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1.
Artif Cells Nanomed Biotechnol ; 47(1): 3847-3853, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556305

RESUMO

Aims: In previous studies, numerous differential lncRNAs in cerebral ischemic reperfusion injury were identified using RNA-Seq analysis. However, little is known about whether and how lncRNAs involved in cerebral I/R injury. In this study, we investigated the function and explored the possible mechanism of lncRNA Gm11974 in cerebral I/R injury. Methods: Oxygen glucose deprivation model in N2a cells were utilized to mimic the cerebral I/R injury in vitro. Trypan blue staining, Tunel, JC-1 and cell viability were measured to evaluate the function of lncRNA Gm11974. Dual-luciferase reporter assay was used to explore the potential mechanism of lncRNA Gm11974. Results: Gm11974 was mainly located in cytoplasm. Knockdown of lncRNA Gm11974 alleviated the apoptosis induced by OGD and cell death rates were significantly reduced. We further provided the possible mechanism that Gm11974/miR-766-3p/NR3C2 axis plays important role in cerebral I/R injury. Conclusions: We evaluated the function and mechanism of lncRNA Gm11974 in ischemic brain injury. LncRNA Gm11974 may serve as a potential target for new therapeutic intervention.

2.
Sensors (Basel) ; 19(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514382

RESUMO

An improved anti-noise morphology vision navigation algorithm is proposed for intelligent tractor tillage in a complex agricultural field environment. At first, the two key steps of guided filtering and improved anti-noise morphology navigation line extraction were addressed in detail. Then, the experiments were carried out in order to verify the effectiveness and advancement of the presented algorithm. Finally, the optimal template and its application condition were studied for improving the image-processing speed. The comparison experiment results show that the YCbCr color space has minimum time consumption of 0.094   s in comparison with HSV, HIS, and 2R-G-B color spaces. The guided filtering method can effectively distinguish the boundary between the tillage soil compared to other competing vanilla methods such as Tarel, multi-scale retinex, wavelet-based retinex, and homomorphic filtering in spite of having the fastest processing speed of 0.113   s . The extracted soil boundary line of the improved anti-noise morphology algorithm has the best precision and speed compared to other operators such as Sobel, Roberts, Prewitt, and Log. After comparing different sizes of image templates, the optimal template with the size of 140   ×   260 pixels could achieve high-precision vision navigation while the course deviation angle was not more than 7.5 ° . The maximum tractor speed of the optimal template and global template were 51.41   km / h and 27.47   km / h , respectively, which can meet the real-time vision navigation requirement of the smart tractor tillage operation in the field. The experimental vision navigation results demonstrated the feasibility of the autonomous vision navigation for tractor tillage operation in the field using the tillage soil boundary line extracted by the proposed improved anti-noise morphology algorithm, which has broad application prospect.

3.
Sci Rep ; 9(1): 9501, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263186

RESUMO

Radiomic features based classifiers and neural networks have shown promising results in tumor classification. The classification performance can be further improved greatly by exploring and incorporating the discriminative features towards cancer into mathematical models. In this research work, we have developed two radiomics driven likelihood models in Computed Tomography(CT) images to classify lung, colon, head and neck cancer. Initially, two diagnostic radiomic signatures were derived by extracting 105 3-D features from 200 lung nodules and by selecting the features with higher average scores from several supervised as well as unsupervised feature ranking algorithms. The signatures obtained from both the ranking approaches were integrated into two mathematical likelihood functions for tumor classification. Validation of the likelihood functions was performed on 265 public data sets of lung, colon, head and neck cancer with high classification rate. The achieved results show robustness of the models and suggest that diagnostic mathematical functions using general tumor phenotype can be successfully developed for cancer diagnosis.

4.
Stroke ; 50(7): 1850-1858, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31167620

RESUMO

Background and Purpose- Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke. Methods- We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke. Results- We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation-treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation-induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-ß-activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1. Conclusions- We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.

5.
J Cell Biochem ; 120(10): 17151-17158, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31134677

RESUMO

AIMS: In previous studies, numerous differential microRNAs (miRNAs) in cerebral ischemic/reperfusion (I/R) injury were identified using the miRNA microarray analysis. However, the relationship between miRNA and cerebral I/R injury remains largely unknown. In this study, we investigated the function and explored the possible mechanism of miR-224-3p in cerebral I/R injury. METHODS: Oxygen glucose deprivation model in N2a cells were used to perform the cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 were measured to evaluate the function of miR-224-3p. RESULTS: Overexpression of miR-224-3p alleviated the apoptosis induced by oxygen glucose deprivation (OGD) and cleaved caspase-3 was significantly reduced. We further provided the possible mechanism that miR-224-3p may protect cells from cerebral I/R injury by targeting FAK family-interacting protein (FIP200). Further rescue experiment proved that overexpression of FIP200 partially blocked the effect of miR-224-3p. CONCLUSIONS: We evaluated the function and mechanism of miR-224-3p in ischemic brain injury. miR-224-3p may serve as a potential target for new therapeutic intervention.

6.
Sensors (Basel) ; 19(3)2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30754697

RESUMO

Real-time tracking of pipeline inspection gauges (PIGs) is an important aspect of ensuring the safety of oil and gas pipeline inline inspections (ILIs). Transmitting and receiving extremely low frequency (ELF) magnetic signals is one of the preferred methods of tracking. Due to the increase in physical parameters of the pipeline including transportation speed, wall thickness and burial depth, the ELF magnetic signals received are short transient (1-second duration) and very weak (10 pT), making the existing above-ground-marker (AGM) systems difficult to operate correctly. Based on the short transient very weak characteristics of ELF signals studied with a 2-D finite-element method (FEM) simulation, a data fusion model was derived to fuse the envelope decay rates of ELF signals by a least square (LS) criterion. Then, a fast-decision-tree (FDT) method is proposed to estimate the fused envelope decay rate to output the maximized orthogonal signal power for the signal detection through a determined topology and a fast calculation process, which was demonstrated to have excellent real-time detection performance. We show that simulation and experimental results validated the effectiveness of the proposed FDT method, and describe the high-sensitivity detection and real-time implementation of a high-speed PIG tracking system, including a transmitter, a receiver, and a pair of orthogonal search coil sensors.

7.
J Clin Neurosci ; 61: 272-274, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30528542

RESUMO

Adults with persistent proatlantal intersegmental artery (PPIA) are rarely seen. We present a case of a special type of PPIA that was in a 57-year-old man who presented with dizziness and episodic vertigo of 9 months duration. The diagnosis relied on computed tomography angiography and digital subtraction angiography, by which a left internal carotid artery stenosis and an ipsilateral PPIA originating from the external carotid artery (ECA) was found. This special type of PPIA can be described as a ''mixed PPIA'' that originated as Type II from the ECA and coursed as Type I. The patient underwent carotid artery stenting and had no relapse during 3 months follow-up. In addition, the literatures on PPIA were reviewed.


Assuntos
Artéria Carótida Externa/anormalidades , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Estenose das Carótidas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Stents
8.
Theranostics ; 8(20): 5758-5771, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555579

RESUMO

In aortic endovascular repair, the prediction of stented vessel remodeling informs treatment plans and risk evaluation; however, there are no highly accurate and efficient methods to quantitatively simulate stented vessels. This study developed a fast virtual stenting algorithm to simulate stent-induced aortic remodeling to assist in real-time thoracic endovascular aortic repair planning. Methods: The virtual stenting algorithm was established based on simplex deformable mesh and mechanical contact analysis. The key parameters of the mechanical contact analysis were derived from mechanical tests on aortic tissue (n=40) and commonly used stent-grafts (n=6). Genetic algorithm was applied to select weighting parameters. Testing and validation of the algorithm were performed using pre- and post-treatment computed tomography angiography datasets of type-B aortic dissection cases (n=66). Results: The algorithm was efficient in simulating stent-induced aortic deformation (mean computing time on a single processor: 13.78±2.80s) and accurate at the morphological (curvature difference: 1.57±0.57%; cross-sectional area difference: 4.11±0.85%) and hemodynamic (similarity of wall shear stress-derived parameters: 90.16-90.94%) levels. Stent-induced wall deformation was higher (p<0.05) in distal stent-induced new entry cases than in successfully treated cases, and this deformation did not differ significantly among the different stent groups. Additionally, the high stent-induced wall deformation regions and the new-entry sites overlapped, indicating the usefulness of wall deformation to evaluate the risks of device-induced complications. Conclusion: The novel algorithm provided fast real-time and accurate predictions of stent-graft deployment with luminal deformation tracking, thereby potentially informing individualized stenting planning and improving endovascular aortic repair outcomes. Large, multicenter studies are warranted to extend the algorithm validation and determine stress-induced wall deformation cutoff values for the risk stratification of particular complications.


Assuntos
Doenças da Aorta/cirurgia , Procedimentos Endovasculares/métodos , Fenômenos Mecânicos , Modelagem Computacional Específica para o Paciente , Stents , Procedimentos Cirúrgicos Torácicos/métodos , Adulto , Idoso , Algoritmos , Angiografia , Simulação por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
9.
Front Psychiatry ; 9: 455, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319462

RESUMO

Objective: This study aimed to investigate the association between cognitive impairment and cerebral haemodynamic changes in patients with chronic vertebra-basilar (VB) stenosis. Methods: Patients with severe posterior circulation VB stenosis and infarction or a history of infarction for more than 2 weeks from January 2014 to January 2015 were enrolled (n = 96). They were divided into three groups, namely, the computed tomography perfusion (CTP) normal group, the CTP compensated group, and the CTP decompensated group. Cognitive function was assessed using a validated Chinese version of the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regression models were used to identify independent risk factors for cognitive impairment. Results: The MMSE and FAB scores of patients in the CTP decompensated group were significantly lower than those of patients in the CTP normal and CTP compensated groups (all p < 0.05). The RBANS total and its domain scores, including immediate memory, visual acuity, and delayed memory, in the CTP compensated and CTP decompensated groups were significantly lower than those in the CTP normal group (all p < 0.05). Multiple regression analyses showed that CTP compensation, CTP decompensation, severe VB tandem stenosis, and multiple infarctions were independent risk factors for cognitive impairment. Conclusions: Low perfusion caused by severe VB stenosis can lead to extensive cognitive impairments in areas such as immediate memory, visual span, and delayed memory.

10.
Neurochem Int ; 121: 140-145, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30291953

RESUMO

Subsequent inflammation in stroke plays an important role in the damage of neurons in the perilesional area. Therapeutic intervention targeting inflammation may be a promising complementary strategy to current treatments of stroke. Here, we explored the possible beneficial effects of tyrosol, a derivative of phenethyl alcohol and natural antioxidant, playing an anti-inflammatory role in astrocyte culture and in vitro oxygen glucose deprivation (OGD) model. MTT, western blot, ELISA and EMSA assays were carried out to investigate cell viability, protein expression level, cytokine expression and NF-κB activity. We found tyrosol protected cultured astrocytes against OGD-induced cell viability loss in MTT test. Meanwhile, tyrosol attenuated the released TNF-α and IL-6 level from astrocyte via regulating Janus N-terminal kinase (JNK). The reduction of cytokines from astrocyte might be due to its inhibition of astrocyte activation and regulation of STAT3 signaling pathway since tyrosol attenuated the expression level of GFAP (glial fibrillary acidic protein) and the phosphorylation of STAT3. Additionally, we demonstrated that tyrosol prevented the degradation of IκBα and the increase of IκBα phosphorylation in astrocytes exposed to OGD, which led to the suppression of NF-κB function during ischemia. Collectively, our results showed that tyrosol may be a promising complementary treatment compound for stroke via modulating the inflammatory response in astrocytes during ischemia.

11.
World Neurosurg ; 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30244073

RESUMO

OBJECTIVE: To estimate the association of different etiologies of cardioembolism (CE), intracranial arterial stenosis (ICAS), or the combination of these conditions with outcomes of mechanical thrombectomy in acute ischemic stroke. METHODS: Data from the intervention group of the Endovascular therapy for Acute ischemic Stroke Trial (EAST) were analyzed. In 140 patients, the presence of CE, ICAS, neither CE nor ICAS, or both conditions was assessed. The primary outcome was a favorable outcome at 90 days (modified Rankin Scale score 0-2); secondary outcomes included successful reperfusion (modified Thrombolysis In Cerebral Infarction grade 2b-3), symptomatic intracerebral hemorrhage, and 90-day mortality. RESULTS: Of 140 patients, 47 had neither CE nor ICAS, 35 had ICAS but not CE, 46 had CE but not ICAS, and 12 had both CE and ICAS. The rate of favorable outcome was 67.1% in the no CE and no ICAS group, 74.3% in the ICAS without CE group, 41.3% in the CE without ICAS group, and 33.3% in the CE and ICAS group. The CE and ICAS group had poor outcomes (odds ratio = 0.20 after adjusting for age, sex, and National Institutes of Health Stroke Scale score; 95% confidence interval, 0.04-0.95; P = 0.043). No significant differences were observed in secondary outcomes. CONCLUSIONS: The presence of both CE and ICAS was associated with poor outcome in patients with anterior circulation large-vessel occlusion treated with endovascular thrombectomy. Future studies are warranted to further explore this association.

12.
Front Psychiatry ; 9: 374, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30177891

RESUMO

Objective: Few studies have examined the association between post-stroke depression (PSD), aphasia, and physical independence in Chinese patients. This study investigated the above association in stroke patients in China at 3-month follow-up. Methods: Altogether 270 patients within 14 days after ischemic stroke were recruited and followed up at 3 months. PSD, aphasia, and physical functional status were measured using the Stroke Aphasia Depression Questionnaire (SADQ), Western Aphasia Battery (WAB), and modified Rankin Scale (mRS), respectively. Patients with mRS total score >2 were considered as having "physical dependence." Results: Out of 248 patients at 3-month follow up, 119 (48%) were rated as having physical dependence. Multiple logistic regression analyses revealed that female (p = 0.04; OR = 2.2; 95% CI: 1.0-5.1), more severe stroke at admission (p < 0.01; OR = 1.4; 95% CI: 1.3-1.5), and more severe PSD at 3 months (p = 0.01; OR = 1.05; 95% CI: 1.01-1.1) were independently associated with physical dependence at 3 months. Conclusions: Greater PSD and stroke severity were independently associated with physical dependence at 3 months after stroke. Aphasia was also associated with physical dependence but the relationship was not significant. Early and effective depression screening, treatment and stroke rehabilitation appear to be important to improve the physical outcome and reduce the burden of stroke survivors.

13.
Nat Commun ; 9(1): 2080, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29802243

RESUMO

Over 80% of diffuse intrinsic pontine gliomas (DIPGs) harbor a point mutation in histone H3.3 where lysine 27 is substituted with methionine (H3.3K27M); however, how the mutation affects kinetics and function of PcG proteins remains elusive. We demonstrate that H3.3K27M prolongs the residence time and search time of Ezh2, but has no effect on its fraction bound to chromatin. In contrast, H3.3K27M has no effect on the residence time of Cbx7, but prolongs its search time and decreases its fraction bound to chromatin. We show that increasing expression of Cbx7 inhibits the proliferation of DIPG cells and prolongs its residence time. Our results highlight that the residence time of PcG proteins directly correlates with their functions and the search time of PcG proteins is critical for regulating their genomic occupancy. Together, our data provide mechanisms in which the cancer-causing histone mutation alters the binding and search dynamics of epigenetic complexes.

14.
CNS Neurosci Ther ; 24(2): 154-161, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29293287

RESUMO

AIMS: To evaluate whether visual field impairment (VFI) can predict stroke recurrence in patients with vertebral-basilar (VB) stroke. METHODS: A total of 326 patients were eligible for a VFI evaluation within 1 week of stroke onset. One-year follow-up data were obtained after VB stroke and other vascular events. All predictors were determined using Cox regression models. RESULTS: The overall incidence of recurrent VB stroke and transient ischemic attack (TIA) was 29% (n = 92). After multivariate adjustment, severe and moderate VFI were predictors of recurrent VB stroke and TIA. CONCLUSIONS: VFI is an independent predictor of recurrent VB stroke and TIA.

15.
Int J Psychiatry Clin Pract ; 22(2): 129-135, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29029570

RESUMO

OBJECTIVE: To investigate clinical characteristics and associations of polydrug abuse among heroin-dependent patients in compulsory isolation settings in China. METHODS: Structured interviews were conducted in 882 heroin-dependent patients in two compulsory isolation settings in Changsha, China. Descriptive statistics were employed to report prevalence and general information of polydrug abuse among the participants. Bivariate associations were examined between polydrug abuse and variables regarding demographics, heroin use profile and psychopathology. Multivariate logistic regressions were conducted to determine independent factors associated with polydrug abuse. RESULTS: Of all the participants, 40.6% reported abuse of/dependence on at least one other type of drug/alcohol than heroin/opioids during the month preceding admission, with benzodiazepines and alcohol being the most common type of drugs abused apart from heroin. Antisocial and depressive personality disorders, as well as more severe heroin use patterns, including younger age at initiate use and larger amount used per day, were found to be independently associated with polydrug abuse. CONCLUSIONS: The prevalence of polydrug abuse and its associated severe heroin use patterns and personality disorders suggests an urgent need of promoting treatment policies and strategies for heroin patients in China to address these issues.


Assuntos
Isolamento de Pacientes/estatística & dados numéricos , Transtornos da Personalidade/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , China/epidemiologia , Feminino , Dependência de Heroína/epidemiologia , Humanos , Masculino
16.
Int J Infect Dis ; 61: 114-120, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28652214

RESUMO

OBJECTIVES: This study aimed to investigate whether von Willebrand factor (vWF) and high mobility group box 1 (HMGB1) are associated with the severity and clinical outcome of scrub typhus and to seek novel biomarkers for surveillance and prediction of the prognosis of this infection. METHODS: Serum concentrations of vWF and HMGB1 were measured twice by ELISA for scrub typhus patients (n=103), once prior to doxycycline therapy and then on day 7 of doxycycline therapy; concentrations were measured once for healthy controls (n=32). RESULTS: Among the total 103 patients enrolled, 38 had disease complicated by multiple organ dysfunction syndrome (MODS). Serum concentrations of vWF and HMGB1 were significantly higher in all the patients than in the healthy controls, both prior to doxycycline treatment and on day 7 of doxycycline treatment (p<0.01). Furthermore, serum levels of vWF, HMGB1, and creatinine (SCr) in the patients with MODS increased distinctly, while the platelet (PLT) count diminished markedly compared to the levels in patients without MODS (p<0.01). The concentration of vWF was positively correlated with that of HMGB1 (r=0.764, p<0.001) and SCr (r=0.528, p<0.001), but negatively correlated with the PLT count (r=-0.632, p<0.001). Both HMGB1 and vWF were significantly associated with mortality in scrub typhus (area under the curve (AUC)=0.864, p=0.001, and AUC=0.862, p=0.001, respectively). CONCLUSIONS: Elevated levels of vWF and HMGB1 are associated with the severity and clinical outcome of scrub typhus. These represent possible new biomarkers for use in the assessment and prognostic prediction of this infection.


Assuntos
Proteína HMGB1/sangue , Tifo por Ácaros/sangue , Fator de von Willebrand/metabolismo , Antibacterianos/uso terapêutico , Biomarcadores/sangue , Doxiciclina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Prognóstico , Tifo por Ácaros/tratamento farmacológico , Tifo por Ácaros/fisiopatologia , Resultado do Tratamento
17.
Oncotarget ; 8(63): 107312-107322, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29291031

RESUMO

Schizophrenia is often considered to be a disconnection syndrome. The abnormal interactions between large-scale functional brain networks result in cognitive and perceptual deficits. The present study investigated event-related functional connectivity networks to compare facial processing in individuals with and without schizophrenia. Faces and tables were presented to participants, and event-related phase synchrony, represented by the phase lag index (PLI), was calculated. In addition, cortical oscillatory dynamics may be useful for understanding the neural mechanisms underlying the disparate cognitive and functional impairments in schizophrenic patients. Therefore, the dynamic graph theoretical networks related to facial processing were compared between individuals with and without schizophrenia. Our results showed that event-related phase synchrony was significantly reduced in distributed networks, and normalized clustering coefficients were significantly increased in schizophrenic patients relative to those of the controls. The present data suggest that schizophrenic patients have specific alterations, indicated by increased local connectivity in gamma oscillations during facial processing.

19.
Anal Chem ; 88(12): 6274-82, 2016 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-27213895

RESUMO

A novel method for lipid analysis called CTS (collisional activation and traveling wave mass spectrometry), involving tandem mass spectrometry of all precursor ions with ion mobility determinations of all product ions, was applied to a sample of human serum. The resulting four-dimensional data set (precursor ion, product ion, ion mobility value, and intensity) was found to be useful for characterization of lipids as classes as well as for identification of specific species. Utilization of ion mobility measurements of the product ions is a novel approach for lipid analysis. The trends and patterns of product mobility values when visually displayed yield information on lipid classes and specific species independent of mass determination. Collection of a comprehensive set of data that incorporates all precursor-product relationships, combined with ion mobility measurements of all products, enables data analysis where different molecular properties can be juxtaposed and analyzed to assist with class and species identification. Overall, CTS is a powerful, specific, and comprehensive method for lipid analysis.


Assuntos
Lipídeos/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/química , Humanos , Íons/química , Triglicerídeos/sangue
20.
Biomed Mater ; 10(1): 015004, 2014 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-25532534

RESUMO

In this work we first developed a murine pancreatic tumor model using CD24(+)CD44(+) pancreatic cancer stem cells (CSC) supported by an electrospun scaffold. Unlike conventional models, the use of CSC and the scaffold, which were biologically and chemically defined, afforded scientists a reliable platform to evaluate novel chemotherapy regimens. CD24(+)CD44(+) CSC successfully initiated tumorigenesis in vitro on the scaffold without suffering apoptosis, evidencing the lack of cytotoxicity of scaffolding materials. Also, the scaffold contributed to the acceleration of in vivo tumorigenesis and increased the likelihood of tumor formation. Using this model, we set out to explore the effectiveness of irinotecan/gemcitabine (IRIN-GEM), a chemotherapy regimen, for pancreatic cancer. Our study showed that IRIN-GEM induced a tumor regression whereas gemcitabine alone could only arrest the tumor growth. Further study suggested that the superior performance of IRIN-GEM could be attributed to its capacity to demolish the CD24(+)CD44(+) CSC sub-population by inducing a large-scale apoptosis. The use of highly proliferative yet homogenous CD24(+)CD44(+) CSC along with a chemically defined scaffold accelerated the tumor formation and significantly reduced the variability associated with conventional murine models. Armed with this new model, we discovered that IRIN-GEM would be a promising chemotherapy candidate for patients with advanced pancreatic cancer.


Assuntos
Antineoplásicos/uso terapêutico , Engenharia Biomédica/métodos , Células-Tronco Neoplásicas/citologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Animais , Antineoplásicos/química , Apoptose , Antígeno CD24/metabolismo , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Proliferação de Células , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Citometria de Fluxo , Humanos , Receptores de Hialuronatos/metabolismo , Irinotecano , Camundongos , Tecidos Suporte/química
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