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1.
Food Chem ; 307: 125546, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639580

RESUMO

Zearalenone (ZEN) is one of the most widely distributed harmful mycotoxins produced by Fusarium species, especially deposited in corn oil. In this study, we systematically tracked the changes of ZEN in the refining of corn oil, and especially during neutralization process. An alkali neutralization process could remove certain amounts of ZEN that was much more than that of others refining steps. In a mimicking condition, ZEN contents decreased continuously and significantly with increasing neutralization temperature. However, when returned to neutral, recoverable ZEN decreased with increasing temperature, which confirmed more degradation of ZEN at high temperature. HPLC-Q/TOF MS and NMR evidence showed that non-reversible hydrolyzate followed decarboxylation was observed in a high-temperature alkali neutralization condition. The results may serve as the scientific basis for the elimination of zearalenone in refined vegetable oils, and provide clues to understanding the oil-safety aspects of elimination of zearalenone.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 589-594, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699187

RESUMO

Objective To investigate the effect of microRNA-133b(miR-133b)on cardiac fibrosis and its mechanism.Methods Human cardiac fibroblasts(CFs)were harvested.The proliferation of CFs was detected by CCK8 during the overexpression and knock-down of miR-133b.The expressions of connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA),collagen Ⅰ,and collagen Ⅲ were detected with qRT-PCR and Western blot analysis after miR-133b overexpression or downexpression.Target genes of miR-133b were predicted by bioinformatics software.Dual-luciferase activity assay were used to verify a target gene of miR-133b.Results qRT-PCR showed that the expression level of miR-133b in the miR-133b mimic group was significantly higher than that in the negative control group(t=26.219,P=0.000).The expression level of miR-133b in the miR-133b inhibitor group was significantly lower than that in the negative control group(t=6.738,P=0.003).After 21,45,69,93,and 117 hours of transfection,the proliferation ability of CFs significantly decreased in the miR-133b mimic group but significantly increased in the miR-133b group(all P<0.05,compared with the negative control group).After overexpression of miR-133b,the mRNA and protein levels of CTGF(t=9.213,P=0.001;t=8.195,P=0.001),α-SMA(t=6.511,P =0.003;t=4.434,P=0.011),collagenⅠ(t=3.172,P=0.034;t=4.053,P=0.015)and collagen Ⅲ(t=6.404,P=0.003;t=5.319,P=0.006)were significantly down-regulated.After the expression of miR-133b was knocked down,the mRNA and protein levels of CTGF(t=9.439,P=0.001;t=14.100,P=0.000),α-SMA(t=4.519,P=0.011;t=4.377,P=0.012),collagen Ⅰ(t=5.966,P=0.004;t=5.514,P=0.005)and collagen Ⅲ(t=4.622,P=0.010;t=4.996,P=0.008)were significantly increased.The relative luciferase activity of the cells co-transfected with miR-133b mimic and WT 3'UTR expression vector was significantly lower than that of the cells co-transfected with mimic control and WT 3'UTR expression vectors(t=5.654,P=0.005);however,there was no significant difference in relative luciferase activity between cells co-transfected with miR-133b mimic and MUT 3'UTR expression vectors and cells co-transfected with mimic control and MUT 3'UTR expression vectors(t=0.380,P=0.724).Conclusion miR-133b may affect the activation and proliferation of CFs by targeting CTGF and thus improve cardiac fibrosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31701626

RESUMO

OBJECTIVE: To investigate the role of driver mechanism and the effect of electrogram dispersion guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression. METHODS: 256 consecutive AF patients who had undergone PVI plus driver ablation or conventional ablation were divided into 3 groups: paroxysmal AF (PAF, Group A, n=51), persistent AF (PsAF) (Group B, n=38); and long-standing persistent AF(LS-PsAF) (Group C, n=39). PVI was performed with guidance of ablation index. The electrogram dispersion was analyzed for driver mapping. RESULTS: The most prominent driver regions were at roof (28.0%), posterior wall (17.6%) and bottom (21.3%). From patients with paroxysmal AF to those with persistent and long-standing persistent AF: the complexity of extra-PV drivers including distribution, mean number and area of dispersion region increased (P<0.001). Patients who underwent driver ablation vs. conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%, P<0.001). With AF progression, the termination rate gradually decreased from group A to C, and the role of PVI in AF termination was also gradually weakened from group A to C (39.6%, 7.4% and 4.3%, P<0.001) in patients with driver ablation. At the end of the follow-up, the rate of SR maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%, P<0.001). CONCLUSION: The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment. This article is protected by copyright. All rights reserved.

4.
Medicine (Baltimore) ; 98(45): e17529, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702612

RESUMO

BACKGROUND: A number of studies have attempted to determine the prognostic value of T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1) in patients with solid cancers, but the reported results were of inconsistency. Thus, we performed a systematic review and meta-analysis to exhaustively evaluate the prognostic role of Tiam1 expression in patients with solid cancers. METHODS: We retrieved literature published in between 1994 and April 22th, 2019 through searching PubMed, Web of Science and China national knowledge infrastructure (CNKI). Hazard ratios (HRs) coupled with 95% confidence intervals (95% CIs) were used to assess the relationship of Tiam1 expression and overall survival (OS), and disease-free survival (DFS). RESULTS: A total of 2647 patients with solid cancers in 20 studies were enrolled in our meta-analysis eventually. The pooled results showed that Tiam1 high expression was closely correlated with poor OS (HR = 2.17, 95% CI: 1.80-2.61, P = .000) and DFS (pooled HR = 1.95, 95% CI = 1.58-2.40, P = .000). Moreover, our subgroup analysis and sensitivity analysis demonstrated the reliability and stability of our pooled results. CONCLUSION: In conclusion, this meta-analysis confirmed that Tiam1 higher expression positively correlated with OS and DFS, suggesting that Tiam1 may act as a valuable prognostic predictor and therapeutic target for patients with solid cancers. Nevertheless, in future more homogeneous and prospective studies should be performed to further support our findings.

5.
Chin Med J (Engl) ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31725459

RESUMO

BACKGROUND: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. METHODS: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. RESULTS: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. CONCLUSION: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. TRIAL REGISTRATION: NCT01962155; https://clinicaltrials.gov.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31671887

RESUMO

Drawing on psychological contract theory, this research contributes to the unethical behavior literature by exploring employees' turnover intentions as a mediator of the relationship between abusive supervision and employees' unethical behavior and the moderating role of the caring climate in the relationship between turnover intentions and unethical behavior. The results from a sample of 679 reveal that turnover intentions mediate relationship between abusive supervision and subordinates' unethical behavior, and caring climate moderates the positive relationship between turnover intentions and subordinates' unethical behavior. We also find that the indirect effect is moderated by the caring climate. The theoretical and practical implications are discussed.

7.
FEBS Lett ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721178

RESUMO

The constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimer's disease (AD) and other tauopathies. Full-length tau requires the addition of anionic cofactors such as heparin to enhance assembly. We have shown that a fragment from the proteolytically stable core of the PHF, tau 297-391 known as "dGAE", spontaneously forms cross-b-containing PHFs and straight filaments under physiological conditions. Here, we have analysed and compared the structures of the filaments formed by dGAE in vitro with those deposited in the brains of individuals diagnosed with AD. We show that dGAE forms PHFs that share a macromolecular structure similar to those found in brain tissue. Thus, dGAEs may serve as a model system for studying core domain assembly and for screening for inhibitors of tau aggregation.

8.
Chemosphere ; 242: 125201, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31677514

RESUMO

Photocatalytic disinfection with high performance is thought to be a promising way for water purification. Herein, plasmonic Ag doped urea-derived graphitic carbon nitride (g-C3N4) composites were fabricated via in-situ photo-deposition at room temperature as the visible-light photocatalyst. Scan electron microscopy and transmission electron microscopy images showed the uniform dispersion of Ag nanoparticles on the surface of g-C3N4 sheet, which facilitated the synergistic effect of antibacterial performance from Ag and photocatalytic property from Ag/g-C3N4 composites. Photocatalytic water disinfection against Escherichia coli with visible light was performed to demonstrate the improved photocatalytic property with assistance of Ag. The 3-Ag/g-C3N4 exhibited the best bactericidal performance by inactivating all bacteria within 120 min with damaged cell membranes of Escherichia coli observed by scan electron microscopy and transmission electron microscopy images. Photoluminescence spectra, steady-state surface photovoltage spectra, photocurrent response, and electrochemical impedance spectra results revealed that Ag nanoparticles inhibited the recombination of photo-generated e- and h+ pairs and further reinforced the photocatalytic performance of g-C3N4. Scavenger experiments indicated that h+ produced on valence band of g-C3N4 dominated the photocatalytic disinfection process against Escherichia coli. This work further proved Ag/g-C3N4 showed great potential in photocatalytic water disinfection under visible-light irradiation.

9.
Brief Bioinform ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31711128

RESUMO

To understand tumor heterogeneity in cancer, personalized driver genes (PDGs) need to be identified for unraveling the genotype-phenotype associations corresponding to particular patients. However, most of the existing driver-focus methods mainly pay attention on the cohort information rather than on individual information. Recent developing computational approaches based on network control principles are opening a new way to discover driver genes in cancer, particularly at an individual level. To provide comprehensive perspectives of network control methods on this timely topic, we first considered the cancer progression as a network control problem, in which the expected PDGs are altered genes by oncogene activation signals that can change the individual molecular network from one health state to the other disease state. Then, we reviewed the network reconstruction methods on single samples and introduced novel network control methods on single-sample networks to identify PDGs in cancer. Particularly, we gave a performance assessment of the network structure control-based PDGs identification methods on multiple cancer datasets from TCGA, for which the data and evaluation package also are publicly available. Finally, we discussed future directions for the application of network control methods to identify PDGs in cancer and diverse biological processes.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31618774

RESUMO

OBJECTIVE: The aim of this study was to document the effects of positive-profile threaded external skeletal fixation (ESF) pin insertion without predrilling on heat generation, structural damage and pullout strength in avian bone than that with predrilling. STUDY DESIGN: This study was an ex vivo study. MATERIALS AND METHODS: Twenty paired tibiotarsi and 40 paired humeri from 20 Mallard duck cadavers were used. Specimens were randomized to have positive-profile threaded ESF pins placed with or without predrilling insertion sites. Heat generation (maximum-baseline temperature) was measured during drilling and pin insertion with infrared thermography. Structural damage (gross trans-cortical damage and thread quality) was evaluated and scored using a visual analog scale (VAS). Mechanical testing was performed to evaluate pullout strength of inserted pins. RESULTS: VAS scores for trans-cortical surfaces were significantly higher than for cis-cortical surfaces; however, no difference was noted between predrilled and non-predrilled specimens. No significant difference in heat generation or pullout strength was noted between pins placed with and without predrilling. CONCLUSION: Pin insertion without predrilling in avian humeri and tibiotarsi does not cause significantly more structural damage or heat generation, or reduced pullout strength, compared with predrilling. Overall, our results indicate that predrilling prior to ESF pin placement provides no obvious advantage in avian bone.

11.
Molecules ; 24(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652602

RESUMO

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.

12.
Theranostics ; 9(22): 6690-6705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588244

RESUMO

Rationale: The idiosyncratic drug-induced liver injury (iDILI) is a major cause of acute liver injury and a key challenge in late-stage drug development. Individual heterogeneity is considered to be an essential factor of iDILI. However, few in vitro model can predict heterogeneity in iDILI. We have previously shown that mouse and human hepatocytes can be converted to expandable liver progenitor-like cells in vitro (HepLPCs). However, the limited proliferation potential of human HepLPCs confines its industrial application. Here, we reported the generation of a novel hepatocyte model not only to provide unlimited cell sources for human hepatocytes but also to establish a tool for studying iDILI in vitro. Methods: Human primary hepatocytes were isolated by modified two-step perfusion technique. The chemical reprogramming culture condition together with gene-transfer were then used to generate the immortalized HepLPC cell lines (iHepLPCs). Growth curve, doubling time, and karyotype were analyzed to evaluate the proliferation characteristics of iHepLPCs. Modified Hepatocyte Maturation Medium and 3D spheroid culture were applied to re-differentiate iHepLPCs. Results: iHepLPCs exhibited efficient expansion for at least 40 population doublings, with a stable proliferative ability. They could easily differentiate back into metabolically functional hepatocytes in vitro within 10 days. Furthermore, under three-dimensional culture conditions, the formed hepatic spheroids showed multiple liver functions and toxicity profiles close to those of primary human hepatocytes. Importantly, we established a hepatocyte bank by generating a specific number of such cell lines. Screening for population heterogeneity allowed us to analyze the in vitro heterogeneous responses to hepatotoxicity induced by molecular targeted drugs. Conclusions: In light of the proliferative capacity and the heterogeneity they represented, these iHepLPCs cell lines may offer assistance in studying xenobiotic metabolism as well as liver diseases in vitro.

13.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3576-3581, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602925

RESUMO

To detect the concentration of triptolide in skin and joint after percutaneous administration,an HPLC-MS/MS method and skin and joint micro-dialysis( MD) method of triptolide were established in this study. The separation was achieved on triple quadrupole( AB QTRAP4500) and phenomenex-C18( 4. 6 mm×150 mm,5 µm,luna) column with acetonitrile-water with 0. 1% formic acid( 65 ∶35) as the mobile phase at a flow rate of 0. 7 m L·min-1. An electrospray ionization( ESI) source was applied and operated in the positive multiple reaction monitoring( MRM) mode. The fragment ion for triptolide was m/z 361. 1→145. 0. The effects of different perfusion [Ringer's,PBS( p H 7. 4),30% ethanol saline]drug concentrations and flow rates on the recovery rate,as well as the relationship between the recovery rate and the loss rate were determined by incremental( dialysis) and reduction( retrodialysis) methods.The reduction method was applied in the in vivo study to investigate and determine the stability of the probe recovery rate in 10 h. The results of HPLC-MS/MS detection method conformed to the requirements of biological samples. The perfusion fluid was 30% ethanol saline. The recovery rate of skin and joint probes in vitro of triptolide increased within the flow rate of 0. 5-2. 5 µL·min-1. In order to increase the timeliness of data and the accuracy,the flow rate was determined to be 1 µL·min-1,and the sample interval was determined to be 0. 5 h. The recovery rate of triptolide in skin and joint probes in vitro and the loss rate were stable and equal despite of change of triptolide concentration within 10-200 µg·L-1. This indicated that the effect of drug concentration on the MD probe recovery rate was small,and the recovery rate could be replaced by the loss rate. The loss rate in vivo using MD method was measured at 10 h,indicating that the transfer rate of triptolide was stable within 10 h. The established method of triptolide in MD and HPLC-MS/MS can be applied to investigate the kinetic in skin and joint after percutaneous administration of triptolide.


Assuntos
Diterpenos/farmacocinética , Articulações/metabolismo , Fenantrenos/farmacocinética , Pele/metabolismo , Cromatografia Líquida de Alta Pressão , Compostos de Epóxi/farmacocinética , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
14.
Nucleic Acids Res ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647101

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

15.
Molecules ; 24(21)2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661883

RESUMO

The yield and quality of goji (Lycium barbarum L.) fruit are heavily dependent on fertilizer, especially the availability of nitrogen, phosphorus, and potassium (N, P, and K, respectively). In this study, we performed a metabolomic analysis of the response of goji berry to nitrogen fertilizer levels using an Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) method. There was no significant difference in the fruit yield or the commodity grade between N0 (42.5 g/plant), N1 (85 g/plant), and N2 (127.5 g/plant). The primary nutrients of the goji berry changed with an increasing nitrogen fertilization. Comparative metabolomic profiling of three nitrogen levels resulted in the identification of 612 metabolites, including amino acids, flavonoids, carbohydrates, organic acids, and lipids/alcohols, among others, of which 53 metabolites (lipids, fatty acids, organic acids, and phenolamides) demonstrated significant changes. These results provide new insights into the molecular mechanisms of the relationship between yield and quality of goji berry and nitrogen fertilizer.

16.
Anal Chem ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31646861

RESUMO

Isolation and analysis of circulating tumor cells (CTCs) from the blood of patients at risk of metastatic cancers is a promising approach to improving cancer treatment. However, CTC isolation is difficult due to low CTC abundance and heterogeneity. Previously, we reported an ensemble-decision aliquot ranking (eDAR) platform for the rare cell and CTC isolation with high throughput, greater than 90% recovery, and high sensitivity, allowing detection of low surface antigen-expressing cells linked to metastasis. Here we demonstrate a sequential eDAR platform capable of isolating rare cells from whole blood with high purity. This improvement in purity is achieved by using a sequential sorting and flow stretching design in which whole blood is sorted and fluid elements are stretched using herringbone features and the parabolic flow profile being sorted a second time. This platform can be used to collect single CTCs in a multiwell plate for downstream analysis.

17.
Microb Cell Fact ; 18(1): 180, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647018

RESUMO

BACKGROUND: Structurally stable α-galactosidases are of great interest for various biotechnological applications. More thermophilic α-galactosidases with high activity and structural stability have therefore to be mined and characterized. On the other hand, few studies have been performed to prominently enhance the AOX1 promoter activity in the commonly used Pichia pastoris system, in which production of some heterologous proteins are insufficient for further study. RESULTS: ReGal2 encoding a thermoactive α-galactosidase was identified from the thermophilic (hemi)cellulolytic fungus Rasamsonia emersonii. Significantly increased production of ReGal2 was achieved when ReGal2 was expressed in an engineered Pastoris pichia expression system with a modified AOX1 promoter and simultaneous fortified expression of Mxr1 that is involved in transcriptionally activating AOX1. Purified ReGal2 exists as an oligomer and has remarkable thermo-activity and thermo-tolerance, exhibiting maximum activity of 935 U/mg towards pNPGal at 80 °C and retaining full activity after incubation at 70 °C for 60 h. ReGal2 is insensitive to treatments by many metal ions and exhibits superior tolerance to protein denaturants. Moreover, ReGal2 efficiently hydrolyzed stachyose and raffinose in soybeans at 70 °C in 3 h and 24 h, respectively. CONCLUSION: A modified P. pichia expression system with significantly enhanced AOX1 promoter activity has been established, in which ReGal2 production is markedly elevated to facilitate downstream purification and characterization. Purified ReGal2 exhibited prominent features in thermostability, catalytic activity, and resistance to protein denaturants. ReGal2 thus holds great potential in relevant biotechnological applications.

18.
Medicine (Baltimore) ; 98(43): e17418, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651844

RESUMO

RATIONALE: Primary aldosteronism (PA) comprises 2 main subtypes: unilateral aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism or named as bilateral adrenal hyperplasia (BAH). An accurate discrimination between APA and BAH is crucial because the former is treated with adrenalectomy (ADX) and the latter is primarily by aldosterone antagonists. We report a case of idiopathic hyperaldosteronism characterized by BAH. PATIENT CONCERNS: A 46-year-old woman had experienced a paroxysmal elevation of blood pressure for the past 2 months, along with an intermittent headache and mild occipital swelling and pain. DIAGNOSES: We performed clinical, laboratory, and imaging tests, as well as bilateral adrenal vein sampling (AVS) on this patient. Specifically, computed tomography scan and magnetic resonance imaging were used to characterize the properties of bilateral adrenal adenoma. Additionally, bilateral AVS was performed to distinguish unilateral from bilateral adrenal abnormality in this patient. INTERVENTIONS: After oral administration of aldosterone antagonists, her blood pressure and potassium levels returned to normal ranges and her condition improved. OUTCOMES: Following differential diagnosis, screening, functional tests, a variety of imaging studies, and bilateral adrenal vein sampling (AVS) typing, she was finally diagnosed with idiopathic hyperaldosteronism. LESSONS: For PA patients with lack of typical hypertension and hypokalemia performance, early identification and accurate diagnosis are of great significance for improving the prognosis of BAH. AVS plays an important role in the classification of PA subtype, especially for the cases with bilateral lesions. In regard to patients with rare bilateral adrenocortical adenoma-type aldosteronism, AVS plays a key role in choosing the appropriate treatment regimen.


Assuntos
Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Hiperaldosteronismo/diagnóstico , Adenoma/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/etiologia , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
19.
Artigo em Inglês | MEDLINE | ID: mdl-31502013

RESUMO

BACKGROUND: Metabolic information obtained through 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used to evaluate malignancy by calculating the glucose uptake rate, and these parameters play important roles in determining the prognosis of non-small cell lung cancer (NSCLC). The expression of immune-related markers in tumor tissue reflects the immune status in the tumor microenvironment. However, there is lack of reports on the association between metabolic variables and intra-tumor immune markers. Herein, we investigate the correlation between metabolic status on 18F-FDG PET/CT and intra-tumor immunomarkers' expression in NSCLC patients. METHODS: From April 2008 to August 2014, 763 patients were enrolled in the analysis to investigate the role of maximum standardized uptake value (SUVmax) in lung cancer. One hundred twenty-two tumor specimens were analyzed by immunohistochemistry (IHC) to intra-tumor immune cells and programmed death protein ligand 1(PD-L1) expression on tumor cells. The correlation between metabolic variables and the expression of tissue immune markers were analyzed. RESULTS: SUVmax values have significant variations in different epidermal growth factor receptor (EGFR) statuses (wild type vs mutant type), high/low neutrophil-to-lymphocyte ratio (NLR) groups, and high/low platelets-to-lymphocyte ratio (PLR) groups (p < 0.001, p < 0.001, p = 0.003, respectively). SUVmax was an independent prognostic factor in lung cancer patients (p = 0.013). IHC demonstrated a statistically significant correlation between SUVmax and the expression of CD8 tumor-infiltrating lymphocytes (p = 0.015), CD163 tumor-associated macrophages (TAMs) (p = 0.003), and Foxp3-regulatory T cells (Tregs) (p = 0.004), as well as PD-1 and PD-L1 (p = 0.003 and p = 0.012, respectively). With respect to patient outcomes, disease stage, BMI, SUVmax, metabolic tumor volume (MTV), TLG (tumor lesion glycolysis), CD163-TAMs, CD11c-dendritic cells (DCs), PD-L1, and Tregs showed a statistically significant correlation with progression-free survival (PFS) (p < 0.001, 0.023, < 0.001, 0.007, 0.005, 0.004, 0.008, 0.048, and 0.014, respectively), and disease stage, SUVmax, MTV, TLG, CD163-TAMs, CD11c-DCs, and PD-L1 showed a statistically significant correlation with overall survival (OS) (p < 0.001, < 0.001, 0.014, 0.012, < 0.001, 0.001, and < 0.001, respectively). CONCLUSION: This study revealed an association between metabolic variable and immune cell expression in the tumor microenvironment and suggests that SUVmax on 18F-FDG PET/CT could be a potential predictor for selecting candidates for immunotherapy.

20.
Clin Breast Cancer ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31521536

RESUMO

The incidence of breast cancer across the world has been on the rise in recent decades. Because identified risk factors can only explain a relatively small portion of the cases, environmental exposure to organic pollutants is suspected to play a role in breast cancer etiology. Polychlorinated biphenyls (PCBs) are among the most abundant pollutants, and the impact of their exposure on breast cancer risk has been extensively studied in recent decades. However, the results of most epidemiologic studies do not support an association between PCB exposure and breast cancer risk. We hypothesized that the effects of PCBs on breast cancer might have been undervalued for reasons such as insufficient recognition of the confounding effects of several factors and lack of attention on the innate heterogeneity of PCB mixtures or breast cancer. After reviewing the evidence in the existing literature, we concluded that early life exposure, known risk factors of breast cancer, and impact of exposure to other pollutants are the main sources of confounding effects and have potentially masked the associations between PCBs and breast cancer. Because PCBs are mixtures of congeners with varied properties, and because breast cancers of different subtypes are etiologically distinct diseases, the absence of stratified subgroup analysis on individual PCBs and patients with specific biological subtypes and insufficient attention paid to the results of these subgroup analyses may result in an underestimation of the correlations between PCBs and breast cancer. In future studies, these factors must be taken into consideration when exploring the effect of PCB exposure on breast cancer risk.

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