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1.
Ann Palliat Med ; 9(1): 8-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32005058

RESUMO

BACKGROUND: Recently, intraoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been demonstrated to be associated with improved outcomes after surgery for several cancers; however, the effect of intraoperative NSAIDs use on bladder cancer (BCa) is not known. Therefore, the present study investigated the association between intraoperative NSAIDs use and oncological outcomes after radical cystectomy (RC). METHODS: We retrospectively analyzed 248 patients with BCa who underwent RC. Kaplan-Meier analysis and a Cox regression model were used to evaluate the association between intraoperative NSAIDs (parecoxib) use and oncological outcomes after RC. RESULTS: After excluding 63 patients, 82 of the remaining 185 patients received parecoxib during surgery. In the parecoxib group, the overall recurrence rate did not decrease significantly (P=0.310). Time to recurrence, cancer-specific mortality, and overall mortality were not significantly different between the groups. Kaplan-Meier analysis showed no association of the intraoperative use of parecoxib with an improved recurrence-free survival (RFS) or overall survival (OS) (P=0.431, P=0.185, respectively). Similarly, the multivariate analysis model showed no association between the administration of parecoxib and RFS [hazard ratio (HR), 0.964; 95% confidence interval (CI), 0.599-1.551, P=0.878] or OS (HR, 1.043; 95% CI, 0.621-1.750; P=0.875). In these patients, elevated preoperative neutrophil-lymphocyte ratio (NLR) was demonstrated to be associated with RFS and OS. CONCLUSIONS: The present study found that intraoperative parecoxib use was not associated with improved outcome after BCa surgery. Prospective, randomized trials should be performed to further evaluate the results of this study.

2.
PLoS One ; 15(2): e0226888, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027663

RESUMO

Camellia oleifera Abel. (C. oleifera), as an important woody tree species producing edible oils in China, has attracted enormous attention due to its abundant unsaturated fatty acids and their associated benefits to human health. To reveal novel insights into the characters during the maturation period of this plant as well as the molecular basis of fatty acid biosynthesis and degradation, we conducted a conjoint analysis of the transcriptome and proteome of C. oleifera seeds from Hainan Island. Using RNA sequencing (RNA-seq) technology and shotgun proteomic method, 59,391 transcripts and 40,500 unigenes were obtained by TIGR Gene Indices Clustering Tools (TGICL), while 1691 protein species were identified from Mass Spectrometry (MS). Subsequently, all genes and proteins were employed in euKaryotic Orthologous Groups (KOG) classification, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to investigate their essential functions. The results indicated that the most abundant pathways were biological metabolic processes. There were 946 unigenes associated with lipid metabolism at the transcriptome level, with 116 proteins at the proteome level; among these, 38 specific proteins were involved in protein-protein interactions, with the majority being related to fatty acid catabolic process. The expression levels of 21 candidate unigenes encoding target proteins were further detected by quantitative real-time polymerase chain reaction (qRT-PCR). Finally, Gas Chromatography Mass Spectrometry (GC-MS) was carried out to determine the fatty acid composition of C. oleifera oil. These findings not only deepened our understanding about the molecular mechanisms of fatty acid metabolism but also offered new evidence concerning the roles of relevant proteins in oil-bearing crops. Furthermore, the lipid-associated proteins recognized in this research might be helpful in providing a reference for the synthetic regulation of C. oleifera oil quality by genetic engineering techniques, thus resulting in potential application in agriculture.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32015432

RESUMO

Inhalation of particulate matter (PM) radioactivity is an important pathway of ionizing radiation exposure. We investigated the associations between short-term exposures to PM gamma radioactivity with oxidative stress in COPD patients. Urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) of 81 COPD patients from Eastern Massachusetts were measured 1-4 times during 2012-2014. Daily ambient and indoor PM gamma activities (gamma-3 through gamma-9) were calculated based on EPA RadNet data and indoor-outdoor infiltration ratios. Linear mixed-effects models were used to examine the associations between biomarkers with PM gamma activities for moving averages from urine collection day to 7 days before. Our results indicate that ambient and indoor PM gamma activities were positively associated with 8-OHdG, with stronger effects for exposure windows closer to urine collection day. For per interquartile range increase in indoor PM gamma activities averaged over urine collection day and 1 day before, 8-OHdG increased from 3.41% (95% CI: -0.88, 7.88) to 8.87% (95% CI: 2.98, 15.1), adjusted for indoor black carbon. For MDA, the timing of greatest effects across the exposure week varied but was nearly all positive. These findings provide insight into the toxigenic properties associated with PM radioactivity and suggest that these exposures promote systemic oxidative stress.

4.
Obes Rev ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32003149

RESUMO

A growing body of research links traffic-related environmental factors to childhood obesity; however, the evidence is still inconclusive. This review aims to fill this important research gap by systematically reviewing existing research on the relationship between traffic-related environmental factors and childhood obesity. Based on the inclusion criteria, 39 studies are selected with environmental factors of interest, including traffic flow, traffic pollution, traffic noise, and traffic safety. Weight-related behaviours include active travel/transport, physical activity (PA), and intake of a high trans-fat diet or stress symptoms; weight-related outcomes are mainly body mass index (BMI) or BMI z-scores and overweight/obesity. Of 16 studies of weight-related behaviours, significant associations are reported in 11 out of 12 studies on traffic flow (two positively and nine negatively associated with PA), five out of six studies on traffic safety (four positively and one negatively associated with PA), one study on traffic pollution (positively with unhealthy food consumption), and one study on traffic noise (negatively associated with PA). Among 23 studies of weight-related outcomes, significant associations are reported in six out of 14 studies on traffic flow (five positively and one negatively associated with obesity outcome), seven out of 10 studies on traffic pollution (all positively associated with obesity outcome), and two out of five on traffic noise (all positively associated with obesity outcome). Our findings show that long-term traffic pollution is weakly positively associated with children's BMI growth, and traffic flow, pollution, and noise could affect weight-related behaviours. Associations between traffic density and noise and weight status are rather inconclusive.

5.
J Mater Chem B ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003397

RESUMO

Mn(iv)-Based nanoparticles (NPs) are effective in improving tumor oxygenation (hypoxia) and reducing endogenous hydrogen peroxide and acidity in the tumor region. However, the optimized reduction conditions of conventional Mn(iv)-based NPs are generally reported at pH ≤ 6.5, while the usual pH range of the tumor microenvironment (TME) is 6.5-7.0. The dissatisfactory imaging performance in the weakly acidic environment may limit their further application in tumor diagnosis. In this study, Mn(iii) was introduced in a nanoplatform, because it is reduced into Mn(ii) in weakly acidic environments. Arg-Gly-Asp (RGD) peptide-decorated bovine serum albumin (BSA) was employed as the stabilizer and scaffold to fabricate Mn(iii)- and Mn(iv)-integrated nanocomposites (RGD-BMnNPs) with suitable size, good stability, and excellent biocompatibility. The as-prepared NPs showed clear contrast enhancement at pH 6.5-6.9 in vitro as well as sensitive and rapid T1-weighted imaging performance within the tumor region in a glioblastoma (U87MG) orthotopic model, owing to the intrinsic disproportionation reaction of Mn(iii) in the weakly acidic environment. In addition, these NPs could be used for efficient siRNA delivery. They showed superior advantages in this process, including increased tumour uptake, improved tumor accumulation and enhanced therapeutic effects with the modulation of the TME. These novel albumin-stabilized manganese-based NPs combined with efficient drug delivery capacity hold great potential to serve as intelligent theranostic agents for further clinical translation.

6.
Anticancer Drugs ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31917700

RESUMO

Derivatives of bis-aryl urea have been widely investigated for their various biological activities, such as antiviral, anti-inflammatory and antiproliferative. We evaluated a new chemical entity consisting of bis-aryl urea moiety, N69B, for its anticancer activities and explored their underlying molecular mechanism. The compound inhibited proliferation of multiple types of murine and human cancer cells in vitro, and reduced tumor growth in mouse 4T1 breast tumor model in vivo. Protein microarray analysis revealed and western blot confirmed that the compound significantly increased protein levels of cathepsins, especially cathepsin D, a lysosomal aspartyl protease known to have various pathophysiological functions. Further studies showed that the compound induced tumor cell apoptosis through the Bid/Bax/Cytochrome C/caspase 9/caspase 3 pathway, in which cathepsin D appeared to be a main mediator. Unlike kinase inhibition commonly seen with many other anticancer bis-aryl urea derivatives, this unique mechanism of N69B may suggest potential of the compound as a novel anticancer drug.

7.
BMC Cancer ; 20(1): 42, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952506

RESUMO

Following publication of the original article [1], the authors reported an error in Fig 5 of this article, graphs presenting FCM and immunofluorescent for CD4T, CD8T and NK cell of the Control Groups (LL2, LL2-irradation, MCS-irradiation) were inadvertently duplicated from another parallel experiment.

8.
J Clin Lab Anal ; : e23218, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31968147

RESUMO

INTRODUCTION: Hemolysis is the main cause of unqualified clinical samples. In this study, we established a method for detecting and evaluating hemolysis in whole blood test. We used a mathematical formula for correcting the influence of hemolysis on complete blood cell count (CBC) so as to avoid re-venipuncture and obtain more accurate parameters of red blood cell detection, reduce the burden of patients, and improve the efficiency of diagnosis and treatment. METHODS: Hemolytic samples were selected and then corrected using the new formula. Plasma free hemoglobin (fHB) was used as the criterion to determine the degree of hemolysis; the uncertainty of measurement is acceptable as the limit value of deviation between the measured value and the revised value. Hemolysis simulation analysis in vitro and continuous monitoring of clinical patients were used to verify the correction effect. RESULTS: A total of 83 clinical samples with hemolysis were collected and analyzed; fHB 1.4 g/L was selected as the unacceptable value for clinical hemolysis detection. In hemolytic samples, the red blood cell parameters corrected by formula are significantly different from those uncorrected and had a good consistency with those before hemolysis. CONCLUSION: The results show that the hemolysis phenomenon of CBC has a significant impact on routine blood testing. By using the new formula, the influence of hemolysis on erythrocyte and related parameters can be quickly and easily corrected, thus avoiding venipuncture again for re-examination, reducing diagnostic errors, and saving medical resources.

9.
Epidemiol Infect ; 148: e1, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31910921

RESUMO

Chlamydia spp. are a group of obligate intracellular pathogens causing a number of diseases in animals and humans. Avian chlamydiosis (AC), caused by Chlamydia psittaci (C. psittaci) as well as new emerging C. avium, C. gallinacea and C. ibidis, have been described in nearly 500 avian species worldwidely. The Crested Ibis (Nipponia nippon) is a world endangered avian species with limited population and vulnerable for various infections. To get a better understanding of the prevalence of Chlamydia spp. in the endangered Crested Ibis, faecal samples were collected and analysed. The results confirmed that 20.20% (20/99) of the faecal samples were positive for Chlamydiaceae and were identified as C. ibidis with co-existence of C. psittaci in one of the 20 positive samples. In addition, ompA sequence of C. psittaci obtained in this study was classified into the provisional genotype Matt116, while that of C. ibidis showed high genetic diversity, sharing only 77% identity with C. ibidis reference strain 10-1398/6. We report for the first time the presence of C. ibidis and C. psittaci in the Crested Ibis, which may indicate a potential threat to the endangered birds and should be aware of the future protection practice.

10.
ESC Heart Fail ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31986240

RESUMO

AIMS: Patients with heart failure (HF) are typically designated as having reduced, mid-range, or preserved ejection fraction (EF) (HFrEF, HFmrEF, or HFpEF, respectively) because of the importance of left ventricular EF (LVEF) on therapeutic decisions and prognosis. However, such designations are not necessarily static, as there are many transitions among the three HF phenotypes during follow-up. This prospective longitudinal cohort study sought to examine the HF transitions over time and their clinical characteristics, prognosis, and response to medical therapy. METHODS AND RESULTS: We identified 1920 patients from a prospective cohort with a primary diagnosis of HF between 1 January 2007 and 31 December 2012. The enrolled HF patients were re-classified into three groups on the basis of baseline and 1 year follow-up echocardiography: HF with improved EF (HFiEF), HF with deteriorated EF (HFdEF), and HF with unchanged EF (HFuEF). The primary outcome was 5 year all-cause mortality. According to 1 year follow-up echocardiography, 490 (25.5%) were diagnosed as HFiEF, 179 (9.3%) as HFdEF, and 1251 (65.2%) as HFuEF. Ischaemic heart disease was an independent predictor of HFdEF, and beta-blocker prescription was an independent predictor of HFiEF. During the 5 year follow-up, patients with HFdEF had higher mortality, whereas patients with HFiEF had lower mortality. After adjustment, HFiEF, compared with HFuEF, was associated with a 62.1% decreased risk for mortality. Finally, the use of beta-blockers was associated with improved prognosis of patients with HFiEF and HFuEF. CONCLUSIONS: In this cohort of patients with HF, LVEF is a dynamic factor related to coexisting conditions and drug therapy. HFiEF and HFdEF are distinct HF phenotypes with different clinical outcomes than other phenotypes.

11.
Int J Biol Macromol ; 147: 233-240, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31923517

RESUMO

The polysaccharide (OJP1), extracted from the root of Ophiopogon japonicus, is a well-known traditional Chinese medicine used to treat cardiovascular diseases. The present study was set up to investigate the cardioprotective effect of OJP1 on isoproterenol (ISO)-induced myocardial ischemia injury in rats. Results showed that pretreatment with OJP1 (100, 200 and 300 mg/kg) significantly reduced ISO-induced ST-segment elevation and the heart index, attenuated the levels of marker enzymes (AST, LDH, CK and CK-MB), along with a significantly enhanced the activities of ATPases. Moreover, pretreatment with OJP1 not only enhanced the activities of SOD, GPx and CAT in serum and myocardium, but also decreased the level of MDA. The biochemical and histopathological analysis also showed that OJP1 can alleviate the myocardial injury induced by ISO. Taken together, our results indicated that oral administration of OJP1 offered significant cardioprotective effect against the damage induced by ISO through enhancement of endogenous antioxidants.

12.
Pharm Biol ; 58(1): 89-97, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31906765

RESUMO

Context: Osteoarthritis (OA) is a degenerative arthrosis sickness. Astragaloside IV (AS-IV) functions by relieving inflammatory damage.Objective: We aimed to investigate the mechanism by which AS-IV protects ATD cells from lipopolysaccharide (LPS)-induced damage.Materials and methods: ATDC5 cells were transfected with miR-203 inhibitor and NC inhibitor (150 nM) or pEX-MyD88 and sh-MyD88 (50 nM) for 48 h, pre-treated by 15 µg/mL AS-IV for 24 h, then treated by 5 µg/mL LPS for 12 h. Dual-luciferase activity testing was used to determine whether miR-203 could bind to MyD88. CCK-8 and flow cytometry were used to detect cell activity and apoptosis, respectively, and qRT-PCR, western blots, and ELISA were performed to detect expression levels of miR-203 and inflammatory cytokines.Results: Based on the 50% inhibiting concentration (IC50), there was no significant difference of AS-IV (0 to 15 µg/mL) on cell viability. Fifteen µg/mL was the optimal concentration of AS-IV in treating LPS-induced inflammatory damage in subsequent experiments since this was a semi-lethal concentration. AS-IV significantly reduces LPS-induced viability, apoptosis and the release of TNF-α, IL-6 and iNOS mainly through up-regulating miR-203. Further, MyD88 was a target gene of miR-203 and negatively regulated by miR-203. Knockdown of MyD88 inhibited LPS-induced inflammatory damage by inhibiting the NF-κB signal pathway.Discussion and conclusions: AS-IV protects ATDC5 cells against LPS-induced damage mainly via regulating miR-203/MyD88. Our results support a theoretical basis for in-depth study of the function of AS-IV and the clinical cure of OA.

13.
Sci Total Environ ; 703: 135523, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767293

RESUMO

Chronic obstructive pulmonary disease (COPD) and tracheal, bronchus, and lung (TBL) cancers are among the leading causes of mortality worldwide. Many environmental factors have been linked to COPD and TBL cancers. This study examined the associations of cumulative environmental quality indices with COPD mortality and TBL cancers mortality, respectively. Environmental Quality Index (EQI) was constructed to represent cumulative environmental quality for the overall environment and 5 major environmental domains (e.g., air, water, built). Associations of each EQI indices with COPD mortality and TBL cancers mortality, across 3109 counties in the 48 contiguous states of the US, were examined using simultaneous autoregressive (SAR) models. Stratified analyses were conducted in females versus males and according to rural-urban continuum codes (RUCC) to assess the heterogeneity across the overall population. Overall poor environmental quality was associated with a percent difference (PD) of 0.75 [95% confidence intervals (95% CI), 0.46, 1.05] in COPD mortality and an PD of 1.22 (95% CI, 0.97, 1.46) in TBL cancers mortality. PDs were higher in females than in males for both COPD and TBL cancers. The built domain had the largest effect on COPD mortality (PD, 0.85; 95% CI, 0.58, 1.12) while the air domain had the largest effect on TBL cancers mortality (PD, 1.54; 95% CI, 1.31, 1.76). The EQI-mortality associations varied among different RUCCs, but no consistent trend was found. This result suggests that poor environmental quality, particularly poor air quality and built environment quality may increase the mortality risk for COPD and that for TBL cancers. Females appear to be more susceptible to the effect of cumulative environmental quality. Our findings highlight the importance of improving overall and domain-specific cumulative environmental quality in reducing COPD and TBL cancer mortalities in the United States.

14.
Environ Res ; 181: 108919, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753466

RESUMO

The health effects associated with human exposure to airborne fine particulate matter (PM2.5) have been linked to the ability of PM2.5 to facilitate the production of excess cellular reactive oxygen species (oxidative potential). Concern about the adverse human health impacts of PM2.5 has led to the increased use of indoor air cleaners to improve indoor air quality, which can be an important environment for PM2.5 exposure. However, the degree to which the oxidative potential of indoor and personal PM2.5 can be influenced by an indoor air cleaner remains unclear. In this study we enrolled 43 children with physician diagnosed asthma in suburban Shanghai, China and collected two paired-sets of 48-h indoor, outdoor, and personal PM2.5 exposure samples. One set of samples was collected under "real filtration" during which a functioning air cleaner was installed in the child's bedroom, and the other ("false filtration") with an air cleaner without internal filters. The PM2.5 samples were characterized by inductively coupled plasma mass spectroscopy for elements, and by an alveolar macrophage assay for oxidative potential. The sources of metals contributing to our samples were determined by the EPA Positive Matrix Factorization model. The oxidative potential was lower under real filtration compared to sham for indoor (median real/sham ratio: 0.260) and personal exposure (0.813) samples. Additionally, the sources of elements in PM2.5 that were reduced indoors and personal exposure samples by the air cleaner (e.g. regional aerosol and roadway emissions) were found by univariate multiple regression models to be among those contributing to the oxidative potential of the samples. An IQR increase in the regional aerosol and roadway emissions sources was associated with a 107% (95% CI: 80.1-138%) and 38.1% (17.6-62.1%) increase in measured oxidative potential respectively. Our results indicate that indoor air cleaners can reduce the oxidative potential of indoor and personal exposure to PM2.5, which may lead to improved human health.

15.
Environ Sci Process Impacts ; 22(1): 131-143, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714569

RESUMO

High concentrations of ground-level ozone (O3) have been measured outdoors across China but there are limited measurements of O3 in microenvironments, including in homes, and for personal exposure. This highlights the need for cheaper methods to accurately make these measurements and to better capture fine-scale spatial variability in O3 across cities. With this in mind, we conducted a pilot study at six homes in Beijing, China, over 12 days to evaluate the use of portable, low-cost, time-resolved monitors for measuring O3 indoors and outdoors. We also assessed personal exposure for one adult in each home for two 48 hour periods using backpack-mounted monitors. Prior to and following sampling we collocated all monitors with a reference analyzer; we used data from these colocations to generate linear calibrations which we applied to all monitor data. Calibration slopes did not change significantly over the study although some intercepts differed. The average limit of detection (LOD) was 7.0 ppb, average root mean square error was 16.7 ppb, mean absolute error was 13.3 ppb and normalized root mean square error was 33%. Performance varied substantially between sensors, underscoring the importance of monitor-specific calibrations and determinations of measurement error. Outdoor concentrations varied spatially, with home-specific peak hourly averages of 32-165 ppb; indoor concentrations ranged from below the LOD to 15 ppb. Hour-averaged personal exposure was generally higher than O3 indoors, and at times exceeded ambient O3 indicating contributions to personal exposure from ambient sources of O3 away from the home. This work illustrates the feasibility of using these monitors to characterize distributions of O3 spatially and temporally when differences in concentrations are large, and outlines considerations for using these monitors to measure personal exposure.

16.
Horm Behav ; 117: 104589, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31593697

RESUMO

Studies have shown that the evolutionarily conserved neuropeptide oxytocin (OT) promotes various prosocial behaviors, yet there are few studies of the effect of OT on social judgments, especially on judgments when the actor's intention and the final outcome are incongruent. In a double-blind, placebo-controlled experiment, participants were asked to play the role of the recipient in a dictator game and to make social judgments about the dictator after intranasal OT administration. To isolate the outcome and the intention of the dictator's allocation, we developed a novel social judgment task in which recipients were told that 50% of the dictators' proposals would be reversed. The results showed that the effect of OT on social judgment was modulated by intention: OT increased goodness ratings only towards dictators with hyperfair intention. Our findings support the affiliative-motivation theory which states that OT enhances the affiliative motivation and recognition of positive-valence social stimuli.

17.
Nicotine Tob Res ; 22(1): 40-47, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-30590728

RESUMO

INTRODUCTION: Both prenatal smoke exposure and depression have been linked to lower birth weight, a risk factor for morbidity and mortality. Few studies have looked at the interaction between these risk factors and none have used a biomarker to objectively measure prenatal smoke exposure. The current study sought to examine independent and interactive effects of cotinine and depression on birth weight. The effect of race was also explored. METHOD: Data were drawn from a prospective study of pregnant women (N = 568) in the southeastern United States. Maternal demographic, health information, depressive symptoms, and birth data were collected via self-report and medical record abstraction. Prenatal blood samples were assayed for cotinine. RESULTS: Controlling for covariates, multiple regression analyses indicated that both cotinine and depressive symptoms independently predicted lower birth weight and a significant interaction was also observed. Upon probing the interaction, a negative association between cotinine levels and birth weight was found in the context of higher depression but not lower depression scores. Similarly, logistic regression analyses revealed a significant interaction between cotinine and depression, such that cotinine predicted having a baby less than 2500 g among women who fell above the indicated cutoff score. African American women had the highest levels of cotinine and lowest weight babies; however, race was not a significant moderator. CONCLUSIONS: Results suggest prenatal smoke exposure has a greater negative effect on birth weight for women endorsing co-occurring depressive symptoms. Findings can inform targeted interventions and assist medical providers with identifying women at increased risk for poor perinatal outcomes. IMPLICATIONS: Despite the common occurrence of smoking during pregnancy and prenatal depression, the interaction between these risk factors on birth weight has rarely been examined. Further, the extant results have been mixed, likely due in part to difficulties in measurement. The current study was the first to use prenatal cotinine to assess bias-free, continuous levels of prenatal smoke exposure. Results indicate that prenatal cotinine was a significant predictor of birth weight only in the context of maternal depressive symptoms. These findings have important implications for mitigating negative perinatal outcomes for pregnant women and their children.

18.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165554, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513833

RESUMO

Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

19.
Int J Hyg Environ Health ; 223(1): 116-123, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31588015

RESUMO

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) are commonly used biomarkers of oxidative stress. However, their associations with air pollutant exposure have not been consistent across studies. We hypothesize that the inconsistency is partly due to confounding of circulating melatonin. We analyzed urinary 6-sulfatoxymelatonin (aMT6s), a surrogate of circulating melatonin, along with 8-OHdG and MDA, in 159 healthy adults who had not taken melatonin supplementation. Within the natural range of endogenously-generated aMT6s (0.3-93.5 ng/mg creatinine) measured in this study, increasing aMT6s levels were significantly associated with increasing concentrations of 8-OHdG and MDA. Measurements of PM2.5, ozone (O3), and nitrogen dioxide (NO2), coupled with time-activity data, were used to calculate time-averaged personal exposures 12 -hour (12h) and 24-hour (24h) prior to urine collection. Without controlling for aMT6s, the relationships between pollutant exposure and 8-OHdG or MDA were not clear. After controlling for aMT6s, an interquartile range (IQR) increase in 12h PM2.5 and 12h NO2 exposure was associated with 6.1% [95%CI: 1.6%-10.8%] and 8.6% [1.3%-16.5%] increase in MDA, respectively. An IQR increase in 12h O3 exposure was associated with a 5.7% [1.9%-9.7%] in 8-OHdG. The findings suggest the need for controlling for aMT6s as a confounder in using urinary 8-OHdG and MDA as biomarkers of oxidative stress related to short-term air pollution exposure.

20.
Cell Death Dis ; 10(12): 948, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827081

RESUMO

Hypoxia and the hypovascular tumor microenvironment are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is of great importance to tumor survival and proliferation. There is little research regarding the role of Nuclear Factor of Activated T Cells 5 (NFAT5) in relation to carcinoma. Here, we explored the impact of NFAT5 on the biological behavior of PDAC and the underlying mechanism. We demonstrated that NFAT5 was highly expressed in PDAC and was related to poorer prognosis. Knockdown of NFAT5 lead to impaired proliferation of tumor cells caused by an aberrant Warburg effect. Mechanically, phosphoglycerate kinase 1 (PGK-1), which is the first enzyme generating ATP in glycolysis, was verified as a target gene of NFAT5. Over-expression of PGK1 compromised the aberrant oncological behavior caused by knockdown of NFAT5 both in vitro and in vivo. Clinical samples underwent positron emission tomography-computed tomography (PET-CT) examination and KrasG12D/+/Trp53R172H/+/Pdx1-Cre (KPC) mice were collected to support our conclusion.

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