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https://www.readbyqxmd.com/read/29334374/transitory-presence-of-myeloid-derived-suppressor-cells-in-neonates-is-critical-for-control-of-inflammation
#1
Yu-Mei He, Xing Li, Michela Perego, Yulia Nefedova, Andrew V Kossenkov, Erik A Jensen, Valerian Kagan, Yu-Feng Liu, Shu-Yu Fu, Qing-Jian Ye, Yan-Hong Zhou, Lai Wei, Dmitry I Gabrilovich, Jie Zhou
Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334310/dendritic-polyglycerol-nanoparticles-show-charge-dependent-bio-distribution-in-early-human-placental-explants-and-reduce-hcg-secretion
#2
Herbert Juch, Liudmila Nikitina, Sabine Reimann, Martin Gauster, Gottfried Dohr, Barbara Obermayer-Pietsch, Denise Hoch, Karin Kornmueller, Rainer Haag
A thorough understanding of nanoparticle bio-distribution at the feto-maternal interface will be a prerequisite for their diagnostic or therapeutic application in women of childbearing age and for teratologic risk assessment. Therefore, the tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG-NPs) with first- trimester human placental explants were analyzed and compared to less sophisticated trophoblast-cell based models. First-trimester human placental explants, BeWo cells and primary trophoblast cells from human term placenta were exposed to fluorescence labeled, ∼5 nm dPG-NPs, with differently charged surfaces, at concentrations of 1 µM and 10 nM, for 6 and 24 h...
January 15, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29333676/ether-%C3%A3-go-go-k-channels-effective-modulators-of-neuronal-excitability
#3
Christiane K Bauer, Jürgen R Schwarz
Mammalian EAG (ether-à-go-go) channels are voltage-gated K+ channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation...
January 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29332417/-concise-history-of-toxicology-from-empiric-knowledge-to-science
#4
Anna Tompa, Péter Balázs
Toxicology is a science of poisonings by xenobiotics and endogenous physiological changes. Its empiric roots may be traced back to the emerging of the human race because the most important pledge of our predecessors' survival was the differentiation between eatable and poisonous plants and animals. In the course of social evolution, there were three main fields of using poisons: 1) hunting and warfare, 2) to settle social tensions by avoiding military conflicts through hiding strategy of eliminating enemies by toxic substances, 3) medicines applied first as anti-poisons and later by introducing strong substances to defeat diseases, but paradoxically active euthanasia is also a part of the whole story...
January 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29332087/adaptive-brain-stimulation-for-movement-disorders
#5
Martijn Beudel, Hayriye Cagnan, Simon Little
Deep brain stimulation (DBS) has markedly changed how we treat movement disorders including Parkinson's disease (PD), dystonia, and essential tremor (ET). However, despite its demonstrable clinical benefit, DBS is often limited by side effects and partial efficacy. These limitations may be due in part to the fact that DBS interferes with both pathological and physiological neural activities. DBS could, therefore, be potentially improved were it applied selectively and only at times of enhanced pathological activity...
2018: Progress in Neurological Surgery
https://www.readbyqxmd.com/read/29331928/being-in-control-a-thematic-content-analysis-of-14-in-depth-interviews-with-2-4-dinitrophenol-users
#6
Neha Prasad Ainsworth, Elisabeth Julie Vargo, Andrea Petróczi
BACKGROUND: 2,4-Dinitrophenol (2,4-DNP) is a compound with multiple industrial purposes. Currently unlicensed for human consumption, it is used by the gym-going population for drastic, short-term body fat loss. Nonetheless, physiological mechanisms can lead to potentially fatal hyperthermia. Reported fatal incidents have caused concern and highlighted the need for intervention. Understanding decision-making leading to 2,4-DNP use alongside the perceived outgroup attitudes is vital to forming effective harm minimisation policies targeting current and potential users...
January 11, 2018: International Journal on Drug Policy
https://www.readbyqxmd.com/read/29331791/magnesium-sulfate-reduces-formalin-induced-orofacial-pain-in-rats-with-normal-magnesium-serum-levels
#7
Dragana P Srebro, Sonja M Vučković, Ivan S Dožić, Branko S Dožić, Katarina R Savić Vujović, Aleksandar P Milovanović, Branislav V Karadžić, Milica Š Prostran
BACKGROUND: In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. METHODS: Male Wistar rats were injected with 1...
August 31, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29331752/synthesis-of-gold-i-phosphine-complexes-containing-the-2-brc6f4pph2-ligand-evaluation-of-anticancer-activity-in-2d-and-3d-spheroidal-models-of-hela-cancer-cells
#8
T Srinivasa Reddy, Steven H Privér, Nedaossadat Mirzadeh, Suresh K Bhargava
Newly synthesised mononuclear gold complexes containing the 2-BrC6F4PPh2 ligand have been fully characterised and their anticancer activity towards five human tumor [prostate (PC3), glioblastoma (U87MG), cervical (HeLa), fibrosarcoma (HT1080), ovarian (SKOV-3)] and normal human embryonic kidney (Hek-293T) cell lines investigated. Some of the synthesised gold complexes displayed higher cytotoxicity than cisplatin towards PC-3, HeLa and U87MG cells and inhibited the thioredoxin reductase (TrxR) enzyme, which is considered a potential target for new compounds in cancer treatment...
December 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29331734/in-vitro-assessment-of-silver-nanoparticles-immunotoxicity
#9
Valentina Galbiati, Laura Cornaghi, Elisabetta Gianazza, Marco A Potenza, Elena Donetti, Marina Marinovich, Emanuela Corsini
This study aimed to characterize unwanted immune effects of nanoparticles (NP) using THP-1 cells, human whole blood and enriched peripheral blood monocytes. Commercially available silver NP (AgNP < 100 nm, also confirmed by Single Particle Extinction and Scattering) were used as prototypical NP. Cells were treated with AgNP alone or in combination with classical immune stimuli (i.e. LPS, PHA, PWM) and cytokine assessed; in addition, CD54 and CD86 expression was evaluated in THP-1 cells. AgNP alone induced dose-related IL-8 production in all models, with higher response observed in THP-1 cells, possibly connected to different protein corona formation in bovine versus human serum...
January 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29331382/improved-human-pharmacokinetic-prediction-of-hepatically-metabolized-drugs-with-species-specific-systemic-clearance
#10
Kana Horiuchi, Shuichi Ohnishi, Takanobu Matsuzaki, Satoko Funaki, Ayahisa Watanabe, Tohru Mizutare, Sayaka Matsumoto, Kenichi Nezasa, Hiroshi Hasegawa
Accurate prediction of human pharmacokinetics (PK) is important for the choice of promising compounds in humans. As the predictability of human PK by an empirical approach is low for drugs with species-specific PK, the utility of a physiologically based pharmacokinetic (PBPK) model was verified using 16 reference drugs hepatically metabolized. After the prediction method for total clearance (CLtot) and distribution volume at steady state (Vdss) in the conventional PBPK model had been optimized, plasma concentrations following a single oral administration of each reference drug to healthy volunteers were simulated and the prediction accuracy for human PK was compared between empirical approaches and the optimized PBPK model...
January 10, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29331020/human-phenotypes-caused-by-piezo1-mutations-one-gene-two-overlapping-phenotypes
#11
Silvia Martin-Almedina, Sahar Mansour, Pia Ostergaard
PIEZO1 is a large mechanosensitive ion channel protein. Diseases associated with PIEZO1 include autosomal recessive Generalised Lymphatic Dysplasia of Fotiou (GLDF) and autosomal dominant Dehydrated Hereditary Stomatocytosis with or without pseudohyperkalemia and/or perinatal oedema (DHS). The two disorders show overlapping features, fetal hydrops/perinatal oedema have been reported in both. Electrophysiological studies suggest opposite mechanisms of action, the mutations identified in GLDF patients cause a loss-of-function mechanism of disease and mutations in DHS patients cause gain-of-function...
January 13, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29330967/the-impact-of-bisphenol-s-on-bovine-granulosa-and-theca-cells
#12
K A Campen, M Lavallee, Cmh Combelles
Bisphenol S (BPS) is an endocrine-disrupting chemical with multiple potential mechanisms of action, including as an oestrogen receptor agonist. BPS is increasingly used in plastics and thermal receipts as a substitute for bisphenol A, which has been phased out due to concerns about human health implications. The ability of BPS to alter female reproductive function in mammals has not been widely studied, despite the importance of normal hormone signalling for female reproduction. The aim of this study was to investigate how BPS (in a wide range of doses, including very low doses) affects granulosa cell and theca cell steroid hormone production and cell viability in the bovine...
January 12, 2018: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29330792/evaluating-the-metabolic-impact-of-hypoxia-on-pancreatic-cancer-cells
#13
Divya Murthy, Enza Vernucci, Gennifer Goode, Jaime Abrego, Pankaj K Singh
Hypoxia is frequently observed in human cancers and induces global metabolic reprogramming that includes an increase in glucose uptake and glycolysis, alterations in NAD(P)H/NAD(P)+ and intracellular ATP levels, and increased utilization of glutamine as the major precursor for fatty acid synthesis. In this chapter, we describe in detail various physiological assays that have been adopted to study the metabolic shift propagated by exposure to hypoxic conditions in pancreatic cell culture model that includes glucose uptake, glutamine uptake, and lactate release by pancreatic cancer cell lines...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330692/a-new-method-for-the-in-vitro-determination-of-the-bile-tolerance-of-potentially-probiotic-lactobacilli
#14
Peng-Li Hu, Ya-Hong Yuan, Tian-Li Yue, Chun-Feng Guo
A new in vitro method was developed to determine the bile tolerance of potentially probiotic lactobacilli. The overnight culture of various lactobacilli strains was inoculated into sterile, half-strength MRS broth supplemented with and without 0.3% (wt/vol) oxgall, buffered with 0.1 M sodium phosphate buffer at a final pH of 7.3, and incubated at 37 °C for 12 h under anaerobic conditions. The bile tolerance ability of the lactobacilli strains was expressed as the percentage of the propagation generations of the bacterial cells in the presence of oxgall to those in the absence of oxgall...
January 12, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29330663/human-cytomegalovirus-encoded-mir-ul112-contributes-to-hcmv-mediated-vascular-diseases-by-inducing-vascular-endothelial-cell-dysfunction
#15
Kai Shen, Liyun Xu, Dongdong Chen, Weiguo Tang, Yanyan Huang
Human cytomegalovirus (HCMV) infection has been linked to the pathogenesis of vasculopathy by inducing dysfunction of vascular cells such as endothelial cells. Hcmv-miR-UL112 is the most well-characterized HCMV-encoded microRNA occurring in the plasma of patients with cardiovascular diseases such as hypertension, while the specific underlying pathophysiological mechanisms are yet to be defined. The current study investigated the effect of hcmv-miR-UL112 on the growth and proliferation of human umbilical vascular endothelial cells (HUVECs); it might also be associated with signaling pathways...
January 12, 2018: Virus Genes
https://www.readbyqxmd.com/read/29330456/20-hete-promotes-glucose-stimulated-insulin-secretion-in-an-autocrine-manner-through-ffar1
#16
Sorin Tunaru, Remy Bonnavion, Isabell Brandenburger, Jens Preussner, Dominique Thomas, Klaus Scholich, Stefan Offermanns
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330367/characterization-of-human-small-heat-shock-protein-hspb1-%C3%AE-crystallin-domain-localized-mutants-associated-with-hereditary-motor-neuron-diseases
#17
Stephen D Weeks, Lydia K Muranova, Michelle Heirbaut, Steven Beelen, Sergei V Strelkov, Nikolai B Gusev
Congenital mutations in human small heat shock protein HSPB1 (HSP27) have been linked to Charcot-Marie-Tooth disease, a commonly occurring peripheral neuropathy. Understanding the molecular mechanism of such mutations is indispensable towards developing future therapies for this currently incurable disorder. Here we describe the physico-chemical properties of the autosomal dominant HSPB1 mutants R127W, S135F and R136W. Despite having a nominal effect on thermal stability, the three mutations induce dramatic changes to quaternary structure...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330218/a-study-on-pharmacokinetics-of-bosentan-with-systems-modeling-part-1-translating-systemic-plasma-concentration-to-liver-exposure-in-healthy-subjects
#18
Rui Li, Mark Niosi, Nathaniel Johnson, David A Tess, Emi Kimoto, Jian Lin, Xin Yang, Keith A Riccardi, Sangwoo Ryu, Ayman F El-Kattan, Tristan S Maurer, Larry M Tremaine, Li Di
Understanding liver exposure of hepatic transporter substrates in clinical studies is often critical as it typically governs pharmacodynamics, drug-drug interactions, and toxicity for certain drugs. However, this is a challenging task since there is currently no easy method to directly measure drug concentration in the human liver. Using bosentan as an example, a new approach has been demonstrated to estimate liver exposure based on observed systemic pharmacokinetics from clinical studies using physiologically-based pharmacokinetic modeling...
January 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29330104/circular-rna-an-emerging-non-coding-rna-as-a-regulator-and-biomarker-in-cancer
#19
Bing Chen, Shenglin Huang
Circular RNA (circRNA) is a type of covalently closed non-coding RNA that may regulate gene expression in eukaryotes. The recent application of high-throughput RNA sequencing and bioinformatics approaches has revealed a large number of circRNAs in human cells. Emerging evidence indicates that many circRNAs have cell-type specific expression and are linked to physiological development and various diseases. Specially, circRNAs can either serve as oncogenic stimuli or tumor suppressors in cancer. circRNAs have also been shown to be enriched and stable in extracellular fluid, indicating the potential of circRNAs as cancer biomarkers...
January 9, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330007/lost-connections-oxytocin-and-the-neural-physiological-and-behavioral-consequences-of-disrupted-relationships
#20
REVIEW
Tobias T Pohl, Larry J Young, Oliver J Bosch
In humans and rodent animal models, the brain oxytocin system is paramount for facilitating social bonds, from the formation and consequences of early-life parent-infant bonds to adult pair bond relationships. In social species, oxytocin also mediates the positive effects of healthy social bonds on the partners' well-being. However, new evidence suggests that the negative consequences of early neglect or partner loss may be mediated by disruptions in the oxytocin system as well. With a focus on oxytocin and its receptor, we review studies from humans and animal models, i...
January 9, 2018: International Journal of Psychophysiology
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