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1.
Thorac Cancer ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729938

RESUMO

BACKGROUND: Activation of ALK leads to a high level of aerobic glycolysis related to crizotinib insensitivity in anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK+ NSCLC). The strategy and mechanism of glycolysis inhibition in sensitizing ALK+ NSCLC cells to crizotinib requires further investigation. METHODS: The levels of glycolysis in H3122 and H2228 cells were evaluated through detection of glucose consumption and lactate production. MTT assay was used to explore the effects of glycolytic inhibitors on crizotinib sensitivity, and the potential mechanism of action were detected by colony formation, Ki67 incorporation assay, transwell assay, small interfering RNA technology and western blot analysis. RESULTS: ALK+ NSCLC cells exhibited significantly higher levels of glycolysis compared to ALK- NSCLC cells. Long-term exposure to crizotinib could decrease the sensitivity of ALK+ NSCLC cells to crizotinib via increasing the levels of glycolysis related to hexokinases II (HK2). Crizotinib in combination with glycolysis inhibitor 2-deoxy-D-glucose (2DG) synergistically inhibited proliferation, glycolysis, colony formation and invasion ability of ALK+ NSCLC cells. 2DG sensitization crizotinib might be associated with the inhibition of HK2-mediated glycolysis and P-ALK/AKT/mTOR signaling pathway in H3122 and H2228 cells. CONCLUSIONS: These results indicate that HK2-mediated glycolysis plays a crucial role in the increased tolerance of ALK+ NSCLC cells to crizotinib. 2DG may sensitize ALK+ NSCLC to crizotinib via suppression of HK2-mediated glycolysis and the AKT/mTOR signaling pathway.

2.
Front Aging Neurosci ; 13: 745381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776930

RESUMO

Mild cognitive impairment (MCI) is a transition between normal cognition (NC) and Alzheimer's disease (AD). Differences in cortical thickness (ΔCT) have been reported in cases that degenerate from MCI to AD. The aspects of genetic and transcriptional variation related to ΔCT are vague. In this study, using an 8-year longitudinal follow-up outcome, we investigated the genetic correlates of ΔCT in MCI subjects with degeneration from MCI to AD (MCI_AD). We employed partial least squares regression (PLSR) on brain T1-weighted magnetic resonance imaging (MRI) images of 180 participants [143 stable MCI (MCI_S) participants and 37 MCI_AD participants] and brain gene expression data from the Allen Institute for Brain Science (AIBS) database to investigate genes associated with ΔCT. We found that upregulated PLS component 1 ΔCT-related genes were enriched in chemical synaptic transmission. To verify the robustness and specificity of the results, we conducted PLSR analysis invalidation and specificity datasets and performed weighted gene co-expression network analysis instead of PLSR for the above three datasets. We also used gene expression data in the brain prefrontal cortex from the Gene Expression Omnibus (GEO) database to indirectly validate the robustness and specificity of our results. We conclude that transcriptionally upregulated genes involved in chemical synaptic transmission are strongly related to global ΔCT in MCI patients who experience degeneration from MCI to AD.

3.
Mol Nutr Food Res ; : e2100728, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787361

RESUMO

SCOPE: Enteral feeding is a primary source of cysteine for intestinal mucosa given negligible transsulfuration activity in enterocytes and furthermore very few cysteine uptake from arterial blood. This study aims to explore the role of cysteine in maintaining intestinal integrity and function. METHODS AND RESULTS: The intestinal porcine enterocytes (IPEC-J2) were cultured in a cysteine-deprived medium with or without glutathione supplementation upon the inhibitions of glutathione synthesis or degradation. As a result, cysteine deprivation impaired mitochondrial function, suppressed mechanistic target of rapamycin (mTOR) signaling and activated general control nonderepressible 2 (GCN2) signaling, and might lead to resultant ferroptosis. Glutathione supplementation could restore the impairment through degradating into cysteine, while glutathione synthesis inhibition did not disturb the role of cysteine in keeping the intestinal epithelial cells. Furthermore, piglets were fed with cysteine-deficient, -adequate and -surplus diet for 28 d as a porcine model. We evidenced that intestinal integrity and individual growth benefit from adequate dietary cysteine. CONCLUSION: Adequate dietary cysteine supply is essential for intestinal mucosal integrity, epithelial cell turnover and amino acid sensing as well as optimal individual growth. Cysteine exerts its role independent of glutathione and glutathione restores the impairment of cysteine-deprivation on intestinal mucosal through degrading into cysteine. This article is protected by copyright. All rights reserved.

4.
ACS Appl Mater Interfaces ; 13(45): 54497-54502, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34726392

RESUMO

Traditional microwave absorbers can hide target objects from the detection of radar waves without tackling optical waves. However, in actual scenarios, the objects might still be observed by a hyperspectral remote sensor or an imaging system from comparison with environmental optical features, in particular for variable backgrounds. For this aspect, a comprehensive stealthing technique able to deal with microwaves and optical features simultaneously adapting to the variable environment is highly desired. In this work, an ultrathin flexible metamaterial that can simultaneously realize wideband microwave absorption and controllable visible and near-infrared luminescence spectra is proposed. The designed artificial coat can absorb more than 80% of the incident energy in the X-band (8-12 GHz) within a large incidence angle range up to 54° at low polarization sensitivity, while its real-time visible and near-infrared luminescence spectrum can be electrically adjusted through an integrated emission system. The method proposed here can be extended to broader wave bands and find important applications in multifunctional stealthing technologies.

5.
Anim Nutr ; 7(4): 1115-1123, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34738042

RESUMO

This study aimed to explore the mechanism underlying arginine-promoted myogenesis of myoblasts. C2C12 cells were cultured with a medium containing 0.1, 0.4, 0.8, or 1.2 mmol/L arginine, respectively. Cell proliferation, viability, differentiation indexes, cytoplasmic Ca2+ concentration, and relative mRNA expression levels of myogenic regulatory factors (MRF) and key Ca2+ channels were measured in the absence or presence of 2 chemical inhibitors, dantrolene (DAN, 10 µmol/L) and nisoldipine (NIS, 10 µmol/L), respectively. Results demonstrated that arginine promoted myogenic differentiation and myotube formation. Compared with the control (0.4 mmol/L arginine), 1.2 mmol/L arginine upregulated the relative mRNA expression levels of myogenin (MyoG) and Myomaker at d 2 during myogenic induction (P < 0.05). Cytoplasmic Ca2+ concentrations were significantly elevated by arginine supplementation at d 2 and 4 (P < 0.05). Relative mRNA expression levels of Ca2+ channels including the type 1 ryanodine receptor (RyR1) and voltage-gated Ca2+ channel (Cav1.1) were upregulated by 1.2 mmol/L arginine during 2-d myogenic induction (P < 0.01). However, arginine-promoted myogenic potential of myoblasts was remarkably compromised by DAN and NIS, respectively (P < 0.05). These findings evidenced that the supplementation of arginine promoted myogenic differentiation and myotube formation through increasing cytoplasmic Ca2+ concentration from both extracellular and sarcoplasmic reticulum Ca2+.

6.
Front Immunol ; 12: 746621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671362

RESUMO

Though significant strides in tumorigenic comprehension and therapy modality have been witnessed over the past decades, glioma remains one of the most common and malignant brain tumors characterized by recurrence, dismal prognosis, and therapy resistance. Immunotherapy advance holds promise in glioma recently. However, the efficacy of immunotherapy varies among individuals with glioma, which drives researchers to consider the modest levels of immunity in the central nervous system, as well as the immunosuppressive tumor immune microenvironment (TIME). Considering the highly conserved property for sustaining energy homeostasis in mammalian cells and repeatedly reported links in malignancy and drug resistance, autophagy is determined as a cutting angle to elucidate the relations between glioma and the TIME. In this review, heterogeneity of TIME in glioma is outlined along with the reciprocal impacts between them. In addition, controversies on whether autophagy behaves cytoprotectively or cytotoxically in cancers are covered. How autophagy collapses from its homeostasis and aids glioma malignancy, which may depend on the cell type and the cellular context such as reactive oxygen species (ROS) and adenosine triphosphate (ATP) level, are briefly discussed. The consecutive application of autophagy inducers and inhibitors may improve the drug resistance in glioma after overtreatments. It also highlights that autophagy plays a pivotal part in modulating glioma and the TIME, respectively, and the intricate interactions among them. Specifically, autophagy is manipulated by either glioma or tumor-associated macrophages to conform one side to the other through exosomal microRNAs and thereby adjust the interactions. Given that some of the crosstalk between glioma and the TIME highly depend on the autophagy process or autophagic components, there are interconnections influenced by the status and well-being of cells presumably associated with autophagic flux. By updating the most recent knowledge concerning glioma and the TIME from an autophagic perspective enhances comprehension and inspires more applicable and effective strategies targeting TIME while harnessing autophagy collaboratively against cancer.

7.
J Agric Food Chem ; 69(43): 12661-12673, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34672544

RESUMO

In this paper, a dual-functional probe, 2-(benzothiazol)-4-(3-hydroxy-4-methylphenyl) imino phenol (BHMH), was synthesized and characterized for the simultaneous detection of Cu2+ and Fe3+ in dimethyl sulfoxide/4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (DMSO/HEPES) (1:4, v/v, pH = 6.0). The limits of detections (LODs) for Cu2+ and Fe3+ were 9.05 and 48 nM, respectively. Based on the competitive coordination, the complex BHMH-Cu2+/Fe3+ exhibited good sensitivity and selectivity for glyphosate. The LODs of BHMH-Cu2+ and BHMH-Fe3+ for glyphosate were 0.41 and 0.63 µM, respectively. The probe quantitatively detected glyphosate in tap water, Songhua River water, local water and soil, and food samples. The colorimetric on-site glyphosate sensing through the probe BHMH-Cu2+ was also studied based on smartphones. BHMH and BHMH-Cu2+/Fe3+ exhibited outstanding imaging capabilities for Cu2+, Fe3+, and glyphosate in living cells with low cytotoxicity, especially the first time for glyphosate.


Assuntos
Cobre , Corantes Fluorescentes , Colorimetria , Glicina/análogos & derivados
8.
Front Mol Biosci ; 8: 720020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540896

RESUMO

Background: The histone deacetylase (HDAC) family limited accessibility to chromatin containing tumor suppressor genes by removing acetyl groups, which was deemed a path for tumorigenesis. Considering glioma remained one of the most common brain cancers with a dichotomy prognosis and limited therapy responses, HDAC inhibitors were an area of intensive research. However, the expression profiles and prognostic value of the HDACs required more elucidation. Methods: Multiple biomedical databases were incorporated, including ONCOMINE, GEPIA, TCGA, CGGA, GEO, TIMER, cBioPortal, and Metascape, to study expression profiles, prognostic value, immune infiltration, mutation status, and enrichment of HDACs in glioma. STRING and GeneMANIA databases were used to identify HDAC1-related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for HDAC1-related signature construction and validation. Results: HDAC1 was significantly overexpressed in glioma, while HDAC11 was downregulated in glioblastoma. Except for HDAC 6/9/10, the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher HDAC1 expression level predicted more dismal overall survival (OS) (p < 0.0001) and disease-free survival (DFS) (p < 0.0001), but a higher level of HDAC11 held more favorable OS (p = 2.1e-14) and DFS (p = 4.8e-08). HDAC4 displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of HDAC1 was validated with ROC achieving 0.70, 0.77, 0.75, and 0.80 as separability for 1-, 3-, 5-, and 10-years OS predictions in glioma, respectively. Moreover, HDAC1 expression positively correlated with neutrophil (r = 0.60, p = 2.88e-47) and CD4+ T cell infiltration (r = 0.52, p = 3.96e-35) in lower-grade glioma. The final HDAC1-related signature comprised of FKBP3, HDAC1 (Hazard Ratio:1.49, 95%Confidence Interval:1.20-1.86), PHF21A, RUNX1T1, and RBL1, and was verified by survival analysis (p < 0.0001) and ROC with 0.80, 0.84, 0.83, and 0.88 as separability for 1-, 3-, 5-, and 10-years OS predictions, respectively. The signature was enriched in chromatin binding. Conclusion: HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, IDH1 mutation, and 1p/19q codeletion. HDAC1 was both a prognostic and immune infiltration indicator and a central component of the HDAC1-related signature for precise prognosis prediction in glioma.

9.
World J Clin Cases ; 9(24): 7251-7260, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34540986

RESUMO

BACKGROUND: The simultaneous occurrence of schwannoma and meningioma in the absence of neurofibromatosis (NF) or a previous history of irradiation is exceedingly rare, as only 10 intracranial cases have been reported to date. Herein, we report a case of a coexistent cavernous sinus meningioma and ipsilateral vestibular schwannoma (VS) in a female patient without NF or a history of exposure to irradiation. CASE SUMMARY: A 63-year-old woman presented with progressive left-side hearing loss and tinnitus over the previous year. In the past 6 mo, she developed facial numbness and intermittent headaches. Magnetic resonance imaging showed two lesions that were located on the left side of the cerebellopontine angle and parasellar region. Both lesions were totally resected via the left retrosigmoid approach. Histopathological examination revealed a VS and a meningioma. The patient did not have a family history or clinical or radiological signs of NF. CONCLUSION: The coincident occurrence of VS and meningioma within close vicinity is very rare, and the pathogenesis is unclear. A careful whole-body examination needs to be conducted to exclude NF. Surgical treatment with the goal of total tumor resection is the best therapy. Additional studies are needed for a better understanding of the mechanisms that lead to the development of tumor growth in multiple locations.

10.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575982

RESUMO

Glyphosate is a highly effective, low-toxicity, broad-spectrum herbicide, which is extensively used in global agriculture to control weeds and vegetation. However, glyphosate has become a potential threat to human and ecosystem because of its excessive usage and its bio-concentration in soil and water. Herein, a novel turn-on fluorescent probe, N-n-butyl-4-(3-pyridin)ylmethylidenehydrazine-1,8-naphthalimide (NPA), is proposed. It efficiently detected Cu2+ within the limit of detection (LOD) of 0.21 µM and displayed a dramatic turn-off fluorescence response in CH3CN. NPA-Cu2+ complex was employed to selectively and sensitively monitor glyphosate concentrations in real samples accompanied by a fluorescence turn-on mode. A good linear relationship between NPA and Cu2+ of glyphosate was found in the range of 10-100 µM with an LOD of 1.87 µM. Glyphosate exhibited a stronger chelation with Cu2+ than NPA and the system released free NPA through competitive coordination. The proposed method demonstrates great potential in quantitatively detecting glyphosate in tap water, local water from Songhua River, soil, rice, millet, maize, soybean, mung bean, and milk with mild conditions, and is a simple procedure with obvious consequences and no need for large instruments or pretreatment.


Assuntos
Técnicas Biossensoriais , Glicina/análogos & derivados , Herbicidas/isolamento & purificação , Naftalimidas/química , Cobre/química , Corantes Fluorescentes/química , Glicina/química , Glicina/isolamento & purificação , Glicina/toxicidade , Herbicidas/química , Herbicidas/toxicidade , Humanos , Limite de Detecção , Pontos Quânticos/química , Rios/química , Poluentes do Solo/isolamento & purificação , Poluentes do Solo/toxicidade , Água/química , Poluentes da Água/isolamento & purificação , Poluentes da Água/toxicidade
11.
BMC Pulm Med ; 21(1): 259, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372824

RESUMO

BACKGROUND: Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests. METHODS: We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis. RESULTS: In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P < 0.001). The odds ratio for having asthma increased progressively with a gradual increase in FeNO or B-Eos count (both P < 0.001; assessed using the Cochran-Armitage trend test). Further analysis of in-series combinations of different threshold values for these biomarkers indicated that moderately elevated biomarker levels (FeNO > 40 ppb and B-Eos > 300 cells/µl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017-2019 data as the internal validation dataset. CONCLUSION: FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/µl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.

12.
Cost Eff Resour Alloc ; 19(1): 44, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281538

RESUMO

OBJECTIVE: The choice between neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) remains controversial in the treatment of non-small cell lung cancer (NSCLC). There is no significant difference in NAC and AC's effectiveness. We investigate the cost-effectiveness of NAC versus AC for NSCLC. METHOD: A decision tree model was designed from a payer perspective to compare NAC and AC treatments for NSCLC patients. Parameters included overall survival (OS), surgical complications, chemotherapy adverse events (AEs), treatment initiation probability, treatment time frame, treatment cost, and quality of life (QOL). Sensitivity analyses were performed to characterize model uncertainty in the base cases. RESULT: AC treatment strategy produced a cost saving of ¥3064.90 and incremental quality-adjusted life-years (QALY) of 0.10 years per patient with the same OS. NAC would be cost-effective at a ¥35,446/QALY threshold if the median OS of NAC were 2.3 months more than AC. The model was robust enough to handle variations to all input parameters except OS. In the probability sensitivity analysis, AC remained dominant in 54.4% of simulations. CONCLUSION: The model cost-effectiveness analysis indicates that with operable NSCLC, AC treatment is more cost-effective to NAC. If NAC provides a longer survival advantage, this treatment strategy may be cost-effective. The OS is the main factor that influences cost-effectiveness and should be considered in therapeutic regimes.

13.
Environ Sci Technol ; 55(15): 10862-10874, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34282905

RESUMO

The global rise and spread of antibiotic resistance greatly challenge the treatment of bacterial infections. Wastewater treatment plants (WWTPs) harbor and discharge antibiotic resistance genes (ARGs) as environmental contaminants. However, the knowledge gap on the host identity, activity, and functionality of ARGs limits transmission and health risk assessment of the WWTP resistome. Hereby, a genome-centric quantitative metatranscriptomic approach was exploited to realize high-resolution qualitative and quantitative analyses of bacterial hosts of ARGs (i.e., multiresistance, pathogenicity, activity, and niches) in the 12 urban WWTPs. We found that ∼45% of 248 recovered genomes expressed ARGs against multiple classes of antibiotics, among which bacitracin and aminoglycoside resistance genes in Proteobacteria were the most prevalent scenario. Both potential pathogens and indigenous denitrifying bacteria were transcriptionally active hosts of ARGs. The almost unchanged relative expression levels of ARGs in the most resistant populations (66.9%) and the surviving ARG hosts including globally emerging pathogens (e.g., Aliarcobacter cryaerophilus) in treated WWTP effluent prioritize future examination on the health risks related to resistance propagation and human exposure in the receiving environment.


Assuntos
Antibacterianos , Purificação da Água , Antibacterianos/farmacologia , Bactérias/genética , Genes Bacterianos , Humanos , Águas Residuárias
14.
Front Oncol ; 11: 692097, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195093

RESUMO

Background: Brainstem glioma is a primary glial tumor that arises from the midbrain, pons, and medulla. The objective of this study was to determine the population-based epidemiology, incidence, and outcomes of brainstem gliomas. Methods: The data pertaining to patients with brainstem gliomas diagnosed between 2004 and 2016 were extracted from the SEER database. Descriptive analyses were conducted to evaluate the distribution and tumor-related characteristics of patients with brainstem gliomas. The possible prognostic indicators were analyzed by Kaplan-Meier curves and a Cox proportional hazards model. Results: The age-adjusted incidence rate was 0.311 cases per 100,000 person-years between 2004 and 2016. A total of 3387 cases of brainstem gliomas were included in our study. Most of the patients were white and diagnosed at 5-9 years of age. The most common diagnosis confirmed by histological review was ependymoma/anaplastic ependymoma. The median survival time was 24 months. Patients with tumors less than 3 cm in size had a better prognosis. Surgery was effective at improving overall survival. There was no evidence that radiotherapy and chemotherapy improved overall survival. Conclusion: Brainstem gliomas can be diagnosed at any age. Ependymoma/anaplastic ependymoma is the most common pathological diagnosis. The prognosis is poor, and timely diagnosis and surgery are effective at improving the prognosis. We suggest that more attention should be given to the treatment of patients with brainstem gliomas.

15.
Front Endocrinol (Lausanne) ; 12: 551493, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168614

RESUMO

Ependymomas are primary glial tumors arising from cells related to the ependymal lining of the ventricular system. They are classified into at least nine different molecular subtypes according to molecular phenotype, histological morphology, and tumor location. Primary sellar ependymoma is an extremely rare malignancy of the central nervous system, with only 12 known cases reported in humans. We herein report a case of ependymoma located at the pituitary region in a 44-year-old female patient and discuss the molecular subtype, natural history, clinical presentation, radiological findings, histological features, immunohistochemical characteristics, ultrastructural examinations, treatment, and prognosis of sellar ependymoma. This case report may serve as a helpful reference for clinicians and radiologists in clinical practice.

16.
J Med Chem ; 64(13): 9078-9099, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34129329

RESUMO

Fibroblast growth factor receptors (FGFRs) have become promising therapeutic targets in various types of cancers. In fact, several selective irreversible inhibitors capable of covalently reacting with the conserved cysteine of FGFRs are currently being evaluated in clinical trials. In this article, we optimized and discovered a novel lead compound 36 with remarkable inhibitory effects against FGFR (1-3), which is a derivative of 2H-pyrazolo[3,4-d]pyrimidine. The irreversible binding to FGFRs was characterized by LC-MS. This compound has been shown to exhibit significant anti-proliferation effects against NCI-H1581 and SNU-16 cancer cell lines both in vitro and in vivo. Compound 36 has also demonstrated a low toxicity profile and adequate pharmacokinetic properties and is currently under validation as a potential drug candidate.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
17.
Front Oncol ; 11: 683021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34109129

RESUMO

Background: Hemangioblastoma is a benign tumor of the central nervous system and may appear as a component of von Hippel-Lindau (VHL) disease. At present, approximately 40 cases of optic nerve HGBs have been reported in the literature. VHL disease is a rare autosomal-dominant inherited cancer syndrome with different phenotypes caused by variants in the VHL gene. Herein, the authors describe a case of a pediatric patient with VHL disease and with optic nerve HGB, a rare phenotypic expression. The purpose of this study was to explore the genotype-phenotype, clinical features, treatment and follow-up of VHL-associated hemangioblastomas in pediatric patients. Case Description: A 12-year-old boy presented with vision loss, headache and dizziness at our hospital. Magnetic resonance imaging (MRI) revealed a large (19.8 mm*18.5 mm*23.5 mm) irregular mass located in the suprasellar region. The mass was successfully removed after craniotomy and microsurgical treatment. The pathological diagnosis was left optic nerve HGB. Genetic analyses showed p.Pro86Leu (c. 257C>T) heterozygous missense mutations in the VHL gene. Conclusion: This is the first reported pediatric case of VHL-associated optic nerve HGB. The genotype-phenotype correlation of VHL disease may provide new evidences for predicting tumor penetrance and survival. Gross tumor resection combined with stereotactic radiosurgery might be the most beneficial treatment.

18.
Front Oncol ; 11: 642683, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094927

RESUMO

Background: Leiomyosarcoma is a highly malignant soft-tissue sarcoma with a poor prognosis. In recent years, treatment for leiomyosarcoma has not shown much progress. Primary intracranial leiomyosarcoma (PILMS) is a much rarer type of neoplasm, which occurs more frequently in immunocompromised patients. PILMS cases reported in the literature are scarce and treatment strategy and prognosis are still under debate. In this study, a case of PILMS secondary to the total resection of giant cell glioblastoma is reported. Case Description: A 38-year-old male was hospitalized with a three-month history of a temporal opisthotic bump. His medical history included a total resection of a tumor located in the right temporal lobe performed 4 years earlier. Pathological examination led to a diagnosis of giant cell glioblastoma, and the patient underwent postoperative chemotherapy with temozolomide for 6 weeks plus simultaneous radiotherapy with 63.66 Gary. Four years later, during regular follow-up, a preoperative MRI brain scan resulted in a well-defined signal pointing out two nodule-like features located at the right temporal lobe and subcutaneous soft tissue, respectively, and near the area where the previous giant cell glioblastoma was located. The mass was completely removed by a transtemporal approach and postoperative pathology revealed that the mass was a leiomyosarcoma. The patient underwent postoperative radiotherapy and no recurrence occurred until now. Conclusions: To date, research on soft-tissue sarcoma, especially PILMS, has not made much progress, and a limited number of studies have provided few details on the management of PILMS. The treatment of choice for PILMS is aggressive multimodal treatment based on total tumor resection and radiotherapy. Moreover, systemic treatment with chemotherapy and targeted therapy, such as olaratumab, as well as further research still needs to be performed as many questions are left unanswered. To our knowledge, this is the first report on a case of PILMS secondary to glioblastoma, which might serve as a potential reference for clinicians and clinical studies.

19.
Angew Chem Int Ed Engl ; 60(30): 16404-16408, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-33979017

RESUMO

Li-CO2 batteries are regarded as next-generation high-energy-density electrochemical devices. However, the greatest challenge arises from the formation of the discharge product, Li2 CO3 , which would accumulate and deactivate heterogenous catalysts to cause huge polarization. Herein, Ru(bpy)3 Cl2 was employed as a solution-phase catalyst for Li-CO2 batteries and proved to be the most effective one screened so far. Spectroscopy and electrochemical analyses elucidate that the RuII center could interact with both CO2 and amorphous Li2 C2 O4 intermediate, thus promoting electroreduction process and delaying carbonate transformation. As a result, the charge potential is reduced to 3.86 V and over 60 discharge/charge cycles are achieved with a fixed capacity of 1000 mAh g-1 at a current density of 300 mA g-1 . Our work provides a new avenue to improve the electrochemical performance of Li-CO2 batteries with efficient mobile catalysts.

20.
Langmuir ; 37(23): 6974-6984, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34048253

RESUMO

A series of cyclic surfactants were synthesized from a poly(ethylene glycol) (PEG) homopolymer and Pluronic surfactants L35, L64, P123, F68, 10R5, and 17R4, and their interfacial activity depending on the topology, chain ends, and block sequence was investigated. The cyclization was performed in a single step through etherification of the PEG homopolymer and the hydrophilic-hydrophobic-hydrophilic (ABA type) poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEG-PPG-PEG), while the hydrophobic-hydrophilic-hydrophobic (BAB type) PPG-PEG-PPG was cyclized via acetalization. The cyclized surfactants were rigorously characterized by nuclear magnetic resonance spectroscopy and size exclusion chromatography. Cyclization of the surfactants induced a significant decrease in the hydrodynamic volume, which was more pronounced than that of the PEG homopolymer. Surface tension (γ) measurements indicated that the interfacial activity of the cyclized surfactants is stronger than their corresponding linear precursors, due to the increase in the surfactant density at the air-water interface as a consequence of the decreased molecular occupational area (A) upon cyclization. In the case of the PEG homopolymer, A considerably decreased from 410 Å2 for the linear PEG prepolymer to 100 Å2 for the cyclized PEG product. While the effects of chain-end groups were found to be limited to surfactants of relatively small molecular weights, the influence of cyclization depended strongly on the hydrophilic/hydrophobic ratio; the higher the PEG composition the surfactants had, the larger the decrease in γ and A; in other words, stronger enhancement in the interfacial activity was observed.

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