BDNF and ARTEMIN are increased in drug-naive non-depressed GAD patients: Preliminary data
INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE
Authors: Pallanti, Stefano; Tofani, Tommaso; Zanardelli, Matteo; Mannelli, Lorenzo Di Cesare; Ghelardini, Carla
Abstract
Objective. While the role of neuronal and glial plasticity are well established in the pathophysiology of mood disorders, the pattern and measures of neuronal and glial cell line-derived neurotrophic factors are unknown in generalized anxiety disorder (GAD). The present study evaluates brain-derived neurotrophic factor (BDNF) and Artemin (ARTN) plasma levels in GAD patients. Methods. Fourteen drug-naive GAD patients without major depression were enrolled and plasmatic levels of BDNF and ARTN mRNA were measured by RT-PCR, and compared to matched healthy controls. Results. The results showed an unexpected increase in mRNA levels of both BDNF and ARTN in patients with GAD, that appeared almost doubled when compared to healthy controls. In comparison, both BDNF and ARTN are reduced in patients with major depressive disorder. Further, the results are intriguing and might involve distinguishing pathophysiological pathways. Conclusions. This is the first report of increased levels of a neurotrophic factor and of a glial cell line-derived neurotrophic factor family member in GAD patients. While further studies to confirm these results and the functional meaning in terms of pathophysiology of GAD are needed, the potential conceptual and clinical meanings are discussed.
Enhanced autophagic activity of artocarpin in human hepatocellular carcinoma cells through improving its solubility by a nanoparticle system
PHYTOMEDICINE
Authors: Tzeng, Cheng-Wei; Tzeng, Wen-Sheng; Lin, Liang-Tzung; Lee, Chiang-Wen; Yen, Feng-Lin; Lin, Chun-Ching
Abstract
Background: Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide, with poor prognosis and resistance to chemotherapy. This gives novel cancer treatment methods an overwhelming significance. Natural products offer great resources of developing new and effective chemopreventive or chemotherapeutic agents. Artocarpus communis extracts and its active constituent, prenylated flavonoid artocarpin induce human hepatocellular carcinoma cell death. However, the poor water solubility drawbacks of artocarpin restrict its clinical application and bioavailability. Purpose: This study developed the artocarpin nanoparticle system to overcome the poor water solubility drawbacks and investigated the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. Methods: Antiproliferative activity of artocarpin was evaluated by MTT assay. Cell morphology observation by microscope, DNA fragmentation assay, cell cycle analysis, Annexin V apoptosis cell staining, monodansylcadaverine and acridine orange staining and immunoblot analysis were used to evaluate the induction of autophagy by artocarpin. The determination of particle size, amorphous transformation, hydrogen-bond formation, yield, encapsulation efficiency and the solubility study were used to investigate the solubility enhancement mechanism of artocarpin. Results: The present study demonstrates that the anticancer effect of artocarpin in HepG2 and PLC/PRF/5 hepatoma cells is mediated through the autophagic cell death mechanism. Results also demonstrated that artocarpin nanoparticles enhanced the solubility of artocarpin by reducing particle size, transforming high energy amorphous state, and forming hydrogen bond with excipients. Additionally, ArtN exhibited better autophagic cytotoxicity compared to free artocarpin. Conclusion: This work reveals the antihepatoma activity of artocarpin by inducing autophagic cell death and the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. The research provided a basis of ArtN could be explored as a low-dose alternative of artocarpin in anticancer treatment and research applications. (C) 2016 Elsevier GmbH. All rights reserved.