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1.
Chemistry ; 29(2): e202202916, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36237174

RESUMO

Dielectric switches have drawn renewed attention to the study of their many potential applications with the adjustable switch temperatures (Ts ). Herein, a novel antimony-based halide semiconductor, (N,N-diisopropylethylamine) tetrachloroantimonate ((DIPEA)SbCl4 , DIPEA+ =N,N-diisopropylethylamine), with dielectric relaxation behavior and dielectric switches has been successfully synthesized. This compound, consisting of coordinated anion S b C l 4 ∞ - ${{\left[{{\rm S}{\rm b}{\rm C}{\rm l}}_{4}\right]}_{\infty }^{-}}$ chains and isolated DIPEA+ cations, undergoes an isostructural order-disorder phase transition and shows a step-like dielectric anomaly, which can function as a frequency-tuned dielectric switch with highly adjustable switch temperature (Ts ). Variable-temperature single-crystal structure analyses and first-principles molecular dynamics simulations give information about the general mechanisms of molecular dynamics. This work enriches the dielectric switch family and proves that hybrid metal halides are promising candidates for switchable physical or chemical properties.

2.
Pathobiology ; 87(3): 161-170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182608

RESUMO

OBJECTIVE: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. METHODS: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. RESULTS: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. CONCLUSION: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.


Assuntos
Hepatoblastoma/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Fator A de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Acta Neurobiol Exp (Wars) ; 82(3): 336-346, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36214716

RESUMO

Hirschsprung's disease (HSCR) is an intestinal disease caused by defects in neural crest cell migration, proliferation, differentiation, and survival. Many reports have proposed that miRNA dysregulation is related to the occurrence of HSCR. However, the roles and mechanisms of miRNAs have not been thoroughly studied. The levels of miR­92a and KLF4 were examined using qRT­PCR and immunohistochemistry, respectively. Cell viability, migration and apoptosis were evaluated by MTT, Transwell and flow cytometry assays, respectively. A dual­luciferase reporter assay was employed to verify the binding relationship between miR­92a and KLF4. Levels of PI3K/AKT signals were further determined by western blot assay. Herein, elevated expression of miR­92a and reduced expression of KLF4 were found in HSCR tissues, and their expression patterns were negatively correlated. Overexpression of miR­92a inhibited cell viability and migration but enhanced cell apoptosis. However, overexpression of KLF4 had the opposite effects. Mechanistically, KLF4 was a target of miR­92a and it negatively affected biological functions by activating PI3K/AKT signaling. These results proved that miR­92a inhibited the proliferation and metastasis of nerve cells by regulating the KLF4/PI3K/AKT axis.


Assuntos
Doença de Hirschsprung , MicroRNAs , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Doença de Hirschsprung/genética , Doença de Hirschsprung/metabolismo , Doença de Hirschsprung/patologia , Humanos , MicroRNAs/genética , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
4.
Mol Med Rep ; 24(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34080023

RESUMO

Hepatoblastoma is the most common malignant hepatic tumour type with hypervascularity in early childhood. In recent decades, emerging evidence has proven that long non­coding RNAs (lncRNAs) serve an important oncogenic role in the pathogenesis of hepatoblastoma. However, the underlying mechanism of lncRNA taurine upregulated 1 (TUG1) in the angiogenesis of hepatoblastoma remains unknown. The expression patterns of TUG1 and microRNA (miR)­204­5p were detected in hepatoblastoma tissues and cell lines via reverse transcription­quantitative PCR and were analysed using a Pearson's correlation test. A tube formation assay was performed using human umbilical vein endothelial cells to assess the vasculogenic activity of treated HuH­6 cells. ELISA was used to detect the level of the secretory proangiogenic factor VEGFA in the culture media of HuH­6 cells. A dual luciferase reporter assay was performed to validate the binding relationships of TUG1/miR­204­5p and miR­204­5p/Janus kinase 2 (JAK2). Moreover, western blotting was conducted to measure the protein expression levels of VEGFA, phosphorylated (p)­JAK2, JAK2, p­STAT3 and STAT3. It was identified that TUG1 was upregulated, while miR­204­5p was downregulated in hepatoblastoma tissues and cells. TUG1 knockdown inhibited angiogenesis induced by hepatoblastoma cells. Furthermore, miR­204­5p was identified as a target of TUG1. The results demonstrated that TUG1 attenuated the inhibitory effect of miR­204­5p on the JAK2/STAT3 pathway and promoted angiogenesis in hepatoblastoma cells. In summary, TUG1 was upregulated in hepatoblastoma and suppressed miR­204­5p, thereby activating the downstream signalling pathway of JAK2/STAT3 to facilitate angiogenesis. The present findings will provide novel targets for the treatment of hepatoblastoma.


Assuntos
Hepatoblastoma/genética , Janus Quinase 2/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Pré-Escolar , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Hepatoblastoma/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Lactente , Neoplasias Hepáticas/metabolismo , Masculino , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Regulação para Cima/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
ACS Appl Mater Interfaces ; 13(1): 2044-2051, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33347285

RESUMO

Low-dimensional hybrid organic-inorganic perovskites (HOIPs) possess more localized electronic states and narrower conduction and valence bands to promote self-trapping of excitons and stronger exciton emission; therefore, they are widely used as building blocks for various applications in the fields of optoelectronics, photovoltaics, light-emitting diodes, luminescence, fluorescence, and so forth. Despite the past decades of intensive study, the discovered low-dimensional chiral HOIPs are rare as of the 1D chiral HOIP single crystals reported in 2003, as well as the low-dimensional chiral HOIP ferroelectrics are particularly scarce since the first chiral two-dimensional (2D) and/or one-dimensional (1D) HOIP ferroelectrics reported. Herein, two new low-dimensional HOIPs with the same conformational formula [R-MPA]2CdCl4 (R-MPA+ = (R)-(-)-1-methyl-3-phenylpropylamine) were successfully synthetized by means of regulating the stoichiometric proportion of R-MPA and CdCl2 in two ways of 1:1 (1) and 2:1 (2). By combining single-crystal X-ray diffraction, circular dichroism (CD) spectroscopy, differential scanning calorimetry, temperature-dependent dielectric constant, temperature-dependent second-harmonic generation (SHG) effect, polarization-dependent SHG response, and P-E hysteresis loop, we reveal that 1 is a 1D nonchiral molecular ferroelectric and 2 is the first zero-dimensional (0D) chiral ferroelectric with distinct CD signals; meanwhile, 2 exhibits increased properties of high-Tc, large dielectric constant, SHG isotropy, and ferroelectricity than that of 1. These results not only shed light on the high tunability of the low-dimensional HOIP ferroelectrics but also open up an avenue to explore multifunctional chiral ferroelectrics.

6.
Bioorg Chem ; 30(6): 443-58, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12642128

RESUMO

The human immunodeficiency virus (HIV) epidemic is an important medical problem. Although combination drug regimens have produced dramatic decreases in viral load, current therapies do not provide a cure for HIV infection. We have used structure-based design and combinatorial medicinal chemistry to identify potent and selective HIV-1 reverse transcriptase (RT) inhibitors that may work by a mechanism distinct from that of current HIV drugs. The most potent of these compounds (compound 4, 2-naphthalenesulfonic acid, 4-hydroxy-7-[[[[5-hydroxy-6-[(4-cinnamylphenyl)azo]-7-sulfo-2-naphthalenyl]amino]carbonyl]amino]-3-[(4-cinnamylphenyl)azo], disodium salt) has an IC(50) of 90 nM for inhibition of polymerase chain extension, a K(d) of 40 nM for inhibition of DNA-RT binding, and an IC(50) of 25-100 nM for inhibition of RNaseH cleavage. The parent compound (1) was as effective against 10 nucleoside and non-nucleoside resistant HIV-1 RT mutants as it was against the wild-type enzyme. Compound 4 inhibited HIV-1 RT and murine leukemia virus (MLV) RT, but it did not inhibit T(4) DNA polymerase, T(7) DNA polymerase, or the Klenow fragment at concentrations up to 200 nM. Finally, compound 4 protected cells from HIV-1 infection at a concentration more than 40 times lower than the concentration at which it caused cellular toxicity.


Assuntos
Transcriptase Reversa do HIV/química , Transcriptase Reversa do HIV/metabolismo , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/farmacologia , Algoritmos , Sítios de Ligação , HIV-1/enzimologia , Humanos , Cinética , Ribonuclease H/metabolismo
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