A Novel Compound,L34, Induced Apoptosis in Human Gastric Cancer Cells

Selectively apoptosis-targeting compounds in gastrointestinal cancers attract broad interest. Here, we investigated a synthetic sulfonamide, 4-bromo-N-(5-ethyl-5H-pyrido[4,3-b]indol-8-yl)benzenesulfonamide (L34). It showed high activity against gastric cancer cells SGC-7901, causing apoptosis, which was associated with downregulation of caspase-3 and XIAP, upegulation of cleaved caspase-3, and cleavage of PARP. Hence, L34 might be a potent chemotherapeutic agent against human gastric cancer.     

Bone marrow mesenchymal stem cell–derived exosomal miR-206 promotes osteoblast proliferation and differentiation in osteoarthritis by reducing Elf3

MicroRNAs (miRNAs) serve as gene silencers involved in essential cell functions. The role of miR-206 and E74-like factor 3 (Elf3) has been identified in osteoarthritis (OA), while the effect of exosomal miR-206 from bone marrow mesenchymal stem cells (BMSCs) in OA remains largely unknown. Thus, we aim to explore the role of exosomal miR-206 from BMSCs in OA with the involvement of Elf3. BMSCs and BMSC-derived exosomes (BMSC-exos) were obtained and identified. OA mouse models were constructed by anterior cruciate ligament transection and then treated with BMSC-exos or BMSC-exos containing miR-206 mimic/inhibitor. The expression of miR-206, Elf3, inflammatory factors, osteocalcin (OCN) and bone morphogenetic protein 2 (BMP2) in mouse femoral tissues was assessed. The pathological changes in mouse femur tissues were observed. The mouse osteoblasts were identified and treated with untransfected or transfected BMSC-exos, and then, the expression of miR-206, Elf3, OCN and BMP2 was determined. The alkaline phosphatase (ALP) activity, calcium deposition level, OCN secretion, proliferation, apoptosis and cell cycle arrest in osteoblasts were measured. MiR-206 was down-regulated while Elf3 was up-regulated in OA animal and cellular models. Exosomal miR-206 ameliorated inflammation and increased expression of OCN and BMP2 in mouse femoral tissues. Moreover, exosomal miR-206 promoted ALP activity, calcium deposition level, OCN secretion and proliferation and inhibited apoptosis in OA osteoblasts. Overexpressed Elf3 reversed miR-206 up-regulation-induced effects on OA osteoblasts. BMSC-derived exosomal miR-206 promotes proliferation and differentiation of osteoblasts in OA by reducing Elf3. Our research may provide novel targets for OA treatment.     

Synergistic interaction between cisplatin and PARP inhibitors in non-small cell lung cancer

The antineoplastic agent cis-diammineplatinum(II) dichloride (cisplatin, CDDP) is part of the poorly effective standard treatment of non-small cell lung carcinoma (NSCLC). Here, we report a novel strategy to improve the efficacy of CDDP. In conditions in which CDDP alone or either of two PARP inhibitors, PJ34 hydrochloride hydrate or CEP 8983, used as standalone treatments were inefficient in killing NSCLC cells, the combination of CDDP plus PJ34 or that of CDDP plus CEP 8983 were found to kill a substantial fraction of the cells. This cytotoxic synergy could be recapitulated by combining CDDP and the siRNA-mediated depletion of the principal PARP isoform, PARP1, indicating that it is mediated by on-target effects of PJ34 or CEP 8983. CDDP and PARP inhibitors synergized in inducing DNA damage foci, mitochondrial membrane permeabilization leading to cytochrome c release, and dissipation of the inner transmembrane potential, caspase activation, plasma membrane rupture and loss of clonogenic potential in NSCLC cells. Collectively, our results indicate that CDDP can be advantageously combined with PARP inhibitors to kill several NSCLC cell lines, independently from their p53 status. Combined treatment with CDDP and PARP inhibitors elicits the intrinsic pathway of apoptosis.     

Protein-lipid interactions glycophorin and dipalmitolyphosphatidylcholine.

The choline methyl groups of dipalmitoylphosphatidylcholine were enriched with ¹³C, and glycophorin extracted from human erythrocytes was included in bilayers of this phospholipid. At temperatures below the transition temperature, the ¹³C nuclear magnetic resonance spectra have two components, one sharp and one broad. The sharp signal is attributed to relatively “fluid” lipids in the immediate vicinity of the glycoprotein. In a defined ternary mixture consisting of ¹³C-labeled dipalmitoylphosphatidylcholine, dielaidoylphosphatidylcholine and glycophorin, the sharp ¹³C resonance signal disappears below the transition temperature of the mixture, indicating that the unsaturated lipid is preferentially associated with the glycoprotein under these conditions.     

Changes in amino acid transport in the rat pancreas in response to fasting and feeding

Transport of amino acids (in vitro) in the rat pancreas is affected by the nutritional state of the animal. A fast of 24 h (young animals) or 48 h (adult animals) reduces the rate of amino acid uptake in the isolated rat pancreas in vitro. In contrast, refeeding of animals after a fast shows an increase in transport in young as well as adult animals.The effects of refeeding after a fast are mimicked to a significant extent by injection of mixtures of pancreozymin and carbamylcholine. Addition of these agents in vitro has no effect.The incorporation of amino acids into the total proteins of the rat pancreas follows the pattern of amino acid uptake. Even at high external levels of glycine (5 mM), incorporation increases although the glycine level in the cell is in excess of 25 mM. Reduction of glycine uptake by ouabain by 75% results in a substantial (44%) diminution of amino acid incorporation into proteins. The data suggest that inhibition of amino acid incorporation under the various metabolic conditions examined is due largely to a decreased availability of amino acids.     

A simple device to measure root growth rates

The construction and use of a simple auxanometer is described. With this instrument students can readily and accurately measure root growth rates of intact seedlings. Typical time course data are presented for the effect of ethylene and indole acetic acid on pea root growth.