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1.
Int J Nanomedicine ; 15: 387-400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021186

RESUMO

Introduction: Rare-earth nanoparticles in the environment and human body pose a potential threat to human health. Although toxic effects of rare-earth nanoparticles have been extensively studied, the effects on the early development are not well understood. In this study, we attempted to explain the toxic effects of neodymium oxide (Nd2O3) nanoparticles on early development. Methods: We added the Nd2O3 nanoparticles at different concentrations and recorded the mortality and malformation rate per 24 hrs under a microscope. The live embryos treated with Nd2O3 nanoparticles were imaged as movies and Z step lapses with a confocal microscope, and heart rates were counted for 30 s to measure the cardiac function. The live Tg (Flk1:EGFP) transgenic embryos exposed to Nd2O3 nanoparticles were observed under confocal microscope to measure the cerebrovascular development. Subsequently, we extracted the total protein for Western blot at 5 days post-fertilisation (dpf). Embryos were collected to undergo TUNEL staining for apoptosis detection. Results: Nd2O3 nanoparticles disturbed embryo development at high concentrations (>200 µg/mL). The mortality and malformation rate gradually increased in a dose-dependent manner by morphological observation, while the Nd2O3 median lethal concentration (LD50) was 203.4 µg/mL at 120 hrs post-fertilisation (hpf). Furthermore, the Nd2O3-treated embryos showed severe arrhythmia and reduced heart rate. We also observed the markedly cerebrovascular disappearance at middle concentration (100 and 200 µg/mL). The downregulated autophagy flux in brain blood vessels and increased apoptosis level in neurons might affect vessels sprouting and contribute to the vanished cerebrovascular. Conclusion: The results suggested that the embryos exposed to Nd2O3 activated the apoptosis pathway and induced toxicity and abnormal cardiac/cerebrovascular development.

2.
J Diabetes Res ; 2020: 8278574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32016123

RESUMO

Objective: The genetic variant rs2237895, located in the Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1) gene, has been replicated to be associated with type 2 diabetes mellitus (T2DM) susceptibility, but the relationship with lipids is conflicting. Furthermore, the common genetic predisposition to T2DM and lipids was not fully detected. Methods: In total, 5839 individuals (2220 were T2DM patients) across 2885 families were included. The effect of rs2237895 on T2DM and lipids was estimated using linear regression and logistic regression models after adjustment for multiple covariates. Mediation analysis was then used to test whether KCNQ1 participated in T2DM pathogenesis via lipid-mediated pathways. Results: Per allele-C of rs2237895 was associated with 17% (11-23%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%. Conclusion: KCNQ1 had pleiotropic effects on lipids and T2DM, and the unexpected genetic effect on association of HDL-C with T2DM was observed, indicating the different pathways to lipids and T2DM. Further research studies are needed to verify potential biological mechanisms.

3.
Atherosclerosis ; 297: 40-46, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32062138

RESUMO

BACKGROUND AND AIMS: Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. METHODS: We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. RESULTS: During an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78-3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53-3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52-16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32-5.05), and total major CV events (HR: 2.72, 95% CI: 2.09-3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36-1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38-1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13-1.82), CV death (HR: 1.77, 95% CI: 1.50-2.11), HF (HR: 1.43, 95% CI: 1.29-1.58), and total major CV events (HR: 1.46, 95% CI: 1.34-1.58). CONCLUSIONS: High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI).

5.
Mol Cell ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32023483

RESUMO

von Hippel-Lindau (VHL) is a critical tumor suppressor in clear cell renal cell carcinomas (ccRCCs). It is important to identify additional therapeutic targets in ccRCC downstream of VHL loss besides hypoxia-inducible factor 2α (HIF2α). By performing a genome-wide screen, we identified Scm-like with four malignant brain tumor domains 1 (SFMBT1) as a candidate pVHL target. SFMBT1 was considered to be a transcriptional repressor but its role in cancer remains unclear. ccRCC patients with VHL loss-of-function mutations displayed elevated SFMBT1 protein levels. SFMBT1 hydroxylation on Proline residue 651 by EglN1 mediated its ubiquitination and degradation governed by pVHL. Depletion of SFMBT1 abolished ccRCC cell proliferation in vitro and inhibited orthotopic tumor growth in vivo. Integrated analyses of ChIP-seq, RNA-seq, and patient prognosis identified sphingosine kinase 1 (SPHK1) as a key SFMBT1 target gene contributing to its oncogenic phenotype. Therefore, the pVHL-SFMBT1-SPHK1 axis serves as a potential therapeutic avenue for ccRCC.

6.
Med Sci Monit ; 26: e921847, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32001666

RESUMO

BACKGROUND This retrospective study investigated the clinical outcomes, radiological outcomes, and bone remodeling patterns associated with a Medial/Lateral Taper (M/L Taper) stem and Link Classic Uncemented (LCU) stem in 1-stage bilateral total hip arthroplasty (THA). MATERIAL AND METHODS The results of 52 patients who underwent 1-stage bilateral THA with a M/L Taper stem on one side and an LCU stem on the other between January 2012 and February 2015 were retrospectively compared. Patients were clinically assessed by the Harris hip score (HHS), visual analogue score (VAS) and incidence of complications. Radiological indicators were measured. Periprosthetic bone remodeling was assessed via bone mineral density (BMD) measurements. RESULTS The mean follow-up time was 5.2 years. At each follow-up, there was no difference in the HHS and VAS between the 2 groups. The neck-shaft angle, offset, vertical height of the rotational center and limb lengthening were lower in the M/L Taper group than in the LCU group (P<0.001). The Engh total score was lower in the LCU group (P=0.039). Significantly higher (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 1, 2, and 6. significantly lower (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 3 and 5. CONCLUSIONS Due to the increased postoperative neck-shaft angle, the full coated dual-wedge classic stem was prone to cause lower limb lengthening. The proximal coated single-wedge new stem patients were more likely to have an insufficient postoperative neck length. The new stem achieved load transfer and proximal fixation, leading to better proximal femoral bone preservation is more in line with human biomechanical characteristics.

7.
Food Funct ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003387

RESUMO

Alzheimer's disease, characterized by neuroinflammation and beta-amyloid protein plaques, is a memory-threatening neurodegenerative disease with no effective treatment. Here, the effect of bilberry anthocyanins (BA) on cognitive functions was evaluated using APP/PSEN1 transgenic Alzheimer's disease model mice and their WT littermates. Our results revealed that BA appreciably improves learning and memory abilities and reverses defects to cognitive functions in APP/PSEN1 mice. Furthermore, BA reverses brain, liver and kidney damage caused by Alzheimer's disease, with no significant changes in oxidative stress and lipid metabolism-related indicators. In addition, BA decreases serum and brain lipopolysaccharide (LPS) levels and increases fecal short-chain fatty acid content. Immunofluorescence and RT-PCR analysis results showed that BA fully activates the microglia and astrocytes, downregulates the expression of inflammatory factors (TNF-α, NF-Kß, IL-1ß, IL-6, COX-2, iNOS and CD33) and chemokine receptor CX3CR1, and upregulates the expression of microglia homeostatic factors (TREM2 and TYROBP) and Toll-like receptors (TLR2 and TLR4). Moreover, western blot analysis revealed that BA significantly upregulates the expression of synaptic and phagocytotic function-related proteins (CD68, synaptophysin and IRF7) in APP/PSEN1 mice. Altogether, we show for the first time that BA consumption reverses Alzheimer's disease-induced cognitive disfunction, decreases hippocampal neuroinflammatory responses, and induces phagocytosis of microglia to beta-amyloid protein plaques by regulating the CD33/TREM2/TYROBP signaling pathway in microglia.

8.
Cell Res ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051560

RESUMO

N6-methyladenine (N6-mA) of DNA is an emerging epigenetic mark in mammalian genome. Levels of N6-mA undergo drastic fluctuation during early embryogenesis, indicative of active regulation. Here we show that the 2-oxoglutarate-dependent oxygenase ALKBH1 functions as a nuclear eraser of N6-mA in unpairing regions (e.g., SIDD, Stress-Induced DNA Double Helix Destabilization regions) of mammalian genomes. Enzymatic profiling studies revealed that ALKBH1 prefers bubbled or bulged DNAs as substrate, instead of single-stranded (ss-) or double-stranded (ds-) DNAs. Structural studies of ALKBH1 revealed an unexpected "stretch-out" conformation of its "Flip1" motif, a conserved element that usually bends over catalytic center to facilitate substrate base flipping in other DNA demethylases. Thus, lack of a bending "Flip1" explains the observed preference of ALKBH1 for unpairing substrates, in which the flipped N6-mA is primed for catalysis. Co-crystal structural studies of ALKBH1 bound to a 21-mer bulged DNA explained the need of both flanking duplexes and a flipped base for recognition and catalysis. Key elements (e.g., an ALKBH1-specific α1 helix) as well as residues contributing to structural integrity and catalytic activity were validated by structure-based mutagenesis studies. Furthermore, ssDNA-seq and DIP-seq analyses revealed significant co-occurrence of base unpairing regions with N6-mA in mouse genome. Collectively, our biochemical, structural and genomic studies suggest that ALKBH1 is an important DNA demethylase that regulates genome N6-mA turnover of unpairing regions associated with dynamic chromosome regulation.

9.
Eur J Radiol ; 124: 108858, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035370

RESUMO

PURPOSE: To verify the feasibility of synthetic MRI in quantitative evaluation of lumbar intervertebral disk (IVD) degeneration, as compared to the conventional CarrPurcell-Meiboom-Gill (CPMG) T2 mapping approach. METHODS: Twenty-four patients with chronic low back pain participated in this study. Patients underwent routine lumbar MRI, CPMG T2 mapping, and synthetic MRI (MAGiC) acquisition. The degree of IVD degeneration was derived from T2-weighted images according to the Pfirrmann classification. The correlation between two T2 measurements was assessed by Pearson correlation and Bland-Altman analysis. Statistical differences of quantitative values obtained from MAGiC data across different degeneration grades were quantified by one-way ANOVA. ROC curves were used to test the sensitivity and specificity of CPMG and MAGiC T2 measurements for assessing Pfirrmann grading. RESULTS: T2 values obtained from CPMG and MAGiC data exhibited strong positive correlation (r = 0.962, p < 0.01). Significant negative correlations were found between quantitative values (p < 0.05) and the Pfirrmann grading. Quantitative values show significant difference across Pfirrmann grading groups (one-way ANOVA, p < 0.001). Additionally, post-hoc tests show significant differences of T1 and T2 between adjacent groups among grades I-IV (p < 0.05), while the significant differences of PD were only observed between adjacent groups among grades II-IV (p < 0.05). There is no significant difference between AUCs of T2 values obtained from CPMG and MAGiC data in differentiating grade I/ II, grade II/ III and grade III/IV. CONCLUSIONS: The synthetic MRI may be used to provide quantitative biomarkers for assessing the level of lumbar intervertebral disc degeneration.

10.
Neurol Sci ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31901124

RESUMO

INTRODUCTION: To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. METHODS: A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. RESULTS: There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P < 0.05). Both TSS and RI-TSS with GBF showed an inverse "S" curve relationship (R2 was 0.839 and 0.843, all P < 0.05). The AUC values of TSS-based and RI-TSS-based predictions of each endpoint were all greater than 0.7 (all P < 0.05), but the differences of the AUC values between TSS, RI-TSS, and GBF were not statistically significant (all P > 0.05). CONCLUSIONS: The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.

11.
Food Res Int ; 128: 108774, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31955744

RESUMO

The present study investigated the anti-obesity effects and its mechanism of capsanthin (CAP) in high-fat diet-induced obese C57BL/6J mice. Compared with untreated mice on a high-fat diet for 12 weeks, CAP at 200 mg kg-1 reduced the body weight by 27.5%, significantly reversed glucose tolerance, effectively decreased the serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and trimethylamine N-oxide levels, markedly increased microbial diversity. Furthermore, 16S rRNA gene sequencing of the cecal microbiota suggested that CAP increased the abundance of Bacteroidetes, Bifidobacterium and Akkermansia, decreased the abundance of Ruminococcus and the ratio of Firmicutes/Bacteroidetes. Moreover, predicted functional domain analysis indicated that CAP increased the gene abundance of replication and repair, and decreased the gene abundance of membrane transports and carbohydrate metabolisms. Therefore, it seems CAP exhibit anti-obesity effect and might be used as a potential agent against obesity.

12.
Postgrad Med ; : 1-9, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900018

RESUMO

Aims: Prevention and control of hypertension can be achieved by improving patient adherence to long-term treatment regimens. Non-adherence is an obstacle to chronic disease management. We studied the impact of value reference point and risk preference on patient adherence and influencing factors from the perspective of behavioral economics so as to offer targeted recommendations to improving patient adherence in low-income areas.Methods: A representative impoverished area, Qianjiang District in Chongqing was selected as the sample district. A cross-sectional survey using questionnaire augmented with an interview was conducted to collect information with 321 patients previously diagnosed with hypertension stage 3. Preference experiments conducted through scenario simulation were used to elicit and measure patients' value and risk preferences. We constructed a structural equation model to verify the impact of value reference points and risk preference on adherence behavior decision-making. Logistic regression models were constructed to analyze other factors that may influence adherence.Results: Adherence was determined by patients' value reference points (path coefficient = 0.876, p < 0.01) and risk preference (path coefficient = 0.715, p < 0.01). The factor loadings of all indicators on the latent variables were significant (p < 0.01). Hypertensive patients in our cohort adhered poorly to health management and were heavily influenced by knowledge of hypertension, expectation, health literacy and opportunity costs. Certainty effect, overconfidence and optimism significantly affected patients' risk preference in decision-making progress. In the face of the uncertain benefits of adherence, patients preferred to delay treatment until condition affected their quality of life, resulting in poor adherence. Satisfaction with current services and relationship with physicians, as well as type of drugs also influenced adherence.Conclusions: Adherence may be improved by changing patients' value reference points and perceptions through health education and better health service resources. One of the key to increasing adherence is through identifying and eliminating bias.

13.
Clin Epigenetics ; 12(1): 19, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992357

RESUMO

BACKGROUND: 5-Hydroxymethylcytosine (5hmC) is a novel epigenetic mark and may be involved in the mechanisms of tumorigenesis and malignant transformation. However, the role of 5hmC in ependymoma, the third most common brain tumor in children, remains unclear. The aim of this study sought to identify the characterization of 5hmC levels in pediatric posterior fossa ependymoma and to evaluate whether 5hmC levels could be a potential factor to predict clinical outcomes. RESULTS: Our results showed that 5hmC levels were globally decreased in posterior fossa ependymoma compared with normal cerebellum tissues (P < 0.001). Group A posterior fossa ependymomas had higher 5hmC levels than group B tumors (P = 0.007). Moreover, 5hmC levels positively correlated with Ki-67 index in posterior fossa ependymoma (r = 0.428, P = 0.003). Multivariate Cox hazards model revealed that patients with high 5hmC levels (> 0.102%) had worse PFS and OS than patients with lower 5hmC levels (< 0.102%) (PFS: HR = 3.014; 95% CI, 1.040-8.738; P = 0.042; OS: HR = 2.788; 95% CI, 0.974-7.982; P = 0.047). CONCLUSIONS: Our findings suggest that loss of 5hmC is an epigenetic hallmark for pediatric posterior fossa ependymoma. 5hmC levels may represent a potential biomarker to predict prognosis in children with posterior fossa ependymoma.

14.
Med Sci Monit ; 26: e918528, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954012

RESUMO

BACKGROUND Romidepsin (FK228) or depsipeptide, is a selective inhibitor of histone deacetylase 1 (HDAC1) and HDAC2. This study aimed to investigate the effects and molecular mechanisms of romidepsin (FK228) in a mouse model of acute kidney injury (AKI) induced by lipopolysaccharide (LPS). MATERIAL AND METHODS The mouse model of AKI was developed by intraperitoneal injection of LPS. The mice were also treated intraperitoneally with romidepsin (FK228) six hours following injection of LPS. Markers of renal injury were measured, including blood urea nitrogen (BUN), serum creatinine (SCR), and serum cystatin C (Cys C) were measured. Histology and transmission electron microscopy were performed to evaluate tissue injury further. Levels of HDACs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays were used to investigate the regulation of CYP2E1 expression. RESULTS Treatment with romidepsin (FK228) significantly reduced the levels of BUN, SCR, and Cys C induced by LPS. Histology of the mouse kidneys showed that treatment with romidepsin (FK228) reduced the degree of renal injury. CYP2E1 significantly reduced following treatment with romidepsin (FK228) in the mouse model of AKI. Also, acetylation of H3 was upregulated following treatment with romidepsin (FK228), and binding of hepatocyte nuclear factor-1 alpha (HNF-1a) on the CYP2E1 promoter was significantly increased. CONCLUSIONS In a mouse model of LPS-induced AKI, treatment with romidepsin (FK228) downregulated the expression of CYP2E1 by inhibiting the binding if HNF-1a with the CYP2E1 promoter to reduce renal injury.

15.
Stem Cell Res Ther ; 11(1): 36, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31973741

RESUMO

BACKGROUND: A growing body of evidence suggests that stem cell-derived exosomal microRNAs (miRNAs) could be a promising cardioprotective therapy in the context of hypoxic conditions. The present study aims to explore how miRNA-144 (miR-144), a miRNA contained in bone marrow mesenchymal stem cell (MSC)-derived exosomes, exerts a cardioprotective effect on cardiomyocyte apoptosis in the context of hypoxic conditions and identify the underlying mechanisms. METHODS: MSCs were cultured using the whole bone marrow adherent method. MSC-derived exosomes were isolated using the total exosome isolation reagent and confirmed by nanoparticle trafficking analysis as well as western blotting using TSG101 and CD63 as markers. The hypoxic growth conditions for the H9C2 cells were established using the AnaeroPack method. Treatment conditions tested included H9C2 cells pre-incubated with exosomes, transfected with miR-144 mimics or inhibitor, or treated with the PTEN inhibitor SF1670, all under hypoxic growth conditions. Cell apoptosis was determined by flow cytometry using 7-ADD and Annexin V together. The expression levels of the miRNAs were detected by real-time PCR, and the expression levels of AKT/p-AKT, Bcl-2, caspase-3, HIF-1α, PTEN, and Rac-1 were measured by both real-time PCR and western blotting. RESULTS: Exosomes were readily internalized by H9C2 cells after co-incubation for 12 h. Exosome-mediated protection of H9C2 cells from apoptosis was accompanied by increasing levels of p-AKT. MiR-144 was found to be highly enriched in MSC-derived exosomes. Transfection of cells with a miR-144 inhibitor weakened exosome-mediated protection from apoptosis. Furthermore, treatment of cells grown in hypoxic conditions with miR-144 mimics resulted in decreased PTEN expression, increased p-AKT expression, and prevented H9C2 cell apoptosis, whereas treatment with a miR-144 inhibitor resulted in increased PTEN expression, decreased p-AKT expression, and enhanced H9C2 cell apoptosis in hypoxic conditions. We also validated that PTEN was a target of miR-144 by using luciferase reporter assay. Additionally, cells treated with SF1670, a PTEN-specific inhibitor, resulted in increased p-AKT expression and decreased H9C2 cell apoptosis. CONCLUSIONS: These findings demonstrate that MSC-derived exosomes inhibit cell apoptotic injury in hypoxic conditions by delivering miR-144 to cells, where it targets the PTEN/AKT pathway. MSC-derived exosomes could be a promising therapeutic vehicle to facilitate delivery of miRNA therapies to ameliorate ischemic conditions.

16.
Environ Int ; 136: 105498, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31991238

RESUMO

Few large multicity studies have assessed acute effect of tropospheric ozone pollution on pneumonia risk. We aimed to examine the relation between day-to-day changes in ozone concentrations and hospital admissions for pneumonia in China. We conducted a national time-series study in 184 major Chinese cities from 2014 to 2017. City-specific relation between ozone concentrations and pneumonia admissions was evaluated using an over-dispersed generalized additive model. Random-effects meta-analysis was conducted to pool the city-specific estimates. Two-pollutant models were fitted to test the robustness of the relations. We also investigated potential effect modifiers. Overall, we observed increased admissions for pneumonia associated with ozone exposure. The national-average estimates per 10-µg/m3 increase in ozone were 0.14% (95% CI: 0.03%-0.25%) at lag 0 day in the whole year, 0.30% (95% CI: 0.17%-0.43%) at lag 0 day in the warm season, and 0.20% (95% CI: 0.05%-0.34%) at lag 1 day in the cool season. Two-pollutant models indicated that the ozone effects were not confounded by PM2.5, SO2, NO2 or CO. The association between ozone and pneumonia was stronger in the elderly. Ozone levels and gross domestic product per capita reduced the effects of ozone, and smoking enhanced the effects of ozone. In conclusion, we estimated an increase in daily pneumonia admissions associated with ozone exposure in China. As the first national study in China to report acute effect of ozone on pneumonia hospitalizations, our findings are incredibly meaningful in terms of both ozone pollution related policy development and pneumonia prevention.

17.
Sci Total Environ ; 704: 135318, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31780162

RESUMO

The level of eutrophication in reservoirs is dependent on their internal and external P loads. Identifying the P pollution characteristics and its fractional composition in sediments is therefore necessary to determine the potential bioavailability and dominant sources of P for effective water pollution control. In this study, we investigated the P pollution characteristics in the overlying water and sediment in a chain of reservoirs (the Panjiakou (PJK), Daheiting (DHT) and Yuqiao (YQ) Reservoirs) in North China. Our results showed that the P concentrations in the overlying water of the YQ Reservoir was higher than that of the PJK and DHT Reservoirs, but the sediment P loading and P bio-availability were lower than the PJK and DHT Reservoirs. However, the sediment P release risk in the YQ Reservoir was higher than the DHT and PJK Reservoirs. The YQ Reservoir was mainly polluted by internal sediment P release and external sources predominantly derived from the inflowing polluted Sha River Basin. Various forms of P in the DHT Reservoir decreased with depth, and the P in the overlying water column was mainly sourced from internal P release due to sediment accumulation of excess P from human activities. In recent years, the proportion of bio-available P (BAP) in the PJK and YQ Reservoirs had increased, and the proportion of the more inert Al-P and Ca-P in the PJK Reservoir decreased. Ca-P in the YQ Reservoir had also decreased, indicating that inert P has been gradually transformed into active P in the PJK and YQ Reservoirs in recent years. The observed differences in P loading and sedimentary P fractions indicate different pollution characteristics and sources between the three reservoirs. We therefore recommend site-specific remediation strategies for effective control on P pollution in the three eutrophic reservoirs.

18.
J Photochem Photobiol B ; 202: 111718, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790883

RESUMO

Metallic nanoparticles were extensively examined to explore their impending exploitations over pharmaceutical purposes. Current work attempting to explores the cytotoxic capacity of zinc oxide (ZnO) nanoparticles besides to human melanoma cell line (A375). Viability of cells was resoluted, and the promising cytotoxicity potential was exhibited by zinc oxide nanoparticles. Cellular adhesion and morphology was determined by propidium iodide assay. Characterization studies like UV-Spectroscopy, X-ray diffraction (XRD) investigation, transmission electron microscope (TEM), energy dispersive X-ray (EDX) Spec, and Fourier transform infrared (FT-IR) examination confirms the accessibility of measurement, form and volume. The mRNA expression of apoptotic genes like caspase 3, 8 and 9 was elevated followed by the exposure to ZnO nanoparticles and it was narrowly proved that ZnO nanoparticles stimulates the apoptotic cell necrosis at the transcriptional stage. Cardiospermum halicacabum down regulated the apoptotic gene expressions. Reactive oxygen species (ROS) accumulation was augmented at concentration reliant mode, that changed normalize numerous indicator pathways and manipulate the kinetic cellular actions. ZnO nanoparticle synthesized Cardiospermum halicacabum might persuades programmed cell necrosis via elevated ROS levels in cells. CH-ZnONPs was further stimulates the markers of apoptosis and aggravates necrosis of cancerous cells, toxicity to cells, and accretion of ROS. With sourced on above whole data, this might accomplished that CH-ZnONPs amalgamated Cardiospermum halicacabum appreciably possessed a toxicity to human melanoma cells (A375) via provoking the apoptotic cell necrosis, entailed feasible efficacy of CH-ZnONPs besides malignancy management.


Assuntos
Antineoplásicos/síntese química , Apoptose , Nanopartículas Metálicas/química , Sapindaceae/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Química Verde , Humanos , Melanoma/metabolismo , Melanoma/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sapindaceae/metabolismo , Óxido de Zinco/química
19.
DNA Cell Biol ; 39(1): 57-62, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794672

RESUMO

Mycobacterium tuberculosis (Mtb) is the causative agent of the disease tuberculosis (TB). Macrophages eliminate the Mtb, delivering it to the degradative, phagolysosomal compartment for degradation, in which reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NADPHO) plays an important role. In our study, we aimed at investigating the association of polymorphisms in neutrophil cytosolic factor 2 (NCF2) gene, the core component of NADPHO, with susceptibility of TB in the Western Chinese Han population. We conducted a case-control study of 900 cases and 1534 controls and genotyped four single-nucleotide polymorphisms within the NCF2 gene. We found that the rs10911362 variants were associated with a decreased TB risk in this population (odds ratio [ORG] = 0.83 [0.72-0.95], ORadd = 0.83 [0.72-0.95], ORdom = 0.78 [0.66-0.93], p < 0.05). rs10911362 might fall in a transcriptional factor binding site associated with ZNF410 and may be the expression quantitative trait loci (eQTL) for the SMG7 gene according to the Ensembl data. Our study demonstrated for the first time that the G allele of NCF2 rs10911362 provided a protective role against TB risk in the Western Chinese Han population.

20.
J Stroke Cerebrovasc Dis ; 29(2): 104537, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31806454

RESUMO

BACKGROUND AND PURPOSE: The safety and efficacy of intravenous thrombolytic therapy (IVT) for posterior circulation stroke (PCS) in the real world are rarely studied. This study was designed to evaluate the prestroke and baseline characteristics, stroke sub-types, complications, and outcomes of PCS patients and compare them with anterior circulation stroke (ACS) after intravenous thrombolysis. METHODS: Data of consecutive patients with PCS and ACS treated with alteplase in a standard dose of 0.9 mg/kg in our stroke center were collected and analyzed retrospectively. Presenting characteristics, hemorrhage transformation, mortality, and favorable outcomes (modified Rankin scale 0 or 1) at 90 days were compared between PCS and ACS patients. RESULTS: A total of 462 patients were included in this study, including 350 (75.8%) in ACS group and 112 (24.2%) in PCS group. A history of coronary artery disease was significantly more common in ACS patients than that in PCS patients (15.1% versus 6.3%, P = .015). There was no significant difference in fast glucose and baseline NIHSS scores between PCS and ACS groups. In PCS group, 7 patients (6.3%) had hemorrhage transformation after IVT and 5 patients (4.5%) were symptomatic versus 32 (9.1%) and 22 (6.3%) in ACS group (P > .05). 75.5% PCS patients versus 72.2% ACS patients had excellent recovery outcomes (mRS 0-1) at 90 days (P = .507). For PCS patients, logistic regression analysis after adjusting the covariates identified age (P = .047, OR .920, 95% CI = .847-.999) and atrial fibrillation (P = .007, OR 12.149, 95% CI = 1.966-75.093) as independent significant predictors of hemorrhage transformation. In addition, atrial fibrillation was also an independent predictor of symptomatic intracranial hemorrhage (P = .008, OR 21.176, 95% CI = 2.228-201.273). Multivariate logistic analysis identified hemorrhage transformation (P = .012; OR .131, 95% CI = .027-.644) and onset to drug time (P = .026, OR 1.006, 95% CI = 1.001-1.011) as independent predictors of functional independence (mRS 0-2). Symptomatic intracranial hemorrhage (P = .007, OR 15.094, 95% CI = 2.097-108.661) and baseline NIHSS score (P = .050; OR 1.070, 95% CI = 1.000-1.145) were independent predictors of mortality. CONCLUSION: Our results suggest that IVT in PCS patients is safe and effective as that in ACS patients. In PCS patients, long onset to needle time and hemorrhage transformation were identified as independent predictors of unfavorable outcomes.

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