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1.
Int J Mol Sci ; 21(5)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143291

RESUMO

Honey bee viruses are associated with honey bee colony decline. Israeli acute paralysis virus (IAPV) is considered to have a strong impact on honey bee survival. Phylogenetic analysis of the viral genomes from several regions of the world showed that various IAPV lineages had substantial differences in virulence. Chronic bee paralysis virus (CBPV), another important honey bee virus, can induce two significantly different symptoms. However, the infection characteristics and pathogenesis of IAPV and CBPV have not been completely elucidated. Here, we constructed infectious clones of IAPV and CBPV using a universal vector to provide a basis for studying their replication and pathogenesis. Infectious IAPV and CBPV were rescued from molecular clones of IAPV and CBPV genomes, respectively, that induced typical paralysis symptoms. The replication levels and expression proteins of IAPV and CBPV in progeny virus production were confirmed by qPCR and Western blot. Our results will allow further dissection of the role of each gene in the context of viral infection while helping to study viral pathogenesis and develop antiviral drugs using reverse genetics systems.

2.
Chem Commun (Camb) ; 56(17): 2614-2617, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32016279

RESUMO

A ruthenium-catalyzed allylic C(sp3)-H activation strategy has been employed to develop an intermolecular coupling of alkenyl sulfonamides with alkynes. This protocol features the diastereoselective construction of [3.3.0] and [4.3.0] bicyclic sultams in one step.

3.
Viruses ; 12(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861567

RESUMO

Since the discovery that honey bee viruses play a role in colony decline, researchers have made major breakthroughs in understanding viral pathology and infection processes in honey bees. Work on virus transmission patterns and virus vectors, such as the mite Varroa destructor, has prompted intense efforts to manage honey bee health. However, little is known about the occurrence of honey bee viruses in bee predators, such as vespids. In this study, we characterized the occurrence of 11 honey bee viruses in five vespid species and one wasp from four provinces in China and two vespid species from four locations in France. The results showed that all the species from China carried certain honey bee viruses, notably Apis mellifera filamentous virus (AmFV), Deformed wing virus (DWV), and Israeli acute paralysis virus (IAPV); furthermore, in some vespid colonies, more than three different viruses were identified. In France, DWV was the most common virus; Sacbrood virus (SBV) and Black queen cell virus (BQCV) were observed in one and two samples, respectively. Phylogenetic analyses of IAPV and BQCV sequences indicated that most of the IAPV sequences belonged to a single group, while the BQCV sequences belonged to several groups. Additionally, our study is the first to detect Lake Sinai virus (LSV) in a hornet from China. Our findings can guide further research into the origin and transmission of honey bee viruses in Vespidae, a taxon of ecological, and potentially epidemiological, relevance.

4.
Exp Ther Med ; 18(1): 172-178, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31258651

RESUMO

The glycyrrhizic acid (GA) epimers 18α- and 18ß-GA exert anti-inflammatory and hepatoprotective activities, which may help to protect against alcoholic liver disease, particularly alcoholic hepatitis (AH). The aim of the present study was to investigate the optimal ratio of 18α- and 18ß-GA for preventing AH in rats. Different groups of rats were administered seven different ratios of 18α- and 18ß-GA (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10; 10.83 mg/kg), vehicle control, or silymarin (22.75 mg/kg) as a positive control, followed by administration of 40% alcohol (10 ml/kg) once a day for four weeks. Subsequently, livers were isolated and routinely processed for histological examination. The serum levels of 23 cytokines and chemokines associated with AH were examined with a Bio-Plex 200 Luminex assay. It was revealed that all ratios of 18α- and 18ß-GA prevented alcohol-induced liver injury, as evidenced by a lesser degree of histopathological changes in the liver as compared with those in the model group. Furthermore, the levels of 15 cytokines/chemokines were significantly altered after alcohol administration, which was significantly inhibited by, pre-treatment with different proportions of 18α- and 18ß-GA, particularly at a ratio of 4:6, for most cytokines/chemokines associated with AH, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-7, IL-6, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-3α, macrophage- and granulocyte macrophage colony-stimulating factor, chemokine (C-X-C motif) ligand 1(GRO/KC), vascular endothelial growth factor and C-C motif chemokine ligand 5 (RANTES). Taken together, based on these results the optimal ratio of 18α- and 18ß-GA to prevent AH in model rats was considered to be 4:6.

5.
Insects ; 10(6)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163665

RESUMO

Honey bees are essential to the functioning of terrestrial ecosystems. However, despite no single factor being blamed for losses of honey bee colonies in Europe and the USA, viruses have been considered as a major driver. Moreover, a virus vector can enhance the titer and virulence of virus such as Varroa destructor can change the virulence of the deformed wing virus. Here, we report molecular evidence for aphid lethal paralysis virus (ALPV) infecting Vespa velutina, which is an important predator of honey bees, especially of Apis cerana. Viral replication and phylogenetic analysis indicated that ALPV can not only replicate in V. velutina and A. cerana, but ALPV from A. cerana (ALPV-Ac) was also significantly associated with that of V. velutina (ALPV-Vv), though distinct from those of Apis mellifera (ALPV-Am). The host state posterior probability displayed that V. velutina is the main viral reservoir between V. velutina and A. cerana. Our results show ALPV had expanded host diversity resulting in potential impacts on the health of pollinators, even on the pollination ecosystem. We suggest further studies should investigate potential risks and impacts on pollinator populations of hornets. These results should have an impact conservation efforts focused on sustaining native pollinator abundance and diversity, and therefore, the crucial ecosystem services that they provide.

6.
Environ Toxicol ; 34(7): 869-877, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31033183

RESUMO

As a human carcinogen, coal tar pitch (CTP) can significantly increase the risk of lung cancer. However, the mechanism underlying CTP-induced lung carcinogenesis has not been well understood. This study aims to explore the role of the LncRNA-ENST00000501520 in the proliferation of malignant-transformed human bronchial epithelial cells (BAES-2B) induced by CTP extract for the first time. BEAS-2B cells were stimulated with 2.4 µg/mL CTP extract, and then passaged for three times, which were named passage 1 and then passaged until passage 30 (named as CTP group). The ENST000001520 of cells in CTP group was interfered using siRNA. The results showed that ENST000001520 located in cell nucleus (>80%) had no or weak ability of protein encoding. After interference of ENST000001520, the migration and proliferation of cells in CTP group were inhibited, and the cell cycle was arrested in the G0/G1 phase; however, the apoptosis of cells in CTP group was promoted. The target genes (SKB1, CLTB, TAP2, PIPK2, and SOCS3) of ENST000001520 were screened out, and the mRNA and protein expression of SBK1 and SOCS3 was significantly decreased after ENST000001520 interference. SBK1 and SOCS3 may play a promoting role in occurrence and development of cancers. The study suggests that LncRNA-ENST00000501520 could promote the proliferation in malignant-transformed BEAS-2B cells induced with CTP extract which may be mediated by target genes. This study may provide a new target for prevention and treatment of lung cancer.


Assuntos
Brônquios/efeitos dos fármacos , Proliferação de Células , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Alcatrão/toxicidade , RNA Longo não Codificante/fisiologia , Mucosa Respiratória/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/patologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transformação Celular Neoplásica/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mucosa Respiratória/metabolismo
8.
Public Health Nurs ; 36(4): 575-586, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30883888

RESUMO

BACKGROUND: Diabetes is a common chronic disease that requires a long-term regimen. However, the management of diabetes by telenursing is limited and inconclusive. OBJECTIVES: To determine the effectiveness of telenursing on control in diabetes. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We searched electronic databases, including PubMed, Embase, Web of Science and Cochrane Library. Studies comparing telenursing with usual care in diabetes patients were included. RESULTS: A total of 17 randomized controlled trials were identified. Glycated hemoglobin (HbA1c) dates were pooled using a random effects meta-analysis method, followed by subgroup analyses to examine heterogeneity. The meta-analysis showed that the use of telenursing (vs. usual care) was associated with a significant reduction in HbA1c levels compared to usual care, with a pooled 0.68% (95% CI: 0.33-1.03, p = 0.0001; I2  = 95%). For the secondary outcome, the SMD of body mass index (BMI) was -0.25% (95% CI: -0.81 to 0.32%, p = 0.39), with no statistically significant change; the fasting blood sugar (FBS) SMD was -0.19% (95% CI: 0.20 to 1.01, p = 0.003), with a statistically significant change; the total cholesterol (TC) SMD was -0.09% (95% CI: -0.03 to 0.21, p = 0.12), with no statistically significant change. CONCLUSIONS: Telenursing, as a useful tool for patient education and behavioral interventions, can help diabetes patients to improve their glycemic control. However, more studies on up-to-date and cost-effective technologies are needed.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Hemoglobina A Glicada/análise , Telenfermagem/métodos , Índice de Massa Corporal , Humanos
9.
Acupunct Med ; 37(1): 16-24, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30845813

RESUMO

OBJECTIVE: Breast cancer-related lymphoedema (BCRL) is a common complication after breast cancer treatment. We investigated whether acupuncture could be used to manage limb oedema in women after breast cancer surgery. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, CINAHL, and four Chinese databases were electronically searched for papers published through November 2017. Randomised controlled trials (RCTs) of acupuncture for BCRL were included. RESULTS: In total, six RCTs with 318 patients were identified. The main analysis revealed a positive overall effect of acupuncture intervention on pre/post-treatment differences in the diameter of the elbow joint, reductions in upper limb lymphoedema and effectiveness index based on arm measurement data in patients with breast cancer. Two studies evaluating the outcome of acupuncture on the diameter of the elbow joint found a significant reduction in diameter between the acupuncture and control groups (weighted mean difference (WMD) 6 cm, 95% CI 5.11 to 6.89 cm; P<0.001). The same two studies investigated the effect of acupuncture on upper limb lymphoedema reduction and found a significant difference between the acupuncture and control groups (risk ratio 1.4, 95% CI 1.17 to 1.67; P<0.001). Two other studies used the effectiveness index to assess the arm and found a significant difference between the acupuncture and control groups (WMD 23.34, 95% CI 10.74 to 35.94; P<0.001). The fifth study used bioelectrical impedance spectroscopy to assess lymphoedema at several points on the arm before and after acupuncture; this study also reported a significant reduction in lymphoedema. The sixth study reported no significant difference in bioimpedance between the groups. CONCLUSIONS: The present meta-analysis and systematic review suggests that acupuncture is effective at reducing BCRL in patients after breast cancer treatment.


Assuntos
Terapia por Acupuntura , Neoplasias da Mama/complicações , Linfedema/terapia , Adulto , Neoplasias da Mama/cirurgia , Feminino , Humanos , Linfedema/etiologia , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
Artif Cells Nanomed Biotechnol ; 46(sup3): S661-S670, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30307317

RESUMO

Hepatocellular carcinoma (HCC) is one of the greatest public health problems worldwide, and chemotherapy remains the major approach for the HCC treatment. Doxorubicin (DOX) is one of the anthracycline antibiotics but its clinical use is limited due to its severe cardiotoxicity. In this study, novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates (PDC-NPs) were fabricated for HCC treatment. The stabilized structure of the PDC-NPs was characterized by methylene blue absorption, the size, zeta potential and the morphology, which was investigated by Zetasizer nanoparticle analyzer and transmission electron microscope (TEM), of nanoparticles. The PDC-NPs achieved a sustained and prolonged release ability, which was illustrated with in vitro drug release profiles, anti-cell proliferation study, cellular uptake assay and in vivo pharmacokinetics analysis. Biocompatibility of the PDC-NPs was assessed with bovine serum albumin (BSA) adsorption test, hemolysis activity examination and viability evaluation of human umbilical vein endothelial cells. Importantly, in vivo studies of the PDC-NPs, which were performed in the athymic BALB/c nude mice, demonstrated that the PDC-NPs significantly reduced the lethal side effect of DOX. Additionally, the H&E staining and serum biochemistry study further confirmed the excellent biological security of the PDC-NPs.


Assuntos
Carcinoma Hepatocelular , Doxorrubicina , Neoplasias Hepáticas , Nanopartículas , Pectinas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Pectinas/química , Pectinas/farmacocinética , Pectinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Nanoscale ; 10(39): 18878-18891, 2018 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-30277486

RESUMO

Black phosphorus surface plasmon (BPSP) is a new promising candidate material for electromagnetic field confinement at the subwavelength scale. Here, we theoretically investigated the light confinement, second-order nonlinearity and lifetimes of tunable surface plasmons in nanostructured black phosphorus nanoflakes with superstrates. The grating structure can enhance the local optical field of the fundamental wave (FW) and second harmonic wave (SHW) due to the surface plasmon resonance. Based on the coupled mode theory (CMT), a theoretical model for the nanostructured black phosphorus was established to study the spectrum features of FW. The lifetimes of the plasmonic resonant modes were investigated with the finite difference time domain (FDTD) simulations and CMT. Since the permittivity of black phosphorus depends on its Fermi energy and electron scattering rate, the lifetimes of plasmonic absorption modes are tunable with both the Fermi energy and scattering rate. The intensity, wavelengths and spectral width of BPSP resonance modes and their lifetimes can be precisely controlled with the Fermi energy, scattering rate, side length and refractive index of the superstrate. The sensitivity is described by varying the refractive index of the superstrate such as an aqueous solution. We have introduced a second-order nonlinear source to investigate the SHW of nanostructured black phosphorus. This paper presents the corner/edge energy distribution and the tunable lifetime of BPSP as well as their unprecedented capability of photon manipulation for second-order nonlinearity within the deep subwavelength scale. The configuration and method are useful for research of the absorption, lifetime of light and nonlinear optical processes in black phosphorus-based optoelectronic devices, especially the modulation and sensing applications.

12.
Front Genet ; 9: 384, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30254665

RESUMO

Infection and transmission of honey bee viruses pose a serious threat to the pollination services of crops and wild plants, which plays a vital role in agricultural economy and ecology. RNA interference (RNAi) is an effective defense mechanism against commonly occurring viral infections of animals and plants. However, recent studies indicate that the effects of RNAi on the honey bee can induce additional impacts and might not always be effective in suppressing the virus. Moreover, the RNAi responses differed in relation to the developmental stage of the insect and the target tissue used, even though the same method of delivery was used. These results indicate that further analysis and field experiments should be performed to characterize the varying effectiveness of RNAi-based methods for treating honey bee viral infections. In this review, we provide an overview of the current knowledge and the recent progress in RNAi-based anti-viral treatments for honey bees, focusing in particular highlight the role of the dsRNA-delivery method used and its effect on RNAi efficiency and demonstrate the potential practical value of this tool for controlling the virus. We conclude studying the gene function and disease control of honey bee by RNAi technology requires a complex consideration from physiology, genetics to environment.

13.
Molecules ; 23(7)2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29973492

RESUMO

Glycyrrhhizic acid (GA), including 18α-glycyrrhizic acid (18α-GA) and 18ß-glycyrrhizic acid (18ß-GA), is the main active ingredient of licorice. GA is generally considered an effective pharmacological strategy protecting against hepatic disease; however, the optimal compatibility proportion of 18α-GA and 18ß-GA against alcoholic liver disease (ALD) and the underlying mechanism are not well established. Hence, this study was designed to explore the optimal compatibility proportion of 18α-GA and 18ß-GA against ALD, followed by investigating the underlying mechanisms. SD rats were administered 40% ethanol once a day, accompanied by treatment with different proportions of 18α-GA and 18ß-GA for four weeks. Then all rats were anesthetized with chloral hydrate and blood samples were taken from the abdominal aorta for biochemical assay. Livers were also collected and the liver function, lipid profile, ROS production, and mRNA and protein levels of related genes involved in lipid metabolism were assessed. The results showed that 18α-GA and 18ß-GA, particularly at a proportion of 4:6, significantly reduced liver damage, lipid accumulation, and oxidative stress in ethanol-induced rats, as indicated by the decreased levels of alanine aminotransferase (ALT) and aminotransferase (AST) in serum, improvement of liver histopathological changes, regulation of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and modulation of superoxide dismutase (SOD), glutathione (GSH), and malonaldehyde (MDA). Moreover, the combination treatment with 18α-GA and 18ß-GA substantially reduced the mRNA and protein levels of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-coal carboxylase (ACC); meanwhile, increased levels of peroxisome proliferators activated receptor-α (PPAR-α) and carnitine palmitoy transferase-1 (CTP-1) in the liver tissues of ethanol-induced rats. In conclusion, our results indicated that the optimal compatibility proportion of 18α-GA and 18ß-GA protecting against ALD was 4:6, and the mechanism was associated with the regulation of oxidative stress and lipid metabolism.


Assuntos
Ácido Glicirrízico/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/sangue , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glicirrízico/química , Ácido Glicirrízico/farmacologia , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/metabolismo , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
14.
Opt Express ; 25(25): 31478-31491, 2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29245823

RESUMO

The confined surface plasmon of fundamental wave and second harmonic wave (SHW) are investigated in graphene grating structure. The linear-optical absorption spectra with various fermi energy and carrier mobility are investigated with the finite difference time domain (FDTD) simulations and coupled mode theory (CMT). Based on the CMT, a theoretical model for the graphene grating is established to study the spectrum features of fundamental wave. The lifetimes of linear-optical resonant modes in theoretical model are investigated through the theoretical fitting of exact values in simulation, which are tunable with both the fermi energy and carrier mobility. We also have investigated the second-order nonlinearity of graphene grating by introducing the second-order nonlinear source. The proposed configuration and method are useful for research of the absorption, local field enhancement factor, lifetime of light, and nonlinear optical processes in highly integrated graphene photoelectric devices.

15.
Drug Deliv ; 24(1): 459-466, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28219253

RESUMO

A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quitosana/análogos & derivados , Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Fluoruracila/análogos & derivados , Fluoruracila/administração & dosagem , Nanopartículas/química , Pró-Fármacos/administração & dosagem , Células A549 , Absorção Fisiológica , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Quitosana/efeitos adversos , Quitosana/farmacocinética , Quitosana/farmacologia , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Fluoruracila/farmacologia , Glicosilação , Meia-Vida , Hemólise/efeitos dos fármacos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Camundongos , Nanopartículas/efeitos adversos , Nanopartículas/ultraestrutura , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Coelhos , Distribuição Aleatória , Ratos Sprague-Dawley , Distribuição Tecidual
16.
Dalton Trans ; 45(43): 17117-17122, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27766333

RESUMO

In order to obtain high-performance energetic materials, in this work, carbonyl groups (C[double bond, length as m-dash]O) have been newly introduced as sole bridging groups in the field of energetic materials. To this end, two tailored green methods for the synthesis of carbonyl-bridged energetic compounds have been developed for the first time. One is a biomimetic synthesis, in which the conversion route of heme to biliverdin has been used to obtain metal-containing energetic compounds. The other one is an organocatalysis, in which guanidinium serves as an energetic catalyst to afford other energetic compounds. Experimental studies and theoretical calculations have shown that carbonyl-bridged energetic compounds exhibit excellent energetic properties, which is promising for the carbonyl group as a new important and effective linker in energetic materials.

17.
Curr Pharm Des ; 22(4): 506-13, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26517529

RESUMO

The development of slow release nano-sized carriers for efficient antineoplastic drug delivery with a biocompatible and biodegradable pectin-based macromolecular pro-drug for tumor therapy has been reported in this study. Pectin-doxorubicin conjugates (PDC), a macromolecular pro-drug, were prepared via an amide condensation reaction, and a novel amphiphilic core-shell micell based on a PDC macromolecular pro-drug (PDC-M) was self-assembled in situ, with pectin as the hydrophilic shell and doxorubicin (DOX) as the hydrophobic core. Then the chemical structure of the PDC macromolecular pro-drug was identified by both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR), and proved that doxorubicin combined well with the pectin and formed macromolecular pro-drug. The PDC-M were observed to have an unregularly spherical shape and were uniform in size by scanning electron microscopy (SEM). The average particle size of PDC-M, further measured by a Zetasizer nanoparticle analyzer (Nano ZS, Malvern Instruments), was about 140 nm. The encapsulation efficiency and drug loading were 57.82% ± 3.7% (n = 3) and 23.852% ±2.3% (n = 3), respectively. The in vitro drug release behaviors of the resulting PDC-M were studied in a simulated tumor environment (pH 5.0), blood (pH 7.4) and a lysosome media (pH 6.8), and showed a prolonged slow release profile. Assays for antiproliferative effects and flow cytometry of the resulting PDC-M in HepG2 cell lines demonstrated greater properties of delayed and slow release as compared to free DOX. A cell viability study against endothelial cells further revealed that the resulting PDC-M possesses excellent cell compatibilities and low cytotoxicities in comparison with that of the free DOX. Hemolysis activity was investigated in rabbits, and the results also demonstrated that the PDC-M has greater compatibility in comparison with free DOX. This shows that the resulting PDC-M can ameliorate the hydrophobicity of free DOX. This work proposes a novel strategy for in-situ one-step synthesis of macromolecular pro-drugs and fabrication of a core-shell micelle, demonstrating great potential for cancer chemotherapy.


Assuntos
Doxorrubicina/síntese química , Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos/métodos , Micelas , Pectinas/síntese química , Pró-Fármacos/síntese química , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Química Farmacêutica , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Portadores de Fármacos/farmacologia , Feminino , Células Hep G2 , Humanos , Substâncias Macromoleculares/síntese química , Masculino , Nanopartículas , Pectinas/farmacologia , Pró-Fármacos/farmacologia , Coelhos
18.
Mol Pharm ; 11(2): 638-44, 2014 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-24383625

RESUMO

The fabrication and evaluation of a natural pectin-based drug delivery system are reported in this study. The drug delivery system displays specific active targeting ability to hepatocellular carcinoma due to the presence of excess galactose residues in the polymer structure as the natural targeting ligands. The system was prepared under very mild conditions in an aqueous medium containing Ca(2+) and CO3(2-) ions, generating uniform pectin-based nanoparticles with an average diameter of 300 nm, and the drug-loading content of anticancer drug 5-fluorouracil (5-FU) is around 24.8%. Cytotoxicity study of the 5-FU-loaded nanoparticles (5-FU-NPs) in HepG2 and A549 cell lines demonstrated their greater potency in killing cancer cells with overexpressed asialoglycoprotein receptor (ASGPR) on the cell surface, compared to that of the free drug. Pharmacokinetics study using Sprague-Dawley (SD) rats further confirmed that the drug-loaded nanoparticles showed a much longer half-life in the circulation fluids than the free drug. Tissue distribution was investigated on Kunming mice, and the results also demonstrated that the 5-FU-NPs has a long circulation effect. Taken together, the pectin-based drug delivery systems exhibit size-induced prolonged circulation as well as ASGP receptor-mediated targeting ability to cancer cell lines; therefore, it is a promising platform for the treatment of hepatocellular carcinoma.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/uso terapêutico , Pectinas/farmacologia , Pectinas/uso terapêutico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Bioensaio , Cápsulas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Concentração Inibidora 50 , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Tamanho da Partícula , Pectinas/química , Ratos
20.
J Biomed Sci ; 2(2): 183-188, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11725055

RESUMO

The cutaneous microcirculation can be divided into thermoregulatory shunt vessels and nutritive skin capillaries. Flux in nonnutritional shunt vessels dominates the signal recorded by the laser Doppler flowmeter. Computerized videophotometric capillaroscopy is a sensitive method for assessing cutaneous nutritive microcirculation. Using patients with blackfoot disease and arteriosclerosis as disease models, we evaluated the sensitivity and clinical usefulness of these relatively new techniques for peripheral vascular disorders. In blackfoot disease, blood flux measured by the laser Doppler flowmeter in the affected toe was lower than that in the nonaffected toe. In symptom-free fingers, blood flow was not significantly different between blackfoot disease and arteriosclerosis. However, blood flow in both diseases was lower than that of the control group. Patients who had the same status of thermoregulatory flow and eyeground arteriosclerotic classification underwent a 1-min arterial occlusion of the digits. The postocclusive reactive hyperemia response (PRH) of nailfold capillary loops was evaluated. All parameters for PRH for the cutaneous nutrient microcirculation including resting capillary blood cell velocity (rCBV), peak capillary blood cell velocity (pCBV) and time to pCBV were more significantly disturbed in the blackfoot disease group than in the arteriosclerotic group. On the basis of the results of this study, dynamic capillaroscopy provides a new approach for the early detection of circulatory disturbances resulting from different mechanisms. Copyright 1995 S. Karger AG, Basel

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