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1.
J Ovarian Res ; 12(1): 92, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601255

RESUMO

AB209371 gene has been characterized as an oncogenic lncRNA in liver cancer. However, its involvement in ovarian carcinoma (OC) is unknown. In the present study, we analyzed the roles of AB209371 in OC. We found that AB209371 gene and Survivin gene were up-regulated in OC and positively correlated with OC development. AB209371 over-expression led to up-regulated Survivin in OC cells, while Survivin over-expression failed to affect AB209371. In addition, AB209371 over-expression led to down-regulated miR-203. However, miR-203 over-expression failed to affect AB209371, but down-regulated the expression of Survivin. In addition, over-expressions of AB209371 and Survivin resulted in the increased proliferation rate of OC cells. Over-expression MiR-203 played the opposite role and attenuated the effects of AB209371 over-expression. Therefore, AB209371 may down-regulate miR-203 to up-regulate Survivin, thereby promoting OC cell proliferation. Our study provided novel insights into the pathogenesis of OC.

2.
J Cell Biochem ; 120(11): 18724-18735, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31219199

RESUMO

Lung cancer is the main cause of cancer-related death, and the proportion of non-small cell lung cancer (NSCLC) on lung cancer is 85%, while more than 80% lung cancer patients are diagnosed with chronic obstructive pulmonary disease (COPD). In this study, we aimed to explore the potential mechanism of COPD induced NSCLC. Luciferase assay and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to study the regulatory relationship between P53 and microRNA-675 (miR-675). Real-time PCR, Western-blot analysis, and MTT assay were performed to explore the impact of H19 and miR-675 in the signaling pathway involved in COPD induced NSCLC. In NSCLC patients with COPD, H19 and miR-675 levels were strikingly upregulated while P53 level was significantly downregulated. P53 was identified as a target gene of miR-675, and H19 remarkably upregulated miR-675, while H19 siRNA notably inhibited miR-675. In addition, miR-675 and H19 dramatically suppressed the expression of P53 and Bax while inducing the expression of Bcl-2. Finally, H19 and miR-675 induced proliferation of A549 and MRC-5 cells. These finding indicated that COPD (hypoxia)-induced H19 promoted expression of miR-675 associated with NSCLC though target apoptosis-related protein P53, BAX, and Bcl-2.

3.
J Exp Clin Cancer Res ; 38(1): 237, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171015

RESUMO

BACKGROUND: Liver cancer stem cells (LCSCs) are a small subset of cells characterized by unlimited self-renewal, cell differentiation, and uncontrollable cellular growth. LCSCs are also resistant to conventional therapies and are thus believed to be held responsible for causing treatment failure of hepatocellular carcinoma (HCC). It has been recently found that long non-coding RNAs (lncRNAs) are important regulators in HCC. This present study aims to explore the underlying mechanism of how lncRNA DLX6-AS1 influences the development of LCSCs and HCC. METHODS: A microarray-based analysis was performed to initially screen differentially expressed lncRNAs associated with HCC. We then analyzed the lncRNA DLX6-AS1 levels as well as CADM1 promoter methylation. The mRNA and protein expression of CADM1, STAT3, CD133, CD13, OCT-4, SOX2, and Nanog were then detected. We quantified our results by evaluating the spheroid formation, proliferation, and tumor formation abilities, as well as the proportion of tumor stem cells, and the recruitment of DNA methyltransferase (DNMT) in LCSCs when lncRNA DLX6-AS1 was either overexpressed or silenced. RESULTS: LncRNA DLX6-AS1 was upregulated in HCC. The silencing of lncRNA DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuate CD133, CD13, OCT-4, SOX2, and Nanog expression in LCSCs. Furthermore, downregulation of lncRNA DLX6-AS1 contributed to a reduction in CADM1 promoter methylation via suppression of DNMT1, DNMT3a, and DNMT3b in LCSCs and inactivating the STAT3 signaling pathway. CONCLUSION: This study demonstrated that down-regulated lncRNA DLX6-AS1 may inhibit the stem cell properties of LCSCs through upregulation of CADM1 by suppressing the methylation of the CADM1 promoter and inactivation of the STAT3 signaling pathway.

4.
J Cell Biochem ; 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31232487

RESUMO

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (Nrf2) can alleviate diffuse axonal injury (DAI)-induced apoptosis by regulating expression of heme oxygenase-1 (HO-1), while sulforaphane (SFN) was shown to reduce oxidative stress by increasing the expression of Nrf2. Therefore, we aimed to investigate therapeutic effect of SFN in the treatment of DAI and the ability of SFN to reduce oxidative stress. METHODS: The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to observe the effects of H2 O 2 and SFN on cell viability. Fluorometric assay, Western blot analysis, and flow cytometry were conducted to validate the protective role of SFN in an animal model of DAI. In addition, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in DAI rats treated by SFN, while Western blot, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were carried out to verify the effect of SFN in different animal groups. RESULTS: Cell viability was reduced by H2 O 2 in a dose-dependent manner, while the treatment by SFN significantly promoted cell growth. Meanwhile the administration of SFN effectively reduced the levels of caspase-3/poly(ADP-ribose) polymerase (PARP) activity increased by the H 2 O 2 treatment, indicating that the protective effect of SFN could be mediated by its ability to suppress caspase-3 activation and PARP cleavage. In addition, the SFN treatment reduced the intracellular reactive oxygen species (ROS) generation induced by H 2 O 2 . Moreover, the MDA levels of SOD/GPx activity in various rat groups showed the protective effects of SFN in DAI rats. It is suspected that the protective effect of SFN was exerted via the activation of the Nrf2/HO-1 signaling pathway. In this study, DAI and DAI + phosphate-buffered saline (PBS) groups also showed the presence of more TUNEL-positive cells compared with the sham-operated group, while the SFN treatment reduced the extent of neuronal apoptosis. CONCLUSIONS: By activating the Nrf2/HO-1 signaling pathway and reducing the activity of caspase-3, SFN reduces the apoptosis of neurons in brain trauma-induced DAI.

5.
Aging (Albany NY) ; 11(8): 2447-2456, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036774

RESUMO

The patients with spinal cord injury (SCI) suffered significantly higher risk of deep vein thrombosis (DVT) than normal population. The aim was to assess the clinical significance of macrophage migration inhibitory factor (MIF) as the risk factor for DVT in acute SCI patients. 207 Chinese patients were enrolled in this study, including thirty-nine (39) patients (18.8 %; 95 %CI: 13.5 %-24.2 %) diagnosed as DVT at the follow-up of 1 month. Nine (9) of the 39 patients (23.1%) were suspected of thrombosis before the screening. The MIF levels in plasma of DVT patients were significantly higher than DVT-free patients. The risks of DVT would be increased by 11 % (OR unadjusted: 1.11; 95% CI, 1.06-1.17, P<0.001) and 8 % (OR adjusted: 1.08; 1.03-1.14, P=0.001), for each additional 1 ng/ml of MIF level. Furthermore, after MIF was combined with established risk factors, area under the receiver operating characteristic curve (standard error) was increased from 0.82(0.035) to 0.85(0.030). The results showed the potential association between the high MIF levels in plasma and elevated DVT risk in SCI patients, which may assist on early intervention.

6.
J Cell Physiol ; 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30790266

RESUMO

Long noncoding RNAs, including HOTAIR, are involved in the pathogenesis of a wide range of diseases. This study aimed to explore the mechanism underlying the involvement of HOTAIR in neonatal bronchial hyperresponsiveness (BHR). A total of 105 newborns were recruited in this study to collect their peripheral blood mononuclear cell and serum samples, which were then divided into different genotype groups based on the genotypes of rs4759314, rs874945, and rs7958904. The real-time polymerase chain reaction, western blot analysis, computational analyses, and luciferase assays were performed to establish the regulatory relationships between the HOTAIR, microRNA-126 (miR-126), and interleukin-13 (IL-13). The level of HOTAIR, miR-126, and IL-13 among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups was similar. However, the level of HOTAIR was increased in the rs7958904 GG group, accompanied by a decreased level of miR-126 and IL-13. In addition, the level of airway responsiveness was comparable among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups. However, the airway responsiveness in the groups rs7958904 CG and CC was much stronger than that of the GG group. We also demonstrated that, by directly binding to miR-126, HOTAIR reduced the expression of miR-126, which in turn decreased the expression of IL-13. In summary, we demonstrated the role of HOTAIR-induced downregulation of miR-126 and IL-13 in the development of BHR in neonates.

7.
Redox Biol ; 21: 101112, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30685709

RESUMO

Intracellular tension activity plays a crucial role in cytotoxic brain edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and protein nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, protein nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and brain edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure brain edema.


Assuntos
Astrócitos/metabolismo , Edema Encefálico/metabolismo , Ácido Glutâmico/metabolismo , Íons/metabolismo , Pressão Osmótica , Proteínas/metabolismo , Animais , Biomarcadores , Linhagem Celular , Humanos , Imuno-Histoquímica , Espaço Intracelular/metabolismo , Modelos Biológicos , Nanopartículas , Ratos , Estresse Fisiológico
8.
Neurobiol Learn Mem ; 96(2): 156-65, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21496491

RESUMO

Evidence indicates that systemic administration of lipopolysaccharide (LPS) induces brain inflammation, ultimately resulting in cognitive deficits. Ursolic acid (UA), a plant-derived pentacyclic triterpenoid, is well known to possess multiple biological functions, including antioxidant, anti-tumor and anti-inflammatory activities. In the present study, we assessed the protective effect of UA against the LPS-induced cognitive deficits in mice. We found that UA significantly improved cognitive deficits of LPS-treated mice in open field, step-through passive avoidance and Morris water maze tasks. One potential mechanism of this action was attributed to the decreased production of pro-inflammatory markers including COX-2, iNOS, TNF-α, IL-1ß, IL-2 and IL-6 in LPS-treated mouse brain. Mechanistically, UA markedly inhibited LPS-induced IκBα phosphorylation and degradation, NF-κB p65 nuclear translocation and p38 activation in mouse brain, but did not affect the activation of TLR4, MyD88, ERK, JNK and Akt. Taken together, these results suggest that UA may be useful for mitigating inflammation-associated brain disorders by inhibiting pro-inflammatory factors production, at least in part, through blocking the p38/NF-κB signaling pathways.


Assuntos
Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Triterpenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Encéfalo/imunologia , Encéfalo/metabolismo , Cognição/fisiologia , Inflamação/imunologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Fosforilação/efeitos dos fármacos , Fosforilação/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
9.
Brain ; 134(Pt 3): 783-97, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21252113

RESUMO

Recent findings suggest that neurotoxicity is the mechanism underlying the induction of neuronal insulin resistance by a high cholesterol diet. Troxerutin, a naturally occurring flavonoid, has been reported to possess biological activity beneficial to human health. Our recent studies have demonstrated that troxerutin attenuates cognitive impairment and oxidative stress induced by D-galactose in mouse brain through decreasing advanced glycation end products, reactive oxygen species and protein carbonyl levels and enhancing phosphoinositide 3-kinase/Akt activation. In this study, we evaluated the effect of troxerutin on cognitive impairment induced by brain insulin resistance in mice fed a high-cholesterol diet, and explored its potential mechanism. Our results showed that oral administration of troxerutin to these mice significantly improved behavioural performance in a step-through passive avoidance task and a Morris water maze task, at least in part, by decreasing the levels of reactive oxygen species, protein carbonyl and advanced glycation end products and blocking endoplasmic reticulum stress via reduced phosphorylation of the pancreatic endoplasmic reticulum-resident kinase and eukaryotic translation initiation factor 2α. Furthermore, troxerutin significantly inhibited the activation of c-jun N-terminal kinase 1 and IκB kinase ß/nuclear factor-κB induced by endoplasmic reticulum stress and enhanced insulin signalling pathway, which prevented obesity, restored normal levels of blood glucose, fatty acids and cholesterol and increased the phosphorylation of cyclic adenosine monophosphate response element-binding protein and the expression levels of c-fos in the hippocampus. Moreover, troxerutin significantly inhibited endoplasmic reticulum stress-induced apoptosis and decreased the activation of caspase-12 and caspase-3, and reduced the mean optical density of the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end label-positive cells in the hippocampus. However, intra-cerebroventricular infusion of PI-103, a specific phosphoinositide 3-kinase 110α inhibitor, significantly inhibited the expression levels of phosphoinositide 3-kinase 110α and phosphoinositide 3-kinase downstream signalling in the hippocampus of mice co-treated with high cholesterol and troxerutin and vehicle control mice. These results suggest that troxerutin could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in type 2 diabetes mellitus and Alzheimer's disease.


Assuntos
Colesterol/toxicidade , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/tratamento farmacológico , Hidroxietilrutosídeo/análogos & derivados , Neuroprostanos/administração & dosagem , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Proteína de Ligação a CREB/metabolismo , Colesterol/sangue , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática/métodos , Ácidos Graxos não Esterificados/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Hidroxietilrutosídeo/administração & dosagem , Imunoprecipitação , Marcação In Situ das Extremidades Cortadas/métodos , Infusões Intraventriculares , Resistência à Insulina/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/sangue
10.
J Pathol ; 222(2): 199-212, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20690163

RESUMO

It is known that a high-cholesterol diet induces oxidative stress, inflammatory response, and beta-amyloid (Abeta) accumulation in mouse brain, resulting in neurodegenerative changes. Quercetin, a naturally occurring flavonoid, has been reported to possess numerous biological activities beneficial to health. Our previous studies have demonstrated that quercetin protects mouse brain against D-galactose-induced oxidative damage. Against this background, we evaluated the effect of quercetin on high-cholesterol-induced neurotoxicity in old mice and explored its potential mechanism. Our results showed that oral administration of quercetin significantly improved the behavioural performance of high-cholesterol-fed old mice in both a step-through test and the Morris water maze task. This is at least in part caused by decreasing ROS and protein carbonyl levels and restoring Cu--Zn superoxide dismutase (Cu, Zn-SOD) activity. Furthermore, quercetin also significantly activated the AMP-activated protein kinase (AMPK) via down-regulation of protein phosphatase 2C (PP2C), which reduced the integral optical density (IOD) of activated microglia cells and CD11b expression, down-regulated iNOS and cyclooxygenase-2 (COX-2) expression, and decreased IL-1beta, IL-6, and TNF-alpha expression in the brains of high-cholesterol-fed old mice through the suppression of NF-kappaB p65 nuclear translocation. Moreover, AMPK activation significantly increased 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and acetyl-CoA carboxylase (ACC) phosphorylation and reduced fatty acid synthase (FAS) expression in the brains of high-cholesterol-fed old mice, which reduced cholesterol levels, down-regulated cholesterol 24-hydroxylase (CYP46A1) and beta-amyloid converting enzyme 1 (BACE1) expression, decreased eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation, and lowered Abeta deposits. However, the neuroprotective effect of quercetin was weakened by intraperitoneal injection of compound C, an AMPK inhibitor. These results suggest that AMPK activated by quercetin may be a potential target to enhance the resistance of neurons to age-related diseases.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Colesterol na Dieta/toxicidade , Doenças Neurodegenerativas/prevenção & controle , Fosfoproteínas Fosfatases/metabolismo , Quercetina/farmacologia , Animais , Encéfalo/metabolismo , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos/métodos , Ativação Enzimática/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Camundongos , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/enzimologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Carbonilação Proteica/efeitos dos fármacos , Proteína Fosfatase 2C , Quercetina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
11.
Food Chem Toxicol ; 48(8-9): 2500-7, 2010 Aug-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20600541

RESUMO

Purple sweet potato color (PSPC) has been shown to possess hepatoprotective effects in our previous study. To clarify the detailed mechanism of hepatoprotective effects of PSPC, we investigated the potential protective effect of PSPC against caspase-3 activation induced by d-gal, as well as its influence on Bcl-2 levels and PI3K/Akt cell survival pathway. The results of TUNEL assay showed that PSPC effectively suppressed the d-gal-induced hepatocytes apoptosis, suggesting that anti-apoptosis mechanism was involved in PSPC-mediated protection against d-gal-induced liver injury in mouse. PSPC significantly increased GSH levels and promoted a marked increase in the activities of GSH related enzymes including GR, GST in d-gal-treated mice. The activation and activity of caspase-3 were markedly inhibited by the treatment of PSPC in the livers of d-gal-treated mice. Furthermore, the level of Bcl-2 was significantly raised, and the levels of PI3K p110 and phosphorylated Akt were also largely enhanced by the treatment of PSPC in the livers of d-gal-treated mice. In conclusion, these results suggested that PSPC could protect mouse liver against d-gal-induced hepatocyte apoptosis via attenuating oxidative stress, inhibiting the activation of caspase-3 and enhancing cell survival signaling (enhancing the level of anti-apoptotic protein Bcl-2 and the activation of PI3K/Akt pathway).


Assuntos
Apoptose/efeitos dos fármacos , Inibidores de Caspase , Galactose/antagonistas & inibidores , Galactose/toxicidade , Ipomoea batatas/química , Fígado/enzimologia , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Western Blotting , Caspase 3/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Marcação In Situ das Extremidades Cortadas , Indicadores e Reagentes , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Transdução de Sinais/efeitos dos fármacos
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