MiR-195 suppression alleviates apoptosis and oxidative stress in CCl4-induced ALI in mice by targeting Pim-1.

BACKGROUND: Acute liver injury (ALI) is associated with the oxidative stress and apoptosis in liver. Recent studies have shown that miR-195, a critical member of miR-15 family, has modulated the apoptosis in various organic diseases. However, it is elusive whether miR-195 regulation exert a hepatic ameliorative effect on ALI by the suppression of apoptosis and oxidative stress levels. We aimed to explore the regulated role of miR-195 in acute liver injury via the current study. METHODS: C57BL/6 J mice (male, seven-week, 18-20 g) were administrated intraperitoneal injection with tetrachloromethane (CCl4) to induce ALI. miR-195 inhibitor or mimics loaded in lentivirus vectors (miR-195 INH or MMC) and Pim-1 loaded in Adeno-associated viral vectors (AAV-Pim-1) were respectively delivered into mouse tail intravenous to establish silence or overexpression of miR-195 and overexpression of Pim-1. Western blotting, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA) technique, Immunohistochemistry (IHC) and Hematoxylin-eosin (H&E) staining were conducted to measure miR-195 and Pim-1 expression, apoptosis and oxidative stress levels, histological and functional change. RESULTS: We found that the expression of miR-195 markedly increased in CCl4-induced ALI. Besides, we demonstrated that the silence of miR-195 attenuated the apoptosis and oxidative stress via up-regulating Pim-1 in CCl4-induced ALI. Moreover, the inhibition of miR-195 protected the integrity and function of liver tissue. CONCLUSIONS: The above results showed that the suppression of miR-195 ameliorated ALI through inhibiting apoptosis and oxidative stress via targeting Pim-1. Our research provided a novel scheme that the miR-195 modulation in process of ALI may be an effective therapy method and verifies a promising target for diagnostic and therapeutic strategy of miRNAs.

Silence of cZNF292 suppresses the growth, migration, and invasion of human esophageal cancer Eca-109 cells via upregulating miR-206.

Circular RNA (circRNA) cZNF292 has been previously revealed as a circular oncogenic RNA. This study attempted to illustrate the functions of cZNF292 in human esophageal carcinoma Eca-109 cells. Eca-109 cells were transfected with the short hairpin RNA specific against cZNF292 (sh-cZNF292) and/or miR-206 inhibitor. cZNF292 and miR-206 expression was examined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Cell counting kit-8 and flow cytometry were performed for detecting cell growth including cell viability as well as apoptosis. Various kinds of factors, which are involved in cell development including proliferation, apoptosis, migration, and invasion were determined by western blot analysis. Besides, the activation of AMP-activated protein kinase (AMPK) and PI3K/AKT signaling was measured by western blot analysis. It was found that cZNF292 silencing decreased Eca-109 cell viability and induced apoptosis. In the meantime, cZNF292 silencing inhibited cell migration and invasion. cZNF292 silencing upregulated miR-206 expression. And miR-206 downregulation impaired the suppressive effects of cZNF292 silence toward Eca-109 cell growth, migration, and invasion. cZNF292 silencing activated AMPK signaling and inactivated PI3K/AKT signaling also via regulating miR-206. In conclusion, silencing of cZNF292 abated growth, migration, and invasion of Eca-109 cells by upregulating miR-206, which subsequently modulated AMPK and PI3K/AKT signaling pathways.

Synthesis of Redox-Responsive Core Cross-Linked Micelles Carrying Optically Active Helical Poly(phenyl isocyanide) Arms and Their Applications in Drug Delivery.

In this manuscript, we designed and synthesized three core cross-linked micelles (M-5L, P-5L, and P-5D) with redox-responsive disulfide bonds in the core and carrying optically active helical polyisocyanide arms. Their arms were different in the helicity of the main chain and the chirality of the side groups. These micelles showed excellent redox-responsiveness to reducing agent. However, because of the different chiralities of the arms, the three micelles exhibited different performances in drug delivery and controlled release. The M-5L micelle carrying left-handed helical arms showed better therapeutic effect than the other two due to the rapid cell membrane permeability.

Dual-functional analogous cis-platinum complex with high antitumor activities and two-photon bioimaging.

Here we have designed and synthesized a novel analogous cis-platinum complex (TDPt) with strong two-photon absorption properties and higher stability upon laser irradiation. Interestingly, a higher cytotoxicity against three types of cancer cells compared to that of commercial cis-platinum was observed. The initial confocal micrographs showed that lysosomes may be the biological targets of such TDPt, except the conventional presumed DNA. This hypothesis was further confirmed by the two-photon microscopy and transmission electron microscopy micrograph. These results form an important basis for future "on-site observation" of the anticancer mechanism of the Pt(II) complex.

Synthesis, crystal structures, photophysical properties, and bioimaging of living cells of bis-ß-diketonate phenothiazine ligands and its cyclic dinuclear complexes.

Two bis-ß-diketones, RCOCH(2)CO-EPTZ-COCH(2)COR (EPTZ = 10-ethylphenothiazine; R = C(6)H(5) for H(2)L(1) and CF(3) for H(2)L(2)) and their cyclic dinuclear Zn(II), Cd(II), Ni(II), Mn(II), Cu(II), Co(II) complexes have been synthesized and fully characterized. Their crystal structures were determined by single crystal X-ray diffraction analysis. Their photophysical properties have been further investigated both experimentally and theoretically. The results revealed that significant enhancement of two-photon absorption cross section values were obtained for the cyclic dinuclear Zn(II) and Cd(II) complexes compared with their free ligands. Additionally, confocal microscopy and two-photon microscopy fluorescent imaging of MCF-7 cells labeled with two ligands and Zn(II) complexes reveal their potential applications as a biological fluorescent probe.

Synthesis, crystal structure, electrochemistry and in situ FTIR spectroelectrochemistry of a bisferrocene pyrazole derivative.

One novel bisferrocene pyrazole derivative, bis [2-(5-trifluoromethyl-3-ferrocenyl) pyrazolyl] methane (abbreviated as (3)), was synthesized and fully characterized. A single crystal of (3) was obtained and solved by X-ray diffraction analysis. The bisferrocene derivative exhibits MLCT (metal to ligand charge transfer) and π→π* transitions in the UV-visible range, which have been verified by density functional theory (DFT) calculations. Its electrochemical properties were studied with the aid of cyclic voltammetry (CV), differential pulse voltammetry (DPV) and rapid scan time-resolved Fourier transform infrared spectroscopy (RS-TRS FT-IR) analysis. Furthermore, the electrochemical mechanism was elucidated based on the results from the cyclic voltabsorptometry (CVA) determination technique. (3) apparently shows a single wave in the cyclic voltammetric experiments which indicates there is no intermediate, however, the intermediate of (3) was observed by employing the RS-TRS FT-IR spectroelectrochemistry technique. The detailed investigation brought us safely to the conclusion that the methylene can also act as a linker, leading to electronic communication in either D-π-D and A-π-A systems.