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Lysyl oxidase like 1

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https://www.readbyqxmd.com/read/28764769/anabolic-role-of-lysyl-oxidase-like-2-in-cartilage-of-knee-and-temporomandibular-joints-with-osteoarthritis
#1
Weam Alshenibr, Mustafa M Tashkandi, Saqer F Alsaqer, Yazeed Alkheriji, Amelia Wise, Sadanand Fulzele, Pushkar Mehra, Mary B Goldring, Louis C Gerstenfeld, Manish V Bais
BACKGROUND: Lysyl oxidase like-2 (LOXL2) is a copper-dependent amine oxidase. Our previous studies showed that LOXL2 is elevated during mouse fracture healing. The goal of this study was to evaluate the potential of LOXL2 to act as an anabolic agent in cartilage affected by osteoarthritis (OA). METHODS: LOXL2 was visualized in tissues from human knee and hip joints and temporomandibular joints (TMJ) by immunofluorescence. The activity of LOXL2 in human articular and TMJ chondrocytes was assessed by cell-based assays, microarray analysis, and RT-qPCR, and LOXL2-mediated activation of NF-κB and extracellular signal-related kinase (ERK) signaling pathways was measured by western blotting...
August 2, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28683690/using-costal-chondrocytes-to-engineer-articular-cartilage-with-applications-of-passive-axial-compression-and-bioactive-stimuli
#2
Le Huwe, Gurdeep Sullan, Jerry C Hu, Kyriacos A Athanasiou
Generating neocartilage with suitable mechanical integrity from a cell source that can circumvent chondrocyte scarcity is indispensable for articular cartilage regeneration strategies. Costal chondrocytes of the rib eliminate donor site morbidity in the articular joint, but it remains unclear how neocartilage formed from these cells responds to mechanical loading, especially if the intent is to use it in a load-bearing joint. In a series of three experiments, this study sought to determine efficacious parameters of passive axial compressive stimulation that would enable costal chondrocytes to synthesize mechanically robust cartilage...
July 6, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28623328/platelet-rich-plasma-induces-post-natal-maturation-of-immature-articular-cartilage-and-correlates-with-loxl1-activation
#3
Yadan Zhang, Ben J Morgan, Rachel Smith, Christopher R Fellows, Catherine Thornton, Martyn Snow, Lewis W Francis, Ilyas M Khan
Platelet-rich plasma (PRP) is used to stimulate the repair of acute and chronic cartilage damage even though there is no definitive evidence of how this is achieved. Chondrocytes in injured and diseased situations frequently re-express phenotypic biomarkers of immature cartilage so tissue maturation is a potential pathway for restoration of normal structure and function. We used an in vitro model of growth factor-induced maturation to perform a comparative study in order to determine whether PRP can also induce this specific form of remodeling that is characterised by increased cellular proliferation and tissue stiffness...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592436/bladder-fibrosis-during-outlet-obstruction-is-triggered-through-the-nlrp3-inflammasome-and-the-production-of-il-1%C3%AE
#4
Francis Monty Hughes, Stephanie J Sexton, Huixia Jin, Vihasa Govada, J Todd Purves
Bladder outlet obstruction (BOO) triggers inflammation in the bladder through the NLRP3 inflammasome. BOO also activates fibrosis, which is largely responsible for the decompensation of the bladder in the chronic state. Because fibrosis can be driven by inflammation, we have explored a role for NLRP3 (and IL-1β produced by NLRP3) in the activation and progression of BOO-induced fibrosis. Female rats were divided into 5 groups: 1) control, 2) sham, 3) BOO + Vehicle, 4) BOO + the NLRP3 inhibitor glyburide or 5) BOO + the IL-1β receptor antagonist anakinra...
June 7, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28559441/apmap-interacts-with-lysyl-oxidase-like-proteins-and-disruption-of-apmap-leads-to-beneficial-visceral-adipose-tissue-expansion
#5
Ariane R Pessentheiner, Katharina Huber, Helmut J Pelzmann, Andreas Prokesch, Franz P W Radner, Heimo Wolinski, Josefine Lindroos-Christensen, Gerald Hoefler, Thomas Rülicke, Ruth Birner-Gruenberger, Martin Bilban, Juliane G Bogner-Strauss
Adipocyte plasma membrane-associated protein (APMAP) has been described as an adipogenic factor in 3T3-L1 cells with unknown biochemical function; we therefore aimed to investigate the physiologic function of APMAP in vivo We generated Apmap-knockout mice and challenged them with an obesogenic diet to investigate their metabolic phenotype. We identified a novel truncated adipocyte-specific isoform of APMAP in mice that is produced by alternative transcription. Mice lacking the full-length APMAP protein, the only isoform that is expressed in humans, have an improved metabolic phenotype upon diet-induced obesity, indicated by enhanced insulin sensitivity, preserved glucose tolerance, increased respiratory exchange ratio, decreased inflammatory marker gene expression, and reduced adipocyte size...
May 30, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28534485/pseudoexfoliation-syndrome-associated-genetic-variants-affect-transcription-factor-binding-and-alternative-splicing-of-loxl1
#6
Francesca Pasutto, Matthias Zenkel, Ursula Hoja, Daniel Berner, Steffen Uebe, Fulvia Ferrazzi, Johannes Schödel, Panah Liravi, Mineo Ozaki, Daniela Paoli, Paolo Frezzotti, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Shinichi Manabe, Erika Salvi, Paolo Manunta, Daniele Cusi, Christian Gieger, Heinz-Erich Wichmann, Tin Aung, Chiea Chuen Khor, Friedrich E Kruse, André Reis, Ursula Schlötzer-Schrehardt
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28503365/genetics-diagnosis-and-monitoring-of-pseudoexfoliation-glaucoma
#7
Niraj Nathan, Rachel W Kuchtey
Recent studies have shed new light on the genetic factors underlying pseudoexfoliation syndrome, growing our understanding of the role of the lysyl oxidase-like 1 (LOXL1) gene and its various polymorphisms as well as identifying new genetic associations. Recent years have brought new insight on how these genetic factors interact with other factors, including environmental, to confer risk to individuals and populations worldwide. All of these findings may hold importance to the screening, diagnosis, and monitoring of pseudoexfoliation and may also help lead to the identification of novel therapeutic targets...
December 2016: Current Ophthalmology Reports
https://www.readbyqxmd.com/read/28471663/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
#8
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 the formation of inter- and intramolecular cross-linkages, a process critical for the 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 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28425924/roles-of-copper-binding-proteins-in-breast-cancer
#9
REVIEW
Stéphanie Blockhuys, Pernilla Wittung-Stafshede
Copper ions are needed in several steps of cancer progression. However, the underlying mechanisms, and involved copper-binding proteins, are mainly elusive. Since most copper ions in the body (in and outside cells) are protein-bound, it is important to investigate what copper-binding proteins participate and, for these, how they are loaded with copper by copper transport proteins. Mechanistic information for how some copper-binding proteins, such as extracellular lysyl oxidase (LOX), play roles in cancer have been elucidated but there is still much to learn from a biophysical molecular viewpoint...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28369002/association-of-lysyl-oxidase-like-1-gene-polymorphism-in-turkish-patients-with-pseudoexfoliation-syndrome-and-pseudoexfoliation-glaucoma
#10
Mahmut Asfuroglu, Busranur Cavdarli, Özlem Gurbuz Koz, Ahmet A Yarangumeli, Emine Y Ozdemir
No abstract text is available yet for this article.
March 31, 2017: Journal of Glaucoma
https://www.readbyqxmd.com/read/28369001/association-of-lysyl-oxidase-like-1-gene-polymorphism-in-turkish-patients-with-pseudoexfoliation-syndrome-and-pseudoexfoliation-glaucoma
#11
Suzan Guven Yilmaz, Melis Palamar, Hüseyin Onay, Orhan Ilim, Ayca Aykut, Feristah F Ozkinay, Ayse Yagci
No abstract text is available yet for this article.
July 2017: Journal of Glaucoma
https://www.readbyqxmd.com/read/28325283/silencing-of-carbohydrate-sulfotransferase-15-hinders-murine-pulmonary-fibrosis-development
#12
Yoshiro Kai, Koichi Tomoda, Hiroyuki Yoneyama, Masahiro Kitabatake, Atsuhiro Nakamura, Toshihiro Ito, Masanori Yoshikawa, Hiroshi Kimura
Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG) has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We show that chondroitin sulfate E-type (CS-E) is involved in fibrogenesis. Small interfering RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) was designed to inhibit CHST15 mRNA and its product, CS-E...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28257048/vanillin-suppresses-cell-motility-by-inhibiting-stat3-mediated-hif-1%C3%AE-mrna-expression-in-malignant-melanoma-cells
#13
Eun-Ji Park, Yoon-Mi Lee, Taek-In Oh, Byeong Mo Kim, Beong-Ou Lim, Ji-Hong Lim
Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 (FN1), lysyl oxidase-like 2 (LOXL2), and urokinase plasminogen activator receptor (uPAR)...
March 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28248847/effect-of-pregnancy-and-delivery-on-cytokine-expression-in-a-mouse-model-of-pelvic-organ-prolapse
#14
Bruna M Couri, Andrew T Lenis, Ali Borazjani, Brian M Balog, Mei Kuang, Robert S Butler, Marc S Penn, Margot S Damaser
OBJECTIVES: The aim of this study was to determine the effect of pregnancy and delivery mode on cytokine expression in the pelvic organs and serum of lysyl oxidase like-1 knockout (LOXL1 KO) mice, which develop pelvic organ prolapse after delivery. METHODS: Bladder, urethra, vagina, rectum, and blood were harvested from female LOXL1 KO mice during pregnancy, after vaginal or cesarean delivery, and from sham cesarean and unmanipulated controls. Pelvic organs and blood were also harvested from pregnant and vaginally delivered wild-type (WT) mice and from unmanipulated female virgin WT controls...
February 28, 2017: Female Pelvic Medicine & Reconstructive Surgery
https://www.readbyqxmd.com/read/28246207/a-phase-ii-randomized-double-blind-placebo-controlled-study-of-simtuzumab-in-combination-with-folfiri-for-the-second-line-treatment-of-metastatic-kras-mutant-colorectal-adenocarcinoma
#15
J Randolph Hecht, Al B Benson, Dmitry Vyushkov, Yingsi Yang, Johanna Bendell, Udit Verma
LESSONS LEARNED: The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic KRAS mutant colorectal carcinoma. BACKGROUND: Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro...
March 2017: Oncologist
https://www.readbyqxmd.com/read/28246206/a-phase-ii-randomized-double-blind-placebo-controlled-study-of-simtuzumab-or-placebo-in-combination-with-gemcitabine-for-the-first-line-treatment-of-pancreatic-adenocarcinoma
#16
Al B Benson, Zev A Wainberg, J Randolph Hecht, Dmitry Vyushkov, Hua Dong, Johanna Bendell, Fred Kudrik
LESSONS LEARNED: The safety profile in the gemcitabine/simtuzumab group was similar to that in the gemcitabine/placebo group.The addition of simtuzumab to gemcitabine does not improve clinical outcomes in patients with metastatic pancreatic adenocarcinoma ABSTRACT: Background.The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. METHODS: Adult patients with metastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m(2), in combination with 200 or 700 mg simtuzumab or placebo...
March 2017: Oncologist
https://www.readbyqxmd.com/read/28220932/a-phase-2-study-of-simtuzumab-in-patients-with-primary-post-polycythaemia-vera-or-post-essential-thrombocythaemia-myelofibrosis
#17
MULTICENTER STUDY
Srdan Verstovsek, Michael R Savona, Ruben A Mesa, Hua Dong, Julia D Maltzman, Shringi Sharma, Jeffrey Silverman, Stephen T Oh, Jason Gotlib
Simtuzumab, a monoclonal antibody inhibitor of extracellular matrix enzyme lysyl oxidase-like-2, showed preclinical promise and was well tolerated in clinical studies. A phase 2, open-label study of simtuzumab was conducted in patients with primary myelofibrosis (MF), post-polycythaemia vera MF and post-essential thrombocythaemia MF. Fifty-four patients were randomized to receive simtuzumab alone (200 or 700 mg [n = 12 each group]) or simtuzumab (200 or 700 mg) with ruxolitinib (n = 15 each group) for 24 weeks...
March 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28203099/a-new-dermocosmetic-containing-retinaldehyde-delta-tocopherol-glucoside-and-glycylglycine-oleamide-for-managing-naturally-aged-skin-results-from-in-vitro-to-clinical-studies
#18
Céline Rouvrais, Daniel Bacqueville, Patrick Bogdanowicz, Marie-José Haure, Laure Duprat, Christine Coutanceau, Nathalie Castex-Rizzi, Hélène Duplan, Valérie Mengeaud, Sandrine Bessou-Touya
INTRODUCTION: Natural aging of skin tissues, the addition of the cumulative action of the time and radiation exposure result in skin atrophy, wrinkles and degeneration of the extracellular matrix (ECM). The aim of the study was to investigate the beneficial effect of a combination containing retinaldehyde (RAL), delta-tocopherol glucoside (delta-TC) and glycylglycine ole-amide (GGO) and of a dermocosmetic containing the combination. MATERIALS AND METHODS: The protective effect of the combination was assessed through in vitro gene expression of ultraviolet (UV)-irradiated fibroblasts...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28196225/blood-vessel-basement-membrane-alterations-in-human-retinal-microaneurysms-during-aging
#19
Mariana López-Luppo, Victor Nacher, David Ramos, Joana Catita, Marc Navarro, Ana Carretero, Alfonso Rodriguez-Baeza, Luísa Mendes-Jorge, Jesús Ruberte
Purpose: Microaneurysms, considered a hallmark of retinal vascular disease, are present in aged retinas. Here, the basement membrane of human retinal microaneurysms has been analyzed during aging. Methods: Retinas were obtained from 17 nondiabetic donors. Whole mount retinas and paraffin sections were marked immunohistochemically with antibodies against the main components of the blood basement membrane. Trypsin digestion and transmission electron microscopy also were performed...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28125844/proteomic-analysis-of-the-bovine-and-human-ciliary-zonule
#20
Alicia De Maria, Phillip A Wilmarth, Larry L David, Steven Bassnett
Purpose: The zonule of Zinn (ciliary zonule) is a system of fibers that centers the crystalline lens on the optical axis of the eye. Mutations in zonule components underlie syndromic conditions associated with a broad range of ocular pathologies, including microspherophakia and ectopia lentis. Here, we used HPLC-mass spectrometry to determine the molecular composition of the zonule. Methods: Tryptic digests of human and bovine zonular samples were analyzed by HPLC-mass spectrometry...
January 1, 2017: Investigative Ophthalmology & Visual Science
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