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1.
Brain Commun ; 6(2): fcae027, 2024.
Article in English | MEDLINE | ID: mdl-38638147

ABSTRACT

Averaging is commonly used for data reduction/aggregation to analyse high-dimensional MRI data, but this often leads to information loss. To address this issue, we developed a novel technique that integrates diffusion tensor metrics along the whole volume of the fibre bundle using a 3D mesh-morphing technique coupled with principal component analysis for delineating case and control groups. Brain diffusion tensor MRI scans of high school rugby union players (n = 30, age 16-18) were acquired on a 3 T MRI before and after the sports season. A non-contact sport athlete cohort with matching demographics (n = 12) was also scanned. The utility of the new method in detecting differences in diffusion tensor metrics of the right corticospinal tract between contact and non-contact sport athletes was explored. The first step was to run automated tractography on each subject's native space. A template model of the right corticospinal tract was generated and morphed into each subject's native shape and space, matching individual geometry and diffusion metric distributions with minimal information loss. The common dimension of the 20 480 diffusion metrics allowed further data aggregation using principal component analysis to cluster the case and control groups as well as visualization of diffusion metric statistics (mean, ±2 SD). Our approach of analysing the whole volume of white matter tracts led to a clear delineation between the rugby and control cohort, which was not possible with the traditional averaging method. Moreover, our approach accounts for the individual subject's variations in diffusion tensor metrics to visualize group differences in quantitative MR data. This approach may benefit future prediction models based on other quantitative MRI methods.

2.
IEEE Trans Med Imaging ; PP2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656865

ABSTRACT

Functional magnetic resonance imaging (fMRI) is a commonly used technique to measure neural activation. Its application has been particularly important in identifying underlying neurodegenerative conditions such as Parkinson's, Alzheimer's, and Autism. Recent analysis of fMRI data models the brain as a graph and extracts features by graph neural networks (GNNs). However, the unique characteristics of fMRI data require a special design of GNN. Tailoring GNN to generate effective and domain-explainable features remains challenging. In this paper, we propose a contrastive dual-attention block and a differentiable graph pooling method called ContrastPool to better utilize GNN for brain networks, meeting fMRI-specific requirements. We apply our method to 5 resting-state fMRI brain network datasets of 3 diseases and demonstrate its superiority over state-of-the-art baselines. Our case study confirms that the patterns extracted by our method match the domain knowledge in neuroscience literature, and disclose direct and interesting insights. Our contributions underscore the potential of ContrastPool for advancing the understanding of brain networks and neurodegenerative conditions. The source code is available at https://github.com/AngusMonroe/ContrastPool.

3.
Nurse Educ Pract ; 75: 103900, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38277802

ABSTRACT

AIMS: Development and evaluation of the effectiveness of a Nurse Navigation programme based on Noddings' Care theory on two dependent variables which were professional identity and career planning among first-year undergraduate nursing students. BACKGROUND: First-year undergraduate nursing students generally have a low sense of professional identity and career planning, resulting in a loss of nursing power after graduation. Implemention of a Nurse Navigation program based on Noddings' Care theory may be potentially useful in cultivating their professional identity and career planning. DESIGN: A quasi-experimental study. METHODS: A convenience sample of 122 first-year undergraduate nursing students from two medical universities was recruited between September 2021 and June 2022. Students in the experimental group (n = 63) participated in the Nurse Navigation programme based on Noddings' Care theory, which contained four core components, spreading over 50 lessons. Those in the control group (n = 59) underwent a traditional training programme with five components across 44 lessons. The two groups were compared in terms of their level of professional identity by Professional identity questionnaire for nurse students (PIQNS) and career planning by Career planning questionnaire (CPQ) after the training using the t-test. RESULTS: The mean score of professional identity in the experimental group increased significantly from 51.02 ± 8.46 at baseline to 58.02 ± 8.81 after the intervention (p < 0.001), with a large effect size (Cohen's d=0.810). Also, this post-intervention score was statistically significantly higher than that (52.86 ± 9.27) in the control group (p = 0.002), with a medium effect size (Cohen's d=0.571). The mean score of career planning in the experimental group increased significantly from 81.76 ± 9.86 at baseline to 94.52 ± 10.81 after the intervention (p < 0.001), with a large effect size (Cohen's d = 1.233). Also, this post-intervention score was statistically significantly higher than that (88.25 ± 9.30) in the control group (p < 0.001), with a medium effect size (Cohen's d=0.623). CONCLUSIONS: The Nurse Navigation programme based on Noddings' Care theory showed effectiveness in enhancing professional identity and career planning among first-year undergraduate nursing students in China. Further rigorous studies are needed to examine its effectiveness and long-term impacts on these students.


Subject(s)
Education, Nursing, Baccalaureate , Students, Nursing , Humans , Education, Nursing, Baccalaureate/methods , Curriculum , China
4.
Angew Chem Int Ed Engl ; 63(7): e202318390, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38117040

ABSTRACT

Luban locks with mortise and tenon structure have structural diversity and architectural stability, and it is extremely challenging to synthesize Luban lock-like structures at the molecular level. In this work, we report the cocrystallization of two structurally related atom-precise fcc silver nanoclusters Ag110 (SPhF)48 (PPh3 )12 (Ag110 ) and Ag14 (µ6 -S)(SPhF)12 (PPh3 )8 (Ag14 ). It is worth noting that the Ag110 cluster is the first compound to simulate the complex Luban lock structure at the molecular level. Meanwhile, Ag110 is the largest known fcc-based silver nanocluster, so far, there is no precedent for fcc silver nanocluster with more than 100 silver atoms. DFT calculations show that Ag110 is a 58-electron superatom with an electronically closed shell1S2 1P6 1D10 2S2 1F14 2P6 1G18 . Ag110 ⋅Ag14 can rapidly catalyze the reduction of 4-nitrophenol within 4 minutes. In addition, Ag110 presents clear structural evidence to reveal the critical size and mechanism of the transformation of metal core from fcc stacking to quasi-spherical superatom. This research work provides an important structural model for studying the nucleation mechanism and structural assembly of silver nanoclusters.

5.
Bioengineering (Basel) ; 10(4)2023 Mar 23.
Article in English | MEDLINE | ID: mdl-37106584

ABSTRACT

BACKGROUND: Magnetic Resonance Imaging (MRI) data collected from multiple centres can be heterogeneous due to factors such as the scanner used and the site location. To reduce this heterogeneity, the data needs to be harmonised. In recent years, machine learning (ML) has been used to solve different types of problems related to MRI data, showing great promise. OBJECTIVE: This study explores how well various ML algorithms perform in harmonising MRI data, both implicitly and explicitly, by summarising the findings in relevant peer-reviewed articles. Furthermore, it provides guidelines for the use of current methods and identifies potential future research directions. METHOD: This review covers articles published through PubMed, Web of Science, and IEEE databases through June 2022. Data from studies were analysed based on the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality assessment questions were derived to assess the quality of the included publications. RESULTS: a total of 41 articles published between 2015 and 2022 were identified and analysed. In the review, MRI data has been found to be harmonised either in an implicit (n = 21) or an explicit (n = 20) way. Three MRI modalities were identified: structural MRI (n = 28), diffusion MRI (n = 7) and functional MRI (n = 6). CONCLUSION: Various ML techniques have been employed to harmonise different types of MRI data. There is currently a lack of consistent evaluation methods and metrics used across studies, and it is recommended that the issue be addressed in future studies. Harmonisation of MRI data using ML shows promises in improving performance for ML downstream tasks, while caution should be exercised when using ML-harmonised data for direct interpretation.

6.
Ann Hum Genet ; 87(1-2): 9-17, 2023 03.
Article in English | MEDLINE | ID: mdl-36317495

ABSTRACT

INTRODUCTION: The α-globin fusion gene between the HBA2 and HBAP1 genes becomes clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combining with α0 -thalassemia (α0 -thal). Due to its uncommon rearrangement in the α gene cluster without dosage changes, this fusion gene is undetectable by common molecular testing approaches used for α-thal diagnosis. METHODS: In this study, we used the single-molecule real-time (SMRT) sequencing technique to detect this fusion gene in 23 carriers identified by next-generation sequencing (NGS) among 16,504 screened individuals. Five primers for α and ß thalassemia were utilized. RESULTS: According to the NGS results, the 23 carriers include 14 pure heterozygotes, eight compound heterozygotes with common α-thal alleles, and one homozygote. By using SMRT, the fusion mutant was successfully detected in all 23 carriers. Furthermore, SMRT corrected the diagnosis in two "pure" heterozygotes: one was compound heterozygote with anti-3.7 triplication, and the other was homozygote. CONCLUSION: Our results indicate that SMRT is a superior method compared to NGS in detecting the α fusion gene, attributing to its efficient, accurate, and one-step properties.


Subject(s)
alpha-Thalassemia , beta-Thalassemia , Humans , alpha-Globins/genetics , Heterozygote , Homozygote , alpha-Thalassemia/diagnosis , alpha-Thalassemia/genetics , alpha-Thalassemia/epidemiology , beta-Thalassemia/diagnosis , beta-Thalassemia/genetics , beta-Thalassemia/epidemiology
7.
Food Chem ; 387: 132907, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35405554

ABSTRACT

Rapeseed oil has a similar oleic acid/linoleic acid ratio to human milk fat (HMF). However, it can hardly be used for human milk fat substitute (HMFS) synthesis due to high erucic acid content. In this study, Candida cylindracea lipase (CCL) was found to strongly discriminate against erucic acid. Free fatty acids containing low erucic acid and high oleic acid and linoleic acid were prepared from rapeseed oil hydrolysis catalyzed by CCL. The erucic acid content was only 1.58% (initial 8.70%), when the degree of hydrolysis reached 79.58%. The free fatty acids were used as acyl-donors in the acidolysis catalyzed by Novozym 40086. Considering acyl incorporation and migration, the optimum conditions were 1:8 (tripalmitin to acyl-donors), 40 °C and 2 h. The erucic acid content dropped to 0.97% in the HMFS. According to the Q-TOF-MS analysis, the HMFS was rich in 1,3-dioleoyl-2-palmitoyl-glycerol (18.20%) and 1-oleoyl-2-palmitoyl-3-linoleoyl-glycerol (17.96%), which was similar to HMF.


Subject(s)
Fat Substitutes , Erucic Acids , Fatty Acids , Fatty Acids, Nonesterified , Humans , Linoleic Acid , Lipase/metabolism , Milk, Human/metabolism , Oleic Acid/metabolism , Plant Oils , Rapeseed Oil , Triglycerides/metabolism
8.
Struct Chem ; 33(3): 795-805, 2022.
Article in English | MEDLINE | ID: mdl-35194353

ABSTRACT

Quantum-chemical calculations based on the density functional theory (DFT) at the B3LYP/6-311 + + G(2d,2p)//B3LYP/6-31G(d,p) level were employed to study the relationship between the antioxidant properties and chemical structures of six dendrocandin (DDCD) analogues in the gas phase and two solvents (methanol and water). The hydrogen atom transfer (HAT), electron-transfer-proton-transfer (ET-PT), and sequential proton-loss-electron-transfer (SPLET) mechanisms are explored. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), reactivity indices (η, µ, ω, ω +, and ω - ), and molecular electrostatic potentials (MEPs) were also evaluated. The results suggest that the D ring plays an important role in mediating the antioxidant activity of DDCDs. For all the studied compounds, indicating that HAT was identified as the most favorable mechanism, whereas the SPLET mechanism was the most thermodynamically favorable pathway in polar solvents. The results of our study should aid in the development of new or modified antioxidant compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-01895-2.

9.
Front Oncol ; 11: 621917, 2021.
Article in English | MEDLINE | ID: mdl-34912696

ABSTRACT

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the preferred treatment strategy for inoperable esophageal cancer (EC). However, the effect of CRT needs to be improved. METHODS: This study comprehensively analyzed targeted agents combined with CRT for the treatment of EC by a network meta-analysis. The search was performed in public databases from incipient to 5 August 2021. Randomized controlled trials comparing the effect of targeted agents combined with CRT and CRT alone on EC patients were included. RESULTS: Ten studies were included. For progression-free survival (PFS), nivolumab (67.4%) and erlotinib (64.6%) had advantages based on Cox analysis. Regarding the frequency of PFS, cetuximab (OR: 1.39; 95% CI: 1.01, 1.91; p=0.042) and nivolumab (OR: 1.81; 95% CI: 1.34, 2.44; p<0.01) were significantly superior to the control. For overall survival (OS), nivolumab (71.6%) in Cox analysis and nimotuzumab (69.7%) in frequency analysis were found to have relative advantages. Nimotuzumab combined with CRT was significantly better than the control with regard to endoscopic and the pathologic complete response (epCR; OR: 2.81; 95% CI: 1.28, 6.14; p=0.011) and objective response rate (ORR; 4.71; 95% CI: 1.45, 15.29; p=0.008). The targeted drugs were not associated with significant SEA risk. CONCLUSION: In conclusion, compared to CRT alone, cetuximab and nivolumab combined with CRT were found to significantly improve the PFS rate only based on the frequency results. However, there was no benefit in terms of OS. For epCR and ORR, nimotuzumab was better than the blank control. Considering the limitations in this study, more well-designed RCTs are needed in the future to validate the results.

10.
Biomed Chromatogr ; 35(2): e4984, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33025603

ABSTRACT

Rosmarinic acid (RA), an ester compound of caffeic acid (CA) and 3,4-dihydroxyphenyllacic acid, is widely distributed in the herbs of the Lamiaceae family and has shown a wide spectrum of pharmacological properties. CA and FA (ferulic acid) are two bioactive metabolites in vivo after oral administration of RA; however, a rapid and robust analytical approach that can enable the quantitative assay of RA and two bioactive metabolites is still lacking. A liquid chromatography/tandem mass spectrometry method was established that was capable of the quantitative determination of RA, CA and FA by negative-mode multiple reaction monitoring within 7 min using a Zorbax SB-C18 column and an isocratic elution. This assay method was validated as linear over the investigated ranges with correlation coefficients (r) > 0.9950. The intra- and inter-day precision was <10.65%, and the accuracies (relative error, %) <-6.41%. The validated approach was applied to a pharmacokinetics study of RA and its two metabolites in rats after oral and intravenous administration. RA was rapidly metabolized in both administration modes, whilst the metabolites CA and FA were only detectable by oral administration. The absolute availability of RA was calculated to be 4.13%.


Subject(s)
Caffeic Acids/blood , Chromatography, Liquid/methods , Cinnamates/blood , Coumaric Acids/blood , Depsides/blood , Tandem Mass Spectrometry/methods , Animals , Caffeic Acids/chemistry , Caffeic Acids/pharmacokinetics , Cinnamates/chemistry , Cinnamates/pharmacokinetics , Coumaric Acids/chemistry , Coumaric Acids/pharmacokinetics , Depsides/chemistry , Depsides/pharmacokinetics , Linear Models , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Rosmarinic Acid
11.
RSC Adv ; 10(67): 41154-41163, 2020 Nov 09.
Article in English | MEDLINE | ID: mdl-35519219

ABSTRACT

Xanthium strumarium L. (XS) is a traditional Chinese medicine (TCM) that has been widely used in Chinese medicine prescription for allergic rhinitis (AR). However, the action mechanisms of XS on the therapeutic effects on AR remain elusive. Herein, an integrated approach of phytochemistry, network pharmacology and metabolomics was first applied to uncover the action mechanisms of XS for AR. The therapeutic effect of XS extract on AR was evaluated in rat models of ovalbumin (OVA)-induced AR. The cytokine levels in rat serum and histopathological changes of nasal mucosa were assessed after oral treatment with XS. Chemical compositions of XS were elucidated by phytochemical methods, and active ingredients were identified via ADME-TOX screening in silico. Network pharmacology was performed to establish and analyze the compound-target-disease network so as to find the possible mechanism of XS in treating AR. In addition, metabolomics analysis was applied to investigate the changes in the endogenous metabolite levels that result from XS treatments. As result, the XS extract significantly increased the serum concentrations of IL-2 and reduced the levels of serum IL-4, while XS could ameliorate inflammation in the nasal sub-mucosal area, indicating that XS has significant therapeutic effects on AR model rats. Furthermore, a total of 119 compounds were isolated from XS, and 59 of these compounds were identified as active ingredients through ADME-TOX screening in silico. An in-depth analysis of the network pharmacology implied that the active ingredients of XS could regulate the inflammatory response via "multi-component, multi-target" patterns. In combination with the results of metabolomics, we found that the active ingredients of XS have a beneficial effect on AR through regulating the metabolism of arachidonic acid, which was reflected by medicating the Fc epsilon RI signaling pathway, and the neuroactive ligand-receptor interaction pathway, as well as the key proteins in arachidonic acid metabolism, such as PTGS2, PTGS1, PTGES and ALOX5. Additionally, molecular docking showed that multiple compounds have better binding with PTGS2 and ALOX5, which might be two crucial targets. Overall, these results suggest that the treatment of XS for AR is realized by regulating the metabolism of arachidonic acid via a combination form. This study provides the basis for clinical applications of XS.

12.
Cell Microbiol ; 22(3): e13148, 2020 03.
Article in English | MEDLINE | ID: mdl-31829498

ABSTRACT

Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. During the HBV life cycle, HBV hijacks various host factors to assist viral replication. In this research, we find that the HBV regulatory protein X (HBx) can induce the upregulation of DExH-box RNA helicase 9 (DHX9) expression by repressing proteasome-dependent degradation mediated by MDM2. Furthermore, we demonstrate that DHX9 contributes to viral DNA replication in dependence on its helicase activity and nuclear localization. In addition, the promotion of viral DNA replication by DHX9 is dependent on its interaction with Nup98. Our findings reveal that HBx-mediated DHX9 upregulation is essential for HBV DNA replication.


Subject(s)
DEAD-box RNA Helicases/metabolism , Hepatitis B virus/physiology , Hepatitis B/metabolism , Neoplasm Proteins/metabolism , Nuclear Pore Complex Proteins/metabolism , Trans-Activators/physiology , Viral Regulatory and Accessory Proteins/physiology , Animals , Cell Line , Cell Nucleus/metabolism , DEAD-box RNA Helicases/genetics , DNA Replication , DNA, Viral , Gene Expression Regulation , HEK293 Cells , Hep G2 Cells , Hepatitis B/genetics , Hepatitis B/virology , Host Microbial Interactions , Humans , Mice , Mice, Transgenic , Neoplasm Proteins/genetics , Up-Regulation , Virus Replication
13.
J Sep Sci ; 42(16): 2592-2601, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31161707

ABSTRACT

A rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed and validated for simultaneous determination of puerarin, daidzin, daidzein, 3'-hydroxy puerarin, and genistein in rat plasma after oral administration of Puerariae lobatae radix extract. The method of protein precipitation with acetonitrile was used for sample preparation. Chromatographic separation was achieved on a C18 column with the mobile phases of acetonitrile/water containing 0.1% formic acid. The analytes were detected by mass spectrometer with an electrospray ionization source operating in the negative ion mode. The linearity, precision, accuracy, dilution reliability, recovery, matrix effects, and stability of the method were within acceptable ranges. The developed method was successfully used to compare the pharmacokinetic characteristics of five analytes in normal and type 2 diabetics rats after oral administration of Puerariae lobatae radix extract. Several pharmacokinetic alterations were observed and this might be caused by the pathological state of type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacokinetics , Isoflavones/blood , Isoflavones/pharmacokinetics , Pueraria/chemistry , Administration, Oral , Animals , Chromatography, Liquid , Diabetes Mellitus, Type 2/pathology , Drugs, Chinese Herbal/administration & dosage , Isoflavones/administration & dosage , Male , Molecular Conformation , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry
14.
J Pharm Biomed Anal ; 168: 155-162, 2019 May 10.
Article in English | MEDLINE | ID: mdl-30807920

ABSTRACT

Icariin, the major flavonoid constituent of the traditional Chinese medicine Epimedii Folium, is extensively researched owing to its comprehensive beneficial effects. This study aimed at identifying the in vivo metabolites and the metabolic profiling in rats after oral administration at a dose of icariin (100 mg/kg) with the aid of an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) and metabolynx™ software. A total of 25 metabolites were detected and 4 of them were compared with standard substances. Among them, 10 metabolites were reported for the first time. The results indicated that the principal metabolism pathways of icariin in rat were hydroxylation and the conjugation with glucuronide. It also confirmed that M2, M14, M18 and M23 were the major circulating forms of icariin in rats following oral administration. Demethylation, dehydrogenation, epoxidation, reduction, oxidation were also observed and the epoxidation and reduction on the isopentenyl were regarded as new metabolic patterns of icariin. Moreover, this study could enrich the understanding of the metabolism of icariin and help to elucidate the metabolic profiling of other prenylflavonoids.


Subject(s)
Chromatography, High Pressure Liquid/methods , Flavonoids/analysis , Metabolomics/methods , Tandem Mass Spectrometry/methods , Administration, Oral , Animals , Bile/metabolism , Flavonoids/administration & dosage , Flavonoids/metabolism , Male , Rats , Rats, Sprague-Dawley
15.
Nat Prod Res ; 33(24): 3485-3492, 2019 Dec.
Article in English | MEDLINE | ID: mdl-29968479

ABSTRACT

Two new isoflavone glucosides, 3'-methoxyneopuerarin A (1) and 3'-methoxyneopuerarin B (2), together with nine known isoflavones including puerarin (3), neopuerarin A (4), neopuerarin B (5), daidzin (6), daidzein (7), 3'-methoxypuerarin (PG-3) (8), puerarin xyloside (9), mirificin (10), 3'-hydroxypuerarin (11) were isolated from the water extraction of the dried roots of Pueraria lobata (Willd.) Ohwi. Their structures were elucidated by the means of spectroscopic and chromatographic analysis methods. All compounds were evaluated for their hepatoprotective activity on HepG2 cells. All of them showed statistically significant hepatoprotective effect.


Subject(s)
Isoflavones/chemistry , Isoflavones/pharmacology , Liver/drug effects , Protective Agents/chemistry , Protective Agents/pharmacology , Pueraria/chemistry , Drug Evaluation, Preclinical , Glucosides/chemistry , Glucosides/isolation & purification , Glucosides/pharmacology , Hep G2 Cells , Humans , Isoflavones/isolation & purification , Liver/cytology , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/chemistry , Plant Roots/chemistry , Spectrometry, Mass, Electrospray Ionization
16.
Molecules ; 23(9)2018 Aug 25.
Article in English | MEDLINE | ID: mdl-30149616

ABSTRACT

Linarin, a flavone glycoside, is considered to be a promising natural product due to its diverse pharmacological activities, including analgesic, antipyretic, anti-inflammatory and hepatoprotective activities. In this research, the metabolites of linarin in rat intestinal flora and biosamples were characterized using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS). Three ring cleavage metabolites (4-hydroxybenzoic acid, 4-hydroxy benzaldehyde and phloroglucinol) were detected after linarin was incubated with rat intestinal flora. A total of 17 metabolites, including one ring cleavage metabolite (phloroglucinol), were identified in rat biosamples after oral administration of linarin. These results indicate that linarin was able to undergo ring fission metabolism in intestinal flora and that hydrolysis, demethylation, glucuronidation, sulfation, glycosylation, methylation and ring cleavage were the major metabolic pathways. This study provides scientific support for the understanding of the metabolism of linarin and contributes to the further development of linarin as a drug candidate.


Subject(s)
Chromatography, High Pressure Liquid , Gastrointestinal Microbiome , Glycosides/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Animals , Apigenin/chemistry , Chromatography, High Pressure Liquid/methods , Flavones/chemistry , Metabolic Networks and Pathways , Methylation , Rats , Tandem Mass Spectrometry
17.
FEBS Lett ; 592(11): 1893-1904, 2018 06.
Article in English | MEDLINE | ID: mdl-29782647

ABSTRACT

SAMHD1 inhibits Hepatitis B virus (HBV) replication by reducing the intracellular dNTP levels. However, how SAMHD1 phosphorylation is regulated to abrogate its restriction of HBV replication in hepatoma cells is poorly understood. Here, we show that HBV replication and SAMHD1 phosphorylation levels are significantly reduced by knocking down cyclin-dependent kinase (CDK) 2 expression or in the presence of a CDK2 inhibitor. SAMHD1 binds to CDK2 in hepatocarcinoma cells, and this interaction does not require the HBV core protein. Furthermore, cyclin E2 participates in regulating viral replication through the CDK2/SAMHD1 phosphorylation pathway in an HBV infection system. Collectively, our results provide evidence that CDK2 has a greater role in regulating SAMHD1 phosphorylation and HBV replication than CDK1 or CDK6.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Cyclin-Dependent Kinase 2/metabolism , Cyclins/metabolism , Hepatitis B virus/physiology , Liver Neoplasms/metabolism , Neoplasm Proteins/metabolism , SAM Domain and HD Domain-Containing Protein 1/metabolism , Virus Replication/physiology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Cyclin-Dependent Kinase 2/genetics , Cyclins/genetics , HEK293 Cells , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/virology , Neoplasm Proteins/genetics , Phosphorylation/genetics , SAM Domain and HD Domain-Containing Protein 1/genetics
18.
Fitoterapia ; 124: 23-33, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28993283

ABSTRACT

Berberrubine, an isoquinoline alkaloid isolated from many medicinal plants, possesses diverse pharmacological activities, including glucose-lowering, lipid-lowering, anti-inflammatory, and anti-tumor effects. This study aimed to investigate the metabolic profile of berberrubine in vivo. Therefore, a rapid and reliable method using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and metabolynx™ software with mass defect filter (MDF) technique was developed. Plasma, bile, urine and feces samples were collected from rats after oral administration of berberrubine with a dose of 30.0mg/kg and analyzed to characterize the metabolites of berberrubine in vivo for the first time. A total of 57 metabolites were identified, including 54 metabolites in urine, 39 metabolites in plasma, 28 metabolites in bile and 18 metabolites in feces. The results indicated that demethylenation, reduction, hydroxylation, demethylation, glucuronidation, and sulfation were the major metabolic pathways of berberrubine in vivo.


Subject(s)
Berberine/analogs & derivatives , Metabolome , Administration, Oral , Animals , Berberine/metabolism , Berberine/pharmacokinetics , Bile/chemistry , Chromatography, High Pressure Liquid , Feces/chemistry , Male , Mass Spectrometry , Plasma/chemistry , Rats , Rats, Sprague-Dawley
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-494625

ABSTRACT

BACKGROUND:Al ogeneic hematopoietic stem cel transplantation (HSCT) is one of the effective methods in the treatment of leukemia. The haploidentical HSCT is an option for the patients who need a HSCT without a human leukocyte antigen (HLA)-matched donor. OBJECTIVE:To study the clinical efficacy of HLA-haploidentical HSCT on leukemia and its complications. METHODS:A total of 23 patients (4 cases of acute lymphoblastic leukemia, 12 of acute myelogenous leukemia, and 7 of chronic granulocytic leukemia) who had been treated with HLA-haploidentical HSCT from November 2007 to March 2015 were enrol ed. Conditioning regimen I was set as cyclohexyl nitrosourea+cytarabine+busulfan+cyclophosphamide; regimen II as cyclophosphamide+total body irradiation;regimen III as fludarabine+cytarabine+busulfan+cyclophosphamide; and regimen IV as busulfan+cyclophosphamide. Cyclosporin A, mycophenlate mofetil, antithymocyte globulin and methotrexate were used to prevent graft-versus-host disease (GVHD). Hematopoietic remodeling, complications and prognosis were observed in al patients undergoing HLA-haploidentical HSCT. RESULTS AND CONCLUSION:Of the 23 patients, 22 achieved reconstitution of the granulocyte series, and 19 achieved reconstruction of the megakaryocyte series. Additional y, there were 7 cases of acute GVHD and 4 of chronic GVHD. Transplant-related mortality was 22%(5/23) within 100 days post transplantation including graft failure, acute GVHD, intracranial hemorrhage and disseminated infections. There were 14 cases of disease-free survival from 100 days to 24 months post transplantation, 2 cases of death due to GVHD and fungal infection, or recurrence and chronic GVHD, and 2 cases of recurrence under treatment. These findings indicate that HLA-haploidentical HSCT is an effective approach for the treatment of patients with leukemia, which is worth further investigation in clinical practice.

20.
Immunology ; 120(4): 447-55, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17244157

ABSTRACT

CD4(+) CD25(+) Foxp3(+) naturally occurring regulatory T cells (nTreg) are potent inhibitors of almost all immune responses. However, it is unclear how this minor population of cells is capable of exerting its powerful suppressor effects. To determine whether nTreg mediate part of their suppressor function by rendering naive T cells anergic or by converting them to the suppressor phenotype, we cocultured mouse nTreg with naive CD4(+) CD25(-) T cells from T-cell receptor (TCR) transgenic mice on a RAG deficient (RAG(-/-)) background in the presence of anti-CD3 and interleukin-4 (IL-4) to promote cell viability. Two distinct responder cell populations could be recovered from the cocultures. One population remained undivided in the coculture and was non-responsive to restimulation with anti-CD3 or exogenous IL-2, and could not up-regulate IL-2 mRNA or CD25 expression upon TCR restimulation. Those responder cells that had divided in the coculture were anergic to restimulation with anti-CD3 but responded to restimulation with IL-2. The undivided population was capable of suppressing the response of fresh CD4(+) CD25(-) T cells and CD8(+) T cells, while the divided population was only marginally suppressive. Although cell contact between the induced regulatory T cell (iTreg) and the responders was required for suppression to be observed, anti-transforming growth factor-beta partially abrogated their suppressive function. The iTreg did not express Foxp3. Therefore nTreg are not only able to suppress immune responses by inhibiting cytokine production by CD4(+) CD25(-) responder cells, but also appear to modulate the responder cells to render them both anergic and suppressive.


Subject(s)
CD5 Antigens/analysis , Immune Tolerance/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Animals , CD8-Positive T-Lymphocytes/immunology , Cell Communication/immunology , Clonal Anergy/immunology , Coculture Techniques , Female , Interleukin-10/immunology , Interleukin-2/biosynthesis , Interleukin-2/genetics , Interleukin-2 Receptor alpha Subunit/analysis , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Mice, Transgenic , RNA, Messenger/genetics , Transforming Growth Factor beta/immunology , Up-Regulation/immunology
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