and Gray competing risks regression in 623 unirradiated patients, a nomogram predicting LRR was conducted for risk quantification. Decision tree analysis was performed for patient grouping. The impact of PMRT was evaluated among three subgroups. RESULTS: With a median follow-up of 74.9 months, the five-year cumulative incidence of LRR, distant recurrence (DR) and breast cancer mortality (BCM) were 3.9%, 8.8% and 6.0% for the entire cohort. Based on nomogram scores, patients were classified into three risk groups in decision tree analysis. In high-risk group, PMRT was found to be associated with a 12.7% risk reduction of 5-year LRR, 9.2% risk reduction of 5-year DR and 7.0% risk reduction of 5-year BCM, while it was not significantly associated with LRR, DR or BCM in low- and intermediate-risk groups. CONCLUSIONS: The nomogram performed individualized risk quantification of LRR in patients with T1-2N1 breast cancer. A newly identified patient subgroup with high risk of LRR were found to derive survival benefit from PMRT.

6.
Breast Cancer ; 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30367358

RESUMO

BACKGROUND: Ovarian function suppression (OFS) plus other endocrine treatment was recommended to hormone receptor (HR)-positive breast cancer by some guidelines recently. We performed this study to validate the survival benefits of OFS plus aromatase inhibitors (AI) or selective estrogen receptor modulators (SERM) in the real world. METHODS: All premenopausal, HR-positive breast cancer patients diagnosed between 1996 and 2017 were identified. Eligible patients were classified into three groups according to their adjuvant endocrine treatment, including OFS plus AI, OFS plus SERM and SERM alone. The primary outcome is invasive disease-free survival (iDFS), whereas the secondary outcome is overall survival (OS). Cox proportional hazards models and propensity score adjusted models were used to compare the survival benefits in three groups. RESULTS: We included 2838 patients, of which 246 received OFS plus AI, 175 received OFS plus SERM, and 2417 received SERM alone. Compared with SERM alone, OFS plus AI was associated with an improved iDFS (HR 0.59, 95% CI 0.36-0.96) and OS (HR 0.26, 95% CI 0.08-0.85). OFS plus SERM, however, was not significantly associated with extended iDFS or OS. Among patients older than 40 years old, OFS plus AI was more effective than OFS plus SERM (HR 0.38, 95% CI 0.17-0.88) or SERM alone (HR 0.44, 95% CI 0.23-0.84) in terms of iDFS. CONCLUSIONS: Our findings suggest that OFS plus AI treatment may extend both iDFS and OS among premenopausal patients with hormone receptor-positive breast cancer in the real world.

7.
Transl Psychiatry ; 8(1): 232, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30352990

RESUMO

Susceptible genetic polymorphisms and altered expression levels of protein kinase C (PKC)-encoding genes suggest overactivation of PKC in autism spectrum disorder (ASD) development. To delineate the pathological role of PKC, we pharmacologically stimulated its activity during the early development of zebrafish. Results demonstrated that PKC hyper-activation perturbs zebrafish development and induces a long-lasting head size deficit. The anatomical and cellular analysis revealed reduced neural precursor proliferation and newborn neuron formation. ß-Catenin that is essential for brain growth is dramatically degraded. Stabilization of ß-catenin by gsk3ß inhibition partially restores the head size deficit. In addition, the neuropathogenic effect of developmental PKC hyper-activation was further supported by the alterations in the behavioral domain including motor abnormalities, heightened stress reactivity and impaired habituation learning. Taken together, by causally connecting early-life PKC hyper-activation to these neuropathological traits and the impaired neurogenesis, these results suggest that PKC could be a critical pathway in ASD pathogenesis.

8.
Chin Clin Oncol ; 7(3): 24, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30056726

RESUMO

It is largely unclear that whether or not surgical resection of the primary tumors could confer survival benefit among patients with metastatic breast cancer at initial presentation. We thoroughly reviewed the up-to-date evidence on surgical resection of the primary lesion in metastatic breast cancer, including comparative studies (of particular interest in risk modifiers, the type, and timing of surgical procedures), Chinese and international guidelines, as well as the progress of clinical trials. Partial modified radical mastectomy and breast-conserving surgery are by far the most common choices for patients with metastatic breast cancer. Patients with certain characteristics, for example, younger than 45 years of age or with oligo-metastasis, might benefit from the surgery. The type and timing of surgical procedures are still in debate according to the guidelines from different countries. Forthcoming evidence from the ongoing clinical trials might help close the knowledge gaps in surgical treatment for patients with metastatic breast cancer and aid the decision-making in clinical practice.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar/estatística & dados numéricos , Mastectomia/estatística & dados numéricos , Adulto , Feminino , Humanos , Mastectomia/métodos , Mastectomia/tendências , Mastectomia Segmentar/tendências , Pessoa de Meia-Idade , Metástase Neoplásica
9.
Cancer Res ; 78(15): 4163-4174, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29735546

RESUMO

Long noncoding RNAs (lncRNA) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here, we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell-cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis.Significance: These findings identify a tumor-suppressive long noncoding RNA in papillary thyroid carcinoma.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4163/F1.large.jpg Cancer Res; 78(15); 4163-74. ©2018 AACR.

10.
Oncotarget ; 8(50): 87151-87162, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29152070

RESUMO

Studies have showed that dysfunction in the breast cancer susceptibility gene (BRCA) is associated with triple-negative breast cancer (TNBC); however, its effect on patient survival remains controversial. We investigated the distribution of BRCA1/2 mutations in unselected Chinese patients with TNBC and explored their roles in prognosis. Then a systematic review and meta-analysis were performed to evaluate the prognostic role of BRCA dysfunction, including BRCA1/2 germline/somatic mutations, BRCA1 promoter methylation, and low BRCA1 protein expression in TNBC patients. Pooled hazard ratios with 95% confidence intervals were estimated to determine the association between BRCA dysfunction and survival. Our results showed a high frequency of BRCA1/2 mutations, especially germline BRCA1 variants, were associated with bilateral breast cancer. Although no correlations were found between BRCA1/2 mutations and recurrence-free survival (RFS) or overall survival (OS). In the meta-analysis, patients with BRCA1 promoter methylation showed poor OS. However, there was a favorable impact on disease free survival (DFS) for TNBC patients with BRCA1 promoter methylation when received adjuvant-chemotherapy. In conclusion, BRCA1/2 mutations were associated with bilateral breast cancer and BRCA1 promoter methylation may have a prognostic effect on TNBC.

11.
Oncotarget ; 8(42): 71587-71596, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069731

RESUMO

The c-Myc transcription factor is involved in cell proliferation, cell cycle and apoptosis by activating or repressing transcription of multiple genes. Circular RNAs (circRNAs) are widely expressed non-coding RNAs participating in the regulation of gene expression. Using a high-throughput microarray assay, we showed that Myc regulates the expression of certain circRNAs. A total of 309 up- and 252 down-regulated circRNAs were identified. Among them, randomly selected 8 circRNAs were confirmed by real-time PCR. Subsequently, Myc-binding sites were found to generally exist in the promoter regions of differentially expressed circRNAs. Based on miRNA sponge mechanism, we constructed circRNAs/miRNAs network regulated by Myc, suggesting that circRNAs may widely regulate protein expression through miRNA sponge mechanism. Lastly, we took advantage of Gene Ontology and KEGG analyses to point out that Myc-regulated circRNAs could impact cell proliferation through affecting Ras signaling pathway and pathways in cancer. Our study for the first time demonstrated that Myc transcription factor regulates the expression of circRNAs, adding a novel component of the Myc tumorigenic program and opening a window to investigate the function of certain circRNAs in tumorigenesis.

12.
Fish Shellfish Immunol ; 69: 1-5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28826621

RESUMO

Triplicate groups of juvenile yellow catfish Pelteobagrus fulvidraco were exposed to three levels of α-ethinylestradiol (EE2) (0, 0.1 and 1 ng L-1) for 56 days. Fish survival rate (>93.33%) was not different among experimental groups. Weight gain and specific growth rate of fish exposed to EE2 were higher than those of control fish. Hepatosomatic index of fish exposed to 1 ng L-1 EE2 was the highest. Serum total protein, albumin, globulin, alanine aminotransferase, aspartate transaminase, cholesterol and triglyceride increased with increasing EE2 exposure levels. Liver total anti-oxidative capacity, malondialdehyde content and lysozyme activity of fish exposed to EE2 were higher than those of control fish. Phagocytic indices of fish exposed to 1 ng L-1 EE2 was lower than that of control fish. This study indicates that although EE2 exposure can promote the growth of yellow catfish in short-term, EE2 exerts its toxic effects by inducing reactive oxygen species generation and malondialdehyde accumulation, leading to blood deterioration and interfering with immune response.


Assuntos
Peixes-Gato , Disruptores Endócrinos/toxicidade , Etinilestradiol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Peixes-Gato/sangue , Peixes-Gato/crescimento & desenvolvimento , Peixes-Gato/imunologia , Peixes-Gato/metabolismo , Relação Dose-Resposta a Droga , Imunidade Inata , Distribuição Aleatória
13.
J Endocrinol ; 234(3): 233-246, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28611209

RESUMO

Gonadotropin signaling plays a pivotal role in the spermatogenesis of vertebrates, but exactly how gonadotropins regulate the process in non-mammalian species remains elusive. Using a gene knockout approach in zebrafish, we have previously demonstrated the non-canonical action of gonadotropin signaling on spermatogenesis by analyzing four single mutant lines (lhb, lhr, fshb and fshr) and three double mutant lines (lhb;fshb, lhr;fshr and fshb;lhr). In this study, we further investigated the actions of gonadotropins on the testis by establishing three other double-mutant zebrafish lines (lhb;lhr, fshb;fshr and lhb;fshr). All lhb;lhr and fshb;fshr mutant males were fertile. Analysis on the gonadosomatic index and testicular histology in these lhb;lhr and fshb;fshr mutants demonstrated that Lh signaling and Fsh signaling could functionally compensate each other in the testis. Intriguingly, it was found that the lhb;fshr mutant male fish were also morphologically and histologically normal and functionally fertile, a phenomenon which could be explained by the cross-activation of Lhr by Fsh. We have demonstrated this cross-reactivity for the first time in zebrafish. Fsh was shown to activate Lhr using three different assay systems, in which Lh-Fshr activation was also confirmed. Taken together, we conclude that the action of Lh signaling and Fsh signaling is redundant in that either alone can support zebrafish spermatogenesis based on two observations. First, that either Lh signaling or Fsh signaling alone is sufficient to support male fertility. Second, that the two gonadotropin ligands could promiscuously activate both receptors. Apart from revealing the complexity of gonadotropin signaling in controlling male reproduction in zebrafish, this study also shed light toward a better understanding on the evolution of gonadotropin signaling in vertebrates from fish to mammals.


Assuntos
Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Espermatogênese , Testículo/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Feminino , Masculino , Receptores do FSH/genética , Receptores do LH/genética , Transdução de Sinais , Testículo/citologia , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-28620419

RESUMO

Periplaneta americana extracts (PAEs) exhibit wound healing properties. However, the underlying molecular mechanisms are not well understood. Here, we treated human skin fibroblasts (HSF) with PAE and the proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The wound healing and transwell migration assays were used to detect cell migration. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) pathways were analyzed by Western blot (WB). Immunofluorescence staining was used to detect the key molecular localization in the cells. The results showed that PAE enhanced the proliferation and migration of HSF cells. The expression and activation of key proteins such as RelA and p-ERK were increased in NF-κB and ERK pathways followed by nuclear translocation. In vivo, both WB and immunohistochemical (IHC) staining showed that PAE enhanced p-IκBα and p-ERK activation and the nuclear translocation of RelA. Our study suggests that the protective function of PAE is mediated via enhanced NF-κB and ERK signaling.

15.
Int J Mol Med ; 40(2): 465-473, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28656220

RESUMO

Periplaneta americana extracts (PAEs) play a crucial role in skin wound healing. However, their molecular effects and signaling pathways in regenerating tissues and cells are not clear. In this study, we refined the PAE from Periplaneta americana to investigate the mechanisms underlying skin wound healing. The human keratinocyte line HaCaT was selected and a mouse model of deep second-degree thermal burn was established for in vitro and in vivo studies, respectively. PAE treatment induced the proliferation and migration of HaCaT cells and wound healing in the burn model. Furthermore, the effects of PAE on wound healing were found to depend on the Janus-activated kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway and Smad3 activities, according to western blot analysis and immunohistochemical (IHC) assays in vitro and in vivo. Pretreatment with a STAT3 inhibitor blocked the cell proliferation and migration induced by PAE. The results indicate the wound-healing function of PAE via enhanced JAK/STAT3 signaling and Smad3 activities. Our studies provide a theoretical basis underlying the role of PAE in cutaneous wound healing.


Assuntos
Queimaduras/tratamento farmacológico , Janus Quinases/metabolismo , Periplaneta , Extratos Vegetais/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Proteína Smad3/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Queimaduras/metabolismo , Queimaduras/patologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Camundongos , Periplaneta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
16.
Medicine (Baltimore) ; 96(22): e7048, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28562563

RESUMO

The International Consensus Guidelines for advanced breast cancer (ABC) considers that the surgery of the primary tumor for stage IV breast cancer patients does not usually improve the survival. However, studies have showed that resection of the primary tumor may benefit these patients. The correlation between surgery and survival remains unclear.The impact of surgery and other clinical factors on overall survival (OS) of stage IV patients is investigated in West China Hospital. Female patients diagnosed with stage IV breast cancer between 1999 and 2014 were included (N = 223). Univariate and multivariate analysis assessed the association between surgery and OS.One hundred seventy-seven (79.4%) underwent surgery for the primary tumor, and 46 (20.6%) had no surgery. No significant differences were observed in age at diagnosis, T-stage, N-stage, histological grade, molecular subtype, hormone receptor (HR), and number of metastatic sites between 2 groups. Patients in the surgery group had dramatically longer OS (45.6 vs 21.3 months, log-rank P < .001). In univariate analysis, survival was associated with surgical treatment, residence, tumor size, lymph node, HR status, hormonal therapy, and radiotherapy. In multivariate analysis, surgery was an independent prognostic factor for OS [hazard ratio (HR), 0.569; 95% confidence interval (CI) 0.329-0.984, P = .044]. Additional independent prognostic factors were hormonal therapy (HR, 0.490; 95% CI 0.300-0.800) and radiotherapy (HR, 0.490; 95% CI 0.293-0.819). In addition, a favorable impact of surgery was observed by subgroup analysis.Our study showed that surgery of the primary breast tumor has a positive impact on OS in with stage IV breast cancer patients.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Adulto , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , China/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Menopausa , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , População Rural , Resultado do Tratamento , População Urbana
17.
Biol Psychol ; 126: 30-40, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28396213

RESUMO

Loss aversion is the tendency to prefer avoiding losses over acquiring gains of the same amount. To shed light on the spatio-temporal processes underlying loss aversion, we analysed the associations between individual loss aversion and electrophysiological responses to loss and gain outcomes in a monetary gamble task. Electroencephalographic feedback-related negativity (FRN) was computed in 29 healthy participants as the difference in electrical potentials between losses and gains. Loss aversion was evaluated using non-linear parametric fitting of choices in a separate gamble task. Loss aversion correlated positively with FRN amplitude (233-263ms) at electrodes covering the lower face. Feedback related potentials were modelled by five equivalent source dipoles. From these dipoles, stronger activity in a source located in the orbitofrontal cortex was associated with loss aversion. The results suggest that loss aversion implemented during risky decision making is related to a valuation process in the orbitofrontal cortex, which manifests during learning choice outcomes.


Assuntos
Comportamento de Escolha , Tomada de Decisões/fisiologia , Potenciais Evocados/fisiologia , Retroalimentação Psicológica/fisiologia , Jogo de Azar/psicologia , Adulto , Afeto/fisiologia , Córtex Cerebral/fisiologia , Eletroencefalografia , Retroalimentação , Feminino , Jogo de Azar/fisiopatologia , Voluntários Saudáveis , Humanos , Aprendizagem/fisiologia , Masculino , Fatores de Tempo , Adulto Jovem
18.
Eur J Med Chem ; 133: 227-239, 2017 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-28390228

RESUMO

A double Claisen rearrangements synthetic strategy was established for the total synthesis of 4,4'-dimethyl medicagenin (compound 6c). A series of its analogs also were prepared, including two novel 3',5'-diprenylated chalcones, in which ring B was replaced by azaheterocycle. The structures of the twenty-two newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. In vitro, the cytotoxicity of the target compounds was evaluated using cancer cells. Noticeably, compound 10 exhibited broad-spectrum cytotoxicity on PC3 prostate cancer cells, MDA-MB-231 breast cancer cells (MDA), HEL and K562 erythroleukemia cells with IC50 values of 2.92, 3.14, 1.85 and 2.64 µM, respectively. Further studies indicated that compound 10 induced apoptosis and arrested the cell cycle phase of the above mentioned four cancer cell lines. By contrast, compound 6g selectively displayed potent inhibitory activity against the proliferation of HEL cells with an IC50 value of 4.35 µM. Compound 6g slightly induced apoptosis and arrested cell cycle phase of HEL cells. Preliminary structure-activity relationship studies indicated that, in all cancer cell lines evaluated, the 3-pyridinyl group was essential for cytotoxicity.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Chalconas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/tratamento farmacológico , Prenilação , Relação Estrutura-Atividade
19.
Cell Mol Life Sci ; 74(13): 2503-2511, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28224202

RESUMO

Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development. Our findings establish that Cre/loxP-mediated tissue-specific gene knockout could be achieved using this BACK strategy and that canonical microRNAs play important roles in early embryonic development in zebrafish.


Assuntos
Cromossomos Artificiais Bacterianos/genética , Técnicas de Inativação de Genes/métodos , Células Germinativas/metabolismo , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Sequência de Bases , Desenvolvimento Embrionário/genética , Éxons/genética , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Marcação de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação/genética , Processamento Pós-Transcricional do RNA/genética , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo
20.
Oncotarget ; 7(38): 61273-61283, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27542224

RESUMO

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is involved in tumor development. However, how ADAMTS6 influences cancer remains unknown. We investigated the biological function and clinical implications of ADAMTs6 in breast cancer (BC). Its functional significance in BC cell lines was confirmed by ADAMTs6 overexpression or downregulation both in vitro and in vivo studies. Enhanced ADAMTS6 expression suppressed cell migration, invasion, and tumorigenesis, whereas knockdown promoted these characteristics. The extracellular signal-regulated kinase (ERK) pathway was partially involved in ADAMTS6-mediated inhibition of BC development, and miR-221-3p was identified as a predicted target for ADAMTS6. Results from the luciferase assay confirmed that miR-221-3p directly inhibited ADAMTS6 expression by binding its 3'-untranslated region. In addition, immunohistochemistry data from specimens from 182 BC patients showed that high ADAMTS6 expression was significantly correlated with favorable disease-free survival (DFS, p = 0.045). Subgroup analysis of patients with ER positive, PR positive or HER-2 negative tumors revealed that high ADAMTS6 expression more strongly extended DFS compared to low expression (p = 0.004, p = 0.009, p = 0.017). Multivariate analyses confirmed that ADAMTS6 expression was an independent risk factor for DFS (p = 0.011). Together, these data demonstrate that ADAMTS6 inhibits tumor development by regulating the ERK pathway via binding of miR-221-3p. Thus, its expression may be a potential prognostic biomarker for BC.


Assuntos
Proteínas ADAMTS/metabolismo , Neoplasias da Mama/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Regiões 3' não Traduzidas , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/genética , Progressão da Doença , Feminino , Células HEK293 , Humanos , Células MCF-7 , MicroRNAs/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Interferência de RNA , Resultado do Tratamento
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