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1.
Medicine (Baltimore) ; 99(3): e18868, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011509

RESUMO

BACKGROUND: Plenty of evidence has suggested that long non-coding RNAs (lncRNAs) have played a vital part may act as prognostic biomarkers in a variety of cancers. The aim of this study was to screen survival-related lncRNAs and to construct a lncRNA-based prognostic model in patients with cutaneous melanoma (CM). METHODS: We obtained lncRNAs expression profiles and clinicopathological data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A lncRNA-based prognostic model was established in training set. The established prognostic model was evaluated, and validated in the validation set. Then, a prognostic nomogram combining the lncRNA-based risk score and clinicopathological characteristics was developed in training set, and assessed in the validation set. The accuracy of the model was evaluated by the discrimination and calibration plots. RESULTS: A total of 212 lncRNAs were identified to be differentially expressed in CM. After univariate analysis, LASSO penalized regression analysis, and multivariate analysis, 3 lncRNAs were used to construct risk score model. The proposed risk score model could divide patients into high-risk and low-risk groups with significantly different survival in both training set and validation set. The ROC curve showed good performance in survival prediction in both sets. Furthermore, the nomogram for predicting 3-, 5-, and 10-year OS was established based on lncRNA-based risk score and clinicopathologic factors. The prognostic accuracy of the risk model was confirmed by the discrimination and calibration plots in both training set and validation set. CONCLUSIONS: We established a novel three lncRNA-based risk score model and nomogram to predict overall survival of CM. The proposed nomogram may provide information for individualized treatment in CM patients.


Assuntos
Melanoma/genética , Melanoma/mortalidade , RNA Longo não Codificante/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Biomarcadores Tumorais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Prognóstico
2.
Anal Chem ; 92(4): 3262-3269, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31957430

RESUMO

A mitochondria targeting and immobilized fluorescent probe (Rd1) using triphenylphosphonium as the targeting group and methoxymaleimide as the fixed site is designed for the detection of ClO-. The methoxymaleimide fixed group can react with nucleophiles, such as the reactive thiol groups present in mitochondrial polypeptides and proteins, and form covalent bonds to immobilize the probe within mitochondria. The immobilization of Rd1 enhances its ability to withstand the risk of leakage from mitochondria. Methoxymaleimide shows better reactivity toward Cys than glutathione (GSH), which decreases the ineffective labeling of GSH when it covalently bonds with the reactive thiol residues of mitochondrial proteins; furthermore, it can resist hydrolysis during a long-term storage in water, compared with the classic benzyl chloride fixed unit. The imaging results indicate that Rd1 displays enhanced retention within the mitochondria of cells and tissues upon the decrease of mitochondrial membrane potential (MMP) caused by different stimulations. Furthermore, it possesses the ability to visualize exogenous and endogenous ClO- in living cells, tissues, and zebrafishes.

3.
Inorg Chem ; 58(20): 14159-14166, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31596576

RESUMO

Triplet U@C1(28324)-C80, violating the isolated pentagon rule, is experimentally recognized as the stable isomer for uranium-based endohedral monometallofullerene U@C80. Here we first verified that triplet U@D3(31921)-C80, following the isolated pentagon rule, was to be another thermodynamically stable isomer via density functional theory in conjunction with statistical thermodynamic analysis. U@D3(31921)-C80 was probably missing in the previous experiment and would be a promising isomer in the to-be experiment because of its excellently thermodynamic stability. In addition, the anomalous metal position was revealed in U@D3(31921)-C80 and U@C1(28324)-C80. Four-electron transfer from U to C80 was also revealed for the two isomers. Thus, two unpaired 5f electrons were still in the U for U@D3(31921)-C80 and U@C1(28324)-C80. Moreover, the covalent interactions between U and C80 in U@D3(31921)-C80 were stronger than those in U@C1(28324)-C80. The electrostatic interactions preponderated in the interaction energy ΔEint between U and C80 for U@C1(28324)-C80, and the orbital interactions dominated in the ΔEint for U@D3(31921)-C80. The electrophilic and nucleophilic reactivities were also analyzed for U@D3(31921)-C80 and U@C1(28324)-C80. Electronic circular dichroism spectra were simulated to distinguish the two enantiomers of U@C1(28324)-C80. We are hopeful that this investigation will be valuable for further identification of the two enantiomers in future experiments.

4.
Inorg Chem ; 58(16): 10769-10777, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31385498

RESUMO

Mixed-metal uranium-based endohedral clusterfullerenes, Sc2UX@C80 (X = C, N), which were recently reported in experiments, have been investigated considering heptagon-containing isomers by density functional theory calculations in conjunction with statistical thermodynamic analysis. The triplet Sc2UC@Ih(31924)-C80 and quartet Sc2UN@Ih(31924)-C80, named after the spiral number (31924), are found to be thermodynamically stable and satisfy aromaticity rules. Furthermore, the restricted movements of the Sc2UX (X = C, N) cluster in Ih(31924)-C80 have been demonstrated via ab initio molecular dynamics simulations. The six-electron transfer from the inner cluster to the cage results in the electronic structures (Sc2UX)6+@C806- (X = C, N), which were also confirmed by natural bond orbital analysis. On the basis of the frontier molecular orbitals, the oxidation states of uranium in Sc2UC@C80 and Sc2UN@C80 are +IV and +III, respectively, with residual electrons in 5f orbitals of U. The chemical bond between U and C (N) of the inner cluster is characterized as a double bond (single bond) by an analysis of the Mayer bond orders. There are covalent interactions between the inner cluster and outer cage, which is clarified by the quantum theory of atoms in molecules. IR spectra of the optimal isomers have also been simulated, which show the clear difference between Sc2UX@C80 (X = C, N). These findings, together with simulated results, are expected to supply useful information in future experiments of mixed-metal uranium-based endohedral clusterfullerenes.

5.
J Comput Chem ; 40(31): 2730-2738, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31433074

RESUMO

The thermodynamic and dynamic stabilities of Sc3 X@C80 (X = C, N, and O) are explored via density functional theory combined with statistical thermodynamic analysis and ab initio molecular dynamics. It is the first time to comprehensively consider the effect of nonmetal atoms on trimetallic endohedral clusterfullerenes. Relative to Sc3 X@Ih (31924)-C80 (X = N and O) with general six-electron transfer, an intriguing electronic structure of unexplored Sc3 C@D5h (31923)-C80 with thermodynamic and dynamic stabilities is clearly disclosed. Natural bond orbitals and charge decomposition analysis simultaneously suggest that one unpaired electron appears on the cage for neutral Sc3 C@D5h (31923)-C80 , which could be prospectively stabilized by effective exohedral derivatization and ionization in the future. Moreover, isoelectronic endohedral clusterfullerenes, (Sc3 C@C80 )- , Sc3 N@C80 , and (Sc3 O@C80 )+ , are also uniquely taken into account. The geometries, electronic structures, reactivities, and reactive sites of isoelectronic species are examined, and it turns out that all the three isoelectronic species would rather electrophilic than nucleophilic reactions. © 2019 Wiley Periodicals, Inc.

6.
Cells ; 7(8)2018 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-30103495

RESUMO

Autophagy, which is an evolutionarily conserved process according to the lysosomal degradation of cellular components, plays a critical role in maintaining cell homeostasis. Autophagy and mitochondria autophagy (mitophagy) contribute to the preservation of cardiac homeostasis in physiological settings. However, impaired or excessive autophagy is related to a variety of diseases. Recently, a close link between autophagy and cardiac disorders, including myocardial infarction, cardiac hypertrophy, cardiomyopathy, cardiac fibrosis, and heart failure, has been demonstrated. MicroRNAs (miRNAs) are a class of small non-coding RNAs with a length of approximately 21⁻22 nucleotides (nt), which are distributed widely in viruses, plants, protists, and animals. They function in mediating the post-transcriptional gene silencing. A growing number of studies have demonstrated that miRNAs regulate cardiac autophagy by suppressing the expression of autophagy-related genes in a targeted manner, which are involved in the pathogenesis of heart diseases. This review summarizes the role of microRNAs in cardiac autophagy and related cardiac disorders. Furthermore, we mainly focused on the autophagy regulation pathways, which consisted of miRNAs and their targeted genes.

7.
Chem Commun (Camb) ; 54(39): 4955-4958, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29701217

RESUMO

A novel reaction-based fluorescent probe (ATC-Hg) was designed and synthesized via the "covalent assembly" principle, which exhibited excellent selectivity and high sensitivity for Hg2+ and CH3Hg+. Moreover, it is the first Hg(ii) sensitive fluorescent probe that has been successfully applied in imaging in both cells and Escherichia coli.


Assuntos
Cumarínicos/farmacologia , Corantes Fluorescentes/farmacologia , Mercúrio/análise , Compostos de Metilmercúrio/análise , Cátions/análise , Cumarínicos/síntese química , Cumarínicos/química , Escherichia coli , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Células HeLa , Humanos , Cinética , Limite de Detecção , Microscopia Confocal
8.
Anal Chem ; 90(9): 5873-5878, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29600703

RESUMO

The viscosity of lysosome is reported to be a key indicator of lysosomal functionality. However, the existing mechanical methods of viscosity measurement can hardly be applied at the cellular or subcellular level. Herein, a BODIPY-based two-photon fluorescent probe was presented for monitoring lysosomal viscosity with high spatial and temporal resolution. By installing two morpholine moieties to the fluorophore as target and rotational groups, the TICT effect between the two morpholine rings and the main fluorophore scaffold endowed the probe with excellent viscosity sensitivity. Moreover, Lyso-B succeeded in showing the impact of dexamethasone on lysosomal viscosity in real time.


Assuntos
Compostos de Boro/química , Fluorescência , Corantes Fluorescentes/química , Imagem Óptica , Fótons , Células HeLa , Humanos , Lisossomos/química , Microscopia Confocal , Estrutura Molecular , Fatores de Tempo , Viscosidade
9.
Clin Cancer Res ; 24(13): 3204-3216, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29514844

RESUMO

Purpose: Hypoxia-inducible factor-2α (HIF2α) is regarded as a preferential target for individualized hepatocellular carcinoma (HCC) treatment and sorafenib resistance. Our study aimed to identify the regulatory mechanisms of HIF2α activity under hypoxic conditions. We sought to determine whether the COX-2/PGE2 axis is involved in the regulatory mechanisms of HIF2α activity and of sorafenib resistance in hypoxic HCC cells.Experimental Design: The cell viability, migration, and invasion abilities were measured to analyze the effects of HIF2α on hypoxic HCC cells. Both in vitro and in vivo HCC models were used to determine whether the COX-2/PGE2 axis is a driver of HIF2α level and activity, which then reduces the sensitivity of sorafenib treatment in hypoxic HCC cells.Results: Under hypoxic conditions, the COX-2/PGE2 axis effectively stabilized HIF2α and increased its level and activity via decreasing von Hippel-Lindau protein (p-VHL) level, and also enhanced HIF2α activity by promoting HIF2α nuclear translocation via MAPK pathway. The activation of HIF2α then led to the enhanced activation of VEGF, cyclin D1, and TGFα/EGFR pathway to mediate HCC development and reduce the sensitivity of sorafenib. More importantly, COX-2-specific inhibitors synergistically enhanced the antitumor activity of sorafenib treatment.Conclusions: Our data obtained demonstrate that the COX/PGE2 axis acts as a regulator of HIF2α expression and activity to promote HCC development and reduce sorafenib sensitivity by constitutively activating the TGFα/EGFR pathway. This study highlights the potential of COX-2-specific inhibitors for HCC treatment and particularly for enhancing the response to sorafenib treatment. Clin Cancer Res; 24(13); 3204-16. ©2018 AACR.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Sorafenibe/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Humanos , Hipóxia/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Neovascularização Patológica/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteólise , Transdução de Sinais/efeitos dos fármacos , Sorafenibe/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Chem Sci ; 9(48): 8969-8974, 2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30647889

RESUMO

Recently, tetraphenylethene, triphenylamine and other man-made core AIE luminescent materials (AIEgens) have attracted significant scientific interest. However, the design and synthesis of natural product based, facile and color tunable AIEgens remains challenging. Herein, a novel series of AIEgens based on purine-core molecular rotors is reported, which can be facilely synthesized and shows color tunable emission. Moreover, these purine-based AIEgens exhibit lipid droplet specific properties in live cellular imaging with low background, high selectivity and excellent biocompatibility.

11.
PPAR Res ; 2018: 8530371, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30622558

RESUMO

Peroxisome proliferator-activated receptors (PPARs) play vital roles in cardiovascular pathophysiology, such as energy balance, cell proliferation/apoptosis, inflammatory response, and adipocyte differentiation. These vital roles make PPARs potential targets for therapeutic prevention of cardiovascular diseases (CVDs). Emerging evidence indicates that the crosstalk of microRNAs (miRNAs) and PPARs contributes greatly to CVD pathogenesis. PPARs are inhibited by miRNAs at posttranscriptional mechanisms in the progress of pulmonary hypertension and vascular dysfunction involving cell proliferation/apoptosis, communication, and normal function of endothelial cells and vascular smooth muscle cells. In the development of atherosclerosis and stroke, the activation of PPARs could change the transcripts of target miRNA through miRNA signalling. Furthermore, the mutual regulation of PPARs and miRNAs involves cell proliferation/apoptosis, cardiac remodeling, and dysfunction in heart diseases. In addition, obesity, an important cardiovascular risk, is modulated by the regulatory axis of PPARs/miRNAs, including adipogenesis, adipocyte dysfunction, insulin resistance, and macrophage polarization in adipose tissue. In this review, the crosstalk of PPARs and miRNAs and their emerging regulatory roles are summarized in the context of CVDs and risks. This provides an understanding of the underlying mechanism of the biological process related to CVD pathophysiology involving the interaction of PPARs and miRNAs and will lead to the development of PPARs/miRNAs as effective anti-CVD medications.

12.
Inorg Chem ; 55(5): 2220-6, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26909549

RESUMO

Among the very recently reported dimetallic oxide fullerenes Sc2O@C2n (n = 35-47), a representative Sc2O@C78 still lacks of further characterizations. Herein, a systematical investigation on Sc2O@C78 has been performed by density functional theory combined with statistical thermodynamic studies. Two isolated pentagon rule (IPR) satisfying isomers, Sc2O@D3h(24109)-C78 and Sc2O@C2v(24107)-C78, are disclosed to possess prominent thermodynamic stabilities at the temperature region of fullerene formation. Significantly, these two structures are related by a single Stone-Wales transformation. Moreover, bonding critical points, bond orders, and delocalization indices have been analyzed to uncover covalent interactions in both isomers. In addition, (13)C NMR spectra and UV-vis-NIR adsorptions of the two stable structures are introduced to assist experimental identification and characterization in the future.

13.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(7): 1705-6, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-20650806

RESUMO

OBJECTIVE: To investigate the indication and effect of the application of Ligasure vessel sealing instrument in laparoscopic hepatectomy for liver cancer. METHODS: Eleven patients with liver cancer undergoing laparoscopic hepatectomy were analyzed for the tumor size and location, operation time, volume of intraoperative bleeding, postoperative hospital stay and short-term clinical outcomes. RESULTS: All the operations were performed successfully in the 11 cases. All the tumors were less than 7 cm in diameter, locating at the segments II, III, V, VI and VII. The mean operation time was 91 min (80-126 min), and the intraoperative blood loss averaged 82 ml (20-200 ml). The average postoperative hospital stay of the patients was 8 days (7-9 days). No complications were observed in these cases. CONCLUSION: Ligasure vessel sealing instrument in laparoscopic hepatectomy is applicable in cases of perimeter liver cancer. This instrument can decrease the operation time, reduce the intraoperative blood loss and postoperative hospital stay with good safety and minimal invasiveness.


Assuntos
Hepatectomia/instrumentação , Laparoscopia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Hepatectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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