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https://www.readbyqxmd.com/read/29908513/evidence-that-microplastics-aggravate-the-toxicity-of-organophosphorus-flame-retardants-in-mice-mus-musculus
#1
Yongfeng Deng, Yan Zhang, Ruxia Qiao, Melvin M Bonilla, Xiaoliang Yang, Hongqiang Ren, Bernardo Lemos
This study was performed to reveal the health risks of co-exposure to organophosphorus flame retardants (OPFRs) and microplastics (MPs). We exposed mice to polyethylene (PE) and polystyrene (PS) MPs and OPFRs [tris (2-chloroethy) phosphate (TCEP) and tris (1,3-dichloro-2-propyl) phosphate (TDCPP)] for 90 days. Biochemical markers and metabolomics were used to determine whether MPs could enhance the toxicity of OPFRs. Superoxide dismutase (SOD) and catalase (CAT) increased (p < 0.05) by 21% and 26% respectively in 10 μg/L TDCPP + PE group compared to TDCPP group...
June 8, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29908485/myeloid-kdm6b-deficiency-results-in-advanced-atherosclerosis
#2
Annette E Neele, Marion J J Gijbels, Saskia van der Velden, Marten A Hoeksema, Marieke C S Boshuizen, Koen H M Prange, Hung-Jen Chen, Jan Van den Bossche, Cindy P P A van Roomen, Annelie Shami, Johannes H M Levels, Jeffrey Kroon, Tina Lucas, Stefanie Dimmeler, Esther Lutgens, Menno P J de Winther
BACKGROUND AND AIMS: Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptional profile of peritoneal foam cells. Given the importance of these cells in atherosclerosis, we now studied the effect of myeloid Kdm6b on disease progression...
June 1, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29908447/fas-activity-mediates-airway-inflammation-during-mouse-adenovirus-type-1-respiratory-infection
#3
Laura J Adkins, Caitlyn T Molloy, Jason B Weinberg
CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice...
June 13, 2018: Virology
https://www.readbyqxmd.com/read/29908367/cell-proliferation-and-anti-apoptosis-essential-processes-for-recruitment-of-the-full-thermogenic-capacity-of-brown-adipose-tissue
#4
REVIEW
Jan Nedergaard, Yanling Wang, Barbara Cannon
In mice living under normal animal house conditions, the brown adipocytes in classical brown adipose tissue depots are already essentially fully differentiated: UCP1 mRNA and UCP1 protein levels are practically saturated. This means that any further recruitment - in response to cold exposure or any other browning agent - does not result in significant augmentation of these parameters. This may easily be construed to indicate that classical brown adipose tissue cannot be further recruited. However, this is far from the case: the capacity for further recruitment instead lies in the ability of the tissue to increase the number of brown-fat cells, a remarkable and highly controlled physiological recruitment process...
June 13, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29908325/dopamine-d2-receptor-activation-potently-inhibits-striatal-glutamatergic-transmission-in-a-g2019s-lrrk2-genetic-model-of-parkinson-s-disease
#5
Alessandro Tozzi, Valentina Durante, Guendalina Bastioli, Petra Mazzocchetti, Salvatore Novello, Alessandro Mechelli, Michele Morari, Cinzia Costa, Andrea Mancini, Massimiliano Di Filippo, Paolo Calabresi
Among genetic abnormalities identified in Parkinson's disease (PD), mutations of the leucine-rich repeat kinase2 (LRRK2) gene, such as the G2019S missense mutation linked to enhanced kinase activity, are the most common. While the complex role of LRRK2 has not been fully elucidated, evidence that mutated kinase activity affects synaptic transmission has been reported. Thus, our aim was to explore possible early alterations of neurotransmission produced by the G2019S LRRK2 mutation in PD. We performed electrophysiological patch-clamp recordings of striatal spiny projection neurons (SPNs) in the G2019S-Lrrk2 knock-in (KI) mouse model of PD, in D1994S kinase-dead (KD), Lrrk2 knock-out (KO) and wild-type (WT) mice...
June 13, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29908308/efficacy-of-whole-cell-pneumococcal-vaccine-in-mice-a-systematic-review-and-meta-analysis
#6
REVIEW
Mona Mohammadzadeh, Babak Pourakbari, Shima Mahmoudi, Abbas Keshtkar, Mahdi Habibi-Anbouhi, Setareh Mamishi
BACKGROUND: Despite the fact that pneumococcal conjugate vaccines (PCVs) have significantly reduced the rate of invasive pneumococcal diseases through the use of vaccine serotypes, infection with Streptococcus pneumoniae remains a major public health hazard. Serotype-independent vaccines that are economically viable species of common protein antigens such as whole-cell vaccines (WCVs) are needed. Considering the ongoing debate about the effectiveness of WCVs, a systematic literature review and meta-analysis was carried out to determine the efficacy of WCVs against colonization in mice...
June 13, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29908303/hemoglobin-adducts-of-furfuryl-alcohol-in-genetically-modified-mouse-models-role-of-endogenous-sulfotransferases-1a1-and-1d1-and-transgenic-human-sulfotransferases-1a1-1a2
#7
Bernhard H Monien, Benjamin Sachse, Walter Meinl, Klaus Abraham, Alfonso Lampen, Hansruedi Glatt
Furfuryl alcohol (FFA) is a heat-induced food contaminant. Conversion by sulfotransferases (SULT) yields 2-sulfoxymethylfuran, which is prone to react with DNA and proteins. In order to monitor the internal FFA exposure we developed a technique for the mass spectrometric quantification of the adduct N-((furan-2-yl)methyl)-valine (FFA-Val) after cleavage from the N-termini of hemoglobin. In the current study the method was applied to investigate the influence of different SULT forms on the adduct formation in wild-type mice and three genetically modified mouse models treated with FFA...
June 13, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29908298/hydrogen-sulfide-epigenetically-mitigates-bone-loss-through-opg-rankl-regulation-during-hyperhomocysteinemia-in-mice
#8
Jyotirmaya Behera, Akash K George, Michael J Voor, Suresh C Tyagi, Neetu Tyagi
Hydrogen sulfide (H2 S) is a novel gasotransmitter produced endogenously in mammalian cells, which works by mediating diverse physiological functions. An imbalance in H2 S metabolism is associated with defective bone homeostasis. However, it is unknown whether H2 S plays any epigenetic role in bone loss induced by hyperhomocysteinemia (HHcy). We demonstrate that diet-induced HHcy, a mouse model of metabolite induced osteoporosis, alters homocysteine metabolism by decreasing plasma levels of H2 S. Treatment with NaHS (H2 S donor), normalizes the plasma level of H2 S and further alleviates HHcy induced trabecular bone loss and mechanical strength...
June 13, 2018: Bone
https://www.readbyqxmd.com/read/29908294/tet2-regulates-osteoclast-differentiation-by-interacting-with-runx1-and-maintaining-genomic-5-hydroxymethylcytosine-5hmc
#9
Yajing Chu, Zhigang Zhao, David Wayne Sant, Ganqian Zhu, Sarah M Greenblatt, Lin Liu, Jinhuan Wang, Zeng Cao, Jeanette Cheng Tho, Shi Chen, Xiaochen Liu, Peng Zhang, Jaroslaw P Maciejewski, Stephen Nimer, Gaofeng Wang, Weiping Yuan, Feng-Chun Yang, Mingjiang Xu
As a dioxygenase, Ten-eleven translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. Tet2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro...
June 13, 2018: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/29908286/il-6-deficiency-alters-spatial-memory-in-4-and-24-month-old-mice
#10
Izabela Bialuk, Andrzej Taranta, Maria Małgorzata Winnicka
Significance of interleukin 6 (IL-6) deficiency in cognitive processes was evaluated in 4- and 24-month-old C57BL/6J IL-6-deficient (IL-6 KO) and control (WT) mice in Morris water maze (MWM), holeboard test (HB) and elevated plus maze (EPM). During 3-day learning escape latency time (ELT) was longer in IL-6 KO than in WT mice, however their swimming was slower, floating longer, and path length did not differ. The comparison of ELT and the distance traveled between the first and the third learning day within each group revealed significant decrease of ELT in all groups with the highest difference in 4-month-old WT mice, and significant decrease of distance travelled only in both groups of WT mice...
June 13, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29908261/a-proteomic-study-of-the-pulmonary-injury-induced-by-microcystin-lr-in-mice
#11
Sujuan Zhao, Hong Sun, Wei Yan, Dexiang Xu, Tong Shen
MCLR has been shown to act as potent hepatotoxin, and recent studies showed that MCs can accumulate in lung tissue and exert adverse effects. However, the exact mechanism still remain unclear. The present study mainly focuses on the impairments of respiratory system after MCLR exposure in mice. After intratracheal instillation with MCLR (0, 10 and 25 μg/kg bw), histological change was examined in MCLR exposure groups. Results indicated that exposure of MCLR led to serious histopathology alteration and apoptosis in lung of mice...
June 13, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29908256/the-protective-effect-of-%C3%AE-lipoic-acid-against-bisphenol-a-induced-neurobehavioral-toxicity
#12
Jasim Khan, Shikha Salhotra, Shahzad Ahmad, Shikha Sharma, Sayed Aliul Hasan Abdi, Basu Dev Banerjee, Suhel Parvez, Sarika Gupta, Sheikh Raisuddin
Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice...
June 13, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29908255/genetic-overexpression-of-glutathione-peroxidase-1-attenuates-microcystin-leucine-arginine-induced-memory-impairment-in-mice
#13
Eun-Joo Shin, Yeong Gwang Hwang, Duc Toan Pham, Ji Won Lee, Yu Jeung Lee, Dongjin Pyo, Xin Gen Lei, Ji Hoon Jeong, Hyoung-Chun Kim
Microcystin-leucine-arginine (MCLR) is the most common form of microcystins, which are environmental toxins produced by cyanobacteria, and its hepatotoxicity has been well-documented. However, the neurotoxic potential of MCLR remains to be further elucidated. In the present study, we investigated whether intracerebroventricular (i.c.v.) infusion of MCLR induces mortality and neuronal loss in the hippocampus of mice. Because we found that MCLR impairs memory function in the hippocampus at a low dose (4 ng/μl/mouse, i...
June 13, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29908244/prompt-treatment-with-uridine-triacetate-improves-survival-and-reduces-toxicity-due-to-fluorouracil-and-capecitabine-overdose-or-dihydropyrimidine-dehydrogenase-deficiency
#14
Rolando A G Garcia, Joel A Saydoff, Michael K Bamat, Reid W von Borstel
Uridine triacetate has been shown to be an effective antidote against mortality and toxicity caused by either overdoses or exaggerated susceptibility to the widely used anticancer agents 5-fluorouracil (5-FU) and capecitabine. However, a direct assessment of efficacy based on when emergency treatment was initiated was not clinically feasible. In this study we used mouse models of 5-FU overdose and of dihydropyrimidine dehydrogenase (DPD) deficiency to compare the efficacy of uridine triacetate in reducing toxicity and mortality when treatment was initiated at time points from 4 to 144 h after administration of 5-FU...
June 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29908243/protective-roles-of-fenofibrate-against-cisplatin-induced-ototoxicity-by-the-rescue-of-peroxisomal-and-mitochondrial-dysfunction
#15
Se-Jin Kim, Channy Park, Joon No Lee, Raekil Park
Cisplatin is an alkylating agent that interferes with DNA replication and kills proliferating carcinogenic cells. Several studies have been conducted to attenuate the side effects of cisplatin; one such side effect in cancer patients undergoing cisplatin chemotherapy is ototoxicity. However, owing to a lack of understanding of the precise mechanism underlying cisplatin-induced side effects, management of cisplatin-induced ototoxicity remains unsolved. We investigated the protective effects of fenofibrate, a PPAR-α activator, on cisplatin-induced ototoxicity...
June 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29908241/environmental-enrichment-enhances-conditioned-place-preference-to-ethanol-via-an-oxytocinergic-dependent-mechanism-in-male-mice
#16
Mariana Rae, Panos Zanos, Polymnia Georgiou, Priti Chivers, Alexis Bailey, Rosana Camarini
Environmental conditions, such as stress and environmental enrichment (EE), influence predisposition to alcohol use/abuse; however, the underlying mechanisms remain unknown. To assess the effect of environmental conditions on the initial rewarding effects of alcohol, we examined conditioned place-preference (CPP) to alcohol following exposure to EE in mice. Since social context is a major factor contributing to initial alcohol-drinking, we also assessed the impact of EE on the levels of the "social neuropeptide" oxytocin (OT) and its receptor, OTR...
June 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29908240/the-gabaergic-gudden-s-dorsal-tegmental-nucleus-a-new-relay-for-serotonergic-regulation-of-sleep-wake-behavior-in-the-mouse
#17
Marine Chazalon, Sylvie Dumas, Jean-François Bernard, Iman Sahly, François Tronche, Alban de Kerchove d'Exaerde, Michel Hamon, Joëlle Adrien, Véronique Fabre, Patricia Bonnavion
Serotonin (5-HT) neurons are involved in wake promotion and exert a strong inhibitory influence on rapid eye movement (REM) sleep. Such effects have been ascribed, at least in part to the action of 5-HT at post-synaptic 5-HT1A receptors (5-HT1A R) in the brainstem, a major wake/REM sleep regulatory center. However, the neuroanatomical substrate through which 5-HT1A R influence sleep remains elusive. We therefore investigated whether a brainstem structure containing a high density of 5-HT1A R mRNA, the GABAergic Gudden's dorsal tegmental nucleus (DTg), may contribute to 5-HT-mediated regulatory mechanisms of sleep-wake stages...
June 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29908222/oral-pemetrexed-facilitates-low-dose-metronomic-therapy-and-enhances-antitumor-efficacy-in-lung-cancer
#18
Foyez Mahmud, Ok-Cheol Jeon, Farzana Alam, Ruby Maharjan, Jeong Uk Choi, Jooho Park, Sojung Lee, Jin Woo Park, Dong Soo Lee, Youngro Byun
There is a growing interest in preclinical research to consider low-dose metronomic chemotherapy as antiangiogenic cancer treatment. Oral metronomic therapy, in particular, has shown much promise with its ease of daily administration and higher therapeutics window. In that regard, we developed oral pemetrexed using the physical complex with the bile acid enhancers (DCK). In a caco-2 permeability study, the oral pemetrexed/DCK complex had significantly higher drug uptake, and inhibited efflux transporter activity as well...
June 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29908151/vaccination-with-a-cd4-and-cd8-t-cell-epitopes-based-recombinant-chimeric-protein-derived-from-leishmania-infantum-proteins-confers-protective-immunity-against-visceral-leishmaniasis
#19
Daniel S Dias, Patrícia A F Ribeiro, Vívian T Martins, Daniela P Lage, Lourena E Costa, Miguel A Chávez-Fumagalli, Fernanda F Ramos, Thaís T O Santos, Fernanda Ludolf, Jamil S Oliveira, Tiago A O Mendes, Eduardo S Silva, Alexsandro S Galdino, Mariana C Duarte, Bruno M Roatt, Daniel Menezes-Souza, Antonio L Teixeira, Eduardo A F Coelho
Vaccination seems to be the best approach to control visceral leishmaniasis (VL). Resistance against infection is based on the development of a Th1 immune response characterized by the production of interferons-γ (IFN-γ), interleukin-12 (IL-12), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α), among others. A number of antigens have been tested as potential targets against the disease; few of them are able to stimulate human immune cells. In the present study, 1 prediction of MHC class I and II molecules-specific epitopes in the amino acid sequences of 3 Leishmania proteins: 1 hypothetical, prohibitin, and small glutamine-rich tetratricopeptide repeat-containing proteins, was performed using bioinformatics tools, and a T-cell epitopes-based recombinant chimeric protein was constructed, synthetized and purified to be evaluated in invitro and in vivo experiments...
May 22, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29908149/a-hexokinase-2-modulator-for-field-directed-treatment-of-experimental-actinic-keratoses
#20
Vered Behar, Hadas Pahima, Adi Kozminsky-Atias, Nir Arbel, Emmanuel Loeb, Max Herzberg, Oren M Becker
Overexpression of hexokinase 2 (HK2), and its binding to VDAC1 on the outer mitochondrial membrane of cancer cells, is key to their metabolic reprogramming to aerobic glycolysis, which enables them to proliferate. We describe Comp-1, an allosteric small molecule that selectively detaches HK2 from the mitochondria. Detachment of HK2 reduces glycolysis and triggers apoptosis in cancer cells, without affecting HK1 expressing normal cells. The anti-cancer activity of Comp-1 was demonstrated in the UVB-damaged skin model in SKH-1 mice...
June 13, 2018: Journal of Investigative Dermatology
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