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1.
Biochem Biophys Res Commun ; 550: 84-91, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33689884

RESUMO

The monopolar spindle 1 ((hMps1/TTK) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To explore the possible relationship between TTK inhibition and radiosensitivity, we examined whether TTK inhibition influences cellular susceptibility of radiation. And we further revealed its mechanisms. We found that the expression of TTK was obviously higher in liver cancer tissues compared to the normal liver tissues. Kaplan-Meier Plotter demonstrated that patients with low TTK expression levels had a longer overall survival than patients with high TTK expression levels. TTK inhibitor AZ3146 could simulated liver cancer cells to accumulate in the G2/M phase, which ultimately enhances DNA damage with more γ-H2AX foci and more apoptosis and necrosis induced by radiation, which prompted that TTK inhibition sensitized liver cancer cells to radiation. In addition, TTK inhibition altered cell-cycle progression and exacerbated centrosome abnormalities, resulting in enhanced mitotic catastrophe (MC) induced by radiation in a p21-mediated manner. In this study, we present evidences that the TTK inhibitor promotes the radiosensitivity of liver cancer cells through regulating cell cycle in p21-mediated manner in vitro, indicating that TTK inhibitor may be an attractive radiosensitizer for the patients with liver cancer.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Proteínas Oncogênicas/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Tolerância a Radiação/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Centrossomo/efeitos dos fármacos , Centrossomo/metabolismo , Centrossomo/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos da radiação , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos da radiação , Necrose/tratamento farmacológico , Necrose/radioterapia , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Análise de Sobrevida
2.
Am J Pathol ; 190(12): 2343-2354, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32971057

RESUMO

The long noncoding RNA DANCR (differentiation antagonizing non-protein coding RNA) displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in nasopharyngeal carcinoma (NPC) remain poorly understood. We found that DANCR is dramatically up-regulated in human NPC, and that it is an indicator for poor survival prognosis. DANCR knockdown suppressed cell proliferation, colony formation in vitro, and tumorigenicity in vivo. Mechanistic analyses demonstrated that DANCR could bind to RNA-binding protein 3 (RBM3) protein and stabilize SOX2 mRNA, resulting in NPC cell proliferation. Our findings indicate that DANCR functions as an oncogene and a potential therapeutic target for NPC.


Assuntos
Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Fatores de Transcrição SOXB1/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Proteínas de Ligação a RNA/metabolismo
3.
World J Surg Oncol ; 17(1): 199, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785609

RESUMO

BACKGROUND: Colorectal cancer is the fourth most common cancer globally and neoadjuvant concurrent chemoradiotherapy (nCRT) and surgery are the standard treatments for locally advanced colorectal carcinoma. This study investigated the association between dynamic changes in absolute lymphocyte counts (ALCs) and disease-free survival (DFS) in rectal cancer patients receiving nCRT and identified factors associated with these changes. METHODS: We retrospectively examined 34 patients with locally advanced rectal cancer who received nCRT followed by surgery and adjuvant chemotherapy. The association between ALCs and DFS and that between ALCs and downstaging were analyzed and potential clinical- and treatment-related factors related to dynamic changes in ALCs were subsequently evaluated. The patient eligibility criteria were as follows: pathologically confirmed rectal adenocarcinoma, clinical stages II-III, ≥ 18 years of age, and so on. Pre-RTL was defined as ALCs obtained before the initiation of nCRT and pre-SL was defined as ALCs obtained before surgery. We measured pre-SL to pre-RTL ratio (pre-SLR), DFS, and ALCs. RESULTS: The median ALC declined significantly during nCRT. A lower pre-SLR was associated with poorer DFS with statistical significance in Kaplan-Meier (p = 0.007), univariate regression (hazard ratio [HR] = 6.287, 95% confidence interval [CI] 1.374-28.781, p = 0.018), and multivariable regression (HR = 7.347, 95% CI 1.595-33.850, p = 0.011) analyses. Neither patient characteristics nor treatment-related factors were related to downstaging. The pelvic bone marrow (PBM) volume receiving at least 30 Gy (V30) was significantly associated with pre-SLR in the univariate (HR = 5.760, 95% CI 1.317-25.187, p = 0.020) and multivariable (HR = 5.760, 95% CI 1.317-25.187, p = 0.020) regression analyses. LIMITATIONS: Our study had several limitations. The sample size was small and the study was performed in a selected population, which may limit the generalization of the findings. CONCLUSIONS: Radiotherapy had a profound impact on the change in ALCs. A lower pre-SLR was significantly associated with poorer DFS in rectal cancer patients receiving nCRT. The V30 of PBM was a predictor of pre-SLR.


Assuntos
Quimiorradioterapia/mortalidade , Linfócitos/patologia , Cuidados Pré-Operatórios , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retais/terapia , Estudos Retrospectivos , Taxa de Sobrevida
5.
J Asthma ; 52(1): 10-5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25158053

RESUMO

UNLABELLED: Abstract Objective: The prevalence of asthma in children age 0-14 years in Fuzhou, a city in Southeast China, was 1.57% in 1990 and 3.28% in 2000. The aim of this study was to investigate the asthma prevalence and risk factors in children in the same city in 2010. METHODS: This was a cross-sectional study with a two-stage, clustered, stratified random sample design. Parents of 12235 children 0-14 years of age in Fuzhou were surveyed using a questionnaire. Children with history and/or symptoms of asthma were then interviewed by pediatricians in a nearby clinic to confirm the diagnosis of asthma, and a second questionnaire listing reported risk factors of asthma was completed by the parents in the clinic. RESULTS: About 11738 questionnaires were completed with a response rate of 95.9%. Among the responders, 648 children had history and/or symptoms of asthma but only 485 (4.13%) were confirmed with asthma. The prevalence was 1.83%, 7.64% and 6.27% in the age groups of 0-1 years, 3-4 years and 13-14 years, respectively. The most significant (binary logistic regression test) factors associated with asthma were presence of atopic or allergic diseases (OR=21.5, 95% CI: 12-38.5), family history of allergy or asthma (OR=29.4, 95% CI: 12.6-68.6), use of at least one course of antibiotics in the first year of life (OR=7.61, 95% CI: 3.4-17.06), supplementary protein feedings before 6 months (OR=1.90, 95% CI: 1.23-2.95). Natural ventilation at home (versus frequent use of air-conditioning) appeared to be a protective factor (OR = 0.5, 95% CI: 0.3-0.8). CONCLUSION: The prevalence of asthma in childhood has increased significantly during the past 20 years in Fuzhou.


Assuntos
Asma/epidemiologia , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Cidades/epidemiologia , Eczema/epidemiologia , Hipersensibilidade Alimentar/epidemiologia , Humanos , Lactente , Recém-Nascido , Razão de Chances , Prevalência , Rinite/epidemiologia , Fatores de Risco , Saúde da População Urbana/tendências , População Urbana/tendências , Urticária/epidemiologia
6.
R Soc Open Sci ; 11(1): 231802, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38204780

RESUMO

Will et al.'s (2021 Proc. Natl Acad. Sci. USA 118, e2106640118 (doi:10.1073/pnas.2106640118)) found the Medusa effect, which refers to the tendency that people evaluate a 'person in picture' more mindful than a 'person in picture of a picture'. The present study tried to directly replicate the Experiments 2 and 5 of Will et al.'s (2021), to examine the reliability, validity and generalization of the Medusa effect, as well as its effect on prosocial behaviour. We used the same stimuli and methodology as the original research, but recruited participants in Japan with a larger sample size (N = 1387 in total) as a registered report. In our two replication experiments, we again found that pictures with lower levels of abstraction (L1) were perceived to convey more mind and lead to higher levels of prosocial behaviour, successfully replicating the original findings. The results of the present study suggested the high reproducibility and generalizability of the Medusa effect. Pre-registered Stage 1 protocol: https://osf.io/xj46z (date of in-principle acceptance: 9 February 2023).

7.
J Mater Chem B ; 11(32): 7739-7749, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37470708

RESUMO

Prolonged and excessive accumulation of ß2-microglobulin (ß2m) in the blood can lead to various kidney-related and other diseases. Currently, the most effective method of removing ß2m from the blood is hemoperfusion. Although some traditional hemoperfusion adsorbents such as cellulose and polystyrene microspheres have been used for the removal of ß2m, their selectivity still needs improvement. Immunosorbents have been developed to address this issue, but high cost and limited application are concerns. TiO2 nanotube arrays (TNTAs) have shown great potential in adsorption-related biomedical applications. In this study, we designed and developed a novel TNTA-based hemoperfusion adsorbent for the removal of ß2m, which has demonstrated good biocompatibility, selectivity, and reusability. We investigated the ß2m adsorption capacities of TNTAs with different pore sizes. The results indicate that TNTAs with a pore size matching the size of ß2m exhibit higher adsorption capacity while also having lower adsorption capacity for albumin, showing the importance of pore size on the selectivity of adsorbents. Additionally, green regeneration of TNTAs is achieved via the photocatalytic activity originating from TiO2. Even after five cycles, the adsorption capacity of TNTAs remained above 70%. Our work demonstrates that inorganic materials with ordered pores are capable to be candidates for hemoperfusion, possessing advantages over traditional organic materials such as high stability, security, and low cost.


Assuntos
Nanotubos , Hemoperfusão/instrumentação , Hemoperfusão/métodos , Nanotubos/química , beta-Globulinas/química , Humanos , Materiais Biocompatíveis/química
8.
Macromol Biosci ; 23(9): e2300184, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37262314

RESUMO

Proper endothelialization and limited collagen deposition on the luminal surface after graft implantation plays a crucial role to prevent the occurrence of stenosis. To achieve these conditions, a biodegradable graft with adequate mechanical properties and the ability to sequentially deliver therapeutic agents isfabricated. In this study, a dual-release system is constructed through coaxial electrospinning by incorporating recombinant human vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) inhibitor into silk fibroin (SF) nanofibers to form a bioactive membrane. The functionalized SF membrane as the inner layer of the graft is characterized by the release profile, cell proliferation and protein expression. It presents excellent biocompatibility and biodegradation, facilitating cell attachment, proliferation, and infiltration. The core-shell structure enables rapid VEGF release within 10 days and sustained plasmid delivery for 21 days. A 2.0-mm-diameter vascular graft is fabricated by integrating the SF membrane with decellularized porcine small intestinal submucosa (SIS), aiming to facilitate the integration process under a stable extracellular matrix structure. The bioengineered graft is functionalized with the sequential administration of VEGF and TGF-ß1, and with the reinforced and compatible mechanical properties, thereby offers an orchestrated solution for stenosis with potential for in situ vascular tissue engineering applications.


Assuntos
Fibroínas , Animais , Humanos , Constrição Patológica , Fibroínas/farmacologia , Fibroínas/química , Seda/química , Suínos , Engenharia Tecidual , Alicerces Teciduais/química , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
9.
Int J Biol Macromol ; 253(Pt 6): 127321, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37820900

RESUMO

Hemoperfusion is a well-developed method for removing bilirubin from patients with hyperbilirubinemia. The performance of adsorbents is crucial during the process. However, most adsorbents used for bilirubin removal are not suitable for clinical applications, because they either have poor adsorption performance or limited biocompatibility. Patients with hyperbilirubinemia usually have distinctive yellow skin, indicating that collagen, a primary component of the skin, may be an effective material for absorbing bilirubin from the blood. Based on this idea, we designed and synthesized collagen (Col) and collagen-polyethyleneimine (Col-PEI) microspheres and employed them as hemoperfusion adsorbents for bilirubin removal. The microspheres have an efficient adsorption rate, higher bilirubin adsorption capacity, and competitive adsorption of bilirubin in the bilirubin/bovine serum albumin (BSA) solution. The maximum adsorption capacities of Col and Col-PEI microspheres for bilirubin are 150.2 mg/g and 258.4 mg/g, respectively, which are higher than those of most traditional polymer microspheres. Additionally, the microspheres exhibit excellent blood compatibility originating from collagen. Our study provides a new collagen-based strategy for the hemoperfusion treatment of hyperbilirubinemia.


Assuntos
Bilirrubina , Hemoperfusão , Humanos , Hemoperfusão/métodos , Hiperbilirrubinemia/terapia , Adsorção
10.
Shanghai Kou Qiang Yi Xue ; 31(1): 104-108, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35587680

RESUMO

PURPOSE: This study was carried out to evaluate the value of comfort nursing in light curing resin-treated dental caries by means of patient satisfaction survey. METHODS: One hundred and twenty-eight cariogenic patients, who were treated from January 2017 to December 2017 in Shanghai Ninth People's Hospital, were enrolled and randomly assigned as experimental group and control group, respectively(n=64). Cariogenic lesions were treated with light-cured resin, patients in the control group received conventional four-handed operation nursing, while patients in the experimental group received modified comfortable nursing throughout the entire treatment course. The self-designed satisfaction questionnaires were issued, and the patients were required to fill them out after the treatment and nursing were definitely completed. The designed questionnaire was divided into two major parts, including nursing care and nursing operation, which was further subdivided into 10 detailed scoring items. The satisfaction survey of nursing was analyzed between two groups statistically to evaluate the effort of comfort nursing using SPSS 19.0 software package. RESULTS: No significant differences in the treatment environment was observed between the two groups(P>0.05), while upgraded satisfaction were observed in patients from the experimental group compared to those from the control group on the aspects of nursing care, namely, appearance, service attitude, explanation and health knowledge promotion(P<0.05). Among the five scoring standards of nursing operation, which was consist of timely initiative nursing, position nursing, eye nursing, effective nursing and nursing procedures, the satisfaction scores from the experimental group were significantly higher than those from the control group(P<0.05). The total collected data demonstrated that the overall satisfaction of the experimental group was significantly improved compared to that of the control group (94% vs 75%, P<0.01). CONCLUSIONS: Comfort nursing not only strengthens the professionalism of oral operation, but also improves the patient's experience, facilitating to promote the harmony between doctors and patients.


Assuntos
Cárie Dentária , China , Cárie Dentária/terapia , Suscetibilidade à Cárie Dentária , Humanos , Satisfação do Paciente
11.
Int J Nanomedicine ; 17: 5947-5990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36510620

RESUMO

Bacterial-infected wounds are a serious threat to public health. Bacterial invasion can easily delay the wound healing process and even cause more serious damage. Therefore, effective new methods or drugs are needed to treat wounds. Nanozyme is an artificial enzyme that mimics the activity of a natural enzyme, and a substitute for natural enzymes by mimicking the coordination environment of the catalytic site. Due to the numerous excellent properties of nanozymes, the generation of drug-resistant bacteria can be avoided while treating bacterial infection wounds by catalyzing the sterilization mechanism of generating reactive oxygen species (ROS). Notably, there are still some defects in the nanozyme antibacterial agents, and the design direction is to realize the multifunctionalization and intelligence of a single system. In this review, we first discuss the pathophysiology of bacteria infected wound healing, the formation of bacterial infection wounds, and the strategies for treating bacterially infected wounds. In addition, the antibacterial advantages and mechanism of nanozymes for bacteria-infected wounds are also described. Importantly, a series of nanomaterials based on nanozyme synthesis for the treatment of infected wounds are emphasized. Finally, the challenges and prospects of nanozymes for treating bacterial infection wounds are proposed for future research in this field.


Assuntos
Infecções Bacterianas , Nanoestruturas , Infecção dos Ferimentos , Humanos , Infecção dos Ferimentos/tratamento farmacológico , Bactérias , Antibacterianos/uso terapêutico , Nanoestruturas/uso terapêutico
12.
Front Chem ; 9: 743637, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692641

RESUMO

Metal-organic frameworks (MOFs) have been extensively used as modified materials of electrochemical sensors in the food industry and agricultural system. In this work, two kinds of copper-based MOFs (Cu-MOFs) with a two dimensional (2D) sheet-like structure and three dimensional (3D) octahedral structure for H2O2 detection were synthesized and compared. The synthesized 2D and 3D Cu-MOFs were modified on the glassy carbon electrode to fabricate electrochemical sensors, respectively. The sensor with 3D Cu-MOF modification (HKUST-1/GCE) presented better electrocatalytic performance than the 2D Cu-MOF modified sensor in H2O2 reduction. Under optimal conditions, the prepared sensor displayed two wide linear ranges of 2 µM-3 mM and 3-25 mM and a low detection limit of 0.68 µM. In addition, the 3D Cu-MOF sensor exhibited good selectivity and stability. Furthermore, the prepared HKUST-1/GCE was used for the detection of H2O2 in milk samples with a high recovery rate, indicating great potential and applicability for the detection of substances in food samples. This work provides a convenient, practical, and low-cost route for analysis and extends the application range of MOFs in the food industry, agricultural and environmental systems, and even in the medical field.

13.
Front Oncol ; 11: 619915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842324

RESUMO

The long noncoding RNA (lncRNA) LINC00152, also known as CYTOR, displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in breast cancer remain insufficiently understood. Our study found that LINC00152 is significantly upregulated in breast cancer, and that it acts as an indicator of poor survival prognosis. Further studies revealed that LINC00152 knockdown suppresses cell proliferation and tumorigenicity in vitro and in vivo. Mechanistic analyses demonstrated that LINC00152 directly binds to KLF5 protein and increases KLF5 stability. Moreover, LINC00152 is also a KLF5-responsive lncRNA, and KLF5 activates LINC00152 transcription by directly binding to its promoter. Our study suggests that LINC00152 promotes tumor progression by interacting with KLF5. LINC00152 may be a valuable prognostic predictor for breast cancer, and the positive feedback loop of LINC00152-KLF5 could be a therapeutic target in pharmacological strategies.

14.
Front Oncol ; 10: 601055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330099

RESUMO

BACKGROUND: The long noncoding RNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is a critical player in various cancers. However, the clinical value and functional mechanisms of AFAP1-AS1 during the tumorigenicity of nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the clinical application and potential molecular mechanisms of AFAP1-AS1 in NPC tumorigenesis and progression. METHODS: The expression level of AFAP1-AS1 was determined by qRT-PCR in 10 paired fresh human NPC tissues and adjacent normal tissues. RNAscope was performed on 100 paired paraffin-embedded NPC and adjacent nontumor specimens. The biological functions of AFAP1-AS1 were assessed by in vitro and in vivo functional experiments. RNA-protein pull-down assays were performed to detect and identify the AFAP1-AS1-interacting protein KAT2B. Protein-RNA immunoprecipitation (RIP) assays were conducted to examine the interaction of AFAP1-AS1 and KAT2B. Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of transcription intermediary factor 1 alpha (TIF1α) and H3K14ac on the RBM3 promoter. RESULTS: AFAP1-AS1 is upregulated in NPC and is a poor prognostic indicator for survival in NPC patients. AFAP1-AS1 was required for NPC proliferation in vitro and tumorigenicity in vivo. Mechanistic investigations suggested that AFAP1-AS1 binds to KAT2B and promotes acetyltransferase activation at two residues (E570/D610). KAT2B further promotes H3K14 acetylation and protein binding to the bromo domain of TIF1α. Consequently, TIF1α acts as a nuclear transcriptional coactivator of RBM3 transcription, leading to YAP mRNA stabilization and enhanced NPC tumorigenicity. CONCLUSIONS: Our findings suggest that AFAP1-AS1 functions as an oncogenic biomarker and promotes NPC tumorigenicity through enhanced KAT2B acetyltransferase activation and YAP mRNA stabilization.

15.
Cell Death Differ ; 27(2): 695-710, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31320749

RESUMO

Long noncoding RNAs (lncRNAs) play important roles in regulating the development and progression of many cancers. However, the clinical significance of specific lncRNAs in the context of nasopharyngeal carcinoma (NPC) and the molecular mechanisms by which they regulate this form of cancer remain largely unclear. In this study we found that the lncRNA PVT1 was upregulated in NPC, and that in patients this upregulation was associated with reduced survival. RNA sequencing revealed that PVT1 was responsible for regulating NPC cell proliferation and for controlling a hypoxia-related phenotype in these cells. PVT1 knockdown reduced NPC cell proliferation, colony formation, and tumorigenesis in a subcutaneous mouse xenograft model systems. We further found that PVT1 serves as a scaffold for the chromatin modification factor KAT2A, which mediates histone 3 lysine 9 acetylation (H3K9), recruiting the nuclear receptor binding protein TIF1ß to activate NF90 transcription, thereby increasing HIF-1α stability and promoting a malignant phenotype in NPC cells. Overexpression of NF90 or HIF-1α restored the proliferation in cells that had ceased proliferating due to PVT1 or KAT2A depletion. Conversely, overexpression of active KAT2A or TIF1ß, but not of KAT2A acetyltransferase activity-deficient mutants or TIF1ß isoforms lacking H3K9ac binding sites, promoted a PVT1-mediated increase in NF90 transcription, as well as increased HIF-1α stability and cell proliferation. PVT1 knockdown enhanced the radiosensitization effect in NPC cells via inhibiting binding between H3K9ac and TIF1ß in a manner. Taken together, our results demonstrate that PVT1 serves an oncogenic role and plays an important role in radiosensitivity in malignant NPC via activating the KAT2A acetyltransferase and stabilizing HIF-1α.


Assuntos
Histona Acetiltransferases/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , RNA Longo não Codificante/metabolismo , Proliferação de Células , Histona Acetiltransferases/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/isolamento & purificação , Transdução de Sinais/genética , Células Tumorais Cultivadas
16.
Cancer Res ; 78(11): 3087-3097, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29572226

RESUMO

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new noncoding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10-8) and CNFN (P = 3.77 × 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087-97. ©2018 AACR.


Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Exoma/genética , Predisposição Genética para Doença/genética , Locos de Características Quantitativas/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
17.
PLoS One ; 9(11): e112936, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25406076

RESUMO

BACKGROUND: Renal fibrosis is the final common pathway of chronic kidney disease (CKD). Moesin is a member of Ezrin/Radixin/Moesin (ERM) protein family but its role in renal fibrosis is not clear. METHOD: Human proximal tubular cells (HK-2) were stimulated with or without TGF-ß1. Moesin and downstream target genes were examined by real-time PCR and western blot. Phosphorylation of moesin and related signaling pathway was investigated as well. Rat model of unilateral ureteral obstruction (UUO) was established and renal moesin was examined by immunohistochemistry. Moesin in HK-2 cells were knocked down by siRNA and change of downstream genes in transfected HK-2 cells was studied. All animal experiments were reviewed and approved by the Ethics Committee for animal care of Ruijin Hospital. RESULT: HK-2 cells stimulated with TGF-ß1 showed up-regulated level of α-SMA and down-regulated level of E-Cadherin as well as elevated mRNA and protein level of moesin. In rat model of UUO, renal moesin expression increased in accordance with severity of tubulointerestital fibrosis in the kidneys with ureteral ligation while the contralateral kidneys were normal. Further study showed that TGF-ß1 could induce phosphorylation of moesin which depended on Erk signaling pathway and Erk inhibitor PD98059 could block moesin phosphorylation. Effects of TGF-ß1 on moesin phosphorylation was prior to its activation to total moesin. RNA silencing studies showed that knocking down of moesin could attenuate decrease of E-Cadherin induced by TGF-ß1. CONCLUSION: We find that moesin might be involved in renal fibrosis and its effects could be related to interacting with E-Cadherin.


Assuntos
Caderinas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Transdução de Sinais/fisiologia , Actinas/metabolismo , Análise de Variância , Animais , Western Blotting , Linhagem Celular , Fibrose/metabolismo , Humanos , Imuno-Histoquímica , Fosforilação , RNA Interferente Pequeno/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1
18.
Zhonghua Er Ke Za Zhi ; 52(4): 282-6, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-24915916

RESUMO

OBJECTIVE: To explore the prevalence and the different risk factors for asthma in children between urban and rural areas in Fuzhou, Fujian province. METHOD: The epidemiological survey of asthma in 0-14 years old children was conducted from October 2009 to October 2010 between Fuzhou urban and rural areas in Fujian province. The investigation subjects were selected in urban and rural areas by phased stratified random cluster sampling. The 2010 third national epidemiological survey questionnaire of children with asthma was used for screening for possible patients. Diagnosis of asthma was confirmed by physical examination. The children with asthma were designated as the positive cases, while non asthmatic children who were age, gender, ethnic, and living environment matched with asthmatic patients were designated as negative control. Comparison of the prevalence of asthma in children between Fuzhou urban and rural areas was performed. The influencing factors of asthma were analyzed and screened by the regression equation model of two element Logistic regression. RESULT: Totally 12 235 questionnaires of children with asthma and allergic disease screening were issued and 11 738 questionnaire were sent back (6 221 were male and 5 517 were female). The return rate was 95.9% in urban Fuzhou; 648 children were diagnosed as asthma. The prevalence of asthma in male was 6.48% and female children was 4.44% (comparison of the prevalence of gender χ(2) = 23.267, P < 0.001) in urban areas . A total of 6 000 questionnaires of children with asthma and allergic disease screening were sent out and 5 860 were responded (male children 3 228, female children 2 632). The recovery rate was 97.7% in rural Fuzhou; 135 children with asthma was diagnosed. The prevalence of asthma in male was 2.73%and female children and was 1.79%. Adding protein supplement before 6 months (OR = 1.908, 95%CI:1.233-2.959), the use of antibiotics in the treatment of asthma (OR = 14.541, 95%CI:8.920-23.705), furniture materials (non wood) (OR = 2.432, 95%CI:1.563-3.785) were the main risk factors of children with asthma in urban. Adding protein supplement before 6 months(OR = 3.021, 95%CI:1.357-6.711), the use of antibiotics in the treatment of asthma(OR = 14.784, 95%CI:3.842-56.885), the use of coal as fuel (OR = 63.339, 95% CI: 7.993-501.943), domesticated livestock (OR = 13.659, 95% CI:1.342-139.068), the family smoking before and after birth (OR = 6.226, 95%CI:2.674-14.495) and chemical fiber pillow (OR = 3.638, 95%CI:1.241-10.666) were the main risk factors of children with asthma in rural areas. CONCLUSION: The prevalence of children with asthma in urban areas was higher than that in rural areas. The prevalence of asthma in male children was higher than in female children. Adding protein food supplement before 6 months, the use of antibiotics and non solid wood furniture material were the main risk factors in children with asthma in urban areas. Adding protein supplement before 6 months, the use of antibiotics, domesticated livestock, the use of coal as fuel and the family smoking before and after birth were the main risk factor of asthma in children in rural areas.


Assuntos
Asma/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Asma/etiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Prevalência , Fatores de Risco , Estudos de Amostragem , Fumar/efeitos adversos , Inquéritos e Questionários
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