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  • Stewart Jessen posted an update 2 days, 8 hours ago

    Antipsychotics are the main line of treatment for schizophrenia. Even though there are significant rates of medication drop out due to side effects and limited response of approximately 50% of patients. This is likely due to incomplete knowledge in how these drugs act at the molecular level. To improve treatment efficacy during the critical early stages of schizophrenia, we aimed to identify molecular signatures at baseline (T0) for prediction of a positive response to the atypical antipsychotics olanzapine and risperidone after 6 weeks (T6) treatment. Blood plasma samples were processed and analyzed by label-free quantitative shotgun proteomics using two-dimensional nano-liquid chromatography, coupled online to a Synapt G2-Si mass spectrometer. Data were obtained in MSE mode (data-independent acquisition) in combination with ion-mobility (HDMSE). We were able to identify a potential panel of proteins that might predict a positive outcome to olanzapine and risperidone treatment. The proteins found to be diffecomparison between good and poor responders at the baseline might compose a signature for prediction of response effectiveness.20 (R)-Dammarane-3β, 12β, 20, 25-tetrol (25-OH-PPD), a ginsenoside, was derived from Panax ginseng (C. A. STA-9090 mw Meyer) and inhibited growth of several cancer cell lines. To improve the anti-cancer activity, we introduced the pyrazine ring to 25-OH-PPD and obtained the compound 20(R)-[2,3-β]-Pyrazine-dammarane-12β,20,25-triol (2-Pyrazine-PPD). we evaluated the anti-cancer activity of 2-Pyrazine-PPD and investigated the main anti-cancer mechanisms of 2-Pyrazine-PPD in gastric cancer cells. We found that 2-Pyrazine-PPD remarkably suppressed the proliferation of gastric cancer cells in a concentration-dependent, and showed little toxicity to the normal cell (human gastric epithelial cell line-GES-1). Further study indicated that 2-Pyrazine-PPD induced apoptosis by mitochondria pathway in BGC-803 cancer cells, and activated unfolded protein response and the protein kinase RNA-activated (PKR)-like ER kinase (PERK)/Eukaryotic translation initiation factor-2α (eIF-2α)/Activating transcription factor 4 (ATF4) axis, the expression level of the protein C/EBP homologous protein (CHOP), the marker of endoplasmic reticulum stress, and the apoptosis inducing by 2-Pyrazine-PPD can partly be inhibited by siRNA-mediated knockdown of CHOP. Moreover, the production of reactive oxygen species was remarkably up-regulated in BGC-803 cancer cells treated with 2-Pyrazine-PPD. N-acetylcysteine (NAC, a reactive oxygen species scavenger) can attenuate 2-Pyrazine-PPD-induced apoptosis and endoplasmic reticulum stress. Taken together, we suggested that 2-Pyrazine-PPD exhibited remarkable anti-cancer activity by reactive oxygen species-mediate cell apoptosis and endoplasmic reticulum stress in gastric cancer cells. Our results uncovered the mechanism of 2-Pyrazine-PPD as a promising anti-tumor candidate for gastric cancer therapy.Semen Vaccariae, the seed of Vaccaria segetalis, is traditionally used in East Asian countries for the treatment of breast milk deficiency, but the underlying molecular mechanism has not been discovered yet. The present study assessed the stimulatory effect of vaccarin, one of the major constituents of Semen Vaccariae, on proliferation of and milk synthesis in bovine mammary epithelial cells (BMECs) and explored the corresponding molecular mechanism. Vaccarin affected cell proliferation and milk fat and protein synthesis in a concentration-dependent manner, with the best stimulatory effects at 0.5 μg/ml concentration. Vaccarin (0.5 μg/ml) had the similar effects as prolactin (Prl, 0.5 μg/ml) on cell proliferation, milk fat and protein synthesis, expression of Cyclin D1, phosphorylation of mechanistic target of rapamycin (mTOR), and expression and maturation of sterol regulatory element binding protein 1c (SREBP-1c). Vaccarin stimulated these signaling pathways via the Prl receptor-phosphatidyl inositol 3-kinase (PI3K) signaling. Vaccarin also concentration-dependently stimulated expression of the Prl receptor, with the best effects at 0.5 μg/ml concentration. In summary, we demonstrate that vaccarin promotes proliferation of and milk synthesis in BMECs through the Prl receptor-PI3K signaling, suggesting that vaccarin might be the main active component promoting milk production of BMECs in Semen Vaccariae.In most retinal diseases, neuronal loss is the main cause of vision loss. Neuroprotection is the alteration of neurons and/or their environment to encourage the survival and function of the neurons, especially in environments that are deleterious to the neuronal health. The area of neuroprotection progresses with a therapeutically-based hope of improving vision and clinical outcomes for patients through the developments in neurotrophic therapy, antioxidative therapy, anti-excitotoxic, anti-ischemic, anti-inflammatory, and anti-apoptotic care. In this review, we summarize the various neuroprotection strategies for the treatment of glaucoma, genetics of glaucoma and the role of various nanoplatforms in the treatment of glaucoma.Tripterygium wilfordii Hook F (TwHF) exhibits anti-tumor efficacy in pancreatic ductal adenocarcinoma (PDAC), however the pharmacological mechanisms are unclear due to complicated formulae and target genes. Using Traditional Chinese Medicine Systems Pharmacology and GeneCards databases, we performed a network pharmacology (NP) of TwHF and screened out 22 ingredients and 25 target genes associated with PDAC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the 25 target genes were performed. Using STRING database, protein-protein interaction network of the 25 target genes was constructed, and indicated that triptolide (TL)-plasminogen activator urokinase (PLAU) as a potential target for PDAC treatment. Hence, in vitro experiments were performed and validated that TL inhibited PDAC cell proliferation and migration by suppressing PLAU expression. The results of Western blot suggested that PLAU activated endothelial-mesenchymal transition (EMT) progression. In two Gene Expression Omnibus datasets (GSE16515 and GSE28735), PLAU was up-regulated in tumor tissues, and PLAU overexpression was associated with poor overall survival of PDAC cohort of The Cancer Genome Atlas (P less then 0.

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