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1.
Discov Med ; 35(178): 868-876, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37811625

RESUMO

BACKGROUND: The key endpoint for treatment efficacy in chronic hepatitis C (CHC) is the absence of a detectable virus at 24 weeks after treatment. This study aims to determine the long-term clinical outcomes in patients with CHC after interferon and ribavirin treatment and the factors that influence them. METHODS: A retrospective study was conducted on 259 patients with CHC between 2003 and 2021, and the patients were divided into treated (n = 159) and untreated (n = 100) groups. The median observation duration was four years for the treated group (range: 1-15 years) and four years for untreated groups (range: 1-14 years). RESULTS: The mean ages of the treated and untreated groups were 47.38 ± 9.07 and 51.17 ± 8.38 years, respectively. Regardless of whether antiviral therapy had been administered, patients with undetectable hepatitis C virus (HCV) load had a lower risk of developing liver cirrhosis and hepatocellular carcinoma (HCC) than patients with detectable HCV load (p < 0.05). Furthermore, patients with HCV genotype 1b were more likely to develop cirrhosis and HCC than patients with HCV non-genotype 1b (p < 0.05). Based on the results of multivariate analysis, age of 50 years and above (hazard ratio [HR] = 6.74, 95% confidence interval [CI] = 2.79-16.28) and infection with HCV genotype 1b (HR = 2.43, 95% CI = 1.06-5.56) were significant predictors of liver cirrhosis and HCC development, whereas undetectable HCV RNA load (HR = 0.14, 95% CI = 0.43-0.46) was a protective factor. CONCLUSIONS: During the long-term follow-up, no cases of HCC were discovered in patients with undetectable HCV RNA load. Nevertheless, long-term monitoring is still required in patients with liver cirrhosis, since it increases the risk for developing liver cancer.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Humanos , Adulto , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Carcinoma Hepatocelular/patologia , Estudos Retrospectivos , Antivirais/uso terapêutico , Neoplasias Hepáticas/patologia , Interferon-alfa/uso terapêutico , Hepacivirus/genética , Cirrose Hepática , Resultado do Tratamento , RNA Viral
4.
Front Bioeng Biotechnol ; 9: 773021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858963

RESUMO

Theoretically, with a high enough drug dosage, cancer cells could be eliminated. However, the dosages that can be administered are limited by the therapeutic efficacy and side effects of the given drug. Herein, a nanomedicine integrating chemotherapeutic sensitization and protection was developed to relieve the limitation of administration dosage and to improve the efficacy of chemotherapy. The nanomedicine was endowed with the function of synergistically controlled release of CO and drugs under near-infrared (NIR) light irradiation. CO photo-induced release system (COPIRS) was synthesized by constructing an electron excitation-electron transfer group-electron-induced CO release structure and was used as the hydrophobic part, and then hydrophilic polymer (polyethylene glycol; PEG) was introduced by a thermal-responsive groups (DA group), forming a near-infrared-induced burst-release nanocarrier. In vitro and in vivo experiments showed that the nanomedicine can distinguish between tumor and normal cells and regulates the resistance of these different cells through the controlled release of carbonic oxide (CO), simultaneously enhancing the efficacy of chemotherapy drugs on tumor cells and chemotherapeutic protection on normal cells. This strategy could solve the current limitations on dosages due to toxicity and provide a solution for tumor cure by chemotherapy.

5.
Stem Cells Int ; 2021: 9993247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054972

RESUMO

Titanium and its alloys are widely used in blood-contacting implantable and interventional medical devices; however, their biocompatibility is still facing great challenges. In the present study, in order to improve the biocompatibility and antibacterial activities of titanium, TiO2 nanotubes were firstly in situ prepared on the titanium surface by anodization, followed by the introduction of polyacrylic acid (PAA) and gentamicin (GS) on the nanotube surface by layer-by-layer assembly, and finally, zinc ions were loaded on the surface to further improve the bioactivities. The nanotubes displayed excellent hydrophilicity and special nanotube-like structure, which can selectively promote the albumin adsorption, enhance the blood compatibility, and promote the growth of endothelial cells to some degree. After the introduction of PAA and GS, although the superhydrophilicity cannot be achieved, the results of platelet adhesion, cyclic guanosine monophosphate (cGMP) activity, hemolysis rate, and activated partial thromboplastin time (APTT) showed that the blood compatibility was improved, and the blood compatibility was further enhanced after zinc ion loading. On the other hand, the modified surface showed good cytocompatibility to endothelial cells. The introduction of PAA and zinc ions not only promoted the adhesion and proliferation of endothelial cells but also upregulated expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO). The slow and continuous release of GS and Zn2+ over 14 days can significantly improve the antibacterial properties. Therefore, the present study provides an effective method for the surface modification of titanium-based blood-contacting materials to simultaneously endow with good blood compatibility, endothelial growth behaviors, and antibacterial properties.

6.
PLoS One ; 15(9): e0238762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966282

RESUMO

With the development of modern cities, roads, and landscapes, it is becoming increasingly important for infrastructure such as tunnels to provide an esthetically pleasing experience. In this respect, it is necessary to conduct studies that consider the esthetic design of tunnel portals using esthetics research. Regarding the esthetic evaluation of tunnel portals, this paper fully considers the dynamic visual effect from the driver's perspective. This study combines the use of Blender, SpeedTree Modeler Cinema, Adobe Photoshop CS6, and other software for secondary development. These programs are connected to the driving simulation platform Euro Truck Simulator 2 (which is equipped with a driving simulator) to construct a set of driving simulation tests that enable the esthetic evaluation of a tunnel portal. The Banlun Tunnel on the Funing-Longliu Expressway in Yunnan Province, China, is used as a case study, and four impact factors that vary significantly in esthetic design are included: the linearity, color, greening and texture of the portal. Using an orthogonal experimental design, the influence of the esthetic degree was simulated and evaluated, and the order of sensitivity to esthetic factors of a headwall tunnel portal was sequentially determined as follows: the portal texture exerts the maximum impact on the beauty degree of the headwall portal, followed by the portal greening and the portal color, while the portal linearity exerts the minimum impact. The results show that the developed driving simulation test system can be used to determine the sensitivity of esthetic factors for a tunnel portal and obtain an optimal collocation of esthetic factors on different levels; hence, it provides feedback for use in designing the optimum esthetic tunnel portal. This test system can be used as a reference when conducting future evaluations and studies on tunnel portal esthetics.


Assuntos
Condução de Veículo , Planejamento Ambiental , Estética , Adulto , Cidades , Humanos , Masculino , Adulto Jovem
7.
Bioact Mater ; 5(3): 611-623, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405576

RESUMO

Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability. However, the in vivo rapid degradation rate and the insufficient biocompatibility restrict its clinical applications. In this study, the magnesium alloy (AZ31B) was modified by combining the surface chemical treatment and in-situ self-assembly of 16-phosphonyl-hexadecanoic acid, followed by the immobilization of chitosan-functionalized graphene oxide (GOCS). Heparin (Hep) and GOCS were alternatively immobilized on the GOCS-modified surface through layer by layer (LBL) to construct the GOCS/Hep bioactive multilayer coating, and the corrosion resistance and biocompatibility were extensively explored. The results showed that the GOCS/Hep bioactive multilayer coating can endow magnesium alloys with an excellent in vitro corrosion resistance. The GOCS/Hep multilayer coating can significantly reduce the hemolysis rate and the platelet adhesion and activation, resulting in an excellent blood compatibility. In addition, the multilayer coating can not only enhance the adhesion and proliferation of the endothelial cells, but also promote the vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression of the attached endothelial cells on the surfaces. Therefore, the method of the present study can be used to simultaneously control the corrosion resistance and improve the biocompatibility of the magnesium alloys, which is expected to promote the application of magnesium alloys in biomaterials or medical devices, especially cardiovascular stent.

8.
Int J Nanomedicine ; 15: 1409-1420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184595

RESUMO

BACKGROUND: Photothermal therapy with accurate and real-time temperature detection is desired in clinic. Upconversion nanocrystals (UCNs) are candidate materials for simultaneous temperature detection and photothermal agents carrying. However, the weak luminescence and multiple laser excitations of UCNs limit their application in thermal therapy. MATERIALS AND METHODS: NaYF4:Yb3+,Er3+,Nd3+, PL-PEG-NH2, IR-806 and folic acid are selected as structural components. A nanoprobe (NP) integrated with efficient photothermal conversion and sensitive temperature detection capabilities is synthesized for precise photothermal therapy. The probes are based on near-infrared upconversion nanocrystals doped with Yb, Er and Nd ions, which can be excited by 808 nm light. IR-806 dye molecules are modified on the surface as molecular antennas to strongly absorb near-infrared photons for energy transfer and conversion. RESULTS: The results show that under an 808 nm laser irradiation upconversion luminescence of the nanocrystals is enhanced based on both the Nd ion absorption and the FRET energy transfer of IR-806. The luminescence ratio at 520 and 545 nm is calculated to accurately monitor the temperature of the nanoparticles. The temperature of the nanoprobes increases significantly through energy conversion of the molecular antennas. The nanoparticles are found successfully distributed to tumor cells and tumor tissue due to the modification of the biocompatible molecules on the surface. Tumor cells can be killed efficiently based on the photothermal effect of the NPs. Under the laser irradiation, temperature at mouse tumor site increases significantly, tissue necrosis and tumor cell death can be observed. CONCLUSION: Precision photothermal therapy can thus be achieved by highly efficient near-infrared light absorption and accurate temperature monitoring, making it promising for tumor treatment, as well as the biological microzone temperature detection.


Assuntos
Nanopartículas/química , Fototerapia/métodos , Termografia/métodos , Animais , Linhagem Celular Tumoral , Érbio/química , Feminino , Raios Infravermelhos , Lasers , Luminescência , Neoplasias Mamárias Experimentais/terapia , Camundongos Endogâmicos BALB C , Neodímio/química , Temperatura , Itérbio/química , Ítrio/química
9.
ACS Biomater Sci Eng ; 6(4): 2072-2083, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33455341

RESUMO

Titanium dioxide nanotube arrays are widely used in biomaterials due to their unique tubular structure and tunable biocompatibility. In the present study, titanium oxide nanotube arrays with different diameters were prepared on the titanium surface by anodization, followed by zinc doping using hydrothermal treatment to enhance the biocompatibility. Both the nanotube dimensions and zinc doping had obvious influences on the hydrophilicity, protein adsorption, blood compatibility, and endothelial cell behaviors of the titanium surface. The increase of the diameter and zinc doping can improve the hydrophilicity of the titanium surface. The increase of nanotube diameter could reduce the albumin adsorption while increasing the fibrinogen adsorption. However, zinc doping can simultaneously promote the adsorption of albumin and fibrinogen, and the effect was more obvious for albumin. Zinc doping can significantly improve the blood compatibility of the titanium oxide nanotubes because it cannot only increase the activity of cyclophosphate guanylate (cGMP) but also significantly reduce the platelets adhesion and hemolysis rate. Moreover, it was also found that both the smaller diameter and zinc doping nanotubes can enhance the endothelial cell adhesion and proliferation as well as up-regulate the expression of NO and VEGF. Therefore, the zinc doped titanium dioxide nanotube array can be used to simultaneously improve the blood compatibility and promote endothelialization of the titanium-based biomaterials and implants, such as intravascular stents.


Assuntos
Nanotubos , Titânio , Materiais Biocompatíveis , Zinco
10.
J Ethnopharmacol ; 249: 112404, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739105

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. AIM OF THE STUDY: The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-ß/Smads pathway. MATERIALS AND METHODS: We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 µM) and treated with ASG (10 µM) simultaneously for 24 h. RESULTS: The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-ß/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-ß/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. CONCLUSIONS: AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-ß/Smads pathway.


Assuntos
Cardiomiopatia Hipertrófica/tratamento farmacológico , Miocárdio/patologia , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Animais Recém-Nascidos , Astrágalo/química , Cardiomiopatia Hipertrófica/induzido quimicamente , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Células Cultivadas , Modelos Animais de Doenças , Fibrose , Humanos , Isoproterenol/toxicidade , Masculino , Medicina Tradicional Chinesa/métodos , MicroRNAs/metabolismo , Miocárdio/citologia , Miofibroblastos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Saponinas/uso terapêutico , Transdução de Sinais/genética , Proteínas Smad/metabolismo , Canais de Cátion TRPM/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Triterpenos/isolamento & purificação , Triterpenos/uso terapêutico
11.
Life Sci ; 236: 116948, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605711

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia , Fármacos do Sistema Nervoso Central/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Peróxido de Hidrogênio/toxicidade , MicroRNAs/genética , Animais , Oxidantes/toxicidade , Células PC12 , Ratos , Transdução de Sinais
12.
Chem Commun (Camb) ; 55(59): 8564-8566, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31271158

RESUMO

Diphenylalanine (FF), as the smallest unit and core recognition motif of ß-amyloid (Aß), could self-assemble into nanofibers, which induces an early onset of Alzheimer's disease (AD). Green/near-infrared fluorescent BODIPY probes were designed and synthesized to detect FF-assembly, providing unique insights into the chemical and molecular mechanism of Aß aggregation and drug development for AD.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Fenilalanina/análogos & derivados , Técnicas Biossensoriais/métodos , Compostos de Boro/síntese química , Dipeptídeos , Corantes Fluorescentes/síntese química , Nanofibras/química , Fenilalanina/análise , Fenilalanina/química , Multimerização Proteica
13.
Environ Int ; 127: 5-12, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30889398

RESUMO

Nanoparticles of four noble metal doped titanium dioxide (i.e., Pd/TiO2, Ag/TiO2, Pt/TiO2 and Cu/TiO2) were synthesized and investigated for their effectiveness to degrade polybrominated diphenyl ethers (PBDEs) under UV light. All the investigated noble metal additives can greatly enhance the performance of TiO2 to degrade 2,2',4',4'-tetrabromodiphenyl ether (BDE-47). However, the debromination pathways of BDE-47 in Ag/TiO2 and Cu/TiO2 systems are just contrary to those in Pd/TiO2 and Pt/TiO2 systems, and there was an induction period in the former systems but not in the latter systems. The hydrogenation experiment suggests a direct H-atom transfer mechanism in Pd/TiO2 and Pt/TiO2 systems, while in Ag/TiO2 and Cu/TiO2 systems, electron transfer is still the dominant mechanism. Electronic method was applied to explain why BDE-47 exhibit different debromination pathways based on different degradation mechanism. In addition, oxygen was proved to be able to capture both electrons and H atoms, and thus can greatly inhibit the degradation of PBDEs in all investigated systems. Finally, the merit and demerit of each metal doped TiO2 were discussed in detail, including the reactivity, stability and the generation of byproducts. We proposed our study greatly enhance our understanding on the mechanisms of PBDE degradation in various metal doped TiO2 systems.


Assuntos
Éteres Difenil Halogenados/química , Nanocompostos/química , Processos Fotoquímicos , Titânio/química , Catálise , Raios Ultravioleta
14.
Zhongguo Gu Shang ; 32(10): 933-936, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-32512965

RESUMO

OBJECTIVE: To investigate the clinical effects of percuteneous endoscopic interlaminar discectomy(PEID)and fenestration discectomy(FD) for the treatment of L5S1 lumbar disc herniation(LDH). METHODS: A retrospective analysis was made on 86 patients with L5S1 LDH from January 2014 to March 2017 and followed up. According to the different surgical methods, the patients were divided into PEID group(43 cases) and FD group(43 cases). All operations were performed under general anesthesia. Forty-three patients in PEID group underwent percuteneous endoscopic interlaminar discectomy (PEID) and other 43 patients in FD group underwent classical fenestration discectomy (FD). Operative incision, operative time, intraoperative blood loss, duration of hospitalization, time of lying in bed after surgery, complication were compared between two groups. Pre- and postoperative visual analogue scale(VAS) of affected extremity pain and lumbar pain were recorded. Postoperative creatine kinase (CK) was observed in two groups. Modified Macnab criteria was used to evaluate the clinical effects. MRI was used to observe the survival rate of paraspinal muscle after operation. RESULTS: The length of skin incision, intraoperative blood loss, duration of hospitalization, time of lying in bed after surgery of PEID group and FD group were(0.7±0.1) cm, (8.0±3.0) ml, (3.0±1.5) d, (1.0±0.5) d and(5.0±1.8) cm, (62.0±50.5) ml, (11.0±2.5) d, (3.0±0.8) d, there was significant differences between two groups(P<0.05). VAS of affected extremity at 24 hours and 1 year after operation was obviously decreased in two groups(P<0.05), but there was no significant difference between groups(P>0.05). VAS of lumbar pain in PEID group and FD group were respectively (2.99±0.32), (5.44±1.31) scores at 24 hours after operation, and (1.56±0.60), ( 3.05±0.24) at 1 year after operation, there was significant differences between two groups(P<0.05). CK at 24, 48 hours after operation of FD group were obviously increased(P<0.05). According the modified Macnab criteria to evaluate the clinical effect, the rate of excellent and good of PEID group and FD group were 93% and 95%, respectively. The survival rate of paraspinal muscle by MRI in PEID group at 1 year after operation was higher than that in FD group(P<0.05). No complications such as spinal dura mater tearing, nerve root injury, vascular injury, intervertebral space infection were found in two groups. CONCLUSIONS: Both of the two methods are safe and can obtain satisfactory effect, but PEID is more in line with concept of minimally invasive and has more advantages in paraspinal muscle protection, operative incision, intraoperative blood loss, duration of hospitalization, time of lying in bed after operation.


Assuntos
Discotomia Percutânea , Discotomia , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares , Neuroendoscopia , Estudos Retrospectivos , Resultado do Tratamento
15.
Colloids Surf B Biointerfaces ; 173: 884-890, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30551305

RESUMO

Application of organic dyes is limited in biomedical fields due to the rapid self-quenching, poor stability and water solubility. In this work, polymer modified organic dyes is developed through the dyes initiating polymerization. The polymer length is studied by tuning the amount of monomer. With an optimal molecule weight of the polymer, the π-π stacking from π-conjugated organic fluorescent dyes and fluorescence quenching are inhibited, resulting in an enhancement of fluorescence intensity and photostability. Nanoparticles are further fabricated to be used for cell uptake based on the optimized organic dyes. Then, long term cellular fluorescence imaging is realized. This work highlights the potential of polymer modification to improve the performance of organic dyes and expand their applications.


Assuntos
Microscopia de Fluorescência , Nanopartículas/química , Compostos Orgânicos/química , Poliésteres/química , Células A549 , Endocitose , Corantes Fluorescentes/química , Humanos , Espectroscopia de Ressonância Magnética , Microscopia Confocal , Nanotecnologia , Fotoquímica
16.
Mol Med Rep ; 18(6): 5221-5228, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30280196

RESUMO

Emerging evidence has demonstrated that the dysregulation of microRNA (miRNA/miR) serves a crucial role in the tumorigenesis and tumor development of osteosarcoma (OS), primarily by affecting various pathological behaviors. Therefore, better knowledge of miRNA in OS may provide novel insights into the pathogenesis of OS, and may facilitate the development of promising therapeutics for patients with this disease. MiRNA­944 is frequently dysregulated in human cancers. However, the expression levels, functions and underlying mechanisms of miR­944 in OS remain largely elusive. In the present study, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to detect miR­944 expression in OS tissues and cell lines. The regulatory influence of miR­944 in OS proliferation and invasion was determined with MTT and Transwell invasion assays. In addition, the mechanisms underlying the action of miR­944 in OS cells were elucidated through a series of experiments, including bioinformatics analysis, luciferase reporter assay, RT­qPCR and western blot analysis. Spearman's correlation analysis was utilized to examine the relationship between miR­944 and VEGF expression levels, and rescue experiments were applied to further verify whether VEGF mediates the role of miR­944 in OS. The results demonstrated that miR­944 was downregulated in cancer tissues and cell lines. Furthermore, exogenous miR­944 expression inhibited cell proliferation and invasion in OS in vitro. Vascular endothelial growth factor (VEGF) was identified as a direct target of miR­944 in OS and was overexpressed in cancer tissues. VEGF expression was inversely correlated with miR­944 expression in cancer tissues. Rescue experiments demonstrated that overexpression of VEGF partially prevented the miR­944­induced inhibition of OS cell proliferation and invasion. These results suggested that miR­944 may serve a tumor suppressive role in OS by directly targeting VEGF. Therefore, miR­944 may be a promising target in the treatment of OS.


Assuntos
Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/genética , Interferência de RNA , Fatores de Crescimento do Endotélio Vascular/genética , Regiões 3' não Traduzidas , Biomarcadores Tumorais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico
17.
Nanomedicine (Lond) ; 13(12): 1495-1512, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29972677

RESUMO

Nanoparticles have promising biomedical applications for drug delivery, tumor imaging and tumor treatment. Pharmacokinetics are important for the in vivo application of nanoparticles. Biodistribution and clearance are largely defined as the key points of pharmacokinetics to maximize therapeutic efficacy and to minimize side effects. Different engineered nanoparticles have different biodistribution and clearance processes. The interactions of organs with nanoparticles, which are determined by the characteristics of the organs and the biochemical/physical properties of the nanoparticles, are a major factor influencing biodistribution and clearance. In this review, the clearance functions of organs and the properties related to pharmacokinetics, including nanoparticle size, shape, biodegradation and surface modifications are discussed.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Humanos , Neoplasias/patologia , Distribuição Tecidual/efeitos dos fármacos
18.
Exp Ther Med ; 15(2): 1934-1940, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434787

RESUMO

The aim of the current study was to investigate the expression and role of microRNA (miR)-1271 in the pathogenesis of osteosarcoma, and the associated underlying mechanisms. Tissue samples from 45 patients with osteosarcoma were collected, while the 143B, MG-63 and U-2 OS osteosarcoma cell lines were also cultured. The expression levels of miR-1271 in the tissues and cells were detected with reverse transcription-quantitative polymerase chain reaction, and 143B osteosarcoma cells were subjected to miR-1271 manipulation. In addition, the cell proliferation, cell cycle progression, and migration and invasion abilities were assessed by Cell Counting Kit-8 assay, flow cytometry and Transwell chamber assay, respectively. Tissue inhibitor of metalloproteinases 2 (TIMP2) expression level was also detected with western blot analysis. Dual-luciferase reporter assay was performed to investigate the interaction between miR-1271 and TIMP2. The results revealed that miR-1271 expression was significantly elevated in the osteosarcoma tissue and was closely correlated with the clinical TNM staging. The expression levels of miR-1271 were also upregulated in the osteosarcoma cells, with the highest expression observed in 143B cells. Inhibition of miR-1271 significantly inhibited the cell proliferation, G1/S phase transition, and the migration and invasion abilities of 143B cells, while it also resulted in upregulated TIMP2 expression in these cells. Furthermore, overexpression of TIMP2 significantly inhibited the cell proliferation, G1/S phase transition, and migration and invasion abilities of 143B cells. Dual-luciferase reporter assay demonstrated that miR-1271 targeted on the 3'-untranslated region of TIMP2 mRNA. In conclusion, the expression levels of miR-1271 were significantly elevated in osteosarcoma tissues and cells. miR-1271 downregulated the expression of TIMP2 to promote the proliferation and enhance the migration and invasion abilities of 143B osteosarcoma cells, functioning as an oncogene.

19.
Colloids Surf B Biointerfaces ; 161: 156-161, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29078164

RESUMO

In this work, permeability of polymersomes was quantified by fluorescence enhancement. The polymersomes were prepared from poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL), and an acid-sensitive hydrophobic dye borondipyrromethene (BODIPY) was encapsulated into the membrane of polymersomes. H+ from trifluoroacetic acid (TFA) would diffuse into the membrane of polymersomes to enhance the fluorescence of BODIPY. Intensity of the enhanced fluorescence could be used for quantifying the H+ permeability of polymersomes. In addition, poly(ε-caprolactone) (PCL) was used to control the permeability ability of the membrane. Such quantitative information on the molecular diffusion of polymersomes is of fundamental importance to many of their potential applications, e.g., nanoreactors and drug delivery.


Assuntos
Compostos de Boro/química , Permeabilidade da Membrana Celular , Etilenoglicóis/química , Membranas Artificiais , Poliésteres/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Permeabilidade
20.
Invest Ophthalmol Vis Sci ; 57(14): 6011-6019, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27820632

RESUMO

PURPOSES: Retinoblastoma (RB) is the most common primary intraocular malignancy of infancy. An alternative RB treatment protocol is proposed and tested. It is based on a photodynamic therapy (PDT) with a designed molecular beacon that specifically targets the murine double minute x (MDMX) high-expressed RB cells. METHODS: A MDMX mRNA triggered photodynamic molecular beacon is designed by binding a photosensitizer molecule (pyropheophorbide-a, or PPa) and a black hole quencher-3 (BHQ3) through a complementary oligonucleotide sequence. Cells with and without MDMX high-expression are incubated with the beacon and then irradiated with a laser. The fluorescence and reactive oxygen species are detected in solution to verify the specific activation of PPa by the perfectly matched DNA targets. The cell viabilities are evaluated with CCK-8 and flow cytometry assay. RESULTS: The fluorescence and photo-cytoxicity of PPa is recovered and significantly higher in the MDMX high-expressed Y79 and WERI-Rb1 cells, compared to that with the MDMX low-expressed cells. CONCLUSIONS: The synthesized beacon exhibits high PDT efficiency toward MDMX high-expressed RB cells. The data suggest that the designed beacon may provide a potential alternative for RB therapy and secures the ground for future investigation.


Assuntos
Técnicas de Sonda Molecular , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Retinoblastoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Inativação Gênica , Humanos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA/metabolismo , RNA Mitocondrial , RNA Neoplásico/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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