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1.
Plant Signal Behav ; : 1987767, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686106

RESUMO

Anthocyanins, a flavonoid group of polyphenolic compounds, have evolved in plants since the land was colonized by plants. These bioactive compounds play critical roles in diverse physiological processes. They are synthesized in the cytosol and transported into the vacuole for storage or to other destinations, where they function as bioactive molecules. The mechanisms of anthocyanin synthesis and transport have been well studied. However, the precise regulation of the mechanisms of anthocyanin degradation remains to be elucidated. In this review, we highlight recent progress in the understanding of the characteristics and functions of anthocyanins and class III peroxidases, as well as of the existing evidence of the effects of class III peroxidases on the degradation of anthocyanins and the possible regulatory mechanisms involved.

2.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1050-1055, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362481

RESUMO

OBJECTIVE: To investigate the effect of sulforaphane (SFN) on G2/M phase arrest of acute myeloid leukemia cells and its molecular mechanism. METHODS: KG1a and KG1cells were treated by different concentrations of SFN for 48 h. Flow cytometry (FCM) was used to analyze the phase distribution of cell cycle. High-throughput sequencing was used to detect the effect of SFN on the expression of cell cycle related genes in KG1a cells. The mRNA expression of P53, P21, CDC2 and CyclinB1 were detected by qPCR. The protein expression of P53, CDC2, P-CDC2 and CyclinB1 were detected by Western blot. RESULTS: Cells in the G2/M phase were increased from 11.9% to 54.0% in KG1a cells and 18.5% to 83.3% in KG1 cells after treated by SFN (8 µ mol / L) for 48 hours(P<0.001). KEGG analysis indicated that P53 pathway was enriched in KG1a cells after treated by SFN. The heat-map graph showed that SFN could change the relevant genes of the cell cycle in KG1a cells. After SFN treatment, the mRNA level of P53 and P21 were significantly increased in KG1 and KG1a cells(P<0.05 or P<0.01). The mRNA level of CDC2 showed a decrease trend with the increasing dose of SFN. At the dosage of 8 µmol /L, the mRNA expression levels of CDC2 was significantly lower than that in control group(P<0.05). At the same time, the protein level of P53 was significantly increased in KG1 and kG1a cells after treated by SFN(P<0.05). The protein level of CDC2 showed a decrease trend with the increasing dose of SFN in a dose manner(r=0.9482 and r=0.8977). The protein levels of CDC2 in SFN 8 and 12 µ mol/L groups were significantly lower than that in control group(P<0.05, P<0.01). The protein levels of P-CDC2 was increased. But the change of mRNA and protein level of CyclinB1 was not significant. CONCLUSION: SFN induces leukemia cells to block in G2/M phase by activating P53 signaling pathway, which can inhibit the expression of CDC2 and the activity of CDC2/cyclinB1.


Assuntos
Isotiocianatos , Leucemia Mieloide Aguda , Ciclo Celular , Humanos , Isotiocianatos/farmacologia , Mitose , Sulfóxidos
4.
Chin Med J (Engl) ; 134(12): 1450-1456, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34091522

RESUMO

BACKGROUND: Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up. METHODS: The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC). RESULTS: A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001). CONCLUSIONS: The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.


Assuntos
Doença da Artéria Coronariana , Reestenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Preparações Farmacêuticas , Constrição Patológica , Angiografia Coronária , Doença da Artéria Coronariana/terapia , Seguimentos , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
5.
Nat Cell Biol ; 23(3): 268-277, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33664495

RESUMO

The sympathetic nervous system-catecholamine-uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1. Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice. The PKA-AIDA-UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.


Assuntos
Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/inervação , Proteínas de Transferência de Fosfolipídeos/metabolismo , Sistema Nervoso Simpático/fisiologia , Termogênese , Proteína Desacopladora 1/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Animais , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Metabolismo Energético , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução , Proteínas de Transferência de Fosfolipídeos/deficiência , Proteínas de Transferência de Fosfolipídeos/genética , Fosforilação , Transdução de Sinais , Proteína Desacopladora 1/deficiência , Proteína Desacopladora 1/genética
6.
Am Surg ; 86(6): 621-627, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32683957

RESUMO

BACKGROUND: To identify the association between the width of the gastric conduit and the benign anastomotic stricture (BAS) after esophagectomy with end-to-side cervical anastomosis for esophageal cancer. METHODS: Patients with esophageal cancer who underwent esophagectomy between July 2013 and July 2014 were included in this study. The gastric conduit was used for reconstruction in all patients and end-to-side cervical anastomosis were performed using a circular stapler. The patients were divided into a narrow group (3-5 cm) and a wide group (>5 cm) based on the gastric conduit width. Univariate and multivariate logistic regressions were used to analyze the possible factors (patients' age, gender, preoperative comorbidities, neoadjuvant chemotherapy, gastric conduit width, anastomotic leakage) that could affect the incidence of BAS. RESULTS: Two-hundred and one patients were included in this study. The median follow-up period was 29 months (17-58 months). Seven cases (3.5%) showed anastomotic leakage in the postoperative period and 38 patients (18.9%) developed BAS; all within the first year of follow-up. In univariate analysis, the width of the gastric conduit was the only risk factor for the development of BAS (odds ratio [OR] = 3.36, P = .005). In multivariate logistic regression analysis, the wide group was an independent significant risk factor for the development of BAS developing compared with the narrow group (OR = 2.84, P = .02). CONCLUSIONS: A wide gastric conduit width (>5 cm) is an independent risk factor for the development of BAS after esophagectomy and stapled cervical end-to-side anastomosis for esophageal cancer.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Constrição Patológica/etiologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Anastomose Cirúrgica/métodos , Esofagectomia/métodos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estômago/cirurgia
7.
Ying Yong Sheng Tai Xue Bao ; 31(5): 1525-1534, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32530230

RESUMO

To explore the water consumption characteristics of trees, the thermal dissipation probe technology was used to monitor sap flow of Populus bolleana in east sandy land of Yellow River, from July to November in 2017. Microclimate variables were monitored. We analyzed the diurnal and seasonal variations of water consumption, and proposed the models for water consumption with back propagation neural network (BPNN) and Elman neural network (ENN) based on fuzzy rules. Results showed that the average sap flow rate of P. bolleana was 4.98 g·cm-2·h-1 in growing season (July to October), with solar radiation (Rs), temperature (T), vapor pressure deficit (VPD) and relative humidity (RH) as the main factors affecting sap flow. Due to the influence of meteorological factors, water consumption was characterized by obvious seasonal variation, with that in summer (July-August) being 1.4 times of that in autumn (September-October). BPNN and ENN models based on fuzzy rules were used to simulate water consumption of P. euphratica. The optimal parameter calibration of two models explained more than 80% of the total variation, which indicated that these two models could more accurately simulate water consumption. Compared with the BP neural network model, the simulated results of ENN model showed that the relative error was reduced by 27.0%, RMSE was reduced by 24.3%, Nash-Sutclife efficiency coefficient increased by 67.9%, R2 was higher than 0.80. The ENN model performed better than BPNN model with a higher efficiency and goodness of fitness. ENN model effectively improved the simulating accuracy of water consumption. Therefore, it could be used as an optimal model to estimate water consumption of P. bolleana in east sandy land of Yellow River.


Assuntos
Populus , China , Ingestão de Líquidos , Redes Neurais de Computação , Transpiração Vegetal , Árvores , Água
8.
Int J Biol Sci ; 16(4): 598-610, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32025208

RESUMO

Our previous study demonstrated a close relationship between the NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). Its receptor gene, NOTCH1, and its downstream gene, HES1, contribute to the proliferation, invasion and metastasis of SACC. Accumulating evidence supports HEY1 as another effector of the signaling pathway. The purpose of this study was to explore the effects of the NOTCH1-HEY1 pathway on the proliferation, invasion and metastasis of SACC cells. Our results verified that HEY1 is a specific molecular target of the NOTCH signaling pathway in SACC cells and that its expression in carcinoma is much higher than that in paracarcinoma tissues. The expression of NOTCH1 and HEY1 are positively correlated in the salivary adenoid cystic carcinoma tissues. NOTCH1 is significantly related to the activation of HEY1 in SACC, and that HEY1 reciprocally regulates NOTCH1 expression in SACC. HEY1 promotes cell proliferation and spheroid formation and inhibits cell apoptosis in vitro. In addition, HEY1 enhances the tumorigenicity of SACC in vivo. Furthermore, HEY1 increases cell invasion and metastasis by driving the expression of epithelial-mesenchymal transition (EMT)-related genes and MMPs. The results of this study indicate that the NOTCH1-HEY1 pathway is specifically upregulated in SACC and promotes cell proliferation, self-renewal, invasion, metastasis and the expression of EMT-related genes and MMPs. Our findings suggest that a NOTCH1-HEY1 pathway inhibitor might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Proteínas de Ciclo Celular/metabolismo , Receptor Notch1/metabolismo , Glândulas Salivares/patologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma Adenoide Cístico/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Receptor Notch1/genética , Glândulas Salivares/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tiazolidinas/farmacologia
9.
Sci Rep ; 9(1): 1963, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760749

RESUMO

LncRNA play important roles in regulation of host immune and inflammation responses in defending bacterial infection. Clostridium perfringens (C. perfringens) type C is one of primary bacteria leading to piglet diarrhea and other intestinal inflammatory diseases. For the differences of host immune capacity, individuals usually show resistance and susceptibility to bacterial infection. However, whether and how lncRNAs involved in modulating host immune resistance have not been reported. We have investigated the expression patterns of ileum lncRNAs of 7-day-old piglets infected by C. perfringens type C through RNA sequencing. A total of 16 lncRNAs and 126 mRNAs were significantly differentially expressed in resistance (IR) and susceptibility (IS) groups. Many lncRNAs and mRNAs were identified to regulate resistance and susceptibility of piglets through immune related pathways. Five lncRNAs may have potential function on regulating the expressions of cytokines, these lncRNAs and cytokines work together to co-regulated piglet immune response to C. perfringens, affecting host resistance and susceptibility. These results provide valuable information for understanding the functions of lncRNA and mRNA in affecting piglet diarrhea resistance of defensing to C. perfringens type C, these lncRNAs and mRNAs may be used as the important biomarkers for decreasing C. perfringens spread and diseases in human and piglets.


Assuntos
Infecções por Clostridium/veterinária , Íleo/imunologia , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Animais , Infecções por Clostridium/imunologia , Clostridium perfringens/imunologia , Citocinas/genética , Citocinas/imunologia , Diarreia/microbiologia , Diarreia/veterinária , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Íleo/microbiologia , Inflamação/genética , Inflamação/imunologia , Análise de Sequência de RNA , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia
10.
PLoS One ; 13(12): e0206135, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30550543

RESUMO

The size distribution of manufactured sand particles has a significant influence on the quality of concrete. To overcome the shortcomings of the traditional vibration-sieving method, a manufactured sand casting/dispersing system was developed, based on the characteristics of the sand particle contours (as determined by backlit image acquisition) and an extraction mechanism. Algorithms for eliminating particles from the image that had be repeatedly captured, as well as for identifying incomplete particles at the boundaries of the image, granular contour segmentation, and the determination of an equivalent particle size, are studied. The hardware and software for the image-based detection device were developed. A particle size repeatability experiment was carried out on the single-grade sands, grading the size fractions of the manufactured sand over a range of 0.6-4.75 mm. A method of particle-size correction is proposed to compensate for the difference in the results obtained by the image-based method and those obtained by the sieving method. The experimental results show that the maximum repeatability error of single-grade fractions is 3.46% and the grading size fraction is 0.51%. After the correction of the image method, the error between the grading size fractions obtained by the two methods was reduced from 7.22%, 6.10% and 5% to 1.47%, 1.65%, and 3.23%, respectively. The accuracy of the particle-size detection can thus satisfy real-world measuring requirements.


Assuntos
Indústria da Construção , Processamento de Imagem Assistida por Computador/métodos , Modelos Teóricos , Tamanho da Partícula
11.
BMC Cancer ; 18(1): 436, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29665790

RESUMO

BACKGROUND: Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC. METHODS: Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples. After HES1-siRNA transfected into SACC LM cells, the cell proliferation and cell apoptosis were tested by suitable methods; animal model was established to detect the change of growth ability of tumor. Transwell and wound healing assays were used to evaluate cell metastasis and invasion. RESULTS: We found that HES1 was strongly linked to NOTCH signaling pathway in SACC cells. The immunohistochemical results implied the high expression of HES1 in cancerous tissues. The growth of SACC LM cells transfected with HES1-siRNAs was significantly suppressed in vitro and tumorigenicity in vivo by inducing cell apoptosis. After HES1 expression was silenced, the SACC LM cell metastasis and invasion ability was suppressed. CONCLUSIONS: The results of this study demonstrate that HES1 is a specific downstream gene of NOTCH1 and that it contributes to SACC proliferation, apoptosis and metastasis. Our findings serve as evidence indicating that HES1 may be useful as a clinical target in the treatment of SACC.


Assuntos
Carcinoma Adenoide Cístico/genética , Oncogenes , Neoplasias das Glândulas Salivares/genética , Fatores de Transcrição HES-1/genética , Adulto , Idoso , Animais , Apoptose/genética , Carcinoma Adenoide Cístico/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Receptor Notch1/genética , Recidiva , Neoplasias das Glândulas Salivares/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Cell Cycle ; 17(2): 216-224, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29117785

RESUMO

OBJECTIVES: Notch1 regulates tumor biology in a complex, context-dependent manner. The roles of Notch1 in tongue cancer are still controversial. The aim of this study is to investigate the roles of Notch1 in tongue cancer. MATERIALS AND METHODS: The expression of Notch1 was tested between tongue cancer and normal samples by using immunohistochemistry. Tongue cancer cells were transfected with siRNA or plasmid, respectively. Cell proliferation, apoptosis, migration and invasion ability were tested in appropriate ways. The subcutaneous tumor model was established to observe the tumor growth. RESULTS: Notch1 was upregulated in tongue carcinoma tissues and the expression of Notch1 was related with tumor stage and differentiation. Overexpression of Notch1 could increase tongue cancer cells proliferation, invasion and migration. But inhibited the expression of Notch1 could decrease cells proliferation, invasion and migration and promote cell apoptosis in vitro and in vivo. CONCLUSION: Our results prove that the oncogenic role of Notch1 in tongue cancer and provide the direction of targeted therapy of tongue cancer.


Assuntos
Carcinoma de Células Escamosas/patologia , Receptor Notch1/fisiologia , Neoplasias da Língua/patologia , Animais , Apoptose , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Receptor Notch1/genética , Receptor Notch1/metabolismo , Neoplasias da Língua/genética , Neoplasias da Língua/metabolismo
13.
Mitochondrial DNA B Resour ; 3(2): 864-865, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-33474346

RESUMO

The complete mitochondrial genome sequence of the Qinghai Tibetan pig was first determined in this study. The total length of the mitogenome is 16,720 bp. Indicating the an A + T(60.5%)-rich feature, including 2 ribosomal RNA genes, 13 protein-coding genes. 22 transfer RNA genes and 1 non-coding control region. The NJ phylogenetic tree analysis showed that the phylogenetic relationship between Qinghai Tibetan pig and Yimenghei pig was the closest, and the relationship with Chinese northeas wildboar was farthest.

14.
Mol Med Rep ; 16(6): 8907-8915, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039489

RESUMO

Previous studies have reported that inhibitor of DNA binding 1 (ID1) exerts an oncogenic role in a number of tumors. In the present study, the role of ID1 in the growth, invasion and migration of salivary adenoid cystic carcinoma (SACC) cells was investigated. ID1 expression in clinical SACC samples was compared with that in normal salivary tissues using immunohistochemical staining, and the correlation between ID1 expression and clinical pathological characteristics was then determined. Subsequently, ID1 was overexpressed or silenced to investigate the effects of ID1 expression on SACC cell proliferation, invasion and migration. In addition, the gene expression levels of known ID1 target genes, including S100A9, CDKN2A and matrix metalloproteinase 1 (MMP1) was measured using reverse transcription­quantitative polymerase chain reaction to elucidate the potential mechanisms of ID1 in SACC. The results of the present study indicated that the protein expression levels of ID1 were significantly increased in the SACC tissues compared with that in the normal salivary tissues (P<0.001), and a positive correlation between ID1 expression and tumor stage (P=0.001), tumor invasion (P=0.002) and metastasis (P=0.019) in SACC was observed. Knockdown of ID1 in SACC cells significantly inhibited cell growth, invasion and migration (all P<0.01), whereas overexpression of ID1 promoted cell proliferation, invasion and migration (all P<0.01). The gene expression level of MMP1 was significantly reduced following ID1 knockdown in SACC­83 cells when compared with negative controls (P<0.05), whereas S100A9 and CDKN2A expression levels were significantly upregulated (both P<0.05). The results suggest that ID1 may regulate the growth, invasion and migration of SACC cells, and that MMP1, S100A9 and CDKN2A may serve as target genes of ID1 and mediate the effects of ID1 in SACC cells. Therefore, ID1 may present a potential target gene for the treatment of patients with SACC to inhibit cancer cell growth and metastasis.


Assuntos
Carcinoma Adenoide Cístico/genética , Proteína 1 Inibidora de Diferenciação/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Genes p16 , Humanos , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia
15.
Oncotarget ; 7(50): 82961-82971, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27783992

RESUMO

The cadherin-4 gene (CDH4) of the cadherin family encodes non-epithelial R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. In this study, we found higher expression of CDH4 mRNA in a salivary adenoid cystic carcinoma (SACC) cell line with low metastatic potential (SACC-83) than in a cell line with high metastatic potential (SACC-LM). By analyzing 67 samples of SACC tissues and 40 samples of paraneoplastic normal tissues, we found R-cad highly expressed in 100% of normal paraneoplastic tissue but only expressed in 64% of SACC tumor tissues (P<0.001). Knockdown of CDH4 expression in vitro promoted the growth, mobility and invasion of SACC cells, and in vivo experiments showed that decreased CDH4 expression enhanced SACC tumorigenicity. Furthermore, CDH4 suppression resulted in down-regulation of E-cadherin (E-cad), which is encoded by CDH1 gene and is a well-known tumor suppressor gene by inhibition of cell proliferation and migration. These results indicate that CDH4 may play a negative role in the growth and metastasis of SACC via co-expression with E-cadherin.


Assuntos
Caderinas/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Animais , Antígenos CD , Caderinas/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/secundário , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Interferência de RNA , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Transdução de Sinais , Fatores de Tempo , Transfecção , Carga Tumoral
16.
Oncol Rep ; 35(2): 1006-12, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25695658

RESUMO

Several studies have reported that FZD2 regulates tumor biology in a complex manner. The aim of the present study was to identify the role of FZD2 in the cell growth and metastasis of salivary adenoid cystic carcinomas (SACCs). The expression of FZD2 in ACC-83 and ACC-LM cells were measured with real-time PCR. Immunohistochemical staining was used to detect the expression of FZD2 in clinical SACC samples with or without metastasis. Cell proliferation and Transwell assays were performed to explore the effects of FZD2 on cell growth and migration following the silencing of FZD2 with small interference RNAs and the overexpression of FZD2 with plasmid. Our data showed that FZD2 was downregulated in ACC-LM cells, which are an adenoid cystic carcinoma cell line with high metastatic potential, compared to ACC-83 cells, which have low metastatic potential. Additionally, the expression of FZD2 was lower in SACC tissues with metastasis compared to SACC tissues without metastasis (P<0.05). Cell proliferation and migration of ACC-83 cells were increased after the knockdown of FZD2 and decreased following overexpression of FZD2. Knockdown of FZD2 downregulated the expression of PAI-1. Our results suggest that FZD2 may be a tumor suppressor gene in SACCs that inhibits cell growth and migration.


Assuntos
Carcinoma Adenoide Cístico/patologia , Receptores Frizzled/fisiologia , Proteínas de Neoplasias/fisiologia , Neoplasias das Glândulas Salivares/patologia , Divisão Celular , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Humanos , Invasividade Neoplásica , Inibidor 1 de Ativador de Plasminogênio/fisiologia , Interferência de RNA , RNA Interferente Pequeno/genética , Proteínas Recombinantes de Fusão/metabolismo , Transfecção , Ensaio Tumoral de Célula-Tronco , Via de Sinalização Wnt
17.
Mol Cell Biochem ; 411(1-2): 135-41, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26427670

RESUMO

Many studies have explored whether the Notch signaling pathway has a tumor-suppressive or an oncogenic role in various tumors; however, the role of the Notch signaling pathway in salivary adenoid cystic carcinoma (SACC) is still unknown. In this study, we attempt to define the role of Notch2 signaling in cell growth, invasion, and migration in SACC. We compared Notch2 expression in clinical SACC samples with that of normal samples by using immunohistochemical staining. Then, we down-regulated Notch2 expression to observe the effect of Notch2 on proliferation, invasion, migration, and the expression of known target genes of Notch signal pathway. According to our results, Notch2 expression was higher in SACC tissues compared with normal tissues. Knockdown of Notch2 inhibited cell proliferation, invasion, and migration in vitro and down-regulated the expression of HEY2 and CCND1. The results of this study suggest that Notch2 has an essential role in the cell growth, invasion, and migration of SACC. Notch2 may therefore be a potential target gene for the treatment of SACC by interfering with cell growth and metastasis.


Assuntos
Carcinoma Adenoide Cístico/patologia , Proliferação de Células , Invasividade Neoplásica , Metástase Neoplásica , Receptor Notch2/metabolismo , Neoplasias das Glândulas Salivares/patologia , Transdução de Sinais , Carcinoma Adenoide Cístico/metabolismo , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Receptor Notch2/genética , Neoplasias das Glândulas Salivares/metabolismo
18.
Oncotarget ; 5(16): 6885-95, 2014 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-25149541

RESUMO

BACKGROUND: Numerous studies have reported both the tumor-suppressive and oncogenic roles of the Notch pathway, indicating that Notch activity regulates tumor biology in a complex, context-dependent manner. The aim of the present study was to identify the role of NOTCH1 in the cell growth and metastasis of SACC. METHODS: We analyzed the expression of NOTCH1 in clinical SACC samples using immunohistochemical staining. We silenced the expression of NOTCH1 and overexpressed activated NOTCH1 to elucidate the effects of NOTCH1 on proliferation, migration and invasion. NOTCH1 target genes were validated by real-time PCR. RESULTS: Our results showed that NOTCH1 was upregulated in SACC tissues when compared with normal tissues, and this upregulation was further enhanced in SACC tissues with metastasis and recurrence when compared with SACC tissues without metastasis. Overexpression of NOTCH1 in SACC cells promoted cell growth, migration and invasion, and knockdown of NOTCH1 inhibited cell proliferation in vitro and tumorigenicity in vivo by inducing cell apoptosis. CONCLUSIONS: The results of this study suggest that NOTCH1 plays a key role in the cell growth, anti-apoptosis, and metastasis of SACC. NOTCH1 inhibitors might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.


Assuntos
Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Receptor Notch1/biossíntese , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Animais , Apoptose/fisiologia , Carcinoma Adenoide Cístico/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Receptor Notch1/genética , Receptor Notch1/metabolismo , Neoplasias das Glândulas Salivares/genética , Transdução de Sinais , Transfecção , Regulação para Cima
19.
Sensors (Basel) ; 13(11): 15172-86, 2013 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-24201318

RESUMO

We formulate a multi-matrices factorization model (MMF) for the missing sensor data estimation problem. The estimation problem is adequately transformed into a matrix completion one. With MMF, an n-by-t real matrix, R, is adopted to represent the data collected by mobile sensors from n areas at the time, T1, T2, ..., Tt, where the entry, Rij, is the aggregate value of the data collected in the ith area at Tj. We propose to approximate R by seeking a family of d-by-n probabilistic spatial feature matrices, U(1), U(2), ..., U(t), and a probabilistic temporal feature matrix, [formula in text]. We also present a solution algorithm to the proposed model. We evaluate MMF with synthetic data and a real-world sensor dataset extensively. Experimental results demonstrate that our approach outperforms the state-of-the-art comparison algorithms.

20.
Artigo em Chinês | MEDLINE | ID: mdl-24148947

RESUMO

OBJECTIVE: To investigate the effect of carbon disulfide (CS(2)) on the mitochondrial respiratory chain in testicular spermatogenic cells in male rats and to explore the possible mechanism of reproductive system damage caused by CS(2) in male rats. METHODS: Twenty-four male Sprague-Dawley rats (clean grade) were randomly divided into four groups: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and mitochondrial protein in spermatogenic cells were extracted; the levels of mitochondrial respiratory chain enzyme complex I∼V were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, all CS(2) exposure groups had significantly increased levels of mitochondrial respiratory chain enzyme complex I∼V in spermatogenic cells (P < 0.05). There were no significant differences in the levels of respiratory chain enzyme complex I∼IV between the CS(2) exposure groups (P < 0.05), but the level of respiratory chain enzyme complex V rose significantly as the concentration of CS(2) increased (P<0.05). CONCLUSION: Various levels of CS(2) exposure may increase the levels of mitochondrial respiratory chain enzyme complex in testicular spermatogenic cells among male rats, thus affecting the normal oxidative phosphorylation in mitochondria.


Assuntos
Dissulfeto de Carbono/toxicidade , Células Germinativas/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Animais , Transporte de Elétrons , Células Germinativas/metabolismo , Masculino , Mitocôndrias/metabolismo , Ratos , Ratos Sprague-Dawley
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