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https://www.readbyqxmd.com/read/29219161/the-atomic-level-mechanism-of-white-phosphorous-demolition-by-di-iodine
#1
Carlo Mealli, Andrea Ienco, Maurizio Peruzzini, Gabriele Manca
A detailed mechanism of the I2-induced transformation of white phosphorus into PI3 emerges from a DFT analysis. This multi-step process implies that at any stage one P-P and two I-I bonds cleavages, associated with the formation of two P-I bonds plus an in situ generated brand new I2 molecule. Significant electron transfer between the atoms is observed at any step, but the reactions are better defined as concerted rather than redox. Along the steepest descent to the product, no significant barrier is encountered except for the very first P4 activation, which costs +14...
December 8, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29212575/oct4-is-crucial-for-transdifferentiation-of-hepatocytes-to-biliary-epithelial-cells-in-an-in-vitro-organoid-culture-model
#2
Mboya Doffou, George Adams, William C Bowen, Shirish Paranjpe, Harish S Parihar, Huy Nguyen, George K Michalopoulos, Vishakha Bhave
BACKGROUND: Hepatocyte to biliary transdifferentiation has been documented in various models of bile duct injury. In this process, mature hepatocytes transform into mature biliary epithelial cells by acquiring biliary phenotypic markers. Several signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown to be involved in the process. However, if Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown. METHODS: We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation...
December 6, 2017: Gene Expression
https://www.readbyqxmd.com/read/29210073/interleukin-17-regulates-matrix-metalloproteinase-activity-in-human-pulmonary-tuberculosis
#3
Shivani Singh, George Maniakis-Grivas, Utpal K Singh, Radha M Asher, Francesco Mauri, Paul T Elkington, Jon S Friedland
Tuberculosis (TB) is characterised by extensive pulmonary matrix breakdown. Interleukin-17 (IL-17) is key in host defence in TB but its role in TB-driven tissue damage is unknown. We investigated the hypothesis that respiratory stromal cell matrix metalloproteinase (MMP) production in TB is regulated by T helper-17 (TH -17) cytokines. Biopsies of patients with pulmonary TB were analysed by immunohistochemistry (IHC) and patient bronchoalveolar lavage fluid (BALF) MMP and cytokine concentrations measured by Luminex assays...
December 6, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29203791/identification-of-insulin-sensitizing-molecules-acting-by-disrupting-the-interaction-between-the-insulin-receptor-and-grb14
#4
Anaïs Gondoin, Cornelia Hampe, Richard Eudes, Cyril Fayolle, Cécile Pierre-Eugène, Maria Miteva, Bruno O Villoutreix, Florence Charnay-Pouget, David J Aitken, Tarik Issad, Anne-Françoise Burnol
Metabolic diseases are characterized by a decreased action of insulin. During the course of the disease, usual treatments frequently fail and patients are finally submitted to insulinotherapy. There is thus a need for innovative therapeutic strategies to improve insulin action. Growth factor receptor-bound protein 14 (Grb14) is a molecular adapter that specifically binds to the activated insulin receptor (IR) and inhibits its tyrosine kinase activity. Molecules disrupting Grb14-IR binding are therefore potential insulin-sensitizing agents...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29200900/genistein-attenuates-isoflurane-induced-neurotoxicity-and-improves-impaired-spatial-learning-and-memory-by-regulating-camp-creb-and-bdnf-trkb-pi3k-akt-signaling
#5
Tao Jiang, Xiu-Qin Wang, Chuan Ding, Xue-Lian Du
Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats...
November 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29198055/phase-ii-study-of-buparlisib-bkm120-and-trastuzumab-in-patients-with-her2-%C3%A2-locally-advanced-or-metastatic-breast-cancer-resistant-to-trastuzumab-based-therapy
#6
B Pistilli, T Pluard, A Urruticoechea, D Farci, A Kong, T Bachelot, S Chan, H S Han, G Jerusalem, P Urban, D Robinson, S L Mouhaër, E D Tomaso, C Massacesi, C Saura
PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab...
December 2, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29196758/the-role-of-oxidative-stress-in-the-crosstalk-between-leptin-and-mineralocorticoid-receptor-in-the-cardiac-fibrosis-associated-with-obesity
#7
Josué Gutiérrez-Tenorio, Gema Marín-Royo, Ernesto Martínez-Martínez, Rubén Martín, María Miana, Natalia López-Andrés, Raquel Jurado-López, Isabel Gallardo, María Luaces, José Alberto San Román, María González-Amor, Mercedes Salaices, María Luisa Nieto, Victoria Cachofeiro
We have investigated whether mineralocorticoid receptor activation can participate in the profibrotic effects of leptin in cardiac myofibroblasts, as well as the potential mechanisms involved. The presence of eplerenone reduced the leptin-induced increase in protein levels of collagen I, transforming growth factor β, connective tissue growth factor and galectin-3 and the levels of both total and mitochondrial of superoxide anion (O2.-) in cardiac myofibroblasts. Likewise, the MEK/ERK inhibitor, PD98059, and the PI3/Akt inhibitor, LY294002, showed a similar pattern...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29181846/golm1-promotes-prostate-cancer-progression-through-activating-pi3k-akt-mtor-signaling
#8
REVIEW
Guang Yan, Yi Ru, Kerong Wu, Fengqi Yan, Qinhao Wang, Jingxiang Wang, Tao Pan, Mei Zhang, Hua Han, Xia Li, Lian Zou
BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Various molecular mechanisms account for PCa progression and elucidation of these mechanisms is key for selection of optimal therapies and improvement of patient outcome. Golgi membrane protein 1 (GOLM1) has been identified as a novel biomarker for PCa, but its biological functions and molecular mechanisms remain poorly understood. METHOD: GOLM1 expression was determined in PCa by tissue microarrays (TMAs) and real-time RT-PCR, Western blot, and immunohistochemistry (IHC) analyses...
November 27, 2017: Prostate
https://www.readbyqxmd.com/read/29180244/dual-loss-of-p110%C3%AE-pi3-kinase-and-skap-knstrn-expression-leads-to-combined-immunodeficiency-and-multisystem-syndromic-features
#9
Nigel Sharfe, Ariana Karanxha, Harjit Dadi, Daniele Merico, David Chitayat, Jo-Anne Herbrick, Spencer Freeman, Sergio Grinstein, Chaim M Roifman
BACKGROUND: We previously reported a novel syndrome characterized by combined immunodeficiency associated with severe developmental defects - subsequently known as Roifman-Chitayat Syndrome (RCS; OMIM 613328). Linkage analysis identified two disease-associated loci. OBJECTIVE: To identify the genetic defect in these patients and characterize their immunological cellular abnormalities. METHODS: Genetic, immunological, protein and cellular functional analyses were used to identify and characterize patient genetic deficiencies and aberrant patient cell behaviour...
November 24, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29175450/crosstalk-between-machrm3-and-%C3%AE-2ar-via-acetylcholine-pi3-pkc-pbep1-raf-1-mek1-2-erk1-2-pathway-activation-in-human-bronchial-epithelial-cells-after-long-term-cigarette-smoke-exposure
#10
Giusy Daniela Albano, Anna Bonanno, Monica Moscato, Giulia Anzalone, Caterina Di Sano, Loredana Riccobono, Sally E Wenzel, Mirella Profita
BACKGROUND: Cigarette smoke extract (CSE) affects the expression of non-neuronal components of cholinergic system in bronchial epithelial cells and, as PEBP1/Raf-mediated MAPK1/2 and ERK1/2 pathway, promotes inflammation and oxidative stress. AIMS: We studied whether Acetylcholine (ACh) is involved in the mechanism of crosstalk between mAChRM3 and β2Adrenergic receptors (β2AR) promoting, via PI3/PKC/PBEP1/Raf/MEK1/2/ERK1/2 activation, β2AR desensitization, inflammation and, oxidative stress in a bronchial epithelial cell line (16HBE) after long-term exposure to cigarette smoke extract (LECSE)...
November 22, 2017: Life Sciences
https://www.readbyqxmd.com/read/29167336/an-insight-into-the-role-of-e3-ubiquitin-ligase-c-cbl-escrt-machinery-and-host-cell-signaling-in-kaposi-s-sarcoma-associated-herpesvirus-kshv-entry-and-trafficking
#11
Binod Kumar, Arunava Roy, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal endothelial cell begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), xCT and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multi-molecular complex of receptors, signal molecules (FAK, Src, PI3-K, RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas and GEF-C3G), and actin/myosin II light chain that leads to virus entry via macropinocytosis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29161318/loss-of-mtorc2-signaling-in-oligodendrocyte-precursor-cells-delays-myelination
#12
Mark D Grier, Kathryn L West, Nathaniel D Kelm, Cary Fu, Mark D Does, Brittany Parker, Eleanor McBrier, Andre H Lagrange, Kevin C Ess, Robert P Carson
Myelin abnormalities are increasingly being recognized as an important component of a number of neurologic developmental disorders. The integration of many signaling pathways and cell types are critical for correct myelinogenesis. The PI3-K and mechanistic target of rapamycin (mTOR) pathways have been found to play key roles. mTOR is found within two distinct complexes, mTORC1 and mTORC2. mTORC1 activity has been shown to play a major role during myelination, while the role of mTORC2 is not yet well understood...
2017: PloS One
https://www.readbyqxmd.com/read/29159829/calcium-hydroxide-regulates-transcription-of-the-bone-sialoprotein-gene-via-a-calcium-sensing-receptor-in-osteoblast-like-ros-17-2-8-cells
#13
Shuang Wang, Keisuke Noda, Yuanyuan Yang, Zhengyan Shen, Zhen Chen, Yorimasa Ogata
Bone sialoprotein (BSP) is a glycoprotein associated with mineralized tissues. In this study, we investigated the regulation of Bsp transcription by calcium hydroxide [Ca(OH)2 ] in rat osteosarcoma-derived osteoblast-like ROS 17/2.8 cells and stromal bone marrow cells. Application of Ca(OH)2 (0.4 mM) increased the levels of runt-related transcription factor 2 (Runx2) and BspmRNAs at 3 and 6 h and the level of BSP protein at 12 h. Transient transfection analyses were performed using chimeric constructs encompassing different regions of the rat Bsp gene promoter ligated to a luciferase reporter gene...
November 21, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/29154826/w9-peptide-enhanced-osteogenic-differentiation-of-human-adipose-derived-stem-cells
#14
Yuki Otsuki, Masaaki Ii, Kazumasa Moriwaki, Masashi Okada, Koichi Ueda, Michio Asahi
W9 is a peptide that abrogates osteoclast differentiation via blockade of nuclear factor-κB ligand (RANKL)-RANK signaling, which activates bone formation. However, W9 stimulated osteogenesis in osteoblasts and mesenchymal stem cells. The present study demonstrated that the W9 peptide promoted osteogenic differentiation of human adipose-derived stem cells (hAdSCs) even under non-osteogenic differentiation culture conditions. W9-treated hAdSCs exhibited several osteocalcin-expressing cells and great mineralization compared to the BMP2-treated hAdSCs, which suggests that the W9 peptide had potent osteogenic potential in hAdSCs...
November 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29144985/a-phase-1-2-study-of-rigosertib-in-patients-with-myelodysplastic-syndromes-mds-and-mds-progressed-to-acute-myeloid-leukemia
#15
Shyamala C Navada, Steven M Fruchtman, Rosalie Odchimar-Reissig, Erin P Demakos, Michael E Petrone, Patrick S Zbyszewski, James F Holland, Lewis R Silverman
This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m(2)/day in 14-day cycles...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29143164/upregulation-of-myelin-gene-expression-by-a-physically-modified-saline-via-phosphatidylinositol-3-kinase-mediated-activation-of-creb-implications-for-multiple-sclerosis
#16
Malabendu Jana, Supurna Ghosh, Kalipada Pahan
An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimulated the expression of myelin-specific genes and proteins (myelin basic protein, MBP; myelin oligodendrocyte glycoprotein, MOG and proteolipid protein, PLP) in primary mouse oligodendroglia and mixed glial cells...
November 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29137423/expression-of-the-%C3%AE-3-subunit-of-na-k-atpase-is-increased-in-gastric-cancer-and-regulates-gastric-cancer-cell-progression-and-prognosis-via-the-pi3-akt-pathway
#17
Li Li, Ru Feng, Qian Xu, Feiyue Zhang, Tong Liu, Jiang Cao, Sujuan Fei
ATP1B3 encodes the β3 subunit of Na(+)/K(+)-ATPase and is located in the q22-23 region of chromosome 3. Na(+)/K(+)-ATPase participates in normal cellular activities but also plays a crucial role in carcinogenesis. In the present study, we found that expression of the β3 subunit of Na(+)/K(+)-ATPase was increased in human gastric cancer tissues compared with that in normal matched tissues and that this increased expression predicted a poor outcome. ATP1B3 expression was elevated at both the mRNA and protein levels in gastric cancer cell lines relative to those in a normal gastric epithelial cell line...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136006/lipopolysaccharide-potentiates-platelet-responses-via-toll-like-receptor-4-stimulated-akt-erk-pla2-signalling
#18
Maria E Lopes Pires, Simon R Clarke, Sisi Marcondes, Jonathan M Gibbins
Lipopolysaccharide (LPS) from the cell envelope of Gram-negative bacteria is a principal cause of the symptoms of sepsis. LPS has been reported to modulate the function of platelets although the underlying mechanisms of LPS action in these cells remain unclear. Platelets express the Toll-like receptor 4 (TLR4) which serves as a receptor for LPS, although the potential role of TLR4 and associated cell signalling in controlling platelet responses to LPS has not been extensively explored. In this study, we therefore investigated the actions of LPS prepared from different strains of Escherichia coli on platelet function, the underlying signalling mechanisms, and the potential role of TLR4 in orchestrating these...
2017: PloS One
https://www.readbyqxmd.com/read/29126698/hybrid-drug-combination-combination-of-ferulic-acid-and-metformin-as-anti-diabetic-therapy
#19
REVIEW
Rakesh Nankar, P K Prabhakar, Mukesh Doble
BACKGROUND AND PURPOSE: Ferulic acid, an anti-oxidant phytochemical present in several dietary components, is known to produce wide range of pharmacological effects. It is approved for use in food industry as a preservative and in sports food. Previous reports from our lab have shown synergistic interaction of ferulic acid with metformin in cell lines and diabetic rats. The purpose of this review is to compile information about anti-diabetic activity of ferulic acid in in vitro and in vivo models with special emphasis on activity of ferulic acid when combined with metformin...
October 24, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29118270/upregulation-of-pir-gene-expression-induced-by-human-papillomavirus-e6-and-e7-in-epithelial-oral-and-cervical-cells
#20
Diego Carrillo, Juan P Muñoz, Hernán Huerta, Gabriel Leal, Alejandro Corvalán, Oscar León, Gloria M Calaf, Ulises Urzúa, Enrique Boccardo, Julio C Tapia, Francisco Aguayo
The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells...
November 2017: Open Biology
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