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1.
J Clin Lab Anal ; : e23070, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691368

RESUMO

BACKGROUND: The sputum saccharide chain antigen (Krebs von den Lungen-6 [KL-6]) is a serum biomarker of lung injury. We aimed to evaluate the clinical performance of the automated immunoassay analyzer HISCL-5000 in detecting KL-6 by comparing it with LUMIPULSE G1200 and determine the diagnostic value of KL-6 in interstitial lung disease (ILD). METHODS: A total of 145 serum samples from patients were tested using the two automated immunoassay analyzers in parallel. RESULTS: With a cutoff level of 500 U/mL, comparing the two systems, the agreement, sensitivity, specificity, and kappa value were 99.20%, 100%, 98.63%, and 0.984 (95% CI, 0.952-1.000), respectively. Spearman's correlation and ICC showed that there was a strong correlation between serum KL-6 levels measured by the two systems (rS  = .991 [95% CI, 0.981-0.995], ICC = 0.984 [95% CI, 0.978-0.989], P < .01). The clinical diagnosis agreement rate in both systems was >80%. The kappa value was 0.707 (95% CI, 0.582-0.832; SYSTEM B) and 0.707 (95% CI, 0.588-0.826; SYSTEM A). The KL-6 level in the ILD group (1339.5, 662.5-2363) was significantly higher than that in the non-ILD groups (252, 158.5-353; Mann-Whitney U = 381.5, P < .01), and the KL-6 level (1558, 726-2772.5) in the ILD group detected by SYSTEM A was significantly higher than that in the lung cancer group (339, 207-424), other respiratory disease group (249, 194-366), and control group (198, 131.5-297; Kruskal-Wallis H = 63.19, P < .01). CONCLUSIONS: HISCL-5000 showed well-concordant results with those of HISCL-5000 in the KL-6 tests. In patients with ILD, KL-6 showed a good diagnostic performance.

2.
EBioMedicine ; 48: 462-477, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31631034

RESUMO

BACKGROUND: The development of a clinically useful fibroblast growth factor 21 (FGF21) hormone has been impeded by its inherent instability and weak FGF receptor (FGFR) binding affinity. There is an urgent need for innovative approaches to overcome these limitations. METHODS: We devised a structure-based chimerisation strategy in which we substituted the thermally labile and low receptor affinity core of FGF21 with an HS binding deficient endocrinised core derived from a stable and high receptor affinity paracrine FGF1 (FGF1ΔHBS). The thermal stability, receptor binding ability, heparan sulfate and ßKlotho coreceptor dependency of the chimera were measured using a thermal shift assay, SPR, SEC-MALS and cell-based studies. The half-life, tissue distribution, glucose lowering activity and adipose tissue remodeling were analyzed in normal and diabetic mice and monkeys. FINDINGS: The melting temperature of the engineered chimera (FGF1ΔHBS-FGF21C-tail) increased by ∼22 °C relative to wild-type FGF21 (FGF21WT), and resulted in a ∼5-fold increase in half-life in vivo. The chimera also acquired an ability to bind the FGFR1c isoform - the principal receptor that mediates the metabolic actions of FGF21 - and consequently was dramatically more effective than FGF21WT in correcting hyperglycemia and in ameliorating insulin resistance in db/db mice. Our chimeric FGF21 also exerted a significant beneficial effect on glycemic control in spontaneous diabetic cynomolgus monkeys. INTERPRETATION: Our study describes a structure-based chimerisation approach that effectively mitigates both the intrinsically weak receptor binding affinities and short half-lives of endocrine FGFs, and advance the development of the FGF21 hormone into a potentially useful drug for Type 2 diabetes.

3.
Cell Death Dis ; 10(9): 665, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511499

RESUMO

Endothelial dysfunction initiates and exacerbates hypertension, atherosclerosis and other cardiovascular complications in diabetic mellitus. FGF21 is a hormone that mediates a number of beneficial effects relevant to metabolic disorders and their associated complications. Nevertheless, it remains unclear as to whether FGF21 ameliorates endothelial dysfunction. Therefore, we investigated the effect of FGF21 on endothelial function in both type 1 and type 2 diabetes. We found that FGF21 reduced hyperglycemia and ameliorated insulin resistance in type 2 diabetic mice, an effect that was totally lost in type 1 diabetic mice. However, FGF21 activated AMPKα, suppressing oxidative stress and enhancing endothelium-dependent vasorelaxation of aorta in both types, suggesting a mechanism that is independent of its glucose-lowering and insulin-sensitizing effects. In vitro, we identified a direct action of FGF21 on endothelial cells of the aorta, in which it bounds to FGF receptors to alleviate impaired endothelial function challenged with high glucose. Furthermore, the CaMKK2-AMPKα signaling pathway was activated to suppress oxidative stress. Apart from its anti-oxidative capacity, FGF21 activated eNOS to dilate the aorta via CaMKK2/AMPKα activation. Our data suggest expanded potential uses of FGF21 for the treatment of vascular diseases in diabetes.

4.
Nano Lett ; 19(10): 7427-7433, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31536361

RESUMO

Demand for the transfer of chirality from a pre-engineered nanoparticle to any other metal is of fundamental importance for developing a wide range of chirality-related applications. Herein, we show that binary alloy chiral nanoparticles (CNPs) with an engineerable composition can be formed from metallic CNPs with intrinsic structural chirality serving as sacrificial templates (STs), via a galvanic replacement reaction (GRR). This GRR-mediated chirality transfer is a general phenomenon and results in the formation of Cu-Ag CNPs with solid morphology and mesoporous CNPs made of Ag-Au, Ag-Pt, and Ag-Pd. Our study imposes a new component, i.e., structural chirality, on the GRR. The insights from our study improve our fundamental understanding of the GRR principle and devise a versatile method to generate mesoporous alloy CNPs for developing prominent chirality-related applications in asymmetric catalysis, enantiodifferentiation, enantioseparation, biodetection, and bioimaging.

5.
J Perinatol ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391526

RESUMO

OBJECTIVE: To evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants. STUDY DESIGN: This was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018. RESULTS: A total of 203 extremely premature infants were included in this study. The rate of BPD was significantly higher in infants with early exposure to ibuprofen (42.5%) compared to infants with no exposure (21.6%, P = 0.001). After adjusting for covariates, the risk of BPD was associated independently with ibuprofen exposure (odds ratios (OR) 2.296, 95% confidence interval (CI): 1.166-4.522, p = 0.016). Further analysis showed a trend towards higher risk of BPD in infants with successful patent ductus arteriosus (PDA) closure after ibuprofen treatment (32.3%) compared to non-treated infants (20.2%, p = 0.162). CONCLUSION: Our findings suggest that ibuprofen exposure may contribute to the occurrence of BPD in extremely preterm infants.

6.
J Clin Lab Anal ; : e22981, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31325210

RESUMO

BACKGROUND: Contradictory results have been reported previously in the analyses of cross-reactivity among Blomia tropicalis (Blo t), Dermatophagoides pteronyssinus (Der p), and Dermatophagoides farinae (Der f). This study aims to investigate the characteristics of co-sensitization and the IgE cross-reactivity among them and attempts to identify whether patients are sensitized to Blo t due to cross-reaction or true sensitization. METHODS: Specific IgE (sIgE) in the sera from 1497 allergenic patients was determined by ImmunoCAP. Cross-reactivity was analyzed and determined by sIgE inhibition with 21 sera samples. RESULTS: Around 85.50% of patients were sensitized to Der p, 85.37% of patients were sensitized to Der f, and 71.54% of patients were sensitized to Blo t. Further, 70.14% of patients were co-sensitized to Blo t, Der p, and Der f, and only seven patients were sensitized solely to Blo t. With increasing sIgE levels for Blo t, the positive rates of severe-level (class 5-6) co-sensitization to Der p or Der f significantly increased. Blo t was moderately associated with Der p and Der f, with correlation coefficients of 0.6998 and 0.6782, respectively. Der p and Der f inhibited IgE binding to Blo t more strongly than Blo t inhibited IgE binding to Der p or Der f in the patient groups CBlo t  < CDer p and CBlo t  < CDer f . CONCLUSIONS: This study has established valuable information about the co-sensitization and cross-reactivity of Blo t with two Dermatophagoides species (Der p and Der f) and helps to provide adequate diagnosis and treatment of the mite-allergic patients.

7.
J Mol Neurosci ; 69(1): 39-48, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321646

RESUMO

Neurosyphilis is a chronic central nervous system infectious disease caused by Treponema pallidum. Our aim was to study the metabolic profiling in the cerebrospinal fluid of neurosyphilis patients and identify specific potential biomarkers. Fifteen cerebrospinal fluid samples from neurosyphilis patients and 14 non-neurosyphilis samples were analyzed by liquid chromatography-mass spectrometer (LC-MS). The LC-MS data were preprocessed by supervised pattern recognition to obtain diagnostic models. Both orthogonal projections to a latent structures discriminant analysis (OPLS-DA) and a t test were used to obtain specific metabolites for neurosyphilis. LC-MS data showed that the metabolites in cerebrospinal fluid (CSF) from neurosyphilis are different from the non-neurosyphilis group. The OPLS-DA model parameters R2Y and Q2Y are both more than 0.7 and indicated a satisfactory diagnostic performance. Bilirubin, L-histidine, prostaglandin E2, alpha-kamlolenic acid, and butyryl-L-carnitine and palmitoyl-L-carnitine were identified as novel potential biomarkers for neurosyphilis. The metabolic study of CSF may provide a new way to explore the pathogenesis of neurosyphilis.

8.
Cell Death Dis ; 10(6): 464, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189876

RESUMO

Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1ΔHBS, which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1ΔHBS exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1WT) in renal tissues. RNA-seq analysis revealed that FGF1ΔHBS inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1ΔHBS prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1ΔHBS on oxidative stress and inflammation were mediated by activation of the GSK-3ß/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1ΔHBS. This finding expands the potential uses of FGF1ΔHBS for the treatment of various kinds of CKD associated with oxidative stress and inflammation.

9.
J Chromatogr A ; 1601: 340-349, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31060783

RESUMO

In this study, three functionalized chiral ionic liquids (CILs) derived from l-valinol, l-prolinol and l-phenylalaninol, namely N,N,N-trimethyl-l-valinol-bis(trifluoromethanesulfon)imide ([TMLV]+[Tf2N]-, CIL1), N,N-dimethyl-l-prolinol-bis(trifluoromethanesulfon)imide ([DMLP]+[Tf2N]-, CIL2) and N,N,N-trimethyl-l-phenylalaninol-bis(trifluoromethanesulfon)imide ([TMLP]+[Tf2N]-, CIL3), were synthesized and subsequently utilized for enantiomeric separation in capillary electrophoresis (CE) with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as chiral selector for the first time. Compared with traditional single HP-ß-CD separation system, the synergistic system exhibited substantially improved separations of six tested drugs. Using the CIL1/HP-ß-CD as a model system, the influence of crucial parameters including the type and proportion of organic modifier, CILs concentration, HP-ß-CD concentration and buffer pH was investigated in detail. Additionally, molecular modeling with AutoDock was applied to elucidate the enhanced enantioselectivity in the presence of CILs, which has certain guiding value in predicting the migration order of the enantiomers and studying the interactions important for the chiral recognition.


Assuntos
Amino Álcoois/química , Eletroforese Capilar/métodos , Líquidos Iônicos/síntese química , 2-Hidroxipropil-beta-Ciclodextrina/química , Concentração de Íons de Hidrogênio , Líquidos Iônicos/química , Estereoisomerismo
10.
Nano Lett ; 19(6): 3676-3683, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31035748

RESUMO

Semiconductor nanomaterials with controlled morphologies and architectures are of critical importance for high-performance optoelectronic devices. However, the fabrication of such nanomaterials on polymer-based flexible electrodes is particularly challenging due to degradation of the flexible electrodes at a high temperature. Here we report the fabrication of nickel oxide nanopillar arrays (NiO x NaPAs) on a flexible electrode by vapor deposition, which enables highly efficient perovskite solar cells (PSCs). The NiO x NaPAs exhibit an enhanced light transmittance for light harvesting, prohibit exciton recombination, promote irradiation-generated hole transport and collection, and facilitate the formation of large perovskite grains. These advantageous features result in a high efficiency of 20% and 17% for the rigid and flexible PSCs, respectively. Additionally, the NaPAs show no cracking after 500 times of bending, consistent with the mechanic simulation results. This robust fabrication opens a new opportunity for the fabrication of a large area of high-performance flexible optoelectronic devices.

11.
J Vis Exp ; (146)2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31058899

RESUMO

Allergic disease is common in both adults and children. Identification of the causative allergens is significant in disease management and prevention. However, a specific immunoglobulin E (IgE) measurement system with a high price-performance ratio is lacking in mainland China, especially in the primary care hospitals. This paper describes the principle and operation procedures of using a microfluidic cartridge-based chemiluminescence system to detect allergen-specific IgE in serum. The results were compared with those from ImmunoCAP (System 1), the industrial standard, and the reproducibility of the system to detect patients sensitized to common allergens is evaluated. The results showed that in comparison with ImmunoCAP (System 1), the BioIC System (System 2) has good precision and sensitivity in detecting serum-specific IgE against various inhalant and food allergens but with a significantly lower cost. It can serve as a good alternative to System 1 in primary care hospitals in mainland China who have lower financial affordability.

12.
BMC Genomics ; 20(1): 260, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940069

RESUMO

BACKGROUND: The different leaf type associated traits of soybean (Glycine max L.) including leaf area, leaf length, leaf width, leaf shape and petiole length are considered to be associated with seed yield. In order to identify quantitative trait loci (QTLs) affecting leaf type traits, two advanced recombinant inbred line (RIL, ZH, Zhonghuang 24 × Huaxia 3; GB, Guizao 1 × Brazil 13) populations were introduced to score phenotypic values in plants across nine different environments (years, seasons, locations and soybean growth stages). Two restriction site-associated DNA sequencing (RAD-seq) based high-density genetic linkage maps with an average distance of 1.00 centimorgan (cM) between adjacent bin markers were utilized for QTL fine mapping. RESULTS: Correlation analysis showed that most of the traits were correlated with each other and regulated both by hereditary and environmental factors. A total of 190 QTLs were identified for leaf type associated traits in the two populations, of which 14 loci were found to be environmentally stable. Moreover, these detected QTLs were categorized into 34 QTL hotspots, and four important QTL hotspots with phenotypic variance ranging from 3.89-23.13% were highlighted. Furthermore, Glyma04g05840, Glyma19g37820, Glyma14g07140 and Glyma19g39340 were predicted in the intervals of the stable loci and important QTL hotspots for leaf type traits by adopting Gene Ontology (GO) enrichment analysis. CONCLUSIONS: Our findings of the QTLs and the putative genes will be beneficial to gain new insights into the genetic basis for soybean leaf type traits and may further accelerate the breeding process for reasonable leaf type soybean.


Assuntos
Folhas de Planta/genética , Locos de Características Quantitativas , Soja/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Genótipo , Fenótipo , Folhas de Planta/fisiologia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
13.
Phys Rev E ; 99(3-2): 039901, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30999484

RESUMO

This corrects the article DOI: 10.1103/PhysRevE.84.046215.

14.
Anal Bioanal Chem ; 411(6): 1193-1202, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30707270

RESUMO

Magnetic microparticles (MMPs) have been extensively studied and aroused considerable interest in separation science owing to their superior characteristics. In this paper, a novel coated capillary with carboxymethyl-ß-cyclodextrin-functionalized magnetic microparticles (CD-MMPs) as stationary phase was constructed and then applied to establish an open-tubular capillary electrochromatography enantioseparation system. The preparation of the CD-MMP-coated open-tubular column was very convenient because the coating of the magnetic microparticles onto the capillary column could be easily manipulated by an external magnetic field. The preparation conditions of the coated capillary such as magnetic field intensity and coating time are discussed in detail. The new constructed CD-MMP capillary system was applied to separate enantiomers of several racemic drugs. Compared to the uncoated capillary system, obviously preferable separations of tested enantiomers were obtained. Several important parameters affecting the enantioseparation, such as CM-ß-CD concentration, running buffer pH, organic solvent, and applied voltage, were systematically optimized. Furthermore, satisfactory repeatability and chemical stability of this new CD-MMP capillary system were achieved in the experiment. Graphical abstract ᅟ.

15.
Phys Rev E ; 99(1-1): 013302, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30780269

RESUMO

A computational method is developed for the study of mechanical response and fracture behavior of phase field crystals (PFC), to overcome a limitation of the PFC dynamics which lacks an effective mechanism for describing fast mechanical relaxation of the material system. The method is based on a simple interpolation scheme for PFC (IPFC) making use of a condition of the displacement field to satisfy local elastic equilibration, while preserving key characteristics of the original PFC model. We conduct a systematic study on the mechanical properties of a sample nanoribbon system with honeycomb lattice symmetry subjected to uniaxial tension, for numerical validation of the IPFC scheme and the comparison with the original PFC and modified PFC methods. Results of mechanical response, in both elasticity and fracture regimes, show the advantage and efficiency of the IPFC method across different system sizes and applied strain rates, due to its effective process of mechanical equilibration. A brittle fracture behavior is obtained in IPFC calculations, where effects of system temperature and chirality on the fracture strength and Young's modulus are also identified, with results agreeing with those found in previous atomistic simulations of graphene. The IPFC scheme developed here is generic and applicable to the mechanical studies using different types of PFC free-energy functionals designed for various material systems.

16.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(1): 45-51, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30675863

RESUMO

OBJECTIVE: To evaluate the clinical value of droplet digital PCR (ddPCR) in rapid and accurate diagnosis of invasive fungal infection (IFI) in neonates. METHODS: The highly conserved sequence of fungi 18S RNA was selected as the target sequence, and primers were designed to establish a ddPCR fungal detection system. Blood samples were collected from 83 neonates with high-risk factors for IFI and/or related clinical symptoms in the neonatal intensive care unit (NICU) of a hospital in Shenzhen, China. Blood culture and ddPCR were used for fungal detection. RESULTS: The ddPCR fungal detection system had a specificity of 100% and a sensitivity of 3.2 copies/µL, and had a good reproducibility. Among the 22 blood samples from neonates with a confirmed or clinical diagnosis of IFI, 19 were detected positive by ddPCR. Among the 61 blood samples from neonates who were suspected of IFI or had no IFI, 2 were detected positive by ddPCR. CONCLUSIONS: The ddPCR technique can be used for the detection of neonatal IFI and is a promising tool for the screening and even diagnosis of neonatal IFI.


Assuntos
Infecções Fúngicas Invasivas , China , Humanos , Recém-Nascido , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes
17.
Mikrochim Acta ; 186(2): 128, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30694392

RESUMO

The inner wall of a capillary was coated with glycidyl methacrylate (GMA) to form tentacle-type coating, and poly(glycidyl methacrylate) nanoparticles (PGMA NPs) were then immobilized on the film. Ethanediamine-ß-cyclodextrin as chiral selector was covalently bonded into the PGMA NPs through the ring-open reaction. The materials were characterized by SEM, TEM and FT-IR. The modified column was applied to the enantioseparation of the racemates of propranolol, amlodipine and metoprolol. Compared to a capillary with a single layer of CD-PGMA (without GMA coating) and to a CD-GMA system (without PGMA nanoparticles), the performance of the capillary is strongly improved. The effects of buffer pH value and applied voltage were optimized. Best resolutions (propranolol: 1.27, metoprolol: 1.01 and amlodipine: 2.93) were obtained when using the PGMA-coated capillary system. The run-to-run, day-to-day and column-to-column reproducibility were tested and found to be highly attractive. The new stationary phase is likely to have a large potential and scope in that it may also be applied to chiral separations of other enantiomers, such as amino acids and biogenic amines. Graphical abstract Schematic presentation of the preparation of a capillary column with glycidyl methacrylate (GMA) coating which was then immobilized with poly(glycidyl methacrylate) nanoparticles and ethanediamine-ß-cyclodextrin. This novel open tubular column was applied to construct capillary electrochromatography system for separation of basic racemic drugs.


Assuntos
Anlodipino/análise , Eletrocromatografia Capilar/métodos , Metoprolol/análise , Propranolol/análise , Anlodipino/isolamento & purificação , Eletrocromatografia Capilar/instrumentação , Metoprolol/isolamento & purificação , Nanopartículas/química , Ácidos Polimetacrílicos , Propranolol/isolamento & purificação , Estereoisomerismo , beta-Ciclodextrinas
18.
ChemSusChem ; 11(22): 3899-3904, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30300975

RESUMO

Symmetric aqueous high voltage supercapacitors up to 3 V have been demonstrated using concentrated aqueous 1-butyl-3-methylimidazolium chloride ([BMIm]Cl), namely, "water-in-imidazolium chloride", as working electrolytes, and graphene nanoplatelets-coated carbon paper as electrodes. Performance enhancement was further achieved either through adding redox species such as 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (4hT) into the electrolytes (110 Wh kg-1 for a 20 m [BMIm]Cl/H2 O with 0.1 m 4hT) or by pre-inserting ClO4 - anions into the graphene platelets. Moreover, the newly studied aqueous electrolytes allow low-temperature operation at -20 °C and even at -32 °C, retaining competitive energy storage capability (maximum energy densities of 36 and 21 Wh kg-1 , respectively).

19.
Biochem Biophys Res Commun ; 504(2): 478-484, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30197006

RESUMO

Hypoxia-induced pulmonary hypertension (HPH) is a progressive disease characterized by a sustained, elevated pulmonary arterial pressure and vascular remodeling. The latter pathogenesis mainly involves overproliferation of pulmonary artery smooth muscle cells (PASMCs). Fibroblast growth factor 21 (FGF21) has recently emerged as a novel regulator that prevents cardiac hypertrophic remodeling. However, its possible role in pulmonary remodeling remains unclear. The activation of peroxisome proliferator activated receptor γ (PPARγ) is reported to attenuate HPH by suppressing proliferative signals. Loss of PPARγ in the lung contributes to abnormal proliferation of PASMCs. FGF21 is a key regulator of PPARγ activity in adipocytes, but its role has not been elucidated in PASMCs. Therefore, we hypothesized that FGF21 may confer therapeutic effects in HPH by upregulating the expression of PPARγ. Sprague-Dawley rats were exposed to hypoxia and treated with FGF21 for 4 weeks. In parallel, hypoxic conditions and FGF21 were administered to rat PASMCs for 48 h. FGF21 attenuated the hypoxia-induced elevation in mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy (RVH), medial thickening and overproliferation of PASMCs. Furthermore, FGF21 abrogated the reductions in PPARγ expression and increases in TNF-α, IL-1 and IL-6 levels in PASMC culture media. Collectively, these results demonstrate that FGF21 could potentially attenuate the pathogenic derangements of HPH by targeting PPARγ and inflammatory cytokines.

20.
Int J Biol Sci ; 14(10): 1389-1398, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123084

RESUMO

It has been reported that overactivation of fibroblast growth factor receptor 1 (FGFR1) is an important characteristic found in most non-small cell lung cancer (NSCLC) samples. Here, we identified a FGFR1 inhibitory peptide R1-P2 and investigated its effects on the lung cancer cells growth and angiogenesis in vitro and in vivo. Our results demonstrate that R1-P2 bound to human FGFR1 protein, and efficiently blocked the binding of FGF2 to FGFR1 in A549 and NCI-H460 cells. Moreover, this peptide significantly decreased the proliferation, migration and invasion, but promoted the apoptosis in both cell lines. In addition, R1-P2 treatment effectively inhibited the tumor growth and neovascularization in nude mice with xenografted A549 cells, and R1-P2 also significantly inhibited the FGF2-induced angiogenesis in tube formation experiment and CAM model. We further demonstrated that R1-P2 suppressed lung tumor growth through anti-angiogenic and anti-proliferative activity. Our data may provide a novle leading molecule with potential application in the treatment of FGFR1 activation related lung cancers.

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