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1.
FASEB J ; 35(10): e21885, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34478585

RESUMO

In a recently published phase III clinical trial, gemcitabine (GEM) plus cisplatin (DDP) induction chemotherapy significantly improved recurrence-free survival and overall survival and became the standard of care among patients with locoregionally advanced NPC. However, the molecular mechanisms of GEM synergized with DPP in NPC cells remain elucidated. These findings prompt us to explore the effect of the combination between GEM and DDP in NPC cell lines through proliferative phenotype, immunofluorescence, flow cytometry, and western blotting assays. In vitro studies reveal that GEM or DPP treated alone induces cell cycle arrest, promotes cell apoptosis, forces DNA damage response, and GEM synergism with DDP significantly increases the above effects in NPC cells. In vivo studies indicate that GEM or DPP treated alone significantly inhibits the tumor growth and prolongs the survival time of mice injected with SUNE1 cells compared to the control group. Moreover, the mice treated with GEM combined with DDP have smaller tumors and survive longer than those in GEM or DPP treated alone group. In addition, P-gp may be the key molecule that regulates the synergistic effect of gemcitabine and cisplatin. GEM synergizes with DPP to inhibit NPC cell proliferation and tumor growth by inducing cell cycle arrest, cell apoptosis, and DNA damage response, which reveals the mechanisms of combined GEM and DDP induction chemotherapy in improving locoregionally advanced NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proliferação de Células/efeitos dos fármacos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Cisplatino/agonistas , Cisplatino/farmacologia , Desoxicitidina/agonistas , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Sinergismo Farmacológico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Exp Biol Med (Maywood) ; : 15353702211037261, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34424090

RESUMO

Non-keratinizing nasopharyngeal carcinoma, the major subtype of nasopharyngeal carcinoma, is characterized by low differentiation and a close relation to Epstein-Barr virus infection, which indicates a link between Epstein-Barr virus oncogenesis and loss of differentiation, and raises our interest in investigating the involvement of Epstein-Barr virus in nasopharyngeal carcinoma dedifferentiation. Our previous study showed abundant expression of an Epstein-Barr virus-encoded microRNA, BART10-3p, in nasopharyngeal carcinoma tissues, but the association between BART10-3p and nasopharyngeal carcinoma differentiation remains unknown. Here, we examined the expression and prognostic value of BART10-3p, and undertook bioinformatics analysis and functional assays to investigate the influence of BART10-3p on nasopharyngeal carcinoma differentiation and proliferation and the underpinning mechanism. Microarray analysis identified BART10-3p as the most significantly upregulated Epstein-Barr virus-encoded microRNA in nasopharyngeal carcinoma tissues and the upregulation was confirmed in two public datasets. The expression of BART10-3p was an independent unfavorable prognosticator in nasopharyngeal carcinoma and its integration with the clinical stage showed improved prognosis predictive performance. Bioinformatics analysis suggested a potential role of BART10-3p in tumor differentiation and progression. Functional assays demonstrated that BART10-3p could promote nasopharyngeal carcinoma cell dedifferentiation, epithelial-mesenchymal transition, and proliferation in vitro, and tumorigenicity in vivo. Mechanistically, BART10-3p directly targeted the 3'UTR of ALK7 and suppressed its expression. Reconstitution of ALK7 rescued BART10-3p-induced malignant phenotypes. Overall, our study demonstrates that BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7, suggesting a promising therapeutic opportunity to reverse the malignant phenotypes of nasopharyngeal carcinoma.

3.
Huan Jing Ke Xue ; 42(7): 3328-3337, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212658

RESUMO

At present, there are few reports about how impervious surface microstructure characteristics affect the runoff output process of street dust. Based on field observations of 12 rainfall events, this study quantified the microstructure characteristics of impervious surfaces by structural depth (roughness) and analyzed the correlation between roughness and accumulation characteristics of street dust on sunny days as well as scouring characteristics in rainy days. The results show that the roughness of the underlying surface notably affects dust accumulation on sunny days and scouring in rainy days. The correlation between roughness and street dust accumulation (r=0.664, P<0.01) was enhanced on sunny days, and the correlation between roughness and street dust erosion (r=0.527, P<0.01) was enhanced by rainfall. The correlation of street dust accumulation and roughness of each particle size segment increased as particle size increased (0.529 ≤ r<0.757), and the correlation between street dust scouring amount and roughness decreased as particle size increased (0.603 > R > 0.209). By establishing the linear regression model of roughness and rainfall, the cumulative pollution load of TSS in rainfall runoff can be well predicted. The effects of roughness and rainfall on the cumulative load of grain sizes<20 µm and >250 µm are significant. These results elucidate the role of roughness and rainfall analysis in predicting surface runoff pollution load characteristics, which can provide new information for predicting and evaluating urban non-point source pollution.


Assuntos
Movimentos da Água , Poluentes Químicos da Água , Poeira/análise , Monitoramento Ambiental , Chuva , Poluentes Químicos da Água/análise
4.
Med Sci Monit ; 27: e929791, 2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33895770

RESUMO

BACKGROUND We sought to create a model that incorporated ultrasound examinations to predict the risk of acute kidney injury (AKI) after percutaneous coronary intervention (PCI) or cardiopulmonary bypass (CPB) surgery. MATERIAL AND METHODS A total of 292 patients with AKI after PCI or CPB surgery were enrolled for the study. Afterwards, treatment-related information, including data pertaining to ultrasound examination, was collected. A random forest model and multivariate logistic regression analysis were then used to establish a predictive model for the risk of AKI. Finally, the predictive quality and clinical utility of the model were assessed using calibration plots, receiver-operating characteristic curve, C-index, and decision curve analysis. RESULTS Predictive factors were screened and the model was established with a C-index of 0.955 in the overall sample set. Additionally, an area under the curve of 0.967 was obtained in the training group. Moreover, decision curve analysis also revealed that the prediction model had good clinical applicability. CONCLUSIONS The prediction model was efficient in predicting the risk of AKI by incorporating ultrasound examinations and a number of factors. Such included operation methods, age, congestive heart failure, body mass index, heart rate, white blood cell count, platelet count, hemoglobin, uric acid, and peak intensity (kidney cortex as well as kidney medulla).


Assuntos
Injúria Renal Aguda/epidemiologia , Ponte Cardiopulmonar , Insuficiência Cardíaca/cirurgia , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/epidemiologia , Injúria Renal Aguda/etiologia , Idoso , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Nomogramas , Estudos Retrospectivos , Risco , Ultrassonografia
5.
Mol Cancer ; 20(1): 14, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430876

RESUMO

Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.


Assuntos
Heterogeneidade Genética , Imunoterapia , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Microambiente Tumoral , Estudos de Coortes , Genoma Humano , Humanos , Carcinoma Nasofaríngeo/genética , Prognóstico , Reprodutibilidade dos Testes , Microambiente Tumoral/genética
6.
J Matern Fetal Neonatal Med ; 34(16): 2583-2591, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31533498

RESUMO

OBJECTIVES: We conducted this study to investigate the risk factors for spontaneous abortion among rural Chinese women. METHODS: Risk factors prior to pregnancy associated with spontaneous abortion were identified among 17,248 rural women enrolled in a prospective population-based follow-up study. The risk of spontaneous abortion was estimated with odds ratio (OR) and 95% confidence interval (CI) for several factors. A nonconditional logistic regression analysis was then performed to identify the independently associated factors. RESULTS: The total sample of this study population consisted of 17,248 pregnant women including 921 of them whose pregnancies resulted in spontaneous abortion and the incidence of spontaneous abortion was 5.04%. After the adjustment of confounding factors, menarche age, serum creatinine, family genetic diseases or maternal congenital defects was associated with an increased risk of spontaneous abortion while folic acid supplementation reduced the risk among rural Chinese women. CONCLUSIONS: The findings of our study suggest that multiple modifiable factors may increase the risk of spontaneous abortion which may help relevant departments better to guide detailed effectively prevention strategies toward spontaneous abortion to improve the reproductive quality of rural population. Further studies are required to elaborate these risk factors for spontaneous abortion.


Assuntos
Aborto Espontâneo , Aborto Espontâneo/epidemiologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Gravidez , Estudos Prospectivos , Fatores de Risco , População Rural
7.
Environ Res ; 193: 110599, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33307084

RESUMO

BACKGROUND: The amount of natural vegetation surrounding homes (residential greenness) has been proposed as a mitigation measure to buffer the adverse health effects of urban living, associated with promoting health and wellbeing including birth outcomes. This study aimed to systematically review the epidemiological evidence on the association of residential greenness with birth outcomes and quantitatively provide summary effect estimates of the current literature. METHODS: We extensively searched epidemiological studies related to residential greenness and birth outcomes in three electronic databases (EMBASE, Web of Science, and PubMed) using terms related to residential greenness and birth outcomes before July 10, 2020. Summary effect estimates of residential greenness on birth outcomes including SGA (small for gestational age), PTB (preterm birth), LBW (low birth weight), and birth weight were calculated for each 0.1 unit increase in residential greenness exposure, as well as comparing the highest to the lowest categories using random-effects meta-analyses. We assessed the risk of bias of each individual study, and the overall quality of the body of evidence and level of evidence for each exposure-outcome were also evaluated. RESULTS: The initial search identified 161 studies, of which 29 studies were finally included. Meta-analysis for continuous exposure suggested that an increase in residential greenness, measured by NDVI (normalized difference vegetation index) with different buffer sizes, was generally associated with higher birth weights ranging from 7.99 g [95% confidence interval (CI) = 4.29-11.70] to 15.35 g (95% CI = 11.41-19.29) and lower odds of LBW ranging from 0.79 (95% CI = 0.65-0.96) to 0.93 (95% CI = 0.86-1.00), but associations between residential greenness and PTB or SGA were not significant. When introducing the exposure as high versus low categories, similar results were found. The overall evidence for each exposure-outcome combination was considered to be of "moderate" certainty. CONCLUSIONS: This study indicated a potential positive association between residential greenness and several birth outcomes. However, because of the moderate to high between-study heterogeneity, further studies with better adjustment of covariates, improved residential greenness assessment in a longitudinal approach throughout pregnancy rather than a cross-sectional approach at time of delivery, and accounting thoroughly for socioeconomic status, are warranted to replicate these findings as well as to explore in greater detail in their implications.


Assuntos
Resultado da Gravidez , Nascimento Prematuro , Peso ao Nascer , Estudos Transversais , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia
9.
Environ Res ; 189: 109900, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32980000

RESUMO

BACKGROUND: Although the effects of seasonal variations and ambient temperature on the incidence of tuberculosis (TB) have been well documented, it is still unknown whether ambient temperature change is an independent risk factor for TB. The aim of this study was to assess the association between ambient temperature change and the risk of TB admissions. METHOD: A distributed lag non-linear model (DLNM) combined with Poisson generalized linear regression model was performed to assess the association between ambient temperature change and the risk of TB admissions from 2014 to 2018 in Hefei, China. Two temperature change metrics including temperature change between neighboring days (TCN) and diurnal temperature range (DTR) were used to assess the effects of temperature change exposure. Subgroup analyses were performed by gender, age and season. Besides, the attributable risk was calculated to evaluated the public health significance. RESULTS: The overall exposure-response curves suggested that there were statistically significant associations between two temperature change metrics and the risk of TB admissions. The maximum lag-specific relative risk (RR) of TB admissions was 1.088 (95%CI: 1.012-1.171, lag 4 day) for exposing to large temperature drop (TCN= -4 °C) in winter. Besides, the overall cumulative risk of TB admissions increased continuously and peaked at a lag of 7 days (RR=1.350, 95%CI: 1.120-1.628). Subgroup analysis suggested that exposure to large temperature drop had an adverse effect on TB admissions among males, females and adults. Similarly, large level of DTR exposure (DTR=15 °C) in spring also increased the risk of TB admissions on lag 0 day (RR=1.039, 95%CI: 1.016-1.063), and the cumulative RRs peaked at a lag of 1 days (RR=1.029, 95%CI: 1.012-1.047). We also found that females and elderly people were more vulnerable to the large level of DTR exposure. Additionally, the assessment of attributable risk suggested that taking target measures for the upcoming large temperature drop (b-AF = 4.17%, 95% eCI: 1.24%, 7.22%, b-AN = 1195) may achieve great public health benefits for TB prevention. CONCLUSION: This study suggests that ambient temperature change is associated with the risk of TB admissions. Besides, TCN may be a better predictor for the TB prevention and public health.


Assuntos
Benchmarking , Tuberculose , Idoso , China , Feminino , Hospitalização , Humanos , Masculino , Temperatura , Tuberculose/epidemiologia
10.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32690665

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes have been reported as prognostic markers in tumors. We aimed to assess the prognostic value of total T cell (CD3+) density, cytotoxic T cell (CD8+) density and memory T cell (CD45RO+) density in patients with nasopharyngeal carcinoma (NPC). METHODS: The expression of CD3, CD8 and CD45RO was detected by immunohistochemistry in the training (n=221) and validation cohorts (n=115). The densities of these three markers were quantified by digital pathology both in the tumor and stroma. Then, we developed the immune score based on the density of these three markers and further analyzed its prognostic value. RESULTS: The high density of CD3+, CD8+ and CD45RO+ T cells both in the tumor and/or stroma were significantly associated with the decrease in mortality in the training cohort, respectively. High immune score predicted a prolonged overall survival (OS) (HR 0.34, 95% CI 0.18 to 0.64, p=0.001, disease-free survival (DFS) (HR 0.44, 95% CI 0.25 to 0.78, p=0.005) and distant metastasis-free survival (DMFS) (HR 0.43, 95% CI 0.21 to 0.87, p=0.018) in NPC patients. The findings were confirmed in the validation cohort. Multivariate analysis revealed that immune score remained an independent prognostic indicator for OS, DFS and DMFS. In addition, we established a nomogram with the integration of all independent variables to predict individual risk of death. CONCLUSIONS: We established an immune score model, which provides a reliable estimate of the risk of death, disease progress and distant metastasis in NPC patients.

11.
Cell Res ; 30(11): 1024-1042, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32686767

RESUMO

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A+ dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A+ DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.

12.
Cancer Sci ; 111(6): 1991-2003, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232887

RESUMO

Alternative polyadenylation (APA), which induces shortening of the 3'-UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA-induced 3'-UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3'-UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3'-UTR could escape from miRNA-mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3'-UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/ß-catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3'-UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B-MYH9-Wnt/ß-catenin axis could represent potential targets for individualized treatment in NPC.


Assuntos
Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Cadeias Pesadas de Miosina/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Regiões 3' não Traduzidas , Animais , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Fibronectinas/genética , Xenoenxertos , Humanos , Camundongos , MicroRNAs , Cadeias Pesadas de Miosina/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Via de Sinalização Wnt/fisiologia
13.
Chemosphere ; 253: 126668, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32278917

RESUMO

BACKGROUND: Congenital heart defects (CHDs) has a multifactorial causation with a strong genetic component and many environmental triggers. Emerging body of empirical studies suggest that air pollution is an important contributor to the development of CHDs, however, there still remains some controversy over the current evidence, and to the authors' knowledge, no studies have reviewed the most recent evidence. OBJECTIVES: We performed a systematic review and meta-analysis of epidemiological literature to investigate the relationship between maternal air pollution exposure and CHDs risk in offspring. The presence of heterogeneity and publication bias across available studies were also examined. METHODS: An extensive literature search of epidemiological studies pertaining to air pollution and CHDs, published in English language, until August 1, 2019 was conducted. Summary risk estimates of pollution-outcome combinations were calculated for i) risk per specific increment of concentration and ii) risk at high versus low exposure level in each study using fixed-effect model or random-effects model. RESULTS: A total of 26 studies were finally included. In the meta-analyses, high versus low carbon monoxide (CO) exposure was associated with an increased risk of tetralogy of Fallot [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.04-1.41], yet particulate matter ≤ 5 µm (PM2.5) exposure was marginally associated with it. Increased risk of atrial septal defects (ASDs) was found for each 10 µg/m3 and 10 ppb increment in particulate matter ≤ 10 µm (PM10) and ozone (O3) exposure, respectively (OR = 1.04, 95% CI: 1.00-1.09; OR = 1.09, 95% CI: 1.02-1.17). Categorical nitrogen dioxide (NO2) exposure was associated with an increased risk of coarctation of the aorta (OR for high versus low = 1.14, 95% CI: 1.02-1.26). Analyses for other combinations yielded none statistically significant associations. Sensitive analyses showed similar findings. CONCLUSIONS: The summary effect estimates from this study suggest statistically significant associations between increased risk of specific CHDs subtypes and PM2.5, PM10, NO2, CO, and O3 exposures. Further studies, especially conducted in developing countries, with improvements in exposure assessing, outcome harmonizing, and mechanistic understanding are needed to elaborate the suggestive associations.


Assuntos
Poluição do Ar/estatística & dados numéricos , Cardiopatias Congênitas/epidemiologia , Exposição Materna/estatística & dados numéricos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monóxido de Carbono/análise , Exposição Ambiental/análise , Feminino , Cardiopatias Congênitas/induzido quimicamente , Humanos , Dióxido de Nitrogênio/análise , Razão de Chances , Ozônio/análise , Material Particulado/análise
14.
Environ Res ; 184: 109343, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32192989

RESUMO

BACKGROUND: The current evidence has presented mixed results between air pollutants exposure and the progression of tuberculosis (TB). The purpose of this study was to explore the association between short-term exposure to air pollutants and the risk of TB outpatient visits in Hefei, China. METHODS: Time-series analysis was used to assess the effect of short-term exposure to ambient air pollutants on the risk of TB outpatient visits. A Poisson generalized linear regression model combined with a distributed lag non-linear model (DLNM) was applied to explore the association. The effects of different gender (male, female), age (≤65 years old, >65 years old) and season (cold season, warm season) on the risk of TB were investigated by stratified analysis. Sensitivity analyses were conducted to test the robustness of our findings. RESULTS: A total of 22,749 active TB cases were identified from November 1, 2013 to December 31, 2018 in Hefei. The overall exposure-response curve showed that the concentration of particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) exposure were positively correlated with the risk of TB outpatient visits, while ozone (O3) and sulfur dioxide (SO2) exposure were negatively correlated with the risk of TB outpatient visits. The maximum lag-specific and cumulative relative risk (RR) of TB outpatient visits were 1.057 [95%CI: 1.002-1.115, lag 3 day] and 1.559 (95%CI: 1.057-2.300, lag 13 days) for each 10 µg/m³ increase in PM2.5; 1.026 (95% CI: 1.008-1.044, lag 0 day) and 1.559 (95%CI: 1.057-2.300, lag 07 days) for each 10 µg/m³ increase in NO2; 0.866 (95% CI: 0.801-0.935, lag 5 day) and 0.852 (95%CI: 1.01-1.11, lag 0-14 days) for each 10 µg/m³ increase in SO2 in the single-pollutant model. There was only a negative association between O3 exposure and the cumulative risk of TB outpatient visits (RR = 0.960, 95%CI: 0.936-0.984, lag 07 days). Stratified analyses showed that the effects of SO2 and O3 exposure were different between warm and cold seasons. The effect of NO2 exposure remained statistically significant in male, younger, and cold season subgroups. Besides, elderly people are more susceptible to PM2.5 exposure. CONCLUSION: This study suggests that exposure to PM2.5, NO2, SO2, and O3 are associated with the risk of TB outpatient visits. Seasonal variation may have a greater impact on the risk of TB outpatient visits compared with gender and age.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Tuberculose , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Material Particulado/análise , Material Particulado/toxicidade , Tuberculose/induzido quimicamente , Tuberculose/epidemiologia
15.
Cells ; 9(3)2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120844

RESUMO

Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment.


Assuntos
Cortactina/metabolismo , Metilação de DNA/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Proteólise , Ubiquitina Tiolesterase/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Lisina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Regiões Promotoras Genéticas , Ligação Proteica , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação
16.
Environ Res ; 180: 108843, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670082

RESUMO

BACKGROUND: Previous studies have shown that ambient air pollution exposure can increase the risk of type 2 diabetes mellitus (T2DM) significantly. In consideration of the common underlying pathophysiologic mechanisms, exposure to air pollution may also increase the risk of gestational diabetes mellitus (GDM), but the current evidence was inconsistent and has not well been systematically reviewed. Our goal was to perform a systematic review and meta-analysis assessing the association between air pollution exposure and GDM. METHODS: An extensive literature search was conducted in selected electronic databases for related human epidemiological studies published in English language. Summary effect estimates were calculated using random-effect models for a) risk per unit increase in continuous air pollutant concentration and b) risk of high versus low exposure level in individual study if each exposure that had been examined in ≥2 studies. We evaluated the heterogeneity using Cochran's Q test and quantified it by I2 statistic. Publication bias was also evaluated through the funnel plot when sufficient number of studies are available. RESULTS: A total of 11 studies evaluating the association between GDM and exposure to air pollution were identified finally. The summary odds ratio (OR) for incidence of GDM following a 10 µg/m3 increase in PM2.5 exposure during the second trimester was 1.04 (95% Confidence Interval (CI): 1.01, 1.09) and in NOx during the first trimester was 1.03 (95%CI: 1.00, 1.07) per 10 ppb increase, while for high versus low SO2 exposure during the second trimester was 1.25 (95%CI: 1.02, 1.53). High heterogeneity among study-specific results in majority of the analyses were observed, and attributed to different exposure assessment methods, populations, study locations, and covariates adjustment. Publication bias cannot be excluded because of the inclusion of small number of studies. CONCLUSIONS: The present study supports the evidence that air pollution exposure increases the risk the GDM, albeit the existence of high heterogeneity. Further studies are necessary to elaborate the suggestive associations. These results are of public health significance since worsening air pollution in developing countries has been expected to increase the risk of GDM development.


Assuntos
Poluição do Ar/estatística & dados numéricos , Diabetes Mellitus Tipo 2 , Diabetes Gestacional/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Poluentes Atmosféricos , Feminino , Humanos , Material Particulado , Gravidez
17.
Biomed Res Int ; 2019: 4860268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032347

RESUMO

Hematological malignancies including leukemia and lymphoma can severely impact human health. With the current therapies combined with chemotherapy, stem cell transplantation, radiotherapy, and immunotherapy, the prognosis of hematologic malignancies improved significantly. However, most hematological malignancies are still incurable. Therefore, research for novel treatment options was continuing with the natural product as one source. Icaritin is a compound extracted from a traditional Chinese herb, Epimedium Genus, and demonstrated an antitumor effect in various neoplasms including hematological malignancies such as leukemia, lymphoma, and multiple myeloma. In hematological malignancies, icaritin showed multiple cytotoxic effects to induce apoptosis, arrest the cell cycle, inhibit proliferation, promote differentiation, restrict metastasis and infiltration, and suppress the oncogenic virus. The proved underlying mechanisms of the cytotoxic effects of icaritin are different in various cell types of hematological malignancies but associated with the critical cell signal pathway, including PI3K/Akt, JAK/STAT3, and MAPK/ERK/JNK. Although the primary target of icaritin is still unspecified, the existing evidence indicates that icaritin is a potential novel therapeutic agent for neoplasms as with hematological malignancies. Here, in the field of hematology, we reviewed the reported activity of icaritin in hematologic malignancies and the underlying mechanisms and recognized icaritin as a candidate for therapy of hematological malignancies.


Assuntos
Produtos Biológicos/uso terapêutico , Epimedium/química , Flavonoides/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Flavonoides/química , Humanos , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Medicina Tradicional Chinesa , Mieloma Múltiplo/tratamento farmacológico
18.
Neoplasia ; 21(3): 311-321, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30772768

RESUMO

DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.


Assuntos
Metilação de DNA , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Integrina alfa6/genética , Fatores de Transcrição NFATC/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Ativação Transcricional , Linhagem Celular Tumoral , Epigênese Genética , Perfilação da Expressão Gênica , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Interferência de RNA , Transcriptoma
19.
Eur J Obstet Gynecol Reprod Biol ; 235: 42-48, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784826

RESUMO

OBJECTIVE: To compare the effects and complications of caesarean section (CSD) and vaginal delivery (VD) for pelvic floor function of parturients. METHODS: Multiple databases were searched for full-text articles regarding the clinical effects and complications of CSD and VD. Review Manager 5.0 was used for meta-analyses, sensitivity analysis and bias analysis. RESULTS: In total, 4491 patients were included in nine studies that met the eligibility criteria. Of these, 1527 women underwent CSD and 2944 women had a VD. The meta-analyses suggested significant differences in pelvic floor muscle strength [mean difference (MD) -11.94, 95% confidence interval (CI) -12.48 to -11.39, p < 0.00001, p for heterogeneity <0.00001, I² = 93%], vaginal muscle voltage (MD -9.45, 95% CI -9.73 to -9.16, p < 0.00001, p for heterogeneity <0.00001, I² = 94%), maximum urinary flow rate (MD -5.67, 95% CI -5.94 to -5.39, p < 0.00001, p for heterogeneity <0.00001, I² = 96%), stress urinary incontinence [odds ratio (OR) 0.45, 95% CI 0.37-0.55, p < 0.00001, p for heterogeneity = 0.79, I² = 0%] and pelvic organ prolapse (OR 0.59, 95% CI 0.50-0.70, p < 0.00001, p for heterogeneity = 0.24, I² = 23%) between the CSD group and the VD group. CONCLUSION: This study demonstrated that CSD is the preferred mode of delivery for pregnant woman in terms of pelvic floor function.


Assuntos
Cesárea/efeitos adversos , Parto Obstétrico/efeitos adversos , Distúrbios do Assoalho Pélvico/etiologia , Diafragma da Pelve/fisiopatologia , Parto Obstétrico/métodos , Feminino , Humanos , Força Muscular , Razão de Chances , Parto , Diafragma da Pelve/cirurgia , Gravidez , Vagina/fisiopatologia
20.
J Exp Clin Cancer Res ; 38(1): 11, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621723

RESUMO

BACKGROUND: Increasing evidence support an important role for DNA methylation in nasopharyngeal carcinoma (NPC). Here, we explored the role of circadian clock gene Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL) methylation in NPC. METHODS: We employed bisulfite pyrosequencing to determine the epigenetic change of ARNTL in NPC cell lines and tissues. ARNTL mRNA and protein expression in cell lines and tissues were detected by real-time PCR and western blotting. Then, we constructed cell lines overexpressing ARNTL and knocked down ARNTL to explore its function and effect on chemotherapy sensitivity of NPC cell lines to cisplatin in vitro and vivo. Finally, we investigated the potential molecular mechanism of ARNTL by gene set enrichment analysis (GSEA), dual Luciferase reporter assay and chromatin immunoprecipitation assay. RESULTS: ARNTL was hypermethylated, and its mRNA and protein were significantly down-regulated in NPC cell lines and tissues. When treated by 5-aza-2'-deoxycytidine, mRNA expression was up-regulated. Overexpression of ARNTL could suppress NPC cells proliferation in vitro and vivo while silencing of ARNTL using shRNA achieved opposite results. GSEA assay found that ARNTL was associated with cell cycle and ectopic ARNTL overexpression could induce G2-M phase arrest. Then, we identified and validated cyclin-dependent kinase 5 (CDK5) as the targeting gene of ARNTL by dual Luciferase reporter assay and chromatin immunoprecipitation assay. When transiently infected ARNTL-overexpression cells with PENTER-vector or PENTER-CDK5 plasmids, the later could reverse the suppressive effects of ARNTL on NPC cell proliferation. Moreover, ARNTL significantly enhanced sensitivity to cisplatin in NPC cells. CONCLUSIONS: ARNTL suppresses NPC cell proliferation and enhances sensitivity to cisplatin by targeting CDK5. ARNTL may represent a novel therapeutic target for NPC.


Assuntos
Fatores de Transcrição ARNTL/genética , Cisplatino/farmacologia , Quinase 5 Dependente de Ciclina/genética , Metilação de DNA , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase 5 Dependente de Ciclina/biossíntese , Resistencia a Medicamentos Antineoplásicos , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Distribuição Aleatória , Transcrição Genética
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