Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 130
Filtrar
1.
Chemosphere ; 250: 126256, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32114341

RESUMO

Nitrated phenols in particulate matters are among the major components of brown carbon, harm plant growth and human health. To understand the size distributions of nitrated phenols in the polluted coastal region and the factors influencing these distributions, size-resolved particulate matters were collected from a rural site in the coastal city of Qingdao, China, in January 2019, and analyzed for the presence of 11 nitrated phenols. The average concentrations of total nitrated phenols in fine- and coarse-mode particles were 123.6 and 37.2 ng m-3, respectively. 4-Nitrophenol was found to be the dominant nitrated phenol, followed by 3-methyl-6-nitrocatechol, 3-methyl-4-nitrophenol, and 4-nitrocatechol. On average, maximum concentrations of nitrated phenols were in condensation-mode particles, whereas a minor concentration peak of nitro-salicylic acids was present in droplet-mode particles. In addition, a minor concentration peak of 4-methyl-2,6-dinitrophenol was noticed in coarse-mode particles. Comparisons of the size distributions under different situations confirmed that both primary emissions and secondary formation had significant effects on the abundances and particle-sizes of nitrated phenols. Coal combustion in residential villages and firework burning during a festival led to a sharp increase of nitrated phenols in condensation-mode particles, whereas dust promoted their heterogeneous formation in coarse-mode particles, and high humidity in the coastal area facilitated their aqueous formation in droplet-mode particles.

2.
Cancer Sci ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187778

RESUMO

Tumor microenvironment (TME) are vital components of tumor tissue. Increasing evidence suggest their significance in predicting outcomes and guiding therapies. However, no studies have reported a systematic analysis of clinicopathological significance of TME in lung adenocarcinoma (LUAD). Here, we inferred tumor stromal cells in 1,184 LUAD patients using computational algorithms based on bulk tumor expression data, and evaluated clinicopathological significance of stromal cells. We found LUAD patients showed heterogeneous abundance in stromal cells. Infiltration of stromal cells was influenced by clinicopathological features, such as age, gender, smoking and TNM stage. By clustering stromal cells, we identified two clinically and molecularly distinct LUAD subtypes with immune active and immune repressed features. The immune active subtype is characterized with repressed metabolism and repressed proliferation of tumor cells, while the immune repressed subtype is characterized with active metabolism and active proliferation of tumor cells. Differentially expressed gene analysis of the two LUAD subtypes identified an immune-activation signature. To diagnose TME subtypes practically, we constructed TME score using principal component analysis based on the immune-activation signature. The TME score predicted TME subtypes effectively in three independent datasets with areas under the curves (AUCs) of 0.960, 0.812, and 0.819, respectively. In conclusion, we proposed two clinically and molecularly distinct LUAD subtypes based on tumor microenvironment that may be valuable in predicting clinical outcome and guiding immunotherapy.

3.
Sci Total Environ ; 714: 136760, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31982756

RESUMO

Nitrated phenols are a major class of brown carbon in the atmosphere and have adverse effects on human and plants health. They are emitted from combustion sources or produced by oxidation of phenolic precursors. In this study, fine particulates, total suspended particulates, and gas-phase samples were collected in urban Jinan in winter, spring, and summer, and UHPLC-MS analysis was used to determine 8 phenolic compounds and 12 nitrated phenols in these samples. The seasonal average concentrations of total phenolic compounds and total nitrated phenols were in the ranges of 2.6-18.7 ng m-3 and 13.5-105.4 ng m-3, respectively. The concentrations of phenolic compounds and nitrated phenols were highest in winter, followed (in decreasing order) by spring, and summer. Phenol and salicylic acid were the most abundant phenolic species in both gaseous and particulate samples. 4-Nitrophenol was the most abundant nitrated phenols in particulate matters, followed by 4-nitrocatechol and 5-nitrosalicylic acid, while 4-nitrophenol and 2,4-dinitrophenol were the dominant species in the gas phase. The distributions of phenolic compounds and nitrated phenols in fine and coarse particles and in gas and particle phases were largely dependent on the aerosol size distribution, the ambient temperature, and the compound volatility. More of them were distributed in fine particles and gas-phase in summer than in spring. It was found that phenol, catechol, methyl-catechols, 4-nitrophenol, and methyl-nitrophenols mainly derived from coal combustion, while biomass burning was the main source of cresols, 2,6-dimethyl-4-nitrophenol, 4-nitrocatechol, and methyl-nitrocatechols. In addition, secondary formation contributed the largest fraction of nitrosalicylic acids and vehicle exhaust was the major source of cresols, 2,6-dimethyl-4-nitrophenol, and 4-methyl-2,6-dinitrophenol. Further correlation analysis revealed positive correlations between nitrated phenols and corresponding phenolic precursors, indicating the important roles that phenolic precursors played in the secondary formation and abundance of nitrated phenols in the atmosphere.

4.
Endocrine ; 67(2): 503-505, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31939092

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

5.
Cancer Lett ; 470: 95-105, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31644929

RESUMO

Immune checkpoint inhibitors against PD-1/PD-L1 yield improved survival rates of KRAS-mutant NSCLC patients, who conferred a poor prognosis without effective targeted therapy until now. Yet, the underlying association between KRAS mutations and immune responses remains unclear. We performed an integrated analysis of the data from publicly available repositories and from clinical center cohorts to explore the association between KRAS mutation status and tumor immunity-associated features, including PD-L1 expression, CD8+ tumor-infiltrating lymphocytes (TILs) and tumor mutational burden (TMB). Our results revealed that KRAS mutations are correlated with an inflammatory tumor microenvironment and tumor immunogenicity, resulting in superior patient response to PD-1/PD-L1 inhibitors. Meanwhile, three-pool analysis further confirmed that KRAS-mutant NSCLC patients show remarkable clinical benefit from anti-PD-1/PD-L1 immunotherapy. In addition, a KRAS-mutant lung adenocarcinoma mouse model was established to estimate the relative efficacy of anti-PD-L1 monoclonal antibody monotherapy or combination treatment with docetaxel versus docetaxel alone. Most surprisingly, we found that PD-L1 blockade combined with docetaxel did not promote an anti-tumor response. These findings uncover that PD-1/PD-L1 blockade monotherapy may be the optimal therapeutic schedule in NSCLC patients harboring KRAS mutations.

6.
Chemosphere ; 240: 124883, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726606

RESUMO

A coupled algal-osmosis membrane treatment system was studied for recovering potable-quality water from municipal primary effluent. The core components of the system included a mixotrophic algal process for removal of biochemical oxygen demand (BOD) and nutrients, followed by a hybrid forward osmosis (FO)-reverse osmosis (RO) system for separation of biomass from the algal effluent and production of potable-quality water. Field experiments demonstrated consistent performance of the algal system to meet surface discharge standards for BOD and nutrients within a fed-batch processing time of 2-3 days. The hybrid FO-RO system reached water productivity of 1.57 L/m2-h in FO using seawater as draw solution; and permeate flux of 3.50 L/m2-h in brackish water RO (BWRO) and 2.07 L/m2-h in seawater RO (SWRO) at 2068 KPa. The coupled algal-membrane system achieved complete removal of ammonia, fluoride, and phosphate; over 90% removal of calcium, sulfate, and organic carbon; and 86-89% removal of potassium and magnesium. Broadband characterization using high resolution mass spectrometry revealed extensive removal of organic compounds, particularly wastewater surfactants upon algal treatment. This study demonstrated long-term performance of the FO system at water recovery of 90% and with membrane cleaning by NaOH solution.


Assuntos
Reatores Biológicos/microbiologia , Água Potável/análise , Membranas Artificiais , Rodófitas/crescimento & desenvolvimento , Purificação da Água/métodos , Filtração/métodos , Compostos Orgânicos/análise , Osmose , Águas Salinas/química , Água do Mar/química , Águas Residuárias/química , Poluentes Químicos da Água/análise
7.
Onco Targets Ther ; 12: 8955-8960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802905

RESUMO

Chimeric antigen receptor (CAR)-modified T cell therapy is increasingly administered for hematological malignancies. Cytokine release syndrome (CRS) is a common and severe complication of CAR-T therapy. In the present case, a 62-year-old male patient was diagnosed with relapsed and refractory multiple myeloma (RRMM). Treated with CART-CD19/BCMA therapy, his symptoms remitted, during which occasional but severe CRS associated with coagulation disorder still appeared, as evidenced by the coexistence of a huge thrombosis and bleeding tendency. Through the First Generation Sequencing, we extracted genomic DNA from the patient's peripheral blood to analyze the distribution of polymorphism at the -572C/G site of the promoter of IL-6 gene. The results showed that the genotype of -572C/G promoter polymorphism was CC, indicating that high level of IL-6 and -572C/G polymorphism might be associated with the risk of thrombotic disorders. We concluded that immediate diagnosis and appropriate treatment of coagulopathy could reduce CRS-related mortality.

8.
Front Immunol ; 10: 2282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608066

RESUMO

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is a serious threat to human health. γδT cells, which are characterized by major histocompatibility complex (MHC) non-restriction, are rapidly activated and initiate anti-infectious immune responses in the early stages of Mtb infection. However, the mechanism underlying the recognition of Mtb by γδT cells remains unclear. In this study, we characterized the pattern of the human T-cell receptor (TCR) γδ complementary determinant region 3 (CDR3) repertoire in TB patients by using high-throughput immune repertoire sequencing. The results showed that the diversity of CDR3δ was significantly reduced and that the frequency of different gene fragments (V/J), particularly the V-segment of the δ-chain, was substantially altered, which indicate that TB infection-related γδT cells, especially the δ genes, were activated and amplified in TB patients. Then, we screened the Mtb-associated epitopes/proteins recognized by γδT cells using an Mtb proteome chip with dominant CDR3δ peptides as probes. We identified the Mtb protein Rv0002 as a potential ligand capable of stimulating the activation and proliferation of γδT cells. Our findings provide a further understanding of the mechanisms underlying γδT cell-mediated immunity against Mtb infection.

9.
Oncoimmunology ; 8(10): e1625689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646071

RESUMO

Objectives: Although low-dose computed tomography has been confirmed to have meaningful diagnostic utility, lung cancer is still the leading cause of cancer-related deaths for both genders worldwide. Thus, a novel panel with a stronger diagnostic performance for lung cancer is needed. This study aimed to investigate the efficacy of a new panel in lung cancer diagnosis. Materials and Methods: The serum levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and seven autoantibodies were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. The 316 candidates enrolled in this study were randomly assigned into two groups for the training and validation of a diagnostic panel. Results: An optimal panel with four biomarkers (CEA, CA125, Annexin A1-Ab, and Alpha enolase-Ab) was established, with an area under the receiver operator characteristic (ROC) curve (AUC) of 0.897, a sensitivity of 86.5%, a specificity of 82.3%, a positive predictive value (PPV) of 88.3%, a negative predictive value (NPV) of 79.7%, and a diagnostic accuracy of 84.8% for the training group. The panel was validated, with an AUC of 0.856 and a sensitivity of 87.5% for the validation group. Furthermore, the new panel performed significantly better in lung cancer screening than did CEA and CA125 in all of the cohorts (p< .05). Conclusion: The diagnostic performance of CEA and CA125 was significantly enhanced through their combination with two autoantibodies (Annexin A1-Ab, and Alpha enolase-Ab). Optimization of the measured autoantibodies is critical for generating a panel to detect lung cancer in patients.

10.
Bioorg Med Chem ; 27(21): 115095, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521461

RESUMO

Resistance-modifying agents (RMAs) offer a promising solution to combat bacterial antibiotic resistance. Here we report the discovery and structure-activity relationships of a new class of RMAs with a novel tryptoline-based benzothiazole scaffold. Our most potent compound in this series (4ad) re-sensitizes multiple MRSA strains to cephalosporins at low concentrations (2 µg/mL) and has low mammalian cytotoxicity with a half growth inhibitory concentration (GI50) > 100 µg/mL in human cervical carcinoma (HeLa) cells. In addition, the same core scaffold with different substitutions also gives good antibacterial activity against MRSA.

11.
Endocrine ; 66(3): 585-595, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31522342

RESUMO

PURPOSE: Whether autophagy plays a key role in thyroxine-induced cardiomyocyte hypertrophy, and whether the role of autophagy in thyroxine-induced cardiomyocyte hypertrophy is related to targeting of Beclin-1 by miR-762 remains unclear. This research focused on testing these two hypotheses. Importantly, the results of this study will help us better understand the molecular mechanisms of thyroxine-induced cardiomyocyte hypertrophy. METHODS: In vivo and in vitro, RT-PCR, western blot, and dual luciferase reporter assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, Masson staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. RESULTS: Our results showed that in vivo, serum TT3, TT4, and heart rate were significantly upregulated in the T4 group compared with the control group. Moreover, the surface area of cardiomyocytes was significantly increased in the T4 group, and the structural disorder was accompanied by obvious hyperplasia of collagen fibers. The expression of ANP, and ß-MHC was significantly upregulated in the T4 group. In addition, LC3 II/LC3 I, Beclin-1 and the count of autophagic vacuoles were significantly upregulated, but miR-762 was significantly downregulated in the T4 group compared to the control group. Subsequently, a dual luciferase reporter assay suggested that Beclin-1 was the target gene of miR-762. In vitro, the results for the T3 group were consistent with the results for the T4 group. Furthermore, cardiomyocyte hypertrophy and autophagic activity were attenuated in the T3 + miR-762 mimic group compared with the T3 group. In contrast, cardiomyocyte hypertrophy and autophagic activity were aggravated in the T3 + miR-762 inhibitor group compared with the T3 group. CONCLUSIONS: miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1.

12.
Environ Res ; 179(Pt A): 108709, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31479872

RESUMO

Nitrated phenols are receiving increasing attention due to their adverse impacts on the environment and human health. Previous measurements have revealed the non-ignorable contribution of vehicle exhaust to atmospheric nitrated phenols in urban areas. However, there is a lack of comprehensive understanding of the emission characteristics and the total emission of nitrated phenols from current on-road traffic. This study investigated the emissions from eight passenger vehicles, eight trucks, and two taxis, with fuel types including diesel, gasoline, and compressed natural gas. Exhaust emissions were collected and measured using a mobile measurement system on two testing routes. Twelve nitrated phenols in the collected fine particulate matter were detected using ultrahigh performance liquid chromatography-mass spectrometry. Overall, the emission profiles of fine particulate nitrated phenols varied with vehicle load and fuel type. The 4-nitrophenol and its methyl derivatives were dominant nitrated phenol species emitted by the vehicles with proportions of 38.4%-68.0%, which is significantly different from the proportions of nitrated phenols emitted from biomass burning and coal combustion. The emission factors also exhibited large variations across vehicle type, fuel type, and emission standards, with relatively low values for gasoline vehicles and taxis fueled by compressed natural gas and high values for diesel vehicles. Based on the emission factors of nitrated phenols from different vehicles, the estimated total emission of nitrated phenols from on-road vehicles in China was 58.9 Mg (-86%-85% within 95% confidence interval), with diesel trucks contributing the most substantial fractions. This work highlights the very high level of emissions of nitrated phenols from diesel vehicles and provides an essential basis for atmospheric modeling and effective pollution control.

13.
Natl Sci Rev ; 6(2): 275-288, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31258952

RESUMO

Allopatric speciation requiring an unbroken period of geographical isolation has been the standard model of neo-Darwinism. While doubts have been repeatedly raised, strict allopatry without any gene flow remains a plausible mechanism in most cases. To rigorously reject strict allopatry, genomic sequences superimposed on the geological records of a well-delineated geographical barrier are necessary. The Strait of Malacca, narrowly connecting the Pacific and Indian Ocean coasts, serves at different times either as a geographical barrier or a conduit of gene flow for coastal/marine species. We surveyed 1700 plants from 29 populations of 5 common mangrove species by large-scale DNA sequencing and added several whole-genome assemblies. Speciation between the two oceans is driven by cycles of isolation and gene flow due to the fluctuations in sea level leading to the opening/closing of the Strait to ocean currents. Because the time required for speciation in mangroves is longer than the isolation phases, speciation in these mangroves has proceeded through many cycles of mixing-isolation-mixing, or MIM, cycles. the MIM mechanism, by relaxing the condition of no gene flow, can promote speciation in many more geographical features than strict allopatry can. Finally, the MIM mechanism of speciation is also efficient, potentially yielding m n (m > 1) species ather n cycles. SIGNIFICANCE STATEMENT: Mechanisms of species formation have always been a conundrum. Speciation between populations that are fully geographically isolated, or allopatric speciation, has been the standard solution in the last 50 years. Complete geographical isolation with no possibility of gene flow, however, is often untenable and is inefficient in generating the enormous biodiversity. By studying mangroves on the Indo-Malayan coasts, a global hotspot of coastal biodiversity, we were able to combine genomic data with geographical records on the Indo-Pacific Barrier that separates Pacific and Indian Ocean coasts. We discovered a novel mechanism of speciation that we call mixingisolation-mixing (MIM) cycles. By permitting intermittent gene flow during speciation,MIMcycles can potentially generate species at an exponential rate, thus combining speciation and biodiversity in a unified framework.

14.
Phys Chem Chem Phys ; 21(27): 15215-15221, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31250850

RESUMO

The bistetrazole N-oxide energetic ionic salt dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) has attracted great interest as it breaks through the limitations of the traditional nitro group, high detonation velocity and moderate impact sensitivity. Reports show that TKX-50 transforms into the 5,5'-bis(2-hydroxytetrazole) (BTO) precursor, which is further decomposed and partly converted to diamino 5,5'-bistetrazole-1,1'-diolate (ABTOX). Studying the effects of H+, NH3OH+ and NH4+ on the thermal decomposition mechanism of bistetrazole N-oxide anion would provide a more comprehensive understanding of the TKX-50 decomposition mechanism. Herein, TKX-50, BTO and ABTOX decomposition rates, on-line analysis of the gas products, as well as quantitative analysis, are presented. It was found that the presence of two H+ decreases the decomposition temperature, whereas NH3OH+ greatly increases the decomposition rate. In the presence of NH3OH+, the bistetrazole N-oxide anion completely decomposes without producing C2N2; however, NH4+ promotes the polymerization of C2N2 generated by the bistetrazole N-oxide anion, and the amount of NO produced is greater than that of N2O. Therefore, in the TKX-50 decomposition process, the bistetrazole N-oxide anion does not receive two H+ simultaneously and converts into BTO. Furthermore, the competition between cations and their decomposition products for the H+ affects the degree of decomposition, which is important in understanding the energy release mechanism.

15.
Cancer Lett ; 459: 86-99, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31173852

RESUMO

Interferons (IFNs) play crucial roles in the development and treatment of cancer. Long non-coding RNAs (lncRNAs) are emerging molecules involved in cancer progression. Here, we identified and characterized an IFN-inducible nuclear lncRNA IRF1-AS (Interferon Regulatory Factor 1 Antisense RNA) which was positively correlated with IRF1 expression. IFNs upregulate IRF1-AS via the JAK-STAT pathway. Knockdown and overexpression of IRF1-AS revealed that IRF1-AS inhibits oesophageal squamous cell carcinoma (ESCC) proliferation and promotes apoptosis in vitro and in vivo. Mechanistically, IRF1-AS activates IRF1 (Interferon Regulatory Factor 1) transcription through interacting with ILF3 (Interleukin Enhancer Binding Factor 3) and DHX9 (DExH-Box Helicase 9). In turn, IRF1 binds to the IRF1-AS promoter directly and activates IRF1-AS transcription. Global analysis of IRF1-AS-regulated genes indicated that IRF1-AS activates the IFN response in vitro and in vivo. IRF1 knockdown in IRF1-AS-overexpressing cells abolished the antiproliferative effect and activation of the IFN response. Furthermore, IRF1-AS was downregulated in ESCC tissues, and low expression correlated with poor prognosis. In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1.

16.
Transl Oncol ; 12(8): 1086-1091, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31174059

RESUMO

PURPOSE: Elevated IL-17 produced by Th17 cells was reported to promote myeloma cell growth and inhibit immune function in multiple myeloma (MM). IL-17A was also reported to promote MM growth through IL-17 receptors and enhance adhesion to bone marrow stromal cells (BMSCs). Spleen tyrosine kinase (Syk) influences MM cell survival and migration. Herein we aimed to investigate whether Syk was involved in the regulative role of IL-17A in the viability of MM cells. METHODS: Cell viability was determined using CCK8 assay. The production of cytokine including IL-17A was evaluated with ELISA. Western blotting assay was used to determine protein expression levels of Syk and nuclear factor κB (NF-κB) related molecules. mRNA expression level of RORγt was detected with reverse transcription quantitative polymerase chain reaction. RESULTS: IL-17Awas highly expressed in MM patients and was able to induce MM cell viability. Following analysis indicated that the effects of IL-17A were mediated by Syk/ nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Immunoprecipitation also indicated that Syk is involved in IL-17A-induced Act1-TRAF6 complex formation and TRAF6 polyubiquitination in MM cells. CONCLUSIONS: Taken together, our study indicated that IL-17A increases MM cell viability through activating NF-κB signal pathway via positively regulating Syk expression. Syk also participates in the formation of IL-17R-proximal signaling complex (IL-17R-Act1-TRAF6), which is essential for IL-17A-mediated NF-kB activation. These investigations highlight that inhibition of Syk may be a potential therapeutic option for neoplastic diseases such as MM.

17.
Molecules ; 24(10)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108973

RESUMO

Mahonia bealei (Fort.) Carr. is an economically important plant that is widely cultivated in Southwest China. Its leaves are commonly used for tea and contain an abundance of antioxidant compounds. However, methods of the systematic purification of antioxidants from M. bealei are lacking. In this study, antioxidants from this plant were effectively and rapidly enriched. First, antioxidants were screened using online 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH)-high performance liquid chromatography (HPLC), followed by separation using high-speed countercurrent chromatography with an optical solvent system composed of n-hexane/ethyl acetate/methanol/water (1:5:1:5, v/v/v/v). Three phenolics-chlorogenic acid (1, 8.3 mg), quercetin-3-O-ß-d-glucopyranoside (2, 20.5 mg), and isorhamnetin-3-O-ß-d-glucopyranoside (3, 28.4 mg)-were obtained from the ethyl acetate-soluble fraction (240 mg) by one-step separation. The chemical structures of the phenolics were characterized by MS and NMR techniques, and the purity of each compound was >92.0% as determined by HPLC. The isolated compounds were assessed by scavenging activities on DPPH and superoxide radicals as well as cytoprotective assays, all of which showed similar trends regarding the antioxidant capacities of the compounds. Moreover, compounds 1-3 significantly attenuated the lipid peroxidation and antioxidant enzyme activities in H2O2-treated RAW264.7 cells. Our study demonstrated the efficiency of a newly developed integrative system for the comprehensive characterization of pure compounds from M. bealei, which will allow their use as reference substances.


Assuntos
Antioxidantes/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Mahonia/química , Fenóis/isolamento & purificação , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Peróxido de Hidrogênio/efeitos adversos , Camundongos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células RAW 264.7
18.
Sci Total Environ ; 677: 637-647, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31071666

RESUMO

Nitrate radical (NO3) and dinitrogen pentoxide (N2O5) play crucial roles in the nocturnal atmosphere. To quantify their impacts, we deployed a thermal-dissociation chemical ionization mass spectrometry (TD-CIMS), to measure their concentration, as well as ClNO2 at a coastal background site in the southern of China during the late autumn of 2012. Moderate levels of NO3, N2O5 and high concentration of ClNO2 were observed during the study period, indicating active NOx-O3 chemistry in the region. Distinct features of NO3, N2O5 and ClNO2 mixing ratios were observed in different airmasses. Further analysis revealed that the N2O5 heterogeneous reaction was the dominant loss of N2O5 and NO3, which showed higher loss rate compared to that in other coastal sites. Especially, the N2O5 loss rates could reach up to 0.0139 s-1 when airmasses went across the sea. The fast heterogeneous loss of N2O5 led to rapid NOx loss which could be comparable to the daytime process through NO2 oxidization by OH, and on the other hand, to rapid nitrate aerosol formation. In summary, our results revealed that the N2O5 hydrolysis could play significant roles in regulating the air quality by reducing NOx but forming nitrate aerosols.

19.
Curr Med Sci ; 39(2): 237-242, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016516

RESUMO

Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28-0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.


Assuntos
Cardiomiopatias/tratamento farmacológico , Infecções por Enterovirus/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Selênio/administração & dosagem , Adulto , Cardiomiopatias/fisiopatologia , Doença Crônica , Suplementos Nutricionais , Eletrocardiografia/métodos , Infecções por Enterovirus/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos
20.
Cancer Med ; 8(5): 2429-2441, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30932358

RESUMO

Alternative splicing (AS) and the regulation of AS by splicing factors play critical roles in cancer. Plant homeodomain (PHD)-finger domain protein PHF5A, a critical splicing factor involved in AS, has been demonstrated to play an oncogenic role in glioblastoma multiforme and breast cancer, but its biological function in lung cancer remains unclear. In the present study, we systematically analyzed the biological function and clinical relevance of PHF5A in non-small cell lung cancer (NSCLC). We found that PHF5A was significantly upregulated in NSCLC tumors compared with normal tissues in both TCGA data set and tissue microarrays. Upregulation of PHF5A was negatively correlated to the overall survival (OS) of lung adenocarcinoma (LUAD) patients. Loss-of-function and gain-of-function experiments confirmed that PHF5A functioned as an oncoprotein by promoting LUAD cell proliferation, migration and invasion, inducing G0/G1 cell cycle progression and inhibiting cisplatin-induced apoptosis. RNA-seq analysis identified many essential genes whose AS was dysregulated by PHF5A, including cell cycle-associated genes such as SKP2, CHEK2, ATR and apoptosis-associated genes such as API5 and BCL2L13. Additionally, pladienolide, a small molecular inhibitor of PHF5A, inhibited LUAD cell proliferation in a dose-dependent manner and induced AS changes similar to PHF5A knockdown. In conclusion, we validated that PHF5A played an oncogenic role via AS in LUAD and suggested that PHF5A might serve as a potential drug target with a promising anticancer therapeutic effect.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA