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1.
Sci Total Environ ; 750: 142347, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33182206

RESUMO

BACKGROUND: Short-term exposure to PM2.5 has been widely associated with human morbidity and mortality. However, most up-to-date research was conducted at a daily timescale, neglecting the intra-day variations in both exposure and outcome. As an important fraction in PM2.5, PM1 has not been investigated about the very acute effects within a few hours. METHODS: Hourly data for size-specific PMs (i.e., PM1, PM2.5, and PM10), all-cause emergency department (ED) visits and meteorological factors were collected from Guangzhou, China, 2015-2016. A time-stratified case-crossover design with conditional logistic regression analysis was performed to evaluate the hourly association between size-specific PMs and ED visits, adjusting for hourly mean temperature and relative humidity. Subgroup analyses stratified by age, sex and season were conducted to identify potential effect modifiers. RESULTS: A total of 292,743 cases of ED visits were included. The effects of size-specific PMs exhibited highly similar lag patterns, wherein estimated odds ratio (OR) experienced a slight rise from lag 0-3 to 4-6 h and subsequently attenuated to null along with the extension of lag periods. In comparison with PM2.5 and PM10, PM1 induced slightly larger effects on ED visits. At lag 0-3 h, for instance, ED visits increased by 1.49% (95% confidence interval: 1.18-1.79%), 1.39% (1.12-1.66%) and 1.18% (0.97-1.40%) associated with a 10-µg/m3 rise, respectively, in PM1, PM2.5 and PM10. We have detected a significant effect modification by season, with larger PM1-associated OR during the cold months (1.017, 1.013 to 1.021) compared with the warm months (1.010, 1.005 to 1.015). CONCLUSIONS: Our study provided brand-new evidence regarding the adverse impact of PM1 exposure on human health within several hours. PM-associated effects were significantly more potent during the cold months. These findings may aid health policy-makers in establishing hourly air quality standards and optimizing the allocation of emergency medical resources.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Estudos Cross-Over , Serviço Hospitalar de Emergência , Exposição Ambiental/análise , Humanos , Material Particulado/análise , Material Particulado/toxicidade
2.
Sci Total Environ ; 750: 141672, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32862003

RESUMO

Contaminations by heavy metals in the environment always exist as a mixture of both metal and metalloid. Thus, it is a challenge to simultaneously remove both components due to their adverse chemical behaviors. Herein, effective cadmium (Cd) and arsenic (As) removal in aqueous solution was achieved by use of a novel composite, which was synthesized by Bacillus sp. K1 loaded onto Fe3O4 biochar (MBB). The combination with Bacillus sp. K1 provided new biosorption sites such as amine and hydroxyl groups in the composite surface, which significantly increasing the removal capability of Cd(II) by 230% when compared with the raw magnetic biochar. Both competition and synergy effects were found in binary system. Adsorption of As(III) extended active sites for capturing Cd(II), which appeared on the surface of the MBB as type B ternary surface complexes. The maximum adsorption capacity of Cd(II) and As(III) reached 25.04 and 4.58 mg g-1 in a binary system, respectively. In summary, this environmentally friendly composite is promising for simultaneous Cd(II) and As(III) remediation.


Assuntos
Arsênico , Poluentes Químicos da Água , Adsorção , Cádmio/análise , Carvão Vegetal , Fenômenos Magnéticos , Poluentes Químicos da Água/análise
3.
J Exp Med ; 218(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33104171

RESUMO

ILC2s are present in adipose tissue and play a critical role in regulating adipose thermogenesis. However, the mechanisms underlying the activation of adipose-resident ILC2s remain poorly defined. Here, we show that IL-33, a potent ILC2 activator, stimulates phosphorylation of AMPK at Thr172 via TAK1 in primary ILC2s, which provides a feedback mechanism to inhibit IL-33-induced NF-κB activation and IL-13 production. Treating ILC2s with adiponectin or an adiponectin receptor agonist (AdipoRon) activated AMPK and decreased IL-33-NF-κB signaling. AdipoRon also suppressed cold-induced thermogenic gene expression and energy expenditure in vivo. In contrast, adiponectin deficiency increased the ILC2 fraction and activation, leading to up-regulated thermogenic gene expression in adipose tissue of cold-exposed mice. ILC2 deficiency or blocking ILC2 function by neutralization of the IL-33 receptor with anti-ST2 diminished the suppressive effect of adiponectin on cold-induced adipose thermogenesis and energy expenditure. Taken together, our study reveals that adiponectin is a negative regulator of ILC2 function in adipose tissue via AMPK-mediated negative regulation of IL-33 signaling.

4.
BMC Oral Health ; 20(1): 316, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172456

RESUMO

BACKGROUND: To investigate the effects of Er:YAG laser pre-treatment on the dentin structure and shear bond strength of primary teeth. METHODS: Dentin specimens were prepared using freshly extracted intact primary molars and divided randomly into four groups based on the surface treatment applied. The control and etchant groups received no treatment and conventional acid etching treatment, respectively, while the energy and frequency groups received laser surface treatment with variable energy (50-300 mJ) and frequency (5-30 Hz) parameters. The morphology was observed using scanning electron microscopy. The surface-treated dentin slices were bonded to resin tablets, followed by thermocycle treatment. The shear strength was determined using a universal testing machine and de-bonded surfaces were observed using a stereomicroscope. RESULTS: SEM observation showed that the surface morphology of the dentin slices changed after etching as well as after Er:YAG laser pre-treatment with different energy and frequency values. The dentin tubules opened within a specific energy (50-200 mJ) and frequency (5-20 Hz) range. Beyond this range, the intertubular dentin showed cracks and structural disintegration. Shear strength tests showed no significant changes after acid etching. The shear strength increased significantly (P < 0.05) after Er:YAG laser pre-treatment compared with that of the control group. The shear strength increased within the same energy (50-200 mJ) and frequency (5-20 Hz) range as the tubule opening, but not significantly (P > 0.05). The most common mode of interface failure was adhesive (interface) failure, followed by mixed and resin cohesive failure. CONCLUSIONS: Pre-treatment using Er:YAG laser opens the dentinal tubules without the formation of a smear layer and improves the bonding strength between the primary teeth dentin and the resin composites.

5.
Front Immunol ; 11: 585094, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193406

RESUMO

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein in mammals. When released into the extracellular space, it acts as a damage-associated molecular pattern. This study investigates whether increased HMGB1 levels are found in the intestinal mucosa of ulcerative colitis (UC) patients, and whether an anti-HMGB1 neutralizing-antibody (HnAb) can inhibit the intestinal inflammation elicited by dextran sulfate sodium (DSS) in mice. Because toll-like receptor 4 (TLR4) is implicated in HMGB1-mediated immune cell activation, DSS colitis was also elicited in TLR4-deficient mice in the presence and absence of HnAb. The expression of HMGB1 in UC patients was examined. HnAb was administered via intraperitoneal injection to TLR4 deficient mice and their wild-type littermates, both being induced to colitis with DSS. Finally, the protective effect of HnAb and TLR4 deficiency were evaluated. In UC patients, HMGB1 was up-regulated in the inflamed colon. When administered during DSS application, HnAb alleviated the severity of colitis with a lower disease activity index, limited histological damages, and reduced production of proinflammatory cytokines. This antibody also limited colonic barrier loss, decreased colonic lamina propria macrophages and partially reversed the DSS treatment-associated dysbiosis. The protective effect of this antibody was enhanced in TLR4-deficient mice in some aspects, indicating that both additional HMGB1-mediated as well as TLR4-mediated inflammatory signaling pathways were involved in the induction of colitis by DSS. HnAb ameliorated colitis via macrophages inhibition and colonic barrier protection. It may therefore be a novel treatment option in colitis.

6.
Food Chem ; : 128565, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33199121

RESUMO

The aroma changes in instant white tea resulting from ß-glucosidase treatment was investigated by quantitative descriptive analysis (QDA), gas chromatography-mass spectrometry (GC-MS), odour activity value analysis (OAV), aroma reconstruction and omission tests. The grassy, floral and sweet notes increased significantly (P < 0.05), and the roasted note decreased significantly (P < 0.05) upon ß-glucosidase treatment. Quantitative analysis showed that the concentrations of benzaldehyde, benzeneacetaldehyde, (Z)-3-hexen-1-ol, linalool, phenylethyl alcohol, cis-linalool oxide, trans-linalool oxide, hexanol, hotrienol and (E)-2-hexen-1-ol increased significantly (P < 0.05) after treatment; however, (Z)-3-hexen-1-ol isomerized to (E)-2-hexen-1-ol. OAV analysis, aroma reconstruction and the omission test showed that the grassy, floral and sweet notes increased as the (Z)-3-hexen-1-ol, cis/trans-linalool oxide and benzeneacetaldehyde increased, whereas the roasted note declined under the same conditions. The enzymatic hydrolysis of glycosidic precursors and the auto-isomerization of volatile compounds provide new information for understanding how ß-glucosidase treatment improves the aroma of tea products.

7.
Biomater Sci ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201163

RESUMO

Cancer immunotherapy, which provides durable clinical responses by restoring or boosting the patient's immune system to fight cancer, has become a promising strategy for cancer treatment. However, modest response rates and on-target off-tumor toxicity largely limit extensive implementation of this approach in clinical settings. Advances in drug delivery and combination with other cancer treatments are able to effectively promote the potency of cancer immunotherapy. Engineered natural particulates, such as cells and their derivatives, have been recently developed as prospective drug delivery systems that comprehensively combine genetic engineering, synthetic materials, and nanotechnology to enhance anticancer efficacy. Here, recent advances in improving cancer immunotherapy have been summarized with a focus on using functionalized intact cells and cell derivatives including cell membranes and extracellular vesicles as drug vehicles. The advantages and challenges of these unique systems have been further elucidated in terms of clinical translation. The results presented in this review would contribute to the development of advanced therapies for treating cancers.

8.
FASEB J ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201521

RESUMO

Nucleophosmin (NPM1) mutations are the most frequent genetic alteration in acute myeloid leukemia (AML) and aberrant cytoplasm-dislocated NPM1 mutant is a distinct biological characterization of this disease. Our group previously reported that NPM1 mutant elevated autophagy activity and autophagy activation contributed to leukemic cell survival. However, the molecular mechanisms by which cytoplasmic NPM1 mutant involving in the autophagy pathway has not been fully elucidated. Here, we showed that Unc-51-like kinase 1 (ULK1) as a core autophagy protein was highly expressed in NPM1-mA positive OCI-AML3 cells and primary NPM1-mutated AML blasts. Meanwhile, we found that NPM1-mA could interact with ULK1 protein and positively regulated ULK1 protein levels. Mechanically, NPM1-mA promoted TRAF6-dependent K63 ubiquitination and further maintained ULK1 stability and kinase activity via miR-146a. In addition, ULK1 high expression-mediated autophagy activation and facilitated to leukemic cell proliferation. Finally, we demonstrated that restoring ULK1 expression, ULK1 inhibitor SBI-0206965 treatment and using shULK1 partially rescued the effect of NPM1-mA on autophagy and cell survival. In conclusion, our findings suggest that NPM1 mutant interacts with ULK1, and thus, maintains its protein stability, which is required for NPM1 mutant-mediated autophagic cell survival. These data extend our understanding of the functions of NPM1 mutant in the regulation of autophagy activation in NPM1-mutated AML.

9.
Small ; : e2005754, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201581

RESUMO

Nanoscale titanium nitride TiN is a metallic material that can effectively harvest sunlight over a broad spectral range and produce high local temperatures via the photothermal effect. Nanoscale indium oxide-hydroxide, In2 O3- x (OH)y , is a semiconducting material capable of photocatalyzing the hydrogenation of gaseous CO2 ; however, its wide electronic bandgap limits its absorption of photons to the ultraviolet region of the solar spectrum. Herein, the benefits of both nanomaterials in a ternary heterostructure: TiN@TiO2 @In2 O3- x (OH)y are combined. This heterostructured material synergistically couples the metallic TiN and semiconducting In2 O3- x (OH)y phases via an interfacial semiconducting TiO2 layer, allowing it to drive the light-assisted reverse water gas shift reaction at a conversion rate greatly surpassing that of its individual components or any binary combinations thereof.

11.
Int J Infect Dis ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33130209

RESUMO

OBJECTIVES: We described the prevalence of clofazimine (CFZ) resistance in a multidrug-resistant tuberculosis (MDR-TB) cohort in China. We also aimed to identify dynamic changes in CFZ susceptibility and its molecular mechanism after exposure to bedaquiline (BDQ) and/or CFZ. METHODS: The experimental settings were conducted based on our MDR-TB cohort receiving BDQ-containing regimens. Sequential isolates were obtained from patients. CFZ and BDQ susceptibility of isolates were determined using the minimum inhibitory concentration (MIC) method. The fragments of Rv0678 and pepQ were sequenced. RESULTS: A total of 277 patients infected with MDR-TB were included in our study. CFZ resistance was noted in 23 (23/277, 8.3%) isolates. The rate of acquired CFZ resistance (12/189, 6.3%) was significantly greater than that of primary resistance (11/88, 12.5%, P = 0.028). Out of 23 CFZ-resistant isolates, five (5/23) were BDQ-resistant, and the other 18 (18/23) were susceptible to BDQ. Of note, nine 9/23) out of 23 CFZ-resistant isolates had mutations within either target genes. Kaplan-Meier analysis demonstrated that the baseline CFZ resistance had no influence on time to culture conversion in our cohort (P = 0.828). Acquired CFZ resistance emerged in eight (8/94, 8.5%) patients during treatment for MDR-TB, including three patients receiving regimens without CFZ. CONCLUSIONS: Our results demonstrate the high rate of CFZ resistance among MDR-TB patients in China. Patients treated with BDQ-containing regimens achieve comparative culture conversion rate regardless of baseline CFZ susceptibility. The presence of acquired CFZ-resistance following BDQ treatment without known mutation indicates that other mechanisms conferring cross resistance to these two compounds may exist.

12.
Oxid Med Cell Longev ; 2020: 7875396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178387

RESUMO

Ischemic stroke is the major type of cerebrovascular disease usually resulting in death or disability among the aging population globally. Oxidative stress has been closely linked with ischemic stroke. Disequilibrium between excessive production of reactive oxygen species (ROS) and inherent antioxidant capacity leads to subsequent oxidative damage in the pathological progression of ischemic brain injury. Acupuncture has been applied widely in treating cerebrovascular diseases from time immemorial in China. This review mainly lays stress on the evidence to illuminate the possible mechanisms of acupuncture therapy in treating ischemic stroke through regulating oxidative stress. We found that by regulating a battery of molecular signaling pathways involved in redox modulation, acupuncture not only activates the inherent antioxidant enzyme system but also inhibits the excessive generation of ROS. Acupuncture therapy possesses the potential in alleviating oxidative stress caused by cerebral ischemia, which may be linked with the neuroprotective effect of acupuncture.

13.
Crit Care ; 24(1): 643, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172477

RESUMO

BACKGROUND: The impact of corticosteroid therapy on outcomes of patients with coronavirus disease 2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. METHODS: In this single-center retrospective observational study, patients with ARDS caused by COVID-19 between January 20, 2020, and February 24, 2020, were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. RESULTS: A total of 382 patients [60.7 ± 14.1 years old (mean ± SD), 61.3% males] were analyzed. The median of sequential organ failure assessment (SOFA) score was 2.0 (IQR 2.0-3.0). Of these cases, 94 (24.6%) patients had invasive mechanical ventilation. The number of patients received systemic corticosteroids was 226 (59.2%), and 156 (40.8%) received standard treatment. The maximum dose of corticosteroids was 80.0 (IQR 40.0-80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0-12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. CONCLUSION: In this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS.

14.
Opt Lett ; 45(22): 6190-6193, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186947

RESUMO

We report a photonic scheme to generate multiband and multi-format microwave signals based on a commercial dual-polarization Mach-Zehnder modulator (DP-MZM). The key novelty of this work is the compact signal generator benefitting from the single modulator and the flexible multi-format signals at the multiband. The upper Mach-Zehnder modulator (MZM) of the DP-MZM is used to generate an optical frequency comb, while the lower MZM is driven by baseband electrical coding or single-chirp signal to obtain the multi-format modulated optical signal. The proposed scheme is theoretically analyzed and experimentally demonstrated. A multiband phase-coded microwave signal with a bit rate of 2 Gb/s and complementary linearly chirped microwave waveform pairs with a time duration of 1 µs and a bandwidth of 2 GHz have been successfully generated. The performance of pulse compression of generated signals is also demonstrated.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33187993

RESUMO

Seagrasses can form mutualisms with their microbiomes that facilitate the exchange of energy sources, nutrients, and hormones, and ultimately impact plant stress resistance. Little is known about community succession within the belowground seagrass microbiome after disturbance and its potential role in the plant's recovery after transplantation. We transplanted Zostera marina shoots with and without an intact rhizosphere, and cultivated plants for four weeks while characterizing microbiome recovery and effects on plant traits. Rhizosphere and root microbiomes were compositionally distinct, likely representing discrete microbial niches. Furthermore, microbiomes of washed transplants were initially different from those of sod transplants, and recovered to resemble an undisturbed state within fourteen days. Conspicuously, changes in microbial communities of washed transplants corresponded with changes in rhizosphere sediment mass and root biomass, highlighting the strength and responsive nature of the relationship between plants, their microbiome, and the environment. Potential mutualistic microbes that were enriched over time include those that function in the cycling and turnover of sulfur, nitrogen, and plant-derived carbon in the rhizosphere environment. These findings highlight the importance and resiliency of the seagrass microbiome after disturbance. Consideration of the microbiome will have meaningful implications on habitat restoration practices. Importance Seagrasses are important coastal species that are declining globally, and transplantation can be used to combat these declines. However, the bacterial communities associated with seagrass rhizospheres and roots (the microbiome) are often disturbed or removed completely prior to transplantation. The seagrass microbiome benefits seagrasses through metabolite, nutrient, and phytohormone exchange, and contributes to the ecosystem services of seagrass meadows by cycling sulfur, nitrogen, and carbon. This experiment aimed to characterize the importance and resilience of the seagrass belowground microbiome by transplanting Zostera marina with and without intact rhizospheres and tracking microbiome and plant morphological recovery over four weeks. We found the seagrass microbiome to be resilient to transplantation disturbance, recovering after fourteen days. Additionally, microbiome recovery was linked with seagrass morphology, coinciding with increases in rhizosphere sediment mass and root biomass. Results of this study can be used to include microbiome responses in informing future restoration work.

16.
Physiol Behav ; : 113236, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33137345

RESUMO

BACKGROUND: Some evidence suggests that depression is more common in obese patients. This fact gives us a hint that obesity might be a promoter of depression, though a conclusion can not be drawn. The aim of the study was: (1) to confirm whether obesity induced by high-fat diet (HFD) promotes depression-like behaviors in mice, (2) to explore the protective role of insulin-like growth factor-1 (IGF-1) in such behavioral disorder of the animals and (3) to reveal whether mitochondrial mechanism was involved in such protective effect of the reagent. METHODS: C57BL/6 J mice were fed with HFD to establish a model of obesity. Then, the animals were separately or simultaneously treated with PEG-IGF-1, 666-15 (CREB blocker) and SR-18292 (PGC-1α blocker). After that, depression-like behaviors were assessed using sucrose preference test and tail suspension test. In hippocampus, respiratory control ratio, ATP generation and red/green fluorescence ratio were adopted to reveal mitochondrial function. Also in hippocampus, expressions of p-CREB and PGC-1α were measured using western blotting. RESULTS: HFD mice showed depression-like behaviors compared with control mice. Such diet also caused mitochondrial dysfunction and inhibition of CREB/PGC-1α signal pathway in hippocampus of these animals. After PEG-IGF-1 intervention, all the abnormalities mentioned above can be partly reversed. After 666-15 or SR-18292 treatment, such protective effect of PEG-IGF-1 can be attenuated, and the mice suffered from the re-deterioration of behavioral and mitochondrial abnormalities in hippocampus. CONCLUSION: IGF-1 alleviated depression-like behaviors and mitochondrial dysfunction through the activation of CREB/PGC-1α signal pathway in HFD mice.

18.
AAPS PharmSciTech ; 21(8): 318, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175290

RESUMO

The study is designed to formulate, optimize, and evaluate astaxanthin (ASTA)-loaded nanostructured lipid carrier (NLC) with an aim to improve its stability, water solubility, skin permeability and retention and reduce drug-related side effects. ASTA was extracted from Haematococcus pluvialis. ASTA-NLC was formulated by the technique of melt emulsification-ultrasonic and optimized taking solid:liquid lipid ratio, total lipid:drug ratio, drug concentration, emulsifier types, and amounts as independent variables with particle sizes (PS) and entrapment efficiency (EE) as dependent variables. The optimized formulation (N21) exhibited spherical surfaced stable nanoparticles of 67.4 ± 2.1 nm size and 94.3 ± 0.5% EE. Formulation N21 was then evaluated for its physiological properties, physicochemical properties, drug content, in vitro release and skin penetration, and retention analysis. The ASTA-NLC was found to be nonirritating, homogenous, and with excellent stability and water solubility. In vitro release studies showed the cumulative release rate of NLC was 83.0 ± 3.4% at 48 h. The skin penetration and retention studies indicated that cumulative permeability was 174.10 ± 4.38 µg/cm2 and the retention was 8.00 ± 1.62 µg/cm2 within 24 h. It can be concluded that NLC serves as a promising carrier for site specific targeting with better stability and skin penetration.

19.
Eur J Neurol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176022

RESUMO

BACKGROUND: Uric acid (UA) is an important endogenous free radical scavenger, which has been found to have neuroprotective effect. However, there is uncertainty about the relationship between UA change and outcome in acute ischemic stroke (AIS) patients with reperfusion therapy. METHODS: We consecutively enrolled AIS patients with reperfusion therapy. UA was measured upon admission and during hospitalization. The change of UA levels (ΔUA) was determined by calculating the difference between admission UA and the lowest UA among all follow-up measurements, with a positive ΔUA suggesting a decrease in UA levels. Functional outcome was assessed by modified Rankin Scale (mRS) at 3 months. Poor outcome was defined as mRS > 2. RESULTS: A total of 361 patients were included (mean age 68.7 ± 13.9 years, 54.3% males). The mean UA on admission was 355 ± 96.1 µmol/L. The median ΔUA was 121 µmol/L (IQR 50-192 µmol/L) and 18 (5%) patients had increased UA levels. UA on admission was positively associated with good outcome (p for trend=0.017). When patients were classified into quartiles by ΔUA, patients with the largest decrease of UA (Q4: 199-434 µmol/L) had a higher risk of poor outcome at 3 months compared to patients with the least decrease of UA (Q1: 0-57 µmol/L) (OR 2.55, 95% CI 1.09-5.98, p=0.031). The risk of poor outcome increased with ΔUA (p for trend=0.048). CONCLUSIONS: In patients with reperfusion therapy, high UA on admission was associated with a good 3-month outcome, while a more decrease in UA was associated with poor outcome.

20.
Environ Pollut ; : 115961, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33160737

RESUMO

Ambient fine particulate matter (PM2.5) can change the expression profile of microRNAs (miRs), which may play important roles in mediating inflammatory responses. The present study attempts to investigate the roles of miR-146a-5p in regulating cytokine expression in a human monocytic leukemia cell line (THP-1). Four types of PM2.5 extracts obtained from Beijing, China, were subjected to cytotoxic tests in THP-1 cells. These four PM2.5 extracts included two water extracts collected from non-heating and heating season (WN and WH), and two organic extracts from non-heating and heating season (DN and DH). Firstly, the four PM2.5 extracts caused cytotoxicity, oxidative stress responses, cytokine gene expressions and interleukin 8 (IL-8) release in THP-1 cells, with WH showing the highest cytotoxicity, WN showing the highest oxidative stress and inflammatory responses. Additionally, we observed expression of miR-146a-5p was significantly increased, with the maximal response of six folds in WN group. Cellular autophagy was initiated by PM2.5 indicated by related protein and gene expressions. Both RNA interference and autophagy inhibitor were applied to interrupt autophagy process in THP-1 cells. Autophagy dysfunction could alleviate IL-8 expression, suggesting autophagy process regulated cytokine expression and inflammatory response caused by PM2.5. A chemical inhibitor was applied to inhibit the function of miR-146a-5p, and then the expressions of IL-8 and autophagic genes were significantly aggravated. Meanwhile, two target genes of miR-146a-5p, interleukin-1 associated-kinase-1 (IRAK1) and tumor-necrosis factor receptor-associated factor-6 (TRAF6) were increased dramatically, which also played important roles in regulation of autophagy. These data suggested miR-146a-5p negatively modulated cytokine expression caused by PM2.5 via autophagy process through the target genes of IRAK1 and TRAF6. Our findings raised the concerns of the changes of miR expression profile and following responses caused by PM2.5.

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