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1.
Int J Nanomedicine ; 14: 5109-5123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371950

RESUMO

Background: Renal cell carcinoma (RCC) is notorious for its resistance towards chemotherapy and radiation therapy in general. Combination therapy is often helpful in alleviating the resistance mechanisms by targeting multiple signaling pathways but is usually more toxic than monotherapy. Co-encapsulation of multiple therapeutic agents in a tumor-targeted drug delivery platform is a promising strategy to mitigate these limitations. Methods: A tumor-targeted liposomal formulation was prepared using phospholipids, cholesterol, DSPE-(PEG)2000-OMe and a proprietary tumor-targeting-peptide (TTP)-conjugated lipopeptide. An efficient method was optimized to encapsulate everolimus and vinorelbine in this liposomal formulation. Single drug-loaded liposomes were also prepared for comparison. Finally, the drug-loaded liposomes were tested in vitro and in vivo in two different RCC cell lines. Results: The tumor-targeted liposomal formulation demonstrated excellent tumor-specific uptake. The dual drug-loaded liposomes exhibited significantly higher growth inhibition in vitro compared to the single drug-loaded liposomes in two different RCC cell lines. Similarly, the dual drug-loaded liposomes demonstrated significantly higher suppression of tumor growth compared to the single drug-loaded liposomes in two different subcutaneous RCC xenografts. In addition, the dual drug-loaded liposomes instigated significant reduction in lung metastasis in those experiments. Conclusion: Taken together, this study demonstrates that co-delivery of everolimus and vinorelbine with a tumor-targeted liposomal formulation is an effective approach to achieve improved therapeutic outcome in RCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Everolimo/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Vinorelbina/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Antígeno Ki-67/metabolismo , Lipossomos , Neoplasias Pulmonares/secundário , Camundongos SCID , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Int J Syst Evol Microbiol ; 69(11): 3492-3499, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31418678

RESUMO

A bacterial strain, 17J42-9T, was isolated from a soil sample collected on Jeju Island, Republic of Korea. Cells were observed to be Gram-stain negative and rod-shaped. Colonies were observed to be orange in colour on R2A agar. Analysis of 16S rRNA gene sequences showed that high levels of 16S rRNA sequence similarity were shared between 17J42-9T and Emticicia fontis IMCC1731T (98.2 %), Emticicia ginsengisoliGsoil 085T (98.2 %) and Emticicia soli ZZ-4T (97.8 %). Growth of strain 17J42-9T was observed at 10-37 °C, pH 6.0-8.5 and in the presence of 0-0.5 % NaCl. The genomic G+C content was calculated to be 38.6 mol%. The predominant respiratory quinone of the isolate was found to be MK-7; the major fatty acids were identified as summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) (34.1 %), C15 : 0iso (23.4 %) and C17 : 0iso 3-OH (10.8 %). The major polar lipids were found to be phosphatidylethanolamine, two unidentified aminolipids and an unidentified lipid. The phenotypic and chemotaxonomic data support the affiliation of strain 17J42-9T with the genus Emticicia. However, the DNA-DNA relatedness between the isolate and its closest phylogenetic neighbours was lower than 46 %. The results of 16S rRNA gene sequence similarity analysis, DNA-DNA hybridization analysis and the observed differentiating phenotypic properties from other closely related taxa clearly indicate that strain 17J42-9T represents a novel species in the genus Emticicia, for which the name Emticiciaagri sp. nov. is proposed. The type strain is 17J42-9T (=KCTC 62270T=JCM 33056T).


Assuntos
Cytophagaceae/classificação , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Cytophagaceae/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Ilhas , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , Pigmentação , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA
3.
Int J Syst Evol Microbiol ; 69(11): 3603-3608, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31433288

RESUMO

A novel actinomycete, designated strain GLM-1T, was isolated from arbuscular mycorrhizal fungal spores from Funneliformis mosseae RYA08, collected from Aquilaria crassna Pierre ex Lec. rhizosphere soil in Klaeng, Rayong Province, Thailand. Morphological characteristics of this strain included long chains of rod-like cells and squarish elements. The cell-wall composition of this novel isolate contained meso-diaminopimelic acid. The whole-cell diagnostic sugars were arabinose and galactose. The predominant menaquinone was MK-9(H4). The major fatty acids were iso-C16 : 0 and iso-C15 : 0. Only phosphatidylethanolamine was detected as a polar lipid. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain GLM-1T was closely related to Amycolatopsis rhabdoformis SB026T (99.11 %) with a low DNA-DNA hybridization value of 22.6-34.7 %. Genome sequencing revealed a genome size of 10 Mbp. There were obvious distinctions in the average nucleotide identity values between stain GLM-1T and its closely related strains at around 86-93 % (ANIb) and 89-94 % (ANIm). The digital DNA-DNA hybridization values between strain GLM-1T and type strains of phylogenetically related species were 34-55 %. The G+C content of the genomic DNA was 71.8 mol%. Based on these data, strain GLM-1T is considered to represent a novel species of the genus Amycolatopsis, for which the name Amycolatopsiseburnea sp. nov. is proposed. The type strain is GLM-1T (=TBRC 9315T=NBRC 113658T).


Assuntos
Actinobacteria/classificação , Micorrizas , Filogenia , Microbiologia do Solo , Esporos Fúngicos , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Rizosfera , Análise de Sequência de DNA , Tailândia , Vitamina K 2/análogos & derivados , Vitamina K 2/química
4.
Int J Syst Evol Microbiol ; 69(11): 3609-3615, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31436526

RESUMO

A Gram-stain-negative, rod-shaped, red-coloured and aerobic bacterium, designated 2b14T, was isolated from rhizosphere soil of Saxifraga oppositifolia sampled at the Chinese Arctic Yellow River Station in Norway. Optimal growth occurred at 28 °C (range, 4-37 °C) and pH 7.0-7.5 (pH 6.5-8.5). The strain could tolerate up to 2.5 % (w/v) NaCl concentration. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 2b14Thad the highest similarity value of 96.0 % to Pontibacter diazotrophicus CCTCC AB 2013049T. The major fatty acids were summed feature 4 (anteiso-C17 : 1 B and/or iso-C17 : 1 I), iso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipid was found to be phosphatidylethanolamine. The genomic DNA G+C content of strain 2b14T was 45.5 mol%. The sole respiratory quinone was MK-7. The combined results of physiological, genotypic, phylogenetic and chemotaxonomic analyses showed that strain 2b14T represents a novel species within the genus Pontibacter, for which the name Pontibacter arcticus sp. nov. is proposed. The type strain is 2b14T (=KCTC 62596T=MCCC 1H00304T).


Assuntos
Bacteroidetes/classificação , Filogenia , Rizosfera , Saxifragaceae/microbiologia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Noruega , Fosfatidiletanolaminas/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
Biomater Sci ; 7(9): 3729-3740, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403142

RESUMO

Targeted delivery of immunosuppressants to allografts can increase the concentrations of drugs in pathological tissues, improve therapeutic effects and reduce unfavorable side effects. Therefore, we synthesized FK506-loaded microbubbles (FK506-MBs) for site-specific release of FK506 into transplanted hearts by the ultrasound-targeted microbubble destruction (UTMD) technique. The average particle size of FK506-MBs was 1.65 ± 0.32 µm and they had high drug loading and encapsulation efficiency. The in vivo drug concentration in transplanted hearts that were treated with FK506-MBs plus UTMD was about 1.64-fold higher than that in grafts that received free FK506 at the same dosage. The degree of graft rejection in the FK506-MB plus UTMD group was lower than those of other groups. Both infiltration of T cells and secretion of inflammatory cytokines were significantly reduced in the FK506-MB plus UTMD group. More importantly, the mean survival time of the grafts was significantly longer (16.00 ± 0.89 day) than those of the PBS group (6.66 ± 1.36 day) and the FK506 group (12.83 ± 1.17 day). In addition, we also found that the concentration of FK506 in whole blood was lower in the FK506-MB plus UTMD group than that in the FK506 group, which would be beneficial for reducing the side effects. Hence, our results showed that combining FK506-MBs with UTMD was an effective strategy to deliver FK506 to transplanted hearts, which can increase the local drug concentration and enhance its efficacy on rejection. Ultrasound-targeted drug release is safe and radiation-free, with great potential for clinical transformation, and could also be extended to the treatment of other graft rejection cases, such as liver transplantation, kidney transplantation and so on.


Assuntos
Portadores de Fármacos/química , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração , Imunossupressores/farmacocinética , Miocárdio/metabolismo , Tacrolimo/farmacocinética , Animais , Liberação Controlada de Fármacos , Estudos de Viabilidade , Imunossupressores/administração & dosagem , Masculino , Microbolhas , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos , Tacrolimo/administração & dosagem , Ultrassonografia
6.
Int J Syst Evol Microbiol ; 69(11): 3508-3511, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31424381

RESUMO

Arthrobacterenclensis was reported to cluster with species of the genus Pseudarthrobacter but the peptidoglycan containing lysine, alanine and glutamic acid and the presence of minor amounts of menaquinone MK-8(H4) were not in line with the description of the genus. Re-analysis of these traits revealed a peptidoglycan with l-Lys-l-Ser-l-Thr-l-Ala and no MK-8(H4), but major amounts of MK-9(H2) in the quinone system of A. enclensis DSM 25279T. These data demonstrate that A. enclensis shares the characteristics of the genus Pseudarthrobacter. Since the reported quinone systems of Pseudarthrobacterphenanthrenivorans [MK-8 and MK-9(H2)] and Pseudarthrobacterscleromae [MK-8(H2] were clearly different from those of other species of the genus, the quinone systems of the two species were re-analyzed. Since the polar lipid profile of P. phenanthrenivorans was reported to contain phosphatidylethanolamine, which is unusual for a member of the Micrococcaceae, and the polar lipid profile of P. scleromae was unknown, the polar lipids of these two species were also analysed. The quinone system of P. phenanthrenivorans DSM 18606T was composed of the major menaquinones MK-9(H2), MK-8(H2) and MK-10(H2) and that of P. scleromae DSM 17756T was composed of the major menaquinones MK-9(H2) and MK-8(H2) and MK-9. In the polar lipid profile of P. phenanthrenivorans DSM 18606T no phosphatidylethanolamine could be detected. Based on these results we here propose the reclassification of A. enclensis as Pseudarthrobacterenclensis comb. nov. and emend the descriptions of the genus Pseudarthrobacter and the two species P. phenanthrenivorans and P. scleromae.


Assuntos
Arthrobacter/classificação , Micrococcaceae/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , DNA Bacteriano/genética , Peptidoglicano/química , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
7.
Int J Syst Evol Microbiol ; 69(11): 3478-3484, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31424383

RESUMO

A Gram-stain-negative bacterial strain, designated CA10T, was isolated from bovine raw milk sampled in Anseong, Republic of Korea. Cells were yellow-pigmented, aerobic, non-motile bacilli and grew optimally at 30 °C and pH 7.0 on tryptic soy agar without supplementation of NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain CA10T belonged to the genus Chryseobacterium, family Flavobacteriaceae, and was most closely related to Chryseobacterium indoltheticum ATCC 27950T (98.75 % similarity). The average nucleotide identity and digital DNA-DNA hybridization values of strain CA10T were 94.4 and 56.9 %, respectively, relative to Chryseobacterium scophthalmum DSM 16779T, being lower than the cut-off values of 95-96 and 70 %, respectively. The predominant respiratory quinone was menaquinone-6; major polar lipid, phosphatidylethanolamine; major fatty acids, iso-C15 : 0, summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl), summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c) and iso-C17 : 0 3-OH. The results of physiological, chemotaxonomic and biochemical analyses suggested that strain CA10T is a novel species of genus Chryseobacterium, for which the name Chryseobacterium mulctrae sp. nov. is proposed. The type strain is CA10T (=KACC 21234T=JCM 33443T).


Assuntos
Chryseobacterium/classificação , Leite/microbiologia , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Bovinos , Chryseobacterium/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Feminino , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
8.
Curr Microbiol ; 76(10): 1152-1160, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31350573

RESUMO

A bacterial strain, 17JY9-4T, was isolated from a soil sample collected on Jeju Island, South Korea. Colonies grown on R2A agar are pale pink in color, and cells are Gram-stain negative, short, and rod-shaped. Analysis of 16S rRNA gene sequences identified this strain as a member of the genus Mucilaginibacter in the family Sphingobacteriaceae, with high levels of 16S rRNA sequence similarity shared with Mucilaginibacter lutimaris BR-3T (98.0%), Mucilaginibacter rigui WPCB133T (98.0%), Mucilaginibacter phyllosphaerae PP-F2F-G21T (97.0%), Mucilaginibacter amnicola TAPP7T (96.8%), and Mucilaginibacter soli R9-65T (96.7%). Growth of strain 17JY9-4T occurs at 10-30 °C, pH 6-8, and in the presence of 0-1.0% NaCl. The genomic G+C content is 44.38 mol%. The predominant respiratory quinone of the isolate is MK-7; the major fatty acids are summed feature 3 (C16:1ω7c/C16:1ω6c) (39.7%), iso-C15:0 (22.8%), iso-C17:0 3-OH (7.8%), and C16:0 (7.7%); and the major polar lipid is phosphatidylethanolamine. The phenotypic and chemotaxonomic data support the placement of strain 17JY9-4T within the genus Mucilaginibacter. However, the DNA-DNA relatedness between the isolate and M. rigui, M. lutimaris, M. phyllosphaerae, M. amnicola, and M. soli were 44.3 ± 3.0%, 38.6 ± 3.7%, 23.2 ± 2.9%, 21.9 ± 3.1%, and 18.6 ± 3.7%, respectively. The results of 16S rRNA gene sequence similarity analysis, DNA-DNA hybridization analysis, and the observed differentiating phenotypic properties from other closely related taxa clearly indicate that strain 17JY9-4T represents a novel species in the genus Mucilaginibacter, for which the name Mucilaginibacter terrigena sp. nov. is proposed. The type strain is 17JY9-4T (= KCTC 62294T = JCM 33049T).


Assuntos
Bacteroidetes/classificação , Bacteroidetes/fisiologia , Filogenia , Bacteroidetes/química , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Genoma Bacteriano/genética , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Microbiologia do Solo , Especificidade da Espécie , Vitamina K 2/análogos & derivados , Vitamina K 2/química
9.
J Agric Food Chem ; 67(33): 9423-9431, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31329442

RESUMO

A high-throughput lipid analysis method was established to comprehensively investigate the lipid profiles of three marine (Scomberomorus niphonius, Scophthalmus maximus, and Oncorhynchus keta) and one freshwater (Ctenopharyngodon idellus) fish species using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Over 700 molecular species from 12 major lipid subclasses were identified. Glycerolipids (73.7-85.6%) and phospholipids (PLs, 13.7-25.6%) were dominant components in total lipids. Polyunsaturated fatty acid PLs, such as phosphatidylethanolamine (PE, 16:0-22:6), PE (18:1-22:6), and phosphatidylcholine (16:0-22:6), were the major molecular species in PLs. The lipid composition of three marine fish (mainly C22:5) was significantly different from that in C. idellus (mainly C20:4 and C20:5). A unique long-chain base of sphingolipids was found in fish (mainly d19:3). These bioactive lipids were proposed to be potential biomarkers for distinguishing different fish species and evaluating nutritional values.


Assuntos
Lipídeos/química , Alimentos Marinhos/análise , Animais , Cromatografia Líquida de Alta Pressão , Cyprinidae , Ácidos Graxos Insaturados/química , Linguados , Espectrometria de Massas , Oncorhynchus keta , Fosfatidiletanolaminas/química , Fosfolipídeos/química , Atum
10.
Int J Syst Evol Microbiol ; 69(10): 3062-3067, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310197

RESUMO

A Gram-stain-negative, aerobic, motile and rod-shaped bacterial strain, designated OISW-25T, was isolated from seawater in Republic of Korea. Strain OISW-25T grew optimally at 25 °C and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain OISW-25T fell within the clade comprising the type strains of Colwellia species. Strain OISW-25T exhibited 16S rRNA gene sequence similarity values of 97.5, 97.2 and 97.1 % to the type strains of C. piezophila, C. maris and C. psychrerythraea, respectively, and of 93.6-96.6 % to the type strains of the other Colwellia species. The average nucleotide identity values between strain OISW-25T and C. piezophila ATCC BAA-637T and two non-type strains of C. psychrerythraea were 78.16-79.35 % and DNA-DNA relatedness value of strain OISW-25T with the type strain of C. maris was 17 %. The DNA G+C content of strain OISW-25T was 39.2 mol% (HPLC) or 38.7 mol% (genome data). Strain OISW-25T contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0 as the major fatty acids. The major polar lipids of strain OISW-25T were phosphatidylethanolamine and phosphatidylglycerol. Distinguished phenotypic properties, along with the phylogenetic and genetic distinctiveness, revealed that strain OISW-25T is distinct from Colwellia species. On the basis of the data presented, strain OISW-25T is considered to represent a novel species of the genus Colwellia, for which the name Colwellia ponticola sp. nov. is proposed. The type strain is OISW-25T (=KCTC 62426T=NBRC 113187T).


Assuntos
Alteromonadaceae/classificação , Filogenia , Água do Mar/microbiologia , Alteromonadaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , Fosfatidilgliceróis/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona/química
11.
J Food Sci ; 84(8): 2042-2049, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313292

RESUMO

It is important to inhibit the food-derived, potentially hazardous chemical glycated lipids by natural products. A model system was established and the products are identified to study the inhibitory mechanism of four types of catechin, resveratrol (RES), and the synthetic antioxidants butylated hydroxylanisole (BHA) and tert-butylhydroquinone (TBHQ) on the formation of carboxymethyl 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (CM-DPPE) by determining hydroxyl radical (OH·), Amadori-1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (Amadori-DPPE) and glyoxal (GO). The results show that the inhibitory rates of catechin and RES on the content of CM-DPPE in the model system are higher than those of BHA and TBHQ. There are at least two inhibitory mechanisms of antioxidants on CM-DPPE. (1) Antioxidants scavenge OH·, which blocks the process of Amadori-DPPE oxidation to form CM-DPPE. (2) Antioxidants trap GO, which blocks the reaction between GO and DPPE to form CM-DPPE. This research will reveal the inhibitory mechanisms of natural antioxidants on glycated lipids from the aspect of scavenging OH· and trapping GO. PRACTICAL APPLICATION: Food manufacturers should pay attention on the production of glycated lipids in food processing. This study will provide the theoretical basis for the use of natural products to inhibit the formation of food-derived glycated lipids. Natural products, such as catechin and resveratrol, can substitute chemical synthesis antioxidants, such as butylated hydroxylanisole and tert-butylhydroquinone, in food processing, which inhibit the formation of glycated lipids.


Assuntos
Hidroxianisol Butilado/química , Catequina/química , Hidroquinonas/química , Fosfatidiletanolaminas/química , Resveratrol/química , Antioxidantes/química , Oxirredução , Fosfatidiletanolaminas/antagonistas & inibidores
12.
Int J Nanomedicine ; 14: 4461-4474, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296986

RESUMO

Background: Vincristine is a potent therapeutic agent with well-defined activity against hematologic malignancies and solid tumors. It is a cell-cycle specific drug with concentration and exposure duration dependent activity. When used by liposomal delivery, it exhibits enhanced anti-tumor activity. However, vincristine liposome formulation in the clinic is supplied as a 3-vial-kit due to lacking sufficient stability. So it has to be prepared in situ prior to use through a multi-step process. Purpose: The purpose here is to develop a more stable and ready-to-use liposomal formulation for vincritstine in one vial. Patients and methods: A series of preparations were investigated based on sphingomyelin/cholesterol/PEG2000-DSPE lipid composition, with different drug/lipid (D/L) ratios (1/10, 1/5, 1/2), using an active sucrose octasulfate triethylamine salt gradient loading method. In this work, compared to generic vincristine sulfate liposome injection (GVM), the stability both in vivo and in vitro and efficacy in vivo of novel vincristine liposomes were investigated. Results: It was shown that the degradation of vincristine during 2-8°C storage was significantly decreased from 8.2% in 1 month (GVM) to 2.9% in 12 months (D/L ratio 1/5). The half-time for sphingomyelin/cholesterol/PEG2000-DSPE liposomes in vivo could be adjusted from 17.4 h (D/L ratio 1/10) to 22.7 h (D/L ratio 1/2) in rats, while the half-time for GVM was only 11.1 h. The increase in drug retention contributed to the lower in vivo toxicity. The antitumor efficacy was evaluated using a human melanoma tumor model and showed remarkable improvement compared to GVM. Conclusion: The study demonstrates that the new formulation with the drug/lipid ratio of 1/5 owns a higher encapsulation efficiency, better stability, lower toxicity and superior antitumor efficacy, which is screened out for further development.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Vincristina/química , Vincristina/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Colesterol/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos Wistar , Esfingomielinas/química , Vincristina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Food Chem ; 298: 125002, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260958

RESUMO

Lipids are only minor wheat flour constituents but play major roles in bread making (BM). Here, the importance of a well-balanced lipid population in BM was studied by applying a lipase from Fusarium oxysporum in the process. Monogalactosyldiacylglycerols and N-acyl phosphatidylethanolamines were the most accessible lipase substrates. Hydrolysis thereof into their corresponding lysolipids was largely if not entirely responsible for loaf volume increases upon lipase application. Degradation of endogenously present lipids and enzymatically released lysolipids caused loaf volume to decrease, confirming that an appropriate balance between different types of lipids is crucial in BM. For optimal dough gas cell stability, the level of lipids promoting lamellar mesophases and, thus, liquid condensed monolayers needs to be maximal while maintaining an appropriate balance between lipids promoting hexagonal I phases, non-polar lipids and lipids promoting hexagonal II or cubic phases.


Assuntos
Pão , Farinha , Lipase/metabolismo , Lipídeos/química , Triticum , Fermentação , Fusarium/enzimologia , Galactolipídeos/química , Galactolipídeos/metabolismo , Hidrólise , Lipase/química , Lisofosfolipídeos/química , Lisofosfolipídeos/metabolismo , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/metabolismo , Triticum/química , Triticum/metabolismo
14.
Int J Nanomedicine ; 14: 4353-4366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354265

RESUMO

Purpose: Gene therapy has become a promising remedy to treat disease by modifying the person's genes. The therapeutic potential of related tools such as CRISPR-Cas9 depends on the efficiency of delivery to the targeted cells. Numerous transfection reagents have been designed and lots of efforts have been devoted to develop carriers for this purpose. Therefore, the aim of the present study was to develop novel cholesterol-rich lipid-based nanoparticles to enhance transfection efficiency and serum stability. Materials and methods: We constructed two-, three- and four-component cationic liposomes (CLs) to evaluate the combined effect of cholesterol domain and DOPE (dioleoyl phosphatidylethanolamine), a fusogenic lipid, and the PEG (polyethylene glycol) moiety location inside or outside of the cholesterol domain on transfection efficiency and other properties of the particle. Lipoplex formation and pDNA (plasmid DNA) entrapment were assessed by gel retardation assay at different N/P ratios (3, 5, 7). Physicochemical characteristics, cytotoxicity, serum stability and endosomal escape capability of the lipoplexes were studied and transfection potential was measured by firefly luciferase assay. Next, HEK293 cell line stably expressing GFP was utilized to demonstrate the editing of a reporter through Cas9 and sgRNA plasmids delivery by the selected CL formula, which showed the highest transfection efficiency. Results: Among the designed CLs, the four-component formula [DOTAP (1,2-dioleoyl-3-trimethylammoniumpropane)/DOPE/cholesterol/Chol-PEG (cholesterol-polyethylene glycol)] showed the highest rate of transfection at N/P 3. Finally, transfection of Cas9/sgRNA by this formulation at N/P 3 resulted in 39% gene-editing efficiency to knockout GFP reporter. The results also show that this CL with no cytotoxicity effect can totally protect the plasmids from enzymatic degradation in serum. Conclusion: The novel PEGylated cholesterol domain lipoplex providing serum stability, higher transfection efficiency and endosomal release can be used for in vivo Cas9/sgRNA delivery and other future gene-therapy applications.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Colesterol/química , Edição de Genes , Nanopartículas/química , Transfecção/métodos , Cátions/química , Morte Celular , Colesterol/análogos & derivados , Ensaio de Desvio de Mobilidade Eletroforética , Endossomos/metabolismo , Ácidos Graxos Monoinsaturados/química , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Lipossomos/química , Tamanho da Partícula , Fosfatidiletanolaminas/química , Plasmídeos/metabolismo , Polietilenoglicóis/química , Compostos de Amônio Quaternário/química , RNA Guia/metabolismo , Eletricidade Estática
15.
Adv Mater ; 31(32): e1900795, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222856

RESUMO

Biomimetic camouflage, i.e., using natural cell membranes for drug delivery, has demonstrated advantages over synthetic materials in both pharmacokinetics and biocompatibility, and so represents a promising solution for the development of safe nanomedicine. However, only limited efforts have been dedicated to engineering such camouflage to endow it with optimized or additional properties, in particular properties critical to a "smart" drug delivery system, such as stimuli-responsive drug release. A pH-responsive biomimetic "platesome" for specific drug delivery to tumors and tumor-triggered drug release is described. This platesome nanovehicle is constructed by merging platelet membranes with functionalized synthetic liposomes and exhibits enhanced tumor affinity, due to its platelet membrane-based camouflage, and selectively releases its cargo in response to the acidic microenvironment of lysosomal compartments. In mouse cancer models, it shows significantly better antitumor efficacy than nanoformulations based on a platesome without pH responsiveness or those based on traditional pH-sensitive liposomes. A convenient way to incorporate stimuli-responsive features into biomimetic nanoparticles is described, demonstrating the potential of engineered cell membranes as biomimetic camouflages for a new generation of biocompatible and efficient nanocarriers.


Assuntos
Antineoplásicos/administração & dosagem , Materiais Biomiméticos/química , Plaquetas/química , Membrana Celular/química , Doxorrubicina/administração & dosagem , Lipossomos/química , Nanopartículas/química , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Feminino , Humanos , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Fosfatidiletanolaminas/química , Distribuição Tecidual
16.
Int J Nanomedicine ; 14: 3645-3667, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190817

RESUMO

Background: Neo-adjuvant chemotherapy is an effective strategy for improving treatment of breast cancers. However, the efficacy of this treatment strategy is limited for treatment of triple negative breast cancer (TNBC). Gene therapy may be a more effective strategy for improving the prognosis of TNBC. Methods: A novel 25 nucleotide sense strand of miRNA was designed to treat TNBC by silencing the Slug gene, and encapsulated into DSPE-PEG2000-tLyp-1 peptide-modified functional liposomes. The efficacy of miRNA liposomes was evaluated on invasive TNBC cells and TNBC cancer-bearing nude mice. Furthermore, functional vinorelbine liposomes were constructed to investigate the anticancer effects of combined treatment. Results: The functional miRNA liposomes had a round shape and were nanosized (120 nm). Functional miRNA liposomes were effectively captured by TNBC cells in vitro and were target to mitochondria. Treatment with functional liposomes silenced the expression of Slug and Slug protein, inhibited the TGF-ß1/Smad pathway, and inhibited invasiveness and growth of TNBC cells. In TNBC cancer-bearing mice, functional miRNA liposomes exerted a stronger anticancer effect than functional vinorelbine liposomes, and combination therapy with these two formulations resulted in nearly complete inhibition of tumor growth. Preliminary safety evaluations indicated that the functional miRNA liposomes did not affect body weight or cause damage to any major organs. Furthermore, the functional liposomes significantly increased the half-life of the drug in the blood of cancer-bearing nude mice, and increased drug accumulation in breast cancer tissues. Conclusion: In this study, we constructed novel functional miRNA liposomes. These liposomes silenced Slug expression and inhibited the TGF-ß1/Smad pathway in TNBC cells, and enhanced anticancer efficacy in mice using combined chemotherapy. Hence, the present study demonstrated a promising strategy for gene therapy of invasive breast cancer.


Assuntos
Inativação Gênica , MicroRNAs/metabolismo , Nanopartículas/química , Tamanho da Partícula , Fatores de Transcrição da Família Snail/genética , Neoplasias de Mama Triplo Negativas/terapia , Animais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Lipossomos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
17.
Pharm Res ; 36(8): 121, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31214786

RESUMO

PURPOSE: ß-elemene and cisplatin combined chemotherapy currently is one of the most important settings available for lung cancer therapy in China. However, the clinical outcome is limited by their pharmacokinetic drawbacks. On the other hand, most of nanomedicines have failed in clinical development due to the huge differences between heterogeneous clinical tumor tissues and homogenous cell-derived xenografts. In this work, we fabricated a ß-elemene and cisplatin co-loaded liposomal system to effectively treat lung cancer. METHOD: In vitro cytotoxicity of co-loaded liposomes was studied by MTT, trypan and Hoechst/PI staining, and western blot in A549, A549/DDP, and LCC cells. In vivo antitumor efficacy was evaluated in cell-derived and clinically relevant patient-derived xenografts. RESULTS: Co-loaded liposomes were more cytotoxic to cancer cells, especially than the combination of single-loaded liposomes, benefiting from their simultaneous drug internalization and release. As a result, they exhibited desirable therapeutic outcome in both cell-derived and patient-derived xenografts. CONCLUSION: ß-elemene and cisplatin co-loaded liposomes are a clinically promising candidate for effective lung cancer therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cisplatino/farmacocinética , Lipossomos/química , Neoplasias Pulmonares/tratamento farmacológico , Sesquiterpenos/farmacocinética , Células A549 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Cisplatino/administração & dosagem , Composição de Medicamentos , Liberação Controlada de Fármacos , Xenoenxertos , Humanos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Sesquiterpenos/administração & dosagem , Distribuição Tecidual
18.
Int J Syst Evol Microbiol ; 69(9): 2750-2754, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31241445

RESUMO

A Gram-stain-negative, aerobic, non-motile and rod-shaped or filamentous bacterial strain, designated SHSM-M15T, was isolated from a salt marsh at Siheung in Republic of Korea and identified by polyphasic taxonomic study. Strain SHSM-M15T grew optimally at 25 °C, at pH 7.0-8.0 and in the presence of 1.0-2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain SHSM-M15T clusters with the type strain of Ancylomarina subtilis, showing 16S rRNA gene sequence similarity of 97.8 %. Strain SHSM-M15T had 16S rRNA gene sequence similarities of less than 93.7 % with the type strains of other recognised species. Strain SHSM-M15T contained MK-7 as the predominant menaquinone and iso-C15 : 0, iso-C15 : 0 3-OH and anteiso-C15 : 0 as the major fatty acids. The major polar lipid detected in strain SHSM-M15T was phosphatidylethanolamine. The DNA G+C content of strain SHSM-M15T from genomic sequence was 36.6 %. Mean DNA-DNA relatedness value between strain SHSM-M15T and the type strain of A. subtilis was 18 % and the average nucleotide identity value between strain SHSM-M15T and the type strain of A. subtilis was 87.98 %. The phylogenetic and genetic data and differential phenotypic properties indicated that strain SHSM-M15T is separated from A. subtilis. On the basis of the polyphasic data presented, strain SHSM-M15T is considered to represent a novel species of the genus Ancylomarina, for which the name Ancylomarina salipaludis sp. nov. is proposed. The type strain is SHSM-M15T (=KACC 19862T=NBRC 113749T).


Assuntos
Bacteroidetes/classificação , Filogenia , Água do Mar/microbiologia , Áreas Alagadas , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
19.
Int J Syst Evol Microbiol ; 69(9): 2781-2786, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31246165

RESUMO

A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, MRS2T, was isolated from an intestine of Nile tilapia (Oreochromisniloticus) collected from the Republic of Korea. Strain MRS2T grew optimally at 30 °C and in the presence of 0-2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain MRS2T clustered with the type strains of Empedobacter species. It exhibited the highest 16S rRNA gene sequence similarity (98.5 %) to the type strain of Empedobacter falsenii and sequence similarities of 97.4-97.6 % to the type strains of two other Empedobacter species. Strain MRS2T contained MK-6 as the predominant ubiquinone and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C17 : 0 3-OH and iso-C15 : 0 as the major fatty acids. The major polar lipids of strain MRS2T were phosphatidylethanolamine, one unidentified lipid and one unidentified aminolipid. The DNA G+C contents of strain MRS2T were 32.2 mol% or 30.65 mol%. Strain MRS2T exhibited DNA-DNA relatedness values of 12-20 % to the type strains of Empedobacter falsenii, Empedobacter brevis and Empedobacter stercoris. The average nucleotide identity values between strain MRS2T and five strains of E. falsenii and E. brevis were 84.8-91.0 %. The phylogenetic, genetic and differential phenotypic properties indicated that strain MRS2T is separated from Empedobacter species. On the basis of the data presented here, strain MRS2T is considered to represent a novel species of the genus Empedobacter, for which the name Empedobactertilapiae sp. nov. is proposed. The type strain is MRS2T (=KCTC 62904T=NBRC 113550T).


Assuntos
Ciclídeos/microbiologia , Flavobacteriaceae/classificação , Intestinos/microbiologia , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Flavobacterium/genética , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
20.
Biol Pharm Bull ; 42(6): 996-1003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155597

RESUMO

A small interfering RNA (siRNA) delivery system using dioleylphosphate-diethylenetriamine conjugate (DOP-DETA)-based liposomes (DL) was assessed for systemic delivery of siRNA to tumors. DL carrying siRNA capable of inducing efficient gene silencing with low doses of siRNA were modified with polyethylene glycol (PEG-DL/siRNA) for systemic injection of siRNA. The biodistribution of DL and siRNA in the PEG-DL/siRNA was studied by using radiolabeled DL and fluorescence-labeled siRNA, respectively. DL in the PEG-DL/siRNA showed a high retention in the plasma, accumulation in the tumor, and low accumulation in the liver and spleen after intravenous injection. The in vivo effects of PEGylation were observed only when distearoylphosphatidylethanolamine (DSPE)-PEG but not distearoylglycerol (DSG)-PEG were used. This result suggests that the electrostatic interaction between lipid molecules on the surface of PEG-DL/siRNA was a critical determinant for the in vivo effect of PEGylation. When PEG-DL/siRNA (0.1 mg/kg siRNA) was intravenously injected into tumor-bearing mice, in vivo gene silencing was observed in subcutaneous tumors. These results indicate that PEG-DL/siRNA designed in this study is a promising formulation for systemic use of siRNA.


Assuntos
Neoplasias/genética , Fosfatidiletanolaminas/administração & dosagem , Polietilenoglicóis/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Animais , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Inativação Gênica , Vetores Genéticos , Humanos , Lipossomos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/farmacocinética , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/sangue , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacocinética , Baço/metabolismo , Distribuição Tecidual
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