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1.
Sleep Med ; 72: 5-11, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32534403

RESUMO

BACKGROUND: The goal of this study was to review relevant randomized controlled trials in order to determine the efficacy of continuous positive airway pressure (CPAP) versus mandibular advancement device (MAD) in the treatment of obstructive sleep apnea (OSA). METHODS: Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane Library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we used odds ratios (ORs), mean difference (MD), and 95% confidence interval (95% CI) to assess and synthesize outcomes. RESULTS: We included 14 RCTs, for a total of 249 patients in the CPAP group and 247 in the MAD group. Compared with MAD, CPAP significantly decreased apnea hypopnea index (AHI) (WMD: -7.08, 95%CI: -9.06∼-5.10) and the percentage of stage 1 and 2 after therapy (WMD: -3.728, 95%CI: -6.912∼-0.543). However, compared with MAD, CPAP significantly decreased the SF-36-social function score (WMD: -3.381, 95%CI: -6.607∼-0.154).There was no significant difference in Epworth sleepiness scale score after therapy between the two groups. CONCLUSION: CPAP has better therapeutic efficacy in OSA patients than MAD.

2.
Protein Pept Lett ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370703

RESUMO

BACKGROUND: Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB), especially the drug-resistant MTB, causes serious challenges for people healthcare worldwide. Cytotoxic T lymphocytes (CTLs) play a vital role in immune defense against MTB. OBJECTIVE: To identify novel CTL epitopes that could induce cellular immunity against MTB infections. METHODS: The HLA-A*0201 restricted CTL epitopes of the drug-resistant protein InhA from MTB were predicted by online algorisms and synthesized by the Fmoc solid phase method. The candidate peptides were used to induce CTLs from human peripheral blood mononuclear cells (PBMCs) of HLA-A*0201 healthy donors and the HLA-2.1/Kb mice. IFN-γ productions of CTLs were detected by enzyme linked immunospot assay (ELISPOT), flow cytometry and enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was analyzed by lactate dehydrogenase (LDH) assay. RESULTS: A group of 4 epitopes were screened out with high affinity to HLA-A*0201. ELISPOT and flow cytometry analysis indicated these peptides significantly induced IFN-γ release of CTLs from the HLA-A*0201+/PPD+ donors, as the mutant analogues had more potent stimulation effects. LDH assay showed that CTLs from PPD+ donors and the immunized mice exhibited significant cytotoxicity and low cross-reactivity. ELISA analysis revealed comparative levels of IFN-γ were released by CTLs isolated from the mice spleen. CONCLUSION: Our study has identified 4 novel CTL epitopes of InhA that could elicited potent CTL immunity, establishing foundation for development for multivalent peptide vaccine against the drug-resistant MTB.

3.
Chem Commun (Camb) ; 56(51): 6969-6972, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32436515

RESUMO

Here, we propose an amplification strategy involving enzyme-mimicking accelerated signal enhancement integrated with a triple-channel volumetric bar-chart chip for visually multiplexed quantitation of telomerase activity. This platform was used for evaluating the telomerase activities from different kinds of cells and a detection limit at the single-cell level was realized without any instrumental assistance.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32386245

RESUMO

The low response rate and adaptive resistance of PD-1/PD-L1 blockade demands the studies on novel therapeutic targets for cancer immunotherapy. We discovered that a novel immune checkpoint TIGIT expressed higher than PD-1 in many tumors especially anti-PD-1 resistant tumors. Here, mirror-image phage display bio-panning was performed using the d-enantiomer of TIGIT synthesized by hydrazide-based native chemical ligation. d-peptide D TBP-3 was identified, which could occupy the binding interface and effectively block the interaction of TIGIT with its ligand PVR. D TBP-3 showed proteolytic resistance, tumor tissue penetrating ability, and significant tumor suppressing effects in a CD8+ T cell dependent manner. More importantly, D TBP-3 could inhibit tumor growth and metastasis in anti-PD-1 resistant tumor model. This is the first d-peptide targeting TIGIT, which could serve as a potential candidate for cancer immunotherapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32285170

RESUMO

Though therapy that promotes anti-tumor response about CD8+ tumor-infiltrating lymphocytes (TILs) has shown great potential, clinical responses to CD8+ TILs immunotherapy vary considerably, largely because of different subpopulation of CD8+ TILs exhibiting different biological characters. To define the relationship between subpopulation of CD8+ TILs and the outcome of antitumor reaction, the phenotype and function of CD103+ CD8+ TILs in esophageal squamous cell carcinoma (ESCC) were investigated. CD103+ CD8+ TILs were presented in ESCC, which displayed phenotype of tissue-resident memory T cells and exhibited high expression of immune checkpoints (PD-1, TIM-3). CD103+ CD8+ TILs were positively associated with the overall survivals of ESCC patients. This population of cells elicited potent proliferation and cytotoxic cytokine secretion potential. In addition, CD103+ CD8+ TILs were elicited potent anti-tumor immunity after anti-PD-1 blockade and were not affected by chemotherapy. This study emphasized the feature of CD103+ CD8+ TILs in immune response and identified potentially new targets in ESCC patients.

6.
Nanomaterials (Basel) ; 10(4)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276389

RESUMO

Quick capacity loss due to the polysulfide shuttle effects is a critical challenge for high-performance lithium-sulfur (Li-S) batteries. Herein, a novel 2D/1D V2O5 nanoplates anchored carbon nanofiber (V-CF) interlayer coated on standard polypropylene (PP) separator is constructed, and a stabilization mechanism derived from a quasi-confined cushion space (QCCS) that can flexibly accommodate the polysulfide utilization is demonstrated. The incorporation of the V-CF interlayer ensures stable electron and ion pathway, and significantly enhanced long-term cycling performances are obtained. A Li-S battery assembled with the V-CF membrane exhibited a high initial capacity of 1140.8 mAh·g-1 and a reversed capacitance of 1110.2 mAh·g-1 after 100 cycles at 0.2 C. A high reversible capacity of 887.2 mAh·g-1 is also maintained after 500 cycles at 1 C, reaching an ultra-low decay rate of 0.0093% per cycle. The excellent electrochemical properties, especially the long-term cycling stability, can offer a promising designer protocol for developing highly stable Li-S batteries by introducing well-designed fine architectures to the separator.

7.
Small ; : e2000852, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323489

RESUMO

Tuning bandgap and phases in the ternary 2D transition metal dichalcogenides (TMDs) alloys has opened up unexpected opportunities to engineer optoelectronic properties and explore potential applications. In this work, a salt-assisted chemical deposition vapor (CVD) growth strategy is reported for the creation of high-quality monolayer W1- x Rex S2 alloys to fulfill a readily phase control from 1H to DT by changing the ratio of Re and W precursors. The structures and chemical compositions of doping alloys are confirmed by combining atomic resolution scanning transmission electron microscopy-annular dark field imaging with energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy, matching well with the calculated results. The field-effect transistors (FETs) devices fabricated based on 1H-W0.9 Re0.1 S2 monolayer exhibit a n-type semiconducting behavior with the mobility of 0.4 cm2 V-1 s-1 . More importantly, the FETs show high-performance responsivity with a value of 17 µA W-1 in air, which is superior to that of monolayer CVD-grown WS2 . This work paves the way toward synthesizing monolayer ternary alloys with controlled phases for potential optoelectronic applications.

8.
J Appl Toxicol ; 40(5): 567-577, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31869448

RESUMO

Due to excellent metal-insulator transition property, vanadium dioxide nanoparticles (VO2 NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO2 NPs exposure through various routes. Herein, the cytotoxicity of VO2 NPs (N-VO2 ) and titanium dioxide-coated VO2 NPs (T-VO2 ) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO2 NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO2 NPs. Under the same conditions, T-VO2 NPs showed slightly lower cytotoxicity than N-VO2 in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO2 NPs. Titanium dioxide coating changed the surface property of VO2 NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO2 NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO2 NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.

9.
Methods Enzymol ; 629: 361-381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31727249

RESUMO

Cancer immunotherapy has recently emerged as one of the hot research field since clinical successes achieved by antibody drugs of immune checkpoints, among which PD-1 and its ligand PD-L1 are the well established molecules. PD-1/PD-L1 pathway induces immune tolerance and immune evasion, especially in tumor microenvironment, cancer cell is capable to escape the immune surveillance by up-regulating the expression level of PD-1 or PD-L1. Blockade of PD-1/PD-L1 can unleash the anti-tumor activity, and the strategy shows great successes in the treatment of various cancer types in the late stage. Beside antibody drugs, many other molecules such as peptides, high affinity PD(L)-1 mutants, chemical compounds, and DNA aptamers are designed for inhibitors of PD-1/PD-L1 pathway. Each modulators show their pros and cons based on their own physiochemical properties. Here we introduced the methods for identifying low molecular weight inhibitors of PD-1/PD-L1 and mainly discussed the cell-based blocking test.

10.
ACS Omega ; 4(9): 13896-13901, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31497707

RESUMO

Humidity-control materials have attracted increasing attention because of energy savings and smart regulation of indoor comforts. The current research is a successive work to face challenges, such as poor performance, limitations for large-scale production, and surface contamination. Here, we report a smart humidity-control wall-brick manufactured from sepiolite using CaCl2 as an additive. Low-temperature sintering generated a super hygroscopic interior structure, and further silane modification produced bricks with superhydrophobic surfaces. These superhydrophobic surfaces can promote the moisture storage and prevent the CaCl2 solution from leaking even after the surface is wiped 100 times. Meanwhile, the superhydrophobic surfaces make the wall-bricks easy to clean; also, these materials possess antifouling and antifungal properties. The 24 h and saturated moisture adsorption-desorption contents reached 630 and 1700 g·m-2, respectively. Furthermore, a test was performed using model houses in a real environment, which indicates that the wall-bricks can narrow the daily indoor humidity fluctuations by more than 20% in both wet and dry seasons. The white wall-brick can also be dyed with different colors and thus shows promise for applications in interior decorations of houses.

11.
Nanomaterials (Basel) ; 9(9)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470597

RESUMO

Novel N-doped carbon nanonet flakes (NCNFs), consisting of three-dimensional interconnected carbon nanotube and penetrable mesopore channels were synthesized in the assistance of a hybrid catalytic template of silica-coated-linear polyethyleneimine (PEI). Resorcinol-formaldehyde resin and melamine were used as precursors for carbon and nitrogen, respectively, which were spontaneously formed on the silica-coated-PEI template and then annealed at 700 °C in a N2 atmosphere to be transformed into the hierarchical 3D N-doped carbon nanonetworks. The obtained NCNFs possess high surface area (946 m2 g-1), uniform pore size (2-5 nm), and excellent electron and ion conductivity, which were quite beneficial for electrochemical double-layered supercapacitors (EDLSs). The supercapacitor synthesized from NCNFs electrodes exhibited both extremely high capacitance (up to 613 F g-1 at 1 A g-1) and excellent long-term capacitance retention performance (96% capacitive retention after 20,000 cycles), which established the current processing among the most competitive strategies for the synthesis of high performance supercapacitors.

12.
Exp Ther Med ; 18(3): 1831-1836, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31410144

RESUMO

The lungs are one of the most common target organs of diabetic injury in patients with diabetes. Long non-coding RNA (lncRNA) smoke and cancer-associated lncRNA 1 (SCAL1), also known as lung cancer associated transcript 1 (LUCAT1), is known to have a pivotal role in lung cancer. The aim of the current study was to investigate the potential involvement of SCAL1 in diabetic lung disease. The expression levels of SCAL1 were determined by reverse transcription-quantitative PCR in serum samples from healthy controls (n=40), diabetic patients without lung disease (n=56) and diabetic patients with diabetic lung disease (n=44). Receiver operating characteristic analysis was used to evaluate the diagnostic value of serum SCAL1 in discriminating diabetic patients with diabetic lung disease from diabetic patients without lung disease and healthy controls. Pearson's correlation analysis was performed to examine the correlation between SCAL1 and inducible nitric oxide synthase (iNOS) mRNA expression levels in blood and lung tissue samples. Expression levels of iNOS and NO production following treatment with high (30 mM) glucose were examined by western blot analysis and NO assay, respectively. The expression levels of SCAL1 were significantly downregulated in diabetic patients with diabetic lung disease, and downregulated serum expression levels of SCAL1 effectively distinguished diabetic patients with diabetic lung disease from diabetic patients without lung disease and healthy controls. Treatment with high glucose significantly upregulated SCAL1 expression in normal lung cells. Furthermore, the overexpression of SCAL1 inhibited iNOS protein expression and reduced NO production in cells treated with high glucose. In conclusion, the current study demonstrated that lncRNA SCAL1 inhibits iNOS protein expression in lung cells under high-glucose conditions, which suggests that SCAL1 may have potential in the treatment of patients with diabetic lung disease.

13.
Nanomaterials (Basel) ; 9(7)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269772

RESUMO

Highly efficient energy-saving windows with high solar modulation properties (ΔTsol) are the everlasting pursuit of research for industrial applications in the smart window field. Hybridization is an effective means of improving both ΔTsol and luminous transmittance (Tlum). In this paper, hybrid thermochromic films were synthesized using tungsten-doped VO2 nanoparticles (NPs) and starch derivatives. Thermoresponsive 2-hydroxy-3-butoxypropyl starch (HBPS) was prepared with a low critical solution temperature (LCST) varying from 32 to 21 °C by the substitution of reactive groups. The hybrid film was obtained by dispersing W-doped VO2 NPs in HBPS hydrogels, which exhibiting remarkable solar modulation property (ΔTsol = 34.3%) with a high average luminous transmittance (Tlum, average = 53.9%).

14.
Heart Lung ; 48(6): 515-518, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31146967

RESUMO

OBJECTIVE: The purpose of this study was to assess the fibrinolytic status after cardiopulmonary bypass in rheumatic valvular heart disease patients, and detect the associated factors of post-cardiopulmonary bypass hyperfibrinolysis. METHODS: According to the fibrinolytic status after cardiopulmonary bypass, 203 rheumatic valvular heart disease patients were divided into two groups: hyperfibrinolysis group (H group, n = 78) and non-hyperfibrinolysis group (NH group, n = 125). The demographic characteristics, operative variables, and postoperative follow-ups were compared between these two groups. RESULTS: The incidence of hyperfibrinolysis was 38.4% after cardiopulmonary bypass. Patients in the H group had a significant higher incidence of preoperative atrial fibrillation than patients in the NH group (92.3% vs. 55.2%, P < 0.01). Furthermore, postoperative daily drainage (655.3 ±â€¯131.5 ml vs. 535.4 ±â€¯161.4 ml, P < 0.01), transfusion volume of fresh frozen plasma (621.8 ±â€¯220.2 ml vs. 455.2 ±â€¯208.5 ml, P < 0.01), and red blood cells (5.9 ±â€¯2.2 u vs. 4.7 ±â€¯2.8 u, P < 0.01) was greater in the H group than in the NH group. Moreover, the logistic regression analysis revealed that preoperative atrial fibrillation was associated with post-cardiopulmonary bypass hyperfibrinolysis (OR = 19.691, 95% CI = 6.849-56.612; P < 0.05). CONCLUSION: Preoperative artial fibrillation is associated with post-cardiopulmonary bypass hyperfibrinolysis in rheumatic valvular heart disease patients.


Assuntos
Fibrilação Atrial/diagnóstico , Ponte Cardiopulmonar/métodos , Doenças das Valvas Cardíacas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Wei Sheng Yan Jiu ; 48(2): 244-258, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31133102

RESUMO

OBJECTIVE: Drawing on the ideas of the adult dietary balance index method, based on the recipes of the kindergartens in Lanzhou City, to establish a dietary balance index that can quickly, accurately and conveniently evaluate the dietary quality of the people in the park. METHODS: The stratified random sampling method was used to select and collect 329 recipes for the 40 kindergartens in different geographical locations, grades and properties(public and private) in Lanzhou City from 2012 to 2017. Used EpiData 3. 1 to enter the main food types of the recipe, the specific cooking ingredients and the supply amount of the ingredients. In combination with the 2016 dietary guidelines for the dietary requirements of the population, determined the components and ranges of values for the dietary balance index appropriate for the population. And used this index to evaluate the quality of some complete recipes. RESULTS: The pre-school children's dietary balance index system in Lanzhou City includes 8 individual indicators: cereals, vegetables and fruits, milk and dairy products, soy products and nuts, animal foods, snacks for food consumption, food types and cooking method. Preliminary application of the index system to evaluate the dietary quality of some kindergartens showed that there were significant differences in LBS and DQD between kindergartens of different grades and different years(P<0. 05), and there was no significant difference in HBS(P>0. 05). The result of the dietary evaluation method were consistent. CONCLUSION: The established dietary balance index for preschool children in Lanzhou City can meet the rapid, accurate and convenient evaluation of the dietary quality of the population during the park. In addition to focusing on establishing relevant indicators for food group classification and evaluation, the establishment of specific indicator systems should also increase indicators on children's dietary types and cooking and processing method.


Assuntos
Inquéritos sobre Dietas , Dieta , Política Nutricional , Recomendações Nutricionais , Adulto , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , China , Frutas , Humanos , Verduras
16.
Polymers (Basel) ; 11(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010177

RESUMO

Silicone rubber composites filled with nano-silica are currently widely used as high voltage insulating materials in power transmission and substation systems. We present a systematic study on the dielectric and mechanical performance of silicone rubber filled with surface modified and unmodified fumed nano-silica. The results indicate that the different interfaces between the silicone rubber and the two types of nano-silica introduce changes in their dielectric response when electrically stressed by a sinusoidal excitation in the frequency range of 10-4-1 Hz. The responses of pure silicone rubber and the composite filled with modified silica can be characterized by a paralleled combination of Maxwell-Wagner-Sillars interface polarization and DC conduction. In contrast, the silicone rubber composite with the unmodified nano-silica exhibits a quasi-DC (Q-DC) transport process. The mechanical properties of the composites (represented by their stress-strain characteristics) reveal an improvement in the mechanical strength with increasing filler content. Moreover, the strain level of the composite with a modified filler is improved.

17.
Nanomaterials (Basel) ; 9(4)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987293

RESUMO

The present investigation reported on a novel oxygen-assisted etching growth method that can directly transform wafer-scale plain VO2 thin films into pyramidal-like VO2 nanostructures with highly improved field-emission properties. The oxygen applied during annealing played a key role in the formation of the special pyramidal-like structures by introducing thin oxygen-rich transition layers on the top surfaces of the VO2 crystals. An etching related growth and transformation mechanism for the synthesis of nanopyramidal films was proposed. Structural characterizations confirmed the formation of a composite VO2 structure of monoclinic M1 (P21/c) and Mott insulating M2 (C2/m) phases for the films at room temperature. Moreover, by varying the oxygen concentration, the nanocrystal morphology of the VO2 films could be tuned, ranging over pyramidal, dot, and/or twin structures. These nanopyramidal VO2 films showed potential benefits for application such as temperature-regulated field emission devices. For one typical sample deposited on a 3-inch silicon substrate, its emission current (measured at 6 V/µm) increased by about 1000 times after the oxygen-etching treatment, and the field enhancement factor ß reached as high as 3810 and 1620 for the M and R states, respectively. The simple method reported in the present study may provide a protocol for building a variety of large interesting surfaces for VO2-based device applications.

18.
Nanoscale ; 11(12): 5535-5547, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30860537

RESUMO

Oxygen defects play a crucial role in a variety of functional transition metal oxides, ranging from photocatalytic materials to photoelectric devices. Tungsten oxide (WO3-x) is a type of transition metal oxide that has rich substoichiometric compositions and possesses oxygen defects. These oxygen defects determine the photon-electron interactions in the WO3-x structures. Therein, WO3-x quantum dots (QDs) exhibit fast carrier-transport for photon-electron interactions due to their strong quantum-size effects. Here, we report the use of non-stoichiometric WO3-x QDs, as a model material, in combination with silver nanowires (Ag NWs) to study photon-electron interactions on the nanoscale. We demonstrate that the incident photon-to-electron conversion efficiency can be increased by 8.5% and that the dye photodegradation performance was improved by 40% in a WO2.72 QD@Ag NW (WO2.72 QDs supported on AgNWs) composite compared to those of individual WO2.72 QDs under simulated AM 1.5G light. Furthermore, the WO3-x QD@Ag NW composite exhibits both photocatalytic activity and surface-enhanced Raman scattering (SERS) features, and the WO3-x QDs can be switched between a "photocatalytic state" and a "SERS state" by changing the stoichiometric ratio. The synergistic effects are ascribed to the "plasmonic state" of WO2.72 QDs upon light irradiation. This work provides new insight into the design of highly efficient transition metal oxide/plasmonic metal nanocomposites for photoelectric devices.

19.
Free Radic Res ; 53(3): 324-334, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30773944

RESUMO

The thunder god vine (Tripterygium wilfordii Hook. F) is traditionally used for inflammation-related diseases in traditional Chinese medicine. In recent years, celastrol (a natural compound from the root of the thunder god vine) has attracted great interest for its potential anticancer activities. The free radical nitric oxide (NO) is known to play a critical role in colorectal cancer growth by promoting tumour angiogenesis. However, how celastrol influences the NO pathway and its mechanism against colorectal cancer is largely unknown. In this study, we investigated the effects and mechanism of celastrol on nitric oxide synthase (NOS) and the angiogenesis pathway in colorectal cancer. Our data show that celastrol inhibited HT-29 and HCT116 cell proliferation, migration, and NOS activity in the cytoplasm. The antiproliferation activity of celastrol was associated with the inhibition of iNOS and eNOS in colorectal cancer cells. Treatment with celastrol inhibited colorectal cancer cell growth and migration, and was associated with suppression of the expression of key genes (TYMP, CDH5, THBS2, LEP, MMP9, and TNF) and proteins (IL-1b, MMP-9, PDGF, Serpin E1, and TIMP-4) involved in the angiogenesis pathway. In addition, combinational use of celastrol with 5-fluorouracil, salinomycin, 1400 W, and L-NIO showed enhanced inhibition of colorectal cancer cell proliferation and migration. In sum, our study suggests that celastrol could suppress colorectal cancer cell growth and migration, likely through suppressing NOS activity and inhibiting the angiogenesis pathway.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Óxido Nítrico Sintase/efeitos dos fármacos , Triterpenos/uso terapêutico , Proliferação de Células , Neoplasias Colorretais/patologia , Humanos , Transdução de Sinais , Tripterygium/metabolismo , Triterpenos/farmacologia
20.
Nitric Oxide ; 83: 33-39, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590117

RESUMO

BACKGROUND: It has been widely accepted that angiogenesis plays fundamental roles in colorectal cancer development, and therapeutic targeting of this pathway has achieved promising outcome. Recent reports have highlighted the involvement of nitric oxide synthases (NOS) in the development of angiogenesis in cancer; however, the mechanism and therapeutic value of NOS inhibitors in colon cancer are largely unknown. OBJECTIVE: In this study, we investigated the effects and mechanism of the NOS inhibitors 1400W and L-NIO on the angiogenesis pathway in colorectal cancer cells. METHODS: Two colorectal cancer cell lines, HT 29 and HCT 116, were used for in vitro study. The expression of iNOS and eNOS in cells was knocked down via shRNA transfection. MTS assays and wound healing assays were performed to assess cell proliferation and migration after shRNA transfection or treatment with 1400W, L-NIO, and 5-fluorouracil. Human angiogenesis PCR arrays and proteome profiler human angiogenesis arrays were used to detect changes in key genes/proteins involved in modulating angiogenesis after 1400W and L-NIO treatment. RESULTS: Knockdown of iNOS and eNOS significantly inhibited colorectal cancer cell growth. Treatment with NOS inhibitors inhibited colorectal cancer cell growth and migration, and was associated with suppression of the expression of key genes/proteins involved in the angiogenesis pathway. In addition, the combined use of NOS inhibitors with 5-fluorouracil showed enhanced inhibition of cell proliferation and migration. CONCLUSION: NOS inhibitors could suppress colorectal cancer cell growth and migration, likely via suppressing the angiogenesis pathway.


Assuntos
Amidinas/farmacologia , Antineoplásicos/farmacologia , Benzilaminas/farmacologia , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Neovascularização Patológica/tratamento farmacológico , Óxido Nítrico Sintase/antagonistas & inibidores , Ornitina/análogos & derivados , Amidinas/química , Antineoplásicos/química , Benzilaminas/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Células HCT116 , Células HT29 , Humanos , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Óxido Nítrico Sintase/metabolismo , Ornitina/química , Ornitina/farmacologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Cicatrização/efeitos dos fármacos
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