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1.
Sheng Wu Gong Cheng Xue Bao ; 40(5): 1548-1558, 2024 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-38783815

RESUMO

In order to generate monoclonal antibodies against the akabane virus (AKAV) N protein, this study employed a prokaryotic expression system to express the AKAV N protein. Following purification, BALB/c mice were immunized, and their splenocytes were fused with mouse myeloma cells (SP2/0) to produce hybridoma cells. The indirect ELISA method was used to screen for positive hybridoma cells. Two specific hybridoma cell lines targeting AKAV N protein, designated as 2C9 and 5E9, were isolated after three rounds of subcloning. Further characterization was conducted through ELISA, Western blotting, and indirect immunofluorescence assay (IFA). The results confirmed that the monoclonal antibodies specifically target AKAV N protein, exhibiting strong reactivity in IFA. Subtype analysis identified the heavy chain of the 2C9 mAb's as IgG2b and its light chain as κ-type; the 5E9 mAb's heavy chain was determined to be IgG1, with a κ-type light chain. Their ELISA titers reached 1:4 096 000. This study successfully developed two monoclonal antibodies targeting AKAV N protein, which lays a crucial foundation for advancing diagnostic methods for akabane disease prevention and control, as well as for studying the function of the AKAV N protein.


Assuntos
Anticorpos Monoclonais , Animais , Feminino , Camundongos , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Escherichia coli/genética , Escherichia coli/metabolismo , Hibridomas/imunologia , Hibridomas/metabolismo , Camundongos Endogâmicos BALB C , Proteínas do Nucleocapsídeo/imunologia , Proteínas do Nucleocapsídeo/genética , Orthobunyavirus/imunologia , Orthobunyavirus/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia
2.
Med Oncol ; 40(11): 322, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37801170

RESUMO

The research of nanomaterials for bio-imaging and theranostic are very active nowadays with unprecedented advantages in nanomedicine. Homologous targeting and bio-imaging greatly improve the ability of targeted drug delivery and enhance active targeting and treatment ability of nanomedicine for the tumor. In this work, lycorine hydrochloride (LH) and magnetic iron oxide nanoparticles coated with a colorectal cancer (CRC) cell membrane (LH-Fe3O4@M) were prepared, for homologous targeting, magnetic resonance imaging (MRI), and chemotherapy. Results showed that the LH-Fe3O4@M and Fe3O4@M intensity at HT29 tumor was significantly higher than that Fe3O4@PEG, proving the superior selectivity of cancer cell membrane-camouflaged nanomedicine for homologous tumors and the MRI effect of darkening contrast enhancement were remarkable at HT29 tumor. The LH-Fe3O4@M exhibited excellent chemotherapy effect in CRC models as well as LH alone and achieved a high tumor ablation rate but no damage to normal tissues and cells. Therefore, our biomimetic system achieved a homologous targeting, bio-imaging, and efficient therapeutic effect of CRC.


Assuntos
Neoplasias Colorretais , Nanopartículas de Magnetita , Nanopartículas , Humanos , Linhagem Celular Tumoral , Óxidos , Biomimética , Imageamento por Ressonância Magnética/métodos , Membrana Celular , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico
3.
Accid Anal Prev ; 191: 107224, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37506406

RESUMO

Incident investigation reports provide information on defects related to the system safety and indications for improvements. Currently, the analysis of these reports relies heavily on expert' experience. The foreseeable work-load and lack of understanding about the importance of near misses have created a situation where severe accidents are rigorously investigated, and minor incidents are often omitted. Consequently, incident reports have not been fully analyzed to provide sufficient solutions. The aim of this research is to propose a framework that uses text mining and multilevel association rules to efficiently structure Chinese incident reports and identify important incident patterns, providing an analysis of trends, rectification strategies, and guidance for safety management. A case study of a construction company in China was conducted using two years of incident data dated 2018-2019, including accidents and near misses. To identify incident elements, a pattern extraction workflow involving TextRank, and domain pertinence was devised based on the linguistic and writing styles of Chinese reports. A concept hierarchy was applied to determine the taxonomic relationships within the risk factors. Multilevel association rule mining was adopted and proven to deliver more comprehensive pattern indications. Comparative and cross-analysis of patterns in different time periods revealed the severity and temporal features of incidents as well as the effectiveness of preventive and precautionary measures. The results also highlight the importance of learning from near miss events. Decision makers can formulate countermeasures and management policies based on these results to improve safety performance.


Assuntos
Acidentes de Trânsito , Gestão de Riscos , Humanos , Gestão da Segurança , Mineração de Dados , China/epidemiologia
4.
Food Chem ; 416: 135732, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36878116

RESUMO

This study prepared a series of polyelectrolyte complexes (PECs) composed of heated whey protein isolate (HWPI) and different polysaccharides for simultaneous encapsulation and copigmentation of anthocyanins (ATC) and their ultimate stabilization. Four polysaccharides including chondroitin sulfate, dextran sulfate, gum arabic, and pectin were chosen due to their abilities to simultaneously complex with HWPI and copigment ATC. At pH 4.0, these PECs were formed with an average particle size of 120-360 nm, the ATC encapsulation efficiency of 62-80%, and the production yield of 47-68%, depending on the type of polysaccharides. The PECs effectively inhibited the degradation of ATC during storage and when exposed to neutral pH, ascorbic acid, and heat. Pectin had the best protection, followed by gum arabic, chondroitin sulfate, and dextran sulfate. The stabilizing effects were associated with the hydrogen bonding, hydrophobic and electrostatic interactions between HWPI and polysaccharides, conferring dense internal network and hydrophobic microenvironment in the complexes.


Assuntos
Antocianinas , Sulfatos de Condroitina , Antocianinas/química , Polieletrólitos/química , Sulfatos de Condroitina/química , Goma Arábica/química , Sulfato de Dextrana , Polissacarídeos/química , Pectinas , Concentração de Íons de Hidrogênio
5.
Int J Mol Sci ; 24(3)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36769013

RESUMO

Zwitterionic materials are widely applied in the biomedical field due to their excellent antimicrobial, non-cytotoxicity, and antifouling properties but have never been applied in bone tissue engineering. In this study, we synthesized a novel zwitterionic hydrogel incorporated with graphene oxide (GO) using maleic anhydride (MA) as a cross-linking agent by grafted L-cysteine (L-Cys) as the zwitterionic material on maleilated chitosan via click chemistry. The composition and each reaction procedure of the novel zwitterionic hydrogel were characterized via X-ray diffraction (XRD) and Fourier transformed infrared spectroscopy (FT-IR), while the morphology was imaged by scanning electron microscope (SEM). In vitro cell studies, CCK-8 and live/dead assay, alkaline phosphatase activity, W-B, and qRT-CR tests showed zwitterionic hydrogel incorporated with GO remarkably enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs); it is dose-dependent, and 2 mg/mL GO is the optimum concentration. In vivo tests also indicated the same results. Hence, these results suggested the novel zwitterionic hydrogel exhibited porous characteristics similar to natural bone tissue. In conclusion, the zwitterionic scaffold has highly biocompatible and mechanical properties. When GO was incorporated in this zwitterionic scaffold, the zwitterionic scaffold slows down the release rate and reduces the cytotoxicity of GO. Zwitterions and GO synergistically promote the proliferation and osteogenic differentiation of rBMSCs in vivo and in vitro. The optimal concentration is 2 mg/mL GO.


Assuntos
Grafite , Células-Tronco Mesenquimais , Osteogênese , Engenharia Tecidual/métodos , Hidrogéis/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Osso e Ossos , Grafite/farmacologia , Grafite/química , Diferenciação Celular , Alicerces Teciduais
6.
Front Immunol ; 14: 1070679, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817446

RESUMO

Introduction: In recent years, numerous studies have confirmed that chronic stress is closely related to the development of cancer. Our previous research showed that high levels of stress hormones secreted in the body during chronic stress could inhibit the cancer-killing activity of granulocytes, which could further promote the development of cancer. Therefore, reversing the immunosuppressive effect of stress hormones on granulocytes is an urgent problem in clinical cancer treatment. Here, we selected noradrenaline (NA) as a representative stress hormone. Methods and results: After screening many traditional Chinese herbal medicine active ingredients, a promising compound, ginsenoside Rg1, attracted our attention. We verified the immunoprotective effect of ginsenoside Rg1 on granulocytes in vitro and ex vivo, and attempted to understand its potential immunoprotective mechanism. We confirmed the immunoprotective effect of ginsenoside Rg1 on granulocytes using cell and animal experiments. Cell counting kit-8 (CCK-8) and ex vivo experiments were performed to investigate the immunoprotective effects of ginsenoside Rg1 on the anti-cancer function of granulocytes inhibited by NA. Transcriptome sequencing analysis and qRT-PCR showed that NA elevated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN in granulocytes, thereby reducing the anti-cancer function of granulocytes. In contrast, ginsenoside Rg1 downregulated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN, and upregulated the mRNA expression of LAMC2, DSC2, KRT6A, and FOSB, thereby enhancing the anti-cancer function of granulocytes inhibited by NA. Transwell cell migration experiments were performed to verify that ginsenoside Rg1 significantly enhanced the migration capability of granulocytes inhibited by NA. Tumor-bearing model mice were used to verify the significant immunoprotective effects in vivo. Finally, CCK-8 and hematoxylin and eosin staining experiments indicated that ginsenoside Rg1 exhibited high biosafety in vitro and in vivo. Discussion: In future clinical treatments, ginsenoside Rg1 may be used as an adjuvant agent for cancer treatment to alleviate chronic stress-induced adverse events in cancer patients.


Assuntos
Ginsenosídeos , Neoplasias , Camundongos , Animais , Metaloproteinase 1 da Matriz , Norepinefrina , Ginsenosídeos/farmacologia , Adjuvantes Imunológicos , Granulócitos/metabolismo , Neoplasias/tratamento farmacológico , RNA Mensageiro , Desmocolinas
7.
Cells ; 12(2)2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36672240

RESUMO

The electrical characteristic of cancer cells is neglected among tumor biomarkers. The development of nanoprobes with opposing charges for monitoring the unique electrophysiological characteristics of cancer cells. Micro-nano size adsorption binding necessitates consideration of the nanoprobe's specific surface area. On the basis of the electrophysiological characteristics of circulating tumor cells (CTCs), clinical application and performance assessment are determined. To demonstrate that cancer cells have a unique pattern of electrophysiological patterns compared to normal cells, fluorescent nanoprobes with opposing charges were developed and fabricated. Graphene oxide (GO) was used to transform three-dimensional (3D) nanoprobes into two-dimensional (2D) nanoprobes. Compare 2D and 3D electrophysiological magnetic nanoprobes (MNP) in clinical samples and evaluate the adaptability and development of CTCs detection based on cell electrophysiology. Positively charged nanoprobes rapidly bind to negatively charged cancer cells based on electrostatic interactions. Compared to MNPs(+) without GO, the GO/MNPs(+) nanoprobe is more efficient and uses less material to trap cancer cells. CTCs can be distinguished from normal cells that are fully unaffected by nanoprobes by microscopic cytomorphological inspection, enabling the tracking of the number and pathological abnormalities of CTCs in the same patient at various chemotherapy phases to determine the efficacy of treatment. The platform for recognizing CTCs on the basis of electrophysiological characteristics compensates for the absence of epithelial biomarker capture and size difference capture in clinical performance. Under the influence of electrostatic attraction, the binding surface area continues to influence the targeting of cancer cells by nanoprobes. The specific recognition and detection of nanoprobes based on cell electrophysiological patterns has enormous potential in the clinical diagnosis and therapeutic monitoring of cancer.


Assuntos
Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais
8.
Adv Colloid Interface Sci ; 311: 102825, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36525841

RESUMO

Sonochemistry shows remarkable potential in the synthesis or modification of new micro/nanomaterials, particularly the cross-linked emulsions for drug delivery. However, the trend of utilizing sonochemical emulsions for delivery of food-derived bioactive compounds has been just started. The extension of sonochemistry as a tool for engineering bioactive delivery systems will make the approach more universal and greatly increase its applications in the food industry. This review summarizes different types of biopolymeric cross-linked emulsions (CLEs) synthesized via sonochemical approach, including CLEs, surface-modified CLEs, cross-linked high internal phase emulsions, and some novel systems templated on CLEs. Special emphasis is directed toward the cross-linking mechanisms of biopolymers at the oil-water interfaces under acoustic cavitation and the physicochemical principles underlying sonochemical fabrication. We also highlight the advantages and challenges associated with the delivery performance of each system for bioactive compounds. The potential in delivering bioactives using sonochemical emulsions has not been fully reached. There are still a number of issues that need to be overcome, including low cross-linking degree of biopolymers, degradation of bioactives in sonochemical process, and unclear biological fate of encapsulated bioactive compounds. This review may guide future trends in exploring efficient sonochemical strategies and multifunctional delivery systems for food applications.


Assuntos
Sistemas de Liberação de Medicamentos , Alimentos , Emulsões/química , Fenômenos Químicos , Biopolímeros/química
9.
Journal of Preventive Medicine ; (12): 943-947, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013262

RESUMO

Objective @#o evaluate the association between Crohn's disease (CD) and frailty using a Mendelian randomization (MR) approach, so as to provide the evidence for prevention and control strategies.@*Methods@#Genetic association data for CD were collected through the International Inflammatory Bowel Disease Genetics Consortium, with 20 883 samples and 12 276 506 single nucleotide polymorphism (SNP), and genetic association data for frailty were collected through a meta-analysis including 175 226 samples and 7 589 717 SNPs. A forward MR analysis was performed using the inverse-variance weighted (IVW) method with 37 CD-associated SNPs as instrumental variables, and frailty as the study outcome, and a reverse MR analysis was performed with 13 frailty-associated SNPs as instrumental variables and CD as the study outcome. The heterogeneity was assessed using the Cochran's Q test, and the horizontal pleiotropy was assessed using the MR-PRESSO global test and MR-Egger regression. In addition, the robustness of the results was verified with the leave-one-out. @*Results@#Forward MR analysis results showed that patients with genetically predicted CD had an increased risk of frailty index relative to those without CD (β=0.018, 95%CI: 0.011-0.026, P<0.05). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Reverse MR analysis showed no association between frailty index and the risk of CD (OR=0.740, 95%CI: 0.206-2.661, P>0.05). @*Conclusions@#Genetically predicted CD is associated with an increased risk of frailty. It is suggested that screening and prevention of frailty should be reinforced among CD patients.

10.
Gov Inf Q ; 39(1): 101646, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34642541

RESUMO

Based on the information-as-coping perspective, we provided a theoretical framework to understand how the quality of government information and citizens' partisanship impact citizens' wellbeing in terms of satisfaction with life and anxiety during COVID-19. With survey data from 705 respondents in Indonesia, we found that government information quality is of vital importance in helping citizens get ready to fight the pandemic, as well as lowering their anxiety. Our results show that higher information quality leads to a higher ability to respond quickly to the crisis, as well as a reduced level of information overload. While partisanship is a significant predictor of information overload, it had no significant impact on perceived quick response ability. Quick response ability and information overload, in turn, predict anxiety and citizen's satisfaction with life.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(6): 1858-1863, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34893123

RESUMO

OBJECTIVE: To investigate the effect of U2AF1 gene mutation to inflammatory cytokine in SKM-1 cell of human myelodysplastic syndromes (MDS), and whether the above effects were mediated by FOXO3a-Bim signaling pathway. METHODS: Wide-type U2AF1 and mutant U2AF1 (the serine residue 34 was replaced by phenylalanine, and named as S34F) recombinant expression plasmids were constructed. Lentiviruses were packaged and transfected into SKM-1 cells. The expression of FOXO3a was up-regulated by lentiviruses, and its transfection rate was investigated. The cell proliferation was detected by CCK-8 method. Flow cytometry was used to detect the apoptosis and cycle of the cells. The expression pro-inflammatory cytokine IL-1ß, IL-6, TNF-α and anti-inflammatory cytokine IL-4 were detected by qRT-PCR. FOXO3a, Bim, Bcl-2 and Bax protein expression levels were detected by Western blot. RESULTS: Compared with the control group, the cell apoptosis rate, pro-inflammatory cytokine IL-1ß and TNF-α transcription levels were significantly increased in the S34F group (P<0.05); cell cycle was blocked at the G2 phase; cell proliferation and the anti-inflammatory cytokine IL-4 transcription level were significantly decreased; the expression levels of FOXO3a, Bim and Bax protein were significantly increased (P<0.05); while the expression level of Bcl-2 protein was significantly decreased (P<0.05). The up-regulation of FOXO3a could significantly inhibited the proliferation and increased cell apoptosis of SKM-1 cells with U2AF1 S34F mutation; cell cycle was blocked at the S and G2 phases; the pro-inflammatory cytokine IL-1ß and TNF-α transcription levels were significantly decreased (P<0.05), and the transcription level of anti-inflammatory cytokine IL-4 showed no statistically significant as compared with control group (P>0.05). CONCLUSION: U2AF1 S34F mutation can regulate inflammatory phenotype in SKM-1 cells, which may be mediated through FOXO3a-Bim signaling pathway.


Assuntos
Citocinas , Transdução de Sinais , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Humanos , Mutação , Fator de Processamento U2AF
12.
Cell Death Dis ; 12(7): 655, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183647

RESUMO

Mutations in the U2 small nuclear RNA auxiliary factor 1 (U2AF1) gene are the common feature of a major subset in myelodysplastic syndromes (MDS). However, the genetic landscape and molecular pathogenesis of oncogenic U2AF1S34F mutation in MDS are not totally understood. We performed comprehensive analysis for prognostic significance of U2AF1 mutations in acute myeloid leukemia (AML) cohort based on The Cancer Genome Atlas (TCGA) database. Functional analysis of U2AF1S34F mutation was performed in vitro. Differentially expressed genes (DEGs) and significantly enriched pathways were identified by RNA sequencing. The forkhead box protein O3a (FOXO3a) was investigated to mediate the function of U2AF1S34F mutation in cell models using lentivirus. Chromatin immunoprecipitation, immunoblotting analyses, and immunofluorescence assays were also conducted. U2AF1 mutations were associated with poor prognosis in MDS and AML samples, which significantly inhibited cell proliferation and induced cellular apoptosis in cell models. Our data identified that U2AF1-mutant cell lines undergo FOXO3a-dependent apoptosis and NLRP3 inflammasome activation, which induces pyroptotic cell death. Particularly, an increase in the level of FOXO3a promoted the progression of MDS in association with restored autophagy program leading to NLRP3 inflammasome activation in response to U2AF1S34F mutation. Based on the result that U2AF1S34F mutation promoted the transcriptional activity of Bim through upregulating FOXO3a with transactivation of cell cycle regulators p21Cip1 and p27Kip1, FOXO3a, a potentially cancer-associated transcription factor, was identified as the key molecule on which these pathways converge. Overall, our studies provide new insights that U2AF1S34F mutation functions the crucial roles in mediating MDS disease progression via FOXO3a activation, and demonstrate novel targets of U2AF1 mutations to the pathogenesis of MDS.


Assuntos
Autofagia , Proteína Forkhead Box O3/metabolismo , Leucemia Mieloide Aguda/metabolismo , Mutação , Síndromes Mielodisplásicas/metabolismo , Fator de Processamento U2AF/genética , Apoptose , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Proteína Forkhead Box O3/genética , Pontos de Checagem da Fase G2 do Ciclo Celular , Regulação Leucêmica da Expressão Gênica , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais
13.
Eur J Med Chem ; 223: 113665, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34192642

RESUMO

New types of antidiabetic agents are continually needed with diabetes becoming the epidemic in the world. Indole alkaloids play an important role in natural products owing to their variable structures and versatile biological activities like anticonvulsant, anti-inflammatory, antidiabetic, antimicrobial, and anticancer activities, which are a promising source of novel antidiabetic drugs discovery. The synthesized indole derivatives possess similar properties to natural indole alkaloids. In the last two decades, more and more indole derivatives have been designed and synthesized for searching their bioactivities. This present review describes comprehensive structures of indole compounds with the potential antidiabetic activity including natural indole alkaloids and the synthetic indole derivatives based on the structure classification, summarizes their approaches isolated from natural sources or by synthetic methods, and discusses the antidiabetic effects and the mechanisms of action. Furthermore, this review also provides briefly synthetic procedures of some important indole derivatives.


Assuntos
Hipoglicemiantes/química , Indóis/química , Carbolinas/química , Carbolinas/metabolismo , Carbolinas/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/uso terapêutico , Indóis/metabolismo , Indóis/uso terapêutico , PPAR alfa/química , PPAR alfa/metabolismo , PPAR gama/química , PPAR gama/metabolismo , Terpenos/química , Terpenos/metabolismo , Terpenos/uso terapêutico
14.
Hematology ; 25(1): 299-308, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32772642

RESUMO

Background: Myelodysplastic syndromes (MDS) are relatively common hematological malignancies characterized by dysplastic hematopoiesis in one or more of the lineages of the bone marrow. This study aimed to identify critical pathogenic biomarkers associated with the carcinogenesis and progression of MDS. Methods: To explore the candidate genes, the expression profiles of GSE2779, GSE4619, and GSE19429 were downloaded from the Gene Expression Omnibus (GEO) database, which contained CD34+ cells isolated from MDS patients and normal controls. The three microarray datasets were integrated to obtain differentially expressed genes (DEGs) and were deeply analyzed by bioinformatics methods. The construction of protein-protein interaction (PPI) network together with module analysis was performed based on Cytoscape software and the Search Tool for the Retrieval of Interacting Genes (STRING) database. Results: Our study identified 114 DEGs, which were highly enriched in various key pathways, including forkhead box protein O (FoxO) signaling pathway, the primary immunodeficiency, and hematopoietic cell lineage. Twelve core genes, such as FOXO1, PAX5 and CXCR4 were identified with a high degree of connectivity. It is plausible that FoxO signaling pathway plays an important role in MDS, and the dysregulation of FOXO1 was significantly associated with TGFß, IL2/STAT5, Notch signaling and apoptosis pathways. Conclusion: The current study for the first time identified twelve latent indicators and their downstream targets, which might become significant biomarkers for worse clinical characteristics in MDS.


Assuntos
Síndromes Mielodisplásicas/genética , Transcriptoma , Biologia Computacional , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Síndromes Mielodisplásicas/metabolismo , Mapas de Interação de Proteínas , Transdução de Sinais
15.
Stress ; 23(1): 87-96, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31311393

RESUMO

Psychological stress may be linked to cancer incidence; however, more direct evidence is required to support this viewpoint. In this study, we investigated the effects of stress on immunosurveillance against cancer cells using a previously established examination stress model. We showed that the cancer killing activity (CKA) of granulocytes (also known as polymorphic nuclear cells, PMNs) is sharply reduced during examination stress stimulation in some donors who are psychologically sensitive to examination stress, with the concentration of plasma stress hormones (cortisone, epinephrine, and norepinephrine) increasing accordingly. The effects of stress hormones on immune cell CKA were also investigated under two in vitro co-incubation conditions, with all three hormones found to exert inhibitory effects on the CKA of PMNs and mononuclear cells. We showed that stress triggered the release of stress hormones which had profound inhibitory effects on the innate anticancer functions of PMNs. These results provide a possible explanation for the relationship between psychological stress and cancer incidence.


Assuntos
Granulócitos/fisiologia , Neoplasias/fisiopatologia , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Epinefrina/sangue , Epinefrina/fisiologia , Humanos , Hidrocortisona/sangue , Hidrocortisona/fisiologia , Norepinefrina/sangue , Norepinefrina/fisiologia
16.
Mol Cancer Ther ; 18(1): 173-184, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30322948

RESUMO

Malignant glioma is an often fatal type of cancer. Elevated expression of the orphan nuclear receptor estrogen-related receptor alpha (ERRα) is an unfavorable factor for malignant progression and poor prognosis in several cancers, although the mechanism by which this receptor affects the pathophysiology of cancers remains obscure. However, few studies have been conducted in regard to the role of ERRα in glioma. In the current study, we found that elevated expression of ERRα was observed in 107 glioma cases by means of IHC. Clinically, high expression of ERRα was associated with later stages of disease progression and clinical outcome of patients with glioma. ERRα had the ability to promote cell proliferation and migration in glioma cell lines. Moreover, in a xenograft model, we also found that silencing ERRα had an inhibitory effect on the growth of glioma. Further investigation confirmed that ERRα was involved in the carcinogenesis of glioma via the regulation of the Wnt5a signal pathway in vitro and in vivo Our study was first to show the overexpression of ERRα in glioma tissues and a direct correlation between ERRα expression and clinical prognosis of glioma. Together, these data reveal that ERRα has prognostic significance in glioma, and targeting ERRα may provide a reliable therapeutic strategy for the treatment for human glioma.


Assuntos
Neoplasias da Mama/patologia , Glioma/patologia , Receptores de Estrogênio/metabolismo , Regulação para Cima , Proteína Wnt-5a/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Camundongos , Gradação de Tumores , Transplante de Neoplasias , Prognóstico , Receptores de Estrogênio/genética , Análise de Sobrevida , Proteína Wnt-5a/genética , Receptor ERRalfa Relacionado ao Estrogênio
17.
Mutagenesis ; 32(6): 547-560, 2017 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-29165592

RESUMO

Folates comprise the essential B9 vitamin that act as cofactors and cosubstrates in one-carbon metabolism for both biosynthesis and methylation of DNA and RNA. Folate deficiency (FD) has been shown to induce chromosomal instability (CIN), yet the underlying mechanisms are poorly understood. Here, we used human NCM460 colon mucosal cells as a model to investigate the effect of FD on spindle assembly checkpoint (SAC), a cell-cycle regulatory pathway preventing CIN during mitosis. Cells were maintained in medium containing 1.36 (FD) and 2260 nM (control, FC) folate for 21 days. CIN was measured by cytokinesis-block micronucleus assay; mitotic infidelity was determined by aberrant mitosis analysis; SAC activity was assessed by nocodazole-challenge assay, and the expression of core SAC genes was examined by real-time quantitative PCR (RT-qPCR). We found that, relative to FC, FD significantly induced CIN in a time-dependent way (P < 0.01). Mitotic cells cultured in FD medium had significant higher frequencies of misalignment, misegregation and spindle multipolarity than those cultured in FC medium (P < 0.01). FD-induced SAC impairment and overriding, resulting premature mitotic exit and cell multinucleation (P < 0.05). Moreover, FD deregulated the expression of several key SAC genes (P < 0.01). Overall, these data are the first to demonstrate that FD substantially compromises SAC network which predisposes cells to mitotic aberrations and CIN. These results establish a new link between folate metabolism and SAC signalling, two pathways that are highly relevant for tumorigenesis.


Assuntos
Instabilidade Cromossômica , Colo/patologia , Deficiência de Ácido Fólico/patologia , Pontos de Checagem da Fase M do Ciclo Celular , Mitose , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Instabilidade Cromossômica/efeitos dos fármacos , Instabilidade Cromossômica/genética , Ensaio de Unidades Formadoras de Colônias , Ácido Fólico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Modelos Biológicos
18.
Nat Genet ; 47(7): 793-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26029870

RESUMO

Pituitary adenoma is one of the most common intracranial neoplasms, and its genetic basis remains largely unknown. To identify genetic susceptibility loci for sporadic pituitary adenoma, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. We first analyzed genome-wide SNP data in 771 pituitary adenoma cases and 2,788 controls and then carried forward the promising variants for replication in another 2 independent sets (2,542 cases and 3,620 controls in total). We identified three new susceptibility loci below the genome-wide significance threshold (P < 5 × 10(-8)) in the combined analyses: 10p12.31 (rs2359536, P(meta) = 2.25 × 10(-10) and rs10828088, P(meta) = 6.27 × 10(-10)), 10q21.1 (rs10763170, P(meta) = 6.88 × 10(-10)) and 13q12.13 (rs17083838, P(meta) = 1.89 × 10(-8)). This study is the first GWAS to our knowledge on sporadic pituitary adenoma, and our results provide insight into the genetic basis of this disease.


Assuntos
Adenoma/genética , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 13/genética , Neoplasias Hipofisárias/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA
19.
Appl Ergon ; 50: 126-32, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25959326

RESUMO

Technological advance in human-computer interaction has attracted increasing research attention, especially in the field of virtual reality (VR). Prior research has focused on examining the effects of VR on various outcomes, for example, learning and health. However, which factors affect the final outcomes? That is, what kind of VR system design will achieve higher usability? This question remains largely. Furthermore, when we look at VR system deployment from a human-computer interaction (HCI) lens, does user's attitude play a role in achieving the final outcome? This study aims to understand the effect of immersion and involvement, as well as users' regulatory focus on usability for a somatosensory VR learning system. This study hypothesized that regulatory focus and presence can effectively enhance user's perceived usability. Survey data from 78 students in Taiwan indicated that promotion focus is positively related to user's perceived efficiency, whereas involvement and promotion focus are positively related to user's perceived effectiveness. Promotion focus also predicts user satisfaction and overall usability perception.


Assuntos
Interface Usuário-Computador , Adolescente , Adulto , Comportamento do Consumidor , Feminino , Humanos , Masculino , Inquéritos e Questionários , Jogos de Vídeo/psicologia , Jogos de Vídeo/normas , Percepção Visual , Adulto Jovem
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