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https://www.readbyqxmd.com/read/28522596/lysyl-oxidase-overexpression-accelerates-cardiac-remodeling-and-aggravates-angiotensin-ii-induced-hypertrophy
#1
María Galán, Saray Varona, Anna Guadall, Mar Orriols, Miquel Navas, Silvia Aguiló, Alicia de Diego, María A Navarro, David García-Dorado, Antonio Rodríguez-Sinovas, José Martínez-González, Cristina Rodriguez
Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic mouse model with a strong cardiac expression of human LOX (TgLOX). TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H2O2 production and with cardiofibroblast reprogramming...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28522412/athero-inflammatory-nanotherapeutics-ferulic-acid-based-poly-anhydride-ester-nanoparticles-attenuate-foam-cell-formation-by-regulating-macrophage-lipogenesis-and-reactive-oxygen-species-generation
#2
Rebecca A Chmielowski, Dalia S Abdelhamid, Jonathan J Faig, Latrisha K Petersen, Carol R Gardner, Kathryn E Uhrich, Laurie B Joseph, Prabhas V Moghe
Enhanced bioactive anti-oxidant formulations are critical for treatment of inflammatory diseases, such as atherosclerosis. A hallmark of early atherosclerosis is the uptake of oxidized low density lipoprotein (oxLDL) by macrophages, which results in foam cell and plaque formation in the arterial wall. The hypolipidemic, anti-inflammatory, and antioxidative properties of polyphenol compounds make them attractive targets for treatment of atherosclerosis. However, high concentrations of antioxidants can reverse their anti-atheroprotective properties and cause oxidative stress within the artery...
May 15, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28522400/impact-of-lysyl-oxidase-g473a-polymorphism-on-diabetic-foot-ulcers
#3
Sivakamasundari Pichu, Jayalalitha Sathiyamoorthy, Selvaraj Vimalraj, Vijay Viswanathan, Suvro Chatterjee
Lysyl oxidase (LOX) is an extra-cellular matrix-modifying enzyme that has been linked to cell proliferation, metastasis, angiogenesis and wound healing. This study was designed to examine the association of LOX gene polymorphism G473A, G>A, (rs1800449) located in exon 1 of the LOX gene in diabetic subjects with and without diabetic foot ulcers (DFU) and its impact of expression on DFU. Genotypic analysis of 906 samples showed a significant increase in the presence of 'A' allele in type 2 diabetes mellitus (T2DM) and DFU when compared to that of control subjects...
May 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28521788/methanol-extract-of-dicranopteris-linearis-l-leaves-impedes-acetaminophen-induced-liver-intoxication-partly-by-enhancing-the-endogenous-antioxidant-system
#4
Zainul Amiruddin Zakaria, Farah Hidayah Kamisan, Maizatul Hasyima Omar, Nur Diyana Mahmood, Fezah Othman, Siti Selina Abdul Hamid, Muhammad Nazrul Hakim Abdullah
BACKGROUND: The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats. METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP)...
May 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28515378/direct-involvement-of-arachidonic-acid-in-the-development-of-ear-edema-via-trpv3
#5
Takao Sanaki, Erika Kasai-Yamamoto, Takeshi Yoshioka, Shota Sakai, Kohei Yuyama, Takuji Fujiwara, Yoshito Numata, Yasuyuki Igarashi
Arachidonic acid (AA) plays a pivotal role in the development of edema via its oxidized metabolites derived from cyclooxygenase (COX) and lipoxygenase (LOX), and is recently recognized as an activator of TRPV3. However, it is not clear whether AA plays some TRPV3-mediated pathological roles in the development of edema. Pharmacological and histological studies using ICR(TRPV3+/+) and ICR(TRPV3-/-) mice indicated that higher ear edema responses to topical application of AA were observed in ICR(TRPV3+/+) mice compared with ICR(TRPV3-/-) mice...
May 17, 2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28515079/impact-of-acetaminophen-consumption-and-resistance-exercise-on-extracellular-matrix-gene-expression-in-human-skeletal-muscle
#6
Shivam H Patel, Andrew C D'Lugos, Erica R Eldon, Donald Curtis, Jared M Dickinson, Chad C Carroll
Acetaminophen (APAP) given during chronic exercise reduces skeletal muscle collagen and cross-linking in rats. We propose that the effect of APAP on muscle ECM may, in part, be mediated by dysregulation of the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). The purpose of this study was to evaluate the impact of APAP consumption during acute resistance exercise (RE) on several regulators of the ECM in human skeletal muscle. In a double-blinded, placebo-controlled, randomized cross-over design, recreationally active men (n=8, 25±2yr) performed two trials of knee extension...
May 17, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28510269/kallikrein-related-peptidase-4-induces-cancer-associated-fibroblast-features-in-prostate-derived-stromal-cells
#7
T Kryza, L M Silva, N Bock, R A Fuhrman-Luck, C R Stephens, J Gao, H Samaratunga, M G Lawrence, J D Hooper, Y Dong, G P Risbridger, J A Clements
The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intra-epithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peri-stromal interface...
May 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28507520/in-vitro-and-in-silico-antidiabetic-and-antimicrobial-evaluation-of-constituents-from-kickxia-ramosissima-nanorrhinum-ramosissimum
#8
Adnan Amin, Emmy Tuenter, Kenn Foubert, Jamhsed Iqbal, Paul Cos, Louis Maes, Vassiliki Exarchou, Sandra Apers, Luc Pieters
Background and Aims:Kickxia ramosissima (Wall.) Janch (or Nanorrhinum ramosissimum (Wall.) Betsche is a well-known medicinal plant in Pakistan that is traditionally used in diabetic and inflammatory conditions. Because little information is available on its phytochemical composition, a range of constituents were isolated and evaluated in vitro in assays related to the traditional use. Methods: Dried whole plant material was extracted and chromatographically fractionated. Isolated constituents were evaluated in silico and in vitro in assays related to the traditional use against diabetes (inhibition of α-glucosidase activity; inhibition of advanced glycation endproducts) and in inflammatory conditions (inhibition of AAPH induced linoleic acid peroxidation, inhibition of 15-LOX, antimicrobial activity)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28503414/adult-onset-deletion-of-the-prader-willi-syndrome-susceptibility-gene-snord116-in-mice-results-in-reduced-feeding-and-increased-fat-mass
#9
Louise Purtell, Yue Qi, Lesley Campbell, Amanda Sainsbury, Herbert Herzog
BACKGROUND: The imprinted small nucleolar RNA (snoRNA) Snord116 is implicated in the aetiology of Prader-Willi syndrome (PWS), a disease associated with hyperphagia and obesity. Germline deletion of Snord116 in mice has been found to lead to increased food intake but not to the development of obesity. To determine the role of Snord116 independent of potential compensatory developmental factors, we investigated the effects of conditional adult-onset deletion of Snord116 in mice. METHODS: Deletion of Snord116 was induced at 8 weeks of age by oral administration of tamoxifen to male Snord(lox/lox); ROSA(cre/+) mice, with vehicle-treated mice used as controls...
April 2017: Translational pediatrics
https://www.readbyqxmd.com/read/28502039/possible-involvement-of-the-lipoxygenase-and-leukotriene-signaling-pathways-in-cisplatin-mediated-renal-toxicity
#10
Osama A Alkhamees, Abdulaziz S Alroujayee, Hatem M Abuohashish, Fatima S Alrojayee, Mohammed M Ahmed
PURPOSE: The present study examined the possible involvement of the lipoxygenase (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after one week. Signs of renal dysfunction, including urea and creatinine clearance levels and renal histological structure, were investigated. Gene and protein expression levels of different LOX pathway enzymes and products, including 5-LOX, 12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4 hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl (cys) LT receptor types 1 and 2, were also determined in the kidneys using real-time PCR and western blotting, respectively...
May 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28501682/the-role-of-arachidonic-acid-cyclooxygenase-cascade-phosphodiesterase-iv-and-rho-kinase-in-h2s-induced-relaxation-in-the-mouse-corpus-cavernosum
#11
Fatma Aydinoglu, Nuran Ogulener
BACKGROUND: Penile corpus cavernosum is an extremely vascularized tissue and cavernosal smooth muscle tone is regulated by the balance between contractile and relaxant factor. We investigated the possible role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV (PDEIV) and Rho-kinase in exogenous hydrogen sulfide (H2S)-induced relaxation in mouse corpus cavernosum. METHODS: The relaxant response to H2S (NaHS as exogenous H2S; 1-1000μM) were obtained in isolated mouse corpus cavernosum tissues which pre-contracted by phenylephrine (5μM)...
February 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28501579/eicosapentaenoic-acid-monoglyceride-resolves-inflammation-in-an-ex-vivo-model-of-human-peripheral-blood-mononuclear-cell
#12
Caroline Morin, Léane Charbonneau, Nicole Ouellet, Hélène Ouellet, Pierre U Blier, France Dufresne, Samuel Fortin
Phosphorylation and activation of p38 MAPK and NFκB pathways, along with the resulting overproduction of interleukin IL-1β, IL-6, and tumor necrosis factor a (TNFα) is a hallmark of inflammatory disorders. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementations are known to exert anti-inflammatory properties by reduction of keys cytokines and enzymes involved in inflammation. Here, we investigated the anti-inflammatory pathways and mediators modulated by eicosapentaenoic acid monoglyceride (MAG-EPA) on human peripheral blood mononuclear cells (PBMCs) from healthy donors and stimulated, ex vivo, with lipopolysaccharide (LPS)...
May 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28500683/induction-of-telomere-mediated-chromosomal-truncation-and-behavior-of-truncated-chromosomes-in-brassica-napus
#13
Xiaohong Yan, Chen Li, Jie Yang, Lijun Wang, Chenghong Jiang, Wenhui Wei
Engineered minichromosomes could be stably inherited and serves as a platform for simultaneously transferring and stably expressing multiple genes. Chromosomal truncation mediated by repeats of telomeric sequence is a promising approach for the generation of minichromosomes. In the present work, direct repetitive sequences of Arabidopsis telomere were used to study telomere-mediated truncation of chromosomes in Brassica napus. Transgenes containing alien Arabidopsis telomere were successfully obtained, and Southern blotting and fluorescence in situ hybridization (FISH) results show that the transgenes successfully resulted in chromosomal truncation in B...
May 13, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28496472/synthesis-and-biological-evaluation-of-n-5-pyridin-2-yl-1-3-4-thiadiazol-2-yl-benzamide-derivatives-as-lipoxygenase-inhibitor-with-potential-anticancer-activity
#14
Alireza Aliabadi, Ahmad Mohammadi-Farani, Sahar Roodabeh, Farahnaz Ahmadi
In the recent years, the role of LOX enzymes in the origin of neoplastic diseases such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized and the cytotoxicity of the members of this series was assessed using MTT protocol. Enzyme inhibitory activity of the prepared compounds was also tested against 15-lipoxygenase-1 as a novel target for the discovery of anticancer drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were compared with doxorubicin...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28495238/uncovering-the-role-of-nuclear-lysyl-oxidase-lox-in-advanced-high-grade-serous-ovarian-cancer
#15
Marta De Donato, Marco Petrillo, Enrica Martinelli, Flavia Filippetti, Gian Franco Zannoni, Giovanni Scambia, Daniela Gallo
OBJECTIVE: Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of collagen and elastin in the extracellular matrix, thus controlling the tensile strength of tissues. Along with this primary function, there are evidences supporting a role for LOX in many critical biological functions, including gene expression regulation, cell growth, adhesion and migration. Accordingly, recent studies have supported a pivotal role for LOX in cancer progression and metastasis. The current study aimed at investigating the prognostic significance and the functional role of intracellular LOX in ovarian cancer...
May 8, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28487402/biological-functions-controlled-by-manganese-redox-changes-in-mononuclear-mn-dependent-enzymes
#16
REVIEW
Wen Zhu, Nigel G J Richards
Remarkably few enzymes are known to employ a mononuclear manganese ion that undergoes changes in redox state during catalysis. Many questions remain to be answered about the role of substrate binding and/or protein environment in modulating the redox properties of enzyme-bound Mn(II), the nature of the dioxygen species involved in the catalytic mechanism, and how these enzymes acquire Mn(II) given that many other metal ions in the cell form more stable protein complexes. Here, we summarize current knowledge concerning the structure and mechanism of five mononuclear manganese-dependent enzymes: superoxide dismutase, oxalate oxidase (OxOx), oxalate decarboxylase (OxDC), homoprotocatechuate 3,4-dioxygenase, and lipoxygenase (LOX)...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28482466/synthesis-structure-elucidation-and-biological-evaluation-of-triple-bridged-dinuclear-copper-ii-complexes-as-anticancer-and-antioxidant-anti-inflammatory-agents
#17
Z Boulsourani, S Katsamakas, G D Geromichalos, V Psycharis, C P Raptopoulou, D Hadjipavlou-Litina, E Yiannaki, C Dendrinou-Samara
Seeking for copper based metallo-therapeutics, three triple bridged dinuclear copper(II) complexes [Cu2(μ2-L2)(bipy)2(μ2-OH)(μ2-H2O)](NO3)2·H2O (1·H2O), [Cu2(μ2-L2)(bipy)2(μ2-OH)(μ2-NO3)](NO3)·0.6MeOH·0.4H2O (2·0.6MeOH·0.4H2O) and [Cu2(μ2-L1)(bipy)2(μ2-OH)(μ2-NO3)(H2O)](NO3)·2H2O (3·2H2O) where L2=2-thiophene acetato, L1=2-thiophene carboxylato and bipy=2,2'-bipyridine were synthesized and structurally characterized. The complexes were subjected in vitro to a pharmacochemical evaluation for their antioxidant/anti-inflammatory activity, cytotoxicity and efficacy against human ovarian, lung, colon, breast, kidney and cervical cancer cell lines along with non tumor human lung and breast cell lines...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28480509/oxidized-low-density-lipoprotein-stimulates-epithelial-sodium-channels-in-endothelial-cells-of-mouse-thoracic-aorta
#18
Chen Liang, Qiu-Shi Wang, Xu Yang, Na Niu, Qing-Qing Hu, Bao-Long Zhang, Ming-Ming Wu, Chang-Jiang Yu, Xiao Chen, Bin-Lin Song, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Epithelial sodium channel (ENaC) is expressed in endothelial cells and acts as a negative modulator of vasodilation. Oxidized low-density lipoprotein (ox-LDL) is a key pathological factor in endothelial dysfunction. The present study is to examine the role of ENaC in ox-LDL-induced endothelial dysfunction and its associated signal transduction pathway. EXPERIMENTAL APPROACH: Patch-clamp techniques combined with pharmacological approaches were used to examine ENaC activity in the endothelial cells of split-open mouse thoracic aorta...
May 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28474779/a-novel-in-vivo-model-for-studying-conditional-dual-loss-of-blimp-1-and-p53-in-b-cells-leading-to-tumor-transformation
#19
Antonio Sacco, Yawara Kawano, Michele Moschetta, Oksana Zavidij, Daisy Huynh, Michaela Reagan, Yuji Mishima, Salomon Manier, Jihye Park, Elizabeth Morgan, Satoshi Takagi, Kwok K Wong, Ruben Carrasco, Irene M Ghobrial, Aldo M Roccaro
The tumor suppressors B-Lymphocyte-Induced Maturation Protein-1 (BLIMP-1) and p53 play a crucial role in B-cell lymphomas, and their inactivation contributes to the pathogenesis of a wide spectrum of lymphoid malignancies, including diffuse large B-cell lymphomas (DLBCLs). Patients with activated B-cell-like (ABC) DLBCL may present with loss of BLIMP-1, c-Myc over-expression, decreased p53, and poor prognosis. Nevertheless, there is a lack of in vivo models recapitulating the biology of high-grade ABC DLBCL...
May 5, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28471663/the-identification-of-4-aminomethyl-6-trifluoromethyl-2-phenoxy-pyridine-derivatives-as-potent-selective-and-orally-efficacious-inhibitors-of-the-copper-dependent-amine-oxidase-lysyl-oxidase-like-2-loxl2
#20
Martin W Rowbottom, Gretchen Bain, Imelda Calderon, Taylor Lasof, David Lonergan, Andiliy Lai, Fei Huang, Janice Darlington, Patricia Prodanovich, Angelina M Santini, Christopher D King, Lance Goulet, Kristen E Shannon, Gina L Ma, Katherine Nguyen, Deidre A MacKenna, Jilly F Evans, John H Hutchinson
LOXL2 catalyzes the oxidative deamination of ε-amines of lysine and hydroxylysine residues within collagen and elastin, generating reactive aldehydes (allysine). Condensation with other allysines or lysines drives formation of inter- and intramolecular cross-linkages, a process critical for remodeling of the ECM. Dysregulation of this process can lead to fibrosis and LOXL2 is known to be upregulated in fibrotic tissue. Small-molecules that directly inhibit LOXL2 catalytic activity represent a useful option for the treatment of fibrosis...
May 4, 2017: Journal of Medicinal Chemistry
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