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Berberine, an isoquinoline alkaloid from Coptidis Rhizoma, has been characterized as a potential anticancer drug due to its good anti-tumor effects. However, the molecular mechanisms involved in anti-gastric cancer remain poorly understood. Herein, the role of berberine in gastric cancer suppression by inducing cytostatic autophagy in vitro and in vivo was first investigated. Results showed that berberine induced an obvious growth inhibitory effect on gastric cancer BGC-823 cells without toxicity to human peripheral blood mononuclear cells. Treatment with berberine triggered cell autophagy, as demonstrated by the punctuate distribution of monodansylcadaverine staining and GFP-LC3, as well as the LC3-II, Beclin-1 and p-ULK1 promotion, and p62 degradation. Inhibition of autophagy by 3-MA, CQ, Baf-A1 and BECN1 siRNA obviously increased cell viability of berberine-exposed gastric cancer cells, which confirmed the anti-cancer role of autophagy induced by berberine. Mechanistic studies showed that berberine inhibited mTOR, Akt and MAPK (ERK, JNK and p38) pathways thereby inducing autophagy. Inhibition of above pathways increases berberine induced autophagy and cytotoxicity. Interestingly, mTOR/p70S6K was inhibited by the MAPK but not Akt. Furthermore, inhibition of autophagy reversed berberine down-regulated mTOR, Akt and MAPK. In xenografts, the berberine induced autophagy leads to suppression of tumor proliferation with no side-effect, and western blotting displayed an apparent attenuation of p-mTOR, p-p70S6K, p-Akt, p-ERK, p-JNK and p-p38 in tumors from berberine treated mice. Briefly, these results indicated that berberine repressed human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt, and provided a molecular basis for the treatment of gastric cancer.Background Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and deformity. Mesenchymal stem cells (MSCs) infusion can improve bone performance mainly due to their differentiation into osteoblasts in OI therapy. The osteoinductive activity of NELL1 have benefited various bone defect and osteoporotic models by promoting bone formation. The present study investigated the efficacy of combined use of NELL1 and adipose-derived mesenchymal stem cells (ADSCs) in OI treatment. Methods Lentiviral vector carrying mouse Nell1 gene was constructed and lentivirus were used to infect ADSCs. The osteogenic capacity of MC3T3-E1 and ADSCs stimulated by recombinant mouse NELL1 protein (rmNELL1) and Nell1 gene genetically modified ADSCs (lenti-Nell1-ADSCs) were estimated by real-time quantitative PCR. Thirty adult male OI type I mice with single Col1a1 gene knockout were randomly divided into five groups and received intravenously injected PBS, rmNELL1 (1.25 mg/Kg), ADSCs (2 × 105 cells pert on stimulating bone formation of OI mice, which might provide an alternative strategy in OI treatment. Compared with dose escalation or multiple administration of rmNELL1, lentivirus-mediated long term expression of NELL1 might be more feasible and convenient. However, further studies are needed to confirm the safety and optimize the therapeutic regime.Selective inhibition of vascular endothelial growth factor receptor (VEGFR), particularly VEGFR-2, is an efficient method for the treatment of ocular neovascularization. Dasatinib in vivo SU1498 is a specific inhibitor of VEGFR-2. In this study, we investigated the role of SU1498 in ocular neovascularization. Administration of SU1498 did not show any cytotoxicity and tissue toxicity at the tested concentrations. Administration of SU1498 reduced the size and thickness of choroidal neovascularization and decreased the mean length and mean number of corneal neovascular vessels induced by alkali burn. Pretreatment of SU1498 significantly reduced the proliferation, migration, and tube formation ability of HUVECs. SU1498 played the anti-angiogenic role through the regulation of p38-MAPK signaling. Taken together, inhibition of VEGFR-2 by SU1498 provides a novel therapeutic approach for ocular neovascularization.Several studies have demonstrated an influence of semantic knowledge on verbal working memory (WM) performance, such as shown by the observation of semantic relatedness (related vs. unrelated words) and word imageability (high vs. low imageability words) effects in working memory. The present study extends these observations by examining in four experiments the extent to which semantic knowledge can protect WM representations against interference. We assessed immediate serial recall performance for semantically related vs. unrelated word lists and for high vs. low imageability word lists, with memory lists being followed by an interfering task after encoding or not. Results show that semantic relatedness leads to a stronger protective effect against interference than word imageability at the item level. Furthermore, the semantic relatedness had a stronger impact on WM performance than word imageability; this was further supported by a meta-analysis of all relevant studies in the field. These results suggest that inter-item associative semantic knowledge can protect WM content against interference, but less so item-level semantic knowledge. This protective effect may result from between-item recurrent reactivation or from reduced cognitive load via the compression of memoranda into conceptual units, as further supported by a series of computational simulations.In our previous study, a novel LMW-GS designated as LMW-N13 with a unique molecular structure was identified from Aegilops uniaristata. LMW-N13 has been characterized as the largest LMW-GS, so far, and possesses an extra cysteine residue compared with typical LMW-GS. In order to analyze the contribution of LMW-N13 to dough quality, in this work, three transgenic wheat lines overexpressing LMW-N13 were generated. Compared with non-transformation (NT) lines, transgenic (TG) lines demonstrated superior dough properties. These superior dough properties were accompanied by the higher contents of glutenin macropolymer (GMP) and total protein. The microstructure of the dough was further investigated by scanning electron microscopy; starch granules in NT lines were smaller than those in transgenic lines. The protein matrix in NT lines was relatively loose and discontinuous. Conversely, the protein matrix in transgenic lines was more continuous and tight. The application of LMW-N13 in wheat breeding is also discussed.
Here's my website: https://www.selleckchem.com/products/Dasatinib.html
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