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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 581-590, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37654138

RESUMO

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and ß diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and ß diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.


Assuntos
Microbioma Gastrointestinal , Neoplasias Gástricas , Humanos , Isobutiratos , Qualidade de Vida , Neoplasias Gástricas/terapia , Imunoterapia , Resultado do Tratamento
2.
Nanomedicine ; 35: 102398, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33901646

RESUMO

Bacterial membrane vesicles (MVs) are particles secreted by bacteria with diameter of 20-400 nm. The pathogen-associated molecular patterns (PAMPs) present on the surface of MVs are capable of activating human immune system, leading to non-specific immune response and specific immune response. Due to the immunostimulatory properties and proteoliposome nanostructures, MVs have been increasingly explored as vaccines or delivery systems for the prevention and treatment of bacterial infections. Herein, the recent progresses of MVs for antibacterial applications are reviewed to provide an overview of MVs vaccines and MVs-related delivery systems. In addition, the safety issues of bacterial MVs are discussed to demonstrate their potential for clinical translation. In the end of this review, the challenges of bacterial MVs as vaccines and delivery systems for clinical applications are highlighted with the purpose of predicting future research directions in this field.


Assuntos
Bactérias , Infecções Bacterianas , Proteínas de Bactérias , Vacinas Bacterianas , Membrana Celular , Nanoestruturas , Bactérias/química , Bactérias/imunologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/uso terapêutico , Vacinas Bacterianas/química , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Membrana Celular/química , Membrana Celular/imunologia , Humanos , Lipossomos , Nanoestruturas/química , Nanoestruturas/uso terapêutico
3.
Pharm Dev Technol ; 24(4): 395-401, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30422727

RESUMO

Recombinant human growth hormone (rhGH) therapy must be administered as a daily injection due to its short half-life. To achieve sustained release of rhGH, the preparation of rhGH-loaded PLGA microspheres was investigated, and the influence of various factors on encapsulation efficiency was tested, including rhGH concentration, the ratio of internal phase to organic phase, stirring speed, PVA concentration, surrounding pH value, and the type of emulsifier and organic solvent. A pharmacokinetic study was performed by subcutaneous administration to explore the sustained release effect. It was found that rhGH-loaded PLGA microspheres were prepared with a narrow size distribution, and optimization of the formulation could enhance encapsulation efficiency. FTIR analysis indicated that the activity of rhGH was maintained after encapsulation. The pharmacokinetic behavior of rhGH solutions was consistent with a two-compartment model, which showed fast absorption and distribution. RhGH-loaded PLGA microspheres achieved a higher bioavailability and a long-term effective concentration by controlling the release, and PLGA 50/50 demonstrated favorable AUC compared with PLGA 75/25. Nevertheless, the higher bioavailability of rhGH-loaded PLGA microspheres lacking Span 80 did not predicate better sustained release behavior, indicating that further investigation is needed to explore the use of bioavailability as the standard in evaluating the sustained release characteristics and in vivo behavior of microspheres.


Assuntos
Hormônio do Crescimento Humano/síntese química , Hormônio do Crescimento Humano/farmacocinética , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/síntese química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Animais , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/síntese química , Proteínas Recombinantes/farmacocinética
4.
Biomaterials ; 309: 122573, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38677222

RESUMO

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) gene editing has attracted extensive attentions in various fields, however, its clinical application is hindered by the lack of effective and safe delivery system. Herein, we reported a cationic micelle nanoparticle composed of cholesterol-modified branched small molecular PEI (PEI-CHO) and biodegradable PEG-b-polycarbonate block copolymer (PEG-PC), denoted as PEG-PC/PEI-CHO/pCas9, for the CRISPR/Cas9 delivery to realize genomic editing in cancer. Specifically, PEI-CHO condensed pCas9 into nanocomplexes, which were further encapsulated into PEG-PC nanoparticles (PEG-PC/PEI-CHO/pCas9). PEG-PC/PEI-CHO/pCas9 had a PEG shell, protecting DNA from degradation by nucleases. Enhanced cellular uptake of PEG-PC/PEI-CHO/pCas9 nanoparticles was observed as compared to that mediated by Lipo2k/pCas9 nanoparticles, thus leading to significantly elevated transfection efficiency after escaping from endosomes via the proton sponge effect of PEI. In addition, the presence of PEG shell greatly improved biocompatibility, and significantly enhanced the in vivo tumor retention of pCas9 compared to PEI-CHO/pCas9. Notably, apparent downregulation of GFP expression could be achieved both in vitro and in vivo by using PEG-PC/PEI-CHO/pCas9-sgGFP nanoparticles. Furthermore, PEG-PC/PEI-CHO/pCas9-sgMcl1 induced effective apoptosis and tumor suppression in a HeLa tumor xenograft mouse model by downregulating Mcl1 expression. This work may provide an alternative paradigm for the efficient and safe genome editing in cancer.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Micelas , Nanopartículas , Edição de Genes/métodos , Nanopartículas/química , Sistemas CRISPR-Cas/genética , Animais , Humanos , Neoplasias/terapia , Neoplasias/genética , Camundongos Nus , Camundongos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Polímeros/química
5.
J Fluoresc ; 23(5): 1053-63, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23715936

RESUMO

A variety of carboxylates were recognized using poly(9-aminofluorene) (P9AF) in the HEPES buffer (pH 7.4), and a proposed possible mechanism was proposed as following. The intermolecular hydrogen bonding interactions resulted in electron transfer between P9AF and carboxylates. P9AF was facilely electrosynthesized in boron trifluoride diethyl etherate and could be used as an efficient fluorescent sensing material for the detection of AcO(-). On binding to AcO(-), fluorescence quenching of P9AF was demonstrated by a maximum 80% reduction in the fluorescence intensity, while no obvious fluorescence change could be observed in the presence of some other common anions. Some different carboxylates could be recognized at different levels by P9AF. Substituent groups in carboxylates could affect the intermolecular interaction between carboxylates and P9AF. These could be explained by a possible mechanism that hydrogen bonding was the main way of intermolecular interactions between P9AF and carboxylates, which was further confirmed by absorption spectra monitoring and density functional calculations. The significant advantage of this strategy is that it does not require a prequenching procedure and the polymer can be used directly for analyte detection.


Assuntos
Ácidos Carboxílicos/análise , Técnicas Eletroquímicas , Fluorenos/química , Fluorescência , Polímeros/química , Elétrons , Fluorenos/síntese química , Ligação de Hidrogênio , Polímeros/síntese química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Água/química
6.
Adv Healthc Mater ; 12(24): e2202903, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37523195

RESUMO

Antibiotic colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. Emergence of colistin resistance in microbes is a critical challenge. Herein, curcumin is discovered, for the first time, to reverse the resistance phenotype of colistin-resistant bacteria via a checkerboard assay. For the co-delivery of curcumin and colistin, negatively charged poly(ethylene glycol)-functionalized liposomes encapsulating both drugs (Lipo-cc) are prepared. Killing kinetics and live/dead assays confirm the antibacterial activity of Lipo-cc against colistin-resistant bacteria, which is more potent than that of the free curcumin and colistin combination. Mechanistical studies reveal that Lipo-cc restores the affinity of colistin for the bacterial membrane and improves the uptake of curcumin, which leads to reduced efflux pump activity, achieving a synergistic effect of colistin and curcumin. At the effective antibacterial dose, Lipo-cc does not exhibit any toxicity. The therapeutic efficacy of Lipo-cc is further demonstrated in an intestinal bacterial infection model induced with colistin-resistant Escherichia coli. Lipo-cc reduces the bacterial burden with over 6-log reduction and alleviated inflammation caused by infection. Importantly, unlike colistin, Lipo-cc does not affect the homeostasis of the intestinal flora. Taken together, Lipo-cc successfully overcame colistin resistance, indicating its potential for the treatment of colistin-resistant bacterial infections.


Assuntos
Curcumina , Infecções por Bactérias Gram-Negativas , Humanos , Colistina/farmacologia , Colistina/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Lipossomos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Escherichia coli , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
7.
Analyst ; 137(19): 4577-83, 2012 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-22900263

RESUMO

A new ferrocene derivative (1-[(4-amino) phenylethynyl]ferrocene, Fc-NH(2)) was synthesized for the first time. The ferrocene derivative molecule contained the phenylethynyl skeleton, ferrocene and amino groups with excellent electrochemical properties. The graphene/Fc-NH(2) nanocomposite was prepared by mixing graphene solution and Fc-NH(2) solution in one pot and the nanocomposite was utilized to construct a Nafion/graphene/Fc-NH(2) modified glassy carbon electrode (GCE). The ferrocene derivative immobilized on the graphene can enhance the charge-transport ability of the nanocomposite, stabilize the graphene and prevent the leakage of ferrocene. The detection signal of dopamine (DA) was significantly amplified on the Nafion/graphene/Fc-NH(2)/GCE. It was experimentally demonstrated that the signal enhancement results from the synergy amplification effect of graphene and the Fc-NH(2). The oxidation peak currents of DA were linearly related to the concentrations in the range of 5 × 10(-8) to 2 × 10(-4) M with the detection limit of 20 nM in the absence of uric acid (UA) and ascorbic acid (AA). In the presence of 10(-3) M AA and 10(-4) M UA, the linear response range was 1 × 10(-7) to 4 × 10(-4) M, and the detection limit was 50 nM at S/N = 3. Using the proposed Nafion/Fc-NH(2)/graphene/GCE, DA was successfully determined in real samples with the standard addition method.


Assuntos
Técnicas Biossensoriais , Dopamina/análise , Técnicas Eletroquímicas , Compostos Ferrosos/química , Grafite/química , Nanocompostos/química , Ácido Ascórbico/química , Eletrodos , Polímeros de Fluorcarboneto/química , Metalocenos , Oxirredução , Ácido Úrico/química
8.
J Mater Chem B ; 9(8): 2016-2024, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33544115

RESUMO

Nanomaterial-based artificial enzyme mimetics have attracted increasing attention because of their robust stability, adjustable activity, and cost-effectiveness. In this study, we developed a simple and effective method for the synthesis of highly dispersed ultrafine PdCo alloys with peroxidase- and catalase-like activities. The aberration-corrected transmission electron microscopy analysis verified that the cyanogel precursor in the mesoporous silica nanospheres (MSNs) was converted to PdCo alloy in NH3 at a high temperature. The PdCo alloy was homogenously distributed in MSNs as ultrafine and monodispersed particles. By selectively removing the Co species from the binary alloy through an acid-leaching approach, the role of each component in the enzyme-like mimetics was systematically studied. Using glutathione (GSH) as the model analyte, the potential application of PdCo@MSNs in GSH detection from complex cell media was confirmed via colorimetric assay. The ultrafine alloy size, double mimetic activities, and abundant loading space of PdCo@MSNs make them promising not only in clinical diagnosis but also in overcoming hypoxia-induced photodynamic therapy resistance in tumor treatment.


Assuntos
Ligas/química , Materiais Biomiméticos/química , Catalase/metabolismo , Desenho de Fármacos , Nanopartículas/química , Peroxidase/metabolismo , Dióxido de Silício/química , Cobalto/química , Glutationa/análise , Paládio/química , Porosidade , Temperatura
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