Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.977
Filtrar
1.
Carbohydr Polym ; 227: 115354, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590849

RESUMO

Certain polysaccharides can serve as bio-active natural polymers that provide health benefits, however their complex structures tend to induce dramatically different activities. In this work, the immunomodulatory activity of the two arabinogalactans from larch was investigated, based upon comparison of native arabinogalactans and those modified to have lesser quantities of side-chain paraphernalia. Various in vitro assays demonstrated that the native arabinogalactans increased the secretion of macrophage-derived biological factors including NO, TNF-α, IL-1ß and IL-6. Methylation analysis and nuclear magnetic resonance spectra results indicated that part side chains of arabinogalactan were successfully removed. Partial removal of the side-chains enhanced immunomodulatory activity, while excessive removal resulted in a sharp decrease in immunomodulatory activity. These results provide new evidence that alludes to the structure-function relationship of bio-active polysaccharides, furthering the case for development of a universal assessment of polysaccharide structure-function proclivities.

2.
J Colloid Interface Sci ; 559: 65-75, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610306

RESUMO

Electroactive nanofibrous scaffold is a vital tool for the study of the various biological research fields from bioelectronics to regenerative medicine, which can provide cell preferable 3D nanofiber architecture and programmed electrical signal. However, intrinsic non-biodegradability is a major problem that hinders its widespread application in the clinic. Herein, we designed, synthesized, and characterized shell/core poly (3,4-ethylenedioxythiophene) (PEDOT)/chitosan (CS) nanofibers by combining the electrospinning and recrystallization processes. Upon incorporating a trace amount of PEDOT (1.0 wt%), the resultant PEDOT/CS nanofibers exhibited low interfacial charge transfer impedance, high electrochemical stability, high electrical conductivity (up to 0.1945 S/cm), and ultrasensitive piezoelectric property (output voltage of 22.5 mV by a human hair prodding). With such unique electrical and conductive properties, PEDOT/CS nanofibers were further applied to brain neuroglioma cells (BNCs) to stimulate their adhesion, proliferation, growth, and development under an optimal external electrical stimulation (ES) and a pulse voltage of 400 mV/cm. ES-responsive PEDOT/CS nanofibers indeed promoted BNCs growth and development as indicated by a large number and density of axons. The synergetic interplay between external ES and piezoelectric voltage demonstrates new PEDOT-based nanofibers as implantable electroactive scaffolds for numerous applications in nerve tissue engineering, human health monitoring, brain mantle information extraction, and degradable microelectronic devices.

3.
Toxicol In Vitro ; 62: 104660, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629066

RESUMO

Herba Epimedii is a famous Chinese edible herb, and due to its potential hepatotoxic effects, the safety associated with this herb has attracted a great deal of attention. In this study, the components of four types of the Herba Epimedii extracts were identified by HPLC-MS/MS. Among these components, 11 components that were present in all four extracts and could be obtained as reference substances were evaluated for their ability of cytotoxicity in HL-7702 and HepG2 cells, resulting in the identification of icarisid I and sagittatoside A as the most relevant with respect to the toxicity of the extracts. The targeted toxicological effects were further investigated using a series of correlated biological indicators to elucidate potentially hepatotoxic mechanisms. The results showed that the extracts and the selected compounds had varying degrees of influence on the leakage of ALT, AST and LDH; the activity of SOD, GSH and MDA; the increase in intercellular ROS; and the decrease in MMP. Among the tested substances, the ethanol extracts exhibited stronger hepatotoxicity, with icarisid I and sagittatoside A correlating with this toxic effect, and the hepatoxic mechanisms of which may be associated with damaged cell structure, increased oxidative stress and induction of apoptosis.

4.
Pharm Dev Technol ; 25(1): 76-88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31556338

RESUMO

The objective of this research is to understand how the properties of magnesium stearate (MgSt) affect product performance in a quantitative manner using a multivariate modeling approach. In addition, we explored the feasibility of using NIR and Raman spectra as a surrogate measurement of physiochemical properties in prediction of performance in tablet direct compression. Partial least square models to predict performance attributes (PAs) from MgSt properties or spectra were developed and validated. The model input variables are MgSt physiochemical properties, spectra, key formulation and process parameters. Material physiochemical properties include fatty acid composition, loss on drying, densities, particle size distribution, specific surface area, and solid state properties. The key formulation and process parameters include MgSt concentration, filler type and compression force. The output variables are PAs including tablet ejection force, breaking force and disintegration time. It was found that the prediction of MgSt performance from its properties greatly depends on filler type and PAs of interest. NIR spectra successfully predicted lubricant performance in lactose tablet; however, predictions from Raman spectra were not acceptable. In the cases that the contributing physiochemical properties in performance prediction are sufficiently captured in the spectra, the spectra can be used as an alternative tool to predict excipient performance.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117467, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31425863

RESUMO

Herein, we presented two novel turn-on colorimetric and fluorescent probes based on a F- triggered SiO bond cleavage reaction, which displayed several desired properties for the quantitative detection for F-, such as high specificity, rapid response time (within 3 min) and naked-eye visualization. The fluorescence intensity at 574 nm (absorbance at 544 nm) of the solution was found to increase linearly with the concentration of F- (0.00-30.0 µM) with the detection limit was estimated to be 0.47 µM/0.48 µM. Based on these excellent optical properties, the probes were employed to monitor F- in real water samples and tea samples with satisfactory. Furthermore, it was successfully applied for fluorescent imaging of F- in living nude mice, suggesting that it could be used as a powerful tool to predict and explore the biological functions of F- in physiological and pathological processes.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117671, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31670043

RESUMO

In this paper, a simple, economical, and green strategy is developed for producing nitrogen doped graphene quantum dots (N-GQDs) with multicolor light emission by hydrothermal treatment of Passiflora edulia Sims. The synthesized N-GQDs exhibit ideal ionic stability, hydrophilicity and anti-photobcleaching properties, and the quantum yield reaches up to about 29%. Because of with the fluorescence quenching effect, the achieved N-GQDs allow to detect Ag+ in a linear range of 10 nM-160 µM, and the limit of detection is calculated to be 1.2 nM according to the S/N of 3. Noteworthy, N-GQDs with blue, green and yellow light emissions are demonstrated via regulating the reaction time and temperature, implying a promising fluorescence adjustability. Furthermore, the N-GQDs-based fluorescent probe exhibits low cytotoxicity and favorable biocompatibility. Depending on the superior properties, our N-GQDs are applied in fluorescent ink and multicolor cell imaging. Eventually, the developed sensor is highly selective and accurate for Ag+ analysis in real water, which demonstrates the promising practical use in environmental determination and/or biomedical engineering.

7.
ACS Nano ; 13(11): 13100-13108, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31702896

RESUMO

Effective droplet emission is of fundamental importance for practical application, such as agricultural sprays to painting, atomization, emulsification, and catalytic action. Highly viscous liquids are commonly used, such as printing inks, which hinder the ejection at the nozzle. A big challenge faced by people is how to obtain stable and controllable liquid droplets in a wide range of viscosities. Inspired by the rotation shaking of droplets on fiber clusters and the rotary spraying disk technique, here, we demonstrate uniform microdroplet (1-2000 mPa·s) generation in a tip-guided way that replaces the commonly confined nozzle by a double-layer spinning "sandwich" multitip disk (SSMD). A surface energy gradient induced by the margin structure of the alternating gas wedge and solid tip guides liquid to move along the solid tip, which is ejected at the end of the tip, forming a ring of droplet clusters. SSMD improves the effective droplet-jet process to 7/10 of the whole drainage process and enhances the efficiency with a production drop volume of ∼3.19 × 107 µL/h and production droplet numbers of ∼3.3 × 104 per second. Droplets can be fine-tuned between 0.1 and 1.0 mm via the tip structure, liquid property, and spinning angular velocity with a narrow size distribution. This facile tip-guided design could inspire the possibility of energy-efficient droplet production techniques in various fluid applications, such as spraying and printing. It may further improve other fluid systems that serve as a crucial component for high-speed droplet manipulation, liquid transport, and water vapor capturing.

8.
Biochim Biophys Acta Proteins Proteom ; 1868(2): 140301, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678194

RESUMO

Heparin is a naturally occurring glycosaminoglycan isolated from animal tissues and is medically used as an anticoagulant drug. Adulteration attempts of isolated heparin with chondroitin sulfate in the past resulted in great safety concerns. Also, increasing demands on batch-to-batch homogeneity for better evaluation and control of its pharmacodynamic and pharmacokinetic properties kindled the development of synthetic routes for the production of heparin and its derivatives. The discovery of enzymes involved in glycosaminoglycan biosynthesis and their application in chemoenzymatic synthesis makes it feasible to generate low molecular weight heparins (LMWHs) and ultra-low molecular weight heparins (ULMWHs). Understanding the scope and limitations of these enzymes currently used in the production of synthetic heparins will help to achieve more defined heparins with controlled medicative properties. Here, we summarized the recent advances in the chemoenzymatic synthesis of LMW/ULMW heparins.

9.
Brain Res Bull ; 154: 106-115, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31722250

RESUMO

Single-nucleotide polymorphism (SNP) and Alternative splicing (AS) were found to be implicated in certain diseases, nevertheless, the contributions of mRNA SNPs and AS to pathogenesis in developing rat brains with hypoxic-ischemic encephalopathy (HIE) remained largely vague. Additionally, the disease associated with Tacr3 was normosmic congenital hypogonadotropic hypogonadism, while the relationship between HIE and Tacr3 remained largely elusive. The current study was designed to investigate the differentially expressed mRNAs and related SNPs as well as AS in neonatal rats subjected to HIE to identify if the exhibition of AS was associated with SNPs under pathological condition. Firstly, we used postnatal day 7 Sprague-Dawley rats to construct neonatal HIE model, and analyzed the expression profiles of SNP mRNA in hypoxic-ischemic (HI) and sham brains by using RNA sequencing. Then four genes, including Mdfic, Lpp, Bag3 and Tacr3, connecting with HIE and exhibiting SNPs and AS were identified by bioinformatics analysis. Moreover, combined with exonic splicing enhancer (ESE) and alternative splice site predictor (ASSP) analysis, we found that Tacr3 is associated specifically with HIE through 258547789 G > A SNP in inside the Alt First Exon and 258548573 G > A SNP in outside the Alt First Exon. Taken together, our study provides new evidence to understand the role of Tacr3 in HIE and it is possibly a potential target for the treatment of HIE in future clinic trial.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31774502

RESUMO

AIMS: In patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin, the UK National Institute of Health and Care Excellence (NICE) defines poor anticoagulation as a TTR of < 65%, any 2 INRs within a 6 month period of ≤ 1.5 ("low"), 2 INRs ≥5 within 6months, or any INR ≥ 8 ("high").Our objectives were to (i) quantify the number of patients with poor INR control and (ii) describe the demographic and clinical characteristics associated with poor INR control. METHOD AND RESULTS: Linked anonymised health record data for Wales (2006-2017) was used to evaluate patients prescribed warfarin who had at least 6 months of INR data.32,380 patients were included. In total, 13,913 (43.0%) patients had at least one of the NICE markers of poor INR control. Importantly, in the 24,123 (74.6%) of the cohort with an acceptable TTR (≥65%), 5,676 (23.5%) had either low or high INR readings at some point in their history. In a multivariable regression female gender, age (≥75), excess alcohol, diabetes heart failure, ischaemic heart disease and respiratory disease were independently associated with all markers of poor INR control. CONCLUSION: Acceptable INR control according to NICE standards is poor. Of those with an acceptable TTR (>65%) one quarter still had unacceptably low or high INR levels according to NICE criteria. Thus, only using TTR to assess effectiveness with warfarin has the potential to miss a large number of patients with non-therapeutic INRs who are likely to be at increased risk.

11.
J Anal Toxicol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776560

RESUMO

In this study, the relationships between the concentrations of R/S-methamphetamine (R/S-MA) and its metabolite R/S-amphetamine (R/S-AP), the AP/MA ratio in hair samples, and MA dependence were investigated by performing segmental hair analysis in MA users. Authentic hair samples collected from ten chronic MA abusers were cut into 1-cm sections (total of 120 segments). The concentrations of MA and AM enantiomers were quantitatively measured by the LC-MS/MS method. The S-MA concentrations ranged from 1.17 to 256.41 ng/mg and the S-AP concentrations ranged from 0.11 to 23.31 ng/mg in the 120 segments. S-MA and S-AP were the most common analytes identified in hair; no R-MA or R-AP was found. The S-AP/S-MA ratios ranged from 0.03 to 0.32, indicating that the subjects primarily consumed S-MA rather than R-MA or AP. The S-AP/S-MA ratios in the long hair of all chronic MA abusers showed some variation, but there was an overall trend of gradual increase from the distal to the proximal end. This trend was independent of the drug concentrations. Therefore, we could conclud that the AP/MA ratios increased with the duration of MA abuse, and a higher AP/MA ratio suggested high MA dependence There was no chiral conversion of MA or AP in the hair matrix. The segmental hair analysis showed that all subjects continuously used S-MA, and some users showed an increase in drug dose or frequency of use.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31776607

RESUMO

L-Theanine is a unique non-protein amino acid found in tea plants that has been shown to possess numerous functional properties relevant to food science and human nutrition. L-Theanine has been commercially developed as a valuable additive for use in food and beverages, and its market is expected to expand substantially if the production cost can be lowered. Although the enzymatic approach holds considerable potential for use in L-theanine production, demand exists for developing more tractable methods (than those currently available) that can be implemented under mild conditions and will reduce operational procedures and cost. Here, we sought to engineer fermentative production of L-theanine in Corynebacterium glutamicum, an industrially safe host. For L-theanine synthesis, we used γ-glutamylmethylamide synthetase (GMAS), which catalyzes the ATP-dependent ligation of L-glutamate and ethylamine. First, distinct GMASs were expressed in C. glutamicum wild-type ATCC 13032 strain and GDK-9, an L-glutamate overproducing strain, to produce L-theanine upon ethylamine addition to the hosts. Second, the L-glutamate exporter in host cells was disrupted, which markedly increased the L-theanine titer in GDK-9 cells and almost eliminated the accumulation of L-glutamate in the culture medium. Third, a chromosomally gmasMm-integrated L-alanine producer was constructed and used, attempting to synthesize ethylamine endogenously by expressing plant-derived L-serine/L-alanine decarboxylases; however, these enzymes showed no L-alanine decarboxylase activity under our experimental conditions. The optimal engineered strain that we ultimately created produced ~ 42 g/L L-theanine, with a yield of 19.6%, in a 5-L fermentor. This is the first report of fermentative production of L-theanine achieved using ethylamine supplementation.

13.
Biochem Cell Biol ; : 1-7, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31770017

RESUMO

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3ß (GSK-3ß), to evaluate the role of the Wnt-ß-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood-brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of ß-catenin and downstream proteins while suppressing the expression of GSK-3ß. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt-ß-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.

14.
Environ Int ; 134: 105296, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759273

RESUMO

BACKGROUND: There is a paucity of mechanistic information on the DNA methylation and particulate matter (PM) exposure. This study aimed to investigate the association of PM and its component with DNA methylation, and the roles of DNA methyltransferase (DNMTs). METHODS: There were 240 high-exposed, 318 low-exposed and 210 non-exposed participants in this study. Individual concentrations of PM, polycyclic aromatic hydrocarbons (PAHs) and metals were identified by the monitoring data in their workplaces. Urinary 1-OHP and metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, DNMT3A and DNMT3B were measured. We used mediation analysis to evaluate the role of DNMTs expression on DNA methylation alteration induced by PAHs and metals components. RESULTS: The decreasing trend of % 5mC was associated with increment of PM exposure in all subjects. We found that one IQR increase in total PAHs (3.82 µg/m3) and urinary 1-OHP (1.06 µmol/mol creatinine) were associated with a separate 6.08% and 7.26% decrease in % 5mC (P = 0.009, P < 0.001), and one IQR increase in urinary Ni (27.75 µmol/mol creatinine) was associated with a 3.29% decrease in % 5mC (P = 0.03). The interaction of urinary 1-OHP with Ni on global DNA methylation (%5mC) was not found (P interaction = 0.89). PM exposure was significantly associated with decreased mRNA level of DNMT3B, but the mediated effect of the PAHs and Ni levels on % 5mC through the DNMT3B pathway was not observed. CONCLUSIONS: We found the decrement of global DNA methylation and DNMT3B expression with elevated PM levels in population. The independent mode of action on DNA hypomethylation was found from PAHs and metal components. Global DNA hypomethylation might be a potential biomarker for evaluation of adverse health effects in response to PM exposure.

15.
Lung Cancer ; 139: 103-110, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31760351

RESUMO

OBJECTIVES: To evaluate the diagnostic accuracy of radiomics method and frozen sections (FS) for the pathological classification of peripheral lung adenocarcinoma manifesting as ground-glass nodules (GGNs) in computer tomography (CT). MATERIALS AND METHODS: A dataset of 831 peripheral lung adenocarcinoma manifesting as GGNs in CT were divided into two cohorts: training cohort (n = 581) and validation cohort (n = 250). Combined with clinical features, the radiomics classifier was trained and validated to distinguish the pathological classification of these nodules. FS diagnoses in the validation cohort were collected. Diagnostic performance of the FS and radiomics methods was compared in the validation cohort. The predictive factors for the misdiagnosis of FS were determined via univariate and multivariate analyses. RESULTS: The accuracy of radiomics method in the training and validation cohorts was 72.5 % and 68.8 % respectively. The overall accuracy of FS in the validation cohort was 70.0 %. The concordance rate between FS and final pathology when FS had a different diagnosis from radiomics classifier was significantly lower than when FS had the same diagnosis as radiomics classifier (46 vs. 87 %, P < 0.001). Univariate and Multivariate analyses showed that different diagnosis between FS and radiomics classifier was the independent predictive factor for the misdiagnosis of FS (OR: 7.46; 95%CI: 4.00-13.91; P < 0.001). CONCLUSIONS: Radiomics classifier predictions may be a reliable reference for the classification of peripheral lung adenocarcinoma manifesting as GGNs when FS cannot provide a timely diagnosis. Intraoperative diagnoses of the cases where FS had a different diagnosis from radiomics method should be considered cautiously due to the higher misdiagnosis rate.

16.
J Orthop Surg Res ; 14(1): 368, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727110

RESUMO

BACKGROUND: To compare the biomechanical properties of a novel height-adjustable nano-hydroxyapatite/polyamide-66 vertebral body (HAVB) with the titanium mesh cage (TMC) and artificial vertebral body (AVB), and evaluate its biomechanical efficacy in spinal stability reconstruction. METHODS: A 3D nonliner FE model of the intact L1-sacrum was established and validated. Three FE models which instrumented HAVB, TMC, and AVB were constructed for surgical simulation. A pure moment of 7.5 Nm and a 400-N preload were applied to the three FE models in 3D motion. The peak von Mises stress upon each prosthesis and the interfaced endplate was recorded for analysis. In addition, the overall and intersegmental range of motion (ROM) of each model was investigated to assess the efficacy of each model in spinal stability reconstruction. RESULTS: AVB had the greatest stress concentration compared with TMC and HAVB in all motions (25.6-101.8 times of HAVB, 0.8-8.1 times of TMC). The peak stress on HAVB was 3.1-10.3% of TMC and 1.6-3.9% of AVB. The maximum stress values on L2 caudal and L4 cranial endplates are different between the three FE models: 0.9-1.9, 1.3-12.1, and 31.3-117.9 times of the intact model on L2 caudal endplates and 0.9-3.5, 7.2-31.5, and 10.3-56.4 times of the intact model on L4 cranial endplates in HAVB, TMC, and AVB, respectively, while the overall and segmental ROM reduction was similar between the three models, with AVB providing a relatively higher ROM reduction in all loading conditions (88.1-84.7% of intact model for overall ROM and 69.5-82.1% for L1/2, 87.0-91.7% for L2/4, and 71.1-87.2% for L4/5, respectively). CONCLUSIONS: HAVB had similar biomechanical efficacy in spinal stability reconstruction as compared with TMC and AVB. The material used and the anatomic design of HAVB can help avoid stress concentration and the stress shielding effect, thus greatly reducing the implant-associated complications. HAVB exhibited some advantageous biomechanical properties over TMC and AVB and may prove to be a potentially viable option for spinal stability reconstruction. Further in vivo and vitro studies are still required to validate our findings and conclusions.

17.
J Exp Med ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31753849

RESUMO

The intestine plays an important role in nutrient digestion and absorption, microbe defense, and hormone secretion. Although major cell types have been identified in the mouse intestinal epithelium, cell type-specific markers and functional assignments are largely unavailable for human intestine. Here, our single-cell RNA-seq analyses of 14,537 epithelial cells from human ileum, colon, and rectum reveal different nutrient absorption preferences in the small and large intestine, suggest the existence of Paneth-like cells in the large intestine, and identify potential new marker genes for human transient-amplifying cells and goblet cells. We have validated some of these insights by quantitative PCR, immunofluorescence, and functional analyses. Furthermore, we show both common and differential features of the cellular landscapes between the human and mouse ilea. Therefore, our data provide the basis for detailed characterization of human intestine cell constitution and functions, which would be helpful for a better understanding of human intestine disorders, such as inflammatory bowel disease and intestinal tumorigenesis.

18.
AAPS PharmSciTech ; 21(1): 6, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754916

RESUMO

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.

19.
Nat Prod Res ; : 1-7, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755785

RESUMO

A phytochemical study on the fruits of Artocarpus heterophyllus caused the isolation of a previously undescribed steroid, artoheterophoid (1), together with seven known analogues (2 - 8). The chemical structure of 1 was elucidated on the basis of comprehensive spectroscopic methods and the known compounds (2 - 8) were identified by comparing their spectroscopic data with those reported in the literatures. All known compounds (2-8) were separated from A. heterophyllus for the first time. All isolated compounds (1-8) were assessed for their anti-inflammatory activities in vitro by measuring the inhibitory effect against nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells. Compounds 1-8 displayed remarkable inhibitory effects against NO production with the IC50 values in the range of 0.72 ± 0.07 to 5.93 ± 0.12 µM.

20.
Oncogene ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740781

RESUMO

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly prolong the survival time of non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations, but resistance develops universally. Activation of the phosphatidyl inositol-3 kinase (PI3K)/AKT signaling pathway and phenotypic alterations in epithelial-mesenchymal transition (EMT) are both mechanisms of acquired resistance to EGFR-TKIs. However, the mechanisms underlying this resistance remain unclear. In this study, EHD1 depletion significantly increased NSCLC cell sensitivity to EGFR-TKI, which was accompanied by EMT reversal. Microarray analysis showed that the PTEN/PI3K/AKT signaling pathway is a crucial pathway regulated by EHD1. Moreover, a PTEN inhibitor abolished EHD1 shRNA regulation of EGFR-TKI sensitivity, EMT, and cancer progression. Mass spectrometry showed that TUBB3 is a novel EHD1-interacting protein. EHD1 modulated microtubule stability by interacting with TUBB3. Furthermore, TUBB3 depletion significantly attenuated EHD1-induced EGFR-TKI resistance and EMT. Bioinformatics analysis revealed that EHD1 is significantly associated with the gene set, "Cellular Response to Interleukin-1ß (IL-1ß)". As expected, treatment with IL-1ß led to increased expression of EHD1, activation of PTEN/PI3K/AKT signaling, and induction of EMT in NSCLC cells. In patient specimens, EHD1 was highly expressed in EGFR-TKI-refractory specimens. EHD1 was positively associated with TUBB3 and IL-1R1 but negatively associated with PTEN. In addition, targeting the IL-1ß/EHD1/TUBB3 axis mitigated cancer progression by inhibiting cell proliferation and metastasis and promoting apoptosis. Our study demonstrates the involvement of the IL-1ß/EHD1/TUBB3 axis in EGFR-TKI resistance and provides a potential therapeutic approach for treating patients with NSCLC that has acquired EGFR-TKI resistance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA