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https://www.readbyqxmd.com/read/29323501/the-pivotal-role-of-copper-in-neurodegeneration-a-new-strategy-for-the-therapy-of-neurodegenerative-disorders
#1
Roberta Giampietro, Francesco Spinelli, Marialessandra Contino, Nicola Antonio Colabufo
Copper is an essential trace element for human body since it is a cofactor of several enzymes and proteins and plays a pivotal role in several biological functions (e.g., respiration, protection from oxidative damage, iron metabolism, etc.), also including the central nervous system development and functioning (e.g. synthesis of neurotransmitters, myelination, activation of neuropeptides, etc.). Therefore, copper dysmetabolism is associated with different toxic effects, mainly represented by oxidative stress, and it has been reported in many neurodegenerative disorders, such as Wilson's disease, Menkes disease, Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis...
January 11, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29318879/intelligent-mos2-nanotheranostic-for-targeted-and-enzyme-ph-nir-responsive-drug-delivery-to-overcome-cancer-chemotherapy-resistance-guided-by-pet-imaging
#2
Xinghua Dong, Wenyan Yin, Xiao Zhang, Shuang Zhu, Xiao He, Jie Yu, Jiani Xie, Zhao Guo, Liang Yan, Xiangfeng Liu, Qing Wang, Zhanjun Gu, Yuliang Zhao
Chemotherapy resistance remains a major hurdle for cancer therapy in clinic due to poor cellular uptake, insufficient intracellular release of drugs. Herein, an intelligent, multifunctional MoS2 nanotheranostic (MoS2-PEI-HA) ingeniously decorating with biodegradable hyaluronic acid (HA) assisted by polyethyleneimine (PEI) is reported to combat drug-resistant breast cancer (MCF-7-ADR) after loading with chemotherapy drug doxorubicin (DOX). The HA can not only target CD44-overexpressing MCF-7-ADR, but also be degraded by hyaluronidase (HAase) that is concentrated in the tumor microenvironment and thus to accelerate doxorubicin (DOX) release...
January 10, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29318368/increased-levels-of-advanced-glycation-end-products-positively-correlate-with-iron-overload-and-oxidative-stress-markers-in-patients-with-%C3%AE-thalassemia-major
#3
Maryam Sadat Mirlohi, Hamid Yaghooti, Saeed Shirali, Ali Aminasnafi, Samaneh Olapour
The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects...
January 9, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29305959/enhanced-in-vitro-tigecycline-activity-in-the-presence-of-chelating-agents
#4
Amelia N Deitchman, Ravi Shankar Prasad Singh, Kenneth H Rand, Hartmut Derendorf
Lack of availability of novel antibiotic agents and the rise of resistance to existing therapies has led clinicians to utilize combination therapy to adequately treat bacterial infections. Here we examine how chelators may impact the in vitro activity of tigecycline (TIG) against Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. Minimum inhibitory concentrations (MICs) were determined by broth dilution with and without various combinations of chelators (EDTA and other tetracyclines), and metal ions (i...
January 3, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29303755/the-effect-of-edta-on-the-antibacterial-activity-of-sodium-hypochlorite
#5
Rita Azevedo Senna, Andressa Raquel Spohr, Andressa Heberle Gastmann, Fernanda Geraldo Pappen, Regina Karla de Pontes Lima, Renata Dornelles Morgental
The combination of ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite (NaOCl) has been suggested as an irrigant for root canal therapy. However, the chemical interaction between these agents is a complex subject that is not completely understood. The aim of this study was to evaluate the interference of an EDTA chelating agent in the antibacterial ability of NaOCl, while also considering variations in methodology. Various concentrations of NaOCl and EDTA solutions were prepared from 6% and 17% solutions, respectively...
January 2018: General Dentistry
https://www.readbyqxmd.com/read/29303588/photochemical-activation-of-enediyne-warheads-a-potential-tool-for-targeted-antitumor-therapy
#6
Prabuddha Bhattacharya, Amit Basak, Adam Campbell, Igor V Alabugin
This review outlines recent approaches to further fine-tuning photoactivated enediyne "warheads" by using a variety of factors such as the release of internal strain, chelation, pH changes, modulations of photophysical approaches. Enediynes are shown to be a highly modifiable motif, and this review establishes a foundation upon which more advancements can be made to increase their efficacy. Many of the recent advances came from a productive interplay between oxidative DNA modification chemistry and unique properties of C-lysine conjugates, enabled by the presence of multiple amino groups of different basicity...
January 5, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29302691/amelioration-of-endotoxin-induced-inflammatory-toxic-response-by-a-metal-chelator-in-rat-eyes
#7
Mohammad Shoeb, Min Zhang, Tianlin Xiao, Misha F Syed, Naseem H Ansari
Purpose: Metal ions play a key role in exacerbating toxicity associated with oxidative stress and inflammation. This study examines the effects of a formulation containing the metal chelator ethylenediaminetetraacetic acid (EDTA) and permeability enhancer methyl sulfonyl methane (MSM) on the early course of inflammation in endotoxin-induced uveitis (EIU). The proprietary MSM/EDTA formulation of Livionex, Inc., which was used for this study, is covered by several patents and pending patent applications...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29301806/inherited-haemochromatosis-with-c282y-mutation-in-a-patient-with-alpha-thalassaemia-a-treatment-dilemma
#8
Mohammed Abdullah Al Qasem, Fayez Hanna, Usira S Vithanarachchi, Alhossain A Khalafallah
A Caucasian 24-year-old female patient suffers from two hereditary disorders: alpha-thalassaemia, which is prevalent in Asia and rare in Europe, and haemochromatosis, which is prevalent among northern Europe and rare in Asia. The clinical presentation and management of one of these diseases is controversial for the other. She presented 5 years ago with a clinical picture of refractory iron-deficiency anaemia secondary to menorrhagia. On treating her with the standard iron therapy, her anaemia persists although with adquate iron stores...
January 4, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29301755/copper-64-labeled-daratumumab-as-a-pet-ct-imaging-tracer-for-multiple-myeloma
#9
Enrico Caserta, Junie Chea, Megan Minnix, Domenico Viola, Steven Vonderfecht, Paul Yazaki, Desiree Crow, Jihane Khalife, James F Sanchez, Joycelynne M Palmer, Susanta Hui, Nadia Carlesso, Jonathan Keats, Young Kim, Ralf Buettner, Guido Marcucci, Steven Rosen, John Shively, David Colcher, Amrita Krishnan, Flavia Pichiorri
As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often non-predictable, attention has increasingly focused on developing novel diagnostic criteria to also account for disease dissemination. Positron emission tomography/computed tomography (PET/CT) is often used as a non-invasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluoro-deoxyglucose (18F-FDG) is a function of the metabolic activity of both malignant and non-malignant cells, results frequently lack sufficient specificity...
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29291165/construction-of-multifunctional-fe3o4-mtx-hbc-nanoparticles-for-mr-imaging-and-photothermal-therapy-chemotherapy
#10
Qiang Zhang, Wenjun Shan, Chaochao Ai, Zhiwei Chen, Tiantian Zhou, Xiaolin Lv, Xi Zhou, Shefang Ye, Lei Ren, Xiumin Wang
To accomplish effective cancer imaging and integrated therapy, the multifunctional nanotheranostic Fe3O4-MTX@HBc core-shell nanoparticles (NPs) were designed. A straightforward method was demonstrated for efficient encapsulation of magnetic NPs into the engineered virus-like particles (VLPs) through the affinity of histidine tags for the methotrexate (MTX)-Ni2+ chelate. HBc144-His VLPs shell could protect Fe3O4-MTX NPs from the recognition by the reticuloendothelial system as well as could increase their cellular uptake efficiency...
2018: Nanotheranostics
https://www.readbyqxmd.com/read/29290983/bottom-up-synthesis-of-ultra-small-molybdenum-disulfide-polyvinylpyrrolidone-nanosheets-for-imaging-guided-tumor-regression
#11
Jiulong Zhao, Chunhua Zhou, Mao Li, Jialing Li, Guixiang Li, Dan Ma, Zhaoshen Li, Duowu Zou
The two-dimensional molybdenum disulfide (MoS2) nanosheet has been extensively studied as a novel photothermal transducing agent. However, top-down exfoliation to produce MoS2 nanosheets is inefficient, and MoS2 nanosheet surface modification procedures are complex. Here, we report the synchronous synthesis and surface modification of 2D MoS2 nanosheets with a polyvinylpyrrolidone (PVP)-assisted one-pot hydrothermal method. Due to the chelating-coordinating effect between the lone-pair electrons of the PVP carbonyl oxygen and the unoccupied 4d orbitals of molybdenum, the PVP chains could graft onto the surface of MoS2 and guide the growth of the nanosheets...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29289598/why-should-neuroscientists-worry-about-iron-the-emerging-role-of-ferroptosis-in-the-pathophysiology-of-neuroprogressive-diseases
#12
REVIEW
Gerwyn Morris, Michael Berk, André F Carvalho, Michael Maes, Adam J Walker, Basant K Puri
Ferroptosis is a unique form of programmed death, characterised by cytosolic accumulation of iron, lipid hydroperoxides and their metabolites, and effected by the fatal peroxidation of polyunsaturated fatty acids in the plasma membrane. It is a major driver of cell death in neurodegenerative neurological diseases. Moreover, cascades underpinning ferroptosis could be active drivers of neuropathology in major psychiatric disorders. Oxidative and nitrosative stress can adversely affect mechanisms and proteins governing cellular iron homeostasis, such as the iron regulatory protein/iron response element system, and can ultimately be a source of abnormally high levels of iron and a source of lethal levels of lipid membrane peroxidation...
December 28, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29287249/multifunctional-thiosemicarbazones-and-deconstructed-analogues-as-a-strategy-to-study-the-involvement-of-metal-chelation-sigma-2-%C3%AF-2-receptor-and-p-gp-protein-in-the-cytotoxic-action-in%C3%A2-vitro-and-in%C3%A2-vivo-activity-in-pancreatic-tumors
#13
Maria Laura Pati, Mauro Niso, Dirk Spitzer, Francesco Berardi, Marialessandra Contino, Chiara Riganti, William G Hawkins, Carmen Abate
The aggressiveness of pancreatic cancer urgently requires more efficient treatment options. Because the sigma-2 (σ2) receptor was recently proposed as a promising target for pancreatic cancer therapy, we explored our previously developed multifunctional thiosemicarbazones, designed to synergistically impair cell energy levels, by targeting σ2 and P-gp proteins and chelating Iron. A deconstruction approach was herein applied by removing one function at a time from the potent multifunctional thiosemicarbazones 1 and 2, to investigate the contribution to cytotoxicity of each target involved...
December 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29285884/two-year-observational-study-of-deferiprone-in-superficial-siderosis
#14
Remi A Kessler, Xu Li, Kateryna Schwartz, Hwa Huang, Maureen A Mealy, Michael Levy
INTRODUCTION: Superficial siderosis is a rare, neurodegenerative disease caused by toxic accumulation of hemosiderin on the surface of the brain and the spinal cord, most commonly from chronic subarachnoid hemorrhage. AIMS: The aim of this study was to assess the clinical and radiological outcomes of superficial siderosis patients using deferiprone, a cell permeant iron chelator. Subjects obtained pre- and post-treatment brain MRIs and weekly laboratory tests. Osirix software was used to develop a method of quantifying hemosiderin deposition...
December 28, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29261151/iron-overload-and-chelation-therapy-in-non-transfusion-dependent-thalassemia
#15
REVIEW
Rayan Bou-Fakhredin, Abdul-Hamid Bazarbachi, Bachar Chaya, Joseph Sleiman, Maria Domenica Cappellini, Ali T Taher
Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading...
December 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29247906/long-term-monitoring-of-breath-methane
#16
Daniela Polag, Frank Keppler
In recent years, methane as a component of exhaled human breath has been considered as a potential bioindicator providing information on microbial activity in the intestinal tract. Several studies indicated a relationship between breath methane status and specific gastrointestinal disease. So far, almost no attention has been given to the temporal variability of breath methane production by individual persons. Thus here, for the first time, long-term monitoring was carried out measuring breath methane of three volunteers over periods between 196 and 1002days...
December 13, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29235740/thalassemia-major-and-intermedia-in-patients-older-than-35-years-a-single-center-experience
#17
Liat Shargian-Alon, Oren Pasvolsky, Pia Raanani
BACKGROUND: During the past decades, beta thalassemia major (TM) and beta thalassemia intermedia (TI) have transformed from a universally fatal disease at a young age into a chronic disease. This advancement is attributed to improved chelation therapy as well as enhanced management strategies, with focused attention on disease and treatment-related complications. OBJECTIVES: To describe characteristics of adults with thalassemia as well as treatment modalities, disease and treatment-related complications, and socioeconomic information of the patients...
December 2017: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/29235162/iron-chelating-effect-of-silymarin-in-patients-with-%C3%AE-thalassemia-major-a-crossover-randomised-control-trial
#18
Hadi Darvishi-Khezri, Ebrahim Salehifar, Mehrnoush Kosaryan, Hossein Karami, Mohammadreza Mahdavi, Abbas Alipour, Aily Aliasgharian
This study aimed to determine the potential iron-chelating effects of silymarin in patients with β-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups...
December 13, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29233652/synthesis-and-evaluation-of-a-class-of-1-4-7-triazacyclononane-derivatives-as-iron-depletion-antitumor-agents
#19
Sheng Wang, Yongkang Gai, Shasha Zhang, Lei Ke, Xiang Ma, Guangya Xiang
Iron depletion has been confirmed as an efficient strategy for cancer treatment. In the current study, a series of 1,4,7-triazacyclononane derivatives HE-NO2A, HP-NO2A and NE2P2A, as well as the bifunctional chelators p-NO2-PhPr-NE3TA and p-NH2-PhPr-NE3TA were synthesized and evaluated as iron-depleting agents for the potential anti-cancer therapy against human hepatocellular carcinoma. The cytotoxicity of these chelators was measured using hepatocellular cancer cells and compared with the clinically available iron depletion agent DFO and the universal metal chelator DTPA...
November 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29230857/chemical-aspects-of-metal-ion-chelation-in-the-synthesis-and-application-antibody-based-radiotracers
#20
Eszter Boros, Jason P Holland
Radiometals are becoming increasingly accessible and are utilized frequently in the design of radiotracers for imaging and therapy. Nuclear properties ranging from the emission of γ-ray and ®+ -particles (imaging) to Auger electron, ®- and α-particles (therapy) in combination with long half-lives are ideally matched with the relatively long biological half-life of monoclonal antibodies in vivo. Radiometal labelling of antibodies requires the incorporation of a metal chelate onto the monoclonal antibody...
December 12, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
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