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https://www.readbyqxmd.com/read/29345897/design-synthesis-and-biological-evaluation-of-1-benzylamino-2-hydroxyalkyl-derivatives-as-new-potential-disease-modifying-multifunctional-anti-alzheimer-s-agents
#1
Dawid Panek, Anna Więckowska, Jakub Jończyk, Justyna Godyń, Marek W Bajda, Tomasz Wichur, Anna Pasieka, Damijan Knez, Anja Pislar, Jan Korabecny, Ondrej Soukup, Vendula Sepsova, Raimon Sabaté, Janko Kos, Stanislav Gobec, Barbara Malawska
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, β-secretase, β-amyloid and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets - inhibition of β-secretase (IC50 hBACE-1 = 41...
January 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29330688/hepatocyte-nuclear-factors-as-possible-c-reactive-protein-transcriptional-inducer-in-the-liver-and-white-adipose-tissue-of-rats-with-experimental-chronic-renal-failure
#2
Elzbieta Sucajtys-Szulc, Alicja Debska-Slizien, Boleslaw Rutkowski, Ryszard Milczarek, Iwona Pelikant-Malecka, Tomasz Sledzinski, Julian Swierczynski, Marek Szolkiewicz
Inflammation related to chronic kidney disease (CKD) is an important clinical problem. We recently determined that hepatocyte nuclear factor 1α (HNF1α) was upregulated in the livers of chronic renal failure (CRF) rats-experimental model of CKD. Considering that the promoter region of gene encoding C-reactive protein (CRP) contains binding sites for HNF1α and that the loss-of-function mutation in the Hnfs1α leads to significant reduction in circulating CRP levels, we hypothesized that HNF1α can activate the Crp in CRF rats...
January 12, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29324682/malnutrition-inflammation-atherosclerosis-syndrome-mia-and-diet-recommendations-among-end-stage-renal-disease-patients-treated-with-maintenance-hemodialysis
#3
Małgorzata Maraj, Beata Kuśnierz-Cabala, Paulina Dumnicka, Agnieszka Gala-Błądzińska, Katarzyna Gawlik, Dorota Pawlica-Gosiewska, Anna Ząbek-Adamska, Małgorzata Mazur-Laskowska, Piotr Ceranowicz, Marek Kuźniewski
Malnutrition-inflammation-atherosclerosis syndrome is one of the causes of increased mortality in chronic kidney disease (CKD). The aim of the study was to assess the inflammation and nutritional status of patients in end-stage kidney disease treated with maintenance hemodialysis. The study included a group of 98 hemodialyzed patients with stage 5 CKD (38 women and 60 men). Albumin, prealbumin (PRE), and C-reactive protein (CRP) were measured in serum samples collected before mid-week dialysis. Fruit and vegetables frequency intakes were assessed with a questionnaire...
January 11, 2018: Nutrients
https://www.readbyqxmd.com/read/29322795/analysis-of-dna-methylation-and-microrna-expression-in-nut-nuclear-protein-in-testis-midline-carcinoma-of-the-sinonasal-tract-a-clinicopathological-immunohistochemical-and-molecular-genetic-study
#4
J Laco, H Kovarikova, M Chmelarova, H Vosmikova, K Sieglova, I Bubancova, P Dundr, K Nemejcova, J Michalek, P Celakovsky, R Mottl, I Sirak, M Vosmik, I Marek, T Geryk, J Mejzlik, J Satankova, A Ryska
The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0)...
2018: Neoplasma
https://www.readbyqxmd.com/read/29320517/explaining-the-decline-in-coronary-heart-disease-mortality-rates-in-the-slovak-republic-between-1993-2008
#5
Marek Psota, Piotr Bandosz, Eva Gonçalvesová, Mária Avdičová, Mária Bucek Pšenková, Martin Studenčan, Jarmila Pekarčíková, Simon Capewell, Martin O'Flaherty
OBJECTIVE: Between the years 1993 and 2008, mortality rates from coronary heart disease (CHD) in the Slovak Republic have decreased by almost one quarter. However, this was a smaller decline than in neighbouring countries. The aim of this modelling study was therefore to quantify the contributions of risk factor changes and the use of evidence-based medical therapies to the CHD mortality decline between 1993 and 2008. METHODS: We identified, obtained and scrutinised the data required for the model...
2018: PloS One
https://www.readbyqxmd.com/read/29317752/epstein-barr-virus-encoded-rnas-ebers-complement-the-loss-of-herpesvirus-telomerase-rna-vtr-in-virus-induced-tumor-formation
#6
Ahmed Kheimar, Benedikt B Kaufer
Marek's disease virus (MDV) is an alphaherpesvirus that causes fatal lymphomas in chickens and is used as a natural virus-host model for herpesvirus-induced tumorigenesis. MDV encodes a telomerase RNA subunit (vTR) that is crucial for efficient MDV-induced lymphoma formation; however, the mechanism is not completely understood. Similarly, Epstein Barr-virus (EBV) encodes two RNAs (EBER-1 and EBER-2) that are highly expressed in EBV-induced tumor cells, however their role in tumorigenesis remains unclear. Intriguingly, vTR and EBER-1 have interaction partners in common that are highly conserved in humans and chickens...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317059/pathophysiological-significance-of-protein-hydrophobic-interactions-an-emerging-hypothesis
#7
Marek Kieliszek, Boguslaw Lipinski
Fibrinogen is a unique protein that is converted into an insoluble fibrin in a single enzymatic event, which is a characteristic feature of fibrinogen due to its susceptibility to fibrinolytic degradation and dissolution. Although thrombosis is a result of activated blood coagulation, no explanation is being offered for the persistent presence of fibrin deposits in the affected organs. A classic example is stroke, in which the thrombolytic therapy is effective only during the first 3-4 h after the onset of thrombosis...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29313564/clinical-presentation-surgical-management-and-outcomes-of-patients-treated-for-aortic-stenosis-and-coronary-artery-disease-does-age-matter
#8
Bartłomiej Perek, Veronica Casadei, Mateusz Puślecki, Sebastian Stefaniak, Dawid Maison, Adrian Gwizdała, Anna Perek, Łukasz Szarpak, Marek Jemielity
BACKGROUND: Aortic stenosis and coronary artery disease (CAD) sharing similar risk factors are associated with aging of human population. AIM: The purpose of this study was to examine if age affects clinical presentation, intraoperative management and outcomes of patients that undergo simultaneous operations of aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). METHODS: The study involved 452 consecutive patients with the age of 64...
January 9, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29305587/consensus-molecular-subtypes-of-colorectal-cancer-are-recapitulated-in-in-vitro-and-in-vivo-models
#9
Janneke F Linnekamp, Sander R van Hooff, Pramudita R Prasetyanti, Raju Kandimalla, Joyce Y Buikhuisen, Evelyn Fessler, Prashanthi Ramesh, Kelly A S T Lee, Grehor G W Bochove, Johan H de Jong, Kate Cameron, Ronald van Leersum, Hans M Rodermond, Marek Franitza, Peter Nürnberg, Laura R Mangiapane, Xin Wang, Hans Clevers, Louis Vermeulen, Giorgio Stassi, Jan Paul Medema
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed...
January 5, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29300536/autoimmune-polyendocrine-syndrome-type-2-in-patient-with-severe-allergic-asthma-treated-with-omalizumab
#10
Anna Rams, Marek Żółciński, Weronika Zastrzeżyńska, Stanisław Polański, Agnieszka Serafin, Joanna Wilańska, Jacek Musiał, Stanisława Bazan-Socha
Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis...
January 4, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29297472/the-effect-of-hybrid-treatment-on-the-rehabilitation-and-clinical-condition-of-patients-with-multi-vessel-coronary-artery-disease
#11
Joanna Foik, Anna Brzęk, Marek J Gierlotka, Michał O Zembala, Mariusz Gąsior, Marian Zembala
INTRODUCTION    Rehabilitation after coronary revascularization procedures is an intrinsic element of treatment during the in-hospital period. OBJECTIVES    The aim of this study was to compare the course and effects of rehabilitation in patients receiving hybrid or classical treatment during the in-hospital period. PATIENTS AND METHODS    Two hundred patients participating in a prospective, random-ized clinical trial (POLMIDES), that assessed the effect of hybrid treatment on in-hospital outcomes and remote results in patients with multi-vessel coronary artery disease were ana-lysed...
January 2, 2018: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/29289896/from-instruction-to-output-wnt-pcp-signaling-in-development-and-cancer
#12
REVIEW
Ashley Ceinwen Humphries, Marek Mlodzik
Planar cell polarity (PCP) provides positional information to direct tissue patterning and morphogenesis. While much of the molecular detail of the pathway has been delineated in Drosophila, ensuing studies have shown considerable conservation of both the components and mechanisms of signaling in vertebrates. A recognized feature of PCP is the asymmetric localization of components that translates a global directional cue into a polarized downstream output. Here we discuss recent advances in the PCP field, from the organization of these asymmetric complexes to their upstream directional regulation by Wnt ligands...
December 28, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29287680/monitoring-the-uptake-of-live-avian-vaccines-by-their-detection-in-feathers
#13
Irit Davidson, Amira Natour-Altory, Israel Raibstein, Eitan Kin, Yaad Dahan, Haim Krispin, Nati Elkin
Protection against diseases caused by the avian viruses, Marek's disease, Infectious laryngotracheitis, chicken anemia and turkey meningoencephalitis is achieved by live vaccines. The application quality is important to assure proper uptake in commercial flocks. We describe a novel evaluation method for the vaccination process by sequential monitoring the vaccine viruses in feathers. Feather collection is easy, non-invasive and non-lethal for the birds, therefore advantageous for monitoring purposes. To demonstrate the vaccine virus presence, an innovative assay of nested real-time amplification was approached because vaccine viruses presence in vivo is less abundant comparing to virulent wild-type isolates...
December 26, 2017: Vaccine
https://www.readbyqxmd.com/read/29285347/patient-specific-simulations-for-planning-treatment-in-congenital-heart-disease
#14
Claudio Capelli, Emilie Sauvage, Giuliano Giusti, Giorgia M Bosi, Hopewell Ntsinjana, Mario Carminati, Graham Derrick, Jan Marek, Sachin Khambadkone, Andrew M Taylor, Silvia Schievano
Patient-specific computational models have been extensively developed over the last decades and applied to investigate a wide range of cardiovascular problems. However, translation of these technologies into clinical applications, such as planning of medical procedures, has been limited to a few single case reports. Hence, the use of patient-specific models is still far from becoming a standard of care in clinical practice. The aim of this study is to describe our experience with a modelling framework that allows patient-specific simulations to be used for prediction of clinical outcomes...
February 6, 2018: Interface Focus
https://www.readbyqxmd.com/read/29284675/test-retest-reproducibility-for-the-tau-pet-imaging-agent-flortaucipir-f-18
#15
Michael D Devous, Abhinay D Joshi, Michael Navitsky, Sudeepti Southekal, Michael J Pontecorvo, Haiqing Shen, Ming Lu, William R Shankle, John P Seibyl, Ken Marek, Mark A Mintun
Background: Alzheimer's disease (AD) is characterized by beta-amyloid plaques (Aβ) and tau neurofibrillary tangles (NFTs). There are several PET imaging biomarkers for Aβ including 11C-PiB and 18F florbetapir. Recently, PET tracers for tau NFTs have become available and have shown utility in detection and monitoring of neurofibrillary pathology over time. Flortaucipir F 18 is one such tracer. Initial clinical studies indicated greater tau binding in AD and MCI patients compared to controls in a pattern consistent with tau pathology observed at autopsy...
December 28, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29282648/a-scintigraphic-demonstration-of-a-solitary-orbital-paget-s-disease
#16
Ewa Cyranska-Chyrek, Ewelina Szczepanek-Parulska, Marek Ruchala
No abstract text is available yet for this article.
December 27, 2017: Endocrine
https://www.readbyqxmd.com/read/29277835/serum-levels-of-visfatin-omentin-and-irisin-in-patients-with-end-stage-lung-disease-before-and-after-lung-transplantation
#17
Marek Ochman, Marcin Maruszewski, Jacek Wojarski, Sławomir Żegleń, Wojtek Karolak, Anita Stanjek-Cichoracka, Piotr Przybyłowski, Marian Zembala, Michał Kukla
BACKGROUND The aim of this study was to investigate serum concentrations of visfatin, irisin, and omentin in patients with end-stage lung diseases (ESLD) before and after lung transplantation (LTx) and to find relationship between adipokines levels and clinical outcomes. MATERIAL AND METHODS Fourteen consecutive lung transplant recipients (six males and seven females; age 32.0±14.2 years; body mass index (BMI) 21.8±5.3 kg/m²) who underwent lung transplantation with initial diagnosis of respiratory failure due to cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) were included...
December 26, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29274027/chemotherapy-and-echocardiographic-indices-in-patients-with-non-hodgkin-lymphoma-the-onco-echo-study
#18
Katarzyna Mizia-Stec, Marek Elżbieciak, Maciej T Wybraniec, Monika Różewicz, Artur Bodys, Wojciech Braksator, Zbigniew Gąsior, Piotr Gościniak, Tomasz Hryniewiecki, Jarosław Kasprzak, Andrzej Wojtarowicz, Barbara Zdziarska, Edyta Płońska-Gościniak
The cardiotoxicity of chemotherapy (CTx) for non-Hodgkin's lymphomas is not well recognized. In order to facilitate individual risk counseling for patients, we analyzed the effect of CTx on echocardiographic indices in regard to clinical data in patients treated for non-Hodgkin's lymphoma (NHL). A prospective multicenter ONCO-ECHO trial included 67 patients with NHL (45 patients with DLBCL (diffuse large B cell lymphoma) and 22 with non-DLBCL). Patients received standard CTx, primarily R-CHOP, CHOP, R-COP and COP regimens...
December 22, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29261783/somatic-instability-of-the-expanded-gaa-repeats-in-friedreich-s-ataxia
#19
Ashlee Long, Jill S Napierala, Urszula Polak, Lauren Hauser, Arnulf H Koeppen, David R Lynch, Marek Napierala
Friedreich's ataxia (FRDA) is a genetic neurodegenerative disorder caused by transcriptional silencing of the frataxin gene (FXN) due to expansions of GAA repeats in intron 1. FRDA manifests with multiple symptoms, which may include ataxia, cardiomyopathy and diabetes mellitus. Expanded GAA tracts are genetically unstable, exhibiting both expansions and contractions. GAA length correlates with severity of FRDA symptoms and inversely with age of onset. Thus, tissue-specific somatic instability of long GAA repeats may be implicated in the development of symptoms and disease progression...
2017: PloS One
https://www.readbyqxmd.com/read/29259247/ras-pathway-mutation-patterns-define-epigenetic-subclasses-in-juvenile-myelomonocytic-leukemia
#20
Daniel B Lipka, Tania Witte, Reka Toth, Jing Yang, Manuel Wiesenfarth, Peter Nöllke, Alexandra Fischer, David Brocks, Zuguang Gu, Jeongbin Park, Brigitte Strahm, Marcin Wlodarski, Ayami Yoshimi, Rainer Claus, Michael Lübbert, Hauke Busch, Melanie Boerries, Mark Hartmann, Maximilian Schönung, Umut Kilik, Jens Langstein, Justyna A Wierzbinska, Caroline Pabst, Swati Garg, Albert Catalá, Barbara De Moerloose, Michael Dworzak, Henrik Hasle, Franco Locatelli, Riccardo Masetti, Markus Schmugge, Owen Smith, Jan Stary, Marek Ussowicz, Marry M van den Heuvel-Eibrink, Yassen Assenov, Matthias Schlesner, Charlotte Niemeyer, Christian Flotho, Christoph Plass
Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome...
December 19, 2017: Nature Communications
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