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1.
Methods Mol Biol ; 2198: 349-367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32822044

RESUMO

Here, we provide a detailed protocol for our previously published technique, APOBEC-Coupled Epigenetic Sequencing (ACE-Seq), which localizes 5-hydroxymethylcytosine at single nucleotide resolution using nanogram quantities of input genomic DNA. In addition to describing suggested troubleshooting workflows, these methods include four important updates which should facilitate widespread implementation of the technique: (1) additionally optimized reaction conditions; (2) redesigned quality controls which can be performed prior to resource-consumptive deep sequencing; (3) confirmation that the less active, uncleaved APOBEC3A (A3A) fusion protein, which is easier to purify, can be used to perform ACE-Seq ; and (4) an example bioinformatic pipeline with suggested filtering strategies. Finally, we have provided a supplementary video which gives a narrated overview of the entire method and focuses on how best to perform the snap cool and A3A deamination steps central to successful execution of the method.

2.
Med Oncol ; 37(11): 99, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040185

RESUMO

Angiogenesis is a prerequisite for multiple myeloma development. Tumor cells can stimulate angiogenesis by secreting vascular endothelial growth factor A (VEGFA), but we previously reported that tumor angiogenesis was not significantly reduced when VEGFA expression was inhibited in myeloma cells. Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment and have been reported to be involved in the regulation of angiogenesis. In this study, we performed in vitro macrophage coculture studies and studies with RPMI 8226 and TAMs cell-conditioned media to explore their effects on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Our results showed that M2 macrophages and RPMI 8226 cells could synergistically promote HUVEC proliferation, migration, and tube formation, and that VEGFA depletion in both cell types suppressed HUVEC tube formation ability. Conversely, M1 macrophages inhibited the tube formation in HUVECs. Mechanistically, M2 macrophage secretion of VEGFA may affect vascular endothelial growth factor receptor 1 signaling to regulate angiogenesis. In summary, our results suggest that macrophage clearance or inducing of transformation of M2 macrophages into M1 macrophages are potential treatment strategies for multiple myeloma.

3.
Br J Nutr ; : 1-29, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33046150

RESUMO

High carbohydrate diet could achieve protein sparing effect, but it may cause negative impacts on the growth condition of fish due to their poor utilization ability of carbohydrate. How to reduce the adverse effects caused by high carbohydrate diet is important for the development of aquaculture. In the present study, we aimed to identify whether inulin could attenuate metabolic syndrome caused by high-carbohydrate diet in fish. Nile tilapia (Oreochromis niloticus) (1.19 ± 0.01 g) were supplied with 35% carbohydrate (CON), 45% carbohydrate (HC) and 45% carbohydrate + 5g/kg inulin (HCI) diets for ten weeks. The results showed that addition of inulin improved the survival rate when fish were challenged with Aeromonas hydrophila, indicating inulin had an immunostimulatory effect. Compared with HC group, HCI group had lower lipid accumulation in liver and the gene expression analyses indicated that addition of inulin downregulated genes related to lipogenesis and upregulated genes relevant to ß-oxidation significantly (P < 0.05). Higher liver glycogen and glucose tolerance were found in HCI group compared with HC group (P < 0.05). These results indicated that inulin could alleviate the metabolic syndrome induced by high-carbohydrate diet. Furthermore, addition of inulin in high-carbohydrate diet changed the intestinal bacterial composition and significantly increased the concentration of acetic acid and propionic acid in fish gut which have the potential to increase pathogen resistance and regulate metabolic characteristics in fish. Collectively, our results demonstrated a possible causal role for the gut microbiome in metabolic improvements induced by inulin in fish.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 118988, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33065449

RESUMO

In this paper, a simple, rapid, low-cost and potential method was established for the simultaneous quantitative analysis of dabigatran etexilate (DABE) and dabigatran (DAB) in spiked biological fluids. It combined excitation-emission matrix fluorescence (EEMF) with different second-order calibration methods, including the self-weighted alternating normalized residue fitting (SWANRF) algorithm based on trilinear decomposition model, the multivariate curve resolution - alternating least-squares (MCR-ALS) based on bilinear decomposition model and the unfolded partial least-square coupled with residual bilinearization (U-PLS/RBL) based on latent variables model. The proposed method showed "second-order advantage", that is, satisfactory quantitative results were successfully obtained even in the presence of unknown interferences and serious spectral overlap. The recoveries of DABE and DAB in spiked biological fluids were 91.7%-101.7% for SWANRF, 95.9%-117.8% for MCR-ALS, 83.0%-109.6% for U-PLS/RBL, respectively. Figures of merit and other statistical parameters were also calculated to assess the performance of the proposed method. Moreover, the modeling procedures and characteristics of three different models in EEMF analysis were discussed and compared.

5.
NPJ Digit Med ; 3: 135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083570

RESUMO

The rate of disability accumulation varies across multiple sclerosis (MS) patients. Machine learning techniques may offer more powerful means to predict disease course in MS patients. In our study, 724 patients from the Comprehensive Longitudinal Investigation in MS at Brigham and Women's Hospital (CLIMB study) and 400 patients from the EPIC dataset, University of California, San Francisco, were included in the analysis. The primary outcome was an increase in Expanded Disability Status Scale (EDSS) ≥ 1.5 (worsening) or not (non-worsening) at up to 5 years after the baseline visit. Classification models were built using the CLIMB dataset with patients' clinical and MRI longitudinal observations in first 2 years, and further validated using the EPIC dataset. We compared the performance of three popular machine learning algorithms (SVM, Logistic Regression, and Random Forest) and three ensemble learning approaches (XGBoost, LightGBM, and a Meta-learner L). A "threshold" was established to trade-off the performance between the two classes. Predictive features were identified and compared among different models. Machine learning models achieved 0.79 and 0.83 AUC scores for the CLIMB and EPIC datasets, respectively, shortly after disease onset. Ensemble learning methods were more effective and robust compared to standalone algorithms. Two ensemble models, XGBoost and LightGBM were superior to the other four models evaluated in our study. Of variables evaluated, EDSS, Pyramidal Function, and Ambulatory Index were the top common predictors in forecasting the MS disease course. Machine learning techniques, in particular ensemble methods offer increased accuracy for the prediction of MS disease course.

6.
Biosci Rep ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33083827

RESUMO

BACKGROUND: Ovarian cancer is the most lethal cancer in the female reproductive system. It has been shown that "time chemotherapy" of ovarian cancer has an important impact on the chemotherapy effect and prognosis of patients, but the specific mechanism is not known. Methods: We designed a case-control study in strict accordance with epidemiological principles. We collected resection samples of ovarian-cancer patients who worked night-shifts and those who did not, and analyzed the differences in protein expression. Through construction of a normal/circadian-rhythm disorder model of ovarian cancer in nude mice, we explored the molecular mechanism of a "biological clock" rhythm on treatment of ovarian cancer. Results: Expression of interleukin-6, programmed cell death receptor-1 and programmed death ligand 1 increased, and expression of tumor necrosis factor-α, Period 1 (Per1) and Per2 decreased in the night-shift group. Methylation of CpG islands in the promoter of Per2 could result in its decreased expression in SKOV3/DDP(Cisplatin) cells. Dysrhythmia of the circadian clock: (i) had a negative effect on the chemotherapy effect against ovarian cancer; (ii) affected expression of immune factors and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Conclusion: The Per2 gene can affect the drug resistance of ovarian cancer by inhibiting the PI3K/Akt signaling pathway and then acting on its downstream drug-resistance factors, thereby providing a new target for ovarian-cancer treatment.

7.
J Agric Food Chem ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084305

RESUMO

Acyl migration occurs in many reactions and is the main obstacle for structured lipid synthesis. In this study, 2-monoacylglycerol (2-MAG) was prepared by enzymatic ethanolysis in three different media to evaluate the effect of environment on product composition. The contents of 2-MAG obtained in ethanol, hexane + ethanol, and t-butanol + ethanol systems were 30.6, 15.7, and 32.4%, respectively, after 3 h reaction. Afterward, the acyl migration kinetics of 2-MAG were studied in solvent and solventless systems without the use of lipase. Results indicate that 2-MAG in the solventless system had the highest acyl migration rate. The isomerization was efficiently prevented by the use of polar solvents, especially t-butanol. The rate constants were shown to be the highest and activation energy values were the lowest in solventless systems. The novel finding in this study was that solvent had inhibitory effect on 2-MAG isomerization, but the nonpolar hexane had the lowest inhibition of acyl migration compared to other solvents.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33057728

RESUMO

OBJECTIVES: To determine the epidemiological cut-off values (ECOFFs) of norvancomycin for Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus hominis. METHODS: We collected 1199 clinical isolates of Staphylococcus species from five laboratories located in four cities in China. MICs and inhibitory zone diameters of norvancomycin were determined by broth microdilution and the disc diffusion method, separately. ECOFFs of norvancomycin for four species were calculated by ECOFFinder software following EUCAST principles. Methicillin and vancomycin resistance genes (mecA/mecC and vanA/vanB/vanC/vanD/vanE) were screened for by PCR in all isolates. Pearson correlation and χ2 test were used to calculate the correlation of MICs and inhibition zone diameters, and MICs and resistance genes, respectively. RESULTS: MICs of norvancomycin for all strains from five laboratories fell in the range of 0.12-2 mg/L. ECOFFs of norvancomycin were determined to be 2 mg/L for S. epidermidis and S. haemolyticus and 1 mg/L for S. aureus and S. hominis. A weak correlation was observed between MIC values and zone diameters for S. haemolyticus (r = -0.36) and S. hominis (r = -0.26), while no correlation was found for S. epidermidis and S. aureus. The mecA gene was detected in 63.1% of Staphylococcus, whereas no isolate carried mecC, vanA, vanB, vanC, vanD or vanE. ECOFFs of norvancomycin were not correlated with mecA gene carriage in Staphylococcus species. CONCLUSIONS: ECOFFs of norvancomycin for four Staphylococcus species were determined, which will be helpful to differentiate WT strains. The correlation of MICs and zone diameters of norvancomycin was weak in Staphylococcus species.

9.
J Hazard Mater ; 404(Pt A): 124046, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33035906

RESUMO

With the wide use of graphene-like nanosheets, especially in agriculture, their release into the environment, it is crucial to grasp the fate of nanosheets in soil and minimum ecological risks. The present work discovered that leaching and migration of nanosheets (rGO) in soil is affected by soil porosity and adsorption processes. And the contents of rGO-Pd in soil layers and leachate increased and then decreased with the decreased of soil porosity. Moreover, physicochemical properties of rGO-Pd nanosheets changed by leaching processes, especially the changes of morphology, thickness and oxygen functional groups. Leaching of rGO-Pd also interfered the soil microbial homeostasis accompanied by the increase of microbial species richness and community diversity. In addition, rGO-Pd altered the usage of carbon sources by edaphon. The utilization of carbon sources by soil microbes, such as polymers, sugars, phenolic acids, carboxylic acids, amino acids, and amines, was also reduced by nanosheets. These findings provide new insights into environmental behaviors of nanomaterials and nanogeochemistry.

10.
Nat Ecol Evol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077929

RESUMO

As a heritable sequence-specific adaptive immune system, CRISPR-Cas is a powerful force shaping strain diversity in host-virus systems. While the diversity of CRISPR alleles has been explored, the associated structure and dynamics of host-virus interactions have not. We explore the role of CRISPR in mediating the interplay between host-virus interaction structure and eco-evolutionary dynamics in a computational model and compare the results with three empirical datasets from natural systems. We show that the structure of the networks describing who infects whom and the degree to which strains are immune, are respectively modular (containing groups of hosts and viruses that interact strongly) and weighted-nested (specialist hosts are more susceptible to subsets of viruses that in turn also infect the more generalist hosts with many spacers matching many viruses). The dynamic interplay between these networks influences transitions between dynamical regimes of virus diversification and host control. The three empirical systems exhibit weighted-nested immunity networks, a pattern our theory shows is indicative of hosts able to suppress virus diversification. Previously missing from studies of microbial host-pathogen systems, the immunity network plays a key role in the coevolutionary dynamics.

11.
Food Chem ; : 128235, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33051102

RESUMO

This paper proposed excitation-emission matrix fluorescence spectroscopy coupled with multi-way chemometric techniques for characterization and classification of Chinese pale lager beers produced by different manufacturers. The undiluted and diluted beer samples presented different fluorescence fingerprints. Three-way and four-way parallel factor analysis (PARAFAC) were used to decompose the skillfully constructed three-way and four-way data arrays, respectively, to further achieve beer characterization and feature extraction. Based on the features extracted in different ways, four strategies for beer classification were proposed. In each strategy, three supervised classification methods including linear discriminant analysis (LDA), partial least squares discriminant analysis (PLS-DA) and k-nearest neighbor (kNN) were used to build discriminant models. By comparison, PARAFAC-data fusion-kNN method in strategy 3 and four-way PARAFAC-kNN method in strategy 4 obtained the best classification results. The classification strategy based on four-way sample-excitation-emission-dilution level data array was proposed to solve the problem of beer classification for the first time.

12.
J Am Chem Soc ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021373

RESUMO

This work describes a strategy to produce circularly polarized thermally activated delayed fluorescence (CP-TADF). A set of two structurally similar organic emitters SFST and SFOT are constructed, whose spiro architectures containing asymmetric donors result in chirality. Upon grafting within the spiro frameworks, the donor and acceptor are fixed proximally in a face-to-face manner. This orientation allows intramolecular through-space charge transfer (TSCT) to occur in both emitters, leading to TADF properties. The donor units in SFST and SFOT have a sulfur and oxygen atom, respectively; such a subtle difference has great impacts on their photophysical, chiroptical, and electroluminescence (EL) properties. SFOT exhibits greatly enhanced EL performance in doped organic light-emitting diodes, with external quantum efficiency (EQE) up to 23.1%, owing to the concurrent manipulation of highly photoluminescent quantum efficiency (PLQY, ∼90%) and high exciton utilization. As a comparison, the relatively larger sulfur atom in SFST introduces heavy atom effects and leads to distortion of the molecular backbone that lengthens the donor-acceptor distance. SFST thus has lower PLQY and faster nonradiative decay rate. The collective consequence is that the EQE value of SFST, i.e., 12.5%, is much lower than that of SFOT. The chirality of these two spiro emitters results in circularly polarized luminescence. Because SFST has a more distorted molecular architecture than SFOT, the luminescence dissymmetry factor (|glum|) of circularly polarized luminescence of one enantiomer of the former, namely, either (S)-SFST or (R)-SFST, is almost twice that of (S)-SFOT/(R)-SFOT. Moreover, the CP organic light-emitting diodes (CP-OLEDs) show obvious circularly polarized electroluminescence (CPEL) signals with gEL of 1.30 × 10-3 and 1.0 × 10-3 for (S)-SFST and (S)-SFOT, respectively.

13.
Zhongguo Zhen Jiu ; 40(10): 1119-21, 2020 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-33068357

RESUMO

Professor XUE Li-gong's clinical experiences were summarized in treatment of painful bi syndrome of meridian muscle region with the "unknotting" method of long-round needle. It is believed that painful bi syndrome of meridian muscle region is related chiefly with the invasion of wind, cold and damp pathogens, exertion and traumatic injury. These pathogenic factors induce the "transverse-collateral" entrapment in the local and result in refractory painful bi syndrome of meridian muscle region. The "unknotting" method is adopted with long-round needle, which can either separate bluntly the knotted lesions or cut them sharply. "Taking the painful sites as the points" is the principle of point selection in treatment of meridian muscle disorder. Regarding needling techniques, joint needling, lateral needling and short needling are predominated.

14.
Sci Total Environ ; : 142740, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33071125

RESUMO

Mechanisms for hematotoxicity and health effects from exposure to low doses of benzene (BZ) remain to be identified. To address the information gap, our investigation was focused onto using appropriate populations and cell cultures to investigate novel BZ-induced effects such as disruption of DNA repair capacity (DRC). From our study, abnormal miRNAs were identified and validated using lymphocytes from 56 BZ-poisoned workers and 53 controls. In addition, 173 current BZ-exposed workers and 58 controls were investigated for key miRNA expression using RT-PCR and for cellular DRC using a challenge assay. Subsequently, the observed activities in lymphocytes were verified using human HL-60 (p53 null) and TK6 (p53 wild-type) cells via 1,4-benzoquinone (1,4-BQ) treatment and miR-222 interferences. The targeting of MDM2 by miR-222 was validated using a luciferase reporter. Our results indicate induction of genotoxicity in lymphocytes from workers with low exposure doses to BZ. In addition, miR-222 expression was up-regulated among both BZ-poisoned and BZ-exposed workers together with inverse association with DRC. Our in vitro validation studies using both cell lines indicate that 1,4-BQ exposure increased expression of miR-222 and Comet tail length but decreased DRC. Loss of miR-222 reduced DNA damage, but induced S-phase arrest and apoptosis. However, silencing of MDM2 failed to activate p53 in TK6 cells. In conclusion, our in vivo observations were confirmed by in vitro studies showing that BZ/1,4-BQ exposures caused genotoxicity and high expression of miR-222 which obstructed expression of the MDM2-p53 axis that led to failed activation of p53, abnormal DRC and serious biological consequences.

15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1754-1757, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018337

RESUMO

White matter hyperintensities (WMH) are important biomarkers for cerebral small vessel disease and closely associated with other neurodegenerative process. In this paper, we proposed a fully automatic WMH segmentation method based on U-net architecture. CRF were combined with U-net to refine segmentation results. We used a new anatomical based spatial feature produced by brain tissue segmentation based on T1 image, along with intensities of T1 and T2-FLAIR images to train our neural network. We compared 8 forms of automated WMH segmentation methods, range from traditional statistical learnng methods to deep learning based methods, with different architecture and used different features. Results showed our proposed method achieved best performance in terms of most metrics, and the inclusion of anatomical based spatial features strongly increase the segmentation performance.


Assuntos
Leucoaraiose , Substância Branca , Algoritmos , Hormônio Liberador da Corticotropina , Humanos , Imagem por Ressonância Magnética , Substância Branca/diagnóstico por imagem
16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2368-2371, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018482

RESUMO

It has been widely accepted that Parkinson's disease (PD) is triggered and shaped by propagation of misfolded α-synuclein. Converging neurophysiological evidence suggests that leucine-rich repeat kinase 2 (LRRK2) is involved in membrane transport of PD pathogenesis. This study proposed an agent-based computational model by integrating structural connections and gene expression to investigate whether LRRK2 would affect the PD pathology propagation in central nervous system. Gene expression profiles from the Allen Human Brain Atlas (AHBA) and multimodal brain MRI images from Parkinson's Progression Markers Initiative (PPMI) and Human Connectome Project (HCP) were employed for the model construction. The model results exhibit the involvement of LRRK2 gene expression remarkably elevated model fitting (r = 0.73) compared with the traditional susceptible-infected-removed (S-I-R) model (r=0.60). Specifically, our model revealed that LRRK2 is more likely to modulate pathology secretion out of neurons, rather than spreading into neurons. The findings support the theory of LRRK2 gene expression modulating cell-to-cell propagation of misfolded proteins. As a result, the proposed model would bring new insights of understanding PD mechanism in terms of misfolded α-synuclein propagation.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Encéfalo/diagnóstico por imagem , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Neurônios/metabolismo , Doença de Parkinson/genética , alfa-Sinucleína/genética
17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2679-2682, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018558

RESUMO

Pulse transit time (PTT) based continuous cuff-less blood pressure (BP) monitoring has attracted wide interests owing to its potential in improving the control and early prevention for cardiovascular diseases. However, it is still impractical in large-scale clinical application due to the concern of BP measurement accuracy. Since such approach strongly relies on the PTT-BP model under certain theoretical assumptions, the accuracy would be affected by the vessel properties alterations induced by cardiovascular disorders. Atrial fibrillation (AF) is one of the most common cardiac diseases which often coexist with hypertension. The present study sought to examine the Impact of AF on the PTT and BP, validate the capability of PTT based cuff-less methods on AF patients. By investigating the PTT and BP on 74 critically ill patients with AF, we found that parameters including PTT, R-R interval and diastolic BP (DBP) were significantly changed when AF occurs, while the systolic BP (SBP) value and photoplethysmography intensity ratio (PIR) changed little. Further, by performing two cuff-less BP estimation method, we found that the estimated accuracy is decreased on PTT based method when AF occurs, but there is little change on PIR based method. The findings demonstrated that the impact of AF on PTT is significant, which would also influence the PTT-BP relationship. But the PIR would still be a predictive factor for BP estimation for AF patients.


Assuntos
Fibrilação Atrial , Fibrilação Atrial/diagnóstico , Pressão Sanguínea , Determinação da Pressão Arterial , Humanos , Fotopletismografia , Análise de Onda de Pulso
18.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3711-3714, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018807

RESUMO

One crucial key of developing an automatic sleep stage scoring method is to extract discriminative features. In this paper, we present a novel technique, termed common frequency pattern (CFP), to extract the variance features from a single-channel electroencephalogram (EEG) signal for sleep stage classification. The learning task is formulated by finding significant frequency patterns that maximize variance for one class and that at the same time, minimize variance for the other class. The proposed methodology for automated sleep scoring is tested on the benchmark Sleep-EDF database and finally achieves 97.9%, 94.22%, and 90.16% accuracy for two-state, three-state, and five-state classification of sleep stages. Experimental results demonstrate that the proposed method identifies discriminative characteristics of sleep stages robustly and achieves better performance as compared to the state-of-the-art sleep staging algorithms. Apart from the enhanced classification, the frequency patterns that are determined by the CFP algorithm is able to find the most significant bands of frequency for classification and could be helpful for a better understanding of the mechanisms of sleep stages.


Assuntos
Processamento de Sinais Assistido por Computador , Fases do Sono , Algoritmos , Eletroencefalografia , Sono
19.
Cell Chem Biol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33053370

RESUMO

Despite widespread interest for understanding how modified bases have evolved their contemporary functions, limited experimental evidence exists for measuring how close an organism is to accidentally creating a new, modified base within the framework of its existing genome. Here, we describe the biochemical and structural basis for how a single-point mutation in E. coli's naturally occurring cytosine methyltransferase can surprisingly endow a neomorphic ability to create the unnatural DNA base, 5-carboxymethylcytosine (5cxmC), in vivo. Mass spectrometry, bacterial genetics, and structure-guided biochemistry reveal this base to be exclusively derived from the natural but sparse secondary metabolite carboxy-S-adenosyl-L-methionine (CxSAM). Our discovery of a new, unnatural DNA modification reveals insights into the substrate selectivity of DNA methyltransferase enzymes, offers a promising new biotechnological tool for the characterization of the mammalian epigenome, and provides an unexpected model for how neomorphic bases could arise in nature from repurposed host metabolites.

20.
Anal Methods ; 12(37): 4562-4571, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33001064

RESUMO

Xuebijing (XBJ) is a compound Chinese medicine that contains Paeoniae Radix Rubra, ChuanXiong Rhizoma, Salvia Miltiorrhiza Radix et Rhizoma, Carthami Flos, and Angelicae Sinensis Radix. It is widely used in China to treat sepsis. Previous studies have demonstrated that XBJ can decrease mortality in patients with moderate paraquat poisoning. However, the mechanism by which it exerts this effect is not completely clear. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based metabolomics approach was used to perform a metabolic profiling analysis. Principal component analysis (PCA), random forest (RF), and partial least squares discriminant analysis (PLS-DA) were used to identify metabolites to clarify the mechanism of XBJ's activity. XBJ clearly alleviated lung injury in a Sprague Dawley (SD) rat model of paraquat (PQ) poisoning. Seven metabolites related to four pathways, including those involved in sphingolipid and phospholipid metabolism, amino acid metabolism, unsaturated fatty acid metabolism, and pantothenic acid and CoA biosynthesis, were present at different levels in PQ-poisoned rats treated with XBJ compared with untreated rats. XBJ can ameliorate the effects of PQ poisoning in SD rats. Using a metabolomics approach enabled us to gain new insight into the mechanism underlying this effect.

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