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https://www.readbyqxmd.com/read/29334419/a-metallo-pro-drug-to-target-cu-ii-in-the-context-of-alzheimer-s-disease
#1
Amandine Conte-Daban, Vinita Ambike, Régis Guillot, Nicolas Delsuc, Clotilde Policar, Christelle Hureau
Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn(II)-based superoxide dismutase mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target Cu(II) associated events, i.e. Cu(II)-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-beta (Abeta) peptide aggregation. Complex 1+ is able to remove Cu(II) from Abeta, stop ROS and prevent alteration of Abeta aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity...
January 15, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29329711/colorimetric-logic-gate-for-alkaline-phosphatase-based-on-copper-ii-based-metal-organic-frameworks-with-peroxidase-like-activity
#2
Caihong Wang, Jie Gao, Yili Cao, Hongliang Tan
Nanozymes have been extensively exploited in the construction of colorimetric sensors in the past decade. However, as lack of specific recognition element, these sensors are mostly limited in the detection of hydrogen peroxide and its related agents. In this work, a colorimetric assay for the detection of alkaline phosphatase (ALP) activity was developed by employing copper (II)-based metal-organic frameworks (Cu-MOFs) as peroxidase mimic and pyrophosphate (PPi) as recognition element. Benefiting from its intrinsic porosity, Cu-MOFs built from one-step self-assembly showed a superior catalytic activity over horseradish peroxidase...
April 3, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29327922/a-constrained-tetrapeptide-as-a-model-of-cu-i-binding-sites-involving-cu4s6-clusters-in-proteins
#3
Edit Mesterházy, Colette Lebrun, Attila Jancsó, Pascale Delangle
Peptide design is an efficient strategy to create relevant models of natural metal binding sites found in proteins. The two short tetrapeptides Ac-Cys-dPro-Pro-Cys-NH2 (CdPPC) and Ac-Cys-Pro-Gly-Cys-NH2 (CPGC) were synthesized and studied as mimics of Cu(I) binding sites involved in Cu homeostasis. Both sequences contain β turn inducing motifs to rigidify the peptide backbone structure and thereby preorganize the metal-binding side chains. The more constrained structure of the peptide CdPPC with respect to CPGC was evidenced by the measurements of the temperature coefficients of the amide protons by 1H NMR, which suggest a solvent-shielded intramolecular hydrogen bond in CdPPC, and no H-bond in CPGC...
January 12, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29327381/oxidative-stress-impairs-myocyte-autophagy-resulting-in-myocyte-hypertrophy
#4
Jia-Pu Wang, Rui-Fang Chi, Ke Wang, Teng Ma, Xiao-Fei Guo, Xiao-Li Zhang, Bao Li, Fu-Zhong Qin, Xue-Bin Han, Bian-Ai Fan
Insufficient or excessive myocyte autophagy is associated with left ventricular (LV) hypertrophy. Reactive oxygen species mediate myocyte hypertrophy in vitro and pressure overload-induced LV hypertrophy in vivo. In the present study, we tested the hypothesis that oxidative stress induces autophagy impairment that results in myocyte hypertrophy. H9C2 cardiomyocytes were exposed to 10 and 50 μm hydrogen peroxide (H2 O2 ) for 48 h pretreated with autophagy inhibitor 3-methyladenine (3-MA). Male Sprague-Dawley rats underwent abdominal aortic constriction (AAC) or sham operation...
January 12, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29320615/an-intervertebral-disc-whole-organ-culture-system-to-investigate-proinflammatory-and-degenerative-disc-disease-condition
#5
Gernot Lang, Yishan Liu, Janna Geries, Zhiyu Zhou, David Kubosch, Norbert Südkamp, R Geoff Richards, Mauro Alini, Sibylle Grad, Zhen Li
OBJECTIVE: The aim of this study was to compare the effect of different disease initiators of degenerative disc disease (DDD) within an intervertebral disc (IVD) organ culture system, and to understand the interplay between inflammation and degeneration in the early stage of DDD. DESIGN: Bovine caudal IVDs were cultured within a bioreactor for up to 11 days. Control group was cultured under physiological loading (0.02-0.2 MPa; 0.2 Hz; 2h/day) and high glucose (4...
January 10, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29315946/assemblies-of-bodipy-porphyrin-phthalocyanine-and-c60-moieties-as-artificial-models-of-photosynthesis-synthesis-supramolecular-interactions-and-photophysical-studies
#6
Dennis K P Ng, Xiao-Fei Chen, Mohamed El-Khouly, Kei Ohkubo, Shunichi Fukuzumi
A series of light-harvesting conjugates based on a zinc(II) phthalocyanine core with either two or four boron dipyrromethene (BODIPY) or porphyrin units have been synthesized and characterized. The conjugation of BODIPY/porphyrin units can extend the absorptions of the phthalocyanine core to cover most of the visible region. Upon addition of an imidazole-substituted C60 (C60Im), it can axially bind to the zinc(II) center of the phthalocyanine core via metal-ligand interactions. The resulting complexes form photosynthetic antenna-reaction center mimics in which the BODIPY/porphyrin units serve as the antennas to capture the light and transfer the energy to the phthalocyanine core via efficient excitation energy transfer...
January 6, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29308051/microrna-200c-3p-regulates-autophagy-via-upregulation-of-endoplasmic-reticulum-stress-in-pc-3-cells
#7
Eun Jung Sohn
Background: Autophagy is a response to cellular and environmental conditions and facilitates cell survival. Here, we investigated the role of ectopic expression of microRNA (miRNA) 200c-3p in autophagy. Methods: miRNA mimics were used to overexpress miRNAs. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed to analyze miRNA expression. RT-qPCR and western blotting were performed to determine the expression levels of inositol requiring protein-1 (IRE1α), activating transcription factor-6 (ATF6), C/EBP homologous protein (CHOP), and light chain-3 (LC3)...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29291403/electrical-stimulation-as-a-conditioning-strategy-for-promoting-and-accelerating-peripheral-nerve-regeneration
#8
J L B Senger, V M K Verge, H S J Macandili, J L Olson, K M Chan, C A Webber
The delivery of a nerve insult (a "conditioning lesion") prior to a subsequent test lesion increases the number of regenerating axons and accelerates the speed of regeneration from the test site. A major barrier to clinical translation is the lack of an ethically acceptable and clinically feasible method of conditioning that does not further damage the nerve. Conditioning electrical stimulation (CES), a non-injurious intervention, has previously been shown to improve neurite outgrowth in vitro. In this study, we examined whether CES upregulates regeneration-associated gene (RAG) expression and promotes nerve regeneration in vivo, similar to a traditional nerve crush conditioning lesion (CCL)...
December 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29290532/thrombolysis-alert-in-hassan-ii-university-teaching-hospital-of-fez-morocco-a-prospective-study-of-2-years
#9
Moussa Toudou Daouda, Siham Bouchal, Naima Chtaou, Aouatef Midaoui, Zouahyr Souirti, Faouzi Belahsen
BACKGROUND: Thrombolysis alert (TA) is a procedure triggered every time a patient consults for sudden focal neurological deficit within 4.5 hours. OBJECTIVE: We aimed to determine firstly the etiological profile of TA and secondly to evaluate the delays in the management not only of thrombolyzed patients but also of nonthrombolyzed patients to determine the intrahospital delays to optimize. METHODS: Patients aged over 18 years who consulted for sudden focal neurological deficit within 4...
December 29, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29288416/anticancer-activity-of-schiff-base-poloxamer-p85-combination-against-kidney-cancer
#10
Ayşegül Doğan, Selami Demirci, Dilek Telci, Serli Canikyan, Merve Kongur, Bülent Dede, Fikrettin Şahin
PURPOSE: Renal cell carcinoma (RCC) accounts for approximately 80% of the primary renal cancers, and current treatment strategies are not sufficient to provide a certain solution. Since there are not many treatment options, interest in discovery of alternative drugs has increased. METHODS: In the current study, anticancer activity of a novel heterodinuclear Cu(II)-Mn(II) complex (Schiff base-SB) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (pluronic) P85 was tested against RCC...
December 29, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29286428/stenosis-of-the-inferior-vena-cava-a-murine-model-of-deep-vein-thrombosis
#11
Holly Payne, Alexander Brill
Deep vein thrombosis (DVT) and its devastating complication, pulmonary embolism, are a severe health problem with high mortality. Mechanisms of thrombus formation in veins remain obscure. Lack of mobility (e.g., after surgery or long-haul flights) is one of the main factors leading to DVT. The pathophysiological consequence of the lack of mobility is blood flow stagnation in venous valves. Here, a model is described that mimics such flow disturbance as a thrombosis-driving factor. In this model, partial flow restriction (stenosis) in the inferior vena cava (IVC) is created...
December 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285288/synthetic-nickel-containing-superoxide-dismutase-attenuates-para-phenylenediamine-induced-bladder-dysfunction-in-rats
#12
Bing-Juin Chiang, Tien-Wen Chen, Shiu-Dong Chung, Way-Zen Lee, Chiang-Ting Chien
Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285287/mertk-inhibition-by-rxdx-106-in-mertk-activated-gastric-cancer-cell-lines
#13
Jung Eun Kim, Youjin Kim, Gary Li, Seung Tae Kim, Kyung Kim, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Hyuk Lee, Tae Sung Sohn, Kyoung-Mee Kim, Won Ki Kang, Jeeyun Lee
RXDX-106 is a potent and selective type II pseudo-irreversible (slow off-rate) inhibitor of TYRO3, AXL, MER and c-MET. MER tyrosine kinase (MerTK) is expressed in a variety of malignancies, including gastric cancer (GC). The oncogenic potential of MerTK is supported by various lines of evidence. First, we surveyed 10 GC cell lines for MerTK protein overexpression and MerTk phosphorylation. We next evaluated the change of downstream signaling molecules including (p)-ERK and (p)-AKT, following RXDX-106 treatment...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281262/binding-of-zn-ii-to-tropomyosin-receptor-kinase-a-in-complex-with-its-cognate-nerve-growth-factor-insights-from-molecular-simulation-and-in-vitro-essays
#14
Adriana Pietropaolo, Antonio Magrì, Valentina Greco, Valeria Losasso, Diego La Mendola, Sebastiano Sciuto, Paolo Carloni, Enrico Rizzarelli
The binding of the human nerve growth factor (NGF) protein to the tropomyosin-receptor-kinase A (TrkA) is associated with Alzhemeir's development. Owing to the large presence of zinc(II) ions in the synaptic compartments, the zinc ions might be bound to the complex in vivo. Here, we have identified a putative zinc binding site using a combination of computations and experiments. First, we have predicted structural features of the NGF/TrkA complex in aqueous solution by molecular simulation. Metadynamics free energy calculations suggest that these are very similar to those in the X-ray structure...
December 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29259754/discovery-of-new-sulfonamide-carbonic-anhydrase-ix-inhibitors-incorporating-nitrogenous-bases
#15
Alessio Nocentini, Silvia Bua, Carrie L Lomelino, Robert McKenna, Marta Menicatti, Gianluca Bartolucci, Barbara Tenci, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Paola Gratteri, Claudiu T Supuran
Incorporation of the purine/pyrimidine moieties as tails to classical benzenesulfonamide scaffolds afforded two series of human (h) carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The compounds were designed according to the molecular hybridization approach, in order to modulate the interaction with different CA isozymes and exploit the antitumor effect of uracil and adenine derivatives in parallel and synergic mode to the inhibition of the tumor-associated hCA IX. The sulfonamides were investigated as inhibitors of four isoforms, cytosolic hCA I/II and transmembrane hCA IV/IX...
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29233731/do-different-diagnostic-criteria-cause-impact-polycystic-ovary-syndrome-diagnosis-for-adolescents
#16
Sinem Akgül, Yasemin Düzçeker, Nuray Kanbur, Orhan Derman
OBJECTIVE: While early diagnosis of polycystic ovary syndrome (PCOS) in adolescents may allow for earlier treatment and prevention of chronic disorders, incorrect or premature diagnosis carries risks of unnecessary treatment and psychological distress. There is no consensus concerning which diagnostic criteria to use for adolescents and current criteria vary. The objective of this study was to determine whether using different diagnostic criteria will affect PCOS diagnosis in adolescents...
December 9, 2017: Journal of Pediatric and Adolescent Gynecology
https://www.readbyqxmd.com/read/29232694/hyperbranched-poly-%C3%AF%C2%B5-lysine-substrate-presenting-the-laminin-sequence-yigsr-induces-the-formation-of-spheroids-in-adult-bone-marrow-stem-cells
#17
Valeria Perugini, Steve T Meikle, Anna L Guildford, Matteo Santin
Unlike the fibroblast-like cells formed upon monolayer culture of human mesenchymal stem cells, the natural stem cell niche of the bone marrow and other types of tissues favours the formation of 3-dimensional (3D) cell clusters. The structuring and biological activity of these clusters are regulated by the contacts established by cells with both the basement membrane and neighbour cells and results in their asymmetric division and the consequent maintenance of both a stem population and a committed progeny...
2017: PloS One
https://www.readbyqxmd.com/read/29222438/new-insights-into-the-mechanism-of-nickel-superoxide-degradation-from-studies-of-model-peptides
#18
Daniel Tietze, Jana Sartorius, Banabithi Koley Seth, Kevin Herr, Pascal Heimer, Diana Imhof, Doreen Mollenhauer, Gerd Buntkowsky
A series of small, catalytically active metallopeptides, which were derived from the nickel superoxide dismutase (NiSOD) active site were employed to study the mechanism of superoxide degradation especially focusing on the role of the axial imidazole ligand. In the literature, there are contradicting propositions about the catalytic importance of the N-terminal histidine. Therefore, we studied the stability and activity of a set of eight NiSOD model peptides, which represent the major model systems discussed in the literature to date, yet differing in their length and their Ni-coordination...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29216403/staphylococcus-aureus-impacts-pseudomonas-aeruginosa-chronic-respiratory-disease-in-murine-models
#19
C Cigana, I Bianconi, R Baldan, M De Simone, C Riva, B Sipione, G Rossi, D M Cirillo, A Bragonzi
Background: Staphylococcus aureus and Pseudomonas aeruginosa are key bacterial pathogens of the respiratory tract in patients with cystic fibrosis (CF). While P. aeruginosa chronic bronchial infection is associated with a poorer prognosis, the consequences of S. aureus colonization on CF outcomes are controversial. Methods: In this paper, murine models of infection resembling traits of the CF human airways disease have been revisited using an infection schedule that mimics the sequence of events of pulmonary disease in CF patients...
December 5, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29215706/map-and-correlate-intracellular-calcium-response-and-matrix-deposition-in-cartilage-under-physiological-oxygen-tensions
#20
Jin Zhou, Danyang Yue, Yuying Bai, Fei Kong, Jun Pan
Face to the limited repair capability of cartilage, we intended to find out signaling responsible for its matrix synthesis. Since spontaneous calcium response likes a label of cell status, here it was mapped in fresh and 24 h cultured in situ chondrocytes under oxygen tensions of 20%, 5% and 1% as well as mimic hypoxia conditions. The calcium source was traced using ethylene glycol-bis (β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and thapsigargin (TG) to treat cartilage. Their relative matrix of type II collagen (COLL-II) and glycosaminoglycan (GAG) were quantified after cultured for three and seven days...
December 7, 2017: Journal of Cellular Physiology
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