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https://www.readbyqxmd.com/read/28203140/tamoxifen-activation-of-cre-recombinase-has-no-persisting-effects-on-adult-neurogenesis-or-learning-and-anxiety
#1
Peter Rotheneichner, Pasquale Romanelli, Lara Bieler, Sebastian Pagitsch, Pia Zaunmair, Christina Kreutzer, Richard König, Julia Marschallinger, Ludwig Aigner, Sébastien Couillard-Després
Adult neurogenesis is a tightly regulated process continuously taking place in the central nervous system of most mammalian species. In neuroscience research, transgenic animals bearing the tamoxifen-inducible CreER(T2)-Lox system are widely used. In this study, we made use of a Nestin-CreER(T2)/R26R-YFP transgenic mouse model in which the CreER(T2) activates the expression of YFP in multipotent neural stem cells upon tamoxifen application. Humoral factors, such as the levels of estrogens, have been reported to affect the hippocampal neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#2
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202387/varenicline-enhances-oxidized-ldl-uptake-by-increasing-expression-of-lox-1-and-cd36-scavenger-receptors-through-%C3%AE-7-nachr-in-macrophages
#3
Yuki Kanaoka, Mitsuhisa Koga, Keita Sugiyama, Kaoru Ohishi, Yasufumi Kataoka, Atsushi Yamauchi
Varenicline is a widely used and effective drug for smoking cessation. It is a partial agonist of the α4β2 nicotinic acetylcholine receptor (nAChR) and full agonist of α7 nAChR. We have reported that varenicline aggravates formation of atherosclerotic plaques through α7 nAChR in apolipoprotein E knockout mice. However, little is known about its effects on macrophages in atherosclerotic plaques. Here, we ascertained whether varenicline promotes oxidized low-density lipoprotein (oxLDL) uptake in mouse peritoneal macrophages in vitro and clarified its mechanism...
February 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28199967/pre-clinical-evaluation-of-small-molecule-loxl2-inhibitors-in-breast-cancer
#4
Joan Chang, Morghan C Lucas, Lidia E Leonte, Marc Garcia-Montolio, Lukram Babloo Singh, Alison D Findlay, Mandar Deodhar, Jonathan S Foot, Wolfgang Jarolimek, Paul Timpson, Janine T Erler, Thomas R Cox
Lysyl Oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases is known to be important in normal tissue development and homeostasis, as well as the onset and progression of solid tumors. Here we tested the anti-tumor properties of two generations of novel small molecule LOXL2 inhibitor in the MDA-MB-231 human model of breast cancer. We confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. Inhibition of LOXL2 activity inhibited the growth of primary tumors and reduced primary tumor angiogenesis...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199510/endothelial-lox-1-activation-differentially-regulates-arterial-thrombus-formation-depending-on-oxldl-levels-role-of-the-oct-1-sirt1-and-erk1-2-pathways
#5
Alexander Akhmedov, Giovanni G Camici, Martin F Reiner, Nicole Bonetti, Sarah Costantino, Erik W Holy, Remo D Spescha, Simona Stivala, Ariane Schaub Clerigué, Thimoteus Speer, Alexander Breitenstein, Jasmin Manz, Christine Lohmann, Francesco Paneni, Juerg-Hans Beer, Thomas F Lüscher
No abstract text is available yet for this article.
February 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28197798/inhibition-of-proinflammatory-pathways-by-bioactive-fraction-of-tinospora-cordifolia
#6
Jenny Jacob, Bashi M Babu, Mohind C Mohan, A P Abhimannue, B Prakash Kumar
Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thomson, a known immunomodulatory agent extensively used in ayurveda, has not been effectively validated for the mechanisms involved in immunomodulation and the identification of the active principles. The bioactive fraction of T. cordifolia (TBF) in methanol was used for nitric oxide (NO) radical scavenging activity, lipoxygenase (LOX) and cyclooxygenase (COX) dual inhibition and cytotoxicity studies. Production of the proinflammatory cytokines, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in dendritic cell (DC) suspensions treated with lipopolysaccharide (LPS) was also studied...
February 15, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28196857/deletion-of-hypoxia-inducible-factor-1%C3%AE-in-myeloid-lineage-exaggerates-angiotensin-ii-induced-formation-of-abdominal-aortic-aneurysm
#7
Yusuke Takahara, Tomotake Tokunou, Hiroshi Kojima, Yoshitaka Hirooka, Toshihiro Ichiki
Hypoxia-inducible factor (HIF)-1α is a transcription factor that regulates various genes responding to hypoxic conditions. We previously reported that myeloid-specific activation of HIF-1α had protective effects on hypertensive cardiovascular remodeling in mice. However the role of myeloid lineage HIF-1α in the development of abdominal aortic aneurysm (AAA) has not been determined. Myeloid-specific HIF-1α knockout (HIF-1KO) mice were created using a Cre-lox recombination system in the background of apolipoprotein E-deficient mice...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28191448/a-food-grade-expression-system-for-d-psicose-3-epimerase-production-in-bacillus-subtilis-using-an-alanine-racemase-encoding-selection-marker
#8
Jingqi Chen, Zhaoxia Jin, Yuanming Gai, Jibin Sun, Dawei Zhang
BACKGROUND: Food-grade expression systems require that the resultant strains should only contain materials from food-safe microorganisms, and no antibiotic resistance marker can be utilized. To develop a food-grade expression system for d-psicose 3-epimerase production, we use an alanine racemase-encoding gene as selection marker in Bacillus subtilis. RESULTS: In this study, the d-alanine racemase-encoding gene dal was deleted from the chromosome of B. subtilis 1A751 using Cre/lox system to generate the food-grade host...
2017: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/28189063/the-nf-%C3%AE%C2%BAb-inhibitor-celastrol-attenuates-acute-hepatic-dysfunction-induced-by-cecal-ligation-and-puncture-in-rats
#9
Ghada S El-Tanbouly, Mohammed S El-Awady, Nermeen A Megahed, Hatem A Salem, Hassan A El-Kashef
Acute hepatic dysfunction associating sepsis is mediated mainly by toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB) inflammatory pathway. This study explores potential hepatoprotective effect of the NF-κB inhibitor celastrol in cecal ligation and puncture (CLP) model in rats. Protective effect of celastrol (1mg/kg, i.p., 1h before CLP) was illustrated after 24h by preventing CLP-induced hepatic histopathological changes and elevation in serum hepatic biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB) and gamma aminotransferase (γ-GT)] without affecting mortality...
February 4, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28188225/inflammation-induced-caveolin-1-and-bmprii-depletion-promotes-endothelial-dysfunction-and-tgf%C3%AE-driven-pulmonary-vascular-remodeling
#10
Suellen Darc Santos Oliveira, Maricela Castellon, Jiwang Chen, Marcelo G Bonini, Xiaowu Gu, Michael H Elliott, Roberto F Machado, Richard D Minshall
Endothelial cell (EC) activation and vascular injury are hallmark features of Acute Lung Injury and Acute Respiratory Distress Syndrome (ALI/ARDS). Caveolin-1 (Cav-1) is highly expressed in pulmonary microvascular ECs and plays a key role in maintaining vascular homeostasis. The aim of this study was to determine whether the lung inflammatory response to Escherichia coli lipopolysaccharide (LPS) promotes priming of ECs via Cav-1 depletion and whether this contributes to the onset of pulmonary vascular remodeling...
February 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28187270/epithelial-myeloid-differentiation-factor-88-is-dispensable-during-klebsiella-pneumonia
#11
Adam A Anas, Theodora A M Claushuis, Rajiv A Mohan, Vincent M Christoffels, Vassilis Aidinis, Sandrine Florquin, Cornelis Van't Veer, Baidong Hou, Alex F de Vos, Tom van der Poll
Klebsiella (K.) pneumoniae is a common cause of pneumonia. Previous studies have documented an important role for Toll-like receptors (TLRs) expressed by myeloid cells in the recognition of K. pneumoniae and the initiation of a protective immune response. Lung epithelial cells also express TLRs and can participate in innate immune defense. The aim of this study was to examine the role of the common TLR adaptor protein myeloid differentiation factor (MyD)88 in lung epithelium during host defense against K. pneumoniae induced pneumonia...
February 10, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28185540/medicinal-chemistry-approaches-of-controlling-gastrointestinal-side-effects-of-non-steroidal-anti-inflammatory-drugs-endogenous-protective-mechanisms-and-drug-design
#12
Paraskevi Tziona, Panagiotis Theodosis-Nobelos, Eleni A Rekka
BACKGROUND: Non steroidal anti-inflammatory drugs are of the oldest and most widely used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX) inhibition, in combination with the weekly acidic character of most of them, major protective mechanisms of the gastrointestinal system are suppressed and deregulated. OBJECTIVE: In this review, several compounds designed to retain anti-inflammatory activity, but devoid of gastrointestinal side effects, are presented...
February 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28185186/eicosacell-an-imaging-based-assay-to-identify-spatiotemporal-eicosanoid-synthesis
#13
Christianne Bandeira-Melo, Ligia Almeida Paiva, Natália R T Amorim, Peter F Weller, Patricia T Bozza
Eicosanoids are bioactive lipids derived from enzymatic metabolism of arachidonic acid via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. These lipids are newly formed and nonstorable molecules that have important roles in physiological and pathological processes. The particular interest to determine intracellular compartmentalization of eicosanoid-synthetic machinery has emerged as a key component in the regulation of eicosanoid synthesis and in delineating functional intracellular and extracellular actions of eicosanoids...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28182779/o-prenylated-3-carboxycoumarins-as-a-novel-class-of-15-lox-1-inhibitors
#14
Atena Jabbari, Mina Mousavian, Seyed Mohamad Seyedi, Mehdi Bakavoli, Hamid Sadeghian
Allyloxy, Isopentenyloxy, geranyloxy and farnesyloxy derivatives of 3-carboxycoumarin, at position 5, 6, 7, and 8, were synthesized and their inhibitory potency against human 15-lipoxygenase-1 (human 15-LOX-1) were determined. Among the synthetic coumarins, O-allyl and O-isopentenyl derivatives demonstrated no considerable lipoxygenase inhibition while O-geranyl and O-farnesyl derivatives demonstrated potent inhibitory activity. 5-farnesyloxy-3-carboxycoumarin demonstrated the most potent inhibitory activity by IC50 = 0...
2017: PloS One
https://www.readbyqxmd.com/read/28182113/evaluation-of-an-aqueous-extract-from-horseradish-root-armoracia-rusticana-radix-against-lipopolysaccharide-induced-cellular-inflammation-reaction
#15
Corinna Herz, Hoai Thi Thu Tran, Melinda-Rita Márton, Ronald Maul, Susanne Baldermann, Monika Schreiner, Evelyn Lamy
Horseradish (Armoracia rusticana) is a perennial crop and its root is used in condiments. Traditionally, horseradish root is used to treat bacterial infections of the respiratory tract and urinary bladder. The antiphlogistic activity, determined in activated primary human peripheral blood mononuclear cells (PBMC), was evaluated for an aqueous extract and its subfractions, separated by HPLC. Compound analysis was done by UHPLC-QToF/MS and GC-MS. The aqueous extract concentration-dependently inhibited the anti-inflammatory response to lipopolysaccharide (LPS) in terms of TNF-α release at ≥37 μg/mL...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28177760/ceruloplasmin-derived-peptide-is-the-strongest-regulator-of-oxidative-stress-and-leukotriene-synthesis-in-neutrophils
#16
Ekaterina Golenkina, Alexey Livenskyi, Galina Viryasova, Yulia Romanova, Galina Sud'ina, Alexey Sokolov
Ceruloplasmin, an acute-phase protein, can affect the activity of leukocytes through its various enzymatic activities and protein-protein interactions (with lactoferrin, myeloperoxidase, eosinophil peroxidase, serprocidins, and 5-lipoxygenase (5-LOX), among others). However, the molecular mechanisms of ceruloplasmin activity are not clearly understood. In this study, we tested the ability of two synthetic peptides, RPYLKVFNPR (883-892) (P1) and RRPYLKVFNPRR (882-893) (P2), corresponding to the indicated fragments of the ceruloplasmin sequence, to affect neutrophil activation...
January 10, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28172697/p066-fibrostenotic-phenotype-of-fibroblasts-in-crohn-s-disease-is-dependent-on-tissue-stiffness-and-reversed-by-lox-inhibition
#17
J de Bruyn, G van den Brink, J Steenkamer, C Buskens, W Bemelman, S Meisner, V Muncan, A Te Velde, G D'Haens, M Wildenberg
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28168011/semipurified-ethyl-acetate-partition-of-methanolic-extract-of-melastoma-malabathricum-leaves-exerts-gastroprotective-activity-partly-via-its-antioxidant-antisecretory-anti-inflammatory-action-and-synergistic-action-of-several-flavonoid-based-compounds
#18
Noor Wahida Ismail Suhaimy, Ahmad Khusairi Noor Azmi, Norhafizah Mohtarrudin, Maizatul Hasyima Omar, Siti Farah Md Tohid, Manraj Singh Cheema, Lay Kek Teh, Mohd Zaki Salleh, Zainul Amiruddin Zakaria
Recent study has demonstrated the gastroprotective activity of crude methanolic extract of M. malabathricum leaves. The present study evaluated the gastroprotective potential of semipurified extracts (partitions): petroleum ether, ethyl acetate (EAMM), and aqueous obtained from the methanolic extract followed by the elucidation of the gastroprotective mechanisms of the most effective partition. Using the ethanol-induced gastric ulcer assay, all partitions exerted significant gastroprotection, with EAMM being the most effective partition...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28162041/n-hexanal-and-z-3-hexenal-are-generated-from-arachidonic-acid-and-linolenic-acid-by-a-lipoxygenase-in-marchantia-polymorpha-l
#19
Moataz M Tawfik, Katsuyuki T Yamato, Takayuki Kohchi, Takao Koeduka, Kenji Matsui
Most terrestrial plants form green leaf volatiles (GLVs), which are mainly composed of six-carbon (C6) compounds. In our effort to study the distribution of the ability of lipoxygenase (LOX) to form GLVs, we found that a liverwort, Marchantia polymorpha, formed n-hexanal and (Z)-3-hexenal. Some LOXs execute a secondary reaction to form short chain volatiles. One of the LOXs from M. polymorpha (MpLOX7) oxygenized arachidonic and α-linolenic acids at almost equivalent efficiency and formed C6-aldehydes during its catalysis; these are likely formed from hydroperoxides of arachidonic and α-linolenic acids, with a cleavage of the bond between carbon at the base of the hydroperoxy group and carbon of double bond, which is energetically unfavorable...
February 6, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28159417/design-synthesis-and-cytotoxicity-of-stabilized-mycolactone-analogs
#20
Vaddela Sudheer Babu, Ya Zhou, Yoshito Kishi
On exposure to visible light, mycolactone A/B, the causative toxin of Buruli ulcer, rearranges to a mixture of four photo-mycolactones apparently via a rare photochemically-induced [4πs+2πa] cycloaddition. In order to prevent the rearrangement, two C6'-C7' dihydromycolactone analogs 6'α-15 and 6'β-15 were designed and synthesized. 6'α-15 and 6'β-15 were shown to be stable under not only photochemical, but also acidic and basic conditions. Cytotoxicity was tested against arbitrarily chosen four cell lines (human Hek-293, human lung carcinoma A-549, human melanoma LOX-IMVI, and mouse L-929), thereby revealing that: (1) both analogs maintain potent cytotoxicity; (2) 6'β-15 exhibits significantly higher potency against human cell lines than 6'α-15; (3) in comparison with parent mycolactone A/B, 6'β-15 exhibits equal potency against human Hek-293, whereas significantly lower potency against human lung carcinoma A-549 and human melanoma LOX-IMVI...
January 17, 2017: Bioorganic & Medicinal Chemistry Letters
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