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https://www.readbyqxmd.com/read/29689241/pharmacologic-inhibition-of-s1p-attenuates-atf6-expression-causes-er-stress-and-contributes-to-apoptotic-cell-death
#1
Paul Lebeau, Jae Hyun Byun, Tamana Yousof, Richard C Austin
Mammalian cells express unique transcription factors embedded in the endoplasmic reticulum (ER) membrane, such as the sterol regulatory element-binding proteins (SREBPs), that promote de novo lipogenesis. Upon their release from the ER, the SREBPs require proteolytic activation in the Golgi by site-1-protease (S1P). As such, inhibition of S1P, using compounds such as PF-429242 (PF), reduces cholesterol synthesis and may represent a new strategy for the management of dyslipidemia. In addition to the SREBPs, the unfolded protein response (UPR) transducer, known as the activating transcription factor 6 (ATF6), is another ER membrane-bound transcription factor that requires S1P-mediated activation...
April 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29687875/evaluation-of-thyroid-nodule-characteristics-in-subclinical-hypothyroid-patients-under-a-myo-inositol-plus-selenium-treatment
#2
M Nordio, S Basciani
OBJECTIVE: The anticancer effect of myo-inositol (MI) is catching researchers' attention worldwide. Thyroid nodules (TNs) have been detected by ultrasound (US) in up to 76% of the general population and, although most of them are benign, thyroid cancer is the most common malignancy of the endocrine system. PATIENTS AND METHODS: A retrospective, observational study was conducted in 642 patients with suspected hypothyroidism undergoing US. The analysis was addressed exclusively to patients with subclinical hypothyroidism (SCH) or thyroid-stimulating hormone (TSH) levels borderline associated to TNs classified as class I and II; 1 group (control, no...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29687835/use-of-alpha-lactalbumin-for-the-management-of-pcos-in-inositols-resistant-women
#3
V Unfer
No abstract text is available yet for this article.
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29683647/structure-activity-relationships-of-pan-g%C3%AE-q-11-coupled-muscarinic-acetylcholine-receptor-positive-allosteric-modulators
#4
Alice Berizzi, Aaron M Bender, Craig W Lindsley, P Jeffrey Conn, Patrick M Sexton, Christopher Langmead, Arthur Christopoulos
Recent years have seen a large increase in the discovery of allosteric ligands targeting muscarinic acetylcholine receptors (mAChRs). One of the challenges in screening such compounds is to understand their mechanisms of action and define appropriate parameter estimates for affinity, cooperativity and efficacy. Herein we describe the mechanisms of action and structure-activity relationships for a series of "pan-Gq-coupled" muscarinic acetylcholine (ACh) receptor (mAChR) positive allosteric modulators (PAMs)...
April 23, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29681901/putting-on-the-brakes-regulatory-kinases-and-phosphatases-maintaining-b-cell-anergy
#5
REVIEW
S Elizabeth Franks, John C Cambier
B cell antigen receptor (BCR) signaling is a tightly regulated process governed by both positive and negative mediators/regulators to ensure appropriate responses to exogenous and autologous antigens. Upon naïve B cell recognition of antigen CD79 [the immunoreceptor tyrosine-based activation motif (ITAM)-containing signaling subunit of the BCR] is phosphorylated and recruits Src and Syk family kinases that then phosphorylate proximal intermediaries linked to downstream activating signaling circuitry. This plasma membrane localized signalosome activates PI3K leading to generation of PIP3 critical for membrane localization and activation of plecktrin homology domain-containing effectors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29679940/nmr-based-metabolic-toxicity-of-low-level-hg-exposure-to-earthworms
#6
Ronggui Tang, Changfeng Ding, Fei Dang, Yibing Ma, Junsong Wang, Taolin Zhang, Xingxiang Wang
Mercury is a globally distributed toxicant to aquatic animals and mammals. However, the potential risks of environmental relevant mercury in terrestrial systems remain largely unclear. The metabolic profiles of the earthworm Eisenia fetida after exposure to soil contaminated with mercury at 0.77 ± 0.09 mg/kg for 2 weeks were investigated using a two-dimensional nuclear magnetic resonance-based (1 H-13 C NMR) metabolomics approach. The results revealed that traditional endpoints (e.g., mortality and weight loss) did not differ significantly after exposure...
April 18, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29679279/role-of-inositol-polyphosphates-in-programed-cell-death-in-dictyostelium-discoideum-and-its-developmental-life-cycle
#7
Qudes Al-Anbaky, Zeiyad Al-Karakooly, Richard Connor, Lisa Williams, Azure Yarbrough, John Bush, Nawab Ali
Programed cell death or apoptosis is a key developmental process that maintains tissue homeostasis in multicellular organisms. Inositol polyphosphates (InsPs) are key signaling molecules known to regulate a variety of cellular processes including apoptosis in such organisms. The signaling role of InsPs in unicellular organisms such as Dictyostelium discoideum (D. discoideum) is not well understood. We investigated whether InsPs also play any role in apoptosis in D. discoideum and whether InsPs-mediated apoptosis follows a mechanism similar to that present in higher multicellular eukaryotes...
April 20, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29678789/molecular-modeling-and-docking-of-recombinant-hap-phytase-of-a-thermophilic-mould-sporotrichum-thermophile-reveals-insights-into-molecular-catalysis-and-biochemical-properties
#8
Bijender Singh, K K Sharma, Amit Kumari, Anil Kumar, S K Gakhar
A thermostable and protease-resistant HAP-phytase of Sporotrichum thermophile was over-expressed in Pichia pastoris ×33. Purified recombinant phytase displayed all its biochemical properties similar to wild type. Molecular modeling and docking of phytase with various substrates showed differential binding patterns with GoldScore values ranging from 40.61 to 79.78. Docking with different substrates revealed strong binding affinity with ATP and phytic acid, while the lowest with AMP and phosphoenol pyruvate...
April 17, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29678654/4tm-trpm8-channels-are-new-gatekeepers-of-the-er-mitochondria-ca-2-transfer
#9
Gabriel Bidaux, Dmitri Gordienko, George Shapovalov, Valerio Farfariello, Anne-Sophie Borowiec, Oksana Iamshanova, Loic Lemonnier, Maxime Gueguinou, Roseline Guibon, Gaelle Fromont, Mélanie Paillard, Yves Gouriou, Christophe Chouabe, Etienne Dewailly, Dimitra Gkika, Pilar López-Alvarado, J Carlos Menéndez, Laurent Héliot, Christian Slomianny, Natalia Prevarskaya
Calcium (Ca2+ ) release from the endoplasmic reticulum plays an important role in many cell-fate defining cellular processes. Traditionally, this Ca2+ release was associated with the ER Ca2+ release channels, inositol 1,4,5‑triphosphate receptor (IP3 R) and ryanodine receptor (RyR). Lately, however, other calcium conductances have been found to be intracellularly localized and to participate in cell fate regulation. Nonetheless, molecular identity and functional properties of the ER Ca2+ release mechanisms associated with multiple diseases, e...
April 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29676177/acetylcholine-induced-ciliary-beat-of-the-human-nasal-mucosa-is-regulated-by-the-pannexin-1-channel-and-purinergic-p2x-receptor
#10
Ba H Do, Toyoaki Ohbuchi, Tetsuro Wakasugi, Hiroki Koizumi, Mitsuru Yokoyama, Nobusuke Hohchi, Hideaki Suzuki
Background Airway mucociliary transport is an important function for the clearance of inhaled foreign particulates in the respiratory tract. The present study aimed at investigating the regulatory mechanism of acetylcholine (Ach)-induced ciliary beat of the human nasal mucosa in ex vivo. Methods The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic surgery. The mucosa was cut into thin strips, and ciliary movement was observed under a phase-contrast light microscope with a high-speed digital video camera...
January 1, 2018: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29675957/endoplasmic-reticulum-stress-induces-spatial-memory-deficits-by-activating-gsk-3
#11
Li Lin, Jie Cao, Shu-Sheng Yang, Zheng-Qi Fu, Peng Zeng, Jiang Chu, Lin-Na Ning, Teng Zhang, Yan Shi, Qing Tian, Xin-Wen Zhou, Jian-Zhi Wang
Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague-Dawley (SD) rats to induce the unfolded protein response (UPR), demonstrated by the enhanced phosphorylation of pancreatic ER kinase (PERK), inositol-requiring enzyme-1 (IRE-1) and activating transcription factor-6 (ATF-6). We observed that UPR induced spatial memory deficits and impairments of synaptic plasticity in the rats...
April 19, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29674969/-in-vitro-functional-characterization-of-get73-as-possible-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-5
#12
Sarah Beggiato, Andrea C Borelli, Maria C Tomasini, M Paola Castelli, Nicholas Pintori, Roberto Cacciaglia, Antonella Loche, Luca Ferraro
The present study was aimed to further characterize the pharmacological profile of N-[4-(trifluoromethyl) benzyl]-4-methoxybutyramide (GET73), a putative negative allosteric modulator (NAM) of metabotropic glutamate subtype 5 receptor (mGluR5) under development as a novel medication for the treatment of alcohol dependence. This aim has been accomplished by means of a series of in vitro functional assays. These assays include the measure of several down-stream signaling [intracellular Ca++ levels, inositol phosphate (IP) formation and CREB phosphorylation (pCREB)] which are generally affected by mGluR5 ligands...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29674261/acclimatization-of-pisum-sativum-l-grown-in-soil-contaminated-with-veterinary-antibiotics-an-attribute-of-dose-hormetic-response-of-root-metabolites
#13
R P Tasho, W T Shin, J Y Cho
Plant-veterinary antibiotic interaction has been widely studied, however, to the best of our knowledge acclimatization studies with regard to changes in plant root metabolites has not been reported so far. The purpose of this study was to examine the changes in the metabolome of pea roots under antibiotic stress and their role in acclimatization. Pisum sativum L. was grown in soil contaminated with three commonly used veterinary antibiotics - kanamycin (KA), sulfamethazine (SA), and tetracycline (TC). In response to antibiotic stress, plants accumulated different types of low molecular weight compounds that provided protection from stress by contributing to ROS detoxification, protection of membrane integrity, efficient signaling, cell wall function, and cellular osmotic adjustment (glucose, galactose, myo-inositol, stigmasterol, octadecadienoic acid, l-proline)...
April 16, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29673059/the-tlr4-ire1%C3%AE-pathway-activation-contributes-to-palmitate-elicited-lipotoxicity-in-hepatocytes
#14
Chen Shen, Wang Ma, Lei Ding, Songtao Li, Xiaobing Dou, Zhenyuan Song
Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be clearly elucidated. Toll-like receptor (TLR) 4 plays a fundamental role in activating the innate immune system. Intriguingly, hepatocytes express TLR4 and machinery for TLR4 signalling pathway. That liver-specific TLR4 knockout mice are protective against diet-induced NAFLD suggests that hepatocyte TLR4 signalling pathway plays an important role in NAFLD pathogenesis...
April 19, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29666506/insights-into-aluminum-tolerance-pathways-in-stylosanthes-as-revealed-by-rna-seq-analysis
#15
Caode Jiang, Lusheng Liu, Xiaofeng Li, Rongrong Han, Yunmin Wei, Yongxiong Yu
Stylo has a great potential for Al3+ resistance in acidic soils through secretion of citrate from the roots. To get insight into the molecular mechanisms responsible, transcriptomic changes were investigated in the roots after treatment with T01 (-Al3+ , pH6.0), T02 (-Al3+ , pH4.3) and T03 (50 µM AlCl3 , pH4.3). In total, 83,197 unigenes generated from 130,933 contigs were obtained. Of them, 282, 148 and 816 differentially expressed unigenes (DEGs) were revealed in T01_vs_T02, T02_vs_T03 and T01_vs_T03 comparison, respectively (FDR < 0...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29665893/-effect-of-ship-1-on-invasion-migration-and-pi3k-akt-signaling-pathway-of-leukemic-cells
#16
Xi-Chun Xiao, Yue-Li Gu, Shu-Xia Chen, Gen-Jie Wang, Lin Yuan
OBJECTIVE: To investigate the effect of SH2-containing inositol phosphatase-1 (SHIP-1) on the proliferation, invasion and migration of human leukemia cells as well as phosphatidylinositol-3 kinase (PI3K) / protein kinase B (AKT) signaling pathway. METHODS: The overexpression vector pCDNA3.1-SHIP1 was transfected into THP-1 cells by Lipofectamine 2000. The experiment was divided into 3 groups: control group (untreated cells) and empty vector group (transfected with empty vector pCDNA3...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665822/toxoplasma-gondii-dense-granule-protein-15-induces-apoptosis-in-choriocarcinoma-jeg-3-cells-through-endoplasmic-reticulum-stress
#17
Wei Wei, Fangfang Zhang, He Chen, Yuanyuan Tang, Tian Xing, Qingli Luo, Li Yu, Jian Du, Jilong Shen, Linjie Zhang
BACKGROUND: Toxoplasma gondii, a single-celled parasite commonly found in mammals, has been shown to induce trophoblast cell apoptosis and subsequently cause fetal damage and abortion. Although dense granule protein 15 (GRA15) has been identified as a key component in innate immunity to T. gondii infection and its pathogenesis, its role in host cell apoptosis remains unclarified. METHODS: Type II GRA15 (GRA15II ) cDNA was inserted into a plasmid encoding enhanced green fluorescent protein (pEGFP)...
April 17, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29664361/pseudaeromonas-paramecii-sp-nov-isolated-from-the-ciliate-paramecium-caudatum-and-emendation-of-the-genus-pseudaeromonas
#18
Sumi Akter, Mann Kyoon Shin
A Gram-stain-negative, oxidase-negative and catalase-negative, motile, rod-shaped bacterial strain, designated PCS8T , hosted by the ciliate Paramecium caudatum was investigated by using a polyphasic approach. Strain PCS8T was observed to be able to grow at 12-44 °C (optimum, 36-37 °C), at pH 6.0-10.0 (optimum, 7.0) and in the presence of 0-3 % NaCl (optimum, 1-2 %). It could hydrolyse starch and aesculin and produce acid from d-sorbitol, myo-inositol, glycerol and l-rhamnose. The sequence similarity of the new isolate was 96...
April 17, 2018: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/29664331/handheld-raman-spectrometer-instrumentation-for-quantitative-tuberculosis-biomarker-detection-a-performance-assessment-for-point-of-need-infectious-disease-diagnostics
#19
Nicholas A Owens, Lars B Laurentius, Marc D Porter, Qun Li, Sean Wang, Delphi Chatterjee
Techniques for the detection of disease biomarkers are key components in the protection of human health. While work over the last few decades has redefined the low-level measurement of disease biomarkers, the translation of these capabilities from the formal clinical setting to point-of-need (PON) usage has been much more limited. This paper presents the results of experiments designed to examine the potential utility of a handheld Raman spectrometer as a PON electronic reader for a sandwich immunoassay based on surface-enhanced Raman scattering (SERS)...
January 1, 2018: Applied Spectroscopy
https://www.readbyqxmd.com/read/29664285/core-shell-au-metal-organic-framework-for-promoting-raman-detection-sensitivity-of-methenamine
#20
Yanzheng Cai, Yiping Wu, Tong Xuan, Xiaoyu Guo, Ying Wen, Hai-Feng Yang
Abuse of methenamine in foodstuff is harmful to the health of people. Routine methods recommended by national standard are indirect assay with complicated pretreatment of sample or less sensitivity. In this work, core-shell Au nanoparticles@inositol hexaphosphate@MIL-101(Fe) nanoparticles, designated as Au@MIL-101, are successfully synthesized by layer-by-layer assembly. Metal-organic framework (MOF, MIL-101) modified AuNPs could narrow the distance between neighboring Au@MIL-101, which increases the amount of "hot spots and contributes excellent enhancement of Raman scattering...
April 17, 2018: ACS Applied Materials & Interfaces
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