Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway.

We investigated the effects of aquaporin 5 (AQP5) gene silencing on the proliferation, migration and apoptosis of human glioma cells through regulating the EGFR/ERK/p38MAPK signaling pathway. qRT-PCR was applied to examine the mRNA expressions of AQP5 in five human glioma cell lines. U87-MG, U251 and LN229 cells were selected and assigned into blank, vector, AQP5 siRNA and FlagAQP5 groups. MTT assay was used to measure cell proliferation. Flow cytometry (FCM) with AnnexinV-FITC/PI double staining and PI staining were employed to analyze cell apoptosis and cell cycle respectively. Scratch test was used to detect cell migration. Western blotting was performed to determine the EGFR/ERK/p38 MAPK signaling pathway-related proteins. Results showed that the positive expression of AQP5 in primary glioblastoma was associated with the tumor size and whether complete excision was performed. The mRNA expressions of AQP5 in cell lines of U87-MG, U251 and LN229 were significantly higher than in U373 and T98G. The proliferation rates of U87-MG, U251 and LN229 cells in the AQP5 siRNA group were lower than in the vector and blank groups. The apoptosis rate increased in the AQP5 siRNA group compared with the vector group. Scratch test demonstrated that AQP5 gene silencing could suppress cell migration. Compared with the vector and blank groups, the AQP5 siRNA group showed decreased expressions of the ERK1/2, p38 MAPK, p-ERK1/2 and p-p38 MAPK proteins. AQP5 gene silencing could inhibit the cell proliferation, reduce cell migration and promote the cell apoptosis of U87-MG, U251 and LN229 by suppressing EGFR/ERK/p38 MAPK signaling pathway.

Two bisthienylethene-Ir(III) complexes showing acid/base-induced structural transformation and on-off luminescence switching in solution.

Complexes [Ir(dfppy)2(pbdtiH)](PF6)·2CHCl3 (1-H) and [Ir(dfppy)2(pbdti)] (1) were synthesized by the reaction of bisthienylethene pbdtiH and an [Ir(dfppy)2Cl]2 dimer under neutral and basic conditions, respectively. Thus, the {Ir(dfppy)2}(+) unit is coordinated by pbdtiH in 1-H, and by pbdti(-) in 1, which are confirmed by their crystal structures. The structures of 1-H and 1 could be interconverted in solution, upon alternately adding NEt3 and TFA, thus resulting in reversible luminescence switching between the on-state of 1-H and the off-state of 1 at room temperature. In addition, both 1-H and 1 show solid-state luminescence, with a broad emission at 534 nm and 525 nm, respectively. The free pbdtiH ligand shows photochromic behavior in CH2Cl2 solution. However, no photochromism has been observed in 1-H and 1, indicating that the coordination of the pbdtiH/pbdti(-) ligand to the {Ir(dfppy)2}(+) unit could suppress their photochromic behaviors.

IDH1R¹³²H decreases the proliferation of U87 glioma cells through upregulation of microRNA-128a.

Mutations in isocitrate dehydrogenase 1 (IDH1) are found in >70% of secondary glioblastomas and lower-grade gliomas (grades II-III). Among the numerous phenotypic differences between IDH1 mutant and wild-type glioma patients, the most salient is an improved survival rate for patients with a mutation. MicroRNAs (miRNAs) are a class of small, non­coding, single­stranded RNAs that can negatively regulate gene expression at the post­transcriptional level, predominantly by binding to the 3'­untranslated region of their target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression; however, it is unclear whether mutations in IDH1 regulate glioma cell proliferation through miRNA dysregulation. In the present study, stable overexpression of IDH1WT or IDH1R132H was established in the U87 glioma cell line. It was found that IDH1R132H decreased cell proliferation of U87 glioma cells by inducing the expression of the miRNA miR­128a. This process was dependent on the transcription factor hypoxia inducible factor­1α (HIF­1α), which binds to a hypoxia response element in the promoter of miR­128a. Furthermore, miR­128a negatively regulated the expression of B­cell­specific Moloney murine leukemia virus integration site 1 protein (Bmi­1), which is involved in suppressing cell proliferation. These findings suggest that the IDH1R132H­HIF­1α­miR­128a­Bmi­1 pathway is involved in glioma cell proliferation.

Multifunctional mononuclear bisthienylethene-cobalt(II) complexes: structures, slow magnetic relaxation and photochromic behavior.

Based on two new bisthienylethenes containing N,O-donor binding sites, 2-(2-hydroxy-5-bromo-phenyl)-4,5-bis(2,5-dimethyl(3-thienyl))-1H-imidazole (BrLH) and 2-(2-hydroxy-5-diethylphosphono-phenyl)-4,5-bis(2,5-dimethyl(3-thienyl))-1H-imidazole (PLH), multifunctional mononuclear complexes Co(BrL)2·3CH3OH (1) and Co(PL)2·2CH3OH (2) have been synthesized and characterized by crystallographic analysis. In the molecular structures of 1 and 2, the Co(II) ion adopts a distorted tetrahedral coordination geometry, and is coordinated by two nonequivalent bisthienylethene molecules (BrL− in 1, PL− in 2), showing non-photoactive parallel and photoactive antiparallel conformations, respectively. Compounds 1 and 2 show a distinct distortion of Co(II) coordination geometry, with bond angles of N­Co­N = 112.71(12)° and O­Co­O = 99.87(11)° for 1 and N­Co­N = 119.93(12)° and O­Co­O = 107.31(13)° for 2. Thus, 1 and 2 revealed different magnetic behaviors, which are demonstrated by the χMT vs. T plots, and the frequency dependence of the χ'M and χ''M signals at low temperature. Besides the field-induced slow magnetic relaxation, both 1 and 2 also showed photochromic behavior. Upon irradiation with 360 nm light for 1 and 343 nm light for 2, their CH2Cl2­CH3CN solutions could change color from being nearly colorless to blue purple. It was demonstrated that the substituent groups of Br atom and ­PO(OEt)2 in 1 and 2, respectively, could significantly influence their crystal structures, magnetic relaxations and photochromic properties.

Heteroleptic Ir(III) complexes based on 2-(2,4-difluorophenyl)-pyridine and bisthienylethene: structures, luminescence and photochromic properties.

Two bisthienylethenes 2-(2-hydroxyphenyl)-4,5-bis[2,5-dimethyl(3-thienyl)]-1H-imidazole (L1H) and 2-(2-hydroxyphenyl)-4,5-bis(2,5-dimethyl(3-thienyl))-1-phenyl-imidazole (L2H), which have a chelating N,O-donor binding site attached to the photochromic core, have been synthesized using a one-pot condensation reaction, and used to prepare the heteroleptic complexes [Ir(dfppy)2(L1)]·2CH3OH (1) and [Ir(dfppy)2(L2)] (2) [dfppyH = 2-(2,4-difluorophenyl)-pyridine]. In the crystal structures of all four compounds, two thiophene groups of each bisthienylethene molecule adopt parallel conformation. Neighboring molecules in L1H and 1 are linked into supramolecular chains through hydrogen bonds. Particularly, the packing structure of 1 contains right- and left-handed 21 helical chains. In contrast, neighboring molecules in L2H and 2 interact only through van der Waals interactions. At room temperature, L1H and L2H in CH2Cl2 show fluorescence emission at 442 nm and 469 nm, respectively. Compounds 1 and 2 in CH2Cl2 reveal broad emission band characteristics of the Ir(III)/dfppy(-) chromophores at 508 nm and 494 nm, respectively, with a mixing of (3)MLCT and (3)LC characters. At room temperature, the photochromism ability of L2H in CH2Cl2 is clearly weaker than that of L1H. Moreover, no photochromism has been observed in 1 and 2. It has been demonstrated that both the substituent group and {Ir(dfppy)2}(+) coordination could significantly influence the crystal structures, luminescence and photochromic properties of L1H, L2H, 1 and 2.