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https://www.readbyqxmd.com/read/28823092/inhibition-of-p2x7-receptors-improves-outcomes-after-traumatic-brain-injury-in-rats
#1
Xiaofeng Liu, Zhengqing Zhao, Ruihua Ji, Jiao Zhu, Qian-Qian Sui, Gillian E Knight, Geoffrey Burnstock, Cheng He, Hongbin Yuan, Zhenghua Xiang
Traumatic brain injury (TBI) is the leading cause of death and disability for people under the age of 45 years worldwide. Neuropathology after TBI is the result of both the immediate impact injury and secondary injury mechanisms. Secondary injury is the result of cascade events, including glutamate excitotoxicity, calcium overloading, free radical generation, and neuroinflammation, ultimately leading to brain cell death. In this study, the P2X7 receptor (P2X7R) was detected predominately in microglia of the cerebral cortex and was up-regulated on microglial cells after TBI...
August 19, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28822990/%C3%AE-%C3%AE-mangostins-induces-autophagy-and-shows-synergistic-effectwith-gemcitabine-in-pancreatic-cancer-cell-lines
#2
Myoungjae Kim, Young-Won Chin, Eun Joo Lee
Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of α-mangostin (αM) and γ-mangostin (γM) extracted from the pericarp of Garcinia mangostana L.. Both αM and γM reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels...
August 21, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28822984/tbk1-mutations-in-italian-patients-with-amyotrophic-lateral-sclerosis-genetic-and-functional-characterisation
#3
Laura Pozzi, Fabiola Valenza, Lorena Mosca, Andrea Dal Mas, Teuta Domi, Alessandro Romano, Claudia Tarlarini, Yuri Matteo Falzone, Lucio Tremolizzo, Gianni Sorarù, Federica Cerri, Pilar M Ferraro, Silvia Basaia, Federica Agosta, Raffaella Fazio, Mauro Comola, Giancarlo Comi, Maurizio Ferrari, Angelo Quattrini, Christian Lunetta, Silvana Penco, Dario Bonanomi, Paola Carrera, Nilo Riva
BACKGROUND: TANK-binding kinase 1 (TBK1) gene has been recently identified as a causative gene of amyotrophic lateral sclerosis (ALS). METHODS: We sequenced the TBK1 gene in a cohort of 154 Italian patients with ALS with unclear genetic aetiology. We subsequently assessed the pathogenic potential of novel identified TBK1 variants using functional in vitro studies: expression, targeting and activity were evaluated in patient-derived fibroblasts and in cells transfected with mutated-TBK1 plasmids...
August 19, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28822960/loss-of-perilipin-2-in-cultured-myotubes-enhances-lipolysis-and-redirects-the-metabolic-energy-balance-from-glucose-oxidation-towards-fatty-acid-oxidation
#4
Yuan Z Feng, Jenny Lund, Yuchuan Li, Irlin K Knabenes, Siril S Bakke, Eili Tranheim Kase, Yun K Lee, Alan R Kimmel, G Hege Thoresen, Arild Christian Rustan, Knut Tomas Dalen
Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2-/- mice contain reduced content of LDs and accumulate less oleic acid in triacylglycerol (TAG), due to elevated LD hydrolysis compared to Plin2+/+ myotubes. The reduced ability to store TAG in LDs in Plin2-/- myotubes is accompanied by a shift in energy metabolism...
August 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28822838/scavenging-reactive-oxygen-species-inhibits-status-epilepticus-induced-neuroinflammation
#5
Pallavi B McElroy, Li-Ping Liang, Brian J Day, Manisha Patel
Inflammation has been identified as an important mediator of seizures and epileptogenesis. Understanding the mechanisms underlying seizure-induced neuroinflammation could lead to the development of novel therapies for the epilepsies. Reactive oxygen species (ROS) are recognized as mediators of seizure-induced neuronal damage and are known to increase in models of epilepsies. ROS are also known to contribute to inflammation in several disease states. We hypothesized that ROS are key modulators of neuroinflammation i...
August 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28822817/rosiglitazone-promotes-cardiac-hypertrophy-and-alters-chromatin-remodeling-in-isolated-cardiomyocytes
#6
Lama Fawaz Pharaon, Naglaa Fathi El-Orabi, Muhammad Kunhi, Nadya Al Yacoub, Salma Mahmoud Awad, Coralie Poizat
Rosiglitazone is an anti-diabetic agent that raised a major controversy over its cardiovascular adverse effects. There is in vivo evidence that Rosiglitazone promotes cardiac hypertrophy by PPAR -γ-independent mechanisms. However, whether Rosiglitazone directly alters hypertrophic growth in cardiac cells is unknown. Chromatin remodeling by histone post-translational modifications has emerged as critical for many cardiomyopathies. Based on these observations, this study was initiated to investigate the cardiac hypertrophic effect of Rosiglitazone in a cellular model of primary neonatal rat cardiomyocytes (NRCM)...
August 16, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28822809/inhibition-of-soluble-epoxide-hydrolase-lowers-portal-hypertension-in-cirrhotic-rats-by-ameliorating-endothelial-dysfunction-and-liver-fibrosis
#7
Wensheng Deng, Yiming Zhu, Jiayun Lin, Lei Zheng, Chihao Zhang, Meng Luo
Epoxyeicostrienoic acids (EETs) are arachidonic acid derived meditators which are catalyzed by soluble epoxide hydrolase (sEH) to less active dihydroeicostrienoics acids (DHETS). The aim of our study is to investigate the effects of sEH inhibition on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4 cirrhotic rats. The sEH inhibitor,trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB) was administered to stabilize hepatic EETs by gavage at a dose of 1mg/kg/d...
August 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28822801/microarray-gene-expression-study-in-fibroblast-and-lymphoblastoid-cell-lines-from-antipsychotic-na%C3%A3-ve-first-episode-schizophrenia-patients
#8
Patricia Gassó, Sergi Mas, Natalia Rodríguez, Daniel Boloc, Susana García-Cerro, Miquel Bernardo, Amalia Lafuente, Eduard Parellada
Schizophrenia (SZ) is a chronic psychiatric disorder whose onset of symptoms occurs in late adolescence and early adulthood. The etiology is complex and involves important gene-environment interactions. Microarray gene-expression studies on SZ have identified alterations in several biological processes. The heterogeneity in the results can be attributed to the use of different sample types and other important confounding factors including age, illness chronicity and antipsychotic exposure. The aim of the present microarray study was to analyze, for the first time to our knowledge, differences in gene expression profiles in 18 fibroblast (FCLs) and 14 lymphoblastoid cell lines (LCLs) from antipsychotic-naïve first-episode schizophrenia (FES) patients and healthy controls...
August 5, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28822757/quercetin-exerts-synergetic-anti-cancer-activity-with-10-hydroxy-camptothecin
#9
Qin Tang, Fangling Ji, Jingyun Wang, Lianying Guo, Yachen Li, Yongming Bao
Quercetin (Qu) is known as a dietary antioxidant with numerous bioactivities, but its function in anti-cancer has not been fully investigated. Here, we show that Qu at low doses (≤10μM) significantly enhances the inhibition of 10-hydroxy camptothecin (HCPT) on the proliferation of MCF7, BGC823 and HepG2 cells. A plasmid DNA relaxation assay indicates that the inhibition of HCPT on the catalytic activity of topoisomerase I (Topo I) is increased by Qu at 10μM. Compared to the treatment by Qu or HCPT alone, phosphorylation at Ser(139) of γH2A...
August 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28822352/vibrio-vulnificus-martx-cytotoxin-causes-inactivation-of-phagocytosis-related-signaling-molecules-in-macrophages
#10
Chun-Liang Chen, Shu-Chun Chien, Tzeng-Horng Leu, Hans I-Chen Harn, Ming-Jer Tang, Lien-I Hor
BACKGROUND: Vibrio vulnificus is a marine bacterial species that causes opportunistic infections manifested by serious skin lesions and fulminant septicemia in humans. We have previously shown that the multifunctional autoprocessing repeats in toxin (MARTXVv1) of a biotype 1 V. vulnificus strain promotes survival of this organism in the host by preventing it from engulfment by the phagocytes. The purpose of this study was to further explore how MARTXVv1 inhibits phagocytosis of this microorganism by the macrophage...
August 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28822279/chemical-synthesis-of-guanosine-diphosphate-mannuronic-acid-gdp-mana-and-its-c-4-o-methyl-and-c-4-deoxy-congeners
#11
Qingju Zhang, P Lynne Howell, Herman S Overkleeft, Dmitri V Filippov, Gijsbert A van der Marel, Jeroen D C Codée
Described is the first synthesis of guanosine diphosphate mannuronic acid (GDP-ManA), the sugar donor used by algae and bacteria for the production of alginate, an anionic polysaccharide composed of β-d-mannuronic acid (ManA) and α-l-guluronic acid (GulA). Understanding the biosynthesis of these polyanionic polysaccharides on the molecular level, opens up avenues to use and modulate the biosynthesis machinery for biotechnological and therapeutic applications. The synthesis reported here delivers multi-milligram amounts of the GDP-ManA donor that can be used to study the polymerase (Alg8 in Pseudomonas aeruginosa) that generates the poly-ManA chain...
August 11, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#12
Alexandre Vallée, Rémy Guillevin, Jean-Noël Vallée
The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas...
August 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28822137/studying-the-function-of-the-phosphorylated-pathway-of-serine-biosynthesis-in-arabidopsis-thaliana
#13
Stephan Krueger, Ruben M Benstein, Sabine Wulfert, Armand D Anoman, María Flores-Tornero, Roc Ros
Photorespiration is an essential pathway in photosynthetic organisms and is particularly important to detoxify and recycle 2-phosphoglycolate (2-PG), a by-product of oxygenic photosynthesis. The enzymes that catalyze the reactions in the photorespiratory core cycle and closely associated pathways have been identified; however, open questions remain concerning the metabolic network in which photorespiration is embedded. The amino acid serine represents one of the major intermediates in the photorespiratory pathway and photorespiration is thought to be the major source of serine in plants...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28822126/dimethyl-labeling-based-quantification-of-the-lysine-acetylome-and-proteome-of-plants
#14
Ines Lassowskat, Markus Hartl, Fabian Hosp, Paul J Boersema, Matthias Mann, Iris Finkemeier
Photorespiratory enzymes in different cellular compartments have been reported to be posttranslational modified by phosphorylation, disulfide formation, S-nitrosylation, glutathionylation, and lysine acetylation. However, not much is known yet about the function of these modifications to regulate the activities, localizations, or interactions of the proteins in this metabolic pathway. Hence, it will be of great importance to study these modifications and their temporal and conditional occurrence in more detail...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28822073/isorhynchophylline-attenuates-mpp-induced-apoptosis-through-endoplasmic-reticulum-stress-and-mitochondria-dependent-pathways-in-pc12-cells-involvement-of-antioxidant-activity
#15
Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong
Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP(+)-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP(+)-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway...
August 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28822039/stimulation-of-nachr%C3%AE-7-receptor-inhibits-tnf-synthesis-and-secretion-in-response-to-lps-treatment-of-mast-cells-by-targeting-erk1-2-and-tace-activation
#16
F Guzmán-Mejía, C López-Rubalcava, C González-Espinosa
The cholinergic anti-inflammatory pathway is recognized as one of the main mechanisms of neuromodulation of the immune system. Activation of the α7 nicotinic acetylcholine receptor (nAchRα7) suppresses cytokine synthesis in distinct immune cells but the molecular mechanisms behind this effect remain to be fully described. Mast cells (MCs) are essential players of allergic reactions and innate immunity responses related to chronic inflammation. Activation of TLR4 receptor in MCs leads to the rapid secretion of pre-synthesized TNF from intracellular pools and to the activation of NFκB, necessary for de novo synthesis of TNF and other cytokines...
August 18, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28822032/synthesis-of-rigid-polyurethane-foams-from-phosphorylated-biopolyols
#17
Juan Carlos de Haro, Daniel López-Pedrajas, Ángel Pérez, Juan Francisco Rodríguez, Manuel Carmona
Renewable resources are playing a key role on the synthesis of biodegradable polyols. Moreover, the incorporation of covalently linked additives is increasing in importance in the polyurethane (PU) market. In this work, previously epoxidized grape seed oil and methyl oleate were transformed into phosphorylated biopolyols through an acid-catalyzed ring-opening hydrolysis in the presence of H3PO4. The formation of phosphate polyesters was confirmed by FT-IR and (31)P-NMR. However, the synthesis of a high-quality PU rigid foam was not possible using exclusively these polyols attending to their low hydroxyl value...
August 18, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28822019/gypenoside-ix-suppresses-p38-mapk-akt-nf%C3%AE%C2%BAb-signaling-pathway-activation-and-inflammatory-responses-in-astrocytes-stimulated-by-proinflammatory-mediators
#18
Xiaoshuang Wang, Liu Yang, Li Yang, Faping Xing, Hua Yang, Liyue Qin, Yunyi Lan, Hui Wu, Beibei Zhang, Hailian Shi, Cheng Lu, Fei Huang, Xiaojun Wu, Zhengtao Wang
Gypenoside IX (GP IX) is a pure compound isolated from Panax notoginseng. Gypenosides have been implicated to benefit the recovery of enormous neurological disorders. By suppressing the activation of astrocytes, gypenosides can improve the cognitive impairment. However, so far, little is known about whether GP IX could restrain the inflammatory responses in astrocytes or reactive astrogliosis. In present study, the anti-inflammatory effects of GP IX were investigated in reactive astrocytes induced by proinflammatory mediators both in vitro and in vivo...
August 18, 2017: Inflammation
https://www.readbyqxmd.com/read/28821799/plk1-bound-to-bub1-contributes-to-spindle-assembly-checkpoint-activity-during-mitosis
#19
Masanori Ikeda, Kozo Tanaka
For faithful chromosome segregation, the formation of stable kinetochore-microtubule attachment and its monitoring by the spindle assembly checkpoint (SAC) are coordinately regulated by mechanisms that are currently ill-defined. Here, we show that polo-like kinase 1 (Plk1), which is instrumental in forming stable kinetochore-microtubule attachments, is also involved in the maintenance of SAC activity by binding to Bub1, but not by binding to CLASP2 or CLIP-170. The effect of Plk1 on the SAC was found to be mediated through phosphorylation of Mps1, an essential kinase for the SAC, as well as through phosphorylation of the MELT repeats in Knl1...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821788/bioenergetic-adaptations-in-chemoresistant-ovarian-cancer-cells
#20
Sajad Dar, Jasdeep Chhina, Ismail Mert, Dhananjay Chitale, Thomas Buekers, Hareena Kaur, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan
Earlier investigations have revealed that tumor cells undergo metabolic reprogramming and mainly derive their cellular energy from aerobic glycolysis rather than oxidative phosphorylation even in the presence of oxygen. However, recent studies have shown that certain cancer cells display increased oxidative phosphorylation or high metabolically active phenotype. Cellular bioenergetic profiling of 13 established and 12 patient derived ovarian cancer cell lines revealed significant bioenergetics diversity. The bioenergetics phenotype of ovarian cancer cell lines correlated with functional phenotypes of doubling time and oxidative stress...
August 18, 2017: Scientific Reports
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