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1.
Org Biomol Chem ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030393

RESUMO

An enantioselective (92-99% ee) Michael/aldol cascade reaction between 4,4,4-trifluoroacetoacetates and α,ß-unsaturated enones was established in the presence of cinchona alkaloid-based primary amines. Various ß-CF3-cyclohexanones were constructed in high yields (81-99%) as a couple of separable diastereomers. This tandem reaction was sensitive to acidic co-catalysts, with a Michael/aldol condensation process favorably occurring to generate ß-CF3-cyclohexenones (42-69% yield, 84-96% ee) in the presence of trifluoroacetic acid.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32003555

RESUMO

Developing multicomponent transition-metal phosphides has become an efficient way to improve the capacitive performance of single-component transition-metal phosphides. However, reports on quaternary phosphides for supercapacitor applications are still scarce. Here, we report high capacity and energy density of Zn-Ni-Co-P quaternary phosphide nanowire arrays on nickel foam (ZNCP-NF) composed of highly conductive metal-rich phosphides as an advanced binder-free electrode in aqueous asymmetric supercapacitors. In a three-electrode system using the new electrode, a high specific capacity of 1111 C g-1 was obtained at a current density of 10 A g-1. Analysis of this aqueous asymmetric supercapacitor with ZNCP-NF as the positive electrode and commercial activated carbon as the negative electrode reveals a high energy density (37.59 Wh kg-1 at a power density of 856.52 W kg-1) and an outstanding cycling performance (capacity retention of 92.68% after 10 000 cycles at 2 A g-1). Our results open a path for a new design of advanced electrode material for supercapacitors.

3.
J Mater Chem B ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31998926

RESUMO

Stimuli-responsive hydrogel strain sensors that synergize the advantages of both soft-wet hydrogels and smart functional materials have attracted rapidly increasing interest for exploring the opportunities from material design principles to emerging applications in electronic skins, health monitors, and human-machine interfaces. Stimuli-responsive hydrogel strain sensors possess smart and on-demand ability to specifically recognize various external stimuli and convert them into strain-induced mechanical, thermal, optical, and electrical signals. This review presents an up-to-date summary over the past five years on hydrogel strain sensors from different aspects, including material designs, gelation/fabrication methods, stimuli-responsive principles, and sensing performance. Hydrogel strain sensors are classified into five major categories based on the nature of the stimuli, and representative examples from each category are carefully selected and discussed in terms of structures, response mechanisms, and potential medical applications. Finally, current challenges and future perspectives of hydrogel strain sensors are tentatively proposed to stimulate more and better research in this emerging field.

4.
Chemosphere ; 242: 125209, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31677519

RESUMO

The fungicide myclobutanil (MYC) is a common contaminant found in surface water. The aim of this study was to determine the acute toxicity, developmental effects, bioconcentration factor (BCF) and potential bio-molecular mechanisms of MYC toxicity in zebrafish. Susceptibility to MYC toxicity was life-stage dependent with adult fish being the most sensitive (96 h-LC50, 6.34 mg/L) followed by 72 h post-hatch (hph) larvae (8.90 mg/L), 12 hph larvae (20.53 mg/L) and embryos (42.54 mg/L). Zebrafish embryos and larvae (12 hph) responded with decreased hatching, heartbeat and growth, as well as abnormal spontaneous movement and development. BCFs were calculated by quantifying MYC concentrations from different tissues of adult zebrafish exposed to MYC for up to 11 days. Highest BCFs were obtained from gills (18.25 ±â€¯0.07), followed by viscera (16.78 ±â€¯0.04), head (13.13 ±â€¯0.08) and muscle (8.96 ±â€¯0.10). MYC (0.5 mg/L) inhibited gene expression related to cholesterol synthesis pathway, including 24-dehydrocholesterol reductase (DHCR24), 7-dehydrocholesterol reductase (DHCR7), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCRa), HMGCRb, farnesyl-diphosphate farnesyltransferase 1(FDFT1), squa-lene epoxidase (SQLE), isopentenyl-diphosphate delta isomerase 1 (IDI1) and CYP51, while no cholesterol changes were observed in the MYC treated group. These results will contribute to the literature assessing the environmental risk of MYC in aquatic environment.

5.
Environ Pollut ; 257: 113555, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31733957

RESUMO

(±) - PEN is a chiral fungicide widely used to control powdery mildew in agriculture. Currently, only a few studies have investigated the toxic effects of (±) - penconazole ((±) - PEN) on non-target organisms, and whether (±) - PEN from the enantiomeric level have toxic effects remains unclear. In this study, we systematically evaluated the effects of exposure to (±) - PEN, (+) - PEN and (-) - PEN on liver function in mice. Biochemical and histopathological analyses showed that exposure to (±) - PEN and (-) - PEN led to significant liver damage and inflammation. However, exposure to (+) - PEN treatment did not cause no adverse effects on liver function and inflammation. 1H-NMR-based metabolomics revealed that exposure to (±) - PEN, (+) - PEN and (-) - PEN led to the animals developing liver metabolic disorder that was caused by changes in glycolipid metabolism. Quantitative analysis of genes regulating glycolipid metabolism revealed that expression of gluconeogenesis and glycolytic pathway genes were altered in individuals exposed to (±) - PEN, (+) - PEN and (-) - PEN. We also found that (±) - PEN, (+) - PEN and (-) - PEN have different effects on lipid metabolism of the liver. Exposure to (±) - PEN and (-) - PEN resulted in significant accumulation of lipids by regulating fatty acid synthesis, triglyceride synthesis, and fatty acid ß oxidation pathways. In summary, we found different toxicological effects in individuals exposed to (±) - PEN, (+) - PEN and (-) - PEN. The results of this study are important for assessing the potential health risks of (±) - PEN.

6.
Chemosphere ; 240: 124900, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563099

RESUMO

Spirotetramat (SPT) is a new tetronic acid derivative insecticide used to control scales and aphids; the potential for endocrine disruptor effects in fish could not be finalized with the available data. In this study, zebrafish were selected to assess the endocrine-disrupting effects. Significant decrease of plasma estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were observed in both male and female following the spirotetramat exposure; the vitellogenin (VTG) level in females significantly decreased. The expression of the hypothalamic-pituitary-gonad (HPG) axis genes fshr, lhr and esr1 showed significant increase in the gonads, which expression in males is higher than in females. In addition, the activities of capspase-3 and caspase-9 significantly decreased in both males and females liver, while the capspase-3 and caspase-9 were increased in male testis, the mRNA expression levels of genes expression related to the apoptosis pathway were also significantly altered after the spirotetramat exposure. Additionally, we found the parental zebrafish exposed to spirotetramat induced the development delay of its offspring. Above all, the adverse effects induced by spirotetramat suggesting that spirotetramat is a potential exogenous hazardous agent.


Assuntos
Compostos Aza/toxicidade , Inseticidas/toxicidade , Compostos de Espiro/toxicidade , Animais , Apoptose , Disruptores Endócrinos/toxicidade , Estradiol/metabolismo , Estrogênios/farmacologia , Feminino , Expressão Gênica , Gônadas/efeitos dos fármacos , Fígado/metabolismo , Masculino , Testículo/efeitos dos fármacos , Testosterona/análogos & derivados , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
7.
J Colloid Interface Sci ; 563: 33-41, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31865046

RESUMO

HYPOTHESIS: Novel Pickering emulsions stabilized by self-assembled nano-objects of amphiphilic copolymers are attractive in many applications. However, it is not clear to what extent those nano-objects could stay at the oil/water interface. Owing to the twisted intramolecular charge transfer state (TICT) property of Nile red, the distinguishable fluorescent characteristics of Nile red dissolved in n-dodecane and solubilized in copolymer micelles benefit the investigation of the oil/water interfacial nature of Pickering emulsions in situ. EXPERIMENTS: Two amphiphilic diblock copolymers PNMP53-b-PFMA5 and PNMP53-b-PFMA10 named poly(N-(2-methacryloylxyethyl) pyrrolidone)-block-poly(2-(perfluorooctyl) ethyl methacrylate) were synthesized, they can form spherical and wormlike micelles in water spontaneously, respectively. Oil in water (O/W) emulsions were generally produced at different conditions by employing these copolymer micelles as emulsifiers. The size and morphology of prepared emulsions were studied by light scattering and microscope techniques in detail. Moreover, the effect of emulsification conditions on the interfacial morphology evolution of prepared emulsions were characterized systematically in situ by the proposed method based on the confocal laser scanning microscopy (CLSM) measurements. FINDINGS: We clarified the progressive transition from Pickering emulsions to classic emulsions through the sustained changes of emulsification conditions by the developed CLSM method, in which block copolymer monomers and their assemblies were played as emulsifiers to stabilize emulsion droplets synergistically. Generally speaking, Pickering emulsions were produced in the presence of sufficient micelles at low emulsification shear rates. Otherwise, common emulsions stabilized by block copolymer monomers would be formed.

8.
Comp Immunol Microbiol Infect Dis ; 68: 101404, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31874355

RESUMO

Fowl adenovirus (FAdV), as the causative agent of hepatitis-hydropericardium syndrome (HHS), poses a significant threat to the poultry industry in China in recent years. In this study, we investigated the immunopathogenesis of a FAdV-4 strain HN/151025 in 60-day-old chickens. The virus was highly virulent in chickens, with a broader tissue tropism in chickens, causing 60 % mortality. Postmortem findings of dead chickens showed mild HHS and liver degeneration and necrosis. Importantly, FAdV-4 infection induced significant upregulation of genes encoding most toll-like receptors, some cytokines (interleukin-1ß, 2, 6, 8, and 18, and interferon-γ), most of avian ß-defensins, myeloid differentiation primary response protein 88, p38 mitogen-activated protein kinases, and inducible nitric oxide synthase, in tissues of infected chicken, especially in spleen and bursa of Fabricius. There was also a significant positive correlation between FAdV-4 genome load and the mRNA expression levels of most of these factors in specific infected tissues. The results indicated the potential role of these proteins in host immune response against FAdV-4 infection. However, overexpression of these proteins might contribute to tissue damage of FAdV-4 infected chickens, and eventually lead to chicken death.

9.
PLoS One ; 14(12): e0225531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31881060

RESUMO

Cytochrome P450 2E1 (CYP2E1) plays an important role in both alcohol-induced and immune-mediated liver injury. However, the mechanism underlying CYP2E1 transcriptional regulation has not been clarified. This study focused on the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways in alcohol-induced and immune-mediated liver injury rat models. Male Sprague-Dawley rats were used in pharmacokinetic, molecular pharmacology, and morphology experiments. A rat model of alcohol-induced liver injury (AL) was established by feeding an ethanol-containing diet (42 g/kg/day) for 5 weeks as indicated. A rat immune-mediated liver injury (IM) model was established by the sequential injection of bacillus Calmette-Guérin (BCG, 125 mg/kg, once) via the tail vein after test day 21 and 10 µg/kg LPS 13 days later. HPLC, real-time PCR, western blot and ELISA analyses were performed. CYP2E1 expression was enhanced during the process of alcohol-induced liver injury (increased by 56%, P < 0.05) and significantly reduced during that of immune-mediated liver injury (reducedby52%, P < 0.05). NF-κB was activated in both the AL and IM groups (increased by 56% and76%, respectively, P < 0.05). Compared to those in the livers of AL model rats, the interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and iNOS levels in IM model rat livers were increased (increased by 26%, 21% and 101%, respectively, P < 0.05). The differential changes in CYP2E1 in the processes of alcohol-induced and immune-mediated liver injury may result from the differential expression of inflammatory cytokines and iNOS after NF-κB activation, leading to the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways.

10.
Data Brief ; 27: 104747, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31763403

RESUMO

Fusarium head blight (FHB) is one of the most prevalent diseases of wheat and other small grain cereals that is predominantly caused by the fungal pathogen Fusarium graminearum. Extraction of total proteins were from tissues of A061-3 and A061-4 plants. Three biological replicates were carried out for each line at four time points. Samples were performed using iTRAQ (Isobaric tags for relative and absolute quantification). This data is being made available to increase the understanding of FHB resistance proteomics. The data from this study are related to the research article "Isobaric tags for relative and absolute quantification-based proteomic analysis of defense responses triggered by the fungal pathogen Fusarium graminearum in wheat" [1].

11.
Anal Bioanal Chem ; 411(29): 7879-7887, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31691847

RESUMO

A biomass nitrogen and sulfur codoped carbon dots (NS-Cdots) was prepared by a simple and clean hydrothermal method using leek, and was employed as efficient fluorescent probes for sensitive detection of organophosphorus pesticides (OPs). The leek-derived NS-Cdots emitted blue fluorescence, but was quenched by H2O2. Due to acetylcholinesterase/choline oxidase-based cascade enzymatic reaction that produces H2O2 and the inhibition effect of OPs on acetylcholinesterase activity, a NS-Cdots-based fluorescence "off-on" method to detect OPs-dichlorvos (DDVP) was developed. More sensitivity and wider linear detection range were achieved from 1.0 × 10-9 to 1.0 × 10-3 M (limit of detection = 5.0 × 10-10 M). This developed method was applied to the detection of DDVP in Chinese cabbage successfully. The average recoveries were in the range of 96.0~104.0% with a relative standard deviation of less than 3.3%. In addition, the NS-Cdots fluorescent probes were also employed successfully in multicolor imaging of living cells, manifesting that the NS-Cdots fluorescent probes have great application potential in agricultural and biomedical fields. Graphical Abstract.


Assuntos
Inibidores da Colinesterase/análise , Diclorvós/análise , Corantes Fluorescentes/química , Cebolas/química , Pontos Quânticos/química , Linhagem Celular Tumoral , Humanos , Limite de Detecção , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta
12.
Acta Biochim Biophys Sin (Shanghai) ; 51(11): 1134-1141, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31650158

RESUMO

The widely used inhalation anesthetic, isoflurane, potentially induces neuronal injury in clinical practice. Previous studies showed multiple forms of cell death that resulted from isoflurane-induced cytotoxicity, but the precise underlying mechanism remains poorly understood. Ferroptosis has recently been identified as a non-apoptotic form of regulated cell death. Here, we found that ferroptosis inhibitors, ferrostatin-1 and deferoxamine mesylate (DFOM), showed great efficiency in maintaining cell viability in SH-SY5Y neuroblastoma cells exposed to a high concentration of isoflurane for 24 h. We also observed that cellular chelatable iron and lipid peroxidation were increased in a concentration-dependent manner in response to isoflurane. In addition, isoflurane upregulated Beclin1 phosphorylation, followed by the formation of a Beclin1-solute carrier family 7 member 11 (SLC7A11) complex, which affected the activity of cystine/glutamate antipoter and further regulated ferroptotic cell death. Accordingly, Beclin1 overexpression aggravated isoflurane-induced cell damage by upregulating ferroptosis. This phenomenon was significantly attenuated by silencing of Beclin1 in SH-SY5Y cells. These findings indicate that Beclin1 may regulate ferroptosis in a manner involving inhibition of glutamate exchange activity of system xc(-), which is implicated in isoflurane-induced toxicity. In particular, when isoflurane is administrated at high concentrations and for an extended duration, ferroptosis is more likely to play a crucial role in isoflurane-induced toxicity.

13.
J Biopharm Stat ; 29(5): 749-759, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31590626

RESUMO

A question that routinely arises in medical device clinical studies is the homogeneity across demographic subgroups, geographical regions, or investigational sites of the enrolled patients in terms of treatment effects or outcome variables. The main objective of this paper is to discuss statistical concepts and methods for the assessment of such homogeneity and to provide the practitioner a statistical framework and points to consider in conducting homogeneity assessment. Demographic subgroups, geographical regions, and investigational sites are discussed separately as each has its unique issues. Specific considerations are also given to randomized controlled trials, non-randomized comparative studies, and single-arm studies. We point out that judicious use of statistical methods, in conjunction with sound clinical judgment, is essential in handling the issue of homogeneity of treatment effect in medical device clinical studies.

14.
Cell Death Differ ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570854

RESUMO

Metastasis is one of the main contributors to the poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC metastasis remains largely unknown. Here, we showed that TXNDC12, a thioredoxin-like protein, was upregulated in highly metastatic HCC cell lines as well as in portal vein tumor thrombus and lung metastasis tissues of HCC patients. We found that the enforced expression of TXNDC12 promoted metastasis both in vitro and in vivo. Subsequent mechanistic investigations revealed that TXNDC12 promoted metastasis through upregulation of the ZEB1-mediated epithelial-mesenchymal transition (EMT) process. We subsequently showed that TXNDC12 overexpression stimulated the nuclear translocation and activation of ß-catenin, a positive transcriptional regulator of ZEB1. Accordingly, we found that TXNDC12 interacted with ß-catenin and that the thioredoxin-like domain of TXNDC12 was essential for the interaction between TXNDC12 and ß-catenin as well as for TXNDC12-mediated ß-catenin activation. Moreover, high levels of TXNDC12 in clinical HCC tissues correlated with elevated nuclear ß-catenin levels and predicted worse overall and disease-free survival. In summary, our study demonstrated that TXNDC12 could activate ß-catenin via protein-protein interaction and promote ZEB1-mediated EMT and HCC metastasis.

15.
Chin Med ; 14: 36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572488

RESUMO

Background: Shunxinzufang decoction is tutors, empirical formula and has been used in Chinese patients of HFpEF for several years. The aim of this study was to make into sustained release granules and select the best formula for the preparation of Shunxin sustained release granules and to evaluate its in vivo and in vitro drug release behavior. Methods: Response surface methodology and Center composite design were applied to screen the optimal formula of Shunxin sustained release granules. HPLC was used to detect indicative ingredients-paeoniflorin, calycosin-7-glucoside and ferulic acid in Shunxin sustained release granules. The in vitro sustained release character of indicative ingredients was investigated in simulated digestive fluids. In-vivo process of active components was studied through pharmacokinetics. Results: The optimal formula of Shunxin sustained release granules consisted of 35% shunxinzufang extract and 65% HPMC/starch (HPMC/starch ratio = 2:1). Three indicative components can be separated well under selected HPLC conditions. Compared with Shunxinzufang extract, the active components of Shunxin sustained release granules have obvious sustained-release character and improved bioavailability. Conclusion: Shunxin sustained release granules has obvious sustained-release character and improved bioavailability.

16.
ACS Appl Mater Interfaces ; 11(42): 39179-39191, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31573786

RESUMO

Advances in personalized medicine will require custom drug formulations and delivery mechanisms. Herein, we demonstrate a new type of personalized capsule comprising of printed concentric cylindrical layers with each layer having a distinctive functional drug component. Poly ε-caprolactone (PCL) with paracetamol (APAP) and chlorpheniramine maleate (CM), synergistic drugs commonly used to alleviate influenza symptoms, are printed as an inner layer and outer layer, respectively, via microscaled electrohydrodynamic (EHD) printing. Polyvinylpyrrolidone (PVP) nanofibers are embedded as interlayers between the two printed PCL-drug layers using electrospinning (ES) techniques. The complete concentric cylindrical capsule with a 6 mm inner diameter and 15 mm length can be swallowed for oral drug delivery. After dissolution of the PVP interlayer, the capsule separates in two, with inner and outer capsules for continuous drug dosing and targeting. Imaging was achieved using a 3T MRI system which allowed temporal observations of the targeted release through the incorporation of nanoparticles (Fe3O4). The morphology and structure, chemical composition, mechanical properties, and biocompatibility of the capsules were studied in vitro. In summary, this new type of custom printed and electrospun capsule that enabled component separation, targeted drug release may advance personalized medicine via multidrug oral delivery.

17.
Cell Death Differ ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31527798

RESUMO

Sonic hedgehog (SHH) signaling is crucial for the maintenance of the physiological self-renewal of granule neuron progenitor cells (GNPs) during cerebellar development, and its dysregulation leads to oncogenesis. However, how SHH signaling is controlled during cerebellar development is poorly understood. Here, we show that Trim32, a cell fate determinant, is distributed asymmetrically in the cytoplasm of mitotic GNPs, and that genetic knockout of Trim32 keeps GNPs at a proliferating and undifferentiated state. In addition, Trim32 knockout enhances the incidence of medulloblastoma (MB) formation in the Ptch1 mutant mice. Mechanistically, Trim32 binds to Gli1, an effector of SHH signaling, via its NHL domain and degrades the latter through its RING domain to antagonize the SHH pathway. These findings provide a novel mechanism that Trim32 may be a vital cell fate regulator by antagonizing the SHH signaling to promote GNPs differentiation and a tumor suppressor in MB formation.

18.
Soft Matter ; 15(38): 7686-7694, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31498364

RESUMO

We report a simple and facile self-assembly approach to fabricate polyelectrolyte complex (PEC) hydrogel films with positively charged chitosan (CS) and negatively charged heparin sodium (HS) by combining hydrogen bonding and electrostatic interactions. The CS/HS hydrogel films exhibited excellent tensile strength and toughness, good self-recovery ability, superior water absorbency, and pH-dependent surface charge characteristics. The gelation mechanism was investigated by zeta potential measurements. The CS/HS hydrogel films exhibited high antibacterial efficacy against E. coli at selected pHs or when coordinated with various metal ions and a significant effect on accelerating wound healing. The self-assembly approach presented in this work may serve as a generic strategy for the fabrication of novel multi-functional PEC hydrogels for broad biomedical applications.


Assuntos
Antibacterianos/química , Quitosana/química , Heparina/química , Polieletrólitos/química , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Cátions , Escherichia coli/efeitos dos fármacos , Humanos , Hidrogéis , Concentração de Íons de Hidrogênio , Membranas Artificiais , Metais/química , Pele , Propriedades de Superfície , Resistência à Tração , Água
19.
PLoS One ; 14(8): e0220643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404074

RESUMO

To study the strengthening mechanism and effect underlying the reinforcement of a fractured rock mass with grouting, compressive shear tests were conducted with an RMT-150B rock mechanics test system. Prefabricated structural surfaces were strengthened with a new inorganic dual-liquid grouting material at five water-cement ratios (0.6-1.5). The effects of these water-cement ratios of the grouting on the deformation, strength, and failure characteristics of the prefabricated structural surface were analyzed. The results show that reinforcement with grouting significantly influenced the bearing capacity of the structural surface. The shear strength of the structure was significantly improved and the deformation resistance of the structural surface was enhanced. The shear stress-displacement curves, generated in compressive shear tests of the grouting-reinforced structures, were all nonlinear. The shearing process comprised three stages: elasticity, yield, and failure. Decreasing the water-cement ratio of the grouting material weakened the plasticity of the grouted structural surface and enhanced its brittleness. The deformation type changed from plastic slip to brittle shear. The shear strength, cohesion, and angle of internal friction of the grouting-reinforced structural surface increased with decreasing water-cement ratio.

20.
Mediators Inflamm ; 2019: 5497467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467485

RESUMO

Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC) treatment, radioresistance is still a major threat for some subsets of patients. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is tightly regulated and plays critical roles in mediating cell proliferation, growth, and survival. Thus, IGF-1R may be a potential therapeutic target for patients with different malignancies. However, its mechanism in NPC is not fully investigated. Linsitinib is an oral small molecule and is a tyrosine kinase inhibitor (TKI) of IGF-1R, which has been known for antitumor effects used widely. Here, we evaluated the proliferation and radiosensitivity of NPC cell lines (CNE-2 and SUNE-1) after linsitinib treatment. We found that linsitinib suppresses IGF-1-induced cell proliferation through inhibiting Akt and ERK phosphorylation. Moreover, linsitinib further boosted IR-induced DNA damage, G2-M cell cycle delay, and apoptosis in NPC cells. Finally, linsitinib reversed radioresistant NPC cells by decreasing the phosphorylation of IGF-1R. Our data indicated that the combination of linsitinib and IR and targeting IGF-1R by linsitinib could be a promising therapeutic strategy for NPC.


Assuntos
Carcinoma Nasofaríngeo/metabolismo , Receptor IGF Tipo 1/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Humanos , Imidazóis/farmacologia , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/farmacologia , Radiação Ionizante
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