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Xia Chen, Hua Guo, Fuxia Li, Di Fan
BACKGROUND: The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-β-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis. METHODS: Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of β-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR...
September 13, 2016: Pharmacological Reports: PR
Fufa Qu, Zhiming Xiang, Yang Zhang, Jun Li, Shu Xiao, Yuehuan Zhang, Fan Mao, Haitao Ma, Ziniu Yu
p38 mitogen-activated protein kinases (MAPKs) are conserved serine/threonine-specific kinases that are activated by various extracellular stimuli and play crucial regulatory roles in immunity, development and homeostasis. However, the function of p38s in mollusks, the second most diverse group of animals, is still poorly understood. In this study, a novel molluscan p38 (designated Chp38) was cloned and characterized from the Hong Kong oyster Crassostrea hongkongensis. Its full-length cDNA encoded a putative protein of 353 amino acids with a calculated molecular weight of approximately 40...
October 18, 2016: Molecular Immunology
Swarupa Kancherla, William J Kohler, Yolandi van der Merwe, Kevin C Chan
Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0...
2016: PloS One
Michael Chalick, Oded Jacobi, Edward Pichinuk, Christian Garbar, Armand Bensussan, Alan Meeker, Ravit Ziv, Tania Zehavi, Nechama I Smorodinsky, John Hilkens, Franz-Georg Hanisch, Daniel B Rubinstein, Daniel H Wreschner
Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C- sequences flanking it differ entirely from those of MUC1-TM...
2016: PloS One
Ferit Dogan, Dilek Sen Dokumaci, Ali Yildirim, Erol Bozdogan, Fatima Nurefsan Boyaci, Bulent Koca, Ekrem Karakas
OBJECTIVES: This preliminary study aimed to evaluate whether there are changes in the Apparent Diffusion Coefficient (ADC) values of the brain in patients presenting with Eisenmenger syndrome (ES). METHODS: This cross-sectional study included 10 consecutively recruited patients with ES and 10 healthy control subjects. In the patients and controls, 8 distinct neuroanatomical locations were selected for the analysis. Quantitative measurements of ADC values of the frontal and occiptal white matter, lentiform nucleus, thalamus, frontal cortex, anterior and posterior limbs of the internal capsule, caudate nucleus were measured...
October 21, 2016: British Journal of Radiology
Derek Garden, Arianna Rinaldi, Matthew F Nolan
The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex. While it is well established that climbing fibre signals are important for motor coordination, the mechanisms by which neurones in the inferior olive integrate synaptic inputs and the roles of particular ion channels are unclear. Here, we test the hypothesis that neurones in the inferior olive actively integrate glutamatergic synaptic inputs...
October 21, 2016: Journal of Physiology
Rita Meleddu, Simona Distinto, Angela Corona, Enzo Tramontano, Giulia Bianco, Claudia Melis, Filippo Cottiglia, Elias Maccioni
A series of 3-3-{2-[2-3-methyl-4-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene-2,3-dihydro-1H-indol-2-one derivatives has been designed and synthesized to study their activity on both HIV-1 (Human Immunodeficiency Virus type 1) RT (Reverse Transcriptase) associated functions. These derivatives are analogs of previously reported series whose biological activity and mode of action have been investigated. In this work we investigated the influence of the introduction of a methyl group in the position 3 of the dihydrothiazole ring and of a chlorine atom in the position 5 of the isatin nucleus...
October 21, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Sophie Laguesse, Nadege Morisot, Khanhky Phamluong, Dorit Ron
We previously reported that the kinase AKT is activated in the nucleus accumbens (NAc) of rodents in response to excessive consumption of alcohol. One of the important downstream targets of AKT is the mammalian Target Of Rapamycin in Complex 1 (mTORC1), which was also activated by alcohol intake. mTORC1 controls dendritic protein translation, and we showed that the mTORC1-dependent translational machinery is activated in the NAc in response to alcohol intake. Importantly, systemic or intra-NAc inhibition of the AKT/mTORC1 pathway attenuated alcohol-drinking behaviors...
October 20, 2016: Addiction Biology
C Schlenstedt, A Shalash, M Muthuraman, D Falk, K Witt, G Deuschl
The aim of this meta-analysis was to summarize the short- and long-term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post-stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN-DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no...
October 20, 2016: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Atsushi Matsuda, Haruhiko Asakawa, Tokuko Haraguchi, Yasushi Hiraoka
The fission yeast Schizosaccharomyces pombe is a useful experimental system for studying the organization of chromosomes within the cell nucleus. S. pombe has a small genome that is organized into three chromosomes. The small size of the genome and the small number of chromosomes are advantageous for cytological and genome-wide studies of chromosomes; however, the small size of the nucleus impedes microscopic observations owing to limits in spatial resolution during imaging. Recent advances in microscopy, such as super-resolution microscopy, have greatly expanded the use of S...
October 21, 2016: Yeast
Izabela Jatczak-Pawlik, Michal Gorzkiewicz, Maciej Studzian, Dietmar Appelhans, Brigitte Voit, Lukasz Pulaski, Barbara Klajnert-Maculewicz
PURPOSE: Fourth-generation poly(propylene imine) dendrimers fully surface-modified by maltose (dense shell, PPI-m DS) were shown to be biocompatible in cellular models, which is important for their application in drug delivery. We decided to verify also their inherent bioactivity, including immunomodulatory activity, for potential clinical applications. We tested their effects on the THP-1 monocytic cell line model of innate immunity effectors. METHODS: To estimate the cytotoxicity of dendrimers the reasazurin assay was performed...
October 20, 2016: Pharmaceutical Research
Mercedes Garcia-Gil, Elisabetta Albi
In the last 20 years it has been widely demonstrated that cell nucleus contains neutral and polar lipids localized in nuclear membranes, nucleoli, nuclear matrix and chromatin. Nuclear lipids may show specific organization forming nuclear lipid microdomains and have both structural and functional roles. Depending on their localization, nuclear lipids play different roles such as the regulation of nuclear membrane and nuclear matrix fluidity but they also can act as platforms for vitamin and hormone function, for active chromatin anchoring, and for the regulation of gene expression, DNA duplication and transcription...
October 20, 2016: Neurochemical Research
Alfredo Lagunas-Martínez, Enrique García-Villa, Magaly Arellano-Gaytán, Carla O Contreras-Ochoa, Jisela Dimas-González, María E López-Arellano, Vicente Madrid-Marina, Patricio Gariglio
The E6 oncoprotein can interfere with the ability of infected cells to undergo programmed cell death through the proteolytic degradation of proapoptotic proteins such as p53, employing the proteasome pathway. Therefore, inactivation of the proteasome through MG132 should restore the activity of several proapoptotic proteins. We investigated whether in HPV16 E6-expressing keratinocytes (KE6 cells), the restoration of p53 levels mediated by MG132 and/or activation of the CD95 pathway through apoptosis antigen-1 (APO-1) antibody are responsible for the induction of apoptosis...
October 20, 2016: Apoptosis: An International Journal on Programmed Cell Death
Farhad Jahanfar, Akbar Hasani, Dariush Shanebandi, Mohammad Rahmati, Hamed Hamishehkar
Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied...
September 2016: Advanced Pharmaceutical Bulletin
Maike C Herbort, Joram Soch, Torsten Wüstenberg, Kerstin Krauel, Maia Pujara, Michael Koenigs, Jürgen Gallinat, Henrik Walter, Stefan Roepke, Björn H Schott
Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI)...
2016: NeuroImage: Clinical
Jennifer Snaith, Kharis Burns, Jen Kok, Sharon Chen, N Wah Cheung
We document the first case of haematogenous cerebral spread in Rhizopus arrhizus rhino-orbital mucormycosis, and of posaconazole related adrenal insufficiency. A patient presenting with diabetic ketoacidosis and sinusitis was treated with right medial maxillectomy, ethmoidectomy and IV liposomal amphotericin. Orbital exenteration was performed after intraorbital spread of infection. IV caspofungin and posaconazole was added but complicated by adrenal insufficiency. MRI revealed a new left lentiform nucleus and thalamus rim-enhancing lesion indicating haematogenous cerebral spread...
September 2016: Medical Mycology Case Reports
Emilia Pachulec, Vanessa Neitzke-Montinelli, João P B Viola
Nuclear factor of activated T cells (NFAT) 2 null mutant mice die in utero of cardiac failure, precluding analysis of the role of NFAT2 in lymphocyte responses. Only the NFAT2(-/-)/Rag-1(-/-) chimeric mice model gave insight into the role of NFAT2 transcription factor in T lymphocyte development, activation, and differentiation. As reports are mainly focused on the role of NFAT2 in CD4(+) T lymphocytes activation and differentiation, we decided to investigate NFAT2's impact on CD8(+) T lymphocyte responses...
2016: Frontiers in Immunology
Qian-Qian Luo, Zhong-Ming Qian, Yu-Fu Zhou, Meng-Wan Zhang, Dang Wang, Li Zhu, Ya Ke
The inconsistent of responses of IRP1 and HIF-1 alpha to hypoxia and the similar tendencies in the changes of IRP1 and pCREB contents led us to hypothesize that pCREB might be involved in the regulation of IRP1 under hypoxia. Here, we investigated the role of pCREB in IRP1 expression in HepG2 cells under hypoxia using quantitative PCR, western blot, immunofluorescence, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). We demonstrated that 1) Hypoxia increased pCREB levels inside of the nucleus; 2) Putative CREs were found in the IRP1 gene; 3) Nuclear extracts of HepG2 cells treated with hypoxia could bind to CRE1 and CRE3, and 100-fold competitor of putative CREs could abolish the binding activity to varying degrees; 4) pCREB was found in the CRE1 and CRE3 DNA-protein complexes of EMSA; 5) CRE1 and CRE3 binding activity of IRP1 depended on CREB activation but not on HIF-1; 6) Increased IRP1 expression under hypoxia could be prevented by LY294002; 7) ChIP assays demonstrated that pCREB binds to IRP1 promoter; and 8) HIF-1 and/or HIF-2 siRNA had no effect on the expression of pCREB and IRP1 proteins in cells treated with hypoxia for 8 hours...
2016: International Journal of Biological Sciences
Nada Lallous, Eric Leblanc, Ravi Sn Munuganti, Mohamed D H Hassona, Nader Al Nakouzi, Shannon Awrey, Helene Morin, Mani Roshan-Moniri, Kriti Singh, Sam Lawn, Takeshi Yamazaki, Hans H Adomat, Christophe Andre, Mads Daugaard, Robert N Young, Emma S Tomlinson Guns, Paul S Rennie, Artem Cherkasov
The development of new anti-androgens such as enzalutamide or androgen synthesis inhibitors like abiraterone have improved patient outcomes in the treatment of advanced prostate cancer (PCa). However, due to the development of drug resistance and tumor cell survival, the majority of these patients progress to the refractory state of castration-resistant prostate cancer (CRPC). Thus, newer therapeutic agents and a better understanding of their mode of action are needed for treating these CRPC patients. We demonstrated previously that targeting the Binding Function 3 (BF3) pocket of the androgen receptor (AR) has great potential for treating patients with CRPC...
October 7, 2016: Molecular Cancer Therapeutics
Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist, MGS0039 shows antidepressant effects. However, there are no reports comparing these two compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice, after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluA1) and postsynaptic density protein 95 (PSD-95), and dendritic spine density in selected brain regions were measured...
October 7, 2016: International Journal of Neuropsychopharmacology
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