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https://www.readbyqxmd.com/read/28822990/%C3%AE-%C3%AE-mangostins-induces-autophagy-and-shows-synergistic-effectwith-gemcitabine-in-pancreatic-cancer-cell-lines
#1
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
#2
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/28822962/glucose-transporter-4-glut4-deficient-hearts-develop-maladaptive-hypertrophy-in-response-to-physiologic-or-pathologic-stresses
#3
Adam Raymond Wende, Jaetaek Kim, William Holland, Benjamin E Wayment, Brian T O'Neill, Joseph Tuinei, Manoja K Brahma, Mark E Pepin, Mark A McCrory, Ivan Luptak, Ganesh V Halade, Sheldon E Litwin, E Dale Abel
Pathological cardiac hypertrophy may be associated with reduced expression of the GLUT4 glucose transporter in contrast to exercise-induced cardiac hypertrophy, where GLUT4 levels are increased. However, mice with cardiac specific deletion of GLUT4 (G4H-/-) have normal cardiac function in the unstressed state. This study tested the hypothesis that cardiac GLUT4 is required for myocardial adaptations to hemodynamic demands. G4H-/- and control littermates (Con) were subjected to either a pathological model of left ventricular pressure overload (transverse aortic constriction; TAC) or a physiological model of endurance exercise (swim training)...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28822888/apatinib-enhances-antitumour-activity-of-egfr-tkis-in-non-small-cell-lung-cancer-with-egfr-tki-resistance
#4
Fang Li, Tengjiao Zhu, Baoshan Cao, Jiadong Wang, Li Liang
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-rechallenged therapy for EGFR-mutant non-small cell lung cancer (NSCLC) patients who acquired resistance showed moderate efficacy. Considering the high interrelation between EGFR and vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathways, we firstly evaluated EGFR-TKI combined with apatinib (a highly selective VEGFR2 inhibitor) in EGFR-TKI-resistant model and patients...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28822887/the-changing-diagnostic-pathway-for-lung-cancer-patients-in-shanghai-china
#5
REVIEW
Tao Jiang, Shengxiang Ren, Xuefei Li, Chunxia Su, Caicun Zhou, Mary O'Brien
Accumulating evidence suggest that patients with advanced non-small-cell lung cancer (NSCLC) and specific genomic alterations including epidermal growth factor receptor and microtubule-associated protein-like 4 anaplastic lymphoma kinase could significantly benefit from molecular-targeted therapies compared with chemotherapy. Recently, immunotherapy based on programmed cell death 1 (PD-1) and its ligand (PD-L1) blockade prolong survival in patients with advanced NSCLC, especially in those patients with positive expression of PD-L1 and when used in the first-line setting...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28822855/tetrandrine-cardioprotection-in-ischemia-reperfusion-i-r-injury-via-jak3-stat3-hexokinase-ii
#6
Tie-Jun Zhang, Rui-Xia Guo, Xia Li, Yan-Wei Wang, Yong-Jun Li
Tetrandrine(TET), a bisbenzylisoquinoline alkaloid has been used for the treatment of cardiovascular diseases and hypertension. This study was to investigate whether tetrandrine exerts cardioprotection in ischemia-reperfusion (I/R) injury and the mechanisms involved. The cardioprotection effect and mechanisms of tetrandrine was evaluated by I/R injury cardiac cell model. Hexokinase II (HKII) is the critical regulators of mitochondrial dysfunction in cardiac I/R injury and it participate in the regulation of glycolysis and energy metabolism...
August 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28822832/combined-immunodeficiency-with-ebv-positive-b-cell-lymphoma-and-epidermodysplasia-verruciformis-due-to-a-novel-homozygous-mutation-in-rasgrp1
#7
Craig D Platt, Ari J Fried, Rodrigo Hoyos-Bachiloglu, G Naheed Usmani, Birgitta Schmidt, Jennifer Whangbo, Roberto Chiarle, Janet Chou, Raif S Geha
RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Like the previously described patient, our proband also presented with CD4(+) T cell lymphopenia, impaired T cell proliferation to mitogens and antigens, reduced NK cell function, and EBV-associated lymphoma...
August 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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/28822766/pseudomonas-aeruginosa-increases-muc1-expression-in-macrophages-through-the-tlr4-p38-pathway
#9
Kosuke Kato, Alec D Hanss, Marina A Zemskova, Nicole E Morgan, Marianne Kim, Kenneth S Knox, Yong Lin, Erik P Lillehoj, Kwang Chul Kim
Alveolar macrophages (AMs) play a critical role in the clearance of Pseudomonas aeruginosa (Pa) from the airways. However, hyper-activation of macrophages can impair bacterial clearance and contribute to morbidity and mortality. MUC1 mucin is a membrane-tethered, high molecular mass glycoprotein expressed on the apical surface of mucosal epithelial cells and some hematopoietic cells, including macrophages, where it counter-regulates inflammation. We recently reported that Pa up-regulates the expression of MUC1 in primary human AMs and THP-1 macrophages, and that increased MUC1 expression in these cells prevents hyper-activation of macrophages that appears to be important for host defense against severe pathology of Pa lung infection...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28822725/berberine-modulates-amyloid-%C3%AE-peptide-generation-by-activating-amp-activated-protein-kinase
#10
Haijing Zhang, Chunhui Zhao, Guoqiong Cao, Limin Guo, Shuai Zhang, Yuexia Liang, Chunxia Qin, Ping Su, Hang Li, Wensheng Zhang
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by memory deficits and cognitive decline. Excessive amyloid-β (Aβ) peptide aggregates and forms soluble oligomers and insoluble cerebral amyloid plaques, which is widely thought to be the underlying pathogenic mechanism of AD. Therefore, effective regulation of Aβ metabolism is an important aspect of preventing and improving AD. Berberine, which is the main active component of the traditional medicinal herb Coptidis rhizoma, has a positive effect on reducing Aβ levels...
August 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28822684/cross-reactivity-and-inhibition-myotoxic-effects-induced-by-bothrops-snake-venoms-using-specific-polyclonal-anti-bnsp7-antibodies
#11
Lamartine L Melo, Mirian M Mendes, Lívia M Alves, Thais F Isabel, Sâmela A P B Vieira, Sarah N C Gimenes, Andreimar M Soares, Veridiana M Rodrigues, Luiz F M Izidoro
Polyclonal antibodies raised in Balb-c mice against BnSP-7, a Lys-49 phospholipase A2, were used to measure cross reactivity against other snake venoms. Using ELISA, these antibodies were able to recognize PLA2s isoforms present in venoms of botropic snakes at 1:6400, 1:3200 and 1:100 ratios (w/w). These antibodies highly recognized proteins of low molecular weight (∼14,000) from crude snake venom Bp and Bm by Western Blotting. PLA2 these venoms, by alignment of primary structures demonstrated high identity with BnSP-7 PLA2, especially in the C-terminal region...
August 16, 2017: Biologicals: Journal of the International Association of Biological Standardization
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/28822176/-cerebral-microangiopathy-of-diabetes
#13
REVIEW
Yuan Li, Ke-Wu Zeng, Xue-Mei Wang
Diabetes mellitus, a kind of chronic metabolic disease, has become one of major threats to human health with an increasing incidence. As a basic pathology of chronic complications related to diabetes mellitus, cerebral microangiopathy is mainly found in patients with Alzheimer's disease and lacunar infarction, and becomes one of the main reasons of death and disability in diabetic patients. The pathogenesis of cerebral microangiopathy is complicated, involving such signal pathways as metabolic abnormalities of polyol, saccharification hyperactivity, oxidative stress, abnormal transport of amyloid-β across blood-brain barrier and protein kinase C activation...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28822081/expression-profiling-of-the-map-kinase-phosphatase-family-reveals-a-role-for-dusp1-in-the-glioblastoma-stem-cell-niche
#14
Bradley N Mills, George P Albert, Marc W Halterman
The dual specificity phosphatases (DUSPs) constitute a family of stress-induced enzymes that provide feedback inhibition on mitogen-activated protein kinases (MAPKs) critical in key aspects of oncogenic signaling. While described in other tumor types, the landscape of DUSP mRNA expression in glioblastoma (GB) remains largely unexplored. Interrogation of the REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) revealed induction (DUSP4, DUSP6), repression (DUSP2, DUSP7-9), or mixed (DUSP1, DUSP5, DUSP10, DUSP15) DUSP transcription of select DUSPs in bulk tumor specimens...
August 18, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
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
#15
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/28822000/effects-of-fusariotoxin-co-exposure-on-thp-1-human-immune-cells
#16
Marie-Caroline Smith, Stéphanie Madec, Samuel Troadec, Emmanuel Coton, Nolwenn Hymery
Deoxynivalenol (DON), nivalenol (NIV), T-2 toxin (T2), fumonisin B1 (FB1), zearalenone (ZEA), and moniliformin (MON) mycotoxins are common food and feed contaminants produced by Fusarium spp. However, while they are usually found to co-occur in a large range of commodities, only few data are available on mycotoxin co-exposure effects and cellular response mechanisms. In this study, the individual and combined toxic effects of these fusariotoxins were evaluated on the THP-1 human immune cell line as major fusariotoxins are mostly potent immunomodulators...
August 18, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28821999/developmental-neurotoxicity-of-the-hippocampus-following-in-utero-exposure-to-methylmercury-impairment-in-cell-signaling
#17
Luana Heimfarth, Jeferson Delgado, Moara Rodrigues Mignori, Daniel Pens Gelain, José Cláudio Fonseca Moreira, Regina Pessoa-Pureur
In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2.0 mg/kg MeHg by gavage in alternated days from gestational day 5 until parturition. We found increased anxiety-like and decreased exploration behavior evaluated by open field test and deficit of both short- and long-term memories by novel object recognition task, respectively, in MeHg-treated pups. Downregulated PI3K/Akt/mTOR pathway and activated/hypophosphorylated (Ser9) GSK3β in MeHg-treated pups could be upstream of hyperphosphorylated Tau (Ser396) destabilizing microtubules and contributing to neural dysfunction in the hippocampus of these rats...
August 18, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28821876/transcriptomic-biochemical-and-physio-anatomical-investigations-shed-more-light-on-responses-to-drought-stress-in-two-contrasting-sesame-genotypes
#18
Komivi Dossa, Donghua Li, Linhai Wang, Xiaomin Zheng, Aili Liu, Jingyin Yu, Xin Wei, Rong Zhou, Daniel Fonceka, Diaga Diouf, Boshou Liao, Ndiaga Cissé, Xiurong Zhang
Sesame is an important oilseed crop with a high oil quality. It is prone to drought stress in the arid and semi-arid areas where it is widely grown. This study aims to decipher the response of tolerant (DT) and sensitive (DS) genotypes to progressive drought based on transcriptome, biochemical and physio-anatomical characterizations. Results indicated that under severe stress, DT relied on a well-functioning taproot while DS displayed a disintegrated root due to collapsed cortical cells. This was attributed to a higher accumulation of osmoprotectants and strong activity of antioxidant enzymes especially peroxidases in DT...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821869/trpm6-and-trpm7-differentially-contribute-to-the-relief-of-heteromeric-trpm6-7-channels-from-inhibition-by-cytosolic-mg-2-and-mg%C3%A2-atp
#19
Silvia Ferioli, Susanna Zierler, Joanna Zaißerer, Johann Schredelseker, Thomas Gudermann, Vladimir Chubanov
TRPM6 and its homologue TRPM7 are α-kinase-coupled divalent cation-selective channels activated upon reduction of cytosolic levels of Mg(2+) and Mg·ATP. TRPM6 is vital for organismal Mg(2+) balance. However, mechanistically the cellular role and functional nonredundancy of TRPM6 remain incompletely understood. Comparative analysis of native currents in primary cells from TRPM6- versus TRPM7-deficient mice supported the concept that native TRPM6 primarily functions as a constituent of heteromeric TRPM6/7 channels...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821818/an-essential-role-for-tagln2-in-phagocytosis-of-lipopolysaccharide-activated-macrophages
#20
Hye-Ran Kim, Hyun-Su Lee, Kyung-Sik Lee, In Duk Jung, Min-Sung Kwon, Chang-Hyun Kim, Seong-Min Kim, Myung-Han Yoon, Yeong-Min Park, Sang-Myeong Lee, Chang-Duk Jun
Activated macrophages have a greater ability of phagocytosis against pathogens that is mediated by large-scale actin rearrangement. However, molecular machineries that conduct this task have not been fully identified. Here, we demonstrate an unanticipated role of TAGLN2, a 22-kDa actin-binding protein, in Toll-like receptor (TLR)-stimulated phagocytosis. TAGLN2 was greatly induced in macrophages in response to lipopolysaccharide (LPS), a ligand for TLR4, partly via the NF-κB pathway. TAGLN2-deficient macrophages (TAGLN2 (-/-)) showed defective phagocytic functions of IgM- and IgG-coated sheep red blood cells as well as bacteria...
August 18, 2017: Scientific Reports
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