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1.
Cell Death Dis ; 11(4): 213, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238802

RESUMO

Nasopharyngeal carcinoma (NPC) induced by latent infection with Epstein-Barr virus (EBV) remains the most common head and neck cancer in Southeast Asia, especially in the southern part of China. It is well known that persistent expression of two EBV latent membrane proteins (LMP1/LMP2A) plays a key role in nasopharyngeal carcinogenesis. Therefore, the therapeutic approach of targeting the LMP1/LMP2A protein and subsequently blocking the LMP1/LMP2A-mediated signalling pathway has been considered for treating patients with NPC. Recently, affibody molecules, a new class of small (~6.5 kDa) affinity proteins, have been confirmed to be powerful generalisable tools for developing imaging or therapeutic agents by targeting specific molecules. In this study, three EBV LMP2A N-terminal domain-binding affibody molecules (ZLMP2A-N85, ZLMP2A-N110 and ZLMP2A-N252) were identified by screening a phage-displayed peptide library, and their high affinity and specificity for the EBV LMP2A N-terminal domain were confirmed by surface plasmon resonance (SPR), indirect immunofluorescence, co-immunoprecipitation and near-infrared small animal fluorescence imaging in vitro and in vivo. Moreover, affibody molecules targeting the EBV LMP2A N-terminal domain significantly reduced the viability of the EBV-positive cell lines C666-1, CNE-2Z and B95-8. Further investigations showed that affibody ZLMP2A-N110 could inhibit the phosphorylation of AKT, GSK-3ß and ß-catenin signalling proteins, leading to suppression of ß-catenin nuclear translocation and subsequent inhibition of c-Myc oncogene expression, which may be responsible for the reduced viability of NPC-derived cell lines. In conclusion, our findings provide a strong evidence that three novel EBV LMP2A N-terminal domain-binding affibody molecules have great potential for utilisation and development as agents for both molecular imaging and targeted therapy of EBV-related NPC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32248097

RESUMO

In this paper, we propose an end-to-end deep learning architecture that generates 3D triangular meshes from single color images. Limited by the nature of the prevalent deep learning techniques, the majority of previous works usually represent 3D shapes in 3D volumes or point clouds. However, it is non-trivial to convert them to compact and ready-to-use mesh models. Unlike the existing methods, our network represents 3D shapes in meshes, which are essentially graphs and well suited for graph-based convolutional neural network. Leveraging on perceptual features extracted from the input image, our network produces correct geometry by progressively deforming an ellipsoid. To make the whole deformation procedure stable, we adopt a coarse-to-fine strategy, and define various mesh/surface related losses to capture properties of different levels; this guarantees visually appealing and physically accurate 3D geometry. In addition to producing accurate 3D shape on the 3D ShapeNet dataset, our model by nature can be adapted to objects in specific domains, e.g. human face, and easily extended to learn per-vertex properties, e.g. color. Extensive experiments show that our method not only qualitatively produces mesh model with better details, but also achieves higher 3D shape estimation accuracy compared to the state-of-the-art.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32328467

RESUMO

Objective: Pathogen infection plays a role in the development and progression of systemic lupus erythematosus (SLE). Previous studies showed that peripheral blood mononuclear cells (PBMCs) harbor many viral communities. However, little is known about the viral components and the expression profiles of SLE-associated virome. We aimed to identify viral taxonomic markers of SLE that might be used in the detection of disease or in predicting its outcome. Methods: Non-human sequence data from high-throughput transcriptome sequencing of PBMC samples from 10 SLE patients and 10 healthy individuals were used for taxonomic alignment against an integrated virome reference genome database. Based on abundance profiles of SLE-associated virome species, genera, or host, Random Forests model was used to identify the viruses associated with SLE diagnostic markers. Spearman's correlation and functional clustering was used to analyze the interaction of candidate virome dysbiosis and SLE-associated differentially expressed genes. Results: A total of 419 viruses (38 human associated viruses, 350 phage, and 31 other viruses) was detected and the diversity of the PBMC virome was significantly increased in patients with SLE compared to the healthy controls (HCs). Viral taxa discriminated the cases from the controls, with an area under the receiver operating characteristic curve of 0.883, 0.695, and 0.540 for species, genus, and host, respectively. Clinical subgroup analysis showed that candidate PBMC viral markers were associated with stable- and active-stage SLE. Functional analyses showed that virome dysbiosis was mainly relevant to cellular and metabolic processes. Conclusion: We identified virome signatures associated with SLE, which might help develop tools to identify SLE patients or predict the disease stage.

4.
Appl Microbiol Biotechnol ; 104(10): 4417-4433, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32215704

RESUMO

Here, we used codon usage technology to generate two codon-modified human papillomavirus (HPV)16 E7 genes and, together with wild-type E7, to construct three HPV16 E7 gene plasmids: Wt-E7, HB1-E7, and HB2-E7. The three HPV 16 E7 plasmids were used to investigate how HPV16 E7 protein was expressed in different cells and how this oncoprotein deregulated cellular and molecular events in human keratinocytes to induce carcinogenesis. We discovered that codon usage of HPV16 E7 gene played a key role in determining expression of E7 oncoprotein in all tested cells. HPV16 E7 inhibited significantly expression of pRb to impair keratinocyte differentiation and disrupted development of skin epidermis in mice. HPV16 E7 increased substantially the number of G0/G1 cells associated with upregulation of cyclin D2 and downregulation of cyclin B1 in keratinocytes. HPV16 E7 not only inhibited expression of involucrin and α-spectrin but also disrupted the organization of involucrin filaments and spectrin cytoskeleton. Furthermore, HPV16 E7 inhibited expression of ß-adducin, destroyed its cytoskeletal structure and induced phosphorylation of ß-adducin(Ser662) in keratinocytes. Importantly, HPV16 E7 induced carcinogenesis in mice associated with expression of phosphorylated ß-adducin(Ser662) and its nucleus-translocation. In conclusion, we provided evidence that HPV16 E7 oncoprotein inhibited keratinocyte differentiation in vitro and in vivo leading to carcinogenesis through cell cycle arrest and disruption of pRb/involucrin/spectrin/adducin cascade.

5.
Curr Med Chem ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32003657

RESUMO

BACKGROUND: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. METHODS: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. RESULTS: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. CONCLUSION: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body's immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

6.
Biosci Rep ; 40(2)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32016349

RESUMO

The present study investigated the role of abnormally expressed mRNA and long noncoding RNA (lncRNA) in the development of colorectal cancer (CRC). We used lncRNA sequencing to analyze the transcriptome (mRNA and lncRNA) of five pairs of CRC tissues and adjacent normal tissues. The total expression of mRNAs and lncRNAs in each sample was determined using the R package and the gene expression was calculated using normalized FPKM. The structural features and expression of all detected lncRNAs were compared with those of mRNAs. Differentially expressed mRNAs were selected to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The functional analysis of differentially expressed lncRNAs was performed by analyzing the GO and KEGG enrichment of predicted cis-regulated target genes. A total of 18.2 × 108 reads were obtained by sequencing, in which the clean reads reached ≥ 94.67%, with a total of 245.2 G bases. The number of mRNAs and lncRNAs differentially expressed in CRC tissues and normal tissues were 113 and 6, respectively. Further predictive analysis of target genes of lncRNAs revealed that six lncRNA genes had potential cis-regulatory effects on 13 differentially expressed mRNA genes and co-expressed with 53 mRNAs. Up-regulated CTD-2256P15.4 and RP11-229P13.23 were the most important lncRNAs in these CRC tissues and involved in cell proliferation and pathway in cancer. In conclusion, our study provides evidence regarding the mRNA and lncRNA transcription in CRC tissues, as well as new insights into the lncRNAs and mRNAs involved in the development of CRC.

7.
J Cancer Res Clin Oncol ; 146(3): 555-568, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32025866

RESUMO

PURPOSE: We previously found that human cytomegalovirus (HCMV) infection is associated with gastric cancer (GC) development. UL111A plays a role during HCMV productive or latent infection. However, UL111A expression profiles in GC tissues and their relationship with this disease are unknown. METHODS: PCR and nested RT-PCR were performed to verify UL111A expression in 71 GC tissues and its transcripts in 16 UL111A-positive GC samples. UL111A expression levels in GC patients were evaluated by immunohistochemistry on a tissue microarray for 620 GC patients. The correlations among UL111A expression levels, clinicopathological characteristics, and prognosis were analyzed. Further, the effects of overexpression of latency-associated viral interleukin-10 (LAcmvIL-10) and cmvIL-10 on GC cell proliferation, colony formation, migration, and invasion were assessed. RESULTS: The UL111A detection rate in GC tissues was 32.4% (23/71) and that of its mRNA expression was 68.75% (11/16). High expression of UL111A was also related to better overall and disease-free survival in GC patients. GC patients with TNM II/III stage expressing higher UL111A levels might benefit from adjuvant chemotherapy (ACT) after surgery. Moreover, high UL111A expression was also associated with increased CD4+ , CD8+ T-lymphocyte and Foxp3+ T-cell infiltration. In vitro assays further demonstrated that LAcmvIL-10 and cmvIL-10 overexpression inhibits GC cell line proliferation, colony formation, migration, and invasion. CONCLUSIONS: High UL111A expression changes the number of infiltrating T cells and is associated with favorable survival. Therefore, UL111A could be used as an independent prognostic biomarker and might be a potential therapeutic target for GC.


Assuntos
Carcinogênese , Infecções por Citomegalovirus/complicações , Neoplasias Gástricas/virologia , Proteínas do Envelope Viral/biossíntese , Adulto , Citomegalovirus , Infecções por Citomegalovirus/metabolismo , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Linfócitos T/imunologia
8.
PLoS Pathog ; 16(1): e1008223, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905218

RESUMO

Epstein-Barr virus (EBV) infection is closely linked to several human malignancies including endemic Burkitt's lymphoma, Hodgkin's lymphoma and nasopharyngeal carcinomas (NPC). Latent membrane protein 2 (LMP-2) of EBV plays a pivotal role in pathogenesis of EBV-related tumors and thus, is a potential target for diagnosis and targeted therapy of EBV LMP-2+ malignant cancers. Affibody molecules are developing as imaging probes and tumor-targeted delivery of small molecules. In this study, four EBV LMP-2-binding affibodies (ZEBV LMP-212, ZEBV LMP-2132, ZEBV LMP-2137, and ZEBV LMP-2142) were identified by screening a phage-displayed LMP-2 peptide library for molecular imaging and targeted therapy in EBV xenograft mice model. ZEBV LMP-2 affibody has high binding affinity for EBV LMP-2 and accumulates in mouse tumor derived from EBV LMP-2+ xenografts for 24 h after intravenous (IV) injection. Subsequent fusion of Pseudomonas exotoxin PE38KDEL to the ZEBV LMP-2 142 affibody led to production of Z142X affitoxin. This fused Z142X affitoxin exhibits high cytotoxicity specific for EBV+ cells in vitro and significant antitumor effect in mice bearing EBV+ tumor xenografts by IV injection. The data provide the proof of principle that EBV LMP-2-speicifc affibody molecules are useful for molecular imaging diagnosis and have potentials for targeted therapy of LMP-2-expressing EBV malignancies.


Assuntos
Herpesvirus Humano 4 , Imunotoxinas/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Proteínas da Matriz Viral/metabolismo , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Imunotoxinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Imagem Molecular , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/virologia , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/terapia , Biblioteca de Peptídeos , Ligação Proteica , Proteínas da Matriz Viral/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Mol Carcinog ; 59(4): 339-352, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31989722

RESUMO

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Movimento Celular/genética , Proteínas do Citoesqueleto/genética , Citoesqueleto/metabolismo , Neoplasias Gástricas/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Interferência de RNA , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
10.
IEEE Trans Pattern Anal Mach Intell ; 42(2): 371-385, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31329547

RESUMO

Person re-identification (re-id) aims to match people across non-overlapping camera views in a public space. This is a challenging problem because the people captured in surveillance videos often wear similar clothing. Consequently, the differences in their appearance are typically subtle and only detectable at particular locations and scales. In this paper, we propose a deep re-id network (MuDeep) that is composed of two novel types of layers - a multi-scale deep learning layer, and a leader-based attention learning layer. Specifically, the former learns deep discriminative feature representations at different scales, while the latter utilizes the information from multiple scales to lead and determine the optimal weightings for each scale. The importance of different spatial locations for extracting discriminative features is learned explicitly via our leader-based attention learning layer. Extensive experiments are carried out to demonstrate that the proposed MuDeep outperforms the state-of-the-art on a number of benchmarks and has a better generalization ability under a domain generalization setting.

11.
IEEE Trans Pattern Anal Mach Intell ; 42(2): 398-412, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31199252

RESUMO

In this paper, we propose Deeply Supervised Object Detectors (DSOD), an object detection framework that can be trained from scratch. Recent advances in object detection heavily depend on the off-the-shelf models pre-trained on large-scale classification datasets like ImageNet and OpenImage. However, one problem is that adopting pre-trained models from classification to detection task may incur learning bias due to the different objective function and diverse distributions of object categories. Techniques like fine-tuning on detection task could alleviate this issue to some extent but are still not fundamental. Furthermore, transferring these pre-trained models across discrepant domains will be more difficult (e.g., from RGB to depth images). Thus, a better solution to handle these critical problems is to train object detectors from scratch, which motivates our proposed method. Previous efforts on this direction mainly failed by reasons of the limited training data and naive backbone network structures for object detection. In DSOD, we contribute a set of design principles for learning object detectors from scratch. One of the key principles is the deep supervision, enabled by layer-wise dense connections in both backbone networks and prediction layers, plays a critical role in learning good detectors from scratch. After involving several other principles, we build our DSOD based on the single-shot detection framework (SSD). We evaluate our method on PASCAL VOC 2007, 2012 and COCO datasets. DSOD achieves consistently better results than the state-of-the-art methods with much more compact models. Specifically, DSOD outperforms baseline method SSD on all three benchmarks, while requiring only 1/2 parameters. We also observe that DSOD can achieve comparable/slightly better results than Mask RCNN [1] + FPN [2] (under similar input size) with only 1/3 parameters, using no extra data or pre-trained models.

12.
Front Immunol ; 10: 2368, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681276

RESUMO

Tumor-infiltrating immune cells (TIICs) play essential roles in cancer development and progression. However, the association of TIICs with prognosis in colorectal cancer (CRC) patients remains elusive. Infiltration of TIICs was assessed using ssGSEA and CIBERSORT tools. The association of TIICs with prognosis was analyzed in 1,802 CRC data downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/) databases. Three populations of TIICs, including CD66b+ tumor-associated neutrophils (TANs), FoxP3+ Tregs, and CD163+ tumor-associated macrophages (TAMs) were selected for immunohistochemistry (IHC) validation analysis in 1,008 CRC biopsies, and their influence on clinical features and prognosis of CRC patients was analyzed. Prognostic models were constructed based on the training cohort (359 patients). The models were further tested and verified in testing (249 patients) and validation cohorts (400 patients). Based on ssGSEA and CIBERSORT analysis, the correlation between TIICs and CRC prognosis was inconsistent in different datasets. Moreover, the results with disease-free survival (DFS) and overall survival (OS) data in the same dataset also differed. The high abundance of TIICs found by ssGSEA or CIBERSORT tools can be used for prognostic evaluation effectively. IHC results showed that TANs, Tregs, TAMs were significantly correlated with prognosis in CRC patients and were independent prognostic factors (P DFS ≤ 0.001; P OS ≤ 0.023). The prognostic predictive models were constructed based on the numbers of TANs, Tregs, TAMs (C-indexDFS&OS = 0.86; AICDFS = 448.43; AICOS = 184.30) and they were more reliable than traditional indicators for evaluating prognosis in CRC patients. Besides, TIICs may affect the response to chemotherapy. In conclusion, TIICs were correlated with clinical features and prognosis in patients with CRC and thus can be used as markers.

13.
Front Immunol ; 10: 2281, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608065

RESUMO

Background: Accumulating evidence suggests that differentially expressed non-coding circular RNAs (circRNAs) play critical roles in the progress of autoimmune diseases. However, the role of circRNAs in systemic lupus erythematosus (SLE) remains unclear. Methods: We initially used next-generation sequencing (NGS) to comprehensively analyze circRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from 10 SLE patients, stratified by their disease activity characteristics (stable or active SLE), and 10 healthy controls (HCs). Candidate circRNAs identified were first validated by quantitative reverse-transcription (qRT)-PCR in PBMC samples from a training-phase cohort of five SLE patients and five HCs. The significantly dysregulated circRNAs were then confirmed by qRT-PCR in a validation cohort of 23 SLE patients and 21 HCs, and in an external validation cohort with 64 SLE patients, 58 HCs, and 50 patients with rheumatoid arthritis (RA). In addition, we conducted bioinformatics analysis and western blotting investigating the relationships between the candidate circRNAs and SLE progression. Results: Multilayer integrative analysis of circRNA regulation showed that 84 circRNAs were upregulated and 30 were downregulated in patients with SLE compared with HCs. We then analyzed the intersection of these differentially expressed circRNAs in an SLE-stable cohort, an SLE-active cohort, and HCs. This enabled us to narrow down dysregulated circRNAs to 15 upregulated circRNAs. Only hsa_circ_0000479 was significantly upregulated in PBMCs of patients with SLE compared with HCs (P < 0.05). Furthermore, the diagnostic potential of hsa_circ_0000479 expression to distinguish SLE patients from HCs and RA patients was also significantly increased in the validation-phase and external-validation-phase cohorts (P < 0.05). When distinguishing SLE patients from HCs, the diagnostic specificities of hsa_circ_0000479 were 0.619 and 1.0 in two validation cohorts, respectively (AUCs = 0.731 and 0.730, respectively). It was also significantly increased in either stable SLE patients or active SLE patients compared with HCs in these two cohorts (P < 0.05). We also used bioinformatics analysis to show that hsa_circ_0000479 regulates SLE progression by modulating metabolic pathways and the Wnt signaling pathway. Western blotting revealed that the expression of Wnt-16 protein was significantly decreased in SLE. Conclusion: Our results suggest that hsa_circ_0000479 has potential as a novel biomarker for the diagnosis of SLE.

14.
Oncol Lett ; 18(5): 5499-5507, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612058

RESUMO

The biological characteristics and clinical outcomes of gastric cancer (GC) are largely dependent on the histopathological type and degree of differentiation. The identification of the molecular mechanisms underlying the histological grade of GC may provide information about tumorigenesis and tumor progression, and may subsequently be used to develop novel therapeutic agents. The present study obtained the RNA sequencing data and clinical characteristics of patients with GC from The Cancer Genome Atlas. A total of 1,400 differentially expressed genes (DEGs) were screened between two histological grades. Weighted gene co-expression network analysis (WGCNA) was subsequently used to identify nine co-expressed gene modules, and the black module was found to be the most significant for prognosis prediction of tumor. Additionally, the black module was associated with overall survival time, death event, N stage and tumor-node-metastasis (TNM) stage. Functional enrichment analysis revealed that the biological processes of the genes in the black module included 'Wnt signaling pathway' and 'structural molecule activity'. Additionally, 10 network hub genes that were significantly associated with the progression of GC were identified from the black module, and the significance of each hub gene was determined across different TNM stages. Kaplan-Meier survival curves revealed that keratin 40 and glycine decarboxylase were significantly associated with patient prognosis (P<0.05), suggesting that these genes may serve as potential progression and prognosis biomarkers in GC. The present study identified molecular markers that correlated with histological grade in GC. Therefore, the results obtained in the present study may have important clinical implications on treatment selection, risk stratification and prognosis prediction in patients with GC.

15.
Viral Immunol ; 32(7): 308-317, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381497

RESUMO

The human papillomavirus (HPV) vaccine has not been widely used in developing countries because of its high cost and multiple subtype restrictions. The present study aimed to develop an economical, convenient, and effective vaccine to produce neutralizing antibodies. Using late protein 1 (L1) from the HPV16 subtype as the target antigen (HPV16L1) and Pichia pastoris as the antigen release system, integrated P. pastoris expressing HPV16L1 (named yeast-HPV16L1) was prepared and vaccinated directly into mice by subcutaneous multipoint injection. After immunization was performed thrice, high titers (greater than 1:40,960) of specific anti-HPV16L1 antibodies were obtained in immune serum and were observed to continuously rise over time. The indirect hemagglutination test and indirect hemagglutination inhibition test were used to detect neutralizing antibody activity in vitro, and the results demonstrated the hemagglutination ability of the immune serum and the reduction in or loss of the hemagglutination ability if preneutralized antigen was added to the immune serum. The protection conferred by immune serum to tumor-bearing mice at the early stages was confirmed, but the neutralizing activity disappeared when the tumor reached a size of 1 mm3. The neutralization activity of the immune serum was confirmed both in vitro and in vivo.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31199251

RESUMO

Despite significant progress in object categorization, in recent years, a number of important challenges remain; mainly, ability to learn from limited labeled data and ability to recognize object classes within large, potentially open, set of labels. Zero-shot learning is one way of addressing these challenges, but it has only been shown to work with limited sized class vocabularies and typically requires separation between supervised and unsupervised classes, allowing former to inform the latter but not vice versa. We propose the notion of vocabulary-informed learning to alleviate the above mentioned challenges and address problems of supervised, zero-shot, generalized zero-shot and open set recognition using a unified framework. Specifically, we propose a weighted maximum margin framework for semantic manifold-based recognition that incorporates distance constraints from (both supervised and unsupervised) vocabulary atoms. Distance constraints ensure that labeled samples are projected closer to their correct prototypes, in the embedding space, than to others. We illustrate that resulting model shows improvements in supervised, zero-shot, generalized zero-shot, and large open set recognition, with up to 310K class vocabulary on AwA and ImageNet datasets.

17.
BMC Infect Dis ; 19(1): 512, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182037

RESUMO

BACKGROUND: The methods routinely used to detect trichomonads in the lungs are not sensitive enough, and an effective method is urgently needed. METHOD: Primers were first designed to match the conserved area of the 18S rRNA gene of trichomonads. Then, nested PCR was carried out to detect trichomonads in bronchoalveolar lavage fluid (BALF). Finally, all positive specimens were subjected to DNA sequencing and phylogenetic analysis. RESULTS: Among 115 bronchoalveolar lavage fluid samples, ten samples tested positive in nested PCR (10/115), while no samples were positive in wet mount microscopy (0/115) (P < 0.01). Among the ten positive specimens, two were identified as Tetratrichomonas spp. and the other eight as Trichomonas tenax in phylogenetic analysis. CONCLUSIONS: Nested PCR is an effective way to detect trichomonads in bronchoalveolar lavage fluid.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Reação em Cadeia da Polimerase/métodos , Trichomonas/genética , DNA/química , DNA/metabolismo , Humanos , Filogenia , Análise de Sequência de DNA , Trichomonas/classificação , Trichomonas/isolamento & purificação , Tricomoníase/diagnóstico , Tricomoníase/microbiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-30969924

RESUMO

The ability to quickly recognize and learn new visual concepts from limited samples enables humans to quickly adapt to new tasks and environments. This ability is enabled by semantic association of novel concepts with those that have already been learned and stored in memory. Computers can start to ascertain similar abilities by utilizing a semantic concept space. A concept space is a high-dimensional semantic space in which similar abstract concepts appear close and dissimilar ones far apart. In this paper, we propose a novel approach to one-shot learning that builds on this core idea. Our approach learns to map a novel sample instance to a concept, relates that concept to the existing ones in the concept space and, using these relationships, generates new instances, by interpolating among the concepts, to help learning. Instead of synthesizing new image instance, we propose to directly synthesize instance features by leveraging semantics using a novel auto-encoder network we call dual TriNet. The encoder part of the TriNet learns to map multi-layer visual features from CNN to a semantic vector. In semantic space, we search for related concepts, which are then projected back into the image feature spaces by the decoder portion of the TriNet. Two strategies in the semantic space are explored. Notably, this seemingly simple strategy results in complex augmented feature distributions in the image feature space, leading to substantially better performance. The codes and models are released in the github: https://github.com/tankche1/ Semantic-Feature-Augmentation-in-Few-shot-Learning.

19.
Cancer Manag Res ; 11: 25-36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30588108

RESUMO

Background and aim: Periostin is a protein from the Fascilin family. It is commonly present in normal tissues and is responsible for cell adhesion. Evidence has emerged showing that changes in periostin expression play an important role in tumor initiation, development, and progression. This study aims to investigate the effect of periostin in gastric cancer (GC) patients who underwent gastrectomy. Seven hundred and forty-seven GC patients who underwent gastrectomy between December 2006 and July 2011 were included in this study. Methods: Seven hundred and forty-seven cancer tissues and 70 paired adjacent normal tissues were collected. Periostin expression was evaluated by immunohistochemistry. The Gene Expression Omnibus database was used to study the association between the mRNA level and patient's overall survival. The tumor microenvironment was also studied. Results: Periostin expression in stroma was downregulated in tumor tissues but it was upregulated in the epithelial cells. After dividing the tissues according to the Lauren Classification, we found that periostin expression in stroma and epithelial cells was higher in intestinal type than in diffuse type (P<0.001 and P=0.010, respectively). Periostin was an independent predictor of lymph node (LN) metastasis in GC patients. The study of CD163(+) tumor-associated macrophages (TAMs) revealed that in diffuse type GC, periostin expression was associated with CD163(+) TAMs. Conclusion: We found that the periostin expression can predict LN metastasis in patients undergoing curative gastrectomy. Intestinal type GC patients with high periostin level had both a favorable survival and lesser LN metastasis.

20.
J Transl Med ; 16(1): 370, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577810

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with various clinical manifestations. MicroRNAs (miRNAs) and immunometabolism are recognized as key elements in SLE pathogenesis; however, the relationship between miRNAs in peripheral blood mononuclear cells (PBMCs) and metabolism in SLE remains unclear. METHODS: We detected PBMC miRNA and mRNA profiles from 3 pooled SLE patients and 3 healthy controls (HCs) using next-generation sequencing, predicted miRNA targets in dysregulated mRNAs, predicted functions and interactions of differentially expressed genes using bioinformatics analysis, validated candidate miRNAs using qRT-PCR, and investigated the association between the expression of candidate miRNAs and SLE clinical characteristics. Moreover, we validated the direct and transcriptional regulatory effect of NovelmiRNA-25 on adenosine monophosphate deaminase 2 (AMPD2) using a dual-luciferase reporter assay and western blot and confirmed AMPD2 mRNA and protein expression in PBMCs using qRT-PCR and western blot, respectively. RESULTS: Multilayer integrative analysis of microRNA and mRNA regulation showed that 10 miRNAs were down-regulated and 19 miRNAs were up-regulated in SLE patient PBMCs compared with HCs. Bioinformatics analysis of regulatory networks between miRNAs and mRNAs showed that 19 miRNAs were related to metabolic processes. Two candidate miRNAs, NovelmiRNA-25 and miR-1273h-5p, which were significantly increased in the PBMCs of SLE patients (P < 0.05), represented diagnostic biomarkers with sensitivities of 94.74% and 89.47%, respectively (area under the curve = 0.574 and 0.788, respectively). NovelmiRNA-25 expression in PBMCs was associated with disease activity in SLE patients, in both active and stable groups (P < 0.05). NovelmiRNA-25 overexpression downregulated AMPD2 expression in HEK293T cells through direct targeting of the AMPD2 3'UTR (P < 0.01), while inhibition of NovelmiRNA-25 activity led to increased AMPD2 expression (P < 0.01). NovelmiRNA-25 overexpression also downregulated AMPD2 protein expression in HEK293T cells; AMPD2 protein expression in SLE patient PBMCs was decreased. Our results show that differentially expressed miRNAs play an important role in SLE. CONCLUSIONS: Our data demonstrate a novel mechanism in SLE development that involves the targeting of AMPD2 expression by NovelmiRNA-25. miRNAs may serve as novel biomarkers for the diagnosis and evaluation of disease activity of SLE and represent potential therapeutic targets for this disease.


Assuntos
AMP Desaminase/sangue , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/metabolismo , Sequência de Bases , Biomarcadores/sangue , Estudos de Casos e Controles , Ontologia Genética , Redes Reguladoras de Genes , Células HEK293 , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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