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1.
Environ Sci Technol ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793133

RESUMO

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, have frequently been identified in the atmosphere. However, their atmospheric fate and toxicity associated with atmospheric transformations are unclear. Here, we performed quantum chemical calculations and computational toxicology to investigate the reaction mechanism of peroxy radicals of OPEs (OPEs-RO2•), key intermediates in determining the atmospheric chemistry of OPEs, and the toxicity of the reaction products. TMP-RO2• (R1) and TCPP-RO2• (R2) derived from trimethyl phosphate and tris(2-chloroisopropyl) phosphate, respectively, are selected as model systems. The results indicate that R1 and R2 can follow an H-shift-driven autoxidation mechanism under low NO concentration ([NO]) conditions, clarifying that RO2• from esters can follow an autoxidation mechanism. The unexpected autoxidation mechanism can be attributed to the distinct role of the ─(O)3P(═O) phosphate-ester group in facilitating the H-shift of OPEs-RO2• from commonly encountered ─OC(═O)─ and ─ONO2 ester groups in the atmosphere. Under high [NO] conditions, NO can mediate the autoxidation mechanism to form organonitrates and alkoxy radical-related products. The products from the autoxidation mechanism have low volatility and aquatic toxicity compared to their corresponding parent compounds. The proposed autoxidation mechanism advances our current understanding of the atmospheric RO2• chemistry and the environmental risk of OPEs.

2.
IEEE Trans Cybern ; PP2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793316

RESUMO

In recent years, ensemble methods have shown sterling performance and gained popularity in visual tasks. However, the performance of an ensemble is limited by the paucity of diversity among the models. Thus, to enrich the diversity of the ensemble, we present the distillation approach--learning from experts (LFEs). Such method involves a novel knowledge distillation (KD) method that we present, specific expert learning (SEL), which can reduce class selectivity and improve the performance on specific weaker classes and overall accuracy. Through SEL, models can acquire different knowledge from distinct networks with various areas of expertise, and a highly diverse ensemble can be obtained afterward. Our experimental results demonstrate that, on CIFAR-10, the accuracy of the ResNet-32 increases 0.91% with SEL, and that the ensemble trained by SEL increases accuracy by 1.13%. Compared to state-of-the-art approaches, for example, DML only improves accuracy by 0.3% and 1.02% on single ResNet-32 and the ensemble, respectively. Furthermore, our proposed architecture also can be applied to ensemble distillation (ED), which applies KD on the ensemble model. In conclusion, our experimental results show that our proposed SEL not only improves the accuracy of a single classifier but also boosts the diversity of the ensemble model.

3.
medRxiv ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34729567

RESUMO

Background: The COVID-19 pandemic is now dominated by variant lineages; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the risk of hospitalization following infection with nine variants of concern or interest (VOC/VOI). Methods: Our study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System and with available viral genome data, from December 1, 2020 to July 30, 2021. The main analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for the risk of hospitalization following infection with a VOC/VOI, adjusting for age, sex, and vaccination status. Findings: Of the 23,563 cases, 22,068 (93.7%) were sequenced through sentinel surveillance, of which 582 (2.6%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.23, 95% CI 2.19-4.76), Beta (HR 3.03, 95% CI 1.68-5.47), Delta (HR 2.35, 95% CI 1.72-3.22), and Alpha (HR 1.61, 95% CI 1.28-2.03) compared to infections with an ancestral lineage. Following VOC infection, unvaccinated patients show a similar higher hospitalization risk, while vaccinated patients show no significant difference in risk, both when compared to unvaccinated, ancestral lineage cases. Interpretation: Infection with a VOC results in a higher hospitalization risk, with an active vaccination attenuating that risk. Our findings support promoting hospital preparedness, vaccination, and robust genomic surveillance.

4.
Acta Histochem ; 123(8): 151814, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34763116

RESUMO

BACKGROUND: Breast cancer is the most common female cancer worldwide. DNA methylation is a common modification in epigenetics and affects the prognosis of breast cancer by changing gene expression. In the present study, we aim to investigate the role of DNA methylation in TMEM130 gene expression, and the function of TMEM130 in breast cancer cell migration. METHODS: The transcriptional expression of TMEM130 was detected by qRT-PCR in breast cancer cell lines and tissues. Bisulfite sequencing PCR (BSP) was used to confirm the methylation status of TMEM130 promoter. Then, TMEM130 was transfected in breast cancer cell lines and to explore its role in cell migration by Transwell and western blot. RESULTS: TMEM130 mRNA expression was decreased in breast cancer cell lines and tissues, and consistent with the data in The Cancer Genome Atlas (TCGA). The promoter of TMEM130 was hypermethylated in breast cancer and the expression of TMEM130 could be restored by the methyltransferase inhibitor. Overexpression of TMEM130 could inhibit cell migration ability in breast cancer cell lines. CONCLUSION: Taken together, these results indicate TMEM130 downregulation and hypermethylation might contribute to breast cancer migration and TMEM130 might be a promising biomarker for breast cancer.

5.
Mol Clin Oncol ; 15(6): 265, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34777801

RESUMO

The aim of the present study was to compare the metastatic ratio between calcified lymph node stations (CLNS) and non-CLNS (NCLNS) and to explore the impact of CLNS on surgical outcomes. Consecutive patients with non-small cell lung cancer (NSCLC) scheduled to receive surgical treatment between June and December 2020 were included in the present study. Their clinical and radiological data were prospectively collected and analyzed. A total of 91 patients with NCLNS and 64 patients with CLNS were enrolled in the present study. Out of the 91 patients, 38 (24.516%) patients had 61/343 (17.784%) lymph node stations (LNS) that were metastasized. On a per-patient basis, the differences in the LNS metastatic ratio were not significant between the CLNS with NCLNS groups. However, on a per-nodal station basis, all differences in the LNS metastatic ratio between the groups were significant not only in the all-LNS group (P=0.004), but also in the LNS group which in patients with solely CLNS or NCLNS (P=0.009) and in the patients with CLNS (P=0.010). Pathology, T stage and calcification were independent predictive factors for LNS metastasis (P=0.002, P=0.021 and P=0.044, respectively). More patients with CLNS than patients with NCLNS received thoracotomy or conversion from video-assisted thoracoscopic surgery to thoracotomy (P=0.006). The operating time and blood loss were significantly higher in patients with CLNS than in those without (P<0.001 and P<0.001, respectively). Although CLNS are a risk reduction factor for metastasis and their dissection is time- and blood-consuming in patients with NSCLC, their thorough removal is advisable, since metastases were identified in ~15% of patients and 9% of CLNS.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34780337

RESUMO

Contextual bandit is a popular sequential decision-making framework to balance the exploration and exploitation tradeoff in many applications such as recommender systems, search engines, etc. Motivated by two important factors in real-world applications: 1) latent contexts (or features) often exist and 2) feedbacks often have humans in the loop leading to human biases, we formulate a generalized contextual bandit framework with latent contexts. Our proposed framework includes a two-layer probabilistic interpretable model for the feedbacks from human with latent features. We design a GCL-PS algorithm for the proposed framework, which utilizes posterior sampling to balance the exploration and exploitation tradeoff. We prove a sublinear regret upper bound for GCL-PS, and prove a lower bound for the proposed bandit framework revealing insights on the optimality of GCL-PS. To further improve the computational efficiency of GCL-PS, we propose a Markov Chain Monte Carlo (MCMC) algorithm to generate approximate samples, resulting in our GCL-PSMC algorithm. We not only prove a sublinear Bayesian regret upper bound for our GCL-PSMC algorithm, but also reveal insights into the tradeoff between computational efficiency and sequential decision accuracy. Finally, we apply the proposed framework to hotel recommendations and news article recommendations, and show its superior performance over a variety of baselines via experiments on two public datasets.

8.
Clin Imaging ; 82: 67-72, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34798560

RESUMO

PURPOSE: Tissue magnetic susceptibility sign can potentially be detected on susceptibility weighted imaging (SWI) phase (SW-P). This study aims to investigate its performance for depicting brain susceptibility structures. METHODS: A simulation was performed to depict magnetic susceptibility structures of various geometries on SW-P and quantitative susceptibility mapping (QSM). Brain MRI was performed on 25 subjects using SWI on a 3 T MRI system. QSM was generated from the same data. SW-P and QSM were analyzed according to radiological assessment for depicting globus pallidus nuclei, optic radiation white matter tracts, and lateral ventricular choroid plexus calcifications. In 11 of these subjects, CT was available and correlated with SW-P and QSM to assess their performance in quantifying calcifications in the choroid plexus. RESULTS: In simulation, the appearance of a sphere on SW-P ranged from centric nodule to mixed positive and negative values as the diameter increased. Large cylinders also appeared as mixed positive and negative values. In comparison, QSM correctly depicted the susceptibility distribution of all magnetic structures. On human brain images, SW-P depicted the globus pallidus and optic radiation with mixed positive and negative values, consistent with simulation, and small choroid plexus calcifications as either mixed positive and negative values or as centric nodules; QSM depicted all structures as solid structures with the expected signs. For measuring calcification in the choroid plexus, QSM vs CT linear regression had a higher coefficient of determination compared to SW-P vs CT and SW-P vs QSM. CONCLUSION: Appearance of susceptibility sources on SW-P changes with object size. This problem can be overcome using QSM.

9.
Bioorg Chem ; 117: 105423, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34717239

RESUMO

In the present study, a series of 2-phenyl-1H-benzo[d]imidazole-based α-glucosidase inhibitors were synthesized and evaluated for their in vitro and in vivo anti-diabetic potential. Screening of an in-house library revealed a moderated α-glucosidase inhibitor, 6a with 3-(1H-benzo[d]imidazol-2-yl)aniline core, and then the structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased activity than 6a, and the most promising inhibitors were found to be compounds 15o and 22d with IC50 values of 2.09 ± 0.04 and 0.71 ± 0.02 µM, respectively. Fluorescence quenching experiment confirmed the direct binding of compounds 15o and 22d with α-glucosidase. Kinetic study revealed that both compounds were non-competitive inhibitors, that was consistent with the result of molecular docking studies where they located at the allosteric site of the enzyme. Cell viability evaluation demonstrated the non-cytotoxicity of 15o and 22d against LO2 cells. Furthermore, the in vivo pharmacodynamic study revealed that compound 15o showed significant hypoglycemic activity and improved oral sucrose tolerance, comparable to the positive control acarbose.

10.
Quant Imaging Med Surg ; 11(10): 4389-4398, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34603993

RESUMO

Background: The precise pathogenesis of anophthalmia/microphthalmia remains unknown. Prenatal observation of the optic chiasm in fetuses with this malformation would assist in understanding the embryonic development of the condition. The present study aimed to establish the normal fetal size ranges of decussation of the optic chiasm, optic nerves, and optic tracts in the axial plane using two-dimensional transabdominal ultrasound throughout gestation and to compare these ranges to the corresponding values in fetuses with anophthalmia/microphthalmia. Methods: In total, 310 normal fetuses and 16 fetuses with anophthalmia/microphthalmia were included in this study. The widths of the decussation of the optic chiasm, optic nerves, and optic tracts of normal fetuses at 19-40 weeks' gestation were measured in the axial plane by two-dimensional transabdominal ultrasound. The same widths were retrospectively measured in the axial plane using three-dimensional ultrasound in fetuses with anophthalmia/microphthalmia and compared to the results from the normal fetuses. Results: The decussation, optic nerves, and optic tracts of 310 normal fetuses were measured. The normal widths of the decussation of the optic chiasm, optic nerves, and optic tracts increased linearly with gestational age. The interobserver and intraobserver reproducibility was excellent for the decussation but relatively low for the optic nerves and optic tracts. The optic nerve width of fetuses with anophthalmia/microphthalmia was significantly smaller than that of normal fetuses (P<0.001), but the widths of the decussation (P=0.061) and optic tracts (P=0.053) were not significantly different between the two groups. Conclusions: The normal ranges of the decussation of the optic chiasm, optic nerves, and optic tracts established in this study can provide a quantitative basis for prenatal evaluation of the optic pathway. Fetal anophthalmia/microphthalmia may be associated with optic nerve hypoplasia.

11.
Medicine (Baltimore) ; 100(39): e27380, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596157

RESUMO

ABSTRACT: Various disease severity scoring systems were currently used in critically ill patients with acute respiratory failure, while their performances were not well investigated.The study aimed to investigate the difference in prognosis predictive value of 4 different disease severity scoring systems in patients with acute respiratory failure.With a retrospective cohort study design, adult patients admitted to intensive care unit (ICU) with acute respiratory failure were screened and relevant data were extracted from an open-access American intensive care database to calculate the following disease severity scores on ICU admission: acute physiology score (APS) III, Sequential Organ Failure Assessment score (SOFA), quick SOFA (qSOFA), and Oxford Acute Severity of Illness Score (OASIS). Hospital mortality was chosen as the primary outcome. Multivariable logistic regression analyses were performed to analyze the association of each scoring system with the outcome. Receiver operating characteristic curve analyses were conducted to evaluate the prognosis predictive performance of each scoring system.A total of 4828 patients with acute respiratory failure were enrolled with a hospital mortality rate of 16.78%. APS III (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02-1.03), SOFA (OR 1.15, 95% CI 1.12-1.18), qSOFA (OR 1.26, 95% CI 1.11-1.42), and OASIS (OR 1.06, 95% CI 1.05-1.08) were all significantly associated with hospital mortality after adjustment for age and comorbidities. Receiver operating characteristic analyses showed that APS III had the highest area under the curve (AUC) (0.703, 95% CI 0.683-0.722), and SOFA and OASIS shared similar predictive performance (area under the curve 0.653 [95% CI 0.631-0.675] and 0.664 [95% CI 0.644-0.685], respectively), while qSOFA had the worst predictive performance for predicting hospital mortality (0.553, 95% CI 0.535-0.572).These results suggested the prognosis predictive value varied among the 4 different disease severity scores for patients admitted to ICU with acute respiratory failure.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Insuficiência Respiratória/mortalidade , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
12.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2666-2674, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664438

RESUMO

Cover crops are grown in temporal and spatial gaps of agricultural production to reduce or avoid soil exposure. As it can protect farmland soil from wind erosion, water erosion and human disturbance, planting cover crops is considered as a new type of conservation tillage practice. Here, we briefly introduced the planting management of cover crops, including crop species, planting modes, and the returning to farmland after their termination, which could provide a reference for efficiently planting cover crops at large scale during the fallow period. Based on domestic and foreign studies, we summarized the benefits of cover crops on agroecosystem, including cash crops, soil quality, weed control, greenhouse gas emission, and soil microbes. Our review illustrated their importance in improving soil quality and achieving sustainable agricultural development, despite the limitation of cover crops, including unobvious benefits in the short-term and the reduction of crop yield caused by improper management.


Assuntos
Gases de Efeito Estufa , Solo , Agricultura , Produtos Agrícolas , Humanos
13.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2675-2684, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664439

RESUMO

Agricultural tillage practices significantly affect the structure and function of soil micro-bial community, as well as its control over soil carbon cycling. Conservation tillage practice based on no-tillage and crop straw returning is an important measure to improve soil carbon sequestration and fertility, in which soil microorganisms play a key role. Although many previous studies focus on the structure and function of microbial communities under conservation tillage, our overall understanding of soil microbial responses at community level upon conservation tillage is still lacking, due to the complexity of the soil, environmental factors and the different selections of microbial research methods. Furthermore, previous studies paid more attention to the role of soil microorganisms as decomposers and the contribution of plant-derived carbon to the formation of soil carbon pool, but ignored the contribution of microbial-derived carbon to the formation and stability of soil carbon pool. We summarized the paradigm shift in soil organic matter formation and stability theories, reviewed the research methods of soil microbial community, focused on the effects of conservation tillage on soil microbial biomass, community diversity and composition, carbon metabolism, as well as microbial-derived carbon storage, and proposed suggestions for future study, aiming to provide support for future studies regarding microbial responses and its control over soil carbon dynamics in agroecosystem.


Assuntos
Microbiota , Solo , Agricultura , Carbono , Microbiologia do Solo
14.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2685-2692, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664440

RESUMO

We examined carbon chemical composition and stability along soil depth (topsoil 0-5 cm, mid-soil 20-40 cm, and deep soil 60-100 cm) in a no-tillage (NT) agricultural system with various amount of corn stover as mulch for 8 years, including 0 (NT0), 33% (NT33), 67% (NT67) and 100% (NT100), in Northeast China, using mid-infrared spectroscopy. The results showed that, relative to NT0, the treatments of NT33 and NT100 increased polysaccharide content of the top layer and mid-layer soils, the former decreased topsoil carbon component diversity, while the latter maintained soil carbon stability of three soil layers. NT67 increased carbon stability at the deep layer soil. Our results demonstrated that if corn stover resources were sufficient, NT with 100% corn stover mulch could both be beneficial to carbon availability at 0-40 cm soil layer and stability of the whole soil profile. The nonlinear relationship between the amount of corn stover mulch and the mid-infrared spectral characteristics of the soil called for further research on the microbial-control mechanism over soil carbon cycling under different amounts of corn stover mulch.


Assuntos
Carbono , Solo , Ecossistema , Análise Espectral , Zea mays
15.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2693-2702, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664441

RESUMO

We investigated the effects of different biochar application patterns on soil nutrient contents and element transformation, with soil samples being collected from two five-year field experiments in Phaeozem and Luvisol amended with biochar at annual low-rate (AL, 22.5 t·hm-2·a-1) and intervalic high-rate (IH, 112.5 t·hm-2·5 a-1). Changes of soil total carbon (C), nitrogen (N) and phosphorus (P) contents as well as the related enzyme activities were measured under different biochar application patterns to provide fundamental information for the straw utilization and soil fertility improvement in agroecosystem. Results showed that total C and organic N contents in AL treatment were significantly higher than those in IH treatment in Phaeozem soil. Compared with the control, the decreases of dehydrogenase activity in AL treatment was more pronounced than that in IH treatment in Phaeozem soil, and the increases of protease activity in IH treatment was pronounced than that in AL treatment in Luvisol. Compared with Luvisol soil, the application of biochar had stronger effect on total soil C and organic N contents in Phaeozem soil. Application of biochar significantly increased the activities of soil dehydrogenase and protease in Luvisol soil, but decreased the activity of soil dehydrogenase. Soil types and biochar application patterns interacted to affect soil C and N contents, microbial metabolic activity, N- and P-related enzyme activities. In summary, soil types and biochar addition affected soil properties and microbial characteristics, which would provide important information for straw application and soil management.


Assuntos
Nitrogênio , Solo , Carvão Vegetal , Nitrogênio/análise , Nutrientes , Fósforo
16.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2906-2914, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664464

RESUMO

In order to clarify the eco-environmental quality and its evolution characteristics of Keluke Lake basin, we selected 15 factors of physical geography, meteorology, land use/cover and social economy using comprehensive investigation, remote sensing interpretation and inversion, statistical analysis and other technical means, based on the relevant theories of environmental ecology. We used factor analysis and entropy method to calculate the index weight, constructed watershed soil quality model and ecological environment quality diagnosis model, and analyzed the changes of soil and eco-environmental quality in the Keluke Lake basin in 2000, 2005, 2010 and 2015. The results showed that the average eco-environmental quality in four periods was 21, 47, 54, and 72, showing a stable upward trend. The eco-environmental quality level changed from poor to good, while soil quality was at the middle level. Spatially, the eco-environmental quality of the northern mountainous area, the downstream wetland and the surrounding area of the river improved significantly. The change of eco-environmental quality was a result of human activities and natural factors. Soil quality and lake area were key factors indicating the eco-environment of the Keluke Lake basin. The minimum ecological water demand of the Keluke Lake was the basic guarantee to maintain the benign development of the eco-environment of the lake basin.


Assuntos
Lagos , Rios , China , Atividades Humanas , Humanos , Solo
17.
Bioorg Med Chem Lett ; 52: 128413, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34634473

RESUMO

In this present study, a series of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)hydrazine-1-carboxamide derivatives against α-glucosidase were designed and synthesized, and their biological activities were evaluated in vitro and in vivo. Most of the designed analogues exhibited better inhibitory activity than the marketed acarbose, especially the most potent compound 7 with an IC50 value of 9.26 ± 1.84 µM. The direct binding of 7 and 8 with α-glucosidase was confirmed by fluorescence quenching experiments, and the kinetic and molecular docking studies revealed that 7 and 8 inhibited α-glucosidase in a non-competitive manner. Cytotoxicity bioassay indicated compounds 7 and 8 were non-toxic towards LO2 and HepG2 at 100 µM. Furthermore, both compounds were demonstrated to have in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-treated rats.

19.
Arq Bras Cardiol ; 117(3): 476-483, 2021 09.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34550233

RESUMO

BACKGROUND: Cardiovascular disease is the major cause of death worldwide. Hypoxia-mediated apoptosis in cardiomyocytes is a major cause of cardiovascular disorders. Treatment with vascular endothelial growth factor (VEGF) protein has been tested but operational difficulties have limited its use. However, with the advancements of gene therapy, interest has risen in VEGF-based gene therapy in cardiovascular disorders. However, the precise mechanism by which VEGF replenishment rescues post-hypoxia damage in cardiomyocytes is not known. OBJECTIVES: To investigate the effect of post-hypoxia VEGF121 expression using neonatal rat cardiomyocytes. METHODS: Cardiomyocytes isolated from neonatal rats were used to establish an in vitro model of hypoxia-induced cardiac injury. The effect of VEGF overexpression, alone or in combination with small-molecule inhibitors targeting calcium channel, calcium sensitive receptors (CaSR), and calpain on cell growth and proliferation on hypoxia-induced cardiomyocyte injury were determined using an MTT assay, TUNEL staining, Annexin V/PI staining, lactate dehydrogenase and caspase activity. For statistical analysis, a value of P<0.05 was considered to be significant. RESULTS: The effect of VEGF121 was found to be mediated by CaSR and calpain but was not dependent on calcium channels. CONCLUSIONS: Our findings, even though using an in vitro setting, lay the foundation for future validation and pre-clinical testing of VEGF-based gene therapy in cardiovascular diseases.


Assuntos
Receptores de Detecção de Cálcio , Fator A de Crescimento do Endotélio Vascular , Animais , Hipóxia , Mitocôndrias , Miócitos Cardíacos/metabolismo , Peptídeo Hidrolases/metabolismo , Ratos , Receptores de Detecção de Cálcio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Artif Cells Nanomed Biotechnol ; 49(1): 596-605, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34514904

RESUMO

Brain glioma is the most common primary tumour of the central nervous system. Complete surgical removal of the brain glioma is virtually impossible. Chemotherapy is still an important treatment for brain glioma. However, blood-brain barrier (BBB) and vasculogenic mimicry (VM) channels remain two hindrances in regular treatments. Herein, we developed a novel nanoscaled dual targeting daunorubicin plus rofecoxib liposomes which could transport across the BBB, and eliminate brain glioma cells along with the VM channels. The liposomes were modified with two functional materials, and showed round in shape with a diameter about 120 nm. Evaluations were performed on human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. The dual targeting liposomes demonstrated a long circulatory effect in the blood system, were able to transport across the BBB, and were accumulated into the brain. The results indicated that the dual targeting daunorubicin plus rofecoxib liposomes could inhibit the brain glioma VM channels and exhibited a significant efficacy in the treatment of intracranial glioma-bearing nude mice. The mechanisms are related to down regulations MMP-2, MMP-9, FAK and HIF-α. Hence, the established dual targeting liposomes could be a potential formulation to treat the brain glioma along with eliminating VM channels.

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