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https://www.readbyqxmd.com/read/28432518/correlation-between-heavy-metal-exposure-and-gstm1-polymorphism-in-iranian-multiple-sclerosis-patients
#1
Mehdi Aliomrani, Mohammad A Sahraian, Hamid Shirkhanloo, Mohammad Sharifzadeh, Mohammad R Khoshayand, Mohammad H Ghahremani
Multiple sclerosis (MS) is an immune-mediated chronic inflammatory disease of the central nervous system. Various exposures to heavy metals can lead to toxicity and oxidative stress. While glutathione-S-transferases are known as oxidative stress-related genes and involved in metal biotransformation. The aim of the present study is to investigate the correlation of GSTM1 polymorphism in MS patients and the possible association with blood concentration of arsenic (As) and cadmium (Cd) as major heavy metal pollutants...
April 21, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28432099/acute-hepatopancreatic-necrosis-disease-ahpnd-causing-vibrio-parahaemolyticus-strains-maintain-an-antibacterial-type-vi-secretion-system-with-versatile-effector-repertoires
#2
Peng Li, Lisa N Kinch, Ann Ray, Ankur B Dalia, Qian Cong, Linda M Nunan, Andrew Camilli, Nick V Grishin, Dor Salomon, Kim Orth
Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp disease that has severely damaged the global shrimp industry. AHPND is caused by toxic strains of Vibrio parahaemolyticus (V. parahaemolyticus) that have acquired a "selfish plasmid" encoding the deadly binary toxins PirA(vp)/PirB(vp) To better understand the repertoire of virulence factors in AHPND-causing V. parahaemolyticus, we conducted a comparative analysis using genome sequences of the clinical strain RIMD2210633, environmental non-AHPND and toxic AHPND isolates of V...
April 21, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28432017/dual-functional-nanoparticles-for-precise-drug-delivery-to-alzheimer-s-disease-lesions-targeting-mechanisms-pharmacodynamics-and-safety
#3
Xiaoyao Zheng, Chi Zhang, Qian Guo, Xu Wan, Xiayan Shao, Qingfeng Liu, Qizhi Zhang
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the cerebral accumulation of extracellular amyloid plaques. In a previous study, this histopathological hallmark was used as a target on a dual-functional nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide, a β-sheet breaker, to AD lesions precisely. This delivery system could reduce the amyloid-β (Aβ) burden in the brains of AD model mice, as well as ameliorated the memory impairment of the mice...
April 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28431999/novel-method-to-rapidly-and-efficiently-lyse-escherichia-coli-for-the-isolation-of-recombinant-protein
#4
Himanshu Joshi, Vikas Jain
Rapid and high-throughput protein purification methods are required to explore structure and function of several uncharacterized proteins. Isolation of recombinant protein expressed in Escherichia coli strain BL21 (DE3) depends largely on the efficient and speedy bacterial cell lysis, which is considered as the bottleneck during protein purification. Cells are usually lysed by either sonication or high pressure homogenization, both of which are slow, require special equipment, lead to heat generation, and may result in loss of protein's biological activity...
April 18, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#5
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28431877/synthesis-and-evaluation-of-pyridinium-polyoxometalates-as-anti-hiv-1-agents
#6
Shunyi Wang, Wuji Sun, Qin Hu, Hong Yan, Yi Zeng
The unique properties of polyoxometalates, such as molecular polarity, redox potential, surface charge distribution, shape and acidity, influence their response of recognition to targeted biological macromolecules. By using PM-19 (K7PTi2W10O40) as a lead-compound, a series of novel pyridinium polyoxometalates (A7PTi2W10O40), which hadn't been reported in literatures, were designed and synthesized. The evaluation was conducted using the single-cycle pseudovirus infection assay (TZM-bl assay), CCK-8 method was used for determining the cytotoxicity...
April 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28431555/reduction-of-pulmonary-toxicity-of-metal-oxide-nanoparticles-by-phosphonate-based-surface-passivation
#7
Xiaoming Cai, Anson Lee, Zhaoxia Ji, Cynthia Huang, Chong Hyun Chang, Xiang Wang, Yu-Pei Liao, Tian Xia, Ruibin Li
BACKGROUND: The wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties...
April 21, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28431387/cypermethrin-toxication-leads-to-histopathological-lesions-and-induces-inflammation-and-apoptosis-in-common-carp-cyprinus-carpio-l
#8
Harun Arslan, Selçuk Özdemir, Serdar Altun
Cypermethrin (Cyp), a known neurotoxic pesticide, is widely used in agricultural applications. In the present study, the aim was to determine the histopathological effects of Cyp toxication and evaluate the activation of inducible nitric oxide synthetase (iNOS) and 8-hydroxy-2-deoxyguanosine (8-OHdG) using an immunofluorescence assay. Thereafter, we identified the expressions of caspase 3, capsase 8, iNOS, and metallothionein 1 (MT1) genes in common carp using quantitative reverse transcription polymerase chain reaction (qRT-PCR)...
April 14, 2017: Chemosphere
https://www.readbyqxmd.com/read/28431070/emerging-molecular-therapies-targeting-myocardial-infarction-related-arrhythmias
#9
Helen E Driessen, Toon A B van Veen, Gerard J J Boink
Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate...
April 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#10
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430339/characterization-of-a-rare-nonpathogenic-sequence-variant-c-1905c-t-of-the-dihydropyrimidine-dehydrogenase-gene-dpyd
#11
Raffaele Palmirotta, Domenica Lovero, Erica Silvestris, Claudia Carella, Claudia Felici, Davide Quaresmini, Paola Cafforio, Franco Silvestris
BACKGROUND: In the era of precision medicine, the suitability of fluoropyrimidine therapies in clinical oncology can be checked by pharmacogenetic investigations of single patients, thus optimizing resources and indicating the appropriate drugs to personalize their chemotherapy. For example, the presence of dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms in cancer patients may lead to adverse effects when adopting fluoropyrimidine-based therapies. METHODS: We detected in a cancer patient a rare germline synonymous heterozygous variant of DPYD (c...
April 11, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28429726/verteporfin-induced-formation-of-protein-cross-linked-oligomers-and-high-molecular-weight-complexes-is-mediated-by-light-and-leads-to-cell-toxicity
#12
Eleni K Konstantinou, Shoji Notomi, Cassandra Kosmidou, Katarzyna Brodowska, Ahmad Al-Moujahed, Fotini Nicolaou, Pavlina Tsoka, Evangelos Gragoudas, Joan W Miller, Lucy H Young, Demetrios G Vavvas
Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429653/clinical-development-of-fenretinide-as-an-antineoplastic-drug-pharmacology-perspectives
#13
Jason P Cooper, C Patrick Reynolds, Hwangeui Cho, Min H Kang
Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved <10 µmol/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB®, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28429452/real-world-experience-of-the-feasibility-and-tolerability-of-the-2-1-dosing-schedule-with-sunitinib-in-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-in-australia
#14
Megan Crumbaker, Alexander Guminski, Howard Gurney, Dhanusha Sabanathan, Shirley Wong, Nick Pavlakis
AIM: Sunitinib is a first-line treatment option for metastatic renal cell carcinoma (mRCC) funded by the Australian Pharmaceutical Benefits Scheme. Toxicities are common with the standard schedule leading to alternative dosing schedules to be suggested. We reviewed Australian treatment practices to evaluate the safety and outcomes of patients on a 2 weeks on, 1 week off treatment schedule (2/1). METHODS: We performed a retrospective review of 63 patients with mRCC treated with first-line sunitinib on a 2/1 schedule at four Australian centers...
April 21, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28429185/high-content-assessment-of-cardiac-function-using-heart-on-a-chip-devices-as-drug-screening-model
#15
Genevieve Conant, Benjamin Fook Lun Lai, Rick Xing Ze Lu, Anastasia Korolj, Erika Yan Wang, Milica Radisic
Drug discovery and development continues to be a challenge to the pharmaceutical industry despite great advances in cell and molecular biology that allow for the design of better targeted therapeutics. Many potential drug compounds fail during the clinical trial due to inefficacy and toxicity that were not predicted during preclinical stages. The fundamental problem lies with the use of traditional drug screening models that still largely rely on the use of cell lines or animal cell monolayers, which leads to lack of predictive power of human tissue and organ response to the drug candidates...
April 20, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28428773/mutation-at-g103-of-mtbftsz-altered-their-sensitivity-to-coumarins
#16
Duggirala Sridevi, Karpagam U Sudhakar, Ragamanvitha Ananthathatmula, Rakesh P Nankar, Mukesh Doble
Coumarins are natural polyphenol lactones comprising of fused rings of benzene and α-pyrone. The current study demonstrates the inhibitory effect of coumarins with various substitutions on Mycobacterium smegmatis mc(2) 155. We also demonstrate the effect of pomegranate (Punica granatum) extract containing ellagic acid, on M. smegmatis as well as their affect on MtbFtsZ (FtsZ from Mycobacterium tuberculosis). The ellagic acid extracts from pomegranate peels inhibit mycobacteria with a MIC of 25 μM and 0.3 to 3...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28428704/lead-poisoning-due-to-herbal-medications
#17
Shailja Chambial, Pankaj Bhardwaj, Abbas Ali Mahdi, Praveen Sharma
Lead ranks as one of the most serious environmental poisons all over the world amongst toxic heavy metals with no known biological function useful for the human body. A case of lead toxicity due to consumption of herbal medicine is being discussed. The case presented with gastrointestinal complaints and history of intake of herbal medicines for diabetes control for past 8 months. The analysis of the powdered herbal medicine procured from ayurveda practitioner was found to have high content of lead responsible for the lead toxicity...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28428562/dehydroascorbic-acids-modified-polymer-micelles-target-cancer-cells-to-enhance-anti-tumor-efficacy-of-paclitaxel
#18
Xiaoyu Pei, Feifei Luo, Jun Zhang, Wulian Chen, Chen Jiang, Jie Liu
Paclitaxel (PTX), especially albumin-bound PTX in clinical, has displayed significant inhibition of tumor growth in patients. But the systemic distribution and poor water solubility of PTX often lead to severe side effects, consequently limiting the anti-tumor efficacy. In this study, we developed a novel PTX-loaded polymeric micelle drug delivery system. These self-assembled polymeric micelles from core to outside consisted of poly L-phenylalanine (pPhe), DTSSP linked poly L-lysine (pLys), poly ethylene glycol (PEG) and dehydroascorbic acids (DHA)...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428071/development-of-novel-in-silico-model-for-developmental-toxicity-assessment-by-using-na%C3%A3-ve-bayes-classifier-method
#19
Hui Zhang, Ji-Xia Ren, Yan-Li Kang, Peng Bo, Jun-Yu Liang, Lan Ding, Wei-Bao Kong, Ji Zhang
Toxicological testing associated with developmental toxicity endpoints are very expensive, time consuming and labor intensive. Thus, developing alternative approaches for developmental toxicity testing is an important and urgent task in the drug development filed. In this investigation, the naïve Bayes classifier was applied to develop a novel prediction model for developmental toxicity. The established prediction model was evaluated by the internal 5-fold cross validation and external test set. The overall prediction results for the internal 5-fold cross validation of the training set and external test set were 96...
April 17, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28427959/beneficial-effects-of-heparin-and-l-arginine-on-dermonecrosis-effect-induced-by-vipera-lebetina-venom-involvement-of-no-in-skin-regeneration
#20
Nouara Bennacef-Heffar, Fatima Laraba-Djebari
It is well known that snake venoms such as Viperidae caused severe local effects such as hemorrhage, myonecrosis and dermonecrosis which can lead to permanent tissue loss or the disability. The aim of this study is to evaluate the skin regeneration using heparin and L-arginine as well as the dermonecrotic effects induced by Vipera lebetina venom (VLV). To better understand the toxic effects induced by VLV and to prevent or treat these effects, we evaluate the local effects and the skin regeneration with or without drugs...
April 17, 2017: Acta Tropica
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