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1.
Acta Diabetol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728736

RESUMO

AIMS: This study aimed to explore the level of and changes in the 1,5-anhydroglucitol × glycated hemoglobin A1c/100 (AH index, AHI) associated with different glucose metabolism statuses and to evaluate the islet function and insulin sensitivity of patients with type 2 diabetes (T2DM) with different AHI levels. METHODS: Of the 3562 subjects enrolled in this study, 1697 had T2DM. The disposition index (DI) was the product of islet secretion function and insulin sensitivity-related indexes. RESULTS: The mean AHI level was 1.0 (0.7-1.3) in the general population, while the mean AHI level in the T2DM group was 0.8 (0.5-1.2), which was significantly lower than that in the impaired glucose regulation and normal glucose tolerance group (both 1.2 (0.9-1.5), both P < 0.01). We further divided patients with T2DM into four subgroups according to the quartile of AHI. The results showed that with the increase in AHI level, the homeostasis model assessment of insulin resistance (HOMA-IR) decreased, while HOMA-ß, insulin generation index, insulin sensitivity index, and DI increased (all Pfor trend < 0.01). Multivariate logistic regression showed that the odds ratios for a low DI for increasing levels of AHI were 1.00, 0.22 (0.16-0.29), 0.16 (0.11-0.22), and 0.09 (0.06-0.13), showing a decreasing trend (Pfor trend < 0.05). CONCLUSION: The AHI could reflect the variation in glycemic disorder and the function of islet ß cells. The lower the AHI, the worse the glycemic disorder, as well as the islet ß-cell function.

2.
Sci Total Environ ; : 134475, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31759721

RESUMO

Organic molecular composition of fine aerosols in the free troposphere is poorly understood. Here, PM2.5 (particles with aerodynamic diameters ≤ 2.5 µm) samples were collected at the summit of Mt. Emei (3080 m a.s.l.) in the Southwestern China on a daytime and nighttime basis during summer 2016 (June-July). The samples were analyzed by solvent-extraction followed by derivatization and gas chromatography/mass spectrometry (GC/MS). Four classes of organic compounds, i.e. n-alkanes, fatty acids, saccharides and lignin/resin acids were measured quantitatively. Fatty acids were found to be the most abundant species with an average concentration of 401 ±â€¯419 ng m-3 (range 25.7-1490 ng m-3) in the daytime, similar to the average concentration at night (399 ±â€¯447 ng m-3, 19.6-1970 ng m-3). However, the concentrations of biomass burning tracers (e.g., levoglucosan), primary biological aerosol tracers (e.g., mannitol and arabitol) and low molecular weight n-alkanes derived from fossil fuel combustion in daytime samples were obviously higher than those in nighttime samples. The results suggest that valley breezes transported a large number of aerosols and their precursors from the ground surface to the summit of Mt. Emei in the daytime. Estimated with tracer-based methods, the contributions of biogenic primary sources (plant debris, fungal spore, and biomass burning) to organic carbon was in the range of 3.28-83.5% (22.0 ±â€¯17.5%) in the daytime and 3.45-37.4% (10.9 ±â€¯8.97%) at night. As the largest contributor, biomass burning was an important anthropogenic/natural source of aerosol particles in the free troposphere over Mt. Emei. CAPSULE: Valley/mountain breeze is an important constraint to the temporal variations in organic aerosols over Mt. Emei.

3.
Anal Biochem ; 589: 113493, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682794

RESUMO

Reduced nicotinamide adenine dinucleotide (NADH) plays a pivotal role in the electron-transfer chain of biological system. Analysis of many biological markers is based on the detection of the enzymatically generated NADH. In this paper, a sensitive hydrogen peroxide (H2O2) biosensor, fabricated by carbon nanotubes (CNTs)/tetrathiafulvalene (TTF)/horseradish peroxidase (HRP), was applied for detecting the NADH in a buffer containing methylene blue (MB) at low operating potential of - 0.3 V (vs. Ag/AgCl). Since the NADH could be oxidized by MB to release H2O2, the electrochemical biosensor enables to detect the NADH in the MB buffer. And the low working potential made the biosensor avoid the interference from other electroactive substances. Linear response ranges from 10 µM to 790 µM, with a sensitivity of 4.76 µA mM-1 and a detection limit of 1.53 µM were obtained under the optimum conditions. The proposed sensor provided a promising approach for sensitively detecting the NADH.

4.
Aging (Albany NY) ; 11(19): 8463-8473, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31586991

RESUMO

PURPOSE: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma. RESULTS: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients' age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages. CONCLUSIONS: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age. PATIENTS AND METHODS: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

5.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3478-3485, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602912

RESUMO

Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.


Assuntos
Cuscuta/química , Flavonoides/farmacologia , Genitália/efeitos dos fármacos , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , DNA (Citosina-5-)-Metiltransferases/genética , Feminino , Genitália/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Ratos , Sementes/química , Transdução de Sinais , Comprimidos , Hormônios Tireóideos/genética , Transcriptoma
6.
Subst Abus ; : 1-8, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638882

RESUMO

Objectives: The purpose of the study was to investigate whether Group Music Therapy (GMT) could enhance the treatment motivation and change the negative emotion among female patients with methamphetamine use disorder in a randomized clinical trial. Methods: Participants (N = 60) were randomized to the group of GMT combined with treatment as usual (TAU) or the group with TAU only. Questionnaire of Motivation for Abstaining from Drugs was used to measure the motivation for abstaining from drugs of the female patients. And Self-Rating Depression Scale and Self-Rating Anxiety Scale were used to measure negative emotion of participants. The measurements were conducted at T0 (baseline), T1 (post 13 sessions of intervention) and T2 (3-month follow-up after T1) by the independent trained researcher. Results: The postintervention and 3-month follow-up results according to the intention-to-treat principle indicated that GMT + TAU intervention showed significantly positive group-by-time effect on the scores of the subscale-tending to rehabilitation-internal motivation (p = 0.01) and avoiding abuse-external motivation (p = 0.04). In 3-month follow-up, total scores of the questionnaire of motivation for abstaining from drugs (p = 0.02), scores of avoiding abuse-internal motivation subscale (p = 0.05), and scores of confidence of abstaining from drugs subscale (p = 0.01) in GMT + TAU were also presented with significantly positive group x time effect. The changes of total score of Questionnaire of Motivation for Abstaining from Drugs (from baseline to 3-month follow-up) was significantly positive association with the changes of scores of SAS in GMT + TAU group (r = -0.55, p = 0.00). Conclusions: The present study suggests that GMT could be used as an effective treatment strategy to enhance treatment motivation of female patients with methamphetamine use disorder.

7.
Environ Sci Technol ; 53(22): 13257-13264, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31589819

RESUMO

Characteristic particle size, fluorescence intensity, and fluorescence spectra are important features to detect and categorize bioaerosols. A prototype size-resolved single-particle fluorescence spectrometer (S2FS) was developed to simultaneously measure aerodynamic diameters and fluorescence spectra. Emission spectra are dispersed in 512 channels from 370 to 610 nm, where a major portion of biological fluorescence emission occurs. The S2FS consists of an aerodynamic particle sizer and a fluorescence spectrometer with a 355 nm laser excitation source and an intensified charge-coupled device as the detector. Highly fluorescent particles, such as Ambrosia artemisiifolia pollen and Olea europaea pollen, can be distinguished by the S2FS on a single-particle level. For weakly fluorescent particles, fluorescence spectra can only be obtained by averaging multiple particles (between 100 and 3000) of the same kind. Preliminary ambient measurements in Mainz (Germany, central Europe) show that an emission peak at ∼440 nm was frequently observed for fluorescent fine particles (0.5-1 µm). Fluorescent fine particles accounted for 2.8% on average based on the number fraction in the fine mode. Fluorescent coarse particles (>1 µm) accounted for 8.9% on average based on the number fraction, with strongest occurrence observed during a thunderstorm and in the morning.

8.
ACS Appl Mater Interfaces ; 11(41): 38255-38264, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529951

RESUMO

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become an indispensable tool for high-throughput analysis of macromolecules, but many challenges still remain in detection of small molecules due to the severe matrix-related background interference in the low-molecular-weight ranges (MW < 700 Da). Herein, a gallic acid (GA)-functionalized zirconium 1,4-dicarboxybenzene metal-organic framework (MOF) (denoted as UiO-66-GA) was designed to serve as a new substrate, and a novel strategy on the basis of the synergistic effect of MOF and GA was developed to enhance the LDI process. In comparison with conventional organic matrices, the UiO-66-GA substrate showed superior LDI performance in the analysis of a wide variety of molecules including amino acids, unsaturated fatty acids, bisphenols (BPs), oligosaccharides, peptides, protein, and polyethylene glycol (PEG) of various average molecular weights from 200 to 10000. Perfluorooctanoic sulfonate (PFOS) was used to evaluate the ability of quantitative analysis, and its corresponding limit of detection as low as 1 fmol was achieved. High sensitivity and good salt tolerance of the UiO-66-GA-assisted LDI-MS were allowed to determine ultratrace PFOS in the spiked human urine and serum samples. In addition, the synergistic mechanism of MOF and GA in the enhanced LDI process was investigated by comprehensively comparing GA- and its analogue-functionalized UiO-66, and the results revealed that two aspects contributed to the enhanced LDI process: (1) an enhancement in the metal-phenolic coordination system of UiO-66-GA promoted laser absorption and energy transfer; (2) introduction of carboxyl and hydroxyl groups of GA onto UiO-66 facilitated the LDI process in both positive and negative ion modes. This work expands a new domain for the MOF applications and provides a promising alternative for various molecule analyses.

9.
Emerg Microbes Infect ; 8(1): 1361-1369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522608

RESUMO

Rapid and simple-to-use diagnostic methods for tuberculosis are urgently needed. Recent development has unveiled the diagnostic power of the CRISPR system in the detection of viral infections. However, its potential use in detecting the Mycobacterium tuberculosis complex (MTB) remained unexplored. We developed a rapid CRISPR-based assay for TB detection and conducted a retrospective cohort study of 179 patients to evaluate the CRISPR-MTB test for identifying MTB in various forms of direct clinical samples. Its diagnostic performance was compared, in parallel with culture and the GeneXpert MTB/RIF assay (Xpert). The CRISPR-MTB test is highly sensitive with a near single-copy sensitivity, demands less sample input and offers shorter turnaround time than Xpert. When evaluated in the clinical cohort of both pulmonary and extra-pulmonary tuberculosis, the CRISPR-MTB test exhibited an overall improved sensitivity over both culture (79% vs 33%) and Xpert (79% vs 66%), without comprise in specificity (62/63, 98%). The CRISPR-MTB test exhibits an improved overall diagnostic performance over culture and Xpert across a variety of sample types, and offers great potential as a new diagnostic technique for both pulmonary and extra-pulmonary tuberculosis.

10.
Chem Commun (Camb) ; 55(78): 11699-11702, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31508612

RESUMO

A series of gold/palladium nanoalloys stabilized by secondary phosphine oxides have been prepared for the first time. The nanocatalysts exhibit excellent regio- and chemo-selectivity in the hydrogenation of conjugated enynes, providing a mild and highly efficient way to access phosphinyl (Z) and (Z,Z)-[3]dendralenes.

11.
Sensors (Basel) ; 19(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470521

RESUMO

As a significant role in healthcare and sports applications, human activity recognition (HAR) techniques are capable of monitoring humans' daily behavior. It has spurred the demand for intelligent sensors and has been giving rise to the explosive growth of wearable and mobile devices. They provide the most availability of human activity data (big data). Powerful algorithms are required to analyze these heterogeneous and high-dimension streaming data efficiently. This paper proposes a novel fast and robust deep convolutional neural network structure (FR-DCNN) for human activity recognition (HAR) using a smartphone. It enhances the effectiveness and extends the information of the collected raw data from the inertial measurement unit (IMU) sensors by integrating a series of signal processing algorithms and a signal selection module. It enables a fast computational method for building the DCNN classifier by adding a data compression module. Experimental results on the sampled 12 complex activities dataset show that the proposed FR-DCNN model is the best method for fast computation and high accuracy recognition. The FR-DCNN model only needs 0.0029 s to predict activity in an online way with 95.27% accuracy. Meanwhile, it only takes 88 s (average) to establish the DCNN classifier on the compressed dataset with less precision loss 94.18%.

12.
Environ Sci Technol ; 53(21): 12506-12518, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31536707

RESUMO

Highly oxygenated molecules (HOMs) play an important role in the formation and evolution of secondary organic aerosols (SOA). However, the abundance of HOMs in different environments and their relation to the oxidative potential of fine particulate matter (PM) are largely unknown. Here, we investigated the relative HOM abundance and radical yield of laboratory-generated SOA and fine PM in ambient air ranging from remote forest areas to highly polluted megacities. By electron paramagnetic resonance and mass spectrometric investigations, we found that the relative abundance of HOMs, especially the dimeric and low-volatility types, in ambient fine PM was positively correlated with the formation of radicals in aqueous PM extracts. SOA from photooxidation of isoprene, ozonolysis of α- and ß-pinene, and fine PM from tropical (central Amazon) and boreal (Hyytiälä, Finland) forests exhibited a higher HOM abundance and radical yield than SOA from photooxidation of naphthalene and fine PM from urban sites (Beijing, Guangzhou, Mainz, Shanghai, and Xi'an), confirming that HOMs are important constituents of biogenic SOA to generate radicals. Our study provides new insights into the chemical relationship of HOM abundance, composition, and sources with the yield of radicals by laboratory and ambient aerosols, enabling better quantification of the component-specific contribution of source- or site-specific fine PM to its climate and health effects.

13.
Sensors (Basel) ; 19(17)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438529

RESUMO

In robot control with physical interaction, like robot-assisted surgery and bilateral teleoperation, the availability of reliable interaction force information has proved to be capable of increasing the control precision and of dealing with the surrounding complex environments. Usually, force sensors are mounted between the end effector of the robot manipulator and the tool for measuring the interaction forces on the tooltip. In this case, the force acquired from the force sensor includes not only the interaction force but also the gravity force of the tool. Hence the tool dynamic identification is required for accurate dynamic simulation and model-based control. Although model-based techniques have already been widely used in traditional robotic arms control, their accuracy is limited due to the lack of specific dynamic models. This work proposes a model-free technique for dynamic identification using multi-layer neural networks (MNN). It utilizes two types of MNN architectures based on both feed-forward networks (FF-MNN) and cascade-forward networks (CF-MNN) to model the tool dynamics. Compared with the model-based technique, i.e., curve fitting (CF), the accuracy of the tool identification is improved. After the identification and calibration, a further demonstration of bilateral teleoperation is presented using a serial robot (LWR4+, KUKA, Germany) and a haptic manipulator (SIGMA 7, Force Dimension, Switzerland). Results demonstrate the promising performance of the model-free tool identification technique using MNN, improving the results provided by model-based methods.

14.
Fish Shellfish Immunol ; 93: 492-499, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31381973

RESUMO

TANK-binding kinase 1 (TBK1) is an important kinase that regulates the activation of interferon regulatory factor 3/7 (IRF3/7) to induce type I interferon (IFN-I) production in antiviral immune responses. However, in long-term virus-host crosstalk, viruses have evolved elaborate strategies to evade host immune defense mechanisms. In the present study, we found that grass carp (Ctenopharyngodon idella) reovirus (GCRV) hijacks TBK1 to escape IRF7-IFN-Is signaling activation. In brief, GCRV inhibited TBK1 activation by restaining K63-linked ubiquitination of TBK1 and promoting its K48-linked ubiquitination. This regulation resulted in that under low titer of GCRV infection, TBK1 overexpression specifically supressed promoter activity and phosphorylation of IRF7 and induction of downstream IFN1and IFN3. qRT-PCR data uncovered that TBK1 negatively regulated IRF7, IFN1 and IFN3 transcription levels under low viral titer infection. Along with enhancement of GCRV titers, TBK1 swiched its function to up-regulate IRF7, IFN1 and IFN3 mRNA levels. Accordingly, TBK1 promoted GCRV replication at low infected titer, but inhibited GCRV replication at high infected titer. All these results revealed a viral evasion strategy that GCRV utilizes TBK1 to block cellular IFN responses at low titers or early stages in fish species, which will lay a foundation for further researching on host-virus interactions and developing novel antiviral strategies in lower vertebrates.

15.
Nanoscale ; 11(27): 12846-12852, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31265048

RESUMO

Tin(ii) sulfide (SnS) is considered to be one of the most promising anode materials for lithium/sodium ion batteries (LIBs/SIBs) due to its high theoretical capacity and low-cost. However, its practical applications are severely impeded by its low electrical conductivity and large volume change upon cycling. Herein, we demonstrate a high-performance SnS/TiO2 encapsulated by a carbon shell (SnS/TiO2@C) synthesized by facile coprecipitation and annealing treatment. The exterior carbon coating can not only improve the conductivity, but also effectively relieve volume variation to maintain the structural integrity during cycling. Significantly, the internal SnS/TiO2 heterostructure formed a built-in electric field to provide favorable driving force for ion transfer. Consequently, the synthesized SnS/TiO2@C delivered a reversible capacity of 672.4 mA h g-1 at 0.5 A g-1 after 100 cycles for lithium storage and 331.2 mA h g-1 at 0.2 A g-1 after 200 cycles for sodium storage. Meanwhile, ultra-long lifespans of 3000 cycles at 5.0 A g-1 with a capacity of 394.5 mA h g-1 for LIBs and 750 cycles at 5.0 A g-1 with a capacity of 295 mA h g-1 for SIBs were achieved. The electrochemical reaction mechanisms of the SnS/TiO2@C electrode have been investigated by in situ XRD, ex situ XRD, and ex situ HRTEM. Our work may offer further understanding of the hierarchical structure to boost the electrochemical properties of the electrode materials.

16.
Nat Commun ; 10(1): 2753, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266936

RESUMO

Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Sistemas CRISPR-Cas , Infecções por HIV/terapia , HIV-1/genética , Transferência Adotiva , Animais , Terapia Combinada , DNA Viral/genética , DNA Viral/imunologia , Edição de Genes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/fisiologia , Humanos , Camundongos , Resultado do Tratamento , Latência Viral
17.
Mol Med Rep ; 20(3): 2143-2150, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322181

RESUMO

Estradiol (E2) is a first­line drug for osteoporosis (OP) treatment via promotion of osteoblastic proliferation and differentiation. However, a long­term use of E2 would produce side effects thus, it is imperative to discover safer and more effective drugs. Pinoresinol (PINO) has a similar chemical structure to E2. The present study aimed to investigate whether PINO could promote osteoblastic proliferation and differentiation and the potential mechanisms. After treatment with 0.1 µg/l PINO for 2 days, MC3T3­E1 cell migration was assessed by wound healing assay. Estrogen (E2) treatment served as a positive control. RT­qPCR and western blotting were used for mRNA and protein expression analyses. Alkaline phosphatase (ALP) activity assay and Alizarin red staining were performed to investigate the calcification and mineralization, and the cyclic AMP (cAMP) level was detected by enzyme­linked immunosorbent assay (ELISA). H89, an inhibitor of protein kinase A (PKA), was introduced to verify the role of cAMP/PKA in the effect of PINO on MC3T3­E1 cells. Cell viability was the highest under 48 h of 0.1 µg/l PINO treatment. After treatment with PINO, a significant increase was observed in the migration rate and the expression of collagen type I (Col­I), ALP, osteopontin (OPN), runt­related transcription factor 2 (Runx2) and bone morphogenetic protein­2 (BMP­2) (P<0.01). The ALP activity and Alizarin red size in PINO and E2 groups were notably increased. The increased cAMP, PKA and phosphorylated cAMP response element­binding protein (CREB) levels were also observed in the PINO group. Furthermore, H89 co­treatment abolished the positive effects of PINO on cell viability and migration. PINO had similar effects to E2 on the osteoblastic proliferation and differentiation, and these positive effects may be attributed to the regulation of the cAMP/PKA signaling pathway.

18.
J Agric Food Chem ; 67(30): 8332-8338, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31298538

RESUMO

The excretion, tissue distribution, and metabolic profile of astilbin in rat were studied by HPLC and UPLC-QTOF-MS. Astilbin underwent isomerization in the small intestine, and its four isomers were found in feces. Besides, taxifolin, the aglycone of astilbin, and its further metabolites by gut microbes through hydrogenation, dehydration, and ring-fission were found. The total feces excretion of astilbin was about 14.4% of administration. The forming of zein-caseinate nanoparticles can significantly delay and reduce the feces excretion of astilbin. Astilbin and its isomers were absorbed in their intact form. The main metabolites found in plasma and tissues were the methylated products. Astilbin was rapidly distributed in various tissues including brain and maintained relatively high concentration in heart. Compared with other tissues, significantly higher concentration and longer duration of astilbin were found in the gastrointestinal tract. Astilbin and its isomers were excreted in their intact and methylated form in urine.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Flavonóis/farmacocinética , Maianthemum/química , Nanopartículas/química , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Feminino , Flavonóis/administração & dosagem , Flavonóis/química , Masculino , Espectrometria de Massas , Ratos Sprague-Dawley , Rizoma/química , Distribuição Tecidual , Zeína/química , Zeína/farmacocinética
19.
PLoS Pathog ; 15(7): e1007914, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31356650

RESUMO

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause disability in newborns and serious clinical diseases in immunocompromised patients. HCMV has a large genome with enormous coding potential; its viral particles are equipped with complicated glycoprotein complexes and can infect a wide range of human cells. Although multiple host cellular receptors interacting with viral glycoproteins have been reported, the mechanism of HCMV infection remains a mystery. Here we report identification of adipocyte plasma membrane-associated protein (APMAP) as a novel modulator active in the early stage of HCMV infection. APMAP is necessary for HCMV infection in both epithelial cells and fibroblasts; knockdown of APMAP expression significantly reduced HCMV infection of these cells. Interestingly, ectopic expression of human APMAP in cells refractory to HCMV infection, such as canine MDCK and murine NIH/3T3 cells, promoted HCMV infection. Furthermore, reduction in viral immediate early (IE) gene transcription at 6 h post infection and delayed nucleus translocation of tegument delivered pp65 at 4 h post infection were detected in APMAP-deficient cells but not in the wildtype cells. These results suggest that APMAP plays a role in the early stage of HCMV infection. Results from biochemical studies of APMAP and HCMV proteins suggest that APMAP could participate in HCMV infection through interaction with gH/gL containing glycoprotein complexes at low pH and mediate nucleus translocation of tegument pp65. Taken together, our results suggest that APMAP functions as a modulator promoting HCMV infection in multiple cell types and is an important player in the complex HCMV infection mechanism.

20.
BMC Cancer ; 19(1): 702, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315676

RESUMO

BACKGROUND: The epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer has been successfully treated with tyrosine kinase inhibitors (TKIs). Acquired resistance becomes a tough issue when patients fail to respond to the third-generation TKI osimertinib. This study aimed to report a case baring acquired EGFR L858R/L718Q mutation in the central nervous system induced by osimertinib, which was successfully overcome using afatinib. CASE PRESENTATION: A 65-year-old female patient was diagnosed with stage IV non-small-cell lung adenocarcinoma with synchronic brain metastasis in February 2015. Before and during treatment, 416 tumor-related genes were monitored dynamically by liquid biopsies using next-generation sequencing, and the treatment strategy was decided according to the gene status. At baseline, an EGFR L858R mutation in exon 21 was detected, so treatment with icotinib was started. After 8 months, she experienced disease progression with leptomeningeal metastasis and switched to osimertinib based on an acquired EGFR T790 M mutation. After 9 months, her disease progressed and an EGFR L718Q mutation was found in the cerebrospinal fluid. The patient was then challenged with afatinib, and her disease was under control for 4 months. In January 2017, the patient passed away, with an overall survival time of 23 months, 15 months after leptomeningeal metastasis. CONCLUSION: The acquired EGFR L718Q mutation in the cerebrospinal fluid resulted in subsequent resistance to osimertinib and could be partly overcome using afatinib, indicating a promising treatment option in the clinic.

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