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1.
ACS Appl Mater Interfaces ; 13(33): 38979-38989, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433249

RESUMO

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.


Assuntos
Antibacterianos/química , Verde de Indocianina/química , Nanocápsulas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/radioterapia , Células A549 , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Masculino , Metacrilatos/química , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/efeitos dos fármacos
2.
Biomacromolecules ; 22(9): 3704-3717, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34380309

RESUMO

Bacterial keratitis is a serious bacterial infection of the cornea that can cause sight loss in severe cases because of the sharp decline of efficacious antibiotics. Herein, a targeted photosensitizer based on BODIPY severing as a photobactericidal agent was developed for treating bacterial keratitis. The water solubility of the material was as high as 10 mg/mL, which was attributable to the introduction of pathogen-targeting galactose and fucose. The photosensitizer was able to preferentially bind Pseudomonas aeruginosa instead of mammalian cells and trigger the aggregation of bacteria, which ultimately facilitated effective pathogen ablation upon the generation of reactive oxygen species (ROS) via laser irradiation. Photoexcited targeted photosensitizers can promote wound healing by eradicating P. aeruginosa in rat eyes and reducing the inflammatory response, thus exhibiting the significant therapeutic effect on bacterial keratitis. We also performed molecular level mechanistic studies using the unique field-induced droplet ionization mass spectrometry methodology and confirmed that the generated ROS were mainly singlet oxygen that caused lipid peroxidation (Type II mechanism). We anticipate that the targeted photosensitizer will have great potential in the application of clinical photodynamic therapy to ocular infection.


Assuntos
Ceratite , Fotoquimioterapia , Animais , Ceratite/tratamento farmacológico , Luz , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Pseudomonas aeruginosa
3.
ACS Appl Mater Interfaces ; 13(29): 33790-33801, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34254513

RESUMO

Hypoxia, a common characteristic of bacterial infections, is known to be closely associated with the emergence of multidrug-resistant bacteria, which hastens the need to develop advanced microbicides and antibacterial techniques. Photodynamic therapy is a promising strategy to reduce bacterial antibiotic resistance and employs photosensitizers, excitation light sources, and sufficient oxygen to generate toxic reactive oxygen species (ROS). The inherent limitation of PDT is that the generation of ROS is restricted by the hypoxic microenvironment in infection sites. Here, an oxygen self-supplying nanotherapeutic is developed to enhance antibacterial activity against multidrug-resistant bacteria on the basis of fluorinated boron dipyrromethene (BODIPY)-based glycomimetics. The nanotherapeutic not only could capture the bacteria efficiently but also was able to act as an oxygen carrier to relieve the hypoxic microenvironment of bacterial infections, thus achieving enhanced PDT efficacy. In a Pseudomonas aeruginosa infection of a rat cornea, typical administration of the nanotherapeutic decreased the infiltrate and showed a faster healing capacity in comparison with BODIPY-based glycomimetics. Self-supplying oxygen nanotherapeutics that relieve the hypoxic microenvironment and interfere with bacterial colonization have been shown to be a promising candidate for the management of drug-resistant microbial keratitis.

4.
J Mater Chem B ; 9(17): 3689-3695, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33861292

RESUMO

Exogenous reactive oxygen species (ROS) generation is a promising antibacterial strategy. The short diffusion distance coupled with the transient existence of ROS restrict their precise release at inflammation sites, so it is imperative to regulate the reactive sites of ROS donors. In this work, we developed a glycomimetic-decorated fluorescent nanobiocide to mediate the release of ROS generated from CuInS/ZnS quantum dots. The introduction of glycomimetics innovatively improved the biocompatibility of the hydrophobic quantum dots, allowing pathogenic bacteria to be targeted. The functionalized CuInS/ZnS quantum dots allowed simultaneous fluorescent reporting and sterilization under 660 nm illumination. Moreover, the nanobiocide can serve as a cell-binding glue causing bacterial aggregation, disrupting bacterial adhesion to host cells and inhibiting biofilm formation. Collectively, this work indicated the far-reaching future of ROS-generating biomimetic design for multifunctional nanobiocides to combat bacterial infections.


Assuntos
Antibacterianos/química , Corantes Fluorescentes/química , Infecções/tratamento farmacológico , Pontos Quânticos/química , Células 3T3 , Adesivos/química , Animais , Antibacterianos/farmacologia , Biofilmes , Cobre/química , Eritrócitos , Humanos , Índio/química , Camundongos , Imagem Óptica , Pseudomonas aeruginosa/efeitos dos fármacos , Esterilização , Sulfetos/química , Propriedades de Superfície , Compostos de Zinco/química
5.
J Mater Chem B ; 9(5): 1364-1369, 2021 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-33458729

RESUMO

Obstinate infections caused by drug-resistant bacteria severely threaten human health. And the emergence of multidrug-resistant bacteria increases the morbidity and mortality of patients, thus necessitating the development of innovative or alternative therapeutics. Here, a light-activated nanotherapeutic with broad-spectrum bacterial recognition is established as an antibiotic-free therapeutic agent against pathogens. The nanotherapeutic with external phenylboronic acid-based glycopolymers increases the stability and biocompatibility and shows the ability of bacterial recognition. Once irradiated with near-infrared light, this nanotherapeutic with high photothermal conversion efficiency disrupts the cytoplasmic membrane, thus killing bacterial cells. Importantly, it also eliminates the biofilms formed by both drug-resistant Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus) effectively. Thus, this antibiotic-free nanotherapeutic with hypotoxicity offers a promising approach to fight increasingly serious antimicrobial resistance.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Bactérias Gram-Positivas/patogenicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanotecnologia/métodos , Antibacterianos/farmacologia , Humanos
6.
J Agric Food Chem ; 68(39): 10550-10559, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32886503

RESUMO

Herbicide safeners enhance herbicide detoxification in crops without affecting target weed sensitivity. To enhance crop tolerance to the toxicity-related stress caused by the herbicide acetochlor (ACT), a new class of substituted phenyl isoxazole derivatives was designed by an intermediate derivatization method as herbicide safeners. Microwave-assisted synthesis was used to prepare the phenyl isoxazole analogues, and all of the structures were confirmed via IR, 1H NMR, 13C NMR, and HRMS. Compound I-1 was further characterized by X-ray diffraction analysis. Bioassay results showed that most of the obtained compounds provided varying degrees of safening against ACT-induced injury by increasing the corn growth recovery, glutathione content, and glutathione S-transferase activity. In particular, compound I-20 showed excellent safener activity against ACT toxicity, comparable to that of the commercial safener benoxacor. Gaussian calculations have been performed and the results indicated that the nucleophilic ability of compound I-20 is higher than that of benoxacor, thus the activity is higher than that of benoxacor. These findings demonstrate that phenyl isoxazole derivatives possess great potential for protective management in cornfields.


Assuntos
Herbicidas/síntese química , Isoxazóis/química , Desenho de Fármacos , Herbicidas/química , Herbicidas/farmacologia , Isoxazóis/farmacologia , Oxazinas/química , Oxazinas/farmacologia , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/crescimento & desenvolvimento
7.
Medicine (Baltimore) ; 96(37): e7925, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28906372

RESUMO

BACKGROUND: The purpose of this study was to compare the efficacy and safety of laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct (CBD) stones exploration (LCBDE) with LC plus endoscopic sphincterotomy (EST) in the treatment of patients with gallstones and CBD stones. METHODS: The authors searched PubMed, Web of Science, and Embase to identify relevant studies. Risk ratios (RRs) were pooled to compare stone clear, retained stone, conversion to other procedures, and complications. Weighted mean differences (WMDs) were pooled to compare operative time, and length of hospital stay. A fixed-effects model or random-effects model was used to pool the estimates, according to the heterogeneity among the included studies. RESULTS: A total of 11 randomized controlled trials (RCTs) involving 1663 patients were included in this meta-analysis. The pooled estimate suggested that LC-LCBDE had comparable effects with LC-EST in terms of CBD stone clear rate (RR = 1.02, 95% CI: 0.95, 1.09; P = .583), retained stones rate (RR = 1.27, 95% CI: 0.51, 3.19; P = .607), and length of hospital stay (WMD = -0.96 days, 95% CI: -2.20, 0.28). In addition, LC-LCBDE was associated with significantly higher conversion rate (RR = 1.59, 95% CI: 1.08, 2.35; P = .019) and less operative time (WMD = -11.55 minutes, 95% CI: -16.68, -6.42; P < .001) than LC-EST. The incidence of complications was not significant difference between the 2 surgical approaches (RR = 1.07, 95% CI: 0.86, 1.34; P = .550). CONCLUSION: Based on the current evidence, both LC-LCBDE and LC-EST were highly effective in detecting and removing CBD stones and were equivalent in complications. However, our results might be biased by the limitations. Large-scale well-designed RCTs are needed to confirm our findings.


Assuntos
Colecistectomia Laparoscópica , Colecistolitíase/cirurgia , Cálculos Biliares/cirurgia , Esfinterotomia Endoscópica , Colecistectomia Laparoscópica/efeitos adversos , Colecistolitíase/complicações , Cálculos Biliares/complicações , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Esfinterotomia Endoscópica/efeitos adversos , Resultado do Tratamento
8.
Tumour Biol ; 37(10): 13983-13993, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27492459

RESUMO

Cysteine-rich protein 61 (CYR61) and metastasis associated in colon cancer (MACC1) protein promoted human colorectal cancer (CRC) cell metastasis and closely related to the patient's prognosis in colorectal cancer. The purpose of this article is to investigate whether CYR61 and MACC1 can serve as dual potential targets for gene therapy of human CRC. In this study, microRNA (miRNA) targeting for both CYR61 and MACC1 was used to investigate the mechanism and therapeutic effects for CRC cells and mice with CRC. We observed that silencing miRNA for CYR61 and MACC1 inhibited the epithelial-mesenchymal transition (EMT) process, and co-treatment strengthened this effect. MTT assay showed that the growth of colorectal tumor cells was decreased due to miRNA treatment. Apoptosis assay revealed that miRNA for CYR61 and MACC1 promoted CRC cells apoptotic. The animals' study results showed that the expression levels of CYR61 and MACC1 were significantly decreased after miRNA-100 and miRNA-143 treatment, respectively. The expression levels of apoptosis-promoting protein were increased significantly after treatment with miRNA-100 and miRNA-143, which suggested that both miRNA-100 and miRNA-143 may induce apoptosis by mitochondria-dependent pathway. In addition, metastasis and invasion assays showed that miRNA-100 and miRNA-143 treatment inhibited obviously migratory and invasive abilities of CRC cells. Furthermore, our data also showed that the tumor growth was significantly inhibited and survival rate of tumor-bearing mice was greatly improved by common treatments of miRNA-100 and miRNA-143. In conclusion, the abilities of apoptosis, metastasis, and invasion in CRC tumor cells were significantly suppressed by miRNA-100 and miRNA-143 targeting CYR61 and MACC1, respectively. As a result, CYR61 and MACC1 may serve as potential targets for gene therapy in human CRC treatments.


Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteína Rica em Cisteína 61/metabolismo , MicroRNAs/genética , Fatores de Transcrição/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Western Blotting , Movimento Celular , Neoplasias Colorretais/metabolismo , Proteína Rica em Cisteína 61/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Zhonghua Yi Xue Za Zhi ; 88(29): 2041-4, 2008 Jul 29.
Artigo em Chinês | MEDLINE | ID: mdl-19080431

RESUMO

OBJECTIVE: To investigate the effects of preoperative carbohydrate loading and new fasting protocol treatment on the postoperative changes in serum tumor necrosis factor receptor1 (sTNFR1), sTNFR2, and insulin resistance (IR) in patients of colon carcinoma. METHODS: 51 patients of colon carcinoma were randomly divided into 2 groups: carbohydrate-rich beverage group (n = 24), undergoing fasting 6 h before operation and water deprivation 2 h before operation, receiving carbohydrate-rich beverage 3 h before operation and fluid therapy with glucose post-operatively, and placebo group (n = 27) undergoing routine fasting and water deprivation pre-operatively. Peripheral blood samples were collected before, during, and 1, 4, and 7 d after operation. ELISA was used to detect the sTNFR1 and sTNFR2 of preoperative, 1, 4, 7day Insulin sensitivity index (S1) was calculated. RESULTS: The S(1) levels at different post-operational time points of the treatment group were not significantly different from those preoperatively (all P > 0.05), while the S(1) levels of the control group decreased significantly compared to those before operation (all P < 0.05). The sTNFR1 level of the treatment group increased postoperatively and did not return to the pre-operative level 7 d after operation(all P < 0.05). The sTNFR1 levels at different post-operative time points of the treatment group were all significantly higher than those of the control group (all P < 0.05). The sTNFR2 level of the treatment group decreased postoperatively and did not return to the pre-operative level 7d after operation (all P < 0.05). The sTNFR2 levels at different post-operative time points of the treatment group were all significantly lower than those of the control group (all P < 0.05). There was not significant differences in the sTNFR1 level in the control group before and after operation (all P > 0.05). The time to first flatus and days staying in hospital of the treatment group were (77 +/- 15) hours and (11 +/- 1.2) gays respectively, both significantly shorter than those of the control group [(86 +/- 13) hours and (15.1 +/- 3.8) days respectively, both P < 0.05]. CONCLUSION: Preoperative carbohydrate loading and new fasting protocol reduce the degree and course of IR, increase the sTNFR1 level, and decrease the sTNFR2 level and days of staying in hospital.


Assuntos
Neoplasias do Colo/sangue , Carboidratos da Dieta/administração & dosagem , Resistência à Insulina , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto , Idoso , Bebidas , Glicemia/metabolismo , Neoplasias do Colo/cirurgia , Ensaio de Imunoadsorção Enzimática , Jejum , Feminino , Intolerância à Glucose , Humanos , Insulina/sangue , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos
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