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1.
Sci Rep ; 10(1): 5396, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214162

RESUMO

As the second largest carbon flux in terrestrial ecosystems, the soil CO2 flux is closely related to the atmospheric CO2 concentration. The soil CO2 flux is the sum of biotic respiration and abiotic geochemical CO2 exchange; however, little is known about abiotic CO2 fluxes in arid areas. To investigate the relative contribution of abiotic and biotic soil CO2 fluxes over a diurnal course, the abiotic CO2 flux was distinguished by autoclaving sterilization in both saline and alkaline soils at an arid site in northwestern China. The results demonstrated that: (1) Over the diurnal course, the abiotic CO2 was a significant component of the soil CO2 flux in both saline and alkaline soil, which accounted for more than 56% of the diurnal soil CO2 flux. (2) There was a dramatic difference in the temperature response between biotic and abiotic CO2 fluxes: the response curves of biotic respiration were exponential in the saline soil and quadratic in the alkaline soil, while the abiotic CO2 flux was linearly correlated with soil temperature. They were of similar magnitude but with opposite signs: resulting in almost neutral carbon emissions on daily average. (3) Due to this covering up effect of the abiotic CO2 flux, biotic respiration was severely underestimated (directly measured soil CO2 flux was only one-seventh of the biotic CO2 flux in saline soil, and even an order of magnitude lower in alkaline soil). In addition, the soil CO2 flux masked the temperature-inhibition of biotic respiration in the alkaline soil, and veiled the differences in soil biological respiration between the saline and alkaline soils. Hence, the soil CO2 flux may not be an ideal representative of soil respiration in arid soil. Our study calls for a reappraisal of the definition of the soil CO2 flux and its temperature dependence in arid or saline/alkaline land. Further investigations of abiotic CO2 fluxes are needed to improve our understanding of arid land responses to global warming and to assist in identifying the underlying abiotic mechanisms.

2.
Pituitary ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062801

RESUMO

PURPOSE: This study was designed to develop a computer-aided diagnosis (CAD) system based on a convolutional neural network (CNN) to diagnose patients with pituitary tumors. METHODS: We included adult patients clinically diagnosed with pituitary adenoma (pituitary adenoma group), or adult individuals without pituitary adenoma (control group). After pre-processing, all the MRI data were randomly divided into training or testing datasets in a ratio of 8:2 to create or evaluate the CNN model. Multiple CNNs with the same structure were applied for different types of MR images respectively, and a comprehensive diagnosis was performed based on the classification results of different types of MR images using an equal-weighted majority voting strategy. Finally, we assessed the diagnostic performance of the CAD system by accuracy, sensitivity, specificity, positive predictive value, and F1 score. RESULTS: We enrolled 149 participants with 796 MR images and adopted the data augmentation technology to create 7960 new images. The proposed CAD method showed remarkable diagnostic performance with an overall accuracy of 91.02%, sensitivity of 92.27%, specificity of 75.70%, positive predictive value of 93.45%, and F1-score of 92.67% in separate MRI type. In the comprehensive diagnosis, the CAD achieved better performance with accuracy, sensitivity, and specificity of 96.97%, 94.44%, and 100%, respectively. CONCLUSION: The CAD system could accurately diagnose patients with pituitary tumors based on MR images. Further, we will improve this CAD system by augmenting the amount of dataset and evaluate its performance by external dataset.

3.
J Pharmacol Exp Ther ; 373(1): 149-159, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32015160

RESUMO

Aberrant activation of the Wnt/ß-catenin pathway leads to the development of multiple cancers, including breast cancer. Development of therapeutic agents against this signaling pathway is an urgent need. In this study, we found that 2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oic acid-methyl ester (CDDO-Me) could inhibit Wnt/ß-catenin signaling mainly through targeting the low-density lipoprotein receptor-related protein (LRP) 6 and Frizzled (FZD) 7 receptor complex. This compound induced the degradation and ubiquitination of LRP6 and Fzd7 via the lysosomal pathway. We further showed that CDDO-Me mediated the degradation of FZD7 in an LRP6 ectodomain-dependent manner. In breast cancer cells, treatment with CDDO-Me increased the degradation of LRP6 and FZD7 and reduced the levels of phosphorylated Disheveled (DVL) 2 and active ß-catenin, resulting in the downregulation of Wnt target genes and several cancer stem cell (CSC) marker genes. In a murine xenograft bearing mouse mammary tumor virus (MMTV)-Wnt1-driven mammary tumor, administration of CDDO-Me significantly inhibited tumor growth and was accompanied by reduced expression of phosphorylated and total LRP6, phosphorylated and unphosphorylated DVL2, active ß-catenin, several Wnt target genes, and CSC marker genes. Collectively, the results of our study present that CDDO-Me is a potent Wnt/ß-catenin signaling inhibitor that may be a promising therapeutic agent against breast cancer. SIGNIFICANCE STATEMENT: Blocking the membrane receptor complex consisting of low-density lipoprotein receptor-related protein (LRP) 6 and Frizzled (FZD) 7 may help developing therapeutic approaches for cancers, including breast cancers. Our study indicates that 2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oic acid-methyl ester (CDDO-Me) can inhibit Wnt/ß-catenin signaling by inducing the ubiquitination and degradation of LRP6/FZD7 membrane receptor complex via a lysosomal pathway. We also found that the ectodomain of LRP6 is essential for CDDO-Me-induced FZD7 degradation. Defining CDDO-Me as a novel inhibitor of Wnt/ß-catenin signaling, our results provide insight into the mechanism of its anticancer activity.

4.
FASEB J ; 34(3): 4189-4203, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31957105

RESUMO

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Abnormal energy metabolism in microvascular endothelium is involved in the progression of diabetic retinopathy. Bile Acid G-Protein-Coupled Membrane Receptor (TGR5) has emerged as a novel regulator of metabolic disorders. However, the role of TGR5 in diabetes mellitus-induced microvascular dysfunction in retinas is largely unknown. Herein, enzyme-linked immunosorbent assay was used for analyzing bile acid (BA) profiles in diabetic rat retinas and retinal microvascular endothelial cells (RMECs) cultured in high glucose medium. The effects of TGR5 agonist on streptozotocin (STZ)-induced diabetic retinopathy were evaluated by HE staining, TUNEL staining, retinal trypsin digestion, and vascular permeability assay. A pharmacological inhibitor of RhoA was used to study the role of TGR5 on the regulation of Rho/Rho-associated coiled-coil containing protein kinase (ROCK) and western blot, immunofluorescence and siRNA silencing were performed to study the related signaling pathways. Here we show that bile acids were downregulated during DR progression in the diabetic rat retinas and RMECs cultured in high glucose medium. The TGR5 agonist obviously ameliorated diabetes-induced retinal microvascular dysfunction in vivo, and inhibited the effect of TNF-α on endothelial cell proliferation, migration, and permeability in vitro. In contrast, knockdown of TGR5 by siRNA aggravated TNF-α-induced actin polymerization and endothelial permeability. Mechanistically, the effects of TGR5 on the improvement of endothelial function was due to its regulatory role on the ROCK signaling pathway. An inhibitor of RhoA significantly reversed the loss of tight junction protein under TNF-α stimulation. Taken together, our findings suggest that insufficient BA signaling plays an important pathogenic role in the development of DR. Upregulation or activation of TGR5 may inhibit RhoA/ROCK-dependent actin remodeling and represent an important therapeutic intervention for DR.

5.
Int J Mol Sci ; 21(3)2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991793

RESUMO

Circular RNAs (circRNAs) are endogenous noncoding RNAs with covalently closed continuous loop structures that are formed by 3'-5' ligation during splicing. These molecules are involved in diverse physiological and developmental processes in eukaryotic cells. Jasmonic acid (JA) is a critical hormonal regulator of plant growth and defense. However, the roles of circRNAs in the JA regulatory network are unclear. In this study, we performed high-throughput sequencing of Arabidopsis thaliana at 24 h, 48 h, and 96 h after methyl JA (MeJA) treatment. A total of 8588 circRNAs, which were distributed on almost all chromosomes, were identified, and the majority of circRNAs had lengths between 200 and 800 bp. We identified 385 differentially expressed circRNAs (DEcircRNAs) by comparing data between MeJA-treated and untreated samples. Gene Ontology (GO) enrichment analysis of the host genes that produced the DEcircRNAs showed that the DEcircRNAs are mainly involved in response to stimulation and metabolism. Additionally, some DEcircRNAs were predicted to act as miRNA decoys. Eight DEcircRNAs were validated by qRT-PCR with divergent primers, and the junction sites of five DEcircRNAs were validated by PCR analysis and Sanger sequencing. Our results provide insight into the potential roles of circRNAs in the MeJA regulation network.

6.
Biomaterials ; 232: 119709, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31896513

RESUMO

Wnt/ß-catenin signaling cascade is highly associated with tumorigenesis and progression of various cancers. Targeting Wnt/ß-catenin signaling exhibits a promising way for cancer treatment. Herein, dual-stimuli responsive nanotheranostics was synthesized, which was composed of melanin coated magnetic nanoparticles (MMNs) and Wnt signaling inhibitor obatoclax (OBX) for multimodality imaging guided mild hyperthermia-enhanced chemotherapy. The MMNs could be used as contrast agents for magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) guided photothermal therapy. In addition, OBX-loaded MMNs (OBX-MMNs) were specific response to both pH changes and near-infrared (NIR) light illumination, which could trigger OBX release. Most intriguingly, tumor tissue accumulation and cellular internalization of this nanotheranostics could be dramatically enhanced through mild hyperthermia generated by laser-irradiated MMNs. Laser irradiation exhibited efficient chemotherapeutic outcome through enhancing OBX-mediated inhibition of the Wnt/ß-catenin signaling. Our results indicated the as-prepared OBX-MMNs hold great potential for MR/PA dual-modal imaging guided mild hyperthermia-enhanced chemotherapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31613757

RESUMO

Free viewpoint video (FVV) has received considerable attention owing to its widespread applications in several areas such as immersive entertainment, remote surveillance and distanced education. Since FVV images are synthesized via a depth image-based rendering (DIBR) procedure in the "blind" environment (without reference images), a real-time and reliable blind quality assessment metric is urgently required. However, the existing image quality assessment metrics are insensitive to the geometric distortions engendered by DIBR. In this research, a novel blind method of DIBR-synthesized images is proposed based on measuring geometric distortion, global sharpness and image complexity. First, a DIBR-synthesized image is decomposed into wavelet subbands by using discrete wavelet transform. Then, the Canny operator is employed to detect the edges of the binarized low-frequency subband and high-frequency subbands. The edge similarities between the binarized low-frequency subband and high-frequency subbands are further computed to quantify geometric distortions in DIBR-synthesized images. Second, the log-energies of wavelet subbands are calculated to evaluate global sharpness in DIBR-synthesized images. Third, a hybrid filter combining the autoregressive and bilateral filters is adopted to compute image complexity. Finally, the overall quality score is derived to normalize geometric distortion and global sharpness by the image complexity. Experiments show that our proposed quality method is superior to the competing reference-free state-of-the-art DIBR-synthesized image quality models.

8.
Oncol Rep ; 42(5): 1735-1744, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31436297

RESUMO

Emetine, an amoebicidal drug, exerts potent anticancer activity against various solid tumors, however, the underlying molecular mechanism remains unclear. In the present study, the effects of emetine were investigated on various proteins involved in the Wnt/ß­catenin signaling pathway, which has been linked to various human cancers. It was revealed that emetine blocked Wnt/ß­catenin signaling by targeting components of this pathway, including the low­density lipoprotein­receptor­related protein 6 (LRP6) and disheveled (DVL). Moreover, nanomolar concentrations of emetine decreased phosphorylation of these proteins and suppressed the expression of Wnt target genes, including fibronectin, frizzled­7 (Fzd7), c­Myc, Nanog and CD133 in MDA­MB­231 and MDA­MB­468 breast cancer cells. Additionally, emetine treatment induced apoptosis and suppressed the viability, migration, invasion, and sphere formation of breast cancer cells. Collectively the present results indicated that emetine antagonizes Wnt/ß­catenin signaling, providing insight into the molecular mechanism underlying the anticancer activity of emetine.

9.
Neurology ; 93(11): e1112-e1122, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405905

RESUMO

OBJECTIVE: To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response. METHODS: In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients. RESULTS: Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset. CONCLUSIONS: Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Conectoma/métodos , Epilepsia Generalizada/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Adolescente , Adulto , Córtex Cerebral/fisiopatologia , Epilepsia Generalizada/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Rede Nervosa/fisiopatologia , Estudos Prospectivos , Tálamo/fisiopatologia , Adulto Jovem
10.
Br J Pharmacol ; 176(17): 3390-3406, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236922

RESUMO

BACKGROUND AND PURPOSE: Salinomycin is a well-known inhibitor of human cancer stem cells (CSCs). However, the molecular mechanism(s) by which salinomycin targets colorectal CSCs is poorly understood. Here, we have investigated underlying antitumour mechanisms of salinomycin in colorectal cancer cells and three tumour models. EXPERIMENTAL APPROACH: The inhibitory effect of salinomycin on the Wnt/ß-catenin pathway was analysed with the SuperTopFlash reporter system. The mRNA expression of Wnt target genes was evaluated with real-time PCR. Effects of salinomycin on ß-catenin/TCF4E interaction were examined using co-immunoprecipitation and an in vitro GST pull-down assay. Cell proliferation was determined by BrdU incorporation and soft agar colony formation assay. The stemness of the cells was assessed by sphere formation assay. Antitumour effects of salinomycin on colorectal cancers was evaluated with colorectal CSC xenografts, APCmin/+ transgenic mice, and patient-derived colorectal tumour xenografts. KEY RESULTS: Salinomycin blocked ß-catenin/TCF4E complex formation in colorectal cancer cells and in an in vitro GST pull-down assay, thus decreasing expression of Wnt target genes. Salinomycin also suppressed the transcriptional activity mediated by ß-catenin/LEF1 or ß-catenin/TCF4E complex and exhibited an inhibitory effect on the sphere formation, proliferation, and anchorage-independent growth of colorectal cancer cells. In colorectal tumour xenografts and APCmin/+ transgenic mice, administration of salinomycin significantly reduced tumour growth and the expression of CSC-related Wnt target genes including LGR5. CONCLUSIONS AND IMPLICATIONS: Our study suggested that salinomycin could suppress the growth of colorectal cancer by disrupting the ß-catenin/TCF complex and thus may be a promising agent for colorectal cancer treatment.

11.
J Cell Biochem ; 120(10): 18370-18377, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190333

RESUMO

BACKGROUND: Nicotine, an important component of tobacco, is a major risk factor of lung cancer, but the mechanism through which nicotine promotes lung cancer development remains unclear. METHODS: Eighty patients with lung cancer were enrolled in this study, 34 of whom did not smoke and the others did. The expression of miR-218 and CDK6 messenger RNA (mRNA) was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A luciferase reporter system was used to identify the direct target of miR-218. The protein expression of CDK6 was analyzed by using Western blotting. Cell proliferation was analyzed using an approach of calculation of cell number under a microscope. RESULTS: Nicotine decreased miR-218 expression in non-small cell lung cancer (NSCLC) cells and promoted proliferation of NSCLC cells. Smoking patients with NSCLC had lower expression of miR-218 in tumor compared with NSCLC patients who did not smoke. We found that miR-218 directly targeted the CDK6 mRNA 3'untranslated region and inhibited its expression in NSCLC cells and also observed a negative correlation between the expression of miR-218 and CDK6 mRNA in lung cancer tissues. Furthermore, miR-218- or nicotine-induced proliferative effects of NSCLC cells were rescued by the recovery of the expression level of CDK6. CONCLUSION: Nicotine promotes proliferation of NSCLC cells through regulating the miR-218/CDK6 axis, which may be a potential therapeutic target for lung cancer.

12.
Neuroreport ; 30(10): 700-706, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31116131

RESUMO

The aim of this study was to better understand the imaging features of drug-resistant epilepsy (DRE), especially in idiopathic generalized tonic-clonic seizure (GTCS), as well as to discover the associated mechanisms and functional connectivity (FC). A total of 31 idiopathic generalized epilepsy-GTCS patients and 17 healthy controls were enrolled. For each patient, resting-state functional MRI was performed. After a 12-month follow-up observation, patients were further divided into either drug-resistant (DR) or drug-sensitive (DS) groups. Compared to the DS group, DR patients had previously received more types of antiepileptic drugs and had taken more types of failed antiepileptic drugs. There were distinct FC changes toward the left thalamus, left putamen, left precuneus, and right precentral gyrus in the left hippocampus between DR and DS patients. FCs in the DR group largely decreased or remained unchanged, while DS patients exhibited compensatory enhancement. Disease duration was negatively correlated with FC between the left hippocampus and the left thalamus-putamen in patients with DRE. Further, DRE patients had an extremely high area under the curve (0.978) and a cut-off FC between the left hippocampus and thalamus-putamen of 0.282. Together, hippocampal FCs in patients with DR GTCS were impaired and time-dependently correlated with disease duration. Hippocampal FCs in DS patients showed overall compensatory enhancement, which could be used as a sensitive and specific marker to identify and predict DR GTCS.

13.
Sensors (Basel) ; 19(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067660

RESUMO

With the popularity of location-based services and applications, a large amount of mobility data has been generated. Identification through mobile trajectory information, especially asynchronous trajectory data has raised great concerns in social security prevention and control. This paper advocates an identification resolution method based on the most frequently distributed TOP-N (the most frequently distributed N regions regarding user trajectories) regions regarding user trajectories. This method first finds TOP-N regions whose trajectory points are most frequently distributed to reduce the computational complexity. Based on this, we discuss three methods of trajectory similarity metrics for matching tracks belonging to the same user in two datasets. We conducted extensive experiments on two real GPS trajectory datasets GeoLife and Cabspotting and comprehensively discussed the experimental results. Experimentally, our method is substantially effective and efficiency for user identification.

14.
Pharmacol Rep ; 71(2): 319-329, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826573

RESUMO

BACKGROUND: The increased influx of free fatty acids (FFAs) into the kidney is a risk factor for diabetes nephropathy (DN). In the present study we investigated the effects of astragaloside IV (AS-IV) on FFA-induced lipid accumulation, oxidative stress, and activation of TGF-ß1 signaling in human glomerular mesangial cells (HMCs). METHODS: A DN model was induced in Sprague Dawley rats by the administration of a high-fat diet and streptozocin, and HMCs were stimulated with palmitate. Lipid accumulation and FFA uptake were detected using Oil Red O and BODIPY™ FL C16 staining, respectively. The expression levels of TGF-ß1, p-Smad2/3, FN, Col4 A1, NOX4, p22phox, and CD36 were evaluated by western blotting or immunofluorescence/immunohistochemistry. The level of reactive oxygen species (ROS) was detected using 2',7'-dichlorofluorescein diacetate and dihydroethidium. RESULTS: Exposure to palmitate induced marked lipid accumulation in HMCs, whereas co-treatment with AS-IV significantly attenuated this phenomenon. Moreover, AS-IV suppressed palmitate-induced expression of TGF-ß1, p-Smad2/3, FN, Col4 A1, NOX4, and p22phox, in addition to ROS production. Notably, AS-IV reduced the palmitate-induced expression of CD36 in HMCs and DN rats. Treatment of HMCs with the CD36 inhibitor, sulfo-N-succinimidyl oleate (SSO), significantly attenuated FFA uptake, oxidative stress, and fibrosis. Nevertheless, the combined use of SSO and AS-IV did not enhance the efficacy. CONCLUSION: AS-IV inhibited palmitate-induced HMCs oxidative stress and fibrosis via the downregulation of CD36 expression, mediating FFA uptake and lipid accumulation.


Assuntos
Antígenos CD36/genética , Nefropatias Diabéticas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Nefropatias Diabéticas/patologia , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos não Esterificados/metabolismo , Fibrose/patologia , Humanos , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/patologia , Palmitatos/toxicidade , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
15.
Cancer Cell Int ; 19: 55, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911286

RESUMO

Background: Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a member of microfilament-related formins and mediates cell motility in breast cancer (BrCa). However, the genetic mutation status of DAAM1 mRNA and its correlation with pathological characteristics are still unclearly. Methods: A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of DAAM1 3'-UTR and underlying mechanism in BrCa metastasis. Methods: A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of DAAM1 3'-UTR and underlying mechanism in BrCa metastasis. Results: The expression and activation of DAAM1 increased markedly in lymphnode metastatic tissues. A genetic variant (rs79036859 A/G) was validated in the miR-208a-5p binding site of DAAM1 3'-UTR. The G genotype (AG/GG) was a risk genotype for the metastasis of BrCa by reducing binding affinity of miR-208a-5p for the DAAM1 3'-UTR. Furthermore, the miR-208a-5p expression level was significantly suppressed in lymphnode metastatic tissues compared with that in non-lymphnode metastatic tissues. Overexpression of miR-208a-5p inhibited DAAM1/RhoA signaling pathway, thereby leading to the decrease of the migratory ability. Conclusion: Overall, the rs79036859 G variant of DAAM1 3'-UTR was identified as a relevant role in BrCa metastasis via the diversity of miR-208a-5p binding affinity.

16.
Onco Targets Ther ; 12: 993-1005, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30787621

RESUMO

Background: CK1 is involved in regulating Wnt/ß-catenin signaling and represents a promising target for the treatment of breast cancer. A purine derivative longdaysin has recently been identified as a novel modulator of cellular circadian rhythms through targeting the protein kinases CK1δ, CK1α, and ERK2. However, the antitumor activity of longdaysin and its underlying mechanisms remain unclear. Methods: The inhibitory effect of longdaysin on Wnt/ß-catenin signaling was investigated using the SuperTOPFlash reporter system. The levels of phosphorylated LRP6, total LRP6, DVL2, active ß-catenin, and total ß-catenin were examined by Western blot. The expression of Wnt target genes was determined using real-time PCR. The ability of colony formation of breast cancer cells was measured by colony formation assay. The effects of longdaysin on cancer cell migration and invasion were assessed using transwell assays. The effect of longdaysin on cancer stem cells was tested by sphere formation assay. The in vivo antitumor effect of longdaysin was evaluated using MDA-MB-231 breast cancer xenografts. Results: Longdaysin suppressed Wnt/ß-catenin signaling through inhibition of CK1δ and CK1ε in HEK293T cells. In breast cancer Hs578T and MDA-MB-231 cells, micromolar concentrations of longdaysin attenuated the phosphorylation of LRP6 and DVL2 and reduced the expression of active ß-catenin and total ß-catenin, leading to the downregulation of Wnt target genes Axin2, DKK1, LEF1, and Survivin. Furthermore, longdaysin inhibited the colony formation, migration, invasion, and sphere formation of breast cancer cells. In MDA-MB-231 breast cancer xenografts, treatment with longdaysin suppressed tumor growth in association with inhibition of Wnt/ß-catenin signaling. Conclusion: Longdaysin is a novel inhibitor of the Wnt/ß-catenin signaling pathway. It exerts antitumor effect through blocking CK1δ/ε-dependent Wnt signaling.

17.
IEEE Trans Neural Netw Learn Syst ; 30(11): 3275-3286, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30703043

RESUMO

Convolutional neural networks (CNNs) have wide applications in pattern recognition and image processing. Despite recent advances, much remains to be done for CNNs to learn a better representation of image samples. Therefore, constant optimizations should be provided on CNNs. To achieve a good performance on classification, intuitively, samples' interclass separability, or intraclass compactness should be simultaneously maximized. Accordingly, in this paper, we propose a new network, named separability and compactness network (SCNet) to rectify this problem. SCNet minimizes the softmax loss and the distance between features of samples from the same class under a jointly supervised framework, resulting in simultaneous maximization of interclass separability and intraclass compactness of samples. Furthermore, considering the convenience and the efficiency of the cosine similarity in face recognition tasks, we incorporate it into SCNet's distance metric to enable sample features from the same class to line up in the same direction and those from different classes to have a large angle of separation. We apply SCNet to three different tasks: visual classification, face recognition, and image superresolution. Experiments on both public data sets and real-world satellite images validate the effectiveness of our SCNet.

18.
Biomed Pharmacother ; 109: 84-92, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30396095

RESUMO

Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Renal tubular injury plays an important role in the development and progression of DN. And apoptosis of renal tubular epithelial cells (RTEC) contribute to the loss of renal function, increased levels of serum creatinine (SCr), blood urea nitrogen (BUN), urine total protein to urine creatinine and microalbuminuria and reduction of creatinine clear rate (CCr). Moreover, recent findings suggested that endoplasmic reticulum (ER) stress may lead to apoptosis of renal cells. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-apoptosis. Thus, in this study we investigated the effects and mechanisms of AS-IV on apoptosis of RTEC in high-fat diets (HFD) and low-dose streptozotocin (STZ)-induced type 2 DN rats. The results showed that AS-IV (40, 80 mg/kg) could alleviate RTEC apoptosis in DN rats. Furthermore, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney were also improved by AS-IV. And AS-IV could reduce the expression of apoptosis-related proteins cleaved caspase-3, Bax/Bcl-2 ratio. ER stress-related proteins GRP78, p-PERK, ATF4 and CHOP were also inhibited by AS-IV in kidney of DN rats. Taken together, our study suggests that the protective effects of AS-IV may be related to inhibit ER stress-induced apoptosis through down-regulating the expression of p-PERK, ATF4 and CHOP. And our study provides a new theoretical basis for the clinical treatment of patients with kidney diseases.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Saponinas/farmacologia , Triterpenos/farmacologia , Fator 4 Ativador da Transcrição/genética , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina , Fator de Transcrição CHOP/genética , eIF-2 Quinase/genética
19.
Brain Behav Immun ; 76: 48-60, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30414952

RESUMO

Germinal centers (GC) are vital to adaptive immunity. BCL6 and miR-155 are implicated in control of GC reaction and lymphomagenesis. FBXO11 causes BCL6 degradation through ubiquitination in B-cell lymphomas. Chronic psychological stress is known to drive immunosuppression. Corticosterone (CORT) is an adrenal hormone expressed in response to stress and can similarly impair immune functions. However, whether GC formation is disrupted by chronic psychological stress and its molecular mechanism remain to be elucidated. To address this issue, we established a GC formation model in vivo, and a GC B cell differentiation model in vitro. Comparing Naive B cells to GC B cells in vivo and in vitro, the differences of BCL6 and FBXO11 mRNA do not match the changes at the protein level and miR-155 levels that were observed. Next we demonstrated that CORT increase, induced by chronic psychological stress, reduced GC response, IgG1 antibody production and miR-155 level in vivo. The effect of chronic psychological stress can be blocked by a glucocorticoid receptor (GR) antagonist. Similarly, impaired GC B cell generation and isotope class switching were observed. Furthermore, we found that miR-155 and BCL6 expression were downregulated, but FBXO11 expression was upregulated in GC B cells treated with CORT in vitro. In addition, we demonstrated that miR-155 directly down-regulated FBXO11 expression by binding to its 3́-untranslated region. The subsequent overexpression of miR-155 significantly blocked the stress-induced impairment of GC response, due to changes in FBXO11 and BCL6 expression, as well as increased apoptosis in B cells both in vivo and in vitro. Our findings suggest perturbation of GC reaction may play a role in chronic psychological stress-induced immunosuppression through a glucocorticoid pathway, and miR-155-mediated post-transcriptional regulation of FBXO11 and BCL6 expression may contribute to the impaired GC response.


Assuntos
Centro Germinativo/metabolismo , MicroRNAs/metabolismo , Estresse Psicológico/metabolismo , Animais , Apoptose/fisiologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Diferenciação Celular/imunologia , Proteínas de Ligação a DNA/genética , Proteínas F-Box/metabolismo , Feminino , Centro Germinativo/fisiologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Estresse Psicológico/fisiopatologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-30571634

RESUMO

Video super-resolution (SR) is focused on reconstructing high-resolution (HR) frames from consecutive lowresolution (LR) frames. Most previous video SR methods based on convolutional neural network (CNN) use a direct connection and single-memory module within the network, and they thus fail to make full use of spatio-temporal complementary information from LR observed frames. To fully exploit spatio-temporal correlations between adjacent LR frames and reveal more realistic details, this paper proposes a multi-memory convolutional neural network (MMCNN) for video SR, cascading an optical flow network and an image-reconstruction network. A serial of residual blocks engaged in utilizing intra-frame spatial correlations are proposed for feature extraction and reconstruction. Particularly, instead of using single-memory module, we embed convolutional long short-term memory (ConvLSTM) into the residual block, thus form a multi-memory residual block to progressively extract and retain inter-frame temporal correlations between consecutive LR frames. We conduct extensive experiments on numerous testing datasets with respect to different scaling factors. Our proposed MMCNN shows superiority over the state-of-the-art methods in terms of PSNR and visual quality and surpasses the best counterpart method 1 dB at most. The code and datasets are available at https://github.com/psychopa4/MMCNN.

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