Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mater Sci Eng C Mater Biol Appl ; 108: 110393, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923982

RESUMO

The simple method to manufacture a flexible multi-drug with hydrophilic and hydrophobic molecules-loaded composite membrane via three dimensional (3D) electrohydrodynamic (EHD) printing has been demonstrated in this study. The composite membrane consists of two different drug-loaded sections: cellulose acetate-ibuprofen (CA-IBU) and cellulose acetate-paracetamol (CA-Para), respectively, with an intermediate polycaprolactone (PCL) folding component. The composite membranes can be folded and housed in commercial capsules to aid swallowing. By changing the number of PCL layers in the intermediate layers, it is possible to control and modify the mechanical and unfolding properties of the composite membrane. IBU and Para are loaded into the CA polymeric matrix in their amorphous states, with the matrices exhibiting Higuchi and first order release kinetics, respectively. The combination of IBU and Para can potentially be used as analgesic for patients. Magnetic nanoparticles as a functional material can be incorporated into the PCL matrix for wide targeting and traceable applications. The composite membrane here possesses good biocompatibility and flexibility; enabling extensive application prospects in drug combination therapy and personalized medicine.

2.
Opt Express ; 27(22): 31874-31888, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684411

RESUMO

A dual-optimized adaptive Kalman filtering (DO-AKF) algorithm based on back propagation (BP) neural network and variance compensation was developed for high-sensitivity trace gas detection in laser spectroscopy. The BP neural network was used to optimize the Kalman filter (KF) parameters. Variance compensation was introduced to track the state of the system and to eliminate the variations in the parameters of dynamic systems. The proposed DO-AKF algorithm showed the best performance compared with the traditional multi-signal average, extended KF, unscented KF, KF optimized by BP neural network (BP-KF) and KF optimized by variance compensation (VC-KF). The optimized DO-AKF algorithm was applied to a QCL-based gas sensor system for an exhaled CO analysis. The experimental results revealed a sensitivity enhancement factor of 23. The proposed algorithm can be widely used in the fields of environmental pollutant monitoring, industrial process control, and breath gas diagnosis.

3.
BMC Cancer ; 19(1): 988, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647032

RESUMO

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

4.
ACS Appl Mater Interfaces ; 11(8): 7823-7835, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30730130

RESUMO

Yolk-shell particles (YSPs) have attracted increasing attention from various research fields because of their low density, large surface area, and excellent loading capacity. However, the fabrication of polymer-based porous YSPs remains a great challenge. In this work, multifunctional polycaprolactone YSPs were produced using trineedle coaxial electrospraying with a simple nonsolvent process. TiO2-Ag nanoparticles and Ganoderma lucidum polysaccharides (GLPs) were encapsulated into the outer shell of the YSPs as the major antibacterial and antioxidant components, whereas iron oxide (Fe3O4) nanoparticles were incorporated into the inner core to act as a photothermal agent. The morphology and structure, chemical composition, biocompatibility, antioxidant, and antibacterial effects of the fabricated YSPs, photothermal effects, and the release profile of the encapsulated GLP were studied in vitro. Furthermore, the in vivo wound healing effects of the YSPs and the laser-assisted therapy were explored based on a burn wound model on c57 mice.


Assuntos
Materiais Biocompatíveis/farmacologia , Cicatrização/efeitos dos fármacos , Saco Vitelino/química , Animais , Antioxidantes/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Queimaduras/terapia , Óxido Ferroso-Férrico/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos C57BL , Fototerapia , Poliésteres/química , Polissacarídeos/química , Porosidade , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Reishi/metabolismo , Prata/química , Titânio/química
5.
Mater Sci Eng C Mater Biol Appl ; 97: 776-783, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678967

RESUMO

Recent advances in selective integration of micro and nano-scaled features towards material design have paved way to enhance desirable properties or functions of biomaterials. For drug delivery applications these include improved active component encapsulation, controlled drug release and managed interaction with the intended host environment. Electrohydrodynamic (EHD) direct-printing technique is a one-step on demand fiber deposition method which enables precise micron-scaled topographic and structural enhancement during material fabrication. In this study, core-sheath composite fibers comprising polycaprolactone, polyvinyl pyrrolidone and the drug tetracycline hydrochloride were prepared using the coaxial format of EHD direct-printing. Once positioned and aligned; multi-stacked fibers gave rise to patches. Coaxial fiber (diameter range ~13-25 µm) optimization (deposition and integrity) involved parameter-structure (e.g. collector speed, flow rate, working distance and applied voltage) impact analysis. Water contact angle measurements, tensile testing and Fourier transform infrared spectroscopy were used to analyze core-sheath integrated patches. In-vitro drug release studies clearly elude to the impact of core-shell and patterned architectures; demonstrating their viability and the forming method as emerging tools for advanced drug delivery system design and fabrication.


Assuntos
Portadores de Fármacos/química , Materiais Biocompatíveis/química , Liberação Controlada de Fármacos , Tamanho da Partícula , Poliésteres/química , Povidona/química , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração , Tetraciclina/química , Tetraciclina/metabolismo
6.
Drug Deliv Transl Res ; 9(1): 204-214, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30341763

RESUMO

In this study, a dual rotation centrifugal electrospinning system (DRCES) is designed, developed, and used to prepare medicated fabrics. Through simultaneous rotation of both spinneret and collector, multi-directional blended fiber matrices (PVP and TPU) were deposited directly on the rotating collector. To detail the process, key stages of the centrifugal electrospinning process are elaborated, and the influence of gas infusion and collector rotation speed on resulting fiber morphologies was explored. Multi-directional fibrous structures show in vitro biocompatibility (fibroblast). Regulation of drug release rate was achieved using polymer composition and filament alignment. This study demonstrates a rapid fabrication method (~ 50 g/h) to engineer layered fibrous structures using DRCES, which provides a foundation for preparing complex drug matrices (single and multi-directional) for tailored active component release.


Assuntos
Materiais Biocompatíveis/química , Fibroblastos/ultraestrutura , Nanofibras/química , Centrifugação , Teste de Materiais , Nanofibras/ultraestrutura , Tamanho da Partícula , Polímeros/química , Rotação , Propriedades de Superfície , Difração de Raios X
7.
Int J Biol Macromol ; 121: 1160-1178, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30342128

RESUMO

Ganoderma, has been used for clinical applications for thousands of years as a highly-nutritious and significantly-effective medicinal herb. The active components and efficacy of Ganoderma are constantly being explored and supplemented every year. In recent years, more and more literature has reported the pharmacological effects of Ganoderma on anti-tumor, liver protection and immunity enhancement, especially on neuroprotection. Numerous research works on the neuroprotective effects of Ganoderma have been documented (e.g., modulation of neurogenesis, amelioration of Alzheimer's disease, therapeutic effect on epilepsy, the protective effect on neural cells in stroke injury, etc.) thus it has drawn increasing attention. However, an integrated and comprehensive review of recent research findings has not been detailed in any great depth. Therefore, the purpose of this review is to summarize and elucidate recent progress of neuroprotective effects of natural Ganoderma and its extracts.


Assuntos
Produtos Biológicos/farmacologia , Ganoderma/química , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Humanos
8.
Sci Rep ; 8(1): 14608, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279587

RESUMO

Chitosan is an extremely valuable biopolymer and is usually obtained as a byproduct from the shells of crustaceans. In the current work, chitosan is obtained from an herbal source (Ganoderma lucidum spore powder (GLSP)) for the first time. To show this, both standard (thermochemical deacetylation, (TCD)) and emerging (ultrasound-assisted deacetylation (USAD)) methods of chitosan preparation were used. The obtained chitosan was characterized by elemental analysis, XRD (X-ray diffraction), FT-IR (Fourier transform infrared spectroscopy) and thermogravimetric measurements. The process resulted in chitosan possessing comparable values of DD, [η] and [Formula: see text] to the commercial product. Chitosan obtained via both processes (TCD and USAD) displayed excellent biocompatibility; although the USAD prepared biopolymer exhibited significantly improved fibroblast (L929 cell) viability and enhanced antibacterial zones for both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The findings of new herbal chitosan mark key developments of natural biomaterials; marking a potential shift from conventional sea-based organisms.


Assuntos
Quitosana/farmacologia , Reishi/química , Esporos Fúngicos/química , Acetilação , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/síntese química , Quitosana/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Pós , Sonicação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
9.
World J Nephrol ; 7(5): 96-107, 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30211028

RESUMO

AIM: To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model. METHODS: At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments. RESULTS: Compared to the wild-type cohort, the PCK kidney (Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort. CONCLUSION: These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.

10.
Eur J Pharm Sci ; 125: 64-73, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30248388

RESUMO

Chronic lung diseases (e.g. chronic obstructive pulmonary disease and asthma) are associated with oxidative stress and common treatments include various types of inhalation therapies. In this work Ganoderma lucidum polysaccharide (GLP), a naturally occurring antioxidant is loaded into porous Poly (ε-caprolactone) (PCL) particles using a single step tri-needle coaxial electrospray process (Tri-needle CES); with a view to develop therapies to combat oxidative stress. Based on the core-shell structure of porous yolk shell particles (YSPs), GLP-loaded YSPs displayed a bi-phasic release pattern. In vitro cell studies indicate GLP-loaded porous YSPs display good biocompatibility and positive attributes towards H2O2-induced oxidative stress in MRC-5 cells and dramatically attenuate intracellular reactive oxygen species (ROS) levels as well as significantly increase cell viability. In vivo inhalation studies indicate that GLP-loaded porous YSPs can be delivered to deep lung tissue and remain deposited for over 48 h and are subsequently removed by natural clearance mechanisms. Based on current findings GLP-loaded porous YSPs are suitable for pulmonary delivery and display good inhalation therapy potential to treat chronic lung diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Poliésteres/administração & dosagem , Polissacarídeos/administração & dosagem , Reishi , Administração por Inalação , Animais , Linhagem Celular , Humanos , Pulmão/metabolismo , Masculino , Camundongos , Agulhas , Estresse Oxidativo/efeitos dos fármacos , Poliésteres/farmacocinética , Polissacarídeos/farmacocinética , Tecnologia Farmacêutica
11.
J Biomed Inform ; 86: 1-14, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30103028

RESUMO

BACKGROUND AND OBJECTIVE: Clinical prognosis prediction plays an important role in clinical research and practice. The construction of prediction models based on electronic health record data has recently become a research focus. Due to the lack of external validation, prediction models based on single-center, hospital-specific datasets may not perform well with datasets from other medical institutions. Therefore, research investigating prognosis prediction model construction based on a collaborative analysis of multi-center electronic health record data could increase the number and coverage of patients used for model training, enrich patient prognostic features and ultimately improve the accuracy and generalization of prognosis prediction. MATERIALS AND METHODS: A web service for individual prognosis prediction based on multi-center clinical data collaboration without patient-level data sharing (POPCORN) was proposed. POPCORN focuses on solving key issues in multi-center collaborative research based on electronic health record systems; these issues include the standardization of clinical data expression, the preservation of patient privacy during model training and the effect of case mix variance on the prediction model construction and application. POPCORN is based on a multivariable meta-analysis and a Bayesian framework and can construct suitable prediction models for multiple clinical scenarios that can effectively adapt to complex clinical application environments. RESULTS: POPCORN was validated using a joint, multi-center collaborative research network between China and the United States with patients diagnosed with colorectal cancer. The performance of the models based on POPCORN was comparable to that of the standard prognosis prediction model; however, POPCORN did not expose raw patient data. The prediction models had similar AUC, but the BMA model had the lowest ECI across all prediction models, indicating that this model had better calibration performance than the other models, especially for patients in Chinese hospitals. CONCLUSIONS: The POPCORN system can build prediction models that perform well in complex clinical application scenarios and can provide effective decision support for individual patient prognostic predictions.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Sistemas de Apoio a Decisões Clínicas , Registros Eletrônicos de Saúde , Internet , Acesso à Informação , Idoso , Algoritmos , Teorema de Bayes , Calibragem , China , Diagnóstico por Computador , Feminino , Humanos , Disseminação de Informação , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Reprodutibilidade dos Testes , Estados Unidos
12.
ACS Appl Mater Interfaces ; 10(29): 24876-24885, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29953813

RESUMO

A simple method to rapidly customize and to also mass produce oral dosage forms is arguably a current bottleneck in the development of modern personalized medicine. Specifically, delayed-release mechanisms with well-controlled dosage profiles for combinations of traditional Chinese herbal extracts and Western medications are not well established. Herein, we demonstrate a novel multidrug-loaded membrane sandwich with structures infused with ibuprofen (IBU) and Ganoderma lucidum polysaccharide (GLP) using three-dimensional electrohydrodynamic printing and electrospinning techniques. The resulting flexible membrane consists of microscaled, multilayered cellulose acetate (CA) membranes loaded with IBU in the shape of either concentric squares or circles, as the top and bottom layers of a sandwich structure. In between the CA-IBU layers are randomly electrospun polyvinyl pyrrolidone (PVP) layers loaded with GLP. The complete fibrous membrane sandwich can be folded and embedded into a 0-size capsule to achieve oral compliance. Simulated in vitro testing of gastric and intestinal fluids demonstrated a triphasic release profile. There was an immediate release of GLP after gastric juices dissolved the capsule shell and the PVP, followed by the short-term release of 60% of the IBU within an hour afterward, and the remaining IBU was released in a sustained manner following a Fickian diffusion profile. In summary, this multidrug (both hydrophilic and/or hydrophobic) oral system with precision-designed structures should enable personalized therapeutic dosing.


Assuntos
Impressão Tridimensional , Cápsulas , Ibuprofeno , Povidona
13.
J Biomed Inform ; 83: 33-39, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29793070

RESUMO

End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD) and requires hemodialysis (HD) for survival. Intradialytic blood pressure (IBP) measurements are necessary to ensure patient safety during HD treatments and have critical clinical and prognostic significance. Studies on IBP measurements, especially IBP patterns, are limited. All related studies have been based on a priori knowledge and artificially classified IBP patterns. Therefore, the results were influenced by subjective concepts. In this study, we proposed a new approach to identify IBP patterns to classify ESRD patients. We used the dynamic time warping (DTW) algorithm to measure the similarity between two series of IBP data. Five blood pressure (BP) patterns were identified by applying the density peak clustering algorithm (DPCA) to the IBP data. To illustrate the association between BP patterns and prognosis, we constructed three random survival forest (RSF) models with different covariates. Model accuracy was improved 3.7-6.3% by the inclusion of BP patterns. The results suggest that BP patterns have critical clinical and prognostic significance regarding the risk of cerebrovascular events. We can also apply this clustering approach to other time series data from electronic health records (EHRs). This work is generalizable to analyses of dense EHR data.


Assuntos
Determinação da Pressão Arterial , Falência Renal Crônica/diagnóstico , Reconhecimento Automatizado de Padrão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Pressão Sanguínea , Criança , Análise por Conglomerados , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
14.
Int J Legal Med ; 132(3): 791-798, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28717963

RESUMO

To establish population-specific age estimation models in adults from costal cartilage for contemporary Chinese by using three-dimensional volume-rendering technique. Five hundred and twelve individuals (254 females and 258 males) with documented ages between 20 and 85 years were retrospectively included. Their clinical CT examinations (1 mm slice thickness) were used to develop the sex-specific age prediction model. A validation sample comprising 26 female and 24 male individuals was then used to test the predictive accuracy of the established models. Simple linear regression (SLR), multiple linear regression (MLR), gradient boosting regression (GBR), support vector machine (SVM), and decision tree regression (DTR) were utilized to build the age diagnosis models from calibration samples. By comparison, the decision tree regression was the relatively more accurate age prediction model for male, with mean absolute error = 5.31 years, least absolute error = 0.10 years, correct percentage within 5 years = 54%, and the correct percentage within 10 years = 88%. The stepwise multiple linear regression equations was the relatively more accurate one for female, with mean absolute error = 6.72 years, least absolute error = 0.68 years, correct percentage within 5 years = 42%, and correct percentage within 10 years = 77%. Our results indicated that the present established age estimation model can be applied as an additional guidance for age estimation in adults.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Cartilagem Costal/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Adulto , Idoso , Idoso de 80 Anos ou mais , Árvores de Decisões , Feminino , Medicina Legal/métodos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Caracteres Sexuais , Máquina de Vetores de Suporte , Adulto Jovem
15.
J Biomed Inform ; 72: 45-59, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28676255

RESUMO

OBJECTIVE: Chronic diseases are complex and persistent clinical conditions that require close collaboration among patients and health care providers in the implementation of long-term and integrated care programs. However, current solutions focus partially on intensive interventions at hospitals rather than on continuous and personalized chronic disease management. This study aims to fill this gap by providing computerized clinical decision support during follow-up assessments of chronically ill patients at home. METHODS: We proposed an ontology-based framework to integrate patient data, medical domain knowledge, and patient assessment criteria for chronic disease patient follow-up assessments. A clinical decision support system was developed to implement this framework for automatic selection and adaptation of standard assessment protocols to suit patient personal conditions. We evaluated our method in the case study of type 2 diabetic patient follow-up assessments. RESULTS: The proposed framework was instantiated using real data from 115,477 follow-up assessment records of 36,162 type 2 diabetic patients. Standard evaluation criteria were automatically selected and adapted to the particularities of each patient. Assessment results were generated as a general typing of patient overall condition and detailed scoring for each criterion, providing important indicators to the case manager about possible inappropriate judgments, in addition to raising patient awareness of their disease control outcomes. Using historical data as the gold standard, our system achieved a rate of accuracy of 99.93% and completeness of 95.00%. CONCLUSIONS: This study contributes to improving the accessibility, efficiency and quality of current patient follow-up services. It also provides a generic approach to knowledge sharing and reuse for patient-centered chronic disease management.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Diabetes Mellitus , Gerenciamento Clínico , Doença Crônica , Seguimentos , Humanos
16.
Cancer Med ; 6(8): 1882-1892, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28707427

RESUMO

The survival risk following curative surgery for nonmetastatic colorectal cancer (CRC) may be over- or underestimated due to a lack of attention to nonlinear effects and violation of the proportional hazards assumption. In this paper, we aimed to detect and interpret the shape of time-dependent and nonlinear effects to improve the predictive performance of models of prognoses in nonmetastatic CRC patients. Data for nonmetastatic CRC patients diagnosed between 2004 and 2012 were obtained from the Surveillance Epidemiology End Results registry. Time-dependent and nonlinear effects were tested and plotted. A nonlinear model that used random survival forests was implemented. The estimated 5-year cancer-specific death rate was 17.95% (95% CI, 17.70-18.20%). Tumor invasion depth, lymph node status, age at diagnosis, tumor grade, histology and tumor site were significantly associated with cancer-specific death. Nonlinear and time-dependent effects on survival were detected. Positive lymph node number had a larger effect per unit of measurement at low values than at high values, whereas age at diagnosis showed the opposite pattern. Moreover, nonproportional hazards were detected for all covariates, indicating that the contributions of these risks to survival outcomes decreased over time. The nonlinear model predicted prognoses more accurately (C-index: 0.7934, 0.7933-0.7934) than did the Fine and Gray model (C-index: 0.7550, 0.7510-0.7583). The three-dimensional cumulative incidence curves derived from nonlinear model were used to identify the change points of the risk trends. It would be useful to implement these findings in treatment plans and follow-up surveillance in nonmetastatic CRC patients.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Dinâmica não Linear , Prognóstico , Programa de SEER , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
17.
World J Gastroenterol ; 23(23): 4181-4190, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28694658

RESUMO

AIM: To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD). METHODS: We have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis. RESULTS: Upregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid-driven HepG2 cell death. (P < 0.05 vs control) supporting the finding that Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson's trichrome staining (P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models. CONCLUSION: These data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.


Assuntos
Acetamidas/farmacologia , Regulação Neoplásica da Expressão Gênica , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Compostos de Tritil/farmacologia , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Dieta Hiperlipídica , Fibrose , Células Hep G2 , Humanos , Inflamação , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido Palmítico , Ratos , Ratos Wistar , Tioacetamida , Regulação para Cima
18.
ACS Appl Mater Interfaces ; 9(25): 21485-21495, 2017 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-28589726

RESUMO

Particulate platforms capable of delivering multiple actives as well as providing diagnostic features have gained considerable interest over the last few years. In this study, magnetic polymer yolk-shell particles (YSPs) were engineered using a tri-needle coaxial electrospraying technique enabling dual-mode (ultrasonic and magnetic resonance) imaging capability with specific multidrug compartments via an advanced single-step encapsulation process. YSPs comprised magnetic Fe3O4 nanoparticles (MNPs) embedded in the polymeric shell, an interfacing oil layer, and a polymeric core (i.e., composite shell-oil interface-polymeric core). The frequency of the ultrasound backscatter signal was modulated through YSP loading dosage, and both T1- and T2-weighted magnetic resonance imaging signal intensities were shown to decrease with increasing MNP content (YSP outer shell). Three fluorescent dyes (selected as model probes with varying hydrophobicities) were coencapsulated separately to confirm the YSP structure. Probe release profiles were tuned by varying power or frequency of an external auxiliary magnetic field (AMF, 0.7 mT (LAMF) or 1.4 mT (HAMF)). In addition, an "inversion" phenomenon for the AMF-enhanced drug release process was studied and is reported. A low YSP cytotoxicity (5 mg/mL) and biocompatibility (murine, L929) was confirmed. In summary, magnetic YSPs demonstrate timely potential as multifunctional theranostic agents for dual-imaging modality and magnetically controlled coactive delivery.

19.
J Food Sci ; 82(6): 1412-1422, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28471056

RESUMO

A novel antimicrobial composite material was prepared by encapsulating orange essential oil (OEO) in zein prolamine (ZP) via the coaxial electrospinning (ES) technique. By manipulating process parameters, the morphological features of ZP/OEO fibers were modulated. Fine fibers with diameters ranging from 0.7 to 2.3 µm were obtained by regulating ZP solution concentration and process parameters during the ES process. Optimal loading capacity (LC) and encapsulation efficiency (EE) of OEO in fibrous ZP mats were determined to be 22.28% and 53.68%, respectively, and were achieved using a 35 w/v% ZP ES solution. The encapsulation of OEO was found to be reliant on ZP solution concentration (the enveloping medium). SEM analysis indicates the surface morphology of ZP/OEO electrospun fibers is dependent on ZP solution loading volume, with lower ZP concentrations yielding defective fibrous structures (for example, beaded and spindled-string like morphologies). Furthermore, this loading volume also influences OEO LC, EE, mat water contact angle and oil retention. CCK-8 assay and cell morphology assessment (HEK293T cells) indicate no significant change with electrospun ZP and ZP/OEO fibrous membranes over an 8 h period. Antimicrobial activity assessment using Escherichia coli, suggests composite nonwovens possess sterilization properties; elucidating potential application in active food packaging, food preservation and therefore sustainability.


Assuntos
Fenômenos Mecânicos , Membranas Artificiais , Óleos Vegetais/química , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Embalagem de Alimentos , Células HEK293 , Humanos , Óleos Voláteis/química , Fenilpropanolamina/química , Zeína/química
20.
Int J Pharm ; 524(1-2): 148-158, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28359818

RESUMO

Ganoderma lucidum polysaccharide (GLP) is a functional food source deployed in preventative medicine. However, applications utilizing GLP are limited due to oxidative and acidic environmental damage. Advances in preserving GLP structure (and therefore function), in situ, will diversify their applications within biomedical fields (drug and antibacterial active delivery via the enteral route). In this study, GLP loaded sodium alginate (NaAlg) micro-particles (size range 225-355µm) were generated using the electrospray (ES) process. The loading capacity and encapsulation efficiency of GLP for composite particles (collected at different temperatures) were ∼23% and 71%, respectively. The collection substrate (CaCl2, 1-20w/v%) concentration was explored and preliminary findings indicated a 10w/v% solution to be optimal. The process was further modified by manipulating the collection environment temperature (∼25 to 50°C). Based on this, NaAlg/GLP micro-particles were engineered with variable surface morphologies (porous and crinkled), without effecting the chemical composition of either material (GLP and NaAlg). In-vitro release studies demonstrated pH responsive release rates. Modest release of GLP from micro-particles in simulated gastric fluid (pH ∼1.7) was observed, while rapid release was exhibited under simulated intestinal conditions (pH ∼7.4). Release of GLP from NaAlg beads was the greatest from samples prepared at elevated environmental temperatures. These findings demonstrate a facile route to fabricate GLP-NaAlg loaded micro-particles with various shapes, surface topographies and release characteristics via a one-step ES process.


Assuntos
Alginatos/química , Polissacarídeos/química , Reishi/química , Química Farmacêutica , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Microesferas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA