Efficient and selective microwave-assisted copper-catalyzed synthesis of quinazolinone derivatives in aqueous

Microwave-assisted copper-catalyzed cascade reactions between 2-halobenzoic acids and amidines to synthesize quinazolinone derivatives in water are reported. A variety of target products were obtained in good to excellent yields up to 94%. Its application was performed by the synthesis of 4-(1H-benzo[d]imidazol-2-ylthio)-6-methoxypteridine, which displayed significant anti-proliferation effect.</p

An Efficient Copper-Catalyzed Carbon−Sulfur Bond Formation Protocol in Water

An efficient protocol of copper-catalyzed C−S bond formation between aryl halides and potassium thiocyanate leading to diaryl sulfides is reported. A variety of diaryl sulfides can be synthesized in good to excellent yields up to 94%

LINC01234 regulates microRNA-27b-5p to induce the migration, invasion and self-renewal of ovarian cancer stem cells through targeting SIRT5

LINC01234 has been suggested to correlate with the survival of ovarian cancer (OS), but its role in the properties of OC stem cells (OCSCs) has been rarely described. We aim to investigate the effect of LINC01234 on the differentiation and self-renewal of OCSCs through adsorption of microRNA (miR)-27b-5p to target sirtuins 5 (SIRT5). Expression of LINC01234 and SIRT5 in OC and normal samples included in TCGA and GTEx was searched through the GEPIA2 database. Bioinformatics analysis was conducted to predict the relation of LINC01234, miR-27b-5p and SIRT5. Expression of LINC01234, miR-27b-5p and SIRT5 in OC tissues and cells was detected. OCSCs were cultured and identified. CD133+ OCSCs were introduced with related oligonucleotides or vectors of LINC01234 or miR-27b-5p and SIRT5 to figure out their roles in OCSCs progression and tumorigenesis in vivo. The interaction of miR-27b-5p with LINC01234 or SIRT5 was analyzed. Bioinformatics analysis suggested that LINC01234 was very likely to influence SIRT5 and regulate the development of OC through miR-27b-5p. Up-regulated LINC01234 exhibited in OC tissues and cells. Down-regulated LINC01234 or elevated miR-27b-5p suppressed OCSCs progression and tumorigenesis in vivo. LINC01234 could restore SIRT5 expression by binding to miR-27b-5p. Down-regulated miR-27b-5p reversed the effect of silenced LINC01234 on OCSCs development and tumorigenesis in vivo. Up-regulation of SIRT5 reduced the effects of elevated miR-27b-5p on OCSCs progression and tumorigenesis in vivo. LINC01234 regulates miR-27b-5p to induce the migration, invasion and self-renewal of OCSCs through targeting SIRT5.</p

XN4 induces apoptosis in CML or normal primitive and committed progenitors <i>in vitro</i>.

<p>(A) XN4 induced apoptosis in CML CD34⁺CD38^—primitive and CML CD34⁺CD38⁺-committed progenitors. CML CD34⁺CD38^- primitive and CD34⁺CD38⁺ committed progenitors were exposed to XN4 at the indicated concentrations for 48 h. (B) Apoptosis in CML primitive and committed progenitors was analyzed by FACS as the percentage of cells positively labeled with Annexin V-APC (** <i>p<</i>0.01 vs control group, n = 3). (C) Apoptosis in normal primitive and committed progenitors from normal bone marrow was analyzed by FACS as the percentage of cells positively labeled with Annexin V-APC (n = 3).</p

The effect of XN4 on DSBs of DNA damage.

<p>(A) Representation of the fluorescence shift of rH2AX and cleaved PARP. K562 and K562/G01 cells were treated with XN4 for 12 h, 5 mM NAC for 12 h, or 5 mM NAC for 1 h followed by 6 μM XN4 for 12 h. After the treatment, the cells were washed, and then incubated with Alexa Fluor 647-conjugated mouse anti-H2AX (pS139) antibody and 5μl of a PE-conjugated anti-cleaved PARP (Asp214) antibody for 20 minutes at room temperature. The cells were washed once more before flow cytometry. (B, C) Quantification of rH2AX-positive ratio. The data are expressed as the mean±SD (*** <i>p<</i>0.001, ** <i>p<</i>0.01 vs control group, <i>p</i> = NS no significance, n = 3). (D) Representation of DSBs by neutral comet assay. Cells were collected after XN4 treatment for 12 h and processed for neutral comet assay using a CometAssay kit. Approximately 100 nucleus images were captured for each slide and processed by a Zeiss Axio Observer.Z1 microscope. The tail moments from the cells were measured by the TriTek CometScore software. (E) Quantification of the average tail moments (mean±SD) from three independent experiments are presented (** <i>p<</i>0.01 vs control group).</p

The primer sequences.

<p>The primer sequences.</p

Image_1_Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC.pdf

Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.</p

Effects of XN4 on apoptosis induction in CML cells.

<p>K562 and K562/G01 cells were incubated 6 μM XN4 or 5 mM NAC for 48 h, and 5 mM NAC pre-treated for 1 h then added 6μM XN4 for 48 h. The cells were harvested, then double-stained with PI and Annexin V-FITC, and subsequently analyzed by flow cytometry. All tests were performed three times, and the data are expressed as the mean±SD (** <i>p<</i>0.01, * <i>p<</i>0.05 vs control group, # <i>p<</i>0.01 XN4 group vs NAC+XN4 group, n = 3).</p

DataSheet_1_Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC.zip

Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.</p

Effects of XN4 on intracellular ROS levels and expression of <i>Nox</i> genes in CML cells.

<p>The fluorescence of DCF shifted after XN4 treatment for 12 h (A, C, D) or 24 h (B, E, F), with or without 5 mM NAC pre-treatment for 1 h. Quantification of DCF intensity fold-change after XN4 treatment. All data are expressed as the mean±SD. (** <i>p<</i>0.01 vs control group, # <i>p<</i>0.01 XN4 group vs NAC+XN4 group, n = 3). (G) The levels of <i>Nox1</i>, <i>Nox2</i>, <i>Nox3</i>, <i>Nox4</i>, and <i>Nox5</i> mRNA were determined using real-time quantitative RT-PCR. The data are presented as fold-changes, which are normalized to <i>GAPDH</i> expression and expressed as the mean±SD. (** <i>p<</i>0.01 vs control group, # <i>p<</i>0.01 XN4 group vs NAC+XN4 group, n = 3).</p