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3.
Ann Surg Oncol ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591226

RESUMO

BACKGROUND: Hepatectomy with tumor thrombectomy is the preferred treatment option for hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT); however, the impact of BDTT on their prognosis is unclear. OBJECTIVE: We aimed to investigate the long-term surgical outcomes of HCC patients with BDTT. METHODS: The data of HCC patients with and without BDTT who underwent hepatectomy were retrospectively reviewed and the long-term outcomes were compared. For propensity score matching (PSM) analysis, patients were matched in a 1:1 ratio. Subgroup analysis was conducted according to the American Joint Committee on Cancer (AJCC) staging system. RESULTS: Before PSM, HCC patients with BDTT had more advanced tumor stages and adverse clinicopathological features. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the non-BDTT group before PSM (RFS, p < 0.001; OS, p < 0.001), while after PSM, the BDTT group had significantly poorer RFS (p = 0.025). There was no difference in OS between the groups (p = 0.588). Subgroup analysis showed that RFS and OS in AJCC stage I-II patients were significantly poorer in the BDTT group; no differences were found in the AJCC stage III group before or after PSM. When the presence of BDTT was recommended to increase the AJCC staging system by one stage in AJCC stage I-II patients, the predictive ability for RFS and OS was higher. CONCLUSIONS: BDTT was associated with significantly poorer long-term surgical outcomes in AJCC stage I-II patients. A modified AJCC staging system including BDTT status in stage I-II might have a better prognostic ability.

4.
Oxid Med Cell Longev ; 2021: 5633514, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457116

RESUMO

This study sought to perform integrative analysis of the immune/methylation/autophagy landscape on breast cancer prognosis and single-cell genotypes. Breast Cancer Recurrence Risk Score (BCRRS) and Breast Cancer Prognostic Risk Score (BCPRS) were determined based on 6 prognostic IMAAGs obtained from the TCGA-BRCA cohort. BCRRS and BCPRS, respectively, were used to construct a risk prediction model of overall survival and progression-free survival. Predictive capacity of the model was evaluated using clinical data. Analysis showed that BCRRS is associated with a high risk of stroke. In addition, PPI and drug-ceRNA networks based on differences in BCPRS were constructed. Single cells were genotyped through integrated scRNA-seq of the TNBC samples based on clustering results of BCPRS-related genes. The findings of this study show the potential regulatory effects of IMAAGs on breast cancer tumor microenvironment. High AUCs of 0.856 and 0.842 were obtained for the OS and PFS prognostic models, respectively. scRNA-seq analysis showed high expression levels of adipocytes and adipose tissue macrophages (ATMs) in high BCPRS clusters. Moreover, analysis of ligand-receptor interactions and potential regulatory mechanisms were performed. The LINC00276&MALAT1/miR-206/FZD4-Wnt7b pathway was also identified which may be useful in future research on targets against breast cancer metastasis and recurrence. Neural network-based deep learning models using BCPRS-related genes showed that these genes can be used to map the tumor microenvironment. In summary, analysis of IMAAGs, BCPRS, and BCRRS provides information on the breast cancer microenvironment at both the macro- and microlevels and provides a basis for development of personalized treatment therapy.


Assuntos
Autofagia , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Metilação de DNA , Análise de Célula Única/métodos , Acidente Vascular Cerebral/patologia , Microambiente Tumoral/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Genótipo , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Medição de Risco/métodos , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/terapia , Taxa de Sobrevida , Transcriptoma
5.
Ann Surg Oncol ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929619

RESUMO

BACKGROUND: Anatomic resection (AR) of the liver is generally recommended in hepatocellular carcinoma (HCC) patients. However, the benefits of AR and nonanatomic resection (NAR) in HCC patients with bile duct tumor thrombus (BDTT) are unknown. This study aimed to compare long-term outcomes of AR and NAR in HCC patients with BDTT after curative resection. PATIENTS AND METHODS: A total of 175 consecutive HCC patients with BDTT after curative resection between April 2009 and December 2017 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Recurrence-free survival (RFS) and overall survival (OS) were compared between the cohorts. RESULTS: After PSM, 120 patients were analyzed. The AR group had better RFS than the NAR group (P = 0.010). Even though there was no statistically significant difference in OS (P = 0.140, power = 0.33), the 3- and 5-year OS rates in the AR group (52.4% and 44.2%, respectively) were obviously higher than those in the NAR group (35.4% and 30.4%, respectively). When patients were further stratified according to tumor size, better RFS and OS were observed in patients with small (≤ 5 cm) tumors after AR (P < 0.001 and P = 0.004, respectively). Multivariate analysis identified AR (P = 0.024) as an independent favorable prognostic factor for RFS in HCC patients with BDTT. CONCLUSIONS: AR is recommended for HCC patients with BDTT, especially in patients with small (≤ 5 cm) tumors.

6.
BMC Cancer ; 21(1): 272, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711965

RESUMO

BACKGROUND: Bile duct invasion is a relatively rare event and is not well characterised in hepatocellular carcinoma (HCC). It remains very difficult to diagnose HCC with bile duct tumour thrombus (BDTT) before surgery. Increasing evidence has revealed that inflammation plays a critical role in tumorigenesis. This study aimed to develop nomograms based on systemic and hepatic inflammation markers to predict microscopic BDTT (micro-BDTT) before surgery in HCC. METHODS: A total of 723 HCC patients who underwent hepatectomy as initial therapy between January 2012 and June 2020 were included in the study. Logistic regression analysis was used to identify independent risk factors for micro-BDTT. The nomograms were constructed using significant predictors, including α-fetoprotein (AFP), alkaline phosphatase (ALP), direct bilirubin (DB), prognostic nutritional index (PNI), and γ-glutamyl transferase (γ-GT)/alanine aminotransferase (ALT). The prediction accuracies of the nomograms were evaluated using the area under the receiver operating characteristic (ROC) curve. RESULTS: AFP, ALP, DB, PNI, and γ-GT/ALT were independent risk factors for predicting micro-BDTT (P = 0.036, P = 0.004, P = 0.013, P = 0.012, and P = 0.006, respectively), which were assembled into the nomograms. The area under the ROC curve of the nomograms combining PNI and γ-GT/ALT for predicting micro-BDTT was 0.804 (95% confidence interval [CI]: 0.730-0.878). The sensitivity and specificity values when used in predicting micro-BDTT before surgery were 0.739 (95% CI: 0.612-0.866) and 0.781 (95% CI: 0.750-0.813), respectively. CONCLUSIONS: The nomogram based on combining systemic and hepatic inflammation markers is suitable for predicting micro-BDTT before surgery in HCC patients, leading to a rational therapeutic choice for HCC.


Assuntos
Carcinoma Hepatocelular/complicações , Colestase Intra-Hepática/epidemiologia , Icterícia Obstrutiva/epidemiologia , Neoplasias Hepáticas/complicações , Nomogramas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/patologia , Colestase Intra-Hepática/cirurgia , Feminino , Hepatectomia , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/patologia , Icterícia Obstrutiva/cirurgia , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estudos Retrospectivos , Medição de Risco/métodos
7.
Food Chem ; 338: 128144, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33092004

RESUMO

A weak ion-exchange membrane (P-COOH) was synthesized by alkaline hydrolysis of a polyacrylonitrile nanofiber membrane prepared by electrospinning process. The P-COOH membrane was characterized for its physical properties and its application for purification of lysozyme from chicken egg white was investigated. The lysozyme adsorption efficiency of the P-COOH membrane operating in a stirred cell contactor (Millipore, Model 8010) was evaluated. The effects of key parameters such as the feed concentration, the rotating speed, the flow rate of feed and the operating pressure were studied. The results showed successful purification of lysozyme with a high recovery yield of 98% and a purification factor of 63 in a single step. The purification strategy was scaled-up to the higher feedstock loading volume of 32.7 and 70 mL using stirred cell contactors of Model 8050 and 8200, respectively. The scale-up processes achieved similar purification results, proving linear scalability of the purification technique adopted.


Assuntos
Fracionamento Químico/instrumentação , Clara de Ovo , Membranas Artificiais , Muramidase/isolamento & purificação , Nanofibras/química , Resinas Acrílicas/química , Adsorção , Animais , Troca Iônica , Muramidase/química
8.
Entropy (Basel) ; 22(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-33286656

RESUMO

An adaptive method for quantum state fidelity estimation in bipartite higher dimensional systems is established. This method employs state verifier operators which are constructed by local POVM operators and adapted to the measurement statistics in the computational basis. Employing this method, the state verifier operators that stabilize Bell-type entangled states are constructed explicitly. Together with an error operator in the computational basis, one can estimate the lower and upper bounds on the state fidelity for Bell-type entangled states in few measurement configurations. These bounds can be tighter than the fidelity bounds derived in [Bavaresco et al., Nature Physics (2018), 14, 1032-1037], if one constructs more than one local POVM measurements additional to the measurement in the computational basis.

9.
ACS Omega ; 5(46): 29795-29800, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33251414

RESUMO

A PAA/ZnO/Ag heterostructure composite material was prepared by a reduction method. The properties of composite particles are analyzed by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), UV-visible spectroscopy, and Raman spectroscopy. Ag nanoparticles play an important role in PAA/ZnO/Ag composite microspheres, conferring new SERS properties and functions to PAA/ZnO/Ag. The intensity of the SERS signal of PAA/ZnO/Ag irradiated with UV light decreased from 10 000 to below 500. The SERS detection limit of R6G obtained was reduced to 1 × 10-6 M. The PAA/ZnO/Ag composite particles show a very good degradation effect on R6G under UV light irradiation. This study has developed a new synthesis method to prepare SERS signal enhancement materials with self-cleaning effects. According to the experimental results, the PAA/ZnO/Ag composite material has higher sensitivity than the PAA/ZnO composite material.

10.
Zhen Ci Yan Jiu ; 45(12): 1006-9, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33415861

RESUMO

OBJECTIVE: To investigate the anesthetic effect of combined acupuncture-medicine anesthesia in microwave ablation of benign thyroid nodules and its effect on serum ß-endorphin. METHODS: A total of 60 patients who met the inclusion criteria and received microwave ablation of benign thyroid nodules were randomly divided into the treatment group and the control group, with 30 patients in each. The patients in the treatment group were given combined acupuncture-medicine anesthesia, and those in the control group were given intravenous anesthesia. The two groups were compared in terms of the sedative and analgesic effects of anesthesia, amount of anesthetics used, incidence rate of intraoperative snore and respiratory depression, and change in serum ß-endorphin level before anesthesia, before surgery, and after the surgery. RESULTS: Both groups obtained satisfactory anesthetic effects. Compared with the control group, the sedation score, the amounts of fentanyl and propofol used, the incidence rates of intraoperative snore and respiratory depression in the treatment group were obviously lower (P<0.05, P<0.01). The treatment group had an increase in serum ß-endorphin level before surgery and at the end of surgery (P<0.05), while the control group showed no significant change in serum ß-endorphin level at each time point. CONCLUSION: In microwave ablation of benign thyroid nodules, combined acupuncture-medicine anesthesia has good sedative and analgesic effects and can reduce the amounts of anesthetics used as well as the incidence rates of intraoperative snore and respiratory depression. The analgesic effect of acupuncture anesthesia is associated with increased ß-endorphin secretion.


Assuntos
Analgesia por Acupuntura , Anestesia , Medicina , Nódulo da Glândula Tireoide , Anestésicos Intravenosos , Humanos , beta-Endorfina
11.
J Phys Chem A ; 123(50): 10700-10713, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31815475

RESUMO

In this study we explore the photoionization-induced proton transfer (PT) dynamics in the hydrogen-bonded complex of phenol (PhOH) and a simple amide, dimethylformamide (DMF). Neutral PhOH-DMF complexes produced in a supersonic expansion are photoionized by femtosecond 1 + 1 resonance-enhanced multiphoton ionization via its S1 state, and the subsequent PT dynamics occurring in the [PhOH-DMF]+ cation is probed by delayed pulses that lead to ion fragmentation. The experiments and density functional theory calculations reveal that the photoionization-induced PT proceeds in two consecutive steps of very different time scales. Upon femtosecond ionization the [PhOH-DMF]+ cation is initially prepared with a non-PT geometry close to that of the dominant neutral complex. The ionic system then rapidly relaxes into a configuration possessing both non-PT and PT characteristics in ∼0.5 ps. This partial-PT intermediate then undergoes a much slower barrier crossing in ∼25 ps to a more stable structure in which PT is more complete. The slow isomerization step not only corresponds to PT but also to a hydrogen-bonding site switching. The present study simulates a scenario of suddenly bringing a strong acid to the close vicinity of an amide to watch how protonation occurs. Our results suggest that the initial protonation of a peptide-like unit in acid-induced protein processes requires a relaxation time of ∼0.5 ps, which must be taken into account in complete descriptions of protein dynamics.

12.
ACS Appl Mater Interfaces ; 11(40): 36895-36904, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31532617

RESUMO

A series of σ-π-conjugated polymers composed of biphenyl and X atom as backbone repeat unit (where X is the group IV-A atom: carbon, silicon, germanium, or tin) grafted with two alkoxy-substituted biphenyls at the X atom as side chains are synthesized and their optoelectronic properties are studied systematically. We choose biphenyl rather than alkyl as the side chain because its frontier molecular orbital distributions are close to those of our previously reported σ-π-conjugated polymer grafted with transport moieties. The present σ-π polymers with various X atoms show significant differences in triplet energy (ET) ranging from 2.58 to 2.83 eV with the sequence Ge > Si > C > Sn and in charge mobilities from 10-9 to 10-7 cm2/(V s) with the sequence Si > Ge > Sn > C, indicating that the properties of the σ-π polymers are largely affected by their X atoms. The Ge- and Sn-based σ-π-conjugated polymers show the highest and lowest ET values, respectively, due to their different levels of π-electron delocalization caused by size effects and (d-p)π orbital interaction. For their charge transport properties, the Si-based conjugated σ-π polymer gives the highest hole and electron mobilities due to the stronger σ-π conjugation and shorter Si-C bond length between the attached carbon atom in biphenyl and Si. On the contrary, the C-based σ-π-conjugated polymer gives the lowest charge mobilities due to a lack of d orbital in the C atom leading to a poor σ-π conjugation characteristic. These σ-π polymers with different ET levels and charge transport properties show a significant effect on their electroluminescence characteristics. Among them, the Ge-based σ-π-conjugated polymer when used as host shows the best device performance due to its higher ET and reasonable charge mobility. Such findings of different optoelectronic properties of these σ-π-conjugated polymers provide useful guidelines for the selection of backbone for designing σ-π-conjugated polymer host grafted with charge transport moieties.

13.
Front Pharmacol ; 10: 714, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354473

RESUMO

Background: A host of systematic reviews and meta-analyses were carried out to estimate the role of corticosteroids in sepsis and septic shock. Discordant opinions were investigated to determine whether patients who experienced sepsis and septic shock could benefit from corticosteroids treatment. Our purpose is to perform a systematic review of overlapping meta-analyses, to explore the role of corticosteroids in the treatment of sepsis and septic shock. Method: Ovid MEDLINE, EMBase, Cochrane Database of Systematic Reviews, and LILACS were searched for eligible studies. Two authors individually extracted the relevant data and evaluated the quality of the meta-analysis using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2) and ROBIS. The Jadad decision algorithm was implemented to identify the meta-analyses that offered the optimal level of evidence. Result: Sixteen meta-analyses met the eligibility criteria. None of the studies that reported mortality illustrated a significant improvement on mortality (14-day and 90-day), but a 28-day mortality on a long course of a low dose corticosteroids was described. Only four studies stated that a long course of low-dose corticosteroids had advantageous effect on 28-day mortality. A meta-analysis by Fang et al. was regarded as the highest level of evidence in the Jadad decision algorithm among the meta-analyses that were investigated in this systematic review. Conclusion: The 28-day mortality was reduced, as well as the mortality in the ICU and hospital and the length of stay in the ICU, using a long course of low-dose corticosteroids. This was demonstrated by a meta-analysis of the current optimal available evidence. Additionally, significant improvements on the adverse events of hyperglycemia and hypernatraemia have been made.

14.
Angew Chem Int Ed Engl ; 58(33): 11317-11323, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31120618

RESUMO

We propose the novel σ-π conjugated polymer poly(biphenyl germanium) grafted with two electron-donating acridan moieties on the Ge atom for use as the host material in a polymer light-emitting diode (PLED) with the sky-blue-emitting thermally activated delayed fluorescence (TADF) material DMAC-TRZ as the guest. Its high triplet energy (ET ) of 2.86 eV is significantly higher than those of conventional π-π conjugated polymers (ET =2.65 eV as the limit) and this guest emitter (ET =2.77 eV). The TADF emitter emits bluer emission than in other host materials owing to the low orientation polarizability of the germanium-based polymer host. The Ge atom also provides an external heavy-atom effect, which increases the rate of reverse intersystem crossing in this TADF guest, so that more triplet excitons are harvested for light emission. The sky-blue TADF electroluminescence with this host/guest pair gave a record-high external quantum efficiency of 24.1 % at maximum and 22.8 % at 500 cd m-2 .

15.
Hepatobiliary Pancreat Dis Int ; 18(3): 255-265, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31027910

RESUMO

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1 (SphK1) phosphorylates sphingosine to sphingosine-1-phosphate (S1P) which participates in multiple bioactive processes. However, little is known about the role of SphK1 in hepatic I/R injury. This study aimed to investigate the effect of SphK1 knockout on liver I/R injury and to explore underlying mechanisms. METHODS: SphK1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3 (STAT3). Western blotting was used to determine the expression of S1P receptor 1 (S1PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. RESULTS: SphK1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in SphK1 knockout mice as demonstrated by attenuated expression of S1PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1ß, interleukin-6 and tumor necrosis factor-α were also inhibited by SphK1 genetic deletion. The oxidative stress markers were lower in SphK1 knockout mice after I/R injury than wild type mice. CONCLUSIONS: Knockout of SphK1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. SphK1 may be a novel and potent target in clinical practice in I/R-related liver injury.


Assuntos
Mediadores da Inflamação/metabolismo , Fígado/irrigação sanguínea , Estresse Oxidativo , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Citocinas/metabolismo , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Hepatite/enzimologia , Hepatite/genética , Hepatite/patologia , Fígado/enzimologia , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Receptores de Esfingosina-1-Fosfato/metabolismo , Fator de Transcrição RelA/metabolismo
16.
Front Pharmacol ; 10: 96, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30853910

RESUMO

Background: Currently, although non-steroidal anti-inflammatory drugs (NSAIDs) were recommended for acute renal colic in the 2018 European Association of Urology guidelines, there are no specific NSAIDs and no specific routes of administration in this guideline. The clinical practice of advocating intravenous opioids as the initial analgesia is still common out of the fear of adverse events from NSAIDs. Objectives: To comprehensively assess the efficacy and safety of NSAIDs, opioids, paracetamol, and combination therapy for acute renal colic. Methods: Ovid MEDLINE, Ovid EMbase, the Cochrane Library, Clinical Trials Registry Platform for Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched through February 2, 2018. Two reviewers selected all randomized controlled trails (RCTs) regarding NSAIDs, opioids, paracetamol, combination therapy, and placebo were identified for analysis. We designed a three-stage strategy based on classification and pharmacological mechanisms in the first stage, routes of administration in the second stage, and specific drug branches with different routes in the third stage using network meta-analysis. The pain variance at 30 min was seen as the primary outcome. Results: 65 RCTs with 8633 participants were involved. Comparing different classification and pharmacological mechanisms, combination therapy with more adverse events was more efficient than NSAIDs for the primary outcomes. Opioids gave rise to more nonspecific adverse events and vomiting events. NSAIDs were superior to opioids, paracetamol, and combination therapy after a full consideration of all outcomes. Comparing different routes of administration, NSAIDs with IV or IM route ranked first from efficacy and safety perspective. Comparing different specific drug branches with different routes, ibuprofen via IV route, ketorolac via IV route and diclofenac via IM route were superior for the management of acute renal colic. The results from diclofenac using IM route were more than those from ibuprofen used with IV route and ketorolac with IV route. Conclusions: In patients with adequate renal function, diclofenac via the IM route is recommended for patients without risks of cardiovascular events. Ibuprofen and ketorolac with IV route potentially superior to diclofenac via IM route remain to be investigated. Combination therapy is an alternative choice for uncontrolled pain after the use of NSAIDs.

18.
Int J Nanomedicine ; 13: 1265-1280, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29551896

RESUMO

Purpose: FTY720, known as fingolimod, is a new immunosuppressive agent with effective anticancer properties. Although it was recently confirmed that FTY720 inhibits cancer cell proliferation, FTY720 can also induce protective autophagy and reduce cytotoxicity. Blocking autophagy with Beclin 1 siRNA after treatment with FTY720 promotes apoptosis. The objective of this study was to enhance the anticancer effect of FTY720 in hepatocellular carcinoma (HCC) by targeted co-delivery of FTY720 and Beclin 1 siRNA using calcium phosphate (CaP) nanoparticles (NPs). Materials and methods: First, the siRNA was encapsulated within the CaP core. To form an asymmetric lipid bilayer structure, we then used an anionic lipid for the inner leaflet and a cationic lipid for the outer leaflet; after removing chloroform by rotary evaporation, these lipids were dispersed in a saline solution with FTY720. The NPs were analyzed by transmission electron microscopy, dynamic light scattering and ultraviolet-visible spectrophotometry. Cancer cell viability and cell death were analyzed by MTT assays, fluorescence-activated cell sorting analysis and Western blotting. In addition, the in vivo effects of the NPs were investigated using an athymic nude mouse subcutaneous transplantation tumor model. Results: When the CaP NPs, called LCP-II NPs, were loaded with FTY720 and siRNA, they exhibited the expected size and were internalized by cells. These NPs were stable in systemic circulation. Furthermore, co-delivery of FTY720 and Beclin 1 siRNA significantly increased cytotoxicity in vitro and in vivo compared with that caused by treatment with the free drug alone. Conclusion: The CaP NP system can be further developed for co-delivery of FTY720 and Beclin 1 siRNA to treat HCC, enhancing the anticancer efficacy of FTY720. Our findings provide a new insight into HCC treatment with co-delivered small molecules and siRNA, and these results can be readily translated into cancer clinical trials.


Assuntos
Proteína Beclina-1/genética , Carcinoma Hepatocelular/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Cloridrato de Fingolimode/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Autofagia/genética , Fosfatos de Cálcio/química , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Cloridrato de Fingolimode/farmacocinética , Humanos , Lipídeos/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos Nus , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Sci Rep ; 8(1): 2471, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29410409

RESUMO

The liver has great regenerative capacity after functional mass loss caused by injury or disease. Many studies have shown that primary hepatocyte-derived exosomes, which can deliver biological information between cells, promote the regenerative process of the liver. However, the yield of exosomes is very limited. Recent studies have demonstrated that exosome-mimetic nanovesicles (NVs) can be prepared from cells with almost 100 times the production yield compared with exosomes. Thus, this study investigated the therapeutic capacity of exosome-mimetic NVs from primary hepatocytes in liver regeneration. Exosome-mimetic NVs were prepared by serial extrusions of cells through polycarbonate membranes, and the yield of these NVs was more than 100 times that of exosomes. The data indicated that the NVs could promote hepatocyte proliferation and liver regeneration by significantly enhancing the content of sphingosine kinase 2 in recipient cells. To the best of our knowledge, this is the first time that exosome-mimetic NVs from primary hepatocytes have been prepared, and these NVs have components similar to exosomes from primary hepatocytes and, in some respects, biofunctions similar to exosomes. Strategies inspired by this study may lead to substitution of exosomes with exosome-mimetic NVs for biofunctional purposes, including utilization in tissue repair and regeneration.


Assuntos
Materiais Biomiméticos/administração & dosagem , Exossomos/transplante , Hepatócitos/química , Regeneração Hepática/fisiologia , Nanoestruturas/administração & dosagem , Animais , Materiais Biomiméticos/química , Proliferação de Células , Centrifugação com Gradiente de Concentração/métodos , Exossomos/química , Expressão Gênica , Hepatectomia/métodos , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Injeções Intravenosas , Fígado/metabolismo , Fígado/cirurgia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanoestruturas/química , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Cultura Primária de Células , Ácidos Tri-Iodobenzoicos , Ultracentrifugação/métodos , Regulação para Cima/efeitos dos fármacos
20.
ACS Appl Mater Interfaces ; 10(5): 4851-4859, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29285939

RESUMO

We use a mixed host, 2,6-bis[3-(carbazol-9-yl)phenyl]pyridine blended with 20 wt % tris(4-carbazoyl-9-ylphenyl)amine, to lower the hole-injection barrier, along with the bipolar and high-photoluminescence-quantum-yield (Φp= 84%), blue thermally activated delay fluorescence (TADF) material of 9,9-dimethyl-9,10-dihydroacridine-2,4,6-triphenyl-1,3,5-triazine (DMAC-TRZ) as a blue dopant to compose the emission layer for the fabrication of a TADF blue organic-light-emitting diode (BOLED). The device is highly efficient with the following performance parameters: maximum brightness (Bmax) = 57586 cd/m2, maximum current efficiency (CEmax) = 35.3 cd/A, maximum power efficiency (PEmax) = 21.4 lm/W, maximum external quantum efficiency (EQEmax) = 14.1%, and CIE coordinates (0.18, 0.42). This device has the best performance recorded among the reported solution-processed TADF BOLEDs and has a low efficiency roll-off: at brightness values of 1000 and 5000 cd/m2, its CEs are close, being 35.1 and 30.1 cd/A, respectively. Upon further doping of the red phosphor Ir(dpm)PQ2 (emission peak λmax = 595 nm) into the blue emission layer, we obtained a TADF-phosphor hybrid white organic-light-emitting diode (T-P hybrid WOLED) with high performance: Bmax = 43594 cd/m2, CEmax = 28.8 cd/A, PEmax = 18.1 lm/W, and CIE coordinates (0.38, 0.44). This Bmax = 43594 cd/m2 is better than that of the vacuum-deposited WOLED with a blue TADF emitter, 10000 cd/m2. This is also the first report on a T-P hybrid WOLED with a solution-processed emitting layer.

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