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1.
Artigo em Inglês | MEDLINE | ID: mdl-31713966

RESUMO

Lithium-sulfur (Li-S) batteries are well known as one of the most promising next-generation batteries owing to its ultra-high theoretical energy density and abundant sulfur resources. During the past 20 years, various sulfur materials have been reported. As the representative of molecular scale sulfur composite cathode, sulfurized pyrolyzed poly(acrylonitrile) (S@pPAN) exhibits several competitive advantages in terms of electrochemical behaviors. Currently, S@pPAN attracts increasing attentions although it was first reported in 2002. In this review, we firstly summarize its molecular model, which benefits to elucidate the correlation between structure property and exceptional electrochemical performance. Secondly, we classify the modification strategies into three parts, including material improvement, binder and electrolyte screening. In consideration of promising future of S@pPAN, several research and development directions are also suggested.

2.
ACS Appl Mater Interfaces ; 11(36): 33419-33427, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31423761

RESUMO

Rechargeable lithium-metal batteries have gained significant attention as potential candidates of energy storage systems; however, severe safety issues including flammable electrolyte and dendritic lithium formation hinder their further practical application. In this work, we develop a novel intrinsic flame-retardant electrolyte, which enables a stable and dendrite-free cycling with lithium plating/stripping Coulombic efficiency of up to 99.1% over 500 cycles. Raman spectra indicate that no free molecular solvent exists, and X-ray photoelectron spectroscopy reveals the LiF-rich interphase on the Li-metal anode. When coupled with sulfurized pyrolyzed poly(acrylonitrile) cathode, it shows a benign electrochemical reversibility with the areal capacity of up to 3.41 mAh cm-2 after 70 cycles. To further check its compatibility with sulfur cathode, a higher sulfur content (51.6%) is examined with the areal capacity of 3.92 mAh cm-2 and sulfur utilization of 81.7%. This work provides an alternative for safe and high-performance Li-S batteries via a novel electrolyte strategy.

3.
Mol Carcinog ; 58(1): 144-155, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30259564

RESUMO

Although the CXCL12-CXCR4/CXCR7 chemokine axis is demonstrated to play an integral role in tumor progression, the controversy exists and the role of CXCL12-CXCR4/CXCR7 signaling axis in epithelial-mesenchymal transition (EMT) of human ovarian cancer has not been explored. Here, we showed that in ovarian cancer CXCL12 induced EMT phenotypes including the spindle-like cell morphology, podia and stress fiber formation, a decrease in E-cadherin expression, and increases in mesenchymal N-cadherin and vimentin expressions. These effects of CXCL12 could be antagonized by the CXCR4 antagonist AMD3100, but not by the anti-CXCR7 antibody. The expressions of the EMT markers were significantly down-regulated by the CXCR4 siRNA, and up-regulated by the pcDNA3.1/CXCR4 plasmid, whereas not affected by the CXCR7 siRNA. Furthermore, intraperitoneal administration of AMD3100 inhibited tumor dissemination and growth in the nude mice inoculated with ovarian IGROV-1 cells with a concomitant reduction in EMT marker expressions. Collectively, these data suggest that CXCR4, rather than CXCR7, plays a key role in CXCL12-activated EMT phenotypes, and targeting the CXCL12-CXCR4 chemokine axis represents a potential therapeutic strategy to prevent ovarian cancer progression.


Assuntos
Quimiocina CXCL12/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Compostos Heterocíclicos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/metabolismo , Receptores CXCR4/antagonistas & inibidores , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Artigo em Inglês | MEDLINE | ID: mdl-30426649

RESUMO

Safety concern poses a significant challenge for the large-scale employment of lithium-sulfur batteries. Extreme flammable conventional electrolyte and dendritic lithium deposition cause severe safety issues. Herein, we report an intrinsic flame-retardant (IFR) electrolyte consisting of 1.1 M lithium bis(fluorosulfonyl)imide in a solvent mixture of flame-retardant triethyl phosphate and high flash point solvent 1,1,2,2-tetrafluoroethyl 2,2,3,3-tetrafluoropropyl (1:3, v/v) for safe lithium-sulfur (Li-S) batteries. This electrolyte exhibits favorable flame-retardant property and high reversibility of lithium metal anode (Coulombic efficiency >99%). Importantly, this IFR electrolyte enables stable lithium plating/stripping behavior with micro-sized and dense-packing lithium deposition at high temperatures. When coupled with sulfurized pyrolyzed poly(acrylonitrile) cathode (sulfur content: 52.6 wt%), Li-S batteries deliver high composite capacity (840.1 mAh g-1) and high sulfur utilization of 95.6%. More advantages of this system are its enhanced energy conversion efficiency and energy density under high temperature operation.

5.
Int J Oncol ; 53(6): 2590-2604, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30280201

RESUMO

Metastasis accounts for the majority of cancer-related mortalities, and the complex processes of metastasis remain the least understood aspect of cancer biology. Metabolic reprogramming is associated with cancer cell survival and metastasis in a hostile envi-ronment with a limited nutrient supply, such as solid tumors. Little is known regarding the differences of bioenergetic adaptation between primary tumor cells and metastatic tumor cells in unfavorable microenvironments; to clarify these differences, the present study aimed to compare metabolic reprogramming of primary tumor cells and metastatic tumor cells. SW620 metastatic tumor cells exhibited stronger bioenergetic adaptation in unfavorable conditions compared with SW480 primary tumor-derived cells, as determined by the sustained elevation of glycolysis and regulation of the cell cycle. This remarkable glycolytic ability of SW620 cells was associated with high expression levels of hexokinase (HK)1, HK2, glucose transporter type 1 and hypoxia-inducible factor 1α. Compared with SW480 cells, the expression of cell cycle regulatory proteins was effectively inhibited in SW620 cells to sustain cell survival when there was a lack of energy. Furthermore, SW620 cells exhibited a stronger mesenchymal phenotype and stem cell characteristics compared with SW480 cells; CD133 and CD166 were highly expressed in SW620 cells, whereas expression was not detected in SW480 cells. These data may explain why metastatic cancer cells exhibit greater microenvironmental adaptability and survivability; specifically, this may be achieved by upregulating glycolysis, optimizing the cell cycle and reprogramming cell metabolism. The present study may provide a target metabolic pathway for cancer metastasis therapy.

6.
J Pharm Biomed Anal ; 154: 108-115, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29544105

RESUMO

Mifepristone (RU486) is developed originally as a contraceptive used by hundreds of millions of women world-wide, and also reported as a safe and long-term psychotic depressant, or as a cancer chemotherapeutic agent used by both sexes. In our preliminary study aimed at developing mifepristone as a cancer metastatic chemopreventive, we coincidentally observed that blood mifepristone concentrations in female rats seem to be higher than those in male ones post administration. To substantiate if the pharmacokinetic differences between sexes exist, we established a fast UPLC-MS/MS method to determine mifepristone concentrations in plasma, and analyzed blood concentrations of mifepristone over time in rats and dogs of both sexes. Mifepristone in plasma or incubation liquid was recovered by liquid-liquid extraction using 1 mL of ethyl acetate. Chromatographic separation was performed on a C18 column at 35 °C, with a gradient elution consisting of methanol and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. And pharmacokinetic parameters such as elimination half-life, and mean residence time were calculated by using the non-compartmental pharmacokinetics data analysis software. In this work, administrations of mifepristone to rats and beagle dogs revealed that the plasma concentrations of mifepristone (AUC, Cmax) were significantly higher (P < 0.05) in females than that in males. In vitro liver microsomal incubation experiments showed that the metabolic rate of mifepristone in males was higher than that in females, which was consistent with the results of in vivo experiments. In general, we first found the sex-related differences about pharmacokinetic properties of mifepristone and revealed the metabolism difference of hepatic microsomal enzyme is the main reason.


Assuntos
Antipsicóticos/farmacocinética , Antagonistas de Hormônios/farmacocinética , Mifepristona/farmacocinética , Animais , Antipsicóticos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Cães , Feminino , Meia-Vida , Antagonistas de Hormônios/metabolismo , Masculino , Microssomos Hepáticos , Mifepristona/metabolismo , Modelos Animais , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Espectrometria de Massas em Tandem/métodos
7.
Oncotarget ; 8(35): 59123-59135, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28938623

RESUMO

SDF-1/CXCR4 signaling axis determines the proliferative potential and site-specific cancer metastasis. Recent studies suggest involvement of the axis and steroidal hormone in ovarian cancer metastasis. Here we hypothesize that mifepristone (RU486), a well-known progesterone-based abortifacient, might interfere this axis and inhibit ovarian cancer metastasis. Mifepristone at concentrations < IC50 inhibited expression of CXCR4 on cell surface of ovarian cancer SKOV-3 and IGROV-1, and reduced expression of the intracellular CXCR4 protein and its related mRNA activated by SDF-1. SDF-1 significantly stimulated proliferation of SKOV-3 and IGROV-1 cells with concomitant increases in intracellular phosphorylation of Akt and ERK. SDF-1 activated cell chemotatic migration and actin polymerization, and up-regulated expression of MMP-2, MMP-9, COX-2, VEGF without influencing the adhesion molecules ICAM-1 and integrins ß1, α1, α3, α5, and α6. The above-mentioned effects of SDF-1 could be antagonized by mifepristone concentration-dependently, and CXCR4 antagonist AMD3100. Mifepristone suppressed the SDF-1-induced migration, invasion and adhesion of the cancer cells to extracellular matrixes. Three-day pretreatment of nude mice with mifepristone (5 and 20 mg/kg/day) followed by a single intraperitoneal IGROV-1 inoculation, along with repeated SDF-1 and mifepristone administrations in turn every other day for 36 days significantly reduced ascitic fluid, metastatic foci, tumor weight and immunoreactivity of CXCR4 in comparison with the SDF-1-treated control. Our results suggest that mifepristone inhibit SDF-1/CXCR4 signaling axis, may have preventive and therapeutic effects on ovarian cancer metastasis.

8.
AAPS J ; 19(6): 1779-1790, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28842850

RESUMO

Metastasis remains the leading cause of death from lung carcinoma. It is urgent to find safe and efficient pre-metastasis preventive agents for cancer survivors. We isolated a flavonoid glycoside, hexamethoxy flavanone-o-[rhamnopyranosyl-(1 â†’ 4)-rhamnopyranoside (HMFRR), from the traditional Chinese medicine (TCM) Murraya paniculata (L.) that can effectively inhibit the adhesion, migration, and invasion of lung adenocarcinoma A549 cells in vitro. Molecular and cellular studies demonstrated that HMFRR significantly downregulated the expressions of cell adhesion-related and invasion-related molecules such as integrin ß1, EGFR, COX-2, MMP-2, and MMP-9 proteins. Additionally, HMFRR effectively downregulated the expressions of epithelial-mesenchymal transition (EMT) markers (N-cadherin and vimentin) and upregulated that of E-cadherin. Moreover, these inhibitions were mediated by interrupting STAT3/NF-κB/COX-2 and EGFR/PI3K/AKT signaling pathways. Furthermore, HMFRR counteracted the expressions of cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin) stimulated by interleukin-1ß in human pulmonary microvascular endothelial cells (HPMECs). As a result, HMFRR interrupted the adhesion of A549 cells to HPMECs. Collectively, these results indicate that HMFRR may become a good candidate for cancer metastatic chemopreventive agents by interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways.


Assuntos
Anticarcinógenos/farmacologia , Ciclo-Oxigenase 2/fisiologia , Receptores ErbB/fisiologia , Flavonoides/farmacologia , Glicosídeos/farmacologia , Murraya/química , NF-kappa B/fisiologia , Metástase Neoplásica/prevenção & controle , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/fisiologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Medicina Tradicional Chinesa
9.
Biomed Pharmacother ; 90: 339-349, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28376402

RESUMO

Uncontrolled cell proliferation and metastasis are the two well-known manifestations of melanoma. We hypothesized that metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486), had a dual function to fight cancer. In the present study, our findings clearly demonstrated that metapristone had modest cytostatic effect in melanoma cells. Metapristone inhibited cell viability and induced both early and late apoptosis in B16F10 and A375 cells in a time- and concentrate-dependent manner. Metapristone-treatment caused the cell arrest at the G0/G1 stage, and the inhibition of colony formation in B16F10 cells. Western blot analysis further revealed that metapristone treatment elicited a decline of Akt and ERK phosphorylation and Bcl-2, and facilitated expression of total P53 and Bax in A375 cells. In addition, cell migration and invasion were significantly suppressed by metapristone through down-regulating the expression of MMP-2, MMP-9, N-cadherin and vimentin, whereas up-regulating E-cadherin expression. Notably, metapristone exhibited anti-metastatic activity in melanoma B16F10 cells in vivo. Our results reveal metapristone, having the dual function of anti-proliferation and anti-migration for melanoma cell lines, may be a useful chemopreventive agent to reduce the risk of melanoma cancer metastasis.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Melanoma/tratamento farmacológico , Mifepristona/análogos & derivados , Mifepristona/farmacologia , Metástase Neoplásica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Fase G1/efeitos dos fármacos , Melanoma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
10.
Mol Carcinog ; 56(8): 1896-1908, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28277622

RESUMO

Recent global epidemiological studies revealed the lower ovarian cancer death from long-term use of oral contraceptives. However, the underlying mechanism of action is not clear. Here, we use the abortifacient metapristone (RU486 derivative) to test the hypothesis that the contraceptives might interrupt CXCL12/CXCR4 chemokine axis to inhibit ovarian cancer metastasis. Metapristone at concentrations (

Assuntos
Antineoplásicos/uso terapêutico , Quimiocina CXCL12/metabolismo , Mifepristona/análogos & derivados , Invasividade Neoplásica/prevenção & controle , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Receptores CXCR4/metabolismo , Abortivos/química , Abortivos/farmacologia , Abortivos/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Epitelial do Ovário , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimioprevenção , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mifepristona/química , Mifepristona/farmacologia , Mifepristona/uso terapêutico , Invasividade Neoplásica/patologia , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Peritônio/efeitos dos fármacos , Peritônio/metabolismo , Peritônio/patologia , Transdução de Sinais/efeitos dos fármacos
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