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1.
Environ Health Perspect ; 128(1): 17011, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31939705

RESUMO

BACKGROUND: Pesticide residues have contaminated our environment and nutrition over the last century. Although these compounds are present at very low concentrations, their long-term effects on human health is of concern. The link between pesticide residues and Alzheimer's disease is not clear and difficult to establish. To date, no in vivo experiments have yet modeled the impact of this chronic contamination on neurodegenerative disorders. OBJECTIVES: We investigated the impact of fungicide residues on the pathological markers of Alzheimer's disease in a transgenic mouse model. METHODS: Transgenic (J20, hAPPSw/Ind) mice were chronically exposed to a cocktail of residues of cyprodinil, mepanipyrim, and pyrimethanil at 0.1µg/L in their drinking water for 9 months. We assessed the effects of fungicide residues on the pathological markers of the disease including Aß aggregates, neuroinflammation, and neuronal loss. Then, we studied the dynamics of Aß aggregation in vivo via a longitudinal study using two-photon microscopy. Finally, we investigated the molecular mechanisms involved in the production and clearance of Aß peptides. RESULTS: We found that a chronic exposure to three fungicide residues exacerbated aggregation, microgliosis, and neuronal loss. These fungicides also increased vascular amyloid aggregates reminiscent of cerebral amyloid angiopathy between 6 and 9 months of treatment. The mechanism of action revealed that fungicides promoted Aß peptide fibril formation in vitro and involved an in vivo overexpression of the levels of the ß-secretase-cleaving enzyme (BACE1) combined with impairment of Aß clearance through neprylisin (NEP). CONCLUSIONS: Chronic exposure of the J20 mouse model of Alzheimer's disease to a cocktail of fungicides, at the regulatory concentration allowed in tap water (0.1µg/L), strengthened the preexisting pathological markers: neuroinflammation, Aß aggregation, and APP ß-processing. We hypothesize prevention strategies toward pesticide long-term exposure may be an alternative to counterbalance the lack of treatment and to slow down the worldwide Alzheimer's epidemic. https://doi.org/10.1289/EHP5550.

2.
Int J Legal Med ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802193

RESUMO

Custodial deaths refer to the death of an individual who is in prison, a detention center, or a police station. The present study aims to retrospectively analyze cases of custodial deaths examined at Tongji Medico Legal Expertise Center in Hubei (TMECH). A total of 172 out of 5853 cases were screened at TMECH from January 1999 to December 2016. Male preponderance was observed in 172 cases (male-female ratio: 5:1). Natural deaths accounted for the majority (70.93%), followed by suicide (16.28%), accidents (3.49%), homicides (4.65%), and undetermined causes (4.65%). The most common natural cause was cardiovascular disease. Custodial deaths occurred more frequently in prisons and detention houses than in police cells (63%, 63%, and 46%, respectively). Among the 172 cases, 105 deaths occurred after resuscitation failure despite the individual being sent to the hospital. The average age across cases was 36.3 years, and 90% of the deceased were aged under 50 years. Since there is no officially reported data regarding the prevalence of causes and manners of custodial deaths in China, our analysis contributes to enhancing the understanding of such deaths in central China and serves as a reference for law enforcement to develop a prevention program to reduce incidents of mortality in custody.

3.
J Cancer ; 10(27): 6910-6914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839826

RESUMO

CCL18 is a cytokine secreted by M2 type tumor associated macrophages, which frequently over-expressed in diverse human cancers. However, the clinical significance of serum CCL18 in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, serum CCL18 was initially quantified by enzyme-linked immunosorbent assay (ELISA) in 146 patients with LSCC, 25 patients with precancerous lesions and 72 healthy volunteers. In addition, the correlations between serum CCL18 and clinicopathological parameters were analyzed. Our data revealed that serum CCL18 was obviously increased in patients with LSCC. Moreover, serum CCL18 level was significantly associated with primary tumor site (Glottic vs Others), T classification (T1+T2 vs T3+T4), clinical stage (I+II vs III+IV) and lymph node metastasis (N0 vs N+). Survival analysis demonstrated that patients with high serum CCL18 displayed a shorter survival time than those in patients with low serum CCL18. Importantly, serum CCL18 level and clinical stage were independent prognostic factors in patients with LSCC. Taken together, serum CCL18 could be used as a promising biomarker in patients with LSCC.

4.
Biomed Res Int ; 2019: 5049248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886221

RESUMO

Background: Rapid on-site evaluation (ROSE) is commonly used to evaluate the adequacy of biopsy materials in fine-needle aspiration; however, the diagnostic performance of ROSE during fiber optic bronchoscopy (FOB) biopsy under direct vision is rarely reported. Here, we evaluated the role of ROSE during FOB biopsy of visible lesion in trachea or bronchi. Methods: The role of ROSE was prospectively evaluated in consecutive bronchoscopy specimens obtained between January 2016 and January 2018. The agreement and accuracy between ROSE and final histopathological interpretation were assessed. The frequency and possible reasons for discrepancy between ROSE and definitive histopathology results were identified. Histological and cytological classification was performed according to the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) criteria of lung ADCs classification. Results: The study enrolled 651 patients, of which 33 were excluded because of insufficient cells. Final diagnosis of malignancy was achieved in 462 cases (74.8%), whereas 156 cases (25.2%) were nonmalignant. ROSE and pathology were well correlated for the diagnosis of squamous cell carcinoma (SCC) (Kappa = 0.718, p < 0.05), adenocarcinoma (AdC) (Kappa = 0.662; p < 0.05) and small cell lung cancer (SCLC) (Kappa = 0.955; p < 0.05). In 24 cases diagnosed as malignant by ROSE and nonmalignant by pathology, the lesion tissues were surgically excised and re-analyzed, and the 24 cases were finally confirmed as malignant by pathology. Conclusions: ROSE technique allows bronchoscopists to obtain viable and adequate material for the diagnosis of histopathology, and provides them with an onsite preliminary diagnosis especially in cases with inconclusive macroscopic appearance. ROSE and pathology should be used in combination to increase the accuracy of diagnosis.

5.
Mil Med Res ; 6(1): 34, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31718713

RESUMO

BACKGROUND: Both periodontal disease and benign prostatic hyperplasia are age-related diseases that affect millions of people worldwide. Hence, this study aimed to investigate the association between periodontal disease and the risk of benign prostatic hyperplasia. METHODS: A total of 4930 participants were selected from an available health examination that was carried out in 2017, only males were considered for further analysis. All eligible males were divided into benign prostatic hyperplasia and normal groups, the benign prostatic hyperplasia group was then divided into prostate volume ≤ 60 g and > 60 g subgroups; all their periodontal status was extracted and then into normal (CPI score of 0), periodontal disease (CPI score between 1 and 4), and periodontitis (CPI score between 3 and 4) groups. The correlation between periodontal disease and benign prostatic hyperplasia was investigated using logistic regression analyses and greedy matching case-control analysis. Subgroup analysis based on prostate volume was also performed. All analyses were conducted with SAS 9.4 software. RESULTS: A total of 2171 males were selected for this analysis. The presence of periodontal disease significantly increased the risk of benign prostatic hyperplasia by 1.68 times (OR = 1.68, 95% CI: 1.26-2.24), and individuals with periodontitis showed a higher risk (OR = 4.18, 95% CI: 2.75-6.35). In addition, among matched cases and controls, this association remained robust (periodontal disease: OR = 1.85, 95% CI: 1.30-2.64; periodontitis: OR = 4.83, 95% CI: 2.57-9.07). Subgroup analysis revealed that periodontal disease significantly increased benign prostate hyperplasia risk as well (for prostate volume ≤ 60 g: OR = 1.64, 95% CI: 1.22-2.20; for volume > 60 g: OR = 2.17, 95% CI: 1.04-4.53), and there was a higher risk in the group with a prostate volume greater than 60 g. CONCLUSION: Periodontal disease is significantly and positively associated with an increased risk of benign prostatic hyperplasia. Further validation studies should be performed to explore the relationship between periodontal treatment and benign prostate hyperplasia.

6.
Cancer Sci ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778279

RESUMO

Metastasis is a critical determinant for the treatment strategy and prognosis in patient with squamous cell carcinoma of the head and neck (SCCHN). However, mechanisms underlying SCCHN metastasis are poorly understood. Our study sought to find out the key microRNAs and their functional mechanisms involved in SCCHN metastasis. The Cancer Genome Atlas (TCGA) data analysis, qPCR was used to quantify the level of miR-30e-5p in SCCHN and its clinical significance was further analyzed. A series of in vitro and in vivo experiments were applied to determine the effects of miR-30e-5p and its target AEG-1 on SCCHN metastasis. Mechanism investigation further revealed that AEG-1 was implicated in the angiogenesis and metastasis mediated by miR-30e-5p. Overall, our study validates that miR-30e-5p is a valuable predictive biomarker and potential therapeutic target in SCCHN metastasis.

7.
BMC Cancer ; 19(1): 1054, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694589

RESUMO

BACKGROUND: Bladder cancer (BC) has become a major worldwide public health issue, especially non-muscle-invasive bladder cancer (NMIBC). A flood of related clinical practice guidelines (CPGs) have emerged; however, the quality and recommendations of the guidelines are controversial. We aimed to appraise the quality of the CPGs for NMIBC within the past 5 years and compare the similarities and differences between recommendations for therapies. METHODS: A systematic search to identify CPGs for NMIBC was performed using electronic databases (including PubMed, Embase, Web of Science), guideline development organizations, and professional societies from January 12, 2014 to January 12, 2019. The Appraisal of Guidelines Research & Evaluation (AGREE) II instrument was used to evaluate the quality of the guidelines. Intraclass correlation coefficient (ICC) analysis was performed to assess the overall agreement among reviewers. RESULTS: Nine CPGs were included. The overall agreement among reviewers was excellent. The interquartile range (IQR) of scores for each domain were as follows: scope and purpose 69.44% (35.42, 85.42%); stakeholder involvement 41.67% (30.56, 75.00%); rigour of development 48.96% (27.08, 65.63%); clarity and presentation 80.56% (75.00, 86.11%); applicability 34.38% (22.92, 40.63%) and editorial independence 70.83% (35.42, 85.42%). The NICE, AUA, EAU and CRHA/CPAM clinical practice guidelines consistently scored well in most domains. It was generally accepted that the transurethral resection of bladder tumour (TURBT) and intravesical chemotherapy should be performed in the management of bladder cancer. The application of chemotherapy was highly controversial in high risk NMIBC. The courses of BCG maintenance were similar and included 3 years of therapy at full maintenance doses. CONCLUSIONS: The quality of NMIBC guidelines within the past 5 years varied, especially regarding stakeholders, rigour and applicability. Despite many similarities, the recommendations had some inconsistencies in the details.

8.
Vision Res ; 164: 44-52, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31585388

RESUMO

In this study, we aimed to explore an objective, sensitive and quantitative measurement of interocular suppression in strabismic amblyopia. We compared 11 strabismic subjects with 12 normal vision subjects to explore the different response characterizations in normal eyes, nondominant and dominant eyes of strabismic subjects by using steady-state motion visual evoked potentials (SSMVEPs). Stimulation at different temporal frequencies was presented to two eyes by using an interocular dichoptic technique. Furthermore, canonical correlation analysis (CCA), signal-to-noise ratio (SNR) and some statistical methods, such as the paired t-test, analysis of variance (ANOVA) and correlation analysis, were used to analyze electroencephalography (EEG) signals. We proposed two indices-divergence J and suppression imbalance (SI) to describe the deficits in interocular suppression-and one index - mask attenuation coefficient (MAC)- to describe the influence of a dichoptic mask from the dominant eyes to nondominant eyes of strabismic subjects. A significant difference was found between nondominant and dominant eyes of strabismic subjects in SSMVEP response and SNR value while no apparent difference was observed between the two eyes in subjects with normal vision. There was a strong linear correlation between divergence J, SI and visual acuity difference of two eyes both in strabismic amblyopia and normal vision. A linear correlation was also found between visual acuity difference and MAC in patients with strabismic amblyopia. Our findings suggest that SSMVEPs can be an objective and quantitative method for measuring the interocular suppression in strabismus and assessing the deficits of strabismic amblyopia.

9.
Genes (Basel) ; 10(10)2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581635

RESUMO

Root system plays an essential role in water and nutrient acquisition in plants. Understanding the genetic basis of root development will be beneficial for breeding new cultivars with efficient root system to enhance resource use efficiency in maize. Here, the natural variation of 13 root and 3 shoot traits was evaluated in 297 maize inbred lines and genome-wide association mapping was conducted to identify SNPs associated with target traits. All measured traits exhibited 2.02- to 21.36-fold variations. A total of 34 quantitative trait loci (QTLs) were detected for 13 traits, and each individual QTL explained 5.7% to 15.9% of the phenotypic variance. Three pleiotropic QTLs involving five root traits were identified; SNP_2_104416607 was associated with lateral root length (LRL), root surface area (RA), root length between 0 and 0.5mm in diameter (RL005), and total root length (TRL); SNP_2_184016997 was associated with RV and RA, and SNP_4_168917747 was associated with LRL, RA and TRL. The expression levels of candidate genes in root QTLs were evaluated by RNA-seq among three long-root lines and three short-root lines. A total of five genes that showed differential expression between the long- and short-root lines were identified as promising candidate genes for the target traits. These QTLs and the potential candidate genes are important source data to understand root development and genetic improvement of root traits in maize.

10.
Ecol Indic ; 1072019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31478008

RESUMO

Understanding the effects of plant species diversity and trait composition on aboveground biomass is a central focus of ecology and has important implications for biodiversity conservation. However, the simultaneous direct and indirect effects of soil nutrients, species asynchrony, functional trait diversity, and trait composition for explaining the community temporal stability of aboveground biomass remain underrepresented in natural forests. Here, we hypothesized that species asynchrony relative to soil nutrients, functional trait diversity, and trait composition plays a central role in stabilizing the community temporal stability of natural forests. We tested this hypothesis using a structural equation model based on 10-year continuous monitoring data (i.e., three-time repeated forest inventories) in both second-growth and old-growth temperate forests in northeast China. Our results showed that the community temporal stability of aboveground biomass was driven by a strong direct positive effect of species asynchrony in both second-growth and old-growth temperate forests, whereas functional trait diversity and composition (i.e. community-weighted mean of leaf nitrogen content) were of additional importance in an old-growth forest only. Functional trait diversity decreased community-weighted mean of leaf nitrogen content in an old-growth forest, whereas this relationship was non-significant in a second-growth forest. Soil nutrients had non-significant effects on the community temporal stability of both second-growth and old-growth forests. Species asynchrony was the direct determinant of the community temporal stability of aboveground biomass in temperate forests. The direct effect of species asynchrony increased with forest succession, implying that temporal niche differentiation and facilitation increase over time. This study suggests that managing forests with mixtures of both early and late successional species or shade intolerant and tolerant species, not only species diversity, is important for maintaining forest stability in a changing environment. We argue that the species asynchrony effect is crucial to understand the underlying ecological mechanisms for a diversity-biomass relationship in natural forests.

11.
J Cancer ; 10(19): 4633-4638, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528227

RESUMO

As a classical ligand in the canonical Wnt/ß-catenin signaling pathway, the role of Wnt3a in laryngeal squamous cell carcinoma (LSCC) remains unclear. Therefore, the expression pattern of the Wnt3a protein in 222 primary LSCC, and 19 corresponding adjacent non-carcinoma specimens, was detected by immunohistochemistry and further correlated with clinicopathological parameters. The results showed that LSCC tissue expressed higher levels of the Wnt3a protein when compared to the corresponding adjacent non-cancerous tissues. High expression of Wnt3a was closely related to histological grade (P = 0.031), clinical stage (I+II / III+IV; P = 0.004), and lymph node metastasis (P = 0.03). Kaplan-Meier analysis evidenced that a worse overall survival (OS) was correlated to the group with high Wnt3a expression (P = 0.003). When stratified survival analyses were performed, patients with lymph node metastasis/advanced clinical stages and high Wnt3a expression had worse OS rates than patients with other features (P < 0.001). Finally, multivariate analysis showed that Wnt3a expression was an independent prognosis factor for LSCC patients. The current findings suggest that Wnt3a is tightly related to the LSCC progression and could serve as a valuable clinic biomarker for LSCC patients.

12.
Medicine (Baltimore) ; 98(35): e16972, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464942

RESUMO

Single nuclear polymorphism (SNP) of programmed cell death 1 (PD-1) was reported associated with hepatitis B virus (HBV) infection, but the SNP sites studied were limited. Whether the combination of 2 or more SNP sites could better represent the relationship between PD-1 SNP and HBV infection was not studied.Eight hundred ninety-eight HBV-infected patients (222 asymptomatic carriers [AsC], 276 chronic hepatitis B, 105 acute-on-chronic liver failure, and 295 liver cirrhosis) and 364 health controls of South China were enrolled in this study. Four PD-1 SNPs (rs10204525, rs2227982, rs41386349, and rs36084323) were selected and detected by TaqMan probe. The frequency of allele, genotype, and combination of different SNPs were compared between different groups.For allele frequency analysis, G allele of rs10204525 was protective factor (odds ratio (OR) = 0.823, 95% confidence interval (CI) = 0.679-0.997, P = .046) and T allele of rs2227982 was predisposing factor (OR = 1.231, 95% CI = 1.036-1.463, P = .018) in HBV infection. When analyzed in genotype frequency, the genotype GG of rs10204525 and CC of rs2227982 were protective factor of HBV infection. Combination of rs10204525 GG and rs2227982 CC was potent protective factor of HBV infection (OR = 0.552, 95% CI = 0.356-0.857, P = .007) and was also associated with lower HBV load (OR = 0.201, 95% CI = 0.056-0.728, P = .008) in AsC. The 4 SNP sites were not associated with progression of HBV-related liver disease.Rs10204525 and rs2227982 of PD-1 associate with HBV infection and combination of the 2 SNP sites can better predict host susceptibility in HBV infection.


Assuntos
Hepatite B/genética , Receptor de Morte Celular Programada 1/genética , Fatores Etários , Alelos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Testes de Função Hepática , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Fatores Sexuais
13.
Front Genet ; 10: 706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428137

RESUMO

Objective: The current study is aimed at exploring the relationship between chronic periodontitis and serotonin transporter (5-HTT) gene polymorphisms (rs6354 and rs12449783) in the Chinese Han population. Methods: This study included a total of 120 patients with chronic periodontitis and 125 healthy control subjects. The 5-HTT gene (rs6354 and rs12449783) was genotyped using oral mucosal tissue with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium was examined using Haploview. Genotype and allele frequencies were compared between the cases and controls using a χ2 test. Results: Genotype distribution of the 5-HTT gene polymorphisms rs6354 and rs12449783 in the control group conformed to Hardy-Weinberg equilibrium. The frequency of the AC genotype, the AC + CC genotype and C allele of the 5-HTT rs6354 polymorphism was higher in cases (P < 0.05) vs. the healthy control. The adjusted odds ratio (OR) was 1.910 (95%CI = 1.049-3.476) for the AC genotype, 2.026 (95%CI = 1.115-3.680) for the AC+CC genotype, and 1.875 for the C allele (95%CI = 1.089-3.228. Such an association was particularly strong in women for the AC genotype (OR = 2.167, 95%CI = 1.034-4.542). The genotype and allele frequencies of rs12449783 did not differ between the cases and controls. Haplotype C-C (rs6354-rs12449783) was also more frequent in the cases (OR = 2.372, 95%CI = 1.154-4.875, P = 0.016). Conclusion: Chronic periodontitis is associated with the 5-HTT gene rs6354 polymorphism, as well as rs6354/rs12449783 interaction.

14.
Hepatobiliary Pancreat Dis Int ; 18(5): 403-411, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31303562

RESUMO

BACKGROUND: Acute-on-chronic liver failure (ACLF) refers to the acute deterioration of liver function that occurs in patients with chronic liver disease. ACLF is characterized by acute decompensation, organ failure and high short-term mortality. Numerous studies have been conducted and remarkable progress has been made regarding the pathophysiology and pathogenesis of this disease in the last decade. The present review was to summarize the advances in this field. DATA SOURCES: A comprehensive search in PubMed and EMBASE was conducted using the medical subject words "acute-on-chronic liver failure", "ACLF", "pathogenesis", "predictors", and "immunotherapy" combined with free text terms such as "systemic inflammation" and "immune paralysis". Relevant papers published before October 31, 2018, were included. RESULTS: ACLF has two marked pathophysiological features, namely, excessive systemic inflammation and susceptibility to infection. The systemic inflammation is mainly manifested by a significant increase in the levels of plasma pro-inflammatory factors, leukocyte count and C-reactive protein. The underlying mechanisms are unclear and may be associated with decreased immune inhibitory cells, abnormal expression of cell surface molecules and intracellular regulatory pathways in immune cells and increased damage-associated molecular patterns in circulation. However, the main cause of susceptibility to infection is immune paralysis. Immunological paralysis is characterized by an attenuated activity of immune cells. The mechanisms are related to elevations of immune inhibitory cells and the concentration of plasma anti-inflammatory molecules. Some immune biological indicators, such as soluble CD163, are used to explore the pathogenesis and prognosis of the disease, and some immunotherapies, such as glucocorticoids and granulocyte colony-stimulating factor, are effective on ACLF. CONCLUSIONS: Overwhelming systemic inflammation and susceptibility to infection are two key features of ACLF. A better understanding of the state of a patient's immune system will help to guide immunotherapy for ACLF.

15.
Front Neurol ; 10: 670, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293507

RESUMO

Posterior cortical atrophy (PCA) is characterized predominantly by visual dysfunction that arises from bilateral impairments in occipital, parietal, and temporal regions of the brain. PCA is clinically identified based primarily on visual symptoms and neuroimaging findings. Region-specific gray and white matter deficits have been discussed in detail, and are associated with clinical manifestations that present with similar patterns of perfusion and metabolic findings. Here, we discuss both structural and functional changes in the ventral and dorsal visual streams along with their underlying relationships. We also discuss the most recent developments in neuroimaging characteristics and summarize correlations between distinct neuroimaging presentations.

16.
Cancer Med ; 8(10): 4782-4791, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31250987

RESUMO

PURPOSE: In the present study, we evaluated the expression and function of human long noncoding RNA (lncRNA) activated by DNA damage (NORAD) in human epithelial ovarian cancer (EOC). METHODS: NORAD expression was evaluated by qRT-PCR in EOC cell lines and in situ EOC clinical samples. Lentivirus-mediated NORAD downregulation was conducted in OVCAR-3 and ES-2 cells, and its effect on cancer cell proliferation, bufalin chemoresistance, cell-cycle transition in vitro, and xenotransplantation in vivo were examined, respectively. The likelihood of an lncRNA-microRNA (miRNA) signaling pathway was examined by probing the possible downstream competing target of NORAD, hsa-miR-155-5p. Moreover, hsa-miR-155-5p was knocked down in NORAD-downregulated EOC cells to functionally evaluate the correlation between NORAD and hsa-miR-155-5p in EOC. RESULTS: We found that NORAD was substantially upregulated in both EOC cell lines and human tumors. In OVCAR-3 and ES-2 cells, lentivirus-mediated NORAD downregulation had significant anticancer effects, as it suppressed cell proliferation, decreased bufalin chemoresistance, arrested cell-cycle transition, and inhibited xenograft growth. Also, hsa-miR-155-5p was confirmed to be the competing target of NORAD in EOC, and its knockdown in OVCAR-3 and ES-2 cells reversed the NORAD downregulation-induced anticancer functions. CONCLUSIONS: NORAD is upregulated in EOC. Inhibition of NORAD, possibly through endogenously competing against hsa-miR-155-5p, can be a new tumor-suppressing strategy in EOC.

17.
Doc Ophthalmol ; 139(2): 123-136, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31214918

RESUMO

PURPOSE: The traditional assessment of visual acuity and contrast sensitivity depends more on subjective judgments. Steady-state motion visual evoked potentials (SSMVEPs) can provide an objective and quantitative method to evaluate visual functions such as visual acuity and contrast sensitivity. Here, we explored the possibility of objective SSMVEP visual acuity and contrast sensitivity testing, and compared its performance with that of psychophysical methods. METHODS: In this study, we designed a specific concentric ring with oscillating expansion and contraction SSMVEP paradigm to assess visual acuity and contrast sensitivity. By changing the parameters of the paradigm, the SSMVEP paradigm with different contrasts and spatial frequencies corresponding to different visual acuity and contrast sensitivity was designed. Moreover, we proposed a threshold determination criterion to define the corresponding objective SSMVEP visual acuity and contrast sensitivity. RESULTS: We tested visual acuity and contrast sensitivity of sixteen healthy adults utilizing this paradigm with an electroencephalography system. Our data suggested that there was no significant difference between objective visual acuity and contrast sensitivity measurements based on the SSMVEPs and subjective psychophysical ones. CONCLUSION: Our study proved that SSMVEPs can be an objective and quantitative method to measure visual acuity and contrast sensitivity.


Assuntos
Sensibilidades de Contraste/fisiologia , Potenciais Evocados Visuais/fisiologia , Percepção de Movimento/fisiologia , Acuidade Visual/fisiologia , Adulto , Eletroencefalografia , Eletrorretinografia , Feminino , Humanos , Masculino , Psicofísica , Limiar Sensorial , Testes Visuais , Adulto Jovem
18.
PLoS Biol ; 17(5): e3000277, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31107867

RESUMO

Chz1 is a specific chaperone for the histone variant H2A.Z in budding yeast. The ternary complex formed by Chz1 and H2A.Z-H2B dimer is the major in vivo substrate of Swi2/snif2-related 1 (SWR1), the ATP-dependent chromatin remodeling enzyme that deposits H2A.Z into chromatin. However, the structural basis for the binding preference of Chz1 for H2A.Z over H2A and the mechanism by which Chz1 modulates the histone replacement remain elusive. Here, we show that Chz1 utilizes 2 distinct structural domains to engage the H2A.Z-H2B dimer for optimal and specific recognition of H2A.Z. The middle region of Chz1 (Chz1-M) directly interacts with 2 highly conserved H2A.Z-specific residues (Gly98 and Ala57) and dictates a modest preference for H2A.Z-H2B. In addition, structural and biochemical analysis show that the C-terminal region of Chz1 (Chz1-C) harbors a conserved DEF/Y motif, which reflects the consecutive D/E residues followed by a single aromatic residue, to engage an arginine finger and a hydrophobic pocket in H2A.Z-H2B, enhancing the binding preference for H2A.Z-H2B. Furthermore, Chz1 facilitates SWR1-mediated H2A.Z deposition by alleviating inhibition caused by aggregation of excess free histones, providing insights into how Chz1 controls the bioavailability of H2A.Z to assist SWR1 in promoter-specific installation of a histone mark. Our study elucidates a novel H2A.Z-recognition mechanism and uncovers a molecular rationale for binding of free histone by specialized histone chaperones in vivo.

19.
Biomed Pharmacother ; 115: 108891, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082772

RESUMO

Accumulating evidence has indicated the vital roles of long noncoding RNA (lncRNA) in the epithelial ovarian cancer (EOC). However, the function of lncRNA HAS2-AS1 in EOC is still unclear. This study aims to investigate the expression and role of HAS2-AS1 in EOC. In the cells and tissue of EOC, HAS2-AS1 expression was markedly up-regulated. Besides, the overexpression of HAS2-AS1 indicated the poor clinical outcome of EOC patients. Transcription factor CREB1 could bind with the promoter of HAS2-AS1 and activate its transcriptional expression. Functionally, HAS2-AS1 knockdown suppressed the proliferation, invasion and tumor growth of EOC cells in vitro and in vivo. Mechanical investigation found that HAS2-AS1 could relive the RUNX2 protein expression via sponging the miR-466, acting as miRNA sponge. In conclusion, this finding suggests the CREB1/HAS2-AS1/miR-466/RUNX2 axis in the in the EOC tumorigenesis, providing the novel insight for the molecular mechanism of EOC.

20.
J Thorac Dis ; 11(3): 744-752, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31019762

RESUMO

Background: This study aims to observe the effects of the intracoronary and peripheral venous administration of nicorandil for the postoperative myocardial microcirculation and short-term prognosis of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) treatment. Methods: A total of 140 STEMI patients were divided into three groups according to different patterns of administration: sequential nicorandil group, intracoronary nicorandil group and control group. The main observation indexes included coronary blood flow and myocardial perfusion immediately after PPCI, while the secondary observation indexes included major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF) during the period of hospitalization. Results: After PPCI, the difference in the proportion of patients with thrombolysis in myocardial infarction (TIMI) flow grade 3 among the three groups was statistically significant (P=0.036), where this proportion was higher in the sequential nicorandil group and intracoronary nicorandil group than in the control group (P=0.022 and P=0.047); The difference in corrected TIMI frame count (CTFC) among the three groups was statistically significant (P=0.022), where CTFC was lower in the sequential nicorandil group and intracoronary nicorandil group than in the control group (P=0.010, P=0.031); The differences in the proportion of patients with complete ST resolution (STR) and advancing of enzyme peak time to within 12 h between each two groups were statistically significant (P<0.001), where this proportion was the highest in the sequential nicorandil group; The difference in the CK-MB peak among the three groups was statistically significant (P=0.036), where the CK-MB peak was lower in the sequential nicorandil group than in the control group (P=0.012); The difference in the incidence of MACE between each two groups was statistically significant (P<0.001), where this incidence was the lowest in the sequential nicorandil group; The differences in the proportion of patients with advancing of enzyme peak time to within 14 h and LVEF among the three groups were not statistically significant (P=0.722 and P=0.284). Conclusions: Compared with intracoronary use alone, the intracoronary and peripheral intravenous use of nicorandil can better improve myocardial microcirculation and short-term prognosis.

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