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https://www.readbyqxmd.com/read/28728104/design-synthesis-and-evaluation-of-coumarin-pargyline-hybrids-as-novel-dual-inhibitors-of-monoamine-oxidases-and-amyloid-%C3%AE-aggregation-for-the-treatment-of-alzheimer-s-disease
#1
Hua-Li Yang, Pei Cai, Qiao-Hong Liu, Xue-Lian Yang, Fan Li, Jin Wang, Jia-Jia Wu, Xiao-Bing Wang, Ling-Yi Kong
A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC50, 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test...
July 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28727574/flexible-ligated-ruthenium-ii-self-assemblies-sensitizes-glioma-tumor-initiating-cells-in-vitro
#2
Palani Elumalai, Neha Kaushik, Dong Hwan Kim, Hyunuk Kim, Su Jae Lee, Eun Ha Choi, Ki-Whan Chi, Nagendra Kumar Kaushik
The tumorigenic potentials of residual cancer stem-like cells within tumors represent limitations of current cancer therapies. Here, the authors describe the effects of synthesized flexible, ligated, supramolecular self-assembled chair type tetranuclear ruthenium (II) metallacycles (2-5) on glioblastoma and glioma stem like cells. These self-assemblies were observed to be selectively toxic to glioma cells and CD133-positive glioma stem like cells population. Of the self-assembled compounds tested, metallacycle 4 more efficiently induced glioma stem like cells death within a brain cancer cell population and simultaneously inhibited the formation of free-floating gliospheres by reducing the sphere size...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28727355/-perfusion-imaging-of-acute-ischemic-stroke
#3
Carlo W Cereda, Patrik Michel, Karl-Olof Lovblad, Emmanuel Carrera
Multi-modal imaging in acute ischemic stroke includes structural imaging, perfusion imaging and angiographic assessment of brain arteries. Perfusion imaging discriminates brain tissue that is critically hypo-perfused but salvageable (ischemic penumbra) from irreversibly injured tissue (ischemic core). In acute reperfusion therapies (intravenous or endovascular), patients who have substantial penumbra and a small core (target mismatch pattern) are most likely to have a good clinical outcome. Patient selection based on multi-modal imaging is not proven mandatory for acute treatment in patients admitted within the established time-window...
April 26, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28727285/adapting-vmat-plans-optimized-for-an-hd120-mlc-for-delivery-with-a-millennium-mlc
#4
Samuel B French, Stephen Bhagroo, Daryl P Nazareth, Matthew B Podgorsak
Linac downtime invariably impacts delivery of patients' scheduled treatments. Transferring a patient's treatment to an available linac is a common practice. Transferring a Volumetric Modulated Arc Therapy (VMAT) plan from a linac equipped with a standard-definition MLC to one equipped with a higher definition MLC is practical and routine in clinics with multiple MLC-equipped linacs. However, the reverse transfer presents a challenge because the high-definition MLC aperture shapes must be adapted for delivery with the lower definition device...
July 20, 2017: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28726821/the-whole-genome-landscape-of-medulloblastoma-subtypes
#5
Paul A Northcott, Ivo Buchhalter, A Sorana Morrissy, Volker Hovestadt, Joachim Weischenfeldt, Tobias Ehrenberger, Susanne Gröbner, Maia Segura-Wang, Thomas Zichner, Vasilisa A Rudneva, Hans-Jörg Warnatz, Nikos Sidiropoulos, Aaron H Phillips, Steven Schumacher, Kortine Kleinheinz, Sebastian M Waszak, Serap Erkek, David T W Jones, Barbara C Worst, Marcel Kool, Marc Zapatka, Natalie Jäger, Lukas Chavez, Barbara Hutter, Matthias Bieg, Nagarajan Paramasivam, Michael Heinold, Zuguang Gu, Naveed Ishaque, Christina Jäger-Schmidt, Charles D Imbusch, Alke Jugold, Daniel Hübschmann, Thomas Risch, Vyacheslav Amstislavskiy, Francisco German Rodriguez Gonzalez, Ursula D Weber, Stephan Wolf, Giles W Robinson, Xin Zhou, Gang Wu, David Finkelstein, Yanling Liu, Florence M G Cavalli, Betty Luu, Vijay Ramaswamy, Xiaochong Wu, Jan Koster, Marina Ryzhova, Yoon-Jae Cho, Scott L Pomeroy, Christel Herold-Mende, Martin Schuhmann, Martin Ebinger, Linda M Liau, Jaume Mora, Roger E McLendon, Nada Jabado, Toshihiro Kumabe, Eric Chuah, Yussanne Ma, Richard A Moore, Andrew J Mungall, Karen L Mungall, Nina Thiessen, Kane Tse, Tina Wong, Steven J M Jones, Olaf Witt, Till Milde, Andreas Von Deimling, David Capper, Andrey Korshunov, Marie-Laure Yaspo, Richard Kriwacki, Amar Gajjar, Jinghui Zhang, Rameen Beroukhim, Ernest Fraenkel, Jan O Korbel, Benedikt Brors, Matthias Schlesner, Roland Eils, Marco A Marra, Stefan M Pfister, Michael D Taylor, Peter Lichter
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28726525/working-memory-capacity-and-addiction-treatment-outcomes-in-adolescents
#6
Jon M Houck, Sarah W Feldstein Ewing
BACKGROUND: Brief addiction treatments including motivational interviewing (MI) have shown promise with adolescents, but the factors that influence treatment efficacy in this population remain unknown. One candidate is working memory, the ability to hold a fact or thought in mind. This is relevant, as in therapy, a client must maintain and manipulate ideas while working with a clinician. Working memory depends upon brain structures and functions that change markedly during neurodevelopment and that can be negatively impacted by substance use...
July 20, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28726511/how-do-probiotics-and-prebiotics-function-at-distant-sites
#7
G Reid, T Abrahamsson, M Bailey, L B Bindels, R Bubnov, K Ganguli, C Martoni, C O'Neill, H M Savignac, C Stanton, N Ship, M Surette, K Tuohy, S van Hemert
The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effects and the extent to which early life microbiome programming influences how the gut microbiota communicates with distant sites. In addition, we examined how probiotics and prebiotics might affect the skin, airways, heart, brain and metabolism...
July 20, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28726172/combined-treatment-for-non-small-cell-lung-cancer-and-breast-cancer-patients-with-brain-metastases-with-whole-brain-radiotherapy-and-temozolomide-a-systematic-review-and-meta-analysis
#8
REVIEW
Jingru Tian, Yien Luo, Juanjuan Xiang, Jingqun Tang
Brain metastasis is the leading cause of death among advanced non-small cell lung cancer (NSCLC) and breast cancer patients. The standard treatment for brain metastases is radiotherapy. The combination of radiotherapy and chemotherapy has been tested. However, the management of brain metastases has yet to be successful. Here, we aimed to determine the efficacy and safety of whole brain radiotherapy (WBRT) alone or in combination with temozolomide (TMZ) in NSCLC and breast cancer patients with brain metastases...
July 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#9
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28725965/medulloblastoma-experimental-models-and-reality
#10
REVIEW
Julia E Neumann, Fredrik J Swartling, Ulrich Schüller
Medulloblastoma is the most frequent malignant brain tumor in childhood, but it may also affect infants, adolescents, and young adults. Recent advances in the understanding of the disease have shed light on molecular and clinical heterogeneity, which is now reflected in the updated WHO classification of brain tumors. At the same time, it is well accepted that preclinical research and clinical trials have to be subgroup-specific. Hence, valid models have to be generated specifically for every medulloblastoma subgroup to properly mimic molecular fingerprints, clinical features, and responsiveness to targeted therapies...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28725655/cell-replacement-therapy-is-the-remedial-solution-for-treating-parkinson-s-disease
#11
REVIEW
Venkatesan Dhivya, Vellingiri Balachandar
The selective degeneration of dopaminergic (DA) neurons in Parkinson's disease (PD) has made an idol target for cell replacement therapies and other emerging surgical treatments. Certainly, by transplantation method, the therapeutic regimens such as human fetal ventral midbrain (hfVM) cells, human embryonic stem cells (hESCs), human neural stem/precursor/ progenitor cells (hNSCs/hNPCs), human mesenchymal stem cells (hMSCs), human induced neural stem cells (hiNSCs), and human induced pluripotent stem cells (hiPSCs) have been used into DA deficient striatum...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28725211/critical-evaluation-of-the-lund-concept-for-treatment-of-severe-traumatic-head-injury-25%C3%A2-years-after-its-introduction
#12
REVIEW
Per-Olof Grände
When introduced in 1992, the Lund concept (LC) was the first complete guideline for treatment of severe traumatic brain injury (s-TBI). It was a theoretical approach, based mainly on general physiological principles-i.e., of brain volume control and optimization of brain perfusion and oxygenation of the penumbra zone. The concept gave relatively strict outlines for cerebral perfusion pressure, fluid therapy, ventilation, sedation, nutrition, the use of vasopressors, and osmotherapy. The LC strives for treatment of the pathophysiological mechanisms behind symptoms rather than just treating the symptoms...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28724796/host-interleukin-6-production-regulates-inflammation-but-not-tryptophan-metabolism-in-the-brain-during-murine-gvhd
#13
Ludovic Belle, Vivian Zhou, Kara L Stuhr, Margaret Beatka, Emily M Siebers, Jennifer M Knight, Michael W Lawlor, Casey Weaver, Misato Hashizume, Cecilia J Hillard, William R Drobyski
Graft-versus-host disease (GVHD) induces pathological damage in peripheral target organs leading to well-characterized, organ-specific clinical manifestations. Patients with GVHD, however, can also have behavioral alterations that affect overall cognitive function, but the extent to which GVHD alters inflammatory and biochemical pathways in the brain remain poorly understood. In the current study, we employed complementary murine GVHD models to demonstrate that alloreactive donor T cells accumulate in the brain and affect a proinflammatory cytokine milieu that is associated with specific behavioral abnormalities...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#14
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28723864/sacral-neuromodulation-for-fecal-incontinence-a-review-of-the-central-mechanisms-of-action
#15
Paul T J Janssen, Niels Komen, Jarno Melenhorst, Nicole D Bouvy, Ali Jahanshahi, Yasin Temel, Stephanie O Breukink
OBJECTIVE: Fecal incontinence (FI) has a devastating effect on the quality of life and results in social isolation. Sacral neuromodulation (SNM) is proven to be an effective, minimal invasive treatment modality for FI. Despite the increasing application of SNM, the exact mechanisms of action remain unclear. The initial assumption of peripheral motor neurostimulation is not supported by increasing evidence, which report effects of SNM outside the pelvic floor. A new hypothesis states that afferent signals to the brain are essential for a successful therapy...
July 18, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28723725/meningeal-melanomatosis-following-discontinuation-of-dabrafenib-implications-for-the-maintenance-of-long-term-complete-remission
#16
Victoria Grätz, Nadine Lüttmann, Ozan Haase, Ewan A Langan, André Kemmling, Detlef Zillikens, Patrick Terheyden
A subset of 10-20% of patients under continuous BRAF inhibitor monotherapy achieve long-term progression-free and overall survival. Definitive criteria for the safe cessation of BRAF inhibitor monotherapy in treatment-responsive melanoma patients are lacking. We report a patient who remained in complete remission (CR) for 5 years under dabrafenib. The treatment was withdrawn because of concerns about cardiac toxicity. Four months thereafter the patient developed neurological symptoms, including diplopia and bilateral visual loss...
July 18, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28723673/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#17
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723559/kmt2a-and-kmt2b-mediate-memory-function-by-affecting-distinct-genomic-regions
#18
Cemil Kerimoglu, M Sadman Sakib, Gaurav Jain, Eva Benito, Susanne Burkhardt, Vincenzo Capece, Lalit Kaurani, Rashi Halder, Roberto Carlos Agís-Balboa, Roman Stilling, Hendrik Urbanke, Andrea Kranz, A Francis Stewart, Andre Fischer
Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723281/imaging-correlates-of-adult-glioma-genotypes
#19
Marion Smits, Martin J van den Bent
Primary brain tumors, most commonly gliomas, are histopathologically typed and graded as World Health Organization (WHO) grades I-IV according to increasing degrees of malignancy. These grades provide prognostic information and guidance on treatment such as radiation therapy and chemotherapy after surgery. Despite the confirmed value of the WHO grading system, results of a multitude of studies and prospective interventional trials now indicate that tumors with identical morphologic criteria can have highly different outcomes...
August 2017: Radiology
https://www.readbyqxmd.com/read/28722240/an-mri-hyperintense-acute-reperfusion-marker-is-related-to-elevated-peripheral-monocyte-count-in-acute-ischemic-stroke
#20
Zurab Nadareishvili, Marie Luby, Richard Leigh, Jignesh Shah, John K Lynch, Amie W Hsia, Richard T Benson, Lawrence L Latour
BACKGROUND AND PURPOSE: Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke...
July 19, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
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