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1.
BMC Cancer ; 19(1): 1063, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703647

RESUMO

BACKGROUND: Prostate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer. METHODS: Relevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. RESULTS: The meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93-1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42-3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76-1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12-2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61-0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89-1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86-1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups. CONCLUSION: Results suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.

2.
Acta Pharmacol Sin ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705124

RESUMO

Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and 89zirconium (89Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100-200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson's disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies.

3.
Int Immunopharmacol ; 77: 105984, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31677501

RESUMO

Ampelopsin (Amp), a natural flavonoid found in the vine tea of Ampelopsis grossedentata, exhibited anti-cancer, anti-oxidant, anti-inflammatory, anti-apoptosis and hepatoprotective properties. The current study instigates the protective effect of Amp on carbon tetrachloride (CCl4)-induced hepatic fibrosis and explores its underlying mechanisms. The results indicated Amp decreased the levels of liver injury markers. Amp inhibited liver fibrosis, as indicated by decreases in hepatic collagen deposition, extracellular matrix (ECM) deposition and α-smooth muscle actin (α-SMA). Amp blocked the activation of hepaticstellate cells (HSCs) by decreasing the expression of collage I, α-SMA, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, transforming growth factor (TGF)-ß1, phosphorylated Smad3 (p-Smad3) and increasing the expression of matrix metalloproteinases (MMPs) 9 and SIRT1 in the model of liver fibrosis and cultured HSCs. The sirtuin 1 (SIRT1) specific inhibitor Sirtinol activated the TGF-ß1/Smad3 pathway and enhanced ECM accumulation. Attractively, Amp up-regulates the expression of autophagy-related proteins microtubule-associated protein light chain three II (LC3-II) and Beclin-1 in vivo and in vitro. However, depletion of autophagy by specific inhibitor 3-MA obviously abolished the inhibiting effect of Amp on HSC activation and hepatic fibrosis. Conclusively, these results suggest that Amp could decrease CCl4-induced hepatic fibrosis through regulating the SIRT1/TGF-ß1/Smad3 and autophagy pathway.

4.
Carbohydr Polym ; 226: 115302, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582049

RESUMO

Hydrogels could be promising wound healing dressings that maintain a moist environment in the wound site and accelerate wound healing. However, the lack of antibacterial effect, suitable mechanical property and adhesiveness limits their applications. Here, we designed a quaternized chitosan-Matrigel-polyacrylamide (QCS-M-PAM) hydrogel with multi-functions. The morphology, swelling ratio, mechanical test, antimicrobial property, hemostatic performance and biocompatibility of the hybrid hydrogel were investigated in vitro and vivo. The hybrid hydrogel showed a three-dimensional (3D) microporous structure, high swelling ratio, excellent stretchable and compressive property, similar modulus to human skin, good adhesiveness, and low cytotoxicity. The results of histology and molecular testing in vivo demonstrated that the hybrid hydrogel could significantly enhance wound healing, collagen deposition, and induce skin adnexal regeneration by upregulating anti-inflammatory factors, and downregulating proinflammatory factors. Together, the present antibacterial hydrogels with hemostatic and adhesive properties are considered to have promising potential used as wound dressings for full-thickness skin defect.

5.
Rev Sci Instrum ; 90(9): 094704, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31575239

RESUMO

A three-layer aperture coupled microstrip antenna array (ACMA) is designed and fabricated for wideband high-power microwave (HPM) application, which has not been reported in the field of HPM. In this paper, the proposed antenna array overcomes the disadvantage of low power capacity of traditional microstrip antenna arrays. Moreover, based on the H-shaped aperture coupled structure, it enhances the relative bandwidth up to more than 50%. Compared with traditional HPM antennas, it has advantages of being low-profile (less than 0.2λ), wideband, lightweight, and easy to manufacture. The proposed antenna array consists of 60 elements; each element has four aperture coupled patch antennas fed by a four-way microstrip line power divider. In order to realize the modular design, the antenna array is divided into 10 identical modules; benefiting from this design, machining and assembling become easier. Additionally, cold tests and high-power tests are carried out, and the experimental results show that the ACMA achieves a relative bandwidth of 51.2% for voltage standing-wave ratio < 2 from 1.52 to 2.57 GHz. Consistent with simulation results, the measured gain is more than 28.8 dB in the whole bandwidth and it reaches a maximum of 32.1 dB. Finally, the high-power tests show that the power capacity of the proposed ACMA is greater than 140 MW, which proves the feasibility of the design in wideband HPM application.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 996-998, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598944

RESUMO

OBJECTIVE: To explore the genetic basis for an infant with early-onset argininemia. METHODS: Potential variant was detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases. Suspected variants were verified by Sanger sequencing. RESULTS: Genetic testing indicated that he has carried c.560+2T>C and c.811T>C compound heterozygous variant of the AGR1 gene, which were inherited from his father and mother, respectively. Among these, c.560+2T>C was suspected to be pathogenic, while c.811T>C was of unknown clinical significance, and both were not reported previously. CONCLUSION: The c.560+2T>C and c.811T>C compound heterozygous variants of the AGR1 gene probably underlies the argininemia in this child. Above finding has enriched the variant spectrum of the AGR1 gene.


Assuntos
Arginase/genética , Hiperargininemia/genética , Feminino , Testes Genéticos , Humanos , Lactente , Masculino
7.
Langmuir ; 35(44): 14324-14331, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31580079

RESUMO

Photodynamic therapy is a promising approach for fighting bacterial infections because it can induce few side effects, develop no drug resistance, and realize precise treatment. However, most photosensitizers (PSs) have the disadvantages of poor water-solubility, severe self-quenching, and potential toxicity. Here, the cationic polymer polyethyleneimine (PEI) was used to prepare a cholesterol- and chlorin e6 (Ce6, a common PS)-conjugated compound via the carboxyl-amine reaction or the acyl chloride-amine reaction (abbreviated as Chol-PEI-Ce6). The as-prepared Chol-PEI-Ce6 molecules can self-assemble into close-to-spherical nanoparticles (NPs) with an average diameter of ∼15 nm and can bind to the bacterial surfaces via the synergistic hydrophobic insertion of the cholesterol moieties and electrostatic interaction between the cationic amine groups of PEI and the bacterial surfaces. Upon light irradiation, the NPs can effectively inactivate both Gram-positive and Gram-negative bacteria. Besides, the interaction between Chol-PEI-Ce6 NPs and bacteria markedly enhances the production of intracellular reactive oxygen species after light irradiation, which may account for the excellent antibacterial performance of the NPs. More importantly, the NPs possess negligible dark cytotoxicity and good hemocompatibility. Therefore, the present work may have strong implications for developing novel antibacterial agents to fight against bacterial infections.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31588738

RESUMO

Radiotherapy and chemotherapy are both common clinical treatment methods. The combination of the two treatments can decrease tumor recurrence. In this study, bismuth-based mesoporous litchi-shaped Na0.2Bi0.8O0.35F1.91:20%Yb (NBOF) nanoparticles (NPs) have been reported as a radiosensitizer and as a nanovehicle for loading and slow-releasing doxorubicin (DOX). After assembling with amphiphilic poly(ethylene glycol) (PEG), NBOF-DOX-PEG qualified with excellent aqueous dispersibility and the enhanced tumor radiation and chemo-synergistic therapy characteristics. The formation of NBOF revealed the oxygen element in NBOF came from H2O and air in the synthesis and post-treatment process, and the size of NBOF could be adjusted by changing the concentration of doped Yb ion. The average size of NBOF was ca. 80 nm. Brunauer-Emmett-Teller results demonstrated the mesoporous structure of NBOF. So DOX could be loaded in NBOF and the optimized loading content was 39%. Then, NBOF-PEG exhibited a strong computed tomography signal whitening ability and enhanced radiotherapy effect. Combined with the chemotherapy ability of DOX, NBOF-DOX-PEG NPs presented remarkable synergistic tumor elimination ability. Meanwhile, NBOF-DOX-PEG NPs qualified for excellent biosafety. Our study not only proved the combined chemo- and radiotherapy for enhancing therapeutic effect but also supplied a functional Bi-based mesoporous nanovehicle for constructing an intelligent theranostic platform.

9.
Comput Methods Programs Biomed ; 183: 105096, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31586789

RESUMO

BACKGROUND AND OBJECTIVES: The retinal fundus contains intricate vascular trees, some of which are mutually intersected and overlapped. The intersection and overlapping of retinal vessels represent vascular junctions (i.e. bifurcation and crossover) in 2D retinal images. These junctions are important for analyzing vascular diseases and tracking the morphology of vessels. In this paper, we propose a two-stage pipeline to detect and classify the junction points. METHODS: In the detection stage, a RCNN-based Junction Proposal Network is utilized to search the potential bifurcation and crossover locations directly on color retinal images, which is followed by a Junction Refinement Network to eliminate the false detections. In the classification stage, the detected junction points are identified as crossover or bifurcation using the proposed Junction Classification Network that shares the same model structure with the refinement network. RESULTS: Our approach achieves 70% and 60% F1-score on DRIVE and IOSTAR dataset respectively which outperform the state-of-the-art methods by 4.5% and 1.7%, with a high and balanced precision and recall values. CONCLUSIONS: This paper proposes a new junction detection and classification method which performs directly on color retinal images without any vessel segmentation nor skeleton preprocessing. The superior performance demonstrates that the effectiveness of our approach.

10.
Cancer Med ; 8(16): 6933-6944, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566899

RESUMO

BACKGROUND: Portal vein tumor thrombus (PVTT) is a common complication in hepatocellular carcinoma (HCC), signaling dismal outcomes. This study was conducted to evaluate the survival benefit of postoperative portal vein perfusion chemotherapy (PVC) in patients with HCC and PVTT. METHODS: A retrospective review was conducted in 401 consecutive patients with HCC and PVTT who underwent hepatic resection between January 2009 and December 2015 and 67 patients received adjuvant postoperative PVC. A propensity score matching (PSM) was used to match patients with and without PVC at a ratio of 1:1. RESULTS: After PSM, the median time to recurrence (TTR) and overall survival (OS) were significantly longer in PVC group compared with control group (12.3 vs 5.8 months, P = .001; 19.0 vs 13.4 months, P = .037; respectively). At 1, 2, 3, and 5 years, the cumulative recurrence rates in PVC group were 48.1%, 86.5%, 92.3% ,96.2%, respectively, with OS rates of 63.8%, 37.9%, 24.4%, 18.3%, respectively; whereas cumulative recurrence rates of 76.6%, 91.5%, 94.3%, and 97.2%, respectively and OS rates of 55.4%, 23.0%, 12.4%, and 12.4%, respectively were recorded for the control group. In multivariate analysis, postoperative PVC emerged as a significant predictor for TTR (hazard ratio [HR], 0.523; P = .001) and OS (HR, 0.591; P = .010). PVC could reduce early recurrence (≤1 year) rate after surgical resection (40.3% vs 64.2%, P = .006) and clinical outcomes were further enhanced by adding sorafenib to postoperative PVC. CONCLUSIONS: Compared with surgical resection alone, postoperative adjuvant PVC treatment boosts survival and reduces early tumor recurrences in patients surgically treated for HCC and PVTT.

11.
Rev Sci Instrum ; 90(8): 084703, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472644

RESUMO

A novel compact E-shaped wideband planar antenna array (CEWPA) is designed and fabricated for high-power microwave (HPM) application. The CEWPA is a kind of planar antenna and it has a lot of advantages such as low profile, wideband, high efficiency, easy to manufacture, and light weight. Compared with traditional planar antenna arrays, it overcomes the disadvantage of low power capacity through special metal structure designs. The CEWPA consists of 60 antenna elements and achieved miniaturization by an innovative array layout. In addition, it has reached a relative bandwidth of 33% (VSWR < 2) at a center frequency of 2.1 GHz in simulation and over 20% in experiment. On the other hand, the measured gain at the cold test is greater than 20 dB in the whole bandwidth while the radiation patterns are in agreement with the simulation. In addition, excited by nanosecond level pulses, the power capacity of the whole system is more than 140 MW in a high-power test.

12.
Glycobiology ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31504486

RESUMO

In this work, we investigated the functions of structural modules within alginate lyase by truncating an endo-type alginate lyase into two successive catalytic modules. The effects of module deletion on biochemical characteristics and product distributions were further investigated. The N-terminal module (Aly7B-CDI) exhibited no activity toward alginate, polyM, or polyG, but the C-terminal module (Aly7B-CDII) retained its activity. The full-length enzyme (Aly7B) and its truncated counterpart (Aly7B-CDII) had similar substrate specificities, but Aly7B-CDII had lower activity. Moreover, the activity of Aly7B was much higher than Aly7B-CDII at 30°C. Aly7B-CDII, however, possessed higher optimal pH and better pH stability than the full-length enzyme. The final degradation products for Aly7B were unsaturated di-, tri-, and tetra- oligosaccharides, and those for Aly7B-CDII were unsaturated mono-, di-, tri-, tetra-, and penta-oligosaccharides. Therefore, the potential impact of the noncatalytic module Aly7B-CDI on the catalytic module Aly7B-CDII was further elucidated by characterizing Aly7B and its truncations. These data contribute to the functional understanding of these differing modules.

13.
Molecules ; 24(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533323

RESUMO

Tea aroma is a key indicator for evaluating tea quality. Although notable success in tea aroma improvement has been achieved with heterosis breeding technology, the molecular basis underlying heterosis remains largely unexplored. Thus, the present report studies the tea plant volatile heterosis using a high-throughput next-generation RNA-seq strategy and gas chromatography-mass spectrometry. Phenotypically, we found higher terpenoid volatile and green leaf volatile contents by gas chromatography-mass spectrometry in the F1 hybrids than in their parental lines. Volatile heterosis was obvious in both F1 hybrids. At the molecular level, the comparative transcriptomics analysis revealed that approximately 41% (9027 of 21,995) of the genes showed non-additive expression, whereas only 7.83% (1723 of 21,995) showed additive expression. Among the non-additive genes, 42.1% showed high parental dominance and 17.6% showed over-dominance. Among different expression genes with high parental dominance and over-dominance expression patterns, KEGG and GO analyses found that plant hormone signal transduction, tea plant physiological process related pathways and most pathways associated with tea tree volatiles were enriched. In addition, we identified multiple genes (CsDXS, CsAATC2, CsSPLA2, etc.) and transcription factors (CsMYB1, CsbHLH79, CsWRKY40, etc.) that played important roles in tea volatile heterosis. Based on transcriptome and metabolite profiling, we conclude that non-additive action plays a major role in tea volatile heterosis. Genes and transcription factors involved in tea volatiles showing over-dominance expression patterns can be considered candidate genes and provide novel clues for breeding high-volatile tea varieties.

14.
Fish Shellfish Immunol ; 94: 880-888, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31562894

RESUMO

The humpback grouper (Cromileptes altivelis) is a commercially valuable species of the family Epinephelidae; however, its marketization suffers from slow growth speed, low survival rate, and various pathogenic diseases. Lactococcus lactis and Schizochytrium limacinum are commonly used as immunostimulants due to their health benefits for the aquatic organisms. In the present study, we assessed the effects of dietary supplementation with L. lactis HNL12 combined with S. limacinum algal meal on the growth performances, innate immune response, and disease resistance of C. altivelis against Vibrio harveyi. The results showed that fish fed with a combination diet of L. lactis and S. limacinum exhibited significantly higher final weight, percent weight gain, and specific growth rate compared with groups fed with them alone. A bacterial challenge experiment indicated that the group fed with the L. lactis combined with S. limacinum diet achieved the highest relative percent of survival value (68.63%), suggesting that L. lactis and S. limacinum significantly improved the disease resistance against V. harveyi after a 4-week feeding trial. Moreover, the respiratory burst activity of macrophages of fish fed with a L. lactis combined with S. limacinum diet was significantly higher than that of fish fed the control diet after 1, 2, and 3 weeks of feeding. The serum superoxide dismutase of fish fed with a L. lactis combined with S. limacinum diet significantly increased compared to those fed the control diet after 1 and 2 weeks of feeding, while the serum alkaline phosphatase of fish fed with a L. lactis combined with S. limacinum diet after 2 and 4 weeks was significantly increased, compared to the control group. The serum lysozyme activities of fish fed with a L. lactis combined with S. limacinum diet significantly increased compared to the control group after 2 weeks of feeding. Furthermore, transcriptome sequencing of the C. altivelis head kidney was conducted to explore the immune-regulating effects of the L. lactis combined with S. limacinum diet on C. altivelis. A total of 86,919 unigenes, annotated by at least one of the reference databases (Nr, Swiss-Prot, GO, COG, and KEGG), were assembly yielded by de novo transcriptome. In addition, 157 putative differentially expressed genes (DEGs) were identified between the L. lactis combined with S. limacinum group and the control group. For pathway enrichment, the DEGs were categorized into nine KEGG pathways, which were mainly related to infective diseases, antigen processing and presentation, digestive system, and other immune system responses. The findings of this study suggest that the L. lactis combined with S. limacinum diet can induce positive effects on the growth, immunity, and disease resistance of C. altivelis against V. harveyi. This study expands our understanding of the synergistic combinations of probiotics and prebiotics in aquaculture.

15.
EBioMedicine ; 47: 352-364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31473185

RESUMO

BACKGROUND: NOS1AP is an adaptor protein and its SNP rs12742393 was associated with type 2 diabetes (T2D). However, it remains uncertain whether NOS1AP plays a role in regulation of insulin sensitivity. Hepatic insulin resistance contributed to the development of T2D. Here, our investigation was focused on whether NOS1AP is involved in the regulation of hepatic insulin sensitivity and its underlying mechanisms. METHODS: Liver specific NOS1AP condition knockout (CKO) and NOS1AP overexpression mice were generated and given a high fat diet. SNPs of NOS1AP gene were genotyped in 86 human subjects. FINDINGS: NOS1AP protein is expressed in human and mouse liver. CKO mice exhibited impaired pyruvate, glucose and insulin tolerance, and increased lipid deposits in the liver. Conversely, NOS1AP overexpression in livers of obese mice improved pyruvate and/or glucose, and insulin tolerance, and attenuated liver lipid accumulation. Moreover, hepatocytes from CKO mice exhibited an elevated glucose production and mRNA expressions of Pc and Pck1. Overexpression of NOS1AP potentiated insulin-stimulated activation of IR/Akt in livers from obese mice. The insulin sensitizing effect of NOS1AP could be mimicked by overexpression of C-terminal domain of NOS1AP in ob/ob mice. Furthermore, NOS1AP overexpression in liver significantly inhibited p38 MAPK phosphorylation, and maintained ER homeostasis through p-eIF2a-ATF4-CHOP pathway. Subjects with rsl2742393 of NOS1AP have higher risk to develop hepatic steatosis. INTERPRETATION: Our data demonstrate a novel role of NOS1AP in regulating hepatic insulin sensitivity and p38 MAPK inactivation in obese mice, which makes NOS1AP a potential therapeutic target for the prevention and treatment of T2D. FUND: This work was supported by the National Natural Science Foundation of China (81670707, 31340072) (to C. Wang), and National Basic Research Program of China (Nation 973 Program) (2011CB504001) (to W. Jia).

16.
Fish Shellfish Immunol ; 93: 863-870, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422178

RESUMO

Interleukins (ILs) are a subgroup of cytokines, which are molecules involved in the intercellular regulation of the immune system. These cytokines have been extensively studied in mammalian models, but systematic analyses of fish are limited. In the current study, 3 IL genes from golden pompano (Trachinotus ovatus) were characterized. The IL-1ß protein contains IL-1 family signature motif, and four long helices (αA - αD) in IL-11 and IL-34, which were well conserved. All 3 ILs clustered phylogenetically with their respective IL relatives in mammalian and other teleost species. Under normal physiological conditions, the expression of IL-1ß, IL-11, and IL-34 were detected at varied levels in the 11 tissues examined. Most of the 3 ILs examined were highly expressed in liver, spleen, kidney, gill, or skin. Following pathogenic bacterial, viral, or parasitic challenge, IL-1ß, IL-11, and IL-34 exhibited distinctly different expression profiles in a time-, tissue-, and pathogen-dependent manner. In general, IL-1ß was expressed at higher levels following challenge with all pathogens examined than was observed for IL-11 and IL-34. Furthermore, Streptococcus agalactiae and Cryptocaryon irritans caused higher levels of IL-1ß and IL-11 expression than Vibrio harveyi and viral nervous necrosis virus (VNNV). The increased expression of IL-34 caused by VNNV and C. irritans were higher than that caused by V. harveyi and S. agalactiae. These results suggest that these 3 ILs in T. ovatus may play different effect pathogen type specific responses.

17.
BMC Cancer ; 19(1): 760, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370822

RESUMO

BACKGROUNDS: The role of sphere-forming culture in enriching subpopulations with stem-cell properties in hepatocellular carcinoma (HCC) is unclear. The present study investigates its value in enriching cancer stem cells (CSCs) subpopulations and the mechanism by which HCC CSCs are maintained. METHODS: HCC cell lines and fresh primary tumor cells were cultured in serum-free and ultra-low attachment conditions to allow formation of HCC spheres. In vitro and in vivo experiments were performed to evaluate CSC characteristics. Expression levels of CSC-related genes were assessed by qRT-PCR and the correlation between sphere formation and clinical characteristics was investigated. Finally, gene expression profiling was performed to explore the molecular mechanism underlying HCC CSC maintenance. RESULTS: We found that both cell lines and primary tumor cells formed spheres. HCC spheres possessed the capacity for self-renewal, proliferation, drug resistance, and contained different subpopulations of CSCs. Of interest, 500 sphere-forming Huh7 cells or 200 primary tumor cells could generate tumors in immunodeficient animals. Sphere formation correlated with size, multiple tumors, satellite lesions, and advanced stage. Further investigation identified that the PPARα-SCD1 axis plays an important role in maintenance of the CSC properties of HCC sphere cells by promoting nuclear accumulation of ß-Catenin. Inhibition of SCD1 interfered with sphere formation, down-regulated expression of CSC-related markers, and reduced ß-Catenin nuclear accumulation. CONCLUSIONS: Sphere-forming culture can effectively enrich subpopulations with stem-cell properties, which are maintained through activation of the PPARα-SCD1 axis. Therefore, we suggest that targeting the SCD1-related CSC machinery might provide a novel insight into HCC treatment.

18.
Planta ; 250(5): 1671-1686, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31410553

RESUMO

MAIN CONCLUSION: Genome-wide identification and characterization of nuclear factor-Y family in tea plants, and their expression profiles and putative targets provide the basis for further elucidation of their biological functions. The nuclear factor-Y (NF-Y) transcription factors (TFs) are crucial regulators of plant growth and physiology. However, the NF-Y TFs in tea plant (Camellia sinensis) have not yet been elucidated, and its biological functions, especially the putative target genes within the genome range, are still unclear. In this study, we identified 35 CsNF-Y encoding genes in the tea plant genome, including 10 CsNF-YAs, 15 CsNF-YBs and 10 CsNF-YCs. Their conserved domains and motifs, phylogeny, duplication event, gene structure, and promoter were subsequently analyzed. Tissue expression analysis revealed that CsNF-Ys exhibited three distinct expression patterns in eight tea tree tissues, among which CsNF-YAs were moderately expressed. Drought and abscisic acid (ABA) treatment indicated that CsNF-YAs may have a greater impact than other subunit members. Furthermore, through the genome-wide investigation of the presence of the CCAAT box, we found that CsNF-Ys may participate in the development of tea plants by regulating target genes of multiple physiological pathways, including photosynthesis, chlorophyll metabolism, fatty acid biosynthesis, and amino acid metabolism pathways. Our findings will contribute to the functional analysis of NF-Y genes in woody plants and the cultivation of high-quality tea plant cultivars.

19.
BMC Plant Biol ; 19(1): 379, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455203

RESUMO

BACKGROUND: Metabolic pathways are interconnected and yet relatively independent. Genes involved in metabolic modules are required for the modules to run. Study of the relationships between genes and metabolic modules improves the understanding of metabolic pathways in plants. The WIN transcription factor activates the cuticle biosynthesis pathway and promotes cuticle biosynthesis. The relationship between the WIN transcription factor and other metabolic pathways is unknown. Our aim was to determine the relationships between the main genes involved in cuticle biosynthesis and those involved in other metabolic pathways. We did this by cloning a cotton WIN gene, GhWIN2, and studying its influence on other pathways. RESULTS: As with other WIN genes, GhWIN2 regulated expression of cuticle biosynthesis-related genes, and promoted cuticle formation. Silencing of GhWIN2 resulted in enhanced resistance to Verticillium dahliae, caused by increased content of salicylic acid (SA). Moreover, silencing of GhWIN2 suppressed expression of jasmonic acid (JA) biosynthesis-related genes and content. GhWIN2 positively regulated the fatty acid biosynthesis pathway upstream of the JA biosynthesis pathway. Silencing of GhWIN2 reduced the content of stearic acid, a JA biosynthesis precursor. CONCLUSIONS: GhWIN2 not only regulated the cuticle biosynthesis pathway, but also positively influenced JA biosynthesis and negatively influenced SA biosynthesis.

20.
Pancreas ; 48(8): 985-995, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31425484

RESUMO

Current evidence on cigarette smoking associated with pancreatic cancer mortality is limited. We searched MEDLINE, Web of Science, and Embase databases to identify relevant studies published through January 31, 2018. A random-effects model was used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 20 studies were retrieved, involving 2,517,623 participants. Of these, more than 15,341 patients with pancreatic cancer died. Compared with never smokers, current (summary HR, 1.56; 95% CI, 1.34-1.83) and former (summary HR, 1.15; 95% CI, 1.06-1.26) smokers had elevated risk of total mortality in patients diagnosed with pancreatic cancer. This effect of cigarette smoking is observed both in the Western regions and the Asia-Pacific regions. This effect of smoking is independent of alcohol use, body mass index, and history of diabetes but is modified by tumor stage and study settings. Dose-response associations between smoking and pancreatic cancer mortality were revealed for smoking intensity, cumulative amount of cigarettes smoked, and duration of smoking. Cigarette smoking was associated with an increase in total mortality for patients with pancreatic cancer. Future studies should further clarify the role of smoking as an effect modifier in treatment trials of pancreatic cancer.

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