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1.
Environ Pollut ; 343: 123238, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38159629

RESUMEN

Exposure to pesticides has been associated with several cardiovascular complications in animal models. Neonicotinoids are now the most widely used insecticide globally, while the impact of neonicotinoids on cardiovascular function and the role of mitochondrial dynamics in neonicotinoids-induced cardiotoxicity is unclear. In the present study, Xenopus laevis tadpoles were exposed to environmental related concentrations (0, 5, and 50 µg/L) of typical neonicotinoid dinotefuran, with two enantiomers, for 21 days. We evaluated the changes in heart rate and cardiomyocyte apoptosis in exposed tadpoles. Then, we performed the transcriptome, metabolomics, transmission electron microscopy (TEM), and protein immunoblot to investigate the potential adverse impact of two enantiomers of dinotefuran on cardiotoxicity associated with mitochondrial dynamics. We observed changes in heart rate and increased cardiomyocyte apoptosis in exposed tadpoles, indicating that dinotefuran had a cardiotoxic effect. We further found that the cardiac contractile function pathway was significantly enriched, while the glucose metabolism-related pathways were also disturbed significantly. TEM observation revealed that the mitochondrial morphology of cardiomyocytes in exposed tadpoles was swollen, and mitophagy was increased. Mitochondria fusion was excessively manifested in the enhanced mitochondrial fusion protein. The mitochondrial respiratory chain was also disturbed, which led to an increase in ROS production and a decrease in ATP content. Therefore, our results suggested that dinotefuran exposure can induce cardiac disease associated mitochondrial disorders by interfering with the functionality and dynamics of mitochondria. In addition, both two enantiomers of dinotefuran have certain toxicity to tadpole cardiomyocytes, while R-dinotefuran exhibited higher toxicity than S-enantiomer, which may be attributed to disparities in the activation capacities of the respiratory chain.


Asunto(s)
Cardiotoxicidad , Guanidinas , Dinámicas Mitocondriales , Animales , Neonicotinoides/toxicidad , Nitrocompuestos/toxicidad , Larva
2.
Colloids Surf B Biointerfaces ; 229: 113469, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37536167

RESUMEN

The novel histone deacetylase drug chidamide (CHI) has been proven to regulate gene expression associated with oncogenesis via epigenetic mechanisms. However, huge side effects such as non-targeting, poor intracellular accumulation and low nuclear entry efficiency severely restrict its therapeutic efficacy. Dual-targeted nanodrug delivery systems have been proposed as the solution. Herein, we developed a CHI-loaded drug delivery nanosystem based on Prussian blue (PB) nanocarrier, which combines surface-enhanced Raman scattering (SERS) tracking function with cancer cell/nuclear-targeted chemotherapy capability. With the property of background-free SERS mapping, PB nanocarriers can serve as tracking agents to localize intracellular CHI. The incorporation of targeted molecules specifically enhances the cancer cell/nuclear internalization and chemotherapeutic effects of CHI-loaded PB nanocarriers. In vitro cytotoxicity assay clearly shows that the constructed CHI-loaded PB nanocarriers have significant inhibitory on Jurkat cell proliferation. Furthermore, SERS spectral analysis of Jurkat cells incubated with the CHI-loaded PB nanocarriers reveals obvious features of cellular apoptosis: DNA skeleton fragmentation, chromatin depolymerization, histone acetylation, and nucleosome conformation change. Importantly, this CHI-loaded PB nanocarrier will provide a new insight for lymphoblastic leukemia targeted chemotherapy.


Asunto(s)
Aminopiridinas , Sistemas de Liberación de Medicamentos , Humanos , Benzamidas , Portadores de Fármacos , Línea Celular Tumoral
3.
Front Immunol ; 14: 1139601, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37063908

RESUMEN

Background: Cerebral microbleeds (CMBs) are an early sign of many neurological disorders and accompanied by local neuroinflammation and brain damage. As important regulators of immune response and neuroinflammation, the biological behavior and role of γδ T cells after CMBs remain largely unknown. Methods: We made a spot injury of microvessel in the somatosensory cortex to mimic the model of CMBs by two-photon laser and in vivo tracked dynamical behaviors of γδ T cells induced by CMBs using TCR-δGFP transgenic mice. Biological features of γδ T cells in the peri-CMBs parenchyma were decoded by flow cytometry and Raman spectra. In wildtype and γδ T cell-deficient mice, neuroinflammation and neurite degeneration in the peri-CMBs cortex were studied by RNAseq, immunostaining and in vivo imaging respectively. Results: After CMBs, γδ T cells in the dural vessels were tracked to cross the meningeal structure and invade the brain parenchyma in a few days, where the division process of γδ T cells were captured. Parenchymal γδ T cells were highly expressed by CXCR6 and CCR6, similar to meningeal γδ T cells, positive for IL-17A and Ki67 (more than 98%), and they contained abundant substances for energy metabolism and nucleic acid synthesis. In γδ T cell-deficient mice, cortical samples showed the upregulation of neuroinflammatory signaling pathways, enhanced glial response and M1 microglial polarization, and earlier neuronal degeneration in the peri-CMBs brain parenchyma compared with wildtype mice. Conclusion: CMBs induce the accumulation and local proliferation of γδ T cells in the brain parenchyma, and γδ T cells exert anti-neuroinflammatory and neuroprotective effects at the early stage of CMBs.


Asunto(s)
Encéfalo , Hemorragia Cerebral , Ratones , Animales , Ratones Transgénicos , Regulación hacia Arriba , Proliferación Celular
4.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-995901

RESUMEN

Objective:To analyze the symmetry of different reference planes in the surgical simulation design of patients with protrusive jaw deformity with high and low eyes.Methods:Fifteen patients with partial jaw deformity were selected from January 2019 to June 2020, including 3 males and 12 females, aged 18-26 years, with average 23.78 years. Inclusion criteria were that the patients, aged more than 18 years, were diagnosed as protrusive jaw deformity with maxillary occlusal plane tilt and high and low eyes by clinical and imaging analysis. Three different 3D reference plane systems were established by different modeling methods. The distance between the landmarks of soft and hard tissues and the median sagittal plane was measured. The symmetry of skull was qualitatively analyzed by mirror image technique. The difference of three reference planes in surgical simulation symmetry of patients with protrusion jaw and high and low eyes was evaluated by one-way ANOVA.Results:Qualitative analysis showed that in the three measurement planes, the symmetry of the third reference plane was the best, and the symmetry of the second and the first was poor. Quantitative analysis showed that in measurement index of hard tissue, there was statistical difference between the distance of each landmark in the reference plane established by Method 3 and Method 1, Method 2 [(1.65±1.19) mm; (3.37±1.58) mm; (3.26±2.36) mm, P<0.05], but there was no statistical difference between Method 1 and Method 2 (P > 0.05). The measurement result of soft tissue was consistent with that of hard tissue, and the distance of each landmark in Method 3 from the median sagittal plane was very small, and the mean error was less than 0.5 mm, which was consistent with the clinical results. Conclusions:Digital model surgery technology can assist orthognathic surgeons in the design and prediction of surgical scheme, especially for patients with special partial jaw deformity.

5.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-995900

RESUMEN

Objective:To analyze the anatomical morphology of the zygomatic arch for reduction malarplasty.Methods:Computed tomography (CT) data were obtained from the electronic records of 45 patients in the Tianjin Stomatological Hospital from January 2018 to February 2020. Among them, there were 30 patients with normal protrusion of zygoma (group A) and 15 patients with prominent protrusion of zygoma (group B). The data were imported into modeling and analysis software (Mimics). Left and right three-dimensional (3D) zygoma models were created through standard procedures. In the 3D models, a vertical cut of the zygomatic arch was done, and anatomical morphological characteristics of the zygomatic arch were obtained through bone data measurement and morphological observation. Mean values with 95% confidence intervals ( CI) were calculated for the positional data. Independent sample T-test was conducted on the positional data and anatomical morphology data of the zygomatic arch in the two groups. P< 0.05 was considered as statistically significant. Results:In group B, the anterior edge of the stabilization area was located in front of the articular tubercle point (15.12 mm, 17.16 mm). The posterior edge of the stabilization area was located in front of the articular tubercle point (7.11 mm, 8.24 mm). The posterior edge of the enlarged area was located in front of the articular tubercle point (3.17 mm, 3.94 mm). There were significant differences between group A and group B in the posterior edge of the stabilization area ( t= 2.41, P= 0.018), the posterior edge of the enlarged area ( t=2.58, P= 0.012), and the width of the unilateral face ( P<0.01). Conclusions:There exists a stabilization area of bone morphology and enlargement area in zygomatic arch. The anatomical morphology of the zygomatic arch is different in width of the unilateral face and location of the enlarged area between populations with normal protrusion and prominent protrusion of the zygoma.

6.
Nanomaterials (Basel) ; 12(19)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36234432

RESUMEN

All-dielectric optical antenna with multiple Mie modes and lower inherent ohmic loss can achieve high efficiency of light manipulation. However, the silicon-based optical antenna is not reconfigurable for specific scenarios. The refractive index of optical phase-change materials can be reconfigured under stimulus, and this singular behavior makes it a good candidate for making reconfigurable passive optical devices. Here, the optical radiation characteristics of the V-shaped phase-change antenna are investigated theoretically. The results show that with increasing crystallinity, the maximum radiation direction of the V-shaped phase-change antenna can be continuously deflected by 90°. The exact multipole decomposition analysis reveals that the modulus and interference phase difference of the main multipole moments change with the crystallinity, resulting in a continuous deflection of the maximum radiation direction. Thus, the power ratio in the two vertical radiation directions can be monotonically reversed from -12 to 7 dB between 20% and 80% crystallinity. The V-shaped phase-change antenna exhibits the potential to act as the basic structural unit to construct a reconfigurable passive spatial angular power splitter or wavelength multiplexer. The mechanism analysis of radiation directivity involving the modulus and interference phase difference of the multipole moments will provide a reference for the design and optimization of the phase-change antenna.

8.
Opt Express ; 29(13): 20092-20104, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34266106

RESUMEN

The strongly localized electric field achieved in metallic nanoparticles (NPs) and nanostructures are commonly employed to realize surface-enhanced Raman scattering. However, the heat originating from the Ohmic loss of metals may lead to the damage of the analyzed molecules, which severely limits the practical applications of pure-metallic nanostructures. Here, we propose a dielectric-metallic hybrid nanocavity placing silicon (Si) NPs onto a gold (Au) film to realize broadband Raman scattering enhancement with significantly reduced heat generation. Our results reveal that the heat generation is dramatically reduced in the hybrid nanocavity as compared with its pure-metallic counterpart while a significantly enhanced electric field is maintained. We demonstrate numerically and experimentally that the optical resonances, which arise from the coherent coupling of the electric and magnetic dipoles excited inside the Si NP with their mirror images arisen from the Au film, can be employed to enhance the excitation and radiation of Raman signals, respectively. We find that the enhancement in the radiation of Raman signals plays a crucial role in enhancing the total Raman scattering. We also show that the hybrid nanocavity acts as a nano-antenna which effectively radiates Raman signals into the far-field. These findings indicate the advantages of such hybrid nanocavities in temperature-sensitive Raman scattering characterization and supply new strategies for designing nanoscale photonic devices of other functionalities with hybrid nanocavities.

9.
J Craniofac Surg ; 32(7): 2553-2556, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33770028

RESUMEN

OBJECTIVE: To analyze the value of simulated surgery in predicting the outcome of individualized surgical reduction of a prominent zygomatic arch. METHODS: Computed tomography data were obtained from the electronic records of 15 patients who underwent surgery at Tianjin Stomatological Hospital for prominent zygoma. The data were imported into Mimics 23.0. Left and right three-dimensional (3D) zygoma models were created through standard procedures. In the 3D models, a wedge-shaped cut of the zygomatic bone was pushed inward, and the osteotomy position of the zygomatic arch was taken as a variable to simulate the reduction malarplasty. The reduction effect was calculated from the simulated movement of the fracture end of the zygomatic arch from internal pushing forces. Stable versus high-efficiency internal pushing areas were defined based on the amount of movement. Mean values with 95% confidence intervals (CI) were calculated for the areas data. RESULTS: The anterior edge of the stable internal pushing osteotomy area was located in front of the articular tubercle point (95% CI: 10.64-11.89 mm). The posterior edge of the stable internal pushing area was located in front of the articular tubercle point (95% CI: 7.8-9.13 mm). The posterior edge of the high-efficiency internal pushing area was located in front of the articular tubercle point (95% CI: 4.7-5.73 mm). CONCLUSION: Stable and high-efficiency internal pushing areas were detected above the zygomatic arch. The simulation showed that osteotomy in these areas can provide different degrees of zygomatic arch reduction.


Asunto(s)
Procedimientos de Cirugía Plástica , Cigoma , Hospitales , Humanos , Osteotomía , Tomografía Computarizada por Rayos X , Cigoma/diagnóstico por imagen , Cigoma/cirugía
10.
Colloids Surf B Biointerfaces ; 199: 111550, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33385819

RESUMEN

Phototherapy, especially the photothermal therapy (PTT) and the photodynamic therapy (PDT), have become very promising in cancer treatment due to its low invasiveness and high efficacy. Both PTT and PDT involve the utilization of light energy, and their synergistic treatment should be a good solution for cancer treatment by ingenious design. The therapeutic effect of phototherapy is closely associated with the amount and location of anticancer-nanodrugs accumulated in tumor cells, and the receptor-mediated endocytosis should be an excellent candidate for enhancing anticancer-nanodrugs internalization. Surface enhanced Raman spectroscopy (SERS) imaging is suitable for tracing nanodrugs due to its high selectivity, sensitivity and reliability. In this paper, we hope to construct a receptor-mediated PTT/PDT synergistic anticancer nanodrugs and evaluate the corresponding efficacy through SERS tracing function. Here, the receptor-mediated PTT/PDT synergistic anticancer nanodrugs are prepared by the chemical modification of gold nanorods (GNRs), involving protoporphyrin IX (PpIX), 4-mecaptobenzoic acid (MBA), and folic acid (FA). The achieved results show that the receptor-mediated endocytosis can greatly facilitate the internalized amount and intracellular distribution of the nanodrugs, thus lead to the anti-cancer efficacy improvement. Importantly, this receptor-mediated PTT/PDT synergistic treatment with SERS tracing function will provide a simple and effective strategy for the design and application of anticancer phototherapy nanodrugs.


Asunto(s)
Nanotubos , Fotoquimioterapia , Oro , Fototerapia , Reproducibilidad de los Resultados
11.
Clin Epigenetics ; 12(1): 173, 2020 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-33203470

RESUMEN

BACKGROUND: Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, and molecular mechanisms in breast cancer. METHODS: We examined ZNF471 expression by RT-PCR and qPCR. Methylation-specific PCR determined its promoter methylation. Its biological functions and related molecular mechanisms were assessed by CCK-8, clonogenicity, wound healing, Transwell, nude mice tumorigenicity, flow cytometry, BrdU-ELISA, immunohistochemistry and Western blot assays. RESULTS: ZNF471 was significantly downregulated in breast cell lines and tissues due to its promoter CpG methylation, compared with normal mammary epithelial cells and paired surgical-margin tissues. Ectopic expression of ZNF471 substantially inhibited breast tumor cell growth in vitro and in vivo, arrested cell cycle at S phase, and promoted cell apoptosis, as well as suppressed metastasis. Further knockdown of ZNF471 verified its tumor-suppressive effects. We also found that ZNF471 exerted its tumor-suppressive functions through suppressing epithelial-mesenchymal transition, tumor cell stemness and AKT and Wnt/ß-catenin signaling. CONCLUSIONS: ZNF471 functions as a tumor suppressor that was epigenetically inactivated in breast cancer. Its inhibition of AKT and Wnt/ß-catenin signaling pathways is one of the mechanisms underlying its anti-cancer effects.


Asunto(s)
Neoplasias de la Mama/genética , Metástasis de la Neoplasia/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Represoras/genética , Vía de Señalización Wnt/genética , Animales , Apoptosis/genética , Neoplasias de la Mama/patología , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral/metabolismo , Proliferación Celular/genética , Metilación de ADN , ADN-Citosina Metilasas/metabolismo , Regulación hacia Abajo , Epigenómica , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Ratones , Ratones Desnudos/genética , Modelos Animales , Metástasis de la Neoplasia/patología , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Represoras/farmacología , Dedos de Zinc/genética
12.
Fitoterapia ; 111: 29-35, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27085303

RESUMEN

Nine new sesquiterpenoids, clitocybulol derivatives, clitocybulols G-O (1-9) and three known sesquiterpenoids, clitocybulols C-E (10-12), were isolated from the solid culture of the edible fungus Pleurotus cystidiosus. The structures of compounds 1-12 were determined by spectroscopic methods. The absolute configurations of compounds 1-9 were assigned via the circular dichroism (CD) data analysis. Compounds 1, 6 and 10 showed moderate inhibitory activity against protein tyrosine phosphatase-1B (PTP1B) with IC50 values of 49.5, 38.1 and 36.0µM, respectively.


Asunto(s)
Inhibidores de Glicósido Hidrolasas/química , Pleurotus/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Sesquiterpenos/química , Agaricales/química , Animales , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Humanos , Estructura Molecular , Ratas , Sesquiterpenos/aislamiento & purificación
13.
Planta Med ; 82(7): 639-44, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26872321

RESUMEN

One new perhydrobenzannulated 5,5-spiroketal sesquiterpene, pleurospiroketal F (1), as well as six new modified bisabolene sesquiterpenes pleurotins A-F (2-7) were isolated from solid-state fermentation of Pleurotus citrinopileatus. The structures of compounds 1-7 were determined by NMR and MS spectroscopic analysis. The absolute configuration of 1 was determined by X-ray diffraction analysis, while the absolute configurations of 3-7 were assigned using the in situ dimolybdenum circular dichroism method and circular dichroism data comparison. Protein tyrosine phosphatase 1B plays a crucial role as a negative regulator of the insulin-dependent signal cascades. Therefore, the protein tyrosine phosphatase 1B inhibitor can be used for treating type 2 diabetes mellitus and obesity. Compounds 2 and 6 showed moderate inhibitory effects on protein tyrosine phosphatase 1B with IC50 s of 32.1 µM and 30.5 µM, respectively. The kinetic study confirmed compound 2 to be a noncompetitive inhibitor. Compounds 1-7 did not show cytotoxic activity against cancer cell lines (IC50 > 50 µM).


Asunto(s)
Antineoplásicos/aislamiento & purificación , Pleurotus/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Sesquiterpenos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Células K562 , Estructura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacología
14.
Org Lett ; 17(10): 2538-41, 2015 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-25915800

RESUMEN

Ten new ergosteroids, gloeophyllins A-J (1-10), have been isolated from the solid cultures of Gloeophyllum abietinum. The absolute configurations of 1, 2, and 9 were determined by X-ray crystallographic analysis. Compound 1 has a rare C-nor-D-homosteroid skeleton. Compound 9 possesses an unusual ergostane skeleton having a 10-oxabicyclo [4.3.1] decane moiety replacing 6/5 fused C/D rings. Compound 10 represents the first ergosteroid featuring the cleavage of a C8-C14 bond. The cytotoxicity of 1-10 was tested against the human cancer cell lines K562 and HCT116. The biosynthetic pathway for 1-10 is postulated.


Asunto(s)
Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Basidiomycota/química , Esteroides/aislamiento & purificación , Esteroides/farmacología , Antineoplásicos/química , China , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Células K562 , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Esteroides/química , Tibet
15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(2): 160-3, 2014 03.
Artículo en Chino | MEDLINE | ID: mdl-24782371

RESUMEN

OBJECTIVE: To determine the enantiomeric impurity contents of domestic timolol maleate in bulk drugs and eye drops. METHODS: Enantiomer impurity of timolol was assayed by chiral high performance liquid chromatography. The chromatographic conditions were as follows:chiralcel OD chiral column (4.6 mm ×150 mm, 5µm), detection wavelength:297 nm, mobile phase:hexane-isopropanol-diethylamine (480:20:1), column temperature:25 ℃, flow rate:1.0 ml/min, sample injection volume:5 µl. RESULTS: The resolution between R- and S-timolol was more than 4. The enantiomeric impurity contents were less than 0.67% on average in two batches of timolol maleate bulk drugs, and 0.31% on average in three batches of timolol maleate eye drops. CONCLUSION: Enantiomeric impurity contents in each batch of products all meet European Pharmacopoeia criteria, which can be used as references in Chinese Pharmacopoeia criteria.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Contaminación de Medicamentos , Soluciones Oftálmicas/análisis , Timolol/análisis , Soluciones Oftálmicas/normas , Estereoisomerismo , Timolol/normas
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(2): 164-7, 2014 03.
Artículo en Chino | MEDLINE | ID: mdl-24782372

RESUMEN

OBJECTIVE: To determine the contents of L-enantiomer impurity in valaciclovir hydrochloride. METHODS: Valaciclovir enantiomers were separated and determined by using chiral high performance liquid chromatography. Chromatographic conditions were as follows:CROWNPAK(®) CR(+) chiral column (4 mm×150 mm, 5 µm), detection wavelength:254 nm, mobile phase:water-methanol-perchloric acid (19:1:0.1), flow rate:0.75 ml/min, sample injection volume:10 µl. RESULTS: D-valaciclovir was completely separated from L-enantiomer impurity. The contents of L-enantiomer impurity were 0.65%-2.62% on average in 8 batches of valaciclovir hydrochloride. CONCLUSION: Enantiomeric impurity contents in each batch of products were all meet criteria of United States Pharmacopeia, which can be used in criteria of Chinese Pharmacopeia as references.


Asunto(s)
Aciclovir/análogos & derivados , Cromatografía Líquida de Alta Presión/métodos , Valina/análogos & derivados , Aciclovir/análisis , Estereoisomerismo , Valaciclovir , Valina/análisis
17.
Chinese Journal of Virology ; (6): 346-352, 2014.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-280361

RESUMEN

Bel1, a transactivator of prototype foamy virus (PFV), plays pivotal roles in the replication of PFV. Previous studies have shown that Bel1 bears a nuclear localization signal (NLS), but its amino acid sequence remains unclear and the corresponding importins have not been identified. In this report, we inserted various fragments of Bel1 into an EGFP-GST fusion protein and investigated their subcellular localization by fluorescence microscopy. We found that the 215PRQKRPR221 fragment could direct nuclear localization, which accords with the consensus sequence K(K/R)X(K/R) of monopartite NLS. Point mutation experiments revealed that K218, R219, and R221 are essential for the nuclear localization of Bel1. The results of the GST-pulldown showed that the Bel1 fragment with residues 215-223, which bears the NLS, interacts with KPNA1, KPNA6, and KPNA7. This result suggests that KPNA1, KPNA6, and KPNA7 maybe involved in Bel1 nuclear translocation.


Asunto(s)
Humanos , Línea Celular , Núcleo Celular , Genética , Metabolismo , Virología , Señales de Localización Nuclear , Genética , Metabolismo , Unión Proteica , Transporte de Proteínas , Infecciones por Retroviridae , Genética , Metabolismo , Virología , Proteínas de los Retroviridae , Química , Genética , Metabolismo , Spumavirus , Química , Genética , Fisiología , Transactivadores , Química , Genética , Metabolismo , alfa Carioferinas , Genética , Metabolismo
18.
Chinese Journal of Virology ; (6): 44-50, 2013.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-339976

RESUMEN

Vpr, an auxiliary protein of HIV-1(Human immunodeficiency virus type 1), exerts important functions to promote viral replication and AIDS progression. In this study, we performed a yeast two-hybrid screening assay using human cDNA library to further investigate the molecular mechanism of various functions of Vpr RelB, a key protein in NF-kappaB signaling pathway, was identified as a Vpr interaction protein by co-immunoprecipitation. Further investigations indicated that RelB not only promoted the Vpr-mediated activation of NF-kappaB reporter gene, but also enhanced the transactivation of HIV LTR. Moreover, the results showed that RelB promoted Vpr-induced cell cycle G2/M arrest. Collectively, these results indicated that RelB might interact with Vpr and regulate its transcriptional activation and cell cycle arrest.


Asunto(s)
Humanos , Puntos de Control del Ciclo Celular , División Celular , Fase G2 , Duplicado del Terminal Largo de VIH , Células HeLa , FN-kappa B , Genética , Factor de Transcripción ReIB , Fisiología , Activación Transcripcional , Productos del Gen vpr del Virus de la Inmunodeficiencia Humana , Fisiología
19.
J Med Chem ; 52(23): 7732-52, 2009 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-19673490

RESUMEN

A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared for comparison. The cell viability of PC12 cells, Fe(2+) chelation, lipid peroxidation (LPO), free radical scavenging, and xanthine oxidase inhibition models were utilized to evaluate their antioxidative and neuron protective properties. The study revealed that the diether at C7-OH and C20-OH as well as the monoether at C7-OH, which possess aliphatic substituted acetamides, demonstrated more potent LPO inhibition and Fe(2+) chelation compared to DHS and quercetin. Conversely, the diallyl ether at C7-OH and C20-OH was more potent in protection of PC12 cells against H(2)O(2)-induced injury than DHS and quercetin. Overall, the more lipophilic alkenylated DHS analogues were better performing neuroprotective agents than the acetamidated derivatives. The results in this study would be beneficial for optimizing the therapeutic potential of lignoflavonoids, especially in neurodegenerative disorders such as Alzheimer's and Parkinson's disease.


Asunto(s)
Alquenos/química , Amidas/química , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/farmacología , Silimarina/síntesis química , Silimarina/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Diseño de Fármacos , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/uso terapéutico , Humanos , Quelantes del Hierro/síntesis química , Quelantes del Hierro/química , Quelantes del Hierro/farmacología , Quelantes del Hierro/uso terapéutico , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Modelos Moleculares , Conformación Molecular , Neuronas/citología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/uso terapéutico , Células PC12 , Enfermedad de Parkinson/tratamiento farmacológico , Ratas , Silimarina/química , Silimarina/uso terapéutico , Relación Estructura-Actividad , Xantina Oxidasa/antagonistas & inhibidores
20.
Chinese Medical Journal ; (24): 2874-2879, 2009.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-266023

RESUMEN

<p><b>BACKGROUND</b>The CRF07_BC recombinant strain has been one of the most predominantly circulated HIV-1 strains in China, it is therefore necessary and urgent to develop a relevant animal model to evaluate candidate vaccines targeting HIV-1 CRF07_BC. A highly replication-competent simian/human immunodeficiency viruses (SHIV) construct containing the Chinese CRF07_BC HIV-1 env gene with the ability to infect Chinese rhesus monkeys would serve as an important tool in the development of HIV vaccines. The aim of this study was to examine whether SHIV XJDC6431 with the env fragment from a Chinese HIV-1 isolate virus could infect the human and monkey peripheral blood mononuclear cell (PBMC), establish infection in Chinese rhesus macaque.</p><p><b>METHODS</b>A SHIV strain was constructed by replacing the rev/env genes of SHIV KB9 with the corresponding fragment derived from the HIV-1 CRF07_BC strain. The infectious activity of the SHIV clones was determined in vitro in PBMCs from both non-human primate animals and humans. Finally, one Chinese rhesus macaques (Macaca mulatta) was infected with one SHIV via intravenous infusion.</p><p><b>RESULTS</b>One SHIV clone designated as SHIV XJDC6431, was generated that could infect macaque and human PBMC. The virus produced from this clone also efficiently infected the CCR5-expressing GHOST cell lines, indicating that it uses CCR5 as its coreceptor. Finally, the virus was intravenously inoculated into one Chinese rhesus macaque. Eventually, the animal became infected as shown by the occurrence of viremia within 3 of infection. The viral load reached 105 copies of viral RNA per ml of plasma during the acute phase of infection and lasted for 10 weeks post infection.</p><p><b>CONCLUSIONS</b>We conclude that SHIV XJDC6431 is an R5-tropic chimeric virus, which can establish infection not only in vitro but also in vivo in the Chinese rhesus macaque. Although the animal inoculated with SHIV XJDC6431 became infected without developing a pathologic phenotype, the virus efficiently replicated with a persistent level of viral load in the plasma. This suggested that the SHIV could be used as a tool to test candidate AIDS vaccines targeting the Chinese HIV-1 CRF_07BC recombinant strain.</p>


Asunto(s)
Animales , Humanos , Quimera , Genes env , VIH-1 , Genética , Fisiología , Macaca mulatta , Provirus , Genética , Receptores CCR5 , Fisiología , Virus de la Inmunodeficiencia de los Simios , Genética , Fisiología
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