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1.
J Proteome Res ; 18(5): 2321-2330, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-30966751

RESUMO

Dry eye syndrome (DES) is a growing public health concern with a high global prevalence; however, the fundamental processes involved in its pathogenic mechanisms remain poorly understood. In the present study, we applied nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies on tear samples obtained from 18 dry eye patients and 19 healthy controls for integrated proteomic and metabolomic analyses. Overall, 1031 tear proteins were detected, while 190 proteins were determined to be significantly expressed in dry eye patients. Further functional analysis suggested that various biological processes were highly expressed and involved in the pathogenesis of DES, especially immune and inflammatory processes. In total, 156 named metabolites were identified, among which 34 were found to be significantly changed in dry eye patients. The results highlighted the key elements, especially inflammatory-related proteins and metabolites that played important roles in the development of DES. Further, the regulatory roles of primary pathways, including complement and coagulation cascades, glycolysis/gluconeogenesis, and amino acid metabolism, were also identified as processes involved in DES. Collectively, our work not only provided insight into the potential biomarkers of DES for diagnostic and prognostic purposes but extended our knowledge of the physiopathology of this syndrome.

2.
Leukemia ; 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

3.
Redox Biol ; 22: 101157, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30844644

RESUMO

Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-regulated in both human cataract capsule tissues and HLECs treated with UVB, whereas the expression of p53 protein exhibited an opposite trend. Ectopic expression of TRIM69 in HLECs significantly suppressed UVB-induced apoptosis and ROS production, whereas knockdown of TRIM69 promoted apoptosis and ROS production. TRIM69 can interact with p53 and induce its ubiquitination. The effects of TRIM69 overexpression in UVB-induced cell apoptosis and ROS production was clearly weakened by p53 overexpression, thus suggesting a role for p53 in TRIM69 functions. Furthermore, inhibition of ROS mitigated the effects of UVB irradiation on ROS production, cell apoptosis, forkhead box protein 3a (Foxo3a) phosphorylation, and TRIM69 expression. Additionally, Foxo3a overexpression significantly enhanced TRIM69 promoter activity, whereas Foxo3a knockdown had the opposite effect. In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation.

4.
Carbohydr Polym ; 208: 513-520, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30658831

RESUMO

An effective and green method to incorporate graphene oxide into quaternized hemicelluloses to form a hemicelluloses based film was introduced in this study. Tight, homogeneous, and smooth surfaces of the film were obtained from the SEM image. Data on the mechanical properties of the films indicated that the hybrid films prepared from QH and GO (component of GO was 4.8%) exhibited a high tensile strength of 43.83 MPa. This finding suggested that addition of GO contributed to the desirable mechanical properties of the hybrid film. The hybrid films exhibited high sensitivity to humidity; they could be bent spontaneously under wet conditions within seconds and stretched under dry conditions. In addition, the results of DMA indicated that the storage modulus of the hybrid films had an order of magnitude change in value at different humidities. These characteristics show that films can be potentially used in bio-medicine, packaging materials, and humidity sensors.

5.
Lipids Health Dis ; 18(1): 1, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30611256

RESUMO

BACKGROUND: Excess energy intake contributes to metabolic disorders. However, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. Here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys. METHODS: Four groups of adult cynomolgus monkeys were fed regular chow plus emulsion with combinations of high sugar (HS) or low sugar (HS) and low fat (LF) or high fat (HF) for 7 months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and blood glucose were measured for all the four groups of animals during the experiment. RESULTS: Plasma levels of TC and LDL-C gradually increased in all 4 diets groups, with the highest increase found in the LSHF group compared to the other three groups (P = 0.0018 and P = 0.0005 respectively). HF induced increased fasting glucose (P = 0.0077) and HS induced higher TG (P = 0.0227) respectively. Intriguingly, HSHF led to dramatically smaller magnitude of increase in LDL-C and TC levels compared to LSHF, while such difference was absent between the LSLF and LSHF groups. Our findings thus indicate interactive effects of HS and HF on TC and LDL-C. In addition, HF exhibited stronger effects on lipid abnormalities than HS. CONCLUSIONS: In the current study, our prospective feeding experiment in adult cynomolgus monkeys revealed effects of different fat-to-sugar ratios on diet-induced metabolic abnormalities. Furthermore, our findings suggest that not only excess dietary energy but also the balance of dietary fat-to-sugar ratio matters in diet-induced lipid abnormalities.


Assuntos
Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Açúcares/administração & dosagem , Administração Oral , Animais , Glicemia/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Macaca fascicularis , Masculino , Estudos Prospectivos , Triglicerídeos/sangue
6.
Open Med (Wars) ; 13: 605-609, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519638

RESUMO

Objective: To investigate the expression and clinical significance of CD5 and CD43 in diffuse large B cell lymphoma (DLBCL) (unspecified). Methods: Sixty - five patients with diagnosed DLBCL were enrolled. The expressions of CD5, CD43, CD10, Bcl-6 and Mun-1 were detected by immuno histochemistry. The relationship between CD5 and CD43 and clinicopathological features and prognosis of DLBCL was analyzed. Results: In sixty - five adult DLBCL patients , 6 cases of DLBCL (9.2%) were CD5 positive, 24 cases of DLBCL (36.9%) were CD43 positive, 5 cases of DLBCL (7.7%) were both CD5 and CD43 positive. 40 cases of DLBCL (61.5%) were CD5 and CD43 negative. CD5 expression was not related to age, sex, clinical stage, type of immunophenotype (Hans typing), location, and whether infected with hepatitis B virus (HBV); CD43 expression was correlated with immunophenotyping and HBV i nfection, but was not correlated with the age, sex, clinical stage, and site. Median survival time was significantly lower in CD5- and CD43- positive DLBCL patients than CD5- and CD43-negative patien ts. Conclusion: The prognosis of DLBCL patients may be worse with positive CD5 and CD43 expression.

7.
J Zhejiang Univ Sci B ; 19(9): 718-725, 2018 Sept..
Artigo em Inglês | MEDLINE | ID: mdl-30178638

RESUMO

OBJECTIVE: McKeown esophagectomy followed by cervical and abdominal procedures has been commonly used for invasive esophageal carcinoma. This minimally-invasive operative procedure in the lateral prone position has been considered to be the most appropriate method. We describe our experiences in minimally invasive McKeown esophagectomy (MIME) for esophageal cancer. METHODS: Between March 2016 and February 2018, a total of 82 patients underwent MIME by a single group in our department (a single center). All procedure, operation, oncology, and complication data were reviewed. RESULTS: All MIME procedures were completed successfully, with no conversions to open surgery. The median operative time was 260 min, and median blood loss was 100 ml. The average number of total harvested lymph nodes was 20.1 in the chest and 13.5 in the abdomen. There were no deaths within 30 postoperative days. Twenty cases (24.4%) developed postoperative complications, including anastomotic leak in 4 (4.9%), single lateral recurrent nerve palsy in 4 (4.9%), bilateral recurrent nerve palsy in 1 (1.2%), pulmonary problems in 3 (3.7%), chyle leak in 1 (1.2%), and other complications in 7 (including pleural effusions in 4, incomplete ileus in 2, and neck incision infection in 1; 8.54%). Average postoperative hospitalization time was 12 d. Blood loss, operation time, morbidity rate, and the number of harvested lymph nodes were analyzed by evaluating learning curves in different periods. Significant differences were found in operative time (P=0.006), postoperative hospitalization days (P=0.015), total harvested lymph nodes (P=0.003), harvested thoracic lymph nodes (P=0.006), and harvested abdominal lymph nodes (P=0.022) among different periods. CONCLUSIONS: Surgical outcomes following MIME for esophageal cancer are safe and acceptable. The MIME procedure for stages I and II could be performed proficiently and reached an experience plateau after approximately 25 cases.

8.
Lab Invest ; 98(8): 989-998, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29884911

RESUMO

Epithelial-mesenchymal transition (EMT) plays a critical role in initiating tumor invasion and metastasis of colorectal cancer (CRC), although the underlying mechanisms remain to be clarified. Herein, we demonstrate that the active form of Rac family small GTPase 1 (RAC1-GTP) is overexpressed in CRCs and promotes the EMT-mediated invasion of CRC cells through activation of the signal transducers and activators of transcription 3 (STAT3) pathway. Increased expression of RAC1-GTP in CRC tissues was positively correlated with the TNM stages of CRCs and indicated poor prognosis of CRC patients. Targeting RAC1-GTP activity by its specific inhibitor NSC23766 markedly suppressed the migration and invasion of CRC cells. Mechanistically, RAC1-GTP directly interacted with STAT3 to promote STAT3 phosphorylation, thus promoted EMT of CRC cells. Enforced expression of constitutively activated STAT3 (STAT3-C) abrogated the suppressive effect of RAC1-GTP disruption on the migration and invasion of CRC cells. Importantly, NSC23766 disrupted EMT in CRC cells and significantly diminished growth of CRC xenografts. Taken together, our data indicate that RAC1-GTP is an important player in EMT-mediated tumor invasion and a potential therapeutic target for CRCs.

9.
Cell Physiol Biochem ; 46(4): 1317-1330, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29689551

RESUMO

BACKGROUND/AIMS: Induction of oxidative stress and reactive oxygen species (ROS) mediated-apoptosis have been utilized as effective strategies in anticancer therapy. Macranthoidin B (MB) is a potent inducer of ROS-mediated apoptosis in cancer, but its mechanism of action is poorly understood. METHOD: Superoxide production with MB exposure in colorectal cancer (CRC) cells was measured using lucigenin chemiluminescence and real-time PCR. MB's inhibitory effect on proliferation and viability of CRC cells was determined by proliferation assays. MB's effect on apoptosis of CRC cells was determined by Western blotting and annexin V-FITC/PI staining. MB's effect on the growth of CRC xenografts in mice was assessed. An established metabolomics profiling platform combining ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS) with gas chromatography-mass spectrometry (GC-MS) was performed to determine MB's effect on total metabolite variation in CRC cells. RESULTS: We found that MB increases ROS generation via modulating key metabolic pathways. Using metabolomics profiling platform combining LC-MS with GC-MS, a total of 236 metabolites were identified in HCT-116 cells in which 31 metabolites were determined to be significantly regulated (p ≤ 0.05) after MB exposure. A number of key metabolites revealed by metabolomics analysis include glucose, fructose, citrate, arginine, phenylalanine, and S-adenosylhomocysteine (SAH), suggesting specific modulation of metabolism on carbohydrates, amino acids and peptides, lipids, nucleotide, cofactors and vitamins in HCT-116 CRC cells with MB treatment highly associated with apoptosis triggered by enhanced ROS and activated caspase-3. CONCLUSION: Our results demonstrate that MB represses CRC cell proliferation by inducing ROS-mediated apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Saponinas/toxicidade , Aminoácidos/análise , Aminoácidos/metabolismo , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Caspase 3/metabolismo , Cromatografia Líquida de Alta Pressão , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Análise Discriminante , Cromatografia Gasosa-Espectrometria de Massas , Glutationa Peroxidase/metabolismo , Células HCT116 , Humanos , Análise dos Mínimos Quadrados , Metabolismo dos Lipídeos/efeitos dos fármacos , Espectrometria de Massas , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Nus , Ácido Oleanólico/química , Ácido Oleanólico/uso terapêutico , Ácido Oleanólico/toxicidade , S-Adenosil-Homocisteína/análise , S-Adenosil-Homocisteína/metabolismo , Saponinas/química , Saponinas/uso terapêutico , Superóxido Dismutase/metabolismo , Transplante Heterólogo
10.
Phys Chem Chem Phys ; 20(6): 4579-4586, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29376537

RESUMO

Proton conductors are widely used in different electrochemical devices including fuel cells and redox flow batteries. Compared to conventional proton conducting polymer membranes, protic organic ionic plastic crystal (POIPC) is a novel solid-state proton conductor with high proton conductivity even under anhydrous conditions. In this work, different organic protic salts based on the same parent di-functional cation with different anions were synthesized and characterized. It is found that the di-protonated cation plays an important role in defining the thermal properties, leading to stronger plastic crystal behavior and a higher melting point. Static solid-state NMR and the synchrotron XRD results show that the di-protonated cation allows greater dynamics in the crystal in contrast to the mono-protonated counterparts. The 1-(N,N-dimethylammonium)-2-(ammonium)ethane triflate ([DMEDAH2][Tf]2) has the highest ionic conductivity of 1.1 × 10-4 S cm-1 at 50 °C, whereas the bis(trifluoromethanesulfonyl)amide counterpart [DMEDAH2][TFSA]2 has the lowest ionic conductivity (2.8 × 10-7 S cm-1 at 50 °C) with no measureable mobile ion component at this temperature. The fraction of mobile species is significantly suppressed in the TFSA containing salts as against the Tf systems.

11.
Cell Physiol Biochem ; 44(1): 255-266, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29190611

RESUMO

BACKGROUND/AIMS: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). METHODS: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. RESULTS: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss- and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. CONCLUSIONS: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment.


Assuntos
Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo , Transição Epitelial-Mesenquimal , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transplante Heterólogo , Proteínas com Motivo Tripartido/antagonistas & inibidores , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/antagonistas & inibidores
12.
Oncotarget ; 8(29): 47619-47631, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28496003

RESUMO

Peiminine, a compound extracted from the bulbs of Fritillaria thunbergii and traditionally used as a medication in China and other Asian countries, was reported to inhibit colorectal cancer cell proliferation and tumor growth by inducing autophagic cell death. However, its mechanism of anticancer action is not well understood, especially at the metabolic level, which was thought to primarily account for peiminine's efficacy against cancer. Using an established metabolomic profiling platform combining ultra-performance liquid chromatography/tandem mass spectrometry with gas chromatography/mass spectrometry, we identified metabolic alterations in colorectal cancer cell line HCT-116 after peiminine treatment. Among the identified 236 metabolites, the levels of 57 of them were significantly (p < 0.05) different between peiminine-treated and -untreated cells in which 45 metabolites were increased and the other 12 metabolites were decreased. Several of the affected metabolites, including glucose, glutamine, oleate (18:1n9), and lignocerate (24:0), may be involved in regulation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway and in the oxidative stress response upon peiminine exposure. Peiminine predominantly modulated the pathways responsible for metabolism of amino acids, carbohydrates, and lipids. Collectively, these results provide new insights into the mechanisms by which peiminine modulates metabolic pathways to inhibit colorectal cancer cell growth, supporting further exploration of peiminine as a potential new strategy for treating colorectal cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cevanas/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Cevanas/química , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Metabolismo Energético/efeitos dos fármacos , Células HCT116 , Humanos , Metaboloma , Metabolômica/métodos , Camundongos
13.
Exp Eye Res ; 159: 147-155, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28322828

RESUMO

High myopia is the common eye disorder worldwide, which may contribute to increase the risk of serious disorders including glaucoma and cataract. Although various studies including genomics, transcriptomics, and proteomics have been implicated to identify potential biomarkers (genes or proteins) for predicting high myopia and to reveal the underlying mechanism, the comprehensive metabolomics in relation to high myopia is very limited. In this study, we identified 242 metabolites in aqueous humor (AH) from a set of 40 cataract patients (including 20 with high myopia and 20 for controls), using a non-targeted metabolomic technology, gas chromatography coupled to time-of-flight mass spectrometer (GC/TOF MS). Further statistical analysis showed that 29 metabolites were significantly changed (Variable important for the projection, VIP ≥ 1 and p ≤ 0.05), between those two groups, while only 2 decreased metabolites were included. Moreover, for the first time, metabolite-metabolite correlations for AH were analyzed, which may dissect key regulatory elements or pathways involved in metabolism of amino acids, carbohydrates, and lipids. Accordingly, metabolic network was constructed based on those 29 changed metabolites in patients with high myopia. More than half of the changed metabolites were highly and positively associated, suggesting important roles of pathways involved in the metabolism of these metabolites in relation to high myopia. Altogether, this work not only provided potential biomarkers for the diagnosis and monitoring of high myopia formation, but also provided new insights into the underlying mechanisms.


Assuntos
Humor Aquoso/metabolismo , Biomarcadores/metabolismo , Proteínas do Olho/metabolismo , Metabolômica/métodos , Miopia Degenerativa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/diagnóstico
14.
Cell Physiol Biochem ; 39(6): 2275-2286, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27855397

RESUMO

BACKGROUND/AIMS: Ultraviolet B (UVB) irradiation can easily induce apoptosis in human lens epithelial cells (HLECs) and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1) gene in UVB irradiation induced-apoptosis in HLECs. METHODS: Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. RESULTS: After UVB irradiation, the percentage of primary apoptotic cells was obviously fewer in CRTAC1 interference group. Meanwhile, inhibition of CRTAC1 also reduced both reactive oxygen species (ROS) production and intracellular Ca2+ concentration, but the level of mitochondrial membrane potential (Δψm) was increased in HLECs. Further studies indicated that superoxide dismutase (SOD) activity and total antioxidative (T-AOC) level were significantly increased in CRTAC1-inhibited cells, while the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) were significantly decreased. ELISA analysis of CRTAC1-inhibited cells showed that the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly decreased, but the concentration of interleukin-10 (IL-10) was significantly increased. Western blot analyses of eight apoptosis-associated proteins including Bax, Bcl-2, p38, phospho-p38 (p-p38), Jun amino-terminal kinases (JNK1/2), phospho-JNK1/2 (p-JNK1/2), calcium-sensing receptor (CasR), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) indicated that the inhibition of CRTAC1 alleviated oxidative stress and inflammation response, inactivated calcium-signaling pathway, p38 and JNK1/2 signal pathways, and eventually reduced UVB irradiation induced-apoptosis in HLECs. CONCLUSION: These results provided new insights into the mechanism of cataract development, and demonstrated that CRTAC1 could be a potentially novel target for cataract treatment.


Assuntos
Apoptose/efeitos da radiação , Proteínas de Ligação ao Cálcio/metabolismo , Células Epiteliais/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Cristalino/citologia , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Raios Ultravioleta , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antioxidantes/metabolismo , Western Blotting , Cálcio/metabolismo , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/enzimologia , Células Epiteliais/efeitos da radiação , Citometria de Fluxo , Humanos , Espaço Intracelular/metabolismo , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
15.
Chem Commun (Camb) ; 52(98): 14097-14100, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27819080

RESUMO

Two protic organic ionic plastic crystalline materials based on the mono- and di-protonated cations of N,N-dimethylethylenediamine, (DMEDA) and the triflate anion have been studied. The symmetrical di-protonated cation salt shows 54 °C higher melting point and 24-fold higher conductivity at room temperature as compared to the mono-protonated cation salt, making it a promising candidate for a solid-state proton conductor. The conductivity of this salt was further enhanced by acid doping.

16.
Sci Rep ; 6: 20942, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26860358

RESUMO

Seed development dedicates to reserve synthesis and accumulation and uncovering its genetic and biochemical mechanisms has been a major research focus. Although proteomic and transcriptomic analyses revealed dynamic changes of genes and enzymes involved, the information regarding concomitant metabolic changes is missing. Here we investigated the dynamic metabolic changes along the rice grain development of two japonica and two indica cultivars using non-targeted metabolomics approach, in which we successfully identified 214 metabolites. Statistical analyses revealed both cultivar and developmental stage dependent metabolic changes in rice grains. Generally, the stage specific metabolic kinetics corresponded well to the physiological status of the developing grains, and metabolic changes in developing rice grain are similar to those of dicot Arabidopsis and tomato at reserve accumulation stage but are different from those of dicots at seed desiccation stage. The remarkable difference in metabolite abundances between japonica and indica rice grain was observed at the reserve accumulation stage. Metabolite-metabolite correlation analysis uncovered potential new pathways for several metabolites. Taken together, this study uncovered both conserved and diverse development associated metabolic kinetics of rice grains, which facilitates further study to explore fundamental questions regarding the evolution of seed metabolic capabilities as well as their potential applications in crop improvement.


Assuntos
Evolução Biológica , Grão Comestível , Metaboloma , Metabolômica , Oryza/metabolismo , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Cromatografia Gasosa-Espectrometria de Massas , Redes e Vias Metabólicas , Metabolômica/métodos , Sementes/metabolismo
17.
Plant Cell Rep ; 35(2): 429-37, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26581949

RESUMO

KEY MESSAGE: Non-targeted metabolomics analysis revealed only intended metabolic changes in transgenic maize over-expressing the Aspergillus niger phyA2. Genetically modified (GM) crops account for a large proportion of modern agriculture worldwide, raising increasingly the public concerns of safety. Generally, according to substantial equivalence principle, if a GM crop is demonstrated to be equivalently safe to its conventional species, it is supposed to be safe. In this study, taking the advantage of an established non-target metabolomic profiling platform based on the combination of UPLC-MS/MS with GC-MS, we compared the mature seed metabolic changes in transgenic maize over-expressing the Aspergillus niger phyA2 with its non-transgenic counterpart and other 14 conventional maize lines. In total, levels of nine out of identified 210 metabolites were significantly changed in transgenic maize as compared with its non-transgenic counterpart, and the number of significantly altered metabolites was reduced to only four when the natural variations were taken into consideration. Notably, those four metabolites were all associated with targeted engineering pathway. Our results indicated that although both intended and non-intended metabolic changes occurred in the mature seeds of this GM maize event, only intended metabolic pathway was found to be out of the range of the natural metabolic variation in the metabolome of the transgenic maize. Therefore, only when natural metabolic variation was taken into account, could non-targeted metabolomics provide reliable objective compositional substantial equivalence analysis on GM crops.


Assuntos
6-Fitase/genética , 6-Fitase/metabolismo , Aspergillus niger/genética , Regulação da Expressão Gênica de Plantas , Sementes , Zea mays/enzimologia , Zea mays/genética , Cromatografia Gasosa-Espectrometria de Massas , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Sementes/genética , Sementes/metabolismo , Espectrometria de Massas em Tandem
18.
Proc Natl Acad Sci U S A ; 112(47): E6525-34, 2015 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-26553993

RESUMO

Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. (64)Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (∼ 2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (χ(2) = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.


Assuntos
Anticorpos Monoclonais/farmacologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/imunologia , Antígeno CD146/metabolismo , Glioma/diagnóstico por imagem , Glioma/imunologia , Tomografia por Emissão de Pósitrons , Animais , Formação de Anticorpos/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Células Clonais , Radioisótopos de Cobre , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Citometria de Fluxo , Imunofluorescência , Glioma/patologia , Humanos , Imagem por Ressonância Magnética , Camundongos Nus , Gradação de Tumores , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Fenótipo , Biossíntese de Proteínas/efeitos dos fármacos , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/metabolismo , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacos , Tomografia Computadorizada por Raios X , Transcrição Genética/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Clin Cancer Res ; 21(17): 4004-13, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26023083

RESUMO

PURPOSE: To identify the miRNA regulators of C-X-C motif chemokine receptor 4 (CXCR4) and the underlying mechanism as well as the therapeutic and prognostic values in human glioblastoma (GBM). EXPERIMENTAL DESIGN: miRNA profile analyses and bioinformatics predictions were used to identify the mediators of CXCR4, which were confirmed by luciferase reporter assay, Western blot assay and immunohistochemistry. The effects of miR-663 on CXCR4-mediated GBM malignancy were investigated by gain-of-function experiments. Orthotopic xenografts derived from constitutive or induced miR-663-expressing GBM cells were used to determine the antitumor effects of miR-663 and CXCR4-specific antagonist AMD3100. Bivariate correlation analyses were used to examine the correlation of miR-663 and CXCR4 levels in glioma. The prognostic values of miR-663 and CXCR4 were examined in 281 cases of astrocytic glioma from our hospital and 476 cases of GBM from The Cancer Genome Atlas database using the multivariate Cox regression analysis and Kaplan-Meier analysis. RESULTS: miR-663 negatively regulated CXCR4 expression by targeting its coding sequence in GBM and compromised the proliferative and invasive capacities of GBM cells induced by CXCR4 overexpression. Constitutive or induced miR-663 overexpression combined with CXCR4 antagonist AMD3100 suppressed orthotopic GBM growth and prolonged tumor-bearing mice survival. Clinically, miR-663 and CXCR4 were inversely correlated in GBM and composed a valuable biomarker set in predicting the outcomes of GBM patients. CONCLUSIONS: miR-663 negatively regulated CXCR4 to inhibit its oncogenic effect. Combination of miR-663 and CXCR4 can serve as a valuable prognostic biomarker set as well as molecular targets for therapeutic intervention of GBM.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , MicroRNAs/genética , Receptores CXCR4/genética , Animais , Sequência de Bases , Sítios de Ligação , Biomarcadores Tumorais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/mortalidade , Glioblastoma/patologia , Camundongos , MicroRNAs/química , Prognóstico , Interferência de RNA , RNA Mensageiro/química , RNA Mensageiro/genética , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Pathol ; 236(4): 467-78, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25866254

RESUMO

Semaphorin-3F (SEMA3F), an axonal repulsant in nerve development, has been shown to inhibit the progression of human colorectal cancer (CRC); however, the underlying mechanism remains elusive. In this study we found a negative correlation between the levels of SEMA3F and CXCR4 in CRC specimens from 85 patients, confirmed by bioinformatics analysis of gene expression in 229 CRC samples from the Cancer Genome Atlas. SEMA3F(high) /CXCR4(low) patients showed the lowest frequency of lymph node and distant metastasis and the longest survival. Mechanistically, SEMA3F inhibited the invasion and metastasis of CRC cells through PI3K-AKT-dependent down-regulation of the ASCL2-CXCR4 axis. Specifically, ASCL2 enhanced the invasion and metastasis of CRC cells in vitro and expression of ASCL2 correlated with distant metastasis, tumour size and poor overall survival in CRC patients. Treatment of CRC cells with the CXCR4 antagonist AMD3100 attenuated SEMA3F knockdown-induced invasion and metastasis of CRC cells in vitro and in vivo. Our study thus demonstrates that SEMA3F functions as a suppressor of CRC metastasis via down-regulating the ASCL2-CXCR4 axis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Movimento Celular , Neoplasias Colorretais/enzimologia , Neoplasias Hepáticas/enzimologia , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais , Animais , Antineoplásicos/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Biologia Computacional , Feminino , Regulação Neoplásica da Expressão Gênica , Genômica , Células HCT116 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Proteínas de Membrana/genética , Camundongos Nus , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/genética , Fosfatidilinositol 3-Quinase/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/genética , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção , Carga Tumoral
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