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INTRODUCTION: Liver fibrosis is a major cause of morbidity and mortality among in patients with chronic hepatitis. Radiomics, particularly of the spleen, may improve diagnostic accuracy and treatment strategies. External validations are necessary to ensure reliability and generalizability. METHODS: In this retrospective study, we developed 3 radiomics models using contrast-enhanced computed tomography scans from 167 patients with liver fibrosis (training group) between January 2020 and December 2021. Radiomic features were extracted from arterial venous, portal venous, and equilibrium phase images. Recursive feature selection random forest and the least absolute shrinkage and selection operator logistic regression were used for feature selection and dimensionality reduction. Performance was assessed by area under the curve, C-index, calibration plots, and decision curve analysis. External validation was performed on 114 patients from 2 institutions. RESULTS: Twenty-five radiomic features were significantly associated with fibrosis stage, with 80% of the top 10 features originating from portal venous phase spleen images. The radiomics models showed good performance in the validation cohort (C-indices 0.723-0.808) and excellent calibration. Decision curve analysis indicated clinical benefits, with machine learning-based radiomics models (Random Forest score and support vector machine based radiomics score) providing more significant advantages. DISCUSSION: Radiomic features offer significant benefits over existing serum indices for staging virus-driven liver fibrosis, underscoring the value of radiomics in enhancing diagnostic accuracy. Specifically, radiomics analysis of the spleen presents additional noninvasive options for assessing fibrosis, highlighting its potential in improving patient management and outcomes.
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For Caucasian women, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) cutpoint value for classifying osteoporosis is 80 mg/ml. At the age of approximate 78 years, US Caucasian women QCT LS BMD population mean is 80 mg/ml, while that of Chinese women and Japanese women is around 50 mg/ml. Correlation analyses show, for Chinese women and Japanese women, QCT LS BMD of 45 mg/ml corresponds to the dual-energy X-ray absorptiometry cutpoint value for classifying osteoporosis. For Chinese and Japanese women, if QCT LS BMD 80 mg/ml is used as the threshold to classify osteoporosis, then the specificity of classifying subjects with vertebral fragility fracture into the osteoporotic group is low, whereas threshold of 45 mg/ml approximately achieve a similar separation for women with and without vertebral fragility fracture as the reports for Caucasian women. Moreover, by using 80mg/ml as the cutpoint value, LS QCT leads to excessively high prevalence of osteoporosis for Chinese women, with the discordance between hip dual-energy X-ray absorptiometry and LS QCT measures far exceeding expectation. Considering the different bone properties and the much lower prevalence of fragility fractures in the East Asian women compared with Caucasians, we argue that the QCT cutpoint value for classifying osteoporosis among older East Asian women will be close to and no more than 50 mg/ml LS BMD. We suggest that it is also imperative the QCT osteoporosis classification criterion for East Asian male LS, and male and female hips be re-examined.
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Densidade Óssea , População do Leste Asiático , Vértebras Lombares , População Branca , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Absorciometria de Fóton , Vértebras Lombares/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Prevalência , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
Background: Pulmonary nodular consolidation (PN) and pulmonary cavity (PC) may represent the two most promising imaging signs in differentiating multidrug-resistant (MDR)-pulmonary tuberculosis (PTB) from drug-sensitive (DS)-PTB. However, there have been concerns that literature described radiological feature differences between DS-PTB and MDR-PTB were confounded by that MDR-PTB cases tend to have a longer history. This study seeks to further clarify this point. Methods: All cases were from the Guangzhou Chest Hospital, Guangzhou, China. We retrieved data of consecutive new MDR cases [n=46, inclusive of rifampicin-resistant (RR) cases] treated during the period of July 2020 and December 2021, and according to the electronic case archiving system records, the main PTB-related symptoms/signs history was ≤3 months till the first computed tomography (CT) scan in Guangzhou Chest Hospital was taken. To pair the MDR-PTB cases with assumed equal disease history length, we additionally retrieved data of 46 cases of DS-PTB patients. Twenty-two of the DS patients and 30 of the MDR patients were from rural communities. The first CT in Guangzhou Chest Hospital was analysed in this study. When the CT was taken, most cases had anti-TB drug treatment for less than 2 weeks, and none had been treated for more than 3 weeks. Results: Apparent CT signs associated with chronicity were noted in 10 cases in the DS group (10/46) and 9 cases in the MDR group (10/46). Thus, the overall disease history would have been longer than the assumed <3 months. Still, the history length difference between DS patients and MDR patients in the current study might not be substantial. The lung volume involvement was 11.3%±8.3% for DS cases and 8.4%±6.6% for MDR cases (P=0.022). There was no statistical difference between DS cases and MDR cases both in PN prevalence and in PC prevalence. For positive cases, MDR cases had more PN number (mean of positive cases: 2.63 vs. 2.28, P=0.38) and PC number (mean of positive cases: 2.14 vs. 1.38, P=0.001) than DS cases. Receiver operating characteristic curve analysis shows, PN ≥4 and PC ≥3 had a specificity of 86% (sensitivity 25%) and 93% (sensitivity 36%), respectively, in suggesting the patient being a MDR cases. Conclusions: A combination of PN and PC features allows statistical separation of DS and MDR cases.
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AIM: To describe the lived experiences of family caregivers of individuals with dementia during the coronavirus disease (COVID-19) outbreak in China. DESIGN: This study used a descriptive phenomenological research method. METHODS: Between May and September 2021, semi-structured interviews were conducted with 22 family caregivers of people with dementia. Colaizzi's method was used for manual analysis. RESULTS: Qualitative data revealed an overarching experience of finding 'There is always good fortune in misfortune to encourage us in coping with difficulties'. Three themes emerged: family reactions to the COVID-19 outbreak, feeling supported by multiple resources performing respective functions and resilient adaptation to new situations. CONCLUSION: During the COVID-19 outbreak, family caregivers of people living with dementia in China looked for positive aspects among difficulties and experienced corresponding reactions, social support resources and resilient adapted coping styles. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses in China and other countries facing similar pandemic characteristics, cultures or economic development levels, can guide family caregivers to look at family hardships from a positive perspective, develop interventions to rapidly respond to families' reactions after a disaster and help them identify social support resources and form adapted coping styles. IMPACT: We identified the resilience and the positive experiences of Chinese family caregivers of individuals with dementia during the COVID-19 outbreak. The results can inform countries with similar cultures and economic levels, offering measures to support their adaptation to pandemics. REPORTING METHOD: This study followed the COREQ guidelines. PATIENT OR PUBLIC CONTRIBUTION: Family caregivers of people with dementia who met the inclusion criteria and who were interested in sharing their understanding of their experiences, participated in the study.
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COVID-19 , Demência , Humanos , Cuidadores , COVID-19/epidemiologia , Pesquisa Qualitativa , Capacidades de Enfrentamento , China/epidemiologia , Surtos de Doenças , Demência/epidemiologia , FamíliaRESUMO
In the context of Pharma 4.0, pharmaceutical quality control (PQC) is beset by issues such as uncertainties from ever-changing critical material attributes and strong coupling between variables in the multi-unit pharmaceutical tablet manufacturing process (PTMP), and how to timely adjust the operational variables to deal with such challenges has become a key problem in PQC. In this study, we propose a novel data-knowledge-driven modeling and operational adjustment framework for PTMP by integrating Bayesian network (BN) and case-based reasoning (CBR). At the modeling level, first, a distributed concept is introduced, i.e., the BN model for each subunit of PTMP is established in accordance with the operation process sequence, and the transition variables are given by the BN model established first and retrieved as the new query for the next unit. Once the BN models of all subunits are built, they are integrated into a global BN model. At the operational adjustment level, by taking the expected critical quality attributes (CQAs) and related prior information as evidence, the operational adjustment is achieved through global BN reasoning. Finally, the case study in a sprayed fluidized-bed granulation-based PTMP demonstrates the feasibility and effectiveness in improving the terminal CQAs of the proposed method, which is also compared with other methods to showcase its efficacy and merits.
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Purpose: Our aim is to build and validate a clinical-radiomic model for non-invasive liver steatosis prediction based on non-contrast computed tomography (CT). Methods: We retrospectively reviewed 342 patients with suspected NAFLD diagnoses between January 2019 and July 2020 who underwent non-contrast CT and liver biopsy. Radiomics features from hepatic and splenic regions-of-interests (ROIs) were extracted based on abdominal non-contrast CT imaging. The radiomics signature was constructed based on reproducible features by adopting the least absolute shrinkage and selection operator (LASSO) regression. Then, multivariate logistic regression analysis was applied to develop a combined clinical-radiomic nomogram integrating radiomics signature with several independent clinical predictors in a training cohort of 124 patients between January 2019 and December 2019. The performance of models was determined by the area under the receiver operating characteristic curves and calibration curves. We conducted an internal validation during 103 consecutive patients between January 2020 and July 2020. Results: The radiomics signature was composed of four steatosis-related features and positively correlated with pathologic liver steatosis grade (p < 0.01). In both subgroups (Group One, none vs. steatosis; Group Two, none/mild vs. moderate/severe steatosis), the clinical-radiomic model performed best within the validation cohort with an AUC of 0.734 and 0.930, respectively. The calibration curve confirmed the concordance of excellent models. Conclusion: We developed a robust clinical-radiomic model for accurate liver steatosis stage prediction in a non-invasive way, which may improve the clinical decision-making ability.
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Oxygen (O2) in the air is a green oxidant, and utilization of air for pollutant removal is highly desired. Herein, we report the preparation and utilization of a novel biomass-based three-dimensional (3D) Ni@NiO/carbon composite for the electro-activation of O2 under room condition. The carbon-coated Ni@NiO nanoparticles are fabricated on a hierarchical 3D porous loofah sponge-derived carbon (LSC) support as the bifunctional catalyst for the activation of O2 via both the electro-oxidation and electro-reduction reactions. An electrocatalytic air oxidation coupling system is constructed with the Ni@NiO/LSC shell-core electrodes for pollutant degradation. A variety of organic pollutants, including pharmaceutics and personal care products (PPCPs), dyes, phenolic compounds, and real waters are mineralized by more than 60% with significantly enhanced biodegradability. Notably, the coupling system obtains high mineralization efficiency of 70.2 ± 1.9% on landfill leachate with significant biodegradability enhancement. The specific energy consumptions of the coupling system are only 6.8 ± 0.7 to 60.2 ± 3.6 kWh kg-TOC-1 in mineralizing different pollutants. The hollow structure of the LSC fibers endows the loaded Ni@NiO with superior intrinsic catalytic activity, which is associated with low reaction resistance and facile electron transfer. The Ni@NiO on LSC presents an electrocatalytic wet air oxidation (ECWAO) catalytic activity higher by 35.8% and cathodic air oxidation (CAO) catalytic activity higher by 22.7% as compared to that loaded on commercial graphite felt.
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Poluentes Ambientais , Grafite , Luffa , Carbono/química , Oxirredução , Grafite/química , OxigênioRESUMO
The issue of pervasively enhanced drug resistance of pancreatic cancer is fundamental to a better understanding of gemcitabine-based chemotherapy. Currently available treatment plans involving injectable therapeutics are mainly engineered to improve the performance and broaden their applications in the domain of biomedicine. Fixed-dose-rate infusion of free gemcitabine (Gem) has drawn appropriate attention for its potent anti-tumor efficacy against various solid tumors, whereas it remains a considerable challenge to extend its application and achieve better treatment. Here, we have prepared and demonstrated a long-acting delivery system using gemcitabine and injectable in situ hydrogel for the localized treatment of pancreatic cancer. The hydrogel was prepared using polysaccharide derivatives, oxidized-carboxymethylcellulose (OCMC) and carboxymethylchitosan (CMCS) at optimal ratios by a dopamine-functionalized method for the controlled release of Gem. In vitro drug release behaviors for up to a week indicated sustained drug release of the Gem delivery system. Moreover, desirable apoptosis promotion and apparent cellular proliferation inhibition associated with the drug depot have been found in vitro against BxPC-3 pancreatic cancer cells, bringing minimized side effects to systemic normal tissues. The current findings manifested that the release out of the localized delivery platform in a sustained pattern afforded a durable gemcitabine-based chemotherapy effect and inhibited tumor metastasis more persistently after intratumoral injection of the Gem@Gel system, thereby advancing the development of novel drug-loaded materials with properties not accessed previously.
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Hidrogéis , Neoplasias Pancreáticas , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Humanos , Hidrogéis/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Gencitabina , Neoplasias PancreáticasRESUMO
BACKGROUND: To establish and validate a radiomics-based model for staging liver fibrosis at contrast-enhanced CT images. MATERIALS AND METHODS: This retrospective study developed two radiomics-based models (R-score: radiomics signature; R-fibrosis: integrate radiomic and serum variables) in a training cohort of 332 patients (median age, 59 years; interquartile range, 51-67 years; 256 men) with biopsy-proven liver fibrosis who underwent contrast-enhanced CT between January 2017 and December 2020. Radiomic features were extracted from non-contrast, arterial and portal phase CT images and selected using the least absolute shrinkage and selection operator (LASSO) logistic regression to differentiate stage F3-F4 from stage F0-F2. Optimal cutoffs to diagnose significant fibrosis (stage F2-F4), advanced fibrosis (stage F3-F4) and cirrhosis (stage F4) were determined by receiver operating characteristic curve analysis. Diagnostic performance was evaluated by area under the curve, Obuchowski index, calibrations and decision curve analysis. An internal validation was conducted in 111 randomly assigned patients (median age, 58 years; interquartile range, 49-66 years; 89 men). RESULTS: In the validation cohort, R-score and R-fibrosis (Obuchowski index, 0.843 and 0.846, respectively) significantly outperformed aspartate transaminase-to-platelet ratio (APRI) (Obuchowski index, 0.651; p < .001) and fibrosis-4 index (FIB-4) (Obuchowski index, 0.676; p < .001) for staging liver fibrosis. Using the cutoffs, R-fibrosis and R-score had a sensitivity range of 70-87%, specificity range of 71-97%, and accuracy range of 82-86% in diagnosing significant fibrosis, advanced fibrosis and cirrhosis. CONCLUSION: Radiomic analysis of contrast-enhanced CT images can reach great diagnostic performance of liver fibrosis.
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Cirrose Hepática , Tomografia Computadorizada por Raios X , Idoso , Biomarcadores , Fibrose , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos RetrospectivosRESUMO
Hydraulic axial piston pump is broadly-used in aerospace, ocean engineering and construction machinery since it is the vital component of fluid power systems. In the light of the undiscoverability of its fault and the potential serious losses, it is valuable and challenging to complete the fault identification of a hydraulic pump accurately and effectively. Owing to the limitations of shallow machine learning methods in the intelligent fault diagnosis, more attention has been paid to deep learning methods. Hyperparameter plays an important role in a deep learning model. Although some manual tuning methods may represent good results in some cases, it is hard to reproduce due to the differences of datasets and other factors. Hence, Bayesian optimization (BO) algorithm is adopted to automatically select the hyperparameters. Firstly, the time-frequency images of vibration signals by continuous wavelet transform are taken as input data. Secondly, by setting some hyperparameters, a preliminary convolutional neural network (CNN) model is established. Thirdly, by identifying the range of each hyperparameter, BO based on Gaussian process is employed to construct an adaptive CNN model named CNN-BO. The performance of CNN-BO is verified by comparing with traditional LeNet 5 and improved LeNet 5 with manual optimization. The results indicate that CNN-BO can accomplish the intelligent fault diagnosis of a hydraulic pump accurately.
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Hydraulic piston pump is the heart of hydraulic transmission system. On account of the limitations of traditional fault diagnosis in the dependence on expert experience knowledge and the extraction of fault features, it is of great meaning to explore the intelligent diagnosis methods of hydraulic piston pump. Motivated by deep learning theory, a novel intelligent fault diagnosis method for hydraulic piston pump is proposed via combining wavelet analysis with improved convolutional neural network (CNN). Compared with the classic AlexNet, the proposed method decreases the number of parameters and computational complexity by means of modifying the structure of network. The constructed model fully integrates the ability of wavelet analysis in feature extraction and the ability of CNN in deep learning. The proposed method is employed to extract the fault features from the measured vibration signals of the piston pump and realize the fault classification. The fault data are mainly from five different health states: central spring failure, sliding slipper wear, swash plate wear, loose slipper, and normal state, respectively. The results show that the proposed method can extract the characteristics of the vibration signals of the piston pump in multiple states, and effectively realize intelligent fault recognition. To further demonstrate the recognition property of the proposed model, different CNN models are used for comparisons, involving standard LeNet-5, improved 2D LeNet-5, and standard AlexNet. Compared with the models for contrastive analysis, the proposed method has the highest recognition accuracy, and the proposed model is more robust.
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Glioblastoma multiforme (GBM) is a highly lethal and aggressive tumor of the brain that carries a poor prognosis. Temozolomide (TMZ) has been widely used as a first-line treatment for GBM. However, poor brain targeting, side effects, and drug resistance limit its application for the treatment of GBM. We designed a Temozolomide-conjugated gold nanoparticle functionalized with an antibody against the ephrin type-A receptor 3 (anti-EphA3-TMZ@GNPs) for targeted GBM therapy via intranasal administration. The system can bypass the blood-brain barrier and target active glioma cells to improve the glioma targeting of TMZ and enhance the treatment efficacy, while reducing the peripheral toxicity and drug resistance. The prepared anti-EphA3-TMZ@GNPs were 46.12 ± 2.0 nm and suitable for intranasal administration, which demonstrated high safety to the nasal mucosa in a toxicity assay. In vitro studies showed that anti-EphA3-TMZ@GNPs exhibited significantly enhanced cellular uptake and toxicity, and a higher cell apoptosis ratio has been seen compared with that of TMZ (54.9 and 14.1%, respectively) toward glioma cells (C6). The results from experiments on TMZ-resistant glioma cells (T98G) demonstrated that the IC50 of anti-EphA3-TMZ@GNPs (64.06 ± 0.16 µM) was 18.5-fold lower than that of TMZ. In addition, Western blot analysis also revealed that anti-EphA3-TMZ@GNPs effectively down-modulated expression of O6-methylguanine-DNA methyltransferase and increased chemosensitivity of T98G to TMZ. The antiglioma efficacy in vivo was investigated in orthotopic glioma-bearing rats, and the results demonstrated that the anti-EphA3-TMZ@GNPs prolonged the median survival time to 42 days and increased tumor-cell apoptosis dramatically compared with TMZ. In conclusion, anti-EphA3-TMZ@GNPs could serve as an intranasal drug delivery system for efficacious treatment of GBM.
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Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioma/tratamento farmacológico , Ouro/química , Nanopartículas Metálicas/química , Receptor EphA3/metabolismo , Temozolomida/farmacologia , Administração Intranasal/métodos , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioblastoma/metabolismo , Glioma/metabolismo , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
As a critical part of a hydraulic transmission system, a hydraulic axial piston pump plays an indispensable role in many significant industrial fields. Owing to the practical undesirable working environment and hidden faults, it is challenging to precisely and effectively detect and diagnose the varying fault in the engineering. Deep learning-based technology presents special strengths in processing mechanical big data. It can simultaneously complete the feature extraction and classification, and achieve the automatic information learning. The popular convolutional neural network (CNN) is exploited for its potent ability of image processing. In this paper, a novel combined intelligent method is developed for fault diagnosis towards a hydraulic axial piston pump. First, the conversion of signals to images is conducted via continuous wavelet transform; the effective feature is preliminarily extracted from the transformed time-frequency images. Second, a novel deep CNN model is constructed to achieve the fault classification. To disclose the potential learning in the disparate layers of the CNN model, the visualization of reduced features is performed by employing t-distributed stochastic neighbor embedding. The effectiveness and stability of the proposed model are validated through the experiments. With the proposed method, different fault types can be precisely identified and high classification accuracy is achieved in a hydraulic axial piston pump.
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A hydraulic axial piston pump is the essential component of a hydraulic transmission system and plays a key role in modern industry. Considering varying working conditions and the implicity of frequent faults, it is difficult to accurately monitor the machinery faults in the actual operating process by using current fault diagnosis methods. Hence, it is urgent and significant to investigate effective and precise fault diagnosis approaches for pumps. Owing to the advantages of intelligent fault diagnosis methods in big data processing, methods based on deep learning have accomplished admirable performance for fault diagnosis of rotating machinery. The prevailing convolutional neural network (CNN) displays desirable automatic learning ability. Therefore, an integrated intelligent fault diagnosis method is proposed based on CNN and continuous wavelet transform (CWT), combining the feature extraction and classification. Firstly, CWT is used to convert the raw vibration signals into time-frequency representations and achieve the extraction of image features. Secondly, a new framework of deep CNN is established via designing the convolutional layers and sub-sampling layers. The learning process and results are visualized by t-distributed stochastic neighbor embedding (t-SNE). The results of the experiment present a higher classification accuracy compared with other models. It is demonstrated that the proposed approach is effective and stable for fault diagnosis of a hydraulic axial piston pump.
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Noninvasive drug delivery is a promising treatment strategy for ocular posterior segment diseases. Many physiological and anatomical barriers of the eye considerably restrict effective diffusion of therapeutics to the target site. To overcome this problem, a novel cyclic arginine-glycine-aspartate (RGD) hexapeptide and penetratin (PEN) co-modified PEGylation polyamidoamine (PAMAM) was designed as a nanocarriers (NCs), and its penetrating and targeting abilities were evaluated. In this study, we show that PAMAM-PEG (reaction molar ratio 1:32) has a relatively high grafting efficiency and low cytotoxicity. The particle size was within the range of 15-20 nm after modification with RGD and PEN. Cellular uptake of RGD-modified NCs involved significant affinity toward integrin αvß3, which validated the targeting of neovasculature. An in vitro permeation study indicated that modification with PEN significantly improved penetration of the NCs (1.5 times higher). In vivo ocular distribution studies showed that, the NCs (modified with PEN or co-modified with RGD and PEN) were highly distributed in the cornea and retina (p < .001), and modification extended retinal retention time for more than 12 h. Therefore, these NCs appear to be a promising noninvasive ocular drug delivery system for ocular posterior segment diseases.
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Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/química , Córnea/efeitos dos fármacos , Dendrímeros/química , Peptídeos Cíclicos/química , Animais , Linhagem Celular , Córnea/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Humanos , Integrina alfaVbeta3/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tamanho da Partícula , Poliaminas/química , Polietilenoglicóis/químicaRESUMO
Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC0-12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p < .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson's disease.
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Antiparkinsonianos/administração & dosagem , Encéfalo/metabolismo , Canfanos , Dopamina/administração & dosagem , Lactoferrina , Nanopartículas/química , Administração Intranasal , Animais , Antiparkinsonianos/farmacocinética , Antiparkinsonianos/farmacologia , Células Cultivadas , Dopamina/farmacocinética , Dopamina/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/toxicidade , Doença de Parkinson/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
The purpose of this study was to solve the plateau phase (the stage in which the drug in the microsphere undergoes a slow release or almost no release after initial release) problem by understanding the effect of polymer blends on the internal pore changes of the microspheres. This study used PLGA 5050 4H (F-1), PLGA 5050 1A: PLGA 5050 4Hâ¯=â¯3:7 (F-2) and PLGA 7525 1A: PLGA 5050 4Hâ¯=â¯3:7 (F-3) as a carrier, respectively. Microspheres (MS) were obtained by O/W emulsion solvent evaporation technique and characterized by scanning electron microscopy (SEM), particle size, drug loading, fluorescence characteristics, and in vitro and in vivo release. Accelerated tests in vitro showed that the size and number of core pores significantly affected drug release in the first and second phases. After intramuscular administration, F-2 and F-3 showed effective blood concentration levels and their bioavailability was higher than that of the RLD (Sandostatin Lar). In general, our data indicate that pore formation is unevenly distributed throughout PLGA MS prepared using polymer blends, and the use of polymer blends is instructive for the development of sustained smooth release microspheres. Therefore, the octreotide MS described in this study has a good clinical application potential for the treatment of acromegaly.
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Octreotida/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polímeros/química , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Emulsões/química , Masculino , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Solventes/químicaRESUMO
BACKGROUND: The sensitivity of the commonly used immunochromatographic fecal occult blood test (iFOBT) is critical in the routine screening of digestive tract cancers. OBJECTIVE: To determine whether the performance of the iFOBT might be improved by optimizing detergents and buffers in stool solution. METHODS: We tested different buffers and detergents in stool solution. The specificity of the new solution condition was confirmed by dot immunoblotting. A total of 1122 clinical stool specimens were collected to evaluate the clinical application of this refined stool solution. RESULTS: The different salts exerted minor effects; also, sodium dodecyl sulfate (SDS) prevented the test from working as designed. However, 1% Triton X-100 improved the sensitivity significantly, as confirmed by dot immunoblot testing. With 1% Triton X-100 in the stool solution, the rate of positive iFOBT results in patients with digestive tract cancers increased, from 40.4% to 49.4%. CONCLUSION: Use of 1% Triton X-100 improves the sensitivity of the iFOBT and thus, this substance should be routinely included in iFOBT for screening of digestive tract cancers.
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Cromatografia de Afinidade/métodos , Sangue Oculto , Hemoglobinas/análise , Humanos , Immunoblotting , Octoxinol , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Cigarette smoking is a well-known risk factor in the development and progression of malignant diseases. Nicotine, the major constituent in cigarette smoke, has also shown negative effects on stem cells. Mesenchymal stem cells (MSCs) have been widely demonstrated to migrate into tumors and play key roles in cancer progression. However, the mechanisms by which nicotine impacts MSCs and tumorigenesis of lung cancer are still undetermined. In this study we investigated the effects of nicotine on human umbilical cord mesenchymal stem cells (hUC-MSCs) and the impacts of nicotine-treated hUC-MSCs on tumor formation and progression. We found that nicotine has a toxic effect on hUC-MSCs and changes the morphology, inhibits proliferation and promotes apoptosis of hUC-MSCs in a dose-dependent manner. Nicotine-treated hUC-MSCs produce higher level of IL-6. Moreover, nicotine promotes migration, stemness and epithelial-mesenchymal transition (EMT) of hUC-MSCs by inhibiting E-cadherin expression and upregulating mesenchymal markers such as N-cadherin and Vimentin, leading to the induction of stem cell markers Sox2, Nanog, Sall4, Oct4 and CD44. Migration and proliferation of non-small cell lung cancer A549 cells and breast cancer MCF-7 cells are promoted after their coculture with nicotine-treated hUC-MSCs in a cell-cell contact-independent manner. Furthermore, nicotine-treated hUC-MSCs promote tumor formation and growth of A549 cells in nude mice. These studies demonstrated that the enhanced stemness and EMT of hUC-MSCs induced by nicotine are critical for the development of tobacco-related cancers.