RESUMO
Rhynchophorus ferrugineus is a quarantine pest that mainly damages plants in tropical regions, which are essential economic resources. Cry3Aa has been used to control coleopteran pests and is known to be toxic to R. ferrugineus. The binding of the Cry toxin to specific receptors on the target insect plays a crucial role in the toxicological mechanism of Cry toxins. However, in the case of R. ferrugineus, the nature and identity of the receptor proteins involved remain unknown. In the present study, pull-down assays and mass spectrometry were used to identify two proteins of aminopeptidase N proteins (RfAPN2a and RfAPN2b) in the larval midguts of R. ferrugineus. Cry3Aa was able to bind to RfAPN2a (Kd = 108.5 nM) and RfAPN2b (Kd = 68.2 nM), as well as midgut brush border membrane vesicles (Kd = 482.5 nM). In silico analysis of both RfAPN proteins included the signal peptide and anchored sites for glycosyl phosphatidyl inositol. In addition, RfAPN2a and RfAPN2b were expressed in the human embryonic kidney 293T cell line, and cytotoxicity assays showed that the transgenic cells were not susceptible to activated Cry3Aa. Our results show that RfAPN2a and RfAPN2b are Cry3Aa-binding proteins involved in the Cry3Aa toxicity of R. ferrugineus. This study deepens our understanding of the action mechanism of Cry3Aa in R. ferrugineus larvae.
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Bacillus thuringiensis , Besouros , Gorgulhos , Humanos , Animais , Besouros/metabolismo , Gorgulhos/metabolismo , Antígenos CD13/metabolismo , Endotoxinas/metabolismo , Endotoxinas/toxicidade , Larva/metabolismo , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/toxicidade , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/toxicidadeRESUMO
BACKGROUND: To systematically assess the quality of reports of clinical trials of stem cell for heart diseases published in Chinese. METHODS: The quality of reports was assessed according to the CONSORT statement and the Jadad score. The association between the CONSORT scores and the reported therapeutic effects was evaluated. RESULTS: A total of 36 randomized clinical trials were identified, and 1552 patients were included. The mean CONSORT score was 7.06 (SD = 2.99). The proportion of reports with a Jadad score of 3 was 8.33%. The improvement of left ventricular function, myocardial perfusion area, left ventricular diastolic diameter, and cardiac output decreased with the increase in the CONSORT score. CONCLUSIONS: The percentages of high-quality reports published in Chinese on stem cell therapy for heart diseases are low. Although stem cell transplantation seems promising for heart diseases, high-quality studies are needed to verify the conclusionsï¼.
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Cardiopatias , Relatório de Pesquisa , China , Cardiopatias/cirurgia , Humanos , Transplante de Células-TroncoRESUMO
In this work, we demonstrated an ultrasensitive detection platform for polychlorinated biphenyls (PCBs) based on DNA microcapsules and a nonlinear hybridization chain reaction (NHCR). In the process, first, electrochemical signal molecules (Methylene Blue, MB) were sealed in the prepared DNA microcapsules. In the presence of PCB-72, DNA microcapsules could be dissociated with the conjugation of the aptamer and target, and meanwhile, the released DNA strand could initiate the NHCR and trigger the chain branching growth of DNA dendrimers. Because the released MBs were intercalated into the DNA dendrimer, enhanced electrochemical responses could be detected. This method exhibited ultrahigh sensitivity to PCB-72 with a detection limit of 0.001 ng mL-1. Furthermore, the present aptasensor was also capable of discriminating different PCB congeners. Therefore, the devised label-free and enzyme-free amplification electrochemical aptasensor strategy has great potential for the detection of PCB-72 in real samples, and this strategy may also become an attractive alternative for sensitive and selective small molecule, protein, nucleic acid and nuclease activity detection.
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Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , DNA/química , Limite de Detecção , Bifenilos Policlorados/análise , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Cápsulas , Eletroquímica , Azul de Metileno/química , Técnicas de Amplificação de Ácido Nucleico , Hibridização de Ácido Nucleico , Bifenilos Policlorados/químicaRESUMO
Karyopherinß1 (KPNB1), one of the cytosolic factors involved in the selective protein transport across nucleus, docked at nuclear pore complex and transported through nuclear envelope in an ATP-dependent style, assisting proteins to be recognized as import substrates. It has been reported to be bound up with the origination and progress of lung cancer, cervical cancer, head and neck cancer and hepatocellular carcinoma. In current study, we demonstrated for the first time that the role of KPNB1 in human glioma. KPNB1 was over-expressed as the well-known trend of Ki-67(p < 0.01) and tightly closed to poor prognosis, as an independent prognostic factor. In vitro, up-regulation of KPNB1 was accompanied by certain rising levels of proliferation markers, employing U251 and U87MG cells as serum-starve models. Silencing KPNB1 in U251 and U87MG led to G1 phase arrested directly via flow cytometry analysis. In the nucleus of KPNB1-depletion cell models, the decreasing expression of KPNB1 and ß-catenin was detected respectively, which indicated that KPNB1 functioned via ß-catenin signal. Besides, the interaction between KPNB1 and ß-catenin was proved clearly by immunoprecipitation. Taken together, it showed that KPNB1 might enhance human glioma proliferation via Wnt/ß-Catenin Pathway.
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Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioma/metabolismo , Glioma/patologia , Via de Sinalização Wnt , beta Carioferinas/metabolismo , Adulto , Ciclo Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Regulação para Baixo/genética , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Ligação Proteica , Transporte Proteico , Análise de Sobrevida , Organização Mundial da Saúde , beta Catenina/metabolismoRESUMO
A turn-on fluorescent chemosensor of Pb(2+) in the near-infrared (NIR) region, which is based on the Pb(2+)-tuned restored fluorescence of a weakly fluorescent fluorophore-gold nanoparticle (AuNPs) assembly, has been reported. In this fluorophore-AuNP assembly, NIR fluorescent dye brilliant cresyl blue (BCB) molecules act as fluorophores and are used for signal transduction of fluorescence, while AuNPs act as quenchers to quench the nearby fluorescent BCB molecules via electron transfer. In the presence of Pb(2+), fluorescent BCB molecules detached from AuNPs and restored their fluorescence due to the formation of a chelating complex between Pb(2+) and glutathione confined on AuNPs. Under the optimal conditions, the present BCB-AuNP assembly is capable of detecting Pb(2+) with a concentration ranging from 7.5 × 10(-10) to 1 × 10(-8) mol L(-1) (0.16-2.1 ng mL(-1)) and a detection limit of 0.51 nM (0.11 ng mL(-1)). The present BCB-AuNP assembly can be used in aqueous media for the determination of Pb(2+) unlike common organic fluorescent reagents, and also shows advantages of NIR fluorescence spectrophotometry such as less interference, lower detection limit, and higher sensitivity. Moreover, the present method was successfully applied for the detection of Pb(2+) in water samples with satisfactory results.
Assuntos
Técnicas de Química Analítica/instrumentação , Corantes Fluorescentes/química , Ouro/química , Raios Infravermelhos , Chumbo/análise , Nanopartículas Metálicas/química , Oxazinas/química , Chumbo/química , Solubilidade , Espectrometria de Fluorescência , Água/químicaRESUMO
OBJECTIVE: To evaluate the efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin A1c (HbA1c) > 9%. METHODS: This was an open-labelled, randomized, parallel-group, treat-to-target trial. Newly diagnosed T2DM patients with HbA1c > 9% were enrolled. These patients were treated with metformin with repaglinide and randomized to receive once-daily liraglutide (LIRA, n=25) or the insulin glargine (IGla, n=24) at bedtime. Efficacy and safety were assessed and compared after 18-month treatment. RESULTS: (1) Compared with the baseline, patients with LIRA had significantly reduced mean body weight,BMI and waist circumference (P < 0.01), whereas, the above indexes were increased (P < 0.01) in patients treated with IGla. (2) After 18 months of treatment, fasting plasma glucose (FPG), 2-hour plasma glucose after a 75g oral glucose load (2hPG) and HbA1c were significantly improved in all patients (P < 0.01), with 2hPG, mean blood glucose (MBG), the largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE) were significantly lower in LIRA group than in IGla group (all P < 0.05). (3) HOMA-IR decreased in both groups (P < 0.05). However, ΔI30/ΔG30, AUCCP180 and Matsuda index were only significantly increased in patients treated with LIRA (respectively, 4.88 ± 1.55 vs 7.60±1.91, 9.23 ± 2.66 vs 13.18 ± 2.72, 39.28 ± 20.35 vs 54.64 ± 23.34, all P < 0.01), while HOMA-IR reduced (4.41 ± 1.58 vs 3.52 ± 1.44, P < 0.05). But in IGla group only HOMA-IR was reduced (4.92 ± 1.84 vs 4.57 ± 1.80, P < 0.05). The index of ΔI30/ΔG30, AUCCP180 and Matsuda index in LIRA group are higher than those of indexes in IGla group(respectively, 7.60 ± 1.91 vs 4.18 ± 1.00, 13.18 ± 2.72 vs 10.53 ± 2.68,54.64 ± 23.34 vs 41.65 ± 17.84, all P < 0.05), while HOMA-IR is lower (3.52 ± 1.44 vs 4.57 ± 1.80, P< 0.05). (4) The rate of HbA1c ≤ 6.5% and the dosages of oral anti-diabetic drugs in LIRA group were significantly better than that in IGla group. (5) No significant differences were observed in hypoglycemic episodes and adverse events between two groups. CONCLUSION: It seems that liraglutide is superior to insulin glargine in newly diagnosed T2DM patients with HbA1c > 9% in improving beta-cell function, insulin sensitivity and glucose homeostasis.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Insulina Glargina , Insulina de Ação Prolongada/uso terapêutico , Liraglutida , Metformina , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the influence of hepatosteatosis on pancreatic P-cell function in type 2 diabetes mellitus (22DM). METHODS: A total of 213 subjects with T2DM from Metabolic Disease Hospital, Tianjin Medical University from January 2013 to December 2013 were included in the study. Non-alcoholic fatty liver disease (NAFLD) was diagnosed with abdominal ultrasonography. Patients were divided into two groups: 22DM with NAFLD and 22DM without NAFLD. ALT, AST, gamma-glutamyltransferase, serum lipid, glycosylated hemoglobin A1c ( HbA1c), fructosamine, fasting glucose, insulin and 2 hours plasma glucose, insulin after 75g glucoseload were detected. The insulin resistance and P-cell function were assessed by HOMA-IR and HOMA-P. RESULTS: Among the 213 22DM subjects, 51% (108 cases) were with NAFLD. The HOMA-IR [4.76(2.83,7.21) vs. 2.79 (1.76, 4.37),P <0.05] and HOMA-P [49.18 (37.78, 85.09) vs. 29.50 (18.09, 45.54), P < 0.05] were significantly higher in 22DM with NAFLD than those in 22DM alone. Within subjects with 22DM and NAFLD,the HOMA-IR [6.28 (2.87, 8.17) vs. 2.95 (2.07, 3.66)P <0. 05] and HOMA-P [59.18 (37.78, 85.09) vs. 30.59 (28.56, 34.49), P < 0.05] levels were higher in subjects with normal liver function than those with abnormal liver function. CONCLUSIONS: T2DM patients with NAFLD have severer insulin resistance than those without NAFLD. The P-cell function of those patients was compensatory increased, which was decreased in subjects with abnormal liver function.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
A homogeneous immunoassay for the sensitive and selective determination of trace amounts of α-fetoprotein (AFP, a cancer marker) by detection in the near-infrared (NIR) region based on luminescence energy transfer (LET) from NaYF4:Yb,Tm/NaGdF4 core-shell upconverting nanoparticles to gold nanorods (GNRs) is presented. The carboxyl-functionalized NaYF4:Yb,Tm/NaGdF4 core-shell upconverting nanoparticles (UCNPs) were excited by a 980 nm continuous wavelength laser, and its emission peak appeared at a near-infrared wavelength (â¼804 nm). The carboxyl-functionalized upconverting nanoparticles were conjugated with the anti-AFP (Ab1) and acted as donor. GNRs with a high absorption band around 790 nm, which was overlapped the UCNPs emission, were synthesized and acted as the acceptor. The donor (negatively charged) interacted with the acceptor (positively charged) via electrostatic interactions to bring them into close proximity. LET could occur, producing a quenching phenomenon. When the AFP antigens were added into the system, the binding affinity between AFP and Ab1 was stronger than the electrostatic interactions, which released the energy acceptors from the energy donors, interrupting luminescence energy transfer, and therefore, the luminescence was recovered. On the basis of the restored luminescence, a turn-on optical immunosening system was developed. Under the optimal conditions, the linear range of detection was from 0.18 to 11.44 ng/mL for AFP (R = 0.99), with a detection limit as low as 0.16 ng/mL. The proposed method has also been used to monitor AFP in human serum samples. Therefore, further study based on the NaYF4:Yb,Tm/NaGdF4 core-shell nanoparticles-GNRs construction may open the way for a new class of NIR-LET biosensors with wide applications.
Assuntos
Biomarcadores Tumorais/sangue , Análise Química do Sangue/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Gadolínio/química , Ouro/química , Nanopartículas/química , Nanotubos/química , Túlio/química , Calibragem , Humanos , Raios Infravermelhos , Limite de Detecção , alfa-Fetoproteínas/análiseRESUMO
A multi-component paclitaxel (PTX) -loaded ß-elemene nanoemulsion by transferrin modification (Tf-PE-MEs) was developed to enhance non-small-cell lung cancer (NSCLC) treatment. After transferrin modification, the particle size of Tf-PE-MEs was (14.87 ± 1.84) nm, and the zeta potential was (-10.19 ± 0.870) mV, respectively. In vitro experiments showed that Tf-PE-MEs induced massive apoptosis in A549 cells, indicating that it had significant cytotoxicity to A549 cells. Through transferrin modification, Tf-PE-MEs accumulated at the tumor site efficiently with overexpressed transferrin receptor (TfR) on the surface of A549 cells. This will allow increasing PTX and ß-elemene concentration in the target cells, enhancing the therapeutic effect. Compared to PTX alone, Tf-PE-MEs displayed good anti-tumor efficacy and diminished systemic toxicity in vivo studies. With favourable therapeutic potential, this study provides a new strategy for the combined anticancer treatment of non-small cell lung cancer.
Assuntos
Antineoplásicos Fitogênicos , Apoptose , Carcinoma Pulmonar de Células não Pequenas , Emulsões , Neoplasias Pulmonares , Nanopartículas , Paclitaxel , Sesquiterpenos , Transferrina , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Paclitaxel/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Transferrina/química , Transferrina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Animais , Células A549 , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/administração & dosagem , Apoptose/efeitos dos fármacos , Nanopartículas/química , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptores da Transferrina/metabolismo , Tamanho da Partícula , Camundongos , Linhagem Celular Tumoral , Masculino , Liberação Controlada de Fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
The increasingly urgent issue of climate change is driving the development of carbon dioxide (CO2) capture and separation technologies in flue gas after combustion. The monolithic adsorbent stands out in practical adsorption applications for its simplified powder compaction process while maintaining the inherent balance between energy consumption for regeneration and selectivity for adsorption. However, optimizing the adsorption capacity and selectivity of CO2 separation materials remains a significant challenge. Herein, we synthesized monolithic polymer networks (N-CMPs) with triphenylamine adsorption sites, acid-base environment tolerance, and precise narrow microchannel pore systems for the selective sieving of CO2 and particulate matter (PM) in flue gas. The inherent continuous covalent bonding of N-CMPs, along with their highly delocalized π-π conjugated porous framework, ensures the stability of the monolithic polymer network's adsorption and separation capabilities under wet and acid-base conditions. Specifically, under the conditions of 1 bar at 273 K, the CO2 adsorption capacity of N-CMP-1 is 3.35 mmol/g. Attributed to the highly polar environment generated by triphenylamine and the inherent high micropore/mesopore ratio, N-CMPs exhibit an excellent ideal adsorbed solution theory (IAST) selectivity for CO2/N2 under simulated flue gas conditions (CO2/N2 = 15:85). Dynamic breakthrough experiments further visualize the high separation efficiency of N-CMPs in practical adsorption applications. Moreover, under acid-base conditions, N-CMPs achieve a capture efficiency exceeding 99.76 % for PM0.3, enabling the selective separation of CO2 and PM in flue gas. In fact, the combined capture of hazardous PM and CO2 from the exhaust gases produced by the combustion of fossil fuels will play a pivotal role in mitigating climate change and environmental issues until low-carbon and alternative energy technologies are widely adopted.
RESUMO
Conjugated microporous polymers have a highly delocalized π-π conjugated porous skeleton connected by covalent bonds, which can combine their excellent stability with high adsorption, in order to be applied to the study of co-capture of harmful particulate matter (PM) and carbon dioxide (CO2) under high temperature and high humidity conditions. In this paper, fluorene-based coupled conjugated microporous polymers (D-CMPs) with functionalized hollow nanotubes and abundant microporous structures were proposed. Through mechanism exploration and molecular electrostatic potential (MESP) calculation, the capture efficiency, adsorption capacity and selectivity of PM and CO2 in the waste gas stream of carbon-based combustion were analyzed. The results indicate that D-CMPs, with their rigid carbon-based π-conjugated framework, exhibit excellent tolerance under prolonged high-humidity conditions, with a capture efficiency exceeding 99.87% for PM0.3 and exceeding 99.99% for PM2.5. Meanwhile, based on its chemical/thermal stability, it can realize the recycling of adsorption-regeneration. On this basis, the "slip effect" induced by the open three-dimensional hierarchical porous structure of D-CMPs significantly enhances airflow dispersion and improves gas throughput (with a minimal permeation resistance of only 15 Pa). At a pressure of 1 bar and a temperature of 273.15 K, D-CMP-2 exhibited a CO2 adsorption capacity of up to 2.69 mmol g-1. The fitting results of three isothermal adsorption models demonstrate that D-CMPs exhibit an outstanding equilibrium selectivity towards CO2. Therefore, prior to the widespread adoption of low-carbon and clean energy technologies, porous solid materials exhibiting excellent structural stability, equilibrium selectivity, environmental tolerance, and high adsorption capacity emerge as optimal candidates for the treatment of industrial waste gases.
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Herein we report a gentle seedless and surfactant-free method for the preparation of clean-surface porous platinum nanoparticles. In terms of electrocatalytic CH(3)OH oxidation, the clean-surface porous platinum exhibited better performance than platinum nanoparticles and a commercial Pt/C catalyst. The porous nanostructures exhibited 2.26-fold higher mass activity and 2.8-fold greater specific activity than the Pt/C catalyst. More importantly, three typical surfactants, cetyltrimethylammonium bromide/chloride (CTAB/C), poly(vinylpyrrolidone), and sodium dodecyl sulfate, were chosen to study the inhibition effect of surfactants on electrocatalytic performance. It was observed that the surfactants led to a clear selective decrease in electrocatalytic performance. CTAB/C inhibited the catalytic activity the most due to the stronger interaction between the OH-enriched platinum surface and the positively charged molecules. Thus, this work indicates that these clean-surface porous platinum nanoparticles may be used as efficient catalysts for direct methanol fuel cells and provides a greater understanding of the inhibition effects of surfactants on catalytic activity.
Assuntos
Nanopartículas Metálicas/química , Platina/química , Tensoativos/química , Catálise , Nanoestruturas/química , Oxirredução , Propriedades de SuperfícieRESUMO
A new luminescence resonant energy transfer (LRET) system has been designed that utilizes near-infrared (NIR)-to-NIR upconversion lanthanide nanophosphors (UCNPs) as the donor, and Au nanorods (Au NRs) as the acceptor. The UCNPs were excited by a near-infrared (980 nm) wavelength and also emitted at a near-infrared wavelength (804 nm) using an inexpensive infrared continuous wave laser diode. The Au NRs showed a high absorption band around 806 nm, which provided large spectral overlap between the donor and the acceptor. Hg(2+) ions were added to an aqueous solution containing the UCNPs and Au NRs that were modified with a Hg(2+) aptamer. Then, a sandwich-type LRET system was developed for the detection of Hg(2+) ions that had high sensitivity and selectivity in the NIR region. The method was successfully applied to the sensing of Hg(2+) ions in water and human serum samples.
Assuntos
Fluoretos/química , Mercúrio/análise , Nanopartículas Metálicas/química , Prata/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Ítrio/química , Transferência de Energia , Íons/análise , Nanotubos/química , Túlio/química , Itérbio/análise , Itérbio/químicaRESUMO
BACKGROUND: Paclitaxel (PTX), voted as the promising natural medicine molecule, is widely used in the treatment of cancers. Nevertheless, its clinical application is strictly limited by its poor water solubility. OBJECTIVE: CP-MEs (Paclitaxel-coix seed oil coloaded microemulsion), a small-sized self-emulsifying nanoemulsion formed from a combination of PTX and coix seed oil (CSO), was developed in order to improve the solubility of paclitaxel and enhance anti-cervical cancer efficacy in vitro. CSO was selected as the oil phase to replace conventional organic solvents and achieve a synergistic anti-tumor effect with paclitaxel. METHODS: Pseudoternary phase diagram was applied to the study of CP-MEs formulation. CP-MEs were prepared and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The encapsulation efficiency and drug loading efficiency (EE and LE) were detected by HPLC. MTT was adopted to evaluate the cytotoxicity of CP-MEs against HeLa cells. The cellular uptake and apoptotic ratio of CP-MEs were evaluated by flow cytometry. Notably, HeLa 3D tumor spheroid was adopted to evaluate tumor permeability of different size microemulsions as the model. RESULTS: The best self-emulsifying ability was exhibited by HS 15: PEG 400 combination. The appearance of CP-MEs was clear and transparent, which exhibited a small size (30.28 ± 0.36) and a slight negative surface charge (-4.40 ± 1.13) mV. The EE and LE of CP-MEs were 98.80% and 0.978%, respectively. The cumulative release rate within 48 h of the CP-MEs was 80.21%. In cellular studies, the uptake of fluorescein isothiocyanate (FITC) labeled CP-MEs (FITC/C-MEs) was 17.86-fold higher than the free FITC group, leading to significant synergistic anticancer activity in terms of cytotoxicity and apoptosis induction in vitro. The apoptotic rate of CP-MEs treated was 1.70-fold higher than PTXtreated. Notably, the penetration of CP-MEs in the HeLa 3D tumor sphere model was enhanced, which was related to deeply penetrated microemulsion of small size mediated at the tumor site. CONCLUSION: With the advantage of the small-sized self-emulsifying system, CP-MEs hold great potential to become an efficient nano drug delivery system for cervical cancer treatment in the clinic.
Assuntos
Coix , Neoplasias , Humanos , Paclitaxel/farmacologia , Células HeLa , Fluoresceína-5-Isotiocianato , Óleos de Plantas/farmacologia , Linhagem Celular TumoralRESUMO
Novel porous gold nanospheres are prepared by calcination of the gold-urea complexes. The enhanced Raman spectra of ethanol catalyzed by different doses of porous gold nanospheres are measured with a 532 nm laser as the excitation source, and an enhanced charge coupled device served in spectral detection and microscopic imaging. The electrochemical experiments show that the catalytic oxidation products of ethanol with porous gold nanoparticles are acetaldehyde, acetic acid, and water, which further proved that the porous gold nanoparticles can activate the -CH2 of ethanol.
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Aim: To explore the predictive value of white blood cell to hemoglobin ratio (WHR) for 30-day mortality in patients with intracerebral hemorrhage (ICH). Methods: In this cohort study, 2,848 patients with ICH were identified in the Medical Information Mart for Intensive Care (MIMIC)-III and MIMIC-IV. Least absolute shrinkage and selection operator (LASSO) regression screened covariates of 30-day mortality of ICH patients. COX regression analysis was used to study the association of different levels of WHR, white blood cell (WBC), and hemoglobin (Hb) with 30-day mortality. The median follow-up time was 30 (20.28, 30.00) days. Results: In total, 2,068 participants survived at the end of the follow-up. WHR was negatively correlated with the Glasgow Coma Score (GCS) (spearman correlation coefficient = -0.143, p < 0.001), and positively associated with the Sepsis-related Organ Failure Assessment (SOFA) score (spearman correlation coefficient = 0.156, p < 0.001), quick SOFA (qSOFA) score (spearman correlation coefficient = 0.156, p < 0.001), and Simplified Acute Physiology Score II (SAPS-II) (spearman correlation coefficient = 0.213, p < 0.001). After adjusting for confounders, WHR >0.833 (HR = 1.64, 95%CI: 1.39-1.92) and WBC >10.9 K/uL (HR = 1.49, 95%CI: 1.28-1.73) were associated with increased risk of 30-day mortality of patients with ICH. The area under the curve (AUC) value of the prediction model based on WHR and other predictors was 0.78 (95%CI: 0.77-0.79), which was higher than SAPSII (AUC = 0.75, 95%CI: 0.74-0.76), SOFA score (AUC = 0.69, 95%CI: 0.68-0.70) and GCS (AUC = 0.59, 95%CI: 0.57-0.60). Conclusion: The level of WHR was associated with 30-day mortality in patients with severe ICH, and the WHR-based prediction model might provide a tool to quickly predict 30-day mortality in patients with ICH.
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Development of lysosomes and mitochondria dual-targeting photosensitizer with the virtues of near-infrared (NIR) emission, highly efficient reactive oxygen generation, good phototoxicity and biocompatibility is highly desirable in the field of imaging-guided photodynamic therapy (PDT) for cancer. Herein, a new positively charged amphiphilic organic compound (2-(2-(5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)vinyl)-3-methylbenzo[d]thiazol-3-ium iodide) (ADB) based on a D-A-π-A structure is designed and comprehensively investigated. ADB demonstrates special lysosomes and mitochondria dual-organelles targeting, bright NIR aggregation-induced emission (AIE) at 736 ânm, high singlet oxygen (1O2) quantum yield (0.442), as well as good biocompatibility and photostability. In addition, ADB can act as a two-photon imaging agent for the elaborate observation of living cells and blood vessel networks of tissues. Upon light irradiation, obvious decrease of mitochondrial membrane potential (MMP), abnormal mitochondria morphology, as well as phagocytotic vesicles and lysosomal disruption in cells are observed, which further induce cell apoptosis and resulting in enhanced antitumor activity for cancer treatment. In vivo experiments reveal that ADB can inhibit tumor growth efficiently upon light exposure. These findings demonstrate that this dual-organelles targeted ADB has great potential for clinical imaging-guided photodynamic therapy, and this work provides a new avenue for the development of multi-organelles targeted photosensitizers for highly efficient cancer treatment.
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Triple-negative breast cancer (TNBC) is always the most challenging breast cancer subtype. Herein, brucine, encapsulated in peptide-modified liposomes, was proposed for treating TNBC by transdermal delivery. For the TD peptide-modified brucine-loaded liposome (Bru-TD-Lip) we developed, it presents high encapsulation efficiency of brucine and stability. In vitro, Bru-TD-Lip shows the enhanced percutaneous permeability of brucine, is able to readily enter TNBC cells, and significantly inhibits the proliferation, migration, and invasion of these cells. In vivo, through transdermal delivery, Bru-TD-Lip presents good biosafety and anti-tumor efficacy. The transdermal delivery of Bru-TD-Lip effectively targets and inhibits subcutaneous mammary carcinogenesis in female nude mice. Compared with oral administration, the transdermal delivery significantly reduces the damage of brucine to major organs and enhances the antitumor outcomes of brucine in treating TNBC. This study provides a new therapeutic strategy for treating triple-negative breast cancer by brucine.
Assuntos
Lipossomos , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Feminino , Lipossomos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Camundongos Nus , Peptídeos/uso terapêuticoRESUMO
In this work, we utilize the galvanic displacement synthesis and make it a general and efficient method for the preparation of Au-M (M = Au, Pd, and Pt) core-shell nanostructures with porous shells, which consist of multilayer nanoparticles. The method is generally applicable to the preparation of Au-Au, Au-Pd, and Au-Pt core-shell nanostructures with typical porous shells. Moreover, the Au-Au isomeric core-shell nanostructure is reported for the first time. The lower oxidation states of Au(I), Pd(II), and Pt(II) are supposed to contribute to the formation of porous core-shell nanostructures instead of yolk-shell nanostructures. The electrocatalytic ethanol oxidation and oxygen reduction reaction (ORR) performance of porous Au-Pd core-shell nanostructures are assessed as a typical example for the investigation of the advantages of the obtained core-shell nanostructures. As expected, the Au-Pd core-shell nanostructure indeed exhibits a significantly reduced overpotential (the peak potential is shifted in the positive direction by 44â mV and 32â mV), a much improved CO tolerance (I(f)/I(b) is 3.6 and 1.63 times higher), and an enhanced catalytic stability in comparison with Pd nanoparticles and Pt/C catalysts. Thus, porous Au-M (M = Au, Pd, and Pt) core-shell nanostructures may provide many opportunities in the fields of organic catalysis, direct alcohol fuel cells, surface-enhanced Raman scattering, and so forth.
RESUMO
It is a known fact that Pd-based bimetallic nanostructures possess unique properties and excellent catalytic performance. In this work, the Au-Pd alloy and core-shell nanostructures have been prepared by a simple one-pot hydrothermal coreduction route, and their formation process and mechanism are discussed in detail. A reducing capacity-induced controlled reducing mechanism is proposed for the formation process of Au-Pd bimetallic nanostructures. CTAB plays a key role in the formation of alloy Au-Pd nanostructures. When CTAB is absent, the products are typical core-shell nanostructures. Moreover, the as-prepared nanostructures exhibit excellent electrocatalytic ORR performance in alkaline media, especially for Au-Pd alloy nanostructures. The overpotential of oxygen reduction gets reduced significantly, and the peak potential is positive-shifted by 44 and 34 mV in comparison with the core-shell ones and Pd/C catalyst, respectively. Thus, the controllable preparation and excellent electrocatalytic properties will make them become a potentially cheaper Pd-based cathodic electrocatalyst for DAFCs in alkaline media.