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1.
Front Biosci (Landmark Ed) ; 25: 564-576, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585904

RESUMO

The incidence of papillary thyroid carcinoma (PTC) has steadily increased over the recent years, making this cancer a common malignant tumor world-wide. We tested the hypothesis that Nuclear Enriched Abundant sh-NEAT1 knock-down ranscript 1 (NEAT1) is involved in the pathogenesis of PTC in vitro and in vivo. We show that NEAT1 is highly expressed in Papillary Thyroid Carcinoma cell line (PTC-1) and anaplastic thyroid cancer cell line (SW1736) as compared with the human thyroid follicular epithelial cell line (Nthy-ori 3-1). shRNA knockdown of NEAT1 led to the inhibition of cell growth, invasion, migration and Epithelial to Mesenchymal Transition (EMT) of thyroid cancer cells. This treatment increased the rate of apoptosis in SW1736 cells. Silencing of NEAT1 increased the level of its regulator, miRNA-126 and down-regulated VEGFA that sets the density of tumor vasculature. Administrtation of sh-NEAT1 also inhibited tumor growth in vivo, increased the miRNA-126 level and down-regulated VEGFA. Taken together, these results indicate that silencing NEAT1 suppresses thyroid carcinoma via miR-126/NEAT1/VEGFA axis.

2.
Food Funct ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696186

RESUMO

Flaxseed oil (FO), enriched in n-3 polyunsaturated fatty acids (PUFAs), is an important oil source for intestinal development and health. We aimed to study the different effects of FO versus soybean oil (SO) on growth, intestinal health and immune function of neonates with intrauterine growth retardation (IUGR) using a weaned piglet model. Forty pairs of male IUGR and normal birth weight piglets, weaned at 21 ± 1 d, were fed diets containing either 4% FO or SO for 3 weeks consecutively. Growth performance, nutrient digestibility and intestinal function parameters, immunology and microbiota composition were determined. IUGR led to a poor growth rate, nutrient digestibility and abnormal immunology variables, whereas feeding FO diet improved systemic and gut immunity, as indicated by increased plasma concentration of immunoglobulin G and decreased CD3+CD8+ T lymphocytes, and down-regulated intestinal expression of genes (MyD88, NF-κB, TNF-α, IL-10). Although IUGR tended to decrease villous height, feeding FO diet tended to increase the villi-crypt ratio and up-regulated expressions of tight junction genes (Claudin-1 and ZO-1), together with increased mucosa contents of n-3 PUFAs and a lower Σn-6/Σn-3 ratio. Besides, FO diet decreased the abundance of pathogenic bacteria Spirochaetes, and increased phylum Actinobacteria, and genera Blautia and Bifidobacterium in colonic digesta. Our findings indicate that IUGR impairs growth rate, nutrient digestibility, and partly immunology variables, whereas feeding FO-supplemented diet could improve intestinal function and immunity of both IUGR and NBW pigs, associated with the altered gut microbiome and mucosal fatty acid profile.

3.
Cancer Res ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690668

RESUMO

The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remains insufficiently understood. In this study we identified an AMP-activated protein kinase (AMPK)-GATA-binding protein 3 (GATA3)-enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid oxidation (FAO) and activation of de novo fatty acid (FA) synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1, de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK-GATA3-ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic.

4.
J Exp Clin Cancer Res ; 38(1): 447, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684985

RESUMO

Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated. This review summarizes the development and progression of molecular targeted and immune-based checkpoint therapies in HCC.

5.
F1000Res ; 8: 872, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681473

RESUMO

Background: Uganda is located in East Africa and is among the countries with the lowest income globally. The ten health centres in this project serve populations in the under-privileged communities of Kampala. The objective of the study was to implement diabetes mellitus (DM) screening among tuberculosis (TB) patients in a routine program setting with limited resources and high human immunodeficiency virus (HIV) prevalence. Methods: A descriptive cross-sectional observational study was conducted in ten health centres in Kampala, Uganda. As part of a project to implement DM screening in a routine setting, TB patients were screened for DM by trained health workers. A fasting blood glucose (FBG) value ≥7.0mmol/l was considered to indicate DM. For this study, aggregate data was collected and analysed using SPSS for Windows, version 13.0. Results:  Among 4,590 TB patients registered, 4,016 (88.0%) were screened with random blood glucose (RBG). Of those with RBG ≥6.1mmol/l, 1,093 (83.3%) were screened with FBG. In total, 92 (2.3%) patients were diagnosed with DM and 66 (71.8%) of them were newly diagnosed. The proportion of TB patients screened with FBG in the health centres varied from 58.2% to 100%. The proportion of patients screened with FBG and the prevalence of DM were significantly higher in private health centres compared with public health centres. The health centres in peri-urban areas screened more patients with RBG than those in urban areas. Health centres without DM services screened a larger number of patients with RBG and FBG than those with DM services. Conclusions: It appears feasible to implement screening TB patients for DM in routine program settings with limited resources and high HIV prevalence. Its introduction requires close collaboration between TB and DM services. The challenges identified need government attention and certain institutional and service-related factors need to be better managed at times.

6.
Food Chem ; : 125718, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31753688

RESUMO

The present study was aimed to investigate the effects of non-covalent and covalent interactions between soy protein isolate (SPI) and different concentrations (1, 2 and 5 mM) of (-)-epigallocatechin gallate (EGCG) regarding the structural and functional properties of the complex. The combination with EGCG caused changes in the secondary structure of SPI. The covalent complexes formed at low concentrations of EGCG tended to form a network structure. Compared with the SPI-EGCG non-covalent complexes, the covalent complexes exhibited higher thermal stability and oxidation resistance and a polyphenol-protective effect. In addition, the corresponding anti-digestive ability of the covalent complexes was strong and would therefore be more stable in the intestinal tract. The findings of this study provide a theoretical reference and research basis for the use of different SPI-polyphenol complexes as functional food ingredients or as bioactive materials.

7.
BMC Pediatr ; 19(1): 423, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31707983

RESUMO

BACKGROUND: The initial episode of angioedema in children can be potential life-threatening due to the lack of prompt identification and treatment. We aimed to analyze the factors predicting the severity and outcomes of the first attack of acute angioedema in children. METHODS: This was a retrospective study with 406 children (< 18 years) who presented in the emergency department (ED) with an initial episode of acute angioedema and who had subsequent follow-up visits in the out-patient department from January 2008 to December 2014. The severity of the acute angioedema was categorized as severe (requiring hospital admission), moderate (requiring a stay in the short-term pediatric observation unit [POU]), or mild (discharged directly from the ED). The associations among the disease severity, patient demographics and clinical presentation were analyzed. RESULT: In total, 109 (26.8%) children had severe angioedema, and the majority of those children were male (65.1%). Most of the children were of preschool age (56.4%), and only 6.4% were adolescents. The co-occurrence of pyrexia or urticaria, etiologies of the angioedema related to medications or infections, the presence of respiratory symptoms, and a history of allergies (asthma, allergic rhinitis) were predictors of severe angioedema (all p < 0.05). Finally, the duration of angioedema was significantly shorter in children who had received short-term POU treatment (2.1 ± 1.1 days) than in those who discharged from ED directly (2.3 ± 1.4 days) and admitted to the hospital (3.5 ± 2.0 days) (p < 0.001). CONCLUSION: The co-occurrence of pyrexia or urticaria, etiologies related to medications or infections, the presence of respiratory symptoms, and a history of allergies were predictors of severe angioedema. More importantly, short-term POU observation and prompt treatment might be benefit for patients who did not require hospital admission.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31733838

RESUMO

In this work, Ag3PO4/PANI/Cr:SrTiO3 photocatalysts were designed to effectively eliminate organic pollutants including Rhodamine B and phenol from high salinity wastewater under visible light. The phase composition, optical properties, and morphology of powders were studied, and the effects of inorganic salts on removal performance of the as-prepared particles were also tested. Results showed that the photocatalytic activities of Ag3PO4/PANI/Cr:SrTiO3 composites for Rhodamine B and phenol reached 100% within 10 min and 18 min, respectively. The reaction rate of pure Ag3PO4 was 7 times less than that of the ternary composite with the adding of PANI and Cr:SrTiO3. The activity of Ag3PO4/PANI/Cr:SrTiO3 remained at 92.25% after five cycles, so the photocatalytic and recyclable performance of ternary composite was greatly improved. In addition, when there was SO42- with a content of ranging from 1% to 21%, the degradation activity of the ternary catalyst under visible light was not changed for Rhodamine B, which indicated that the ternary catalyst exhibited the excellent sulfate resistance ability. Results from ESR and radical trapping experiments showed that O2- and h+ made an important contribution to visible-light photocatalytic activities.

9.
J Nutr Biochem ; 74: 108246, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31671360

RESUMO

The risk of overweight or obesity in association with early exposure of antibiotics remains an important public issue for health-care of children. Low-dose antibiotics (LDA) have been widely used to enhance growth rate of pigs, providing a good animal model to study the underlying mechanism. In present study, 28 female piglets, weaned at 21 d, were randomly classified into two groups, receiving either a control diet or a diet supplemented with LDA for 4 weeks. The total bacterial load and intestinal microbiota were determined by qPCR and 16S rRNA amplicon sequencing. UPLC-QTRAP-MS/MS and RNA-seq were further used to determine the colonic SCFAs and transcriptomes. Results showed that LDA significantly increased growth rate and food intake. The F/B index, Methanosphaera species, and the pathway of "carbohydrate metabolism" were improved by LDA exposure, indicating the better carbohydrate degradation and energy utilization. Furthermore, correlation analysis indicated the microbial community contributing to SCFAs production was enriched upon LDA exposure, associating with increased concentrations of short-chain and branched-chain fatty acids (caproate, 2-methyl butyrate and 4-methyl valerate). A multivariate linear fitting model analysis highlighted that caproate was positively correlated with two genera (Faecalibacterium and Allisonella) and four differentially expressed genes (ZNF134, TBX5, NEU4 and SEMA6D), which were all significantly increased upon LDA exposure. Collectively, our study indicates that the growth-promoting effect of LDA exposure in early life is associated with the shifts of colonic microbiota to increase utilization of carbohydrates and energy, enhanced SCFAs production and colonic functions.

10.
J Am Chem Soc ; 141(46): 18578-18584, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31692351

RESUMO

The activity and accessibility of MoS2 edge sites are critical to deliver high hydrogen evolution reaction (HER) efficiency. Here, a porous carbon network confining ultrasmall N-doped MoS2 nanocrystals (N-MoS2/CN) is fabricated by a self-templating strategy, which realizes synergistically structural and electronic modulations of MoS2 edges. Experiments and density functional theory calculations demonstrate that the N dopants could activate MoS2 edges for HER, while the porous carbon network could deliver high accessibility of the active sites from N-MoS2 nanocrystals. Consequently, N-MoS2/CN possesses superior HER activity with an overpotential of 114 mV at 10 mA cm-2 and excellent stability over 10 h, delivering one of best MoS2-based HER electrocatalysts. Moreover, this study opens a new venue for optimizing materials with enhanced accessible catalytic sites for energy-related applications.

11.
Circulation ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31744317

RESUMO

Background: Air pollution exposure increases cardiovascular morbidity and mortality. Preventing chronic cardiovascular diseases caused by air pollution relies on detecting the early effects of pollutants on the risk of cardiovascular disease development, which is limited by the lack of sensitive biomarkers. We have identified promising biomarkers in experimental animals but comparable evidence in humans is lacking. Methods: Air pollution is substantially worse in Beijing than in Los Angeles. We collected urine and blood samples from 26 non-smoking, healthy adult residents of Los Angeles (mean age, 23.8 years, 14 women) before, during, and after they spent 10 weeks in Beijing during the summers of 2014 and 2015. We assessed a panel of circulating biomarkers indicative of lipid peroxidation and inflammation. Personal exposure to polycyclic aromatic hydrocarbons (PAHs), a group of combustion-originated air pollutants, was assessed by urinary PAHs metabolites. Results: Urinary concentrations of four PAHs metabolites were 176% (95% CI, 103% to 276%) to 800% (95% CI, 509% to 1780%) greater in Beijing than in Los Angeles. Concentrations of six lipid peroxidation biomarkers were also increased in Beijing, among which 5-, 12-, 15-hydroxyeicosatetraenoic (HETE), and 9-, 13-hydroxyoctadecadienoic (HODE) acids reached statistical significance (false discovery rate<5%), but not the 8-isoprostane (20.8%; 95%CI, -5.0% to 53.6%). The anti-oxidative activities of paraoxonase (-9.8%; 95%CI, -14.0% to -5.3%) and arylesterase (-14.5%; 95%CI, -22.3% to -5.8%) were lower, and pro-inflammatory Creactive protein (101%; 95% CI, 3.3% to 291%) and fibrinogen (48.3%; 95% CI, 4.9% to 110%) concentrations were higher in Beijing. Changes in all these biomarkers were reversed, at least partially, after study participants returned to Los Angeles. Changes in most outcomes were associated with urinary PAHs metabolites (p<0.05). Conclusions: Traveling from a less-polluted to a more-polluted city induces systemic prooxidative and pro-inflammatory effects. Changes in the levels of HETEs and HODEs as well as paraoxonase and arylesterase activities in the blood, in association with exposures to PAHs, might have important implications in preventive medicine as indicators of increased cardiovascular risk caused by air pollution exposure.

12.
ChemSusChem ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721466

RESUMO

Two-dimensional (2D) molybdenum disulfide (MoS2) nanosheets raise great interest for lithium-sulfur (Li-S) batteries, due to its unique physical and chemical properties originating from the diversified chemical compositions and unique electronic structures. In the past years, many efforts have been devoted to employing MoS2 as the polysulfide immobilizer and catalyst, functional separator, and Li metal protection for Li-S batteries by structural design and electronic modulation. Fundamental understanding the interplay between structural features, electronic properties and the advanced electrochemical performance is highly crucial to provide valuable insights for the development of Li-S batteries. In this regard, we summarize the recent advances of Li-S batteries using 2D MoS2 materials from the perspective of structural design and electronic modulation. Finally, we also highlight the future prospects and the remaining challenges of MoS2 for Li-S batteries.

13.
Med Sci Sports Exerc ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31764465

RESUMO

PURPOSE: This study aimed to determine whether interrupting prolonged sitting with 3 different walking-bout schedules improves glycemic metabolism relative to continuous prolonged sitting in sedentary adults. METHODS: In a randomized, crossover trial, 16 inactive healthy adults (7 men, 24±3 years old) completed four 26-h laboratory sessions, including 22.5 h in an energy expenditure (EE)-testing calorimeter chamber. The four 9-h intervention periods were as follows: 9-h uninterrupted sitting (SIT); 30-min sitting/3-min brisk (60% VO2max) treadmill walk (WALK3); 45-min sitting/5-min (WALK5); or 60-min sitting/8-min (WALK8). Coprimary outcomes included the difference in the mean interstitial glucose concentration, total areas under the curve (tAUC), and incremental AUC (iAUC) for the entire 26 h and 9 h (intervention period) during three activity-bout conditions compared with SIT. RESULTS: Compared with SIT, the 26-h mean glucose concentration was attenuated in WALK8 (Δmean -0.22 mmol·L [95% CI -0.43--0.001], p= 0.048) without adjustment for EE and attenuated in WALK3 (Δ-0.47 mmol·L [-0.75--0.10]), WALK5 (Δ-0.47 mmol·L [-0.83--0.10]), and WALK8 (Δ-0.53 mmol·L [-0.92--0.13]) after adjustment for EE (all p < 0.01). The 26-h tAUC was reduced in WALK3 (Δ-11.18 mmol·L·h [-20.07--2.29]), WALK5 (2.12.67 mmol·L·h [-22.54--2.79]), and WALK8 (Δ-13.85 mmol·L·h [-24.60--3.10]) (all p < 0.01), as well as the iAUC (all p < 0.05), only after adjustment for EE. The 9-h mean glucose concentration, tAUC, and iAUC decreased in the three activity-break conditions regardless of EE adjustment (all p < 0.05). CONCLUSIONS: All three walking-bout conditions improved glycemic metabolism compared with SIT, independent of EE, in inactive, healthy adults.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1131-1137, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753097

RESUMO

OBJECTIVE: To establish a congenital chloride diarrhea (CCD)-associated SLC26A3 c.392C>G (p.P131R) polymorphism-expressing cell model, and to investigate its biological function. METHODS: The sequence of the SLC26A3 gene in GenBank was used to design the upstream and downstream single-guide RNA (sgRNA) that could specifically recognize the 392 locus of the SLC26A3 gene, and the sgRNA was mixed with the pSpCas9-puro vector after enzyme digestion to construct an eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3). Caco-2 cells were transfected with the recombinant plasmid and synthesized single-stranded DNA oligonucleotides (ssODNs), and Taqman genotyping assay and Sanger sequencing were used to identify the expression of SLC26A3 c.392C>G (p.P131R) in Caco-2 cells. Wild-type Caco-2 cells were selected as normal control group and the Caco-2 cells with successful expression of SLC26A3 c.392C>G (p.P131R) was selected as P131R group. Both groups were treated with 100 ng/mL tumor necrosis factor-α (TNF-α), and then the normal control group was named as TNF-α group, and the P131R group was named as TNF-α+P131R group. Electric cell-substrate impedance sensing (ECIS) assay was used to evaluate the change in the monolayer barrier function of intestinal epithelial cells in the above four groups, and Western blot was used to measure the change in the expression of SLC26A3 protein in the normal control group and the P131R group. RESULTS: The eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3) was successfully constructed. Both Taqman genotyping assay and Sanger sequencing confirmed the successful establishment of the Caco-2 cell model of SLC26A3 c.392C>G (p.P131R) expression. ECIS assay showed that compared with the normal control group, the P131R group had a significant increase in the monolayer permeability of intestinal epithelial cells (P<0.05), and at the same time, the P131R group had a significantly greater increase in cell membrane permeability after the induction with 100 ng/mL TNF-α (P<0.05). Western blot showed that compared with the normal control group, the P131R group had a significant reduction in the expression of SLC26A3 protein (P=0.001). CONCLUSIONS: SLC26A3 c.392C>G (p.P131R) can reduce the expression of SLC26A3 protein, increase the monolayer permeability of intestinal epithelial cells, and thus lead to diarrhea.


Assuntos
Antiportadores de Cloreto-Bicarbonato/genética , Diarreia/congênito , Erros Inatos do Metabolismo , Transportadores de Sulfato/genética , Células CACO-2 , Diarreia/genética , Humanos , Mucosa Intestinal , Erros Inatos do Metabolismo/genética , Polimorfismo de Nucleotídeo Único , Junções Íntimas , Fator de Necrose Tumoral alfa
15.
BMC Biol ; 17(1): 93, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771567

RESUMO

BACKGROUND: Cathepsin L and some other cathepsins have been implicated in the development of obesity in humans and mice. The functional inactivation of the proteases reduces fat accumulation during mammalian adipocyte differentiation. However, beyond degrading extracellular matrix protein fibronectin, the molecular mechanisms by which cathepsins control fat accumulation remain unclear. We now provide evidence from Caenorhabditis elegans and mouse models to suggest a conserved regulatory circuit in which peripheral cathepsin L inhibition lowers fat accumulation through promoting central serotonin synthesis. RESULTS: We established a C. elegans model of fat accumulation using dietary supplementation with glucose and palmitic acid. We found that nutrient supplementation elevated fat storage in C. elegans, and along with worm fat accumulation, an increase in the expression of cpl-1 was detected using real-time PCR and western blot. The functional inactivation of cpl-1 reduced fat storage in C. elegans through activating serotonin signaling. Further, knockdown of cpl-1 in the intestine and hypodermis promoted serotonin synthesis in worm ADF neurons and induced body fat loss in C. elegans via central serotonin signaling. We found a similar regulatory circuit in high-fat diet-fed mice. Cathepsin L knockout promoted fat loss and central serotonin synthesis. Intraperitoneal injection of the cathepsin L inhibitor CLIK195 similarly reduced body weight gain and white adipose tissue (WAT) adipogenesis, while elevating brain serotonin level and WAT lipolysis and fatty acid ß-oxidation. These effects of inhibiting cathepsin L were abolished by intracranial injection of p-chlorophenylalanine, inhibitor of a rate-limiting enzyme for serotonin synthesis. CONCLUSION: This study reveals a previously undescribed molecular mechanism by which peripheral CPL-1/cathepsin L inhibition induces fat loss in C. elegans and mice through promoting central serotonin signaling.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1482-1489, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607302

RESUMO

OBJECTIVE: To investigate the effects and its potential mechanism of asparaginase on proliferation, cell cycle and apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines. METHODS: CCK-8 assay was used to detect the effect of asparaginase on proliferation of DLBCL cell lines. Flow cytometry was used to analyze cell cycle and apoptosis. Western blot was used to analyze apoptosis and its potential mechanism. RESULTS: Asparaginase obviously inhibited the proliferation of multiple DLBCL cell lines and caused G0/G1 cell arrest. Furtherly, asparaginase inhibited the expression of HIF-1α which related to poor prognosis of patients with DLBCL, up-regulated the expression of DR4 and caspase 8, reduce the expression of c-FLIP. Meanwhile, asparaginase induced the expression of pro-apoptotic protein BAX and inhibited the expression of anti-apoptotic protein MCL-1. CONCLUSION: Asparaginase can inhibit the proliferation of DLBCL cell lines, cause the arrest of cells in G0/G1 and induce apoptosis via the endogenous and exogenous apoptotic pathways.


Assuntos
Linfoma Difuso de Grandes Células B , Apoptose , Asparaginase , Linhagem Celular Tumoral , Proliferação de Células , Humanos
17.
ACS Appl Mater Interfaces ; 11(45): 42429-42437, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31625392

RESUMO

Photonic data storage has diverse optoelectronic applications such as optical sensing and recording, integrated image circuits, and multibit-storage flash memory. In this study, we employ conjugated/insulated polymer blends as the charge storage electret for photonic field-effect transistor memory devices by exploring the blend composition, energy level alignment, and morphology on the memory characteristics. The studied conjugated polymers included poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PF), poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), poly[{2,5-di(3',7'-dimethyloctyloxy)-1,4-phenylene-vinylene}-co-{3-(4'-(3″,7″-dimethyloctyloxy)phenyl)-1,4-phenylenevinylene}-co-{3-(3'-(3',7'-dimethyloctyloxy)phenyl)-1,4-phenylenevinylene}] (SY-PPV), and poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)] (F8BT), and the insulated polymers were polystyrene (PS) and poly(methyl methacrylate) (PMMA). The photonic memory device using the PF/PS blend electret exhibited a dynamic switching behavior with light-writing and voltage-erasing processes both within only 1 s, along with a high contrast on the current on/off ratio between "Photo-On" and "Electrical-OFF" over 106 and the decent retention time for more than 3 months. In addition, the multilevel memory behavior could be observed using different light sources of 405, 450, and 520 nm or energy intensity, which was supported by surface potential analysis. The characteristics were superior to those of the devices using PF/PMMA blend due to the higher charge storage behavior of PS supported by fluorescence analysis. The PF/PS blend film prepared from the chlorobenzene solvent exhibited mesh-like and aggregated PF domains in the PS matrix and enhanced the contact surface area between the semiconductor and blend electret, leading to a higher memory window. The photonic memory behavior was also observed in the blend electrets of PS with the low band gap polymer, MEH-PPV, SY-PPV, or F8BT, by changing the photoresponsive light sources. Our study demonstrated a new electret system to apply on the multilevel photonic memory devices.

18.
Phys Chem Chem Phys ; 21(39): 22048-22056, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31565718

RESUMO

Molecules with planar tetracoordinate carbons (ptCs) are exotic in chemical bonding, and they are normally designed according to the 18-electron rule. Here we report on the viability of ptC clusters with as few as 12 valence electrons, which represent the lower limit in terms of electron counting. Specifically, we have computationally designed a class of ternary 12-electron ptC clusters, CBe3X3+ (X = H, Li, Na, Cu, Ag), based on a rhombic CBe32- unit. Computer structural searches reveal that the ptC species are global minima, whose C center is coordinated in-plane by three Be atoms and a terminal X atom via robust C-Be/C-X bonding, either covalent or ionic. The other two X atoms are on the periphery and each bridge two Be atoms. Bonding analyses show that the ptC core is governed by delocalized 2π/6σ bonding, that is, double π/σ aromaticity, which collectively conforms to the 8-electron counting. Additional 4 electrons contribute to peripheral Be-X-Be and Be-Be σ bonding. The delocalized 2π/6σ frameworks appear to be universal for all ptC clusters, ranging from 18-electron down to 12-electron systems. In other words, the ptC species are dictated entirely by the 8-electron counting. Predicted vertical electron affinities of these ptC clusters range from 3.13 to 5.48 eV, indicative of superalkali or pseudoalkali cations.

20.
Sci Rep ; 9(1): 14533, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601864

RESUMO

We determined the effects of insufficient maternal energy on testicular development in offspring in a swine model. Thirty-six sows were divided into control (CON) and low-energy diet (LE) groups during gestation. We observed that the number of Sertoli, germ, and Leydig cells in the offspring of the CON group were significantly higher than those in the LE group at 28 and 120 d after birth. Furthermore, the percentage of apoptotic testis cells was significantly higher in the offspring of the LE group than in the CON group. Transcriptome analysis of differentially expressed mRNAs and long noncoding RNAs in offspring testes indicated that these RNAs were mainly involved in lipid metabolism, apoptosis, cell proliferation, and some pivotal regulatory pathways. Results revealed that AMPK-PI3K-mTOR, MAPK, and oxidative phosphorylation signaling pathways play an important role in mediating the programming effect of insufficient maternal energy on testicular development, and that this effect occurs mainly at an early stage in life. mRNA and protein expression analyses confirmed the importance of certain signaling pathways in the regulation of testicular development. This study provides insights into the influence and possible mechanism underlying the effect of inadequate maternal energy intake on testicular development in the offspring.

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