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1.
Clin Biochem ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786207

RESUMO

OBJECTIVE: The development of blood-based biomarkers for early diagnosis and treatment of Alzheimer's disease (AD) is desirable. In AD model mouse brain and neuronal cells, Abelson helper integration site-1 (AHI1) protein is reduced. AHI1 facilitates intracellular amyloid precursor protein (APP) translocation to inhibit amyloidogenic pathology of AD, and thus may be an AD biomarker. METHODS: This study was conducted among 32 AD patients and 54 healthy control (HC) subjects. AHI1-related protein levels from initially collected serum samples in each group were screened using Western blotting. The protein concentrations of AHI1 and amyloid-ß (Aß), peptide(s) derived from APP, from all serum samples were analyzed using ELISA. RESULTS: In AD serum, AHI1 and a large truncated C-terminal APP fragment were significantly reduced. The average concentrations of serum AHI1 and Aß in AD were significantly lower than those in HC. Notably, AHI1 concentration in HC serum was decreased in an age-dependent manner, while it was consistently low in AD serum and had no correlation with Aß or mini-mental state examination score. The receiver operating characteristic analysis on all subjects demonstrated an area under curve (AUC) value of 0.7 for AHI1 on AD diagnosis, while the AUC increased to 0.82 on the subjects younger than 77 years old, suggesting a good diagnostic performance of serum AHI1 for AD especially at relatively young age. CONCLUSION: An early event of AHI1 reduction in the body of AD patients was observed. Serum AHI1 may be valuable for early diagnosis of AD.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31765304

RESUMO

This paper presents a novel approach for depth map enhancement from an RGB-D video sequence. The basic idea is to exploit the photometric information in the color sequence to resolve the inherent ambiguity of shape from shading problem. Instead of making any assumption about surface albedo or controlled object motion and lighting, we use the lighting variations introduced by casual object movement. We are effectively calculating photometric stereo from a moving object under natural illuminations. One of the key technical challenges is to establish correspondences over the entire image set. We therefore develop a lighting insensitive robust pixel matching technique that out-performs optical flow method in presence of lighting variations. An adaptive reference frame selection procedure is introduced to get more robust to imperfect lambertian reflections. In addition we present an expectation-maximization framework to recover the surface normal and albedo simultaneously, without any regularization term. We have validated our method on both synthetic and real datasets to show its superior performance on both surface details recovery and intrinsic decomposition.

3.
Mol Med Rep ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31746381

RESUMO

As a novel anti­inflammatory cytokine of the interleukin (IL)­1 family, IL­37 protects the human body from diseases characterized by excessive inflammation. The pathologic process of hyperhomocysteinemia (hHcy) is accompanied by persistent inflammation. However, little is known regarding the role of IL­37 in hHcy. In the present study, the levels of cytokines including IL­37, IL­1ß, IL­6 and tumor necrosis factor­α in the supernatant were detected by ELISA. mRNA and protein expression were detected by Reverse transcription­quantitative PCR and western blotting, respectively. LDH level was determined by ELISA and the cell viability was detected through CCK­8 kit. In the present study, mean serum IL­37 levels of patients with hHcy were 32.3% lower than those of controls (P<0.01). In peripheral blood mononuclear cells (PBMCs) from patients with hHcy, mean IL­37 mRNA expression was 73.5% lower (P<0.01) and IL­37 protein expression was 77.7% lower compared with that of healthy controls (P<0.01). Furthermore, the results demonstrated that exogenous homocysteine (Hcy) stimulation markedly downregulated the mRNA and protein expression levels of IL­37 in PBMCs in vitro. In 293T cells, overexpression of IL­37 restored the cell viability impaired by Hcy, and reduced the release of lactate dehydrogenase and the proinflammatory cytokines IL­1ß, IL­6 and tumor necrosis factor­α. In conclusion, IL­37 was downregulated by Hcy in vivo and in vitro, and IL­37 exhibited a protective role against cell injury induced by Hcy.

4.
Psychiatry Res ; 282: 112639, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31685286

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, but the genetic mechanism of ADHD remains elusive now. METHODS: Tissue specific transcriptome-wide association study (TWAS) of ADHD was performed by FUSION utilizing a genome-wide association study (GWAS) dataset of ADHD (including 20,183 ADHD cases and 35,191 healthy controls) and gene expression reference from brain and blood. Furthermore, the genes identified by TWAS were compared with the differently expressed genes detected by mRNA expression profiles of ADHD rat model and autism spectrum disorders (ASD) patients. Functional enrichment and annotation analysis of the identified genes were performed by DAVID and FUMAGWAS tool. RESULTS: For brain tissue, TWAS identified 148 genes with P value < 0.05, such as TDO2 (PTWAS=4.01×10-2), CHD1L (PTWAS=9.64×10-3) and KIAA0319L (PTWAS=4.05×10-4). Further 11 common genes were examined in the mRNA expression datasets, such as ACSM5 (PTWAS=3.62×10-2, PmRNA=0.005), CCDC24 (PTWAS=1.49×10-2, PmRNA=2.35×10-3) and MVP (PTWAS=5.55×10-3, PmRNA=5.40×10-3). Pathway enrichment analysis of the genes identified by TWAS detected 3 pathways for ADHD, including Other glycan degradation (P value=0.021), Viral myocarditis (P value=0.034) and Endocytosis (P value=0.041). CONCLUSIONS: Through integrating GWAS and mRNA expression data, we identified a group of ADHD-associated genes and pathways, providing novel clues for understanding the genetic mechanism of ADHD.

5.
Med Hypotheses ; 135: 109440, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31734379

RESUMO

There are a pretty number of research demonstrating that ADAMTS4 and ADAMTS5 playing primary roles in the degradation of cartilage during inflammatory joint diseases like osteoarthritis (OA). Because Kashin-Beck Disease (KBD) has been found to own the common pathological changes and symptoms with OA, and is regarded as the specific type of osteoarthritis, it's reasonable to believe that ADAMTS4 and ADAMTS5 may exert an enormous functions on the injury of cartilage of the KBD and may be potential molecular therapeutic targets for KBD.

6.
Environ Pollut ; : 113513, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31733959

RESUMO

Fluorotelomer alcohols (FTOHs) are important precursors of perfluorocarboxylic acids (PFCAs) in the environment and biota. With the growing application of 6:2 FTOH [F(CF2)6CH2CH2OH] in product formulation, it is becoming increasingly urgent to investigate its biological fates in different species. In this study, biotransformation of 6:2 FTOH by young soybean plants (Glycine max L. Merrill) were investigated using hydroponic experiments. During the 144 h-exposure, 6:2 FTCA [F(CF2)6CH2COOH], 6:2 FTUCA [F(CF2)5CFCHCOOH], 5:3 FTUCA [F(CF2)5CHCHCOOH], 5:3 FTCA [F(CF2)5CH2CH2COOH], PFHxA [F(CF2)5COOH] and PFPeA [F(CF2)4COOH] were phase I metabolites in soybean. At the end of exposure, 5:3 FTCA (5.08 mol%), PFHxA (2.34 mol%) and PFPeA (0.58 mol%) were three main metabolites in soybean-solution system. 5:3 FTCA was predominant in soybean roots and stems, while PFHxA was the most abundant product in leaves. PFBA [F(CF2)3COOH] and 4:3 FTCA [F(CF2)4CH2CH2COOH] detected in the hydroponic solution most-likely came from the transformation of 5:3 FTCA by root-associated microbes. Moreover, phase II metabolites of 6:2 FTOH were identified and monitored in soybean tissues. Alcohol dehydrogenase, aldehyde dehydrogenase and glutathione S-transferase were found to participate in 6:2 FTOH metabolism. Based on the phase I and phase II metabolism of 6:2 FTOH in soybean, this study for the first time provides evidences for the transformation pathways of 6:2 FTOH in plants.

7.
Mol Cancer ; 18(1): 162, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722712

RESUMO

BACKGROUND: As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. METHODS: circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. RESULTS: circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. CONCLUSION: Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

8.
Environ Pollut ; : 113596, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31771931

RESUMO

ZnO nanoparticles (NPs) have been detected in various wastewater treatment plants. It is widely assumed that size has a crucial effect on the NPs toxicity. Concerns have been raised over probable size-dependent toxicity of ZnO NPs to activated sludge, which could eventually affect the treatment efficiencies of wastewater treatment facilities. The size-dependent influences of ZnO NPs on performance, microbial activities, and extracellular polymeric substances (EPS) from activated sludge were examined in sequencing batch reactor (SBR) in present study. Three different sizes (15, 50, and 90 nm) and five concentrations (2, 5, 10, 30, and 60 mg L-1) were trialled. The inhibitions on COD and nitrogen removal were determined by the particle size, and smaller ZnO NPs (15 nm) showed higher inhibition effect than those of 50 and 90 nm, whereas the ZnO NPs with size of 50 nm showed maximum inhibition effect on phosphorus removal among three sizes of ZnO NPs. After exposure to different sized ZnO NPs, microbial enzymatic activities and removal rates of activated sludge represented the same trend, consistent with the nitrogen and phosphorus removal efficiency. In addition, apparent size- and concentration-dependent effects on EPS contents and components were also observed. Compared with the absence of ZnO NPs, 60 mg L-1 ZnO NPs with sizes of 15, 50, and 90 nm increased the EPS contents from 92.5, 92.4, and 92.0 mg g-1 VSS to 277.5, 196.8, and 178.2 mg g-1 VSS (p < 0.05), respectively. The protein and polysaccharide contents increased with the decreasing particle sizes and increasing ZnO NPs concentrations, and the content of protein was always higher than that of polysaccharide.

9.
Turk J Med Sci ; 2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31655502

RESUMO

BACKGROUND/AIM: We aimed to explore the roles of glycoproteins glycosylation in the pathogenesis of Kashin-Beck disease (KBD) and evaluated the effectiveness of sodium hyaluronate treatment. MATERIALS AND METHODS: Blood and saliva were collected from KBD patients before and after the injection of sodium hyaluronate. Normal healthy subjects were included as controls. Saliva and serum lectin microarrays and saliva and serum microarray verifications were used to screen and confirm the differences in lectin levels among the three groups. RESULTS: In saliva lectin microarray, bindings to Sophora Japonica Agglutinin (SJA), Griffonia (Bandeiraea) Simplicifolia Lectin I (GSL-I), Griffonia (Bandeiraea) Simplicifolia Lectin I (EEL), Maackia Amurensis Lectin II (MAL-II), Sambucus Nigra Lectin (SNA), Hippeastrum Hybrid Lectin (HHL) and Aleuria Aurantia Lectin (AAL) were higher in the untreated KBD patients than in the control group. Increased levels for HHL, MAL-II and GSL-I in the untreated KBD patients discriminated them in particular from the treated ones. Jacalin was lower in the untreated KBD patients compared to the treated KBD and the normal groups. In serum lectin microarray, HHL and Peanut Agglutinin (PNA) were increased in the untreated KBD group in comparison to the control one. AAL, Phaseolus vulgaris Agglutinin(E+L) (PHA-E+L) and PsophocarpusTetragonolobus Lectin I (PTL-I) were lower in the untreated KBD patients compared to the treated KBD and the normal groups. Hyaluronate treatment appeared to normalize SNA, AAL and MAL-II levels in saliva, and HHL, PNA, AAL, PTL-I and PHA-E+L levels in serum. Saliva reversed microarray verification confirmed significant differences between groups in SNA and Jacalin, in particular, GSL-I levels, while serum reversed microarray verification indicated that HHL, PNA and AAL levels returned to normal level after the hyaluronate treatment. Lectin blot confirmed significant differences in HHL, AAL and Jaclin in saliva, and HHL, PNA, PHA-E+L and AAL in serum. CONCLUSION: HHL in saliva and serum may be valuable diagnostic biomarker of KBD, and it may be used to follow-up of the hyaluronate treatment.

10.
FASEB J ; 33(12): 13669-13682, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31585506

RESUMO

The tick- and transfusion-transmitted human pathogen Babesia microti infects host erythrocytes to cause the pathologic symptoms associated with human babesiosis, an emerging disease with worldwide distribution and potentially fatal clinical outcome. Drugs currently recommended for the treatment of babesiosis are associated with a high failure rate and significant adverse events, highlighting the urgent need for more-effective and safer babesiosis therapies. Unlike other apicomplexan parasites, B. microti lacks a canonical lactate dehydrogenase (LDH) but instead expresses a unique enzyme, B. microti LDH (BmLDH), acquired through evolution by horizontal transfer from a mammalian host. Here, we report the crystal structures of BmLDH in apo state and ternary complex (enzyme-NADH-oxamate) solved at 2.79 and 1.89 Å. Analysis of these structures reveals that upon binding to the coenzyme and substrate, the active pocket of BmLDH undergoes a major conformational change from an opened and disordered to a closed and stabilized state. Biochemical assays using wild-type and mutant B. microti and human LDHs identified Arg99 as a critical residue for the catalytic activity of BmLDH but not its human counterpart. Interestingly, mutation of Arg99 to Ala had no impact on the overall structure and affinity of BmLDH to NADH but dramatically altered the closure of the enzyme's active pocket. Together, these structural and biochemical data highlight significant differences between B. microti and human LDH enzymes and suggest that BmLDH could be a suitable target for the development of selective antibabesial inhibitors.-Yu, L., Shen, Z., Liu, Q., Zhan, X., Luo, X., An, X., Sun, Y., Li, M., Wang, S., Nie, Z., Ao, Y., Zhao, Y., Peng, G., Ben Mamoun, C., He, L., Zhao, J. Crystal structures of Babesia microti lactate dehydrogenase BmLDH reveal a critical role for Arg99 in catalysis.

11.
Per Med ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31591920

RESUMO

Aim: Acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) occur frequently in patients with atrial fibrillation (AF). However, the optimal antithrombotic therapy is still debated. Methods & results: We analyzed 976 coronary artery disease patients with AF from 2013 to 2014. ACS+AF patients tend to take dual antiplatelet therapy (p < 0.001), whereas SCAD+AF patients prefer anticoagulation therapy (warfarin: p < 0.001, dabigatran: p < 0.05). Ventricular arrhythmia, congestive heart failure and ACS were the top three reasons for SCAD group patients' readmission, while reinfarction and congestive heart failure were two major factors in readmission of ACS group. Conclusion: ACS+AF group patients more likely choose dual antiplatelet therapy, whereas SCAD+AF group patients prefer anticoagulation therapy. Compared with ACS group, SCAD group had a higher rate of readmission.

12.
Phys Med Biol ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645019

RESUMO

Compared with conventional gastroscopy which is invasive and painful, wireless capsule endoscopy (WCE) can provide noninvasive examination of gastrointestinal (GI) tract. The WCE video can effectively support physicians to reach a diagnostic decision while a huge number of images need to be analyzed (more than 50,000 frames per patient). In this paper, we propose a computer-aided diagnosis method called second glance (secG) detection framework for automatic detection of ulcers based on deep convolutional neural networks that provides both classification confidence and bounding box of lesion area. We evaluated its performance on a large dataset that consists of 1,504 patient cases (the largest WCE ulcer dataset to our best knowledge, 1,076 cases with ulcers, 428 normal cases). We use 15,781 ulcer frames from 753 ulcer cases and 17,138 normal frames from 300 normal cases for training. Validation dataset consists of 2,040 ulcer frames from 108 cases and 2,319 frames from 43 normal cases. For test, we use 4,917 ulcer frames from 215 ulcer cases and 5,007 frames from 85 normal cases. Test results demonstrate the 0.9469 ROC-AUC of the proposed secG detection framework outperforms state-of-the-art detection frameworks including Faster-RCNN (0.9014) and SSD-300 (0.8355), which implies the effectiveness of our method. From the ulcer size analysis, we find the detection of ulcers is highly related to the size. For ulcers with size larger than 1% of the full image size, the sensitivity exceeds 92.00%. For ulcers that are smaller than 1% of the full image size, the sensitivity is around 85.00%. The overall sensitivity, specificity and accuracy are 89.71%, 90.48% and 90.10%, at a threshold value of 0.6706, which implies the potential of the proposed method to suppress oversights and to reduce the burden of physicians.

13.
Comput Math Methods Med ; 2019: 7546215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31641370

RESUMO

Wireless capsule endoscopy (WCE) has developed rapidly over the last several years and now enables physicians to examine the gastrointestinal tract without surgical operation. However, a large number of images must be analyzed to obtain a diagnosis. Deep convolutional neural networks (CNNs) have demonstrated impressive performance in different computer vision tasks. Thus, in this work, we aim to explore the feasibility of deep learning for ulcer recognition and optimize a CNN-based ulcer recognition architecture for WCE images. By analyzing the ulcer recognition task and characteristics of classic deep learning networks, we propose a HAnet architecture that uses ResNet-34 as the base network and fuses hyper features from the shallow layer with deep features in deeper layers to provide final diagnostic decisions. 1,416 independent WCE videos are collected for this study. The overall test accuracy of our HAnet is 92.05%, and its sensitivity and specificity are 91.64% and 92.42%, respectively. According to our comparisons of F1, F2, and ROC-AUC, the proposed method performs better than several off-the-shelf CNN models, including VGG, DenseNet, and Inception-ResNet-v2, and classical machine learning methods with handcrafted features for WCE image classification. Overall, this study demonstrates that recognizing ulcers in WCE images via the deep CNN method is feasible and could help reduce the tedious image reading work of physicians. Moreover, our HAnet architecture tailored for this problem gives a fine choice for the design of network structure.

14.
Sensors (Basel) ; 19(20)2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31635107

RESUMO

Groundwater is an important source of human activities, agriculture and industry. Underwater Acoustic Sensor Networks (UASNs) is one of the important technologies for marine environmental monitoring. Therefore, it is of great significance to study the node self- localization technology of underwater acoustic sensor network. This paper mainly studies the node localization algorithm based on range-free. In order to save cost and energy consumption, only a small number of sensing nodes in sensor networks usually know their own location. How to locate all nodes accurately through these few nodes is the focus of our research. In this paper, combined with the compressive sensing algorithm, a range-free node localization algorithm based on node hop information is proposed. Aiming at the problem that connection information collected by the algorithm is an integer, the hop is modified to further improve the localization performance. The simulation analysis shows that the improved algorithm is effective to improve the localization accuracy without additional cost and energy consumption compared with the traditional method.

15.
Redox Biol ; 28: 101319, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31536951

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The role of antioxidant enzyme peroxiredoxin 2 (PRDX2) in gastric tumorigenesis remains unknown. In vitro (AGS and SNU-1 cell lines) and in vivo mouse models were utilized to investigate the role of PRDX2 in response to H. pylori infection (7.13, J166 or PMSS1 strain). We detected high levels of PRDX2 expression in gastric cancer tissues. Gastric cancer patients with high expression levels of PRDX2 had significantly worse overall and progression-free survival than those with low levels. H. pylori infection induced activation of NF-κB with increased expression of PRDX2, in in vitro and in vivo models. The knockdown of PRDX2 led to an increase in the levels of reactive oxygen species (ROS), oxidative DNA damage, and double-strand DNA breaks, in response to H. pylori infection, as measured by H2DCFDA, 8-oxoguanine, and p-H2AXγ assays. Luciferase reporter and ChIP assays confirmed the presence of a putative binding site of NF-κB-p65 on PRDX2 promoter region. The inhibition of PRDX2 significantly sensitized AGS and SNU-1 cells to cisplatin treatment. Our data suggest that the future development of therapeutic approaches targeting PRDX2 may be useful in the treatment of gastric cancer.

16.
Nat Commun ; 10(1): 4166, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519905

RESUMO

The synergistic nature of bicomponent catalysts remains a challenging issue, due to the difficulty in constructing well-defined catalytic systems. Here we study the origin of synergistic effects in CoOx-Pt catalysts for selective hydrogenation by designing a series of closely contacted CoOxPt/TiO2 and spatially separated CoOx/TiO2/Pt catalysts by atomic layer deposition (ALD). For CoOx/TiO2/Pt, CoOx and platinum are separated by the walls of titania nanotubes, and the CoOx-Pt intimacy can be precisely tuned. Like CoOxPt/TiO2, the CoOx/TiO2/Pt shows higher selectivity to cinnamyl alcohol than monometallic TiO2/Pt, indicating that the CoOx-Pt nanoscale intimacy almost has no influence on the selectivity. The enhanced selectivity is ascribed to the increased oxygen vacancy resulting from the promoted hydrogen spillover. Moreover, platinum-oxygen vacancy interfacial sites are identified as the active sites by selectively covering CoOx or platinum by ALD. Our study provides a guide for the understanding of synergistic nature in bicomponent and bifunctional catalysts.

17.
IEEE Trans Neural Syst Rehabil Eng ; 27(11): 2247-2253, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31562095

RESUMO

An EEG-based Brain-Computer Interface (BCI) is a system that enables a user to communicate with and intuitively control external devices solely using the user's intentions. Current EEG-based BCI research usually involves a subject-specific adaptation step before a BCI system is ready to be employed by a new user. However, the subject-independent scenario, in which a well-trained model can be directly applied to new users without pre-calibration, is particularly desirable yet rarely explored. Considering this critical gap, our focus in this paper is the subject-independent scenario of EEG-based human intention recognition. We present a G raph-based H ierarchical A ttention M odel (G-HAM) that utilizes the graph structure to represent the spatial information of EEG sensors and the hierarchical attention mechanism to focus on both the most discriminative temporal periods and EEG nodes. Extensive experiments on a large EEG dataset containing 105 subjects indicate that our model is capable of exploiting the underlying invariant EEG patterns across different subjects and generalizing the patterns to new subjects with better performance than a series of state-of-the-art and baseline approaches.

18.
Pathol Oncol Res ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512056

RESUMO

EIF4E is the rate-limiting factor in the mRNA translation of specific set of oncogenes. Snail is the core transcription factor of epithelial-mesenchymal transition (EMT), a key step of cancer metastasis. The connection between the two oncoproteins has not been well established in the human cancer tissues and in nasopharyngeal carcinoma (NPC). Here we showed that the positive correlative over-expression was seen between eIF4E and Snail in NPC tissues, and the expression was significantly higher in the metastatic NPC than in the un-metastatic NPC. In NPC cells, eIF4E knockdown significantly reduced Snail mRNA and protein levels, increased the mRNA level of E-cad (a direct downstream gene of Snail and a negative EMT marker), attenuated the invasive ability of the cells, and sensitized the cells to cisplatin in invasion. In contrast, enforced the expression of eIF4E significantly increased Snail mRNA and protein levels, and promoted the invasive ability in NPC cells. Under the condition of the high eIF4E expression, Snail knockdown significantly increased E-cad mRNA level and weaken the invasive ability of NPC cells. Finally, eIF4E directly bound Snail mRNA for translation initiation displayed by the RIP assay. Therefore, the results firstly suggested that eIF4E enhanced the Snail expression in both transcription and translation manner in human cancer tissues and targeting the eIF4E/Snail axis might intervene with the EMT and metastasis of NPC. This finding provided a new clue for further understanding the metastatic mechanism of human cancers and for preventing and treating NPC metastasis.

19.
Ann Hum Genet ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31486066

RESUMO

Rheumatoid arthritis (RA) is an autoimmune chronic disorder manifesting as warm, swollen, and painful joints. Multiple immune cells are implicated in the development of RA. Previous studies demonstrated that integrating the genetic information of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) is capable of identifying new disease-risk loci and providing novel insights into the etiology of complex human disease. In this study, we conducted an integrative pathway association analysis of RA by using GWAS summary data and five immune cell types related to eQTL datasets of RA. After combining the cell-specific eQTLs and GWAS summary of RA and performing a pathway-enrichment analysis, we detected a group of RA-associated pathways with common or cell-specific enriched in the five immune cell types. 41 pathways for B cells, 33 pathways for CD4+ T cells, 27 pathways for CD8+ T cells, 39 pathways for monocyte, and 25 pathways for natural killer cells are significant in RA, among which 48% are common pathways and 32% are cell-specific pathways. We detected a group of RA-associated eQTL pathways related to five different immune cell types. Our findings may provide novel insights into the pathogenesis of RA.

20.
Sci Rep ; 9(1): 12742, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484970

RESUMO

Micropyles in insects are small openings that allow sperm entry into, and the number was usually decreased on unfertilized and (or) undeveloped eggs. However, reports showed that Harmonia axyridis, a reproductive success model, deposited similar number of micropyles on undeveloped and developing eggs. Thus, it was confusing whether micropyles in H. axyridis were unaffected. To solve this confusion, two experiments were conducted here. Firstly, virgin female and four different days delayed mating (DDM) experiments were conducted to reveal the effects of fertilization stimulus and delayed-fertilization. Secondly, intercrosses between a light-colored mutant (HAM, an adaptive deficiency) and wild type (HAW) were conducted to further reveal whether there were female and male interactions. We found that (1) eggs produced by virgin and DDM females had significantly less micropyles than control. Even so, more than 18 micropyles were observed on eggs following fertilization and, consequently, egg production as well as hatch rate was not negatively affected by mating delay; (2) number of micropyles was significantly varied among the four reciprocal crosses and virgin HAW female. Specifically, the heterozygous eggs (Cross-D) and wild-type homozygous eggs (Cross-B) respectively had the least and maximum micropyles, and eggs from virgin HAW female had significantly less micropyles compared to those from HAW female (Cross-B or Cross-C), but the number was significantly higher than those from HAM female (Cross-A or Cross-D). These results informed us that the number of micropyles in H. axyridis is plastic but maintaining a high-quantity that offers many benefits, which should contribute to its reproduction success.

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