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1.
Drug Deliv ; 27(1): 323-333, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32090639

RESUMO

Although microRNAs (miRNAs)-based cancer therapy strategies have been proved to be efficient and superior to chemotherapeutic agents in certain extent, the unstable properties of miRNAs significantly impaired the wide application. Therefore, how to safely deliver the miRNAs to the targeted site of action is the most pivotal step to achieve the ideal treatment effect. In the present work, the miR-128-3p, which is able of inducing chromosomal instability, was loaded into the nanocomplexes developed by the PEG-PDMAEMA (PDMAEMA-NP). By this way, the miR-128-3p was shielded from exposure to various degrading enzymes in bloodstream. Additionally, the PEGylation endowed the PDMAEMA-NP with long time of circulation as demonstrated in vivo by pharmacokinetics investigation. To target and deliver the miR-128-3p to the site of action, a tumor-homing peptide CPKSNNGVC, which specifically targets the monocarboxylate transporter 1 (MCT1), was decorated on the surface of PDMAEMA-NP. Both in vitro and in vivo experiments demonstrated that more efficient delivery of miR-128-3p to cells or tumor tissues was obtained by the PDMAEMA-NP than plasmid. Additionally, modification of C peptides further enhanced the tumor accumulation of miR-128-3p, and in turn contributed to the stronger tumor growth inhibition effect. Underlying mechanisms study revealed that the miR-128-3p inhibited the growth, migration, and invasion of colorectal cancer (CRC) cells and progress of CRC tissues through silence of the activity of PI3K/AKT and MEK/ERK pathway. By this way, the chemotherapy effect of 5-Fluorouracil (5-Fu) was dramatically improved after co-treating the cells with miR-128-3p formulations.

2.
Nat Commun ; 11(1): 606, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001696

RESUMO

Manipulating liquids with tunable shape and optical functionalities in real time is important for electroactive flow devices and optoelectronic devices, but remains a great challenge. Here, we demonstrate electrotunable liquid sulfur microdroplets in an electrochemical cell. We observe electrowetting and merging of sulfur droplets under different potentiostatic conditions, and successfully control these processes via selective design of sulfiphilic/sulfiphobic substrates. Moreover, we employ the electrowetting phenomena to create a microlens based on the liquid sulfur microdroplets and tune its characteristics in real time through changing the shape of the liquid microdroplets in a fast, repeatable, and controlled manner. These studies demonstrate a powerful in situ optical battery platform for unraveling the complex reaction mechanism of sulfur chemistries and for exploring the rich material properties of the liquid sulfur, which shed light on the applications of liquid sulfur droplets in devices such as microlenses, and potentially other electrotunable and optoelectronic devices.

3.
Nat Nanotechnol ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988508

RESUMO

It has recently been shown that sulfur, a solid material in its elementary form S8, can stay in a supercooled state as liquid sulfur in an electrochemical cell. We establish that this newly discovered state could have implications for lithium-sulfur batteries. Here, through in situ studies of electrochemical sulfur generation, we show that liquid (supercooled) and solid elementary sulfur possess very different areal capacities over the same charging period. To control the physical state of sulfur, we studied its growth on two-dimensional layered materials. We found that on the basal plane, only liquid sulfur accumulates; by contrast, at the edge sites, liquid sulfur accumulates if the thickness of the two-dimensional material is small, whereas solid sulfur nucleates if the thickness is large (tens of nanometres). Correlating the sulfur states with their respective areal capacities, as well as controlling the growth of sulfur on two-dimensional materials, could provide insights for the design of future lithium-sulfur batteries.

4.
Am J Orthod Dentofacial Orthop ; 156(6): 823-831, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31784016

RESUMO

INTRODUCTION: An accurate prediction in the soft tissue changes is of great importance for orthodontic treatment planning. Previous studies on the accuracy of the Dolphin visual treatment objective (VTO) in predicting treatment results were mainly focused on orthognathic treatment. The accuracy of Dolphin VTO prediction for orthodontic treatment is, however, poorly understood. The aim of this study was to evaluate the accuracy of Dolphin VTO prediction in soft tissue changes after orthodontic treatment by comparing the changes between predicted and actual values. METHODS: A total of 157 patients were screened for eligibility, and 34 young adult patients (8 males, 26 females; mean age 24.8 ± 3.9 years) were finally included in the study based on the inclusion and exclusion criteria. The landmarks and parameters of the Holdaway soft tissue analysis were used for the cephalometric analyses. The cephalometric tracings of the actual treatment result and the Dolphin predicted treatment outcome were superimposed to calculate the prediction errors. Paired t test was used to compare the statistical differences between the predicted and actual treatment outcomes of the parameters used in the Holdaway soft tissue analysis. RESULTS: There were significant differences between the predicted and actual values in parameters of the Holdaway soft tissue analysis (P < 0.05). The prediction of the landmarks in the lips region (ie, subnasale, soft tissue A-point, upper lip, lower lip, and soft tissue B-point) was inclined to be overestimated horizontally and underestimated vertically, whereas the prediction of the landmarks belonging to the chin region (ie, soft tissue pogonion, soft tissue gnathion, and soft tissue menton) was inclined to be underestimated horizontally and overestimated vertically. The most accurate prediction was found in the soft tissue A-point, whereas the least accurate one was found in the soft tissue in the chin region. The prediction was relatively more accurate in the vertical direction than in the horizontal direction. CONCLUSIONS: The Dolphin VTO prediction in soft tissue changes after the orthodontic treatment in patients with bimaxillary protrusion is the most accurate for the soft tissue A-point and the least accurate for the soft tissue chin region.


Assuntos
Face , Má Oclusão , Ortodontia Corretiva , Adulto , Cefalometria , Queixo , Face/anatomia & histologia , Feminino , Previsões , Humanos , Lábio , Masculino , Software , Adulto Jovem
5.
Onco Targets Ther ; 12: 9239-9248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819473

RESUMO

Background: Ovarian cancer is characterized by high metastatic potential and high mortality. More than 80% of primary ovarian malignancies are epithelial ovarian cancers. There is increasing evidence that Speckle-type POZ protein (SPOP) is highly correlated with the development of various types of cancer. However, the effects of SPOP on epithelial ovarian cancer and the associated molecular mechanisms remain unclear. Materials and methods: We compared SPOP expression between epithelial ovarian cancer tissues and normal ovarian tissues by using immunohistochemical staining. To determine the role of SPOP in epithelial ovarian cancer cells, we overexpressed or knocked down SPOP in the epithelial ovarian cancer cell line OVCAR-3 using lentiviral vectors. Results: Our results from the present study indicated that SPOP expression was significantly downregulated in human epithelial ovarian cancer and was associated with the FIGO stage and the histopathologic grading of the tumor. The overexpression and knockdown experiments revealed that SPOP inhibited proliferation while promoting apoptosis in ovarian cancer cells. Inhibition of SPOP mis-activated the Hedgehog (Hh) signaling pathway, thereby inhibiting apoptosis in ovarian cancer cells. Conclusion: SPOP suppresses proliferation and promotes apoptosis in human ovarian cancer cells by inhibiting the Hh signaling pathway, offering the possibility of new approaches for the treatment of ovarian cancer.

6.
BMC Oral Health ; 19(1): 137, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286897

RESUMO

BACKGROUND: The direct and indirect bonding techniques are commonly used in orthodontic treatment. The differences of the two techniques deserve evidence-based study. MATERIALS AND METHODS: Randomized controlled trials (RCTs), wherein direct and indirect bonding techniques were used in orthodontic patients were considered. The MEDLINE, EMBASE, CENTRAL and Web of Science databases were searched to identify relevant articles published up to December 2018. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using the data collection form. The included trials were assessed using the Cochrane risk of bias assessment tool. RESULTS: Of the 1557 studies screened, 42 full articles were scrutinized and assessed for eligibility. Eight RCTs (247 participants) were finally included for the analyses. The qualitative synthesis showed that no significant difference existed in the accuracy of bracket placement and oral hygiene status between the two bonding techniques. The indirect bonding was found to involve less chairside time but more total working time compared with the direct bonding. The meta-analysis on bond failure rate demonstrated no significant difference between the direct and indirect bonding (RR = 1.13, 95% CI = 0.78-1.64, I2 = 22%, P = 0.50). Consistent results were obtained in the subgroup analyses and sensitivity analyses. CONCLUSION: Weak evidence suggested that the direct and indirect bonding techniques had no significant difference in bracket placement accuracy, oral hygiene status and bond failure rate, for bonding orthodontic brackets. The indirect bonding might require less chairside time but more total working time in comparison with the direct bonding technique. High-quality well-designed randomized controlled trials are needed before a conclusive recommendation could be made.


Assuntos
Colagem Dentária , Braquetes Ortodônticos , Humanos
7.
World J Gastroenterol ; 25(22): 2776-2787, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31236000

RESUMO

BACKGROUND: Aberrant expression of stanniocalcin 2 (STC2) is implicated in colon adenocarcinoma (COAD). A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers, but the role of its overexpression in the development of COAD remains unclear. AIM: To evaluate the regulation mechanism of STC2 overexpression in COAD. METHODS: The expression of STC2 in COAD was assessed by TCGA COAD database and GEO (GSE50760). Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform, and the correlation between STC2 expression and survival rate was investigated with TCGA COAD. Transcription binding site prediction was conducted by TRANSFAC and LASAGNA, and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines, including HEK293T, NCM460, HT29, SW480, and HCT116. Western blotting was performed to evaluate the role of Sp1 on the expression of STC2. RESULTS: The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis. Importantly, the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2. A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2, and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2. Furthermore, inhibition of Sp1 remarkably decreased protein levels of STC2. CONCLUSION: Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity. Taken together, our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.


Assuntos
Adenocarcinoma/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Fator de Transcrição Sp1/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Metilação de DNA/genética , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Prognóstico , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Fator de Transcrição Sp1/genética , Taxa de Sobrevida , Ativação Transcricional , Regulação para Cima
8.
Small ; 15(31): e1900964, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31211511

RESUMO

In the hydrogen evolution reaction (HER), energy-level matching is a prerequisite for excellent electrocatalytic activity. Conventional strategies such as chemical doping and the incorporation of defects underscore the complicated process of controlling the doping species and the defect concentration, which obstructs the understanding of the function of band structure in HER catalysis. Accordingly, 2H-MoS2 and 1T-MoS2 are used to create electrocatalytic nanodevices to address the function of band structure in HER catalysis. Interestingly, it is found that the 2H-MoS2 with modulated Fermi level under the application of a vertical electric field exhibits excellent electrocatalytic activity (as evidenced by an overpotential of 74 mV at 10 mA cm-2 and a Tafel slope of 99 mV per decade), which is superior to 1T-MoS2 . This unexpected excellent HER performance is ascribed to the fact that electrons are injected into the conduction band under the condition of back-gate voltage, which leads to the increased Fermi level of 2H-MoS2 and a shorter Debye screen length. Hence, the required energy to drive electrons from the electrocatalyst surface to reactant will decrease, which activates the 2H-MoS2 thermodynamically.

9.
Drug Des Devel Ther ; 13: 1449-1460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118579

RESUMO

Background: Colorectal cancer (CRC) is a common form of cancer associated with a high mortality rate and poor prognosis. Given the limited efficacy of current therapies for CRC, interest in novel therapeutic agents isolated from natural sources has increased. We studied the anticancer properties of isobavachalcone (IBC), a flavonoid isolated from the herb Psoralea corylifolia, which is used in traditional Chinese medicine, in an in vitro model of CRC. Materials and methods: Cell viability and growth of CRC cells were determined by Cell Counting Kit-8 and colony formation assays following treatment with varying concentrations of IBC, respectively. Apoptosis was examined by 4',6-diamidino-2-phenylindole staining and flow cytometry with Annexin V/propidium iodide double staining. Western blot analysis was used to analyze expression of apoptosis-associated protein pathway and the AKT/GSK-3ß/ß-catenin signaling pathway. Results: Initial experiments showed that IBC inhibited proliferation and colony formation of human CRC cell lines in dose- and time-dependent manners. The antiproliferative effect of IBC resulted from induction of apoptosis, as evidenced by morphological changes in the nucleus, flow cytometry analysis, upregulation of cleaved caspase-3 and cleaved PARP, changes in the ratio of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax, translocation of Bax from the cytosol to the mitochondria, and decreased expression of two inhibitors of apoptosis family proteins, XIAP, and survivin. Western blot analysis of signaling pathway proteins demonstrated that IBC downregulated Wnt/ß-catenin signaling, which has previously been associated with CRC, by inhibiting the AKT/GSK-3ß signaling pathway. Conclusion: This study demonstrated that IBC inhibited cell proliferation and induced apoptosis through inhibition of the AKT/GSK-3ß/ß-catenin pathway in CRC. These results suggest the potential of IBC as a novel therapeutic agent for the treatment of CRC.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Psoralea/química , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chalconas/química , Chalconas/isolamento & purificação , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
10.
Int J Nanomedicine ; 14: 2757-2772, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118609

RESUMO

Background and purpose: Surgery is regarded as the gold standard for patients with advanced ovarian cancer. However, complete surgical removal of tumors remains extremely challenging; fewer than 40% of patients are cured. Here, we developed a new modality of theranostics for ovarian cancer based on a near-infrared light-triggered nanoparticle. Methods: Nanoparticles loading IR780 iodide on base of folate modified liposomes were prepared and used for theranostics of ovarian cancer. Tumor targeting of FA-IR780-NP was evaluated in vitro and in an ovarian xenograft tumor model. A fluorescence stereomicroscope was applied to evaluate the tumor recognition of FA-IR780-NP during surgery. FA-IR780-NP mediated photothermal therapy effect was compared with other treatments in vivo. Results: FA-IR780-NP was demonstrated to specifically accumulate in tumors. IR780 iodide selectively accumulated in tumors; the enhanced permeability and retention effect of the nanoparticles and the active targeting of folate contributed to the excellent tumor targeting of FA-IR780-NP. With the aid of tumor targeting, FA-IR780-NP could be used as an indicator for the real-time delineation of tumor margins during surgery. Furthermore, photothermal therapy mediated by FA-IR780-NP effectively eradicated ovarian cancer tumors compared with other groups. Conclusion: In this study, we present a potential, effective approach for ovarian cancer treatment through near-infrared fluorescence image-guided resection and photothermal therapy to eliminate malignant tissue.


Assuntos
Ácido Fólico/química , Hipertermia Induzida , Indóis/química , Raios Infravermelhos , Nanopartículas/química , Neoplasias Ovarianas/terapia , Fototerapia , Cirurgia Assistida por Computador , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Fluorescência , Humanos , Lipossomos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/toxicidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Distribuição Tecidual/efeitos dos fármacos
11.
Nanoscale ; 11(16): 7761-7770, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30951073

RESUMO

Recently, conducting polymers (CPs) have gained significant attention for their potential applications in micro-supercapacitors (MSCs). Prior to actualizing this potential, however, several critical issues should be resolved, notably their low cycling stability and comparatively low capacitance and energy density. Concurrently, challenges remain in improving the performance of CPs for use in MSCs in terms of their electrical conductivity, energy density, and cycling stability. For this investigation, we fabricated a high-performance MSC based on poly(3,4-ethylenedioxythiophene) (PEDOT)-coated multi-walled carbon nanotube (MWCNT) nanoporous network microelectrodes by photolithography combined with electrochemical co-deposition on micro-current collectors. We then sought to confirm the proposed higher electrochemical performance of this hybrid MSC with the synergetic effect of PEDOT as a pseudo-capacitive material and MWCNTs as electric double-layer capacitive material. As reported herein, the hybrid MSC delivers a maximum specific capacitance of 20.6 mF cm-2 (82.4 F cm-3) and, consequently, a comparatively high areal energy density of 2.82 µW h cm-2 (11.4 mW h cm-3) in a wide voltage window of 1.0 V at a current density of 0.1 mA cm-2, and a maximum power density of 18.55 W cm-3 at an energy density of 8.1 mW h cm-3. Furthermore, the MSC displays remarkable long-term cycling stability, retaining 99.9% of its initial capacitance after 20 000 CV and GCD cycles with a coulombic efficiency of 100%. Additionally, two PEDOT-CNT MSCs are coupled in series to power a red light emitting diode. The results provided herein confirm that the PEDOT-CNT MSCs exhibit improved performance over other CP based MSCs.

12.
Angew Chem Int Ed Engl ; 58(12): 3939-3942, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30614609

RESUMO

The natural Mn4 Ca cluster in photosystem II serves as a blueprint to develop artificial water-splitting catalysts for the generation of solar fuel in artificial photosynthesis. Although significant advances have recently been achieved, it remains a great challenge to prepare robust artificial Mn4 Ca clusters that precisely mimic the structure and function of the biological catalyst. Herein, we report the isolation and structural characterization of two Mn4 CaO4 complexes with polar solvent molecules, acetonitrile or N,N-dimethylformamide, which closely mimics the two water molecules on the calcium ion, as well as the oxidation states of the four manganese ions and the main geometric structure of the natural Mn4 Ca cluster. These new artificial Mn4 Ca complexes provide important chemical clues to understand the structure and mechanism of the biological system.

13.
Cell Physiol Biochem ; 51(4): 1969-1981, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30513513

RESUMO

BACKGROUND/AIMS: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. METHODS: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. RESULTS: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. CONCLUSION: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.


Assuntos
Neoplasias Colorretais/genética , Quinase 4 Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Idoso , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação para Baixo , Feminino , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade
14.
Materials (Basel) ; 11(11)2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30404187

RESUMO

Grain-scale strain heterogeneity characteristics play a critical role in the ductile damage behavior and mechanical properties of two-phase titanium alloys. In this work, the grain-scale strain distribution, strain heterogeneity, and strain localization of titanium alloy with tri-modal microstructure (consisting of equiaxed α (αp), lamellar α (αl), and ß transformed matrix (ßt)) during tensile deformation were experimentally investigated. The results show that the strain probability distribution of the whole microstructure obeys normal distribution during deformation. Significant strain heterogeneities exist in each constituent (αp, αl, and ßt) and the whole microstructure. At lower macro-strain, αp and αl exhibit higher average strain than those of ßt and the whole of the microstructure. Meanwhile, strain heterogeneity of each constituent is small and has a negligible change. The strain heterogeneity of the whole microstructure is mainly determined by αp. At larger macro-strain, some highly deformed regions produce and their positions do not change during further deformation. As a result, the strain heterogeneity of each constituent increases fast, and the strain heterogeneity of whole microstructure is mainly related to αl in this deformation stage. On the other hand, two types of strain localization may be generated within αp and αl and at the αp/ßt and αl/ßt boundaries, respectively. The former type is caused by transgranular intense slip deformation and presents crystal orientation dependence. The latter type is related to the boundary sliding and presents spatial distribution dependence for αl. These strain localizations greatly determine the micro-damages, thus forming the corresponding micro-voids within αp and αl and the micro-cracks at αp/ßt and αl/ßt boundaries in tri-modal microstructure at larger deformation.

15.
Aging (Albany NY) ; 10(8): 2062-2078, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30144787

RESUMO

Colorectal cancer (CRC) is the third most common malignancy in the United States. Chemotherapeutic resistance is a massive obstacle for cancer treatment. The roles and molecular basis of long non-coding RNA BRAF-activated noncoding RNA (BANCR) in CRC progression and adriamycin (ADR) resistance have not been extensively identified. In this study, we found that BANCR and CSE1L expressions were upregulated in CRC tumor tissues. Meanwhile, CSE1L expression was correlated with depth of CRC. BANCR silencing suppressed cell proliferation and invasion capacity, increased apoptotic rate and potentiated cell sensitivity to ADR. CSE1L downregulation triggered a reduction of cell proliferation and invasion ability, and an increase of apoptosis rate and cell sensitivity to ADR. CSE1L overexpression attenuated si-BANCR-mediated anti-proliferation, anti-invasion and pro-apoptosis effects in CRC cells. BANCR acted as a molecular sponge of miR-203 to sequester miR-203 away from CSE1L in CRC cells, resulting in the upregulation of CSE1L expression. CSE1L knockdown inhibited expressions of DNA-repair-related proteins (53BP1 and FEN1) in HCT116 cells. BANCR knockdown also inhibited tumor growth and enhanced ADR sensitivity in CRC mice model. In conclusion, BANCR knockdown suppressed CRC progression and strengthened chemosensitization of CRC cells to ADR possibly by regulating miR-203/CSE1L axis, indicating that BANCR might be a promising target for CRC treatment.


Assuntos
Neoplasias Colorretais/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , RNA Longo não Codificante/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteína de Suscetibilidade a Apoptose Celular/genética , Proteína de Suscetibilidade a Apoptose Celular/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs , Neoplasias Experimentais , RNA Longo não Codificante/genética , Distribuição Aleatória
16.
Acta Neuropathol ; 136(4): 641-655, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29948154

RESUMO

Pediatric low-grade gliomas (PLGGs) consist of a number of entities with overlapping histological features. PLGGs have much better prognosis than the adult counterparts, but a significant proportion of PLGGs suffers from tumor progression and recurrence. It has been shown that pediatric and adult low-grade gliomas are molecularly distinct. Yet the clinical significance of some of newer biomarkers discovered by genomic studies has not been fully investigated. In this study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and examined their clinical relevance. TERT promoter (TERTp), H3F3A and BRAF V600E mutations were detected by direct sequencing. ATRX nuclear loss was examined by immunohistochemistry. CDKN2A deletion, KIAA1549-BRAF fusion, and MYB amplification were determined by fluorescence in situ hybridization (FISH). TERTp, H3F3A, and BRAF V600E mutations were identified in 2.5, 6.4, and 7.4% of PLGGs, respectively. ATRX loss was found in 4.9% of PLGGs. CDKN2A deletion, KIAA1549-BRAF fusion and MYB amplification were detected in 8.8, 32.0 and 10.6% of PLGGs, respectively. Survival analysis revealed that TERTp mutation, H3F3A mutation, and ATRX loss were significantly associated with poor PFS (p < 0.0001, p < 0.0001, and p = 0.0002) and OS (p < 0.0001, p < 0.0001, and p < 0.0001). BRAF V600E was associated with shorter PFS (p = 0.011) and OS (p = 0.032) in a subset of PLGGs. KIAA1549-BRAF fusion was a good prognostic marker for longer PFS (p = 0.0017) and OS (p = 0.0029). MYB amplification was also a favorable marker for a longer PFS (p = 0.040). Importantly, we showed that these molecular biomarkers can be used to stratify PLGGs into low- (KIAA1549-BRAF fusion or MYB amplification), intermediate-I (BRAF V600E and/or CDKN2A deletion), intermediate-II (no biomarker), and high-risk (TERTp or H3F3A mutation or ATRX loss) groups with distinct PFS (p < 0.0001) and OS (p < 0.0001). This scheme should aid in clinical decision-making.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Gradação de Tumores/métodos , Adolescente , Biomarcadores Tumorais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Mutação/genética , Patologia Molecular , Pediatria , Prognóstico , Intervalo Livre de Progressão , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
17.
J Neurooncol ; 139(2): 307-322, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29761369

RESUMO

Although oligodendrogliomas appear histologically similar in adult and pediatric patients, the latter have only been rarely studied and most of those studies did not have long follow-up. We examined 55 oligodendroglial tumors from pediatric and teenage patients for their biomarkers with formalin-fixed paraffin-embedded tissues and studied their survival status. None of the tumors harbored 1p/19q codeletion or IDH mutation. Mutations in TERTp (4%), BRAF (11%), FGFR1 (3%) and H3F3A (5%), fusions of BRAF (8%) and FGFR1 (8%) were found sparingly and almost all in a mutually exclusive manner. Molecular events were exclusively found in tumors with classic oligodendroglial histology. Survival analysis showed remarkably excellent prognosis compared to the adult counterparts. 5-year overall survival was 95% in our cohort with median follow-up of 8.1 years and in nine patients with follow-up more than 10 years, the 10-year overall survival was 100%. The 5-year and 10-year progression-free survivals of our cohort were 89 and 77%, respectively. FGFR1 fusion seemed to confer a poor prognosis in pediatric oligodendrogliomas. Patients receiving adjuvant chemotherapy (p = 0.046) or harboring Grade II histology (p < 0.001) had longer interval to recurrence. Our study demonstrated the distinct indolent clinical course of pediatric and teenage oligodendrogliomas compared to the adult tumors. Molecular markers commonly seen in adult oligodendrogliomas and other pediatric low-grade gliomas were only rarely seen. Since there is no clinical or molecular evidence suggesting that pediatric "oligodendrogliomas" are the same as adult oligodendrogliomas albeit histologic similarity, a case can be made for their separation from adult oligodendrogliomas in the next WHO classification.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Oligodendroglioma/mortalidade , Adolescente , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Oligodendroglioma/tratamento farmacológico , Oligodendroglioma/genética , Oligodendroglioma/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
18.
Front Mol Neurosci ; 11: 9, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29472839

RESUMO

Ketamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to study the effects of ketamine on development. We found that exposure to ketamine from pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in disruption of neural crest (NC) derivatives. Ketamine exposure did not affect mesoderm development as indicated by the normal expression of Chordin, Xbra, Wnt8, and Fgf8. However, ketamine treatment significantly inhibited Zic5 and Slug expression at early neural plate stage. Overexpression of Zic5 rescued ketamine-induced Slug inhibition, suggesting the blockage of NC induction was mediated by Zic5. Furthermore, we found Notch signaling was altered by ketamine. Ketamine inhibited the expression of Notch targeted genes including Hes5.2a, Hes5.2b, and ESR1 and ketamine-treated embryos exhibited Notch-deficient somite phenotypes. A 15 bp core binding element upstream of Zic5 was induced by Notch signaling and caused transcriptional activation. These results demonstrated that Zic5 works as a downstream target gene of Notch signaling in Xenopus NC induction. Our study provides a novel teratogenic mechanism whereby ketamine disrupts NC induction via targeting a Notch-Zic5 signaling pathway.

19.
ChemSusChem ; 10(22): 4403-4408, 2017 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-28921879

RESUMO

The oxygen-evolving center (OEC) in photosystem II (PSII) is a unique biological catalyst that splits water into electrons, protons, and O2 by using solar energy. Recent crystallographic studies have revealed that the structure of the OEC is an asymmetric Mn4 Ca cluster, which provides a blueprint to develop man-made water-splitting catalysts for artificial photosynthesis. Although it is a great challenge to mimic the whole structure and function of the OEC in the laboratory, significant advances have recently been achieved. In this Minireview, recent progress on mimicking the natural OEC is discussed. New strategies are suggested to construct more stable and efficient new generation of catalytic materials for the water splitting reaction based on the artificial Mn4 Ca cluster in the future.


Assuntos
Cálcio/química , Manganês/química , Fotossíntese , Complexo de Proteína do Fotossistema II/química , Energia Solar , Água/química , Catálise , Hidrogênio , Estrutura Molecular , Oxirredução , Oxigênio , Relação Estrutura-Atividade , Luz Solar
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