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3.
Psychol Med ; : 1-9, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33618792

RESUMO

BACKGROUND: Although poverty associated with severe mental illness (SMI) has been documented in many studies, little long-term evidence of social drift exists. This study aimed to unravel the poverty transitions among persons with SMI in a fast change community in China. METHODS: Two mental health surveys, using the International Classification of Disease (ICD-10), were conducted in the same six townships of Xinjin county, Chengdu, China in 1994 and 2015. A total of 308 persons with SMI identified in 1994 were followed up in 2015. The profiles of poverty transitions were identified and regression modelling methods were applied to determine the predictive factors of poverty transitions. RESULTS: The poverty rate of persons with SMI increased from 39.9% to 49.4% in 1994 and 2015. A larger proportion of them had fallen into poverty (27.3%) rather than moved out of it (17.8%). Those persons with SMI who had lost work ability, had physical illness and more severe mental disabilities in 1994, as well as those who had experienced negative changes on these factors were more likely to live in persistent poverty or fall into poverty. Higher education level and medical treatment were major protective factors of falling into poverty. CONCLUSIONS: This study shows long-term evidence on the social drift of persons with SMI during the period of rapid social development in China. Further targeted poverty alleviation interventions should be crucial for improving treatment and mental recovery and alleviating poverty related to SMI.

4.
Cell Death Dis ; 12(2): 150, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542225

RESUMO

Helicobacter pylori (H. pylori) is listed as a class I carcinogen in human gastric cancer; however, the underlying mechanisms are poorly understood. In this study, we identified Protogenin (PRTG) was upregulated in both gastric cancer tissues and H. pylori-infected tissues by analyzing dysregulated genes in TCGA and GEO databases. Importantly, upregulated PRTG predicted poor prognosis of gastric cancer patients and integrative analysis revealed that PRTG served as an oncogenic protein in gastric cancer and was required for H. pylori-mediated tumorigenic activities in in vitro cellular and in vivo tumor-bearing mouse models. Mechanistically, H. pylori infection enhanced PRTG expression by promoting transcriptional factor ZEB1 stabilization and recruitment to the PRTG promoter, and which then activated the sub-following cGMP/PKG signaling pathway in bioinformatic and cellular studies. Cellular studies further confirmed that PRTG depended on activating cGMP/PKG axis to promote proliferation, metastasis, and chemoresistance of gastric cancer cells. The PKG inhibitor KT5823 played synergistic anti-tumor effects with cisplatin and paclitaxel to gastric cancer cells in in vitro cellular and in vivo tumor-bearing mouse models. Taken together, our findings suggested that H. pylori infection depends on ZEB1 to induce PRTG upregulation, and which leading to the development and progression of gastric cancer through activating cGMP/PKG signaling pathway. Blocking PRTG/cGMP/PKG axis, therefore, presents a promising novel therapeutic strategy for gastric cancer.

5.
Poult Sci ; 100(4): 100941, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33607315

RESUMO

Salmonella Enteritidis (SE) are important zoonotic pathogens, and can be easily transferred to humans by contaminated animal products. Epidemic surveys of SE are necessary in current modern large-scale chicken farms. In this study, Salmonella strains were isolated from possibly infected samples collected at 3 independent farms, and their serotype, drug resistances, virulence genes, and genetic similarity were analyzed by molecular genetic analysis technologies including multilocus sequence typing (MLST), clustered regularly interspaced short palindromic repeats (CRISPR), pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS). A total of 346 Salmonella strains were isolated from 3,598 samples (9.61%); 329 isolates were identified as SE (95.09%) and 308 isolates were multidrug resistant (93.62%). Virulotyping based on 6 virulence genes showed high similarity in SE isolates of each farm, with the exception of 2 isolates. All SE isolates were found to be the same ST11 type by MLST, and 22 strains of 150 SE isolates selected at random were found to belong to 1 cluster by PFGE and the same SET1 type by CRISPR. WGS results further revealed that these isolates belonged to the same clonal cluster, with high genetic similarity of 99.80 to 100.00%. All these results indicated that these SE isolates were overwhelmingly dominant and demonstrated high genetic similarity, which revealed that the same SE clone might be transmitted in these farms.

6.
Sci Total Environ ; 775: 145876, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33631590

RESUMO

Secondary vegetation succession can alter soil functions and quality. However, data on changes to soil quality at different stages of vegetation succession in karst areas of southwest China is limited. This study aimed to evaluate the effects of different vegetation succession on soil quality and further to identify the factors that influencing soil quality. Secondary forest, shrub, grass, and cropland (as a reference) were selected and sampled in the subtropical karst of southwest China. Soil quality index (SQI) was developed by two methods of Total Data Set (TDS) and Minimum Data Set (MDS). Based on principal component analysis (PCA), soil organic carbon, silt, available phosphorous, available potassium, soil thickness, and soil water content were identified as the most representative indicators for the MDS. Both methods showed that the highest SQI values were observed in secondary forest, followed by shrub and grass, and the cropland values were the lowest. This showed vegetation succession significantly influenced on soil physiochemical properties and thus on soil quality. MDS could adequately represent TDS to quantify the effects of vegetation succession on soil quality since similar SQI results were derived from the two methods (R2 = 0.68, P < 0.01). The influencing factors explained about 75% of the total variation in SQI using a generalized linear model. Vegetation types accounted for the largest proportion of the SQI variability followed by restoration time, indicating these factors significantly affect soil quality during vegetation succession. In general, vegetation succession significantly influenced soil properties, and also has long-term and positive effects on soil quality during vegetation restoration. This study helps to understand the changes in soil quality during vegetation succession and provides guidance for the sustainable management of revegetation in subtropical karst regions in China.

7.
Neurol Sci ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538915

RESUMO

BACKGROUND: Rigidity is one of the major manifestations of Parkinson's disease (PD), but no quantitative and objective imaging method has been developed to measure rigidity. Ultrasound shear wave elastography (SWE) can reflect the stiffness of tissue by providing a quantitative index. Thus, we conducted this study to evaluate the potential clinical value of SWE in assessing rigidity in PD. METHODS: A total of 63 subjects (44 patients with rigidity-dominant PD and 19 right-dominant-hand normal controls with matched age) were enrolled, and each underwent ultrasound SWE testing. The tests were conducted on the brachioradialis (BR) and biceps brachii (BB) on the more affected side in patients with PD and on the right side in normal controls. Differences in quantitative shear wave velocity (SWV) between patients with PD and normal controls were determined. The relationship of muscle SWV with joint rigidity, UPDRSIII, disease duration, sex, and age in patients with PD was analyzed. The intraclass correlation coefficient (ICC) was used to evaluate the reliability of SWE in assessing muscle stiffness in patients with PD. RESULTS: The mean SWVs of the BB and BR were higher in the PD group (3.65±0.46 and 4.62±0.89 m/s, respectively) than in normal controls (2.79±0.37 and 3.26±0.40 m/s, respectively). Stiffness in BR and BB was correlated with the upper-limb joint rigidity, UPDRSIII, and disease duration but not with sex or age in the PD group. The intraobserver correlation coefficients (ICCs) for interobserver and intraobserver variations in measuring SWV were 0.85 (95% confidence interval 0.56-0.95) and 0.85 (95% confidence interval 0.58-0.95), respectively, for BR and 0.90 (95% confidence interval 0.73-0.97) and 0.86 (95% confidence interval 0.61-0.95), respectively, for BB. CONCLUSIONS: SWV is associated with joint rigidity and disease duration, indicating that SWE can be potentially used as an objective and quantitative tool for evaluating rigidity.

8.
Ultrason Sonochem ; 73: 105484, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33578276

RESUMO

Although the traditional Stoˇber process-based methods are widely used for encapsulation of metal nanoparticles in SiO2, these time-consuming methods are not effective for coating metal microparticles with a uniform SiO2 layer of desired thickness. Herein, an ultrasound-assisted, interface-confined sol-gel method is proposed for fast encapsulation of metal microparticles in SiO2, and the encapsulation of Sn microparticles is chosen as an example to illustrate its feasibility. The proposed method involves covering metal microparticles with liquid films that contain water, alcohol, surfactant (Span-80) and catalyst (NH4F) and then ultrasonically dispersing these particles into cyclohexane, where tetraethylorthosilicate (TEOS) is added. To ensure the hydrolysis-condensation reactions of TEOS occurring at the particle-cyclohexane interface so that the formed SiO2 is coated on the particles, the microparticles should be well dispersed into cyclohexane with the liquid films being not broken away from their surfaces. It is found that the assistance of probe sonication and the addition of surfactant are crucial to achievement of a good dispersion of metal microparticles in cyclohexane. And using high-viscosity alcohol (namely glycerol), controlling the volume ratio of water to alcohol and the amount of water, and choosing a suitable ultrasonic power are essential for preventing the formation of free SiO2 (namely SiO2 that is not coated on the particles), which is a result that the liquid films escape from the particle surfaces under ultrasonic cavitation. Our results have also revealed that the thickness of SiO2 layer can be adjusted by changing the reaction time or the total amount of water. In particular, the thickness of SiO2 layer can be easily raised by simply repeating the encapsulation procedure. Compared with the traditional Stoˇber process-based methods, the proposed method is time-saving (reaction time: about 30 min vs. more than 12 h) and extremely effective for coating microparticles with a continuous, uniform SiO2 layer of desired thickness.

9.
Virol Sin ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616892

RESUMO

Pseudorabies (PR), also called Aujeszky's disease, is a highly infectious disease caused by pseudorabies virus (PRV). Without specific host tropism, PRV can infect a wide variety of mammals, including pig, sheep, cattle, etc., thereby causing severe clinical symptoms and acute death. PRV was firstly reported in China in 1950s, while outbreaks of emerging PRV variants have been documented in partial regions since 2011, leading to significant economic losses in swine industry. Although scientists have been devoting to the design of diagnostic approaches and the development of vaccines during the past years, PR remains a vital infectious disease widely prevalent in Chinese pig industry. Especially, its potential threat to human health has also attracted the worldwide attention. In this review, we will provide a summary of current understanding of PRV in China, mainly focusing on PRV history, the existing diagnosis methods, PRV prevalence in pig population and other susceptible mammals, molecular characteristics, and the available vaccines against its infection. Additionally, promising agents including traditional Chinese herbal medicines and novel inhibitors that may be employed to treat this viral infection, are also discussed.

10.
Anal Methods ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533766

RESUMO

The discharge of wastewater containing surfactants and other industrial pollutants is contaminating the world's water resources which should be taken seriously. This paper describes a paper spray mass spectrometric (PS-MS) method for rapid and quantitative analysis of anionic and cationic surfactants in water samples. Eight cationic surfactants and four anionic surfactants can be simultaneously determined in positive or negative mode without sample pretreatment and chromatographic separation. The PS-MS analysis time was only 10 s. Under optimized conditions, the method presented a suitable linear range (1-80 µg mL-1, linear regression coefficients (R2) higher than 0.995 for cationic surfactants, R2 higher than 0.990 for anionic surfactants), a low limit of detection (0.05-0.35 µg mL-1 for cationic surfactants and 0.20-0.35 µg mL-1 for anionic surfactants), and satisfactory recovery values (97.3-106.1%). The method validation indicated that the method precision and accuracy were satisfactory. The results demonstrated that PS-MS is especially suitable for the high-throughput analysis of surfactants in water samples.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33462973

RESUMO

Layered transition metal dichalcogenide (TMD) nanomaterials are promising alternatives to platinum (Pt) for the hydrogen evolution reaction (HER). However, the family of layered TMDs is mainly limited to Group IV-VII transition metals, while the synthesis of layered TMDs based on metals from other groups still remains a challenge. Herein, we demonstrate by atomic-resolution transmission electron microscopy that hexagonal RuSe2 (h-RuSe2 ) nanosheets with a mixture of 2H and 1T phases can be obtained by a facile bottom-up colloidal synthetic approach. The obtained h-RuSe2 , which can be transformed into the thermodynamically favorable phase of cubic RuSe2 (c-RuSe2 ) only after annealing at 600 °C, exhibits Pt-like HER performance, with a fivefold turnover frequency enhancement compared to the c-RuSe2 in alkaline media. Experimental results and density functional theory (DFT) calculations reveal that the enhanced adsorption free energies of H2 O (ΔG H 2 O * ), optimized adsorption free energies of H (ΔGH* ), and increased conductivity of h-RuSe2 contribute to its superior HER activity.

12.
Eur J Health Econ ; 22(2): 341-350, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33438134

RESUMO

BACKGROUND: This study aims to derive country-specific EQ-5D-5L health status utility (HSU) from the MacNew Heart Disease Health-related Quality of Life questionnaire (MacNew) using both traditional regression analyses, as well as a machine learning technique. METHODS: Data were drawn from the Multi-Instrument Comparison (MIC) survey. The EQ-5D-5L was scored using 4 country-specific tariffs (United States, United Kingdom, Germany, and Canada). The traditional regression techniques, as well as a machine learning technique, deep neural network (DNN), were adopted to directly predict country-specific EQ-5D-5L HSUs (i.e. a direct mapping approach). An indirect response mapping was undertaken additionally. The optimal algorithm was identified based on three goodness-of-fit tests, namely, the mean absolute error (MAE), mean error (ME) and root mean square error (RMSE), with the first being the primary criteria. Internal validation was undertaken. RESULTS: Indirect response mapping and direct mapping (via betamix with MacNew items as the key predictors) were found to produce the optimal mapping algorithms with the lowest MAE when EQ-5D-5L were scored using three country-specific tariffs (United Kingdom, Canada, and Germany for the former and United Kingdom, United States, Canada and Germany for the latter approach). DNN approach generated the lowest MAE and RMSE when using the Germany-specific tariff. CONCLUSIONS: Among different approaches been explored, there is not a conclusive conclusion regarding the optimal method for developing mapping algorithms. A machine learning approach represents an alternative mapping approach that should be explored further. The reported algorithms from response mapping have the potential to be more widely used; however, the performance needs to be externally validated.

13.
Genomics ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33516848

RESUMO

Schizothorax prenanti (S. prenanti) is one of the most important aquaculture species in the southwest of China. However, information of the full-length transcripts in S. prenanti remains unknown. In this study, single-molecule real-time (SMRT) sequencing was performed to generate full-length transcriptomes of S.prenanti. In total, 23.26 Gb of clean reads were generated. A total of 312,587 circular consensus sequences (CCS) were obtained with average lengths of 2634 bp and 84.16% (270,662) of CCS were full-length non-chimeric reads. After being corrected with Illumina library sequencing, 18,005 contigs were obtained, with 17,797 (98.81%) successfully annotated in eight public databases, including 15,839 complete open reading frames (ORFs) with an average length of 1330 bp. Furthermore, a total of 4152 alternative splicing (AS) events and 250 long non-coding RNA (lncRNA) transcripts were detected. Additionally, a total of 1129 putative transcription factors (TFs) members from 56 TF families and 11,660 simple sequence repeats (SSRs) were identified. This study provided a valuable resource of full-length transcripts for further research on S. prenanti.

14.
Cancer Sci ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33393143

RESUMO

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract. In this study, we performed single-cell RNA sequencing (RNA-seq) on intra- and peri-tumor tissues from GIST patients with the aim of discovering the heterogeneity of tumor cells in GIST and their interactions with other cells. We found four predominating cell types in GIST tumor tissue, including T cells, macrophages, tumor cells, and NK cells. Tumor cells could be clustered into two groups: one was highly proliferating and associated with high risk of metastasis, the other seemed "resting" and associated with low risk. Their clinical relevance and prognostic values were confirmed by RNA-seq of 65 GIST samples. T cells were the largest cell type in our single-cell data. Two groups of CD8+ effector memory (EM) cells were in the highest clonal expansion and performed the highest cytotoxicity but were also the most exhausted among all T cells. A group of macrophages were found polarized to possess both M1 and M2 signatures, and increased along with tumor progression. Cell-to-cell interaction analysis revealed that adipose endothelial cells had high interactions with tumor cells to facilitate their progression. Macrophages were at the center of the tumor microenvironment, recruiting immune cells to the tumor site and having most interactions with both tumor and nontumor cells. In conclusion, we obtained an overview of the GIST microenvironment and revealed the heterogeneity of each cell type and their relevance to risk classifications, which provided a novel theoretical basis for learning and curing GISTs.

15.
AAPS PharmSciTech ; 22(1): 42, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33426616

RESUMO

In vitro release studies are commonly used to assess the product performance of topical dosage forms. In such studies, the mass transport of drugs through synthetic membranes into a receiving chamber filled with a release medium is measured. The release medium is also passed through filtration membranes prior to chromatographic analysis. There are no official guidelines directing membrane selection for in vitro release studies or for filtration. Considering the diversity in membrane materials and their physical properties, the aim of this study was to investigate membrane-drug binding and the effect of various membranes on the release performance of a model drug dexamethasone (DEX) using USP dissolution apparatus IV. Seven membranes of different pore sizes (0.45 and 1.2 µm) and materials (cellulose acetate, polyethersulfone, and nylon) were assessed. Two different methods, syringe filter and 24-h incubation, were used for the determination of membrane-drug binding effects at low drug concentrations and saturated concentration conditions. Cellulose acetate and nylon membranes showed significant drug binding after 24-h incubations at both drug concentrations. DEX diffusion through membranes was significantly slowed down in all the tested membranes when compared with DEX solution without membranes. The extent of the retardation varied due to the differences in membrane structures. In conclusion, materials and sources of membranes affected drug dissolution profiles and the results showed membrane-drug binding effects. Proper selection of membranes with low drug binding ability and low diffusion resistance is essential to ensure appropriate and reproducible in vitro release assessments and filtration studies. Graphical Abstract.

16.
Am J Drug Alcohol Abuse ; : 1-9, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33426968

RESUMO

Background: Brain structural findings in chronic methamphetamine users have been inconsistent. Identifying contributing influences (e.g., sex, abstinence duration) can help clarify the clinical course of recovery. Objectives: We studied the effects of long-term methamphetamine abstinence on gray-matter volume. Our hypothesis was that smaller volume early in abstinence would precede long-term recovery. Methods: Individuals who used methamphetamine (≥100 g lifetime use, mandated to residential treatment for methamphetamine-positive urine; 40 men, 21 women), undergoing supervised abstinence (men: 12-400 days; women: 130-594 days), were compared to healthy controls (49 men, 36 women) using T1-weighted MRI. Volumes of orbitofrontal, anterior cingulate and parietal cortex, hippocampus, and striatum were measured using Freesurfer software. Associations of volumes with abstinence duration were tested in males and females separately because their abstinence times differed (121.5 ± 124.5 vs. 348.0 ± 128.6 days, p < 0.001); only males were studied in early abstinence. The General Linear Model was used to test effects of abstinence duration and group (methamphetamine users vs. controls). Results: In males, duration of abstinence was multivariate significant for gray-matter volumes (p = 0.017). Abstinence duration was associated with increases in volumes of the orbitofrontal and parietal cortices (ps = 0.031, 0.016) and hippocampi (ps = 0.044). Irrespective of abstinence, male methamphetamine users had smaller hippocampi than male controls (p = 0.008). Females showed no significant effects of group or abstinence. Conclusions: In males, abstinence from methamphetamine appears to result in volumetric increases in regions important for cognitive function, which may affect recovery during the course of treatment. Data from the period of early abstinence are required to evaluate volumetric changes in females.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33427453

RESUMO

Silicon/graphene nanowalls (Si/GNWs) heterojunctions with excellent integrability and sensitivity show an increasing potential in optoelectronic devices. However, the performance is greatly limited by inferior interfacial adhesion and week electronic transport caused by the horizontal buffer layer. Herein, a diamond-like carbon (DLC) interlayer is first introduced to construct Si/DLC/GNWs heterojunctions, which can significantly change the growth behavior of the GNWs film, avoiding the formation of horizontal buffer layers. Accordingly, a robust diamond-like covalent bond with a remarkable enhancement of the interfacial adhesion is yielded, which notably improves the complementary metal oxide semiconductor compatibility for photodetector fabrication. Importantly, the DLC interlayer is verified to undergo a graphitization transition during the high-temperature growth process, which is beneficial to pave a vertical conductive path and facilitate the transport of photogenerated carriers in the visible and near-infrared regions. As a result, the Si/DLC/GNWs heterojunction detectors can simultaneously exhibit improved photoresponsivity and response speed, compared with the counterparts without DLC interlayers. The introduction of the DLC interlayer might provide a universal strategy to construct hybrid interfaces with high performance in next-generation optoelectronic devices.

18.
Sci Rep ; 11(1): 1890, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479410

RESUMO

We examined the associations of age and serum magnesium, iron, lead, copper, and zinc levels with bone mineral density (BMD) in 2412 children under 3 years of age in order to find a tool to monitor BMD in children without the use of expensive imaging techniques. One-way ANOVA and chi-square tests were used to determine the associations of age and serum trace elements with BMD. Multivariable logistic regression analysis was used to test the correlation of five serum trace elements with BMD after adjustments for potential confounding factors in children under 3 years of age. Significant associations between age and four serum trace elements and BMD were found. Compared to the group with the lowest serum levels detected, the adjusted odds ratio (OR) for the incidence of normal bone mineral density in the third magnesium concentration tertile, the third iron concentration tertile, the fifth copper concentration quintile, the third zinc concentration quintile, and the fifth zinc concentration quintile were 1.30 (95% confidence interval (CI) 1.02-1.67), 1.43 (95% CI 1.11-1.84), 1.42 (95% CI 1.04-1.94), 1.46 (95% CI 1.05-2.04), and 1.48 (95% CI 1.06-2.06), respectively. However, there was no significant correlation between serum lead level and BMD in this study. Age and serum magnesium, iron, copper, and zinc levels are positively associated with BMD in children under 3 years old.

19.
J Int Med Res ; 49(1): 300060520982780, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33513047

RESUMO

OBJECTIVE: This study was performed to evaluate the surgical indications, clinical efficacy, and preliminary experiences of nonstructural bone grafts for lumbar tuberculosis (TB). METHODS: Thirty-four patients with lumbar TB who were treated with nonstructural bone grafts were retrospectively assessed. The operative time, operative blood loss, hospital stay, bone graft fusion time, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, visual analog scale (VAS) score, Oswestry Disability Index (ODI), American Spinal Injury Association (ASIA) impairment grade, and Cobb angle were recorded and analyzed. RESULTS: The mean operative time, operative blood loss, hospital stay, Cobb angle correction, and Cobb angle loss were 192.59 ± 42.16 minutes, 385.29 ± 251.82 mL, 14.91 ± 5.06 days, 9.02° ± 3.16°, and 5.54° ± 1.09°, respectively. During the mean follow-up of 27.53 ± 8.90 months, significant improvements were observed in the ESR, CRP concentration, VAS score, ODI, and ASIA grade. The mean bone graft fusion time was 5.15 ± 1.13 months. Three complications occurred, and all were cured after active treatment. CONCLUSIONS: Nonstructural bone grafts may achieve satisfactory clinical efficacy for appropriately selected patients with lumbar TB.

20.
Phytomedicine ; 80: 153394, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33130472

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1), which can be induced by interferon-gamma (IFN-γ) in the tumor microenvironment, is a critical immune checkpoint in cancer immunotherapy. Natural products which reduce IFN-γ-induced PD-L1 might be exert immunotherapy effect. Licochalcone A (LCA), a natural compound derived from the root of Glycyrrhiza inflata Batalin. (Fabaceae), was found to interfere IFN-γ-induced PD-L1. PURPOSE: The aim of this study is to further clarify the effect and the mechanism of LCA on inhibiting IFN-γ-induced PD-L1 in lung cancer cells. METHODS: The expression levels of PD-L1 were evaluated by flow cytometry, western blot and qRT-PCR. Click-iT protein synthesis assay and luciferase assay were used to identify the effect of LCA on protein synthesis. Jurkat T cell proliferation and apoptosis in the co-culture system were detected by flow cytometry. Flow cytometry was also applied to evaluate reactive oxygen species (ROS) generation. RESULTS: LCA downregulated IFN-γ-induced PD-L1 protein expression and membrane localization in human lung cancer cells, regardless of inhibiting PD-L1 mRNA level or promoting its protein degradation. LCA decreased apoptosis and proliferative inhibition of Jurkat T cells caused by IFN-γ-induced PD-L1-expressing in A549 cells in the co-culture system. Strikingly, LCA was verified as a protein synthesis inhibitor, which reduced both cap-dependent and -independent translation. LCA inhibited PD-L1 translation, likely due to inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α pathway. Furthermore, LCA induced ROS generation in a time-dependent manner in lung cancer cells. N-acetyl-L-cysteine (NAC) not only revered ROS generation triggered by LCA but also restored IFN-γ-induced expression of PD-L1. Both the inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α axis triggered by LCA was restored by co-treatment with NAC. CONCLUSION: LCA abrogated IFN-γ-induced PD-L1 expression via ROS generation to abolish the protein translation, indicating that LCA has the potential to be applied in cancer immunotherapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antígeno B7-H1/metabolismo , Chalconas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Antígeno B7-H1/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Interferon gama/metabolismo , Interferon gama/farmacologia , Células Jurkat , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
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